November 2015 Clinical Advisor

THE CLINICAL ADVISOR • NOVEMBER 2015

A PEER-REVIEWED FORUM FOR NURSE PRACTITIONERS

NEWSLINE

■ Mammography screening ■ Colorectal adenomas ■ Menopause guidelines FEATURE The IUD Rumor Mill

Clearing up misconceptions LEGAL ADVISOR

|

NOVEMBER 2015

| www.ClinicalAdvisor.com

TREATMENT OVERVIEW FOR

PSORIASIS

Options include topical agents, phototherapy, and systemic and biologic agents.

Thyroid cancer misdiagnosed

✶ FREE CE COURSES!

■ Dermatology Clinic

PAINFUL LESIONS WITH FEVER PAGE 67

■ Dermatologic Look-Alikes VOLUME 18, NUMBER 11

DARK ENLARGING LESION PAGE 71 SAVE THE DATE April 7–9, 2016

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Editor Colby Stong, editor@ClinicalAdvisor.com Senior editor Sandhya George Associate digital content editor Hannah Dellabella Assistant editor Lauren Biscaldi Contributing editors Mark P. Brady, PA-C; Philip R. Cohen, MD; Deborah L. Cross, MPH, CRNP, ANP; Sharon Dudley-Brown, PhD, FNP; Abimbola Farinde, PharmD; Laura A. Foster, CRNP, FNP; Abby A. Jacobson, PA; Maria Kidner, DNP, FNP; Joan W. Kiely, MSN, CRNP; Debra August King, PhD, PA; Ann W. Latner, JD; Mary Newberry, CNM, MSN; Claire Babcock O’Connell, MPH, PA; Kathy Pereira, DNP, FNP; Sherril Sego, DNP, FNP; Ann Walsh, PA-C, SCT(ASCP); Kim Zuber, PA-C Production editor Kim Daigneau Group art director, Haymarket Medical Jennifer Dvoretz Production director Ada Figueroa Circulation manager Paul Silver National accounts manager Alison McCauley, 646.638.6098 alison.mccauley @ haymarketmedical.com Publisher Thomas P. Hennessy, 646.638.6085 tom.hennessy @ haymarketmedia.com Editorial director Kathleen Walsh Tulley Senior vice president, digital products and medical magazines Jim Burke, RPh

Unsure about a diagnosis or treatment?

Ask our

EXPERTS If a patient has you stumped, write us and we’ll forward your query to one of our consultants and publish the response in Advisor Forum.You can also use this space to contribute a clinical pearl of your own or comment on another letter.

Advisor Forum These are letters from practitioners around the country who want to share their clinical problems and successes, observations, and pearls with their colleagues. Responding consultants are identified below. We invite you to participate.

CLINICAL PEARLS

INTRA-ARTICULAR INJECTIONS FOR SEVERE OSTEOARTHRITIS Patients with severe osteoarthritis in the knees seem to do better with intra-articular injections if you have them sit up and dangle their legs off the examination table and distract the knee slightly when administering the injection.—ROSEMARY LEDBETTER, PhD, PA, Troy, Ill. (202-3)

GENERIC “CAINE” IS EFFECTIVE FOR WOUND CARE For pain relief, most pharmacies offer a “caine” at 2-510%, and basically nothing higher, for between $5 and $30 per tube. I work in wound care and use Walmart’s Equate brand—vagicaine 20% benzocaine. When using this before debriding a wound, give it three minutes to sedate the nerves, then perform the procedure. I get good results, as patients say. It relieves pain and burning for $1.88.

YOUR COMMENTS SLIPPED CAPITAL FEMORAL EPIPHYSIS IN OBESE ADOLESCENTS I just read the CME/CE article by Marilou Shreve, DNP, APRN, entitled, “Assessing and treating pediatric obesity” [ June 2015]. I was concerned regarding the oversight of a critical issue in obese adolescents: the increased risk of slipped capital femoral epiphysis (SCFE). This was not addressed in the article.

The case study (p. 55) gave incomplete advice regarding the evaluation of an obese adolescent male with knee pain.

The most common etiology of the insidious onset of knee pain in children is the hip, due to referred pain from the

Advisor Fo

Send us your letters with questions and comments to: Advisor Forum, The Clinical Advisor, 114 West 26th Street, 4th Floor, New York, NY 10001. You may contact us by e-mail at editor@ clinicaladvisor.com. If you are writing in response to a published letter, please indicate so by including the number in parentheses at the end of each item. Letters are edited for length and clarity. The Clinical Advisor’s policy is to print the author’s name with the letter. No anonymous contributions will be accepted.

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These are letters from and succe sses, obser practitioners aroun d the count vations, and below. We ry who want OUR CONSULTANTS pearl invite you to participate. s with their collea to gues. Respo share their clinical problems nding consu ltants are identified CONSULT ATIONS

TREATMEN INFECTIO T FOR URIN ARY SGLT2 RECE MALE CHILNS IN THE UNC TRACT IRCUMCIS D FOR DIAB PTOR BLOC If a male ED KERS child contin ETES Deborah L. Cross, MPH, CRNP, Laura A. Foster, CRNP, FNP, Abby A. Jacobson, PA-C, Abimbola Farinde, PhD, PharmD, With the ues istoassociate ANP-BC, program practices family medicine is a physician assistant is a professor redeve advent a circum lop urinar at Columbia ofPrimary SGLT2 recept at Delaware Valley director,cision Gerontology NP Program, Southern modal itywith Palmetto y tract infecfor type be perfor or Physicians Dermatology University of Pennsylvania School blockersGroup University 2 diabetes, med? regard ing inCare as a treatm in Wilmington, Del. is there in Orange Beach, Ala. useCharleston, S.C. ent urology is of Nursing, Philadelphia. any eviden NATHAN in patients with to protect the is well advised ce or data type 1 diabet GARDNER, es mellitu continues to to recommend a circumcupper tracts, the kidney PA-C, CPAA s?— develop ision www.ClinicalAdvisor.com PA, Castlet 44 THE CLINICAL ADVISOR • AUGUST 2015 recurren the male child s. It As it currentl several t urinary tract•on on, N.Y. conside y stands, who for infections. impede the rations that enter into glycemic control SGLT2 receptor There are ability to cleanse this decision blockers in adults with are with diet . Poor hygiene should the and quell type 2 diabete FDA-approved child have may approve and exercise, but phimosis, simpleinfection potential. s in conjunc appropriate the FDA d for use in Moreover, has stated urine AdvisorForum_CA0815.indd 44 9/29/15 tion 2:38 PM catheter patients culture ketoaci ization that with type steroid cream can be a challen they are not dosis, or those to obtain an may tempor ge. Having with severe 1 diabetes, patients with FARIN tion of the arily solve a short trial diabetic steroid the these of informa DE, PhD, PharmD renal function.—AB tendency redevelo issues, though after for infection IMBO (See bottom tion about LA once again.— cessaps, placing Dr. Farind of this page Milwaukee, COLEEN the child at e.) (203-2 for more Wis. (203-1 ) risk ROSEN, DNP, FNP-C ) , CLIN

Write us today.

Philip R. Cohen, MD,

is clinicaltions, associate professor should of dermatology, University of Texas Medical Center, The focus of Houston.

SEND TO The Clinical Advisor 114 West 26th Street, 4th floor New York, NY 10001

ICAL PEAR

Send us your letters Advisor with questio Forum, The New York, Clinical Advisor, ns and comme NY 10001. nts clinicaladvisor.c You may 114 West 26th Street,to: contact please indicate om. If you are 4th Floor, us so by includin writing in responsby e-mail at editor@ each item. e to a g the Letters are policy is edited for number in parenth published letter, to contributionsprint the author’s length and clarity. eses at the end of The will be accepte name with the letter. Clinical Advisor’s d.

No anonym ous

OUR CON

LS

VAGINAL RESULTIN DISCHARGE AND G FROM If a female TAMPON ODOR patient has USE a ask if she uses tampo history of vaginal dischar ns. If she the pelvic ge with says “yes,” exam, when condu odor, that you would do not enter the vagina cting to take in the same rotating of the specul a pap smear. Instead way the cervix um . Most retaine from side to side , start shallow until d tampons are lodged reaching in the fold

SULTAN TS

Philip R.

Cohen, MD, is clinical associate professor of dermatol ogy, of Texas MedicalUniversity Center, Houston.

62 THE CLINIC

Deborah L. Cross, MPH, ANP-BC,

is associate CRNP, director, Gerontolo program gy NP University of Pennsylva Program, nia School of Nursing, Philadelphia.

AL ADVISO

R • SEPTEM

BER 2015

AdvisorFo

E-MAIL: editor@clinicaladvisor.com

It cannot be beat.—TERRI JORDAN, ARNP, Daytona Beach, Fla. (202-2)

NEUTROPHILS AND LYMPHOCYTES In interpreting a complete blood count with differential, anytime the neutrophils and lymphocytes are numerically close, it is a viral cause; when the neutrophils and lymphocytes are numerically distant, it is a bacterial cause.

This is very helpful in determining treatment.—DONNA CARTER, FNP-C, Scottsburg, Ind. (202-1)

Abimbola

Farinde,

PhD, PharmD,

is a professor at Columbia Southern University in Orange Beach, Ala.

• www.C

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Laura A.

Foster,

practices familyCRNP, FNP, with Palmetto medicine Primary Care Physician in Charlesto s n, S.C.

Abby A.

Jacobson

is a physician , PA-C, at Delawareassistant Dermatology Valley in Wilmingt Group on, Del.

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8 THE CLINICAL ADVISOR • NOVEMBER 2015 • www.ClinicalAdvisor.com

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Writers’ Guidelines The Clinical Advisor welcomes submissions from its readers. Writing for us is an opportunity to share your knowledge and experience with your colleagues — and to collect a fee in the bargain! We pay an honorarium for every submission we accept.

We’ll be glad to work with you to develop your ideas into compelling articles. As for length, that depends on which kind of article you submit.

CLINICAL FEATURES update our readers on the latest information about conditions seen in everyday practice. Running approximately 2,500 to 5,000 words, including the references, features can be written either as regular narratives or as a series of questions and answers. Topics should be selected with the busy primary-care clinician in mind; specialists should review specialty topics from the primary-care point of view.

If at all possible, articles should be accompanied by clinical photos.

Charts, tables, and algorithms are also encouraged. Please include your title and affiliation.

CLINICAL CHALLENGE is our popular department comprising histories of difficult cases. Each case is presented as a step-by-step, chronological account, revealing the author’s thought processes along the way. It is divided into sections in this order: the patient presentation; the patient history; the twists and turns eventually leading to a diagnosis; the treatment and outcome; and a discussion of the lessons learned or of the condition in general.

The length should be about 1,500 words, and accompanying images are encouraged. Please include your title and affiliation.

DERMATOLOGY CLINIC is a department that presents photos of actual cases and asks readers to identify the condition. Each case opens with one or two color photos and a 75-to-100-word description of the patient presentation, without giving away the diagnosis.

This is followed by a 750-to-1,000-word summary that includes a fuller description of the ailment, an explanation of how the correct diagnosis was reached, a general review of the condition along with a differential diagnosis, and a description of the patient’s treatment and outcome. Topics must be approved by the editor prior to submission. Please include your title and affiliation.

COMMENTARY is our guest editorial page. It gives you the opportunity to sound off on an issue of importance to your colleagues nationwide. A typical Commentary runs about 600 words in length. Please include your title and affiliation.

To discuss your editorial ideas, contact us by phone at 646.638.6078; by e-mail to editor@ClinicalAdvisor.com; or by mail to The Clinical Advisor, 114 West 26th Street, 4th Floor, New York, NY 10001. www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • NOVEMBER 2015 9

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CONTENTS NOVEMBER 2015

NEWS AND COMMENT

FEATURES

24 Newsline ■■Women with an average risk of breast cancer may begin annual mammography screening at age 45 and get screened less often, according to updated guidelines.

■■Lower doses of beta-blockers are as effective or more effective than higher doses for the survival of patients following acute myocardial infarction.

■■Vitamin D and calcium supplements do not reduce the risk of colorectal adenomas in patients who have had a precancerous colorectal adenoma removed.

■■Providers treating symptoms of menopause in women should assess the individual benefits and risks of therapeutic options, according to new guidelines.

■■Drug-resistant E. coli infections are being increasingly transmitted at community hospitals.

■■Children who have had infections, such as upper respiratory infections, or who have not received their scheduled vaccinations are at higher risk for stroke.

■■The enterovirus D68 (EV-D68) respiratory infection does not increase the risk of death or need for critical care in children.

■■And more.

32 The IUD rumor mill: common misconceptions Disseminating accurate information can help women make informed decisions and potentially increase the overall use of intrauterine devices.

106 Commentary Basal insulin for surgical diabetic patients

MAKING CONTACT

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Follow us on Twitter @ClinicalAdvisor

Revised mammography guidelines 24

44 CME/CE Psoriasis: an overview of current and emerging medications Many therapeutic options are available for psoriasis, ranging from topical agents to phototherapy and systemic and biologic agents.

54 CME/CE Feature posttest

DEPARTMENTS

Drug-resistant E. coli infections 26

20 Web Roundup A summary of our most recent opinion, news, and multimedia content from ClinicalAdvisor.com 63 Legal Advisor A clinician misdiagnoses thyroid cancer as acid reflux.

Continues on page 18

Misconceptions about IUD use 32

Like us on Facebook facebook.com/TheClinicalAdvisor

www.ClinicalAdvisor.com

Visit us on the web ClinicalAdvisor.com

Download the app http://app.lk/AZ6

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CONTENTS DEPARTMENTS, cont’d 66

102 Alternative Meds Update ■■Taurine. A sulphur-containing amino acid, taurine has a number of biochemical roles in human metabolism.

CME/CE Dermatology Clinic ■ Hypertrichosis over a brown patch ■ Painful lesions with fever and malaise

71 CME/CE Dermatologic Look-Alikes Raised, dark, enlarging lesion

ADVISOR FORUM

76

CME/CE Dermatology posttest

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Clinical Challenge ■■Painful red spot and fever in an infant. A child and her twin had tested positive for influenza B infection one week earlier.

Your Comments ■■Stopping prescription drug abuse.

A reader responds to a previously published Commentary, “Narcotic abuse in the emergency department.”

■■Vaccination, parents, and children

94

OTC Corner ■■Omega-3 fatty acids: from fins and fish oil to flax. Omega-3 fatty acids are a healthy subgroup of polyunsaturated fatty acids (PUFAs). Most of the PUFAs that are consumed in the Western world are proinflammatory omega-6 oils, which may be a contributing factor to many chronic diseases.

56

Clinical Pearls ■■How to distinguish bradykinesia from psychomotor retardation ■■Metformin XR for diabetes care

57

Consultations ■■Many patients with coronary-related issues have normal lipid levels, so is the real benefit of statins their antiinflammatory benefits?

Painful red spot and fever in an infant 78

Fish are a source of omega-3 fatty acids 94

HOW TO CONTACT US THE CLINIC AL ADVIS OR • NOVE

TO SUBMIT A CLINICAL QUESTION FOR PUBLICATION:

MBER 2015

TO SUBSCRIBE: • www.ClinicalAdvisor.com/subscribe

A PEER -REV

E

■ Mammog raphy screenin ■ Colorect g al adenoma s ■ Menopa use guideline s

FEATUR E

The IUD

TO CONTACT THE EDITOR: • editor@ClinicalAdvisor.com • Call 646.638.6078

Rumor Mill

Clearing up

misconceptio

ns

LEGAL ADV

ISOR

Thyroid canc er

misdiagnosed

✶ FREE CME COURS

ASSIS TANT

S

|

NOV EMBE

R 2015

| www.Clin icalA

dvisor.com

TREATM

ENT OVER VI

PSORIASIS

EW FOR Options inclu topical agen de ts, photothe rapy, and syste mic and biologic agen ts.

ES!

• Send it by e-mail to editor@ClinicalAdvisor.com

67

ER 11

• Mail it to The Clinical Advisor, 114 W. 26th St., 4th Floor, New York, NY 10001

■ Dermatolo gy Clinic

PAINFUL WITH FEVLESIONS ER PAGE

18, NUMB

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• www.ClinicalAdvisor.com/AdvisorForum

VOLUM E

TO SUBMIT AN ARTICLE: • editor@ClinicalAdvisor.com

IEWE D FORU M FOR PHYS ICIAN

NEWSLIN

■ Dermatolo gic

DARK ENL Look-Alikes LESION PAGEARGING 71 SAVE THE DATE

April 7–9,

2016

For more details ClinicalAdviso , visit rSummit.com

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EXCLUSIVE TO THE WEB AT

ClinicalAdvisor.com The Waiting Room

Web Exclusives

Official Blog of The Clinical Advisor

ClinicalAdvisor.com/News

ClinicalAdvisor.com/WaitingRoom Robyn Carlisle, MSN, CNM Early pregnancy loss deserves empathy and sensitivity After a couple experiences a miscarriage, their grief needs to be treated with sensitivity rather than dismissal.

Jim Anderson, MPAS, PA-C, DFAAPA, ATC No excuses: clinicians should never disrespect patients Medical practitioners should always treat patients with respect, no matter how stressed or annoyed they are.

Jillian Knowles, MMS, PA-C After an accident, when do you need a new car seat?

Car seats must be replaced after moderate and severe car crashes, but often they do not need to be replaced after minor crashes.

Quality of cardiovascular care from NPs, PAs similar to that from physicians Nurse practitioners and physician assistants deliver similar-quality outpatient cardiovascular care compared with physicians.

High number of U.S. children remain unvaccinated against measles Due to a dip in the number of vaccinated individuals, almost a quarter of children younger than age 3 years are currently susceptible to measles.

Influenza vaccine can prevent ­pneumonia hospitalizations The influenza vaccine may be able to prevent approximately 57% of hospitalizations due to influenza pneumonia.

Multimedia ClinicalAdvisor.com/Multimedia Screening for colorectal cancer should begin at 50 Colorectal cancer is the third most common preventable cancer, but it rarely causes pain until the later stages of the disease. Teresa McKamey, RN, MSN, discusses the importance of regularly screening patients for colon cancer starting at 50 years of age. Watch it here: ClinicalAdvisor.com/ColonCancerVid

Communication between clinicians and patients can improve diagnoses A new report from the National Academies of Science, Engineering, and Medicine says that a majority of patients will receive a misdiagnosis in their lifetime. To overcome

MAKING CONTACT

Follow us on Twitter @ClinicalAdvisor

this, health care teams need to communicate and work together with patients and families. Watch it here: ClinicalAdvisor.com/DiagnosisVid

AAP urges health care workers to get flu vaccine Wendy Sue Swanson, MD, MBE, discusses the new influenza vaccine recommendations from the American Academy of Pediatrics. They stress that all health care workers who work with children should be required to get the vaccine.

Watch it here: ClinicalAdvisor.com/FluVaccineVid

Like us on Facebook facebook.com/TheClinicalAdvisor

Visit us on the web ClinicalAdvisor.com

Go mobile with us mobile.ClinicalAdvisor.com

20 THE CLINICAL ADVISOR • NOVEMBER 2015 • www.ClinicalAdvisor.com

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Advisor Dx

EXCLUSIVE TO THE WEB

INTERACT WITH YOUR PEERS by viewing the images and offering your diagnosis and comments. To post your answer, obtain more clues, or view similar cases, visit ClinicalAdvisor.com/AdvisorDx. Learn more about diagnosing and treating these conditions, and see how you compare with your fellow colleagues.

Ortho Dx

In partnership with

TheJopa.org

Journal of Orthopedics for Physician Assistants

Pain and swelling in the right knee A male, aged 20 years, presents with a 10-month history of progressive pain in the right knee and soft-tissue swelling. Images were obtained from anteroposterior x-ray and coronal magnetic resonance imaging.

WHAT IS THE BEST TREATMENT PLAN?

• Curettage and bone grafting • Radiation and chemotherapy • Amputation above the knee with postoperative radiation • Chemotherapy, wide resection, and joint reconstruction with custom implant ● See the full case at ClinicalAdvisor.com/OrthoDx_Nov15

Derm Dx Hyperkeratotic central plaque on the arm A 58-year-old male presents for evaluation and treatment of a lesion on his arm that was first noted about 4 months ago and has continued to enlarge. Physical examination reveals a slightly elevated hyperkeratotic central plaque of 0.6 cm overlying a 1.5-cm dermal nodule.

CAN YOU DIAGNOSE THE CONDITION?

• Epidermoid cyst • Pilomatricoma • Lipoma • Metastatic carcinoma ● See the full case at ClinicalAdvisor.com/DermDx_Nov15

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • NOVEMBER 2015 21

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ADS-01325-001 Rev. 001 Š 2015 Hologic, Inc. All rights reserved. Hologic, Science of Sure, Pap+HPV Together, ThinPrep and associated logos are trademarks and/or registered trademarks of Hologic, Inc. and/or its subsidiaries in the United States and/or other countries. All other trademarks, registered trademarks, and product names are the property of their respective owners.

This information is intended for medical professionals in the U.S. and is not intended as a product solicitation or promotion where such activities are prohibited. Because Hologic materials are distributed through websites, eBroadcasts and tradeshows, it is not always possible to control where such materials appear. For specific information on what products are available for sale in a particular country, please contact your local Hologic representative or write to diagnostic.solutions@hologic.com.

Screening with HPV-Alone invites more risk into women’s lives than you may think.

One out of 5 cases of cervical cancer were missed with HPV-Alone screening in a recent landmark, retrospective study–the largest ever conducted to evaluate the effectiveness of cervical cancer screening strategies in women ages 30-65.1* Additionally, screening with Pap+HPV Together™ (co-testing) identified more than 70% of those missed cancers.1 And it only requires one sample. So is HPV-Alone screening really worth the risk?

Screen your patients with Pap+HPV Together.

Because every woman deserves the best possible protection from cervical cancer.

See more data at PapPlusHPV.com.

* A positive HPV screening result may lead to further evaluation with cytology and/or colposcopy.

Reference: 1. Blatt AJ, Kennedy R, Luff RD, Austin RM, Rabin DS. Comparison of cervical cancer screening results among 256,648 women in multiple clinical practices. Cancer Cytopathol. 2015 April (Study included ThinPrep®, SurePath, Hybrid Capture 2 assay).

Newsline N O V E M B E R 2 015

New treatment guidelines for menopause page 26

High stress jobs are linked to stroke risk page 28

Higher stroke risk for children with infections page 30

WOMEN WITH an average risk of breast cancer may begin annual mammography screening at age 45 and get screened less often, according to new guidelines issued by the American Cancer Society (ACS) and published online ahead of print October 20 in JAMA. In an update to its 2003 breast cancer screening guidelines, the ACS commissioned an interdisciplinary guideline development group made up of clinicians, biostatisticians, epidemiologists, economists, and patient representatives to perform a systematic evidence review of current breast cancer screening literature and a metaanalysis of observational studies and randomized controlled trials.

“The 2015 updated recommendations from the ACS are intended to balance the goal of reducing the burden of breast cancer against the understanding that breast cancer screening is a preventative health intervention applied to the entire eligible population of women, most of whom will not develop breast cancer in their lifetime,” wrote lead investigator Kevin C. Oeffinger, MD, Director of the Adult Long-Term Follow-Up Program at Memorial Sloan Kettering Cancer Center in New York City, and colleagues.

The new recommendations are as follows: 1) Women with an average risk of breast cancer should undergo regular mammography screening

© SHUTTERSTOCK / AKAWATH

Updated guidelines for mammogram screening

Women with an average risk of breast cancer should undergo regular mammography screening beginning at age 45.

beginning at age 45 and continuing yearly until age 54. Women aged 40 to 44 should have the opportunity to begin annual screening, and women age 55 and older should transition to biannual screening; 2) women should continue to undergo mammography screening based on these recommendations so long as their overall health is good and they have a life expectancy of 10 years or longer; and 3) the ACS no longer recommends clinical breast examinations among average-risk women at any age.

Low doses of beta-blockers effective for survival after heart attack LOWER DOSES are as effective or more effective than higher doses of beta-blockers for the survival of patients following acute myocardial infarction, according to a study published online September 21 in the Journal of the American College of Cardiology.

Jeffrey J. Goldberger, MD, MBA, and fellow investigators found that patients who received a quarter of a high dose of betablockers that has been used in previous clinical trials demonstrated decreases in mortality that were as high as 20% to 25%, when compared with patients who received the full dose.

The researchers analyzed data in a multicenter registry on 6,682 patients who had had an acute myocardial infarction; median follow-up for these patients was 2.1 years and 90% were receiving beta-blockers. Patients in the study who took betablockers, regardless of dose, survived longer, compared with

patients who did not receive beta-blockers. The researchers found that within 2 years, death occurred in 14.7% of patients who received the full dose of beta-blockers, 12.9% of those receiving half of that dose, 9.5% of those receiving a quarter of the dose, and 11.5% of those receiving an eighth of the dose.

In addition, beta-blockers have side effects, including fatigue, sexual dysfunction, and depression, which would make prescribing lower doses to patients following a heart attack a more attractive option.

More research is necessary to determine what doses are most effective for different populations, Dr. Goldberger said.

“There is probably not one right dose for every single patient,” he said. “It doesn’t make sense that the same dose will work for an 80-year-old frail man who had a small heart attack as a burly 40-year-old man with a huge heart attack.”

24 THE CLINICAL ADVISOR • NOVEMBER 2015 • www.ClinicalAdvisor.com

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Newsline THE RATE of infections caused by extended-spectrum beta-lactamase-producing (ESBL)-Escherichia coli (E. coli) that is highly resistant to antibiotics has more than doubled in community hospitals, according to a study published online October 13 in Infection Control & Hospital Epidemiology.

Joshua Thaden, MD, PhD, and colleagues studied 26 community hospitals in the southeastern United States, finding that the incidence of ESBL-E. coli infections increased from 5.28 to 10.5 per 100,000 patients from 2009 to 2014. During that period, the number of community hospitals that reported ESBL-E. coli infections increased from 17 (65%) to 20 (77%). The researchers found that approximately three-quarters of the infections

ESBL-E. coli infections more than double in community hospitals.

were picked up after exposure at a hospital or encounters with the health care system, as opposed to community-associated infections.

However, the group did note an increase in community-associated infections of ESBL-E. coli. In comparison, the researchers found that the incidence of infections caused

by ESBL-producing Klebsiella pneumonia remained constant.

Dr. Thaden noted that a lack of active screening for ESBLproducing bacteria in most hospitals results in inadequate infection prevention measures, such as contact isolation and patient cohorting, adding that “silently” colonized patients increase the risk of transmission to vulnerable patients via health care workers or environmental contamination.

New treatment guidelines for menopause PROVIDERS treating symptoms of menopause in women should assess the individual benefits and risks of therapeutic options, according to guidelines issued by the Endocrine Society and published online October 7 in the Journal of Clinical Endocrinology and Metabolism.

Authored by a task force chaired by Cynthia A. Stuenkel, MD, their recommendations for providers include the following: • Women with a uterus who decide to undergo menopausal hormone therapy with estrogen and progestogen should be informed of the risks and benefits of that therapy, including the increased risk for breast cancer once treatment is discontinued.

• All women, including those receiving hormone therapy for menopause, should

be advised to follow guidelines for breast cancer screening.

• Transdermal estrogen therapy by patch, gel, or spray is the recommended treatment; however, it does have an increased risk of venous thromboembolism.

• In women taking estrogen to relieve hot flashes, progestogen prevents uterine cancer; however, it is not necessary for women who have undergone a hysterectomy.

• Selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, gabapentin, or pregabalin are recommended for the management of moderate-to-severe hot flashes in women who prefer not to take or are contraindicated for hormone therapy.

Vitamin D for colorectal adenomas?

VITAMIN D and calcium supplements do not reduce the risk for the development of colorectal adenomas in patients who have had a precancerous colorectal adenoma removed, according to a study published October 15 online ahead of print in the New England Journal of Medicine.

Lead author John A. Baron, MD, and fellow investigators studied 2,259 patients aged 45 years to 75 years and who had had polyps removed from their colon. The patients, who had no remaining polyps at enrollment, were randomly assigned to receive 1,000 IU of vitamin D3 daily, 1,200 mg of calcium daily, both of these, or none of these. Almost half of the patients (43%) had one or more adenomas at follow-up screening colonoscopy in the 3 to 5 years following the initial screening. There was no significant difference in the frequency of new polyps in patients who took vitamin D supplements, calcium supplements, or both, when compared with those who took neither.

Previous research has suggested that vitamin D and calcium supplementation have beneficial effects against colorectal cancer, according to one of the study’s authors Dennis J. Ahnen, MD. “It could be that vitamin D and/or calcium work later in the process of carcinogenesis to prevent dangerous cancers, but not their precancerous predecessors,” he said.

© THINKSTOCK / TINYDEVIL

Drug-resistant E. coli infection rates increase at community hospitals

26 THE CLINICAL ADVISOR • NOVEMBER 2015 • www.ClinicalAdvisor.com

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Newsline Enterovirus D68 does not increase mortality in children

The investigators compared the severity of illness between children with EV-D68 and those with other rhinovirus and enterovirus infections who were admitted to the McMaster Children’s Hospital in Hamilton, Ontario. The study included 297 children, 93 of

High stress jobs are linked to increased stroke risk HIGH STRESS JOBS are associated with a higher risk of stroke, according to a meta-analysis published October 14 online ahead of print in Neurology.

Researchers reviewed six studies with a total of nearly 140,000 participants who were followed for 3 to 17 years. Jobs were classified into 4 groups based on worker control over daily tasks and how hard they worked, as well as on the psychological demands of the job: passive jobs, low stress jobs, high stress jobs, and active jobs. Across all six studies, total participants with high stress jobs ranged from 11% to 27%.

Participants with high stress jobs had a 22% higher risk of stroke, compared with those with low stress jobs; women with high stress jobs had a 33% higher stroke risk. All participants with high stress jobs were 58% more likely to have an ischemic stroke.

Participants with either passive or active jobs had no increased risk of stroke.

In an editorial, Jennifer J. Majersik, MD, MS, recommended interventions aimed at increasing job control and flexibility in job structure, such as telecommuting.

EV-D68 respiratory infection does not increase risk of death in children.

whom tested positive for EV-D68.

Children with EV-D68 were more likely to have respiratory distress, be admitted to the hospital, and receive magnesium sulfate or IV salbutamol, compared with those with other rhinovirus or enterovirus infections. However, rates of admission to the pediatric critical care unit and death among children with EV-D68 were similar to those of children without EV-D68.

Children with EV-D68 were more likely to have a family history of allergies or asthma. This suggests that patients with pre-existing atopic conditions may be more susceptible to EV-D68 than rhinoviruses and other enteroviruses.

Smoking is associated with high risk of type 2 diabetes A HIGH RISK for type 2 diabetes exists among both current smokers and those regularly exposed to second-hand smoke, according to a study published September 18 online ahead of print in The Lancet Diabetes & Endocrinology.

Researchers conducted a metaanalysis of 88 previous studies that investigated the association between smoking and type 2 diabetes risk. The study authors examined the health data of nearly 6 million participants and found that current smoking increased type 2 diabetes risk by 37%. Former smoking increased the risk by 14%, and passive smoking increased the risk by 22%. Those who quit smoking had an 11% increased risk more

than 10 years after quitting. The investigators also noted that the degree of smoking affected the results. Increased type 2 diabetes risk was 21%, 34%, and 57% for light, moderate, and heavy smokers, respectively.

It is estimated that nearly 27.8 million cases of diabetes worldwide can be attributed directly to active smoking. “Cigarette smoke should be considered as a key modifiable risk for diabetes,” said study co-author Frank Hu, MD, professor of nutrition and epidemiology at the Harvard School of Public Health. “Public health efforts to reduce smoking will have a substantial impact on the global burden of type 2 diabetes.”

© THINKSTOCK / SKHUNDA

THE ENTEROVIRUS D68 (EVD68) respiratory infection does not increase the risk of death or need for critical care in children, according to a study published October 13 online ahead of print in the Canadian Medical Association Journal.

In 2014, EV-D68 affected a significant number of children in the United States and Canada. An increase in the number of hospitalizations and admissions to intensive care units led some to believe that the EV-D68 strain was more virulent than other strains of the enterovirus. Researchers tested this hypothesis in a study of children admitted to the hospital with rhinovirus or enterovirus infections.

28 THE CLINICAL ADVISOR • NOVEMBER 2015 • www.ClinicalAdvisor.com

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Register Today April 7-9 2016 Orlando, FL The leading provider of clinical news and information for NPs & PAs presents:

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Best Practices in Effective Healthcare Collaboration The Clinical Advisor Summit is a 3-day conference offering focused sessions in high-demand practice and clinical areas to enhance the professional development of clinicians.

This interactive and informative summit will provide attendees with: • Presentations from expert faculty on evidencebased practice information, incorporating an interprofessional perspective with a focus on primary care

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10/27/15 10:05 AM

Newsline Mammography More Medicaid plans are now without CAD covering post-delivery IUDs EXPANDING Medicaid coverage will offer more women the choice to get an intrauterine device (IUD) or contraceptive implant immediately after giving birth, according to a study published September 28 online ahead of print in Contraception.

Between 40% and 60% of lowincome women who want to get an IUD or implant never attend a follow-up appointment after having their child due to constraints such as transportation and childcare.

By offering reimbursement for an IUD or implant at the same time as delivery, Medicaid will give these women the opportunity to get the birth control they want.

This can help reduce unintended pregnancies too close to the birth of the first child, which can carry risks for both the mother and fetus.

More low-income women may now be able to get an IUD.

Researchers interviewed 40 Medicaid agencies via telephone.

Agencies that did provide postdelivery contraception reimbursement often cited health benefits and cost-savings as key reasons for their decision. Among agencies that did not provide this service, concerns about potential health risks and financial uncertainty were often referenced.

In 3 years, the number of states that offer Medicaid reimbursement for an IUD or contraceptive implant has increased from zero to 19. Medicaid agencies in an additional 8 states are considering offering this reimbursement.

The study authors hope that Medicaid agencies in more states, as well as private insurance companies, will begin to cover postpartum contraception.

Higher stroke risk in children with infections CHILDREN WHO HAVE had infections, such as upper respiratory infections, or who have not received their scheduled vaccinations have a higher risk for stroke, according to research published September 30 online ahead of print in Neurology.

Heather J. Fullerton, MD, and colleagues analyzed data on 355 children aged 29 days to 18 years who had had an arterial ischemic stroke and 354 children who had not had a stroke. The children were enrolled in an international case-control study (The Vascular Effects of Infection in Pediatric Stroke). Of the children who had had a stroke, 18% had infections during the week before their strokes, compared with 3% of

children in the control group. The researchers determined a 6.3-fold increased risk of arterial ischemic stroke in children who had had an infection. The group also found that the children who had strokes were less likely to have received all or most of their recommended vaccinations.

In an accompanying editorial, José Biller, MD, and Geoffrey L. Heyer, MD, wrote, “While further study is needed to clarify how infection increases stroke risk, one can speculate that the physiologic changes related to infection (systemic inflammation, dehydration, and activation of the coagulation system) could tip the balance in a child who is already at risk for stroke.” n

© SHUTTERSTOCK / JPC-PROD

DIGITAL SCREENING mammography is as accurate without computer-aided detection (CAD) as it is with the technology, according to a study published September 28 online ahead of print in JAMA Internal Medicine.

Constance D. Lehman, MD, PhD, and colleagues studied more than 625,000 mammograms with (n=495,818) or without (n=129,807) CAD that were performed on 323,973 women.

Within one year of screening, 3,159 cases of breast cancer were identified. CAD was not associated with improvement in screening performance.

Mammography with CAD had a sensitivity of 85.3%, whereas it was 87.3% without CAD; specificity was 91.6% with CAD and 91.4% without CAD. The researchers observed no difference in the overall rate of detection of breast cancer (4.1 per 1,000 women screened with and without CAD) or in the rate for the detection of invasive breast cancers (2.9 vs. 3.0 per 1,000 women screened with or without CAD, respectively).

Mammography with CAD became widely used following a decision from the Centers for Medicare and Medicaid Services (CMS) to provide increased reimbursements for the technology in 2002. However, data on the value of CAD are limited, the authors said. “Computer-aided detection does not improve the diagnostic accuracy of mammography,” they concluded in their study.

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FEATURE: LIBBY LEVINE, MS, AGNP-BC

The IUD rumor mill: Common misconceptions Disseminating accurate information can help women make informed decisions and potentially increase the overall use of intrauterine devices.

© BRUNO BOISSONNET / SCIENCE SOURCE

L

Long-acting reversible contraception has an efficacy rate greater than 99%.

ong-acting reversible contraception (LARC), which includes both subcutaneous implants and intrauterine devices (IUDs), is the most effective form of contraception. Nurse practitioners and physician assistants who are knowledgeable about IUDs and can anticipate the concerns of patients and other providers are well-positioned to increase IUD use. This may help decrease the number of unplanned pregnancies in the United States.

Around the world, rates of IUD usage are high; for instance, rates in Uzbekistan are 50%, in Vietnam 31%, in China 41%, in Egypt 36%, and in Finland 23%.1 However, in the United States, only 5.2% of women of reproductive age use IUDs.1 This is despite the fact that methods of LARC are the most effective form of birth control aside from abstinence and have an efficacy rate of more than 99%.2 Like vasectomy and female sterilization, methods of LARC are rated Tier 1, the most effective form of contraception, by the World Health Organization and the U.S. Centers for Disease Control and Prevention.3 This article explores potential reasons for the low rates of IUD usage in the United States, despite high rates of usage elsewhere in the world and the high rates of efficacy associated with this method of contraception. Because 98% of women on LARC are using IUDs (as opposed to subcutaneous contraceptive implants),4 this article focuses mainly on IUD usage and perceptions. It will address common patient and provider misconceptions regarding the use of IUDs. Different types of IUDs will be described,

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including what is currently available in the United States and patient satisfaction, contraindications, side effects, and complications with each type, with the intent of clarifying how many of these common concerns are misguided.

Types of IUDs

Of the 3 IUDs currently available in the United States, two are hormonal. These two contain differing amounts of the hormone levonorgestrel (LNG). LNG decreases sperm motility by thickening cervical mucus and also makes changes to the endometrium to prevent implantation.

The first hormonal IUD, the LNG-releasing intrauterine system (Mirena; Bayer HealthCare Pharmaceuticals, Wayne, NJ), contains 52 mg of LNG and releases 15 mcg/d to 20 mcg/d. It can stay in place for up to 5 years. The second hormonal IUD, the LNG intrauterine system 13.5 (Skyla; Bayer HealthCare Pharmaceuticals), contains 13.5 mg of LNG, is slightly smaller, and releases approximately 6 mcg/d.5 It can be left in for no more than 3 years.

Nonhormonal and made of copper, the third IUD (Paragard; Teva Women’s Health, North Wales, PA) can stay in place for up to 10 years. The copper ions in this IUD prevent sperm motility and the activation of enzymes needed for sperm survival.

These spermicidal mechanisms prevent fertilization (Table 1).6 Patient satisfaction

Once a woman decides to use an IUD, studies have shown that she has a very high likelihood of being pleased with her choice. In addition to being a Tier 1 form of birth control, the IUD has been shown to have the highest rates of satisfaction and continued use. The Contraceptive CHOICE Project, which surveyed more than 9,000 women who use contraception, found that approximately 86% of women

who chose a LNG IUD and 81% of women who chose the copper IUD were satisfied with their chosen method.7 This was compared with only half of those who chose non-LARC methods.8 The continuation rates for the LNG and copper IUD at 12 months (88% and 85%, respectively) and 24 months (79% and 77%, respectively) are also much higher, compared with those of non-LARC methods at 12 and 24 months (57% and 41%, respectively; Table 2).7-9 Continuation rates for nulliparous women are approximately the same as continuation rates for multiparous women, according to the Contraceptive CHOICE Project.7 LNG IUD users also have very similar continuation rates at 12 months, regardless of age, with the notable exception that copper IUD users who are aged less than 20 years have a slightly higher discontinuation rate (28%), compared with women older than age 20 years (15%).10 Common reasons for discontinuation within the first 6 months, according to a 2012 study of 5,928 participants by Grunloh et al,11 were pain, cramping, and irregular, frequent, or heavy bleeding.

Recommendations

The American College of Obstetricians and Gynecologists (ACOG) and the U.S. Medical Eligibility Criteria (MEC) for Contraceptive Use state that all 3 IUDs are safe for use in nulliparous women and adolescents. IUDs are also safe in women with a history of pelvic inflammatory disease (PID) or ectopic pregnancy, who are immediately postpartum, or immediately following abortion/miscarriage (except in the presence of puerperal sepsis).9 The ACOG also states that IUDs are safe in women with a history of IUD expulsion. The ACOG, along with 3 recent studies, has recommended LARC as first-line contraception for all women7,9,11; the ACOG endorses LARC methods as the “best form of reversible contraception.”9

TABLE 1.Types of intrauterine devices.

Hormonal

Nonhormonal

NAME

Levonorgestrel-releasing intrauterine system

Levonorgestrel intrauterine system 13.5

Intrauterine copper contraceptive

BRAND NAME (manufacturer)

Mirena (Bayer HealthCare Pharmaceuticals, Wayne, NJ)

Skyla (Bayer HealthCare Pharmaceuticals)

Paragard (Teva Women’s Health, North Wales, PA)

MECHANISM OF ACTION

• Decreases sperm motility by thickening cervical mucus • Makes changes to the endometrium to prevent implantation

• Spermicidal copper ions prevent sperm motility and the activation of enzymes needed for sperm survival • Prevents fertilization

DURATION

Up to 5 years

Up to 10 years

Up to 3 years

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IUD MISCONCEPTIONS

In spite of high efficacy rates, many clinicians are hesitant to provide IUDs due to misconceptions regarding patient populations and side effects.

Several factors potentially contribute to the reluctance of patients and providers to follow expert recommendations and embrace the use of IUDs. The next section will discuss research from studies that examined patient and provider perspectives on IUDs. Provider and patient perspectives

In spite of high efficacy rates, many clinicians are hesitant to provide IUDs due to misconceptions regarding patient populations and side effects. A 2013 global study by Black et al12 found that 1,862 obstetrician–gynecologists (OBGYNs), nurse practitioners (NPs), and physician assistants (PAs) reported not offering IUDs to nulliparous patients for the following reasons: (1) difficulty in insertion; (2) concern about PID; (3) insertion pain; and (4) infertility.

In a study by Harper and associates13 of 812 physicians, NPs, and PAs, more than half of respondents would not consider nulliparous women (54%), women who are postabortion (61%), or women who have had a sexually transmitted infection (STI) in the past 2 years (61%) to be candidates for IUDs; 31% would not offer IUDs to women with a history of ectopic pregnancy, and 48% would not offer IUDs to women who have had PID in the last 5 years.

A third study by Luchowski et al,14 which surveyed 1,552 OBGYNs, found that 46% did not agree that IUDs could be inserted immediately postpartum, 20.4% disagreed that IUDs TABLE 2. Satisfaction, continuation, and discontinuation rates among IUD and non-LARC users.7-11 IUDs LNG, %

Copper, %

NonLARC, %

86

81

53

At 12 months

88

85

57

At 24 months

79

77

41

Adults

12

15

48

Adolescents

15

28

63

Rate Satisfaction rate at 12 months

Continuation rate

Discontinuation rate at 12 months

IUD, intrauterine device; LNG, levonorgestrel; LARC, long-acting reversible contraception

Concerns that both providers and patients share about IUDs.4, 12-15 • Difficult and painful insertions in nulliparous and adolescent women • Increased risk of —ectopic — pregnancy —PID/infertility — IUD, intrauterine device; PID, pelvic inflammatory disease

could be inserted after an abortion or miscarriage, 33.2% would not consider nulliparous women to be appropriate candidates for an IUD, and 57% would not consider adolescents to be appropriate candidates for IUDs. In addition, 15.6% believed IUDs increase a patient’s chance of developing PID. Many providers are hesitant to provide IUDs, and many women are reluctant to use them. A 2010 study of 1,665 women by Hladky et al15 illustrated that their major concerns included increased pelvic pain (33%-43%), infertility (20%33%), and ectopic pregnancy (24%-31%). Another study concluded that adolescents and young adults identify pain with insertion and removal as the most feared side effect of IUDs.4 Studies demonstrate that patients and providers share similar concerns.4,12-15 Both groups are concerned that IUD insertions in nulliparous and adolescent women are more difficult and painful. They are also concerned that IUDs increase a patient’s risk of ectopic pregnancy and infertility through an increased risk for PID. Some providers believe that nulliparous and adolescent women, women who are postpartum and postabortion/ miscarriage, and women with a history of ectopic pregnancy, PID, or STIs are not candidates for IUD use.

The next section reviews the ACOG recommendations and data on contraindications for use and side effects that add to the evidence that these concerns are largely unfounded.

Difficulty and pain with insertion

As discussed above, patients and providers are concerned about difficulty and pain with IUD insertion, especially in the adolescent and nulliparous population. Some nulliparous and adolescent women may have more pain upon insertion; however, providers should be able to perform the insertion without technical difficulty in most women in these populations.8 Difficulty with insertion is rare. In cases in which

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IUD MISCONCEPTIONS

Providers should make every effort to inform patients about the insertion procedure of the IUD during a preinsertion visit. the provider has difficulty, misoprostol may facilitate the insertion.10,16 It is also possible that doses of ibuprofen greater than 600 mg may relieve some pain, although studies have yet to confirm this definitively.16 In adolescents, concerns about pain during insertion have been associated with increased fear before the procedure.

Easing an adolescent’s expectation of pain before insertion may help reduce her anxiety and lead to a less painful experience.15 Adolescents often express anxiety about their first pelvic examination. Ensuring that the adolescent has had a gentle and painless pelvic examination prior to the visit during which the IUD is inserted is another way providers can ease anxiety about the insertion procedure.17 The patient will be more familiar with the pelvic examination before the IUD insertion, and the entire procedure will produce less anxiety.

In summary, providers should make every effort to inform patients about the insertion procedure during a preinsertion visit. Patients who are concerned about insertion pain should be told to take 600 mg to 800 mg of ibuprofen before the procedure and reassured that fear of pain is often worse than the actual pain.16,18 Patients should also be informed that the insertion will not be any more complicated if they are younger or nulliparous, and efforts should be made to ease their anxiety. If providers are able to convey these messages, patients’ fears associated with IUD insertions will likely be reduced.

Contraindications, infections, and infertility

In an effort to clarify common provider and patient misconceptions about contraindications, a summary of actual contraindications follows. IUDs are contraindicated in women with severe uterine distortion, who are or might be pregnant, who are experiencing unexplained abnormal bleeding, who have tuberculosis, and who are immunocompromised.6,19 Although no adverse effects related to Wilson’s disease or copper allergies have been reported, women with these conditions should not use the copper IUD.6 Women who have cervical cancer or untreated endometrial cancer also should not have an IUD inserted. However, in women with cervical cancer, the IUD usually does not need to be removed if it is already in place. Women with breast cancer should not use a LNG IUD.20 In addition to these contraindications, there is one from which many misconceptions stem—infection. IUD insertions are contraindicated in women with an active pelvic infection. However, women who develop PID while an IUD is

in place usually do not have to have the IUD removed, as long as the PID is treated.20 The risk of PID is slightly higher in women who have an IUD inserted in the presence of an STI than in women who have an IUD inserted without an STI.8 However, an IUD can be inserted in the presence of a vaginal STI, as long as it is treated.8 The ACOG states that evidence does not support routine antibiotic prophylaxis or screening for STIs in most patient populations. However, because adolescents aged 15 years to 19 years are at high risk for STIs, they should be screened before insertion.9 Due to potential bacterial contamination from the insertion procedure, women with IUDs are 6 times more likely to contract PID in the fi rst 20 days after an insertion.6 However, after that initial time period, women with IUDs are not at increased risk of PID.9 The LNG IUDs may even reduce PID rates. No studies have found an increased risk of infertility due to PID in nulliparous or adolescent IUD users compared with multiparous or older IUD users.9 It is important to note that, although certain patient populations are at increased risk for STIs and PID, the use of an IUD does not increase the risk of PID or infertility.9 Contrary to many providers’ and patients’ perceptions, IUDs are safe for use in women with a history of ectopic pregnancy6; they do not increase the risk of ectopic pregnancy. IUD users are 50% less likely to have an ectopic pregnancy compared with women who do not use contraception.20 Clarifying this fact and discussing concerns about infection and infertility with accurate and current information allows patients to make better-informed decisions about their contraception methods.

POLL POSITION

IUDs are safe for: n=1,614

■ nulliparous women and adolescents ■ women with a history of ectopic pregnancy ■ women with a history of pelvic inflammatory disease ■ all of the above

34.26% 62.64% 2.35% 0.74%

For more polls, visit ClinicalAdvisor.com/Polls.

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IUD MISCONCEPTIONS

Recommendations on IUDs from the American College of Obstetricians and Gynecologists.7,9,11 • IUDs are safe for —Nulliparous — women —Adolescents — —Women — who are ■■ immediately postpartum ■■ immediately postabortion/miscarriage —Women — with a history of ■■ PID ■■ ectopic pregnancy ■■ IUD expulsion • IUDs should be offered as first-line contraception for all women • IUDs are the best form of reversible contraception IUD, intrauterine device; PID, pelvic inflammatory disease

Side effects and complications

Providing counseling about the side effects of IUDs correlates with satisfaction and continuation rates.19 In her 2013 review, Hillard17 shows that adolescents, early adolescents in particular, tend to disregard warnings unless they are overstated. She suggests counseling adolescents to expect side effects rather than warning them that they may experience side effects. It is important that adolescents are informed that bleeding will decrease with LNG IUDs and that cramping from the copper IUD will most likely decrease over time and can be subdued with nonsteroidal anti-inflammatory drugs.18 Providers should explain the side effects of each type of IUD, paying close attention to common concerns among all patient groups and with a particular focus on clarifying those concerns. Providers should note that the LNG IUDs have been shown to reduce bleeding and pain from dysmenorrhea17; however, the copper IUD will likely increase bleeding and cramping, especially in the first few months after insertion. Patients with a history of menorrhagia or dysmenorrhea may be better served by one of the LNG IUDs.6 If patients are informed of side effects ahead of time, they will be less likely to react strongly to them if they occur.

Providers are less concerned about IUD expulsion and uterine perforation.12-14 However, IUD expulsions and uterine perforations can develop into severe complications and are consequences for which providers should be vigilant. Of the two complications, expulsion is more common, occurring in approximately 5% of IUD users.19 Providers should be aware that IUD expulsion rates may be slightly higher in adolescent

women, women with severe dysmenorrhea, most women with a history of expulsions, women who have had an immediate insertion after an abortion or miscarriage in the first trimester (when compared with an abortion or miscarriage in the second trimester), and women who have an immediate postpartum insertion (when compared with delayed insertion). Immediate insertion of an IUD after vaginal delivery also has a higher rate of expulsion than after cesarean deliveries; however, the ACOG states that the benefits of immediate postpartum insertion may outweigh the risks because delayed insertion requires another office visit that patients may not attend.6,9,22 It is also important to note that a previous expulsion is not a contraindication for the use or insertion of an IUD.9 The risk of uterine perforation is rare. Recent studies estimate that as few as 0.4 to 1 perforation occurs in every 1,000 insertions. When they do occur, the perforations are rarely dangerous.16,17,22,23 Perforation in an asymptomatic patient is not an emergency.19 A recent study showed that breastfeeding at the time of insertion created a sixfold increase in the risk of perforation.24 Other risk factors include clinician inexperience in IUD insertion, myometrial defects, an immobile uterus, or a retroverted uterus.25 A previous perforation is not a contraindication for IUD use or insertion.

Conclusions

Surveys and studies have shown that many common provider misconceptions are unfounded. Common misconceptions include the belief that nulliparous women, adolescent women, women who are postpartum or postabortion/miscarriage, women who have a recent history of PID or STIs, and women who have a history of ectopic pregnancy are not appropriate candidates for IUDs. In the United States, providers are often hesitant to offer IUDs to nulliparous and adolescent women because they have concerns about difficult insertions, pelvic pain, infertility, and PID. The data above illustrate that most of these concerns are unsubstantiated.

In addition to a gap in provider knowledge regarding IUDs, there is also an educational gap among patients. In one survey, only 50% of adolescents had heard of LARC.26 Patients frequently fear infertility and an increased risk of ectopic pregnancy, as well as increased pelvic pain and pain upon insertion. However, many of these concerns are unsupported, or can be ameliorated, if providers explain the potential side effects in advance. Providers also note that patients are more satisfied with LARC methods than any non-LARC method.

To potentially increase the use of this efficacious and welltolerated form of contraception, it is important to clarify the

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facts for both patients and providers alike and to address the most common concerns. In spite of the ACOG and MEC recommendations and numerous studies, many continue to hold on to misinformation. Among NPs, PAs, and doctors, it should be reinforced that: (1) IUD insertions in nulliparous and adolescent women are not more difficult than in any other group; (2) IUDs do not increase a patient’s risk of PID or infertility; (3) women who are nulliparous, adolescent, postpartum, or postabortion/miscarriage can safely use IUDs; and (4) a history of ectopic pregnancy, PID, or STIs does not preclude IUD use. Disseminating accurate information that addresses the specific concerns many providers and patients have about IUDs will empower women to make informed decisions and may increase use of IUDs to a rate that is closer to the rest of the world. n

11. Grunloh D, Casner T, Secura GM, et al. Characteristics associated with discontinuation of long-acting reversible contraception within the first 6 months of use. Obstet Gynecol. 2013;122(6):1214-1221.

12. Black KI, Lotke P, Lira J, et al. Global survey of healthcare practitioners’ beliefs and practices around intrauterine contraceptive method use in nulliparous women. Contraception. 2013;88(5):650-656.

13. Harper CC, Blum M, De Bocanegra HT, et al. Challenges in translating evidence to practice: the provision of intrauterine contraception. Obstet Gynecol. 2008;111(6):1359-1369.

14. Luchowski AT, Anderson BL, Power ML, et al. Obstetrician–gynecologists and contraception: Long-acting reversible contraception practices and education. Contraception. 2014; 89(6):578-583.

15. Hladky KJ, Allsworth JE, Madden T, et al. Women’s knowledge about intrauterine contraception. Obstet Gynecol. 2011;117(1):48-54.

16. Smith E, Daley AM. A clinical guideline for intrauterine device use in adolescents. J Am Acad Nurse Pract. 2012;24:453-462.

Ms. Levine received her masters in nursing from Columbia University in February 2015. She can be reached at libbyslevine@gmail.com

17. Hillard PJ. Practical tips for intrauterine devices use in adolescents. J Adolesc Health. 2013;52(4 suppl):S40-S46.

18. Brakman A, Gold M. Teen topic: Consider IUC method for teen

References

contraception. AHC Media Web site. Available at ahcmedia.com/

1. World Contraceptive Patterns 2013. United Nations Web site. Available

articles/21171-teen-topic-consider-iuc-method-for-teen-contraception

at un.org/en/development/desa/population/publications/family/contracep-

19. Yoost J. Understanding benefits and addressing misperceptions and

tive-wallchart-2013.shtml

barriers to intrauterine device access among populations in the United

2. American College of Obstetricians and Gynecologists. ACOG Practice

States. Patient Prefer Adherence. 2014;8:947-957.

bulletin no. 133: Benefits and risks of sterilization. Obstet Gynecol.

20. Dean G, Goldberg AB. Intrauterine contraception: Devices,

2013;121(2 Pt):392-404.

candidates, and selection. UpToDate website. Updated

3. Contraception for adolescents: what’s new? U.S. Department of Health

September 1, 2015. Available at uptodate.com/contents/

& Human Services Web site. Available at hhs.gov/ash/oah/oah-initiatives/

intrauterine-contraception-devices-candidates-and-selection

ta/experience_expertise_curtis.pdf

21. Medical eligibility criteria for contraceptive use. World Health

4. Kavanaugh ML, Frohwirth L, Jerman J, et al. Long-acting reversible con-

Organization Web site. Available at who.int/reproductivehealth/

traception for adolescents and young adults: Patient and provider perspec-

publications/family_planning/MEC-5/en

tives. J Pediatr Adolesc Gynecol. 2013;26(2):86-95.

22. Hardeman J, Weiss BD. Intrauterine devices: An update. Am Fam

5. Sklya [package insert]. Wayne, NJ: Bayer HealthCare Pharmaceuticals

Physician. 2014;89(6):445-450.

Inc; 2013.

23. Kaislasuo J, Suhonen S, Gissler M, et al. Uterine perforation caused

6. Speroff L, Darney PD. A Clinical Guide for Contraception. 5th ed.

by intrauterine devices: Clinical course and treatment. Hum Reprod.

Philadelphia, PA: Lippincott Williams & Wilkins; 2010.

2013;28(6):1546-1551.

7. Peipert JF, Zhao Q, Allsworth JE, et al. Continuation and satisfaction of

24. Heinemann K, Westhoff CL, Grimes DA, Möhner S. Intrauterine devic-

reversible contraception. Obstet Gynecol. 2011;117(5):1105-1113.

es and the risk of uterine perforations: Final results from the EURAS-IUD

8. O’Neil-Callahan M, Peipert JF, Zhao Q, et al. Twenty-four-month contin-

study. Obstet Gynecol. 2014;123(suppl 1):3S.

uation of reversible contraception. Obstet Gynecol. 2013;122(5):1083-1091.

25. Dean G, Goldberg AB. Intrauterine contraception:

9. Committee on Adolescent Health Care Long-Acting Reversible

Management of side effects and complications. UpToDate web-

Contraception Working Group, The American College of Obstetricians

site. Updated July 14, 2015. Available at uptodate.com/contents/

and Gynecologists. Committee opinion No. 539: adolescents and long-

intrauterine-contraception-management-of-side-effects-and-complications

acting reversible contraception: Implants and intrauterine devices. Obstet

26. Teal SB, Romer SE. Awareness of long-acting reversible

Gynecol. 2012;120:983-988.

contraception among teens and young adults. J Adolesc Health. 2013;52

10. American College of Obstetricians and Gynecologists. ACOG Practice

(4 suppl):S35-S39.

Bulletin No. 121: Long-acting reversible contraception: Implants and intrauterine devices. Obstet Gynecol. 2011;118(1):184-196.

All electronic documents accessed on October 5, 2015.

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n LEARNING OBJECTIVES After completing the activity, the participant should be better able to: • Assess the side effects, interactions, and contraindications of the various psoriasis treatments • Demonstrate methods to decrease complications from psoriasis and from the therapies that are available • Identify risk factors, such as smoking or alcohol consumption, that may exacerbate psoriasis and increase the chance of cardiovascular disease n COMPLETE THE POSTTEST: Page 54 n ADDITIONAL CME/CE CREDIT: Page 66, 71, 76

This activity is provided by Haymarket Medical Education (HME) for physician credit.

This activity is co-provided by Medical Education Resources (MER) for nursing contact hours.

Release Date: November 13, 2015 Expiration Date: November 12, 2016 Estimated time to complete the educational activity: 30 minutes Statement of Need: Many health care professionals other than dermatologists may not be aware of the range of therapies, particularly systemic, available for patients with moderate to severe psoriasis, outside of topical therapies, phototherapy, or the older biologics, which can be ineffective or come with significant end-organ toxicities. It is important that clinicians be aware of the common adverse effects of newer treatments.

Target Audience: This activity has been designed to meet the educational needs of primary care health care professionals who will treat patients with psoriasis.

Faculty Eman Bahrani, BA Baylor College of Medicine, Houston Maura Holcomb, MD Baylor College of Medicine, Houston Accreditation Statements Physician Credit: HME is accredited by the Accredita tion Council for Continuing Medical Education (ACCME) to provide continuing medical ­education for physicians.

Credit Designation: HME designates this enduring material for a maximum of 0.5 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Nursing Credit: MER is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation.

Credit Designation: This CE activity provides 0.5 contact hour of continuing nursing education.

MER is a provider of continuing nursing education by the California Board of Registered Nursing, Provider #CEP 12299, for 0.5 contact hour.

This activity qualifies for 0.25 pharmacotherapy credit.

American Academy of Physician Assistants (AAPA) The AAPA accepts certificates of participation for educational activities certified for AMA PRA Category 1 Credit™ from organizations accredited by ACCME or a recognized state medical society. Physician assistants may receive a ­maximum of 0.5 hour of Category I credit for completing this program.

Disclosure Policy In accordance with the ACCME Standards for Commercial Support, HME requires that individuals in a position to control the content of an educational activity disclose all relevant financial relationships with any commercial interest. HME resolves all conflicts of interest in an effort to ensure independence, objectivity, balance, and scientific rigor in all its educational programs.

Furthermore, HME seeks to verify that all scientific research referred to,

CME-Feature-Psoriasis_CA1115.indd 44

reported, or used in a CME/CE activity conforms to the generally accepted standards of experimental design, data collection, and analysis. HME is ­committed to providing its learners with high-quality CME/CE activities that promote improvements in health care and not those of a commercial interest.

The faculty reported the following financial relationships with commercial interests whose products or services may be related to the content of this CME activity: Faculty Disclosures

Name of faculty

Reported Financial Relationship

Eman Bahrani, BA

No relevant financial relationships

Maura Holcomb, MD

No relevant financial relationships

Staff/Planners’ Disclosures The planners, managers, and reviewers for this program reported the following ­financial relationships with commercial interests whose products or services may be related to the content of this CME activity: HME planners, managers, and reviewers have no relevant financial relationships to disclose.

MER planners, managers, and reviewers have no relevant financial relationships to disclose.

Disclosure of Unlabeled Use: This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. HME and MER do not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

Method of Participation: There are no fees for participating in and receiving CME/CE credit for this activity. During the period of November 13, 2015, through November 12, 2016, participants must: 1) read the learning objectives and faculty disclosures; 2) study the educational activity; 3) complete the posttest and submit it online (clinicians may register at www.myCME.com); and 4) complete the evaluation form online.

A statement of credit will be issued only upon receipt of a completed activity evaluation form and a completed posttest with a score of 70% or better.

Disclaimer: The content and views presented in this educational activity are those of the authors and do not necessarily reflect those of HME or MER. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. The information presented in this activity is not meant to serve as a guideline for patient management.

10/27/15 1:55 PM

CME CE FEATURED COURSE: EMAN BAHRANI, BA, AND MAURA HOLCOMB, MD

Psoriasis: an overview of current and emerging medications Many therapeutic options are available for patients with psoriasis, ranging from topical agents to phototherapy and systemic and biologic agents.

© PHOTO COURTESY OF MAURA HOLCOMB, MD

P

Psoriasis is a complex immune-mediated disease that can manifest in the skin and joints.

soriasis is a complex immune-mediated disease that affects approximately 120 million people globally and requires chronic management.1 The condition manifests itself in the skin, joints, or both, and exhibits associated comorbidities that increase risk for early death, including metabolic syndrome, cardiovascular disease, psoriatic arthritis, depression, anxiety, nonalcoholic fatty liver disease, Crohn’s disease, and lymphoma.2 Physicians should encourage lifestyle changes to reduce modifiable cardiovascular risk factors, such as smoking, which has been shown to independently increase risk of onset and exacerbation of psoriasis. Excessive alcohol intake has been reported in up to one-third of patients with psoriasis, likely due to psychologic distress. Excess alcohol ingestion is also a risk factor for cardiovascular disease.3 As emerging research illustrates its increasing complexity, psoriasis is now considered a systemic inflammatory disorder.2 Clinically, there are 5 types of psoriasis: plaque psoriasis, guttate or eruptive psoriasis, inverse psoriasis, pustular psoriasis, and erythrodermic psoriasis.

Plaque psoriasis is the most common form, with monomorphic, well-demarcated erythematous plaques under a silvery scale, typically on the scalp and extensor surfaces. Guttate psoriasis exhibits teardrop shaped lesions with scale. Inverse psoriasis is found in the intertriginous or flexural areas. Pustular psoriasis can present as either palmoplantar pustulosis or as the serious generalized pustular psoriasis. Any form can evolve into erythrodermic psoriasis, a rare

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The prevalence of psoriasis within certain populations ranges from less than 1% to more than 10%, depending on ethnic and geographic factors. and serious complication of the disease with significant risk of mortality. Psoriasis can affect the skin, nails, scalp, and joints to different degrees in each patient.2,4 The prevalence of psoriasis within certain populations ranges from less than 1% to more than 10%, depending on ethnic and geographic factors, with a 2% prevalence rate in Europe and North America.5 Family studies have shown a genetic predisposition for the disease, with the literature illustrating certain susceptibility alleles in immune-related genes.6,7 Dysregulation between the innate and adaptive immune systems, tumor necrosis factor (TNF)-α, and the interleukin (IL)-23–T helper cell 17 (Th17) axis, among other immune reactions in the cells of the skin, have all been shown to be involved in the pathogenesis of psoriasis.2,8 Management varies according to severity and effect on quality of life and should be tailored to each individual patient. There are many therapeutic options available, ranging from topical agents, to phototherapy and systemic and biologic agents.1,2 This article discusses established therapies for psoriasis and their indications for use, as well as emerging treatments that hold promise for the future.

Meet the patient

A 55-year-old postmenopausal woman with a past medical history of hypertension, dyslipidemia, non–insulin-dependent diabetes, and a 30-year history of psoriasis presents to a dermatology clinic with worsening symptoms and spread of her disease that were causing her physical and mental distress. She had been using various topical medications with only partial control. She had tried photochemotherapy in the form of psoralen plus ultraviolet (UV)-A (PUVA) treatments several years ago, but could not maintain weekly treatments because the 40-mile drive to the clinic was too inconvenient. In the last 2 years, she had 1 basal cell carcinoma and 1 squamous cell carcinoma excised. Her medications include metformin and simvastatin. She smoked 1 pack per day (ppd) of cigarettes in her 20s and 30s, but cut down to one-half ppd after being informed that smoking may aggravate her psoriasis. She drinks approximately 3 glasses of wine per night and says they help her sleep.

Her physical examination reveals an obese woman with fair skin and psoriasis involving 25% of her body surface area (BSA), when it had previously involved less than 10% of her BSA. Erythematous, tender patches and plaques with silvery

scales are visible on the trunk, lower back, and upper and lower extremities. Thick plaques with silvery white scale are found throughout the scalp. Her palms and the plantar aspects of her feet also exhibit mild erythematous patches.

There is no onychodystrophy, and no signs or symptoms of psoriatic arthritis are evident.

Mild disease

For mild disease, which affects 70% to 80% of patients with psoriasis, first-line management remains topical treatments.

Glucocorticoids and vitamin D derivatives, or their combination, are typically sufficient for mild psoriasis. Topical calcineurin inhibitors (tacrolimus or pimecrolimus) are reserved for difficult anatomic sites, such as the face and intertriginous areas, which are more prone to the adverse effects of the other topical agents.2 For the scalp, combinations of corticosteroids and vitamin D3 analogues are most effective, though very potent corticosteroids alone are more effective than vitamin D3 derivatives.9 Moderate-to-severe disease

There is no single definition in the literature of what constitutes moderate-to-severe psoriasis. The Psoriasis Area and Severity Index (PASI), percentage of BSA affected, and the Dermatological Life Quality Index provide physicians with some metrics to differentiate mild disease from moderate-or-severe psoriasis. However, these guidelines and their numeric cutoffs are cumbersome to calculate and use in daily practice and may not take into account the full clinical and subjective picture of disease burden.

For example, although predominant psoriatic nail involvement may not constitute a significant percentage of BSA, it can negatively affect quality of life and be difficult to treat topically.2,10 The Consensus Guidelines of the National Psoriasis Foundation Medical Board thus define moderateto-severe psoriasis as disease that “cannot or would not be expected to achieve adequate control using topical agents, with adequacy defined by the patient’s own perception of the disease and its burdens.”10 Patients with moderate-to-severe psoriasis are often treated with a combination of phototherapy and topical or systemic therapy. Table 1 summarizes some key points regarding systemic therapies discussed in this article.

Narrow-band UV-B (311 nm and 313 nm) is the more widely used phototherapy, whereas photochemotherapy,

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Conventional systemic therapies for psoriasis include acitretin, methotrexate, and cyclosporine, which have been used for more than 10 years. such as PUVA (320-400 nm), is used less frequently.

Although phototherapy is effective, it is time consuming, as it is performed 2 to 5 times per week in a clinical environment. Therefore, phototherapy is mainly used for acute disease control rather than chronic management.2,11 PUVA increases the risk of skin cancers, especially after 200 treatments, which also limits its chronic use.11 Absolute contraindications to phototherapy include genetic defects that increase light sensitivity or risk of skin cancer, lupus erythematosus, and pregnancy or lactation (for pregnancy, the contraindication applies to oral PUVA only).

Phototherapy was developed based on the observation that exposure to sunlight helped reduce the symptoms of many skin diseases. Phototherapy has been shown to inhibit keratinocyte proliferation, induce apoptosis in cells of the immune system, and inhibit Th1 and Th17 proliferation, as well as stimulation of the Th2 system.2,12 Conventional systemic therapies. Conventional systemic therapies used for psoriasis treatment include acitretin, methotrexate, and cyclosporine, which have been used for more than 10 years.2,13 Acitretin is an oral retinoid and is teratogenic, limiting its use in women of childbearing age. Dosing starts at 10 mg/d to 25 mg/d and is increased according to the patient’s ability to tolerate its side effects. However, in the case of generalized pustular psoriasis, it should be started at a high dose and titrated down if a lower dose is effective. Its adverse effects include increases in xerosis and triglyceride level and abnormal liver function tests. Acitretin is also classified as Pregnancy Category X and inappropriate for use in women of childbearing age or men who wish to conceive; in rare cases, the drug has been associated with decreased night vision, skeletal hyperostosis, or pseudotumor cerebri.13,14 Acitretin is more effective when used in combination with topical vitamin D3 derivatives such as calcipotriene, or phototherapy or biologics. Among the drawbacks of acitretin are that it has a slow onset of action and may only thin psoriatic plaques, rather than effectively eliminating them, when used alone. It is not as effective a monotherapy as methotrexate or cyclosporine at tolerable doses,2,14 but acitretin is helpful in treating specific subtypes of psoriasis, such as generalized, palmoplantar, pustular, and hyperkeratotic psoriasis.14 One advantage of acitretin is that it has less potential for end-organ toxicity than methotrexate or cyclosporine.10

Methotrexate inhibits DNA replication by disrupting cellular folic acid metabolism and is the oldest systemic therapy for moderate-to-severe psoriasis. Although it is cytostatic, it also leads to reduced T-cell gene expression, increases endogenous levels of adenosine, and decreases antibody responses, which are direct anti-inflammatory effects. Methotrexate is available in 2.5-mg tablets, prescribed as 7.5 mg to 25 mg taken once weekly. Subcutaneous methotrexate, also dosed once weekly, exhibits improved bioavailability, efficacy, and tolerability in patient studies of rheumatoid arthritis.13 Cumulative use of methotrexate increases risk of liver toxicity, but folate supplementation can reduce that risk,15 as well as the risks of bone marrow suppression and gastrointestinal side effects.10 A multicenter, randomized controlled trial found that 40% of subjects achieved a 75% reduction in PASI scores (PASI 75) at 24 weeks.13,16 The most common side effects of methotrexate include nausea, diarrhea, fatigue, and headaches. Additionally, liver function tests should be performed every 4 to 12 weeks, as hepatotoxicity may manifest early as elevated transaminases.

Guidelines from the American Academy of Dermatology have reduced the need for liver biopsies in patients without risk factors for hepatic fibrosis to every 3.5 g to 4.0 g of total cumulative dose.17 Some European countries have standardized the measurement of classic and newly validated serum biomarkers, such as amino terminal propeptide of type III procollagen. A complete blood count is necessary to screen for myelosuppression and kidney function must be monitored prior to and during use because methotrexate is renally excreted.

Methotrexate is an abortifacient and classified as Pregnancy Category X; it is also contraindicated during lactation. The drug should be discontinued in both men and women at least 3 months prior to attempting to conceive.

Methotrexate can be combined with other systemic medications or phototherapy for additive or synergistic responses.

Combinations allow for lower doses of the individual drugs and improved overall efficacy.13 Cyclosporine is an oral calcineurin inhibitor that lowers the production of IL-2 and other proinflammatory cytokines that activate T cells. It is used in many immune-mediated disease states, including moderate-to-severe psoriasis. It is typically dosed at 2.5 mg/kg/d to 5.5 mg/kg/d.13 Cyclosporine is fast acting and is therefore considered a first-line treatment for types of pustular psoriasis and erythrodermic psoriasis as a

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TABLE 1. Summary of major systemic medications for moderate-to-severe psoriasis.

Systemic drug

Mechanism of action

FDA approval for moderate-severe psoriasis Side effects and risks

CYCLOSPORINE2,10,13,18,34

Oral calcineurin inhibitor

1997, severe psoriasis

Nephrotoxicity, headache, hypertension, elevated triglyceride level, hirsutism, gum hyperplasia, electrolyte changes, increased risk of squamous and basal cell carcinoma

METHOTREXATE10,13,15,16,17,34 Inhibits DNA replication by disrupting folate metabolism

1970s, severe psoriasis

Hepatotoxicity, nausea, diarrhea, fatigue, headaches, myelosuppression

ACITRETIN2,10,13,14,34

Oral retinoid that regulates epithelial cell growth

1997, psoriasis

Xerosis, elevated triglyceride level, elevated liver enzymes, decreased night vision, headache, pseudotumor cerebri, skeletal hyperostosis

ETANERCEPT2,10,34

TNF-α inhibitor

2004, psoriasis; 2002, PsA

Flu-like symptoms, URIs, injection site reactions, increased risk of infections, autoimmune disorders, lymphoma

ADALIMUMAB2,10,19,20,34

TNF-α inhibitor

2005, PsA; 2008, psoriasis

Flu-like symptoms, URIs, injection site reactions, increased risk of infections, autoimmune disorders, lymphoma

INFLIXIMAB2,10,19,20,21,34

TNF-α inhibitor

2005, PsA; 2006, psoriasis

Flu-like symptoms, URIs, injection-site reactions, increased risk of infections, autoimmune disorders, lymphoma

ALEFACEPT10,22,23,34

Interferes with T-cell surface proteins, triggering apoptosis

2003, plaque psoriasis

Risk of CD4 T lymphocyte depletion

USTEKINUMAB10,24,25,26,34

Blocks IL-12 and IL-23, disrupting development of Th17 lymphocytes

2009, psoriasis; 2013, PsA

No significant risks due to immunosuppression, but long-term data lacking

SECUKINUMAB2,27,34

Inhibits IL-17A, cytokine produced

by Th17, and other immune cells

2015, plaque psoriasis

Rates and severity of infection no higher than that of etanercept; increased risk of URIs

APREMILAST2,13,28,29,34

Oral small molecule PDE4 inhibitor

2014, plaque psoriasis, psoriatic arthritis

5%-10% weight loss, diarrhea, nausea, headache

TOFACITINIB13,30,31

Oral small molecule JAK1/ JAK3 inhibitor

Under FDA review

Cytopenias, anemias, increased liver test results, increased cholesterol level, increased creatinine level, increased rates of herpes zoster outbreaks and infection, such as URI

CBC, complete blood count; FDA, U.S. Food and Drug Administration; IL, interleukin; JAK, janus kinase; PASI, Psoriasis Area Severity Index; PASI 75, percentage of subjects achieving a 75% reduction in PASI scores; PDE, phosphodiesterase; PsA, psoriatic arthritis; SCC/BCC, squamous cell carcinoma/basal cell carcinoma; TB, tuberculosis; Th17, T helper cell 17; TNF, tumor necrosis factor; UPT, urine pregnancy test; URI, upper respiratory infection

rescue drug. A dose of approximately 5 mg/kg/d has shown a reliable average PASI 75 rate of 70%.13,18 Once a course of cyclosporine is complete, management is switched to a therapy with fewer long-term adverse effects. Long-term use and high doses of cyclosporine are associated with renal damage, hypertension, hypertriglyceridemia, electrolyte abnormalities, and increased risk of squamous and basal cell carcinomas. Therefore, it is used intermittently for no longer than 12 weeks at a time and is effective for management of flares. Baseline laboratory and blood pressure tests are necessary prior to its use. While

on the medication, weekly blood pressure measurements and monthly comprehensive metabolic panels with lipids, magnesium, and potassium are necessary.

Cyclosporine has many relative contraindications and is metabolized through the cytochrome P450 liver system; thus, it is important to be aware of a patient’s medical history, diagnoses, and current medications and potential interactions prior to its use.2,10,13 Because cyclosporine can only be used temporarily, it is often combined with or titrated down while also using overlapping therapy, such as methotrexate, acitretin, or biologic agents.13

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Monitoring before and during use

FDA pregnancy category

Comments

Kidney function tests, blood pressure measurements

Category C; can only be given when benefits outweigh the risks to the fetus

Fast-acting; used first-line for pustular and erythrodermic psoriasis as a rescue drug; used intermittently for no longer than 12 weeks for flares due to side effects

Liver function tests, CBC, kidney function liver biopsy for every 3.5–4.0g total cumulative dose, or more often for those with risk factors of hepatic fibrosis

Abortifacient, category X; men should wait 3 months and women 4 months after stopping methotrexate before trying to conceive

Common first-line systemic drug for continuous management of chronic plaque psoriasis; can be combined with other systemic medications or phototherapy for additive or synergistic effects

Women must have 2 negative UPT results prior to use and use 2 effective forms of birth control while on this medication

Category X; should not be taken for 3 years before pregnancy

More effective when used in combination with topical vitamin D3 derivatives or phototherapy or biologics; helpful in generalized, palmoplantar, pustular, and hyperkeratotic subtypes of psoriasis

Screen for latent TB, occasional blood tests recommended

Category B; no proven risk in humans

Biologic agent that can be used as a first-line systemic medication for chronic plaque psoriasis

Screen for latent TB, occasional blood tests recommended

Category B; no proven risk in humans

Biologic agent that can be used as a first-line systemic medication for chronic plaque psoriasis

Screen for latent TB, regular blood tests recommended

Category B; no proven risk in humans

Administered as intravenous infusion; drug with fastest onset of action, typically used as a second- or third-line biologic agent for chronic plaque psoriasis or first-line for erythrodermic psoriasis

Monitor CBC and CD4 counts regularly

Category B; no proven risk in humans

Like cyclosporine, prescribed for intermittent 12-week courses; has shown few adverse effects, so may be used first line; often combined with phototherapy for increased effect

Screen for latent TB before starting medication

Category B; no proven risk in humans

PASI score reduction comparable with that of etanercept; may be used as a first-line systemic medication for chronic plaque psoriasis

Screen for latent TB before starting medication

Category B; no proven risk in humans

More patients on secukinumab reached PASI 75 at week 12 than with etanercept; other IL-17 inhibitors (brodalumab and ixekizumab) are currently in phase 3 trials

Monitor weight regularly, no laboratory monitoring necessary

Category C; can only be given when benefits outweigh the risks to the fetus

Oral administration may be favored by patients and has shown efficacy with psoriatic arthritis

Screen for latent TB prior to starting; regular laboratory monitoring of complete blood count, livery function tests, basic metabolic panel

Category C; can only be given when benefits outweigh the risks to the fetus

Has shown noninferiority to etanercept; although laboratory abnormalities have been reported, all have been reversible with drug disconitnuation; currently approved for rheumatoid arthritis; has a black box warning for serious infections and malignancy

Biologic agents. The biologic agents are a newer class of medications available to patients with moderate-to-severe psoriasis and are effective long-term treatment options.

They have increased safety, efficacy, and tolerability when compared with the classical agents, especially because they show no cumulative toxicity or significant interactions with other drugs. As a result, they are no longer reserved as second-line treatments, but their cost may delay their use until after conventional therapies have been exhausted.2 The risks of biologics include a small increase in opportunistic infections, so they should not be used in

immunocompromised individuals or those with active infections. Patients should be tested for latent tuberculosis prior to use. Common side effects include flu-like symptoms and injection site reactions. Cost, the severity of disease, and the medical history of the individual patient should determine their use.2,10 TNF-α inhibitors approved for use in moderate-to-severe psoriasis and psoriatic arthritis include etanercept, adalimumab, and infliximab. Given their mechanism of immunosuppression, they share a heightened risk of causing infection (including sepsis and tuberculosis), autoimmune disorders

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Although secukinumab has been shown to increase the risk of infection, its rates and severity of infection are no higher than those of etanercept. (eg, lupus), and lymphoma.2 Etanercept reaches a PASI 75 in a majority of patients at 24 weeks when dosed at 50 mg twice weekly and then reduced to 50 mg/wk after 12 weeks.

The twice-weekly dosing can be maintained if the patient’s improvement is inadequate after 24 weeks.10 Adalimumab and infliximab are administered subcutaneously and have shown effective control of plaque psoriasis and rapid onset of action, respectively. A loading dose of 80 mg of adalimumab is followed 1 week later by 40-mg injections every other week.

For infliximab, 3 intravenous induction infusions (5 mg/ kg) are given at weeks 0, 2, and 6, with infusions thereafter every 8 weeks. Adalimumab and infliximab have shown greater efficacy than methotrexate with regard to PASI score improvement.10,19,20 Furthermore, infliximab has the greatest short-term efficacy and most rapid onset of action, followed closely by adalimumab and ustekinumab, making it an ideal medication for treatment of erythrodermic psoriasis.21 Alefacept is a biologic agent approved for use in patients with psoriasis and interferes directly with T-cell surface proteins, such as CD2 and its costimulatory molecule, thereby triggering the apoptosis of pathogenic T lymphocytes. Alefacept carries the risk of CD4 T lymphocyte depletion, so CD4 counts must be regularly checked; alefacept should be discontinued when the count is less than 250 CD4 T cells/uL. Like cyclosporine, alefacept is prescribed for intermittent 12-week courses, leading to a 50% to 75% reduction in PASI scores in approximately 25% of patients, an effect that may last for more than 12 months. Each course can be repeated twice a year. As long as CD4 counts are regularly supervised, alefacept has shown few adverse effects10,22 and is often combined with phototherapy regimens for increased efficacy.23 Ustekinumab is a human monoclonal antibody that blocks IL-12 and IL-23 and has been approved for the treatment of psoriasis and psoriatic arthritis. By blocking these interleukins, ustekinumab interrupts the development of Th17 lymphocytes involved in the psoriasis inflammatory process. Trials have shown no significant risks due to its method of immunosuppression, but long-term data are lacking.10,24 After 2 initial doses of 45 mg at weeks 0 and 4, health care providers give patients an injection of the same dose once every 12 weeks for those weighing 100 kg or less. Patients weighing more than 100 kg are given 90-mg injections every 12 weeks. In 67% to 81% of patients who have a prolonged response, PASI 75 was reached, and many achieved a reduction in PASI scores of 50% by week 2.10,25,26

Secukinumab is a human monoclonal antibody that is approved by the U.S. Food and Drug Administration (FDA) for psoriasis; the drug targets IL-17A, a cytokine produced

by TH17 and other immune system cells.2,27 At a subcutaneously administered dose of 3 mg/kg, it has been shown to reduce the PASI score by 58% in 1 month and sustain this improvement by week 12, at which point the average PASI score reduction was 63%. In randomized control trials, more patients on secukinumab reached PASI 75 at week 12 than with either placebo or etanercept. Patients received either 150 mg or 300 mg of the medication once weekly for 5 weeks, then once every 4 weeks. Although secukinumab has been shown to increase risk of infection, its rates and severity of infection are no higher than those of etanercept. Brodalumab and ixekizumab are 2 other IL-17 inhibitors that are currently undergoing phase 3 randomized, controlled trials and clinical trials, respectively.27 Small molecule therapies. Apremilast is a small, oral phosphodiesterase-4 (PDE4) inhibitor effective for the treatment of psoriasis and psoriatic arthritis;2 it showed a minimum 75% reduction in PASI scores in approximately 30% of subjects dosed at 30 mg twice daily after 16 weeks.

PDE4 is active in the immune cells and keratinocytes and increases the production of inflammatory cytokines, so its inhibition improves inflammation in psoriasis. Patients in apremilast trials may have had side effects of nausea, vomiting, diarrhea, headaches, and upper respiratory tract infections, but no significant laboratory changes are seen in those taking apremilast, so no monitoring is necessary.13,28 One interesting side effect seen in 10% of subjects treated with apremilast was a decrease of 5% to 10% in body weight at baseline, the cause of which remains unknown.29 Janus kinase (JAK) inhibitors, such as tofacitinib (a JAK1/ JAK3 inhibitor), have recently gained approval for use in rheumatoid arthritis and show promise in the treatment of psoriasis. JAK molecules are proteins within cells that transmit signals from extracellular cytokines to the cellular nucleus. By inhibiting JAK, cytokine effects on the cell are reduced. Tofacitinib thus interrupts signaling via several interleukin receptors, such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21.13,30 Tofacitinib has undergone phase 3 multicenter trials for psoriasis, which showed an average week-16 PASI 75 response of approximately 40% at 5 mg twice daily and approximately 60% at 10 mg twice daily.

Furthermore, oral tofacitinib, 10 mg twice daily showed

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A majority of second-tier systemic agents are antimetabolites and thus are contraindicated in women who are pregnant. aforementioned medications due to their significant side effect profiles and drug窶電rug interactions: mycophenolate mofetil, leflunomide, fumaric acid esters, hydroxyurea, 6-thioguanine, and sulfasalazine.13 Of note, fumaric acid esters are approved for psoriasis treatment in several other countries,2 but larger randomized, double-blind controlled trials are necessary to confirm the extent of their efficacy. Mycophenolate mofetil has shown substandard efficacy as a monotherapy, but may be used in those who cannot tolerate other medications or in combination with other treatment regimens. Leflunomide may prove helpful as an adjunctive medication for those patients also suffering from psoriatic arthritis. A majority of second-tier systemic agents are antimetabolites and thus, contraindicated in pregnant women. Furthermore, many require frequent monitoring of laboratory values due to their substandard safety profiles and lower quality of data available on their utility in psoriasis treatment specifically.13

ﾂｩ PHOTOS COURTESY OF MAURA HOLCOMB, MD

noninferiority to etanercept dosed at 50 mg subcutaneously twice weekly. Unlike apremilast, tofacitinib has shown laboratory abnormalities, especially when doses are more than 5 mg twice daily. Cytopenias and anemias, increased liver enzyme test abnormalities, and increased cholesterol and creatinine levels have been reported in a small number of patients, but have all been reversed with discontinuation of the drug. Additionally, patients on tofacitinib have increased rates of herpes zoster outbreaks, infections, and certain malignancies, prompting a boxed FDA warning.

Patients prescribed this medication should therefore receive regular monitoring of their laboratory results so that abnormalities can be addressed early with a dose reduction or complete discontinuation of the medication.13,31 Second-tier systemic agents. The following agents have not been approved by the FDA for treatment of psoriasis and are reserved only for those cases refractory to the

FIGURE 1. The list of medications used to treat patients with psoriasis continues to increase, with several other drugs having recently completed phase 3 clinical trials, providing hope and more personalized options for patients with this serious cutaneous disease. It is important to be able to identify the nuances of treating psoriasis in patients with many comorbid conditions.

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Pregnancy

Due to hormonal changes, most women have symptomatic improvement of their psoriatic symptoms during pregnancy.

For those women who do require therapy during pregnancy, topical agents such as corticosteroids are preferred.

UV-B phototherapy is safe to use in pregnant women with moderate-to-severe disease.12,32 Although more data are necessary, biologic agents are the favored systemic medications for pregnant patients whose disease is not well-controlled with topical agents or phototherapy, including bath PUVA.32 Cyclosporine is classified as a Pregnancy Category C agent, so its potential benefits may warrant its use.

Approaching our patient

The patient described earlier highlights important clinical points regarding the complex management of psoriasis.

First, we must recognize that her obesity, hypertension, dyslipidemia, and non–insulin-dependent diabetes indicate she most likely has metabolic syndrome. Metabolic syndrome and the systemic burden of inflammation caused by her psoriasis increase her risk for infection, cardiovascular disease, and overall mortality.

Additionally, although she has decreased her daily cigarette smoking, complete cessation of tobacco intake should be advised with the reasoning explained to the patient—that is, that smoking has been shown to exacerbate psoriasis and increase risk of cardiovascular disease and myocardial infarction. The patient should also be encouraged to decrease her daily alcohol intake, as excessive alcohol ingestion is also associated with cardiovascular disease.

Given these risk factors, many of which are modifiable, patients should see their primary care providers regularly for better control of these comorbidities and to inspire healthy lifestyle changes.

Although her psoriasis may have been mild in the past, it is now moderate-to-severe given the distress it is causing her and the large percentage of BSA it now covers. She has a history of not adhering to phototherapy treatment regimens and has expressed that it is a burden to come into the clinic weekly for treatment. Furthermore, her recent history of skin cancer is a relative contraindication to phototherapy, which heightens the risk of skin cancer with increased ultraviolet light exposure. She is thus a good candidate for systemic therapies.

Let us consider the conventional systemic therapies.

Although the patient in this vignette is postmenopausal, it is always important to perform urine pregnancy tests and to ascertain the female patient’s potential and desire for pregnancy while medicated. Acitretin, an oral retinoid, has

been shown to elevate serum transaminases and triglycerides in a significant number of patients. Furthermore, to be used as a monotherapy, it must be given in high doses that cause many patients significant mucocutaneous xerosis and other side effects. It is not a wise option in a patient who already has several laboratory abnormalities, especially when more effective monotherapies are available.

Methotrexate and cyclosporine have the lowest monthly costs per number of patients needed to treat to achieve PASI 75, whereas biologic agents such as infliximab and ustekinumab have costs that are more than 10 times greater.33 As previously stated, cyclosporine has many risk factors that could exacerbate chronic illnesses that our patient already has. That is, renal damage, hypertension, hypertriglyceridemia, electrolyte abnormalities, and increased risk of squamous and basal cell carcinomas. Furthermore, cyclosporine could interfere with her current medications, particularly simvastatin, which is also metabolized through the cytochrome P450 system in the liver. Although none of these are absolute contraindications to the use of cyclosporine, it is, nonetheless, typically reserved as a rescue medication rather than being utilized for long-term maintenance.

Methotrexate is one of the oldest and most commonly used systemic agents for moderate to severe psoriasis.

However, this patient’s obesity indicates she may already have steatohepatitis, which would further increase her risk of liver toxicity from the methotrexate. Furthermore, her moderate alcohol intake and use of simvastatin may have already elevated her liver enzymes, which also increases her risk for liver toxicity from methotrexate and is a relative contraindication. Methotrexate, like cyclosporine and acitretin, is no longer a favorable option.

Biologics are advantageous in patients with significant comorbidities and complex medical histories, because they show no cumulative toxicity or significant interactions with other drugs. For many patients, cost may be the distinguishing factor, and their insurance plans should be taken into account. TNF-α inhibitors are a good choice for this patient, because they will not further exacerbate her existing conditions. Infliximab has weight-based dosing and may be more effective in an obese patient, though etanercept and adalimumab are both options. Should a TNF antagonist not result in adequate disease remission, newer biologic agents remain as options. TNF-α inhibitors increase the risk for infection, so patients should be screened appropriately prior to and during treatment. Apremilast is tempting to use in an obese patient given its potential side effect of weight loss, but

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it is not as effective in eliminating disease and has a lower PASI 75 than the other biologic agents. Nonetheless, some patients may find its oral form more favorable than an injectable medication, even if it offers partial control.

As more patients are diagnosed with chronic diseases, it is wise to understand psoriasis in their context and to be able to identify the nuances of treating psoriasis in patients with many comorbid conditions. The list of medications used to treat psoriasis continues to grow, with several other drugs having recently completed phase 3 clinical trials, providing hope and more personalized options for patients with this serious cutaneous disease. n

13. Kelly JB 3rd, Foley P, Strober BE. Current and future oral systemic therapies for psoriasis. Dermatol Clin. 2015;33(1):91-109.

14. Dogra S, Yadav S. Acitretin in psoriasis: an evolving scenario. Int J Dermatol. 2014;53(5):525-538.

15. van Ede AE, Laan RF, Rood MJ, et al. Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty eight week, multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2001;44(7):1515-1524.

16. Reich K, Langley RG, Papp KA, et al. A 52-week trial comparing briakinumab with methotrexate in patients with psoriasis. N Engl J Med. 2011;365(17):1586-1596.

17. Strober BE. Methotrexate-induced liver toxicity: replacing the liver biopsy. JAMA Dermatol. 2014;150(8):862-863.

Ms. Bahrani is a medical student and Dr. Holcomb is a dermatology resident at Baylor College of Medicine in Houston.

18. Heydendael VM, Spuls PI, Opmeer BC, et al. Methotrexate versus cyclosporine in moderate-to-severe chronic plaque psoriasis. N Engl J Med. 2003;349(7):658-665.

References

19. Menter A, Tyring SK, Gordon K, et al. Adalimumab therapy for moder-

1. Menter MA, Griffiths CE. Psoriasis: the future. Dermatol Clin.

ate-to-severe psoriasis: a randomized, controlled phase III trial. J Am Acad

2015;33(1):161-166.

Dermatol. 2008;58(1):106-115.

2. Boehncke WH, Schön MP. Psoriasis. Lancet. 2015;386(9997):983-994.

20. Saurat JH, Stingl G, Dubertret L, et al; CHAMPION Study

3. Ryan C, Kirby B. Psoriasis is a systemic disease with multiple cardiovas-

Investigators. Efficacy and safety results from the randomized controlled

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comparative study of adalimumab vs methotrexate vs placebo in patients

4. Wolff K, Johnson RA, Saavedra AP, eds. Fitzpatrick’s Color Atlas and

with psoriasis (CHAMPION). Br J Dermatol. 2008;158(3):558-566.

Synopsis of Clinical Dermatology. 7th ed. New York, NY: McGraw-Hill

21. Nast A, Sporbeck B, Rosumeck S, et al. Which antipsoriatic drug has

Medical; 2013.

the fastest onset of action? Systematic review on the rapidity of the onset

5. Christophers E. Psoriasis—epidemiology and clinical spectrum. Clin Exp

of action. J Invest Dermatol. 2013;133(8):1963-1970.

Dermatol. 2001;26(4):314-320.

22. Sugiyama H, McCormick TS, Cooper KD, Korman NJ. Alefacept in the

6. Nair RP, Stuart PE, Nistor I, et al. Sequence and haplotype analysis

treatment of psoriasis. Clin Dermatol. 2008;26(5):503-508.

supports HLA-C as the psoriasis susceptibility 1 gene. Am J Hum Genet.

23. Lui H, Gulliver W, Tan J, et al. A randomized controlled study of combi-

2006;78:827-851.

nation therapy with alefacept and narrow band UVB phototherapy (UVB)

7. Capon F, Burden AD, Trembath RC, Barker JN. Psoriasis and other com-

for moderate to severe psoriasis: efficacy, onset, and duration of response.

plex trait dermatoses: from loci to functional pathways. J Invest Dermatol.

J Drugs Dermatol. 2012;11(8):929-937.

2012;132(3 Pt 2):915-922.

24. Yiu ZZ, Warren RB. Efficacy and safety of emerging immunotherapies

8. Lowes MA, Kikuchi T, Fuentes-Duculan J, et al. Psoriasis vulgaris lesions

in psoriasis. Immunotherapy. 2015;7(2):119-133.

contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol.

25. Krueger GG, Langley RG, Leonardi C, et al; CNTO 1275 Psoriasis

2008;128(5):1207-1211.

Study Group. A human interleukin-12/23 monoclonal antibody for the

9. Mason AR, Mason JM, Cork MJ, et al. Topical treatments for chronic

treatment of psoriasis. N Engl J Med. 2007;356(6):580-592.

plaque psoriasis of the scalp: a systematic review. Br J Dermatol.

26. Leonardi CL, Kimball AB, Papp KA, et al; PHOENIX 1 study inves-

2013;169(3):519-527.

tigators. Efficacy and safety of ustekinumab, a human interleukin-12/23

10. Hsu S, Papp KA, Lebwohl MG, et al; National Psoriasis Foundation

monoclonal antibody, in patients with psoriasis: 76-week results from a

Medical Board. Consensus guidelines for the management of plaque pso-

randomised, double-blind, placebocontrolled trial (PHOENIX 1). Lancet.

riasis. Arch Dermatol. 2012;148(1):95-102.

2008;371(9625):1665-1674.

11. Racz E, Prens EP. Phototherapy and photochemotherapy for psoriasis.

27. Gooderham M, Posso-De Los Rios CJ, Rubio-Gomez GA, Papp K.

Dermatol Clin. 2015;33(1):79-89.

Interleukin-17 (IL-17) inhibitors in the treatment of plaque psoriasis: a

12. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the

review. Skin Therapy Lett. 2015;20(1):1-5.

management of psoriasis and psoriatic arthritis: Section 5. Guidelines of

28. Reich K, Griffiths C, Leonardi C, et al. Long-term safety and tolerability

care for the treatment of psoriasis with phototherapy and photochemo-

of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moder-

therapy. J Am Acad Dermatol. 2010;62(1):114-135.

ate to severe psoriasis: results from a phase III, randomized, controlled trial

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(ESTEEM 1). Poster presented at: 72nd American Academy of Dermatology

32. Hoffman MB, Farhangian M, Feldman SR. Psoriasis during pregnancy:

Annual Meeting; March 21-25, 2014; Denver, CO. Abstract P8296.

characteristics and important management recommendations. Expert Rev

29. Otezla [package insert]. Summit, NJ: Celgene Corporation; 2014.

Clin Immunol. 2015;11(6):709-720.

30. Papp KA, Menter A, Strober B, et al. Efficacy and safety of tofacitinib, an

33. D’Souza LS, Payette MJ. Estimated cost efficacy of systemic treat-

oral Janus kinase inhibitor, in the treatment of psoriasis: a Phase 2b random-

ments that are approved by the US Food and Drug Administration for

ized placebo-controlled dose-ranging study. Br J Dermatol. 2012;167(3):668-677.

the treatment of moderate to severe psoriasis. J Am Acad Dermatol.

31. A phase 3, multi site, randomized, double blind, placebo controlled

2015;72(4):589-598.

study of the efficacy and safety comparing CP-690,550 and etanercept in

34. Psoriasis treatments. National Psoriasis Foundation website. Available

subjects with moderate to severe chronic plaque psoriasis. ClinicalTrials.

at psoriasis.org/about-psoriasis/treatments. Accessed October 1, 2015.

gov website. Available at clinicaltrials.gov/ct2/show/NCT01241591.

Accessed October 1, 2015.

All electronic documents accessed on October 1, 2015.

CME CE

POSTTEST Expiration date: November 12, 2016

FEATURED COURSE CREDITS: 0.5

For more credit information, please turn to p. 44.

1. A 29-year-old woman who is 17-weeks pregnant presents stating that topical corticosteroids have not helped control her moderate-to-severe plaque psoriasis. She has been distressed throughout her pregnancy and is asking for other safe, yet effective, treatment options. Which of the following is a safe option for pregnant patients with moderate-to-severe psoriasis? a. Acitretin b. Methotrexate c. Ultraviolet (UV)-B phototherapy d. Oral psoralen plus UV-A exposure (PUVA) therapy 2. A 34-year-old overweight man with hypertension and a 10-year history of psoriasis, well-controlled on etanercept for the last 7 months, states that he is sick of injecting himself and would like a different medication to maintain control of his psoriasis. Cutaneous examination reveals plaque psoriasis covering 5% of his body surface area, with erythematous, scaly plaques on his elbows and scalp.

Furthermore, he states that he and his wife are trying to conceive a child. Which of the following is a reasonable medication to offer the patient in place of the etanercept? a. Apremilast c. Cyclosporine b. Methotrexate d. Secukinumab

3. Which of the following mechanisms of action reflects that of tofacitinib? a. Tumor necrosis factor-α antagonist b. Phosphodiesterase-4 inhibitor c. Interleukin-17A inhibitor d. Janus kinase inhibitor 4. Which of the following combinations most accurately describes laboratory abnormalities and/or end-organ toxicities and/or common side effects seen with systemic agents for psoriasis? a. Methotrexate (nephrotoxicity); tofacitinib (cytopenia); adalimumab (liver toxicity) b. Methotrexate (liver toxicity); cyclosporine (nephrotoxicity); apremilast (nausea, weight loss); secukinumab (increased risk of infection) c. Methotrexate (nephrotoxicity); acitretin (hyperlipidemia); apremilast (injection-site reaction) d. Cyclosporine (hypertension); alefacept (increased CD4 counts)

TO TAKE THE POSTTEST please go to: myCME.com/Nov15CAfeature

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Advisor Forum These are letters from practitioners around the country who want to share their clinical problems and successes, observations, and pearls with their colleagues. Responding consultants are identified below. We invite you to participate.

YOUR COMMENTS STOPPING PRESCRIPTION DRUG ABUSE After reading the commentary by Jessica Dare Evans [“Narcotic abuse in the emergency department,” October, p. 138], I feel I need to contact you. I am a PA with more than 20 years’ experience in emergency medicine and am currently involved in the treatment of mostly substance abuse and hepatitis C. I am in complete agreement with Ms. Evans that prescription drug abuse is a monumental problem and will almost certainly get worse before it gets better. I find that she has made some assertions in her column that are not supported by the literature and has made some statements that are not correct regarding the Drug Abuse Warning Network (DAWN).

I agree that emergency providers need to be responsible prescribers and must play a role in containing prescription drug diversion, but data from the CDC show that emergency rooms are actually one of the lesser sources of diverted medications. A large majority of diverted medications are acquired by Send us your letters with questions and comments to: Advisor Forum, The Clinical Advisor, 114 West 26th Street, 4th Floor, New York, NY 10001. You may contact us by e-mail at editor@ clinicaladvisor.com. If you are writing in response to a published letter, please indicate so by including the number in parentheses at the end of each item. Letters are edited for length and clarity. The Clinical Advisor’s policy is to print the author’s name with the letter. No anonymous contributions will be accepted.

recurring prescriptions written by a single ongoing prescriber.

Most often this is a primary care provider or pain clinic.

DAWN, unfortunately, does not provide a searchable database of patient prescription histories. DAWN is a database maintained by the Substance Abuse and Mental Health Services Administration (samhsa.gov) that compiles information on emergency room visits that can be attributed to some form of substance abuse. It is used by public health entities, hospital systems, and law enforcement to track trends and look for increasing or changing abuse patterns. No mechanism exists for looking at individual encounters or prescriptions.

Currently, there is no national database or network that will perform this function. Forty-nine states, the District of Columbia, and the territory of Guam have prescription drug monitoring programs that allow searches of prescriptons for controlled substances that are either written or filled by providers in those jurisdictions. Only a few states, such as Tennessee, allow searches of more than one state, and many states allow access only to providers licensed in that state. In addition, the requirements and mechanism for reporting to the database varies from state to state, and profiles can sometimes be several weeks out of date or missing data entirely.

I wholeheartedly agree with Ms. Evans’ closing sentence. If we are to proceed successfully, we need to set targets based on accurate, complete information. The CDC (cdc.gov), the National Association of State Controlled Substance Authorities (nascsa.org), and the Prescription Drug

OUR CONSULTANTS

Philip R. Cohen, MD,

is clinical associate professor of dermatology, University of Texas Medical Center, Houston.

Deborah L. Cross, MPH, CRNP, ANP-BC, is associate program

director, Gerontology NP Program, University of Pennsylvania School of Nursing, Philadelphia.

Abimbola Farinde, PhD, PharmD,

is a professor at Columbia Southern University in Orange Beach, Ala.

Laura A. Foster, CRNP, FNP,

Abby A. Jacobson, PA-C,

practices family medicine with Palmetto Primary Care Physicians in Charleston, S.C.

is a physician assistant at Delaware Valley Dermatology Group in Wilmington, Del.

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Monitoring Program Training and Technical Assistance Program (pdmpassist.org) all have extensive information on their websites, and I highly recommend that anyone practicing medicine, and particularly anyone who prescribes controlled substances, look at these websites.—WILLIAM KELLEY, PA-C, Cherokee, N.C. (205-1)

several patients who experienced improved A1c and better glycemic control by taking Metformin XR 2 g once daily at a time they can remember every day, rather than taking Metformin SR 1 g twice daily, often only remembering one dose.—JEN GRENELL, APRN, CNP, Rochester, Minn. (205-4)

VACCINATION, PARENTS, AND CHILDREN I’m sorry, you can’t equate antibiotics with vaccines [The Waiting Room blog, “Are Immunizations Negotiable,” Oct. 22, 2015, www.clinicaladvisor.com] as, presumably, you are giving antibiotics when a patient is already sick. Not so with vaccines. Apples and oranges. Using an analogy that makes sense would go a long way in educating the public.

Also, yes, I believe in harm reduction. You cannot forcefully push the parents out of the room and vaccinate their child. If slow will get the job done, then slow it is.—JEN BEECKMAN, NP, Pleasanton, Calif. (205-2)

CONSULTATIONS

CLINICAL PEARLS HOW TO DISTINGUISH BRADYKINESIA FROM PSYCHOMOTOR RETARDATION Look at the patient’s blink rate. If a patient is truly bradykinetic or parkinsonian, his or her blink rate will be decreased. If this is due to psychiatric depression or psychogenic movement disorder, then the blink rate will be normal.—DIANA FERMAN, PA-C, Los Angeles. (205-3) METFORMIN XR FOR DIABETES CARE Consider changing to the Metformin XR formulation with once daily dosing for patients who find it difficult to remember to take the Metformin SR formulation twice daily. I have had

Debra August King, PhD, PA,

is senior physician assistant at New York-Presbyterian Hospital, New York City.

Mary Newberry, CNM, MSN,

provides well-woman gynecologic care as a midwife with Prima Medical Group, Greenbrae, Calif.

THE ANTI-INFLAMMATORY EFFECTS OF STATINS What evidence do we have that statin agents’ effects are not anti-inflammatory and not related to lipid lowering?

Everyone gets a 30% reduction in mortality risks no matter what their level of LDL. This is in addition to large studies’ findings in which 135,000 patients who were treated with coronary interventions in hospitals averaged an LDL of 105.

Many coronary patients have normal lipids, so is the real benefit of statins their anti-inflammatory benefits?—PAUL BATTLE, PA-C, Denver.

The anti-inflammatory action of statins is recognized as one of the most effective treatments for atherosclerosis and lowering of cardiovascular risk. More recent experimental and clinical investigations have indicated that statins can exert a number of cholesterol-independent, cardioprotective actions. Because nitric oxide derived from endothelial nitric oxide synthase (eNOS) represents a highly potent anti-inflammatory signaling pathway, the investigation of statins as anti-inflammatory agents is very logical and a path of continued research. After the landmark finding that statins upregulate eNOS function, a number of studies have reported very powerful anti-inflammatory actions of statins that are largely related to eNOS-dependent activity.—Abimbola Farinde, PhD, PharmD (See photo at bottom of page 56 for more information about Dr. Farinde.) (205-5) n

Claire O’Connell, MPH, PA-C,

Katherine Pereira, DNP, FNP,

teaches in the PA Program at the New Jersey Medical School and Rutgers University, Piscataway, N.J.

is assistant professor, Duke University School of Nursing, Durham, N.C.

Sherril Sego, FNP-C, DNP,

is an independent consultant in Kansas City, Mo.

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LEGAL ADVISOR CASE

Complaints not taken seriously

BY ANN W. LATNER, JD

Mrs. G, a patient in her late 60s, had been coming in frequently with minor complaints to a clinician’s group for which Mr. N, a 38-year-old nurse practitioner, worked.

Mr. N liked Mrs. G, but it was difficult to get her in and out of the office in a reasonable amount of time. Mrs. G was a talkative woman who would discuss health concerns in great detail, as well as tell him about her family and hobbies.

Usually, Mrs. G would only come in once a year for a wellness check, and Mr. N was happy to exchange pleasantries and catch up on the year’s events. However, over the last 6 months, Mrs. G had been returning every few weeks with different complaints, and the clinician had been forced to stay late at work several times to catch up after spending large chunks of time with the patient.

Mr. N had not been able to find a cause for Mrs. G’s numerous and varied complaints. He was beginning to wonder whether Mrs. G was exaggerating or possibly imagining her symptoms. Still, he always listened and noted her symptoms and tried to come up with an appropriate solution. Over the last several months, Mrs. G had complained

© ISTOCK / PATRICK HEAGNEY

A clinician misdiagnoses thyroid cancer as acid reflux in a patient who often comes to the clinic.

Mr. N had not been able to find a cause for Mrs. G’s numerous and varied complaints and was beginning to wonder if she was imagining her symptoms.

of sore throat, a lump in her throat, acid reflux, vomiting, difficulty breathing, a persistent cough, and fatigue. However, she had never exhibited signs of an inflamed throat or a lump in her throat.

At the latest of her visits, she launched into what Mr. N believed was a familiar stream of complaints.

“I’m so tired,” she said, “I can’t get anything done in the house. I don’t even have the energy to play with my grandchildren. Did I show you pictures of them?”

Mr. N assured her that she had.

“I don’t sleep well,” she continued. “I’m driving my husband, George, crazy because of it. And I feel like I have a lump in my throat, and this annoying cough.” She demonstrated the cough.

Mr. N saw nothing unusual in the patient’s throat and was unable to palpate a throat lump. Despite this, the clinician decided to refer Mrs. G to an ear, nose, and throat (ENT) specialist for further Cases presented are based on actual occurrences.

Names of participants and details have been changed.

Cases are informational only; no specific legal advice is intended. Persons pictured are not the actual individuals mentioned in the article.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • NOVEMBER 2015 63

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LEGAL ADVISOR

Dismissing, or negating, the complaints of a patient who is known as a “complainer” is dangerous for a clinician. to improve, and she was a familiar face in the waiting room over the next year as Mr. N tried to manage her condition.

After approximately 2 years of steady visits, Mrs. G stopped coming into the office, and Mr. N heard nothing more until the day he received notice that he was being sued for medical malpractice. His former patient had gone to the emergency department one day complaining of difficulty breathing and was diagnosed with stage 4 thyroid cancer. An obstructing lesion was causing respiratory issues. Mrs. G died from cardiopulmonary arrest as a consequence of thyroid cancer and tracheal stenosis 7 months after receiving the diagnosis.

Mr. N then contacted the defense attorney provided by his malpractice insurance. The attorney subpoenaed the records, depositions were taken, and medical experts were hired.

As the case drew closer to trial, both sides prepared their testimony. Mr. N and his medical expert were prepared to testify that because neither Mr. N nor the ENT could palpate a lump in Mrs. G’s throat, a biopsy was not warranted. The expert was prepared to testify that acid reflux is the most common cause of Mrs. G’s symptoms and that the diagnosis was reasonable and met the standard of care. The plaintiff’s experts were prepared to testify that Mr. N had failed to recognize the signs and symptoms of thyroid cancer and failed to order the right tests. They were also ready to testify that because of the delay in the patient’s diagnosis, the cancer was allowed to grow, resulting in tracheal stenosis and difficulty breathing.

Just before trial, Mr. N’s attorney called him and said, “the plaintiff is willing to settle for the limits of your policy.”

When Mr. N asked the attorney what he advised, the attorney told him that settling would be the wiser choice. The case settled before trial.

Legal background

Trials are expensive, stressful, and extremely time consuming, but worst of all, the outcome is unpredictable—particularly when a jury is involved. Unless it’s a very clear-cut case (which is relatively rare), it’s hard to know how a jury may react. Juries are made up of people, and people, whether they intend to be or not, are swayed by emotion and other factors.

The vast majority (as high as 90%) of medical malpractice cases are settled out of court. Aside from the cost of trial and the chances of losing, the emotional toll of being a defendant in a medical malpractice case is significant. Even if a clinician wins at trial and is found not liable, the psychological cost can be high.

Protecting yourself

Mr. N was wise to refer the patient to an ENT to further evaluate her symptoms. However, when the ENT’s workup revealed nothing, and the patient continued to have symptoms after Mr. N’s diagnoses and treatments for acid reflux and sleep apnea, Mr. N should have looked further.

Mr. N was correct that acid reflux was a good guess, and a common cause, for Mrs. G’s symptoms. However, the most common cause for symptoms is not always the right one. In this case, when the patient’s complaints did not resolve or improve with treatment, the clinician should have explored alternative theories for why they were occurring. Dismissing, or negating, the complaints of a patient known as a “complainer” is dangerous for a clinician, because one never knows if those complaints might be legitimate and serious, as they were here. n Ms. Latner, a former criminal defense attorney, is a freelance medical writer in Port Washington, N.Y.

“Whoa! Move over, Thoreau.”

© The New Yorker Collection 2015 from cartoonbank.com. All Rights Reserved.

evaluation. A week after seeing Mrs. G, the ENT specialist called Mr. N to report that he was unable to palpate any type of throat lump or nodule. The remainder of the workup failed to reveal an obvious cause for the patient’s symptoms, he told Mr. N. Mrs. G returned to see Mr. N several weeks later with the same complaints. Ultimately, Mr. N concluded that the patient’s complaints were symptoms of acid reflux and sleep apnea, and he proceeded to treat Mrs. G for those diagnoses.

Despite various treatments, Mrs. G’s symptoms did not seem

64 THE CLINICAL ADVISOR • NOVEMBER 2015 • www.ClinicalAdvisor.com

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CME CE DERMATOLOGY COURSES

n LEARNING OBJECTIVES After completing the activity, the participant should be better able to:

For Dermatology Clinic

• Examine the etiology and clinical presentation of Becker nevus and lepromatous leprosy • Formulate diagnostic procedures and treatment protocols for patients presenting with Becker nevus and lepromatous leprosy

For Dermatologic Look-Alikes

• Differentiate between skin manifestations of pigmented basal cell carcinoma and nodular melanoma while considering their underlying cause • Demonstrate proficiency in identifying and treating pigmented basal cell carcinoma and nodular melanoma n COMPLETE THE POSTTEST: Page 76 n ADDITIONAL CME/CE CREDIT: Page 44

This activity is provided by Haymarket Medical Education (HME) for physician credit.

This activity is co-provided by Medical Education Resources (MER) for nursing contact hours.

Release Date: November 13, 2015 Expiration Date: November 12, 2016 Estimated time to complete the educational activity: 30 minutes Statement of Need: Undertraining in dermatology for primary-care providers is a common phenomenon. Thus, primary-care clinicians need additional educational outlets devoted to the diagnosis and treatment of specific dermatologic conditions. For clinicians out of training, CME becomes the most accessible route.

Target Audience: This activity has been designed to meet the educational needs of primary-care health-care professionals who treat patients with various dermatologic conditions.

Faculty Shehni Nadeem, BA, medical student, Baylor College of Medicine, Houston Maura Holcomb, MD, dermatology resident, Baylor College of Medicine, Houston Tiffany Shih, MD, resident physician, University of Minnesota in Minneapolis Danielle Brown, BA, medical student, Baylor College of Medicine, Houston Accreditation Statements Physician Credit: HME is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Credit Designation: HME designates this enduring material for a maximum of 0.5 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Nursing Credit: MER is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation.

Credit Designation: This CE activity provides 0.5 contact hour of continuing nursing education.

MER is a provider of continuing nursing education by the California Board of Registered Nursing, Provider #CEP 12299, for 0.5 contact hour.

This activity qualifies for 0.25 pharmacotherapy credit.

American Academy of Physician Assistants (AAPA) The AAPA accepts certificates of participation for educational activities certified for AMA PRA Category 1 Credit™ from organizations accredited by ACCME or a recognized state medical society. Physician assistants may receive a maximum of 0.5 hour of Category I credit for completing this program.

Disclosure Policy In accordance with the ACCME Standards for Commercial Support, HME requires that individuals in a position to control the content of an educational activity disclose all relevant financial relationships with any commercial interest.

HME resolves all conflicts of interest to ensure independence, objectivity, balance, and scientific rigor in all its educational programs.

committed to providing its learners with high-quality CME/CE activities that promote improvements in health care and not those of a commercial interest.

The faculty reported the following financial relationships with commercial interests whose products or services may be related to the content of this CME activity: Faculty Disclosures

Name of faculty

Reported Financial Relationship

Shehni Nadeem, BA

No relevant financial relationships

Maura Holcomb, MD

No relevant financial relationships

Tiffany Shih, MD

No relevant financial relationships

Danielle Brown, BA

No relevant financial relationships

Staff/Planners’ Disclosures The planners, managers, and reviewers for this program reported the following financial relationships with commercial interests whose products or services may be related to the content of this CME activity: HME planners, managers, and reviewers have no relevant financial relationships to disclose.

MER planners, managers, and reviewers have no relevant financial relationships to disclose.

Disclosure of Unlabeled Use: This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. HME and MER do not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

Method of Participation: There are no fees for participating in and receiving CME/CE credit for this activity. During the period of November 13, 2015, through November 12, 2016, participants must: 1) read the learning objectives and faculty disclosures; 2) study the educational activity; 3) complete the posttest and submit it online (clinicians may register at www.myCME.com); and 4) complete the evaluation form online.

A statement of credit will be issued only upon receipt of a completed activity evaluation form and a completed posttest with a score of 70% or better.

Disclaimer: The content and views presented in this educational activity are those of the authors and do not necessarily reflect those of HME or MER. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. The information presented in this activity is not meant to serve as a guideline for patient management.

Furthermore, HME seeks to verify that all scientific research referred to, reported, or used in a CME/CE activity conforms to the generally accepted standards of experimental design, data collection, and analysis. HME is

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Dermatology Clinic

CME CE DERMATOLOGY COURSES

CASE #1

Hypertrichosis over a brown patch SHEHNI NADEEM, BA, AND MAURA HOLCOMB, MD

A 13-year-old male presents with a 10-cm area of brown pigmentation on his left abdomen that he states became more apparent a year ago. Although the lesion is painless, its appearance is displeasing to the patient and concerning for his parents. On physical examination, he has no other associated findings or similar lesions. No muscle hypoplasia or limb abnormalities are noted. The lesion of interest has an irregular border with pronounced hypertrichosis overlying a brown patch.

What is your diagnosis? Turn to page 68.

CASE #2

Painful lesions with fever and malaise TIFFANY SHIH, MD

A 45-year-old man presents with fever, malaise, and painful patches, plaques, and nodules on the face, trunk, and upper and lower extremities. He emigrated from Burma a few months ago and is staying with family. He states that no other individual living with him has similar symptoms. On examination, the patient has a temperature of 100.7 degrees Fahrenheit, but his vital signs are otherwise stable. He has scattered tender, pink-to-violaceous nodules, patches, and plaques most prominently seen on the ears and extremities but also scattered over the face and trunk. A neurologic examination demonstrates that sensation is intact and there are no tender or enlarged peripheral nerves.

What is your diagnosis? Turn to page 69. www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • NOVEMBER 2015 67

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CME CE

CASE #1

Dermatology Clinic

Becker nevus

A Becker nevus, also referred to as Becker melanosis, is a single, benign brown-colored skin lesion that most commonly appears in peripubertal boys and can be considered a lateonset epidermal nevus. It can principally be defined by the time of onset of the lesion and the pronounced hypertrichosis.

The pigmented lesion that is characteristic of Becker nevus appears as a unilateral patch, typically on the chest or back area. Initially, this patch will be lighter in color.1 However, as the patient nears puberty, it is thought that the increase in circulating androgens plays a role in activating the gene that leads to the development of a progressively darker patch and the characteristic hypertrichosis.2 The growth of the hairs on the patch usually occurs several months after the patch darkens. These hairs are typically brown or black, regardless of the individual’s hair color.

The border of the pigmented lesion is typically irregular and will appear to be composed of many macules blending together. The upper trunk is by far the most common location of a Becker nevus. However, there are reports of cases of Becker nevus occurring on virtually any part of the body.3 These lesions are also often accompanied by small areas of acne within the patch, but this is neither a requirement nor particularly notable, except for the link to the role of androgens. The patch that develops is an amalgamation of over-development of the epidermis and over-expression of both hair follicles and melanocytes.3 Typically, individuals will only have one Becker nevus that will remain for the duration of their lives with minimal decrease in pigmentation. It is painless, but many patients consider the lesion cosmetically displeasing. Having a Becker nevus has not been shown to predispose individuals to development of any particular disease. In addition, the development of a Becker nevus is not thought to be hereditary, so it may not be present in any other members of the patient’s family.

Smooth muscle hamartomas are often associated with a Becker nevus. Additionally, muscular tissue hypoplasia has been associated both in areas around and under a Becker nevus. When a Becker nevus exists in association with hypoplasia of the ipsilateral pectoralis muscle, ipsilateral limb

shortening, adrenal hyperplasia, spina bifida, scoliosis, or accessory scrotum, it is termed Becker nevus syndrome.3,4 This term indicates that ectodermal anomalies extend beyond just the skin and include other ectoderm-derived structures.

Becker nevus syndrome is much more common in women, when compared with Becker nevus that is not associated with abnormalities, which displays a strong male preference.

The male-to-female ratio in Becker nevus syndrome is 2:5, whereas a 6:1 male-to-female ratio is seen in Becker nevus.3 The differential diagnosis of a Becker nevus includes a café-au-lait macule, a congenital melanocytic nevus, erythema dischromium perstans, plexiform neurofibromas,

The growth of the hairs on the patch usually occurs several months after the patch darkens. and smooth muscle hamartomas. Often lichenified skin is considered a part of the differential as well. Clinical assessment of the timing of the pigmented patch, lack of association with scratching, absence of clear genetic link, and presence of hypertrichosis can be helpful.

Although a Becker nevus is typically a clinical diagnosis, obtaining a biopsy to further examine the histology can also be helpful. A Becker nevus should not have any nevus cells; rather, it will show increased numbers of melanosomes in both keratinocytes and melanocytes, greater number of hair follicles, increased melanophages at the upper dermis, and increased dermal smooth muscle.3 There are variable amounts of acanthosis, papillomatosis, and hyperkeratosis. 3 Because a Becker nevus is benign, no intervention or continued care of the nevus is required, unless the patient desires it for cosmetic reasons. Most Becker nevi are greater Features associated with Becker nevus syndrome3,4 Ipsilateral pectoralis muscle hypoplasia Ipsilateral limb shortening Spina bifida Adrenal hyperplasia Scoliosis Accessory scrotum

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than 10 cm in diameter, which is too large for surgical removal. Many patients opt to simply remove the hair. For these patients, electrolysis or laser treatments can be used for hair removal.

Other patients would also like to reduce or remove the pigment in the affected area. Treatment options for these patients include fractionated lasers or the Q-switched ruby laser, erbium:yttrium-aluminum-garnet (Er:YAG), or long-pulsed alexandrite laser. However, dermatologists are cautioned to warn their patients that laser treatments have shown promise but are not effective in all individuals and in many cases, a relapse may occur after treatment (especially with the use of fractionated lasers).5-8 Our patient was determined to have a Becker nevus based on clinical appearance, especially the presence of hypertrichosis.

This patient did not wish to have a confirmatory biopsy. He was advised that a Becker nevus does not require intervention, and he opted not to initiate any therapy.

Ms. Nadeem is a medical student and Dr. Holcomb is a dermatology resident at Baylor College of Medicine in Houston.

References 1. Becker SW. Concurrent melanosis and hypertrichosis in a distribution of nevus unius lateris. Arch Derm Syphilol. 1949;60(2):155-160.

2. Person JR, Longcope C. Becker’s nevus: An androgen-mediated hyperplasia with increased androgen receptors. J Am Acad Dermatol.

1984;10(2 Pt 1):235-238.

3. Rapini RP, Bolognia JL, Jorizzo JL. Dermatology: 2-Volume Set. St. Louis, Mo.: Mosby; 2007:1715.

4. Dasegowda BS, Basavaraj G, Nischel, K, et al. Becker’s nevus syndrome.

Indian J Dermatol. 2014:59(4):421. Available at ncbi.nlm.nih.gov/pmc/articles/ PMC4103296 5. Kopera D, Hohenleutner U, Landthaler M. Quality-switched ruby laser treatment of solar lentigines and Becker’s nevus: A histopathological and immunohistochemical study. Dermatology. 1997;194(4):338-343.

6. Trelles MA, Allones I, Moreno-Arias GA, Vélez M. Becker’s naevus: A comparative study between erbium:YAG and Q-switched neodymium:YAG; clinical and histopathological findings. Br J Dermatol.

2005;152(2):308-313.

7. Choi JE, Kim JW, Seo SH, Son SW, Ahn HH, Kye YC. Treatment of Becker’s nevi with a long-pulse alexandrite laser. Dermatol Surg.

2009;35(7):1105-1108.

8. Meesters AA, Wind BS, Kroon MW, et al. Ablative fractional laser therapy as treatment for Becker nevus: A randomized controlled pilot study. J Am Acad Dermatol. 2011;65(6):1173-1179.

All electronic documents accessed on October 1, 2015.

CASE #2

Lepromatous leprosy

Leprosy, also known as Hansen’s disease, is a chronic infectious disease caused by Mycobacterium leprae. Infection by these mycobacteria often involve the skin and nerves, which can ultimately lead to deforming, disabling, and stigmatizing disease.

Today, leprosy is endemic in tropical and subtropical areas such as Central and South America, Africa, and Asia. In the 1980s, there was an estimated 11 million to 15 million people worldwide with leprosy. By 2010, there was an estimated 250,000 cases per year.1 In the United States, most cases are imported, but a small fraction of cases are endemic in the southeastern region of the United States and in Hawaii, possibly due to exposure to armadillos.2 Leprosy spreads when there is a contagious patient, a susceptible patient, and close or intimate contact. There is an estimated 25% risk of acquiring the disease from household contacts.1 This bacillus spreads predominantly through nasal and oral droplets or less often, through eroded skin.1,2 Of note, there could still be viable bacilli in dried secretions for up to 7 days. However, approximately 90% of exposed individuals never develop the disease.2 This variance in development of the disease may be due to genetic susceptibilities. For example, it is hypothesized that individuals with human leukocyte antigen (HLA)DR2 and HLA-DR3 genes are more likely to develop the tuberculoid form of leprosy, whereas those carrying the HLA-DQ1 gene develop the lepromatous form of leprosy.1 In addition, correlations have been found between leprosy and the parkin RBR E3 ubiquitin protein ligase (PARK2) gene and the lymphotoxin-alpha gene, which are also associated with the development of Parkinson’s disease and malaria parasitemia, respectively.2,3 M. leprae is a small, weakly acid-fast, obligate, intracellular rod bacterium that tends to colonize macrophages and Schwann cells. The peripheral nerves, mucous membranes, skin, bones, and viscera are often the most likely areas that are involved. Interestingly, these mycobacteria thrive in cooler regions of the body, such as the nose, testicles, ear lobes, and superficial peripheral nerves in the skin.1,2 If untreated, lepromatous leprosy will continue to progress and cause deforming and disabling symptoms. Patients in advanced stages of the disease can demonstrate madarosis,

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CME CE

Dermatology Clinic

or loss of hair from the outer third of the eyebrows, leonine facies, saddle nose, infiltration of bilateral earlobes, acquired ichthyosis of the lower extremities, gynecomastia, papal and claw hand due to flexion contractures, orchitis leading to sterility, neurotrophic ulcers, foot drop, and hammer toes.

A rare complication known as Lucio’s phenomenon can occur in diffuse lepromatous leprosy, where purpuric macules evolve into bullae that subsequently ulcerate. This phenomenon is also associated with fever, splenomegaly, glomerulonephritis, hypoalbuminemia, hypocalcemia, polyclonal gammopathy, and anemia.1-3 These lesions are quite painful and often occur below the knees. Biopsy of these lesions will show organisms teeming not only in the skin but also within blood vessels.2

Lepromatous leprosy may present on a broad clinical spectrum based on immunologic response or resistance.

Although lepromatous leprosy often does not have initial nervous system involvement, neuropathy in a symmetric stocking glove distribution will eventually develop if untreated. Debilitating ocular involvement can lead to lagophthalmos (ie, inability to close eyes), keratitis, episcleritis, corneal and conjunctival anesthesia, and eventual blindness.1,2,4,5 Lepromatous leprosy may present on a broad clinical spectrum based on immunologic response or resistance.

The patient in our case had the lepromatous type of leprosy that represents the multibacillary end of the spectrum due to depressed cell-mediated immunity. On the other hand, tuberculoid leprosy represents a strong immunologic response that leads to few or no organisms in the lesions of patients who have the condition.

Lepromatous leprosy can be differentiated from tuberculoid leprosy by clinical presentation. The lepromatous form often presents with numerous macules, papules, and nodules in a symmetric distribution without loss of sensation or nerve involvement.1,2,4,5 A biopsy of these skin lesions would demonstrate many of these organisms as globi on histopathology.1 On the other hand, patients with tuberculoid leprosy often have asymmetric, well-demarcated, infiltrative plaques with some loss of sensation due to nerve inflammation or destruction leading to anesthetic areas. Biopsy of these skin lesions would demonstrate few organisms, if any. Furthermore, peripheral nerves can become enlarged and palpable and are important in physical examination.

Between these two extremes, there are many permutations in clinical presentation, constituting the borderline spectrum.1,4,5 Borderline disease is often known to be unstable and moves over time from the tuberculoid end of the spectrum toward the lepromatous end. This is a process known as downgrading.1-2,4-5 Differential diagnoses for lesions as seen in the patient in our case may include mycosis fungoides, leishmaniasis, syphilis, sarcoidosis, cellulitis, erythema nodosum, and cutaneous tuberculosis. Nerve involvement may be mistaken as a peripheral neuropathy that is secondary to diabetes, nutritional deficiencies, vasculitis, syringomyelia, and poliomyelitis.1-2,4-5 Ideally, a punch biopsy should be performed down to the subcutaneous fat over an active border of one of the lesions. A Fite stain often can help accentuate these acid-fast bacilli.1-2,4-5 It is important to note that M. leprae cannot be cultured, and polymerase chain reaction testing has not been very useful due to lack of sensitivity.2 Since multidrug therapy is extremely effective and this patient had lepromatous leprosy, a regimen of 3 drugs was initiated: rifampin at 600 mg by mouth every month; clofazimine at 300 mg by mouth each month and 50 mg by mouth every day; and dapsone at 100 mg by mouth daily.1 The regimen was planned for 1 to 2 years,1 followed by observation for 5 years. However, the patient then developed fever, myalgia, joint swelling, and nodular skin lesions that were thought to be due to a treatment-induced type-2 skin reaction called erythema nodosum leprosum. Therapy with thalidomide at 200 mg by mouth every day was initiated.1-2,4-5 The patient’s lesions eventually resolved completely, but he will need long-term suppressive therapy and follow-up. n Dr. Shih is a resident physician at the University of Minnesota in Minneapolis.

References 1. Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. Philadelphia, Pa.: Elsevier Saunders; 2012:1221-1228.

2. James WD, Berger TG, Elston DM, eds. Andrews’ Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia, Pa.: Saunders Elsevier; 2011: 334-344.

3. Rodrigues LC and Lockwood DNj. Leprosy now: Epidemiology, progress, challenges, and research gaps. Lancet Infect Dis. 2011;11(6): 464-470.

4. Moschella SL. An update on the diagnosis and treatment of leprosy.

J Am Acad Dermatol. 2004;51(3):417-426.

5. Eichelmann K, González González SE, Salas-Alanis JC, OcampoCandiani J. Leprosy. An update: Definition, pathogenesis, classification, diagnosis, and treatment. Actas dermo-sifiliográficas. 2013; 104(7):554-563.

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Dermatologic Look-Alikes

CME CE DERMATOLOGY COURSES

Raised, dark, enlarging lesion DANIELLE BROWN, BA, AND MAURA HOLCOMB, MD

CASE #1

CASE #2

A white male, aged 65 years, presents with a slowly enlarging, dark lesion on his temple. He has no history of skin cancer. However, as a child, the patient spent many summers on the beach. On physical examination, a well-demarcated, 8-mm lesion with raised, waxy hyperpigmented borders and central indentation is noted on the right temple. No other lesions are noted on examination.

A 55-year-old white male presents with a rapidly enlarging black lesion on his back that he first noticed one month earlier. The patient reports intermittent pruritus of the lesion. He has a history of numerous moles but no history of skin cancer. In his youth, the patient had many blistering sunburns. Physical examination reveals a 6.5-mm, raised, hyperpigmented lesion with asymmetric borders.

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CME CE

CASE #1

Dermatologic Look-Alikes

Pigmented basal cell carcinoma

Basal cell carcinoma (BCC) is a slow-growing, locally invasive malignant skin tumor originating from basal keratinocytes in the epidermis. The risk of metastasis is low, ranging from 0.003% to 0.6%.1 When metastasis does occur, it is most frequently to the lymph nodes or the lungs.

The major histologic subtypes of BCC are nodular, superficial, micronodular, infiltrative, and morpheaform.

Pigmented BCC is a variation of the nodular subtype. In the United States, the lifetime risk of BCC is approximately 30%.2 BCC is the most common form of all cancers, with more than one million cases identified every year.1 Exposure to light in the ultraviolet B (UVB) spectrum leads to development of BCC. Mutations in the cell cycle regulator protein, p53, caused by UVB radiation are found in half of all BCCs.3 Additionally, development of BCC involves changes to the hedgehog signaling pathway and alterations in the patched 1 (PTCH1) and smoothened, frizzled class receptor (SMO) genes in 90% and 10% of BCCs, respectively.4 In contrast to squamous cell carcinoma, in which cumulative sun exposure is the main contributing factor, the development of BCC rests heavily on intermittent sun exposure or sunburns.1 Exposure to UV radiation is the greatest risk factor for the development of BCC. The use of tanning beds increases the chance for the development of BCC by 1.5 times.5 Additionally, males have a two-fold increased risk for developing BCCs, compared with females.6 Other risk factors include fair complexion, ability to freckle, increased age, immunosuppression, arsenic exposure, and chronic local inflammation.7 Furthermore, there are genetic syndromes, such as Bazex-Dupré-Christol or Rombo syndromes, with a predisposition for BCC. The average age at which BCCs develop is 62 years, but approximately 20% of these tumors occur in individuals aged less than 50 years.8 Pigmented BCC is most common in dark-skinned individuals and may be difficult to distinguish from nodular melanoma.9 BCCs typically develop on sun-exposed areas. Lesions most commonly develop on the nose, periorbital region, and cheek.6 They appear as one or more brown, black, or blue waxy, pearly, and typically translucent papules surrounding a central indentation or ulceration.9 The

discrete border of these lesions frequently has a rolled appearance.1 Telangiectasias are frequently seen.

The differential diagnosis for pigmented BCC includes melanoma, compound nevus, and blue nevus.1 Dermoscopy criteria for BCC include the lack of a pigmented network along with one additional finding, such as leaf-like regions, branching vessels, or ulceration.7 Definitive diagnosis of BCC is obtained with biopsy, with shave biopsy being the preferred method. Histopathology shows tumor nests composed of uniform cells with large basophilic nuclei. Histologically, pigmented BCC shows melanin in the tumor cells. The pigmentation in pigmented BCC is derived from melanophages in the tumor and the phagocytosis of melanosomes by the tumor.7

The use of tanning beds increases the chance for the development of basal cell carcinoma by 1.5 times.

Following biopsy, BCCs can be removed via standard surgical excision, curettage and desiccation, radiation, cryotherapy, or Mohs surgery. Curettage and desiccation is most effective when used for low-risk tumors that are less than 2 cm on the trunk or extremities. Cryotherapy is reserved for lesions that are less than 3 mm in depth.10 Surgical excision is recommended for primary tumors that are less than 2 cm in diameter on the trunk or extremities.11 To achieve a cure rate of 95%, appropriate margins for excision are 4 mm for tumors that are less than 2 cm in diameter.12 Mohs micrographic surgery is reserved for tumors on the face, high-risk subtypes, or recurrent tumors.1 The recurrence rate for BCC ranges from 5% to 14%.6 The major risk factor for recurrence is the histopathologic subtype; nodular BCC are considered to be the low-risk subtypes for recurrence.10 Recurrence rates are lowest following Mohs microscopic surgery.

BCC generally has a very good prognosis. However, in individuals who develop a BCC, the chance of developing another primary BCC within the following 5 years is as high as 50%.1 For the patient in our case, a shave biopsy was taken of the lesion, and a diagnosis of pigmented BCC was confirmed.

He then underwent Mohs microscopic surgery for removal of the lesion. At his 6-month follow-up appointment, the patient had no recurrence.

72 THE CLINICAL ADVISOR • NOVEMBER 2015 • www.ClinicalAdvisor.com

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CASE #2

Nodular melanoma

Comparison of characteristics of pigmented basal cell carcinoma and nodular melanoma1,19

Melanoma is a malignant cancer derived from the malignant transformation of melanocytes.

Nodular melanomas originate at the interface between the dermis and epidermis. They rapidly grow vertically into the dermis.13 Although malignant melanomas are the least prevalent skin cancers, they are the most deadly, causing approximately 75% of all skin cancer deaths.14 In the United States, melanoma is the fifth most common cancer in males and the seventh most common cancer in females.15 Rates of melanoma have been steadily increasing, with the current lifetime risk estimated at greater than 1:30 for the development of melanoma.13 There are 7 subtypes of malignant melanoma. In order of decreasing prevalence, these subtypes are superficial spreading melanoma, nodular melanoma, lentigo maligna and lentigo maligna melanoma, amelanotic melanoma, acral lentiginous melanoma, and subungual melanoma.16 Although only 10% to 15% of melanomas are nodular melanomas, nodular melanomas are responsible for more than 35% of deaths associated with melanoma.16,17 Nodular melanomas are 1.5 times more likely to be fatal than superficial spreading melanomas, and they grow four times faster than other subtypes.18,19 Most melanomas develop following a sequence of events in which a benign melanocytic nevus progresses to have atypical characteristics. The atypical nevi may grow radially before progressing to a stage of vertical growth. Following the vertical growth state, the melanoma may metastasize. The vertical growth phase is a time of aggressive growth. This vertical growth pattern is rapidly displayed by nodular melanomas.

Furthermore, in contrast to the other melanoma subtypes, nodular melanomas frequently do not arise from pre-existing nevi.

Nodular melanomas display mutations in the B-Raf protooncogene (serine/threonine kinase; BRAF), neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS), hypoxia-inducible factor 1 alpha subunit (basic helix-loop-helix transcription factor; HIF1A), and vascular endothelial growth factor (VEGF).

These mutations are not found in other types of melanomas and contribute to the poor prognosis of nodular melanomas.20 The most significant risk factor for development of melanoma is exposure to excessive ultraviolet radiation, specifically a history of intermittent blistering sunburns.13 Individuals who use tanning beds have a 1.25 increased risk for the development of

Pigmented basal cell carcinoma

Nodular melanoma

Lifetime risk in United States

30%

3.3%

Incidence

Most commonly diagnosed skin cancer

Least commonly diagnosed skin cancer but most deadly

Relative potential to metastasize

Low

High

Rate of growth

Slow

Rapid

Average age of diagnosis

62 years

52 years

Factor posing greatest risk

Cumulative ultraviolet light exposure

Intermittent, intense ultraviolet light exposure

Malignant cell

Basal keratinocyte

Melanocyte

Known mutations

• Patched 1 (PTCH1) gene • Smoothened, frizzled class receptor (SMO) gene

• B-Raf proto-oncogene, serine/threonine kinase (BRAF) • Neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) • Hypoxia-inducible factor 1, alpha subunit (basic helixloop-helix transcription factor; HIF1A) • Vascular endothelial growth factor (VEGF)

Most common anatomical sites

Nose, periorbital region, cheek

Head, neck, trunk

Characteristic features

• Pigmented, pearly, translucent papules surrounding a central area of indentation or ulceration • Rolled border • Associated telangiectasias

ABCDE criteria (>1) •Asymmetry •Border irregularities •Color variations •Diameter >6mm •Evolving morphology

Diagnostic method

Shave biopsy

Elliptical excisional biopsy

Histopathology

Tumor nests composed of uniform cells with large basophilic nuclei

Atypical melanocytes in the dermis

Determination of surgical margins

Diameter of lesion

Breslow thickness (also determines need for sentinel lymph node biopsy)

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CME CE

Dermatologic Look-Alikes

melanoma.21 The most common age of diagnosis of melanoma is 52 years.13 Risk factors for the development of melanoma include fair complexion, age, personal or family history of skin cancer, and presence of numerous moles or dysplastic nevi.16 The ABCDE mnemonic helps clinicians screen for melanomas. These criteria are asymmetry, irregular border, variation in color, diameter greater than 6 mm, and evolving morphology of the lesion.16 The “E” criterion is particularly of use when diagnosing nodular melanomas for which the other criteria are not notable. Approximately 78% of nodular melanomas display evolving characteristics.22 An evolving lesion is one with any change in color, structure, or symptoms. A new development of bleeding, pain, or itching from the lesion fulfills this criterion.

The differential diagnosis for pigmented nodular melanoma includes pigmented basal cell carcinoma, pigmented Spitz nevus, blue nevus, or common nevus.13 Nodular melanoma typically presents as a fast-growing nodule on the head, neck, or trunk.16 The diagnosis of nodular melanoma is obtained through histopathology showing atypical melanocytes in the dermis.13 Elliptical excisional biopsy is the gold standard of diagnosis.16 Following biopsy, the tumor is staged based on Breslow’s thickness, mitotic rate, and the presence of ulceration.

of less than 1, and no ulceration. The patient underwent surgical excision and sentinel lymph node biopsy. The sentinel lymph node biopsy was negative. The patient shows no sign of recurrence at the 6-month follow up. n Ms. Brown is a medical student and Dr. Holcomb is a dermatology resident at Baylor College of Medicine in Houston.

References 1. Carucci JA, Lefell DJ, Pettersen JS. Basal cell carcinoma. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K, eds. Fitzpatrick’s Dermatology in General Medicine. 8th ed. New York, N.Y.: McGraw-Hill Medical; 2012: Chap. 115.

2. Miller DL, Weinstock MA. Nonmelanoma skin cancer in the United States: Incidence. J Am Acad Derm. 1994;30(5 Pt 1):774-778.

3. Benjamin CL, Ananthaswamy HN. p53 and the pathogenesis of skin cancer. Toxicol Appl Pharmacol. 2007;224(3):241-248. Available at ncbi.nlm. nih.gov/pmc/articles/PMC2080850 4. Epstein EH. Basal cell carcinomas: Attack of the hedgehog. Nat Rev Cancer.

2008:8(10):743-754. Available at ncbi.nlm.nih.gov/pmc/articles/PMC4457317 5. Karagas MR, Stannard VA, Mott LA, Slattery MJ, Spencer SK, Weinstock MA. Use of tanning devices and risk of basal cell and squamous cell skin cancers. J Natl Cancer Inst. 2002;94(3):224-226. Available at jnci.oxfordjournals.org/content/94/3/224.long

The most significant risk factor for development of melanoma is exposure to excessive ultraviolet radiation.

6. Demirseren DD, Ceran C, Aksam B, Demirseren ME, Metin A. Basal cell carcinoma of the head and neck region: A retrospective analysis of completely excised 331 cases. J Skin Cancer. 2014: Article ID 858863.

Available at hindawi.com/journals/jsc/2014/858636 7. Mackiewicz-Wysocka M, Bowszyc-Dmochowska M, Strzelecka-Węklar D, Dańczak-Pazdrowska A, Adamski Z. Basal cell carcinoma—diagnosis.

Contemp Oncol (Pozn). 2013;17(4): 337-342. Available at ncbi.nlm.nih.gov/

Breslow’s thickness determines the appropriate margins for excision. If Breslow’s thickness is greater than 2 mm, a 2-cm margin can be used. If Breslow’s thickness is 1.01 mm to 2 mm, a margin of 1 cm to 2cm can be used.16 For lesions with a Breslow’s thickness that is less than 1 mm, a 1-cm margin is considered appropriate. Patients with a Breslow’s thickness of 1 mm or greater should undergo a sentinel node biopsy. Ulceration and presence of micrometastasis to the sentinel lymph node are the two most important indicators for poor prognosis.20 Following surgical excision of the tumor with appropriate margins, the tumor is staged using the TNM staging system. This system takes into account the depth of the primary tumor, lymph node involvement, and the presence of metastatic disease. Follow-up and additional studies are based on the TNM stage of the cancer.16 For the patient in our case, a diagnosis of pigmented nodular melanoma was made following an excisional biopsy. The melanoma displayed a 1.69-mm Breslow’s thickness, mitosis

pmc/articles/PMC3934050 8. Leman JA, McHenry PM. Basal cell carcinoma: Still an enigma. Arch Dermatol. 2001;137(9):1239-1240.

9. Matz, H, Orion E, Ruocco V, Wolf R. Clinical simulators of melanoma.

Clin Dermatol. 2002;20(3):212-221.

10. Firnhaber JM. Diagnosis and treatment of basal cell and squamous cell carcinoma. Am Fam Physician. 2012:86(2);161-168. Available at aafp.org/ afp/2012/0715/p161.html 11. Thissen MR, Neumann MH, Schouten LJ: A systematic review of treatment modalities for primary basal cell carcinomas. Arch Dermatol. 1999;135(10):11771183. Available at archderm.jamanetwork.com/article.aspx?articleid=478044 12. Johnson TM, Tromovitch TA, Swanson NA: Combined curettage and excision: A treatment method for primary basal cell carcinoma. J Am Acad Dermatol. 1991:24(4);613-617.

13. Bailey EC, Sober AJ, Tsao H, Mihm Jr. MC, Johnson TM. Cutaneous Melanoma. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K, eds. Fitzpatrick’s Dermatology in General Medicine. 8th ed. New York, N.Y.: McGraw Hill Medical; 2012: Chap. 124.

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14. Sladden MJ, Balch C, Barzilai DA, et al. Surgical excision mar-

19. Liu W, Dowling JP, Murray WK, et al. Rate of growth in melanomas:

gins for primary cutaneous melanoma. Cochrane Database Syst Rev.

Characteristics and associations of rapidly growing melanomas. Arch

2009;(4):CD004835.

Dermatol. 2006;142(12):1551-1558. Available at archderm.jamanetwork.

15. American Cancer Society. Cancer Facts & Figures 2014. Atlanta:

com/article.aspx?articleid=410160

American Cancer Society; 2014. Available at cancer.org/acs/groups/con-

20. Egger ME, Dunki-Jacobs EM, Callender GG, et al. Outcomes and prog-

tent/@research/documents/webcontent/acspc-042151.pdf

nostic factors in nodular melanomas. Surgery. 2012;152(4):652-660.

16. Shenenberger DW. Cutaneous malignant melanoma: A primary care

21. International Agency for Research on Cancer Working Group on artifi-

perspective. Am Fam Physician. 2012;85(2):161-168. Available at aafp.org/

cial ultraviolet (UV) light and skin cancer. The association of use of sunbeds

afp/2012/0115/p161.html

with cutaneous malignant melanoma and other skin cancers: A systematic

17. Shaikh WR, Xiong M, Weinstock MA. The contribution of nodular

review. Int J Cancer. 2007;120(5):1116-1122. Available at onlinelibrary.wiley.

subtype to melanoma mortality in the United States, 1978 to 2007. Arch

com/doi/10.1002/ijc.22453/full

Dermatol. 2012;148(1):30-36. Available at archderm.jamanetwork.com/

22. Chamberlain AJ, Fritschi L, Kelly JW. Nodular melanoma: Patients’ per-

article.aspx?articleid=1105209

ceptions of presenting features and implications for earlier detection. J Am

18. Mar V, Roberts H, Wolfe R, English DR, Kelly JW. Nodular melanoma:

Acad Dermatol. 2003;48(5):694-701.

A distinct clinical entity and the largest contributor to melanoma deaths in Victoria, Australia. J Am Acad Dermatol. 2013:68(4):568-575.

All electronic documents accessed on October 1, 2015.

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CME CE

POSTTEST

Expiration date: November 12, 2016

DERMATOLOGY COURSES CREDITS: 0.5

For more credit information, please turn to p. 66.

Dermatology Clinic

page 67

Case #1: Becker nevus 1. A 14-year-old male presents with a dark brown, hairy patch on his left shoulder that is unattractive to him.

Childhood photos reveal that this lesion was not previously present. A biopsy reveals that this is a Becker nevus. Upon further examination, you find that the patient has hypoplasia of the left pectoralis major muscle and an accessory scrotum. What condition should be considered? a. McCune-Albright syndrome b. Neurofibromatosis c. Congenital melanocytic nevus d. Becker nevus syndrome 2. Which of the following treatments would result in the greatest risk of recurrence of a pigmented lesion in a patient with a Becker nevus? a. Q-switched ruby laser b. Long-pulsed alexandrite laser c. Fractionated laser d. Erbium:yttrium-aluminum-garnet (Er:YAG) Case # 2: Lepromatous leprosy 3. A 35-year-old Kenyan man presents with erythematous macules, papules, and nodules scattered over the face, bilateral upper and lower extremities, and buttocks. A biopsy of one of these lesions would show numerous bacilli in what type of cell? a. Lymphocytes b. Macrophages c. Red blood cells d. Keratinocytes 4. A 40-year-old Brazilian woman presents after multidrug treatment for lepromatous leprosy that began several days ago. She complains of new-onset severe joint pain and swelling, fevers, myalgias, and nodular lesions. What is the most likely cause of her symptoms? a. Lucio phenomenon b. Downgrading c. Type 2 reaction, likely erythema nodosum leprosum d. Secondary bacterial superinfection

Dermatologic Look-Alikes

page 71

Case #1: Pigmented basal cell carcinoma 1. A 70-year-old man presents with a 1.0-cm, recurrent, biopsy-proven pigmented basal cell carcinoma on his shoulder. What is the most appropriate course of treatment? a. The lesion should be removed via cryotherapy. b. The lesion should be surgically excised with 8-mm margins. c. The lesion should be removed by Mohs micrographic surgery. d. The area should be treated with radiation therapy to prevent recurrence 2. Which is the greatest risk factor for the development of pigmented basal cell carcinoma? a. Male sex b. Female sex c. Increased age d. Ultraviolet radiation Case #2: Nodular melanoma 3. During a comprehensive skin check on a patient with numerous nevi, you ask if any of the lesions have been bothering him. He points out that one of them has recently been causing him pain. This lesion is 6.5 mm, hyperpigmented, and raised. You perform an excisional biopsy of the lesion. Which of the following Breslow thicknesses correlates to the correct subsequent treatment? a. Breslow 0.7 mm: Surgical excision with 0.3-cm margin b. Breslow 1.1 mm: Surgical excision with 2.0-cm margin c. Breslow 0.7 mm: Surgical excision with 0.3-cm margin, along with sentinel lymph node biopsy d. Breslow 1.1 mm: Surgical excision with 2.0-cm margins, along with sentinel lymph node biopsy 4. Which of the following is the greatest risk factor for nodular melanoma? a. Age b. A history of intermittent blistering sunburns c. Personal or family history of skin cancer d. Presence of numerous moles or dysplastic nevi

TO TAKE THE POSTTEST please go to: myCME.com/Nov15CAderm

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2/26/15 9:46 AM

Clinical Challenge Painful red spot and fever in an infant LAURA A. FOSTER, CRNP, FNP

The child and her twin tested positive for influenza B infection one week earlier.

The child’s pulse, respirations, and blood pressure were within normal limits.

Microorganisms can enter the bone through an injury or infection.

The parents of twin infants brings one of them, Juliet, a 5-month-old female, to the clinic. The baby has a painful red spot on her right elbow and a fever of 100.5°F.

CASE

HISTORY Juliet’s parents report that her bottle intake was moderately less than usual. The infant became very fussy when her mother tried to put her down, and she would not sleep in her crib. The infant was most content in her mother’s arms.

One week prior, Juliet and her twin brother tested positive for influenza B infection. Both infants were treated with oseltamivir phosphate.

PHYSICAL EXAMINATION On examination, her pulse, respirations, and blood pressure were within normal limits; her tympanic temperature was 100.9°F. The infant was alert, albeit more quiet than usual, according to her mother. She did not appear toxic.

The erythematous macule measured 1.2 cm and was without increased warmth, edema, or pus. There was no pain to light touch. However, Juliet was noticeably uncomfortable with a more firm palpation of the distal humerus just above the annular lesion. The remainder of her physical examination was unremarkable.

Acute hematogenous osteomyelitis was suspected, and the infant was sent to a local facility for urgent initial workup.

© MARTIN ROTKER / PHOTOTAKE

LABORATORY TESTS AND IMAGING A radiograph of the right elbow showed no acute process. Her C-reactive protein (CRP) level was within normal limits, at 3.10 mg/dL. Her erythrocyte sedimentation rate (ESR) was elevated, at 77 mm/h. Her leukocyte count was elevated, at 19.6. Results of her blood culture were pending. Juliet was promptly transferred 78 THE CLINICAL ADVISOR • NOVEMBER 2015 • www.ClinicalAdvisor.com

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Clinical Challenge to a nearby children’s hospital for admission, further evaluation, and treatment.

An ultrasound of the infant’s right elbow showed no joint effusion or extra-articular soft tissue fluid collection.

Magnetic resonance imaging (MRI), performed under general anesthesia, demonstrated abnormal low T1-weighted and bright T2-weighted marrow signals within the distal right humerus metaphysis with periosteal reaction extending along the shaft of the humerus.

DIAGNOSIS AND TREATMENT The MRI findings were in keeping with acute osteomyelitis and periostitis of the distal right humerus. Secondary inflammation of the elbow joint synovitis and soft tissue cellulitis is likely present as well.

No definite drainable abscess is present. Her blood culture identified the presence of Staphylococcus aureus. Intravenous cefazolin, 260 mg every 8 hours, was initiated. A peripherally inserted central catheter (PICC) line was placed under anesthesia before hospital discharge.

DISCUSSION Clinical features. Acute osteomyelitis in children is primarily a clinical diagnosis based on the rapid onset and localization of symptoms. Acute hematogenous osteomyelitis results from bacteremic seeding of bone. Children are most often affected because the metaphyseal or growing regions of the long bones are highly vascular and susceptible to even minor trauma. More than one-half of cases of acute hematogenous osteomyelitis in children occur in patients aged less than 5 years.1 Osteomyelitis is an infection localized to bone.

Microorganisms, predominantly bacteria that enter the bone hematogenously, usually cause it. Other pathogenetic mechanisms include direct inoculation, such as trauma or surgery, or local invasion from a contiguous infection, such as decubitus ulcer, sinusitis, or periodontal disease.

Children with hematogenous osteomyelitis usually present acutely with fever, constitutional symptoms such as irritability and decreased appetite or activity, and focal findings of bone inflammation such as warmth, redness over the infection site, point tenderness, and limited function. It should be noted, however, that initial symptoms can be nonspecific in children of all ages (eg, malaise and low-grade fever). Once the infection becomes established in bone, the symptoms are more localized.2

In a systematic review by Dartnell J et al3 that included more than 12,000 children with acute and subacute osteomyelitis, presenting features included pain (81%), reduced range of motion (50%), localizing signs and symptoms (70%), reduced weight bearing (50%), and fever (82%).

Hematogenous osteomyelitis generally occurs at only one site. Long or tubular bones are affected more frequently than nontubular bones, such as flat, irregular, and sesamoid bones. The sites of involvement in children in order of most common to least common include the femur (27%), tibia (26%), pelvis (9%), feet (8%), humerus (8%), radius/ ulna (5%), vertebrae (4%), fibula (4%), and the hands (2%).3 Laboratory features. Elevations in peripheral leukocyte count in osteomyelitis are variable and nonspecific.

Findings from the systematic review by Dartnell J et al3 indicated that the leukocyte count was elevated in 36% of patients at the time of presentation. The leukocyte count tends to be higher and take longer to normalize in children with osteomyelitis caused by methicillin-resistant S. aureus (MRSA), group A Streptococcus, or Streptococcus pneumoniae infection, and in children with concomitant septic arthritis.

Elevation of CRP occurs in most children with osteomyelitis. In the review by Dartnell et al3, CRP was elevated in 81% of children at the time of presentation, peaked on day 2, and normalized over 1 week. In one of the studies in their analysis, the mean CRP level was 87 mg/dL at the time of presentation.

Elevation of the ESR to greater than 20 mm/h occurs in most children with osteomyelitis. Dartnell et al3 found that ESR was elevated in 91% of children at the time of presentation, peaked on days 3 to 5, and normalized over 3 or 4 weeks; the mean ESR was 51 mm/h at the time of presentation.4 Imaging modalities. A plain radiograph has a sensitivity of 16% to 20% and a specificity of 80% to 100%. However, a plain radiograph will not show abnormal findings at the onset of symptoms, and a normal radiographic result does not exclude osteomyelitis.

MRI is the preferred imaging modality to establish the diagnosis of osteomyelitis; it has a sensitivity of 80% to 100% and a specificity of 70% to 100%. This test identifies early changes in the bone marrow cavity and the location and extent of osteomyelitis. Therefore, osteomyelitis is unlikely if the MRI result is normal. The disadvantage of MRI is that young children may require sedation or anesthesia for an optimal study result.

Computed tomography (CT) only has a sensitivity of 67% and a specificity of 50% for osteomyelitis. A disadvantage of CT is radiation exposure.

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Clinical Challenge

FIGURE 1. More than one-half of pediatric cases of osteomyelitis occur in children younger than age 5 years.

Ultrasonography is useful to evaluate fluid collections in the adjacent structures, but this imaging modality does not penetrate the bone cortex. Therefore, it has a low sensitivity and specificity of 55% and 47%, respectively.5 Epidemiology. In high-income countries, acute osteomyelitis occurs in approximately 8 out of 100,000 children per year, but it is considerably more common in low-income countries. Boys are affected twice as often as girls, and hematogenous osteomyelitis is more common in children than adults.

More than one-half of pediatric cases occur in children aged younger than 5 years, and one-quarter of cases occur in children aged younger than 2 years. Osteomyelitis is uncommon in infants aged younger than 4 months without underlying risk factors.

Unless acute osteomyelitis is diagnosed promptly and treated appropriately, it can be a devastating or even fatal disease with a high rate of sequelae, especially in resourcepoor countries where patients present with advanced disease and survivors often have complications that are serious and long lasting.5 Treatment. Antimicrobial therapy for osteomyelitis often is initiated before the diagnosis is confirmed. The risk of delaying treatment for bacteremic patients may be significant, particularly for those with community-associated S. aureus.

Cultures should be obtained from blood and suspected foci of infection before initiating empiric antimicrobial therapy.

Initial antimicrobial therapy for acute hematogenous osteomyelitis is usually administered parenterally. The empiric regimen is determined by the child’s age, clinical features, and organisms prevalent in the community. The cure rate

for osteomyelitis in children is greater than 95%, when the appropriate empiric therapy is chosen.3 Empiric intravenous antimicrobial therapy for infants from birth to age 3 months should be directed against S. aureus, gram-negative bacilli, and group B streptococci, the most common causes of hematogenous osteomyelitis in this age group.

Empiric intravenous antimicrobial therapy for children aged older than 3 months should be directed against S. aureus, the most common cause of hematogenous osteomyelitis in this age group, and other gram-positive organisms such as group A streptococci and streptococcal pneumonia. Agents that act against Staphylococcus and Streptococcus include nafcillin, oxacillin, cefazolin, clindamycin, and vancomycin.

Kingella kingae infection should be considered as a possible pathogen in children aged 6 to 36 months, especially those attending day care and those with indolent osteomyelitis or a history of oral ulcers preceding the onset of musculoskeletal findings. K. kingae infection is usually susceptible to cephalosporin antibiotics but is consistently resistant to vancomycin, and often resistant to clindamycin and antistaphylococcal penicillins such as nafcillin and oxacillin.

The antimicrobial regimen can be tailored to a specific pathogen when culture and susceptibility results are available.

No organism is identified in approximately 50% of children with suspected osteomyelitis. The decision to continue empiric antibiotic therapy is based on initial clinical suspicion, advanced imaging studies, and response to empiric therapy.6 Surgical intervention may be required at the time of presentation or during antimicrobial therapy if the child fails to respond as expected. Indications for surgical intervention may include drainage of subperiosteal and soft tissue abscess or debridement of contiguous foci of infection.7 Complications. Possible musculoskeletal complications of osteomyelitis vary with age, site of involvement, pathogen, and duration of infection. They include extension of infection into the soft tissue, septic arthritis, abnormal bone growth, pathogenic fracture, collapse of vertebral bodies, chronic osteomyelitis, and venous thrombosis.

Response to therapy. The response to therapy is assessed by serial clinical examination (fever, pain, erythema, and new sites of infection), peripheral leukocyte count, ESR, and/or CRP measurement. The frequency of these evaluations depends on the clinical status of the child.

Some experts prefer to monitor both ESR and CRP levels in children with acute osteomyelitis. ESR usually increases during the first several days of treatment and then declines slowly in the weeks that follow. CRP level also increases early

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in the infection but returns to normal range more rapidly than ESR, which makes it more useful in monitoring the course of illness. An increase in CRP level on or after day 4 of treatment may be associated with a complicated clinical course. The peripheral leukocyte count, if initially elevated, usually normalizes within 7 to 10 days after initiation of effective antimicrobial and/or surgical therapy.5 There is no minimum duration of intravenous therapy for treatment of osteomyelitis. Children with uncomplicated osteomyelitis can be switched from intravenous to oral therapy after they have demonstrated clinical improvement, such as no fever for 48 hours, decreased pain and erythema, normalization of leukocyte count, and a 50% reduction in CRP level.8 Current literature suggests administering antimicrobial therapy for 4 weeks or until the ESR and CRP levels normalize, whichever is longer. However, courses of treatment that are longer than 4 weeks may be necessary in children who require surgical debridement or who have delayed clinical improvement, persistent elevation of CRP level, MRSA, or Panton-Valentine leukocidin-positive osteomyelitis (a cytotoxin produced by S. aureus that causes necrotic lesions), or underlying medical conditions.9

3. Dartnell J, Ramachandran M, Katchburian M. Haematogenous acute and subacute paediatric osteomyelitis: A systematic review of the literature. J Bone Joint Surg Br. 2012;94(5):584-595.

4. Pääkkönen M, Kalio MJ, Kallio PE, Peltola H. Sensitivity of erythrocyte sedimentation rate and C-reactive protein in childhood bone and joint infections. Clin Orthop Relat Res. 2010;468(3):861-866.

5. Peltola H, Pääkkönen M. Acute osteomyelitis in children. N Engl J Med. 2014;370(4):352.

6. Howard-Jones AR, Isaacs D. Systematic review of duration and choice of systemic antibiotic therapy for acute therapy for haematogenous bacterial osteomyelitis in children. J Paediatr Child Health. 2013;49(9):760-768.

7. Faust SN, Clark J, Pallett A, Clarke NM. Managing bone and joint infection in children. Arch Dis Child. 2012;97(6):545-553.

8. Arnold JC, Cannavino CR, Ross MK, et al. Acute bacterial osteoarticular infections: eight-year analysis of C-reactive protein for oral step-down therapy. Pediatrics. 2012;130(4):821-828.

9. Peltola H, Pääkkönen M, Kallio P, Kallio MJ; Osteomyelitis-Septic Arthritis Study Group. Short- versus long-term antimicrobial treatment for acute hematogenous osteomyelitis of childhood: Prospective, randomized trial on 131 culture-positive cases. Pediatr Infect Dis J. 2010;29(12):1123-1128.

CONCLUSION AND FOLLOW-UP

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In this case, Juliet’s mother was concerned that she would not be able to get the drops of oral antibiotic into her infant without spilling; therefore, it was decided early to insert a PICC line. After 4 nights in the hospital, the infant was discharged from the hospital with a schedule of weekly visits by a registered nurse to their home. Intravenous cefazolin, 260 mg every 8 hours via PICC line, was administered for a total of 4 weeks. A complete blood count, basic metabolic panel, ESR, and CRP were measured weekly.

Her levels normalized quickly. The PICC line was removed and, except for a minor case of contact dermatitis from adhesive tape, the infant had no complications.

Juliet made a full recovery and required no follow-up. n Ms. Foster is a family nurse practitioner with Palmetto Primary Care in Charleston, South Carolina.

References 1. Gustierrez K. Bone and joint infections in children. Pediatr Clin North Am. 2005;52(3):779-794.

2. Goergens ED, McEvoy A, Watson M, Barrett IR. Acute osteomyelitis and septic arthritis in children. J Paediatr Child Health. 2005;41(1-2):59-62.

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Beyond Rx: OTC Corner Omega-3 fatty acids: From fins and fish oil to flax LYNN GREEN, APNP-BC, MSN, MHC

Omega-3 fatty acids have structural and anti-inflammatory roles in the human body.

Omega-3 fatty acids are a healthy subgroup of polyunsaturated fatty acids (PUFAs), the highest concentration of which is found in fish. Most of the PUFAs consumed in the Western world are proinflammatory omega-6 oils, which may be a contributing factor to many chronic diseases.

OMEGA-3 FATTY ACIDS Omega-3 fatty acids are composed of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and are primarily found in fatty fish, krill, green-lipped mussels, and algae. Omega3 fatty acids are considered “good” fats, and have both structural and anti-inflammatory roles in the body.

Plant sources of omega-3 fatty acids are predominantly derived from alpha-linolenic acid (ALA), which are primarily found in fl axseed, hemp, chia, canola, soy, pumpkin seed, and walnuts. ALA needs to be converted into omega-3 fatty acids in the body. The human body, however, can only convert a limited amount—in the range of 5% to 10% of plant-based ALA—into useful omega-3 fatty acids. Although both marine- and plant-based sources of omega-3 fatty acids are of value, the amount of useful omega-3 fatty acids that can be obtained from plant sources is limited by this necessary metabolic conversion.

OMEGA-6 FATTY ACIDS

© THINKSTOCK / JEFF J MITCHELL

Omega-6 fatty acids are proinflammatory oils, typically derived from vegetable oils and grains.

Common food sources of omega-6 fatty acids

Omega-3 fatty acids are primarily found in fatty fish.

This article is part of an ongoing series entitled, Beyond Rx: OTC Corner, which will include topics such as OTC medications, dietary supplements, and other health care approaches that will help nurse practitioners and physician assistants provide patients with tools to manage their health.

Robert D. Sheeler, MD, is guest editor of the series. He is an associate professor of family medicine, Mayo Clinic, in Rochester, Minn. He is board certified in family medicine, integrative medicine, and holistic medicine.

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are soybean oil, sunflower oil, and cottonseed oil. These oils lead to more arachidonic acid production and an increase in inflammatory mediators such as cyclooxygenase, lipoxygenase, leukotrienes, and glutamic acid, among others; this results in increased inflammation. Chronic inflammation is often associated with obesity, metabolic syndrome, diabetes, depression, arthritis, asthma, cardiovascular disease, and inflammatory bowel disease.1 The standard American diet has a ratio of omega-6 to omega-3 fatty acids that is approximately 20:1, which is significantly proinflammatory. Humans evolved with much lower ratios of omega-6 to omega-3 fatty acids in their diets.

Some studies suggest an optimal ratio is approximately 5:1 or lower.2

SOURCES OF OMEGA-3 FATTY ACIDS Consumption of fatty fish is by far the best proven way to increase levels of omega-3 fatty acids. Wild Alaskan salmon (sockeye) is a particularly good source, as this fish has the optimal lipid profile. Herring, sardines, and black cod are also high in omega-3 fats. Broiling, baking, and grilling are the best preparation methods. Frying healthy fish in unhealthy oils negates some or all of its beneficial effects.

Supplementation should be suggested for individuals who do not consume fish 2 to 3 times per week; fish oil is the best source of supplementation. Research has shown that there are more consistent benefits derived from consuming whole fish than isolated EPA/DHA. Fish oil comes in many forms; gelatin capsules and liquids are most common. Liquid forms typically have a higher concentration of omega-3 fats and should be considered especially for individuals for whom higher dosages are recommended. For the best absorption, fish oil in its natural or re-esterified triglyceride form should be considered.

Differing amounts of EPA and DHA have been used for different medical problems. According to ConsumerLab. com, dosages range from 300 mg to 4,000 mg of EPA and DHA per day. As with most other foods, whether plant or animal, many of the beneficial effects are derived from the synergy of the combinations of nutrients. In attempting to isolate the “active constituents,” the supplement may not be as beneficial as the whole item. This may also be true for cold-water fish. Study findings on EPA/DHA are controversial regarding their therapeutic effects3,4; however, the data on human populations that eat whole fish are not. Whole fish contains not only beneficial omega-3 fatty acids, but also omega-7 fatty acids, which play a role in metabolism and decreasing inflammation, as well as

omega-9 fatty acids, which have a role in lipid and blood sugar metabolism. Consuming whole fish oil rather than isolated EPA/DHA omega-3 supplements may offer more benefit because it is closer to the composition of fish than isolated components. Whole fish oil supplements that contain omega-7 and omega-9 components may offer additional benefits beyond supplements that only contain omega-3 fatty acids.

BENEFITS OF OMEGA-3 FATTY ACIDS Research has shown that a healthy intake of omega-3 fatty acids can be beneficial in triglyceride management, asthma, attention deficit disorder, bipolar disease, and other conditions. Consumption of whole fish has shown the greatest benefit in cardiovascular and cerebrovascular disease. Eating whole fish has also been shown to decrease the symptoms of rheumatoid arthritis early in the disease process.

Diets high in omega-6 fatty acids are associated with a 2.3-times increased risk of ulcerative colitis. Preliminary data indicate that omega-3 fatty acid supplementation has been associated with decreases in rates of breast cancer. One large study (N = 30,000) showed a 42% decrease in the risk of age-related macular degeneration with one serving of fish per week. The benefit was greatest with canned tuna or dark-meat fish (eg, mackerel, salmon, sardines, bluefish, and swordfish).

Higher levels of EPA have been shown to be beneficial in mitigating the symptoms of major and moderate depression, TABLE 1. Fish and supplement sources of omega-3 fatty acids Fatty fish, 4 oz (suggested 8 oz/wk)

Alaskan sockeye salmon

Approx. 1,316 mg (EPA, 390 mg; DHA, 764 mg; astaxanthin, 4.52 mg)

Whole fish oil supplement

• New Chapter

• 2 softgels;

• Wholemega™ (Brattleboro, VT)

• 2,000 mg wild Alaskan salmon oil (EPA, 180 mg; DHA, 220 mg; astaxanthin, 5 mcg)

Omega-3 supplement

• Nordic Naturals

• 2 softgels;

• ProOmega® (Watsonville, CA)

• 2,000 mg (EPA, 650 mg; DHA, 450 mg); 1 tsp (EPA, 1,450 mg; DHA, 1,060 mg)

DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid

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Beyond Rx: OTC Corner as well as bipolar disorder; depression in elderly patients has also been associated with low levels of EPA. Higher levels of omega-3 fatty acids from fish have been shown to be beneficial in age-related cognitive decline and memory enhancement. Acne severity has been shown to decrease with higher levels of omega-3 fatty acids. In prenatal studies, higher DHA levels have been associated with better neurologic development in the fetus. DHA has been found to be concentrated in the nervous system, particularly in photoreceptors and synaptic membranes.5

CHOOSING A SUPPLEMENT When choosing a supplement, it is imperative to avoid contaminants, as neurotoxins and carcinogens can accumulate in fish. Consumers should look at labels or manufacturers that meet Good Manufacturing Practice standards. To avoid contaminants, supplements made from small, oily fish that are low on the food chain should be chosen; anchovies and sardines are common. Fish liver oils can contain high levels of vitamin A, in the form of retinol, which can be toxic in high dosages over time; molecularly distilled products generally contain the highest concentrations. Clinicians should research the brands they recommend and have confidence in their manufacturing process and testing procedures for contaminants. n Ms. Green is a fellow with the University of Arizona Center for Integrative Medicine and a member of Green & Associates, Consultants, LLC.

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References chronic disease determinants [published online April 7, 2014]. Biomed Res Int. doi: 10.1155/2014/731685.

2. Simopoulos AP. The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med (Maywood). 2008;233(6):674-688.

3. Rizos EC, Ntzani EE, Bika E, et al. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis. JAMA. 2012;308(10):1024-1033.

4. Filion KB, El Khoury F, Bielinski M, et al. Omega-3 fatty acids in high-risk cardiovascular patients: A meta-analysis of randomized controlled trials.

BMC Cardiovasc Disord. 2010;10:24.

5. Bazan NG, Molina MF, Gordon WC. Docosahexaenoic acid signalolipidomics in nutrition: Significance in aging, neuroinflammation, macular degeneration, Alzheimer’s, and other neurodegenerative diseases. Annu Rev Nutr. 2011;31:321-351.

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1. Egger G, Dixon J. Beyond obesity and lifestyle: A review of 21st century

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ALTERNATIVE MEDS UPDATE

What you should know about the herbs and supplements patients use

By Sherril Sego, FNP-C, DNP Ms. Sego is an independent consultant in Kansas City, Mo.

Taurine

© SHUTTERSTOCK / STEFAN HOLM

A sulphur-containing amino acid, taurine has a number of biochemical roles in human metabolism. The amino acid was first named for the Latin Taurus, which means bull or ox, because it was first described in ox bile by a German scientist in 1827.1 Taurine is one of the major ingredients in most of the common energy drinks, and concerns over the safety of these drinks and questions as to the ingredients’ role in human cellular function have sparked renewed interest in this compound.

Background Like several other amino acids, taurine is often not found in its functional state in foods. However, it is a derivative of cysteine, which is another, more widely occurring amino acid. Taurine has multiple roles in the body, including membrane stabilization, calcium signaling, and regulation of cardiac and skeletal muscle function; it is also a potent antioxidant.2 As a result of these functions, taurine is thought to influence blood pressure, cardiac muscle function, liver function, and exercise tolerance.

Science Because of its role in energy drinks, interest in taurine has grown. Consumption of energy drinks, which are marketed under a wide variety of brands and names, has increased dramatically in the last few years. One source quotes a 240% increase in sales from 2004 to 2009, with the brand Red Bull claiming that more than 4 billion units were sold worldwide in 2011.3

Of the popular energy drinks available today, the major ingredients are sugar, caffeine, and taurine. Taurine concentrations in these drinks are usually between 1,000 mg and 2,000 mg per serving, with some brands containing as much as 3,000 mg to 4,000 mg per serving. Consumers’ claims of increased alertness and endurance were initially attributed to the caffeine content of the energy drinks. However, studies are finding that the effects of the ingredients in these drinks, especially caffeine and taurine, are more synergistic, bringing into play the effect of taurine.4 In a small study of healthy college-aged volunteers in which participants were randomly assigned to placebo or daily intake of a standardized energy drink, researchers evaluated the effect of the ingredients in the energy drinks on designated behavioral tasks that involve motor skills, judgment, and stamina.4 The findings of the study were somewhat vague, however. It appeared that taurine attenuated the effects of caffeine, thereby moderating the “buzz” typically reported with heavy caffeine intake but extending its effects of increased concentration and energy.

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ALTERNATIVE MEDS UPDATE Taurine also plays a significant role in skeletal and cardiac muscle contractility, making it important in the management of most cardiovascular functions. These functions are of a protective nature due to taurine’s calcium channel blocking function.5 This same action controls hypertension at the vascular level by reducing vasoconstriction and decreases the incidence of cardiac arrhythmias.

In a small but compelling study, researchers found improvements in exercise and metabolic measures after 2 weeks of oral supplementation with taurine.6 Taurine has also been found to have a role as an antioxidant. Another small study of healthy young men evaluated the pre- and post-exercise plasma levels of thiobarbituric-acid-reactive substances (TBARS), which can serve as an indicator of oxidative cell damage.7 The participants performed a session of ergometric exercise on bicycles until exhaustion. Plasma levels of taurine and TBARS had inverse correlations in the pre-exercise group. Participants then underwent a 7-day course of taurine supplementation and repeated the exercise routine. Following the supplementation and exercise, there were statistically significant increases in exercise time to exhaustion and maximal workload, correlating with a reduced serum TBARS level.7

doses for taurine, the cost of a month’s supply ranges from $20 to $50.

Dietary sources of taurine are almost exclusively meats and fish, but nutritional data indicate that most Americans do not consume enough of these foods on a daily basis to supply necessary amounts of taurine.8

Summary

Dietary sources of taurine are almost exclusively meats and fish.

Taurine plays a significant role in skeletal and cardiac muscle contractility and may also function as an antioxidant.

Safety, interactions, side effects

The number of different vitamin and herbal supplements available today is large, and it is not often that one is identified with almost no downside. Taurine is possibly one such supplement.

Although only a few of its benefits were mentioned here, its implications for cellular physiology are very intriguing. By following proper safety and medication reviews, clinicians may recommend taurine as a beneficial supplement for patients. n References 1. Taurine. Natural Medicines Comprehensive Database Web site. Updated October 6, 2015. Available at naturaldatabase.therapeuticresearch.com/nd/Search.aspx?cs=&s= ND&pt=100&sh=3&id=1024 2. Boukenooghe T, Remacle C, Reusens B. Is taurine a functional nutrient? Curr Opin Clin Nutr Metab Care. 2006;9(6):728-733.

3. Burrows T, Pursey K, Neve M, Stanwell P. What are the health implications associated with the consumption of energy drinks? A systematic review. Nut Rev. 2013. 71(3): 135-148.

Even though taurine is a naturally occurring amino acid, for supplemental use, it is considered “possibly safe,” and it is not recommended for pregnant or nursing women and infants.1 In sufficient quantities, taurine can reduce blood pressure. Consequently, the intake of large doses of taurine in conjunction with other antihypertensive agents is not recommended.

Dose, how supplied, cost

4. Peacock A, Martin FH, Carr A. Energy drink ingredients: Contribution of caffeine and taurine to performance outcomes. Appetite. 2013;64:1-4.

5. Higgins JP, Tuttle TD, Higgins CL. Energy beverages: Content and safety. Mayo Clin Proc. 2010. 85(11):1033-1041.

6. Beyranvand MR, Khalafi MK, Roshan VD, et al. Effect of taurine supplementation on exercise capacity of patients with heart failure. J Cardiol. 2011;57(3):333-337.

7. Zhang M, Izumi I, Kagamimori S, et al. Role of taurine supplementation to prevent exercise-induced oxidative stress 8. Spitze AR, Wong DL, Rogers QR, Fascetti AJ. Taurine concentrations in animal feed ingredients; cooking influences taurine content. J Anim Physiol Anim Nutr (Berl).

2003;87(7-8):251-262.

All electronic documents accessed October 6, 2015.

© THINKSTOCK / IRMAN

in healthy young men. Amino Acids. 2004;26(2):203-207.

Taurine is most commonly found as a tablet or powder-filled capsule. It is widely available. Dose levels vary widely, depending on the condition being treated and the patient’s medical profile.

Divided doses of 2 g to 6 g daily have been welltolerated. Due to the relatively large range of 104 THE CLINICAL ADVISOR • NOVEMBER 2015 • www.ClinicalAdvisor.com

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NPACE programs are jam-packed with clinical pearls for NPs and APRNs who need CE credits and want to learn about the latest updates from world-class faculty!

Take advantage of this great opportunity for learning and networking and earn the CEs you need.

Plan now to attend an NPACE conference in 2016!

Attend every fourth conference for free!

2016 Conferences February 15-16 San Antonio, TX Pharmacology Update March 11-14 New Orleans, LA Primary Care Conference with Workshops April 3-6 Orlando, FL Primary Care Conference with Workshops May 5-8 Phoenix, AZ Primary Care Conference & Pharmacology Update June 27-July 1 Cape Cod, MA Primary Care Conference & Pharmacology Update July 21-22 Providence, RI Pharmacology Update September 11-14 Indianapolis, IN Primary Care Conference with Workshops October 5-8 Myrtle Beach, SC Primary Care Conference & Pharmacology Update November 16-19 Boston, MA Primary Care Conference with Workshops

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Learn more and register online www.npace.org

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COMMENTARY Jennifer Schomaker, DNP, APRN-BC, FNP, ACNS, is a nurse practitioner at Hennepin County Medical Center in Minneapolis, Minn., and Sharon Fruh, PhD, RN, FNP-BC, is a professor at the University of South Alabama College of Nursing in Mobile, Ala.

Basal insulin for surgical diabetic patients Diabetes, whether diagnosed or undiagnosed, is often a comorbidity requiring care during hospitalization and is a major concern in the surgical population. A large number of patients admitted for surgical problems have diabetes (Crawford K. Crit Care Nurs Clin North Am. 2013;25[1]:1-6). The goal of care for these patients is to maintain blood glucose levels between 140 mg/dL and 180 mg/dL, based on recommendations set by the American Diabetes Association (ADA) in 2015. However, elevated blood glucose levels, which can result in postoperative infections, extended hospital stays, readmissions, and death, continue to be a problem in the care of these patients.

Basal insulin with or without nutritional correction is the best approach to manage blood glucose in noncritically ill surgical patients.

Studies have shown that hyperglycemia and poorly managed blood glucose levels occurred in 25% to 42% of surgical patients (Coan KE, et al. J Diabetes Sci Technol. 2013;7[4]:880-887) with sustained blood glucose levels of 180 mg/ dL to greater than 200 mg/dL. Hyperglycemia in surgical patients is an independent predictor of perioperative complications and can lead to death. The first and second postoperative days carry the highest risk for elevated blood glucose. These 2 days are the greatest predictors of serious infection and postoperative complications (Moghissi ES. Am J Health Syst Pharm. 2010;67[suppl 8]:S3-S8).

Prescribing basal insulin instead of sliding-scale insulin coverage in the surgical inpatient setting has been shown to decrease postoperative complications and length of hospital stay. The 2015 ADA guidelines support prescribing basal insulin for inpatient blood glucose management and discourage the use of sliding-scale insulin therapy and oral agents for glucose management in hospitalized patients. Oral agents lack efficacy in the inpatient setting and are associated with multiple side effects. They also offer a slow onset of action and do not allow for rapid glycemic control or dose adjustments to meet the needs of acutely ill patients. The use of standardized order sets with generalized guidelines for insulin needs, management of hypoglycemia, and regimen modifications is the best method for implementation.

One concern surrounding the use of basal insulin is hypoglycemia. However, basal insulin best mimics the body’s own insulin secretion and, as a result, has a low incidence of hypoglycemia.

Basal insulin should be continued without regard to a patient’s ability to take food or fluids by mouth.

Continuing basal insulin improves mean daily blood glucose without increasing hypoglycemic episodes (Harbin M, Dossa A, de Lemos J, et al.

Can J Diabetes. 2015;39[3]:210-215). Standardized order sets should include general guidelines for insulin adjustments for patients undergoing procedures and for those who can take nothing by mouth for prolonged periods, and guidelines for management of hypoglycemia. Insulin should be adjusted daily as needed based on the previous day’s blood glucose measurements. These measurements should be taken before meals and at bedtime for patients taking oral nutrition, or every 4 to 6 hours for patients who can take nothing by mouth.

The use of basal insulin with or without nutritional correction is the best approach to blood glucose management for noncritically ill surgical patients. This approach improves overall blood glucose and, thereby, improves outcomes by decreasing length of hospital stay, postoperative complications, and long-term complications associated with poor blood glucose control. Basal insulin best mimics the body’s own insulin secretion, and evidence shows that its use does not result in an increase in hypoglycemic episodes. n

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