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■■Valvular heart disease ■■Vertigo guideline ■■Septic shock treatment FEATURE

Developmental trauma disorder: effects of child abuse LEGAL ADVISOR

A patient is not informed of lab results of kidney damage

n Dermatologic Look-Alikes




n Feature



M AY 2 017



ARTHRITIS Swollen joints in the fingers of a patient with rheumatoid arthritis.

Editor Colby Stong, Senior editor Sandhya George Associate editor Lauren Grygotis Assistant editor Madeline Morr 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 manager Krassi Varbanov Circulation manager Paul Silver National accounts manager Alison McCauley, 973.224.6414 alison.mccauley @ Publisher Kathleen Hiltz, 201.774.1078 Editorial director Kathleen Walsh Tulley Senior vice president, digital products and medical magazines Jim Burke, RPh CEO, Haymarket Media, Inc. Lee Maniscalco All correspondence to: The Clinical Advisor 275 7th Avenue, 10th Floor, New York, NY 10001 For advertising sales, call 646.638.6085. For reprints, contact Wright’s Reprints at 877.652.5295. Persons appearing in photographs in “Newsline,” “The Legal Advisor,” and “Clinical Challenge” are not the actual individuals mentioned in the articles.They appear for illustrative purposes only. The Clinical Advisor ® (USPS 017-546, ISSN 1524-7317), Volume 20, Number 5, is published 12 times a year, monthly, for $75.00 per year in the United States; $85.00 in Canada; $110.00 for all other foreign, in U.S. dollars, by Haymarket Media, Inc., 275 7th Avenue, 10th Floor, New York, NY 10001. Single copy: $20 U.S.; $30 foreign. To order or update your paid subscription, call 800.436.9269. Periodicals postage rate paid at New York, NY, and additional mailing offices. POSTMASTER: Send address change to DMD Data Inc., 10255 W. Higgins Rd, Suite 280, Rosemont, IL 60018. Subscription inquiries: call 800.430.5450 to change your address or make other subscription inquiries. Requests for subscriptions from outside the United States must be accompanied by payment. All rights reserved. Reproduction in whole or in part without permission is prohibited. Copyright © 2017

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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.


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) 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

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)

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

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.

Advisor F

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@ 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.


These are lette and successe rs from practitioners s, observat around the below. We ions, and country who OUR CONSULTANTS pearls with invite you want to shar to participa their colle e their clinic agues. Resp te. al problems onding cons ultants are identified CON SULTAT IONS

TREATM ENT FOR INFECT URINAR ION SGLT2 REC MALE CHI S IN THE UNC Y TRACT IRCUMCI LD FOR DIA EPTOR BLOCKE If a male SED child conti Deborah L. Cross, MPH, CRNP, Laura A.BET Foster,ES CRNP, FNP, Abby A. Jacobson, PA-C, RS Abimbola Farinde, PhD, PharmD, With the nues toassociate ANP-BC, is practices family medicine is a physician assistant is a professor redevprogram adven t ofPrimary circu SGLT2 recep at Delaware Valley urinaryattract director, Gerontology NP elop Program, mcisi Columbia Southern moda litywith Palmetto on be perfo for type tor infecPhysicians Dermatology University of Pennsylvania School blockersGroup University 2 diabe rmed? regarding inCare as a treatm in Wilmington, Del. in Orange Beach, Ala. useCharleston, S.C. tes, is there ent urology is of Nursing, Philadelphia. any evide NATHAN in patients with to protect the is well advise nce or data type 1 diabe GARDNE d tes mellitus?— R, PA-C, continues to to recommend a circum upper tracts, the kidne CPAAPA, ys. develo cision It p recurr•ent 44 THE ADVISOR AUGUST 2015 •on Castleton, severaCLINICAL l consideration urinary tract the male child who As it currently stands N.Y. , SGLT2 s that infections. for glycemic impede the receptor blocke There are control in ability to cleansenter into this decisio rs are FDA adults with n. Poor hygien should the e and quell -approved child have e may appro diet and exercise, but with type 2 diabetes phimosis, simpl infection potential. appropriate the in ved conjun FDA for use in patien Moreover, AdvisorForum_CA0815.indd urine 44 9/29/15ction 2:38 PM e cathet culture can ts with type has stated that they ketoacidosi steroid cream be a challenge. erization to obtain s, or those are not may tempo an FAR with severe 1 diabetes, patients with Having a short tion of the rarily solve renal functi diabetic steroid the trial of informINDE, PhD, Pharm these issues tenden , though after for infection D (See bottom on.—ABIMBOL ation about once again.—C cy redevelops, placin cessaA Dr. Farinde.) of this page Milwaukee g (203-2) for more , Wis. (203- OLEEN ROSEN, the child at risk 1) DNP, FNP -C, CLI Philip R. Cohen, MD,

is clinicaltions associate professor , shou ld of dermatology, University a of Texas Medical Center, The focus of Houston.


Send us your letter Advisor Forum, The s with questions New York, and comm Clinical Advisor ents to: , 114 clinicaladvisoNY 10001. You may contacWest 26th Street , please If you are writing in t us by e-mail at 4th Floor, each item. e so by including response editor@ to a the Letters are policy is edited for number in parent published letter, to heses at length and contribution print the author ’s name with clarity. The Clinicathe end of s will be accepted. l Advisor the letter. No anonym ’s ous

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VAGINA L RESULT DISCHARGE AND ING FRO If a female M TAMPON ODOR patient has USE a ask if she uses tamp history of vaginal disch ons. If she the pelvic arge with says “yes,” exam when cond odor, that you woul , do not enter ucting the rotating of d to take a pap smea vagina in the same the specu way r. Instead, the cervix. lum Most retain from side to side start shallow until reach ed tampons ing are lodge d in the fold

Philip R.

Cohen, MD, is clinical associa te profess of dermat or ology, of Texas MedicaUniversity l Center, Houston.

SEND TO The Clinical Advisor 275 7th Avenue, 10th floor New York, NY 10001


Deborah L. Cross, MPH, ANP-B

CRNP, C, is associa te program director, Geronto logy NP Program University of Pennsyl vania School , of Nursing , Philadelphia.





MBER 2015

Abimbo la Farinde

, PhD,

is a profess PharmD, or at Columb ia Souther n Univers in Orange ity Beach, Ala.

• www.Clinic



Laura A.


practices familyCRNP, FNP, with Palmett medicine o Primary Care Physicia ns in Charles ton, S.C.

Abby A.


is a physicia n, PA-C, n at Delawa assistant re Dermatology Valley in Wilmington,Group Del.

.indd 62


2:44 PM




Newsline ■■Valvular heart disease: 2017 updated guideline from the American Heart Association and American College of Cardiology ■■Benign paroxysmal positional vertigo: a clinical practice guideline from the American Academy of Otolaryngology–Head and Neck Surgery foundation ■■Functional hypothalamic amenorrhea: a clinical guideline ■■Screening for celiac disease: A USPSTF recommendation statement ■■Dabigatran linked to fewer bleeding complications in patients with atrial fibrillation compared with warfarin ■■Septic shock: early, goal-directed therapy versus usual care

Benign paroxysmal positional vertigo 16


CME/CE Pharmacologic therapy


CME/CE Feature posttest


Web Roundup A summary of our most recent opinion, news articles, and multimedia content available at


Dermatology Clinic n A diffuse rash in a man with paraproteinemia n Discoloration in a postmenopausal woman’s breast


Dermatologic Look-Alikes Blister-like lesion on the finger in two elderly women


Developmental trauma disorder in children 26

Rheumatoid arthritis: diagnosis and treatment Early diagnosis and aggressive treatment are essential to mitigate the cascading events that lead to irreversible joint erosion in rheumatoid arthritis.

Continues on page 12

6 DTD: the effects of child abuse 2 and neglect Developmental trauma disorder, not yet officially recognized, results from child maltreatment and has many neurobiologic consequences.


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for obesity management Part 3 of a three-part series on issues regarding obesity management. As part of a multimodal treatment strategy, anti-obesity drugs can help patients achieve and maintain their weight-loss goals.

A patient not informed of his lab results 62

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Legal Advisor Lab results never given to a patient. An NP does not inform her patient about his lab results, which showed extensive kidney damage.


Alternative Meds Update Alfalfa. Long-term use has an immunestimulating effect and may worsen autoimmune conditions such as lupus.

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Consultations ■ Evidence-based practices for suicide prevention


Your Comments ■ The ACA: clinicians weigh in on whether to repeal or preserve ■ Being frank on frankincense and its role in cancer prevention

“On second thought, dear, Daddy thinks it might be best if you and Freddie eloped.”











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FDA approves first direct-to-consumer genetic health risk test The 23andMe test will provide information on an individual’s genetic predisposition to 10 diseases or conditions. Celiac disease is linked to a diagnosis of anorexia nervosa The researchers observed a bidirectional association between diagnosis of anorexia nervosa and celiac disease.

Sharon M. O’Brien, MPAS, PA-C Identifying parasomnias in the sleep cycle Parasomnias are undesirable physical or experiential events that occur during sleep as movements, emotions, perceptions, and dreams.

Vitamin D and calcium supplements may not lower cancer risk among postmenopausal women Vitamin D and calcium did not result in a significantly lower risk of all-type cancer in postmenopausal women.

Jillian Knowles, MPAS, PA-C Working with multiple attending physicians in the emergency department Physicians develop their own practice styles, which makes working with a large number of attending physicians one of the biggest difficulties of being an advanced practice provider.

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Canadian PAs: A new profession with new educational insight Canada’s educational training programs are some of the most innovative in the world and use techniques that promote the skills that future clinicians need. However, these healthcare professionals are still working toward successful integration into the healthcare system. Listen to the podcast here: NASEM report aims to eliminate hepatitis B and C by 2030 Aggressive testing, diagnosis, treatment, and prevention methods such as needle exchange are some of the options that the NASEM explored to target hepatitis elimination. Watch the video here:

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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 Learn more about diagnosing and treating these conditions, and see how you compare with your fellow colleagues.

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Which finding indicates cervical myelopathy? An 85-year-old man presents with severe right upper extremity pain. The pain is worse over the right scapula and posterior arm and seems to radiate to the ulnar side of the forearm. Conservative treatment with ice and nonsteroidal anti-inflammatory drugs has not provided relief. WHICH FINDING MARKS THE DIAGNOSIS?

• Positive Spurling test • Positive Hoffman test • Changes in bowel and bladder function • Hyporeflexia of the lower extremities ● See the full case at

Derm Dx A baby with a rash on the hands and feet A 3-month-old Hispanic male is brought to the office for evaluation of an itchy rash located on the hands and feet. The child is otherwise healthy. On physical examination, scattered flesh-colored papules and pustules, some with slight overlying scale, are noted on his palms and soles. CAN YOU DIAGNOSE THIS CONDITION?

• Syphilis • Incontinentia pigmenti • Infantile acropustulosis • Bullous impetigo ● See the full case at • THE CLINICAL ADVISOR • MAY 2017 15

Newsline M AY 2 0 1 7

Guideline: benign paroxysmal positional vertigo page 17

Functional hypothalamic amenorrhea page 17

Screening for celiac disease: evidence lacking page 18

THE AMERICAN HEART Association (AHA) and American College of Cardiology (ACC) have released a 2017 focused update to their 2014 Guideline for the Management of Patients with Valvular Heart Disease. The updated guideline, published in the Journal of the American College of Cardiology and in Circulation, includes recent advances in diagnostic imaging and improvements in catheter-based and surgical interventions. New and modif ied recommendations have been made regarding indications for antibiotic prophylaxis for infective endocarditis (IE), the use of direct oral anticoagulants (DOACs) in patients with atrial fibrillation and heart valve disease, indications for transcatheter aortic valve replacement (TAVR), surgical management of patients with primary and secondary mitral regurgitation (MR), and management of patients with a heart valve prosthesis. A summary of the key recommendations, provided by the ACC, includes the following: IE prophylaxis

• Antibiotic prophylaxis before dental procedures now is also recommended for patients with transcatheter prosthetic valves

and for patients with prosthetic material used in valve repair (including an annuloplasty ring or artificial chords) (Class IIa, Level of Evidence [LOE] C-LD). Anticoagulation for atrial fibrillation

• In patients with atrial fibrillation  and rheumatic mitral stenosis, anticoagulation with a vitamin K antagonist still is indicated (Class I, LOE B-NR). • Anticoagulation should be used among patients with atrial fibrillation and a CHA2DS2VASc score ≥2 in the setting of native aortic valve disease, tricuspid valve disease, or MR (Class I, LOE C-LD). • Use of a DOAC is reasonable in patients with native aortic valve disease, tricuspid valve disease, or MR; and atrial fibrillation with a CHA2DS2-VASc score ≥2 (Class IIa, LOE C-LD). Aortic stenosis

• The recommendation for either surgical AVR or TAVR among high-risk  patients with severe, symptomatic AS (stage D), after consideration by a heart valve team, was changed from Class IIa (LOE  B) to Class I (LOE A).



Valvular heart disease: an updated guideline from the AHA/ACC Updates • After consideration by a heart valve team, TAVR is a reasoninclude able alternative to surgical AVR recent for patients with severe, sympadvances in tomatic aortic stenosis (stage D) diagnostic and intermediate surgical risk imaging and (Class IIa, LOE B-R). improved surgical Primary MR intervention. • In asymptomatic patients with severe primary MR with preserved left ventricular (LV) systolic function (LV ejection fraction [LVEF] >60%, LV endsystolic dimension <40 mm [stage C1]), mitral valve surgery is reasonable in the setting of serial imaging studies that reveal a progressive increase in LV size or decrease in LVEF (Class IIa, LOE C-LD). Secondary MR

• The definition of severe secondary MR is now the same as for severe primary MR (­effective regurgitant orifice area ≥0.4 cm2, regurgitant volume ≥60 mL, regurgitant fraction ≥50%). u    For more detailed information about these recommendations, please see our expanded coverage at

New guideline for benign paroxysmal positional vertigo THE AMERICAN ACADEMY of O t ol a r y n g olog y – He a d and Neck Surgery foundation has released a clinical practice guideline for benign paroxysmal positional vertigo (BPPV). The revised guideline, an update to the previous guideline issued in 2008, is published in Otolaryngology– Head and Neck Surgery. The new recommendations emphasize diagnostic accuracy and efficiency, decreasing the inappropriate use of vestibular suppressant medications, decreasing the inappropriate use of ancillary testing, and increasing appropriate therapeutic repositioning maneuvers. The guidelines include the following recommendations: • Clinicians should diagnose posterior semicircular canal BPPV when vertigo associated with torsional, upbeating

Increasing appropriate therapeutic repositioning maneuvers is recommended by researchers.

nystagmus is provoked by the Dix-Hallpike maneuver. The maneuver should be performed by bringing the patient from an upright position to a supine position with the head turned 45 degrees to the side and the neck extended 20 degrees with the affected ear down. If the initial maneuver is negative, the

maneuver should be repeated with the opposite ear down. • Clinicians should perform a supine roll test to assess for lateral semicircular canal BPPV if the patient has a history compatible with BPPV and the Dix-Hallpike test exhibits horizontal or no nystagmus. • Clinicians should differentiate BPPV from other causes of imbalance, dizziness, and vertigo. • Clinicians should assess patients with BPPV for factors that modify management, such as impaired mobility or balance, central nervous system disorders, a lack of home support, and an increased risk for falling. • Clinicians should treat patients with posterior canal BPPV with a canalith repositioning procedure.

Functional hypothalamic amenorrhea: a clinical guideline more than 3 months should undergo diagnostic evaluation for FHA. • In patients with suspected FHA, pregnancy should be excluded and a full physical should be performed, including a gynecologic examination. • The following screening laboratory tests should be obtained in women or adolescents with suspected FHA: β-human chorionic gonadotropin, complete blood count, electrolytes, glucose, bicarbonate, blood urea nitrogen, creatinine, liver panel, and sedimentation rate or C-reactive protein levels.

Diagnosis of • The following laboratory tests should be obtained for the FHA should initial endocrine evaluation only be for patients with FHA: serum made after thyroid-stimulating hormone, excluding free thyroxine, prolactin, the anatomic luteinizing hormone, follicleor organic stimulating hormone, estradiol, pathology of and anti-Mullerian hormone. amenorrhea. • A progestin challenge should be administered in patients after excluding pregnancy to induce withdrawal bleeding and ensure integrity of outflow tract. • Patients should avoid oral contraceptive pills for the sole purpose of regaining menses or improving bone mineral density. • THE CLINICAL ADVISOR • MAY 2017 17


THE ENDOCRINE SOCIETY has released a clinical practice guideline for the diagnosis and treatment of patients with functional hypothalamic amenorrhea (FHA). The guideline has been published in the Journal of Clinical Endocrinology and Metabolism. A summary of the recommendations includes the following: • Clinicians should only make the diagnosis for FHA after excluding the anatomic or organic pathology of amenorrhea. • Adolescents and women whose menstrual cycle interval persistently exceeds 45 days or who present with amenorrhea for

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; or by mail to The Clinical Advisor, 275 7th Avenue, 10th Floor, New York, NY 10001.

Newsline EVIDENCE IS insufficient to assess the benefits and harms of screening for celiac disease in asymptomatic adults, adolescents, and children, according to a statement from the US Preventive Services Task Force (USPSTF) that was published in JAMA. The USPSTF evaluated the benefits and harms of screening vs not screening and targeted vs universal screening; and the benefits and harms of treatment of screen-detected celiac disease. The USPSTF found inadequate evidence on the effectiveness of screening for celiac disease in asymptomatic adults, adolescents, and children regarding morbidity, mortality, or quality of life. Potential harms of screening in asymptomatic populations include false-positive, inconclusive, or unnecessary serologic test results and biopsies, with possible anxiety or complications from testing. The USPSTF also found inadequate evidence on the effectiveness of treatment of screen-detected, asymptomatic celiac disease to improve morbidity, mortality, or quality of life compared with no treatment or treatment initiated after clinical diagnosis. Treatment studies in screendetected, asymptomatic persons are needed to understand the effects of adherence to a glutenfree diet  (compared with no dietary intervention), as well as the effects of immediate vs delayed dietary changes (ie, at the time of screen-detected diagnosis vs when symptoms develop).

Dabigatran vs warfarin in atrial fibrillation ANTICOAGULATION with uninterrupted dabigatran was associated with fewer bleeding complications compared with uninterrupted warfarin among patients undergoing ablation for atrial fibrillation, according to a study published in the New England Journal of Medicine. Hugh Calkins, MD, from Johns Hopkins Medical Institutions in Baltimore, and colleagues investigated the safety of uninterrupted dabigatran compared with warfarin in 635 patients undergoing paroxysmal or persistent ablation of atrial fibrillation across 104 sites. The patients were randomly assigned to receive either dabigatran 150 mg twice daily or warfarin (target international normalized ratio 2.0 to 3.0). Patients underwent ablation after 4 to 8 weeks

Dabigatran is associated with fewer bleeding events than warfarin.

of uninterrupted anticoagulation, which was continued during and for 8 weeks after ablation. Researchers measured the incidence of major bleeding events during and up to 8 weeks after ablation as the primary end point. Secondary end points included thromboembolic and other bleeding events. The rate of major bleeding events during ablation and up to 8 weeks afterward was lower with dabigatran compared with warfarin (1.6% vs 6.9%; absolute risk difference, –5.3 percentage points). Dabigatran was also associated with fewer periprocedural pericardial tamponades and groin hematoma compared with warfarin. Both treatment groups had a similar rate of minor bleeding events, and 1 thromboembolic event occurred in the warfarin group.

Septic shock: comparing EGDT with usual care EARLY, GOAL-DIRECTED therapy (EGDT) did not result in better outcomes than usual care for patients undergoing septic shock and was associated with higher hospitalization costs, according to a study published in the New England Journal of Medicine. Investigators from three multicenter trials conducted a meta-analysis of individual patient data from each trial to determine the effect of EGDT vs usual care on 90-day mortality and secondary clinical end economic outcomes. From March 2008 through July 2014, the three trials enrolled 4211 patients at 138 international hospitals. A total of 3723 patients (98.9%) were included in the primary analysis, and 3511 (93.3%) were


followed up to 1 year. Mortality at 90 days did not differ significantly between the two groups. Death occurred in 462 of 1852 patients (24.9%) in the EGDT group and in 475 of 1871 (25.4%) in the usual-care group. Duration of stay in the intensive care unit and receipt of cardiovascular support were greater in the EGDT group than in the usual-care group. Duration of stay in the emergency department was shorter in the EGDT group than in the usual-care group in the ARISE trial but not in the ProCESS or ProMISE trials. Subgroup analyses showed no benefit from EGDT for patients with worse shock or for hospitals with a lower propensity to use vasopressors or fluids during usual resuscitation. n


Screening for celiac disease


Rheumatoid arthritis: diagnosis and treatment Early diagnosis and aggressive treatment are essential to mitigate the cascading events that lead to irreversible joint erosion in rheumatoid arthritis.


Computer-enhanced X-ray of severe rheumatoid arthritis in a patient’s hand.


heumatoid arthritis (RA) is a chronic and debilitating autoimmune disease that affects the joints, and lives, of more than 1.5 million Americans, or 1 in every 100. The lubricating synovium, which is the tissue that lines the joints, becomes inflamed and thickened when attacked by the immune system, so that painful swelling develops around the joints. This inflammatory process damages the cartilage and erodes the joint spaces between bones, leading to unstable, immobile, deformed, and painful joints.1 The joint destruction of RA is a cascading event, in which pannus, hyperplastic synovial tissue, and cartilage erosion result in subchondral bone, articular capsule, tendon, and ligament damage.2 The joint erosion is irreversible; therefore, early diagnosis and aggressive initial treatment are imperative. This article discusses the most prevalent risk factors, as well as the clinical signs and symptoms, associated with RA. Current treatment modalities for and the prognosis of patients with RA are also discussed. Epidemiology and etiology

RA is a chronic condition with no known specific cause; however, gender, heredity, genetics, and initiating factors are known risk determinants.3 RA is three times more likely to affect women than men. The peak age at onset in women is in the fourth to fifth decades; in men, the prevalence increases in the sixth to eighth decades. Although RA is not hereditary, certain genetic features can affect the risk for the development of • THE CLINICAL ADVISOR • MAY 2017 19


Early symptoms of rheumatoid arthritis include fatigue, muscle pain, low-grade fever, weight loss, and numbness and tingling in the hands.


this disease. Research indicates that the presence of rheumatoid factor (RF) in healthy individuals is of a greater significance than was initially understood, as the presence of both immunoglobulin M (IgM) and IgA RF is associated with a seven‐fold risk for seropositive RA.4 Moreover, it has been found that people with specific variants of the human leukocyte antigen (HLA) genes are at higher risk for the development of RA. Today, the best-known genetic risk factor for RA is inheritance of certain HLA-DRB1 alleles, which encode a “shared epitope” that is detected as a distinguishing five-amino-acid sequence.5 Although the presence of the HLA-DRB1 alleles is not a specific indicator of disease, certain factors can enhance an individual’s susceptibility to the development of RA. These include infection, cigarette smoking, and stress, which are all very common in today’s society. Bacterial infections, primarily those involving the mouth and/or gut, are environmental factors hypothesized to increase the risk for RA.6 However, the most significant environmental risk factor for RA is smoking.7 In a Finnish population study, it was found that elevated RF levels were found twice as often in both current and former smokers as in nonsmokers; moreover, the proportion of smokers increased among those persons with higher RF titers.6 Other studies have also demonstrated an association between RF production and frequent cigarette smoking. Even if cigarette smoking is discontinued, once it has induced RF production, the process is irreversible.8 Stress can also exacerbate RA; research indicates that the onset of RA is often preceded by traumatic and/or stressful lifetime events.3

Swan neck deformities in the fingers of an elderly woman with rheumatoid arthritis.

Furthermore, painful flare-ups of RA have been linked to exacerbations of stress. Stress management should be a critical component of the RA treatment plan, as living with a “painful, chronic, and somewhat unpredictable disease can be a significant source of stress in itself.”9 History and clinical presentation

Before the symptoms of RA become bothersome enough to cause someone to seek medical attention, early symptoms of RA, such as fatigue, muscle pain, low-grade fever, weight loss, and numbness and tingling in the hands, are often present.3 RA is described to have an “insidious” onset characterized by morning stiffness and a vague, prodromal pain in the affected joints. Morning stiffness characteristically lasts longer than 30 minutes. RA presents most commonly as a symmetric polyarthritis affecting both small and large joints but particularly, the small joints of the hands and feet.5 The peripheral joints, especially the diarthrodial joints, are most commonly affected. The diarthrodial joints are lined with inflamed synovial membrane, and their bony surfaces are surrounded by hyaline cartilage. In RA, the diarthrodial joints most often involved are the proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints of the fingers; the wrists, knees, and ankles; and the metatarsophalangeal (MTP) joints of the toes. The pathologic processes causing the red, inflamed, and dysmorphic joints observed on physical examination include synovial membrane proliferation, angiogenesis, endothelial cell activation, chemotactic stimuli, and the production of proinflammatory cytokines.6 The joint symptoms of RA typically are gradual in onset and include pain, stiffness, redness, warmth to the touch, and swelling. When the hands are assessed during physical examination, grip strength is often noted to be reduced.3 Two distinguishing features of long-standing RA are “swan neck” deformities and boutonniere deformities of the fingers (Figure 1).3 Swan neck deformities develop with hyperextension of the PIP joint and flexion of the distal interphalangeal (DIP) joint, whereas boutonniere deformities develop with flexion of the PIP joint and hyperextension of the DIP joint.12 A bowstring sign, which is the presence of prominent and tight tendons on the dorsum side of the hand, may also be evident on physical examination. The wrist is the arm joint that is most commonly affected by RA. Difficulty bending the wrist backward is an early


A distinguishing feature of rheumatoid arthritis is that although the disease can affect the neck, it does not involve other areas of the spine. indicator of the disease, and movement requiring manipulation of the wrist is often arduous for patients with RA. Swelling of the elbow joint is also seen in RA; this can cause a tingling sensation running up the arm as a result of compression of the ulnar nerve. A limited range of motion in the shoulder may be noted on physical examination in the later stages of RA. In the lower extremities, the bases of the toes are commonly affected at the onset of RA. Having a patient stand on his or her toes will elicit pain; moreover, the plantar surface of the foot may appear swollen and erythematous. Swelling and difficulty flexing the knee may also be evident on examination. Baker’s cysts are frequently observed in patients with RA. In progressive and late cases, RA may involve the hips, causing walking to be both painful and difficult. Although not extremely common, involvement of the cervical spine may cause inflammation between the shoulders and base of the head, resulting in a painful and stiff neck along with limited range of motion. Lastly, and perhaps most interestingly, the cricoarytenoid joint is involved in the RA process in 30% of patients. Because this joint is situated near the windpipe, the inflammation can cause difficulty breathing and hoarseness.3 Risks to articular structures in RA are tendon rupture and the formation of synovial cysts. Moreover, median nerve entrapment in the carpal tunnel is commonly seen. A distinguishing feature of RA is that although the disease can affect the neck, it does not involve other areas of the spine, as occurs in other forms of inflammatory arthritis. Another distinguishing examination finding is the presence of subcutaneous rheumatoid nodules, which are found in 20% of patients with RA. These nodules are most often seen over bony prominences; however, they can develop in the lungs, sclerae, and other tissues unrelated to joints. The RA nodules mirror the laboratory findings, as they are related to the presence of RF in serum.5 RA is more than a disease of the joints; it is known to cause problems in many other systems. Sjögren syndrome, characterized by dryness of the eyes, mouth, and mucous membranes, is observed in advanced RA. Scleral nodules can cause other ocular conditions, such as episcleritis, scleritis, and scleromalacia. Cough and progressive dyspnea on examination often indicate the presence of interstitial lung disease in patients with RA. Pericarditis and pleural disease are other comorbidities occasionally seen in RA. It is not uncommon to note mild vasculitis appearing as small hemorrhagic infarcts in the nail folds or finger pulp of patients

with RA.4 The current criteria for a diagnosis of RA are presented in Table 1. A score higher than 6 in a possible total of 10 indicates an RA diagnosis.12 Laboratory workup

From 70% to 80% of patients with established RA have serologic titers of anti-cyclic citrullinated peptide (CCP) antibody and RF, which is an IgM antibody that antagonizes the Fc fragment of IgG. RF has a sensitivity of 50% for the detection of RA; anti-CCP antibodies are 95% specific for the disease, and anti-CCP measurement is therefore the most specific blood test for RA. Determining the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level in patients with suspected RA is also an integral component of the laboratory workup. The degree of elevation of both these markers tends to mirror the extent of RA pathology in the body.5 Antinuclear antibody (ANA) measurement, complete blood cell (CBC) count, platelet count, serum uric acid measurement, and HLA tissue testing aid in the differential diagnosis of RA and distinguish it from other arthritic and immunologic pathologies. Leukocytosis (white blood cell [WBC] count >11,000/μL) and thrombocytosis (platelet count ≥450 × 109/L) Continues on page 24

TABLE 1. American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) criteria for the diagnosis of rheumatoid arthritis Parameter



Joint involvement

1 large joint 2-10 large joints 1-3 small joints 4-10 small joints >10 joints (at least 1 small joint)

0 1 2 3 5


Negativity for RF and anti-CCP Low level of RF or anti-CCP High level of RF or anti-CCP

0 2 3

Acute-phase reactants

Normal CRP level and ESR Abnormal CRP level or ESR

0 1

Duration of symptoms

<6 wk ≥6 wk

0 1

CCP = cyclic citrullinated peptide; CRP = C-reactive protein; ESR = erythrocyte sedimentation rate; RF = rheumatoid factor; wk = week. *A total score of more than 6 indicates a diagnosis of rheumatoid arthritis. • THE CLINICAL ADVISOR • MAY 2017 21



Which of the following do you most frequently prescribe for patients with rheumatoid arthritis? n = 409

■ Methotrexate ■ TNF inhibitors ■ Abatacept, rituximab, or tocilizumab


8.56% 8.31%

For more polls, visit

are commonly noted in the CBC count.13 Iron levels should be monitored because a moderate hypochromic normocytic anemia is commonly seen in RA. The joint fluid should be assessed to quantify inflammation and rule out gout or septic arthritis. Whereas osteoarthritic joint fluid typically appears yellow, RA joint fluid tends to be more yellow to opalescent, with a higher WBC count and platelet count than osteoarthritic joint fluid.2 Arthrocentesis is a needed diagnostic measure to rule out septic arthritis, a severe complication of RA. Clinicians should suspect septic arthritis when one joint is significantly more inflamed than other problematic joints.5 Radiographic changes are the most specific diagnostic measure for RA and are therefore of the utmost importance. Although little radiologic change is observed in the first 6 months after onset, initial changes are noted in the hands and feet as the soft tissue swells and juxta-articular demineralization occurs. As the disease progresses, decreased joint spaces and erosive processes become evident. The ulnar styloid and juxta-articular margins are the loci where bone erosion is often first identified on radiographs. Although magnetic resonance imaging and ultrasonography are more sensitive than radiography, the value of these modalities in the diagnosis of early RA has yet to be determined in comparison with plain film.5 Treatment options

If RA is suspected, the patient should promptly be referred to a rheumatologist for diagnosis, treatment initiation, and the development of a long-term strategy. Treatment should be initiated as soon as a diagnosis has been established to diminish pain, preserve joint function, and avoid future/further deformity. Besides pharmacologic treatment, the patient should be referred to physical and occupational therapy for holistic benefit.2

Disease-modifying antirheumatic drugs (DMARDs) are the established initial treatment for RA. This pharmacologic class has been shown to have a suppressive effect on disease activity. The DMARD of choice is methotrexate (MTX). Positive effects usually are noticed between the second and sixth weeks after treatment initiation. The initial prescribed dose is 7.5 mg, administered orally once weekly. If no notable difference occurs in the first month of MTX treatment, the dose can be increased to 15 mg once weekly; however, the dose should not exceed 20 to 25 mg/wk. Common MTX side effects include stomach irritation and gastritis. Patients with liver disease should not take MTX because it is known to cause hepatotoxicity with fibrosis and cirrhosis. MTX is a category X medication; therefore, women who are pregnant or wish to become pregnant are not candidates for this treatment option. Monitoring liver function as well as the WBC and platelet counts is an important aspect of prescribing MTX. Other prescribed DMARDs for the treatment of RA include sulfasalazine, leflunomide, antimalarial agents (hydroxychloroquine), minocycline, and tofacitinib. In addition to these synthetic DMARDs mentioned above, biologic DMARDs are another treatment option for patients with RA. Drugs in this class include abatacept, rituximab, tocilizumab, and the tumor necrosis factor (TNF) inhibitors. TNF inhibitors are pro-inflammatory cytokines often administered to patients whose disease does not respond appropriately to MTX, or to patients with severe disease. The following TNF inhibitors are administered as subcutaneous injections: etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol. The ideal treatment regimen for patients with RA consists of a combination of MTX and a TNF inhibitor. It is well documented that a combination of the two drugs is superior to the use of either drug alone.5 For those who cannot tolerate TNF inhibitors, DMARD triple drug therapy, with MTX, sulfasalzine, and hydroychloroquine, has shown to be efficacious.11 Although nonsteroidal anti-inflammatory drugs (NSAIDs) relieve pain and reduce inflammation, they do not alter disease progression, nor do they serve to prevent erosive processes. Unfortunately, NSAIDs cannot be used as monotherapy or in conjunction with DMARDs, so their role in the treatment of RA is limited. Low-dose corticosteroids are another treatment option for patients with RA because they have been shown to prevent disease progression and to provide anti-inflammatory effects. Commonly, corticosteroids are used as an adjunct to DMARDs, reducing disease activity until the DMARDs have reached peak performance. However, corticosteroid treatment is of limited use in the long-term treatment of RA


because prolonged steroid use is not advised. A taper should be implemented when corticosteroids are discontinued. If one or two joints are particularly bothersome to the patient, intraarticular corticosteroid injections are beneficial in offering symptomatic relief; however, the injections can be given only four times each year and therefore should be used sparingly.5

5. Papadakis M, McPhee S, Rabow M. Current Medical Diagnosis and Treatment 2015. 54th ed. New York, NY: McGraw-Hill Education; 2015. 6. Cush J, Weinblatt M, Kavanaugh A. Rheumatoid Arthritis: Early Diagnosis and Treatment. West Islip, NY: Professional Communications; 2010. 7. Masdottir B, Jonsson T, Manfredsdottir V, Vikingsson A, Brekkan A, Valdimarsson H. Smoking, rheumatoid factor isotypes and severity of rheumatoid arthritis. Rheumatology. 2000;39:1202-1205.


8. Hutchinson D, Moots R. Cigarette smoking and severity of rheumatoid

The outcomes of RA are variable and include remission, fluctuating disease, and progressively worsening disease. A well-documented study regarding the debilitation of RA indicates that 20% to 30% of patients diagnosed with the disease qualify for work disability 2 to 3 years from disease onset. In addition, 15 years from disease onset, 67% of patients are disabled.10 Complete disease remission has been documented but is rare. However, disease remission commonly occurs during pregnancy, though more than 90% of women experience increased arthritic symptoms 3 months postpartum.3 Early pharmacologic treatment greatly improves patients’ quality of life, because certain drugs can arrest joint damage and relieve the signs and symptoms of RA.5 If left untreated, RA can shorten life expectancy. So early, consistent treatment as the standard of care is essential. Studies indicate that the high mortality rates observed in patients with RA are due mainly to cardiovascular disease.5 The management of risk factors with smoking cessation, blood pressure control, a healthy diet, and stress management is paramount in decreasing the prevalence of cardiovascular disease in patients with RA. n

arthritis. Rheumatology. 2001;4:1426-1427. 9. Evers AWM, Kraaimaat FW, Geenen R, Bijlsma JWJ. Determinants of psychological distress and its course in the first year after diagnosis in rheumatoid arthritis patients. J Behav Med. 1997;20:489-504. 10. Sokka T, Kautiainen H, Mottonen T, Hannonen P. Work disability in rheumatoid arthritis 10 years after the diagnosis. J Rheumatol. 1999;26(8):1681–1685. 11. Upchurch KS, Kay J. Evolution of treatment for rheumatoid arthritis. Rheumatology (Oxford). 2012;51(suppl 6):vi28-vi36. doi: 10.1093/ rheumatology/kes278 12. Steinberg DR. Swan-neck deformity. Merck Manual Professional Version. Updated November 2016. Accessed March 27, 2017. 13. Wilder ML, Ebert CC, Clifford CE. Topic review: diagnostic work-up of early rheumatoid arthritis in the foot and ankle patient. Foot Ankle. 2014;7(1):6. Accessed March 27, 2017.

Emily Parker, PA-C, is a physician assistant specializing in general and plastic surgery in Columbia, South Carolina, and Alicia Elam, PharmD, is associate admissions director, Physician Assistant Department, Augusta University, Georgia. References 1. Arthritis Foundation. What is rheumatoid arthritis? http://www.arthritis. org/about-arthritis/types/rheumatoid-arthritis/what-is-rheumatoid-arthritis.php. Accessed March 27, 2017. 2. O’Connell CB. A Comprehensive Review for the Certification and Recertification Examinations for Physician Assistants. 5th ed. Q&A Review for PANCE and PANRE Powered by prepU. Philadelphia, PA: Wolters Kluwer; 2015. symptoms and diagnosis (beyond the basics). UpToDate. Updated March 23, 2017. Accessed March 27, 2017. 4. Halldorsdottir HD, Jonsson T, Thorsteinsson J, Valdimarsson H. A prospective study on the incidence of rheumatoid arthritis among people with persistent increase of rheumatoid factor. Ann Rheum Dis. 2000;59:149-151. • THE CLINICAL ADVISOR • MAY 2017 25

© Harley Schwadron, 2017

3. Maini RN, Venables PJW. Patient information: rheumatoid arthritis


DTD: the effects of child abuse and neglect Developmental trauma disorder, not yet officially recognized, results from child maltreatment and has many neurobiologic consequences.



Child neglect and abuse is a significant community health challenge.


hild neglect and abuse are perhaps the most significant community health challenge in the United States.1 Mental health experts in trauma continue to investigate and apply a condition known as developmental trauma disorder (DTD), which is characterized by permanent changes in the neurobiologic system of children and adolescents who have been chronically exposed to various types of maltreatment during sensitive periods of childhood development.1 It is believed that a specific criterion is urgently needed to improve recognition of the unique profi le DTD victims encompass and to avoid misdiagnosis or confusion with other psychological syndromes, such as posttraumatic stress disorder (PTSD).1 In addition, the effects of DTD continue in adulthood and tend to correlate with multiple health problems.1 Medical providers may consider DTD an underlying cause of several conditions, including depression, anxiety, attention-deficit disorder (ADD), borderline personality disorder (BPD), chronic pain or fatigue, various addictions, and eating disorders.1 During clinical assessment, identifying a history of childhood trauma may broaden therapeutic choices and improve patient outcomes. This article describes some of the neurobiologic consequences of DTD, including cognitive, emotional, social, and somatic manifestations. Common treatment modalities for DTD are discussed, including reasons to support or oppose DTD as an official diagnosis in the Diagnostic and Statistical Manual of Mental Disorders (DSM).

Child maltreatment statistics

The National Child Abuse and Neglect Data System (NCANDS) is a federally supported organization that analyzes and records statistical data regarding claims of child maltreatment.2 For calculation purposes, duplicate counts indicate the frequency a child is deemed a victim of abuse, and unique counts represent one incident of abuse, despite the number of times a child was officially reported as maltreated.2 In 2014, the NCANDS revealed that from a population of 6.6 million children, approximately 3.6 million cases of alleged child maltreatment were referred to child protection services (CPS).2 Among 3.9 million reports considered as duplicate counts, a total of 2.1 million cases warranted CPS involvement.2 An additional 3.2 million reports assessed as unique counts also warranted further CPS investigation.2 A final analysis from these reviews concluded 702,000 children were considered victims of maltreatment. The alarming findings revealed millions of potential child maltreatment reports requiring social service’s attention. In the majority of cases, maltreatment consisted of neglect (75.0%) and physical abuse (17.0%), occurring predominantly in children from birth to 1 year.2 Victim gender rates included females (50.6%) and males (48.9%). Racial frequency comprising more than 88% of reported victims involved Caucasians (44.0%), African Americans (21.4%), and Hispanics (22.7%).2 It was further estimated that 98.9% of child maltreatment acts are committed by a main caregiver; 54.1% of the perpetrators are women and 44.8% are men, and the average age of offenders is 18 to 44 years.2 Most complaints of maltreatment were reported by a professional (62.7%), such as a legal associate, or academic and social service employees.2 The national mortality rates occurring from 2010 to 2014 are shown in Table 12 and only involve children who died as a result of maltreatment committed by a parent (79.3%) or other major caregiver.3 Sadly, the latest victim fatality figures equated that more than four children die every day as the result of mainly neglect and/or physical abuse, or in

conjunction with another type of maltreatment.3 The most vulnerable groups are children aged 4 years or younger, with 70.7% of deaths occurring in children aged younger than 3 years.3 A breakdown of ethnicity rates reveals that 88.4% of total deaths were Caucasian (43.0%), African American (30.3%), and Hispanic (15.1%).2 In addition, a shocking study regarding childhood mortality suggests that “50% of deaths reported as “unintentional injury deaths” are reclassified after further investigation by medical and forensic experts as deaths due to maltreatment.”3 It is certainly worth noting that only a fraction of child maltreatment cases and related deaths are referred to CPS, indicating formal statistics do not identify the other countless instances of neglect and abuse, or the inappropriate dismissal of child maltreatment by a social worker, healthcare provider, family member, or other bystander. Children are often unable to report mistreatment for many causes, such as insufficient language capability, self-blame, feelings of guilt, and/or fear of retribution from the perpetrator. For these, and many other reasons, child neglect and abuse can be considered a serious and silent epidemic.1 What is developmental trauma disorder?

Bessel van der Kolk, MD,1 and colleagues are pioneers in developing DTD philosophy and diagnostic criteria, and they have shared their knowledge globally with the intent to improve the identification, treatment, and prognosis for children who have suffered traumatic experience. Van der Kolk describes DTD as a distinct condition affecting children, adolescents, and adults who have been repeatedly subjected to various forms of childhood maltreatment, including neglect and/or physical, emotional, and sexual abuse, during specific periods of their neurophysiological development.1 Child maltreatment is particularly traumatizing if it was committed by a significant caretaker, such as a parent.4 Other causes of DTD include witnessing acts of violence, permanent loss of an essential caregiver, institutionalization,

TABLE 1. National rates of fatality from child maltreatment: 2010-20143 Year

Reporting states

Child population

Child fatalities

Fatality rate per 100,000

National child population

Estimate of child fatalities



































1,580 • THE CLINICAL ADVISOR • MAY 2017 27


Due to a lack of self-protection and unable to escape their plight, traumatized children develop other defenses, or maladaptive personalities. and experiencing inconsistent custodians, such as multiple and abusive foster parents.1 Among other numerous examples, exposure to poverty, serious illness, multiple surgeries, warfare, or a life-threatening natural disaster or motor vehicle accident can traumatize a child’s psyche.1 Van der Kolk has proposed that DTD is manifested in various ways that negatively affects a victim’s capacity to relate to oneself and others.1 The following sections address some of the adverse consequences of DTD, including impaired cognitive, emotional, and social functioning, and common somatic symptoms. Cognitive, emotional, social, and somatic effects

Children are critically dependent on the quality of their relationship with caregivers for normal development, and when they are repetitively traumatized, their psyche becomes damaged.1 They naturally internalize a caregiver’s facial expressions, emotions, and actions that serve as a “mirror” reflecting to a child his or her personal worth and identity. If caretakers are deficient or inconsistent in areas of sensitivity and emotion, or if they are violent or negligent, children endure tremendous stress. This stress is often exhibited in victims as persistent psychological states of hyper-arousal, nervousness, and agitation, and/or hypo-arousal or feeling emotionally numb.1,4 Dissociation or tainted consciousness is a characteristic defense mechanism and survival skill that DTD victims use to escape overwhelming emotion and the impact of abuse.1,4 Dissociation includes “thought suppression, minimization, and outright denial.”5 Depersonalization or feeling disengaged from oneself and the world are other described symptoms of dissociation.4,5 As a result, children learn to ignore their authentic emotions, while missing important opportunities to develop the capacity for introspection and self-managing abilities.1,6 They also learn not to trust their thoughts and feelings, causing self-perception and discernment of others to be confusing or distorted.1,6 Due to a lack of self-protection and unable to escape their plight, traumatized children develop other defenses, or maladaptive personalities, described as fight, flight, freeze, and fawn types (4-Fs).6 Fight responders possess a considerable need to control their environment, are typically disruptive or argumentative, and may display violent or aggressive behavior toward others, such as bullying.1,6 Flight personalities will flee or avoid their chaotic life, as seen in children who run

away from home, become overactive, develop a compulsive or obsessive nature, or strive for perfectionism.1,6 Freeze types isolate themselves, engaging in dissociative activities such as excessive sleeping or constant use of the television or computer.1,6 Fawn responders are considered submissively co-dependent, sacrificing self-identity and healthy personal boundaries to sustain relationships or avoid rejection.6 Behaviors resulting from the 4-Fs often unjustifiably cause a child to be characterized as difficult, disobedient, rebellious, withdrawn, lazy, shy, or hyperactive.1,6 Within a traumatized and defenseless environment, the 4-Fs may be used interchangeably and serve as a child’s primary coping skills, while causing intellectual, social, sensory, and/or motor developmental delay or arrest.1,6 In an attempt to avoid abuse, children become hypervigilant of their surroundings, which further creates anxiety and tension.1,6 When caregivers are unable to provide a predictable and safe environment for their children, or offer relief to their stress, victims develop a limited capacity for emotional self-regulation and impulse control, their ability to experience healthy interpersonal bonds is restricted, and the process of learning from experience becomes fragmented and indistinct.1 These consequences are the primary origins of DTD.1 Other reactions to interpersonal trauma include high-risk and self-destructive behaviors, emotional instability, attention deficit, depression, and eating disorders.1 Deficient school or work performance, a proneness to accidents, and decreased sensitivity to pain are other signs of childhood trauma.1,7 Unexplained and persistent backache, abdominal or pelvic pain, headache, and insomnia are frequent somaticrelated symptoms,4,6-7 and these may alert a health provider to identify a psycho-traumatic cause. Ultimately, many perpetrators consistently induce intense emotions within their victims, including fear, humiliation, and unnecessary remorse resulting in poor self-esteem, or self-hatred. Above all, these children learn not to rely on themselves and others and lack a broader interpretation of life apart from their trauma-induced version. As a result, victims may develop a host of physical and psychological impairments affecting their health and ability to interact successfully with themselves and others.1,6,8 Neurobiologic system effects

Scientific research has provided considerable evidence involving the destructive effects of chronic child maltreatment that


The hippocampus is susceptible to atrophy or lesser development when glucocorticoid levels are elevated in response to traumatic experience. permanently alter brain maturation and interfere with its normal structural formation and function.9,11 These damaging consequences influence the capacity to regulate cognition, emotion, and behavior.10 There are four essential and vulnerable stages in brain development: early childhood (15 months-4 years), late childhood (6-10 years), puberty, and adolescence.10 Any significant or prolonged environmental disruption that occurs during these stages will ultimately produce harmful neurobiologic results. A brief summary regarding some of the features of cerebral development includes neurogenesis, which involves the proliferation of several neural networks that provide pathways for processing information and occurs mainly in utero, with not much further development after birth.11 Neurons initially migrate to the brainstem, or lower brain, then to the cortex, or higher brain.11 This migration occurs in utero, during the perinatal period, throughout childhood, and possibly into adulthood.11 Arborization is the process of dendrite formation that assists neural activity.11 The degree of dendrite density is related to the amount and type of external input children receive while their brains are programmed to incorporate or assimilate complex stimuli.11 During synaptogenesis, the evolving neurons form axons and synapses, which enhance brain function and determine how vast the brain organizes and utilizes information.11 Differentiation involves the production of several neurotransmitters, such as dopamine, norepinephrine, serotonin, corticotropin-releasing factor, and substance P, which are released in response to stress and other emotions.10,11 The levels of these neurochemicals fluctuate widely in children reacting to a traumatic environment, affecting the neurobiologic system. In addition, response to stress affects the levels of many hormones, such as adrenalin and glucocorticoids—specifically cortisol, which is typically elevated in trauma victims.10 Consequently, the erratic production of neurochemicals and hormones may increase heart rate and gastrointestinal activity, induce chronic depression and/or anxiety, or cause immunodeficiency disease, to name only a few effects, while impairing or damaging the neuroendocrine system and various anatomical structures.10,11 A newborn’s external experience promotes “neural differentiation, arborization, and synaptogenesis,” helping to “create functional neural networks.”11 Within the first 8 months of life, synaptic density increases eightfold as neurons form proper connections, indicating that a neurobiologic susceptibility to trauma is enhanced during the first

year of life.11 Stimulation of the developing brain induces neural activity and the formation of synaptic connections. When external stimuli is overly stressful, negative, or sparse, as with neglected or abused children, neurons die, and their correct placement fails and/or are displayed in a disorderly fashion (Figure 1),12 while hyper-synaptic activity occurs.10,11 Among several essential parts of the brain, the prefrontal cortex is responsible for developing memory, controlling impulses, and allows one to learn from negative experience.10 These specific cortical functions are compromised in traumatized children who experienced elevated norepinephrine levels, due to chronic hyper-arousal states.10 In addition to decreased brain volume, a history of childhood trauma may cause deficient growth within areas of the limbic system involving the hippocampus and amygdala, also known as the “emotional brain” ( uploads/2014/01/Perry_Psychopathology_Chapter_08.pdf ).10-11 The hippocampus is susceptible to atrophy or lesser development when glucocorticoid levels are elevated in response to traumatic experience. Injury to this subcortical structure compromises the ability to control emotion and the capacity for cognitive or verbal memory.10,11 The amygdala begins Continues on page 33

Typical neuron— many connections


Damaged neuron— fewer connections

Toxic stress

Prefrontal cortex and hippocampus

FIGURE 1. Brains subjected to toxic stress have underdeveloped or fewer neural connections in areas of the brain most important for successful learning and behavior in school and the workplace.12 • THE CLINICAL ADVISOR • MAY 2017 29

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Any considerable disturbance that occurs during neurologic development, such as high levels of stress, will have a profound effect in the brain. to function at birth and permits an infant to sense danger, inducing the release of cortisol and adrenalin, and the ensuing fight-or-flight response.10 As a result of a traumatized upbringing, increased or persistent activation of the amygdala occurs, causing victims to miscalculate the severity of a dangerous situation or person.10 This eventually produces a general unrealistic interpretation of a victim’s environment and perceptions of oneself and others.6,10 Further explanation regarding a victim’s altered self-misconception and of his or her surroundings, is the occurrence of flashbacks, which are conscious or unconscious recollections of abuse triggered by internal or external stimuli involving “affect, vision, tactile, taste, smell, auditory, and motor systems.”9 During a flashback, victims inaccurately respond to emotions, situations, and others due to their distorted insights that confuse past trauma with present experience.1,6,9 Other compromised states of cognizance include an inability to read social cues, memory loss, hypermnesia (atypical vivid memory), and trauma-related nightmares.1 Affect attunement is the bond between a child and his or her primary caregiver and is crucial for healthy neurobiologic development.10 It plays a critical role in helping a child learn to regulate emotion, behavior, and affect, and it determines the ability to control reactions to stress.9,10 Parental attachments are considered a gateway into a child’s inner self and character formation—the “more disorganized the parent, the more disorganized the child.”10 When these bonds are deficient, dangerous, or overwhelming, a child enters a world of irrational and inflexible responses to nominal tension and circumstances.9 In addition, fragmented relations with caregivers compromise a child’s abstract reasoning, visual-spatial skills, attention or concentration abilities, and capacity for verbal learning.1 Any considerable disturbance that occurs during neurologic development, such as abuse, neglect, or high levels of stress or violence, will have a profound effect in the brain and lead to various types of psychopathology.11 Primarily, a child’s stage of development at the time of victimization, the degree and nature of the maltreatment, and whether the abuser is an essential caretaker are significantly correlated with the extent of cerebral injury or compromise.4,10,11 Overall, the neurobiologic impact of DTD appears to extensively interfere with a child’s cognitive, emotional, and sensory development and performance that generally continues into adulthood.

Developmental trauma disorder in adults

Adult victims who were subjected to years of abuse and betrayal as children, and who believed important caretakers could not be trusted, often remain guarded as adults. Some of the most significant consequences of DTD in adults are inner conflict regarding emotional self-regulation and an inability to develop and maintain healthy interpersonal relationships.9 The aftereffects of childhood maltreatment are thought to be the result of an unconscious compulsion to preserve or resolve past trauma.6,9,13 The 4-F survival skills are expressed inappropriately as a consequence of imprinted trauma experiences and habitual reactions within the brain, or from vague or repressed memories of trauma.1,6,13 A psychologically ingrained cycle of abuse continues long after a victim is free from his or her original abuser(s). According to van der Kolk, “In behavioral re-enactment of the trauma, the self may play the role of either victim or victimizer.”13 Examples of trauma re-enactment include enduring domestic violence or dysfunctional relationships, consistent feelings of helplessness or possessing a dependent personality, drug or alcohol addiction, suicide, chronic pain and fatigue, depression, anxiety, and panic or phobic disorders.1,7,9,13 Among sex offenders, 75% report a history of childhood incest or sexual assault.1 This particular type of trauma is a major reason why victims engage in prostitution or pornography, both of which serve to perpetuate past abuse.12 Unfortunately, many mimic the offender’s destructive conduct, engaging in illegal activity or violent behavior and crimes, encompassing the majority of inmates residing in our prison and juvenile detention systems today.1,7,10,13 In addition to victims reenacting their abuse, they have an urgent need to avoid it; this coupled with their societal mistrust, causes the emotional and physical isolation that many DTD victims endure.1 One of the largest research analyses regarding the frequency of childhood trauma and its effects in adults is the Adverse Childhood Experiences (ACE).14 The ACE study was led by Kaiser Permanente (KP) and the Centers for Disease Control and Prevention (CDC) and included 17,337 KP members aged older than 50 years. A questionnaire regarding childhood neglect and abuse and other family dysfunction was offered to each participant. Omitting a third of the subjects who denied a history of childhood maltreatment, survey respondents reported physical abuse (26%), sexual abuse (21%), emotional and physical neglect (20%), and emotional abuse • THE CLINICAL ADVISOR • MAY 2017 33


DTD is a permanent condition, and without treatment, adult victims are highly prone to replicating generations of traumatized families. (10%).14 In addition, 28% were subjected to a caretaker who abused a substance, 20% were exposed to a caregiver with mental illness, and 13% witnessed violence against a maternal figure.13 It was also discovered common for more than one of these types of maltreatment to co-exist in the same person.14 In summary, ACE researchers concluded that a history of childhood neglect and abuse is often under-recognized in adult victims, and the consequences are substantial.1 Many of the subjects reported depression, suicide attempts, drug use, alcoholism, sexual promiscuity, domestic violence, cigarette smoking, obesity, and sexually transmitted diseases.13 Furthermore, a history of childhood trauma carries a 10% to 15% increased risk for developing heart and lung disease, cancer, and diabetes.10,14 It is also linked to liver disorders, stroke, and bone fractures.1 Victims’ frequent use of medical and psychological services are typical.9 Also noted, because of societal taboos regarding the topic of child maltreatment, healthcare providers are often reluctant to discuss histories or issues of neglect and abuse with patients or their families.1,14 In essence, this averseness only serves to exacerbate a victim’s solitude and self-justify his or her mistrust of others. Unfortunately, DTD is a permanent condition, and without treatment, adult victims exhibit a multitude of emotional, social, and health-related complications, and are highly prone to replicating generations of traumatized families. Developmental trauma disorder and the Diagnostic and Statistical Manual

Van der Kolk and colleagues submitted an in-depth proposal to the board of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) advocating for the inclusion of DTD as a diagnosis, specifying the following in their statement of purpose:7 “The goal of introducing the diagnosis of Developmental Trauma Disorder is to capture the reality of the clinical presentations of children and adolescents exposed to chronic interpersonal trauma and thereby guide clinicians to develop and utilize effective interventions and for researchers to study the neurobiology and transmission of chronic interpersonal violence. Whether or not they exhibit symptoms of PTSD, children who have developed in the context of ongoing danger, maltreatment, and inadequate caregiving systems are illserved by the current diagnostic system, as it frequently leads to no diagnosis, multiple unrelated diagnoses, an emphasis on behavioral control without recognition of interpersonal trauma

and lack of safety in the etiology of symptoms, and a lack of attention to ameliorating the developmental disruptions that underlie the symptoms.”

In May 2013, despite vast support from experts in the psychiatric community for the recognition of DTD as a diagnosis and more than 20 years of relevant clinical research and practice indications, the DSM-V committee elected not to include DTD as a formal diagnosis. Consequently, there is no current diagnostic criteria that entirely describe the unique effects of chronic maltreatment occurring in children and adolescents and in whom other numerous primary disorders are often misdiagnosed.1,7,9 Examples of such disorders include depression, BPD, ADD, attention-deficit/hyperactivity disorder (ADHD), bipolar and attachment disorders, separation anxiety disorder (SAD), and oppositional defiant disorder (ODD).7,9,15 Symptoms of these conditions often reflect the dysfunctional coping skills of DTD victims, such as hyperactivity and poor attention span in ADHD and self-mutilation in BPD.1,7 For instance, patients in whom BPD is diagnosed have mainly a history of childhood trauma, especially sexual and/or physical abuse.1,5,7,15 It is believed that chronic child maltreatment causes a risk for most of the personality disorders listed in the DSM, including psychosis, BPD, ADD, ADHD, depression, and addictive personality.1,6,9,11 An unclear or inadequate analysis may lead to treatment that is insufficient or unnecessary, such as psychotropic drugs, because treatment is often focused on a patient’s symptoms or behavior rather than a patient’s trauma experiences.1,7,9 In contrast, among various possible reasons why DTD was not accepted as a diagnosis in the DSM-V is that clinicians may focus too much on trauma history causing a misdiagnosis, particularly in patients without a history of child maltreatment or in those who possess a biologic or congenital basis for mental illness.15 In addition, opposing views speculate that DTD comprises an array of symptoms related to other DSM-specified disorders, such as BPD, attachment disorder, and ODD.14 However, as mentioned, many patients diagnosed with these, and other psychological disorders, often have histories of child maltreatment.1,6-7,9,15 Deliberated further, DTD develops during specific phases in a child’s life, but the diagnosis fails to address distinct symptoms for each stage.14 However, a precise list of signs may lack in other disorders, due to limited capacity for subjective


Continues on page 36


Theories regarding human psychological trauma became increasingly recognized in the mid-1970s, due to emotionally stressed Vietnam veterans. reporting and the capacity of self-analysis in children.7,15 Regardless of a professional vindication for DTD as a sole diagnosis, at the present time, debate and resolution for DSM acknowledgment continues. Developmental trauma disorder versus posttraumatic stress disorder

Theories regarding human psychological trauma became increasingly recognized in the mid-1970s, due to emotionally distressed Vietnam veterans, and eventually led to the concept of PTSD.9 However, interpersonal childhood trauma did not become the focus of attention within the mental health community until the late 1980s or early 1990s.4,5 PTSD is defined as being caused by a single event or specific type of trauma, such as experiencing the effects from war or rape.16 However, DTD, also paralleled with complex PTSD (CPTSD),5-6,9 is caused by chronic and multifaceted traumatic events that occur during childhood that permanently influence a developing brain, affecting emotional and cognitive function and behavior. Traumatized children meet the DSM diagnostic criteria for many disorders, such as PTSD, but the various symptoms of DTD or CPTSD are not completely listed in the PTSD criteria and are often labeled as comorbidities.1,9,15 Common symptoms that distinguish PTSD and CPTSD are listed in Table 2.17 Most recently, DSM modifications for PTSD included a subtype group for children aged younger than 6 years.18 Research has shown when diagnostic criteria that are sensitive to child developmental stages were used, together with an appropriate behavioral assessment, more children qualified for a diagnosis of the child PTSD subtype than any other PTSD groups.18 Child PTSD evaluation include a lack of verbal skills in reporting abuse and the manner in which

trauma-related symptoms and memory are expressed.18 For example, decreased interest in routine activities and play or “restricted play” are considered, and severe temper tantrums are noted to represent increased arousal behavior.18 Other childhood signs of PTSD include “loss of interests, restricted range of affect, detachment from loved ones, and avoidance of thoughts or feelings related to the trauma.”18 These symptoms are tyical for children but are less distinct in adults with PTSD.18 In short, victims of childhood trauma exhibit many symptoms of PTSD, including dissociation, guilt, and hopelessness, but the diagnostic criteria for PTSD does not accurately include all the important indicators of DTD.1,5,6 Support and treatment

In 2000, Congress developed the National Child Traumatic Stress Network (NCTSN) to offer education and resources to victims and families and to increase public and professional awareness regarding childhood trauma.19 In addition, NCTSN provides patient assessment tools for non-mental health professionals to help them identify specific types of trauma and initiate appropriate remedies. Treatment options for victims provide new and safe ways for them to experience the world and increase their selfawareness and self-esteem. Play or art therapy encourages young children to emote safely, while allowing victims to express trauma experience according to their language capacity and maturity level.1,10 Educating victims in alternative ways of relating to themselves and others, rather than inaptly engaging in the 4-F personalities, is crucial1,6,10 and helps to break destructive habits regarding personal and social interaction, restructure disorganized brain patterns, and offer a sense of self-empowerment.1,6

TABLE 2. Common symptoms of posttraumatic stress disorder and complex posttraumatic stress disorder17 Posttraumatic stress disorder

Complex posttraumatic stress disorder

Persistence of: • Recollections and/or dreams of event • Acting or feeling a reoccurrence of event • Psychological distress at exposure to cues • Physiological reactivity at exposure to cues • Avoidance of associated stimuli • Symptoms of increased arousal

Dysregulation of: • Affect and impulses • Attention and consciousness • Perception of self and perpetrator • Relations with others • Somatization • Systems of meaning


Early detection of trauma can significantly help avoid or minimize the various emotional, social, and medical issues that victims encounter. Psychotherapy with a certified trauma specialist is essential for evaluating and grieving past damaging events. It is also beneficial for identifying self-defeating and trauma-related thoughts and behaviors, reducing dissociative tendencies, and improving the ability to manage emotions.1,5,6 Common psychotherapeutic methods include cognitive behavioral therapy (CBT), dialectical behavior therapy (DBT), and eye movement desensitization and reprocessing (EMDR).4,18 In addition, medications may be used appropriately to regulate mood without causing further dissociation or dulling the emotions required for personal growth and recovery. Yoga can be included to enhance integration of the mind, body, and spirit, and to improve a patient’s overall affect.20 Meditation or mindfulness techniques are used to increase self-connection with feelings and sensory and physical sensations, improve ability to control emotions, and reduce anxiety and dissociative or reactive tendencies, thereby greatly improving self-management skills.6,9,21 Most importantly, the human brain is remarkably resilient, particularly the minds of children; therefore, early detection of a trauma history and instituting suitable treatment plans can significantly help avoid or minimize the various emotional, social, and medical issues that victims encounter.

for DTD philosophy, including serious recognition from the DSM officials. Often, the only voice trauma victims possess is an empathetic and astute professional, and it is vital that appropriate action and interventions are implemented. n Maureen Kilrain, MPAS, PA-C, is a practicing physician assistant in the Cleveland, Ohio, area. References 1. Van der Kolk BA. Developmental trauma disorder. Psychiatric Ann. 2005;35:401-408. Trauma_Disorder.pdf. Accessed April 10, 2017. 2. Child maltreatment 2014. U.S. Department of Health and Human Services, Administration for Children and Families, Administration on Children, Youth and Families Children’s Bureau website. https://www.acf. Accessed April 10, 2017. 3. Child abuse and neglect fatalities 2015: Statistics and interventions. Children’s Bureau Child Welfare website. pubPDFs/fatality.pdf#page=2&view=How%20many%20children%20 die%20each%20year%20from%20child%20abuse%20or%20neglect? Accessed April 10, 2017. 4. Spermon D, Darlington Y, Gibney P. Psychodynamic psychotherapy for complex trauma: Targets, focus, applications, and outcomes. Psychol Res Behav Manag. 2010;3:119-127.


Accessed April 10, 2017.

Undoubtedly, a tremendous health and safety crisis exists within the vast population of maltreated children, many of whom suffer as adults. Frequently, the aforementioned effects of DTD will prevail without proper aid and support. Establishing DTD as a distinct syndrome may prevent confusion with other psychiatric illnesses, offer more insightful solutions for victims, and create a compassionate consciousness among professionals and the public regarding the numerous problems childhood trauma produces. Furthermore, awareness of DTD may offer healthcare providers trauma-focused consideration that may enhance treatment or referral options and improve the prognosis of common ailments encountered in their practice. Although negative aspects regarding DTD have been considered, such as enmeshment of other DSM-defined disorders, there remains the dilemma of formulating an explicit condition for the enormous population of abused and neglected children—many of whom tragically lost their lives due to caretakers who were trauma victims themselves. According to Bremness,22 there is an urgent requirement for a more flexible diagnostic system regarding environmental influences and

5. Herman JL. Complex PTSD: A syndrome in survivors of prolonged and repeated trauma. J Trauma Stress. 1992;5:377-391. boundary/Childhood_trauma_and_PTSD/complex_PTSD.pdf. Accessed April 10, 2017. 6. Walker P. Complex PTSD: From Surviving to Thriving: A Guide and Map for Recovering From Childhood Trauma. 1st ed. Lafayette, CA: Azure Coyote; 2013. 7. Van der Kolk BA, Pynoos RS. Proposal to include a developmental trauma disorder diagnosis for children and adolescents in DSM-V. http:// Published February 1, 2009. Accessed April 10, 2017. 8. Gabowitz D, Zucker M, Cook A. Neuropsychological assessment in clinical evaluation of children and adolescents with complex trauma. J Child Adolesc Trauma. 2008;1:163-178. http://dx.doi. org/10.1080/19361520802003822. Accessed April 10, 2017. 9. Van der Kolk BA. The assessment and treatment of complex PTSD. In: Yehuda R, ed. Traumatic Stress. Washington, DC: American Psychiatric Press; 2001;1-29. complex_ptsd.pdf. Accessed April 10, 2017. 10. Van der Kolk BA. The neurobiology of childhood trauma and abuse. Child Adolesc Psychiatr Clin N Am. 2003;12:293-317. https://www. • THE CLINICAL ADVISOR • MAY 2017 37

DTD:THE EFFECTS OF CHILD ABUSE AND NEGLECT trauma_and_abuse. Accessed April 10, 2017. 11. Perry BD. Child maltreatment: A neurodevelopmental perspective on the role of trauma and neglect in psychopathology. In: Beauchaine T, Hinshaw SP, eds. Child and Adolescent Psychopathology. Hoboken, NJ: John Wiley & Sons; 2008:93-129. Perry_Psychopathology_Chapter_08.pdf. Accessed April 10, 2017. 12. The science of early childhood development (InBrief). Harvard University Center on the Developing Child website. http://developingchild. Accessed April 10, 2017. 13. Van der Kolk B. The compulsion to repeat the trauma: Re-enactment, revictimization, and masochism. Psychiatr Clin North Am. 1989;12:389-411. pdf. Accessed April 10, 2017. 14. Anda RF, Felitti VJ. Adverse childhood experiences study. Ace Reporter.

“I’m getting awfully tired of reality T.V.”

2003;1:1-4. acestudy.pdf. Accessed April 10, 2017. 15. Schmid M, Petermann F, Fegert JM. Developmental trauma disorder: Pros and cons of including formal criteria in the psychiatric diagnostic systems. BMC Psychiatry. 2013;13:3. Accessed April 10, 2017. 16. American Psychiatric Association. What is posttraumatic stress disorder? In: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington, VA: American Psychiatric Publishing; 2013. https://www. 17. Scheg KE. Complex posttraumatic stress disorder and emotional regulation. Core Transformation Counseling website. http://www. Published 2016. Accessed April 10, 2017. 18. Scheeringa M. PTSD for children 6 years and younger. PTSD: National Center for PTSD. U.S. Department of Veterans Affairs website. http:// younger.asp. Accessed April 10, 2017. 19. Assessment of complex trauma. The National Child Traumatic Stress Network. assessment. Accessed April 10, 2017. 20. Emerson D, Sharma R, Chaudhry S, Turner J. Trauma-sensitive yoga: Principles, practice, and research. Int J Yoga Ther. 2009;19:123-128. Accessed April 10, 2017. 21. Davis M, Hayes J. What are the benefits of mindfulness? A practice review of psychotherapy-related research. Psychotherapy. 2011;48:198-208. pdf. Accessed April 10, 2017. 22. Bremness A. Commentary: Developmental trauma disorder: a missed opportunity in DSM V. J Can Acad Child Adolesc Psychiatry. 2014;23:142-145. http: // Accessed April 10, 2017.


“I feel like bad guys aren’t as scared of me in the summer.”

Top, middle: © Harley Schwadron. Bottom: © The New Yorker Collection 2017 from All Rights Reserved. Accessed April 10, 2017.


n LEARNING OBJECTIVES After completing the activity, the participant should be better able to: • Describe the potential benefits of anti-obesity medications, including and beyond their impact on weight loss • Utilize anti-obesity medications in appropriate patients n COMPLETE THE POSTTEST: Page 48

FEATURED COURSE This activity is supported by an educational grant from Novo Nordisk and is a result of a collaborative effort between Haymarket Medical Education, Global Education Group, and the American Society of Endocrine Physician Assistants (ASEPA). Release Date: May 8, 2017 Expiration Date: May 7, 2018 Estimated time to complete the educational activity: 1 hour Target Audience: This activity has been designed to meet the educational needs of Physician Assistants, Nurse Practitioners, and Dietitians. Faculty Ken Fujioka, MD Director Nutrition and Metabolic Research Center and the Center for Weight Management Scripps Clinic La Jolla, CA Accreditation Statements Physician Credit: Haymarket Medical Education 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 1.00 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. For Registered Dietitians/Registered Dietetic Technicians The following activity has been approved by the ACCME, whose approval is recognized by the Commission on Dietetic Registration and, as such, RDs/DTRs will be able to receive 1.00 CPEU. Nursing Credit: Global Education Group is accredited with distinction as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. Credit Designation: This educational activity for 1.00 contact hours is provided by Global Education Group. Nurses should claim only the credit commensurate with the extent of their participation in the activity. This activity is jointly provided by Global Education Group and Haymarket for ANCC credit. Disclosure Policy In accordance with the ACCME Standards for Commercial Support, HME and Global Education require that individuals in a position to control the content of an educational activity disclose all relevant financial relationships

with any commercial interest. HME and Global Education resolve all conflicts of interest to ensure independence, objectivity, balance, and scientific rigor in all its educational activities. The faculty reported the following financial relationships with commercial interests whose products or services may be mentioned in this CME/CE activity. Faculty Disclosures Ken Fujioka, MD, receives consultant fees from Novo Nordisk, Orexigen, Eisai, and KVK-Tech. He is also on the speakers’ bureau for Novo Nordisk and Orexigen. Staff/Planners’ Disclosures Haymarket Medical Education staff involved in the planning and content review of this activity have no relevant financial relationships to disclose. CME Reviewer, Priya Wanchoo, MD, has no relevant financial relationships to disclose. Global Education Group staff, Ashley Marostica, RN, MS, Andrea Funk, and Lindsay Borvansky, 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 Global Education Group 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: To obtain credit, a score of 70% or better on the post-test is required. This activity is offered at no cost to participants. Please proceed with the activity until you have successfully completed this program, answered all test questions, completed the post-test and evaluation, and have received a digital copy of your credit certificate. Your online certificate will be saved on myCME within your Profile/Exam History, which you can access at any time. Disclaimer: The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of Novo Nordisk, Global Education Group, and Haymarket Medical Education. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings. If you have any questions relating to the accreditation of this activity, please contact



Pharmacologic therapy for obesity management As part of a multimodal treatment strategy, anti-obesity drugs can help patients achieve and maintain their weight-loss goals.


■ Case Study

Patient description: Susan T. is a 48-year-old female patient who is new to your practice. She weighs 210 lb and her body mass index (BMI) is 36 kg/m 2 . She has a history of high LDL (low-density lipoprotein) cholesterol, which is being treated with a statin. Her blood pressure is 142/90 mmHg, and her fasting blood glucose is 119 mg/dL. She complains of chronic pain in her right knee. She says that she has gained 12 lb in the last year because she has been working increased hours. She knows that losing weight would be good for her health but she has not been able to stick to a diet, even though she has tried numerous times. She says that each time she tries to go on a diet, she usually loses 5 lb but “hates feeling hungry all the time.” Also, the pain in her right knee makes it hard for her to be physically active. She has heard that there are several medications that may help her lose weight and asks if any of them would be appropriate for her to take. Introduction to anti-obesity medications

Anti-obesity medications are a useful tool to help patients achieve meaningful weight loss.

In patients with obesity, weight loss of as little as 5% to 10% through intensive lifestyle modification reduces body fat content, improves measures of cardiovascular risk, delays or prevents the development of type 2 diabetes mellitus (T2DM), and improves quality of life, mobility, and other weight-related comorbidities.1-6 Greater weight loss is associated with larger reductions in cardiometabolic risk.7 For this reason, obesity management should be a priority in this particular patient. • THE CLINICAL ADVISOR • MAY 2017 41



Primary care providers are in a unique position to diagnose obesity in patients and initiate appropriate treatment, from lifestyle modification to prescribing and managing AOMs. Obesity should be considered a chronic condition in which a patient’s physiology favors weight regain. Longterm changes in hormonal signals that encourage weight regain have been documented in weight-reduced patients.8 These changes account for the difficulty in achieving and maintaining clinically significant weight loss with lifestyle intervention alone over the long term.9 Anti-obesity medications (AOMs) are a useful tool in assisting patients in achieving clinically meaningful weight loss and should be used as an adjunct to lifestyle modification.10-14 AOMs are approved for use by the FDA in patients with obesity (BMI ≥30 kg/m 2) or patients with BMI ≥27 and 1 weight-related comorbidity such as hypertension, dyslipidemia, or type 2 diabetes. The American College of Cardiology, American Heart Association, The Obesity Society, Endocrine Society, and Obesity Medicine Association support the use of AOMs to treat obesity.15-17 Despite treatment recommendations and the recent approval of several new AOMs for long-term use, prescribing rates remain low.18 Primary care providers are in a unique position to diagnose obesity and initiate appropriate treatment, from providing lifestyle modification to prescribing and managing AOMs.10,19,20 There are 5 medications approved for long-term treatment of obesity: orlistat,21 lorcaserin,22 phentermine/topiramate,23 naltrexone/bupropion,24 and liraglutide.25 Because of limited efficacy and unpleasant side effects, orlistat is used relatively rarely.26,27 The other 4 medications were approved TABLE 1. Treatment options for patients with obesity15,17 BMI (kg/m2)


25 or higher

Lifestyle modification

27 or higher and a weightrelated comorbidity

Eligible for treatment with AOM

30 or higher

Eligible for treatment with AOM

35 or higher and a weightrelated comorbidity

Eligible for surgery and/or AOM

40 or higher

Eligible for surgery and/or AOM

by the FDA beginning in 2012. The primary mechanism for weight loss with these agents is mainly attributed to their effects on various brain pathways that affect appetite and reduce food intake.15,28-31 Because each AOM has a different specific mechanism of action, efficacy and tolerability will vary across patients. In this article, we review the long-term pharmacologic and surgical treatments for obesity, with a focus on the 4 centrally acting long-term AOMs, their indications for use, strategies for improving efficacy, and managing side effects. Selecting AOMs based on patient characteristics and preferences, adjusting dose, and switching medications when appropriate may improve efficacy, tolerability, and patient adherence. ■ Case Study, continued

The clinician explains that Susan’s excess weight, hypertension, prediabetes, and dyslipidemia require intervention to prevent progression to T2DM and the development of other weight-related health problems such as heart disease. The healthcare provider explains that, if Susan is successful in achieving a healthy weight, she may be able to reduce the dose of her cholesterol medication and also experience an improvement in knee pain. The clinician says that there have been many recent advances in surgical and drug treatments that can help her manage her appetite and achieve a healthy weight, and asks Susan if she is interested in learning more about these treatment options. Susan has stated that she wants to begin obesity treatment and expressed interest in medications. She is also eligible for bariatric surgery. Before deciding which type of therapy to select, the clinician reviews the general benefits and risks of surgery and AOMs with Susan so she can decide what is appropriate for her. Treatment options for patients with obesity

Susan meets the criteria for treatment with AOMs or surgery (Table 1). The indications for treatment with AOMs are failure to achieve and maintain at least 5% weight loss, and a BMI of at least 27 kg/m 2 with 1 or more weight-related comorbidities (eg, T2DM, hypertension) or a BMI of greater than 30 kg/m 2 .15,17 Patients who have a BMI greater than 35 kg/m 2 and at least 1 weight-related comorbid condition, who have not responded to lifestyle intervention and medical management of obesity, are candidates for bariatric surgery.15,17,32


Anti-obesity medications are indicated for chronic weight management, along with diet and physi­cal activity, to promote weight loss and maintenance of a healthy weight. Benefits and risks of surgery

Bariatric surgery is the most effective treatment option for patients with morbid obesity.32 Since the introduction of lower-risk laparoscopic procedures, surgical treatment of obesity has become increasingly common. However, because it is associated with the most risk, surgery should only be considered in patients with more severe forms of obesity (Table 1). The amount of weight loss, improvement in weight-related comorbidities, and relative risk vary by procedure (Table 2).33 In addition to substantial weight loss, bariatric surgery is associated with consistent improvements in cardiovascular risk and mortality, glucose control (including remission of T2DM), quality of life, and other weight-related comorbidities.34-36 Benefits and risks of anti-obesity medications

AOMs increase the likelihood of achieving clinically meaningful weight loss of at least 5%. Depending on the specific AOM, mean placebo-adjusted 1-year weight loss in clinical trials ranged from 3% to over 9%.22-25 Because clinical trials report mean weight loss and are not designed to provide individualized patient care, greater weight loss is possible in many individuals. In a clinical trial that combined the AOM naltrexone/bupropion with intensive lifestyle modification, patients achieved greater weight loss than was seen when naltrexone/bupropion was combined with less intensive lifestyle modification.37 Although all AOMs are associated with improvements in weight-related comorbidities, the degree of improvement is less than with bariatric surgery. However, if Susan achieves the recommended 5% to 10% weight loss, she can expect measurable improvements in glucose control,

blood pressure, and lipids.38,39 Side effects vary with each of the newer AOMs, and many can be managed by dose adjustment. Other side effects may resolve over time.22-25 For Susan, treatment goals should include: reducing blood pressure, improving lipids, and improving glucose control. Improvements in risk factors are generally correlated with the amount of weight loss and may be achieved through either surgical intervention or treatment with an AOM.38-41 For example, bariatric surgery and treatment with the AOMs liraglutide and phentermine/topiramate reduced or slowed the progression to T2DM.42-46 Finally, both surgery and AOMs should be viewed as long-term chronic treatments. AOMs are indicated for chronic weight management, or long-term use, along with diet and physical activity, to promote weight loss and maintenance of a healthy weight.22-25 Thus, patients will likely need AOMs for an extended period of time, possibly lifelong, because these medications may be necessary to prevent weight regain.15 For patients such as Susan with a BMI above 35 kg/m 2 and comorbidities, the best treatment for her weight and weight-related comorbidities should be based on patient preference.47 ■ Case Study, continued

After reviewing the differences between surgery and AOMs, Susan decides to try AOMs because she says she is not ready for surgery. The clinician explains that AOMs are a tool to help her adhere to a reduced-calorie diet and make lifestyle changes and that she will likely need to keep taking the AOM even after she loses weight to prevent weight regain. Furthermore, the clinician explains that she can expect to achieve at least 5% to 10% weight loss

TABLE 2. Surgical procedures for treatment of obesity33 3-year Change in BMI

30-day Mortality Rate

>30-day Mortality Rate

Reoperation Rate

Rate of Complications

Adjustable gastric banding

−11.4 (−18.1 to −4.7)

0.1% (0.0 to 0.1)

0.2% (0.1 to 0.4)

7.0% (4.0 to 11.2)

7.8% (3.9 to 13.0)

Sleeve gastrectomy

−16.8 (−20.6 to −13.0)

0.3% (0.1 to 0.6)

0.3% (0.1 to 0.6)

3.0% (1.7 to 4.7)

8.9% (5.6 to 13.0)

Roux-en-Y gastric bypass

−21.9 (−28.0 to −15.8)

0.4% (0.2 to 0.6)

0.4% (0.0 to 0.9)

5.3% (4.5 to 6.5)

12.0% (7.3 to 17.0) • THE CLINICAL ADVISOR • MAY 2017 43



Anti-obesity medications act primarily in the brain to influence appetite, although some may also have peripheral actions. with the medications in the first 6 months, but that greater weight loss may be possible. Overview of anti-obesity medications

Of the 5 AOMs approved for long-term use, orlistat is the only agent that acts solely in the gastrointestinal tract (ie, has a peripheral mechanism of action). Orlistat is a lipase inhibitor that impairs dietary fat breakdown and absorption.21 Weight loss with orlistat (60 or 120 mg orally 3 times a day before meals) is approximately 3% greater than placebo; adverse events are gastrointestinal in nature, and orlistat is generally safe, with very rare cases of liver injury reported.14,48 Patients should take a multivitamin to ensure adequate levels of fat-soluble vitamins. The other 4 AOMs approved for long-term use are shown in Table 3. These medications act primarily in the brain to influence appetite, although some may also have peripheral actions. Lorcaserin is a serotonin 2c receptor agonist that is notable for producing the lowest mean weight loss of the 4 medications but also generally has a low rate of side effects.22,49-51 Phentermine/topiramate is comprised of phentermine and topiramate extended release.23 Phentermine is a sympathomimetic, and topiramate is an anticonvulsant. The weight-loss effect is attribute to a combined effect of the 2 drugs. Phentermine/ topiramate produces the greatest mean weight loss of the 4 newer AOMs.31,52,53 Because topiramate is associated with fetal toxicity (oral clefts), regular monitoring of pregnancy is recommended.54

Naltrexone/bupropion is another combination AOM comprised of fixed-dose sustained-release tablets.24 Bupropion is a dopamine and norepinephrine reuptake inhibitor (and antidepressant medication), and naltrexone is an opioid antagonist. The combination of bupropion and naltrexone produces a greater reduction in body weight than either drug alone.29 In clinical trials, the most common side effect, nausea, is related to naltrexone dose and can be mitigated by slowing dose titration.37,55-57 Liraglutide is a glucagon-like receptor-1 (GLP-1) agonist that was previously developed for glucose management in T2DM at doses up to 1.8 mg. Liraglutide has both central and peripheral actions that reduce food intake and improve glucose control.25 Liraglutide is administered via daily subcutaneous injection at doses titrated up to 3.0 mg for the treatment of obesity.25,44,58-60 The most common side effect, nausea, can be managed by slowing dose escalation.25 In addition, liraglutide is associated with a small increase in heart rate. Anti-obesity medications: risk/benefit management

The clinician plays an important role in setting the stage for patient success with AOMs by evaluating the individual response to an AOM and making adjustments to the drug titration schedule and dose. As there are many causes of obesity, and AOMs all have different mechanisms, the clinician may have to switch AOM if the first or second does not work to influence long-term patient success. To

TABLE 3. Overview of long-term anti-obesity medications22-25 Common Side Effects*



Dizziness, fatigue, nausea, dry mouth, and constipation

Should not be used with monoamine oxidase inhibitors; use caution with other serotonergic drugs


Paresthesias, dizziness, dysgeusia, insomnia, constipation, and dry mouth

Teratogen. Should not be used with monoamine oxidase inhibitors. Patients can have problems with mood or memory


Nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea

Can increase blood pressure


Nausea, hypoglycemia, diarrhea, constipation, vomiting, headache, decreased appetite, dyspepsia, fatigue, dizziness, abdominal pain, and increased lipase

Injectable. Should not be prescribed in patients with history of medullary thyroid cancer, multiple endocrine neoplasia syndrome type 2 (MEN 2) or history of pancreatitis

Data based on prescribing information. *Adverse events reported in â&#x2030;Ľ5% of drug-treated patients in clinical trials.

44 THE CLINICAL ADVISOR â&#x20AC;˘ MAY 2017 â&#x20AC;˘

Individuals who fail to achieve the target weight loss early in AOM treatment are less likely to lose weight and should discontinue the medication. improve tolerability, AOMs (except for lorcaserin, which does not need titration) should be initiated at the lowest recommended dose and increased as described in the prescribing information (Table 4) based on individual patient efficacy and tolerability.22-25 The prescribing information for discontinuing AOMs shown in Table 4 is based on previous research that shows patients who achieve weight loss early in treatment (with AOMs or other weight-loss interventions such as lifestyle modification) are more likely to experience greater weight loss during continued treatment for up to 1 to 2 years.61-64 Consistent with this, studies of lorcaserin, naltrexone/ bupropion, and liraglutide have demonstrated that patients who experience greater weight loss within the first 3 to 4 months of initiating treatment are more likely to achieve clinically significant weight loss after 1 year.38,39,65 Furthermore, patients who experienced greater weight loss early in treatment were more likely to experience meaningful improvements in cardiometabolic risk factors.38,39 For phentermine/topiramate, increasing the dose to the maximum recommended dose may also increase the likelihood that a patient will achieve the target weight loss of about 3% to 5% in 12 to 16 weeks as described in the administration schedule.23,24 Conversely, individuals who fail to achieve the target weight loss early in AOM treatment are less likely to experience weight loss and other health benefits and should

not continue taking the medication. Stopping an inappropriate medication can allow for switching to another AOM or treatment that may yield appreciable benefits to warrant patient exposure to medication risks and side effects as well as justify cost. Because side effects may be dose-related, prolonging the titration schedule (with phentermine/topiramate, naltrexone/bupropion, or liraglutide) or prescribing a lower dose (with phentermine/topiramate or naltrexone/bupropion) is recommended under certain circumstances and may improve tolerability in some patients.23-25 Note that the prescribing information for liraglutide recommends discontinuing administration if the patient cannot tolerate the 3-mg dose because efficacy has not been established at lower doses.25 ■ Case Study, continued

The clinician reviews the benefits and risks of AOMs with Susan and recommends an AOM. The clinician also reviews the drug administration recommendations and follow-up schedule. In addition, the clinician and Susan discuss the importance of engaging in lifestyle modification, and Susan is referred to a lifestyle modification program. A follow-up visit is scheduled in 1 month, at which point the change in Susan’s weight and any side effects will be discussed. Additional monthly follow-ups are scheduled over the next 4 months to evaluate efficacy and side effects. The clinician

TABLE 4. Anti-obesity medications: dosing and administration22-25 Dosing




10 mg BID, oral


Discontinue if 5% weight loss not achieved by Week 12


Recommended dose: 7.5 mg/46 mg, oral


Discontinue or escalate dose if 3% weight loss is not achieved after 12 weeks on recommended dose

Maximum dose: 15 mg/92 mg, oral


Discontinue if 5% weight loss is not achieved after 12 weeks on maximum dose


Maintenance dose: 32 mg/360 mg, oral


Discontinue if 5% weight loss is not achieved after 12 weeks on maintenance dose


3.0 mg injection


Discontinue if 4% weight loss is not achieved 16 weeks after initiating drug administration

Data based on prescribing information. • THE CLINICAL ADVISOR • MAY 2017 45



will decide whether to continue with the current medication and dose, adjust the dose, or switch medications.

13. Kushner RF. Weight loss strategies for treatment of obesity. Prog Cardiovasc Dis. 2014;56:465-472. 14. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity:


a systematic and clinical review. JAMA. 2014;311:74-86.

Since 2012, the introduction of 4 AOMs to the US market has greatly increased patient options for achieving a healthy weight. Primary care clinicians are uniquely positioned to identify patients who may benefit from treatment with an AOM. By educating patients about these new treatment options and initiating treatment where appropriate, primary care clinicians can play a critical role in treating obesity. Regular patient visits early in treatment to monitor side effects and efficacy are an essential component of AOM treatment. By intervening early to maximize tolerability and monitor efficacy, the clinician can provide a foundation for optimizing patient adherence, efficacy, and health benefits over the long term. n

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33. Chang SH, Stoll CR, Song J, et al. The effectiveness and risks of bariatric

mellitus: the BLOOM-DM study. Obesity. 2012;20:1426-1236.

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34. Sjostrom L, Peltonen M, Jacobson P, et al. Bariatric surgery and


long-term cardiovascular events. JAMA. 2012;307:56-65.

52. Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-

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36. Sjostrom L, Narbro K, Sjostrom CD, et al. Effects of bariatric surgery

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on mortality in Swedish obese subjects. N Engl J Med. 2007;357:741-752.

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ER combination therapy. Int J Obes. 2016;40:1369-375. • THE CLINICAL ADVISOR • MAY 2017 47


POST-TEST Expiration date: May 7, 2018

Credit Designation: HME is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. HME designates this educational activity for a maximum of 1.0 AMA PRA Category l Credit™. The following activity has been approved by the AACME, whose approval is recognized by the Commission on Dietetic Registration and, as such, RDs/DTRs will be able to receive 1.0 CPEU. Global Education Group is accredited with distinction as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. This educational activity for 1.0 contact hours is provided by Global Education Group. Participants should only claim credit commensurate with the extent of their participation in the activity. 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. Posttest must be completed and submitted online. Please go to CREDITS: 1.00 | Pharmacologic Therapy for Obesity Management 1. Which of the following statements is true? a. For patients with obesity, the degree of weight loss does not correlate with the amount of reduction in cardiometabolic risk. b. It has been demonstrated that changes in hormonal signals that encourage weight regain do not persist in weight-reduced patients over the long term. c. In patients with obesity, weight loss of as little as 5% to 10% reduces body fat content, and improves various measures of cardiovascular risk. d. None of the above. 2. The most recently approved anti-obesity medications (AOMs): a. Should not be used in patients with T2DM. b. Are approved for use in patients with obesity or in patients with BMI ≥27 kg/m2 and 1 weight-related comorbidity such as hypertension, dyslipidemia, or type 2 diabetes. c. Cannot be used long term. d. Are not recommended for use in obesity per evidence-based guidelines. 3. Currently, ___ medications are approved for the long-term treatment of obesity. a. 0 b. 2 c. 3 d. 5 4. Patients who have a BMI greater than 35 kg/m2 and at least 1 weight-related comorbid condition, who have not responded to lifestyle intervention and medical management of obesity: a. Are candidates for bariatric surgery. b. Should be advised to begin a vigorous, structured exercise program at least 6 days per week. c. Are likely to have better results with one or more AOM vs bariatric surgery. d. Are unlikely to be successful at maintaining weight loss at one year no matter the treatment plan.

5. Which of the following statements is true? a. Surgical treatment of obesity has become less common over the last decade. b. The amount of weight loss, improvement in weightrelated comorbidities, and relative risk that can be achieved are fairly identical among the various bariatric surgery procedures. c. Bariatric surgery is associated with substantial weight loss but minimal and transient improvements in cardiovascular risk. d. Because it is associated with the most risk, surgery should only be considered in patients with more severe forms of obesity. 6. Orlistat: a. Is associated with a weight loss of approximately 7% vs placebo. b. Impairs dietary fat breakdown and absorption. c. Is a sympathomimetic agent. d. Is associated with increased heart rate. 7. Liraglutide: a. Is administered via once-weekly subcutaneous injection. b. Can be titrated up to a 2-mg dose for the treatment of obesity. c. Has both central and peripheral actions that reduce food intake and improve glucose control. d. All of the above. 8. Naltrexone/bupropion: a. May increase blood pressure in some individuals. b. Can increase pulse rate. c. Should not be used with monoamine oxidase inhibitors. d. All of the above.

TO TAKE THE POST-TEST please go to:


Dermatology Clinic CASE #1

A diffuse rash in a man with paraproteinemia MATTHEW M. WALLACE, BSC, AND ALEX G. ORTEGA-LOAYZA, MD

A 56-year-old man presents with diffuse pruritic papules on his upper body. He has been evaluated by multiple specialists for dysphagia, reflux, chronic kidney disease, hypertension, and dyspnea on exertion. Examination results are significant for generalized firm, fleshy, dome-shaped papules. Relevant laboratory findings include monoclonal gammopathy on serum immunofixation, consisting of immunoglobulin (Ig) Gκ and IgAκ, and unremarkable thyroid panel findings. What is your diagnosis? Turn to page 50.


Discoloration in a postmenopausal woman’s breast ESTHER STERN, NP

A 61-year-old woman presents concerned about a white discoloration on her left breast that she first noticed 6 months earlier. It itches at times, and she is worried it might be cancerous. She showed it to her gynecologist at her annual visit, and he referred her to the dermatology clinic. Physical examination of the left breast reveals a 10-cm white, smooth, porcelain-like plaque. There is no associated erythema and no noticeable scale. What is your diagnosis? Turn to page 51. • THE CLINICAL ADVISOR • MAY 2017 49

Dermatology Clinic CASE #1


Scleromyxedema is the generalized form of lichen myxedematosus, which presents with widespread eruption of shiny, firm, dome-shaped or flattopped papules; these papules do not affect the palms, scalp, or mucous membranes.1,2 Other clinical findings can include the doughnut sign, characterized by skin thickening with a central depression overlying the proximal interphalangeal joints, and decreased range of motion of the hands, lips, mouth, and extremities.1,2 There is no sex predilection in scleromyxedema.3 Mean age at onset of the condition is typically the fifth decade of life, but onset can present between the second and seventh decades.4,5 On average, the condition is diagnosed 3 years after initial onset.5 The localized form of lichen myxedematosus is papular mucinosis.1 Although papular mucinosis is not associated with extracutaneous findings, scleromyxedema has systemic manifestations in up to 77% of patients; in some cases, these manifestations are fatal.2,5 In a retrospective study of 26 patients with scleromyxedema, gastrointestinal involvement was the most common finding in 60% of patients—specifically, dysphagia due to esophageal dysmotility.2,5 In another retrospective study of 30 patients with scleromyxedema, other extracutaneous findings included neurologic abnormalities in 30% (eg, carpal tunnel syndrome and dermatoneuro syndrome [fever, seizures, and coma]), rheumatologic abnormalities in 23% (eg, arthralgias with or without arthritis), and cardiac abnormalities in 20% (eg, myocardial ischemia, congestive cardiomyopathy, and inflammatory cardiomyopathy). 3 Dyspnea on exertion and myopathy presenting as proximal or generalized weakness is present in approximately 32% and 26% of patients, respectively.4 Scleromyxedema is highly associated with hematologic abnormalities, especially monoclonal gammopathy. Up to 88% of patients have a paraproteinemia, most commonly the IgGλ subtype.5 Paraproteinemia consisting of the IgGκ, IgMκ, IgAκ, and IgAλ subtypes have also been reported.5 Underlying hematologic malignancies include leukemia, multiple myeloma, Hodgkin lymphoma, and non-Hodgkin lymphoma.3,5 Less common extracutaneous manifestations include renal dysfunction and ocular involvement.3,4 Several other conditions can present with similar features. The differential diagnosis of scleromyxedema includes

primary (limited) cutaneous mucinoses, scleroderma, scleredema, nephrogenic systemic fibrosis, and underlying disorders presenting with leonine facies.6,7 Limited cutaneous mucinoses are focal and lack systemic features, including paraproteinemia.7 Mucinous papules in scleromyxedema classically involve the hands and face, predominantly the glabella and ears, which differentiates the condition from scleroderma and scleredema clinically.7 In advanced disease, the central back and digits are typically not involved in scleroderma and scleredema, respectively.7 Patients with nephrogenic systemic fibrosis have a history of renal insufficiency and gadolinium exposure, and commonly do not have paraproteinemia or facial involvement.8 Characteristic cutaneous, extracutaneous, and histopathologic findings, in addition to monoclonal gammopathy in the absence of thyroid abnormalities, provide a definitive diagnosis of scleromyxedema.3,7 Biopsy reveals irregularly arranged stellate fibroblasts with collagen deposition and diffuse mucin concentrated primarily in the mid-to-upper dermis.7,9 Mucin stains with Alcian blue at a pH of 2.5.5 Several hypotheses have been proposed regarding the pathogenesis of scleromyxedema; however, its etiology remains elusive. Treatment is largely based on outcomes from case series and reports secondary to the rarity of the condition. Kaffenberger and Kirby10 suggest first-line treatments including melphalan, plasmapheresis, intravenous immunoglobulin (IVIG), and systemic corticosteroids. High-dose dexamethasone, in particular, has produced good outcomes.11,12 Isotretinoin, etretinate, topical calcineurin inhibitors, topical corticosteroids, and intralesional corticosteroids are considered second-line agents.10 Third-line therapies include various immunosuppressants and chemotherapies (eg, cyclophosphamide, cyclosporine, methotrexate, chlorambucil, bortezomib, and vincristine), as well as interferon α-2b, radiation, psoralen and ultraviolet A radiation, extracorporeal photopheresis, and autologous stem cell transplantation.10 Regimens incorporating autologous stem cell transplantation have shown promising results; resolution of skin findings and partial to complete remission of the extracutaneous manifestations have been reported in several patients with scleromyxedema.13 The patient in our case was initially treated with weekly 40-mg pulse dexamethasone. He had an impressive response as his papules flattened and induration softened. However, this response was short-lived. After 12 weeks of dexamethasone, he started a monthly 5-day cycle of IVIG, 400 mg/kg. After completion of cycle seven of IVIG, his skin manifestations have improved. On examination, he


Dermatology Clinic had residual papules on his ears and significant decrease in induration of his forehead, glabella, and nose. Although his dysphagia and dyspnea are nearly resolved, his renal function remains impaired. At the time of this writing, the IVIG is being decreased to every other month, with ongoing consideration of autologous stem cell transplantation. Matthew M. Wallace, BSc, is a medical student at Virginia Commonwealth University in Richmond, VA, and Alex G. Ortega-Loayza, MD, is an assistant professor of dermatology at Oregon Health & Science University in Portland, OR. Acknowledgments

The authors would like to thank the patient for graciously providing permission to publish his case and clinical photos. References 1. Rongioletti F, Rebora A. Updated classification of papular mucinosis, lichen myxedematosus, and scleromyxedema. J Am Acad Dermatol. 2001;44:273-281. 2. Cokonis Georgakis CD, Falasca G, Georgakis A, Heymann WR. Scleromyxedema. Clin Dermatol. 2006;24:493-497. 3. Rongioletti F, Merlo G, Cinotti E, et al. Scleromyxedema: a multicenter study of characteristics, comorbidities, course, and therapy in 30 patients. J Am Acad Dermatol. 2013;69:66-72. 4. Gabriel SE, Perry HO, Oleson GB, Bowles CA. Scleromyxedema: a scleroderma-like disorder with systemic manifestations. Medicine (Baltimore). 1988;67:58-65. 5. Dinneen AM, Dicken CH. Scleromyxedema. J Am Acad Dermatol. 1995;33:37-43. 6. Boin F, Hummers LK. Scleroderma-like fibrosing disorders. Rheum Dis Clin North Am. 2008;34:199-220. 7. Hummers LK. Scleromyxedema. Curr Opin Rheumatol. 2014;26:658-662. 8. Cowper SE, Su LD, Bhawan J, Robin HS, LeBoit PE. Nephrogenic fibrosing dermopathy. Am J Dermatopathol. 2001;23:383-393. 9. Rongioletti F, Rebora A. Cutaneous mucinoses: microscopic criteria for diagnosis. Am J Dermatopathol. 2001;23:257-267. 10. Kaffenberger JA, Kirby JS. Lichen myxedematosus. In: Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I, Kaffenberger JA, Kirby JS, eds. Treatment of Skin Disease: Comprehensive Therapeutic Strategies. 4th ed. Philadelphia, PA: Elsevier Saunders; 2014. 11. Horn KB, Horn MA, Swan J, Singhal S, Guitart J. A complete and durable clinical response to high-dose dexamethasone in a patient with scleromyxedema. J Am Acad Dermatol. 2004;51(2 Suppl):S120-S123. 12. Kreuter A, Altmeyer P. High-dose dexamethasone in scleromyxedema: report of 2 additional cases. J Am Acad Dermatol. 2005;53:739-740. 13. Donato ML, Feasel AM, Weber DM, et al. Scleromyxedema: role of high-dose melphalan with autologous stem cell transplantation. Blood. 2006;107:463-466.


Lichen sclerosus et atrophicus

Lichen sclerosus (LS), also known as lichen sclerosus et atrophicus, is a chronic inflammatory dermatitis presenting with white patches, atrophy, and, sometimes, scarring. The condition predominantly involves the genital and perianal skin. Extragenital involvement, which is less common, mostly appears on the neck, shoulders, and trunk. A recent case study presented involvement on the plantar aspect of the foot.1 LS can occur in patients of all ages; girls and women are affected at a significantly higher rate, particularly during the prepubertal and postmenopausal stages.2 One author estimates that 10% to 15% of girls are affected before age 13 years.3 LS of the penis, also termed balanitis xerotica obliterans, is almost exclusive to uncircumcised or incompletely circumcised individuals. The etiology of LS is unknown; however, several theories have been suggested, including hormonal activity, self-immunity phenomena, and genetic predisposition.4 Risk factors can include a history of trauma to the area or a family history of autoimmune disease. Extragenital LS is usually asymptomatic, although patients may complain of mild itching. In contrast, patients with vulvar involvement often complain of intolerable pain and itching, and sometimes report dyspareunia, dysuria, or genital bleeding. Involvement of the anal region can cause painful defecation, diarrhea, or constipation. LS of the penis can cause phimosis and urinary obstruction resulting from stenosis of the urethral meatus. Clinically, LS presents with macules or polygonal papules in a characteristic ivory or porcelain white color. Dermoscopy reveals comedo-like openings scattered in a white homogenous patch.5 As the condition progresses, the plugs disappear and the papules coalesce, leaving a large shiny, atrophic patch. With vulvar involvement, the whitening and atrophy often occur in an hourglass distribution around the vulva and anus, causing obliteration of the labia minora and stenosis of the introitus. In addition, fissuring and ecchymosis is sometimes present, particularly in pediatric cases. The differential diagnoses to consider include all conditions that present with white patches, such as tinea versicolor, vitiligo, morphea, lichen planus, lichen nitidus, idiopathic guttate hypomelanosis, and discoid lupus. Genital involvement can â&#x20AC;˘ THE CLINICAL ADVISOR â&#x20AC;˘ MAY 2017 51

Dermatology Clinic mimic an irritant dermatitis; genital squamous cell carcinoma and sexual abuse in children must always be ruled out. LS of the penis can be confused with Bowen disease and balanitis. Although vulvar LS can be diagnosed clinically, skin biopsy is often necessary for diagnosis of extragenital lesions. Histologic examination reveals epidermal atrophy, t­ hickening of the papillary dermis by altered collagen bundles, and vacuolar interface dermatitis with a lichenoid inflammatory cell infiltrate. First-line treatment of LS involves topical corticosteroids. Generally, a high-potency corticosteroid such as clobetasol 0.05% cream is the therapy of choice. Treatment starts with a once-daily application and tapers down to once- or twiceweekly application. Although topical immunomodulators, such as tacrolimus and pimecrolimus, are often considered, one study6 showed that topical clobetasol was significantly more effective in treating the signs and symptoms of LS.

(approximately 5% or less2) of malignant transformation of genital LS to genital squamous cell carcinoma; therefore, these patients should be carefully educated and examined annually. The patient in our case was educated regarding the condition. She was treated with clobetasol cream, applied once daily for 4 weeks and twice weekly thereafter. At the 3-month follow-up visit, she reported resolution of the itching and her skin appeared moderately, although not completely, improved. As the condition was no longer bothersome, the patient chose to stop treatment and elected to monitor herself for any further progression. n Esther Stern, NP, is a family nurse practitioner at Advanced Dermatology & Skin Surgery, P.C., in Lakewood, N.J. References

First-line treatment of lichen sclerosus involves topical corticosteroids, such as high-potency clobetasol 0.05% cream.

1. Lopez RE, Troutman DL, Hossler EW. Plantar lichen sclerosus et ­atrophicus. J Am Acad Dermatol. 2013;68(Suppl 1):AB57. 2. James WD, Berger TG, Elston DM. Epidermal nevi, neoplasms, and cysts. In: James WD, Berger TG, Elston DM, eds. Andrews’ Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia, PA: Saunders-Elsevier; 2011. 3. Paller AS, Mancini AJ. Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence. 4th ed. Philadelphia, PA: Elsevier Saunders; 2011. 4. Makaron T, Viscomi B, Matayoshi L, Michalany N, Petri V. Genital lichen sclerosus et atrophicus in childhood treated by tacrolimus. J Am Acad Dermatol. 2009;60(Suppl 1):AB151. 5. Lacarrubba F, Pellacani G, Verzì AE, Pippione M, Micali G. Extragenital lichen sclerosus: clinical, dermoscopic, confocal microscopy, and histologic correlations. J Am Acad Dermatol. 2015;72(1 Suppl):S50-S52. 6. Funaro D, Lovett A, Leroux N, Powell J. A double-blind, randomized prospective study evaluating topical clobetasol propionate 0.05% versus topical tacrolimus 0.1% in patients with vulvar lichen sclerosus. J Am Acad Dermatol. 2014;71:84-91.

“Anyone here named Hippity?” 52 THE CLINICAL ADVISOR • MAY 2017 •

© The New Yorker Collection 2017 from All Rights Reserved.

Intralesional corticosteroids should be considered in appropriate cases. Resistant cases may respond to topical tretinoin, oral isotretinoin, or photodynamic therapy. Surgical treatment is reserved for severe cases with scarring. Asymptomatic extragenital cases may not require treatment, as the skin appearance frequently does not improve, even with topical steroid use. In addition, it is important to note that most cases of LS in the pediatric population resolve spontaneously during puberty. Patients using potent topical steroids should be monitored closely for signs of skin atrophy. There is an increased risk

Dermatologic Look-Alikes Blister-like lesion on the finger ESTHER STERN, NP



A 64-year-old woman presents with a lesion on her finger. It appeared 3 months earlier and is occasionally tender at times. At one point, she observed a thick mucus-like substance draining from the lesion. Physical examination reveals a translucent 6-mm nodule with surrounding erythema over the distal interphalangeal joint of the left fifth finger. In addition, there is a corresponding thin, vertical depression of the nail plate.

A 76-year-old woman presents with a new blister-like bubble on her middle finger. She notes that it appeared 2 weeks earlier and that it was slightly sore and moderately itchy. Other than hypertension and hypothyroidism, the patient’s medical history is unremarkable. Physical examination reveals a cystic papule with superficial umbilication over the lateral aspect of the right third middle finger. • THE CLINICAL ADVISOR • MAY 2017 53

Dermatologic Look-Alikes CASE #1

Digital mucous cyst

Digital mucous cyst, also known as a myxoid cyst, is a benign tumor of the digits, representing a focal accumulation of mucin. Although these cysts usually occur on the fingers, occurrences on the toes have been reported. Digital mucous cysts present throughout adulthood; frequency is highest in the sixth and seventh decades of life. Women are affected at a significantly higher rate than men.1 The etiology of digital mucous cysts is unknown. Although some of these cysts are associated with degenerative changes in the involved joint, with communication between the cyst and overlying joint space, other cysts are independent and are associated with a metabolic derangement of fibroblasts and increased production of hyaluronic acid.2 Radiologic studies often reveal osteoarthritis of the adjacent joint in association with myxoid cysts.3 In addition, trauma to the area may be a risk factor for cyst formation. Clinically, a digital mucous cyst appears as a solitary, soft, 5- to 7-mm translucent or white dome-shaped nodule. The lesion is filled with a thick, clear, viscous fluid that can be expressed with a small incision, although occasionally the cyst drains spontaneously. The dorsal aspect of the distal finger is the most common site of presentation, specifically over the distal interphalangeal joint or at the proximal nail fold. Often, there is a vertical depression in the corresponding area of the nail plate, which results from pressure of the lesion on the underlying nail matrix. A subungual myxoid cyst is an uncommon variant of the typical myxoid cyst. It develops below the nail plate, disturbing the limited submatrix space. Clinically, a subungual myxoid cyst presents with a discolored lunula, increased transverse curvature of the nail plate, and, sometimes, impaired nail integrity.4 Digital mucous cysts must be differentiated from similarappearing lesions, such as an epidermal cyst, fibrokeratoma, rheumatoid nodule, or Heberden node. Malignancy, such as basal cell carcinoma, squamous cell carcinoma, and melanoma, must also be ruled out. Diagnosis is usually clinical, and incision of the lesion with resulting mucoid drainage assists in confirming the correct diagnosis. Imaging can play a role in diagnosis, particularly

if surgical treatment is considered. Ultrasound study results reveal a hypoechoic rounded mass with a visible tapering margin representing the neck of the cyst. Magnetic resonance imaging is excellent to study the soft tissue cyst structures. Skin biopsy results demonstrate a pseudocyst with a fibrous capsule. There is no true cyst wall. A poorly defined mass of collagen or myxoid stroma is associated with interspersed stellate or spindle-shaped fibroblasts.5 Special mucin stain techniques, such as colloidal iron and Alcian blue, will reveal the mucin. Myxoid cysts are often asymptomatic, and no treatment is needed; however, some patients report associated pain and tenderness and request management. There are several simple treatments that can be performed in an office setting, but these are often associated with higher rates of recurrence. Repeated needling involves puncturing the lesion,

Myxoid cysts are often asymptomatic, and no treatment is needed; however, some patients report pain and tenderness. draining the gelatinous contents, and applying an occlusive pressure bandage. This is repeated on several occasions until the cyst ceases to recur. Aspiration and injection refers to drainage of the cyst followed by intralesional injection of triamcinolone acetonide. Cryotherapy with liquid nitrogen can be performed with a 15- to 30-second freeze time after unroofing the cyst. However, this procedure is often associated with more pain and scarring. Several surgical treatments are available; some, particularly more aggressive techniques, are associated with nail deformity, joint stiffness, loss of motion, and higher risk of infection. One surgical technique, which involves a skin flap designed to include tissue from the undersurface of the cyst and the tissues between the joint and the cyst and which does not require excision or osteophyte removal, boasts a 92% success rate.6 Another small study proposed intralesional photodynamic therapy with injection of 5-aminolevulinic acid and subsequent laser radiation.7 In cases of benign neglect, no further follow-up is needed. Surgical patients require close observation to prevent postoperative complications. The patient in Case 1 was educated regarding the diagnosis and chose to observe the lesion, as it was asymptomatic.

54 THE CLINICAL ADVISOR â&#x20AC;˘ MAY 2017 â&#x20AC;˘

Continues on page 56

Dermatologic Look-Alikes CASE #2

Perforating collagenosis

Reactive perforating collagenosis (RPC), first described in 1967 by Mehregan et al,8 is an uncommon cutaneous condition resulting from abnormal collagen protruding through the epidermal layer of the skin. RPC is grouped with the other three major perforating diseases: elastosis perforans serpiginosa, perforating folliculitis, and Kyrle disease.9 The inherited form of the disease presents in childhood, whereas the acquired form, on which Case 2 focuses, presents in adulthood. In 1994, Faver et al10 proposed three criteria for the diagnosis of RPC: (1) histopathologic findings of elimination of necrotic basophilic collagen tissue into a cup-shaped epidermal depression; (2) clinical presentation of umbilicated papules or nodules with a central adherent keratotic plug; and (3) onset of skin lesions after age 18 years. The typical clinical presentation of RPC involves fleshcolored papules or nodules that first appear pinhead-sized and slowly expand over the course of a few weeks, reaching 4 to 6 mm. Depending on the stage of evolution, the lesion will exhibit an umbilicated surface or a central keratotic crust. These usually heal spontaneously, sometimes with scarring. In most cases, multiple lesions appear; distribution is common over the extensor surfaces of the extremities, on the dorsum of the hands, and scattered on the trunk. Lesions in a linear pattern may demonstrate the Koebner phenomenon. The precise etiology is unknown, although most cases of acquired RPC appear to involve superficial trauma to the skin, predominantly in association with pruritus and excoriation. The disrupted collagen is then transformed into foreign material and it is removed by transepithelial elimination via the inflammatory response system.11 Acquired RPC is strongly associated with diabetes and renal failure. There is a small association with hypothyroidism, hyperparathyroidism, malignancies, and liver dysfunction.12 Although the overall incidence is rare, frequency has been estimated13 to be 10% in patients with renal failure who are on hemodialysis. Age and sex distribution is equal. When multiple lesions of RPC are seen, as occurs commonly, other diagnoses to rule out include folliculitis, pityriasis lichenoides et varioliformis acuta, excoriated arthropod assault, neurodermatitis, or a disseminated vesicular disorder. When a solitary lesion appears, as in our patient’s case, other diagnoses

to consider include digital mucous or epidermal inclusion cyst, lesion of perniosis, and molluscum contagiosum. Skin biopsy is necessary for diagnosis. Histopathologic examination reveals expulsion of vertically arranged collagen fibers into an overlying keratin plug in association with a cup-shaped invagination of the epidermis and inflammatory debris. Depending on the stage of evolution, only some of these findings may be present. Additional workup should be considered to rule out other associated disorders. Renal function tests will indicate kidney health, and ferritin and complete blood count values will rule out anemia. Glucose screening is essential to exclude diabetes. Screening for malignancy should be considered if no other etiology is identified.

The typical clinical presentation of reactive perforating collagenosis involves flesh-colored papules or nodules. Most lesions heal spontaneously, possibly with scarring, but the condition is often recurrent. When pruritus is present, treatment must be aimed at relieving the itching and scratching. Often, pruritus control alone is sufficient to induce remission of the condition. Emollients, antihistamines, and topical or intralesional corticosteroid injection may offer improvement.14 Anecdotal reports have reported success with retinoids, bleomycin, doxycycline, and ultraviolet B phototherapy.10 For the patient in this case, skin biopsy results of the lesion were consistent with prurigo nodularis, with features of RPC. The patient was questioned regarding associated diseases and referred to her primary physician for further workup. The biopsied lesion healed well without any evidence of recurrence. The patient was advised to avoid scratching and to follow up if new lesions appeared. She has since been lost to follow-up. ■ Esther Stern, NP, is a family nurse practitioner at Advanced Dermatology & Skin Surgery, P.C., in Lakewood, N.J. References 1. James WD, Berger TG, Elston DM. Seborrheic dermatitis, psoriasis, recalcitrant palmoplantar eruptions, pustular dermatitis, and erythroderma. In: James WD, Berger TG, Elston DM, eds. Andrews’ Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia, PA: Saunders-Elsevier; 2011:189.


2. Paller AS, Mancini AJ. Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence. 4th ed. Philadelphia, PA: Elsevier Saunders; 2011. 3. Lin YC, Wu YH, Scher RK. Nail changes and association of osteoarthritis in digital myxoid cyst. Dermatol Surg. 2008;34:364-369. 4. de Berker D, Goettman S, Baran R. Subungual myxoid cysts: clinical manifestations and response to therapy. J Am Acad Dermatol. 2002;46:394-398. 5. Li K, Barankin B. Digital mucous cysts. J Cutan Med Surg. 2010;14:199-206. 6. Lawrence C. Skin excision and osteophyte removal is not required in the surgical treatment of digital myxoid cysts. Arch Dermatol. 2005;141:1560-1564. 7. Suárez Valladares MJ, Rodríguez Prieto MÁ. Treatment of myxoid cysts with intralesional photodynamic therapy: a case series. J Am Acad Dermatol. 2017;76:359-360. 8. Mehregan AH, Schwartz OD, Livingood CS. Reactive perforating collagenosis. Arch Dermatol. 1967;96:277-282. 9. Briggs PL, Fraga S. Reactive perforating collagenosis of diabetes mellitus.

“I could have been a big celebrity but for my fear of public speaking.”

J Am Acad Dermatol. 1995;32:521-523. 10. Faver IR, Daoud MS, Su WP. Acquired reactive perforating collagenosis: report of six cases and review of the literature. J Am Acad Dermatol. 1994;30:575-580. 11. Cohen RW, Auerbach R. Acquired reactive perforating collagenosis. J Am Acad Dermatol. 1989;20:287-289. 12. Bang SW, Kim YK, Whang KU. Acquired reactive perforating zoster. J Am Acad Dermatol. 1997;36(5 Pt 1):778-779. 13. Morton CA, Henderson IS, Jones MC, Lowe JG. Acquired perforating dermatosis in a British dialysis population. Br J Dermatol. 1996;135:671-677. 14. James WD, Berger TG, Elston DM. Diseases of the skin appendages. In: James WD, Berger TG, Elston DM, eds. Andrews’ Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia, PA: Saunders-Elsevier; 2011:774-775.

Case Study Library Check out all of our case studies in obesity, diabetes, and other important topics in primary care — along with our clinical challenges — by visiting us at: “Actually, it’s a very funny story.” • THE CLINICAL ADVISOR • MAY 2017 57

Top, Bottom: © The New Yorker Collection 2017 from All Rights Reserved. Middle: © Harley Schwardron

collagenosis: unilateral umbilicated papules along the lesions of herpes

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.



EVIDENCE-BASED PRACTICES FOR SUICIDE PREVENTION What are effective evidence-based practices for preventing suicide?—SHARON VALENTE, PhD, PMHCNS-BC, FAAN, Los Angeles

THE ACA: CLINICIANS WEIGH IN ON WHETHER TO REPEAL OR PRESERVE My concern is that while Dr Tom Price has stated that he wants to strengthen the “doctor/patient” relationship, he has shown himself to be less than supportive of including nurse practitioners (NPs) with their/our full range of practice. He is for balance billing to allow an MD to charge patients beyond the amount allowed by the insurer and to enable the provider to collect his/her chosen fee. My understanding is that Obama’s concession to the GOP members of Congress was to retain the insurance companies (whose interest is NOT in our health, but in the health of their individual bottom lines), so there will be inevitable increases in the deductibles, co-pays, and premiums while reducing the amount of the service that they cover. Unless we have a single-payer healthcare system that would allow one large entity to standardize costs across the healthcare delivery system, costs will continue to increase, and without some sort of mandate to bring more healthy persons into the insurance panels, the increased illnesses of aging baby boomers will overwhelm the system. Likewise, Dr Price’s preference for giving states “block grants” to manage their Medicaid patients would be sending us back decades and hurting our most vulnerable members of the population.

A systematic review was published by JAMA in 2005 evaluating 93 studies on suicide prevention using the following factors: physician education in depression recognition and treatment; restricting access to lethal methods; screening tools for the at-risk individual; treatment of psychiatric disorders; and responsible media reporting of suicide. Physician education and restricting access were found to have significant data to support their effectiveness. The remaining factors had mixed results and need more research (Mann JJ, Apter A, Bertolote J, et al. Suicide prevention strategies: a systematic review. JAMA. 2005;294[16]:2064-2074.)—CLAIRE O’CONNELL, MPH, PA-C (223-1) Send us your letters with questions and comments to: Advisor Forum, The Clinical Advisor, 275 7th Avenue, 10th Floor, New York, NY 10001.You may contact us by e-mail at 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.


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, MS, PA-C,

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

is an assistant professor at Thomas Jefferson University and a dermatology PA at Family Dermatology of Reading, Pa.

All in all, Dr Price’s proposal strikes me as a rather selfserving, “let them eat cake” response.—BETTE KISNER, RNCS, Boston (223-2) Our President is not taking anything away from the poor or needy. He sincerely wants better coverage and better prices. As an NP, I have laughed at those who tell me that 20 million more persons were covered by ACA. First, most of them are getting Medicaid, which has limited coverage and limited providers that will take it. Second, many of those forced to pay premiums never get to use their actual insurance, as they never meet the large deductibles. So what they have is an insurance card, not health coverage. The ACA was slapped together in haste and by those who had a narrow focus on only those it would help, not on those who would be hurt.—ROBERT EISENBART, RN, MSN, FNP, Union Grove, Wisc. (223-3) I wish there were a healthcare plan that truly focused on preventive medicine to reduce healthcare costs. I don’t know what that looks like in terms of implementation, but I try my best as a provider to discuss this at every patient visit in some way. We spend so much in ER visits and tertiary care, and we live in a culture in which many people cannot afford basic health needs, let alone have the money or means to eat a healthful meal each day. I have a love/hate relationship with the ACA, and I’m willing to listen to what the proposed healthcare plan is now. But I hope it will benefit the patients, because so far it sounds like it may not be what America needs.—AMIRA EVANS, FNP-C, Indianapolis (223-4) [Editor’s note: The preceding comments regarding the Affordable Care Act were received before House Speaker Paul Ryan withdrew an initial attempt of legislation to repeal it.]

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.

BEING FRANK ON FRANKINCENSE AND ITS ROLE IN CANCER PREVENTION It is nice to see alternative therapies being represented in a medical publication. However, I do have to comment on the article regarding frankincense [Alt Meds Update, March 2017, page 59]. The article eludes to frankincense essential oil as being a cure or preventive for some types of cancer. The antitumoral component of frankincense is boswellic acid. Boswellic acid is not found in the essential oil, but it is in the gum resin. In an article by Robert Tisserand, an essential oil expert, he states: “They are being told, in videos and blog posts, that frankincense oil contains boswellic acid—the antitumoral active ingredient in frankincense gum resin. But it doesn’t, and the simple reason is that boswellic acid is much too heavy a molecule to be volatile.” (Retrieved from: While it is true that there have been studies using frankincense essential oil in vitro, this does not equate to in vivo studies. We are a long way from that. Many of the more recent studies use the gum resin or extract. Frankincense essential oil is a wonderful anti-inflammatory. I have used it in pain blends. It is also very skin friendly and is used in many facial creams. It has immune-stimulating properties and antioxidant properties. Energetically, it supports focus and emotional healing, and it quiets the mind. Internal use of essential oils should only be done under the supervision of a person who specializes in medical aromatherapy. There are OTC forms of the resin. You can also burn the resin just like incense. Most healthcare providers are not familiar with the safe use of essential oils. Just as in nutrition, there are certified aromatherapists who can assist providers in helping their patients use essential oils safely.—THERESA A. LOHMAN, DNP, FNP-BC, CNM (ret), Maumee, Ohio (223-5) n

Claire O’Connell, MPH, PA-C,

an associate professor at the Rutgers University Physician Assistant Program, Piscataway, N.J.


Katherine Pereira, DNP, FNP,

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

Sherril Sego, FNP-C, DNP,

is an independent consultant in Kansas City, Mo. • THE CLINICAL ADVISOR • MAY 2017 61


Lab results never given to a patient


Ms D, 42, was a nurse practitioner (NP) working in a federally funded clinic in a low-income area. When she first became an NP, about 15 years prior, she had big dreams about her role in improving patients’ health. She knew right away that she wanted to work in an underserved community and began her career with great enthusiasm. Ms D had begun her current position with the clinic 10 years ago. She had been optimistic when she started, imagining that she was going to make a big difference in her patients’ lives, and sometimes she did. But after a few years, she started to feel irritable at work. She was annoyed when patients were noncompliant with their medication or did not show up for follow-up appointments. She began to feel taken advantage of — she could have taken a job in a better area or with higher pay, but she had chosen to do this. After 10 years in her job, her heart was no longer in it. Ms D functioned as a primary care provider, treating patients for a variety of conditions. She typically saw between 15 and 20 patients per day. Although she worked under the direction of a collaborating physician, she did not find it


An NP does not inform her patient about his lab results, which showed extensive kidney damage. He collapsed 2 months later. A patient’s lab results revealed extensive kidney damage, but the clinician never informed the patient about the results.


necessary to consult with him that often. Every day was starting to feel like the next, a series of patients, mostly uneducated, some barely speaking English, who did not listen to her recommendations, did not follow her advice, and did not heed her warnings. One day in the spring of 2008, a new patient came in. Mr K was a heavy-set, 28-year old, African-American man who had been referred to the clinic after a pre-employment screening revealed very high blood pressure. At the clinic, Mr K’s blood pressure was 210/170 mm Hg. Ms D gave the patient clonidine in the office, which immediately lowered his blood pressure to 200/130 mm Hg. “You need to watch what you eat,” she told him. She ordered routine lab work, noted “hypertension and obesity” in his file, and gave him some blood pressure Continues on page 64

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.

ClinAd CMF [NP 2016] 4.18.16.qxp_ClinAd[PA]CMF 3.16.10 4/18/16 11:49 AM Page 1

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LEGAL ADVISOR medication to take home. She told him to come back in a week. When he did not return, Ms D was not surprised. But two years later, Mr K showed up again. He had not taken any blood pressure medication within the last 2 years. Again, his blood pressure was flagged during a screening at work, and he returned to the clinic. Ms D quietly wrote “noncompliant” in his file. Mr K’s blood pressure was 240/150 mm Hg. Ms D gave the patient clonidine, which lowered his blood pressure to 200/110 mm Hg and wrote him a prescription for hypertension medication. She instructed the patient to return in a week, but he did not return for three weeks.

A judge ruled in favor of the plaintiff in that the clinician had deviated from the standard of care in numerous ways. Ms D saw the patient 10 times between July 2010 and October 2012. His blood pressure was consistently extremely high. The patient and clinician occasionally argued about his medication. Periodically, he would stop taking one of his medications because he thought it was not working or was causing side effects. Ms D noted in his file that his hypertension was “uncontrolled” and that he was noncompliant. Mr K’s original lab work was done in 2008. Ms D did not order any new lab work until 2011, but she failed to look at the results, which never made it into the patient’s file. In 2012, Ms D ordered lab tests and reviewed the results a few days later. They showed extensive kidney damage. Again, Ms D never told the patient about his results. Two months later, Mr K collapsed at work and was hospitalized. He was diagnosed with stage V chronic kidney disease due to poorly controlled hypertension. For the next three years, Mr K required hemodialysis until he was able to receive a kidney transplant. After his years of medical treatment, Mr K consulted with a plaintiff’s attorney who advised Mr K to sue. “The clinic is federally funded, so we will actually be suing the United States in Federal District Court,” the attorney stated. Although Ms D was not being individually sued, the lawsuit was based on her negligence, so she spoke to the defense attorney. After reviewing all the information, the patient’s medical records, and the reports from the medical experts, the attorney looked grim. “Honestly, I don’t think we have a great case here, but our best argument is that Mr K contributed to his own kidney disease by being noncompliant,” he said. The case went to trial in front of a federal judge.

Legal background

At trial, Mr K testified that he was never told that there was a connection between high blood pressure and kidney disease, that he was not given any patient education, and that he had not known there was a risk of kidney disease if he did not take his medication daily (even when he was feeling fine.) He thought that if he felt okay, it meant that he did not have to take his medication. Ms D testified that she had provided patient education, but the notes in the chart included nothing other than a 2008 notation of “healthy eating habits.” The judge believed the plaintiff’s medical experts who testified that Ms D had deviated from the standard of care in numerous ways, including the failure to: provide proper education, recommend home blood pressure monitoring, order labs or respond to lab results, and consult the collaborating physician or refer the patient to a specialist. The experts were also critical of Ms D’s decision to give Mr K clonidine in the office on multiple occasions. The judge dismissed the defense’s argument that Mr K contributed to his own medical condition. Ultimately, the court awarded more than $29 million in damages to Mr K. Protecting yourself

Ms D allowed burnout to affect her work and to cause her to make assumptions about her patient. What care should she have given Mr K? The standard of care required: • Patient education and consistent re-education, including: basic information about hypertension, risks of uncontrolled hypertension, the fact that Mr K had an increased risk of kidney damage from uncontrolled hypertension because he was a young African-American male, lifestyle modifications, the importance of taking medications daily, and attending follow-up appointments • Recommendation and instruction for home blood pressure monitoring • Ordering lab tests at least 1 to 2 times a year to monitor for organ damage • Appropriate action in response to lab results • Consultation with the collaborating physician if there is difficulty controlling blood pressure • Referral to a nephrologist when she was unable to control the patient’s blood pressure. In addition, Ms D failed to appropriately document information in the patient’s file. n Ms Latner, a former criminal defense attorney, is a freelance medical writer in Port Washington, N.Y.



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.



Most often known as sprouts on a deli sandwich or a large bale of dried plant clippings to be used as food for livestock, alfalfa is increasingly being studied for a wide range of uses in human alternative therapies. Medicago sativa (alfalfa) leaves contain high concentrations of flavonoids and other phenols. These compounds exert potent antioxidant actions as free radical scavengers and inhibitors of nitric oxide release.1 The list of proposed medicinal uses of alfalfa range from the treatment of arthritis to upset stomach.

Background Alfalfa is a perennial flowering plant and a member of the pea family.1 In its peak growing season, the slender branching stems reach a height of 3 feet with tiny green leaves and small violet flowers.1 In early literature, the Greek herbalist Dioscorides wrote about the nutritional use of alfalfa in the first century AD.2 Our common name for alfalfa is a derivation of the Arabic term meaning ‘father of all foods,’ due to its high concentration of protein and vitamins.3 Alfalfa is thought to have originated in South and Central Asia but now grows in many zones around the world.4 It has been documented in Turkish writings around 1300 BC, Persian ruins from more than 6,000 years ago, and extensively in Chinese medicine.5

Science Reports of numerous in vivo and small animal studies exploring the benefits of alfalfa. One laboratory study of rats fed

diets high in fat found that alfalfa supplementation resulted in greater excretion of cholesterol and bile acids.6 The experimental group of rats excreted significantly more cholesterol and bile acids in their feces than the control group.6 The mechanism of this action was believed to be related to the way in which alfalfa affects the gastric absorption and hepatic storage of cholesterol.6,7 Another area of research that involves alfalfa is in the development of neuroprotective agents. One laboratory study using mice found reduced initial cerebral infarction size with alfalfa pre-treatment.8 Cerebral infarctions were induced in both the control and treatment groups.8 The test group was pre-treated with an extract of Medicago sativa. The mouse brains were then evaluated for size of infarction as well as response to reperfusion and the post-infarction release of specific pathogenic oxidative substances. The mice that were pre-treated with alfalfa extract showed not only reduced initial infarction size but also greater recovery after reperfusion.8 • THE CLINICAL ADVISOR • MAY 2017 65

ALTERNATIVE MEDS UPDATE Other literature suggests a possible use for alfalfa in reducing serum glucose in diabetic subjects. One of the mechanisms involved in diabetes and elevated glucose is the decrease in cellular uptake of serum glucose. This defect in metabolism appears to involve free-radicalmediated pathology. In a review of the chemical and pharmacologic uses of alfalfa, researchers claimed that there was no significant impact of alfalfa on serum glucose levels.9 Another study of human red cells from healthy volunteers showed a small but statistically insignificant decrease in the glycosylation of hemoglobin.10 This information suggests alfalfa might be of some use as adjunctive therapy in patients considered ‘pre-diabetic.’

Safety, interactions, side effects Despite the wealth of valuable nutrients and metabolic compounds, there is still substantial concern about the safety of alfalfa use.11 Long-term use of alfalfa, especially the seeds, has an immunestimulating effect and can worsen autoimmune conditions such as lupus and multiple sclerosis. Weak estrogenic effects make use of alfalfa in patients with risks for breast or uterine cancer inadvisable. Safety has not been established for use in pregnant or nursing mothers or in infants. Alfalfa contains a high concentration of vitamin K, so patients currently taking any anticoagulant medication should seek their healthcare provider’s input before taking any alfalfa product. Also, with the known mild hypoglycemic effect, patients already taking medication for diabetes should be cautioned regarding the potential for unintentional drops in blood glucose.

Summary Although alfalfa does have great potential for a wide variety of conditions, there are safer, better studied herbal supplements that are widely available. Until such time as more human trials showing safety and efficacy are conducted, healthcare providers should not recommend use of this supplement. However, the occasional deli sandwich with alfalfa sprouts should not cause harm. n Alfalfa can be found in many forms, including fresh sprouts.

Long-term use of alfalfa has an immunestimulating effect and can worsen autoimmune conditions such as lupus and multiple sclerosis.

How supplied, dose, cost

References 1. Karimi E, Oskoueian E, Oskoueian A, Omidvar V, Hendra R, Nazeran H. Insight into the functional and medicinal properties of Medicago sativa (alfalfa) leaves extract. Journal of Medicinal Plants Research. 2013;7:290-297. 2. Petrovska BB. Historical review of medicinal plants’ usage. Pharmacogn Rev. 2012;6:1-5. 3. Alfalfa. Health One: Advanced Internal Medicine Physician Care website. Alfalfa. Updated December 15, 2015. Accessed April 12, 2017. 4. Jones T. Alfalfa. Accessed April 12, 2017. 5. Group E. Benefits of alfalfa leaf. Published March 22, 2013. Updated November 24, 2015. Accessed April 12, 2017. 6. Yuan D, Shi Y, Wan C, Guo R, Wang J. Effect of alfalfa saponins on cholesterol metabolism and its molecular mechanism. Acta Practaculturae Sinica. 2013;22(5): 294–301. 7. Shi Y, Guo R, Wang X, et al. The regulation of alfalfa saponin extract on key genes involved in hepatic cholesterol metabolism in hyperlipidemic rats. PLoS ONE. 2014;9:e88282. 8. Bora KS, Sharma A. Evaluation of antioxidant and cerebroprotective effect of Medicago sativa Linn. against ischemia and reperfusion insult. Evid Based Complement Alternat Med. 2011;2011:792167. 9. Duggal J, Khatri P, Tiwari BN, Patel R. Chemo-


2011;2:50-53. 10. Hosseini M, Asgary S, Najafi S. Inhibitory potential of pure isoflavonoids, red clover, and alfalfa extracts on hemoglobin glycosylation. ARYA Atheroscler. 2015;11:133-138. 11. US National Library of Medicine. Alfalfa. https:// Reviewed February 12, 2015. Accessed April 12, 2017.


pharmacological aspects of alfalfa: A review. J Adv Sci Res.

For those without contraindications who wish to use alfalfa as a supplement, a typical recommended dose is 5 to 10 grams steeped as a tea and used three times daily.11 Alfalfa can be found in many forms from seeds and fresh sprouts to dried leaves and powder. Alfalfa tea is a popular form of the plant. Dried leaves for tea cost from $10 to $15 per pound.

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May 2017 Clinical Advisor  
May 2017 Clinical Advisor