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■■Fellowships for APPs ■■Vinpocetine, Fetal Harm ■■Abortion Law Expands to Include APPs CONFERENCE COVERAGE


A Case of Illegal Detention


Freely Moveable Cyst on the Arm


Small, Friable Lesions





Chronic Obstructive Pulmonary Disease: Fighting for Each Breath The most common cause of COPD is a history of tobacco use.

Director Laura Kusminsky, PA-C Associate editor Madeline Morr Assistant editor Rita Aghjayan Production editor Kim Daigneau Group creative director, medical communications Jennifer Dvoretz Senior production manager Krassi Varbanov Director of audience insights Paul Silver National sales manager Alison McCauley, 973.224.6414 alison.mccauley @ Associate account manager Michael Deverin, 732.343.4921 Publisher Kathleen Hiltz, 201.774.1078 Vice president, content, medical communications Kathleen Walsh Tulley General manager, medical communications Jim Burke, RPh President, medical communications Michael Graziani 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/licensing, email or call 800.290.5460. Persons appearing in photographs in “Newsline,” “The Legal Advisor,” and “Features” 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 22, Number 7. Published 10 times a year, by Haymarket Media, Inc., 275 7th Avenue, 10th Floor, New York, NY 10001.

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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 the color of the affected area was normal, the skin CLINICAL PEARLS felt quite thick and inflexible. These skin changes stopped abruptly at the collar line, below which POISON IVY PREVENTION the skin was entirely normal. Poison ivy season is starting! I recommend that Abundant evidence of sun damage — includ- people take an old pair of knee-high tube socks ing weathering, telangiectasias, solar lentiginosis, and cut off the foot part above the heel. Pull the and numerous actinic keratoses on prominent socks over the arms up to the start of their sleeve areas of his cheeks and ears — was noted. Similar (assuming they are wearing a T-shirt) and tuck changes were noted on the dorsa of both hands into gloves. Use the socks to protect arms when but were not present on his arms and trunk working in the yard or other high-risk poison because he wore long-sleeved shirts when in the ivy areas. They can be rolled off the arms and sun. Although he had worn a wide-brimmed hat thrown away, or washed and re-used. I remind while in the sun during his adult life, he had never people to always wear gloves, and to remove worn anything, such as a bandana, on his neck. the gloves before touching anything, including Always wear The posterior neck is especially susceptible door handles. This significantly reduces the gloves to to the effects of the sun, evidence of which fre- exposure area of skin to poison ivy. —JUDITH protect the quently manifests as it did in this patient. This MCINTOSH, MSN, Kokomo, Indiana skin from condition is called cutis rhomboidalis nuchae weath- VERRUCA VULGARIS TREATMENT exposure to (CRN), which represents thickening and weath ering of the epidermis as well as solar elastosis I always recommend candida albicans skin anti- poison ivy, and of the underlying dermis caused by the sun. gen test injections for patients who are not remove them Although this condition is clear evidence of responding well to liquid nitrogen +/- paring for before touching chronic overexposure to the sun, CRN has no verruca vulgaris. A 0.1-mg injection every month anything. malignant potential, and treatment is neither for about 3 months creates an immune response required nor does it exist. against the warts. I have seen resolution of some Besides being common, CRN is unique in its recalcitrant cases that seemed most impossible! presentation, as well as in the patient population —SARAH LUP, PA-C, Chicago, Illinois it affects (eg, older patients with sun damage confined to the posterior neck), so the differen- RETHINKING PRESCRIBING tial is quite narrow. Punch biopsy would resolve DICLEGIS Diclegis is the only FDA-approved prescription any confusion. CRN puts this patient at higher risk for the medication for nausea and vomiting of pregdevelopmentThe of skin caused by sun expo- nancy that is classified as Category A (safe for se cancers are lette rssquamous sure, such asand basal cell carcinoma, cell mom and baby). Before writing a prescription, from prac successe titioconsider ners arou carcinoma, melanoma, and s,others. the price tag. Diclegis with a coupon obseThis nd the coun rvatpatient ions, andcosts approximately and others with similar histories require regular $345 try for 60 tablets. The pearls with who their to share their skin checks by a qualified dermatology provider most common dosagecolle is 2 tablets/dwan but tcan agues. We clinical chall at least once a year. Although this patient would be more. Some patients may obtain insurance invite you enges to participa be advised to protect himself from the sun, this coverage for this medication, but it will likely te. will do little to ward off any future skin cancers still cost something. Let’s break down Diclegis that will have been caused by sun overexposure CONSUL into its 2 active ingredients: doxylamine sucTAT occurring decades earlier. Application of sun- cinate IONand S pyridoxine hydrochloride (vitamin screen to his neck would prevent IRO worsening of B 6). Unless you are writing a prescription for N PILL 2. Cohen SM, Kwo PY, Lim, his CRN. a celebrity, recommend that your patients ON LIVE S AND THEIR JK. ACG clinical of abnorm Send us R ENZ al liver chemis ECT guideline: your purchase over-the-counter doxylamine YMESinsteadEFF Can takin evaluat tries. Am J Gastroe 3. Iron. ion g iron pills nterol. 2017;1 al Institute Reference letters with succinate and vitamin B 6 to take Nation at night elevate liver —AGNES 12:18-35. of Health ques website. https:// enzymes? MURPHY, tm. Access for nausea. —AMBER PA-C, Bolognia JL, Jorizzo JL,tions Rapini RP. Dermatology. 1st ed. NewDEW, PCA and , Americus, livertox. ed April 3, commen 2019. Georgia Birmingham, Michigan York: Mosby, 2003;1380-1381. ts to: Liver enzym es Advisor Forum aspartate aminosuch as alanine amino , CASE FILE transfe The Clinica l Advisor, phatase are transferase (AST), and rase (ALT), S • THE CLINICAL ADVISOR • MAY 2019 45 275 7th Aven markers of alkaline phosfunction, and hepat ue, 10th CUTIS RHO should be referre ic injury, not hepat Floor, New Albumin, MBO ic York, d to as liver bilirubin, and chemistries. Contributed by Joe Monr IDALIS NY 10001 measures of prothrombin .You oe, MPAS, hepatocellu time are direct A 78-year-old may conta PA-C lar appropriately ct us heavily lined man presented characterized synthetic function and with thick e-mail at edito by skin on enzymes may are as “liver functio r@ be abnormal n tests.” Liver been present for an his posterior neck ened, clinicaladvis liver diseas that had even in patien indet Although e. The differe ts without the striking erminate period of Letters are ntial for elevat broad with time. skin chang tomatic, edited many be further define potential causative ed enzymes is insiste they were concerning es were asympfor length factors and and d that he be to his relativ d by the patien should risk factors. 1 clarity. The seen es who t’s by a medical histor The Clinical y and the patient had spent dermatology provider. Almost all Advisor’s policy nearl sun, farmi medications ng, ranching, y his whole life small risk of are associated is to print to his in elevat fishing, and the hepatotoxic 2 ed liver chemistries with at least a a histo property in rural tending author’s name Okla ity. Oral with ry homa or of witho iron skin cance . replacement with the letter r and claim He denied doses has little supplementation at typicaut good health. ed to be . liver or serum or No anony in The skin on enzyme elevati no adverse effects on l mous the patien or overdoses, the ons. However, contributio it in high doses lined and thickened t’s nuchal area was ns will of iron poison can cause acute hepato heavily . The multiple overla toxicity as a ing. be accepted. pping rhom lines joined to form result of ferrous sulfate Toxicity occurs after boidal shape ingestion of (approximat ≥3 g s. toxicity with Altho ely 10 tablets ugh aminotransf ). Severe the upper limit erases greate r overdoses and of normal typically than 25 times occurs with high initial larger serum iron dL). Mild levels to usually self-limmoderate cases of iron (>1000 ug/ whereas severe iting and resolve with poisoning are suppo KUSMIN cases become fatal rapidl 3 rtive care, SKY, PA-C y. —LAURA Referenc es

Advisor F


Write us today.

1. Approach to the patient with abnorm and functio n tests. UptoD al liver bioche mical websit e. https://www. /contents/app roach-to-theabnormal-liver patient-with-biochemical -and-functionApril 2, 2019. tests. Access ed


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Copyright © 2019 • THE CLINICAL ADVISOR • JULY/AUGUST 2019 1

CONTENTS J U LY / A U G U S T 2 0 1 9


Newsline ■■APP Fellowships in Hospital Medicine Increasing ■■Dietary Supplement Ingredient May Cause Miscarriage ■■Maine Abortion Law Authorizes APPs to Administer Procedure

10 AANP Conference Roundup 7 More Fellowships for APPs

12 AAPA Conference Roundup

FEATURE 13 Chronic Obstructive Pulmonary Disease: Fighting for Each Breath Patients with COPD present with symptoms of chronic bronchitis, emphysema, and asthma.

10 Exploring the Gut-Brain Connection


Web Roundup A summary of our most recent opinion, news, and multimedia content from

23 Dermatology Clinic ■■Freely Moveable Cyst on the Arm ■■Yellow, Brittle Toenails in a Man

27 Small, Friable Lesions

33 A Case of Illegal Detention

27 Dermatologic Look-Alikes Small, Friable Lesions 33 Legal Advisor A Case of Illegal Detention

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ACG Guideline Update for Crohn Disease

Tau and Amyloid Deposition in Former NFL Players Detecting chronic traumatic encephalopathy in the brains of living individuals could improve our understanding of the disease and inform research.

Newly supported therapies for Crohn disease in adults outlined in updated guidelines may be associated with rare and harmful adverse events.

USPSTF: Guidance for PrEP in Persons at High Risk for HIV The guidance provides useful recommendations for which patients should be considered for PrEP according to demographic group and risk.

Prepregnancy Obesity Linked to Child Obesity In a systematic review of 79 studies, researchers assessed the association between maternal preconception body mass index and the risk for obesity in offspring.

Mood Instability Linked to Stress, Decreased QoL in Bipolar Disorder Patients used a smartphone-based selfmonitoring system that captured daily mood via a 6-point self-evaluation scale.

AHA Guidelines for Prevention, Management of CVD in HIV A scientific statement from the American Heart Association was published in Circulation, with the purpose of providing a thorough review of available evidence on HIVassociated cardiovascular disease.


Official Blog of The Clinical Advisor Sharon M. O’Brien, MPAS, PA-C Managing Controlled Substances in Everyday Prescribing The landscape of prescribing practices is constantly evolving, and clinicians must stay informed to ensure responsible prescribing of controlled substances.


Brady Pregerson, MD Lesions on the Finger and Buttocks of a Boy A 4-year-old boy is brought to the emergency department for a cough. His mother states that he also has had a rash on his buttocks and finger for many weeks. Physical examination reveals rhinorrhea and approximately 15 small papules clustered together on the buttocks that are identical in size and shape; one lesion is also noted on the patient’s middle finger. See the full case at:




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. Check out some of our latest cases below!


Asymptomatic Growth on the Eyelid A 57-year-old woman presents for removal of a growth on her right eyelid. The lesion was first noted several months ago and has been slowly increasing in size. Examination reveals a 0.5-cm hyperpigmented papule with a slightly crusted center. No similar lesions are noted elsewhere. CAN YOU DIAGNOSE THIS CONDITION?

• • • •

Pigmented basal cell Hidrocystoma Inverted follicular keratosis Merkel cell carcinoma

● See the full case at


In partnership with

Finger Dislocation Following a Tennis Injury A 45-year-old man presents to the office after sustaining a dislocation in his right small finger, which was reduced and splinted in the emergency department one week ago. He was playing tennis when he fell and struck the fi nger. Anteroposterior and lateral radiographs of the right hand show a proximal interphalangeal (PIP) joint dislocation. WHICH IS THE NEXT BEST STEP IN TREATMENT?

• • • •

Observation Buddy taping with early motion Immobilization in a cast Surgical repair of the volar plate

● See the full case at


Journal of Orthopedics for Physician Assistants



The majority of fellows have been out of NP or PA school for <1 year.

APP Fellowships in Hospital Medicine Increasing HOSPITAL medicine fellowship programs to further the clinical training and foster retention of advanced practice providers (APPs) — including nurse practitioners (NPs) and physician assistants (PAs) — in the hospital system are becoming more prevalent as APPs continue to become an increasingly larger part of the healthcare workforce, according to research findings published in the Journal of Hospital Medicine. However, little is known about how these programs are structured. To describe the characteristics of the existing APP fellowships, researchers distributed an online survey to program directors of all adult and pediatric fellowship programs in hospital medicine. The survey tool was influenced by prior validated surveys of postgraduate medical fellowships and consisted of 25 multiple choice questions on fellowship and learner characteristics, program rationales, curricula, and fellow assessment methods.

A total of 11 fellowships comprising 10 adult programs and 1 pediatric program were identified, and a 91% response rate from program directors was obtained. The majority of programs had been in existence for ≤5 years, with 80% in existence for 1 year. A total of 60% of fellowships enroll 2 to 4 fellows per year, while 40% enroll ≥5. Salaries range from $55,000 to >$70,000, with half of the programs paying >$65,000. A total of 80% of fellows are aged 26 to 30 years, and 90% have been out of NP or PA school for <1 year. All programs reported that training and retaining applicants is the main driver for developing a fellowship, and 50% offer financial incentives for retention on successful completion of the program. In the last 5 years, 89% of graduates were invited to take a full-time position after program completion. Other rationales for program development included building an interprofessional team (50%),

managing patient volume (30%), and reducing overhead (20%). Of the 9 adult programs, 67% teach to the Society of Hospital Medicine (SHM) core competencies and 33% send the fellows to SHM NP/PA Boot Camp. Of the 9 programs with active physician residencies, 6 offer shared educational experiences for the medical residents and APPs. However, differences in clinical rotations between the programs were identified. General hospital medicine is required in all adult fellowships, but no other clinical rotation is universally required.The majority (80%) of programs offer at least 1 elective. Six programs reported mandatory rotations outside of general medicine; the most common were neurology or the stroke service. Differences were also found in educational experiences and learning formats; 90% of programs offer or require fellow presentations, journal clubs, reading assignments, or scholarly projects. Presentations and journal club attendance are required in more than half of programs, but reading assignments and scholarly projects are rarely required. Each program has a unique method of fellow assessment, with 90% using more than 1 method. Faculty reviews are the most commonly used form of assessment and are conducted in all rotations in 80% of fellowships. Both self-assessment exercises and written examinations are used in some rotations by the majority of programs, and capstone projects are required in 30% of programs. “Despite their similarities, fellowships have striking variability in their methods of teaching and assessing their learners,” the investigators concluded.“Best practices have yet to be identified, and further study is required to determine how to standardize curricula across the board.” • THE CLINICAL ADVISOR • JULY/AUGUST 2019 7

Newsline Dietary Supplement Ingredient May Cause Miscarriage Vinpocetine, an ingredient found in some dietary supplements, may be associated with adverse reproductive effects, according to a safety communication from the US Food and Drug Administration (FDA). The warning comes after the Agency reviewed a report by the National Institute of Health’s (NIH) National Toxicology Program, which evaluated the “developmental and/or reproductive toxicity of selected substances in laboratory animals.” Results showed vinopocetine decreased fetal weight and increased the chance for miscarriage in pregnant animals. As the blood levels of vinpocetine measured in the animals were similar to those reported in individuals who consumed a single dose of vinpocetine, it can be inferred that the risks would apply to humans as well.

Vinpocetine is derived from Vinca minor, also known as periwinkle.

Dietary supplements containing vinpocetine have been marketed for improving memory, focus, and energy, as well as for promoting weight loss. Because products containing vinpocetine are sold as dietary supplements,

they are not reviewed by the FDA under the same standards that apply to drug products. The number of vinpocetine products has grown recently, leading the FDA to expedite an evaluation (started in 2016) of whether vinpocetine is legal for sale as a dietary supplement in the United States (in some countries it is regulated as a prescription drug). Earlier this year, the FDA created the Dietary Supplement Ingredient Advisory List to alert the public of unlawful ingredients in supplements. Based on recent findings, the Agency is advising pregnant women and women who may become pregnant not to take vinpocetine. In addition, companies marketing these products are being advised to evaluate product labeling to ensure safety information is clearly stated regarding the risks to women of child-bearing age.

Maine Abortion Law Authorizes APPs to Administer Procedure stated Governor Mills.“These health care professionals are trained in family planning, counseling, and abortion procedures, the overwhelming majority of which are completed without complications.” Maine will join the list of states — including New Hampshire, Vermont, California, and NewYork — in ­permitting

assistants to perform abortion services. “This law will allow women to receive the care they need from a provider they trust and eliminate the financial and logistical hurdles they face today,” said Speaker Gideon. The executive director of the Christian Civic League of Maine, Carroll Conley,

Maine will join the list of states — including New Hampshire, Vermont, California, and New York — in permitting nurse practitioners and physician assistants to perform abortions. nurse practitioners and physician assistants to perform abortions. Numerous other organizations, such as the World Health Organization and the American College of Obstetricians and Gynecologists, support the authorization of nurse practitioners and physician


expressed concerns about whether these providers will be able to undergo the necessary training by September to administer these procedures and whether patients living in rural areas may be compromised if they experience medical complications during an abortion.


A MAINE LAW signed on June 10, 2019 will increase access to abortions by allowing healthcare professionals other than physicians, such as nurse practitioners and physician assistants, to perform the procedure, according to an article in the New York Times. Signed by Democratic Governor Janet Mills and sponsored by Speaker of the House Sara Gideon, the law will go into effect in September and will permit advanced practice providers to perform abortions using oral medication or inclinic aspiration procedures. “Allowing qualified and licensed medical professionals to perform abortions will ensure that Maine women, especially those in rural areas, are able to access critical reproductive health care services when and where they need them from qualified providers they know and trust,”

Conference Roundup AANP 2019


American Association of Nurse Practitioners Annual Meeting Indianapolis, Indiana

THE AMERICAN Association of Nurse Practitioners (AANP) held their 2019 Annual Meeting at the Indiana Convention Center in Indianapolis, Indiana, from June 18 to June 23. The association hosted approximately 5000 NPs and students and showcased more than 400 sessions and workshops delivered by leading NPs, offered 38 contact hours of continuing education, and provided networking opportunities for all attendees. The official kickoff session was held in the grand hall of the convention center on June 19. Members gathered as a community of NPs who were welcomed formally by CEO David Hebert, JD. Mr Hebert introduced the 2019 keynote speaker, Elizabeth Smart, who captivated the audience by sharing her story of perseverance after she was abducted as a child. Her speech conveyed a message of hope to the audience and emphasized the importance of not allowing your past to dictate your future. In an early morning session the following day, Theresa Mallick-Searle, MS, ANP-BC, from the Division of Pain Medicine at Stanford Health Care, explored the prevalent role that the microbiome plays in pain and mood by explaining the gut-brain connection. She included practical ways for NPs to treat patients who present with an imbalanced microbiome. Dr Leslie Davis gave a seminar on managing treatmentresistant hypertension, in which she described treatment regimens specifically for patients in rural areas similar to the

one where she practices. Because patients with treatment-resistant hypertension may present with additional comorbidities, NPs should stress lifestyle modifications in addition to appropriate medications. In a robust discussion on benzodiazepine prescribing practices for patients with anxiety, Dr Cathleen Crowley-Koschnitzki discussed the different types of anxiety and the correct benzodiazepine that should be prescribed for a specific condition. She stressed that in some cases, patients may not need a benzodiazepine; rather, cognitive-based therapy, a selective serotonin reuptake inhibitor, or a beta-blocker may be more appropriate treatment options. On Friday afternoon, Drs Ryan Mallo and Vanessa Pomarico-Denino spoke about caring for and treating LGBTQI

The microbiome has been found to play an important role in pain and mood.


patients in primary care, providing the tools the NP needs to understand the unique and evolving health needs specific to this community. As more patients move away from identifying as strictly male or female, NPs need to tailor their approach to care by using appropriate communication and language, adhering to guideline-based screening and immunizations — specifically for sexually transmitted infections — and asking questions about intimate partner violence. Legislation was an important topic at the meeting, and NPs were urged to show their support for ongoing legislation to improve access to care. Currently, The Home Health Care Planning Improvement Act has 68 cosponsors in the House of Representatives and 29 in the United States Senate.This act will authorize NPs to certify their patients’ eligibility for home health services. Other legislation currently being reviewed in Washington, DC, is The Promoting Access to Diabetic Shoes Act and the Accountable Care Organizations Assignment Improvement Act, both of which are gaining support from state and federal officials. “Keeping Health Care on Track” was the theme of the 2019 meeting, with the goal of guiding NPs on the path to career success. NPs left Indianapolis with practice pearls, tips, and tricks that will allow them to do just that. The 2020 meeting, which will be held next June in New Orleans, Louisiana, will continue to foster the growth of NPs and ensure that they are destined for success. ■

Conference Roundup AAPA 2019


American Academy of Physician Assistants Annual Meeting Denver, Colorado

THE 2019 AMERICAN Academy of Physician Assistants (AAPA) Annual Meeting, held May 18-22 in Denver, Colorado, hosted more than 7000 PAs and students at the Colorado Convention Center. Up to 275 hours of continuing medical education were available, and attendees were able to participate in meetings for the House of Delegates, Student Academy Board, and the Assembly of Representatives. The 2019 keynote speaker, Allison Massari, is a leading healthcare educator, artist, and activist who spoke at the General Session. In 1998, Ms Massari survived a severe automobile accident; 3 years later, she experienced a traumatic brain injury in another accident. Ms Massari provided her perspective as a patient, recalling the compassion and kindness her caregivers showed during her difficult recovery. Following her tragic accidents, she developed strength, resolve, and a renewed will to live. Ms Massari’s take-away message was for PAs to always remember to put their patient’s well-being first. Throughout the meeting, attendees had the opportunity to view poster presentations submitted by PAs and students from programs throughout the country. Researchers from The Betty Irene Moore School of Nursing at University of California Davis presented findings suggesting the need for more doctoral programs as a trend toward an expectation of doctoral degrees for PA faculty is emerging. Another study conducted by

PA students at Long Island University concluded that students in PA programs should be screened for prescription stimulant misuse, as 1 in 10 students was found to have misused these medications. Obesity was a prominent topic at the meeting in both poster presentations and speaker seminars. In a survey conducted by PA students, obese individuals were found to be more likely to overestimate the caloric content of food compared with individuals with lower body mass indices. Amy Ingersoll, PA-C, MMS, and Sandra Christensen, MSN, ARNP, FNPBC, presented a lecture on prescribing anti-obesity medications to prevent further weight gain and obesity-related complications, and to improve existing comorbidities.Additional topics covered in the presentation included how to initiate, titrate, and monitor the response to anti-obesity medications approved by the US Food and Drug Administration. The opioid epidemic was a hot-­ button topic at the meeting. Student researchers from the University of California Davis found that initiating buprenorphine in the emergency department may improve retention rates in opioid use disorder treatment programs, reduce illicit opioid use, and curb mortality rates. In addition, students enrolled in the behavioral medicine course at Mercer College of Health Professions found that PA students who completed their core clinical rotation were more confident in patient communication and clinical


assessment skills after receiving training on opioid-use disorder. On Sunday, May 19, investigators from the public relations company WPP presented the efforts that are underway to change the PA title.The investigators conducted a survey of more than 700 PAs and students and found that, although PAs are satisfied with their role and the benefits it provides, the title of the profession does not accurately represent their function. Three key points emerged as a result of the research: 1) the title “physician assistant” does not capture all of the clinical skills that PAs possess; 2) the word “assistant” may be demeaning to some clinicians and is associated with rational, emotional aversions; and 3) there is a general lack of education and awareness about what a PA is capable of, specifically from patients. Next steps toward changing the PA title include implementing strategies to capture the PA brand, which will support and elevate the profession in conjunction with the new title. The team will then decide on appropriate alternative titles for the profession and present the findings to the AAPA House of Delegates. Planning has already begun for the 2020 meeting to be held May 16-20 in Nashville,Tennessee. Along with setting new goals in collaboration and care, discovering the next big PA moment, and taking stock of what the profession has achieved, the new PA title will be unveiled. Although high expectations were set for this year’s meeting, 2020 is on track to be even more successful. ■


Chronic Obstructive Pulmonary Disease: Fighting for Each Breath As primary care clinicians are on the front lines of care for patients with COPD, they should educate them on disease management.

Smoking cessation is considered the most important intervention in COPD.


hronic obstructive pulmonary disease (COPD) is a leading cause of death in the United States, affecting 16 million persons and many others living with the condition undiagnosed.1 In 2017, the National Institutes of Health (NIH) declared COPD one of the most urgent health care problems facing Americans. Since 1969, the death rate for COPD has doubled; however, the number of deaths attributed to other chronic conditions has declined.2 Chronic lower respiratory disease, primarily COPD, is projected to be the third leading cause of death by 2020.3


Etiology and Risk Factors

COPD is most commonly due to a history of tobacco use, with approximately 80% of deaths related to smoking.4 Approximately 25% of persons with COPD have no history of smoking but may have been exposed to lung irritants or passive smoke.5 Exposure to cigarette smoke, air pollution, dust, chemicals, or other fumes contribute to the development of COPD. Any factor that affects lung growth during gestation or childhood can also predispose a person to COPD. Persons with alpha-1 antitrypsin deficiency, a rare genetic disorder, are at increased risk for COPD. Many persons with this disorder are young adults in whom the condition is undiagnosed. Approximately 20% of patients with COPD report a history of asthma, which is likely a contributing factor.6 Prevalence of COPD is greater in older age groups (>65 years) and women.7 • THE CLINICAL ADVISOR • JULY/AUGUST 2019 13

right-hand column like this one does at the top



Three pathologic conditions within the lungs — chronic bronchitis, emphysema, and hyperreactive airway disease — make up COPD (Figure). In chronic bronchitis, the airways become inflamed, and excessive mucus production obstructs air from entering the lungs. Contraction of smooth muscle in the airways causes narrowing that further limits air entry. Difficulty clearing mucus and obstruction of ventilation leads to hypoxia8 and ventilation-perfusion mismatching, in which parts of the lung do not receive oxygenation. This leads to pulmonary arteriole vasoconstriction, which places increased resistance against the right ventricle of the heart (ie, pulmonary hypertension).9 Increasing pulmonary artery pressure can eventually result in right ventricular failure (ie, cor pulmonale).8 The disease process in chronic bronchitis is different from that in emphysema, in which alveolar membranes lose integrity and become overly distended. Smoking destroys antiproteolytic enzymes and antioxidants in the lungs, which in turn allows proteolytic enzymes and oxidizing agents to weaken alveolar membranes to the point that they become unable to recoil with exhalation.10 The reduction in elasticity and recoil of lung tissue causes excessive accumulation of CO2, as it is not adequately removed with exhalation. This increases residual volume and blood levels of CO2, potentially disrupting acidbase balance and increasing the risk for respiratory acidosis.8

Emphysema causes widely distended, non-recoiling alveoli.


Chronic bronchitis causes excessive mucus and narrowed airways.

Hyperreactive airways in COPD are easily triggered by inhaled irritants. Episodic bronchospasms develop, creating an asthmatic component of the disease process.8 With advancing disease, the airway walls thicken and become filled with white blood cells, which secrete inflammatory mediators such as interleukins and tumor necrosis factor-alpha. Epigenetic changes are theorized to cause permanent remodeling of the airways and alveoli.11 Remodeling leads to fibrotic changes in the airways and alveoli that cause progressive ventilatory obstruction. Clinical Manifestations

Patients with COPD present with symptoms of chronic bronchitis, emphysema, and asthma. Chronic bronchitis causes productive cough, dyspnea, and cyanosis. Due to the stasis of mucus and secretions, patients are at increased risk for pulmonary infection. Many patients with COPD report increased episodes of “winter bronchitis.” Patients often exhibit tachypnea, noisy breathing, open-mouth breathing, clubbing of the nails, and orthopnea.12 With time, findings due to right ventricular failure — such as jugular venous distension, ascites, hepatomegaly, splenomegaly, and ankle or sacral edema — may develop. Air-filled lungs from emphysema can cause an enlarged, barrel-shaped chest to develop. The patient commonly exhales slowly through pursed lips. Wheezing can often be auscultated or heard without a stethoscope. Patients will often report chronic cough and shortness of breath, particularly with exercise.12 Diagnosis

The patient history commonly is notable for more than 30 pack-years of smoking. Pulmonary function testing (PFT) is required to make a diagnosis of COPD; it measures the different volumes involved in a patient’s ventilation. Forced expiratory volume and forced vital capacity are the focus in PFT. Forced expiratory volume during 1 second (FEV1) is the amount of air exhaled in the first second of exhalation, and forced vital capacity (FVC) is the volume of air exhaled with maximal effort. The ratio of FEV1 to FVC is measured before and after the patient uses a bronchodilator to maximally open their airways. An FEV1/FVC <70% after using a bronchodilator establishes the presence of airflow limitation, confirming the diagnosis of COPD.13 COPD severity is classified according to criteria established by the Global Strategy for the Diagnosis, Management, and Prevention of COPD, 2019 (Table 1).13 Nonpharmacologic Treatment

FIGURE. Difficulty clearing mucus and obstruction of ventilation lead to hypoxia in COPD.

Smoking Cessation Regardless of the severity of COPD, smoking cessation is considered the most important intervention, and patients


right-hand column like this one does at the top

should receive education, support, and follow-up to facilitate this. Nicotine patches, gum, and lozenges can be recommended as a step-down approach to smoking cessation. Patients may be referred to the tobacco-quit line sponsored by the Centers for Disease Control and Prevention. Medications that have been shown to decrease the urge to smoke include varenicline and bupropion.14 Oxygen Therapy Prescription of supplemental oxygen should be made according to the patient’s needs and best possible outcome. Patients with advanced COPD become desensitized to high CO2 levels and develop a hypoxic drive to breathe when oxygen levels diminish in the bloodstream. To avoid hypoxemia, titrated oxygen therapy to achieve an SaO2 of 88% to 92% is recommended for patients with severe COPD (Table 2).15 Lifestyle Modifications Symptom management to reduce disease progression includes counseling about eating a healthy diet and obtaining regular exercise. Malnutrition coupled with advancing COPD can lead to worsening respiratory muscle function, dyspnea, and decreased exercise capacity.As a result, muscle mass decreases and respiratory muscles become overloaded during ventilation, which can lead to exacerbations or ultimately respiratory failure.16 Omega-3 fatty acids promote anti-inflammatory activities and are considered protective nutritional elements. Patients with COPD should increase their intake of dietary omega-3 fatty acids to help control inflammation.This can be achieved by incorporating more cold water fish — such as salmon, sardines, tuna, herring, halibut, and mackerel — into the diet. Soybeans, walnuts, flaxseeds, and canola oil are also rich in omega-3 fatty acids.17 Patients with cachexia may benefit from consuming supplemental nutritional drinks with meals. Small, frequent meals dense in nutrient content with sufficient calories that meet basal energy expenditure requirements and induce weight gain, meals that require little preparation (eg, liquid nutritional supplements, microwaveable), resting before meals, and taking a daily dose of multivitamins are all recommended.18 Ambulatory patients should be encouraged to walk as tolerated. Patients should be advised to start slowly and see how far they can walk before becoming breathless. They should attempt to increase their walking distance by a few feet per day or by a minute or two per day.The goal is to engage in a brisk walk for 20 to 30 minutes 3 to 4 days per week. Patients should also be advised to exhale through pursed lips.17 Since cold air can irritate the lungs and trigger bronchospasm, patients who walk outdoors in cold weather should use a rescue inhaler 15 to 30 minutes prior to exercise and bring the

rescue inhaler with them. On extremely cold days, exercising indoors is recommended. Pulmonary Rehabilitation Patients with COPD benefit from pulmonary rehabilitation and maintenance of physical activity. Pulmonary rehabilitation is generally recommended for all symptomatic patients, regardless of disease severity. It involves exercise training, patient education, nutritional advice, and psychosocial support. Early initiation of exercise training could reduce future disability by addressing the spiral of lung function decline, deconditioning, and inactivity associated with COPD progression.19,20 Vaccinations Vaccinations against influenza and pneumococci are necessary as patients with COPD are highly susceptible to lower respiratory infections.The injectable trivalent, inactivated influenza vaccine is composed of seasonal H3N2, H1N1, and influenza B and is available each year as an annual dose. It is effective in reducing hospitalizations in patients with COPD. The adult TABLE 1. Classification of Severity of Airflow Limitation in COPD13 GOLD Classification


PFT Results



FEV1 ≥80% predicted



50% ≤FEV1 <80% predicted



30% ≤ FEV1 <50% predicted


Very Severe

FEV1 <30% predicted

*In patients who have FEV1 /FVC <70% after use of bronchodilator.

TABLE 2. Normal Ranges of Arterial Blood Gases Blood pH

7.35 to 7.45


35 to 45 mm Hg


90 to 100 mm Hg


22 to 26 mEq/L


95% to 100% • THE CLINICAL ADVISOR • JULY/AUGUST 2019 15


Since 1969, the death rate for COPD has doubled; however, the number of deaths attributed to other chronic conditions has declined. pneumococcal, 23-valent-polysaccharide vaccine (PPSV23), which includes the most serotypes, is recommended21, 22 and has been shown to decrease the incidence of community-acquired pneumonia in patients who have an FEV1 <40% predicted.23 Surgical and Nonsurgical Interventions In patients with advanced disease, surgical intervention can be considered. In select patients with upper lobe emphysema, lung volume reduction surgery (LVRS) may be appropriate. In this procedure, nonfunctional alveoli are removed to decrease the nonventilated areas of the lung. In advanced emphysema, LVRS has been shown to improve lung and respiratory muscle function, exercise performance, quality of life, and mortality in select patients.24

Nonsurgical lung volume reduction coil treatment is a bronchoscopic procedure that can be implemented in patients with advanced emphysema.This procedure involves inserting coil-like devices into bronchioles, restoring elasticity to lung tissue.25 Lung transplantation is available to a limited number of patients, with end-stage COPD accounting for 40% of all adult lung transplantations performed worldwide.26 The prevalence of lung transplantation procedures is limited by organ availability and access to specialized tertiary care centers.24 Pharmacologic Treatment

Inhaled medications such as bronchodilators and corticosteroids are the primary treatment modality in COPD (Table 3).13 Continues on page 18

TABLE 3. Common Inhaled Medications for COPD27,37 Type of Inhaler




Short-acting beta2-adrenergic agonist

Rapid stimulation of sympathetic nervous system bronchodilation

Rescue medication for acute attacks of bronchospasm

• Albuterol • Levalbuterol

Short-acting antimuscarinic agent

Rapid anticholinergic action that opposes bronchoconstriction

Rescue medication for acute attacks of bronchospasm

• Ipratropium

Long-acting beta2-adrenergic agonist

Long-acting stimulation of sympathetic nervous system bronchodilation

Maintenance medication used once or twice daily

• Salmeterol • Formoterol • Arformoterol • Indacaterol • Olodaterol • Vilanterol

Long-acting antimuscarinic agent

Long-acting anticholinergic action that opposes bronchoconstriction

Maintenance medication used once or twice daily

• Ipratropium • Tiotropium • Aclidinium • Umeclidinium • Glycopyrrolate

Inhaled corticosteroids

Long-acting anti-inflammatory action

Maintenance medication used once or twice daily

• Fluticasone • Budesonide • Mometasone

Combination inhalers

Bronchodilator plus corticosteroid

Maintenance medication used once daily

• Albuterol/ipratropium • Salmeterol/fluticasone • Formoterol/budesonide • Formoterol/mometasone • Vilanterol/fluticasone • Ipratropium/albuterol • Umeclidinium/vilanterol



Chronic lower respiratory disease, primarily chronic obstructive pulmonary disease, is projected to be the third leading cause of death by 2020. Long-acting bronchodilators include long-acting beta2adrenergic agonists (LABAs) and long-acting antimuscarinic (ie, anticholinergic) agents (LAMAs). Beta2-adrenergic agonists stimulate the sympathetic nervous system action of bronchodilation, whereas antimuscarinic agents counteract bronchoconstriction of the airways. Long-acting bronchodilators are used as daily maintenance therapy; short-acting beta2-adrenergic agonists (SABAs) and short-acting antimuscarinic agents (SAMAs) are bronchodilators used for rapid control of intermittent episodes of bronchospasm. Inhaled corticosteroids (ICS) are also used for maintenance therapy daily,27 and a combination of long-acting bronchodilators and corticosteroids dispensed from one inhaler is commonly used. Inhaled medications are usually delivered using pressurized metered-dose inhalers (MDIs) and dry powder inhalers (DPIs).28 Due to the chronic nature of COPD, long-term self-administration of medications is paramount for preventing disease progression. Patients should be taught which inhaler is used for rapidaction, rescue treatment and which is used daily for maintenance treatment. If a bronchodilator and an inhaled corticosteroid are used separately, the bronchodilator should be used first to open the airways. Most medications are easy to use because they consist of a combination of a bronchodilator and a corticosteroid. Adherence to medication is essential for optimal disease management. MDIs and DPIs require specific inhalation

POLL POSITION Which of the following is the most important intervention for COPD? 3.97% 3.68% ■ Adherence to medication ■ Increasing physical activity ■ Smoking cessation



■ Use of supplemental oxygen

For more polls, visit

techniques to obtain the full effect of the medication. However, correct inhaler technique can be difficult for many patients to achieve, particularly older adults with comorbidities as they often cannot mount the inspiratory force needed to inhale the medication sufficiently.29 MDIs are the most commonly prescribed inhalation device, but these can be difficult to use due to the high level of coordination required to activate the device while taking a slow and deep inhalation. Studies show that up to 94% of patients demonstrate incorrect inhaler technique with either conventional pressurized MDIs or DPIs.28 Primary care clinicians should demonstrate proper inhaler use, ask patients for a return demonstration, and distribute a handout depicting the correct technique. Patients can also be referred to online resources for learning the appropriate use of inhalers. Using a spacer with an MDI may be helpful for patients who have difficulty with this type of device; it is the preferred method of delivery. When using an MDI with a spacer, the medication is delivered by pushing down on the canister to produce a measured “puff ” of medication into the holding container.The medication is then inhaled through a mouthpiece, which allows for a higher and more accurate dose to be delivered into the lungs.30 Nebulizers If patients are unable to use MDIs or DPIs properly, they may not receive accurate treatment and should be evaluated for nebulized therapy instead. Both rescue and maintenance therapies can be delivered with a nebulizer, which is a motorized apparatus that converts medications from a liquid form to a mist. Nebulizers are handheld devices that do not require a specific breathing technique for effective drug delivery and offer a convenient way of delivering a higher dose of medication to the airways. Nebulizers are also effective for maintenance dosing in populations who are unable to use other devices, particularly patients with cognitive, neuromuscular, or ventilatory impairments.31 Acute Exacerbations of COPD

Acute exacerbations of COPD (AECOPD) are defined as an acute worsening of respiratory symptoms that require additional therapy and usually last 7 to 10 days. Bacterial infection is the most common cause, contributing to approximately 70% of AECOPD cases, with viral causes responsible for approximately 30%.32 A change in color of the sputum and


Chronic obstructive pulmonary disease is most commonly due to a history of tobacco use, with approximately 80% of deaths related to smoking. increase in purulence is a good marker for a bacterial cause of exacerbation. Common bacteria responsible for AECOPD include Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Patients with the most impaired lung function (lowest FEV1) may have other bacterial infectious causes, such as Pseudomonas aeruginosa or Gram-negative bacteria. Upper respiratory infections caused by viruses, usually rhinovirus, can also trigger AECOPD. It is important to recognize that a viral infection can subject the patient with COPD to a bacterial infection.32 Major findings associated with an exacerbation include increased dyspnea, sputum volume, and/or sputum purulence. Patients may also have increased cough, fever, myalgia, and pharyngitis.33 Diagnosing exacerbations relies on patients reporting their symptoms; as they often do not report these to their clinician, AECOPD can go untreated. The COPD Assessment test (CAT) is an 8-item questionnaire that can be completed by the patient to evaluate their current state of symptoms of COPD. Serum biomarkers, C-reactive protein, and procalcitonin are commonly elevated in patients with positive bacterial sputum cultures.34 Exacerbations can have a negative effect on a patient’s health status, increase the risk for hospitalization, decrease quality of life, and reduce exercise capacity and lung function. Recovery can take several weeks, and significant mortality is associated with AECOPD. Exacerbations most commonly occur in patients with moderate or severe COPD, GOLD grade 3

or 4.35 AECOPD is classified as mild, moderate, or severe, and each classification is associated with different treatment recommendations (Table 4).33,36 Managing AECOPD

More than 80% of AECOPD can be managed on an outpatient basis with standard treatment of bronchodilators, oral corticosteroids, and antibiotics.37 Several factors warrant referral to a local emergency department and/or hospital admission: severe symptoms, heart failure, acute respiratory failure, onset of new physical signs, failure of exacerbation to respond to initial medical management, presence of serious comorbidities, and inadequate home support.38 Bronchodilators Inhaled SABAs (eg, albuterol, levalbuterol) are the mainstay of therapy for AECOPD because of their rapid onset of action and efficacy in producing bronchodilation.These medications may be administered via a nebulizer or MDI with a spacer device and may be combined with a SAMA (eg, ipratropium). Clinicians often prefer nebulized therapy on the presumption of more reliable delivery of drug to the airway.37 Antibiotics For patients who continue to have frequent exacerbations despite optimal therapy with bronchodilators and anti-inflammatory agents, antibiotic prophylaxis has been considered and

TABLE 4. Classification of AECOPD Severity36,37 Classification


Treatment Recommendations


One of the following: • Increased dyspnea • Increased sputum volume • Increased sputum purulence

Short-acting bronchodilators


Two of the following: • Increased dyspnea • Increased sputum volume • Increased sputum purulence

Short-acting bronchodilators plus oral corticosteroids and antibiotics


Acute respiratory failure and at least 2 of the following: • Increased dyspnea • Increased sputum volume • Increased sputum purulence

Emergency department/hospitalization • THE CLINICAL ADVISOR • JULY/AUGUST 2019 19


Symptom management to reduce disease progression includes counseling about eating a healthy diet and obtaining regular exercise. debated. Studies have shown that macrolides are most effective as they have anti-inflammatory as well as antibacterial effects; azithromycin 250 mg/d or 500 mg 3 times per week or erythromycin 500 mg twice daily has been shown to reduce the risk of exacerbations.39-41 However, the development of hearing loss and the potential to develop antibiotic resistance are key issues of concern. Clinicians therefore need to weigh the benefits vs the risks associated with antibiotic treatment for AECOPD.39-41 Oxygen Therapy Short-term oxygen therapy is recommended for patients hospitalized with acute exacerbations of chronic bronchitis, and long-term oxygen therapy is recommended for patients with stable, very severe COPD who remain hypoxemic at discharge. Continuous oxygen is generally recommended for patients whose PaO2 is ≤55 mm Hg (normal 90-100 mm Hg) or patients whose oxygen saturation levels are ≤88% (normal = >95%). Oral Corticosteroids In the treatment of AECOPD, systemic corticosteroids have been shown to reduce length of hospital stay, provide earlier improvement in lung function and symptoms, and reduce the risk of treatment failure or relapse. A dosage of prednisone 40 mg/d for 5 days is recommended.42 Occasionally, patients may benefit from a higher dose or a longer course depending on the severity of the exacerbation and response to prior courses of glucocorticoids.

respiration), worsening or new onset of central cyanosis, development of peripheral edema, and hemodynamic instability. With these severe respiratory findings, transferring the patient to the closest emergency department is necessary for more intense management.35,37 Conclusion

A combination of chronic bronchitis, emphysema, and hyperreactive airway disease, COPD requires a precise medical regimen that patients need to fully comprehend to avoid exacerbations.Acute exacerbations often require hospitalization and result in high mortality rates. Primary care clinicians are on the front lines caring for patients with COPD and as such, should educate them regarding the disease process, medication regimen, and nonpharmacologic treatments. They also should assess patients with acute exacerbations to determine the need for hospitalization. ■ Theresa Capriotti, DO, MSN, CRNP, is a clinical professor at the ML Fitzpatrick College of Nursing at Villanova University, in Villanova, Pennsylvania; Dana Galgano, BSN, and Lynne Kelley, BSN, are students. References 1. Murphy SL, Xu J, Kochanek KD, Curtin SC, Arias, E. Deaths: final data for 2015. Natl Vital Stat Rep. 2017;66(6):1-75. 2. Ma J, Ward EM, Siegel RL, Jemal A. Temporal trends in mortality in the United States, 1969-2013. JAMA. 2015;314(16):1731-1939. 3. Health, United States, 2015: with special feature on racial and ethnic health disparities. Hyattsville, MD: National Center for Health Statistics; 2016.

Oral Phosphodiesterase-4 Inhibitor Roflumilast is an oral phosphodiesterase-4 inhibitor that is indicated for maintenance treatment as an add-on to bronchodilator therapy for adults with severe COPD associated with chronic bronchitis and a history of frequent exacerbations. Results of the 1-year REACT study showed that in symptomatic patients with severe COPD and a history of exacerbations, roflumilast significantly reduced the risk for severe exacerbations in those already receiving an ICS-LABA fixed combination and a LAMA (tiotropium) as background treatment.39

4. Ford ES, Croft JB, Mannino DM, Wheaton AG, Zhang X, Giles WH. COPD surveillance—United States, 1999-2011. Chest, 2013;144(1):284-305. 5. Wheaton AG, Cunningham TJ, Ford ES, Croft JB. Employment and activity limitations among adults with chronic obstructive pulmonary disease--United States, 2013. MMWR Morb Mortal Wkly Rep. 2015;64(11):289-295. 6. Kosacz NM, Punturieri A, Crozton TL, et al. Chronic obstructive pulmonary disease among adults — United States, 2011. MMWR Morb Mortal Wkly Rep. 2012;61(46):938-943. 7. Chronic obstructive pulmonary disease (COPD): basics about COPD. Centers for Disease Control and Prevention website. https://www. Updated June 5, 2018. Accessed June 6, 2019.

Referral for Hospitalization Impending respiratory failure may manifest with use of accessory muscles, paradoxical chest wall/abdominal movements (chest and abdominal motion are asynchronous with

8. Berg K, Wright JL. The pathology of chronic obstructive pulmonary disease: progress in the 20th and 21st centuries. Arch Pathol Lab Med. 2016;140(12):1423-1428.


Continues on page 22


9. Blanco I, Piccari L, Barberà JA. Pulmonary vasculature in COPD: the silent

27. Ferguson GT, Make B. Management of stable chronic obstructive

component. Respirology. 2016;21(6):984-994.

pulmonary disease. UpToDate website.

10. Decramer M, Janssens W, Miravitlles M. Chronic obstructive pulmonary

management-of-stable-chronic-obstructive-pulmonary-disease. Updated

disease. Lancet. 2012;379(9823):1341-1351.

January 16, 2019. Accessed June 13, 2019.

11. Brusselle GG, Maes T, Bracke KR. Eosinophils in the spotlight: eosinophilic

28. Lavorini F. Inhaled drug delivery in the hands of the patient. J Aerosol Med

airway inflammation in nonallergic asthma. Nat Med. 2013;19(8): 977-979.

Pulm Drug Deliv. 2014;27(6):414-418.

12. Gentry S, Gentry B. Chronic obstructive pulmonary disease: diagnosis and

29. Taffet GE, Donohue JF, Altman PR. Considerations for managing

management. Am Fam Physician. 2017;95(7):433-441.

chronic obstructive pulmonary disease in the elderly. Clin Interv Aging. 2014;

13. Global Initiative for Chronic Obstructive Lung Disease. Pocket guide to


COPD diagnosis, management, and prevention: a guide for health care pro-

30. Togger DA, Brenner PS. Metered dose inhalers. Am J Nurs. 2001;

fessionals. Global Initiative for Chronic Obstructive Lung Disease, Inc. https://


31. Tashkin DP. A review of nebulized drug delivery in COPD. Int J Chron

DRAFT-v1.7-14Nov2018-WMS.pdf. Published 2019. Accessed June 6, 2019.

Obstruct Pulmon Dis. 2016;11:2585-2596.

14. Ebbert JO, Hatsukami DK, Croghan IT, et al. Combination varenicline and

32. Miravitlles M, Anzueto A. Role of infection in exacerbations of

bupropion SR for tobacco-dependence treatment in cigarette smokers: a

chronic obstructive pulmonary disease. Curr Opin Pulm Med. 2015;21(3):

randomized trial. JAMA. 2014;311(2):155-163.


15. Pavlov N, Haynes AG, Stucki A, Jüni P, Ott SR. Long-term oxygen therapy

33. Bartlett JG, Sethi S. Management of infection in exacerbations of

in COPD patients: population-based cohort study on mortality. Int J Chron

chronic obstructive pulmonary disease. UpToDate website. https://www.

Obstruct Pulmon Dis. 2018;12:979-988.

16. DeBellis HF, Fetterman JW Jr. Enteral nutrition in the chronic obstructive

chronic-obstructive-pulmonary-disease. Updated November 19, 2018.

pulmonary disease (COPD) patient. J Pharm Pract. 2012;25(6):583-585.

Accessed June 6, 2019.

17. American Lung Association. 2018. Lung Health & Diseases: Nutrition

34. Çolak A, Yilmaz C, Toprak B, Aktoğu S. Procalcitonin and CRP as biomark-

and COPD. American Lung Association website.

ers in discrimination of community-acquired pneumonia and exacerbation of


COPD. J Med Biochem. 2017;36(2):122-126.

Updated March 13, 2018. Accessed June 6, 2019.

35. Kaufman JS. Acute exacerbation of COPD. Nurse Pract.

18. Rawal G, Yadav S. Nutrition in chronic obstructive pulmonary disease: a


review. J Transl Int Med. 2015;3(4):151-154.

36. Rangelov K, Sethi S. Role of infections. Clin Chest Med. 2014;35(1):

19. O’Donnell DE, Gebke KB. Activity restriction in mild COPD: a challenging


clinical problem. Int J Chron Obstruct Pulmon Dis. 2014;9:577-588.

37. Stoller JK, Barnes PJ, Hollingsworth H. Management of exacerbations

20. Egan C, Deering BM, Blake C, et al. Short term and long term effects

of chronic obstructive pulmonary disease. UpToDate website.

of pulmonary rehabilitation on physical activity in COPD. Respir Med.


chronic-obstructive-pulmonary-disease. Updated April 6, 2018. Accessed

21. Campos-Outcalt D. Pneumococcal vaccines for older adults: getting the

June 6, 2019.

timing right. J Fam Pract. 2014;63(12):730-733.

38. Global Initiative for Chronic Obstructive Lung Disease. Global strategy

22. Pesek R, Lockey R. Vaccination of adults with asthma and COPD. Allergy.

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23. Qureshi H, Sharafkhaneh A, Hanania NA. Chronic obstructive pulmo-

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24. Marchetti N, Criner GJ. Surgical approaches to treating emphysema: lung

39. Halpin DMG, Miravitlles M, Metzdorf N, Celli B. Impact and prevention

volume reduction surgery, bullectomy, and lung transplantation. Semin Respir

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25. Simon M, Harbaum L, Oqueka T, Kluge S, Klose H. Endoscopic lung volume

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Dermatology Clinic CASE #1


A 22-year-old white man notices a bump on his skin and seeks medical attention. He reports a 1-month history of an asymptomatic lesion on his upper arm.Aside from a diagnosis of acne vulgaris, his medical and family history is unremarkable. He does not smoke. On examination, the lesion measures approximately 3 mm in diameter and is freely moveable, with a visible central punctum. His scalp, neck, back, nails, hair, oral mucosa, and genitals are normal. What is your diagnosis? Turn to page 24



A 70-year-old man with a medical history significant for diabetes presents to the clinic with a complaint of yellowing of his toenails. He reports that he has difficulty trimming the nails. He denies prior nail trauma or pain. Upon examination, the nails of both feet are yellow, with breakages and subungual hyperkeratosis of the nail bed. No surrounding erythema or tenderness is noted. The patient is otherwise in good health. What is your diagnosis? Turn to page 25 • THE CLINICAL ADVISOR • JULY/AUGUST 2019 23

Dermatology Clinic CASE #1

Epidermal Inclusion Cysts

Epidermal inclusion cysts — also known as epidermoid, infundibular, and keratin cysts — are the most commonly diagnosed cutaneous cysts.1,2 These cysts are freely moveable, slowgrowing masses with a central punctum that may present as painful, inflamed, and fluctuant nodules if rupture of the cyst occurs.2 These lesions commonly present on the face and trunk of young to middle-aged men; however, any location or age group can be affected.1,2 Diagnosis is made clinically and removal is typically not necessary.2 Treatment options include surgical excision, triamcinolone injections, and cyst drainage. Prognosis is excellent, although recurrence of excised lesions is common. Milia are tiny epidermal inclusion cysts that are commonly present in neonates but can occur throughout life.1 Although not genetically linked, epidermal inclusion cysts can present alongside rare genetic conditions like Gardner syndrome and Gorlin syndrome.1-3 These cysts are more prevalent in patients with chronic sun-damaged skin, those who smoke, and those receiving treatment with BRAF inhibitors such as imiquimod and cyclosporine.2,4,5 Most notably, epidermal inclusion cysts are associated with acne vulgaris and other conditions that result in inflamed or irritated hair follicles.2 Epidermal inclusion cysts are lined with stratified squamous epithelium and filled with distinct keratin debris.6 They occur anywhere on the body, including the face, scalp, neck, back, and genitals and are considered sporadic, benign, and noncontagious cutaneous lesions.1,2,4,7,8 These lesions can range in size from a few millimeters to several centimeters in diameter, but one cannot predict the size of the lesion upon onset.1,2 Epidermal inclusion cysts can be categorized as either primary or secondary lesions.2 Primary cysts arise directly from obstructions in the cavity underlying the hair follicle. Patients with acne vulgaris have a higher prevalence of disrupted hair follicles and obstructed pores, which results in higher rates of primary cysts. Secondary cysts arise from follicular epithelium that implants into the dermis and are most commonly due to trauma. Epidermal inclusion cysts are often infected by normal skin flora including Staphylococcus aureus and S epidermidis.2 Infected nodules are asymptomatic unless ruptured, in which case cyst contents leak into and infect surrounding tissue.1 Almost all cases of epidermal inclusion cysts can be diagnosed by conducting a thorough history and physical examination.2,6 If a genetic condition (ie, Gardner syndrome or Gorlin syndrome)

is suspected, then additional radiographic and ultrasonographic examination may be indicated.1,2 Upon histologic analysis, these cysts are characterized by the presence of epidermal elements in the dermis.2 The cyst wall protrudes into the cavity underlying the hair follicle and is filled with keratin and keratohyalin granules. In some cases, the cyst wall is derived from the hair follicle infundibulum. In infected states and rupture, epidermal inclusion cysts are acutely inflamed and present with invasion of neutrophils or giant cells.2,6 Unlike sebaceous cysts, epidermal cysts do not originate from sebaceous glands and lack sebum, instead containing keratin that has a “cheesy” appearance.1,2 Depending on the cyst’s location, differential diagnoses can range from pilar cysts, ganglion cysts, and lipomas to neuromas and neurofibromas.1 Pilar cysts, unlike epidermal inclusion cysts, are characterized by trichilemmal keratinization. Ganglion cysts often occur at joints and are characterized by hyaluronic acid contents. Lipomas, on the other hand, are benign tumors made of fat tissue that present as soft, movable, and painless lumps.1 Approximately 1% of epidermal inclusion cysts undergo malignant transformation into basal cell carcinomas and squamous cell carcinomas.2,9 Whenever carcinoma is suspected, skin biopsy is recommended for further testing and confirmation. In general, epidermal inclusion cysts are usually benign and surgical excision is often not required. However, since these lesions likely will not resolve on their own, 3 forms of treatment can be considered: definitive treatment, alternative treatment, and conservative treatment.2 Definitive treatment involves surgical excision or punch biopsy, making sure to remove the entire sac of the cyst to avoid recurrence.1,2 Alternative treatment involves triamcinolone injections (10 mg/mL for nodules on the trunk and 3 mg/mL for nodules on the face) into the cyst proper.2 Triamcinolone injections have been found to resolve ongoing inflammation and prevent recurrence of infected epidermoid cysts. Conservative treatment involves draining the cyst and administering oral antibiotics against normal skin flora; such treatment is employed when epidermoid cysts are acutely inflamed.2,10 However, some studies suggest that these inflamed cysts can be safely excised with lower recurrence rates when appropriate washing and wound care are implemented.1 Complete excision of accumulated keratin and the cystic wall within epidermal inclusion cysts has an excellent prognosis. Surgical complications include infection, scarring, and wound dehiscence.2 Additionally, incomplete excision can lead to recurrence.1,2,10 Rupture of the cyst prior to excision can result in cellulitis, swelling, and erythema.2 The patient in this case was told that he had a benign epidermal inclusion cyst; he opted for excision as he was selfconscious about the lesion. He was pleased with the outcome.


Venkata S. Jonnakuti, BS, is a medical student; McKenna E. Boyd, BS, is a medical student; and Christopher Rizk, MD, is a dermatology fellow at Baylor College of Medicine, in Houston,Texas. References 1. Pandya KA, Radke F. Benign skin lesions: lipomas, epidermal inclusion cysts, muscle and nerve biopsies. Surg Clin North Am. 2009;89(3):677-687. 2. Weir CB, St. Hilaire NJ. Epidermal inclusion cyst. StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2019. 3. Morice-Picard F, Sévenet N, Bonnet F, Jouary T, Lancombe D, Taieb A. Cutaneous epidermal cysts as a presentation of Gorlin syndrome. Arch Dermatol. 2009;145(11):1341-1343. 4. Lin S-H, Yang Y-C, Chen W, Wu W-M. Facial epidermal inclusion cysts are associated with smoking in men: a hospital-based case-control study. Dermatol Surg. 2010;36(6):894-898. 5. Richter A, Beideck S, Bender W, Frosch PJ. [Epidermal cysts and folliculitis caused by cyclosporin A]. Hautarzt. 1993;44(8):521-523. 6. Handa U, Chhabra S, Mohan H. Epidermal inclusion cyst: cytomorphological features and differential diagnosis. Diagn Cytopathol. 2008;36(12):861-863. 7. Pehlivan M, Özbay PÖ, Temur M, Yilmaz Ö, Gümüs˛ Z, Güzel A. Epidermal cyst in an unusual site: a case report. Int J Surg Case Rep. 2015;8C:114-116. 8. Apollos JR, Ekatah GE, Ng GS, McFayden AK, Whitelaw SC. Routine histological examination of epidermoid cysts; to send or not to send? Ann Med Surg. 2016;13:24-28. 9. Bajoghli A, Agarwal S, Goldberg L, Mirzabeigi M. Melanoma arising from an epidermal inclusion cyst. J Am Acad Dermatol. 2013;68(1):e6-e7. 10. Zuber TJ. Minimal excision technique for epidermoid (sebaceous) cysts. Am Fam Physician. 2002;65(7):1409-1412.



Onychomycosis is a fungal infection of the nails caused by dermatophytes, nondermatophytes, and yeast. It is the most common nail disease, accounting for up to 50% of all nail disorders.1,2 Approximately 2% to14% of the US population has onychomycosis.3 It is more prevalent in the elderly and is twice as common among men.2 Although onychomycosis is uncommon in children, its prevalence in this population is increasing due to occlusive footwear and exposure to locker rooms, swimming pools, and affected family members.4 Onychomycosis can be caused by various organisms, most commonly dermatophytes.Tinea unguium, or onychomycosis

caused by dermatophytes, accounts for 90% and 50% of toenail and fingernail infections, respectively. Trichophyton rubrum and T mentagrophytes are the predominant dermatophyte species. Nondermatophytes (ie, Scopulariopsis,Aspergillus, Fusarium, and Acremonium) are responsible for 20% of all cases, while species of Candida comprise the remaining 10% to 20%. Complex, multispecies infection is frequent, as is combined bacterialfungal infection.1 Development of onychomycosis starts in the nail bed. Patients often initially have tinea pedis that invades the nail bed via small breakages in the nail.The nail bed attempts to eliminate the fungus through hyperkeratosis, resulting in damage to the nail matrix. The nail plate then separates and becomes distorted in the chronic total dystrophic stage of onychomycosis.5 Biofilm formation plays a role in the pathophysiology, causing increased virulence, antibiotic resistance, and host immune system evasion.6 Risk factors for onychomycosis include prior nail trauma, age, history of tinea pedis, diabetes, psoriasis, malignancy, exposure to infected household members, and genetic association with the HLA-DR8 serotype.1,2,5 Immunocompromised patients are at greater risk, especially those with defects in interleukin (IL)-17 and IL-22 production.7 Patients residing in temperate climates typically present with dermatophyte infection in the toenails, while those residing in hot, humid climates are more susceptible to yeast infection in their fingernails.2 Classic presentation of onychomycosis involves yellow, brittle nails and hyperkeratosis. Onycholysis and nail thickening increase over time and most often involve the big toenail. Patients may experience severe, localized pain. If found in conjunction with a black, violaceous nail plate, trauma likely contributed to the pathogenesis.1 One finding specific to onychomycosis is a dermatophytoma, which is a fungal abscess with yellowish-white or orange-brown streaks along the nail plate. Complications of severe disease include onychodystrophy, onychocryptosis, complete nail loss, cellulitis, osteomyelitis, and sepsis.1,5 The differential diagnosis for onychomycosis includes fungal melanonychia, traumatic onycholysis, psoriasis, lichen planus, onycholysis secondary to thyroid dysregulation, and malignancy.1,5 Dermoscopy can be used to distinguish onychomycosis, which presents with spikes, lines, and keratosis under the nail, from fungal melanonychia, which presents as triangular patterns with yellow-white streaks.8 Pitting, yellowpink discoloration, or psoriatic skin or joint findings are more consistent with psoriasis of the nail.1 While clinical evaluation and dermoscopy can support a diagnosis of onychomycosis, diagnostic tests must be performed because of its similar appearance to other nail pathologies.The potassium hydroxide (KOH) test is a rapid in-office procedure • THE CLINICAL ADVISOR • JULY/AUGUST 2019 25

Dermatology Clinic with high specificity for onychomycosis that involves clipping the nail as proximally as possible and scraping the underside of the nail with a blade.The KOH dissolves large keratinocytes and allows for visualization of fungal hyphae or yeast cells; however, the fungal species cannot be determined. Histopathologic evaluation using a periodic acid-Schiff stain is also a sensitive test for fungus, but similarly cannot determine viability of or identify the causative species. Fungal culture allows for speciation of the causative fungi, but results may not be available for up to 1 month. Polymerase chain reaction, a DNA-amplification test that evaluates genes unique to fungal ribosomal RNA to diagnose onychomycosis, has high sensitivity and specificity, and results are available in several hours. Additional newer technologies include confocal microscopy, flow cytometry, infrared thermography, and mass spectrometry. In practice,

Riyad N.H. Seervai, BA, BS, is a medical student; Michelle Eugene Lee, BA, is a medical student; and Christopher Rizk, MD, is a dermatology fellow at Baylor College of Medicine, in Houston,Texas. References 1. Lipner SR, Scher RK. Onychomycosis: clinical overview and diagnosis. J Am Acad Dermatol. 2019;80(4):835-851. 2. Gupta AK, Versteeg SG, Shear NH. Onychomycosis in the 21st century: an update on diagnosis, epidemiology, and treatment. J Cutan Med Surg. 2017;21(6):525-539. 3. Gupta AK, Mays RR, Versteeg SG, et al. Global perspectives for the management of onychomycosis [published online December 25, 2018]. Int J Dermatol. doi: 10.1111/ijd.14346 4. Solis-Arias MP, Garcia-Romero MT. Onychomycosis in children. A review. Int J Dermatol. 2017;56(2):123-130. 5. Bodman MA, Krishnamurthy K. Onychomycosis. StatPearls [internet].

Onychomycosis is a fungal infection of the nails caused by dermatophytes, nondermatophytes, and yeast.

Treasure Island, FL; 2018. 6. Gupta AK, Foley KA. Evidence for biofilms in onychomycosis. G Ital Dermatol Venereol. 2019;154(1):50-55. 7. Gupta AK, Carviel J, Shear NH. Onychomycosis and chronic fungal disease: exploiting a commensal disguise to stage a covert invasion. J Cutan Med Surg. 2018;22(3):318-322. 8. Ohn J, Choe YS, Park J, Mun JH. Dermoscopic patterns of fungal melanonychia: a comparative study with other causes of melanonychia. J Am Acad Dermatol. 2017;76(3):488-493.e2. 9. Lipner SR, Scher RK. Onychomycosis: treatment and prevention of recurrence. J Am Acad Dermatol. 2019;80(4):853-867.


© The New Yorker Collection 2019 from All Rights Reserved.

KOH is used as the first-line test, followed by fungal culture. If the KOH test is negative initially, periodic acid-Schiff stain followed by fungal culture is the alternative diagnostic path.1,2,5 Antifungal agents are used for the treatment of onychomycosis, with systemic therapy being most effective.5,9 Terbinafine and itraconazole are broad-spectrum systemic antifungal agents approved for dermatophytes, some nondermatophytes, and Candida. Due to the length of time it takes for a nail to regrow, patients may wait 6 months (for fingernails) to 18 months (for toenails) before improvement is seen. Side effects of these drugs include liver toxicity and gastrointestinal symptoms. In particular, patients are advised to undergo liver function testing before starting terbinafine. Fluconazole, used off-label in the United States, is sometimes preferred over itraconazole because it does not depend on food or gastric pH for absorption; however, the drug should be avoided in patients who are breastfeeding.Topical ciclopirox is approved for mild to moderate onychomycosis. Although antifungal agents are necessary for eliminating fungi, laser therapy can help achieve aesthetic improvement of the nail. However, laser therapy requires multiple expensive treatment sessions and has demonstrated lower cure rates.5,9 Plasma therapy and photodynamic therapy are emerging treatments that are being evaluated for efficacy. The patient in this case was diagnosed clinically. He was treated with oral terbinafine 250 mg/d for 90 days. At 1-year follow-up, the patient’s nails had vastly improved. ■

Dermatologic Look-Alikes Small, Friable Lesions YELENA DOKIC, BSA; MCKENNA E. BOYD, BS; CHRISTOPHER RIZK, MD



A 63-year-old white man presents to the dermatologist with a 0.8-cm pink, pearly papule with a central core on the left nasal ala that appeared approximately 1 year ago and has slowly grown in size. The lesion has telangiectasias on the surface and periphery. He states that the lesion occasionally bleeds, especially if accidentally scratched. He is otherwise healthy. The patient has worked as a farmer on his ranch ever since he was a young adult and spends most of his time outside.

A 76-year-old white man presents to the dermatologist with a 1-cm scaly, ulcerative, exophytic plaque on his left arm. The patient first noticed the lesion approximately 5 months ago and reports that it has slowly grown in size. The lesion has a central crust and appears necrotic. He states that the lesion occasionally bleeds, especially if accidentally scratched. He has no other medical problems and denies any surgical history. He is retired and enjoys gardening. He admits to spending most of his time outdoors. • THE CLINICAL ADVISOR • JULY/AUGUST 2019 27

Dermatologic Look-Alikes CASE #1

Basal Cell Carcinoma Skin cancer is the most common type of cancer in the United States, with basal cell carcinoma (BCC) comprising most cases.1-3 The incidence of skin cancer has been increasing over time.1 Millions of BCCs and squamous cell carcinomas are diagnosed each year, with BCCs accounting for 70% of

these nonmelanoma cases.1,4 Typically occurring in non-Hispanic white individuals aged >65 years,4 BCC is more frequently encountered in men than women, which is often attributed to increased occupational exposure to the sun.1,4 The condition tends to occur on the head and neck, hands, and other areas of the body that have increased sun exposure.4 Environmental and genetic factors contribute to the development of BCC, with exposure to ultraviolet (UV) light being the most important risk factor.3,4 Other risk factors include living near the equator, personal or family history of skin cancer, use of tanning beds, therapeutic exposure to psoralen plus ultraviolet light (PUVA) for cutaneous disorders, arsenic, immune-suppressing drugs, photosensitizing drugs such as tetracyclines or diuretics, and inherited syndromes that cause skin cancer such as xeroderma pigmentosum.2,4 The pathophysiology of BCC formation is largely associated with UV-induced mutation that results in uncontrolled growth of precursor cells in the epidermis.2,4 The epidermis is the outermost layer of the skin, and the basal cells found in its bottom layer are responsible for the generation of new skin cells. As new skin cells form, they push the older, more superficial skin cells toward the surface, allowing the oldest cells to die and slough off. When basal cell DNA becomes mutated, typically by UV light, the cell can multiply at an uncontrolled rate and form a tumor.2,4 Some genetic conditions, such as Gorlin syndrome, can increase the risk for BCC through germline mutations in key signaling pathways.4 Although clinical appearance varies, the classic description of BCC is that of a pink, pearly papule with central depression. Other characteristic features include waxy papules; erosion or ulceration; bleeding with or without trauma; oozing or crusting in areas; raised borders; translucency; telangiectasias; slow growth; and areas that are blue, brown, or black.5 Several clinical variants of BCC include nodular, superficial, morpheaform, and pigmented.3,4 Nodular BCC is the most common subtype and resembles a pearly, pink papule that is

translucent with overlying telangiectasia, with or without a central ulceration.3,4 Superficial BCC appears as erythematous, scaly macules and plaques.3 Morpheaform BCC is infiltrative and appears as scar-like plaques with large subclinical extensions under the skin. Pigmented BCC is typically a colored variant of the nodular subtype and can be confused for melanoma. Histologically, BCC is grouped into 4 major subtypes: superficial, fibroepithelial, nodular, and infiltrative.3,6 The nodular subtype is most common and appears as basaloid cells with scant cytoplasm and hyperchromatic nuclei, peripheral palisading, peripheral clefting, and mucinous alteration of surrounding stroma.3 The superficial subtype depicts nests of subdermal basaloid cells that are connected to the epidermis, without infiltration into the reticular dermis.3 The infiltrative

Skin cancer is the most common type of cancer in the United States, with basal cell carcinoma comprising most cases. subtype portrays thin bundles of basaloid cells that infiltrate into the collagen fibers of the dermis. The fibroepithelial subtype reveals trabeculated and elongated branches of basaloid cells that extend into the dermis. The presence of myxoid stroma and peripheral clefting is the most helpful feature for distinguishing BCC from other basaloid tumors.6 As there are many subtypes of BCC, it can often resemble other skin conditions; therefore, the differential diagnosis is broad. The nodular variants of BCC can resemble dermal nevi, epidermal inclusion cysts, sebaceous hyperplasia, molluscum contagiosum, or keratoacanthomas.7 Superficial BCCs may resemble nummular eczema, benign lichenoid keratosis, actinic keratosis, and amelanocytic melanoma. Morpheaform BCCs can resemble scars due to trauma or localized scleroderma. The broad differential diagnosis emphasizes the importance of biopsy for suspected BCCs. The definitive diagnosis of BCC is made with a skin biopsy. Typically, a shave biopsy is sufficient and requires less instrumentation.8 Occasionally, an excisional or punch biopsy may be needed when a more aggressive or invasive pattern is suspected.8 The sample is then examined histologically, looking for the aforementioned findings, such as basaloid cells with large hyperchromatic nuclei, scant cytoplasm, large nuclear-to-cytoplasmic ratio, and cleft formation.3 BCC rarely metastasizes and is generally not staged.4


Continues on page 30

Dermatologic Look-Alikes The goal of treatment for BCC is to remove the tumor while preserving tissue, function, and physical appearance. Several therapies exist for BCC: surgical therapy, topical treatments, radiation therapy, photodynamic therapy, systemic retinoids, and hedgehog pathway inhibitors.4 In most cases, surgery is recommended as it has the highest cure rate and is the most effective treatment method.9 Surgical modalities include electrodesiccation and curettage, excisional surgery, Mohs micrographic surgery, and cryosurgery. Of all the surgical modalities, Mohs micrographic surgery has the lowest recurrence rate.9 Topical treatments that interfere with the growth of BCC and induce tumor cell death include 5-fluorouracil 5%, interferon, and imiquimod. These treatments are reserved for BCCs that are superficial and nonrecurring or for patients who cannot undergo surgery. Radiation therapy is reserved for patients who have lesions that are extensive or advanced or who are not surgical candidates.4 The patient in this case underwent biopsy of the suspicious lesion, which revealed BCC. He was treated with Mohs micrographic surgery, which allowed for tissue preservation and clear margins. To prevent subsequent lesions, his physician advised avoidance of UV sun exposure, especially during the middle of the day, and instructed the patient to wear sun-protective clothing such as long sleeves and hats.10 The patient was also instructed to wear sunscreen with a sun protection factor of 30 or higher and UVA and UVB protection when spending time outdoors.10


Squamous Cell Carcinoma

Squamous cell carcinoma (SCC) is the second most common type of skin cancer after BCC and represents approximately 20% of skin cancers.11 Approximately 700,000 new cases of SCC are diagnosed per year.11 The incidence of SCC is rising due to multifactorial causes including an aging population, use of tanning beds, and increased ability for detection.4,11 SCC tends to occur in older white patients, although individuals from all races are affected.4 The average age of onset is in the mid-60s.12 SCC affects men approximately 2 to 3 times more often than women; this has typically been attributed to increased lifetime UV light exposure in men.13 There is an increased incidence of cases of SCC in populations

that live near the equator.4 Patients who are on immunosuppressive medications, such as organ transplant recipients, are at increased risk for SCC.4 Environmental exposure to arsenic can predispose individuals to SCC.4 Overall, the most important risk factors for SCC development include UV light exposure, increasing age, fair skin, and immunosuppression.4,13 Keratinocytes are the predominant cell types in the epidermis. Repeated damage to keratinocyte DNA, typically by UV radiation, can result in an accumulation of mutations that ultimately results in malignant transformation of these cells.The most commonly mutated gene in SCC is the TP53 tumor suppressor gene.13 Mutated TP53 allows the cell to proliferate in an uncontrolled fashion and resist apoptosis. Malignant transformation of the epidermal keratinocyte can ultimately lead to dysplasia and SCC.13

Squamous cell carcinoma tends to occur in older white patients, although individuals from all races are affected. Actinic keratosis, or solar keratosis, is the premalignant lesion of SCC and presents as a sand-paper like texture of the skin. It may also present with hyperkeratotic papules on an erythematous base. Actinic keratoses should be removed, typically by cryotherapy, or monitored closely for transformation into SCC.14 Bowen disease, or SCC in situ, presents with full thickness atypia without invasion. It appears as scaly, red plaques that are localized and slow-growing.14 Typically, SCC presents as a pruritic, nonhealing ulcer or an abnormal growth in an area of the skin that receives ample sun exposure, such as the face, scalp, neck, trunk, and lower lip. The lesion may also appear as a pink papule or nodule. It may have scales or crust and bleed easily.14 On histologic evaluation, SCC appears as nests of squamous epithelial cells extending down into the dermis. A large nucleus surrounded by abundant eosinophilic cytoplasm indicates malignant cells.15 Occasional keratin pearls may be visualized. A grade of well differentiated, moderately differentiated, or poorly differentiated is assigned based on how closely the carcinoma resembles squamous epithelium. Perineural invasion of SCC occurs in approximately 5% to 14% of cases.14,15 Perineural involvement presents as facial muscle twitching, weakness, or numbness.15 The differential diagnosis for SCC is broad and includes other skin conditions such as proliferative actinic keratosis, basal cell carcinoma, sebaceous carcinoma, Bowenoid


TABLE. Characteristics of Basal Cell Carcinoma and Squamous Cell Carcinoma Basal Cell Carcinoma1-13

Squamous Cell Carcinoma1-13

Dermatologic Presentation

• Pink, pearly papule with overlying telangiectasias ± central ulceration • Erythematous, scaly macules and plaques • Scar-like plaques • Pigmented nodule

• Pruritic, nonhealing ulcer • Pink or skin-colored plaque or nodule with scales or crust


• Most common in older white individuals • More common in men than women • Increased UV light exposure

• Most common in older white individuals • More common in men than women • Increased UV light exposure


• DNA mutation in basal cells

• UV damage of DNA in keratinocytes • TP53 tumor suppressor gene mutation

Characteristic Location

• Head and neck most commonly • Hands • Areas of skin frequently exposed to the sun

• Face, scalp, neck, trunk, and lower lip • Areas of skin frequently exposed to the sun


• Superficial, fibroepithelial, nodular, and infiltrative • Basaloid cells with scant cytoplasm and hyperchromatic nuclei, peripheral palisading, peripheral clefting, and mucinous alteration of surrounding stroma

• Nests of squamous epithelial cells extending down into the dermis • Abundant eosinophilic cytoplasm with large nuclei • Keratin pearls


• Shave biopsy usually, or excisional or punch biopsy • Histologic analysis

• Excisional biopsy, incisional biopsy, or punch biopsy


• Surgical therapy is first line • Mohs micrographic surgery has the highest cure rate • Topical treatments or radiation therapy possible for some cases

• Surgical therapy is first line • Mohs micrographic surgery has the highest cure rate • Electrodesiccation and curettage • Topical treatments or radiation therapy possible for some cases

papulosis, keratoacanthoma, verrucous hyperplasia, inverted follicular keratosis, pseudoepitheliomatous hyperplasia, and amelanocytic melanoma.16 The broad differential diagnosis emphasizes the importance of skin biopsy for suspected SCC, because the histology will be used to differentiate between the potential skin conditions.16 Whenever cutaneous malignancy is suspected, biopsy should be performed.17 Types of biopsy include excisional, incisional, or punch. The most common type of biopsy performed for SCC is excisional biopsy, as it is both diagnostic and therapeutic.17 The full thickness of the skin should be examined in the biopsy; therefore, a shave biopsy is not recommended. Histologic presentation of SCC involves significant squamous cell atypia, abnormal keratinization, and invasive features.17 Of note, for SCC measuring >2 cm in diameter, metastasis to regional lymph nodes should be considered.14 Metastasis is

more likely to occur with SCC vs BCC; however, both are less likely to metastasize than melanoma. The 5-year rate of metastasis for smaller lesions is 5%; it is 30% for lesions >2 cm.14 Several therapies exist for SCC, such as surgical excision, electrodesiccation and curettage, and radiation therapy. The preferred treatment method is surgical excision, which allows for histologic verification of the tumor margins.4,18 Specifically, Mohs micrographic surgery is a surgical technique that allows for removal of the SCC and simultaneous maximization of tissue preservation. Mohs is ideal for SCC that is high risk, poorly defined, or recurrent, and it has the highest cure rate.18 Typically, electrodesiccation and curettage are performed for low-risk, localized, and superficial SCC. It is fast and minimally invasive; however, no specimen is available for margin evaluation, which may result in tumor recurrence.18 Radiation therapy is reserved for patients who are unable to undergo • THE CLINICAL ADVISOR • JULY/AUGUST 2019 31

Dermatologic Look-Alikes surgical removal of the lesion.4,18 Adjuvant chemotherapy may be used for patients with high-risk SCC. Precancerous lesions can be treated topically with 5-fluorouracil, capecitabine, and diclofenac sodium, or with photodynamic therapy.18 For the patient in this case, biopsy of the suspicious lesion revealed SCC, and the patient subsequently underwent wide local excision, allowing for tissue preservation and clear margins. To prevent subsequent lesions, the patient was advised to avoid ultraviolet exposure, especially during the middle of the day, and to wear sun-protective clothing such as long sleeves and hats.10 The patient was also advised to wear sunscreen with a sun protection factor of 30 or higher and UVA and UVB protection if spending time outdoors.10 ■

6. Busam KJ. Dermatopathology. 2nd ed. Philadelphia, PA: Elsevier/Saunders; 2016. 7. Elsherbiny RE, Umair A, Azzeghaiby SN, Alzoghaibi I, Dabour S, Tarakji B. Detection of basal cell carcinoma–a guide line for general practitioners in dentistry. Br J Med Med Res. 2014;4(26):4352-4363. 8. Stratman EJ, Elston DM, Miller SJ. Skin biopsy: identifying and overcoming errors in the skin biopsy pathway. J Am Acad Dermatol. 2016;74(1):19-25. 9. Marzuka AG, Book SE. Basal cell carcinoma: pathogenesis, epidemiology, clinical features, diagnosis, histopathology, and management. Yale J Biol Med. 2015;88(2):167-179. 10. Stratton SP. Prevention of non-melanoma skin cancer. Curr Oncol Rep. 2001;3(4):295-300. 11. Karia PS, Han J, Schmults CD. Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012. J Am Acad Dermatol. 2013;68(6):957-966.

Yelena Dokic, BSA, is a medical student; McKenna E. Boyd, BS, is a medical student; and Christopher Rizk, MD, is a dermatology fellow at Baylor College of Medicine, in Houston,Texas.

12. Xiang F, Lucas R, Hales S, Neale R. Incidence of nonmelanoma skin cancer in relation to ambient UV radiation in white populations, 1978-2012. JAMA Dermatol. 2014;150(10):1063-1071. 13. Que SKT, Zwald FO, Schmults CD. Cutaneous squamous cell carcinoma:


incidence, risk factors, diagnosis, and staging. J Am Acad Dermatol. 2018;78(2):

1. Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence estimate


of nonmelanoma skin cancer (keratinocyte carcinomas) in the US population,

14. Alam M, Ratner D. Cutaneous squamous-cell carcinoma. N Eng J Med.

2012. JAMA Dermatol. 2015;151(10):1081-1086.


2. Cameron MC, Lee E, Hibler BP, et al. Basal cell carcinoma: epidemiology;

15. Yanofsky VR, Mercer SE, Phelps RG. Histopathological variants of cutane-

pathophysiology; clinical and histological subtypes; and disease associations.

ous squamous cell carcinoma: a review. J Skin Cancer. 2011;2011:210813.

J Am Acad Dermatol. 2019;80(2):303-317.

16. Tan K-B, Tan S-H, Aw DC-W, et al. Simulators of squamous cell carcinoma

3. Dourmishev LA, Rusinova D, Botev I. Clinical variants, stages, and manage-

of the skin: diagnostic challenges on small biopsies and clinicopathological

ment of basal cell carcinoma. Indian Dermatol Online J. 2013;4(1):12-17.

correlation. J Skin Cancer. 2013;2013:752864.

4. Garcovich S, Colloca G, Sollena P, et al. Skin cancer epidemics in the elderly

17. Stulberg DL, Crandell B, Fawcett RS. Diagnosis and treatment of basal cell

as an emerging issue in geriatric oncology. Aging Dis. 2017;8(5):643-661.

and squamous cell carcinomas. Am Fam Physician. 2004;70(8):1481-1488.

5. Altamura D, Menzies SW, Argenziano G, et al. Dermatoscopy of basal cell

18. Potenza C, Bernardini N, Balduzzi V, et al. A review of the literature of

carcinoma: morphologic variability of global and local features and accuracy of

surgical and nonsurgical treatments of invasive squamous cells carcinoma.

diagnosis. J Am Acad of Dermatol. 2010;62(1):67-75.

BioMed Res Int. 2018;2018:9489163.

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A Case of Illegal Detention Failure to document a phone call leads to a lawsuit alleging false imprisonment in a mental health case. BY ANN W. LATNER, JD

This month we look at a case with some interesting facts. If you are a regular reader of this column, you’ll know that good notetaking is often mentioned as a way to protect yourself against lawsuits. In this case, however, a note written in a chart led to a charge of false imprisonment by a patient against a hospital. It all started with an off-hand remark. The patient, Mrs A, was leaving an appointment with Ms N, the nurse practitioner who worked with Dr P, Mrs A’s primary care physician. Mrs A’s medical history included high blood pressure, back pain, and pain and swelling in her right leg. The issue with her right leg began 7 years ago, when Mrs A fell while skating. The fall resulted in a sore that did not heal properly and chronic pain and swelling in the leg, for which she often came into the office. As Mrs A was leaving the office, she turned to the nurse practitioner. “I’m so tired of dealing with this pain in my leg,” she said, as she walked out of the office. “I just feel like slitting my wrists.” Alarmed, Ms N made a note about the comment in the patient’s chart and mentioned it to Dr P the next morning. Years earlier, the practice had lost a

If you are going to include comments that a patient made while leaving the office in his or her chart, you must also include notes about what was said during a follow-up call.

patient to suicide, so Dr P was proactive when he heard what he considered “trigger words.” He called Mrs A and suggested that she get counseling or go to the emergency department, but she angrily refused. Dr P also spoke to Mrs A’s husband when he came to the office to pick up paperwork for her. Mr A told the physician that his wife was irritable because of the pain but did not intend to harm herself. Two days later, the patient’s husband called Dr P, saying that his wife wanted to order a device she had seen online that could “suck the fluid out of her leg.” The physician strongly advised against it and warned of the danger of infection and failure rate. He suggested that the patient go to the emergency department, and she grudgingly agreed. In the emergency department, Mrs A was taken to an examination room and had her blood drawn and vital signs taken. She was seen by Dr H, who told her that there was nothing that could be done 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. • THE CLINICAL ADVISOR • JULY/AUGUST 2019 33

LEGAL ADVISOR for her leg in the emergency department and that she should follow up with her family physician. Mrs A was extremely frustrated and said she would do whatever she had to in order to stop the chronic pain, including cutting and draining her own leg. At some point during this encounter, Dr H noticed the notes from her last office visit in which she expressed suicidal ideation. After sitting in an exam room for several hours, Mrs A, who had not been told that she could leave yet, had had enough. She got dressed, walked out, and was walking to her car when a nurse ran out and told her that she could not leave the hospital.

Good notes can protect you from liability, but you must be consistent and document every encounter. “You’re not doing anything for my leg, and I’m tired of sitting here,” said Mrs A. “I have to get home to take care of my sick cat. I’m not staying here any longer.” She continued walking toward her car. At this point, the nurse called hospital security, who in turn called the police. Mrs A was then escorted back to the hospital by a nurse, 2 security guards, and 3 police officers. The nurse told Mrs A that she would have to change back into a hospital gown, relinquish her purse to a security guard, and speak to a mental health counselor. After this, the situation began to spiral even more out of control: as the nurse was insisting that Mrs A put on a gown and hand over her purse, a struggle ensued between Mrs A, who was trying to hold on to her purse, and a police officer who was trying to take it. The police officer was bitten on the finger during the struggle, and Mrs A was arrested for battery. Months after the incident, Mrs A sued the hospital for false imprisonment. The hospital made a motion for summary judgment, arguing that there was no issue of material fact in dispute, and according to the law they were entitled to judgment. The court agreed and dismissed the case. The patient appealed.

According to the state Mental Health Code, treatment may not be performed against a patient’s wishes unless it is “necessary to prevent the patient from causing serious and imminent physical harm.” The court concluded that this should be the deciding factor. The hospital tried to argue that the standard should be whether the hospital had probable cause to believe that the patient might be suicidal, but the court noted that probable cause only applies in the criminal context. “In the mental health context, unlike the criminal context, what makes the detention of an individual lawful is compliance with the provisions of the Mental Health Code,” wrote the court in its decision. The Mental Health Code required, among other things, that a diligent effort be made to persuade the patient to submit to a mental health evaluation voluntarily before deciding to detain her. Because there were material issues of fact as to whether the hospital complied with the Mental Health Code, the appellate court ultimately decided that the case must be sent back to the trial court for a jury to decide whether the hospital had acted appropriately. Protecting Yourself

Good notetaking is important, but this case shows what can happen when initial notetaking is good but follow-up notes aren’t. Dr P never wrote follow-up notes in the chart indicating that he had spoken with the patient and her husband and that they had denied any suicidal ideation. Dr P even had a conversation with the physician in the emergency department during which he told him about the “self-harm comments,” but he did not mention that he had followed up with the patient and her husband, who told him that the patient was not suicidal but simply frustrated with the pain and disability. Good notes can protect you from liability, but you must be consistent and document every encounter. If you are going to include comments that a patient made while leaving the office in his or her chart, you must also include notes about what was said during a follow-up call. ■ Ms Latner, a former criminal defense attorney, is a freelance medical writer in Port Washington, New York.

Legal Background

On appeal, the appellate court disagreed with the lower court and reversed the ruling. The court noted that to prevail on a charge of false imprisonment, a plaintiff must show both that 1) her personal freedom was curtailed against her wishes, and 2) that her detention was unreasonable and unlawful. The court also noted that everyone agreed as to the first point, so it was the second element regarding the lawfulness of the detention that was the issue. The court had to consider the situations in which it is lawful to detain an individual for a mental health evaluation.

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July/August 2019 Clinical Advisor  

July/August 2019 Clinical Advisor