March 2020 Clinical Advisor by The Clinical Advisor

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NEWSLINE

■■ C difficile Burden ■■OA Therapy Update ■■ Best Diets for 2020 ■■ ART During Pregnancy LEGAL ADVISOR

Saved by the Statute of Limitations Q&A: NAPNAP PRESIDENT

Challenges Facing Pediatric Nurse Practitioners

FEATURE

Understanding May-Hegglin Anomaly

DERMATOLOGIC LOOK-ALIKES

Large, Scaly Erythematous Patches

MARCH 2020

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ANOREXIA OF AGING

Malnutrition in the Elderly: Underrecognized and Increasing in Prevalence Understanding the underlying causes of malnutrition helps identify patients at risk.

Director Nikki Kean nikki.kean@haymarketmedia.com Associate editors Rita Aghjayan Madeline Morr 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 @ haymarketmedical.com Associate account manager Michael Deverin, 732.343.4921 michael.deverin@haymarketmedia.com Publisher Kathleen Hiltz, 201.774.1078 kathleen.hiltz@haymarketmedia.com 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 haymarketmedia@theygsgroup.com 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 23, Number 2. Published 10 times a year, by Haymarket Media, Inc., 275 7th Avenue, 10th Floor, New York, NY 10001. For Advertising Sales & Editorial, call 646.638.6000 (M–F, 9am–5pm, ET). The Clinical Advisor is available on a paid subscription basis at the following annual rates: $75 USA, $85 Canada, $110 for all other foreign, in U.S. dollars, Single copy price: USA $20, Foreign $30. To order or update a paid subscription visit our website at www.ClinicalAdvisor.com or call 800.436.9269. Periodicals postage rate paid at NewYork, NY, and additional mailing offices. Postmaster: Send changes of address to The Clinical Advisor, c/o Direct Medical Data, 10255 W. Higgins Rd., Suite 280, Rosemont, IL 60018. All rights reserved. Reproduction in whole or in part without permission is prohibited.

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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 (CRN), which represents thickening and weathweath VERRUCA VULGARIS TREATMENT exposure to 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 any confusion. Diclegis is the only FDA-approved prescription 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 nih.gov/Iron.h 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 www.ClinicalAdvisor.com • 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 or.com. 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

orum

Write us today.

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

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www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2020 1

CONTENTS MARCH 2020

NEWS 6

Newsline ■■Burden of C difficile Infection in United States Grows ■■Updated Guideline for the Management of OA Released ■■Experts Vote on Best Diets for Overall Health in 2020 ■■And more.

8 Mediterranean diet tops Best Diets list

FEATURES 12 NAPNAP President Discusses Challenges Facing Pediatric Nurse Practitioners Rise in uninsured children, vaping, climate change, and more. 4 Malnutrition in the Elderly: Underrecognized and 1 Increasing in Prevalence Anorexia of aging can lead to increased morbidity and mortality.

29 Mysterious rash under breast

26 May-Hegglin Anomaly: A Case of Thrombocytopenia, Hearing Loss, and Cataracts This rare disorder is caused by mutations in the MYH9 gene.

DEPARTMENTS 4

Web Roundup A summary of our most recent opinion, news, and multimedia content from ClinicalAdvisor.com. Dermatology Clinic ■■Hyperpigmented Patch on the Thigh ■■Crusted Pruritic Rash Under Breast

35 Hyperpigmented patch on the thigh

41 Patient refuses treatment after a fall

Dermatologic Look-Alikes ■■Large, Scaly Erythematous Patches

Legal Advisor ■■Saved by the Statute of Limitations

MORE WAYS TO FIND US!

Like us on Facebook facebook.com/TheClinicalAdvisor Visit us on the web ClinicalAdvisor.com Download the app ClinicalAdvisor.com/App

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ClinicalAdvisor.com

NEWS

FEATURES

ClinicalAdvisor.com/News

ClinicalAdvisor.com/Features

Sunscreen Use: What’s Recommended vs Real World

Health Disparities in Rural America: Current Challenges and Future Solutions Rural Americans have a lower life expectancy than their metropolitan counterparts due to the prevalence of heart disease, cancer, unintentional injury, respiratory disease, and stroke.

Overall, 79.4% of survey respondents reported that they used sunscreen at least sometimes while in the sun, but 87.2% did not follow recommendations for the timing of sunscreen application.

FDA: Weight Loss Drug Possibly Linked to Cancer

Chronic Venous Insufficiency: Early Diagnosis and Nonsurgical Management Early recognition of chronic venous insufficiency helps improve outcome and reduces the need for surgical intervention.

According to a drug safety communication issued by the FDA, over a 5-year follow-up period, a greater proportion of patients taking lorcaserin had been diagnosed with cancer compared with those who received placebo.

Ubrogepant Works Quickly to Relieve Acute Migraine Pain Two hours after treatment, 11.8% of the placebo group, 19.2% of the 50-mg ubrogepant group, and 21.2% of the 100-mg ubrogepant group were free from migraine pain.

Tool Developed to Assess Long-Term CVD Risk, Benefit of Lipid-Lowering Intervention The blood levels of non-high-density lipoprotein cholesterol were found to have a strong association with the long-term risk for a cardiovascular disease event.

Lifestyle Intervention Improves Cardiometabolic Risk Factors in Women With PCOS Lifestyle intervention resulted in significant improvement in insulin resistance and low-density lipoprotein level compared with placebo groups.

THE WAITING ROOM

Official Blog of The Clinical Advisor ClinicalAdvisor.com/WaitingRoom Jim Anderson, MPAS, PA-C, DFAAPA Say Goodbye to High-Stakes Recertification? NCCPA Pilots Alternative Recertification Testing Many providers who are required to take recertification examinations feel as though standard CME is just as effective in skill maintenance as studying and sitting for a 200-question examination.

CASE STUDY ClinicalAdvisor.com/CaseStudy Brady Pregerson, MD Cervical Neck Pain A 71-year-old woman presents to the ED with a 2- to 3-week history of waxing and waning constant pain in her lower posterior neck. The patient reports no fever, weakness, numbness, chest pain, or shortness of breath. Although she did not mention it initially, on further questioning, she states that she experiences occasional chills. See ClinicalAdvisor.com/CervicalNeckPain

4 THE CLINICAL ADVISOR • MARCH 2020 • www.ClinicalAdvisor.com

EXCLUSIVE TO THE WEB AT

Advisor Dx Interact with your peers by viewing the images and offering your diagnosis and comments. To post your answer, obtain more clues, or view similar cases, visit ClinicalAdvisor.com/AdvisorDx. Learn more about diagnosing and treating these conditions, and see how you compare with your fellow colleagues. Check out some of our latest cases below!

DERM DX

Plaque on the Belly Button A 3-month-old Hispanic baby is brought to the office for evaluation of a persistent “sore” on her belly button. The sore emerged shortly after the umbilical stump fell off and occasionally drains clear fluid. Examination reveals a firm, erythematous, well-circumscribed plaque on her belly button. CAN YOU DIAGNOSE THIS CONDITION?

• Omphalitis • Umbilical granuloma

• Fibrosarcoma • Mixed hemangioma

● See the full case at ClinicalAdvisor.com/DermDx_Mar20

In partnership with

ORTHO DX

TheJopa.org

Journal of Orthopedics for Physician Assistants

Crush Injury of the Arm A 35-year-old mechanic presents to the emergency department having sustained a crush injury of his left arm. Earlier that day, the patient was working underneath a car at his garage when the front tire rolled over his left forearm. The patient complains of pain and numbness in the left hand. On examination, the patient is able to make the “OK sign.” THE OK SIGN IS USED TO ASSESS WHICH PERIPHERAL NERVE?

• Radial • Ulnar

• Median • Axillary

● See the full case at ClinicalAdvisor.com/OrthoDx_Mar20

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2020 5

Newsline CLOSTRIDIOIDES difficile infection (CDI) is associated with a large burden on the healthcare system in the United States. Compared with patients without CDI, the mean difference in length of stay in patients with CDI infection varied from 3.0 to 21.6 days, and the burden on the healthcare system was calculated at 8.3 cases per 10,000 patient-days, according to results published in JAMA Network Open. To address gaps in the understanding of the current burden associated with CDI, researchers conducted a review and meta-analysis of databases that included the terms “Clostridioides difficile, length of stay, and incidence.” A total of 66 articles evaluated incidence of CDI and 20 evaluated length

of stay. Thirteen of the 66 studies used patient-days as the denominator; the pooled incidence among hospitalacquired CDI among the 13 studies was 8.3 cases of CDI per 10,000 patient-days and varied greatly from 3.0 days to 10.3 days. Among the 3 pediatric propensity score-matched studies, the CDIassociated mean difference in length of stay days was 21.6 days. “In our meta-analysis of studies that used patient-days as the denominator, we estimated the incidence of CDI in the United States to be 8.3 CDI cases per 10,000 patient-days.” The researchers advised that “these estimates should be interpreted with caution because higher-quality studies should

Burden of C difficile Infection in United States Grows

Hospital-acquired C difficile infection can add 3 to 21 days to hospital stays.

be completed to guide future evaluations of CDI prevention and treatment interventions.” Understanding the burden of CDI infection will help researchers develop better ways to prevent and treat hospital-acquired infections, the researchers concluded.

Updated Guideline for the Management of OA Released UPDATED recommendations for the treatment of osteoarthritis (OA) were released by the American College of Rheumatology (ACR), in collaboration with the Arthritis Foundation (AF). In addition to a panel of experts, for the first time the guideline was developed with the help of patients, emphasizing the importance of shared decision-making. Exercise remains a strong recommendation for all OA patients and is supported by a substantial body of literature. Moreover, the guideline includes updated strong recommendations for the following interventions: self-efficacy and self-management programs for patients with knee, hip, and

hand OA; tai chi for knee and hip OA; topical NSAIDs for knee and hand OA; and oral NSAIDs and intra-articular glucocorticoid injections for knee and hip OA. The panel also strongly recommended against the use of transcutaneous electric nerve stimulation for knee and hip OA and hyaluronic acid injections in patients with hip OA. New conditional recommendations included balance exercises for knee and hip OA and yoga, cognitive behavioral therapy, radiofrequency ablation, and kinesiotaping for first carpometacarpal and knee OA, while the panel conditionally recommended against the use of manual

6 THE CLINICAL ADVISOR • MARCH 2020 • www.ClinicalAdvisor.com

therapy with exercise for knee and hip OA. As for pharmacologic therapies, conditional recommendations for the use of topical capsaicin and oral duloxetine for knee OA were added, while the panel conditionally recommended against the use of intra-articular hyaluronic acid injections in first carpometacarpal and knee OA. Additional updates regarding pharmacologic management advised against the use of bisphosphonates, hydroxychloroquine, methotrexate, platelet-rich plasma (PRP) injections (in hip and knee OA), stem cell injections (in hip and knee OA), tumor necrosis factor inhibitors, and interleukin-1 receptor antagonists.

Newsline Experts Vote on Best Diets for Overall Health in 2020 THE MEDITERRANEAN Diet was picked as the best diet for 2020, according to new rankings released by US News and World Report.An expert panel assessed 35 diets, examining the evidence behind each diet’s claims. Specifically, they evaluated the likelihood of short-term and long-term weight loss, how easy the diet was to follow, how well it conformed to current nutrition standards, and whether it could be an effective tool for diabetes and cardiovascular disease prevention. In addition to the Mediterranean Diet, the diets in the next top spots for best overall diet included the DASH Diet (Dietary Approaches to Stop Hypertension), the Flexitarian Diet (a mostly vegetarian diet), the WW Diet (formerly Weight Watchers), the Mayo Clinic Diet, the MIND Diet

Mediterranean diet, with its emphasis on fish, healthy fats, and vegetables, tops list.

(Mediterranean-DASH Intervention for Neurodegenerative Delay), and the Volumetrics Diet (food is divided into categories based on energy density).

The Keto Diet was ranked at #34, with some experts noting that it could lead to nutritional imbalances and that there was insufficient evidence to suggest longterm weight loss. Other diets that made the bottom of the list included the Raw Food Diet (#31), the Atkins Diet (#32), the Whole30 Diet (#33), and the Dukan Diet (#35), which the experts thought was too restrictive, difficult to follow, and unlikely to result in long-term success. As for diabetes prevention and management, the Mediterranean Diet (#1), DASH Diet (tied for #2), Flexitarian Diet (tied for #2), Mayo Clinic Diet (tied for #2), and Vegan Diet (tied for #2) were at the top of the list, while the Ornish Diet (#1), Mediterranean Diet (#2) and DASH Diet (#3) were voted best heart-healthy diets.

THE IMPLEMENTATION of hospitalbased palliative care services in NewYork State was associated with a 10% decrease in intensive care unit (ICU) use during end-of-life care, according to a study published in JAMA Network Open. “The use of palliative care consultation is associated with a decreased likelihood

a total of 73,370 terminal patients died while hospitalized: 37,628 patients who received care in hospitals that implemented palliative care and 35,742 who did not. For patients in the implementation hospitals, 17,146 received care before implementation and 20,482 received care after implementation.

The findings of the study suggest that the availability of palliative care reduces the physical and psychologic stress of end-of-life care for patients and their loved ones. of patients’ dying in the ICU and shorter ICU stays for patients who died during hospitalization,” wrote the authors, The study included 51 NewYork State hospitals: 24 hospitals that implemented a program of hospital-based palliative care between 2008 and 2014 and 27 hospitals that did not. During the study period,

Prior to the study, admission to an ICU during a terminal illness was frequent, noted the researchers. Patients admitted after implementation of hospital-based palliative care were less likely to receive intensive care than patients admitted before implementation. Hospital-based palliative care was not associated with

8 THE CLINICAL ADVISOR • MARCH 2020 • www.ClinicalAdvisor.com

significant differences in hospital length of stay, use of dialysis, ICU days, or use of mechanical ventilation. “Although the observed difference was small [absolute decrease in ICU stay of 3.5%], on a population level, the association may be magnified,” noted the researchers. “With these estimates, a decrease in ICU use of 3.5% would translate to a difference in cost of approximately $265 million [annually].” The findings of the study suggest that the availability of palliative care may also reduce stress of end-of-life care for both patients and their loved ones.“Lessmedicalized dying has been associated with higher ratings of quality of life, quality of death, and quality of end-oflife care and fewer psychological symptoms in bereaved caregivers, particularly for patients with advanced cancer,” the authors concluded.

Hospital-Based Palliative Care Reduces End-of-Life ICU Stays

Patient Refusal of Observation After Naloxone: An Ethical, Clinical Dilemma

CLINICAL responses to patient refusal of observation following naloxone resuscitation vary widely by provider, illustrating a need for clinical guidelines and education on the topic, according to data published in the Journal of Emergency Medicine. Following resuscitation with naloxone, clinicians commonly recommend an observation period to monitor for rebound apnea and other symptoms. Patient refusal of this recommendation is common, although rarely discussed in the literature. Investigators conducted interviews with emergency physicians at the 2018 American College of Emergency Physicians’ Scientific Assembly. Interviews were structured around 2 primary sections: ascertaining the interviewee’s personal experience with patient refusal of observation and presenting 3 case scenarios to the interviewees. The case scenarios described patients with varying levels of risk for adverse postresuscitation events. For each case, physicians were asked how they would assess patients’ decisionmaking capacity and in what situations they would honor refusal of observation. A total of 59 emergency physicians provided interview data; 61% were

Patient refusal of observation is common but rarely discussed in the literature.

men and 64% were white. All physicians reported that they recommended a period of observation postresuscitation, although the suggested duration varied significantly between physicians from ≤1 hour (25%), to 2 to 4 hours (48%), to ≥6 hours (17%). The majority of emergency physicians expressed feelings of emotional or moral distress when patients refused observation. Many interviewees felt that their duties to “protect patients’ health” conflicted with “duties to honor patients’ autonomy.” Others described what they felt were “legal strictures” preventing them from taking more drastic steps to enforce observation. Interviewee responses to the 3 case scenarios varied significantly: 29% of physicians equated patient decision-making capacity with the ability to walk and talk (29%), while others assessed capacity in terms of the patient understanding the risks of refusing observation (39%). Some emergency physicians indicated that they were willing to let patients leave the hospital even if they lacked decisionmaking capacity (5% to 14% based on case severity), while others displayed a readiness to “refuse…a patient’s wishes” (17% to 46%). Interview respondents expressed significant concern about malpractice risks, in letting patients leave without observation, and in forcing patients to remain against their will.The majority of physicians (92%) indicated that their hospital did not provide institutional guidelines or support for these situations. Although approaches to the issue varied, most clinicians agreed in the need for physician-led guidelines. “The need for further research is acute,” they said, as is the need for “consensus about strategies for navigating patients’ wishes relative to clinical concerns.”

Nurse Navigation Program Increases Colorectal Screening AN INCREASE in colorectal cancer (CRC) screening rates was seen after the implementation of a nurse navigation program, according to study results published in the Journal of Cancer Education. Participants (n=110) were randomly assigned to either an interventional group with access to a nurse navigation program or to a control group receiving usual care. Patients were interviewed at baseline and at 3 and 6 months from baseline. Interviews addressed sociodemographic information, cognitive function, and CRC risk, in addition to medical advice, beliefs, readiness, and behavior as related to CRC screening tests. At 3 months from baseline, the fecal occult blood test (FOBT) had been completed by 81.8% of nurse-navigated participants compared with 9.1% of control participants. At 6 months, 83.6% of nurse-navigated participants and 10.9% of control participants had completed this test. At 3 months, colonoscopies had been completed by 14.5% of nurse-navigated participants and 3.6% of control participants. By 6 months, 21.8% of nursenavigated participants had completed colonoscopies, while there was no change for control participants (3.6%). The group receiving nurse navigation showed statistically significant mean improvements in perceptions regarding CRC screening benefits and barriers after the completion of the program. “CRC screening participation rates were significantly higher in the nursenavigated group” than in the group without a navigator, they wrote.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2020 9

Newsline

Metabolic Syndrome Associated With Poor Sleep in Teens With PCOS

Sleep studies help identify women with PCOS and metabolic syndrome.

METABOLIC SYNDROME is associated with poorer sleep in girls with polycystic ovary syndrome (PCOS) and obesity, according to research results published in The Journal of Clinical Endocrinology & Metabolism. Adolescents with obesity and PCOS have been found to have more disrupted sleep patterns than adolescents without PCOS, but the relationship between sleep and metabolic syndrome status in this age group remains unexamined. Researchers used data obtained from the APPLE (Liver and Fat Regulation in Overweight Adolescent Girls study; ClinicalTrials.gov Identifier: NCT02157974) and PLUM (Post-Prandial Liver Glucose Metabolism in PCOS study; ClinicalTrials.gov Identifier: NCT03041129) trials to study this relationship. A total of 30 patients with and 36 without metabolic syndrome (aged 12-21 years; body mass index in the 90th percentile or higher for age and sex) were included in the analysis. A medical history and physical examination were completed at the initial visit, and activity and sleep patterns were recorded prior to a subsequent overnight study. Hepatic and visceral fat

were measured by abdominal MRI after an overnight fast.A subset of patients (12 with and 9 without metabolic syndrome) was evaluated by polysomnography to characterize their sleep architecture and respiratory patterns. In patients who received polysomnography, no differences were found in sleep behaviors between the 2 groups, including bedtime, wake time, sleep time, number of awakenings, sleep onset latency, and sleep efficiency. However, a higher apneahypopnea index was observed in girls with metabolic syndrome than in girls without metabolic syndrome (6.5 vs 0.7, respectively; P =.02), indicating an increased prevalence of sleep disordered breathing. Researchers also found that sleep variables were highly correlated with markers of metabolic syndrome. Lower weekday and weekend sleep efficiency was associated with higher percent liver fat (P =.02 and P =.013, respectively). Lower weekday sleep was also associated with a higher waist to hip ratio (P =.004) and lower weekend sleep efficiency was associated with higher triglyceride levels (P =.04).When analyzed on a per-patient level, the number of metabolic syndrome components increased continuously as sleep risk score increased (P =.04). “Among girls with PCOS and obesity, sleep disordered breathing was more prevalent in those with metabolic syndrome, and poor sleep behaviors were associated with metabolic dysfunction and more metabolic syndrome symptoms,” the researchers concluded. “Our data suggests the importance of comprehensive assessment of sleep health including [sleep disordered breathing] as well as duration, timing, and quality, in adolescents with PCOS and obesity, given the association with [metabolic syndrome] and metabolic dysfunction.”

10 THE CLINICAL ADVISOR • MARCH 2020 • www.ClinicalAdvisor.com

ART Prescribing May Differ From Guidelines in Pregnant Women PRESCRIBING PRACTICES of antiretroviral therapy (ART) in pregnant women living with HIV do not always align with national guidelines, according to a study report in JAMA Network Open. The use of ART in pregnant women must balance efficacy of preventing perinatal transmission with safety of the mother and fetus.Therefore, the US Perinatal Antiretroviral Medication Treatment guidelines need continual updating, noted the investigators. The study included data from 1867 pregnancies in 1582 women living with HIV who were enrolled in the Pediatric HIV/AIDS Cohort Study Surveillance Monitoring of ART Toxicities study. The investigators found that 49.5% of pregnant women received ART that was designated as preferred or alternative according to the guidelines; 15.9% were prescribed ART recommended for special circumstances; 26.4% involved ART with insufficient evidence for use during pregnancy; 7.3% received ART not recommended during pregnancy; and 0.9% were treated with ART not mentioned in the guidelines. Pregnant women initiating ART were prescribed preferred or alternative ART at a higher rate compared with women resuming ART or women treated with ART before conception (69.9% vs 52.0% vs 35.9%, respectively). Of the women resuming ART, those with viral loads >1000 copies/mL were twice as likely to be prescribed recommended ART compared with women with lower viral loads (≤400 copies/mL). The study found a discordance between guidelines and actual practice, concluded the investigators. ■

Q& A Interview with NAPNAP President Rajashree Koppolu, RN, MSN, CPNP, MSL

NAPNAP President Tackles Challenges Facing Pediatric Nurse Practitioners In addition to being President of the National Association of Pediatric Nurse Practitioners (NAPNAP), Ms Koppolu is the manager of Advanced Practice at Lucile Packard Children’s Hospital Stanford, in Palo Alto, California, where she works with the general surgery service, providing direct clinical care to complex pediatric surgery patients in both inpatient and ambulatory settings.

We are practicing at a time when there are many contextual factors that affect the health outcomes of children.

The Clinical Advisor: What is the biggest challenge facing pediatric-focused advanced practice nurses (APRNs)?

Ms Koppolu: One of the biggest challenges we face as a specialty is the rapidly changing health care environment and increased numbers of uninsured patients. Between 2016 and 2018, more than 400,000 children became uninsured, driven mainly by coverage losses in Medicaid and the Children’s Health Insurance Program (CHIP), which provides low-cost health coverage to children in families that do not qualify for Medicaid. Currently, more than 4 million US children are uninsured. As health care providers, we know the importance of families having access to high-quality, affordable, accessible health care, whether that be preventive or tertiary-based care. To help deal with the new health care landscape, NAPNAP has made it a priority to understand insurance eligibility requirements and renewal processes, as well as what resources are available to families for outreach and enrollment. For example, we’ve been advocating for the reauthorization of programs such as CHIP. On the front lines, our members are helping families navigate the health insurance process and understand their benefits and eligibility requirements. Another big challenge facing advanced practice professionals is understanding the social influencers of health, such as food and housing insecurity and exposure to violence, both domestic and in the

12 THE CLINICAL ADVISOR • MARCH 2020 • www.ClinicalAdvisor.com

community. There are extensive data about the negative effects of adverse childhood experiences, especially when traumas occur during early development.These experiences affect the immediate and long-term health of children—both physical and mental.We are encouraging members to identify and address these issues in their practices. These social challenges are very different than the traditional ones clinicians typically cite, such as ensuring accurate diagnoses and effective treatments. How is NAPNAP addressing these new challenges?

We are practicing at a time when there are many contextual factors that affect the health outcomes of children. As an association, NAPNAP recognizes this and is proactively trying to better understand these trends and find ways to support our members and help them in their practices. Do nurse practitioners have the time to ask about social and environmental factors during office visits or are they feeling too strapped for time?

Many of us have high-volume practices, and we increasingly have a growing number of children with complex medical conditions. Over 30% of US children have a chronic health condition and nearly 20% have a special health care need. Given that, it can be a challenge to ask questions about these issues. But, if we think outside the box, we can

Q&A

become stakeholders in public health and policy. We need to understand these social and environmental factors and work together to have more influence over these issues in our daily clinical practices and as they relate to the broader society. What is the biggest public health issue facing pediatric nurse practitioners?

NAPNAP has been involved in understanding the impact of gun violence in our communities, dealing with the medical-related effects of climate change, and offering members education and resources to work with families that are hesitant about providing vaccines to their children. Some other public health concerns are infectious disease outbreaks that we’ve seen around the country and the world, as well as the growing issue of antimicrobial resistance.The latter issue is particularly relevant to childhood illness.We have to be very thoughtful and mindful about the way we treat disease, becoming antibiotic stewards to prevent the overprescribing of antibiotics in situations in which they are not needed. One issue that we have focused on this year has been the effects of electronic cigarette use and vaping among young children and adolescents. In the fall of 2019, NAPNAP put out an official statement on vaping just as the Centers for Disease Control and Prevention was starting to report on the rise of EVALI (e-cigarette or vaping productassociated lung injury) cases. Vaping has become socially normative in our culture, and a large population of children and youth use these products. But there is limited research and techniques to help patients quit or refrain from using e-cigarettes. We need to educate our members about what, in addition to nicotine, is in these devices, how they work, and the clinical impact of EVALI in adolescents.The types of lung injuries seen with vaping are very different from other types of respiratory illness. As an organization, we’ve been active advocates for better regulation of these devices, specifically when it comes to targeting children. But we need more research and evidence-based recommendations on vaping cessation strategies, similar to our educational efforts related to smoking and smoking cessation.

Can you speak a little bit more on the effects of climate change on childhood illness?

Climate change can affect children in a number of ways. For example, when a natural disaster occurs (wildfires, tornados, hurricanes), children may experience food and water security issues, displacement, and trauma. We also know that children are particularly vulnerable to ground level pollutants because they engage in a lot of crawling and hand-to-mouth activities. Children have a developing immune system, and childhood illness such as asthma and other conditions can be exacerbated by environmental changes. Our role is to support policies, advocate for research, and make sure that our members are well-versed in the latest information and regulations and laws that provide protection to children in order to provide anticipatory guidance to families. Has it been difficult for NAPNAP to address the needs of nurse practitioners in the inpatient and outpatient sectors?

Our role is to support policies and advocate for research... that provide protection to children in order to provide anticipatory guidance to families.

One of our core values as an association is diversity and inclusion. We have more than 9000 members representing more than 18 special interest groups and 50 chapters. Although the majority of our members are working in primary care, rural health, school-based health, or community health practices, we have a growing number of members who work in subspecialty outpatient or inpatient critical care or acute care areas. When we look at our national clinical conferences, regional symposiums, and online teaching forums, we want to make sure that we are offering topics that are applicable to practitioners in inpatient settings as well as those who have an outpatient ambulatory care role. Because pediatric-focused APRNs do such a great job of caring for a diverse patient population, we want to ensure that we develop a pipeline of future practitioners who enter the workforce with a passion for caring for and working with children. So, I think part of that means we have a responsibility to promote the value of pediatricfocused APRNs in these clinical practices. We want to make sure that all the work we’re doing now is carried on by future providers. ■ www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2020 13

FEATURE: JAMES HAINES, MPAS, PA-C; DAVID LEVAN, DHSC, OTR/L, CSRS; MICHELE M. ROTH-KAUFFMAN, JD, MPAS, PA-C

Malnutrition in the Elderly: Underrecognized and Increasing in Prevalence Malnutrition needs to be recognized and treated early to ensure the best possible outcome for elderly patients.

alnutrition in the elderly is an underrecognized condition that is increasing in prevalence as the population ages. The term malnutrition is often used to describe a deficiency in nutrition that causes adverse effects on the body and its normal functions.1,2 Although malnutrition can occur at any age, it is especially prevalent in people >60 years of age.1-4 Poor nutritional status is well established as a negative prognostic indicator in the elderly population, and weight loss in individuals >60 years of age approximately doubles the risk of dying.5 Despite the availability of several validated nutritional screening tests, many cases of malnutrition go undiagnosed, leading to increased morbidity and mortality, prolonged hospital stays, and frequent hospital readmissions.5,6 It is therefore important that healthcare providers be able to identify the causes and signs and symptoms of malnutrition. If identified early, malnutrition can be treated with proper adherence to a nutritional intervention plan.2 Early recognition and treatment of malnutrition are not only beneficial for the patient’s health but can reduce overall cost to the healthcare system.7 Etiology

Malnutrition in the elderly doubles the risk of dying.

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As people get older they tend to become more sedentary and their body composition changes, resulting in an increase in body fat and a decrease in lean muscle mass and extracellular fluid. The body responds to the need for less energy by decreasing appetite, a process known as “anorexia of aging.”2

The etiology of weight loss and malnutrition in the elderly has been attributed to psychologic, physiologic, and environmental factors.1,2 These components are frequently referred to as the “9 Ds” of weight loss in the elderly (Figure).1,2 Dementia Dementia is a cognitive impairment that results in deterioration in memory or executive function and mostly affects the elderly population.8 Individuals with dementia can have impairment in activities of daily living, including the ability to shop, prepare food, manage money, and remember to eat.8,9 Sleep disturbances can affect cognitive and physical function.10-12 Impairments such as decreased arousal, disorientation, and reduced ability to maintain upright posture may make feeding oneself difficult. Patients with dementia are often dependent on another individual to help them meet their nutritional needs. However, many patients do not have the financial resources needed to hire caregivers or have family members who are willing and/ or able to undertake these tasks.4,8,9 Dysgeusia The loss of taste is an impairment in the ability to detect sweet, sour, salty, and bitter tastes.13 Impaired taste buds decrease the

ability of the elderly to differentiate between basic tastes and may lead to a decrease in the pleasure of eating and quality of life.1,13 The cumulative effect of this often results in decreased appetite, leading to poor food intake and weight loss, which contribute to malnutrition. Some common causes of dysgeusia are poor dentition, poor oral hygiene, oral dryness, oral bacterial growth, smoking, and changes in the tongue.13 Diarrhea Chronic diarrhea is defined as diarrhea that is present for longer than 4 weeks.14 Weight loss is commonly seen with many causes of chronic diarrhea and can lead to malnutrition.1,2,14 The most common causes of chronic diarrhea are medication use, osmotic disorders, secretory conditions, inflammatory conditions, malabsorptive conditions, motility disorders, chronic infections, and systemic diseases.14 Depression Depression in the elderly is often underrecognized. There are many variables that affect the incidence of depression, such as sex, marital status, cognitive status, ability to perform activities of daily living, and social interaction.15 Research has found Continues on page 21

1 Diarrhea Dysphagia • Inability to eat, drink, or swallow • Increased anxiety about eating and drinking

• Diarrhea lasting >4 weeks • Chronic discomfort • Weight loss

Depression • Decreased motivation to eat • Reduced social interaction during meals

Disease

Dementia

• Negative effect on nutritional status • Creates increased nutritional demand

• Not remembering to eat • Inability to prepare meals • Sleep disturbances

MALNUTRITION

Drugs

Dentition

• Unwanted adverse effects and interactions • Reduced absorption of nutrients

• Poor oral hygiene • Inability to chew food

• Immunodysfunction • Impaired wound healing • Impaired activities of daily living

• Reduced sense of taste • Decreased appetite • Lack of pleasure when eating

Dysfunction

Dysgeusia

FIGURE. The 9 Ds of malnutrition in the elderly.1,2 www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2020 15

MALNUTRITION IN THE ELDERLY

Findings of malnutrition include weight loss, loss of muscle mass, localized fluid accumulation, loss of function, anemia, and fatigue. an association between depression and decreased nutritional status.15 Although more studies are needed to confirm this relationship, depression has been shown to be an independent predictor of poor nutritional health and a major cause of weight loss leading to malnutrition.2,15 Dysphagia Dysphagia — the inability to eat, drink, or swallow — is often present in the elderly and can be caused by a mechanical obstruction or a neurologic condition affecting the esophagus.16 Normal swallowing involves oral, pharyngeal, and esophageal phases, all of which are performed without conscious effort hundreds of times a day. Dysphagia occurs when normal swallowing is disrupted.16 A study published in 2002 revealed that 50% of participants admitted to eating less because of dysphagia, and 44% had weight loss.17 Dysphagia makes eating an unpleasant experience that contributes to poor eating habits, resulting in malnutrition.16 Disease Any disease can have a negative effect on nutritional status and contribute to malnutrition. Individuals with cardiac disease and chronic obstructive pulmonary disease, as well as those who have experienced a stroke, have been found to have an increased nutritional need but often fail to meet the nutrient and protein goals set for them.18 The American Diabetes Association has specific dietary recommendations that are often difficult for geriatric patients to follow. This results in nutritional imbalance, leading to microvascular disease, which is often manifested in the heart, eyes, and kidneys.2,18 Diabetes has been associated with a faster loss of muscle strength and an increased rate of disability in the elderly population. Dentition Poor dental health and the loss of teeth can affect the ability to chew and limit choice of foods, which can have an adverse effect on maintaining proper nutrition.2,19 A study conducted in Spain revealed that persons with dental defects experienced a higher rate of malnutrition.19 Although these problems can be corrected with dental care and the use of proper-fitting dentures, geriatric patients living on a fixed income often cannot afford proper dental care and/or dentures.19 Drugs As people age, their level of polypharmacy generally increases.20 The 6 most frequently prescribed classes of medications in the

elderly are gastrointestinal agents, antihypertensives, diuretics, analgesics, beta-blockers, and antihyperlipidemic agents.20 Medications may be prescribed by different providers who unknowingly set patients up for unwanted adverse effects and drug interactions that may cause decreased food consumption and nutrient intake and absorption, resulting in poor nutritional status.2,20 Dysfunction Dysfunction of the immune system can lead to increased infection and delayed wound healing, which can directly contribute to malnutrition.1 Altered gut integrity leads to increased intestinal infections that can affect the absorption of nutrients.1 Physical dysfunction that impairs engagement in activities of daily living can hinder a patient’s ability to obtain and prepare food, worsening nutritional status.1,6 Other aspects of malnutrition that are not directly covered in the “9 Ds” are sex, resources to purchase food, accessibility to food, living conditions, and existence/strength of family and social networks.2,19 Identifying Malnutrition

Physical findings of malnutrition include weight loss, decreased muscle mass and subcutaneous fat, localized or generalized fluid accumulation (edema and ascites), compromised functional status, poor wound healing, loose clothes or jewelry, dry and sallow skin, and fatigue.2,5,21 Laboratory tests used to help measure nutritional status include albumin, prealbumin, transferrin, retinal binding protein, insulin-like growth factor-1, and fibronectin.5,21 Other laboratory tests such as C-reactive protein, white blood cell count, and blood glucose levels may aid in diagnosing a specific etiology of malnutrition.21 If a patient’s signs and symptoms indicate malnutrition, a formal nutritional assessment using approved screening tools should be performed by a healthcare professional with nutritional expertise (Table 1, page 22).5,6 Significant advances in the ability to detect malnutrition through the use of screening tests have occurred in the last 30 years.5,6 The Mini Nutritional Assessment (MNA) was created by Vellas and Guigoz in 1989 and has become the best validated and most widely used tool to assess malnutrition.2,5 It is composed of 18 questions that are graded numerically based on an individual’s response, with scores between 17 and 23 reflecting the individual to be considered at risk for malnutrition and scores <17 representing protein energy malnutrition.5 The advantage of the MNA over other screening

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2020 21

MALNUTRITION IN THE ELDERLY

tests is that it does not rely on laboratory testing, making it more accessible and easier to perform.5 A shorter form of the MNA (MNA-SF) is designed especially for the elderly and consists of 6 questions that address weight loss, appetite, mobility, psychologic stress, neuropsychologic problems, and body mass index (BMI).5 It is often used as an initial screening tool that can be combined with the MNA for a more detailed nutritional assessment when warranted.6 The MNA and MNA-SF are not useful for patients who are unable to provide accurate and reliable information about themselves.5,6 Although the MNA is the most widely used screening tool, several other validated tests are available to identify malnutrition.5 The Malnutrition Universal Screening Tool (MUST) TABLE 1. Sample of Nutritional Assessment Screening Tools5,6 Name

Criteria

Scoring System

Year Validated

MNA-SF Decreased food intake, involuntary weight loss, extent of mobility, dementia/ depression, BMI/calf circumference

Each question is assigned point values: • 12-14 normal • 8-11 at risk • 0-7 malnourished

2001

MUST

BMI, unintentional weight loss, acute disease effect

Each parameter is rated between 0 and 2: • 0 low risk • 1 medium risk • 2 high risk

2003

NRI

Serum albumin concentration plus present weight/ usual weight

• >100: well nourished • 97.5-100: mildly malnourished • 83.5-97.5: moderately malnourished • <83.5: severely malnourished

1980

GNRI

Serum albumin concentration plus present weight/ideal weight

• >98: well nourished • 92-98: low risk • 82-92 moderate risk • <82: severe risk

2005

SGA

Weight loss, dietary intake changes, gastrointestinal symptoms

• Grade A: normal • Grade B: moderately malnourished • Grade C: Severely malnourished

1987

BMI, body mass index; GNRI, Geriatric Nutritional Risk Index; MNA-SF, Mini Nutritional Assessment-Short Form; MUST, Malnutrition Universal Screening Tool; NRI, Nutritional Risk Index; SGA, Subjective Global Assessment

uses BMI, weight loss, and acute disease effect. It is validated for all adult patients in any healthcare setting.5,6 The Nutritional Risk Index (NRI) and the Geriatric Nutritional Risk Index (GNRI) use albumin and another nutrition indicator such as weight loss to assess nutritional status.6 These values are then plugged into an equation that varies slightly between the NRI and GNRI, giving a score that can be categorized into well nourished, mildly malnourished, moderately malnourished, and severely malnourished.6 The Subjective Global Assessment gives a grade of malnutrition based on questions asked about weight loss, dietary intake changes, gastrointestinal tract symptoms, physical function, and parameters of physical examination. Grade A refers to normally nourished patients, grade B refers to moderate malnutrition, and grade C is used for severely malnourished patients. Some disadvantages to this test are that it must be administered by a physician and it is subjectively based on the patient’s answers.6 Despite the availability of screening tests that have been developed to detect malnutrition, the condition remains underdiagnosed.2,5,6 Consequences of Malnutrition

Malnourishment is often referred to as “a cause and consequence of adverse outcomes” and affects almost every organ system in the body.1 When the body is not receiving adequate nutrient intake, it relies on nutritional stores to provide fuel and energy for normal functions.1 When these stores run out, the body starts to metabolize protein into a usable energy source, resulting in depleted muscle mass. The patient then becomes more susceptible to disease.1,2 Impaired immune response as a result of malnutrition makes the elderly more susceptible to infection and diminishes the ability to mount a response if infected, which can be life threatening.1,2,4 Because protein in muscles is broken down for energy in a malnourished state, overall muscle strength is decreased, leading to an increase in falls, reduced respiratory function, and the inability to perform tasks such as shopping, cooking, and food preparation, contributing to further nutrient deficit.2 Malnourished patients often lack energy, resulting in decreased activity.2 This sedentary lifestyle increases the risk for pressure ulcers and deep vein thrombosis.2,8 Malnutrition can lead to temperature, salt, and fluid regulatory mechanisms being lost or impaired, which can result in hypothermia, dehydration, or overhydration.2 Inadequate intake of nutrient-dense foods can cause nutrient deficiencies in vitamin C, vitamin B12, folate, vitamin A, potassium, and iron. Inadequate levels of these nutrients may lead to impairment in homeostasis, increasing the risk of mortality if left untreated.2,8,18 Psychosocial function may also be affected, increasing the risk for depression,

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apathy, introversion, loneliness, and hypochondriasis, which can further contribute to poor nutrition in the patient.2,15 Malnutrition has been identified as a preventable risk factor that leads to unnecessary hospital visits and expenditures.3,7 Elderly adults are at high risk for repeat hospitalizations and readmissions, and reducing these occurrences has become a major goal of hospitals and insurance companies.3,7 In hospitalized patients, multiple factors such as disease, trauma, sepsis, and fever can contribute to malnutrition even if adequate oral intake is achieved.7 A retrospective study analyzed whether malnutrition at hospital admission helped predict the clinical outcomes of 2076 patients aged 65 years and older during an 18-month follow-up.1 Nutritional status was determined using the MNA within 72 hours of admission: 30% of patients were malnourished, and 53% were at risk for malnutrition.1 The authors found that malnourished patients had a longer median hospital stay (34 days), at-risk patients’ median stay was 26 days, and well-nourished patients had the shortest stay with a 20-day median.1 The number of readmissions was not significantly associated with malnutrition in this study; however, it should be noted that compared with well-nourished patients, malnourished patients had 6 times the rate of discharge to a high-level care facility.1 Analysis of the survival rate in this study when controlling for age, sex, disease, morbidity, and length of stay revealed that the hazard ratio for death in the malnourished group was 3.4 times that of the well-nourished group.1 A Canadian study evaluating 1022 patients found that malnutrition, as determined by Subjective Global Assessment, was independently associated with prolonged length of hospital stay and readmission.7 Several similar studies investigating the role of malnutrition on clinical outcomes had results consistent with these findings.1,3,7 Managing Malnutrition

Physicians, physician assistants, nurse practitioners, nurses, dietitians, and pharmacists are among the numerous healthcare professionals who manage malnutrition in patients (Table 2).2,21 Together, the team should develop a strategy that is specific and individualized for a given patient.2 The strategy should be compatible with the patient’s lifestyle, financial situation, and resources available for implementation.2,21 Regular evaluations using consistent nutritional parameters are imperative to ensure the best possible outcome is achieved.2 The patient’s healthcare team must communicate often and effectively to make certain an optimal plan is in place that maximizes patient adherence.12,21 Seven elements of patient management are advised for addressing malnutrition.

Rehabilitation Speech-language pathologists and physical and occupational therapists work directly with patients, family members, and caregivers to support overall nutritional intake. Speech-language pathologists assist in the evaluation, diagnosis, and treatment of communication (eg, language comprehension and expression) and dysphagia. Speech-language pathologist interventions may include use of specialized compensatory strategies, altering the patient’s diet, and training and education to improve safe eating and drinking. Physical therapists assist in the evaluation, diagnosis, and treatment of functional limitations such as pain; decreased strength, endurance, and flexibility; poor balance; and insufficient postural control that can compromise the ability to effectively consume meals. Physical therapist interventions may involve exercises and activities that focus on the reduction of physical impairments to improve performance and functional mobility. Occupational therapists evaluate and provide interventions that consider physical, cognitive, social, emotional, TABLE 2. Multidisciplinary Team Management of Malnutrition in the Elderly2,21 Physician

Evaluation, diagnosis, treatment, and management of disease processes that affect overall nutritional status; patient education; referral

PAs/NPs

Evaluation, diagnosis, treatment, and management of disease processes that affect overall nutritional status; patient education; referral; seek input from supervising physician as necessary

Dietitian

Evaluation of diet and nutritional status; provide dietary and nutritional recommendations

Pharmacist

Evaluation of medications for interactions and effect on nutritional status; make recommendations for alternate medications as appropriate

Speech and language pathologist

Evaluation, diagnosis, and treatment of communication and language disorders that affect safe eating, drinking, and feeding

Physical therapist

Evaluation, diagnosis, and treatment of physical impairments that reduce functional mobility skills required for eating, drinking, and feeding

Occupational therapist

Evaluation and treatment of physical, emotional, and psychosocial needs that improve safety, independence, and willingness for eating, drinking, and feeding

NP, nurse practitioner; PA, physician assistant

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2020 23

MALNUTRITION IN THE ELDERLY

POLL POSITION Which of the following is not a sign of malnutrition in the elderly?

■ Decrease in muscle mass ■ Decrease in body fat

9.78% 15.94%

■ Decrease in intracellular fluid ■ Decrease in appetite

38.04%

fiber; these should be chosen on the basis of individual need.2 Supplements come in many forms and flavors, and should be chosen based on the individual’s ability to properly prepare the supplement and taste preferences.2 Although results have not been conclusive, data from studies suggest that nutritional supplements be given at a midway point between meals for optimal results.2 The use of nutritional supplements should be regularly evaluated to ensure the patient is tolerating it well and receiving proper nutritional benefit.2 In the elderly, high-quality supplements have been shown to promote healthy aging and improve age-related problems and diseases.18

36.23%

For more polls, visit ClinicalAdvisor.com/Polls.

environmental, and cultural elements of feeding, eating, and swallowing. Occupational therapist interventions may focus on the reduction of positioning problems, psychosocial needs, and use of adaptive equipment that improve a patient’s ability and willingness to acquire nutrition. Food-First Approach This method is generally used as a first-line approach in patients who are deemed mildly malnourished or at risk for malnourishment and who do not have dysphagia.3 If a patient is unable to give reliable information regarding food and nutrient intake, this information should be obtained from a caregiver or another reliable source.21 This approach calls for 6 small meals to be eaten at approximately equal intervals throughout the day, and for individuals to have access to foods and beverages that meet their nutritional needs and taste preferences.2 Oil, butter, margarine, cream cheese, sauces, honey, and sugar may be added to foods to increase caloric content and improve taste.2 Plain water should be substituted with drinks with more nutritional content such as milk or juices.2 Food should look appealing and have a texture and taste that the individual is able to tolerate well.2 Meals should be consumed in a comfortable and relaxed environment to promote maximum food intake.2 Supplementation For patients who are unable to consume enough protein and nutrients, oral drink supplements are an alternative source to aid in the achievement of daily nutritional requirements.2,18 A variety of different supplements provide a range of nutritional benefits including high energy, high protein, and high

Exercise A continuous program of physical activity including aerobic exercise and resistance training can provide a broad range of physiologic benefits that help maintain or improve overall functional mobility.22,23 Muscle mass is the largest reservoir of body protein and its preservation is important for maintaining nutritional status and physical function.24 Older malnourished patients are at increased risk for muscle mass loss, and a combination of exercise and high protein intake is recommended to help maintain and build these stores.18,24 Strength exercise conducted 2 to 3 times per week over the course of 9 weeks has been shown to be effective in increasing muscle mass in healthy to moderately impaired individuals.24 Consuming a protein supplement directly after exercise has been shown to increase the effect of exercise on muscle mass.18,24 Patients with serious disease complications or a recent catastrophic event may not be able to tolerate exercise and should consult with a physician before beginning a regimen.24 Medical Intervention Appetite stimulants are rarely indicated to help patients achieve increased appetite because of interactions with other medications, resulting in unwanted adverse effects.2 Antidepressants can improve mood and overall well-being and increase the desire to eat and maintain health in elderly patients who demonstrate signs of depression.15 Dentures may be appropriate for individuals with poor dentition to increase the range of foods that can be easily consumed.19 Other pharmacologic therapy and medical interventions should be prescribed according to individual needs. Food Services Programs that provide food to the elderly have been shown to help prevent malnutrition and ensure nutritional needs are met. The Administration on Aging (AOA) provides communal and personal, home-delivered meals and other nutrition-related services to elderly individuals.25 The AOA stipulates that all meals generated with their funds must provide one-third of

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an individual’s daily nutritional requirements.25 The elderly nutrition program provides a range of other services including helping participants learn how to shop, save, and prepare meals that are economical and healthy. Volunteers and paid staff who deliver these meals often spend time with individuals to alleviate loneliness and to identify any additional unrecognized medical problems that should be reported to the appropriate provider.25

8. Kane R, Shamliyan T, Talley K, Pacala J. The association between geriatric syndromes and survival. J Am Geriatr Soc. 2012;60(5):896-904. 9. Riches K, Jeanes Y. The prevalence of malnutrition in elderly residents in a warden-assisted setting compared with home-living environment. Br J Community Nurs. 2014;19(7):324-327. 10. Rose KM, Lorenz R. Sleep disturbances in dementia: what they are and what to do. J Gerontol Nurs. 2010;36(5):9-14. 11. Ronqve A, Boeve BF, Aarsland D. Frequency and correlates of caregiver-

Prevention

reported sleep disturbances in a sample of persons with early dementia. J Am

As described earlier, malnutrition can lead to increased vulnerability to illness and poor clinical outcomes, and can increase mortality.Better outcomes can be achieved through preventive measures in at-risk individuals, rather than attempting to cure malnutrition after its onset. Elderly individuals who are not malnourished or who are at low risk for malnourishment should be regularly monitored for weight loss and screened for signs of malnutrition in an effort to decrease overall incidence.Clinicians should be aware of the signs and symptoms of malnutrition, along with the screening tests that help recognize and diagnose the condition, to prevent further progression. ■

Geriatr Soc. 2010;58(3):480-486. 12. Cole CS, Richards KC. Sleep in persons with dementia: increasing quality of life by managing sleep disorders. J Gerontol Nurs. 2006;32(3):48-53. 13. Solemdal K, Sandvik L, Willumsen T, Mowe M, Hummel T. The impact of oral health on taste ability in acutely hospitalized elderly. PLoS ONE. May 2012;7(5):e36557. 14. McQuaid K, Gastrointestinal disorders. In: Papadakis M, McPhee S. Current Medical Diagnosis and Treatment. 53rd ed. San Francisco, CA: McGraw Hill; 2014;66:556-562. 15.Yoshimura K,Yamada M, Kajiwara Y, Nishiguchi S, Aoyama T. Relationship between depression and risk of malnutrition among community dwelling young-old and old-old elderly people. Aging Ment Health. 2013;17(4):456-460.

James Haines, MPAS, PA-C, specializes in emergency medicine at Lake West Hospital in Willoughby, Ohio. David LeVan, DHSc, OTR/L, CSRS, is an associate professor in the Occupational Therapy Program at Gannon University in Erie, Pennsylvania. Michele M. RothKauffman, JD, MPAS, PA-C, is a founding program director of the Physician Assistant Program at Gannon University in Ruskin, Florida.

16. Cartwright A. Time to recognise dysphagia as a contributing factor to malnutrition. Br J Community Nurs. 2013;Suppl Nutrition:S6. 17. Ekberg O, Hamdy S, Woisard V, Wuttge-Hannig A, Ortega P. Social and psychological burden of dysphagia: its impact on diagnosis and treatment. Dysphagia. 2002;17(2):139-146. 18. Bauer J, Biolo G, Cederholm T, et al. Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the

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PROT-AGE study group. J Am Med Dir Assoc. 2013;14(8):542-559.

1. Agarwal E, Miller M, Yaxley A, Isenring E. Malnutrition in the elderly: a narra-

19. Lopez-Jornet P, Saura-Perez M, Llevat-Espinosa N. Effect of oral health den-

tive review. Maturitas. 2013;76(4):296-302.

tal state and risk of malnutrition in elderly. Geriatr Gerontol Int. 2013;13(1):43-49.

2. Burton-Shepherd A. Preventing malnutrition in the home-dwelling elderly

20. Heuberger RA, Caudell K. Polypharmacy and nutritional status in older

individuals. Br J Community Nurs. 2013;18(10):25-31

adults. Drugs Aging. 2011;28(4):315-323.

3. Legrain S, Tubach F, Bonnet-Zamponi D, et al. A new multimodal geri-

21. White JV, Guenter P, Jensen G, Malone A, Schofield M. Consensus statement

atric discharge-planning intervention to prevent emergency visits and

of the Academy of Nutrition and Dietetics/American Society for Parenteral

rehospitalizations of older adults of older adults: the optimization of medi-

and Enteral Nutrition: characteristics recommended for the identification and

cation in aged multicenter randomized controlled trial. J Am Geriatr Soc.

documentation of adult malnutrition. J Acad Nutr Diet. 2012;112(5):730-738.

2011;59(11):2017-2028.

22. Pahor M, Guralnik JM, Ambrosius WT, et al; for the LIFE study investiga-

4. Bell CL, Tamura BK, Masaki KH, Amella EJ. Prevalence and measures of

tors. Effect of structured physical activity on prevention of major mobil-

nutritional compromise among nursing home patients: weight loss, low body

ity disability in older adults: the LIFE study randomized clinical trial. JAMA.

mass index, malnutrition, and feeding dependency: a systematic review of the

2014;311(23):2387-2396.

literature. J Am Med Dir Assoc. 2013;14(2):94-100.

23. Yeom HA, Keller C, Fleury J. Interventions for promoting mobility in com-

5. Morley JE. Assessment of malnutrition in older persons: a focus on the mini

munity-dwelling older adults. J Am Acad Nurse Pract. 2009;21(2):95-100.

nutritional assessment. J Nutr Health Aging. 2011;15(2):87-90.

24. Carlsson M, Littbrand H, Gustafson Y, et al. Effects of high-intensity exercise

6. Poulia K-A, Yannakoulia M, Karageorgou D, et al. Evaluation of the efficacy of

and protein supplement on muscle mass in ADL dependent older people

six nutritional screening tools to predict malnutrition in the elderly. Clin Nutr.

with and without malnutrition-a randomized controlled trial. J Nutr Health

2012;31(3):378-385.

Aging. 2011;15(7):554-560.

7. Jeejeebhoy KN, Keller H, Gramlich L, et al. Nutritional assessment: compari-

25. Administration for Community Living (ACL). Nutrition services. ACL

son of clinical assessment and objective variables for the prediction of length

website. https://acl.gov/programs/health-wellness/nutrition-services. Updated

of hospital stay and readmission. Am J Clin Nutr. 2015;101(5):956-965.

November 13, 2019. Accessed December 26, 2019.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2020 25

FEATURE: MARY JANE HANSON, PHD, CRNP, FNP-BC, FAANP

May-Hegglin Anomaly: A Case of Thrombocytopenia, Hearing Loss, and Cataracts May-Hegglin anomaly belongs to a group of inherited giant platelet disorders caused by mutations in the MYH9 gene.

The presence of Döhle bodies is a hallmark of May-Hegglin anomaly.

26 THE CLINICAL ADVISOR • MARCH 2020 • www.ClinicalAdvisor.com

56-year-old construction worker presents to his primary care clinician for a routine physical examination. He has no specific complaints, although he mentions that his hearing is slowly getting worse. An audiometry exam confirms bilateral mild to moderate hearing loss at 40 dB. His physical examination is otherwise unremarkable. The patient’s medical history includes a >30year history of a low platelet count but is otherwise unremarkable. When asked about his low platelet count, the patient states that he was told “not to worry about it.” He could not remember any specific laboratory values or when his most recent blood work was done. He denies having a history of petechiae, spontaneous bleeding or bruising, gum or nose bleeding, or increased bleeding with dental procedures or minor injuries. The patient’s medical history also includes bilateral cataract surgery 2 years ago, with no postoperative bleeding complications. He reports that he consumes approximately 2 to 4 beers per week and does not smoke cigarettes or use recreational drugs. The patient is married with 2 grown children. Neither of his parents, both of whom died from a heart attack when they were in their 70s, had any known bleeding disorders, and he has no siblings. Given the patient’s history, a complete blood count (CBC) was ordered. White blood count, red blood count, and indices were within normal

limits. His platelet count was low at 26,000/μL (reference range, 150,000/μL to 400,000/μL). May-Hegglin Anomaly

May-Hegglin anomaly (MHA) is a rare, congenital, autosomaldominant disorder first identified by German physician Richard May in the early 1900s and then later described in more detail by Swiss physician Robert Hegglin in the mid1940s.1 The disorder is characterized by thrombocytopenia, abnormally large and misshapen (giant) platelets, and a defect of leukocytes consisting of the presence of inclusion bodies, also known as Döhle bodies, in the cytoplasm (Figure).1 Some individuals with this disorder are asymptomatic, whereas others may have various bleeding disorders and other abnormalities, such as sensorineural hearing loss, cataracts, and renal insufficiency or failure.2,3 MHA is 1 of 4 overlapping syndromes that belong to a group of inherited giant platelet disorders caused by mutations in the MYH9 gene. The other 3 disorders are Epstein syndrome, Fechtner syndrome, and Sebastian platelet syndrome.3 Common to all 4 syndromes are giant platelets and thrombocytopenia (macrothrombocytopenia). The 4 syndromes are distinguished from one another by the presence or absence of the leukocyte inclusion bodies. MHA is the only syndrome to demonstrate large leukocyte cytoplasmic inclusion bodies, whereas small leukocyte cytoplasmic inclusion bodies are observed in Fechtner syndrome and Sebastian platelet syndrome. Inclusions cannot be observed via standard light microscopy in Epstein syndrome.3 Although MHA was first identified more than a century ago, it has been only 20 years since the genetic basis of MHA was established as a mutation in MYH9, the gene that encodes for the nonmuscular myosin heavy chain IIA (NMMHC-IIA).2-4 A study revealed that the MYH9 mutation causes a loss of myosin IIA function, thus promoting proplatelet formation and possibly triggering premature platelet release, which may result in macrothrombocytopenia.2 Glomerulonephritis, sometimes seen in MHA, also is thought to be caused by defects in the myosin IIA structure. Manifestations of this syndrome (ie, renal disease, hearing loss, and presenile cataracts) are dependent on the position of the mutations within the gene.2 Signs and Symptoms

Although thrombocytopenia occurs in 50% of patients with MHA, severe bleeding is unusual. Individuals may experience easy bruising, recurrent epistaxis, gingival bleeding, menorrhagia, and excessive bleeding associated with surgical procedures.5 In women, iron deficiency anemia caused by menorrhagia is a major problem. In addition, high-tone

hearing loss, renal involvement, and cataracts are, in decreasing order of frequency, clinical features of MHA.6 Petechiae are rare and usually only occur if the already depressed platelet count decreases further due to comorbidities. Platelet counts may vary between <30,000/μL and 100,000/μL.5 In an individual patient, the platelet count may remain rather stable over time. However, a transient decrease in platelet count may occur after a viral infection or other risk factors for thrombocytopenia.7 Even though giant platelets are present from birth in all individuals with an MYH9-related platelet disorder, mild conditions may remain undetected even in adulthood. For those individuals, distinguishing between a congenital or inherited thrombocytopenia and an acquired or secondary thrombocytopenia, such as an immune thrombocytopenia purpura, is essential to avoid unnecessary and potentially harmful treatments, including corticosteroid therapy and splenectomy.6 Identification of patients with probable MYH9-related disorders is possible through the analysis of blood cell count, mean platelet volume, platelet histogram, and platelet morphology in the blood smear.7 The diagnosis of MHA occurs through the identification of characteristic leukocyte inclusion bodies on stained blood smears. If suspected, the disease may be confirmed by the immunofluorescence test for NMMHCIIA distribution within neutrophils. In the case of MYH9-related diseases, the test will demonstrate cytoplasmic aggregates or clusters.6 However, it is not always easy to detect the leukocyte inclusion bodies on stained blood smears, which can lead to a misdiagnosis of immune thrombocytopenia purpura and incorrect treatment.8 Management of MHA

Although most patients with MHA do not experience significant bleeding problems, the recommended precautions for other bleeding disorders apply to MHA. Thus, patients should: • Avoid any medications that impair platelet function, such as aspirin and other nonsteroidal anti-inflammatory drugs; • Have regular dental care to avoid chronic blood loss from bleeding gums; • Have renal function tested annually; and • Have a hearing test every 5 years.7 There is no treatment to prevent the nonhematopoietic manifestations of MYH9-related disorders. It is possible that avoiding very loud noises at a young age may delay the process of hearing loss, and cochlear implants could be an option to improve severe hearing deficits.7 Intravenous immunoglobulin G, corticosteroids, and splenectomy (often used in treatment of immune thrombocytopenia

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2020 27

UNDERSTANDING MAY-HEGGLIN ANOMALY

There is no treatment to prevent the progression of nonhematopoietic manifestations of gene-related May-Hegglin anomaly. purpura) are relatively ineffective for MHA.7 This further supports the need for an accurate diagnosis when platelet counts are low. Given the autosomal dominance of MHA, it is important to assess all first-degree relatives for macrothrombocytopenia. A normal platelet count excludes MHA, and in these cases, the disease cannot be passed to offspring.7

References 1. Saito H, Kunishima S. Historical hematology: May-Hegglin anomaly. Am J Hematol. 2008;83(4):304-306. 2. Kunishima S, Saito H. Advances in the understanding of MYH9 disorders. Curr Opin Hematol. 2010;17(5):405-410. 3. Althaus K, Greinacher A. MYH9-related platelet disorders. Semin Thromb Hemost. 2009;35(2):189-203. 4. Rao AK, Songdej N. Inherited thrombocytopenias: the beat goes on. Blood.

Case Discussion

2015;125(5):748-750.

Upon receipt of the CBC results, the provider immediately contacted the patient, who reported no evidence of bleeding, bruising, or petechiae. An appointment was made for the following morning, and if the patient were to experience any bleeding such as blood in stool or urine, gingival bleeding, hemoptysis, epistaxis, or petechiae, he agreed to go to the emergency department right away. The following day, results of a blood smear were received in the office and revealed Döhle body-like cytoplasmic inclusions in nearly every neutrophil. In addition, the pathologist also observed platelet clumps and giant platelets on the blood smear. Given the patient’s history of “low platelets” and the results of the CBC, the patient was referred to a hematologist, who confirmed the diagnosis of MHA. The patient was followed for 5 years before moving to another state. During that time, his platelet count remained between 20,000/μL and 50,000/μL, and he experienced no untoward bleeding. However, his hearing worsened and his glomerular filtration rate decreased from 62 to 42 mL/min. He was counseled about his diagnosis and instructed to wear a Medic-Alert bracelet to avoid misdiagnosis and inappropriate treatment. In addition, he was referred to a nephrologist for management of stage III chronic kidney disease. Given the inheritance pattern of MHA, both of the patient’s children were tested and had normal platelet counts. An awareness of MYH9-related disorders is important to include as a consideration in the differential diagnosis of thrombocytopenia. Knowledge of MHA is essential to allow health care practitioners to provide specific patient education, observe for possible comorbid conditions, and prevent inappropriate treatment if MHA is confused with acquired thrombocytopenia. ■

5. Ruhoy SM, Yates A. Macrothrombocytopenia with Döhle body-like granulocyte inclusions: a case report of May-Hegglin anomaly in a 33-year-old white woman with an update on the molecular findings of MYH9-related disease. Lab Med. 2016;47(3):246-250. 6. Balduini CL, Pecci A, Savoia A. Recent advances in the understanding and management of MYH9-related inherited thrombocytopenias. Brit J Haematol. 2011;154(2):161-174. 7. Althaus K, Greinacher, A. MYH-9 related platelet disorders: strategies for management and diagnosis. Transfus Med Hemother. 2010;37(5):260-267. 8. Althaus K, Najm J, Greinacher A. MYH9 related platelet disorders – often

Mary Jane Hanson, PhD, CRNP, FNP-BC, FAANP, is a professor and the director of graduate nursing and DNP programs at the University of Scranton and a family nurse practitioner at LVPG Family Medicine, in Albrightsville, Pennsylvania. 28 THE CLINICAL ADVISOR • MARCH 2020 • www.ClinicalAdvisor.com

“Wait — did you wash your hands?”

unknown and misdiagnosed. Klin Padiatr. 2011;223(3):120-125.

Dermatology Clinic CASE #1

Hyperpigmented Patch on the Thigh ALEXANDRIA BROWN, BS; ELEANOR JOHNSON, BA; CHRISTOPHER RIZK, MD

A 15-year-old boy presents with a progressive hyperpigmented patch on his thigh that first appeared several years ago. The patient does not report any pain related to the lesion, but he notes that it feels like a “bag of worms” when palpated. Physical examination reveals multiple café au lait spots on his trunk and axillary freckling. Biopsy of the patch is performed, and the results show peripheral nerve overgrowth and invasion into connective tissue. What is your diagnosis? Turn to page 30

CASE #2

Crusted Pruritic Rash Under Breast KAREN RESNICK, BS;YELENA DOKIC, BSA; CHRISTOPHER RIZK, MD

A 36-year-old woman presents to the clinic for treatment of a crusted pruritic rash located under both of her breasts. She was previously unconcerned about the rash because her mother had a similar type of “acne.” However, after joining her local sports team, she is worried that the heat and sweat of her uniform have worsened her rash. On further physical examination, the patient is found to have mildly greasy, redbrown papules along her nasolabial folds and hairline. Several of her fingernails have white lines running longitudinally from the nail bed. What is your diagnosis? Turn to page 32 www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2020 29

Dermatology Clinic CASE #1

Plexiform Neurofibroma

Plexiform neurofibromas are a subtype of nerve tumors generally associated with the multisystem genetic disorder, neurofibromatosis type 1 (NF1). Due to a lack of consensus, the National Institutes of Health developed the following criteria in 1987 to aid in the diagnosis of this autosomal-dominant disorder1: • At least 6 café au lait spots measuring >5 mm in diameter in children or >15 mm across in adolescents and adults • At least 2 neurofibromas or 1 plexiform neurofibroma • Freckling in the area of the armpit or the groin • At least 2 growths on the iris (Lisch nodules or iris hamartomas) • Optic nerve glioma • Abnormal growth of the spine, the sphenoid bone, or the tibia • A parent, sibling, or child with NF1 The presence of plexiform neurofibromas can serve as a diagnostic criterion for NF1; however, isolated plexiform neurofibromas can occur in the absence of NF1.2 Almost all patients diagnosed with NF1 will go on to develop neurofibromas. Cutaneous neurofibromas are benign tumors, but patients who develop plexiform neurofibroma have a 5% lifetime risk of malignant transformation.3,4 The lesions present early in life and are thought to be congenital defects.3 They can cause significant disfigurement and life-threatening complications involving neurologic, orthopedic, orbital, and airway structures. Therefore, patients should be monitored carefully for any growth or pattern changes in a preexisting plexiform neurofibroma that may indicate possible malignant transformation. In general, a neurofibroma is a benign peripheral nerve sheath tumor composed of Schwann cells, fibroblasts, perineurial cells, and mast cells.5 Plexiform neurofibromas arise from multiple nerves in the trunk or extremities and follow the distribution of the involved peripheral nerves, producing large infiltrative masses.4 These growths can vary in severity from no skin involvement to severe facial disfigurement or elephantiasis with limb hypertrophy.6 They occur in up to 30% of cases of NF1 and commonly involve the orbit, face, neck, back, chest, and abdomen.7 Clinically, a plexiform neurofibroma presents as a diffuse, possibly hyperpigmented overgrowth of skin and soft tissue, often with a deep invasion of nerves and subcutaneous tissue. These bulging and deforming masses are described as feeling like “bags of worms” due to their involvement of connective

tissue and skin folds.7 The involved nerves may become irregularly thickened and grow into a distorted, tortuous structure. Histologically, the lesion will have a loose myxoid background with low cellularity. There are often areas of collagen bundles, which have a “shredded carrot” appearance microscopically.8 The loss of both copies of the NF1 gene in Schwann cells is consistently implicated in the invasive and angiogenic pathogenesis of plexiform neurofibromas.3 The product of the NF1 gene, neurofibromin, functions as a GTPase-activating protein, which inhibits Ras GTPase activity.8 Tumors that are symptomatic and diagnosed at an earlier age are associated with poor prognosis. A study focused on plexiform neurofibroma outcomes in pediatric patients found that patients with symptomatic plexiform neurofibromas have significantly higher mortality rates compared with those with asymptomatic disease.9 In addition, younger patients were found to have the most rapid growth rate of plexiform neurofibromas in another study with a median participant age of 8.3 years.10 A significant concern for plexiform neurofibromas is their potential to transform into malignant peripheral nerve sheath tumors (MPNSTs). These highly malignant tumors are locally invasive with multiple recurrences and eventual metastatic spread.8 This malignant progression occurs in 2% to 16% of cases.7 Plexiform neurofibromas can also compress the spinal cord or airway and cause significant bone erosion.11 Although

Cutaneous neurofibromas are benign tumors, but in 5% of cases the neurofibromas can become cancerous. there are no reliable tests to screen for an MPNST, these tumors often present as a painful expansion of an existing plexiform neurofibroma, hardening of the tumor, and weakness or numbness in an affected arm or leg.12 Magnetic resonance imaging and positron emission tomography imaging with fluorodeoxyglucose may be useful in distinguishing MPNST from benign plexiform neurofibromas in patients with NF1.13 Previously, plexiform neurofibromas were thought to be pathognomonic for NF1, but recent studies have shown that plexiform neurofibromas can be an isolated finding.2 The diagnosis of plexiform neurofibroma is made clinically, and management often involves a multidisciplinary team consisting of a physician, neurologist, surgeon, ophthalmologist, and geneticist.14 Other differential diagnoses for plexiform neurofibroma include neurocutaneous melanosis, congenital smooth

30 THE CLINICAL ADVISOR • MARCH 2020 • www.ClinicalAdvisor.com

Continues on page 32

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AGA=American Gastroenterological Association. References: 1. Schiller LR, Emmett M, Santa Ana CA, Fordtran JS. Osmotic effects of polyethylene glycol. Gastroenterology. 1988;94(4):933-941. 2. Hammer HF, Santa Ana CA, Schiller LR, Fordtran JS. Studies of osmotic diarrhea induced in normal subjects by ingestion of polyethylene glycol and lactulose. J Clin Invest. 1989;84(4):1056-1062. 3. Survey of 672 consumers, August 2017, Bayer Consumer Health. 4. Bharucha AE, Dorn SD, Lembo A, Pressman A; American Gastroenterological Association. American Gastroenterological Association medical position statement on constipation. Gastroenterology. 2013;144(1):211-217.

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Dermatology Clinic muscle hamartoma, Klippel-Trenaunay-Weber syndrome, Proteus syndrome, lipoma, lipomatosis, and neurofibroma.15 The mainstay of treatment for a plexiform neurofibroma includes surgery for symptomatic relief, although its vascularity and intraneural spread make complete excision difficult.11 Once malignant transformation has taken place, chemotherapy can be administered. Radiation is generally not suggested for the treatment of plexiform neurofibromas, as this could promote malignant transformation.16 Unlike schwannomas, it is not possible to separate the lesion from the nerve in plexiform neurofibromas.8 For unresectable, symptomatic cases, good results have been reported with administration of interferon alfa.17 Genetic counseling should be offered to patients to assess family risk, to look for other possible conditions, and whenever the diagnosis is unclear.10 Therapy should be aimed at resecting deforming masses and cancerous tissue when malignant transformation has occurred.7 However, even in the setting of complete excision, approximately 20% of cases reoccur.18 The patient in this case met diagnostic criteria for NF1 and underwent genetic testing as part of his future family planning. There were no concerning features of his plexiform neurofibroma, so no treatment was necessary.

impact on morbidity and mortality in neurofibromatosis type 1. J Pediatr. 2012;160(3):461-467. 10. Dombi E, Solomon J, Gillespie AJ, et al. NF1 plexiform neurofibroma growth rate by volumetric MRI: Relationship to age and body weight. Neurology. 2007;68(9):643-647. 11. Fox CJ, Tomajian S, Kaye AJ, Russo S, Abadie JV, Kaye AD. Perioperative management of neurofibromatosis type 1. Ochsner J. 2012;12(2):111-121. 12. Athanasiou A, Sarlis P, Balogiannis I. Aggressive malignant peripheral nerve sheath tumor of the lower limb in a patient with neurofibromatosis-1 and multiple spinal cord neurofibromas. Hippokratia. 2014;18(4):376. 13. Ferner RE, Golding JF, Smith M, et al. [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) as a diagnostic tool for neurofibromatosis 1 (NF1) associated malignant peripheral nerve sheath tumours (MPNSTs): a long-term clinical study. Ann Oncol. 2008;19(2):390-394. 14. Avery RA, Katowitz JA, Fisher MJ, et al. Orbital/periorbital plexiform neurofibromas in children with neurofibromatosis type 1: multidisciplinary recommendations for care. Ophthalmology. 2017;124(1):123-132. 15. Rodrigues LOC, Batista PB, Goloni-Bertollo EM, et al. Neuro fibromatoses: part 1‑– diagnosis and differential diagnosis. Arq Neuropsiquiatr. 2014;72(3):241-250. 16. Isler MH, Fogaça MF, Mankin HJ. Radiation induced malignant schwannoma arising in a neurofibroma. Clin Orthop Relat Res. 1996;(325): 251-255. 17. Kebudi R, Cakir FB, Gorgun O. Interferon-α for unresectable progres-

Alexandria Brown, BS, and Eleanor Johnson, BA, are medical students at Baylor College of Medicine in Houston, Texas, and Christopher Rizk, MD, is a certified dermatologist at Elite Dermatology in Houston,Texas.

sive and symptomatic plexiform neurofibromas. J Pediatr Hematol Oncol. 2013;35(3):e115-e117. 18. Needle MN, Cnaan A, Dattilo J, et al. Prognostic signs in the surgical management of plexiform neurofibroma: The Children’s Hospital of Philadelphia experience, 1974-1994. J Pediatr. 1997;131(5):678-682.

References 1. National Institutes of Health. Neurofibromatosis. NIH Consens Statement Online. 1987;6(12):1-19. 2. Lin V, Daniel S, Forte V. Is a plexiform neurofibroma pathognomonic of

CASE #2

Darier Disease

neurofibromatosis type I? Laryngoscope. 2004;114(8):1410-1414. 3. Gutmann DH. Recent insights into neurofibromatosis type 1: clear genetic progress. Arch Neurol. 1998;55(6):778-780. 4. Canavese F, Krajbich JI. Resection of plexiform neurofibromas in children with neurofibromatosis type 1. J Pediatr Orthop. 2011;31(3):303-311. 5. Tucker T, Riccardi VM, Sutcliffe M, et al. Different patterns of mast cells distinguish diffuse from encapsulated neurofibromas in patients with neuro fibromatosis 1. J Histochem Cytochem. 2011;59(6):584-590. 6. Rallis E, Ragiadakou D. Giant plexiform neurofibroma in a patient with neurofibromatosis type I. Dermatol Online J. 2009;15(5):7. 7. Tchernev G, Chokoeva AA, Patterson JW, Bakardzhiev I, Wollina U, Tana C. Plexiform neurofibroma: a case report. Medicine (Baltimore). 2016;95(6):e2663. 8. Kumar V, Abbas AK, Aster JC, Cotran RS, Robbins SL. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Amsterdam, Netherlands: Elsevier, Inc; 2015. 9. Prada CE, Rangwala FA, Martin LJ, et al. Pediatric plexiform neurofibromas:

Darier disease, also known as keratosis follicularis, dyskeratosis follicularis, or Darier-White disease, is an autosomaldominant inherited disorder characterized by keratotic plaques and papules.1-3 This genodermatosis results in hyperkeratotic plaques developing in seborrheic areas, as well as associated palmoplantar papules, oral mucosa changes, and nail abnormalities.3,4 The disease was first noted in 1889 by French dermatologist Ferdinand-Jean Darier.5 Independently, dermatologist James C.White noted similar lesions between family members and hypothesized the disease was inherited.6

32 THE CLINICAL ADVISOR • MARCH 2020 • www.ClinicalAdvisor.com

Since then, Darier disease has been observed across ethnic groups and sexes. Estimates of the prevalence of Darier disease vary from 1 in 30,000 to 1 in 100,000.1,3,6 The disease onset is generally during childhood, with most symptoms manifesting before the third decade of life.2 Although Darier disease is an autosomal-dominant condition, 47% of patients with the disease have no known family history.6 For the inherited form, penetrance is estimated at >95%. Researchers believe that sporadic cases may be attributed to variable expressivity, where there might be an underlying family history with a milder subclinical disease presentation.3,6 Darier disease occurs as a result of a mutation of the ATP2A2 gene on chromosome 12. This gene encodes the sarco-endoplasmic reticulum Ca2+ ATPase (SERCA2), which maintains the high calcium concentration of the endoplasmic reticulum lumen and the low calcium concentration of the cell cytoplasm.3,6,7 The SERCA2 pump has been associated with protein synthesis and post-translational modification. Therefore, abnormalities of the pump result in disrupted cell signaling and defective protein production.Two isoforms of SERCA2 (2a and 2b) are located in the epidermis and play a role in the creation of desmosomal proteins.6-8 More than 250 different mutations of ATP2A2 that are associated with Darier disease have been reported in the literature.9 Given the breadth of mutations presenting with a common phenotype, researchers believe Darier disease occurs as a result of haploinsufficiency, where a single gene copy produces insufficient amounts of a gene product.7,8 Although the disease is autosomal dominantly inherited with near-complete penetrance, the wide expressivity of the lesions presents a challenge to clinicians and patients. Two family members with the same mutation may have significantly different clinical disease. The lack of a genotype-phenotype correlation makes genetic counseling and exploration of possible environment or epigenetic factors difficult.7,9,10 Darier disease typically presents with yellow-brown keratotic papules in the seborrheic areas of the face, neck, chest, and scalp. Papules range from pin-size dots to coalescing plaques that are often pruritic. Once coalesced, plaques can develop into large warty and vegetative growths. Plaques involving intertriginous areas (such as skin folds of the digits or breasts) may become macerated and infected, leading to odor. Most cases involve the hands, particularly keratoses of the dorsal surfaces, and pitting of the palmar surfaces can develop.6,7 Nail abnormalities are common in patients with Darier disease and can involve white or red longitudinal lines, V-shaped notches, or longitudinal ridging and splitting.1,11 Mucosal involvement is rarer and includes white papules of the oral mucosa, esophagus, and vulva. The most common

site of involvement is the hard palate; however, gingivae, buccal mucosae, tongue, and parotid gland lesions have also been noted.1,2,6 Under dermoscopy, Darier lesions appear polygonal, star-like, or round-oval shaped and are surrounded by a thin white halo.4 Darier disease is a chronic condition that can be exacerbated by heat, humidity, perspiration, pregnancy, surgery, ultraviolet radiation, and mechanical irritation. Certain medications such as lithium and calcium channel blockers can worsen the disease, as can bacterial, fungal, and viral infections.3,6,12 The diagnosis of Darier disease is confirmed by histologic examination of skin biopsy in the context of clinical features. Histologically, acantholysis resulting from loss of cell adhesions and dyskeratosis from premature differentiation of keratinocytes of the stratum corneum can be seen.

Darier disease typically presents with yellow-brown keratotic papules on the face, neck, chest, and scalp. The stratum spinosum is notably thickened with suprabasal cleavage and acantholytic cells, and abnormal keratinocytes can be appreciated at these cleavage sites. The acantholytic and dyskeratotic cells form corps ronds and grains in the epidermis and corneum.3,4,6 Darier disease presents similarly to Hailey-Hailey disease and Grover disease.3,6 Hailey-Hailey disease is another acantholytic condition that results in a “dilapidated brick wall” appearance of the spinous layer of the epidermis.3 Unlike Darier disease, Hailey-Hailey disease does not affect palmoplantar surfaces, nails, or mucosal surfaces. Grover disease produces temporary papulovesicular lesions that can appear similar to Darier disease. However, Grover disease also does not affect the palmoplantar, nail, or mucosal surfaces, and the lesions do not merge together.3,6 Treatment of Darier disease involves symptom management. For patients with mild disease, avoiding triggers such as heat, sun, and sweating prevents exacerbations. In addition, topical emollients, antibacterial soaps, antifungals, salicylic acid, and retinoids can help manage the disease. Retinoids control hyperkeratosis: topical retinoids are appropriate for mild disease and systemic retinoids can be used for severe disease.3 Oral cyclosporine has also been shown to help in refractory cases. Aside from medical management, dermabrasion and laser therapy can induce disease remission. Although Darier disease is a chronic condition and still poorly understood,

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2020 33

Dermatology Clinic treatment options can significantly improve patients’ quality of life.3,6 The patient in this case was counseled to avoid triggers such as sun and heat. Treatment with topical retinoids resulted in resolution of her symptoms. ■

5. Darier FJ. De la psorospermose folliculaire vegetante. Ann dermatol syphilographie. 1889;10:597-612. 6. Engin B, Kutlubay Z, Erkan E, Tüzün Y. Darier disease: a fold (intertriginous) dermatosis. Clin Dermatol. 2015;33(4):448-451. 7. Hulatt L, Burge SM. Darier’s disease: hopes and challenges. J R Soc Med. 2003;96(9):439-441.

Karen Resnick, BS, and Yelena Dokic, BSA, are medical students at Baylor College of Medicine, and Christopher Rizk, MD, is a certified dermatologist at Elite Dermatology in Houston,Texas.

8. Dhitavat J, Fairclough RJ, Hovnanian A, Burge SM. Calcium pumps and keratinocytes: lessons from Darier’s disease and Hailey-Hailey disease. Br J Dermatol. 2004;150(5):821-828. 9. Green EK, Gordon-Smith K, Burge SM, et al. Novel ATP2A2 mutations

References

in a large sample of individuals with Darier disease. J Dermatol. 2013;40(4):

1. Burge SM, Wilkinson JD. Darier‐White disease: a review of the clinical

259-266.

features in 163 patients. J Am Acad Dermatol. 1992;27(1):40-50.

10. Bchetnia M, Charfeddine C, Kassar S, et al. Clinical and mutational

2. Shwetha V, Sujatha S, Yashoda Devi BK, et al. Spectrum of features in

heterogeneity of Darier disease in Tunisian families. Arch Dermatol. 2009;

Darier’s disease: a case report with emphasis on differential diagnosis. J Oral

145(6):654-656.

Biol Craniofac Res. 2019;9(2):215-220.

11. Munro CS. The phenotype of Darier’s disease: penetrance

3. Takagi A, Kamijo M, Ikeda S. Darier disease. J Dermatol. 2016;43(3):275-279.

and expressivity in adults and children. Br J Dermatol. 1992;127(2):

4. Lacarrubba F, Verzi AE, Errichetti E, Stinco G, Micali G. Darier disease:

126-130.

dermoscopy, confocal microscopy, and histologic correlations. J Am Acad

12. Nath AK, Udayashankar C. Diltiazem worsens Darier’s disease. Int J

Dermatol. 2015;73(3):e97-e99.

Dermatol. 2014;53(1):e1.

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34 THE CLINICAL ADVISOR • MARCH 2020 • www.ClinicalAdvisor.com

Dermatologic Look-Alikes Large, Scaly Erythematous Patches JAY PATEL, BS;YELENA DOKIC, BSA; CHRISTOPHER RIZK, MD

CASE #1

CASE #2

A 65-year-old man presents to the clinic with a large rash on his torso. On physical examination, the patient has multiple scaly erythematous patches on his chest and abdomen.When asked about the history of the rash, the patient mentions that he has had “on and off rashes around this region for several years” and thought the rash was the result of an allergic reaction “to fabrics or washing detergents.” The patient reports that he has tried a number of topical creams to treat the rash, but none has helped his symptoms, and the “rashes would eventually resolve by themselves.”

A 36-year-old woman presents to the dermatology clinic for management of an itchy rash on her right leg. The woman reports that other members of her family have had similar rashes in the past, and she is worried about it spreading to her children. Other than the rash, the patient is in good physical health and denies smoking, drinking, or taking illicit drugs. She is a stay-at-home parent who frequently roughhouses with her children. On physical examination, the patient has an annular erythematous scaly plaque with central clearing on her right upper thigh, with multiple scrapes and nodules in the surrounding area.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2020 35

Dermatologic Look-Alikes CASE #1

Mycosis Fungoides

Cutaneous T-cell lymphomas (CTCLs) are the second most common type of extranodal lymphomas (after primary GI lymphomas).1,2 The incidence of CTCLs increases with age, with a median age of diagnosis in the mid 50s.1 These types of lymphoma affect more men than women and are more common among black individuals than white individuals.3 Mycosis fungoides (MF) is the most common subtype of primary CTCL.1 Also known as Alibert-Bazin syndrome, MF was first described in 1806 by Jean-Louis-Marie Alibert.4 As a T-cell lymphoma, MF is caused by an expansion of malignant skin-homing T cells.1,2 These cancer T cells can extend from the lesions to nearby skin regions, leading to patches, plaques, and tumors. In later stages,T cells can spread to the blood, lymph nodes, and viscera.2 Several risk factors are associated with a predisposition to T-cell lymphoma. In addition to older age and male sex, genetic factors have been associated with MF, such as the presence of HLA-DRB1*11 or HLA-DQB1*03 alleles.4-6 Environmental factors also have been associated with MF. Workers with the highest risk include glass formers, potters, ceramic workers, and factory workers in the paper and wood industries.7 However, specific carcinogens, if any, have yet to be determined. Infectious agents such as human T-cell lymphoma virus-1 (HTLV-1) and Epstein-Barr virus have been identified as risk factors for other cutaneous lymphomas, but current data do not suggest they play a role in the development of MF.8,9 Patients with MF present with multiple patches, plaques, and/or skin tumors in sun-protected areas of the body.1 They often describe a long history (10-15 years) of chronic dermatitis consisting of itchy patches that appear and spontaneously resolve.1 In the early patch stage, patients will have numerous erythematous, scaly patches, as well as macules that vary in size and have well-defined borders.1,2 The lesions, which range in color from orange to purplish red, often erupt and disappear spontaneously without scarring.1,4 In the early stages, diagnosis can be difficult and often requires numerous biopsies.2 Itching is a common complaint during these stages. Differential diagnosis of MF includes tinea corporis, vitiligo, eczema, contact dermatitis, and psoriasis in the early patch or plaque stages and B-cell lymphoma, sarcoidosis, deep fungal infection, carcinoma cutis, and atypical

mycobacterial infection in the tumor stage.1,2 Patients with dark skin can develop hypopigmented MF, which needs to be differentiated from other hypopigmenting diseases, such as vitiligo.1,2 Histologically, MF samples contain an infiltration of reactive T cells and neoplastic T lymphocytes in the upper dermis.1 These cells are characterized by hyperconvoluted cerebriform nuclei. Neoplastic T cells also display an epidermotropism and form intraepidermal Pautrier microabscesses. During the tumor stage of the disease, there can be nodular infiltrates in the dermis. Immunohistologic staining shows CD4+ mature T cells within lesions.1,2 Patients with MF can experience symptoms such as fever, chills, weight loss, and malaise.1,3 Other findings include scaling and cracking of the palms and soles, hair loss, nail dystrophy, and ankle edema.1

In the early phase of mycosis fungoides, the lesions often erupt and disappear spontaneously without scarring. Once patients are diagnosed with MF, workup includes evaluation of the extent of skin lesions, localization and measurement of lymph nodes involved, identification of visceral symptoms, as well as blood work and imaging to assess tumor burden and identify systemic spread.1,2 Treatment for MF depends on the stage of the disease and whether the condition is limited to the skin or has spread to lymph nodes. First-line treatment of topical disease includes topical corticosteroids, ultraviolet B phototherapy, psoralen and ultraviolet A (PUVA), and localized radiotherapy.1,2,10 Systemic treatment includes interferon alfa or gamma, oral retinoids (vitamin A), low-dose methotrexate, total skin electron beam therapy, and/or chemotherapy.1,2,10 Targeted therapies also can be used as alternatives to chemotherapy to debulk large tumors. Alemtuzumab, a monoclonal antibody that binds to CD52 on mature lymphocytes, is an example of targeted therapy.11 In August 2018, the US Food and Drug Administration (FDA) approved mogamulizumab, a monoclonal antibody targeting the CC chemokine receptor 4 on T cells, for patients with relapsed or refractory MF.12 With early detection, the overall prognosis for patients with MF is good. Patients with disease limited to the skin have a 5-year survival rate close to 100%, whereas patients with lymph node or visceral involvement have 5-year survival

36 THE CLINICAL ADVISOR â&#x20AC;˘ MARCH 2020 â&#x20AC;˘ www.ClinicalAdvisor.com

Continues on page 38

Dermatologic Look-Alikes rates of 68% (low risk), 44% (intermediate risk), or 28% (high risk).3,13 The patient in the above case was treated with topical corticosteroids and ultraviolet B phototherapy for the rash. His lesions resolved, and he has not had a relapse.

CASE #2

Tinea Corporis

Tinea corporis (TC), also known as ringworm, is a superficial fungal infection of glabrous skin that usually appears on the arm or legs and is not seen on the palms, soles, or groin.14 Although the disease has existed for millennia, a causative fungus was first described in 1842 by David Gruby.15 He identified Microsporum audouinii as one of the fungi that causes TC.15 Superficial fungal infections are common, affecting 20% to 25% of the world’s population.16 Factors related to TC infection include younger age, sex, and race, but how these factors correlate with susceptibility is not well known.14 TC is more common in men than in women.14 A compromised immune system increases the risk for TC and other superficial fungal infections.14 Although the prevalence of fungal infections is similar in patients with HIV

Minor trauma to the skin can create an environment for these opportunistic fungal species to flourish. and non-HIV-infected individuals, the severity of fungal infections is increased in the former group.17 Several genetic polymorphisms in toll-like receptors (TLRs), including TLR1, TLR3, and TLR4, are associated with an increased risk for fungal disease. However, knowledge about the molecular mechanisms that drive an increased predisposition to TC is lacking.18 Various fungal species, or dermatophytes, can cause TC. Certain fungal species are found worldwide, whereas others are more localized to specific geographic regions.14 In the United States, Trichophyton rubrum is the more common cause

of TC among adults, and the zoophilic pathogen Microsporum canis infects more children.14,19 These fungi express numerous enzymes and factors that adhere to and spread on the skin.20 They use keratin on the skin as a source of nutrients and a vehicle to spread. In response to the fungi and degraded keratin, the body releases inflammatory mediators, leading to the erythematous, pruritic rash.20 In TC, the ringworm pattern is caused by the fungi rapidly spreading outward, with a reduction or clearance of the fungi in the center of the plaque.14 Risk factors for acquiring TC include humid conditions, excessive sweating, and constrictive clothing that does not allow moisture to escape. The fungi that cause TC normally are found on the skin but can develop into an opportunistic infection.14 TC can spread between people, between pets and humans, and between fomites (ie, bed linens or athletic gear) and skin.13,19 In addition, minor trauma, such as that from close contact or mat and carpet burns, can create an environment that allows fungal species to flourish. Thus, individuals who participate in close-contact sports, such as wrestling, football, and rugby, are more likely to develop TC.21 Clinically, patients with TC present with an annular or serpiginous scaly plaque that has central clearing and an erythematous raised ring on the perimeter. The plaque may be accompanied by pruritus, dry and flaky skin around the rash, or even hair loss within the rash.14 Histologically, septate, branching hyphae in the stratum corneum or skin scrapings are visualized.14 In addition, certain fungal species will fluoresce under Wood lamp examination.14 The differential diagnosis for TC includes erythema annulare centrifugum, nummular eczema, tinea versicolor, cutaneous candidiasis, contact dermatitis, pityriasis rosea, seborrhea, MF, and parapsoriasis.14 Majocchi granuloma, a deeper dermatophyte infection that involves hair follicles and is common in immunocompromised individuals,22 also is included in the differential diagnosis.22 TC is most commonly found on shaved surfaces such as the legs of women who apply topical corticosteroids after skin irritation, thus facilitating a fungal infection.14 TC is diagnosed clinically and can be confirmed with Wood lamp examination, as well as microscopic evaluation of skin shavings displaying branched hyphae of fungal species.14 Skin shaving of the scales can be prepared with a potassium hydroxide preparation, which, along with mild heat, will soften keratin and show hyphae.14 Alternative methods of diagnosis include culturing the skin flora, a dermatophyte test medium that changes color in the presence of dermatophyte, or histologic staining with periodic acid-Schiff or

38 THE CLINICAL ADVISOR • MARCH 2020 • www.ClinicalAdvisor.com

TABLE. Mycosis Fungoides vs Tinea Corporis Mycosis Fungoides1-13

Tinea Corporis14-24

Dermatologic presentation

Erythematous, scaly patches and macules with well-defined borders

Annular or serpiginous scaly plaque ± central clearing with an erythematous raised ring

Associations

• Older age • Male sex • HLA-DRB1*11 • HLA-DQB1*03

• Younger age • Participating in contact sports • Tight, restrictive clothing • Humid conditions

Etiology

Cutaneous T-cell lymphoma

Dermatophyte (fungal) infection

Characteristic location

Non-sun-exposed areas

Glabrous skin, excluding palms, soles, and groin

Histology

T-cell infiltration of upper dermis with hyperconvoluted cerebriform nuclei, intraepidermal Pautrier microabscesses

Septate, branching hyphae on KOH prep of plaque shaving

Diagnosis

Histological analysis from biopsy

Clinical diagnosis, Wood lamp fluorescent exam, microscopy

Treatment

• Mild: topical corticosteroids, ultraviolent B, PUVA, and localized radiotherapy • Severe: interferon alfa or gamma, retinoids, low-dose methotrexate, total skin electron beam, and/or chemotherapy

• Mild: Topical antifungal agent • Severe: Oral antifungal agent

KOH, potassium hydroxide preparation; PUVA, psoralen and ultraviolet A

Grocott methenamine silver, which stain fungal elements pink or black, respectively.14 In most cases, treatment with a topical antifungal agent will eliminate the fungal infection. Common agents include fluconazole, griseofulvin, itraconazole, and terbinafine. These usually are applied to the affected area multiple times a day for 2 to 4 weeks.23,24 It is important to continue to treat the region even after the lesion resolves to ensure complete eradication of the fungus.14 For individuals with a compromised immune system or extensive TC, oral antifungal agents such as fluconazole, intraconazole, and terbinafine can be used and have a good cure rate. It is important to note that the oral agents have adverse effects, including liver and renal toxicity, and some are contraindicated in pregnant women.14 The patient in the case was prescribed a topical antifungal agent, which she applied twice daily for 3 weeks, leading to resolution of the rash on her leg. ■

Jay Patel, BS, andYelena Dokic, BSA, are medical students at Baylor College of Medicine, and Christopher Rizk, MD, is a dermatologist affiliated with Elite Dermatology Houston. References 1. Bagot M, Stadler R. Cutaneous lymphoma. In: Fitzpatrick’s Dermatology. 9th ed. New York, NY: McGraw-Hill Education; 2019. 2. Larocca C, Kupper T. Mycosis fungoides and Sézary syndrome: an update. Hematol Oncol Clin North Am. 2019;33(1):103-120. 3. Imam MH, Shenoy PJ, Flowers CR, Phillips A, Lechowicz MJ. Incidence and survival patterns of cutaneous T-cell lymphomas in the United States. Leuk Lymphoma. 2013;54(4):752-759. 4. Alibert JLM Description Des Maladies de La Peau Observées a l’Hôpital SaintLouis, et Exposition Des Meilleures Méthodes Suivies Pour Leur Traitement. Paris, France: Barrois l’ainé; 1806. 5. Hodak E, Lapidoth M, Kohn K, et al. Mycosis fungoides: HLA class II associations among Ashkenazi and non-Ashkenazi Jewish patients. Br J Dermatol. 2001;145(6):974-980.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2020 39

Dermatologic Look-Alikes 6. Jackow CM, McHam JB, Friss A, Alvear J, Reveille JR, Duvic M. HLA-DR5

fda-approves-mogamulizumab-kpkc-mycosis-fungoides-or-sezary-syndrome.

and DQB1*03 class II alleles are associated with cutaneous T-cell lymphoma.

Accessed February 7, 2020.

J Invest Dermatol. 1996;107(3):373-376.

13. Scarisbrick JJ, Kim YH, Whittaker SJ, et al. Prognostic factors, prognostic

7. Morales-Suárez-Varela MM, Olsen J, Johansen P, et al. Occupational

indices and staging in mycosis fungoides and Sézary syndrome: where are we

risk factors for mycosis fungoides: a European multicenter case-control

now? Br J Dermatol. 2014;170(6):1226-1236.

study. J Occup Environ Med. 2004;46(3):205-211.

14. Craddock LN, Schieke SM. Superficial fungal infection. In: Fitzpatrick’s

8. Pawlaczyk M, Filas V, Sobieska M, Gozdzicka-Józefiak A, Wiktorowicz K,

Dermatology, 9th ed. New York, NY: McGraw-Hill Education; 2019.

Breborowicz J. No evidence of HTLV-I infection in patients with mycosis fun-

15. Zakon SJ, Benedek T. David Gruby and the centenary of medical mycology,

goides and Sezary syndrome. Neoplasma. 2005;52(1):52-55.

1841-1941. Butt Hist Med. 1944;16(2).

9. Novelli M, Merlino C, Ponti R, et al. Epstein-Barr virus in cutaneous T-cell

16. Havlickova B, Czaika VA, Friedrich M. Epidemiological trends in skin myco-

lymphomas: evaluation of the viral presence and significance in skin and

ses worldwide. Mycoses. 2008;51(suppl 4):2-15.

peripheral blood. J Invest Dermatol. 2009;129(6):1556-1561.

17. Johnson RA. Dermatophyte infections in human immune deficiency virus

10. Olsen EA, Whittaker S, Kim YH, et al; International Society for Cutaneous

(HIV) disease. J Am Acad Dermatol. 2000;43(5 suppl):S135-S142.

Lymphomas; United States Cutaneous Lymphoma Consortium; Cutaneous

18. Lilic D. Unravelling fungal immunity through primary immune deficiencies.

Lymphoma Task Force of the European Organisation for Research and

Curr Opin Microbiol. 2012;15(4):420-426.

Treatment of Cancer. Clinical end points and response criteria in mycosis

19. Aly R. Ecology and epidemiology of dermatophyte infections. J Am Acad

fungoides and Sézary syndrome: a consensus statement of the International

Dermatol. 1994;31(3 Pt 2):S21-S25.

Society for Cutaneous Lymphomas, the United States Cutaneous

20. Dahl MV. Dermatophytosis and the immune response. J Am Acad

Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the

Dermatol. 1994;31(3 Pt 2):S34-S41.

European Organisation for Research and Treatment of Cancer. J Clin Oncol.

21. Adams BB. Tinea corporis gladiatorum. J Am Acad Dermatol.

2011;29(18):2598-2607.

2002;47(2):286-290.

11. Querfeld C, Mehta N, Rosen ST, et al. Alemtuzumab for relapsed and

22. Elgart ML. Tinea incognito: an update on Majocchi granuloma. Dermatol

refractory erythrodermic cutaneous T-cell lymphoma: a single institution

Clin. 1996;14(1):51-55.

experience from the Robert H. Lurie Comprehensive Cancer Center. Leuk

23. Sahoo AK, Mahajan R. Management of tinea corporis, tinea cruris, and tinea

Lymphoma. 2009;50(12):1969-1976.

pedis: a comprehensive review. Indian Dermatol Online J. 2016;7(2):77-86.

12. FDA approves mogamulizumab-kpkc for mycosis fungoides

24. Khurana A, Sardana K, Chowdhary A. Antifungal resistance in derma-

or Sézary syndrome. US Food and Drug Administration. https://

tophytes: Recent trends and therapeutic implications. Fungal Genet Biol.

www.fda.gov/drugs/resources-information-approved-drugs/

2019;132:103255.

“I think we should be other people.” 40 THE CLINICAL ADVISOR • MARCH 2020 • www.ClinicalAdvisor.com

LEGAL ADVISOR CASE

Saved by the Statute of Limitations

BY ANN W. LATNER, JD

Ms J is a 38-year-old family nurse practitioner who had been working at a large medical center for approximately 5 years. Although she usually enjoyed her work, the pressure to get patients in and out of the office quickly was often challenging. Some patients needed more time in the examination room or had difficulty expressing their medical problems, and she hated to rush through the visit. However, the medical center expected her to see a certain number of patients each day, so she was generally pressed for time. In late February, a new patient came to see Ms J. Mrs H was a 72-year-old widow who was seeking treatment for multiple complaints, including pain and swelling in her left ankle. “I was walking down my front stairs and I twisted my ankle. I don’t know how it happened, but now it hurts when I walk,” complained Mrs H. Ms J examined the patient and recommended that she have radiographs taken, but Mrs H didn’t want any imaging at the time.“I’d rather just wait and see if it gets better,” she said. “I don’t want extra radiation if I don’t need it.”

Appellate court rules that the 2-year statute of limitations had run out before the plantiff sued. Keeping notes that reflect each test, procedure, or referral recommended and then refused by a patient helps protect clinicians from malpractice claims.

The patient returned 2 weeks later and repeat ed her complaint about her left ankle. This time Ms J was able to convince the patient to undergo radiographic imaging, which demonstrated no definite acute fracture or dislocation present. Four months later, Mrs H returned to see Ms J. “I can’t believe this happened again!” said the patient. “I was walking down the stairs about 5 days ago and my ankle gave out — the same ankle as last time — and now it’s swollen and hurts again, and I’m having trouble getting around.” Ms J referred the patient again to radiology for a radiograph of her lower leg. Two radiologists interpreted the images. The first noted soft tissue swelling around Mrs H’s ankle but stated that “no fracture was identified.” The second radiologist’s report also noted soft tissue swelling Cases presented are based on actual occurrences. Names of participants and details have been changed. Cases are informational only; no specific legal advice is intended. Persons pictured are not the actual individuals mentioned in the article.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2020 41

LEGAL ADVISOR and similarly stated that “no acute fracture or dislocation” was observed. One week later, now in late July, Mrs H returned to the medical center complaining about left ankle pain. At this point, Ms J suggested that the patient undergo magnetic resonance imaging, but the patient refused. The nurse practitioner next saw the patient one month later. On this occasion, Ms J recommended referral to an orthopedic specialist as well as magnetic resonance imaging for the unresolved ankle condition.The patient refused both of Ms J’s suggestions. Ms J was now feeling quite frustrated, but she understood that she could not force a patient to take a referral or to undergo a test. At a visit after the Labor Day weekend holiday, Mrs H finally agreed to a referral to a radiologist for magnetic resonance imaging. The radiologist’s report contained no mention of a fracture or dislocation but noted the presence of “extensive edema, arthritis, and erosive changes throughout the joints of the ankle and midfoot.”

There was no dispute that the plaintiff had tendon dysfunction and a stress fracture that had gone undiagnosed. Ms J referred the patient to Dr B, an orthopedic specialist at a sports medicine clinic. Mrs H saw Dr B in late September, at which time he ordered additional radiographs. The physician’s notes indicated that the images showed that Mrs H had “posterior tibial tendon dysfunction with a fibular stress fracture, healing.” Dr B spoke to the patient about the diagnosis and a treatment plan, which involved placing a cast and brace on the patient’s ankle. If the cast and brace failed to control the injury, Dr B told the patient that she would derive long-term benefit from a tibiotalocalcaneal arthrodesis. By late November/early December it became clear that the cast and brace were not working to control the patient’s injury, and surgery was recommended. Mrs H underwent surgery in mid-January, nearly one year following her initial presentation. The patient was unhappy with having to undergo surgery and eventually sought the counsel of a plaintiff ’s attorney. The attorney took the case, and in October of the subsequent year (more than 2.5 years after Mrs H’s first presentation) served Ms J and her employer, the medical center, with a notice of claim informing them that Mrs H intended to pursue a

medical malpractice claim against them. Two months later, the malpractice claim was filed. Ms J met with the defense attorney provided by the medical center. After reviewing the notes, the defense attorney made a motion to dismiss the case on the grounds that the statute of limitations period had run out on Mrs H’s claim. The court agreed and entered an order finding that “the statute of limitations began to run on [date in September in the year when she first reported her injury], when Mrs H became aware of her injury.” Concluding that the statute of limitations period, which is 2 years in the state where Ms J practiced, had expired by the time Mrs H filed her claim, the court dismissed the case. Mrs H immediately appealed. Legal Background

On appeal, Mrs H argued that she failed to discover the full scope of Ms J’s negligence until November/December, when surgery was finally recommended as the only remaining option.Thus, she argued, the statute of limitation should have started running in November/December, rather than in September. The appellate court, however, disagreed. “The statute of limitations should begin to run when the plaintiff should have reasonably known of some negligent conduct, even if the plaintiff does not know with absolute certainty that the conduct was legally negligent,” wrote the court. Thus, the date that Mrs H learned she would need surgery “is not relevant to the running of the statute of limitations if she knew or should have known that the defendant’s alleged negligent conduct caused injury.” There was no dispute that in September, Mrs H learned she had tendon dysfunction and a stress fracture that had been previously undiagnosed despite the treatment she had received from Ms J. Thus, the court concluded that Mrs H should have known about the alleged negligence in September, and the statute of limitations began running from that date. The court concluded that the statute of limitations had run out and that Mrs H could not bring the lawsuit. Protecting Yourself

There were several instances where Ms J recommended tests or referrals that were refused by the patient. Keeping accurate notes of every time a test, procedure, or referral is recommended and then refused by the patient would have been helpful had this case gone to trial. ■ Ann W. Latner, JD, a former criminal defense attorney, is a freelance medical writer in Port Washington, New York.

42 THE CLINICAL ADVISOR • MARCH 2020 • www.ClinicalAdvisor.com