A P E E R - R E V I E W E D F O RU M F O R N U R S E P R AC T I T I O N E R S
■■Primary biliary cholangitis ■■Lyme disease prevention ■■Legionnaire’s disease FEATURE
Necrotizing myopathy: proximal muscle weakness LEGAL ADVISOR
A clinician is fired for refusing to be vaccinated.
n Dermatology Clinic
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J U LY 2 017
Bulbous nose in rhinophyma, a severe form of rosacea.
Editor Colby Stong firstname.lastname@example.org Senior editor Sandhya George Associate editor Lauren Grygotis Assistant editor Madeline Morr Contributing editors Mark P. Brady, PA-C; Philip R. Cohen, MD; Deborah L. Cross, MPH, CRNP, ANP; Sharon Dudley-Brown, PhD, FNP; Abimbola Farinde, PharmD; Laura A. Foster, CRNP, FNP; Abby A. Jacobson, PA; Maria Kidner, DNP, FNP; Joan W. Kiely, MSN, CRNP; Debra August King, PhD, PA; Ann W. Latner, JD; Mary Newberry, CNM, MSN; Claire Babcock O’Connell, MPH, PA; Kathy Pereira, DNP, FNP; Sherril Sego, DNP, FNP; Ann Walsh, PA-C, SCT(ASCP); Kim Zuber, PA-C Production editor Kim Daigneau Group art director, Haymarket Medical Jennifer Dvoretz Production manager Krassi Varbanov
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If a patient has you stumped, write us and we’ll forward your query to one of our consultants and publish the response in Advisor Forum.You can also use this space to contribute a clinical pearl of your own or comment on another letter.
Advisor Forum These are letters from practitioners around the country who want to share their clinical problems and successes, observations, and pearls with their colleagues. Responding consultants are identified below. We invite you to participate.
It cannot be beat.—TERRI JORDAN, ARNP, Daytona Beach, Fla. (202-2)
NEUTROPHILS AND LYMPHOCYTES In interpreting a complete blood count with differential, anytime the neutrophils and lymphocytes are numerically close, it is a viral cause; when the neutrophils and lymphocytes are numerically distant, it is a bacterial cause. This is very helpful in determining treatment.—DONNA CARTER, FNP-C, Scottsburg, Ind. (202-1) GENERIC “CAINE” IS EFFECTIVE FOR WOUND CARE For pain relief, most pharmacies offer a “caine” at 2-510%, and basically nothing higher, for between $5 and $30 per tube. I work in wound care and use Walmart’s
INTRA-ARTICULAR INJECTIONS FOR SEVERE OSTEOARTHRITIS Patients with severe osteoarthritis in the knees seem to do better with intra-articular injections if you have them sit up and dangle their legs off the examination table and distract the knee slightly when administering the injection.—ROSEMARY LEDBETTER, PhD, PA, Troy, Ill. (202-3)
YOUR COMMENTS SLIPPED CAPITAL FEMORAL EPIPHYSIS IN OBESE ADOLESCENTS I just read the CME/CE article by Marilou Shreve, DNP, APRN, entitled, “Assessing and treating pediatric obesity” [ June 2015]. I was concerned regarding the oversight of a critical issue in obese adolescents: the increased risk of slipped capital femoral epiphysis (SCFE). This was not addressed in the article. The case study (p. 55) gave incomplete advice regarding the evaluation of an obese adolescent male with knee pain. The most common etiology of the insidious onset of knee pain in children is the hip, due to referred pain from the
Equate brand—vagicaine 20% benzocaine. When using this before debriding a wound, give it three minutes to sedate the nerves, then perform the procedure. I get good results, as patients say. It relieves pain and burning for $1.88.
Send us your letters with questions and comments to: Advisor Forum, The Clinical Advisor, 114 West 26th Street, 4th Floor, New York, NY 10001. You may contact us by e-mail at editor@ clinicaladvisor.com. If you are writing in response to a published letter, please indicate so by including the number in parentheses at the end of each item. Letters are edited for length and clarity. The Clinical Advisor’s policy is to print the author’s name with the letter. No anonymous contributions will be accepted.
These are lette and successe rs from practitioners s, observat around the below. We ions, and country who OUR CONSULTANTS pearls with invite you want to shar to participa their colle e their clinic agues. Resp te. al problems onding cons ultants are identified CON SULTAT IONS
TREATM ENT FOR INFECT URINAR ION SGLT2 REC MALE CHI S IN THE UNC Y TRACT IRCUMCI LD FOR DIA EPTOR BLOCKE If a male SED child conti Deborah L. Cross, MPH, CRNP, Laura A.BET Foster,ES CRNP, FNP, Abby A. Jacobson, PA-C, RS Abimbola Farinde, PhD, PharmD, With the nues toassociate ANP-BC, is practices family medicine is a physician assistant is a professor redevprogram adven t ofPrimary circu SGLT2 recep at Delaware Valley urinaryattract director, Gerontology NP elop Program, mcisi Columbia Southern moda litywith Palmetto on be perfo for type tor infecPhysicians Dermatology University of Pennsylvania School blockersGroup University 2 diabe rmed? regarding inCare as a treatm in Wilmington, Del. in Orange Beach, Ala. useCharleston, S.C. tes, is there ent urology is of Nursing, Philadelphia. any evide NATHAN in patients with to protect the is well advise nce or data type 1 diabe GARDNE d tes mellitus?— R, PA-C, continues to to recommend a circum upper tracts, the kidne CPAAPA, ys. develo cision It p recurr•ent 44 THE ADVISOR AUGUST 2015 •on www.ClinicalAdvisor.com Castleton, severaCLINICAL l consideration urinary tract the male child who As it currently stands N.Y. , SGLT2 s that infections. for glycemic impede the receptor blocke There are control in ability to cleansenter into this decisio rs are FDA adults with n. Poor hygien should the e and quell -approved child have e may appro diet and exercise, but with type 2 diabetes phimosis, simpl infection potential. appropriate the in ved conjun FDA for use in patien Moreover, AdvisorForum_CA0815.indd urine 44 9/29/15ction 2:38 PM e cathet culture can ts with type has stated that they ketoacidosi steroid cream be a challenge. erization to obtain s, or those are not may tempo an FAR with severe 1 diabetes, patients with Having a short tion of the rarily solve renal functi diabetic steroid the trial of informINDE, PhD, Pharm these issues tenden , though after for infection D (See bottom on.—ABIMBOL ation about once again.—C cy redevelops, placin cessaA Dr. Farinde.) of this page Milwaukee g (203-2) for more , Wis. (203- OLEEN ROSEN, the child at risk 1) DNP, FNP -C, CLI Philip R. Cohen, MD,
is clinicaltions associate professor , shou ld of dermatology, University a of Texas Medical Center, The focus of Houston.
Send us your letter Advisor Forum, The s with questions New York, and comm Clinical Advisor ents to: , 114 clinicaladvisoNY 10001. You may contacWest 26th Street , please indicatr.com. If you are writing in t us by e-mail at 4th Floor, each item. e so by including response editor@ to a the Letters are policy is edited for number in parent published letter, to heses at length and contribution print the author ’s name with clarity. The Clinicathe end of s will be accepted. l Advisor the letter. No anonym ’s ous
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VAGINA L RESULT DISCHARGE AND ING FRO If a female M TAMPON ODOR patient has USE a ask if she uses tamp history of vaginal disch ons. If she the pelvic arge with says “yes,” exam when cond odor, that you woul , do not enter ucting the rotating of d to take a pap smea vagina in the same the specu way r. Instead, the cervix. lum Most retain from side to side start shallow until reach ed tampons ing are lodge d in the fold
Cohen, MD, is clinical associa te profess of dermat or ology, of Texas MedicaUniversity l Center, Houston.
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62 THE CLINI
Deborah L. Cross, MPH, ANP-B
CRNP, C, is associa te program director, Geronto logy NP Program University of Pennsyl vania School , of Nursing , Philadelphia.
SOR • SEPTE
Abimbo la Farinde
is a profess PharmD, or at Columb ia Souther n Univers in Orange ity Beach, Ala.
practices familyCRNP, FNP, with Palmett medicine o Primary Care Physicia ns in Charles ton, S.C.
is a physicia n, PA-C, n at Delawa assistant re Dermatology Valley in Wilmington,Group Del.
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CONTENTS J U LY 2 0 1 7
NEWS AND COMMENT 14
22 Necrotizing myopathy Clinicians in all settings can identify patients with potential myopathic processes and complete an initial diagnostic work-up.
Newsline ■■Primary biliary cholangitis:
Clinical practice guidelines from the European Association for the Study of the Liver (EASL), published in the Journal of Hepatology ■■Preventing Lyme disease and tick bites: tips from the CDC ■■Statins vs usual care for primary cardiovascular prevention in older adults. How beneficial is statin therapy in this population? ■■Screening for thyroid cancer in asymptomatic persons results in more harms than benefits, according to a recommendation statement that was issued by the US Preventive Services Task Force. ■■Legionnaires’ disease is widespread in US healthcare facilities. The CDC has found that 76% of US jurisdictions studied reported healthcare-associated cases of Legionnaires’ disease. ■■Reducing blood pressure below recommended targets significantly reduces CVD and mortality risk.
26 CME Keeping alert to advances in narcolepsy management Optimal approaches are reviewed for a 46-year-old woman with disrupted sleep. Guidelines for primary biliary cholangitis 14
Necrotizing myopathy: a clinical overview 22
Web Roundup A summary of our most recent opinion, news, and multimedia content from ClinicalAdvisor.com
Dermatology Clinic n A baby with blisters on the palmar and plantar surfaces n Rash of the axillae that develops spontaneously
45 Dermatologic Look-Alikes Rubbery plaques
Continues on page 10
17 Photosensitivity diseases: sun-exposed skin rashes An overview of porphyrias, lupus erythematosus, rosacea, drug-induced photosensitivity, polymorphous light eruption, and solar urticaria.
33 CME Feature posttest
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Stat Consult Minor burns. A clinical review of causes, diagnosis, and treatment
Legal Advisor Fired for refusing vaccination. A clinician fi les a lawsuit against her employer after being fired for refusing Tdap immunization.
Top: © The New Yorker Collection 2017 from cartoonbank.com. All Rights Reserved. Bottom: © Harley Schwadron, 2017.
“Someone’s at the hole.”
ADVISOR FORUM 34
Your Comments ■ Making the case for developmental trauma disorder ■ Subungual hematoma or melanoma?
My Most Memorable Patient ■ A young girl with Kawasaki disease
Clinical Pearls ■ Removing a ring from a swollen finger
“An echo is like a voice selfie.”
HOW TO CONTACT US THE CLINIC 2017
F O RU M
■ Primary bilia ■ Lyme dise ry cholangitis ase ■ Legionnaire prevention ’s disease FEATURE
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Necrotizing myo proximal mus pathy: cle weakne ss LEGAL AD VISOR
A clinician is fired for refusing to be vaccinat ed.
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Bulbous nose in rhinoph yma a severe form, of rosacea.
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Home noninvasive ventilation with oxygen therapy effective for COPD and hypercapnia Adding home noninvasive ventilation to home oxygen therapy was effective in patients with persistent hypercapnia following an acute exacerbation of COPD. Weight loss leads to lower cartilage degeneration in osteoarthritis Patients who lost weight over a 48-month period had a lower rate of cartilage degeneration than patients who maintained stable weight.
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Patients treated by older physicians have a higher mortality rate Researchers found that patients treated by older physicians had higher 30-day mortality than those cared for by younger physicians, despite similar patient characteristics.
ClinicalAdvisor.com/WaitingRoom Judi Greif, RN, MS, APNC The House’s healthcare bill: Trumpcare or “Chumpcare”? Public opinion polls support the views of professional organizations, with 60% of Americans opposing the American Health Care Act, 31% supporting it, and 9% undecided. Sharon O’Brien, MPAS, PA-C Catathrenia: Parasomnia or breathing disorder? Individuals with catathrenia experience a moaning, groaning, or high-pitched squeak during sleep. Jillian Knowles, MMS, PA-C Tips for adjusting to the night shift Working through the night and sleeping during the day can be a difficult adjustment.
The Clinical Advisor’s monthly cartoons are also available online.
ClinicalAdvisor.com/Multimedia One alcoholic drink per day may increase breast cancer risk Drinking the equivalent of one small glass of wine or beer a day increases pre-menopausal breast cancer risk by 5% and post-menopausal breast cancer risk by 9%. Watch the video here:
Study finds flu shots less effective for obese adults A study from the University of North Carolina, Chapel Hill, found that flu shots are less effective for obese adults compared with individuals who maintain a healthy weight. Watch the video here: ClinicalAdvisor.com/FluShotObesityVideo
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INTERACT WITH YOUR PEERS by viewing the images and offering your diagnosis and comments. To post your answer, obtain more clues, or view similar cases, visit ClinicalAdvisor.com/AdvisorDx. Learn more about diagnosing and treating these conditions, and see how you compare with your fellow colleagues.
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Would you remove this patient’s fingernail? A 50-year-old woman presents with a fingertip injury after getting her right index finger caught between a board and a cement block. Radiographs taken in the emergency department 4 days previously show a distal phalanx fracture (tuft fracture) of the index finger. She also has a subungual hematoma involving more than 50% of her nail. She rates her pain as 5 out of 10. WOULD YOU REMOVE THIS FINGERNAIL?
• Removal of the nail with nail bed repair • Drainage of the hematoma by nail perforation • Nail trephination • Finger splint ● See the full case at ClinicalAdvisor.com/OrthoDx_Jul17
Derm Dx A growing knot in the palm A 52-year-old woman complains of a “knot” in her palm that has been increasing in size over the past several months. She has also noted progressive tightness of her fourth and fifth fingers. She denies antecedent injury or repetitive trauma to the hand. Examination of the affected palm reveals a firm, fixed, readily palpable cord as well as loss of mobility and contracture of the ring finger. CAN YOU DIAGNOSE THIS CONDITION?
• Verruca vulgaris • Dupuytren contracture
• Xanthoma • Calcinosis cutis
● See the full case at ClinicalAdvisor.com/DermDx_Jul17
www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JULY 2017 13
Newsline J U LY 2 0 1 7
Preventing Lyme disease and tick bites page 15
Legionnaire’s disease in healthcare facilities page 16
Reducing blood pressure below target levels page 16
NEW CLINICAL practice guidelines for primary biliary cholangitis (PBC) have been released by the European Association for the Study of the Liver (EASL) and published in the Journal of Hepatology. The guidelines summarize the evidence of the importance of a structured, lifelong, and individualized approach for clinicians to manage patients with PBC. Recommendations include the following, with grade of evidence and recommendation in parentheses. The evidence and recommendations have been graded according to the grading of recommendations assessment development and evaluation (GRADE system). 1. Take a detailed history and administer a physical examination when evaluating patients with biochemical tests that suggest cholestatic liver disease (III, 1). 2. Ultrasound is recommended as the first-line non-invasive imaging procedure to differentiate intra- from extrahepatic cholestasis (III, 1). 3. Performing serologic screening is recommended for antimitochondrial antibodies (AMA) and PBC-specific antinuclear antibody (ANA) by immunofluorescence in all patients with unexplained cholestasis (III, 1). 4. Imaging by magnetic resonance cholangiopancreatography (MRCP) is recommended
in patients with unexplained cholestasis. Endoscopic ultrasound can be an alternative to MRCP for evaluation of distal biliary disease (III, 1). 5. Consider liver biopsy after serolog ic screening and extended imaging in patients with ongoing unexplained intrahepatic cholestasis (III, 1). 6. Consider genetic tests for inherited cholestatic syndromes in patients when clinically appropriate (III, 1). 7. In adult patients with cholestasis and no likelihood of systemic disease, a diagnosis of PBC can be made based on elevated alkaline phosphatase (ALP) and the presence of AMA at a titer >1:40 (III, 1). 8. In the correct context, a diagnosis of AMA-negative PBC can be made in patients with cholestasis and specific ANA immunofluorescence (nuclear dots or perinuclear rims) or ELISA results (sp100, gp210) (III, 1). 9. Liver biopsy is not recommended for the diagnosis of PBC, unless PBC-specific antibodies are absent, co-existent autoimmune hepatitis (AIH) or non-alcoholic steatohepatitis (NASH) is suspected, or other (usually systemic) comorbidities are present (III, 1). 10. AMA reactivity alone is not sufficient to diagnose PBC.
14 THE CLINICAL ADVISOR • JULY 2017 • www.ClinicalAdvisor.com
© CNRI / SCIENCE SOURCE
Primary biliary cholangitis: Clinical practice guidelines
Bile duct inflammation in cholangitis, which occurs when bile ducts carrying digestive chemicals from the liver to the digestive tracts become blocked.
Follow up with patients who have normal serum liver tests who are AMA-positive with annual biochemical reassessment for the presence of liver disease (III, 1). 11. Therapy in PBC should aim to prevent end-stage complications of liver disease and manage associated symptoms. (III, 1). 12. Evaluate all patients for their risk of developing progressive PBC (III, 1). 13. Recognize that patients at greatest risk of complications from PBC are those with inadequate biochemical response to therapy and cirrhosis (II-2, 1). 14. Actively recognize that the strongest risk factors for inadequate biochemical response to therapy are early age at diagnosis (eg <45) and advanced stage at presentation (III, 1). 15. Evaluate all patients for their stage of disease with use of a combination of non-invasive tests (bilirubin, alkaline phosphatase, aspartate aminotransferase, albumin, platelet count, and elastography) at baseline, and during followup (III, 1).
Tips for preventing Lyme disease and tick bites THE US CENTERS for Disease Control and Prevention (CDC) has released a toolkit to help individuals protect themselves against Lyme and other tick-borne diseases, which are more prevalent from May through July. The risk is greatest in New England, the mid-Atlantic states, and the upper Midwest. “Ticks that spread disease to people can have up to 2- to 3-year lifecycles, and many factors can affect their numbers, including temperature, rainfall, humidity, and the amount of available hosts for the ticks to feed on, such as mice, deer, and other animals,” the agency stated.” Other tick-borne diseases include Rocky Mountain spotted fever, anaplasmosis, ehrlichiosis, Powassan virus, and babesiosis. To prevent against tick
Typical rash that develops in Lyme disease after a bite from a deer tick.
bites, the CDC recommends the following: • Avoid high grass and leaf litter and walk in the center of hiking trails. • Use repellent that contains 20% or more DEET, picaridin, or IR3535 on exposed skin. • Use products that contain permethrin to treat clothing and gear, including boots, pants, socks,
and tents, or look for clothing pretreated with permethrin. • Treat dogs for ticks using tick collars, sprays, shampoos, or monthly “top spot” medications. • Bathe or shower after coming indoors to wash off and easily find any crawling ticks. • Conduct a full-body tick check using hand-held or full-length mirror. Parents should also help children check thoroughly for ticks. Remove any ticks right away. • Dry clothes in a dryer on high heat for 10 minutes to kill ticks on dry clothing. • Individuals who live in high-risk areas should also be alert for an unexpected summer fever or odd rash, as these may be the first signs of Lyme disease. Individuals with these symptoms should contact their healthcare provider.
STATINS DID NOT show benefit in the primary prevention of all-cause mortality or coronary heart disease events in adults older than age 65, according to a study in JAMA Internal Medicine. A total of 2,867 ambulatory adults with hypertension and without atherosclerotic cardiovascular disease were included in the Lipid-Lowering Trial component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Participants were assigned to receive either 40 mg/d of pravastatin sodium (n = 1,467) or usual care (n = 1,400).
The primary outcome of the trial was all-cause mortality, and secondary outcomes included cause-specific mortality and nonfatal myocardial infarction or fatal coronary heart disease. The baseline mean low-density lipoprotein (LDL) cholesterol levels were 147.7 mg/dL in the pravastatin group and 147.6 mg/dL in the usual care group. By 6 years, the LDL cholesterol levels decreased to 109.1 mg/dL in the pravastatin group and 128.8 mg/dL in the usual care group. At 6 years, 16.6% of participants assigned to pravastatin were not taking any statin, and
Statin therapy was not beneficial in preventing all-cause mortality or coronary heart disease events in adults older than age 65 years.
71.0% of the participants assigned to the usual care group were not taking any statin. The hazard ratios for all-cause mortality in the pravastatin group compared with the usual care group were 1.18 for adults older than 65 years of age, 1.08 for adults between 65 and 74 years of age, and 1.34 for adults older than 75 years of age. The researchers note that coronary heart disease event rates were not significantly different among the groups. In addition, they observed a nonsignificant direction toward increased allcause mortality with pravastatin in adults older than 75 years of age.
www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JULY 2017 15
© ANAKOPA / GETTY IMAGES
Statins vs usual care for CV prevention in older adults
Newsline Screening for Legionnaires’ in US healthcare facilities Among the cases that were defithyroid cancer THE CENTERS FOR Disease Control and Prevention (CDC) has found that 76% of US jurisdictions studied reported healthcareassociated cases of Legionnaires’ disease. The analysis, published in the CDC’s Vital Signs report, included exposure data from 20 states and New York City. Exposure information from these 21 jurisdictions were used to determine how often Legionnaires’ disease was associated with healthcare facilities. The results showed that 3% of Legionnaires’ disease cases are definitely associated with healthcare facilities (inpatient stays more than 10 days before symptoms begin). An additional 17% are possibly associated with a healthcare facility (exposure to a healthcare facility for less than 10 days before symptom onset).
Legionella pneumophila bacteria. Legionnaire’s disease is common in US healthcare facilities.
nitely associated with healthcare facilities, 80% were associated with long-term care facilities, 18% were associated with hospitals, and 2% were associated with both. In addition, 88% were in patients older than 60 years of age. The cases were reported from 72 unique facilities, and the number of cases ranged from 1 to 6 per facility. “Legionnaires’ disease in hospitals is widespread, deadly, and preventable,” stated Anne Schuchat, MD, CDC Acting Director. “These data are especially important for healthcare facility leaders, doctors, and facility managers because it reminds them to think about the risks of Legionella in their facility and to take action. Controlling these bacteria in water systems can be challenging, but it is essential to protect patients.”
Reducing BP below recommended targets REDUCING SYSTOLIC BLOOD pressure to levels below the recommended targets can significantly reduce the risk of cardiovascular disease (CVD) and all-cause mortality, according to research published in JAMA Cardiology. The analysis included 42 clinical trials (144,220 patients), with random allocation to an antihypertensive medication, control, or treatment target. Overall, the researchers observed linear associations between mean achieved systolic blood pressure and CVD risk, with the lowest risk at 120 to 124 mm Hg. Participants with a mean achieved systolic blood pressure of 120 to 124 mm Hg had a hazard ratio (HR) for major CVD of 0.71,
16 THE CLINICAL ADVISOR • JULY 2017 • www.ClinicalAdvisor.com
compared with those who had mean levels of 130 to 134 mm Hg (HR, 0.58), compared with those with mean levels of 140 to 144 mm Hg (HR, 0.46), compared with those with mean levels of 150 to 154 mm Hg (HR, 0.36), compared with those with mean levels of 160 mm Hg or more. In addition, individuals with a mean achieved systolic blood pressure of 120 to 124 mm Hg had an HR for all-cause mortality of 0.73, compared with those with mean levels of 130 to 134 mm Hg (HR, 0.59), compared with those with mean levels of 140 to 144 mm Hg (HR, 0.51), compared with those with mean levels of 150 to 154 mm Hg (HR, 0.47), compared with those with mean levels of 160 mm Hg or more. n
© ROYALTYSTOCKPHOTO / SCIENCE PHOTO / GETTY IMAGES
SCREENING for thyroid cancer in asymptomatic persons results in more harms than benefits, according to a recommendation statement from the US Preventive Services Task Force (USPSTF) that was published in JAMA. The USPSTF issued its new statement with moderate certainty (D recommendation), and the recommendation does not apply to patients who have hoarseness, pain, difficulty swallowing, or other throat symptoms or to those who have lumps, swelling, asymmetry of the neck, or other reasons to undergo a neck examination. The recommendation also does not apply to persons who have an increased risk of thyroid cancer due to a history of exposure to ionizing radiation, particularly those with a diet low in iodine, an inherited genetic syndrome associated with thyroid cancer, or a first-degree relative with a history of thyroid cancer. Although the USPSTF found inadequate direct evidence regarding the benefits of screening, it determined that the magnitude of the overall benefits of screening and treatment “can be bounded as no greater than small, given the relative rarity of thyroid cancer, the apparent lack of difference in outcomes between patients who are treated vs monitored (for the most common tumor types), and observational evidence showing no change in mortality over time after introduction of a mass screening program.”
FEATURE: YOUNG MOON, DANIELLE BROWN, MAURA HOLCOMB, MD
Photosensitivity diseases: sun-exposed skin rashes An overview of porphyrias, lupus erythematosus, rosacea, drug-induced photosensitivity, polymorphous light eruption, and solar urticaria.
everal acquired and inherited dermatologic disorders manifest as rashes on sun-exposed skin following exposure to solar radiation. These conditions are referred to as photosensitivity diseases. In this article, we highlight some specific types of photosensitivity dermatosis: the porphyrias, lupus erythematosus, rosacea, drug-induced photosensitivity, polymorphous light eruption, and solar urticaria.
© SCOTT CAMAZINE / MEDICALIMAGES.COM
Rhinophyma, a severe form of rosacea, in a 60-year-old man.
The porphyrias are a group of photosensitivity diseases resulting from an acquired or inherited defect in the enzymes required to produce adequate amounts of heme (found in hemoglobin, myoglobin, and cytochrome P-450 enzymes), with the subsequent accumulation of porphyrins. The accumulation and deposition of porphyrins in the skin leads to photosensitivity.1 Two common types of porphyria with a significant photosensitivity component are porphyria cutanea tarda (PCT) and erythropoietic protoporphyria (EPP). These types of porphyria are described as nonacute because they manifest primarily as rashes on sun-exposed skin. In contrast to the nonacute porphyrias, the acute porphyrias have significant systemic and neurologic manifestations. PCT is the most common nonacute porphyria (prevalence of 1 in 10,000).2 PCT is due to a dysfunction of the enzyme uroporphyrinogen decarboxylase (UROD), which is either genetic or acquired. Acquired dysfunction of UROD has been associated with excess levels of alcohol, www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JULY 2017 17
PHOTOSENSITIVITY DISEASES: SUN-EXPOSED SKIN RASHES
Porphyrias are photosensitivity diseases that result from an acquired or inherited defect in enzymes required to produce adequate amounts of heme. iron, or estrogens. Following exposure to light, pigmentation, vesicles, bullae, erosions, crusts, and scarring of the face, forehead, and forearms may develop. The diagnosis of PCT is aided by the finding of increased porphyrin levels in the plasma, feces, or urine, which may have a characteristic deep-red color. Patients who have PCT may be treated with repeated phlebotomy to reduce blood iron levels or by withdrawal of alcohol, iron, or estrogens.3 EPP is the second most common nonacute porphyria (prevalence between 1 in 50,000 and 1 in 75,000).2 It is due to an inherited dysfunction of the enzyme ferrochelatase, which causes protoporphyrin to combine with iron to form heme. Symptoms usually first appear in early childhood.4 Exposure to light may immediately result in burning, stinging, swelling, and pruritus. With repeated exposure to light, scars, lichen planus, and nail changes may develop.5 EPP can be diagnosed by the finding of increased porphyrins in the plasma or stool. It can be treated with oral ß-carotene and avoidance of the sun.6 Lupus erythematosus
Photosensitivity reactions are very common in patients with lupus. Lupus is an autoimmune disorder with numerous subtypes, defined by whether the disease manifestations are solely dermatologic or both dermatologic and systemic. Cutaneous lupus erythematosus (CLE) is limited to the skin, and systemic lupus erythematosus (SLE) involves both the skin and other organs. The cutaneous manifestations of lupus can include malar rash, discoid rash, and photosensitivity. The systemic
manifestations of lupus can include nonerosive arthritis, serositis, renal disorders, neurologic disorders, hematologic disorders, immunologic disorders, and the presence of antinuclear antibody.7 Following exposure to sunlight, diffuse erythema or exacerbation of the dermatologic manifestations of the disease may develop in patients with lupus. In this article, we will focus on the photosensitivity that can arise in patients with lupus, specifically in those with either of two subtypes of CLE. Subacute cutaneous lupus erythematosus (SCLE) is a subtype of CLE that has a significant photosensitivity component. The rash associated with SCLE appears as plaques and/or papulosquamous lesions on sun-exposed areas, such as the shoulders, chest, and extremities.5 The diagnosis of SCLE can be aided by serologic findings such as elevated levels of antinuclear antibodies, anti-Ro antibodies, anti-La antibodies, and rheumatoid factor.8 The diagnosis can also be made through skin biopsy and subsequent direct immunofluorescence microscopy.9 Although some patients with SCLE may respond to nonsystemic treatment, such as topical tacrolimus and/or the avoidance of natural and artificial ultraviolet (UV) light, most patients require systemic therapy with an antimalarial agent, such as hydroxychloroquine.10 Another subtype of CLE with skin manifestations of significant photosensitivity is discoid lupus erythematosus (DLE). DLE appears as circular (discoid), dark red, scaly plaques that are associated with features such as scarring and loss of skin pigment. The lesions develop on sun-exposed areas, such as the extremities, face, and upper chest.5 A malar rash and alopecia are also common in patients with DLE. The cutaneous signs of DLE are exacerbated by sun exposure. The diagnosis of DLE can be aided by skin biopsy and direct immunofluorescence. Although most patients with DLE respond to the avoidance of sunlight and the application of topical corticosteroids, some may require systemic therapy with an antimalarial agent, such as hydroxychloroquine.10
© MAURA HOLCOMB, MD
Discoid lupus erythematosus is associated with loss of skin pigment.
Rosacea is a dermatologic disease characterized by erythema, solar urticaria, or telangiectasia of the face. Rosacea manifests following repeated exposure to anything that causes facial blushing, such as sunlight, heat or cold, and spicy food. Alcohol consumption and some emotions may also cause facial blushing.11 The manifestations of rosacea differ vastly depending on the subtype. There are four major subtypes of rosacea: erythematotelangiectatic rosacea (ETR), papulopustular
18 THE CLINICAL ADVISOR • JULY 2017 • www.ClinicalAdvisor.com
Phototoxic responses occur within minutes to hours after the first exposure to a drug, and they appear as sunburn-type reactions. rosacea (PPR), phymatous rosacea, and ocular rosacea.12 Patients with ETR present with flushing and telangiectasia of the face, usually accompanied by burning or stinging pain. Those with PPR have erythema of the face, sometimes accompanied by burning or stinging pain. Phymatous rosacea manifests as thickened skin and nodules, most often on the nose. The features of ocular rosacea include conjunctivitis, iritis, scleritis, and other forms of ocular inflammation.11 Despite the different manifestations of the four subtypes, all types of rosacea can be treated topically with azelaic acid, metronidazole, or sodium sulfacetamide with sulfur. Because rosacea is commonly exacerbated by sun exposure, avoidance of sunlight and proper protection from the sun should be recommended.13
Which of the following photosensitivity diseases do you see most frequently in your practice? n=301
4.32% ■ Porphyrias
■ Rosacea ■ Drug-induced photosensitivity
For more polls, visit ClinicalAdvisor.com/Polls.
Numerous drugs can cause rashes in a photodistributed pattern after exposure to solar radiation. These photosensitivity reactions are subdivided into phototoxic and photoallergic reactions. Phototoxic responses occur within minutes to hours after the first exposure to a drug and appear as sunburn-type reactions, with erythema, hyperpigmentation, dermatitis, or blisters. Photoallergic responses are delayed reactions that occur on secondary exposure to a drug and appear as an itchy, erythematous rash that can manifest in numerous different forms, to include papules or vesicles.14 Systemic medications known to cause photosensitivity reactions include many antibiotics, antipsychotics,
chemotherapeutic medications, diuretics, and anti-inflammatory drugs. The reaction induced by these medications is a phototoxic response. The diagnosis can be made after a careful evaluation of the patient’s medications. The rashes disappear when the drug is no longer taken.5 Photosensitive reactions can be induced by applying to the skin substances such as the chemicals in antibacterial solutions, sunscreens, and perfumes. These reactions are typically photoallergic and manifest as an itchy rash in a photodistributed pattern. The diagnosis can be made through a photopatch test, in which the skin is exposed to the specific ingredient and then to sunlight. If the specific allergen cannot be identified and the reaction is relentless, the patient may have to be treated with immunosuppressive medications.15
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Polymorphic light eruption
A case of phototoxic erythema on the face of a young woman.
Polymorphic light eruption (PMLE) is a delayed-type hypersensitivity reaction to UV radiation. It is a relatively common disorder that typically occurs in girls and young women, usually in fair-skinned individuals.16 The etiology of PMLE is unknown. The condition usually develops in individuals experiencing their first yearly prolonged exposure to sunlight.5 The resulting pruritic rash is described as polymorphous because it can manifest as almost any type of lesion, to include papules, plaques, or vesicles. The rash occurs on sun-exposed areas of the body and disappears on its own within two weeks. The differential diagnosis for PMLE includes solar urticaria, atopic dermatitis, and rare inherited photosensitivity diseases. The diagnosis can be made through the patient’s medical www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JULY 2017 19
PHOTOSENSITIVITY DISEASES: SUN-EXPOSED SKIN RASHES
history or with phototesting. PMLE can be prevented with adequate sun protection. After the development of PMLE, corticosteroids can be used to accelerate the recovery process. Some patients with chronic PMLE may benefit from a course of phototherapy before a season of sun exposure.16 Solar urticaria
Solar urticaria is a rare disorder in which a rash develops after exposure to sunlight. The rash initially appears as erythema on sun-exposed areas but then takes the form of raised hives. Solar urticaria is associated with intense pruritus. This is an immediate reaction that can be very severe. Rare cases associated with swelling of the mucosal membranes and difficulty breathing have been reported. The differential diagnosis for solar urticaria includes SCLE, drug reactions, porphyria, and PMLE. Solar urticaria can be diagnosed through phototesting. The most effective treatment is strict protection from the sun, to include the use of UVA- and UVB-blocking sunscreens. With limited success, phototherapy in stepwise doses has been
used in patients to decrease the solar reaction. Other treatments include immunosuppressive medications and plasma exchange.5 Conclusion
In this article, we have reviewed six of the most common classes of conditions and diseases associated with photosensitivity: the porphyrias, lupus erythematosus, rosacea, drug-induced photosensitivity, polymorphous light eruption, and solar urticaria. When a patient presents with a rash on sun-exposed areas, a thorough history must be taken that includes exposure to sunlight, use of medication, and prior personal and family history of manifestations of dermatologic disease. The dermatologic examination further delineates the photosensitive dermatosis. Correctly diagnosing the specific condition associated with a photosensitive rash makes it possible to provide adequate treatment and, depending on the diagnosis, avoid future outbreaks. Clinicians must be aware of the spectrum of photosensitivity diseases because these conditions
Six common photosensitivity diseases/conditions and their typical presentations following exposure to ultraviolet radiation Condition/Disease
Porphyria cutanea tarda
• Pigmentation; vesicles; bullae; erosions; crusts and scarring on face, forehead, and forearms
• Phlebotomy • Avoidance of alcohol, iron, estrogens
• Acute: burning, stinging, swelling, and pruritus • Chronic: scarring, lichen planus, nail changes
• Oral ß-carotene • Avoidance of sun
Subacute cutaneous lupus erythematosus
• Plaques with or without papulosquamous lesions on shoulders, chest, and extremities
• Topical tacrolimus • Avoidance of sun • Hydroxychloroquine
Discoid lupus erythematosus
• Erythematous, scaly, discoid plaques on face, extremities, and chest; worsening of symptoms such as malar rash and alopecia
• Topical corticosteroids • Avoidance of sun • Hydroxychloroquine
• Erythema, solar urticaria, or telangiectasia on face
• Azelaic acid • Metronidazole • Sodium sulfacetamate
Phototoxic response to ystemic medications
• Resembles sunburn, with erythema, hyperpigmentation, or blistering within minutes to hours after first exposure to drug
• Discontinuation of drug
Photoallergic response to topical medications
• Itchy, erythematous rash that appears in delayed fashion on secondary exposure to medication
• Discontinuation of drug
Polymorphic light eruption
• Pruritic, polymorphous rash on sun-exposed areas after first yearly prolonged exposure to sunlight
• Avoidance of sun
• Erythematous macules evolving into pruritic urticaria; rarely associated with mucosal swelling and anaphylactic response
• Avoidance of sun • Phototherapy
20 THE CLINICAL ADVISOR • JULY 2017 • www.ClinicalAdvisor.com
are common and can be associated with systemic diseases, although they are rarely life-threatening. n Young Moon and Danielle Brown are medical students and Maura Holcomb, MD, is a dermatology resident at Baylor College of Medicine in Houston. References 1. Vasil KE, Magro CM. Cutaneous vascular deposition of C5b-9 and its role as a diagnostic adjunct in the setting of diabetes mellitus and porphyria cutanea tarda. J Am Acad Dermatol. 2007;56:96-104. 2. Lecha M, Puy H, Deybach JC. Erythropoietic protoporphyria. Orphanet J Rare Dis. 2009;4:19. 3. Lundvall O. The effect of replenishment of iron stores after phlebotomy
“I got a sneaker contract.”
therapy in porphyria cutanea tarda. Acta Med Scand. 1971;189:51-63. 4. Sassa S, Zalar G, Poh-Fitzpatrick M, Anderson K, Kappas A. Studies in porphyria: functional evidence for a partial deficiency of ferrochelatase activity in mitogen-stimulated lymphocytes from patients with erythropoietic protoporphyria. J Clin Invest. 1982;69:809. 5. Goldsmith L, Katz S, Gilchrest BA, Paller AS, Leffell DJ, Wolff K. Fitzpatrick’s Dermatology in General Medicine, Eighth Edition, 2 Volume set. New York, NY: McGraw-Hill Medical; 2012. 6. Mathews-Roth MM, Pathak MA, Fitzpatrick T, Harber LH, Kass EH. Beta tivity diseases. Arch Dermatol. 1977;113:1229-1232. 7. Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982;25:1271-1277. 8. Pellowski DM, Kihslinger JE, Sontheimer RD. Subacute cutaneous and systemic lupus erythematosus. In: Hertl M, ed. Autoimmune Diseases of the Skin: Pathogenesis, Diagnosis, Management. 3rd ed. New York, NY: Springer; 2011: 223-228. 9. David-Bajar K, Davis B. Pathology, immunopathology, and immunohisto-
“I’m 66 — I don’t want to see puppets in anything.”
chemistry in cutaneous lupus erythematosus. Lupus. 1997;6:145-157. 10. Ruzicka T, Sommerburg C, Goerz G, Kind P, Mensing H. Treatment of cutaneous lupus erythematosus with acitretin and hydroxychloroquine. Br J Dermatol. 1992;127:513-518. 11. Crawford GH, Pelle MT, James WD. Rosacea: I. Etiology, pathogenesis, and subtype classification. J Am Acad Dermatol. 2004;51:327-341. 12. Dahl MV. Rosacea subtypes: a treatment algorithm. Cutis. 2004;74(3 Suppl):21-27, 32-34. 13. Pelle MT, Crawford GH, James WD. Rosacea: II. therapy. J Am Acad Dermatol. 2004;51:499-512. 14. Drucker AM, Rosen CF. Drug-induced photosensitivity. Drug Saf. 2011;34:821-837. 15. Lowe GC, Henderson CL, Grau RH, Hansen CB, Sontheimer RD. A systematic review of drug‐induced subacute cutaneous lupus erythematosus. Br J Dermatol. 2011;164:465-472. 16. Tutrone WD, Spann CT, Scheinfeld N, Deleo VA. Polymorphic light eruption. Dermatol Ther. 2003;16:28-39.
Whale-to-whale resuscitation www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JULY 2017 21
Top: © Harley Schwadron, 2017; middle, bottom: © The New Yorker Collection 2017 from cartoonbank.com. All Rights Reserved.
carotene therapy for erythropoietic protoporphyria and other photosensi-
FEATURE: KATHLEEN WALTER, ANP-BC
Necrotizing myopathy: muscle weakness Clinicians in all settings are in a position to identify patients with potential myopathic processes and complete an initial diagnostic work-up.
© YOAV LEVY / MEDICALIMAGES.COM
Proximal muscle weakness is a feature of necrotizing myopathy.
22 THE CLINICAL ADVISOR • JULY 2017 • www.ClinicalAdvisor.com
diopathic myopathies include polymyositis, dermatomyositis, non-specific myositis, and necrotizing myopathy.1 These are very rare conditions and may be missed if one is unfamiliar with the presenting symptoms. The combined incidence of polymyositis and dermatomyositis is 4 to 10 cases per million population per year.2 The idiopathic inflammatory myopathies share common features, including proximal muscle weakness, elevated muscle enzymes (creatinine phosphokinase, aldolase) and potentially elevated liver functions (aspartate transaminase [AST]/ alanine transaminase [ALT]), resulting from damaged muscle and not actual liver damage. The onset is usually insidious and painless and is characterized by progressive symmetric proximal muscle weakness during the course of 3 to 6 months.3 Patients frequently complain of difficulty walking upstairs, getting up and down from a chair, getting in and out of a car, falling, and difficulty raising their arms over their heads to dress, shower, or comb their hair. Muscles of the throat and upper airway may be affected, resulting in dysphagia, nasal regurgitation of fluids, aspiration, and hoarseness.3-5 History gathering should solicit the patient’s abilities or limitations with these activities of daily living (ADLs). The patient may have mild arthralgias. Lungs are the most common extra muscular organ involved in idiopathic inflammatory myopathies.3 Patients may complain of dyspnea, and pulmonary function tests (PFTs) may demonstrate a restrictive pattern with decreased lung volumes and reduced diffusing
capacity of the lungs for carbon monoxide (DLCO).3 A high resolution CT of the chest typically demonstrates “ground glass opacities” consistent with alveolitis or honeycombing consistent with fibrosis.3 Given dysphagia, patients may develop aspiration pneumonia. Patients may have cardiac involvement most often in the form of rhythm disturbances.2 More rarely, they may experience conduction abnormalities, pericarditis, myocarditis, cardiac arrest, and congestive heart failure.2,3 All of the preceding are often accompanied by fatigue, fever, and weight loss. Dermatomyositis presents similarly to polymyositis, as previously described, but also includes characteristic rashes or skin involvement. A heliotrope rash consists of a purplish discoloration, almost resembling eye shadow, above the eyes with associated periorbital edema. A “shawl sign” consists of an erythema around the neck and upper chest. Gottron’s papules, which are hypertrophied calloused-looking plaques, may occur over the metacarpophalangeal joints (MCPs) and proximal interphalangeal joints (PIPs). Mechanics hands refers to skin cracking and fissuring of the fingers and hands. Patients may also have periungual erythema.2,3 Immune-mediated necrotizing myopathies present with symptoms similar to those of other idiopathic inflammatory myopathies, but the muscle biopsy demonstrates necrosis of muscle fibers, as opposed to inflammatory infiltrates found on muscle biopsy of those with polymyositis or dermatomyositis.4,6 Statin exposure has been associated with necrotizing myopathy. It is thought that the statin may induce an autoimmune process that persists despite withdrawal of the statin.2 This is in contrast to a statin-induced myopathy that improves over weeks to months when the statin is discontinued.5 Specific autoantibodies have been noted in those with necrotizing myopathy, including anti-HMGCR antibody and signal recognition particle (SRP).4,6 Etiology
The etiology of idiopathic inflammatory myopathies is unknown but may involve a genetic/familial component.7 It is thought that environmental triggers (viruses, bacteria, ultraviolet light, physical exertion, psychological stress, medications, and vaccines) may initiate an autoimmune response in those with an underlying genetic susceptibility.7 Diagnosis
Accurate diagnosis is a process that involves a comprehensive history, baseline lab work identifying elevated muscle enzymes, and unilateral electromyogram/nerve conduction study (EMG/NCS) assessing for characteristic changes. It is important to recognize that EMG/NCS may cause changes
that interfere with interpretation of muscle tissue when biopsied. Conducting a unilateral EMG/NCS preserves a contralateral muscle biopsy site for study.3 Imaging, MRI in particular, is the most sensitive in detecting muscle edema associated with myositis.2 A muscle biopsy is the final piece of the diagnostic puzzle. Potential differential diagnoses include metabolic muscle disorders, polymyalgia rheumatica, drug-related myopathy, hypothyroidism, neuromuscular disorders, and paraneoplastic syndrome. Clues to these other etiologies are often apparent in the history. Patients with metabolic muscle disorders (ie, McArdle disease) often complain of muscle fatigue after initiating exercise or activity but have normal strength during an examination.2,8 The possibility of drug-related myopathies has been noted with statins, colchicine, steroids, ipecac, cocaine, alcohol, zidovudine, and D-penicillamine.2 Polymyalgia rheumatica occurs more commonly in older persons and preferentially affects the proximal muscles with markedly elevated measures of inflammation (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]) and normal muscle enzymes.2 Patients with hypothyroidism may have elevated creatine kinase (CK) and complain of fatigue. A thyroid profile should be completed in all patients with muscle complaints. Patients with neuromuscular disorders, such as myasthenia gravis, will have normal muscle enzymes with muscle weakness and fatigue later in the day or with prolonged exertion and characteristic patterns on EMG/ NCS study.2 Malignancies may initially present with muscle weakness and elevated muscle enzymes. Age and genderspecific cancer screening should be completed or updated in those with a myopathic process.9,10 Patients with idiopathic inflammatory myopathies may have other underlying connective tissue disorders such as scleroderma, anti-synthetase syndrome, or mixed connective tissue disorder that will need to be ruled out when referred to rheumatology.5 It should be understood that benign elevations in muscle enzymes occur. The “normal” values for CK and aldolase are a reference range. There will be outliers that do not signal pathology. Patients with larger muscle mass or those who engage in a regular or strenuous fitness routine may have higher muscle enzymes. A history of use of muscle building supplements should be assessed for, as they can affect muscle enzymes. Treatment
Given the autoimmune nature of these diseases, treatment consists of immunosuppression. Initial treatment is almost always prednisone, typically 60 mg daily to start.11 A second
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NECROTIZING MYOPATHY: MUSCLE WEAKNESS
Case Report A 63-year-old woman presented with a history of myalgias and weakness for more than 5 months. Her symptoms had been initially attributed to past medical history that included chronic fatigue and fibromyalgia. She had tripped and fallen 9 months earlier, which was out of character for her. She had lost 40 pounds of weight, beginning 6 months prior to falling. She complained of dysphagia, dysphonia, arthralgias, periorbital “puffiness,” peeling rash of the palms of her hands, and splitting/ cracking of the ends of her fingers. She reported having mild shortness of breath (SOB) and dyspnea on exertion (DOE) for the last 2 to 3 months and denied conversational dyspnea. She stated that she had one episode of palpitations a week prior to her office visit. She denied chest pain, dizziness, or syncope. She was taking a statin, and it had been held for 2 to 3 months prior to referral to rheumatology. Her past medical history included gastroesophageal reflux, esophagitis with antral ulcers, Epstein-Barr virus 3.5 years prior to presentation, chronic fatigue syndrome, fibromyalgia, depression, chronic low back pain, lumbar spinal stenosis, psoriasis, hypertension, and dyslipidemia. On presentation, she had not had a recent EKG. Her last colonoscopy was 7 years prior to presentation. Her mammogram was a year prior to presentation. She had a hysterectomy/oophorectomy and was not sure when her last pelvic exam was. Her work-up was remarkable for a creatine phosphokinase (CPK) greater than 6K (55-170), elevated AST/ALT greater than 3 times normal, complete blood count (CBC) with mildly low mean corpuscular volume (MCV) and mean cell hemoglobin (MCH), but otherwise normal. She had an elevated total iron binding capacity (TIBC) with iron of 47 (28-170) and saturation percentage of 9 (15-50). Thyroid stimulating hormone (TSH) level was normal, and vitamin D 25-OH was low at 19.20 (32100). Sedimentation rate was 16 (0-20), and CRP was <0.5 (0-1.0). HIV and hepatitis B and C screens were negative. Kidney functioning and urinalysis were normal.
glass opacities consistent with nonspecific pneumonitis pattern of pulmonary fibrosis. Her PFTs revealed a reduction in diffusing capacity. On exam, the patient appeared quite ill. She was afebrile, and her other vitals were stable. She had cracking of her distal fingers and peeling of the skin of her palms. She had a slight purplish hue near her eyelashes. There was no evidence of Gottron’s papules or shawl sign, and she had no lymphadenopathy. Cardiac, pulmonary, and abdominal exams were normal. She was unable to get out of a chair without assistance and could not lift her head from the examination table. She had marked upper and lower extremity proximal muscle weakness.
Treatment summary The patient was admitted to the 23-hour unit for pulse dose steroids and began prednisone 60 mg QD after IV methylprednisolone sodium succinate 500 mg IV X1. Simultaneously, methotrexate was started and titrated. She was eventually switched to parenteral methotrexate for better bioavailability. Methotrexate was transitioned to azathioprine when it was discovered that she had interstitial lung disease. Her lung involvement was believed to be unrelated to a potential lung toxicity that exists with methotrexate. However, it is our practice to transition to other agents when there is lung involvement. Over the course of time, the patient’s age-appropriate cancer screening was updated; an EKG and echocardiogram were obtained and were normal. Her low vitamin D was treated, and the patient was started on osteoporosis prevention. The patient responded to treatment and was eventually referred to physical therapy. Today, she is doing quite well and is feeling “stronger than ever.” She easily completes all of her own ADLs and works in the house and yard. Her prednisone taper lasted 14 months, and she remains on azathioprine. She is being followed longitudinally for her concomitant lung disease. She is currently asymptomatic from a pulmonary standpoint despite a reduction in DLCO over time.
Discussion She had MRIs of her bilateral thighs that demonstrated mild, non-specific symmetrical edema. Open muscle biopsy of her left vastus lateralis was done prior to referral, but the results were not available at the time of her initial exam. The muscle biopsy eventually revealed necrotizing myopathy. She had a positive anti-HMGCR antibody but negative anti-SRP antibody. Her high-resolution CT (HRCT) of the chest was done after treatment was initiated and demonstrated reticular and ground
The patient in this case had been symptomatic for months prior to discovery of her markedly elevated CK. Given her weight loss and appearance at initial presentation, we were concerned that she had a malignancy. Her age-appropriate cancer screening was updated and negative. Given the appearance of her hands and possible heliotrope rash, dermatomyositis was included in our differential diagnoses. Her muscle biopsy eventually demonstrated necrotizing myopathy.
24 THE CLINICAL ADVISOR • JULY 2017 • www.ClinicalAdvisor.com
immunomodulator is then added and often titrated over weeks to months and serves as a steroid-sparing agent, allowing the steroid to be slowly tapered over time.5,11 Clinicians caring for these patients, in any setting, need to be aware of potential side effects and risks associated with treatment. Concomitant immune deficiencies (HIV) and other underlying infections (hepatitis C) need to be ruled out prior to initiating treatment. Treatment with a steroid can contribute to the development of diabetes, osteoporosis, cataracts, hypertension, obesity, and fragile skin. Patients should be taught about signs and symptoms of hyperglycemia, and if they are diabetic, primary care providers need to work with rheumatology to adequately control the patients’ elevated blood sugars and similarly be alert for potential hypoglycemia during the tapering of steroids. Vitamin D should be checked and repleted if necessary and regular calcium/vitamin D initiated, along with a bisphosphonate, if not contraindicated. If possible, patients should have vaccinations prior to immunosuppression (ie, influenza, pneumococcal polysaccharide vaccine, shingles). Immunosuppressed patients need to be monitored for infection. The type of immunomodulator will dictate regular toxicity monitoring.
3. Wortman RL. Idiopathic inflammatory myopathies: Clinical features. In: Klippel JH, et al, eds. Primer on the rheumatic diseases. 13th ed. New York, NY: Springer; 2008:363-366. 4. Stenzel W, Goebel HH, Aronica E. Review: Immune-mediated necrotizing myopathies—a heterogeneous group of diseases with specific myopathological features. Neuropathol Appl Neurobiol. 2012;38:632-646. 5. Liang C, Needham M. Necrotizing autoimmune myopathy. Curr Opin Rheumatol. 2011;23:612-619. 6. Ellis E, Ann Tan J, Lester S, Tucker G, Blumbergs P, Roberts-Thomson P, et al. Necrotizing myopathy: clinicoserologic associations. Muscle Nerve. 2012;45:189-194. 7. Rider LG, Miller FW. Idiopathic inflammatory myopathies: Pathology and pathogenesis. In: Klippel JH, et al, eds. Primer on the rheumatic diseases. 13th ed. New York, NY: Springer; 2008:368-374. 8. Baer AN. Metabolic myopathies. In: Klippel JH, et al, eds. Primer on the rheumatic diseases. 13th ed. New York, NY: Springer; 2008:381-388. 9. Baer AN. Paraneoplastic muscle disease. Rheum Dis Clin North Am. 2011;37:185-200. 10. Vu HJ, Pham D, Makary R, Nguyen T, Shuja, S. Paraneoplatic necrotizing myopathy presenting as severe muscle weakness in a patient with small-cell lung cancer: successful response to chemoradiation therapy. Clin Adv Hematol Oncol. 2011;9: 557-560. 11. Oddis CV. Idiopathic inflammatory myopathies: Treatment and assessment. In: Klippel JH, et al, eds. Primer on the rheumatic diseases. 13th ed.
New York, NY: Springer; 2008:375-380.
Clinicians in all settings are in a position to identify patients with potential myopathic processes and complete an initial diagnostic work-up. In this patient’s case, the initial work-up was in progress when an emergency referral to rheumatology was made. Her evaluation continued, and a treatment plan was outlined and then modified as her clinical condition dictated. The patient in this case was markedly debilitated at her initial presentation to rheumatology. Early identification of these patients has the potential to reduce morbidity and excess disability. n Kathleen Walter, ANP-BC, is affiliated with the Pittsburgh VA Health Care System, Department of Rheumatology. References 1. Hoogendijk JE, Amato AA, Lecky BR, Choy EH, Lundberg IE, Rose MR, inflammatory myopathies, with the exception of inclusion body myositis, 10-12 October 2003, Naarden, The Netherlands. Neuromuscul Disord. 2004;14:337-345. 2. Khan S, Christopher-Stine L. Polymyositis, dermatomyositis, and autoimmune necrotizing myopathy: clinical features. Rheum Dis Clin North Am. 2011;37:143-158.
“Although the tortoise beat the hare, the tortoise was later disqualified for taking anabolic steroids, so the hare was declared the winner.”
www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JULY 2017 25
© Harley Schwadron, 2017
et al. 119th ENMC international workshop: trial design in adult idiopathic
n EDUCATIONAL OBJECTIVES At the conclusion of this activity, participants should be better able to: • Identify the 5 core symptoms of narcolepsy and recognize them in patient presentations • Distinguish narcolepsy from other disorders with similar or overlapping signs and symptoms • Apply contemporary diagnostic criteria and assessment protocols for narcolepsy to improve the accuracy and timeliness of diagnosis • Implement and monitor the impact of individualized narcolepsy treatment plans
n COMPLETE THE POST-TEST: Page 33
Release Date: April 28, 2017 Expiration Date: April 28, 2018 Estimated Time to Complete: 45 minutes Accredited Provider: This program is provided by Haymarket Medical Education. Commercial Supporter: This activity is supported by an educational grant from Jazz Pharmaceuticals. Program Description: Although narcolepsy is highly burdensome and associated with multiple negative sequelae, it is widely underrecognized and underdiagnosed, or misdiagnosed, even among sleep specialists. As a result, effective treatment may be long delayed, prolonging and exacerbating the negative impact of narcolepsy. Clinicians should be prepared to recognize its signs and symptoms to ensure that it is included in differential diagnoses and that patients are assessed using contemporary diagnostic protocols for narcolepsy. This Case Clinic activity illustrates optimal approaches to management in a 46-year-old woman with daytime fatigue and disrupted sleep. Intended Audience: Psychiatrists, neurologists, pulmonologists, sleep specialists, and other clinicians who provide care to patients with narcolepsy Conflict of Interest Disclosure Policy: In accordance with the ACCME Standards for Commercial Support, HME requires that individuals in a position to control the content of an educational activity disclose all relevant financial relationships with any commercial interest. HME resolves all conflicts of interest to ensure independence, objectivity, balance, and scientific rigor in all its educational activities. Faculty Michael J. Thorpy, MB, ChB Professor of Clinical Neurology Albert Einstein College of Medicine Director, Sleep-Wake Disorders Center Montefiore Medical Center Bronx, NY Richard K. Bogan, MD, FCCP, FAASM Associate Clinical Professor University of South Carolina School of Medicine Chief Medical Officer SleepMed Inc. Columbia, SC
Accredited Provider Disclosure: Haymarket Medical Education staff involved in the planning and content review of this activity have no relevant financial relationships to disclose. Accreditation Statement: Haymarket Medical Education is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Designation Statement: Haymarket Medical Education designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credit(s)TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Disclosure of Unlabeled Use: This CME activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME activity is for continuing medical education purposes only and is not meant to substitute for the independent medical judgment of a physician relative to diagnostic and treatment options for a specific patient’s medical condition. Disclaimer: The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of Jazz Pharmaceuticals or Haymarket Medical Education. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings. If you have any questions relating to the accreditation of this activity, please contact email@example.com. Instructions: There are no fees for participating in and receiving CME credit for this activity. During the period April 28, 2017 through April 28, 2018, participants must: 1) read the learning objectives and faculty disclosures; 2) complete the pre-assessment test; 3) study the educational activity; 4) complete the poll questions; and 5) complete the post-test and submit it online. A statement of credit will be issued only upon receipt of the above elements and a post-test score of 70% or higher. All components must be completed and submitted online at ClinicalAdvisor.com/July17feature.
Faculty Disclosures: Dr. Thorpy has been a consultant for Jazz Pharmaceuticals, Merck, and Teva Pharmaceuticals. He has also served on a speakers’ bureau for Merck and has conducted research funded by Jazz Pharmaceuticals and Flamel Technologies. Dr. Bogan has been a consultant for Jazz Pharmaceuticals, Vanda, and XenoPort and has served on speakers’ bureaus for Jazz Pharmaceuticals and Merck. He has also conducted research funded by ApniCure, Balance, Eisai, Fresca Medical Inc, GSK, Jazz Pharmaceuticals, Merck, Novo Nordisk, Phillips, ResMed, Sensory Medical, Vanda, and XenoPort.
FEATURED COURSE: MICHAEL J. THORPY, MB, ChB; RICHARD K. BOGAN, MD, FCCP, FAASM
Keeping alert to advances in narcolepsy management Optimal approaches to the management of narcolepsy are illustrated through the case of a 46-year-old woman with daytime fatigue and disrupted sleep.
© JAMES KING-HOLMES / SCIENCE SOURCE
Excessive daytime sleepiness is the core symptom of narcolepsy.
arcolepsy is a chronic neurologic condition characterized by excessive daytime sleepiness as well as cataplexy, disturbed nighttime sleep, sleep paralysis, and hypnagogic hallucinations.1 While all symptoms do not present in every patient, excessive daytime sleepiness is the core symptom and generally the first to manifest. Historically, narcolepsy has been characterized as either with or without cataplexy, the sudden loss of muscle tone that leads to feelings of weakness and a loss of voluntary muscle control. The symptoms vary depending on the muscles involved. Some patients undergo a complete physical collapse, while others have much more subtle manifestations, such as transient drooping of the facial muscles. Cataplexy is often triggered by intense emotional responses— usually laughter, happiness, or other positive emotions but also anger or other negative emotions. More recently, the International Classification of Sleep Disorders – Third Edition (ICSD-3) has designated narcolepsy with cataplexy as narcolepsy type 1 and narcolepsy without cataplexy as narcolepsy type 2.2 Even though narcolepsy is the best-studied and bestunderstood of the primary disorders of excessive daytime sleepiness,3 it remains widely underrecognized. The index of suspicion among primary care clinicians is low and public awareness of narcolepsy is incomplete and inaccurate.4 Even sleep medicine specialists are hampered by knowledge gaps about narcolepsy and its symptoms.5 Complicating the diagnostic process is that symptoms of fatigue due to sleepiness and even excessive
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While type 1 narcolepsy is regarded as the most common form of the disorder, that may be inaccurate — it is just more readily diagnosed than type 2. sleepiness itself are very prevalent and they overlap between narcolepsy and many common conditions, including infections, depression, seizure disorders, and lifestyle-induced sleep deprivation. In particular, distinguishing the signs and symptoms of other sleep disorders from those of narcolepsy can be challenging. Comorbid sleep disorders commonly accompanying narcolepsy include obstructive sleep apnea (OSA), sleep-related behaviors such as periodic leg movements, sleeptalking, and rapid eye movement (REM) behavior disorder.6 Type 2 narcolepsy, lacking the specificity of cataplexy, may be a particularly elusive diagnosis. While type 1 narcolepsy was long regarded as the most common form of the disorder, that may be inaccurate, reflecting the fact that type 1 is just more readily diagnosed than type 2. It may take years for patients to receive a definitive narcolepsy diagnosis, and as many as 80% of cases may go undiagnosed.7 The average time from symptom onset to diagnosis ranges from 8 to 15 years,8,9 and patients typically see multiple physicians before getting an accurate diagnosis of narcolepsy.10 Some data show that 60% of patients are initially misdiagnosed with depression, insomnia, or other disorders.1 The patient in this activity represents an example of the types of delays and detours encountered by patients—and clinicians—on the road to a narcolepsy diagnosis. Meet Carol
Carol, aged 46 years, presents with complaints of daytime fatigue and disrupted sleep. She has no trouble falling asleep at night, but awakens frequently and reports never feeling fully rested in the morning. She has been coping with this ongoing problem for many years. A geometry teacher at a large urban high school, Carol is married and is the parent of 14-year-old twin daughters. Her medical history is significant for depression, obesity, and mild hypertension. Carol’s body mass index (BMI) of 28.7 kg/m 2 puts her near the upper end of the overweight range. She notes that she was once an avid tennis player and enjoyed hiking and kayaking. Carol knows she should exercise more and would like to resume those recreational activities, but she’s always too tired, with barely enough energy to carry out her professional and family responsibilities. While she has experienced disrupted sleep patterns for years, awakening several times most nights, Carol says that it seems harder for her to overcome the daytime sleepiness these days. No matter how early she goes to bed or how many cups
of coffee she consumes, she finds herself fighting to stay alert at work. She functions well enough when standing in front of a class to teach, but finds it difficult to avoid drifting off when sitting quietly, as when reviewing her students’ work. Carol was recently reprimanded because she was discovered snoozing while she was supposed to be monitoring students who were taking a test. Three years prior to this visit, Carol had complained of feeling “down in the dumps,” without energy and with diminished enthusiasm. Her primary care physician diagnosed Carol with having mild depression and prescribed a selective serotonin reuptake inhibitor. He also advised her to try to maintain a normal sleep schedule, get regular exercise, and adhere to a healthful diet. Carol had already been trying to incorporate these measures into her daily life, and while the antidepressant boosted her mood, it didn’t seem to make much of a difference in her daytime sleepiness or in achieving more restful nighttime sleep. Eighteen months ago, Carol’s husband reported that she had started to snore and that her snoring had become heavier and her sleep more restless over time. Based on his account, Carol underwent an overnight sleep study to assess for OSA. She was given an OSA diagnosis and subsequently began treatment with continuous positive airway pressure (CPAP) therapy. Carol’s snoring improved and she felt somewhat more rested upon awakening in the morning, although she continued to wake periodically throughout the night. Although Carol has been adherent with her medication and CPAP regimen, her excessive daytime sleepiness remained largely unabated. Recently, she briefly dozed off while driving her children home from afternoon track practice. Although the incident ended with no one being injured, it frightened Carol into seeking further medical help. POLLING QUESTION
Were Carol’s initial diagnoses of mild depression and OSA inaccurate? a. Yes. The symptoms of her underlying narcolepsy were misattributed to those other causes. b. Yes and no. The OSA was confirmed by the sleep study, but Carol’s depressive symptoms were likely a response to her impaired sleep. c. Not necessarily. Depression and OSA may coexist with narcolepsy.
28 THE CLINICAL ADVISOR • JULY 2017 • www.ClinicalAdvisor.com
Narcolepsy’s rarity puts it low on clinicians’ index of suspicion, although it is the underlying cause of up to 5% of cases of excessive daytime sleepiness. Burden of disease
Estimates vary according to the assessment criteria used, but narcolepsy is believed to affect approximately 1 in 2000 people in the United States.8 Its relative rarity puts it low on clinicians’ index of suspicion, although for up to 5% of individuals who present to a sleep laboratory with excessive daytime sleepiness, narcolepsy is the underlying cause. A narcolepsy diagnosis may be overlooked in favor of one of the multiple medical conditions and psychiatric disorders that are more common and thus more familiar to most clinicians.11 In Carol’s case, her signs and symptoms suggested mild depression and sleep apnea well before narcolepsy was considered. Narcolepsy type 1 is characterized by a set of 5 core symptoms: excessive daytime sleepiness, cataplexy, hypnagogic or hypnopompic hallucinations (vivid hallucinations that occur as a person is falling asleep or awakening, respectively), sleep paralysis, and disturbed nocturnal sleep.12 Relatively few patients will present with all symptoms, necessitating careful assessment to make a definitive diagnosis. In some patients, the disorder evolves over time, with cataplexy emerging many years after an initial presentation of excessive daytime sleepiness. Narcolepsy type 2 can be more challenging to diagnose because the symptoms are nonspecific—especially without the telltale presence of cataplexy that distinguishes narcolepsy type 1 from other sleep disorders. Further, there are no useful biomarkers for type 2.13 Delayed diagnosis means, of course, that appropriate treatment is delayed, leaving patients vulnerable to the negative consequences of untreated narcolepsy. Patients have described their difficulty in maintaining a job or attending school, being able to take care of their households, engaging in social situations, and being able to maintain relationships.14 Narcolepsy is costly on a societal and personal level. It is associated with higher rates of healthcare utilization and expenditures. A study found that people with narcolepsy had doubled rates of hospital admissions, outpatient services, and physician visits compared with counterparts without the disorder. Narcolepsy can reduce functional ability and work productivity,1 so it is associated with higher unemployment rates and, among employed people, lower incomes.15 The risk for work- and driving-related accidents—recall that alarm at her own impaired driving motivated Carol to seek
help—is also increased,16 although this risk is mitigated by effective treatment.17 Psychosocial functioning is also negatively affected by the disorder.1 Patients have identified excessive daytime sleepiness as having the most negative impact on daily life, but the unpredictability and loss of control of cataplexy, as well as hallucinations and sleep paralysis, can be terrifying and life-disrupting.14 Patients have described their difficulties in maintaining a job or succeeding in school, being able to take care of their households, engaging in social situations, and being able to maintain relationships. People with narcolepsy report being stigmatized and labeled as lazy or careless, and colleagues consider them unable to perform adequately at work. All of these experiences undermine patients’ quality of life (QoL). Non-sleep–related comorbidities of narcolepsy include diseases of the digestive system, upper respiratory tract diseases/infections, major depressive disorder, social anxiety disorder, and hypertension, hypercholesterolemia, and other cardiovascular conditions.11 Obesity levels are high among children and adults with narcolepsy.18,19 Mortality rates are 1.5-fold higher among those with narcolepsy compared with unaffected persons.20 Criteria and signs and symptoms
According to diagnostic criteria from the ICSD-3, 2 a patient must experience daily periods of an irrepressible need to sleep or daytime lapses into sleep that have occurred for at least 3 months to be diagnosed with type 1 narcolepsy. In addition, one or both of the following must be present: • Cataplexy, a mean sleep latency of less than 8 minutes, and at least 2 sleep-onset REM periods (SOREMPs) on a multiple sleep latency test (MSLT) performed according to standard techniques; a SOREMP (within 15 minutes of sleep onset) on the preceding nocturnal polysomnogram (PSG) may replace one of the SOREMPs on the MSLT • Cerebrospinal fluid (CSF) hypocretin-1 concentrations, measured by immunoreactivity, of less than 110 pg/mL or less than 33% of the mean values obtained in normal subjects with the same assay ——CSF assays are generally conducted only in research settings and are not typically used in clinical practice
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Symptoms associated with narcolepsy can also be caused by other conditions, such as infections, brain injuries, and other sleep disorders. For type 2 narcolepsy, all of the following criteria must be met: • The patient experiences daily periods of an irrepressible need to sleep or daytime lapses into sleep occurring for 3 or more months • The patient has a mean sleep latency of less than 8 minutes and at least 2 SOREMPs on an MSLT performed according to standard techniques; a SOREMP (within 15 minutes of sleep onset) on the preceding nocturnal PSG may replace one of the SOREMPson the MSLT • Cataplexy is absent • Either the CSF hypocretin-1 concentration has not been measured or the CSF hypocretin-1 concentration, measured by immunoreactivity, is less than 110 pg/mL or less than 33% of the mean values obtained in normal subjects with the same standardized assay In addition, the criteria for a narcolepsy diagnosis specify that the hypersomnolence and/or MSLT findings cannot be better explained by another sleep disorder, medical or neurologic disorder, mental disorder, medication use, or substance use disorder. Aside from excessive daytime sleepiness, which is the prominent symptom associated with narcolepsy and is always present, other related symptoms can also assist with a diagnosis.8,21 Hypnagogic hallucinations—vivid dreams that occur at the onset of sleep—are common in narcolepsy. Less frequently reported are hypnopompic hallucinations that are similarly vivid but occur upon awakening.12 These dreamlike sequences often feel very lifelike, can be frightening, and can sometimes be confused with reality. Sleep paralysis can occur at any time in the sleep cycle, from sleep onset to awakening. It is characterized by the inability to move upon falling asleep or waking up and may last from a few seconds to a few minutes. Patient-reported episodes may be mistaken for anxiety attacks or even sleep apnea. Disrupted nighttime sleep is also experienced by a large number of patients with narcolepsy; they awaken multiple times during the night, experience symptoms of sleep apnea and parasomnias, and rise in the morning feeling unrefreshed.21 Other related symptoms include automatic behaviors, defined as episodes in which the person appears to be carrying out waking behaviors but has no memory of doing so, and very frequent and vivid dreams. Dreams often occur during naps and are usually easy to recall. Out-of-body
experiences, dreams that involve flying, and dreams of seeing oneself asleep are more common in narcolepsy than among the general public.21,22 Diagnostic workup
Symptoms associated with narcolepsy can also be caused by other conditions including infections, brain injuries, autoimmune and thyroid disorders, drug and alcohol use, or other sleep disorders. In addition, certain drugs can cause daytime sleepiness. A physical exam and medical history are essential for proper diagnosis of narcolepsy.23 A family history may also be useful, as familial patterns of narcolepsy have been observed.24 Patients should be asked to keep a sleep diary for the clinician to review. The diary should record nighttime sleep patterns, naps, feelings of sleepiness, etc, so the clinician can evaluate sleep quality and exclude other sleep disorders. Patient-completed assessment tools include the Epworth Sleepiness Scale (ESS), which quantifies daytime sleepiness but is not diagnostic for narcolepsy.25 In contrast, the Swiss Narcolepsy Scale shows high specificity and sensitivity when assessing patients for narcolepsy with cataplexy.26 Several specialized tests, which can be performed in a sleep disorders clinic or sleep lab, usually are required before a definitive diagnosis can be established. The 2 tests considered essential in confirming a diagnosis of narcolepsy are the PSG and the MSLT. The value of the MLST in diagnosis of narcolepsy should be stressed: this test is often underutilized in patients with a SOREMP on a routine PSG who may have few of the hallmark characteristics of narcolepsy (ie, severe sleepiness, disrupted sleep continuity, short sleep-onset latency, and some REM-related phenomena).27 An overnight PSG followed by an MSLT the following day can usually exclude other causes of excessive daytime sleepiness, especially sleep apnea. PSG testing will record normal and abnormal physiologic activity over the course of a night and documents the adequacy of sleep. This includes the frequency, duration, and total amounts of sleep at different stages.28 PSG f indings are generally normal in narcolepsy, although some fragmentation of sleep may show up. A SOREMP may be a highly specific marker for narcolepsy if observed on a nighttime PSG and in the absence of another sleep disorder.29,30 The MSLT remains the most important measure; a positive test is defined as a mean sleep
30 THE CLINICAL ADVISOR • JULY 2017 • www.ClinicalAdvisor.com
Comprehensive narcolepsy treatment includes both non-pharmacologic and pharmacologic approaches to minimize daytime sleepiness. latency of 8 minutes or less and 2 or more SOREMPs.13 In people without narcolepsy, mean sleep latency is normally more than 10 minutes and SOREMPs do not usually take place. During the MSLT, measurements are taken during four or five 20-minute nap opportunities at 2-hour intervals. Back to Carol
Carol kept a 2-week sleep diary at the request of her sleep specialist. For each day, she logged when she went to bed and when she got up, how quickly she fell asleep, how often and how long she was awake at night, and how rested she felt upon arising in the morning. She was also asked to include information about her caffeine, alcohol, and medication consumption—what, how much, and at what time—whether and for how long she exercised or napped, and how alert or sleepy she felt during the day. In addition, the sleep specialist asked Carol to complete the ESS. Designed to estimate a person’s self-reported level of daytime sleepiness, it asks users to rate their propensity to doze or fall asleep on a scale of 0 (would never doze or sleep) to 3 (high chance of dozing or falling asleep) in 8 common situations.25 The range of possible scores runs from 0 to 24. Carol’s total was 16, which is consistent with (although not diagnostic for) narcolepsy. A PSG had previously been performed following her initial visit to a sleep specialist, which had resulted in her diagnosis of sleep apnea. At that time, no SOREMPS had been recorded. This time around, Carol’s PSG on CPAP did show SOREMPs, and her MSLT was indicative of narcolepsy. She was subsequently diagnosed with type 2 narcolepsy, due to the absence of cataplexy. Carol’s CPAP therapy was optimized to ensure that she was being effectively treated for her OSA and that she was adherent to this treatment. While Carol was relieved to finally have an answer to her problem of excessive daytime sleepiness, she was overwhelmed to learn of a diagnosis of 2 sleep disorders. Her physician assured her that it is not unusual to have overlapping sleep disorders or other comorbidities with narcolepsy. Comprehensive narcolepsy treatment includes both nonpharmacologic and pharmacologic approaches. Maintaining regular bedtime and observing good sleep hygiene may help to minimize excessive daytime sleepiness. There is some evidence that a regular bedtime and planned naps of 15 to 30 minutes or longer may be beneficial in controlling daytime sleepiness.31
Practicing good sleep habits in general, such as avoiding alcohol and caffeine late in the day and keeping the bedroom cool, quiet, and dark, may also help in improving sleep quality. Regular exercise and exposure to bright light during the day can improve alertness. Such behavioral strategies generally are not sufficiently effective in addressing narcolepsy symptoms on their own, but they are useful adjuncts to pharmaceutical treatment. The first-line treatment for both type 1 and 2 narcolepsy is sodium oxybate, currently the only medication indicated to treat excessive daytime sleepiness and cataplexy. It also has additional documented effects on all other symptoms of narcolepsy, including disturbed nocturnal sleep, sleep paralysis, and hallucinations.31 Second-line treatments for sleepiness include the stimulants modafinil and armodafinil, and for cataplexy, venlafaxine and atomoxetine. Carol’s primary symptoms are excessive daytime sleepiness and, to a lesser extent, fragmented nocturnal sleep. With no signs of cataplexy, she was diagnosed with narcolepsy type 2. Her physician explained that using sodium oxybate in combination with modafinil yields the most effective treatment of excessive daytime sleepiness, but Carol is reluctant to start 2 medications at once. They agree that she will begin with sodium oxybate and she will return for a follow-up visit in 2 weeks after starting the medication to evaluate her response to treatment. She understands the plan to adjust or titrate dosage to effect, recognizing there is a dose response relationship and the time to initial and maximum response may take weeks to months.32 POLLING QUESTION
What additional lifestyle interventions would you advise for Carol? a. None; I want to evaluate the effect of her medication and prefer not to confound the results with other interventions. b. I would recommend that she cease using her CPAP at night. c. I would suggest that she schedule a daytime nap of at least 30 to 45 minutes. d. I would ask her to try to schedule 2 brief daytime naps of 15 to 20 minutes each.
In addition to prescribing sodium oxybate, Carol’s clinician also outlines the various lifestyle interventions she might consider. Carol also expresses concern over
www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JULY 2017 31
her ability to implement all the recommended strategies and that scheduling 2 naps a day seems like the biggest challenge. Nevertheless, Carol says she will try to find a quiet place to nap during lunch breaks or prep periods. At her follow-up visit, Carol reports feeling much better and more alert and believes she is also sleeping better at night. Her ESS is now 10. She is no longer worried about drowsiness while driving, and she has been able to nap on a cot in the school nurse’s office for 15 to 20 minutes during her lunch break. Carol is in the process of rearranging transportation for her daughters’ after-school activities to allow her to fit in a second brief nap in the late afternoon. Carol feels that this is all still a work in progress, and she is experimenting with different lifestyle modifications to see how they affect her sleep and wakefulness. For now, she wants to stay on the sodium oxybate alone, but she will revisit the option of adding modafinil or armodafinil if she feels she needs it. n
14. Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA). The Voice of the Patient: Narcolepsy. http://www.fda.gov/downloads/ForIndustry/UserFees/ PrescriptionDrugUserFee/UCM402907.pdf. Published June 2014. 15. Jennum P, Knudsen S, Kjellberg J. The economic consequences of narcolepsy. J Clin Sleep Med. 2009;5:240-245. 16. Smolensky MM, Di Milia L, Ohayon MM, Philip P. Sleep disorders, medical conditions, and road accident risk. Accid Anal Prev. 2011;43:533-548. 17. Mets MA, Alford C, Verster JC. Sleep specialists’ opinion on sleep disorders and fitness to drive a car: the necessity of continued education. Ind Health. 2012;50(6):499-508. 18. Okun ML, Lin L, Pelin Z, et al. Clinical aspects of narcolepsy/cataplexy across ethnic groups. Sleep. 2002;25:27-35. 19. Kotagal S, Krahn LE, Slocumb N. A putative link between childhood narcolepsy and obesity. Sleep Med. 2004;5(2):147-150. 20. Ohayon MM, Black J, Lai C, et al. Increased mortality in narcolepsy. Sleep. 2014;37:439-444.
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32 THE CLINICAL ADVISOR • JULY 2017 • www.ClinicalAdvisor.com
POST-TEST Expiration date: April 28, 2018
Credit Designation: Haymarket Medical Education designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credit(s)TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. A statement of credit will be issued only upon receipt of a completed pre-assessment test, polling questions, activity evaluation form, and post-test with a score of 70% or higher. All components must be completed and submitted online at ClinicalAdvisor.com/July17feature. CREDITS: 0.75 | Keeping alert to advances in narcolepsy management
1. Which of the following symptoms must be present to make a diagnosis of narcolepsy? a. Cataplexy b. Hypnagogic hallucinations c. Irrepressible lapses into daytime sleep for ≥3 months d. Irrepressible lapses into daytime sleep for ≥6 months
4. Optimal frontline treatment for excessive daytime sleepiness includes : a. Sodium oxybate, modafinil, and good sleep hygiene b. Sodium oxybate, atomoxetine, and avoiding sleeping during daytime hours c. Modafinil monotherapy, as it should not be combined with other drugs d. Armodafinil, venlafaxine, and good sleep hygiene
2. Which of the following statements is true regarding narcolepsy diagnosis? a. The 4 main symptoms tend to be present in most patients. b. It can take up to 15 years for a patient to get a definitive diagnosis. c. Type 2 narcolepsy is generally easier to diagnose because of the presence of cataplexy. d. Patients rarely complain of disrupted nighttime sleep.
5. Which tests are considered essential to confirming a diagnosis of narcolepsy? a. The ESS and the multiple sleep latency test (MSLT) b. A PSG and an electroencephalogram (EEG) c. A PSG and the MSLT d. A PSG and measurement of hypocretin levels
3. The Epworth Sleepiness Scale (ESS) is : a. Diagnostic for narcolepsy b. Administered at the same time as a polysomnogram (PSG) c. Designed to measure how long it takes a person to fall asleep d. A useful measure for daytime sleepiness TO TAKE THE POST-TEST please go to: ClinicalAdvisor.com/July17feature
www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JULY 2017 33
Advisor Forum These are letters from practitioners around the country who want to share their clinical problems and successes, observations, and pearls with their colleagues. Responding consultants are identified below. We invite you to participate.
YOUR COMMENTS MAKING A CASE FOR DEVELOPMENTAL TRAUMA DISORDER Tremendous article. Well written. Comprehensive. Compassionate [“DTD: the effects of child abuse and neglect,” May 2017, p. 26]. Sadly, the author failed to comment on the latest research in the area of epigenetics, which explains the anatomy and physiology behind the central nervous system changes caused by the abuse. Would love to see that covered in the future.— JOHN CASTLE, RN, PA-C, Big Spring, Texas (225-1) ORTHO DX CASE: IS IT A SUBUNGUAL HEMATOMA OR MELANOMA? I am concerned about the image used in the Ortho Dx case regarding a subungual hematoma [see Ortho Dx, page 13; full case available on ClinicalAdvisor.com]. There are features in the image that suggest a diagnosis of melanoma, Send us your letters with questions and comments to: Advisor Forum, The Clinical Advisor, 275 7th Avenue, 10th Floor, New York, NY 10001.You may contact us by e-mail at firstname.lastname@example.org. If you are writing in response to a published letter, please indicate so by including the number in parentheses at the end of each item. Letters are edited for length and clarity. The Clinical Advisor’s policy is to print the author’s name with the letter. No anonymous contributions will be accepted.
specifically, hyperpigmentation that involves the skin of the distal digit adjacent to the hyperpigmented streak and hyperpigmentation of the proximal nail fold (cuticle). These are not features of hematoma, but they are associated with melanoma. This was a therapeutic and not a diagnostic case presentation—ie, we are told this is a subungual hematoma. But as a dermatologist, if I saw this patient, even with the history provided, I would want to do further examination of the hyperpigmented cutaneous areas by microscopy and likely obtain a biopsy of the nail unit.—BARBARA M. MATHES, MD, FACP, Philadelphia (225-2)
MY MOST MEMORABLE PATIENT A YOUNG GIRL WITH KAWASAKI DISEASE: DIAGNOSING A RARE DISORDER Early in my career, I was making rounds regarding a 3-yearold girl who had been admitted for fever and leukocytosis 2 days earlier. I had not seen her previously. I practice in a small rural town and hospital. When I arrived, her mom was awake, but the girl was still sleeping. I started to go over and examine her with the lights off, so as not to wake her. However, something told me to turn on the lights. When I did, she awoke and I noticed that she had bloodshot eyes and conjunctiva without discharge.
Philip R. Cohen, MD,
is clinical associate professor of dermatology, University of Texas Medical Center, Houston.
Deborah L. Cross, MPH, CRNP, ANP-BC, is associate program
director, Gerontology NP Program, University of Pennsylvania School of Nursing, Philadelphia.
Abimbola Farinde, PhD, PharmD,
is a professor at Columbia Southern University in Orange Beach, Ala.
34 THE CLINICAL ADVISOR • JULY 2017 • www.ClinicalAdvisor.com
Laura A. Foster, CRNP, FNP,
Abby A. Jacobson, MS, PA-C,
practices family medicine with Palmetto Primary Care Physicians in Charleston, S.C.
is an assistant professor at Thomas Jefferson University and a dermatology PA at Family Dermatology of Reading, Pa.
I began to also notice that her face was redder than what it should be, and I asked if it had looked like that all along. After obtaining more history, I found that the fever had actually been going on for more than a week before she came to our office. During the examination, I noted that she had a strawberrylooking tongue and bright red lips. She also had a red, slightly papular rash on the palms of her hands. In addition, she had a cardiac murmur that no one else had noted previously. I knew that all of these symptoms were diagnostic of a rare illness, but I could not remember the name of it. I kept thinking that it had a “motorcycle name,” but I couldn’t remember what it was called! I went to the nurses’ station and pulled out a general pediatrics book and began to scan the index. About halfway through, I saw it—Kawasaki disease. I turned to the pages, and everything I read was consistent with my patient. My biggest concern was her new murmur, and I knew that we needed to get her to a higher-level facility so that treatment could be instituted as soon as possible. I phoned my backup physician and began to explain everything to him. I actually heard him chuckle over the phone at my diagnosis. He said he would be in to see her shortly, and I again heard in his voice doubt in my clinical skills and intuition. Once he arrived and began to examine my patient, his doubt changed to surprise, and he said he agreed 100% with my diagnosis. He had been a pediatrician for more than 15 years at that time, and he said that he had only seen one other case of Kawasaki disease. He was very impressed with my diagnosis and never has questioned or chuckled at my thoughts or calls again. The patient was transferred to a children’s hospital about 70 miles away. The hospital confirmed the diagnosis and immediately
Debra August King, PhD, PA,
is senior physician assistant at New York-Presbyterian Hospital, New York City.
Mary Newberry, CNM, MSN,
provides well-woman gynecologic care as a midwife with Prima Medical Group, Greenbrae, Calif.
began treatment with aspirin and intravenous gamma globulin. An echocardiogram revealed coronary artery dilation. Had the symptoms been missed, it may have been too late to prevent coronary artery abnormalities from worsening and her having permanent cardiac damage. This patient is now 13 years old, and I have seen only one other case in my career. She is doing well, and her mom never fails to introduce me to her family as the one who “saved her life.” I always say, “no, that was God working through me.” I had been well trained, and although I did not and sometimes still do not always remember the names of rarely seen illnesses, I do remember the cues and know where to look to find what I need to know. I will never forget this patient, and what she taught me—to be astute when examining a patient. I always turn the lights on when I go to examine a patient now, because if I had not done so that morning, I may not have noticed the changes in her eyes, lips, or tongue. Also, no matter what another provider may think, go with your intuition and the facts that you have and know. This story has become one of my favorites to tell to new students whom I am precepting. I always tell them that you don’t have to remember it all, but you need to remember enough to know you need to find out the rest.—RENNIE RHODES, APRN-BC, DNP, Barnwell, S.C. (225-3)
CLINICAL PEARLS A TIP FOR REMOVING A RING FROM A SWOLLEN FINGER You can remove a ring on a swollen finger with a window cleaner such as Windex.—QUINTON CARROLL, FNPBC, Johnson City, Tenn. (225-4) n
Claire O’Connell, MPH, PA-C,
an associate professor at the Rutgers University Physician Assistant Program, Piscataway, N.J.
Katherine Pereira, DNP, FNP,
is assistant professor, Duke University School of Nursing, Durham, N.C.
Sherril Sego, FNP-C, DNP,
is an independent consultant in Kansas City, Mo.
www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JULY 2017 35
A quick review of common conditions, using the best global evidence
• injury with necrosis of epidermis and dermis after thermal, chemical, electrical, or radiation exposure Types
BY ALAN DRABKIN, MD
Dr. Drabkin is a senior clinical writer for DynaMed (www.ebscohost. com/ dynamed), a database of comprehensive updated summaries covering more than 3,200 clinical topics, and assistant clinical professor of population medicine at Harvard Medical School.
• first-degree (epidermis only) • second-degree (through epidermis and into dermis) ——superficial ——deep • third-degree (all layers of skin including subcutaneous fat) Who is most affected
• children and elderly patients Possible risk factors
• increased age • drug and/or alcohol abuse • photosensitizer medication use, including: amiodarone; chlorpromazine; hydrochlorothiazide; antibiotics (nalidixic acid, fluoroquinolone, doxycycline, tetracycline, voriconazole); naproxen; piroxicam; retinoids • for children < 5 years old, access to hot liquids without adult supervision
© POSITIVEFOCUS / GETTY IMAGES
Caption in here like so and sometimes extends to two lines like this.
36 THE CLINICAL ADVISOR • JULY 2017 • www.ClinicalAdvisor.com
• most common causes of superficial burns ——sunburn ——minor thermal injury • causes of thermal burns ——scalds ■■ i n children »»70% to 80% of burns »»hot liquid, steam, spill, or immersion »»warm air humidifier ■■ in adults »»hot food, water and steam in patients ≥ 65 years old »»hot bath water ——fire (flame or flash) ■■ about 50% of adult burns ■■ associated with trauma/inhalation injury
——contact with hot surfaces • causes of chemical burns ——acids ——alkalis ——petroleum products ——phosphorous ——airbags ——hair dyes ——fabric detergents • causes of radiation burns ——sunburn ——industrial electromagnetic and particle radiation • electrical burn ——may be high voltage, low voltage, or flash History
• Chief concern (CC) ——pain • History of present illness (HPI) ——assess risk for ■■ concomitant injury ■■ inhalation injury ——if non-accidental injury suspected in a child, check for inconsistencies in histories • Medication history ——ask about use of photosensitizing drugs Physical
• Skin ——determine depth of burn ——first-degree burn ■■ tenderness ■■ dry erythema without blisters ■■ brisk capillary refill with pressure ■■ brisk bleeding with 21-gauge needle pin prick ——second-degree burn ■■ superficial partial-thickness (second-degree) burn »»tenderness »»blanching with pressure »»wet, weeping, erythematous skin »»clear blisters »»usually pink but may be white »»brisk bleeding with 21-gauge needle pin prick ■■ deep partial-thickness burn »»no sensitivity to touch or dull sensation »»white or fixed red coloration »»non-blanching with pressure »»blisters »»delayed bleeding with 21-gauge needle pin prick
——third-degree (full-thickness) burn ■■ no sensitivity to touch ■■ dark brown, tan, or white with leathery feel ■■ may be charred and dry or hard and waxy ■■ no blisters ■■ no blanching with pressure, capillary refill ■■ no bleeding with pin prick ——estimate body surface area (BSA) affected for secondand third-degree burns ——Lund-Browder chart of body surface ■■ most accurate ■■ estimated BSA »»neck ——anterior 1% ——posterior 1% »»trunk ——anterior 13% ——posterior 13% »»upper arm ——each posterior 2% ——each anterior 2% »»lower arm ——each anterior 1.5% ——each posterior 1.5% »»each buttock 2.5% »»genitalia 1% »»foot (each top 1.75%; each bottom 1.75%) »»age-based variable percentages for ——each half of head ——each half of 1 thigh ——each half of lower leg ——Wallace rule of nines ■■ fast estimate of medium to large burns in adults ■■ estimated total BSA in adults »»head 9% »»anterior trunk 18% »»posterior trunk 18% »»each upper extremity 9% »»each lower extremity 18% »»genitalia 1% ——palmar surface measurement ■■ assumes palmar surface of patient’s hand is about 0.8% of total BSA for adults and about 1% of total BSA for children ■■ useful for estimation of »»small burns (< 15% total BSA »»small unburned areas in cases of major burn (> 85% total BSA) ■■ inaccurate for medium-sized burn
www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JULY 2017 37
Stat Consult Making the diagnosis
• clinical diagnosis with history of exposure and findings of injured or necrotic skin • criteria for minor burns ——first-degree burns ——second-degree burns affecting ■■ < 5% of total BSA in patients < 10 years old or > 50 years old ■■ < 10% of total BSA in patients who are aged 10 to 50 years ——third-degree burns < 1% of total BSA ——for second- and third-degree burns ■■ no involvement of face, hands, perineum, genitals, or feet ■■ no crossing of a major joint ■■ not circumferential ——no concomitant injury or severe trauma ——no comorbidity Differential diagnosis
• phytocontact dermatitis ——mustard seed ——buttercup • other mimics: leukemia cutis; toxic epidermal necrolysis; pressure necrosis Testing overview
no consensus and limited clinical evidence for management ■■ suggestions for blister management for partialthickness burns »»leave intact if ——blisters < 6 mm ——larger blisters on palms or soles not restricting movement »»debride if ——blisters > 6 mm ——prevent joint movement or likely to rupture »»keep debrided wound moist with topical dressing ——use occlusive dressing or topical agent ■■ non-silver dressings »»insufficient evidence to support the superiority of any type for superficial and partial-thickness burns »»associated with faster healing times compared to silver sulfadiazine ■■ silver sulfadiazine in cream or dressing associated with higher rates of infections in burns compared to other dressings • pain control as needed, • tetanus booster if > first-degree burn • if non-accidental injury suspected in a child, immediately notify social services • refer to burns specialist or reconstructive surgeon if significant scarring or any contracture ■■
• no additional testing required Complications Treatment overview
• for first-degree (superficial) burns ——moist environments ——topical agents and dressings ——comparative efficacy ■■ studies generally of poor quality ■■ insufficient evidence to determine superiority of any single burn dressing • for treatment of second-degree (partial-thickness) burns ——indications for referral to burns specialist ■■ unlikely to heal within 3 weeks (deep partialthickness or full-thickness ) ■■ partial-thickness burns > 10% of total BSA or > 5% in children < 16 years old ■■ worsening over first 72 hours (increased depth or signs of infection) ■■ not healed within 2 weeks ——consider blister management and debridement
• infection • hypo or hyperpigmentation • respiratory-related hospital admission Prognosis
• usual time to healing ——superficial burn, about 3 to 10 days ——superficial partial-thickness burn, about 2 weeks ——deep partial-thickness burn, ≥ 3 weeks Prevention
• evidence-based prevention strategies ——in infants and children ■■ properly installed and maintained smoke detectors ■■ water heater temperature preset to < 130° F (54.4° C) ■■ clinical counseling to increase smoke detector use ——for sunburn ■■ SPF 40 sunscreen more effective than SPF 12 ■■ topical aloe vera cream likely not effective
38 THE CLINICAL ADVISOR • JULY 2017 • www.ClinicalAdvisor.com
Dermatology Clinic CASE #1
A baby with blisters on the palmar and plantar surfaces JAY PATEL, BS, ARIELLE GRAY, BS, AND CHRISTOPHER RIZK, MD
On his second day of life, a 3-day-old boy who was born with no visible skin problems begins to develop erosions and bullae over the palmar and plantar surfaces. These bullae are localized to areas of friction or trauma (eg, where electrocardiogram leads were placed). The mother’s pregnancy was normal, and the birth was without complications. The infant’s parents are healthy and have no medical problems. No one in the infant’s family has had similar dermatologic findings. What is your diagnosis? Turn to page 40
Rash of the axillae that develops spontaneously SARAH SIMPSON, AND JULIA R. NUNLEY, MD
A 35-year-old woman is referred for evaluation and management of a rash involving both axillae. She reports recurring episodes of the rash beginning in her early 20s. Lesions develop and involute spontaneously. Areas affected included the axillae, neck, and groin. Her outbreaks are more common and worse during the summer and after vigorous exercise. Her father and brother have the same problem. Examination reveals moist, red, crusted, and malodorous plaques with fissures in both axillae. What is your diagnosis? Turn to page 42 www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JULY 2017 39
Dermatology Clinic CASE #1
Epidermolysis bullosa (EB) is a rare genetic disorder defined by blister formation after minor or insignificant trauma. EB encompasses different disorders that all share a genetic mode of transmission, mechanical fragility of the skin, and blister formation. It was first described in 1870 by von Hebra and got its current name in 1886 by Koebner.1 With the advent of transmission electron microscopy in the 20th century, distinct forms of EB were first categorized into three major subtypes in 1962 by Pearson, by the skin layer affected.2 These subtypes include EB simplex (EBS), affecting the epidermis; dominant dystrophic/recessive dystrophic EB (DDEB/RDEB), affecting the uppermost papillary dermis; and junctional EB (JEB), affecting the dermoepidermal junction.2,3 The different forms of EB are caused by mutations in proteins that are localized into the specific skin regions listed above. Examples of such proteins include keratin (EBS), laminin ( JEB), and type 7 collagen (DDEB/RDEB).4 All three of the major subtypes have mutations that include both autosomal recessive and autosomal dominant modes of inheritance.3 Thus, as with any genetic disorder, obtaining an in-depth family history can aid in diagnosis. Because the mutated proteins in EB are localized in different layers of skin, transmission electron microscopy and immunofluorescence antigen staining serve as the gold standard for the histologic diagnosis of inherited EB.3 The National Epidermolysis Bullosa Registry was established in 1986 by the National Institutes of Health to facilitate epidemiologic, clinical, and laboratory characterization of EB subtypes. The final estimates from this registry on prevalence and incidence from 3,271 patients were reported in 2016, finding an incidence of EB from 1986 to 2002 of 19.57 cases per 1 million live births and a prevalence of 11.07 per 1 million live births.5 The most common form of EB was EBS, followed by DDEB.5 Across the different forms of EB, the locations, frequency of skin manifestations, and severity vary widely.3 Some forms of EB are relatively mild and localized with little effect on mortality, whereas more severe types of EB can be lethal at a young age. Although the types of EB have differentiating features, it can be difficult or impossible to differentiate them clinically; thus, it is more important to be able to recognize and
rule out EB rather than to try to diagnose a specific subtype. Clinically, mechanically fragile skin, erosions, and visible blisters characterize all forms of EB.3 Slight lateral or rotatory motion can often elicit blister formation, such as rotating a pencil eraser on uninvolved skin.3 Atrophic scarring after blisters are healed is also common.3 Other cutaneous findings in EB patients include dystrophic or absent nails, milia, and scarring scalp alopecia.3 Further cutaneous findings that can aid in diagnosing EB subtypes include hyperpigmented macules, peeling skin without blistering, herpetiform blisters, migratory erythema, and excessive granulation tissue.3,4
Clinically, mechanically fragile skin, erosions, and visible blisters characterize all forms of epidermolysis bullosa. Many of the mutated proteins in EB are highly expressed in other epithelial areas, such as the eye, oral cavity, and gastrointestinal and genitourinary tracts. Common extracutaneous manifestations include corneal blisters, enamel hypoplasia, oral caries, pyloric atresia, constipation, gastrointestinal reflux disease, chronic renal failure, dilated cardiomyopathy osteoporosis, and severe multifactorial anemia.3,4 These manifestations must be closely monitored. The differential diagnosis for neonates with blisters and erosions also includes infectious diseases such as herpes and bullous impetigo, and staphylococcal infections.3 Because it is an inherited genetic disease, genetic counseling for patients and family members is also recommended. Currently, there are no curative therapies for any form of inherited EB. Management is focused on preventing blister formation from mechanical trauma and preventing secondary infection3,6,7; this includes padding bony surfaces and wearing loose clothing.3 Soaking/bathing in either diluted household bleach (0.5 cups of household bleach in a standard tub) or diluted acetic acid (1 part white vinegar to 20 parts water) will reduce bacterial colonization and subsequent blister infections.3,6,7 Chronic antibiotic use, such as topical mupirocin or oral antibiotics, is not recommended.3 For blisters that have already been formed, nonadhesive dressings and soft silicone dressings that incorporate absorbent foam packing can be applied.3,6,7 Dressings containing silver or iodine are also recommended to reduce infection.3,6,7 Appropriate care is also recommended for extracutaneous
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Our info centers contain comprehensive coverage of a wide range of disease states to better prepare you for the myriad conditions that present in a primary care practice. Visit www.ClinicalAdvisor.com for resources to meet your clinical practice needs.
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Dermatology Clinic manifestations. This includes diligent oral hygiene, proper fluid and dietary fiber intake, and adequate nutritional intake through measurement of height, weight, and body mass index.3 All children with EB should be referred to a pediatric dermatologist for continued management and care. Current experimental therapies for EB include gene replacement therapy, allogeneic fibroblast transplantation, bone-marrow-derived stem cell transplantation, and infusion of recombinant proteins.3,8,9 The patient in our case underwent a skin biopsy for routine histologic examination and electron microscopy, which confirmed that he had RDEB, a severe subtype of EB. The patient was referred to a specialized pediatric dermatologist for management and continued care. Jay Patel, BS, is a medical student at Baylor College of Medicine in Houston; Arielle Gray, BS, is a medical student at Loyola University Chicago Stritch School of Medicine in Maywood, Illinois; and Christopher Rizk, MD, is a dermatology resident at Baylor College of Medicine. References 1. Fine JD, Bauer EA, Gedde-Dahl T. Inherited epidermolysis bullosa: definition and historical overview. In: Fine JD, Bauer EA, McGuire J, Moshell A, eds. Epidermolysis Bullosa: Clinical, Epidemiologic, and Laboratory Advances, and the Findings of the National Epidermolysis Bullosa Registry. Baltimore, MD: Johns Hopkins University Press, 1999:1-19. 2. Pearson RW. Studies on the pathogenesis of epidermolysis bullosa. J Invest Dermatol. 1962;39:551-575. 3. Fine JD, Mellerio JE. Epidermolysis bullosa. In: Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012:501-513. 4. Fine JD, Bruckner-Tuderman L, Eady RA, et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol. 2014;70:1103-1126. 5. Fine JD. Epidemiology of inherited epidermolysis bullosa based on incidence and prevalence estimates from the National Epidermolysis Bullosa Registry. JAMA Dermatol. 2016;152:1231-1238. 6. Salavastru CM, Sprecher E, Panduru M, et al. Recommended strategies for epidermolysis bullosa management in Romania. Maedica (Buchar). 2013;8:200-205. 7. Elluru RG, Contreras JM, Albert DM. Management of manifestations of epidermolysis bullosa. Curr Opin Otolaryngol Head Neck Surg. 2013;21:588-593. 8. Ferrari S, Pellegrini G, Mavilio F, De Luca M. Gene therapy approaches for epidermolysis bullosa. Clin Dermatol. 2005;23:430-436. 9. Cutlar L, Greiser U, Wang W. Gene therapy: pursuing restoration of dermal adhesion in recessive dystrophic epidermolysis bullosa. Exp Dermatol. 2014;23:1-6.
Hailey-Hailey disease (HHD), also referred to as familial benign chronic pemphigus, is a rare genodermatosis characterized by recurrent, scaly, and fissuring plaques of intertriginous areas. HHD was first described in 1939 by the Hailey brothers, William and Hugh, as a recurrent pruritic blistering eruption occurring on the necks of two different sets of brothers. Because the basic histologic changes were similar to pemphigus, they called this newly described condition familial benign chronic pemphigus.1 Eventually, Hailey and Hailey reported an additional 22 cases, in two different families, spanning four generations. To avoid confusion with the autoimmune form of pemphigus, this condition is usually referred to as HHD. Inherited as an autosomal dominant trait, HHD has incomplete penetrance2,3; even affected individuals in the same family have varying degrees of severity. Although the actual prevalence is unknown, HHD is estimated to occur in 1 to 30,000 to 50,000 individuals.2,4 It is likely that many patients with HHD are undiagnosed or misdiagnosed. There appears to be no sex, racial, or ethnic predominance. For most individuals, lesions begin between the second to fourth decades of life and typically follow a relapsing and remissive cycle. Although the specific genetic defect has not been isolated, data suggest that mutations in ATP2 C1, a calcium ion transporter on the Golgi apparatus within the keratinocyte, are responsible.2,5 An intact epidermis depends on calcium-mediated transcellular desmosomal structures to facilitate keratinocytekeratinocyte adhesion. The genetic defects in HHD render the desmosome abnormal, resulting in epidermal fragility. HHD is more common in intertriginous areas such as the neck, inframammary folds, and groin, likely due to repetitive trauma from friction. Outbreaks may be triggered, or be more symptomatic, following sweating related to exercise or excessive heat, or other minor traumas.2,3 Classic lesions are characterized by scaly, eroded, fissured plaques. Lesional characteristics of epidermal maceration and occlusion within the intertriginous areas predispose to secondary infection with bacteria and fungi. Although Staphylococcus aureus is the most common pathogen, both Streptococcus and Candida species are also frequently found.5,6 Because secondary infection slows wound healing and promotes odor, it must be addressed in the management of HHD.
42 THE CLINICAL ADVISOR â€˘ JULY 2017 â€˘ www.ClinicalAdvisor.com
Biopsy can show the classic acanthotic epidermis with suprabasal clefting and intraepidermal vesiculation, often described as a “dilapidated brick wall.” The differential diagnosis of HHD includes disorders such as pemphigus vegetans, Darier disease, intertrigo, and herpes simplex virus infection. Pemphigus vegetans, a chronic, vegetative variant of pemphigus vulgaris, is clinically and histologically comparable with HHD. However, the familial association and pathogenesis of HHD are unique and completely unrelated to autoimmune pemphigus. The presence of immunofluorescent staining of the skin biopsy, or measurement of circulating autoantibodies to desmoglein proteins, readily distinguishes pemphigus from HHD.
Treatments to consider in recalcitrant disease include dermabrasion, CO2 laser therapy, and systemic retinoids. Darier disease is another autosomal dominant genodermatosis due to a calcium transporter defect, unique from that of HHD. Although lesion morphologies of these two conditions have some similarities, there are major clinical characteristics that are distinct. Typically, the onset of Darier disease is earlier than HDD. Whereas flexural involvement is characteristic for HHD, it is uncommon in Darier disease; instead, the head, neck, chest, and back are extensively affected. Moreover, histologic changes can definitively differentiate between the two conditions. Intertrigo is a nondiscriminating term used to describe inflammation of the skin folds; it incorporates an assortment of different conditions that are typically classified as either infectious or noninfectious etiologies. Common infectious causes include fungal infections (mostly Candida species and dermatophytes), bacterial infections (mostly S aureus and Streptococcus species), and, occasionally, herpes simplex virus. Noninfectious causes of intertrigo include inverse psoriasis and seborrheic dermatitis. Microscopic analysis, cultures, and (if necessary) a biopsy assist in making the proper diagnosis and ultimately determine the cause of intertrigo, if present. Various modalities have been used to treat HHD, including topical and systemic medications, phototherapy, and both surgical and laser procedures. The first step in therapy, however, is to reduce lesional inflammation and secondary infection, generally with topical corticosteroids, along with either topical or oral antimicrobial medications. In well-established
lesions, steroid use should not be used as monotherapy, as it may exacerbate secondary infection. However, in a review of treatment management, 86% of patients found topical steroids beneficial and believed that, if applied early, they could potentially prevent an exacerbation.3 If topical therapies are ineffective, injection of botulinum toxin A (BTX-A) may prove beneficial. As a neurotoxin, BTX-A effectively blocks activation of eccrine sweat glands and decreases localized areas of sweating, a known trigger of HHD. Effective long-term remission has been reported with BTX-A.6 Glycopyrrolate, an oral antiadrenergic, may be similarly beneficial if used daily. Treatment options to consider in recalcitrant disease include dermabrasion, CO2 laser therapy, systemic retinoids, methotrexate, afamelanotide, and lesional excision. These options should be performed or prescribed by only those familiar with the disease and the risks and benefits of these therapies. Although HHD generally poses no risk of mortality, it negatively impacts the patient’s quality of life. Daily activities can be altered by lesional pain, and lesional unsightliness and odor can cause embarrassment and social ostracization. Although rare, a squamous cell carcinoma may develop within a chronic lesion, so patients should be examined on a regular basis.6 Fortuitously, HDD decreases in intensity and frequency as patients age.1,3 For this patient, the diagnosis of HHD was confirmed by biopsy. Results of direct immunofluorescence were negative. The patient had complete resolution of her lesions with the use of topical fluocinonide, mupirocin, and nystatin creams. n Sarah Simpson is a medical student and Julia R. Nunley, MD, is a professor of dermatology and program director of dermatology at the Medical College of Virginia Hospitals of Virginia Commonwealth University in Richmond. References 1. Hailey H, Hailey H. Familial benign chronic pemphigus. Arch Dermatol Syphilol. 1939;39:679-685. 2. Engin B, Kutlubay Z, Çelik U, Serdarog˘lu S, Tüzün Y. Hailey-Hailey disease: A fold (intertriginous) dermatosis. Clin Dermatol. 2015;33:452-455. 3. Burge SM. Hailey-Hailey disease: the clinical features, response to treatment, and prognosis. Br J Dermatol. 1992;126:275-282. 4. Engin B, Kutlubay Z, Erkan E, Tüzün Y. Darier disease: A fold (intertriginous) dermatosis. Clin Dermatol. 2015;33:448-451. 5. Cialfi S, Le Pera L, De Blasio C, et al. The loss of ATP2 C1 impairs the DNA damage response and induces altered skin homeostasis: consequences for epidermal biology in Hailey-Hailey disease. Sci Rep. 2016;6:31567. 6. Arora H, Bray FN, Cervantes J, Falto Aizpurua LA. Management of familial benign chronic pemphigus. Clin Cosmet Investig Dermatol. 2016;14:281-290.
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Writers’ Guidelines The Clinical Advisor welcomes submissions from its readers. Writing for us is an opportunity to share your knowledge and experience with your colleagues — and to collect a fee in the bargain! We pay an honorarium for every submission we accept. We’ll be glad to work with you to develop your ideas into compelling articles. As for length, that depends on which kind of article you submit. CLINICAL FEATURES update our readers on the latest information about conditions seen in everyday practice. Running approximately 2,500 to 5,000 words, including the references, features can be written either as regular narratives or as a series of questions and answers. Topics should be selected with the busy primary-care clinician in mind; specialists should review specialty topics from the primary-care point of view. If at all possible, articles should be accompanied by clinical photos. Charts, tables, and algorithms are also encouraged. Please include your title and affiliation. CLINICAL CHALLENGE is our popular department comprising histories of difficult cases. Each case is presented as a step-by-step, chronological account, revealing the author’s thought processes along the way. It is divided into sections in this order: the patient presentation; the patient history; the twists and turns eventually leading to a diagnosis; the treatment and outcome; and a discussion of the lessons learned or of the condition in general. The length should be about 1,500 words, and accompanying images are encouraged. Please include your title and affiliation. DERMATOLOGY CLINIC is a department that presents photos of actual cases and asks readers to identify the condition. Each case opens with one or two color photos and a 75-to-100-word description of the patient presentation, without giving away the diagnosis. This is followed by a 750-to-1,000-word summary that includes a fuller description of the ailment, an explanation of how the correct diagnosis was reached, a general review of the condition along with a differential diagnosis, and a description of the patient’s treatment and outcome. Topics must be approved by the editor prior to submission. Please include your title and affiliation. COMMENTARY is our guest editorial page. It gives you the opportunity to sound off on an issue of importance to your colleagues nationwide. A typical Commentary runs about 600 words in length. Please include your title and affiliation. To discuss your editorial ideas, contact us by phone at 646.638.6078; by e-mail to editor@ClinicalAdvisor.com; or by mail to The Clinical Advisor, 275 7th Avenue, 10th Floor, New York, NY 10001. 44 THE CLINICAL ADVISOR • JULY 2017 • www.ClinicalAdvisor.com
Dermatologic Look-Alikes Rubbery plaques ESTHER STERN, NP
A 24-year-old woman presents for treatment of “severe acne” that is unresponsive to all topical treatments, including topical benzoyl peroxide, tretinoin, clindamycin, and dapsone. She notes involvement mostly on her shoulders and back, with a few lesions on her chest. She reports that the lesions are often itchy and hypersensitive to touch. She denies any prior trauma to the area. A physical examination reveals multiple rubbery, erythematous plaques scattered on the shoulders, upper back, and chest. There is no evidence of comedones, pustules, or cysts.
A 62-year-old woman presents for a full skin examination. Specifically, she is concerned about several pink lesions on her right upper arm that had appeared a few months prior to her appointment. She denies having any tenderness, itching, or bleeding associated with the lesions. Her past medical history is significant for hypertension as well as type II diabetes. A physical examination reveals several 2- to 7-mm, pink, indurated papules and plaques, some with a peripheral scale that is present on the right upper arm.
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Dermatologic Look-Alikes CASE #1
Keloids Keloids are benign dermal fibroproliferative tumors that usually develop in areas of trauma (eg, after injury or surgery). Less commonly, keloids m ay develop a s pa r t of system ic d isea se, in fection, or genetic syndromes. Development of spontaneous
keloids, de novo, is rare.1 Keloids occur more commonly in the African American population than in the white population, with an estimated 2:1 to 19:1 ratio, respectively. 2 Both sexes are affected equally, and age of onset is usually between 10 and 30 years. There is likely a genetic component, as keloids have a familial predilection. Keloids present as rubbery or firm, pink or red papules or plaques. Early lesions typically appear more inflamed and red, whereas older lesions are paler and may appear mildly hyperpigmented. Lesions can be symmetric with regular margins, or they can present as irregular claw-like protrusions. The lesions are often pruritic or tender. The chest, back, shoulders, and earlobes are the most common areas of involvement. Unlike hypertrophic scars, keloids extend beyond the borders of the original wound, do not regress spontaneously, and tend to recur after excision.3 Keloids are limited to dermal invasion, except for the rare case of keloid of the cornea. When injury or surgical involvement precedes the development of keloids, clinical diagnosis is made based on the typical overgrowth of scar tissue beyond the boundary of the original wound. When a diagnosis of spontaneous keloidosis is suspected, a skin biopsy is appropriate to confirm the diagnosis. A malignant tumor that is treated like a keloid can yield disastrous or even fatal results. Single keloids can mimic benign lesions such as dermatofibromas or prurigo nodularis. Malignant mimickers to rule out include amelanotic melanoma, Merkel cell carcinoma, carcinoma en cuirasse,4 and cutaneous lymphoma. Dermatologic diseases that may be associated with keloid formation include acne vulgaris, dissecting cellulitis of the scalp, hidradenitis suppurativa, and acne conglobata. Keloidal scleroderma can appear similar to multiple keloids5;
however, the former diagnosis requires a thorough systemic workup and close observation to detect the onset of systemic sarcoidosis. After conducting a histopathologic examination, the clinician found that the keloids revealed a collection of atypical fibroblasts with excessive deposition of extracellular matrix components, especially collagen, fibronectin, elastin, and proteoglycans. Thick, hyalinized collagen bundles are usually seen in the deep dermal portion of the lesion. For patients with a known history of keloid formation, prevention is crucial. Unnecessary surgical procedures, such as skin piercings, should be avoided. Occlusive dressings and compression therapy can be used on new areas of trauma to minimize the likelihood of keloid formation.
Keloids present as rubbery or firm, pink or red papules or plaques. Early lesions typically appear more inflamed and red. Numerous treatment options exist, although success is variable. Traditional treatment is injections of cortisone, such as triamcinolone, directly into the lesion. Concentrations from 10 to 40 mg/mL are appropriate, depending on lesion thickness and location. Surgical excision alone is not recommended, as the risk of keloid recurrence is high. In the appropriate scenario, surgical treatment may be attempted, in combination with early postoperative cortisone injections, radiation treatment, or pressure dressings. Interferon therapy has not been proved to be effective, and cryotherapy is likely to be equally ineffective, with the significant risk of scarring and pigment alteration.6 One older study found topical tretinoin 0.05% cream to be effective at improving the size, thickness, and itching of the lesions.2 Other treatments with variable efficacies include pulsed dye laser, 5-fluorouracil, and calcium channel blockers.4 For the patient in this case, results of a skin biopsy confirmed the diagnosis of keloids. Treatment options were discussed, and the patient chose to undergo intralesional triamcinolone injections at monthly intervals. After 3Â months of treatment, there was significant flattening of most lesions, and the patient reported a significant improvement of itching.
46 THE CLINICAL ADVISOR â€˘ JULY 2017 â€˘ www.ClinicalAdvisor.com
Sarcoidosis is a multiorgan disease characterized by the presence of noncaseating granulomas. Skin involvement is referred to as cutaneous sarcoidosis and occurs in 25% to 30% of cases of systemic sarcoidosis.4 Skin involvement may occur prior to the development of systemic disease, simultaneously, or even years after systemic disease appeared. Approximately 30% of patients with cutaneous sarcoidosis will progress to multiorgan involvement within 1 year.7 Lung disease and hilar lymphadenopathy is the most frequent component of sarcoidosis. Alternately, the skin may be the only organ involved. Women, as well as people of African-American and Scandinavian descent, are at higher risk for the development of sarcoidosis. The disease tends occur most commonly in the third and fourth decades of life.4 Although the exact etiology of sarcoidosis is unknown, it is believed to involve genetic factors as well as environmental exposures, infectious agents, and antigen-immune responses. Traditionally, mycobacteria have been implicated as a possible etiologic agent; more recently Propionibacterium acnes, herpesvirus, and Epstein-Barr virus have been considered. Some noninfectious exposures that have been considered as triggers include injectable dermal fillers,8 contact allergens, and metals. Cutaneous disease often presents within scars, areas of trauma, or areas where foreign material is deposited. Cutaneous sarcoidosis is classified as specific, referring to cases with biopsy-proven noncaseating granulomas, or nonspecific, which is mainly reactive processes that do not exhibit granulomas. Erythema nodosum is the most common nonspecific finding in sarcoidosis. Cutaneous sarcoidosis is often referred to as the great mimicker because its presentation can vary greatly, and it often resembles many common and rare dermatologic conditions.9 Some of the forms of presentation of specific lesions include papular, plaque, photodistributed, psoriasiform, tumoral, mucosal, atrophic, ulcerative, alopecia, and scar-like.9 The papular type usually presents on the face, specifically around the eyes and on the nasolabial folds, with red-brown, flat-topped papules and plaques. Lupus pernio is a variant, and presents with brown to violaceous, smooth, shiny plaques on the head and neck. These lesions
are often most disfiguring and are most strongly associated with systemic disease. A skin biopsy is necessary to diagnose cutaneous sarcoidosis. Sarcoid lesions are characterized as “naked,” noncaseating granulomas with a sparse lymphocytic infiltrate at the margins of granulomas. The granulomas are generally circumscribed and composed of epithelioid cells, some with small foci of necrosis in the center. The histologic differential diagnosis is broad; therefore, a definitive diagnosis requires further workup. Sarcoid skin lesions often present with the same histologic pattern as necrobiosis lipoidica lesions.10 Granulomatous sarcoidosis may also mimic granulomatous secondary syphilis and granulomatous T-cell lymphoma. In a patient diagnosed with cutaneous sarcoidosis, the first step in the workup to exclude systemic involvement should be a chest radiograph, looking for hilar adenopathy and lung involvement. Ophthalmologic evaluation, measurement of serum angiotensin-converting enzyme (ACE) level, electrocardiograph, and other baseline laboratory testing should be considered.
A skin biopsy is necessary to diagnose cutaneous sarcoidosis. Sarcoid lesions are characterized as “naked” granulomas. Although numerous treatment options exist, there are very few published reputable trials to provide clear guidelines. Many lesions resolve spontaneously; therefore, observation alone may be sufficient. Often, however, patients request treatment to improve cosmetic appearance. In addition, disfiguring and symptomatic lesions should be treated. Haimovic and colleagues9 recommend intralesional and topical corticosteroid treatment as a first-line treatment option for localized and mild disease. The usual dose for topical therapy includes potent topical steroids, such as clobetasol or halobetasol, applied with or without occlusion twice weekly. Triamcinolone, 3 to 10 mg/mL, can be injected intralesionally every 3 to 4 weeks until lesions clear. Systemic corticosteroids are helpful. However, the high dosage necessary makes them unsafe for long-term use; therefore, they should be reserved for rapidly progressing cases. Topical tacrolimus and phototherapy may be beneficial for thinner lesions. More recent literature encourages the use of oral doxycycline or minocycline,11 with a maximum
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Dermatologic Look-Alikes response noted at 3 months. The antimalarial agents, chloroquine and hydroquinone, and infliximab infusions,12 are reserved for more serious cases. One case report involved successful treatment with methotrexate after failure to respond to intralesional and systemic steroids.13 The patient in this case was referred for baseline laboratory testing, serum ACE level measurement, electrocardiographic testing, and ophthalmologic evaluation; results of all tests were within normal limits. After discussing treatment options, the patient chose to observe the lesions and not actively treat them unless the cutaneous signs worsened. n Esther Stern, NP, is a family nurse practitioner at Advanced Dermatology & Skin Surgery, P.C., in Lakewood, N.J. References
“Your depression isn’t caused by anything physical. I suggest you root for another pro sports team.”
1. Sage R, Kwon J. Extensive spontaneous keloidosis: a case report. J Am Acad Dermatol. 2010;62(suppl 1):AB32. 2. Halder RM. The role of retinoids in the management of cutaneous conditions in blacks. J Am Acad Dermatol. 1998;39(2 Pt 3):S98-S103. 3. Berman B, Bieley HC. Keloids. J Am Acad Dermatol. 1995;33:117-123. 4. James WD, Berger TG, Elston DM. Andrews’ Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia, PA: Saunders-Elsevier; 2011. spontaneous keloidal scars. J Am Acad Dermatol. 2012;66:e245-e246. 6. Shaffer JJ, Taylor SC, Cook-Bolden F. Keloidal scars: a review with a critical look at therapeutic options. J Am Acad Dermatol. 2002;46(2 suppl):S63-S97. 7. Quaresma MV, Monteiro de Castro G, Regazzi JC. Clinical exuberance of cutaneous sarcoidosis: case report. J Am Acad Dermatol. 2013;68 (suppl 1):AB45. 8. Santos-Alarcón S, Sanchis-Sánchez C, Benavente-Villegas F-C, MateuPuchades A, Camarasa-Lillo N. Cutaneous sarcoidosis during interferon
“You were right — this makes birding way cooler.”
and ribavirin therapy in a patient with hepatitis C virus infection located at silicone injection sites. J Am Acad Dermatol. 2016;74:AB15. 9. Haimovic A, Sanchez M, Judson MA, Prystowsky S. Sarcoidosis: a comprehensive review and update for the dermatologist: part I. Cutaneous disease. J Am Acad Dermatol. 2012;66:699.e1–699.e18. 10. Nappi F, Laurain D, Jalalat S, Saco M, Fenske N. Cutaneous sarcoid with necrobiosis lipoidica-like histology. J Am Acad Dermatol. 2016;74 (suppl 1):AB97. 11. Steen T, English JC. Oral minocycline in treatment of cutaneous sarcoidosis. JAMA Dermatol. 2013;149:758-760. 12. Ahmed A, Morar N. Infliximab treatment for refractory cutaneous sarcoidosis: experience from a tertiary referral center. J Am Acad Dermatol. 2013;68(suppl 1):AB53. 13. Ringger B, Sluzevich J. Recalcitrant cutaneous sarcoidosis successfully treated with methotrexate: a case report. J Am Acad Dermatol. 2012;66(suppl 1):AB60.
48 THE CLINICAL ADVISOR • JULY 2017 • www.ClinicalAdvisor.com
“What’s the point of school? We can just look all this stuff up on Wikipedia.”
© Top, bottom: Harley Schwadron, 2017; middle: The New Yorker Collection 2017 from cartoonbank.com. All Rights Reserved.
5. Heath CR, David JN, Taylor SC. Nodular scleroderma presenting as multiple
LEGAL ADVISOR CASE
Fired for refusing vaccination
BY ANN W. LATNER, JD
Ms R had worked in a large hospital as a nurse since 2008, and her reviews had been consistently positive. In 2011, the hospital changed its policy and began requiring new employees to get the tetanus, diphtheria, and pertussis vaccine (Tdap). In April 2015, the hospital sent a memo to all its employees, including Ms R, notifying them that it was instituting a new policy requiring all clinical employees to obtain the Tdap vaccine. The hospital’s memo explained that pertussis is a highly contagious infectious disease and noted that the Advisory Committee on Immunization Practices (ACIP) recommends that all adults aged 19 years and older should receive a dose of the immunization. The memo stated “this recommendation is especially important for all healthcare workers who have not been previously vaccinated.” Employees were advised to either get vaccinated at the hospital’s employee health services department or to schedule an appointment with their own provider. Employees were given until May 15 to be vaccinated. Ms R had not had the Tdap immunization, and she did not want to get it. After the May 15
© RUBBERBALL / GETTY IMAGES
A clinician files a lawsuit against her employer after being fired for refusing Tdap immunization.
A clinician declined to receive the Tdap vaccine due to medical concerns, which included various allergies and eosinophilic esophagitis.
deadline had passed, the hospital’s employee health services coordinator notified Ms R that her vaccination was overdue. Ms R responded that she had an appointment with her personal physician on June 2 to discuss the vaccine. Ms R’s physician was Dr S, whom she had been seeing for several years. At the appointment, Ms R expressed to her physician that she had great anxiety about potential adverse effects of the vaccine and that she had not been able to sleep the past week due to her concern about it. She reminded the physician that she had various allergies, as well as eosinophilic esophagitis. In response, the physician wrote a note to the hospital asking that Ms R be “medically exempt from receiving the Tdap immunization for medical concerns.” After receiving the physician’s note, the employee health services coordinator wrote back to the 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 • JULY 2017 49
LEGAL ADVISOR physician and explained that the Tdap vaccine was mandatory for Ms R’s employment, and she specified the scientific evidence for why it was necessary. The coordinator listed the manufacturer’s contraindications for vaccination, which included hypersensitivity (anaphylaxis), encephalopathy, latex sensitivity, Guillain-Barré syndrome and brachial neuritis, syncope, progressive or unstable neurologic disorders, Arthustype hypersensitivity, and altered immunocompetence. The coordinator then asked the physician to identify the medical contraindication prohibiting Ms R from getting the mandatory vaccination and to provide documentation reflecting the reason.
The court concluded that the hospital did not violate the ADA by firing Ms R for not getting immunized. The physician did not answer for a month. When the doctor finally wrote back, there was no mention of any of the manufacturer’s contraindications for the immunization. Instead, the physician wrote, “The patient is medically exempt from receiving the Tdap immunization due to severe anxiety with some side effects she read about with this injection, especially with her history of having many food allergies, environmental allergy, and eosinophilic esophagitis. Patient being terrified, I feel the risk of this Tdap injection outweighs the benefits. The patient understands the risks of not getting this immunization.” The employee health services coordinator then told Ms R that the documentation provided by her physician did not meet the definition of medical contraindication as detailed in the manufacturer’s vaccine literature and thus, the Tdap immunization was required or Ms R would lose her job. Ms R did not get the vaccine, and she was fired at the end of the month. Ms R was furious about losing her job and did not understand why the hospital had not given her a waiver based on her medical issues. She sought counsel from an attorney and filed suit against the hospital in Federal Court alleging that her former employer had violated the Americans with Disabilities Act when it fired her for refusing to get vaccinated. The hospital made a motion to dismiss, and the Federal Court granted the dismissal of the claim.
To state a claim for employment discrimination under the ADA, a plaintiff must demonstrate that he/she is a ‘qualified individual with a disability’ and that he/she has suffered an adverse employment decision as a result of the discrimination. The ADA specifies that discrimination includes an employer that is not making reasonable accommodations to the known physical or mental limitations of an otherwise qualified employee unless the employer can demonstrate that the accommodation would cause undue hardship to the employer’s business. What does this mean in plain English? If a nurse breaks an ankle and cannot walk, her employer might move her to a desk job temporarily. If a nurse has hearing loss, the employer may provide assistive devices to help the nurse understand her patients. In this case, the Court held that the hospital had, in fact, offered Ms R an accommodation by listing the contraindications that would prevent the vaccine from being administered and by asking the physician to specify which one of those limited conditions Ms R had. If the physician had been able to specify any of the eight limitations to the vaccine, Ms R would have been exempt. The Court went on to state that while the hospital was willing to exempt employees who had medical contraindications to the vaccine, it was justifiably unwilling to provide an accommodation for an employee who “simply did not want to take the vaccine.” The ADA does not mandate that an employer accommodate what amounts to a “purely personal preference,” the Court stated. Whether the hospital should “require employees to obtain the vaccine is not a question for the Court to determine,” the judges wrote. However, the Court concluded that the hospital did not violate the ADA by firing Ms R for not getting immunized. Protecting yourself
There are valid reasons why people cannot get vaccinations. In these cases, employers have made accommodations, for example, requiring clinicians to wear masks or transferring a nurse from a department that deals with severely immunocompromised patients. Being properly vaccinated when dealing with ill or vulnerable patients is important, and it is not surprising that a hospital would require such vaccinations. Know what your place of employment requires, and if you have a valid contraindication to a vaccine, let your employer know. n
The Americans with Disabilities Act (ADA) was created to address discrimination against people with disabilities.
Ms Latner, a former criminal defense attorney, is a freelance medical writer in Port Washington, N.Y.
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