MILITARY MEDICINE, 178, 8:904, 2013
Pityriasis Versicolor: Avoiding Pitfalls in Disease Diagnosis Diagnos is and Therapy LT Shayna C. Rivard, MC USN Pityriasi Pity riasiss versi versicolor color is commo common n among young active duty members with overa overactive ctive sweat glands working in humid environments and results in pigmentary changes that can be profound in those with darker skin. This article addresses several issues related to making the correct diagnosis and providing appropriate treatment, as well as the specific challenges military providers may face in these cases. ABSTRACT
INTRODUCTION The following case of pityriasis versicolor exemplifies the importanc impor tancee of ruli ruling ng out simi similar lar derm dermatol atologic ogic cond condition itions, s, selecting an optimal treatment plan, and taking into account special considerations military providers face. A 21-year-ol 21-year-old, d, otherwise healthy, active duty Marine Corps man was seen in cli clinic nic for hyp hypopi opigmen gmented ted lesions lesions on his back and neck, initially appearing in 2009. Despite initiating a trial of overthe-counter topical terbinafine in 2011, his symptoms persisted and became more bothersome by January 2012. The patient was evaluated in the same clinic in July 2012, diagnosed with tinea corporis, and prescribed 250 mg oral terbinafine daily for 30 days by a provider who moved soon after. Three months later, the patient was seen with hypopigmented macules and patc pa tche hess wit with h ve very ry th thin in sc scal alin ing g wh when en sc scra rape ped d (F (Fig ig.. 1) 1).. The pa patie tient nt 1 was diagnosed with tinea versicolor (pityriasis versicolor ) and prescribed 2% ketoconazole shampoo with instructions to use the shampoo once daily for 3 consecutive days and follow up. Upon re-evalua re-evaluatio tion, n, the pat patient ient reported reported no cha change nge,, but on examination the lesions did not show scale, suggesting a cure. The pa patie tient nt wa wass fo foll llowe owed d af after ter a fe few w mon months ths of co conti ntinu nued ed ketoconazole ketoco nazole treatment. treatment. He reporte reported d an overall decrease in pruritic symptoms and was counseled that the hypopigmentation might remain for several months. To make the correct diagnosis of pityriasis versicolor, it is important impor tant to disti distingui nguish sh betwe between en two othe otherr derm dermatol atologic ogic 1 conditions: tinea corporis and pityriasis rosea. These three conditio cond itions ns must be diff differen erentiat tiated ed as they require diff differen erentt treatments. Of note, additional differential diagnoses including vitiligo should be considered 1,2; however, only the three aforementioned diagnoses will be discussed further. Pityriasis Pityria sis versicolor is a disease process that occurs when the yeast, Malassezia (a component of normal skin flora), changes to its hyphal form and causes pigmentary changes. 2Keratinase is also produced and causes loosening of the stratum corneum and subsequent scale formation. 3,4 The disease may present as either eith er hyp hypopig opigmen mentati tation on or hyp hyperpi erpigmen gmentati tation. on. If ten tension sion is
Combat Logistics Regiment 17, Box 555607, Building 140199, Camp Pendleton, CA 92055. doi: 10.7205/MILME 10.7205/MILMED-D-13-00057 D-D-13-00057
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placed on skin lesions, a wrinkling of the skin with visible scale may be evident. Scraping the area with a sharp blade or glass slide may reveal a powder or scale attributable to the effect of keratin keratinase. ase. 2,3,5 This obse observa rvation tion can be esp especia ecially lly usef useful ul in aust austere ere env environ ironment mentss with without out the abil ability ity to perf perform orm more 3 definitivee testing definitiv testing.. Wood’s lamp will also show a white to soft yellow glow.1,2,6 The gold standard for diagnosis is a KOH prep, which reveals a “spaghetti and meatball” pattern because of the presence of hyphae and spores. 1,2,4,6 Of mention, fungal cultures will lead to negative results because the fungus does not contain the lipids required for growth in culture media. 5 The mos mostt co commo mmon n fun fungi gi re respo spons nsibl iblee for di disea sease se in inclu clude de M. symp sympodi odialis alis (with predilection for the back and chest) and M. furf furfur ur (with (with pr predi edile lecti ction on fo forr th thee ba back ck an and d ab abdom domen) en).. 7 A hist history ory of rec recurre urrence ncess dur during ing the summer mon months ths and/ and/or or heavy hea vy swe sweati ating ng is typ typica ical, l, as in incr creas eased ed seb sebac aceo eous us gla gland nd involvement causes the humid environment necessary for the growth of the hyphal form. 2,5,8,9 Those with first-degree relatives tiv es wit with h pit pityr yrias iasis is ver versi sicol color or ma may y als also o be mor moree lik likel ely y to develop the disease themselves. 6 Conversel Conve rsely, y, tine tineaa corp corporis oris (caused most commonly by Trichophyton rubrum ) does not usually show the same pigmentary changes nor similar scaling pattern, but rather an annular pattern with an elevated rim of scale surrounding a normal appearing center. 1 Both KOH prep and fungal cultures will be positive. 1 Hyphae will primarily be present, but not the combination of spores and short hyphae (“spaghetti and meatball”) seen with pityriasis versicolor. 4,9 A history of failed oral antifungals including griseofulvin griseofulvin or terbinafine is ev evide idenc ncee tha thatt tin tinea ea cor corpor poris is is lik likely ely no nott res respo ponsi nsible ble.. 2 In the case of pit pityri yriasi asiss ros rosea, ea, on onee ini initia tiall le lesio sion n wil willl be followed weeks later by the appearance of numerous smaller patches/papules on the back along the skin tension lines in a “Christmas tree” pattern and will result in a negative KOH. 1,2 It is espe especial cially ly impor important tant to rule out pity pityrias riasis is vers versicol icolor or before initiating treatment for either tinea corporis or pityriasis rosea. Otherwise, patients, as in our prior case, may be unnecess unne cessaril arily y pres prescrib cribed ed oral trea treatmen tments ts that are not only ineffective, but could lead to harmful side effects. 4 When pityr pityriasis iasis versicolor versicolor is diagn diagnosed, osed, initial treat treatment ment begins with topicals to include selenium sulfate, 1% clotrimazole cream, 2% ketoconazole shampoo or cream, miconazole
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Pityriasis Versicolor
FIGURE 1.
Active duty male with pityriasis versicolor.
cream, and terbinafine cream. 4,5,10 Of note, 1% terbinafine cream works well, but is relatively ineffective when used orally (with minor exceptions such as one subgroup of M. furfur susceptible to oral therapy during experimentation). 11,12 Patients are commonly instructed to apply shampoos daily to monthly, leaving on the skin for 5 to 10 minutes before washing while creams are routinely used once to twice daily for 1 month. Although not routinely used in the United States, beeswax and honey applied for 3 weeks every 8 hours was also found to be effective, resulting in a 79% cure. 13 Also, adapalene gel, though commonly used for acne treatment and overall more expensive, has been shown to eliminate disease, likely through decreasing sebaceous gland activity, removing abnormal keratin producing cells, and acting as an anti-inflammatory agent. 8 Patients should have a fair trial of topical antimycotic shampoos or creams before oral treatment, although even after initially effective therapy, recurrence is common, approaching an estimated 60%. 1,2,10 If topical treatment is ineffective, commonly used oral medications including ketoconazole, itraconazole, and fluconazole can be tried, although none have been granted U.S. Food and Drug Administration approval for this condition. 4 Most effective treatment regimens include 300 mg oral fluconazole every week for 2 to 4 weeks, 200 mg oral ketoconazole daily for 10 days, and 200 mg oral itraconazole daily for 7 days. 1,4,5,10 Out of these 3 choices, fluconazole is the
safest.4 Of note, single doses of 300 mg oral fluconazole or 400 mg oral ketoconazole followed by a workout to sweat the medication onto the skin have been commonly used in the military2; however, single doses are less efficacious than longer oral treatment options. 1,4 Hypopigmentation may last weeks to months after effective treatment. This hypopigmentation may lead the patient to think treatment was ineffective; however, disappearance of the scale is evidence that the hyphal yeast has likely been eradicated. Thus, sun exposure and time is all that is necessary for correction of pigmentation changes. 4–6,10 Because of this, the patient may not need oral therapy (with its respective side effects) for a presumed failed topical trial. Side effects of oral therapy may include headaches, gastrointestinal complaints, hepatotoxicity, congestive heart failure, and cytochrome P-450 interactions with other drugs. 10 Monitoring hepatic enzymes and stopping statins and other medications that may interact should be considered. 4,10 Although not readily available, in those with persistent hyperpigmentation despite therapy, a 5-day twice daily application of cycloserine (an inhibitor of TAM 1 enzyme thought to be a key cause of hyperpigmentation) may be beneficial. 6 Military health care providers have additional considerations when diagnosing and treating active duty members, to include prescribing medications that are easy to use, have favorable safety profiles, and are cost effective for the military. General Medical Officers and Independent Duty Corpsmen often experience constant turnover in clinics as well as transitions to fulfill deployment needs. Thus, the importance of accurate initial diagnoses and adequate medical documentation for continuity in case of failed therapy cannot be overemphasized. Busy clinics with limited provider coverage, equipment, and testing supplies can make this challenging. Because of similar circumstances faced by military patients, failure to follow up is common. Patient compliance is also a challenge, so treatments that are easiest to use, such as single-dose oral therapies, become quite attractive. 2 Because of the previously mentioned challenges, it is important to use the best means available to make a diagnosis before prescribing any medications and start with the most moderate treatment plan first. During deployment to a field environment, where resources and quad containers are limited, bulky topical therapies are not practical to stock. 2 Therefore, instead of subjecting a patient to the potential side effects of oral treatment, in benign conditions with minimal symptoms such as pityriasis versicolor, it may be best to delay therapy until the patient returns to a location where topical treatments are available. Often times with dermatologic conditions, providers may be tempted to use trial-and-error medicine without a working diagnosis, inadvertently subjecting patients to unnecessary adverse reactions rather than taking the time to make the correct diagnosis and provide optimal treatments. Another consideration is cost to the military. Because of a less confining health care system, military providers have the ability to prescribe what is easiest versus what is most effective for overall health care management. For instance, although all
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have similar efficacy, in the civilian sector a shampoo may cost $3 versus an oral medication costing $77. 10,14 Fortunately, military pharmacies are working hard to lessen overall costs by comparing pharmaceutical prices and purchasing in bulk. Providers can help dampen health care costs by determining specific medication price differences in their respective military pharmacy. In speaking with Camp Pendleton pharmacy staff, prices are as follows: 7 days of 200 mg oral itraconazole at $29.57, 10 days of 200 mg oral ketoconazole at $9.08, and 2 weeks of weekly 300 mg oral fluconazole at $8.33. For creams (based on 1 month supply applied twice daily with an estimated 90 g usage) 1% terbinafine cream is the priciest at $25.44, followed by 1% clotrimazole cream at $17.43, 2% miconazole cream at $12.24, and 2% ketoconazole cream at $10.11. Most cost effective are 2% ketoconazole shampoo (120 mL for 7-day course) at $5.09 and 2.5% selenium sulfide lotion (120 mL) at $3.64. With these prices in mind, starting with shampoos and then if no improvement, moving to either ketoconazole cream or weekly oral fluconazole (with its relatively more favorable side effect profile of the orals) 4 would be preferable. In addition, there are potential savings associated with an accurate diagnosis made before initiation of treatment versus attempting numerous medications as a form of diagnosis by trial and error. This is especially important in benign conditions where oral therapy is not necessary. However, one must consider patient compliance and realize that in some cases providing an oral medication to treat the disease quickly is most appropriate. 2,9 Regardless, because of high recurrences, the patient should be committed to maintenance therapy for prevention to see maximal cost savings. Setting expectations for potentially long-term therapies with each patient are important before embarking on a treatment plan. CONCLUSION Considering all the factors with regards to a transient military population, each provider must carefully weigh the pros and cons of providing therapy that is easy, expensive, and with
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possible side effects versus a more complex, cheap therapy with a low risk profile in the less compliant patients. This is especially important pertaining to dermatologic conditions with several treatment options. ACKNOWLEDGMENTS Special thanks to the corpsmen who diligently attend to patients on a daily basis at Combat Logistics Regimen 17.
REFERENCES 1. Kelly B: Superficial fungal infections. Pediatr Rev 2012; 33(4): e22– 37. 2. McNally B, McGraw T: Picture this . . . tinea versicolor. J Spec Oper Med 2010; 10(1): 107–10. 3. Han A, Calcara D, Stoecker WV, Daly J, Siegel DM, Shell A: Evoked scale sign of tinea versicolor. Arch Dermatol 2009; 145(9): 1078. 4. Nevas J: Tinea versicolor: understanding effective treatment options. Nurse Pract 2012: 37(1): 11–3. 5. Haisley-Royster C: Cutaneous infestations and infections. Adolesc Med State Art Rev 2011; 22(1): 129–45. 6. Mayser P, Rieche I: Rapid reversal of hyperpigmentation in pityriasis versicolor upon short-term topical cycloserine application. Mycoses 2009; 52(6): 541–3. 7. Petry V, Tanhausen F, Weiss L, Milan T, Mezzari A, Weber MB: Identification of Malassezia yeast species isolated from patients with pityriasis versicolor. An Bras Dermatol 2011; 86(4): 803–6. 8. Shi TW, Ren XK: Roles of adapalene in the treatment of pityriasis versicolor. Dermatology 2012; 224(2): 184–8. 9. Wahab MA, Ali ME, Rahman MH, et al: Single dose (400mg) versus 7 day (200mg) daily dose itraconazole in the treatment of tinea versicolor: a randomized clinical trial. Mymensingh Med J 2010; 19(1): 72–6. 10. Hu SW, Bigby M: Pityriasis versicolor: a systematic review of interventions. Arch Dermatol 2010; 146(10): 1132–40. 11. Villars V, Jones TC: Clinical efficacy and tolerability of terbinafine (Lamisil)—a new topical and systemic fungicidal drug for treatment of dermatomycoses. Clin Exp Dermatol 1989; 14(2): 124–7. 12. Leeming JP, Sansom JE, Burton JL: Susceptibility of Malassezia furfur subgroups to terbinafine. Br J Dermatol 1997; 137(5): 764–7. 13. Cherniack EP: Bugs as drugs, Part 1: Insects: the “new” alternative medicine for the 21st century? Altern Med Rev 2010; 15(2): 124–35. 14. Stratman EJ: Failure to use available evidence to guide tinea versicolor treatment: comment on “pityriasis versicolor”. Arch Dermatol 2010; 146(10): 1140.
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