SOX-10 and S100 Negative Desmoplastic Melanoma: Apropos a Diagnostically Challenging Case.

An 83-year-old man presented with a tumor of the neck, clinically consistent with an epidermal inclusion cyst. Excisional biopsy revealed a deeply infiltrating spindled cell tumor. Immunohistochemical markers for S100, SOX-10, Melan-A, HMB-45, and NK1/C3 were negative. Based on the presence of an area of lentigo maligna and the histologic pattern of the spindle cell component, a diagnosis of desmoplastic melanoma was made despite the absence of immunophenotypic evidence for melanocytic differentiation. To the best of our knowledge, the complete lack of both S100 and SOX-10 makes this tumor an unprecedented case. To avoid ruling out the diagnosis of desmoplastic melanoma prematurely, physicians should be made aware of this possible immunohistochemical profile.

Uncommon presentations of tinea versicolor.

Tinea versicolor (TV) is a common cutaneous fungal infection characterized by superficial scaling and a mild disturbance of skin pigmentation. It typically affects the chest, upper back, and shoulders. However, involvement of more unusual regions of the body such as the face and scalp, arms and legs, intertriginous sites, genitalia, areolae, and palms and soles has been reported. This report details two such cases observed at our institution: a 32-year-old woman with involvement of the popliteal fossa and a 16-year-old boy with involvement of the groin. The clinician must be aware of these variations in location and perform the appropriate diagnostic workup when lesions have the characteristic morphology of TV despite an unusual location. The etiology, pathophysiology, and epidemiology of TV are reviewed and current literature describing other instances of TV in uncommon locations is discussed.

Management of cutaneous human papillomavirus infection: pharmacotherapies.

A plethora of different treatment modalities for treating human papillomavirus (HPV) are available, offering a range of efficacies and balancing several patient needs. Here we discuss pharmacotherapies for HPV, focusing in particular on the mechanism of action and treatment efficacy. Immunomodulators such as Candida antigen, imiquimod and squaric acid stimulate cell-mediated immunity and induce production of antiviral cytokines. Proapoptotic and antiviral treatments such as podophyllin resin, podophyllotoxin gel, bleomycin, 5-fluorouracil, cidofovir and interferon α interfere with the viral reproduction cycle. Other therapies include trichloroacetic acid, acitretin, cantharidin and sinecatechins, some of which operate by epidermal destruction, effects on cellular proliferation and other mechanisms of which are poorly understood. Overall, given the high HPV recurrence rates, adjunctive use of antiviral agents should be considered in treatment, especially when managing severe or complicated presentations.

Prevalence of the metabolic syndrome in children with psoriatic disease.

Adults with psoriasis have a greater risk of developing metabolic syndrome (MetS) and cardiovascular disease (CVD), but few studies have investigated the prevalence of MetS and other risk factors for CVD in children with psoriasis. In an assessor-blinded study, 20 children ages 9-17 years with a current or previously documented history of psoriasis involving 5% or more of their body surface area or psoriatic arthritis were compared with a cohort of age- and sex-matched controls with benign nevi, warts, or acne. MetS, our primary endpoint, was defined by the presence of abnormal values in at least three of the following measures: triglycerides, high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), waist circumference, and blood pressure. Secondary endpoints included high-sensitivity C-reactive protein (hs-CRP), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Thirty percent (6/20) of children with psoriasis met the criteria for MetS, compared with 5% (1/20) of the control group (p < 0.05). Subjects with psoriasis had higher mean FBG (91.1 mg/dL) than the control group (82.9 mg/dL) (p = 0.01). There were no statistically significant differences in the other four components of MetS, BMI, BMI percentile, hs-CRP, TC, or LDL-C. The results of this trial demonstrate that children with psoriasis have higher rates of MetS than age- and sex-matched controls. It may therefore be important to evaluate children with psoriasis for components of MetS to prevent future CVD morbidity and mortality.

Black dot tinea capitis in an immunosuppressed man.

Tinea capitis is a common superficial fungal infection of the scalp primarily afflicting young children. In adults, this infection may have an atypical presentation that may lead to a delay in diagnosis. The authors present a case report of black dot tinea capitis in an immunosuppressed Asian man with psoriasis and provide a review of the literature.

Assessor-blinded study of the metabolic syndrome and surrogate markers of increased cardiovascular risk in children with moderate-to-severe psoriasis compared with age-matched population of children with warts.

Adult patients with psoriasis have an increased prevalence of the metabolic syndrome (MetS) and cardiovascular disease (CVD) risk factors due to elevations of Tumor Necrosis Factor and other inflammatory cytokines.1,2 Recently, higher rates of hyperlipidemia, obesity, hypertension, and diabetes mellitus were seen in patients with juvenile psoriasis.3 Here, we report the interim results of an ongoing study of MetS and CVD risk factors in pediatric psoriasis patients.

Th17 cells: a new therapeutic target in inflammatory dermatoses.

Th17 cells, named for their secretion of interleukin-17 (IL-17), are a new class of T-cells involved in a wide range of cutaneous autoimmune and inflammatory conditions. An overactive Th17 cell response in the skin can produce damaging results. There appears to be a partial role for the Th17 axis in the pathogenesis of a range of dermatological diseases including allergic contact dermatitis, atopic dermatitis, psoriasis, and scleroderma. Immunologists have also discovered a unique association between Th17 cells and cutaneous T-cell lymphoma. The Th17 branch has been linked to a number of additional systemic inflammatory diseases with significant cutaneous pathology such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, and Behcet's disease. Newly developed treatment modalities for neutralizing the Th17 branch of the immune system are proving to be valuable additions to the current therapeutic armamentarium.

Th17 cells: a new paradigm for cutaneous inflammation.

Inflammatory processes of the skin have classically been segregated to either the cell-mediated, T-helper type 1 (Th1) or the humoral (Th2) branch of the immune system. The recent addition of Th17 cells, a novel T-helper cell named for its secretion of interleukin (IL)-17, to current thinking in autoimmunity has resulted in a significant paradigm shift in immunological thinking. Collectively, Th17 cytokines have been found to stimulate cutaneous immune reactions through an activation of a wide range of downstream inflammatory mediators and an induction of immune cell and keratinocyte proliferation as well as angiogenesis. Newly developed treatment modalities for neutralizing the Th17 branch of the immune system are proving to be valuable additions to the current therapeutic armamentarium. Here we describe a new schema for dermatologic T-cell-mediated immunity. We elucidate experiments confirming the presence of Th17 cells, followed by a discussion of their relevance to cutaneous inflammation and psoriasis.

AN-2690, a novel antifungal for the topical treatment of onychomycosis.

Schering-Plough Corp, under license from Anacor Pharmaceuticals Inc, is developing AN-2690, an antifungal agent with activity against Trichophyton species, in a topical solution formulation, for the potential treatment of onychomycosis. Phase II and IIb trials with AN-2690 are underway.

Onychomycosis in the elderly : drug treatment options.

The prevalence of onychomycosis is nearly 20% in patients aged >60 years. In North America, 90% of toenail onychomycosis is caused by dermatophytes (Trichophyton species). Distal-lateral subungual onychomycosis is the most common clinical presentation. The potassium hydroxide test is the most cost-effective diagnostic method. Although nail clipping for histology using periodic acid-Schiff stain is more sensitive, it is much more expensive. Elderly patients have specific risk factors for poor response to therapy for onychomycosis, including frequent nail dystrophy, slow growth of nails and increased prevalence of peripheral vascular disease and diabetes mellitus. Elderly people with diabetes should be treated for onychomycosis to prevent secondary bacterial infections and subsequent complications. Terbinafine is the drug of choice for dermatophyte onychomycosis, with greater mycological cure rates, less serious and fewer drug interactions, and a lower cost than continuous itraconazole therapy. Adjunct debridement may improve the clinical and complete cure rates compared with terbinafine alone. Common adverse effects of terbinafine in the elderly include nausea, sinusitis, arthralgia and hypercholesterolaemia. For onychomycosis caused by Candida or nondermatophyte moulds, there is no superior systemic therapy. In general, topical nail lacquers, amorolfine and ciclopirox are not practical for elderly patients because of the recommended frequency of application, periodic routine debridement of affected nails and long duration of therapy. However, nail lacquers may be a good option as monotherapy for patients with superficial white onychomycosis or in combination with systemic antifungal therapy for patients with predisposing factors for poor response or recurrence.

Academic dermatology manpower: issues of recruitment and retention.

OBJECTIVE: To assess the total number, recruitment rate, departure rate, and growth rate of full-time academic dermatologists in the United States over the last decade. DESIGN: Mail survey. SETTING: Academic dermatology departments in the United States. PARTICIPANTS: Respondents among 113 chairs or chiefs of academic dermatology departments or their designees. MAIN OUTCOME MEASURES: The total number of full-time academic dermatologists including departures and recruitments in 4 selected academic years (1994-1995, 1998-1999, 2001-2002, and 2003-2004). RESULTS: Of the 113 academic dermatology departments, 89 (79%) responded. During the 4 selected academic years, more dermatologists joined academia (n = 255) than departed (n = 200). Those recruited into academia were predominantly graduating fellows (35%), residents (30%), and in private practice (16%). Of those who left academia, their primary roles were clinician-educator (55%), followed by dermatologic surgeon (16%). Most of those who departed went into private practice (65%). From 1994-1995 to 2001-2002, the recruitment rate increased by 36% (from 10.1% to 13.7%), and the departure rate increased by 88% (from 5.8% to 10.9%), resulting in a 35% decrease in growth rate (from 4.3% to 2.8%). CONCLUSIONS: Retention of academic dermatologists is as important as recruitment. Our results confirm that insufficient retention has contributed to a substantial decrease in the growth rate of academic dermatologists. Future efforts to increase academic manpower must focus on retention as well as recruitment, particularly of clinician-educators. Specific strategies for improving retention include identifying or establishing funding sources for teaching/mentoring and clinical research. Recruitment efforts may be improved by focusing on fellows and private practitioners with academic affiliations.

Systemic antifungal agents: an update of established and new therapies.

Terbinafine is the drug of choice for dermatophyte onychomycosis. Adjunct therapies, such as topical agents or surgical approaches, may improve outcomes in patients who have risk factors for incomplete response or recurrence. Despite many studies of newer antifungal agents for tinea capitis, griseofulvin (20 mg/kg/d) remains the gold standard. Terbinafine (> or = 6 mg/kg/d) and fluconazole (8 mg/kg once weekly) have yet to demonstrate comparable efficacy in large-scale RCTs. The current role of second-generation triazoles and echinocandins is for treatment of invasive candidiasis and invasive aspergillosis in patients who are critically ill and immunocompromised. Strengths of the newer triazoles include increased activity against resistant and emerging pathogens, convenience of oral formulations, and in vivo activity against subcutaneous mycoses, in particular eumycotic mycetoma. Their metabolism via cytochrome P450 isoenzymes increases the risk for significant drug interactions, and their established mechanism of action may lead to development of resistant pathogens. The echinocandins inhibit fungal cell wall synthesis, a novel therapeutic target; thus, they are effective against azole-resistant species. Their metabolism is independent of hepatic cytochrome P450 enzymes, minimizing drug interactions. They are available only as i.v. formulations.

Cutaneous fungal infections in the elderly.

Because of impaired host defenses and a favorable environment at specific anatomic sites, there is an increased prevalence of seborrheic dermatitis, mucosal and cutaneous candidiasis, tinea pedis, and onychomycosis in the geriatric population compared with other age groups. Both KOH and fungal culture are timely, convenient, and cost-effective methods of diagnosis. Sensitivity of these tests depends on proper technique for specimen collection and experience. KOH 20% with DMSO and DTM are highly recommended. Treatment should be tailored to the diagnosis and the individual patient. This includes the targeted spectrum of coverage (dermatophyte or yeast); topical versus systemic therapy; review of the patient's medication list for potential drug interactions; and likelihood of compliance. Checking baseline laboratories and routine monitoring of complete blood count and liver function tests in healthy patients, without a history of liver disease or active hepatitis, and without potential drug interactions, seems unwarranted for rare adverse events. Successful management requires adequate patient education, correction of underlying predisposing factors, and prophylactic measures against recurrence.