Jason E. Frangos

Increased diagnosis of thin superficial spreading melanomas: A 20-year study

BACKGROUND Diagnostic practice by dermatopathologists evaluating pigmented lesions may have evolved over time. OBJECTIVES We sought to investigate diagnostic drift among a group of dermatopathologists asked to re-evaluate cases initially diagnosed 20 years ago. METHODS Twenty nine cases of dysplastic nevi with severe atypia and 11 cases of thin radial growth-phase melanoma from 1988 through 1990 were retrieved from the pathology files of the Massachusetts General Hospital. All dermatopathologists who had rendered an original diagnosis for any of the 40 slides and the current faculty in the Massachusetts General Hospital Dermatopathology Unit were invited to evaluate the slide set in 2008 through 2009. RESULTS The mean number of melanoma diagnoses by the 9 study participants was 18, an increase from the original 11 melanoma diagnoses. A majority agreed with the original diagnosis of melanoma in all 11 cases. In contrast, a majority of current raters diagnosed melanoma in 4 of the 29 cases originally reported as dysplastic nevus with severe atypia. Interrater agreement over time was excellent (kappa 0.88) and fair (kappa 0.47) for cases originally diagnosed as melanoma and severely atypical dysplastic nevus, respectively. LIMITATIONS The unbalanced composition of the slide set, lack of access to clinical or demographic information, access to only one diagnostic slide, and imposed dichotomous categorization of tumors were limitations. CONCLUSIONS A selected cohort of dermatopathologists demonstrated a general trend toward the reclassification of prior nonmalignant diagnoses of severely atypical dysplastic nevi as malignant but did not tend to revise prior diagnoses of cutaneous melanoma as benign.

Acne and oral contraceptives: Update on women's health screening guidelines

Oral contraceptives (OCs) have been shown to be safe and effective for the treatment of acne in most women of childbearing potential, and several have been approved by the Food and Drug Administration for this purpose. However, dermatologists have historically been reluctant to prescribe OCs for acne because of long-standing recommendations requiring a preliminary pelvic examination and Papanicolaou smear before initiation of therapy. In recent guideline shifts, expert panels and major health organizations have reached a consensus that OC provision no longer necessitates the performance of a pelvic examination and Papanicolaou smear. These new guideline revisions could change the way dermatologists treat acne in their healthy female patients of child-bearing age.

Clobetasol propionate emollient formulation foam in the treatment of corticosteroid-responsive dermatoses

Background: Topical corticosteroids are the most common treatment modality for patients with psoriasis and atopic dermatitis; however, the efficacy of topical corticosteroids is often hampered by barriers to patient adherence, such as lack of efficacy, side effects and inconvenience. Recently published studies have investigated the safety and efficacy of a novel emollient foam (EF) formulation of clobetasol propionate (CP), a class I topical corticosteroid in psoriasis and atopic dermatitis. Objectives: To summarize recent literature on CP EF foam, and to evaluate recent Phase II and III clinical trials of CP EF foam in psoriasis and atopic dermatitis. Methods: The MEDLINE (1950 – January 2008) database was searched using the following terms: ‘clobetasol propionate foam’, ‘topical corticosteroids’, ‘topical glucocorticoids’, ‘psoriasis’ and ‘atopic dermatitis’. Results were evaluated for relevance and quality, and additional references were obtained from bibliographies of selected articles. Conclusion: CP EF foam appears to be safe and effective for corticosteroid-responsive dermatoses in adults and children ≥ 12 years of age. As compared to its hydroethanolic foam predecessor, CP EF presents a potential advance for patients who are less likely to tolerate alcohol-based foam. As alcohol-based foams can be irritating and cause stinging in non-hair-bearing areas, this new emollient formulation has the potential to widen the use of CP foam to more patients with atopic dermatitis and to more non-scalp body sites in patients with psoriasis.

Tapering cyclosporine after long-term treatment of atopic dermatitis

Editor Cyclosporine is an effective systemic immunomodulatory therapy used in the treatment of severe refractory atopic dermatitis (AD). Recent studies confirmed its safety during prolonged therapy but found a high relapse rate with treatment discontinuation. To evaluate the effects of long-term cyclosporine treatment and approaches to medication tapering, we retrospectively reviewed the records of 176 AD patients treated at our centre. Since 2005, six patients (two women) aged 21–54 years (mean age ± standard deviation, 45 ± 12.6) with severe AD refractory to topical therapy were treated with oral cyclosporine by the same physician at the Brigham and Women’s Hospital Department of Dermatology outpatient clinics. The patients’ baseline level of cutaneous disease, response to treatment, and adverse effects were obtained from medical records and discussion with the treating clinician. Response of cutaneous disease to cyclosporine therapy was classified as complete (‡75% improvement), partial (25–75% improvement), or no response (£25% improvement). The Partners Institutional Review Board approved this study. Patients initiated therapy at less than 5 mg ⁄ kg ⁄ day (range: 1.0– 4.2); dosing was titrated to a minimal clinically effective dose (Table 1). All patients exhibited a partial or complete response over an average of 11.0 ± 9.5 weeks (range: 2–25 weeks). Treatment continued for an average of 110 ± 65 weeks (range: 39–206 weeks). The most commonly observed adverse effects were hypertension (67%; mean systolic blood pressure increase, 21%), viral infections (67%) and a transient greater-than-30% increase in serum creatinine (33%). For hypertension, pharmacological treatment was given in three patients (patients 1, 3 and 6), and the cyclosporine dose was reduced in patient 2. Serum creatinine increases did not require dose reduction or treatment discontinuation in any patients. One patient was diagnosed with six separate cutaneous squamous cell carcinomas (SCCs) during treatment; surgical excision was curative for all six lesions. Benign generalized lymphadenopathy forced patient 4 to withdraw from therapy. Repeated attempts were made to discontinue treatment in four of the five remaining patients (Table 2). Two patients tapered from cyclosporine and started on mycophenolate mofetil (MMF) had clinical worsening of disease; both restarted cyclosporine treatment. Three patients currently remain on cyclosporine. Two patients successfully discontinued treatment; they were tapered with topical therapy plus either efalizumab or biotin supplements. They have remained in remission for 206 and 18 weeks on topical therapy plus omega 3 and biotin supplements respectively. We found that cyclosporine therapy improved AD but that prolonged treatment was required to maintain the therapeutic effect in the majority of patients. In our limited experience, MMF could not maintain cyclosporine-induced improvements in patients with refractory disease. In two cases, we successfully used efalizumab, now off-market, and biotin supplements to taper and discontinue cyclosporine without disease relapse. Previous reports also have used biotin and omega 3 supplements as successful AD treatment. In contrast to earlier studies of long-term cyclosporine use for AD, we observed cutaneous malignancies in a patient on cyclosporine therapy. SCCs have been reported previously in patients receiving less than 5 mg ⁄ kg ⁄ day of cyclosporine for psoriasis treatment; however, almost all of the tumours developed in patients who received prior treatment with known carcinogens. Our patient developed three invasive SCCs and three SCCs in situ despite a relatively low dose of cyclosporine (<5 mg ⁄ kg ⁄ day), no