Publications

BACKGROUND: Dermatologists provide the bulk of psychocutaneous care; however, recent studies suggest that dermatologists believe they are largely underprepared to treat most psychocutaneous conditions.

OBJECTIVE: We sought to identify gaps in psychodermatologic knowledge among practicing dermatologists in two academic institutions.

METHODS: An online survey was sent to 59 dermatologists at the Massachusetts General Hospital (Boston, MA) and Brigham and Women's Hospital (Boston, MA) from July 2010 through October 2011.

RESULTS: The response rate was 40 of 59 (68%). More than 50% of dermatologists were comfortable making diagnoses for 8 of 10 psychocutaneous disorders. In all, 57% were comfortable making a diagnosis of depression. A total of 11% were comfortable starting antidepressants; 3%, antipsychotics; and 66%, medications for neuropathic pain. In all, 72%, 68%, and 21% of dermatologists never prescribe antidepressants, antipsychotics, or medications for neuropathic pain, respectively. Only 38% believed they were successful treating compulsive skin picking; 15%, body dysmorphic disorder; 27%, delusions of parasitosis; and 24%, depression.

LIMITATIONS: Limitations include small sample size, data extraction from an academic setting, self-reporting of outcome measures, and response bias.

CONCLUSION: Although the majority of the physicians surveyed believed they were capable of diagnosing psychocutaneous disease, very few were comfortable starting psychotropics or thought they were successful treating such conditions.

OBJECTIVE: To evaluate the efficacy and safety of a novel mechlorethamine hydrochloride, 0.02%, gel in mycosis fungoides. DESIGN Randomized, controlled, observer-blinded, multicenter trial comparing mechlorethamine, 0.02%, gel with mechlorethamine, 0.02%, compounded ointment. Mechlorethamine was applied once daily for up to 12 months. Tumor response and adverse events were assessed every month between months 1 and 6 and every 2 months between months 7 and 12. Serum drug levels were evaluated in a subset of patients.

SETTING: Academic medical or cancer centers.

PATIENTS: In total, 260 patients with stage IA to IIA mycosis fungoides who had not used topical mechlorethamine within 2 years and were naive to prior use of topical carmustine therapy.

MAIN OUTCOME MEASURES: Response rates of all the patients based on a primary clinical end point (Composite Assessment of Index Lesion Severity) and secondary clinical end points (Modified Severity-Weighted Assessment Tool and time-to-response analyses).

RESULTS: Response rates for mechlorethamine gel vs ointment were 58.5% vs 47.7% by the Composite Assessment of Index Lesion Severity and 46.9% vs 46.2% by the Modified Severity-Weighted Assessment Tool. By the Composite Assessment of Index Lesion Severity, the ratio of gel response rate to ointment response rate was 1.23 (95% CI, 0.97-1.55), which met the prespecified criterion for noninferiority. Time-to-response analyses demonstrated superiority of mechlorethamine gel to ointment (P< .01). No drug-related serious adverse events were seen. Approximately 20.3% of enrolled patients in the gel treatment arm and 17.3% of enrolled patients in the ointment treatment arm withdrew because of drug-related skin irritation. No systemic absorption of the study medication was detected.

CONCLUSION: The use of a novel mechlorethamine, 0.02%, gel in the treatment of patients with mycosis fungoides is effective and safe.

TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00168064.

BACKGROUND: The cutaneous effects of rapidly accelerated fibrosarcoma kinase B (BRAF) inhibitors are not well understood. Squamous cell carcinoma (SCC), keratoacanthoma, and photosensitivity have been described in patients taking BRAF inhibitors.

PATIENTS AND METHODS: To characterize the timing and frequency of skin lesions in patients receiving BRAF inhibitor therapy, we utilized a retrospective case review of 53 patients undergoing treatment with BRAF inhibitors for 4-92 weeks of therapy. Patients were evaluated at baseline, and then followed at 4- to 12-week intervals. Charts were retrospectively reviewed, and the morphology and timing of cutaneous events were recorded.

RESULTS: Thirty-three of the 53 charts met exclusion/inclusion criteria, 15 were treated with vemurafenib, and 18 were treated with GSK 2118436/GSK 1120212. Of 33 patients treated with BRAF inhibitor, 13 developed photosensitivity (39.4%), 10 developed actinic keratoses (30.3%), 10 developed warts (30.3%), and 6 developed SCC (18.2%).

CONCLUSIONS: Multiple cutaneous findings were observed in the 33 patients taking BRAF inhibitors. The previously described association with SCC and photosensitivity was observed in these patients as well. Over half of the observed SCCs were invasive in nature. Photosensitivity continues to be frequent with BRAF inhibitors. Patients taking BRAF inhibitors should have regular full body skin exams. Further studies are necessary to better elucidate the rates of these adverse cutaneous effects.

Psoriasis is a common chronic dermatological disease whose prevalence varies among different populations worldwide. In epidemiological studies, the factors that potentially account for this variability include climate, genetic susceptibility, and environmental antigen exposure. In this issue, Parisi et al. performed a systematic review to explore the global prevalence and incidence of psoriasis.

OBJECTIVE: To develop and pilot test a screening tool to identify cases of nephrogenic systemic fibrosis (NSF) among patients exposed to gadolinium-containing contrast agents.

METHODS: Sixty English-speaking subjects were enrolled: 10 subjects diagnosed as having NSF, 10 subjects with other fibrosing skin diseases, 20 subjects with nonfibrosing skin diseases, and 20 subjects without a skin disease. Subjects answered a questionnaire with 8 closed-ended (yes/no) questions focusing on cutaneous and musculoskeletal manifestations of NSF. The subjects were evaluated by a dermatologist for the presence of clinical signs of NSF. We compared the number of affirmative responses in the NSF group to those in the other groups, and the optimal cutoff that would differentiate groups was calculated. Discrimination, positive and negative predictive values, and internal consistency were also assessed.

RESULTS: Subjects in the NSF group tended to provide more affirmative answers. Using a cutoff of ≥3 affirmative responses yields a sensitivity of 90% and a specificity of 70%, with an area under the curve of 0.85, indicating good discrimination. Sensitivity analysis using modified control group or weighted scores exhibited only slightly better discriminatory power. The positive predictive value of the questionnaire ranged from 0.3% to 39.7%, and its negative predictive values ranged from 97% to >99% with the different proposed prevalence estimates. The instrument had high internal consistency.

CONCLUSION: This pilot study demonstrates that this questionnaire has both high internal consistency and good discriminatory ability. Thus, it may be used to screen populations for NSF.

BACKGROUND: Etanercept is approved for the treatment of chronic moderate to severe plaque psoriasis in adults.

OBJECTIVE: We sought to evaluate the long-term safety of etanercept in a real-world clinical setting. Assessment of etanercept efficacy was a secondary objective.

METHODS: OBSERVE-5 is a 5-year observational safety registry initiated in May 2006 at multiple sites in the United States and Canada. Data collection includes the number of serious adverse events, serious infectious events, and prespecified events of medical interest. Efficacy data include body surface area assessments, physician and patient global assessments of psoriasis, and the Dermatology Life Quality Index. This interim analysis presents data from the first 3 years of the follow-up period.

RESULTS: A total of 2511 patients were enrolled. Of 1890 patients continuing in the registry after 3 years, 113 were inactive for 1 to 2 years, and 115 were inactive for longer than 2 years. The 3-year incidence proportions of serious adverse events and serious infectious events based on Kaplan-Meier methodology were 0.14 and 0.04, respectively. The observed numbers of patients experiencing lymphoma, serious infectious events requiring hospitalization, nonmelanoma skin cancer, and malignancies excluding nonmelanoma skin cancer were not higher than the expected number of cases estimated from a large US administrative health claims database.

LIMITATIONS: The registry lacks a control group, and the study is too small to measure the frequency of rare events.

CONCLUSION: Etanercept demonstrated good tolerability in patients with plaque psoriasis in the clinical setting in this interim analysis. No new or unexpected safety concerns were observed.

BACKGROUND: Validated epidemiological estimates of the prevalence of skin diseases remain an unmet challenge. Most patients in many health care systems do not see dermatologists for skin problems. Assessments based on claims data or self-report are likely to contain substantial misclassification. Population-based in-person dermatological exams have proven impractical because of the number of patients required. However, in the US, there is a large skin cancer screening program where volunteer dermatologists assess almost 100,000 people annually.

OBJECTIVE: To evaluate the utility of this program for the assessment of other diseases.

METHODS: Information concerning prior diagnosis of psoriasis, type of insurance and physician's current assessment of psoriasis was captured as part of the American Academy of Dermatology National Melanoma/Skin Cancer Screening Program. A modified form was provided to a subset of participant sites. Overall and subgroup prevalence of psoriasis was analysed. Crude and adjusted results are presented for comparison to the US population.

RESULTS: Among the 2991 participants, 86% answered the self-report psoriasis question. A previous diagnosis of psoriasis was reported by 5.1% of them. This proportion was greater than the prevalence of physician documented diagnosis of psoriasis (2.8%). Analyses with different assumptions to account for missing values and weighting based on US population estimates yielded prevalence values ranging from 1.2% to 3.4%.

CONCLUSION: This project, although limited by missing data, is consistent with previous findings that psoriasis prevalence is between 2.2% and 4.6% in the US. It demonstrates the potential to evaluate prevalence of other skin conditions through existing national activities.

Psoriasis is a disease state that may present significant cumulative life course impairment (CLCI). The impact of psoriasis on CLCI can be divided into social factors such as stigmatization, psychological factors such as depression, and physical factors such as pruritis, pain and arthritis. With a bimodal age range at first presentation, psoriasis tends to affect those in the second and fifth decades of life. In accordance with the CLCI model, the age of first presentation may substantially affect an individuals' life course, with younger patients more susceptible to CLCI. Social, psychological, and physical factors also provide protection from CLCI: personality, coping mechanisms, social support, and treatment or therapy may act as positive factors and mitigate these damaging effects. As the time course of most clinical trials encompasses a fraction of a patients' life, the true nature of this impact has not been easily captured. Longitudinal CLCI data in psoriasis is limited and continued life course data is needed.