Search

This case report describes a 78-year old woman with a stage IIA BRAF wild-type melanoma on the left leg who experienced a grade 2 vitiligo, a marked skin thickening, and painful swelling of the limbs.

IMPORTANCE: Hailey-Hailey disease (HHD) is a rare, autosomal-dominant acantholytic dermatosis characterized clinically by development of recurrent blisters and erosions in friction areas. Despite progression in our understanding of the molecular genetics of HHD, therapy remains suboptimal and there is no known cure. OBJECTIVE: To determine whether the novel phosphodiesterase-4 inhibitor apremilast is effective in the treatment of HHD. DESIGN, SETTING, AND PARTICIPANTS: Clinical case series of 4 patients with severe, treatment-resistant HHD at an outpatient clinic in the Department of Dermatology of Nice University Hospital, Nice, France. The patients were treated with apremilast; after the initial titration, the dose was 30 mg, twice daily. MAIN OUTCOMES AND MEASURES: Objective clinical response was assessed by the treating dermatologist using the physician global assessment score; recorded adverse effects were monitored throughout the treatment at intervals of 2 to 3 months. RESULTS: Three women and 1 man, with a mean age of 56 years, were treated and followed up for 6 to 10 months. Family history of the disease was noted in 3 (75%) of the cases. The lesions affected the axillary regions (75%), submammary regions (75%), inguinal regions (100%), and back and neck areas (50%). An improvement in the symptoms was reported by all of the patients after a treatment period of 1 month. After 6 months, the improvement of HHD lesions was reported as moderate to almost cleared among the patients. However, 2 patients developed some flares after 6 to 10 months of treatment and stopped apremilast therapy. One of the patients developed uncontrolled diffuse lesions and apremilast was reintroduced, resulting in partial control of her disease. CONCLUSIONS AND RELEVANCE: Apremilast appears to offer a low-risk therapeutic alternative or adjunct in resistant and severe forms of HHD. A prospective controlled trial with long-term follow-up is required to confirm these preliminary observations.

Importance Cetuximab was recently proposed for advanced cutaneous squamous cell carcinomas (cSCC); however, its efficacy is inconsistent and identification of predictive biomarkers for response is necessary. Objective To search for somatic mutations of the HRAS, KRAS, NRAS, BRAF, and EGFR genes in patients with advanced cSCC treated with cetuximab; and to investigate the efficacy and tolerance of cetuximab according to these mutations. Design, Setting, and Participants A multicentric and retrospective study of 31 patients (22 men, 9 women) with histologically confirmed advanced cSCC carried out in 1 department of dermatology and 2 departments of medical oncology in France between January 2008 and December 2014. The median age of participants was 86 years (range, 48-96 years). Interventions Mutational status was determined by pyrosequencing method, allelic discrimination, or Sanger sequencing. Patients were treated by single-agent cetuximab. Main Outcomes and Measures The primary end point was the incidence of somatic mutations of the RAS, BRAF, and EGFR genes and association of cetuximab efficacy with these mutations was investigated by using Fisher test. Secondary end points were the disease control rate (DCR) at week 6, the progression free-survival (PFS), overall survival (OS), and safety profile of cetuximab. Results Thirty-one samples of cSCC from 31 patients were analyzed. Only 2 RAS mutated samples (6.5%) were identified. The first harbored a NRAS point mutation (c.35G>A) in codon 12, resulting in a p.G12D substitution. The second sample presented a HRAS point mutation (c.38G>T) in codon 13, resulting in a p.G13V substitution. No mutation of KRAS, BRAF, and EGFR genes at the investigated loci was found. Two patients with NRAS and HRAS mutations showed a partial and complete response to cetuximab, respectively. The mean duration of follow-up was 19 months. At week 6, the disease control rate was 67.8%. The median OS was 13 months and the median PFS was 9 months. All patients could continue cetuximab treatment without dose reduction. Conclusions and Relevance Even in elderly patients with advanced cSCC, cetuximab was efficacious and well-tolerated. This suggests that cetuximab is certainly warranted in the treatment of advanced cSCC. However, it is also important to identify tumor specific mutations that may determine response to treatment and prognosis for the disease. We have identified here that the incidence of RAS, BRAF, and EGFR mutations is low in cSCC.