Evaluation of a Pseudoceramide Moisturizer in Patients with Mild-to-Moderate Atopic Dermatitis.

INTRODUCTION: To evaluate the efficacy and safety of a pseudoceramide-containing moisturizer as maintenance therapy in patients with mild-to-moderate atopic dermatitis (AD). METHODS: This was a prospective, single-arm, open-label clinical trial of a twice-daily application of a pseudoceramide-containing moisturizer for 4 weeks as maintenance therapy in 40 patients with stable, mild-to-moderate AD in a tropical climate. Clinical and skin barrier assessment was done at week 0, week 2 and week 4. Any adverse effects were also recorded during the study period. RESULTS: The objective scoring atopic dermatitis decreased from 29.1 [interquartile range (IQR) 21.9-33.7] at week 0 to 22.0 (IQR 21.2-27.8) at week 4 (p < 0.001). There was no detectable difference in transepidermal water loss after 4 weeks; however, stratum corneum (SC) hydration was significantly increased from 39.7 (IQR 35.3-46.4) at week 0 to 49.2 (IQR 41.2-54.6) after 4 weeks (p < 0.001). Both Dermatology Life Quality Index and patient-oriented eczema measure showed significant improvement at week 4 (p < 0.001). The moisturizer was well tolerated with no serious adverse events recorded. CONCLUSION: After 4 weeks of barrier maintenance therapy with a pseudoceramide moisturizer, there was a significant improvement in disease severity, SC hydration and quality of life in both pediatric and adult patients with mild-to-moderate AD.

Successful rechallenge in two patients with BRAF-V600-mutant melanoma who experienced previous progression during treatment with a selective BRAF inhibitor.

The v-raf murine sarcoma viral oncogene homolog B1 (BRAF) gene is mutated at position 600 in about 50% of melanoma. Mutant BRAF activates the downstream effectors of the RAS-RAF-MEK-MAPK pathways and is a driver oncogene in these melanoma cells. Selective BRAF-V600 inhibitors (vemurafenib, dabrafenib) have high antitumor activity against BRAF-V600-mutant melanoma with objective tumor response rates. Resistance, however, develops within less than a year in the majority of patients. Several different mechanisms have been found to mediate acquired resistance, but these do not involve the occurrence of secondary mutations in the BRAF gene. Two patients with BRAF-V600E mutant melanoma who had documented progression during treatment with dabrafenib/GSK1120212 and dabrafenib, respectively, were rechallenged with dabrafenib and vemurafenib after a treatment-free interval of 8 and 4 months during which further progression was documented. Both patients showed a marked clinical response and, in both, objective tumor regression (qualifying as a mixed and a partial response according to RECIST) was documented. These two case observations indicate that resistance to BRAF-selective inhibitors can be reversible following treatment interruption.

Sarcoidosis in a patient with metastatic melanoma sequentially treated with anti-CTLA-4 monoclonal antibody and selective BRAF inhibitor.

A female patient with stage IV-M1c (distant lymph node and breast metastases), chemotherapy-refractory melanoma was treated with the cytotoxic T-lymphocyte antigen 4 (CTLA-4)-inhibitory monoclonal antibody ipilimumab. At first evaluation following induction treatment, there was marked increase in the volume of the lymphadenopathies (including new adenopathies) and strong uptake of (18)Fluorodeoxy-D-glucose ((18)FDG); marked enlargement of the spleen and interstitial lung infiltrates were also observed. Non-necrotising granulomas were discovered on transbronchial mucosal biopsy and cytology on bronchoalveolar lavage established the diagnosis of sarcoidosis. There was a marked clinical and (18)FDG-positron emission tomography/computed tomography ((18)FDG-PET/CT) documented response following six weeks of corticotherapy. At follow-up, progression of subdiaphragmatic melanoma lymph node metastases was documented. Regression of these metastatic sites was observed during treatment with the selective v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor vemurafenib. The patient died due to progressive disease after three months of vemurafenib treatment. Our case report illustrates the need to take into consideration exacerbation of sarcoidosis as a potential confounder in the assessment of tumor response in a melanoma patient treated with the anti-CTLA-4 mononclonal antibody ipilimumab.