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.
Teledermatology was as effective as face-to-face consultation and reduced the PTAT by 90%, resulting in increased patient convenience, operational efficiency and reduced manpower need. Our study supports the safe and cost-effective use of teledermatology for the follow-up of chronic skin conditions in psychiatric patients.
IntroductionTo evaluate the efficacy and safety of a pseudoceramide-containing moisturizer as maintenance therapy in patients with mild-to-moderate atopic dermatitis (AD).MethodsThis 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.ResultsThe 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.ConclusionAfter 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s13555-014-0048-z) contains supplementary material, which is available to authorized users.
Background: ‘Atopic dirty neck' is a poorly understood acquired hyperpigmentation in patients with atopic dermatitis (AD). Objective: To report a single-centre experience with synthesis of this entity's features. Methods: All patients with AD with dirty neck seen over a 5-month period at the National Skin Centre were invited to participate. Results: Out of 544 AD patients examined, 78 (14.3%) had acquired pigmentation of the neck. The majority had moderate-to-severe underlying eczema. Histopathology showed increased epidermal melanin and dermal melanophages, a thickened basement membrane and a dense superficial perivascular infiltrate. Conclusion: Acquired atopic hyperpigmentation has a high prevalence, particularly in adolescent Asian males. Clinico-pathological correlation suggests it results from both frictional melanosis and post-inflammatory hyperpigmentation. The rippled appearance and the onset in adolescence are probably due to accentuation of the juxta-clavicular beaded lines. Optimal control of eczema may improve and potentially prevent the development, which is of importance considering the psychosocial impact of the condition.
Summary Chronic recalcitrant ulcers are associated with severe morbidity, and there are few effective treatment options available. Living skin substitutes are an important form of adjuvant therapy to enhance healing of such wounds. We investigated a novel, simplified, noncultured, autologous, cell grafting procedure, using a six‐well plate technique, to treat chronic recalcitrant wounds. This was a prospective pilot study that involved harvesting an ultrathin split‐skin graft from the gluteal region, which was washed, separated and prepared in six different wells to obtain an autologous mixture of keratinocytes, melanocytes and fibroblasts; this was subsequently applied directly to the wound using a hyaluronic acid (HA) matrix. Eight patients with a total of 14 ulcers were recruited. The primary endpoint assessed was the percentage of re‐epithelialization of the ulcers. Secondary endpoints included quality of life and wound bed indices. At baseline, the median wound surface area was 7.4 cm2 (mean 17.6 ± 23.6 cm2, range 0.5–80.0 cm2) with a median duration of 18 months (mean 70.2 ± 95.9, range 3–216 months). The median wound surface area was reduced by 74.3%, from 7.4–1.9 cm2, at the final visit. Overall, 28.3% of the ulcers achieved complete healing, and 71.3% of the ulcers had reduction in wound size. Post‐graft, there was also improvement in secondary wound bed parameters and all quality of life domains of the Cardiff Wound Impact Schedule. These results suggest that this noncultured autologous six‐well technique might be beneficial for treating recalcitrant ulcers.
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