Toll-like receptor 9 promoter polymorphism as a predictive factor of narrow-band UVB phototherapy response in patients with psoriasis.

BACKGROUND: Prediction of response to ultraviolet B (UVB) phototherapy in psoriatic patients mainly relies on clinical criteria, although some genetic predictors have been identified. Toll-like receptors (TLRs) have been involved in psoriasis pathogenesis through activation of the innate immune system. Their polymorphisms may condition not only the clinical profile of psoriasis but also the response to therapy. METHODS: We analyzed the role of functional single-nucleotide polymorphisms (SNPs) of TLR2, 5, 4, and 9 in clinical response to a standard narrow-band UVB (NBUVB) therapy in 39 patients with moderate to severe psoriasis. RESULTS: We found a significant relationship between TLR9-1486T/C SNP variants and a better response to NBUVB phototherapy. Patients with TC and CC genotype showed a higher improvement of Psoriasis Area and Severity Index (PASI) than patients with TT genotype. Results of multivariate analysis indicate that the differences in PASI improvement at the end of phototherapy attributed to TRL9 SNP genotype were not dependent on the patients' phototype, age, gender, body mass index, basal PASI, or disease evolution. CONCLUSIONS: We describe a functional genetic variant in TLR9 gene that might affect the susceptibility to antipsoriatic treatment. The search of genetic predictive factors may be helpful in therapy selection and optimization of therapeutic regimes in psoriatic patients.

The role of Fcγ receptor polymorphisms in the response to anti­tumor necrosis factor therapy in psoriasis A pharmacogenetic study.

IMPORTANCE: Variability in genes encoding proteins involved in the immunological pathways of biological therapy may account for the differences observed in outcomes of anti­tumor necrosis factor (TNF) treatment of psoriasis. OBJECTIVE: To assess the role of 2 Fcγ receptor (FcγR) polymorphisms in the response to anti-TNF therapy in psoriasis. DESIGN: Retrospective series of patients with psoriasis who received anti-TNF therapy(infliximab, adalimumab, or etanercept) from January 1, 2007, through December 31, 2010. Patients were followed up for 12 weeks. SETTING: Two psoriasis referral centers. PARTICIPANTS: Seventy treatment-naive patients with moderate to severe psoriasis who received anti-TNF agents. INTERVENTION: Patients underwent FcγRIIA-H131R and FcγRIIIA-V158F polymorphism genotyping. MAIN OUTCOMES AND MEASURES: The Psoriasis Area and Severity Index and the body surface area were assessed at baseline and at treatment weeks 6 to 8 and 12. The polymorphism genotypes were correlated with the treatment outcomes. RESULTS: Bivariate analysis showed a nonsignificant association between FcγR low-affinity genotypes and greater improvement in the Psoriasis Area and Severity Index and body surface area at the end of treatment. Conversely, patients harboring high-affinity alleles presented a greater reduction in body surface area at the intermediate point, which remained independent in the multivariate analysis. We also detected an additive effect of both polymorphisms in the multivariate analysis. High-affinity alleles may contribute to a quicker response owing to a more efficient removal of relevant cells expressing TNF. CONCLUSIONS AND RELEVANCE: Preliminary results of this pilot study on the pharmacogenetics of FcγR and biological therapy in psoriasis suggest a role with clinical implications for FcγRIIA-H131R and FcγRIIIA-V158F polymorphisms in the outcome of anti-TNF treatment of psoriasis. These results might help dermatologists in guiding therapeutic decisions, especially in very severe cases where a quick response is needed.

Neonatal erythroderma as a first manifestation of Menkes disease.

Menkes disease is an X-linked recessive lethal multisystemic disorder of copper metabolism. Progressive neurodegeneration, connective tissue disturbances, and peculiar kinky hair are the main manifestations. The low serum copper and ceruloplasmin suggests the diagnosis, which is confirmed by mutation analysis of the ATP7A gene. We report an exceptional presentation of classic Menkes disease with neonatal erythroderma. Genetic study revealed a deletion in exons 8 to 12 in the ATP7A gene. This study could allow pediatricians and pediatric dermatologists to diagnose the disorder as early as possible to establish prompt treatment with parenteral copper-histidine supplementation to improve prognosis.

Multicentric reticulohistiocytosis with elevated cytokine serum levels.

Multicentric reticulohistiocytosis (MRH) is an uncommon non-Langerhans cell histiocytosis of unknown etiology. It is a multisystem disorder characterised by a papulonodular skin eruption, mainly in the extensor surfaces, and destructive polyarthritis. Histologically, either cutaneous lesions or the synovium show a dense dermal infiltrate of histiocytes and multinucleated giant cells with an eosinophilic granular material in the cytoplasm. In the immunohistochemical analysis these cells stain positively with monocyte/macrophage markers (CD68 and CD45), as well as with certain cytokines (tumor necrosis factor-α, interleukin 1ß and interleukin 6). Moreover, recent reports suggest an osteoclastic nature of the infiltrating cells, as they stain strongly with osteoclast tissue lytic markers including tartrate-resistant acid phosphatase and cathepsin K. We report a case of MRH presenting with clinical features of dermatomyositis. Furthermore, the patient showed elevated cytokine serum levels that lowered after therapy.

Prevalence study of nevi in children from Barcelona. Dermoscopy, constitutional and environmental factors.

BACKGROUND: Malignant melanoma is becoming an increasingly important problem in public health as incidence rates have been increasing continuously in Caucasian populations. Childhood and adolescence is an important time of life for the formation and evolution of nevi, and the presence of a higher number of nevi in early life could predict a major risk of developing melanoma. OBJECTIVES: (1) To determine the number of nevi and the dermoscopic pattern predominance in children of our population. (2) To relate it to constitutional and environmental factors. METHODS: Clinical and dermoscopic examinations were performed in 180 children aged 1-15 years. A questionnaire including topics such as past history of sunburns, tanning ability, tendency to sunburn, history of sunlight exposure, use of sunscreens, tendency to freckle and family history of cancer was completed in a face-to-face interview with the parents. On clinical examination, we evaluated hair color, eye color, number of nevi and the presence of nevi in specific locations. All melanocytic lesions were examined dermoscopically, and all patterns were registered as present or absent. We also registered the predominant dermoscopic pattern of the child, defined as being present in more than 40% of all of the individual's nevi. RESULTS: The mean number of moles was 17.5. Male gender, past history of sunburns, facial freckling and family history of breast cancer were independent risk factors for having a higher number of nevi. We found that 61.1% of children had nevi on the face and neck, 17.2% on the buttocks, 11.7% on the scalp, 19.4% had acral nevi and 31.7% had congenital nevi. We found the presence of nevi in some of these locations to be a risk factor for having a higher number of nevi. The most frequent dominant dermoscopic pattern found in our population was the globular type. Interestingly, we found that the homogeneous pattern predominates in the youngest children, the reticular pattern predominates in adolescents and the dominant globular pattern is constant among all ages evaluated. CONCLUSION: This is the first study clinically and dermoscopically characterizing nevi in children from our population, and evaluating constitutional and environmental risk factors.