Marc Julià

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 adolscence 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.

The Role of Fcγ Receptor Polymorphisms in the Response to Anti–Tumor 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 anti–tumor 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.

Mortality of bullous pemphigoid in the first year after diagnosis: a retrospective study in a Spanish medical centre

Background  Prognosis of patients with bullous pemphigoid (BP) is controversial, with a 1‐year mortality rate ranging from 6% to 48%.

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 1β 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.

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

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.

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.

Genetic and experimental evidence for the involvement of the CD6 lymphocyte receptor in psoriasis

Psoriasis is a chronic inflammatory skin disease with a strong genetic background and is triggered by environmental factors. Available evidence supports CD6, a lymphocyte surface receptor mostly expressed by T cells, as a putative target in autoimmunity. Accordingly, a humanized anti-CD6 antibody has been assayed for the treatment of certain autoimmune disorders, including psoriasis. Here, we present novel evidence in mice and humans for a direct involvement of CD6 in psoriasis pathophysiology. First, an attenuated form of imiquimod-induced psoriasis-like skin inflammation was demonstrated in CD6-deficient mice, as deduced from lower epidermal thickness and local reduced production of pro-inflammatory cytokines, namely, interleukin-17A. Thus, isolated CD4+CD62L+ T cells from CD6-deficient mice displayed decreased in vitro T-helper type 17 polarization. Second, a statistically significant association between CD6 single-nucleotide polymorphisms (rs17824933, rs11230563 and rs12360861) and more severe forms of psoriasis was demonstrated in a cohort of 304 patients at three public hospitals from the metropolitan area of Barcelona. Taken together, these results provide new supportive evidence of the contribution of the CD6 lymphocyte receptor in psoriasis at both experimental and clinical levels.

A case of aggressive bullous pemphigoid associated with the defective functional variant of Fc gamma receptor IIb: Implications for pathogenesis?

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