Vitamin D deficiency is associated with greater tumor size and poorer outcome in Merkel cell carcinoma patients.

BACKGROUND: Merkel cell polyomavirus has been recognized to be associated with Merkel cell carcinoma (MCC), but the evolution of this cancer probably depends on various factors. Vitamin D deficiency, defined by serum 25-hydroxyvitamin D levels <50 nmol/L, seems to influence cancer behavior and progression, but has never been assessed in MCC patients. OBJECTIVES: First, to evaluate whether vitamin D deficiency was associated with tumor characteristics and prognosis in a cohort of MCC patients. Second, to assess expression of the vitamin D receptor (VDR) in MCC tumors. METHODS: Clinical findings, Merkel cell polyomavirus markers and vitamin D status were assessed in a cohort of French MCC patients. The study was limited to the 89 patients for whom the serum sample had been collected within 3 years after the diagnosis of MCC. Correlation between vitamin D deficiency and MCC characteristics and outcome were determined in regression analyses. VDR expression in MCC tumours was assessed by immunohistochemistry. RESULTS: Vitamin D deficiency was noted in 65.1% of the patients and was independently associated with greater tumor size at diagnosis (P = 0.006) and with metastasis recurrence (HR, 2.89; 95% CI, 1.03 to 8.13; P = 0.043), but not with death from MCC, although there was a trend (HR, 5.28; 95% CI, 0.75 to 36.96; P = 0.093). VDR was found to be strongly expressed in all 28 MCC tumor specimens investigated. CONCLUSION: The association between vitamin D deficiency and MCC characteristics and outcome, together with detection of the VDR in MCC cells, suggest that vitamin D could influence the biology of MCC.

[Alopecia areata during anti-TNF alpha therapy: Nine cases]. / Pelade au cours d'un traitement par anti-TNF alpha : neuf cas.

BACKGROUND: In recent years, a growing number of biological agents have been introduced for the treatment of various diseases, and their principal adverse events are known. We present nine cases of alopecia areata (AA) developed in patients treated with TNF-α blocking agents. PATIENTS AND METHODS: Nine cases are described: five men and four women of mean age 39.2 years (range: 29-54 years). Two patients had a past history of alopecia areata. The anti-TNF given was adalimumab (Humira(®)) in eight cases and etanercept (Enbrel(®)) in one case. The time lapse to development of AA following introduction of the anti-TNF alpha agent was between six weeks and eight months (mean: 4.2 months). There were five cases of patchy AA and four of AA universalis. Anti-TNF alpha treatment was stopped in all patients. Complete regrowth was seen in five patients. Two patients showed no improvement. In two patients, partial hair regrowth (<50%) was seen after systemic corticosteroid therapy and methotrexate. DISCUSSION: Our nine cases of alopecia areata developed in patients treated with TNF-α blockers constitute the largest series reported to our knowledge. 17 cases of AA during anti-TNF-alpha therapy have previously been described in the literature. AA may be a side effect of anti-TNF-alpha drugs. In our patients, no conclusive triggers could be associated with the development of AA, except a context of stress in four patients. Complete regrowth in three patients after discontinuation of the anti-TNF-alpha (without other therapy) is an additional argument in favour of the implication of biotherapies. However, a random coincidence of AA with anti-TNF-alpha cannot be completely ruled out. The role of anti-TNF-alpha therapy in the pathogenesis of AA is poorly understood. Activation of self-reactive T cells by anti-TNF-alpha could lead to the development of AA.

[Efficacy and risks of topical 5-fluorouracil in Darier's disease]. / Traitement de la maladie de Darier par 5-fluorouracile topique: quelle efficacité, quels risques?

BACKGROUND: Darier's disease, an autosomal dominant disorder, is often resistant to therapy. There have been few encouraging reports in recent years of treatment using topical 5-fluorouracil (5FU) in this indication. We describe three cases of Darier's disease treated with Efudix: though it initially proved very effective, after several months this treatment became inefficacious. PATIENTS AND METHODS: Case 1: a 16-year-old girl with Darier's disease refractory to conventional treatments. Treatment with topical 5FU was initiated. After 3 weeks, her cutaneous lesions had practically disappeared, leaving only pigmented scars. At 6 months, worsening of the disease was controlled by increasing 5FU. At 11 months, the disease worsened and 5FU, which proved inefficient, was stopped. Case 2: a 59-year-old woman presenting treatment-resistant Darier's disease was given 5FU. After 1 week, improvement began and was evident at 4 months. However, after 13 months of treatment, the disease progressed, and increased 5FU proved completely ineffective. Case 3: a 29-year-old woman was hospitalized for inflammatory Darier's disease. Topical 5FU was applied to the left half of the body and a short course of oral corticosteroids was prescribed. After 10 days of treatment, there was a clear improvement. After 6 weeks, the patient showed episodes of healthy skin. However after 3 months, the patient stopped taking her treatment due to inefficacy. DISCUSSION: While topical 5FU seems to be effective initially in treating Darier's disease, this efficacy subsides over time. Although no adverse effects were noted in our patients, use of 5FU can result in serious adverse reactions. Because of the loss of efficacy of this treatment following initial success, coupled with its poorly evaluated safety, caution must be exercised when prescribing it, particularly in patients with dihydropyriminidine dehydrogenase (DPD) deficiency or for use on damaged skin.

[Xanthelasma and juvenile xanthogranuloma in a 7-year-old boy]. / Xanthélasmas et xanthogranulomes juvéniles chez un garçon de sept ans.

BACKGROUND: Palpebrum xanthelasma is the most common type of xanthoma seen in adults but it is extremely rare in children. We report an original case of bilateral xanthelasma palpebrarum associated with juvenile xanthogranuloma (JXG) in a 7-year-old child. Only two cases of xanthelasma in children have been described to date. The association of xanthelasma and JXG has never been described. PATIENTS AND METHODS: A 7-year-old boy presented xanthelasmas on both eyelids. At the same time, pinkish JXG papules appeared on the child's trunk. The boy had been diagnosed at the age of 10 months with myelogenous leukaemia, which was in remission. He also had a familial history of hypercholesterolaemia. The skin lesions were removed and microscopic examination confirmed the diagnosis of xanthelasmas and JXG. DISCUSSION: This patient's presentation is unusual in several respects: the presence of xanthelasma in a child, appearance of JXG at an advanced age, and the association of these two diseases in a child with a past history of leukaemia. The occurrence of these skin lesions did not appear to be linked to the history of malignant blood disease in this patient.