Pre- vs. post-pubertal onset of vitiligo: multivariate analysis indicates atopic diathesis association in pre-pubertal onset vitiligo.

BACKGROUND: Limited epidemiological data exist that compare clinical features of pre- and post-pubertal nonsegmental vitiligo. OBJECTIVES: To compare factors associated with pre- and post-pubertal onset vitiligo. PATIENTS AND METHODS: A prospective observational study was conducted of patients with vitiligo attending the clinic between 1 January 2006 and 1 July 2011. The Vitiligo European Task Force questionnaire was completed for each patient and thyroid function and antithyroid antibodies were screened. Other forms of vitiligo (segmental, focal, mucosal, not classifiable) were excluded. RESULTS: A total of 679 patients were included; 422 had post-pubertal and 257 pre-pubertal onset of vitiligo. Vitiligo universalis was seen only in post-pubertal onset. In univariate analysis, there was no significant statistical difference for sex, Koebner phenomenon or disease activity between both groups; thyroid disease or presence of thyroid antibodies was more frequent in post-pubertal onset [odds ratio (OR) 0·31, P < 0·003] whereas atopic dermatitis was more often associated with or preceding pre-pubertal onset (OR 2·42, P = 0·006). In multivariate analysis, halo naevi, family history of vitiligo, premature hair greying, atopic dermatitis and previous episode of spontaneous repigmentation were independently associated with pre-pubertal onset. In contrast, stress as onset factor, personal history of thyroid disease and acrofacial type were associated with post-pubertal onset. CONCLUSIONS: Pre-pubertal onset vitiligo is strongly associated with personal and family history of atopy, suggesting that the predisposing immune background in vitiligo is not limited to autoimmunity, as also noted in alopecia areata. This study also suggests reconsidering the epidemiological data on sex ratio in vitiligo.

Halo naevi and leukotrichia are strong predictors of the passage to mixed vitiligo in a subgroup of segmental vitiligo.

BACKGROUND: Until now, segmental vitiligo has been considered as a stable entity and mixed vitiligo, the association of segmental and nonsegmental vitiligo, has been reported rarely. OBJECTIVES: The aim of this study was to search for factors associated with the generalization of vitiligo in patients with segmental vitiligo. PATIENTS AND METHODS: This was a prospective observational study conducted in the vitiligo clinic of the Department of Dermatology of Bordeaux, France. The Vitiligo European Task Force questionnaire was completed for each patient attending the clinic with a confirmed diagnosis of segmental vitiligo after exclusion of other forms of vitiligo (focal, mucosal, not classifiable.) Thyroid function and antithyroid antibodies were screened if not obtained in the previous year. RESULTS: One hundred and twenty-seven patients were recruited: 101 had segmental vitiligo and 26 had segmental vitiligo that evolved into mixed vitiligo; 56 were male and 71 were female. Most patients had onset of segmental vitiligo before the age of 18. When conducting multivariate analysis, we found the following to be independent factors associated with the evolution of patients' disease from segmental vitiligo to mixed vitiligo: initial percentage of body surface involvement of the segment >1% [odds ratio (OR) 15·14, P=0·002], the presence of halo naevi (OR 24·82, P=0·0001) and leukotrichia (OR 25·73, P=0·0009). CONCLUSIONS: Halo naevi association and leukotrichia at first consultation in segmental vitiligo are risk factors for the progression of segmental vitiligo to mixed vitiligo. In addition, this progression of segmental vitiligo to mixed vitiligo carries a stronger link if initial segmental involvement is situated on the trunk.

Development and evaluation of a Global Acne Severity Scale (GEA Scale) suitable for France and Europe.

BACKGROUND AND OBJECTIVE: Many acne grading methods exist; however, there is no agreed-upon standard. Our objective was to create and validate a reproducible acne assessment scale for rating the severity of juvenile facial acne suitable for use in France and Europe. METHODS: The scale we created described the different types of acne lesions in a manner similar to global assessment scales used in clinical trials. The scale was then validated by seven expert dermatologists in the field of acne [the Global Evaluation Acne (GEA) group] first on 34 photographic cases of Caucasian acne patients and second by clinical examination of 22 acne patients. RESULTS: There was good agreement in Investigators' assessments of acne both on photographs and patients (R = 0.8057; P < 0.0001, and R = 0.8437; P = 0.0015). CONCLUSION: The GEA Scale is a global scale validated both on photographs and acne patients which can be used either in clinical research or by the dermatologist in his office.

Evolution of clinical and molecular responses to bexarotene treatment in cutaneous T-cell lymphoma.

BACKGROUND: The mechanisms of action of bexarotene are not well understood. METHODS: A retrospective study on patients with cutaneous T-cell lymphoma (CTCL) treated with bexarotene was performed to see if bexarotene could act on the dominant T-cell clones. Thirty-five patients were included. Twenty-three were treated with bexarotene for more than 3 months (300 mg/m(2)). In 7 patients, phototherapy was given with bexarotene. RESULTS: Dominant T-cell clones were observed in 11 patients in peripheral blood and in 19 patients in skin. Our results demonstrate no significant evolution of T-cell clones either in skin or peripheral blood. Furthermore, the detection of T-cell clones in peripheral blood before starting bexarotene was significantly associated with the progression of the disease. UV therapy given with bexarotene significantly improved therapeutic response without any correlation with T-cell clones. CONCLUSION: This is the first study on the evolution of the T-cell clone in blood and skin in CTCL patients during bexarotene therapy.

Cytomegalovirus: its potential role in the development of cutaneous T-cell lymphoma.

To investigate the potential role of CMV in cutaneous T-cell lymphoma (CTCL), we studied cytomegalovirus (CMV) seroprevalence in parapsoriasis (PP), mycosis fungoides (MF) and Sézary syndrome (SS) compared with healthy control patients. In cases where CMV seropositivity was observed, CMV PCR analyses were performed on skin biopsies. CMV seroprevalence was 37.1% in the control group, 50.68% in the PP + MF + SS group (P = 0.08), 56.2% in the MF + SS group (P = 0.07), 40% in the PP group (P = 0.9), 66.67% in the MF group (P = 0.009), 42.86% in the SS group (P = 0.9). CMV PCR in initial skin biopsies were all negative. However, PCR CMV was positive in two SS skin biopsies realized at an advanced stage. Our results show that latent CMV infection may play a role in the susceptibility of MF in predisposed subjects by inducing T-cell proliferation and resistance to apoptosis. Concerning SS, an immunosuppressive state may be responsible for CMV reactivation that in turn may interfere with evolution of the disease.

Anti-inflammatory effects of lithium gluconate on keratinocytes: a possible explanation for efficiency in seborrhoeic dermatitis.

Topical lithium (Li) gluconate has a beneficial effect on seborrhoeic dermatitis (SD), unlike oral lithium (Li) used in psychiatry. SD is an inflammatory dermatitis associated, in most of cases, with colonization by lipophilic yeasts of the genus Malassezia. However, the exact mechanism of action of Li gluconate in SD still remains unknown. The aim of our study was to investigate the effect of topical Li on cytokine secretion and innate immunity. For this purpose, we investigated first the modulatory effect of Li on two pro-inflammatory and two anti-inflammatory cytokine secretion and second, the modulatory effect of Li on Toll-like receptor (TLR) 2 and 4 expression by unstimulated and stimulated keratinocytes. Two different skin models were used: keratinocytes in monolayer and skin explants. In some of them, inflammation was induced with LPS (1 mug/ml) or zymosan (2 mg/ml). Then the skin models were incubated with Li gluconate (Labcatal*, Montrouge, France) at three different concentrations (1.6, 3, 5 mM) determined according to viability MTT test. Expression of TNFalpha, IL6, IL10, TGFbeta1, TLR2 and TLR4 was detected by immunohistochemistry (IHC). Cytokines were quantified by ELISA methods. Our results showed that the effect of Li on keratinocytes is dose-dependent. At low concentration (1.6 mM), Li enhanced TNFalpha secretion, whereas, at higher concentration (5 mM), Li significantly enhanced IL10 expression and secretion. However, there was no significant modulation of Li on IL6 and TGFbeta1 secretion. Moreover, Li at 5 mM significantly decreased TLR2 and TLR4 expressions by differentiated keratinocytes. As Li concentration during topical treatment is probably closer to 5 mM than to 1 mM, the therapeutic effect of Li gluconate in DS may be explained by two anti-inflammatory actions: an increased expression and secretion of IL10 and a decreased expression of TLR2 and TLR4 by keratinocytes. The diminution of TLR2 expression by Li may not allow MF to trigger inflammation response in lesional skin.

[Autoimmunity induced by low doses of interferon in melanoma stage I]. / Auto-immunité induite par l'interféron à faible dose dans le mélanome stade I.

INTRODUCTION: The principal aim of this work was to determine the prevalence of antinuclear antibodies and antinucleosomes antibodies during a treatment by interferon alpha with low dose for 18 months among patients with a melanoma stage I. The secondary objective consisted to seek the existence or not of a correlation with the clinical relapse, to determine the prevalence of appearance of clinical signs of autoimmune diseases and dysthyroidie. PATIENT AND METHODS: It was an exploratory study. The patients included in the study had a melanoma stage I (French classification), whose excision was realized for 6 weeks maximum, with a Breslow index equal or higher than 1,5 mm. The statistical model of logistic regression was used. RESULTS: Eighty-forth patients were included (38 women and 46 men) old from 21 to 75 years. The prevalence of antinuclear antibodies was 39%. None of the following variables: age, sex, phototype, localisation of melanoma in exposed photo zone, index of Breslow or Clark, were significantly associated with the presence of antinuclear antibodies. As the percentage of patients with anti-nucleosomes was low (5%), no statistical study was carried out. The prevalence of clinical and/or biological dysthyroidie was 37%. 60% of the patients presented at a moment in the evolution antinuclear antibodies or a dysthyroidie. The prevalence of relapses and death different was not correlated significantly with antinuclear antibodies and/or a dysthyroidie. DISCUSSION: Many studies report the appearance of antinuclear antibodies, generally without clinical lesions during the treatment by interferon alpha for cancers (tumours carcinoids, hemopathies) and viral chronic hepatitis. Our study is, to our knowledge, the first evaluating the induction of an autoimmunity during the adjuvant treatment by interferon alpha of melanoma stage I. The induction of autoantibody during the treatment by interferon alpha could constitute a marker of effectiveness of the treatment with improvement of the survival of these patients. In our study, however auto immunity markers do not appear as factors of severity of evolution of the melanoma or predictive factors.

Two giant orf lesions in a heart/lung transplant patient.

Orf is an infectious ulcerative stomatitis of sheep and goats. The responsible pathogen, parapoxvirus, may be transmitted to humans. Orf lesions are often atypical in immunocompromised individuals. The present report describes two very large exophytic lesions in a 31-year-old transplant patient receiving oral tacrolimus, mycophenolate mofetil and prednisone. Early surgical excision was successful, with no relapse after 14 months.

Heredity: a prognostic factor for acne.

BACKGROUND: The role of heredity in acne severity and therapeutic response remains unclear. OBJECTIVE: A prospective epidemiologic study was performed to compare clinical and evolutive features of acne and response to treatment in 151 patients with acne with (A+) or without (A-) family history of acne. METHODS: A+ and A- patients were compared on clinical and therapeutic criteria. A+ patients were then distributed into subgroups (M+, F+, M+F+) following the origin of family history (father: F, mother: M). RESULTS: The clinical profile was similar in the A+ and A- populations. Acne occurred earlier and more often before puberty in the A+ population, in which oral treatments and relapse after isotretinoin were more frequent. Retentional lesions (number and extent) were more important in the M+ and M+F+ populations. CONCLUSION: This study confirms the importance of heredity as a prognostic factor for acne. Family history of acne is associated with earlier occurrence of acne, increased number of retentional lesions and therapeutic difficulties.

Neuromuscular ventilatory insufficiency: effect of home mechanical ventilator use v oxygen therapy on pneumonia and hospitalization rates.

The purpose of this study was to determine rates of pneumonia and hospitalization for patients receiving oxygen therapy, patients having indwelling tracheostomy tubes, and those using tracheostomy or noninvasive methods of home mechanical ventilation. Six hundred eighty-four users of assisted ventilation for 13,751 patient-years or 19.8 years per patient were surveyed by mail and twice by telephone over a span of four years. Pneumonia and hospitalization rates were significantly higher for ventilator users with chronic obstructive pulmonary disease or with neuromuscular ventilatory insufficiency and gastrostomy tubes than for ventilator users with neuromuscular ventilatory insufficiency without gastrostomy tubes. Of the latter group, more than 90% of the pneumonias and hospitalizations were triggered by otherwise benign intercurrent upper respiratory tract infections. Oxygen therapy was associated with a significantly (P < 0.001) higher rate of pneumonias and hospitalizations than that seen for untreated patients after initial episodes of respiratory distress or during the use of either tracheostomy intermittent positive pressure ventilation or noninvasive ventilatory assistance methods. The lowest pneumonia and hospitalization rates (P < 0.001) were by full-time, noninvasive intermittent positive pressure ventilation users. We conclude that oxygen therapy is not an effective substitute for assisted ventilation for patients with primarily ventilatory insufficiency. Noninvasive ventilatory aids can be used effectively for up to full-time ventilatory support for patients with neuromuscular conditions whose bulbar muscle function is adequate to avert the need for gastrostomy tube placement.