[Oesophageal bullous detachment with massive haemorrhage revealing acquired haemophilia A in autoimmune bullous dermatosis]. / Décollement bulleux de l'œsophage responsable d'une hémorragie massive révélant une hémophilie A acquise au cours d'une dermatose bulleuse auto-immune.

INTRODUCTION: Acquired haemophilia A (AHA) is a rare coagulopathy caused by the development of factor VIII antibodies. Various aetiologies have been established but a number of cases have been reported in association with autoimmune bullous dermatosis (AIBD). We report a new case of this type of association revealed by oesophageal involvement of AIBD. PATIENTS AND METHODS: A male patient was treated for AIBD. Due to the inefficacy of local steroids and the emergence of oral and laryngeal blisters, the patient was treated with systemic steroids. He developed a gastrointestinal haemorrhage complicated by haemorrhagic shock. Endoscopy revealed complete peeling of the oesophagus. Laboratory tests showed lengthening of ACT, reduced factor VIII levels, and the presence of anti-factor VIII antibodies. A diagnosis was made of AHA associated with AIBD. Prolongation of systemic corticosteroids and initiation of rituximab resulted in normalisation of haemostasis. DISCUSSION: AIBD and AHA frequently develop concomitantly, as was the case with our patient. The haemorrhagic complications were severe. The aim of AHA treatment is to stop acute bleeding and eliminate antibodies, and for this reason rituximab was chosen. CONCLUSION: Oesophageal bullous detachment is rare in AIBD but, as seen here, it may be responsible for massive haemorrhage, especially in the event of associated AHA. This feature underscores the need for evaluation of haemostasis in the early stages and during relapses for all patients with AIBD.

Human orf complicated by epidermolysis bullosa acquisita.

Orf is a DNA parapoxvirus transmitted to humans by contact with infected goats and sheep. Many complications have been reported after orf infection, including erythema multiforme. A few cases of autoimmune bullous dermatosis complicating orf disease have been reported to date. They are usually characterized by tense blister eruptions with or without mucosal involvement; linear deposition of C3, IgG and/or IgA along the basement membrane; and negativity of indirect immunofluorescence analysis and enzyme-linked immunosorbent assay (ELISA) (performed in four of 11 reported cases). These analyses have targeted antigens of bullous pemphigoid, mucous membrane pemphigoid or epidermolysis bullosa acquisita, except one case of mucosal pemphigoid with antilaminin-332 antibodies. We describe the case of a patient who presented with an ulceration on his finger 10 days after direct contact with a lamb during Eid al-Adha. Four weeks later he developed a severe tense blistering eruption associated with mucous membrane erosions. Indirect immunofluorescence analysis using the patient's serum revealed circulating antibasement membrane IgG that bound the dermal side of salt-split skin. ELISA was positive for recombinant immunodominant NC1 domain of type VII collagen. We finally diagnosed epidermolysis bullosa acquisita complicating probable human orf infection.

[Sarcoid-like granulomatosis associated with eosinophilic fasciitis]. / Fasciite de Shulman associée à un infiltrat granulomateux sarcoïdosique.

BACKGROUND: Eosinophilic fasciitis (EF) is a rare condition characterized by swelling of the extremities, sclerodermatous evolution and frequent hypereosinophilia. Hematological disorders, including aplastic anemia, solid tumors and autoimmune diseases, may be associated with EF. EF is usually not associated with granulomatous diseases. CASE REPORT: Herein we describe the case of an 80-year-old man with symmetrical swelling and sclerosis of the legs, typical of EF, associated with skin and lymph node granulomas. Oral prednisone treatment resulted in complete clinical remission. DISCUSSION: Association of EF and granulomatous disease is uncommon. Our case highlights the possible association of EF with sarcoidosis-like reactions.

Predictors of long-term drug survival for infliximab in psoriasis.

BACKGROUND: Limited information is available regarding factors associated with long-term drug survival of infliximab for psoriasis in real life. OBJECTIVES: The main aim pf this study was to identify predictors of long-term (>12 months) drug survival among patients treated with infliximab for psoriasis in a real-world clinical setting. METHODS: Retrospectively collected data, relating to disease, patient characteristics and treatment procedures, in a multicentre observational cohort of patients with moderate-to-severe plaque psoriasis treated with infliximab at eight university hospitals, 120 of whom maintained a response to infliximab for more than 12 months, were compared with prospectively collected data in the same centres from 54 patients who experienced secondary loss of response within a 12-month period. RESULTS: Mean duration of drug survival of infliximab in patients with long-term drug survival was 41.12 months ± 20.64 SD vs. 8.5 months ± 2.43 SD in patients with a secondary loss of response. Multivariate analysis identified greater disease severity at treatment onset (PASI score >12) (OR = 5.18, 95% CI: 1.60-16.77, P = 0.006), high levels of initial psoriasis clearance (PASI-90 reduction or equivalent) (OR = 18.50, 95% CI: 4.56-74.45, P = 0.0001) and combination with methotrexate (OR = 13.15, 95% CI: 1.46-118.79, P = 0.022) as independent predictors of long-term drug survival and sustained efficacy of infliximab. CONCLUSION: Positive predictors for long-term drug survival of infliximab in real life were identified. Their impact on treatment management should be addressed in further prospective trials.

[Teledermatology in a prison setting: A retrospective study of 500 expert opinions]. / Télédermatologie en milieu carcéral : étude rétrospective de 500 télé-expertises.

BACKGROUND: Fresnes prison is one of the largest penitentiary centres in France (around 2300 inmates). Since dermatological consultations are not possible on site, a teledermatology agreement was signed in 2008 between the Kremlin-Bicêtre hospital, used by the Fresnes consultation unit and outpatient care (UCSA) and the Saint-Louis hospital for remote dermatological expertise. We report the results of the last 3 years of teledermatology activity in this prison. PATIENTS AND METHODS: All teledermatology consultations from September 2010 to September 2013 were analysed. The teledermatological consultations requested by UCSA doctors included photos of lesions, patient history and disease history. Applications were sent by e-mail via the secure AP-HP (Paris Hospitals) intranet. In all instances, patients had consented to being photographed and these photos were transmitted for remote expertise. The answers were given in a maximum period of 5 working days. The following data were studied: sex, age, phototype, medical history, diagnoses, assessments requested and treatment received. RESULTS: Five hundred teledermatological consultations were analysed. Among the patients, 94.1% were male with a mean age of 34 years. Phototypes IV and VI constituted the majority, with respective percentages of 30.6% and 28.6%. The dermatoses diagnosed were for the most part mild and varied: cutaneous infections (20.2%), monitoring of nevi (11.5%), genital warts (10%), eczema (8.5%), acne (8.1%) and psoriasis (4.2%). Two cases (basal cell carcinoma and lupus) required ablation. Systemic treatments such as methotrexate and isotretinoin were initiated and monitored remotely. DISCUSSION: The most frequently observed diagnoses were not significantly different from those observed in the general population with comparable characteristics. The high phototype of patients requires extensive experience of the dermatology of black skin. Teledermatology is also important in monitoring nevi among prisoners. The low incidence of scabies is due to its systematic detection in prisoners on initial entry into prison. Furthermore, teledermatology is actively used in the teaching of prison doctors requiring training, and whose requests are becoming more and more relevant with time. CONCLUSION: This study provides greater knowledge of dermatological diseases in prison and shows teledermatology to be a tool suited to the specific constraints of this universe, while providing inmates with medical care as close as possible to that of the general population, and it thus helps ensure that their fundamental human rights are upheld.

Clinical characteristics of molluscum contagiosum in children in a private dermatology practice in the greater Paris area, France: a prospective study in 661 patients.

BACKGROUND: Series regarding the clinical characteristics of molluscum contagiosum (MC) are retrospective and concern small defined populations seen in a hospital setting. METHODS: We prospectively studied patients under 15 years of age with MC seen in 25 private dermatology practices in the greater Paris area during 1 year. RESULTS: Six hundred fifty patients were included. The mean age was 6 years. Of the patients, 30.5% had had MC in the past, 53% had 5-20 MC, 43% had a history of atopic dermatitis (AD), 5% were using topical steroids, 25.5% had coexistent AD, 13% had giant MC (>5 mm), 21% had inflammatory MC, and 19% had MC surrounded by eczema. Bathing with siblings was associated with a higher number of MC. A history of AD was associated with the presence of MC surrounded by eczema. The use of topical steroids was associated with a higher risk of relapse. There was no relation between environmental factors (MC in surrounding people, going to the swimming pool, sports practice) and the number of lesions or between environmental factors and the number of recurrences. CONCLUSION: Atypical lesions are frequent. Bathing with siblings is associated with a higher number of MC. Topical steroid use increases the risk of relapses. AD prevalence is higher than in the general population.

Rapid changes in plasticity across generations within an expanding cedar forest.

We investigated the inter-individual variation of phenotypic plasticity and its evolution across three generations within an expanding forest. Plasticity was assessed in situ from dendrochronological data as the response of radial growth to summer rainfall. A linear mixed model was used to account for spatial effects (environment and stand structure), temporal factors (stand dynamics) and the variation with age. Beyond these effects, our results reveal a significant inter-individual variance of growth and plasticity within each generation. We also show that the mean values and variances of growth and plasticity changed significantly across generations, with different patterns for both traits. The possible environmental and genetic drivers of these changes are discussed. Contrasting with the trade-off between stress tolerance and plasticity generally observed among populations, we detected a positive covariance at the individual level, which does not support the cost of plasticity hypothesis in this case.

Climate-growth relationships in a Larix decidua Mill. network in the French Alps.

A better understanding of the respective role of key climatic variables on tree growth is crucial for an accurate assessment of how ongoing global changes may affect both dynamics and distribution of forest tree species in the future. The aim of this study was (i) to explore growth patterns of European larch (Larix decidua Mill.) through a network of tree-ring chronologies developed for the French Alps and (ii) to identify the main climatic drivers explaining radial growth. Climate-growth relationships were coupled with a hierarchical analysis. This relationship revealed significant variability expressed spatially by the existence of five clusters, initially discriminated by an elevational contrast related to (i) a negative correlation between summer temperatures and larch growth at lower elevations and (ii) a stronger response of low-elevation larch stands to winter precipitation. In the high-elevation clusters, tree growth depends on previous autumn and current summer temperatures and water supply in July. The differentiation, that portrays a strong geographical coherence, is mainly related to the latitudinal gradient; (i) the northwestern stands are mostly sensitive to high temperatures in summer; (ii) the growth of the southernmost clusters is equally driven by temperatures during autumn, winter, and summers; (iii) the populations of a cluster located in a transitional zone of the inner French Alps, subject to both Mediterranean and Continental influences, exhibit negative correlations to late winter and early spring precipitation. This significant spatial heterogeneity of climate-tree ring relationships in L. decidua clearly underlines the high plasticity of the species to adapt its growth to local climate conditions.

[Epidemiology and management of onychomycosis in private dermatological practice in France]. / Epidémiologie et prise en charge des onychomycoses en pratique dermatologique libérale en France.

BACKGROUND: Increasing prevalence of onychomycosis has been observed in recent years and regular epidemiological studies of the disease are thus necessary. In addition, treatment of onychomycosis by private dermatologists needs to be better understood. This study was carried out to improve knowledge about the epidemiology of onychomycosis and its management in private practice in France. PATIENTS AND METHODS: Four hundred and eighty-five private dermatologists practising throughout France took part in the study. Between September 2001 and December 2002, they collected the following data for each patient with clinically diagnosed onychomycosis: age, gender, concomitant diseases, regular practice of sport, clinical type of onychomycosis, mycological sampling and results, treatment type, monotherapy or combined therapy. RESULTS: Forty-seven percent of patients (i.e. 1826) underwent mycological sampling. In 1200 cases, a fungus was identified. The results for these 1200 patients were as follows: 44% of patients had matrix involvement. Associated diseases were: diabetes (5%), psoriasis (4.5%), immunosuppression (1%) and peripheral vasculopathy (5%). Onychomycosis involved the toes in 88.7% of cases, the fingers in 8.7% and both toes and nails in 2.6%. In the toes, the clinical diagnosis was subungual distal onychomycosis in 74.2% of cases, superficial leuconychia in 11.1%, proximal subungual onychomycosis in 3.3%, and total onychomycodystrophy in 11.4%. In the toes, a dermatophyte was isolated in 84% of cases, yeast in 8% and a mould in 6%. In the fingers, a dermatophyte was isolated in 37% of cases, yeast in 55% and a mould in 8%. Monotherapy was prescribed to 35% of patients and combined therapy in 65%. Oral treatment represented 59% of monotherapies. DISCUSSION: The main results of our study are that dermatologists do not perform any mycological sampling before treating onychomycosis in 53% of cases; in 56% of cases, onychomycosis does not involve the nail matrix; onychomycosis is localized in the toes 10 times more often than in the fingers; the distal subungual clinical form represents more than 70% of cases, in fingers and toes; in the toes, the total onychomycodystrophy clinical form represents 11.4% of cases; dermatologists prescribe monotherapy in 35% of cases, with 59% of these monotherapies comprising an oral treatment, while matrix involvement is present in only 44% of cases. CONCLUSION: Continual medical education efforts must be continued concerning onychomycosis diagnosis and management in accordance with the French Dermatological Society recommendations.

Characteristics of toxic epidermal necrolysis in patients undergoing long-term glucocorticoid therapy.

BACKGROUND AND DESIGN: The usefulness of steroid therapy in toxic epidermal necrolysis (TEN) remains controversial. Up to 5% of the TEN cases occur in patients who undergo long-term steroid therapy. We, thus, looked for the potential effect of long-term glucocorticosteroid therapy before the onset of TEN on altering the progression of the disease. The records of 179 patients were reviewed. The characteristics of the 13 patients who were undergoing long-term glucocorticosteroid therapy were compared with those of 166 other patients with TEN. The following parameters were studied: age, mortality, delay between the introduction of the suspect drug and the onset of TEN, length of hospital stay, body surface area involved, time elapsed between the first symptom of TEN and hospital admission, number of medications taken by the patients before the onset of TEN, lymphocyte count, granulocyte count, platelet count, glycemia, serum aspartate aminotransferase level, and total disease duration. RESULTS: Patients who were undergoing long-term glucocorticosteroid therapy differed from other patients with TEN in the administration of more drugs, longer delay between the introduction of the suspect drug and the onset of TEN, and a longer time elapsed between the first symptom of TEN and hospital admission. We observed no differences for the other parameters that were studied. CONCLUSION: Our study shows that long-term steroid therapy may delay the onset of TEN, but it does not halt its progression.

Simultaneous analysis of tyrosinase mRNA and markers of tyrosinase activity in the blood of patients with metastatic melanoma.

Determination of blood tyrosinase mRNA by RT-PCR and markers of tyrosinase activity (L-DOPA/L-tyrosine ratio) by HPLC have been proposed as biological tools for the detection of metastases in melanoma patients. We prospectively evaluated their significance and clinical value in a group of 30 stage III (n = 10) and IV (n = 20) melanoma patients and one with melanosis of Dubreuilh. L-DOPA/L-tyrosine ratio was elevated in 30% of stage III, 41% of stage IV patients (range: 7.5-261.0 x 10(5)) and in melanosis of Dubreuilh (184.8) (reference values: 6-16 X 10(5)). One stage III and four stage IV melanoma patients were positive for tyrosinase mRNA. In stage IV patients, tyrosinase mRNA positivity was associated with disease progression (P<0.01). The presence of tyrosinase mRNA in blood is more related to clinical status than level of melanin precursors, which probably reflects tumor burden.

Effects of diclofenac on experimental streptococcal necrotizing fasciitis (NF) in rabbit.

Aggravation of necrotizing fasciitis (NF) by the administration of non-steroidal antiinflammatory drugs (NSAIDs) has recently been suggested. A rabbit model of streptococcal NF was used to study the effects of parenteral administration of an NSAID on NF evolution and outcome. Of 16 rabbits inoculated with a Streptococcus pyogenes suspension together with staphylococcal alpha toxin, 8 were treated with two doses of 4 mg/kg diclofenac on day 1 after inoculation. Clinical, bacteriological and histological studies were performed until day 10. Under our experimental conditions, NSAID treatment significantly limited NF extension. A specific inverse relationship between the extent of inflammation and bacterial density in NF lesions was observed on day 1 after inoculation in the treated group suggesting that the greater severity of NF in humans treated with an NSAID could be due to the therapeutic delay induced by the misleading clinical effects of the NSAID, and not to inhibition of antibacterial defence.

[Eosinophilic pustulosis in an infant accompanied by immune deficit]. / Pustulose à éosinophiles du nourrisson révélant un déficit immunitaire.

BACKGROUND: Eosinophilic is a skin eruption which occurs in the first years of life, progressing by pruriginous flare-ups with amicrobial papulopustulae on a hairless scalp. Eosinophil infiltration of the skin is variable (follicular or perifollicular dermal infiltration). In adults, eosinophilic pustulosis is often associated with immune deficiency, but this association has not been reported in children. We report two cases. CASE REPORTS: Two boys had a pruriginous papulopustular eruption involving the scalp and the trunk which had progressed with periods of exacerbation since birth. Search for bacteriological or mycological involvement was negative. Histology showed folliculitis with major polynuclear eosinophil infiltration. Both children had a past history of repeated skin and extracutaneous infections strongly suggesting an immune deficit. Buckly syndrome was suspected in the second case. DISCUSSION: Juvenile eosinophilic pustulosis belongs to the spectrum of childhood eosinophilic dermatoses. The presence of eosinophil infiltration in the skin demonstrates localized or systemic immune dysfunction. A hematology and immunology work-up is needed in case of associated skin or deep infections.

PML-RARalpha initiates leukemia by conferring properties of self-renewal to committed promyelocytic progenitors.

Acute promyelocytic leukemia (APL) is characterized by hyperproliferation of promyelocytes, progenitors that are committed to terminal differentiation into granulocytes, making it an ideal disease in which to study the transforming potential of less primitive cell types. We utilized a murine model of APL in which the PML-RARalpha oncogene is expressed from the endogenous cathepsin G promoter to test the hypothesis that leukemia stem cell (LSC) activity resides within the differentiated promyelocyte compartment. We prospectively purified promyelocytes from transgenic mice at various stages of disease and observed that PML-RARalpha-expressing promyelocytes from young preleukemic mice had acquired properties of self-renewal both in vitro and in vivo. Progression to acute leukemia was associated with an expansion of the promyelocyte compartment at the expense of other stem, progenitor and terminally differentiated populations. Leukemic promyelocytes exhibited properties of self-renewal, and were capable of engendering leukemia in secondary recipient mice. These data indicate that PML-RARalpha alone can confer properties of self-renewal to committed hematopoietic progenitors before the onset of disease. These findings are consistent with the hypothesis that cancer stem cells may arise from committed progenitors that lack stem cell properties, provided that the initiating mutation in cancer progression activates programs that confer properties of self-renewal.

Comparative tolerance of adapalene 0.1% gel and six different tretinoin formulations.

Adapalene 0.1% gel (Differin gel) is a recently introduced topical treatment for mild to moderate acne which has been demonstrated to be much better tolerated and at least as effective as tretinoin 0.025% gel. We compared the tolerance of adapalene 0.1% gel with six different formulations and concentrations of tretinoin. A total of 55 healthy human subjects were enrolled in two controlled, randomized, observer blinded, intraindividual comparison studies. In the first study, adapalene 0.1% gel was evaluated for its 21-day cumulative irritation potential compared with tretinoin 0.025%, 0.05% and 0.1% cream, tretinoin 0.01% and 0.025% gel, and petrolatum (control). In the second study, adapalene 0.1% gel was evaluated for its 21-day cumulative irritation potential compared with tretinoin 0.025%, 0.05% and 0.1% cream, tretinoin 0.1% gel microsphere, and petrolatum (control). In both studies, cumulative irritation scores helped to define three groups of common irritancy potential, with significant differences between each group. In study A, the three groups were in descending order of irritancy: tretinoin 0.1% cream and tretinoin 0.05% cream; tretinoin 0.025% gel, tretinoin 0.01% gel and tretinoin 0.025% cream; adapalene 0.1% gel and petrolatum (control). In study B, the three groups were in descending order of irritancy: tretinoin 0.1% cream; tretinoin 0.05% cream, tretinoin 0.025% cream and tretinoin 0.1% gel microsphere; adapalene 0.1% gel and petrolatum (control). The experimental results show that adapalene 0.1% gel is significantly better tolerated than any of six formulations of tretinoin, including two gels, three creams and a microsphere formulation, ranging in potency from 0.01% to 0.1%.

[Impact of the climatic scenario of global warming on the growth of trees]. / Impact d'un scénario climatique de réchauffement global sur la croissance des arbres.

The climatic impact on tree radial growth resulting from an atmospheric CO2 doubling was studied for 24 populations of five tree species in the French Alps and the French Mediterranean area. The Arpege AGCM, which predicts a 3 degrees C increase in mean temperature and a light increase of precipitation, is used to estimate the climatic perturbation. The method is based on the integration of estimated climate in an empirical tree-ring to climate model, involving artificial neural networks. Only a few populations are sensitive to the climatic change; all are located on the boundaries of their ecological area and can be divided in two groups. The first one is composed of high altitude populations which show a growth increase induced by the warmer climate during the growing season. The second one, composed of a single Mediterranean Scots pine population, reacts with a severe growth reduction induced by the stronger water stress in summer.