C. Picard-Dahan

Risk factors for bullous pemphigoid in the elderly: a prospective case-control study.

A rise in the incidence of bullous pemphigoid (BP) was documented recently in Europe, and the main risk factors for BP remain unknown. We conducted a multicenter case-control study to evaluate risk factors for BP. We identified 201 incident BP cases and 345 controls individually matched for age, gender, center, and place of residence (home, nursing home, or extended-care facility). We used univariate and multivariate logistic regression analyses to compare drugs used for over 3 months, comorbidities, and physical and cognitive impairments between cases and controls. Mean age of BP patients was 84.2 (±8.7) years. Factors independently associated with BP by multivariate analysis were major cognitive impairment (odds ratio (OR), 2.19; 95% confidence interval (95% CI), 1.24-3.87), bedridden condition (OR, 2.19; 95% CI, 1.23-3.89), Parkinsons disease (OR, 2.16; 95% CI, 1.09-4.27), unipolar or bipolar disorder (OR, 5.25; 95% CI, 1.21-22.86), and chronic use of spironolactone (OR, 2.30; 95% CI, 1.20-4.46) or phenothiazines with aliphatic side chains (OR, 3.70; 95% CI, 1.21-11.34). Chronic analgesic use was associated with a lower risk of BP (OR, 0.49; 95% CI, 0.30-0.81). Thus, risk factors for BP include neurological disorders, particularly dementia and Parkinsons disease, psychiatric disorders (unipolar and bipolar disorders), bedridden condition, and chronic use of several drugs.

Risk Factors for Relapse in Patients With Bullous Pemphigoid in Clinical Remission: A Multicenter, Prospective, Cohort Study

OBJECTIVE To identify prognostic factors for relapse in the first year after cessation of therapy in bullous pemphigoid (BP). DESIGN Prospective, multicenter, cohort study (January 1, 2000, through December 31, 2006). SETTING Fifteen French dermatology departments. Patients Patients with BP in remission under low doses of topical or systemic corticosteroids. Interventions Cessation of corticosteroid treatment (day 0) followed by a systematic clinical and immunologic follow-up. MAIN OUTCOME MEASURES The end point was clinical relapse within the first year after cessation of therapy. Associations of clinical, biological, and immunologic (including direct immunofluorescence, serum anti-basement membrane zone autoantibodies, and serum BP180 autoantibodies by enzyme-linked immunosorbent assay [ELISA] on day 0) variables with clinical relapse were assessed by means of univariate and multivariate analyses. RESULTS On day 0, 30 of 114 patients (26.3%) still had a positive result of direct immunofluorescence, 63 of 112 (56.3%) had circulating anti-basement membrane zone autoantibodies, and 34 of 57 (60%) had anti-BP180 antibodies by ELISA. At month 12, 22 patients were dead (n = 11) or lost to follow-up (n = 11), 51 were in remission, and 45 had had relapses (mean interval to relapse, 3.2 months). Factors predictive of relapse within 12 months after cessation of therapy were a positive result of direct immunofluorescence microscopy (P = .02), a greater age (P = .01), and high-titer ELISA scores (P = .02) on day 0. In multivariate analysis, the only factor independently predictive of relapse was a high-titer ELISA score on day 0 (odds ratio, 11.00; 95% confidence interval, 1.29-93.76). CONCLUSIONS High-titer anti-BP180 ELISA score and, to a lesser degree, a positive direct immunofluorescence finding are good indicators of further relapse of BP. At least 1 of these tests should be performed before therapy is discontinued.

First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial

BACKGROUND High doses of corticosteroids are considered the standard treatment for pemphigus. Because long-term corticosteroid treatment can cause severe and even life-threatening side-effects in patients with this disease, we assessed whether first-line use of rituximab as adjuvant therapy could improve the proportion of patients achieving complete remission off-therapy, compared with corticosteroid treatment alone, while decreasing treatment side-effects of corticosteroids. METHODS We did a prospective, multicentre, parallel-group, open-label, randomised trial in 25 dermatology hospital departments in France (Ritux 3). Eligible participants were patients with newly diagnosed pemphigus aged 18-80 years being treated for the first time (not at the time of a relapse). We randomly assigned participants (1:1) to receive either oral prednisone alone, 1·0 or 1·5 mg/kg per day tapered over 12 or 18 months (prednisone alone group), or 1000 mg of intravenous rituximab on days 0 and 14, and 500 mg at months 12 and 18, combined with a short-term prednisone regimen, 0·5 or 1·0 mg/kg per day tapered over 3 or 6 months (rituximab plus short-term prednisone group). Follow-up was for 3 years (study visits were scheduled weekly during the first month of the study, then monthly until month 24, then an additional visit at month 36). Treatment was assigned through central computer-generated randomisation, with stratification according to disease-severity (severe or moderate, based on Harmans criteria). The primary endpoint was the proportion of patients who achieved complete remission off-therapy at month 24 (intention-to-treat analysis). This study is registered with ClinicalTrials.gov, number NCT00784589. FINDINGS Between May 10, 2010, and Dec 7, 2012, we enrolled 91 patients and randomly assigned 90 to treatment (90 were analysed; 1 patient withdrew consent before the random assignment). At month 24, 41 (89%) of 46 patients assigned to rituximab plus short-term prednisone were in complete remission off-therapy versus 15 (34%) of 44 assigned to prednisone alone (absolute difference 55 percentage points, 95% CI 38·4-71·7; p<0·0001. This difference corresponded to a relative risk of success of 2·61 (95% CI 1·71-3·99, p<0·0001), corresponding to 1·82 patients (95% CI 1·39-2·60) who would need to be treated with rituximab plus prednisone (rather than prednisone alone) for one additional success. No patient died during the study. More severe adverse events of grade 3-4 were reported in the prednisone-alone group (53 events in 29 patients; mean 1·20 [SD 1·25]) than in the rituximab plus prednisone group (27 events in 16 patients; mean 0·59 [1·15]; p=0·0021). The most common of these events in both groups were diabetes and endocrine disorder (11 [21%] with prednisone alone vs six [22%] with rituximab plus prednisone), myopathy (ten [19%] vs three [11%]), and bone disorders (five [9%] vs five [19%]). INTERPRETATION Data from our trial suggest that first-line use of rituximab plus short-term prednisone for patients with pemphigus is more effective than using prednisone alone, with fewer adverse events. FUNDING French Ministry of Health, French Society of Dermatology, Roche.

Treatment of bullous pemphigoid with dapsone: Retrospective study of thirty-six cases

Bullous pemphigoid (BP) 1 is usually responsive to high-dose systemic steroid therapy. 2 However, side effects from steroid use can often be more severe than the disease itself. 3 This has lea to the search for alternative treatments. 4-9 Dapsone has been widely used because of its antiinflammatory effects 1° and is effective in dermatitis herpetiformis (DH) 11 and linear IgA disease. 12 Its effects are less certain in epidermolysis bullosa acquisita and blistering diseases of the BP group. I3 We therefore undertook a study of the effect of dapsone on BP.

Place of human amniotic membrane immunoblotting in the diagnosis of autoimmune bullous dermatoses

Background  Fine analysis of antiskin autoantibodies can contribute to the differential diagnosis of autoimmune bullous dermatoses.

Corrélation entre présence d’anticorps anti-antigène de type 2 de la pemphigoïde et démence chez les sujets âgés sans manifestation clinique de pemphigoïde☆

Resume Introduction La pemphigoide est une dermatose bulleuse auto-immune caracterisee par la production d’anticorps diriges contre les composants des hemidesmosomes de la membrane basale. La physiopathologie du demasquage de ces antigenes est inconnue. La pemphigoide est plus frequente chez les personnes âgees, souvent debilitees. La prevalence des anticorps anti-antigene de la pemphigoide (anti-PB) est inconnue dans la population âgee indemne de manifestations dermatologiques evocatrices de pemphigoide. Nous avons etudie la prevalence d’anticorps anti-PBAg2 chez des personnes âgees indemnes de manifestations de pemphigoide et le lien entre la presence de ces anticorps et le diagnostic de demence. Patients et methodes Des personnes âgees (plus de 69 ans), sans aucune manifestation de pemphigoide, ont ete recrutees de facon consecutive dans des services de dermatologie ou de geriatrie (138 sujets). Chez chaque sujet etaient recueillies les prises medicamenteuses et un examen clinique etait realise avec calcul du MMS (Mini Mental Score). En fonction de leur MMS, les sujets etaient repartis en deux groupes. Le premier groupe etait compose de sujets sans demence (MMS > 24). Le second groupe etait compose de malades atteints de demence. Les anticorps anti-PBAg2 etaient doses dans les serums par la technique ELISA et par immunofluorescence indirecte et confirmes par un immunoblot. Les anticorps antinucleaires, utilises comme controle d’une reponse immune non specifique, etaient doses dans tous les serums. La prevalence de ces anticorps a ete comparee dans les deux groupes. Resultats Les deux groupes etaient comparables en âge, sexe, et presence de maladies dermatologiques (ulceres, escarres, erysipeles). Chaque groupe comportait 69 sujets. La prevalence globale des anticorps anti-PBAg2 chez ces personnes âgees indemnes de manifestations evoquant une pemphigoide etait de 3,6 p. 100. La presence des anticorps anti-PBAg2 etait associee au diagnostic de demence (p = 0,04 ; 0 p. 100 et 7 p. 100 dans les groupes 1 et 2, respectivement). Aucune association entre la presence d’anticorps anti-PBAg2 et les prises medicamenteuses ou une maladie dermatologique n’etait observee. La prevalence globale des anticorps antinucleaires etait de 14,5 p. 100 et proche dans les deux groupes. Discussion La presence des anticorps anti-PBAg2 pourrait etre associee au diagnostic de demence chez les personnes âgees.

Docetaxel in anthracycline-pretreated AIDS-related Kaposi's sarcoma : a retrospective study

Background  Kaposis sarcoma (KS) is a potentially life‐threatening multifocal neoplasm. Despite the significant decline in the incidence of acquired immune deficiency syndrome (AIDS)‐related KS with the use of highly active antiretroviral therapy (HAART), some patients, even those with a good immune restoration, still have aggressive disease. Liposomal anthracyclines or combination chemotherapy are widely used but adverse effects limit their utilization.

Pemphigoïde du sujet jeune: Étude rétrospective de 74 cas

INTRODUCTION Bullous pemphigoid usually affects elderly people. Only a few isolated cases among people younger than 65 years have been reported. OBJECTIVES Describe the clinical and biological characteristics of patients younger than 60 years suffering from bullous pemphigoid, compare them with the usual characteristics known among elderly people and search for potential pathological associations. PATIENTS AND METHODS Retrospective, national, multicenter study. Clinical, biological and histological characteristics were recorded with a standardised questionnaire as well as treatments and associated pathologies. RESULTS Seventy-four cases of bullous pemphigoid diagnosed between June 1970 and March 2002 were analyzed. Mean age at the beginning of the disease was 46 +/- 11.6 years. Further explorations by indirect immunofluorescence of separated skin and/or immuno-electron microscopy and/or immunoblotting were performed for 42 patients (56.8 p. 100). Clinical characteristics among this restricted population were comparable to those found among the 32 other cases. Compared to usual data on bullous pemphigoid in elderly people, we observed a greater proportion of extensive form of disease (75 p. 100), a more frequent head and neck involvement (39.2 p. 100) and an overexpression of anti-BP180 autoantibodies (48 p. 100). Neoplasm was notified for 7 patients (9.5 p. 100), 18 (24.3 p. 100) suffered from a pathology of the basement membrane zone (6 psoriasis, 6 atopic dermatitis and 6 lichen) and 13 from neurological disease, among which 4 were bedridden. Fourty-six patients (62.2 p. 100) received drugs for the long term (mean 2.12 +/- 2.43), 4 patients were treated by PUVAtherapy and 2 by radiotherapy. DISCUSSION Our results suggest that bullous pemphigoid among young people is more severe and more active than the usual form in the elderly. This particular form could be the result of a higher expression of anti-BP180 autoantibodies, which are considered as a marker of poor prognosis in this disease. We also found a high frequency of pathological associations and physical treatment, all responsible for damage to the basement membrane zone, which can involve auto-immunization against hemidesmosome components.Resume Introduction La pemphigoide touche classiquement les sujets âges. Seules des observations ponctuelles ont ete decrites chez les sujets avant 65 ans. Objectifs de l’etude Decrire les caracteristiques cliniques et biologiques d’une serie de malades âges de moins de 60 ans atteints de pemphigoide, de les comparer aux donnees des pemphigoides du sujet âge et de rechercher d’eventuelles associations pathologiques. Malades et methodes Il s’agissait d’une etude retrospective, nationale, multicentrique. Les caracteristiques cliniques, biologiques et histologiques, les donnees d’immunofluorescence, ainsi que les traitements et les pathologies associees ont ete recueillis grâce a un questionnaire standardise. Resultats Soixante-quatorze cas de pemphigoide chez des malades âges de moins de 60 ans, diagnostiques entre juin 1970 et mars 2002 dans les hopitaux participants, ont ete analyses. L’âge moyen de debut de la maladie etait de 46 ± 11,6 ans. Des explorations complementaires par immunofluorescence indirecte sur peau clivee et/ou par immunomicroscopie electronique et/ou par immunoblot ont ete realisees chez 42 malades (56,8 p. 100) dont les caracteristiques cliniques de pemphigoide etaient superposables a celles des 32 autres malades. Par rapport aux pemphigoides des sujets âges, on observait une plus forte proportion de formes multibulleuses (75 p. 100) avec une atteinte plus frequente de la tete et du cou (39,2 p. 100), et une plus grande frequence d’anticorps anti-BP180 (48 p. 100). Une neoplasie etait notee chez 7 malades (9,5 p. 100), 18 (24,3 p. 100) souffraient d’une autre dermatose (6 psoriasis, 6 dermatites atopiques et 6 lichens) et 13 malades (17,6 p. 100) d’une maladie neurologique dont 4 avec grabatisation. Quarante-six malades (62,2 p. 100) prenaient un traitement au long cours avec en moyenne 2,12 ± 2,43 medicaments, 4 malades avaient ete traites par PUVAtherapie et 2 par radiotherapie. Commentaires Ces donnees suggerent que la pemphigoide du sujet jeune est une maladie plus severe et plus active que la forme classique du sujet âge. Cette expression clinique particuliere pourrait etre la consequence de la plus forte prevalence d’anticorps anti PB-180. Ces anticorps sont consideres comme des marqueurs de mauvais pronostic et correles a l’activite chronique de la pemphigoide. On note aussi une frequence elevee d’associations pathologiques ou de traitements physiques pouvant generer des alterations de la jonction dermo-epidermique et favoriser l’auto-immunisation contre des constituants des hemidesmosomes.

Anévrysmes aortiques multiples au cours d’une polychondrite atrophiante

Resume Introduction Les complications cardiovasculaires de la polychondrite atrophiante sont rares, mais representent la deuxieme cause de mortalite, apres les chondrites du tractus respiratoire ; les plus frequentes sont les valvulopathies et les anevrysmes aortiques. Observation Nous rapportons une observation de polychondrite atrophiante associee a des anevrysmes aortiques multiples, asymptomatiques mais evolutifs en depit d’une corticotherapie generale associee a un traitement immunosuppresseur. Discussion L’evolution des anevrysmes aortiques au cours de la polychondrite atrophiante n’est souvent pas parallele a celle des manifestations extravasculaires. Alors meme que la maladie semble en remission, les lesions vasculaires peuvent continuer a progresser de facon independante. Cette observation illustre les limites du traitement medical dans la prise en charge de ces anevrysmes. Ainsi, l’indication chirurgicale doit etre portee au moment opportun.

Idiopathic linear IgA bullous dermatosis: prognostic factors based on a case series of 72 adults

Linear IgA bullous dermatosis (LABD) is a clinically and immunologically heterogeneous, subepidermal, autoimmune bullous disease (AIBD), for which the long‐term evolution is poorly described.