M.-S. Doutre

Acute generalized exanthematous pustulosis.

Acute generalized exanthematous pustulosis (AGEP) is now a well-known clinical entity, characterized by acute onset with associated fever, and numerous non-follicular pin-head sterile pustules on erythematous background. The biopsy evidences subcorneal pustules resembling those of pustular psoriasis. However, polymorphic aspects such as pseudo-erythema multiforme purpuric lesions, and edema are often associated, and with the rapid self-healing course of this impressive pustulosis, allow the differential diagnosis with pustular psoriasis. Most cases of AGEP are drug induced, particularly by antibiotics and mainly beta-lactams. However, a number of other drugs, of which the list is increasing, may be responsible. Few cases are related to other causative factors such as viral infections or ultraviolet radiation.

Long-Term Remissions of Severe Pemphigus After Rituximab Therapy Are Associated with Prolonged Failure of Desmoglein B Cell Response

Changes in the B cell repertoire mediate long-lasting therapeutic effects of rituximab in pemphigus patients. A Blistering Attack on Autoimmunity The devastating effects of autoimmune diseases like type 1 diabetes and multiple sclerosis are front-page news. However, rare autoimmune diseases may be even more distressing in their relative anonymity. One such condition is pemphigus, which is a severe blistering condition caused by autoantibodies to adhesion proteins in the skin and mucus. The B cell–depleting antibody rituximab has been shown to treat pemphigus short term in early clinical trials. Now, Colliou et al. find that rituximab therapy can help pemphigus patients even after 6 years, in part by reshaping the B cell repertoire during reconstitution. The authors followed pemphigus patients from their early trial out at least 6 years after rituximab therapy. They found that nearly two-thirds of patients achieved a long-term complete response—either completely off of therapy or when treated with low levels of supplementary prednisone. They then compared patients with complete response to those with incomplete response to look at differences in reconstitution of the B cell compartment. Patients with complete response had a greater proportion of naïve and transitional B cells than those with incomplete response, which suggests a barrier to B cell maturation. Indeed, many of these transitional B cells secreted the regulatory cytokine interleukin-10. Moreover, complete responders had a specific loss of anti–desmoglein-specific B cells, which are pathogenic in pemphigus patients, but not B cells that respond to infectious agents. Together, these data suggest that B cell repertoire is reshaped after rituximab therapy, allowing for long-term effects in addition to the short-term loss of pathogenic B cells. If these observations are confirmed in large studies, these data could form the basis for a new frontline therapy for recalcitrant pemphigus. Pemphigus is a severe blistering condition of the skin and mucosa caused by autoantibodies directed against desmogleins, which are a type of keratinocyte adhesion protein. B cell depletion by rituximab has short-term efficacy against pemphigus. We aimed to assess the long-term course of pemphigus patients after B cell depletion and to understand the immunological mechanisms that mediate long-lasting remissions. We evaluated the clinical course of 22 pemphigus patients treated with rituximab after a 79-month median follow-up and compared the anti-desmoglein B cell response and B and T lymphocyte subpopulations and repertoire between patients who achieved complete remission (CR) and those who had incomplete remission (IR). Thirteen patients (59%) experienced CR during the study, including 10 patients off treatment and 3 patients with prednisone doses <10 mg/day; 9 patients had IR. A marked increase was observed in the ratio of CD19+CD27− naïve B cells to CD19+CD27+ memory B cells. Indeed, patients in CR had a fourfold higher number of transitional B cells and interleukin-10–secreting regulatory B cells than those in IR. Furthermore, CR was associated with modification of the initial B cell repertoire and the disappearance of desmoglein-specific circulating immunoglobulin G–positive (IgG+) B lymphocytes, whereas a skewed B cell repertoire was observed in patients in IR. Thus, a blockage of B cell maturation, a prolonged repopulation with naïve B cells, and a delayed reappearance of memory B cells, which resulted in the disappearance of circulating desmoglein-specific IgG+ B lymphocytes, contribute to the long-lasting effectiveness of rituximab for treating pemphigus.

Plasma exchange in bullous pemphigoid.

41 patients with pemphigoid entered a multicentre randomised study of the efficacy of plasma exchange. All patients received 0.3 mg/kg daily oral prednisolone, increased weekly if the disease remained active. 24 patients received plasma exchanges in addition (eight large-volume exchanges over 4 weeks), and 17 had prednisolone only. 4 patients, 2 in each group, were withdrawn from the study. The initial dose of prednisolone was effective in 13 of 22 patients receiving plasma exchange but in none of 15 patients receiving prednisolone only. Control of the disease was obtained with a mean daily prednisolone dose of 0.52 +/- 0.28 mg/kg in the plasma exchange group v 0.97 +/- 0.33 mg/kg in the other group and a mean cumulative dose of 1240 +/- 728 mg v 2770 +/- 1600 mg. This finding suggests that plasma exchange allows a substantial saving of corticosteroids in the management of pemphigoid. This sparing effect was observed whether or not serum anti-basement membrane antibodies had been detected before treatment.

A three-year-analysis of fixed drug eruptions in hospital settings in France

Fixed drug eruption (FDE) is one of the most typical cutaneous drug adverse reactions. This localized drug-induced reaction is characterized by its relapse at the same sites. Few large series of FDE are reported. The aim of this study was to retrospectively collect and analyse well informed cases observed in a hospital setting. This study involved 17 academic clinical centers. A French nation-wide retrospective multicentric study was carried out on a 3-year-period from 2005 to 2007 by collecting data in seventeen departments of dermatology in France. Diagnosis of FDE was based essentially on clinical findings, at times confirmed by pathological data and patch-testing. Records were reviewed for demographics, causative drugs, localization, severity, and patch-tests, when available. Fifty nine cases were analysed. Patients were 59-years-old on average, with a female predilection. The most common drug was paracetamol, followed by the non-steroidal anti inflammatory drugs. The time between drug intake and skin symptoms was, on average, two days. Beside these classical characteristics, some original findings were found including, a frequent non pigmentation course and a sex-dependent pattern of distribution. Women often had lesions on the hands and feet, and men on the genitalia. Given the fact that skin pigmentation is an inconstant feature of FDE, its French name (erythème pigmenté fixe) should be reconsidered. The sex-dependent distribution could help our understanding of the pathophysiology of fixed drug eruption.

Chilblain Lupus erythematosus: Report of 15 Cases

In this retrospective study, the authors describe the clinical, histologic and laboratory features of 15 cases of chilblain or perniotic lupus. In winter, the patients (14 women, 1 man) develop chilblain-like lesions, chiefly in the toes (8 times) and fingers (11 times). Histologic features are identical to those of discoid lupus erythematosus. The damaged skin gives a positive fluorescent band test. Usually, these lesions occur in association with discoid lupus of the face. However, in 8 patients, they were the only cutaneous sign of lupus. This form of lupus can evolve to a systemic form, as was the case with 3 patients.

The Clinical Spectrum and Therapeutic Management of Hypocomplementemic Urticarial Vasculitis: Data From a French Nationwide Study of Fifty‐Seven Patients

Hypocomplementemic urticarial vasculitis (HUV) is an uncommon vasculitis of unknown etiology that is rarely described in the literature. We undertook this study to analyze the clinical spectrum and the therapeutic management of patients with HUV.

Oral Contraceptives and Cyproterone Acetate in Female Acne Treatment

The sebaceous gland is a target of androgens, and hormonal influences play an important role in the multifactorial pathogenesis of acne. In both men and women, acne may be related to an excessive hypersensitivity of the sebaceous end organ to androgens. However, in women, the ovarian and adrenal production and the plasma transport of androgens may be implicated, particularly in late-onset or persistent acne or with associated hirsutism. Many reports have shown that females with acne frequently have abnormal levels of circulating androgens. Hormonal treatment is not usually the first line in female acne. But in relation to the possibilities, particularly the tetracyclines, this may be a choice when one prescribes a pill like Dianette® to a young woman presenting a mild acne and who requests contraception. However, antiandrogen treatment is sometimes mandatory, especially in resistant acne in adult women and/or in female acne which is resistant or relapsing rapidly after treatment with Roaccutane® and which is often related to hyperandrogenism. Finally, in severe prepubertal acne, the possible cause is an adrenal enzymatic block of which the only treatment is hormonal.

Successful Treatment of Subcorneal Pustular Dermatosis (Sneddon-Wilkinson Disease) by Acitretin: Report of a Case

We report a case of subcorneal pustular dermatosis (SPD) first treated with dapsone with poor response. Dapsone was changed to acitretin, which dramatically improved the lesions in a few days. Dapsone is the first-line treatment in SPD, but it may be ineffective in some cases and its toxicity is important. Therapeutic alternatives are limited and less effective (systemic corticosteroids, phototherapy). Our observation underlines the usefulness of retinoids, when dapsone is ineffective or poorly tolerated. Their effectiveness is comparable, but they are effective more rapidly and are better tolerated. A dose maintenance is necessary to avoid relapses. Their action in SPD remains unclear but may be due to the inhibition of neutrophil functions.

Skin Lesion Resembling Malignant Atrophic Papulosis in Lupus erythematosus

This case demonstrates, as do the 3 others reported in literature, that a diagnosis of malignant atrophic papulosis can only be made once the possibility of a lupus erythematosus has been totally excluded.

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.