P. Joly

Subcutaneous changes in dermatomyositis.

We report the case of a 42‐year‐old woman with concomitant panniculitis and dermatomyositis. Painful, indurated lesions on the buttocks, thighs, arms, abdomen and breasts were associated with proximal muscle weakness. Skin biopsy revealed lobular panniculitis, and vacuolar degeneration of epidermal basal cells. Direct immunofluorescence was negative. Serum muscle enzyme (creatine‐phosphokinase) levels were elevated, and electromyography demonstrated a myositic process. Muscle biopsy showed an inflammatory myositis. These results were consistent with dermatomyositis associated with panniculitis. Only tive cases of this association have been reported previously. The relationship between these two conditions is discussed.

Thiopronine‐induced herpetiform pemphigus: report of a case studied by immunoelectron microscopy and immunoblot analysis

Summary We report a case of herpetiform pemphigus induced by thiopronine. Direct immunoelectron microscopy performed on peribullous skin showed IgG deposits predominantly located in the extracellular portion of desmosomes. By immunoblot analysis using bovine tongue extracts as the antigen, the patients serum recognized a 160‐kDa polypeptide which comigrated with desmoglein I. This study underlines the contribution of immunoblot analysis to the diagnosis of atypical cases of pemphigus, and confirms that herpetiform pemphigus may be a clinical variant of pemphigus foliaceus.

Tunisian endemic pemphigus foliaceus is associated with the HLA-DR3 gene: anti-desmoglein 1 antibody-positive healthy subjects bear protective alleles.

Background  Pemphigus foliaceus is an autoimmune blistering skin disease that partly results from genetic factors, especially human leucocyte antigen (HLA) class II genes.

A case of paraneoplastic pemphigus with antidesmoglein 1 antibodies as determined by immunoblotting.

Sir, Paraneoplastic pemphigus (PNP) is a subset of pemphigus in patients with neoplasia, in which clinical and histological features of pemphigus vulgaris (PV) are variably associated with features of erythema multiforme, bullous pemphigoid and lichen planus. PNP autoantibodies are directed against an antigen complex mainly composed of proteins of the plakin family: these are major components of desmosomal and hemidesmosomal plaques. We first described the presence of antidesmoglein 3 (Dsg3) antibodies in PNP sera by immunoblotting. It has recently been demonstrated that pathogenic anti-Dsg3 autoantibodies can be consistently detected in PNP sera by enzyme-linked immunosorbent assay (ELISA). Curiously, whereas antidesmoglein 1 (Dsg1) antibodies have been recovered in more than 50% of PNP sera using ELISA, such autoantibodies have never been detected in PNP sera using immunoblotting or immunoprecipitation assays. We describe a PNP patient with an atypical clinical presentation in whom circulating anti-Dsg1 antibodies were detected by immunoblotting. A 70-year-old man with a history of chronic lymphoid leukaemia and prostate carcinoma presented with a generalized lichenoid eruption. Cutaneous lesions evolved to an exfoliative erythroderma (Fig. 1a) associated with atypical target-like lesions on the lower limbs. The patient had mucosal erosions and extensive cutaneous blisters with a positive Nikolsky sign. He died of infection despite parenteral antibiotics and corticoid therapy. Histological examination of a cutaneous blister showed basilar and suprabasilar cleavage with vacuolar changes and keratinocyte necrosis. Direct and indirect immunofluorescence (IF) showed antiepidermal cell surface antibodies without antibasement membrane zone antibodies. The patients serum stained rat bladder epithelium on indirect IF. Immunoblot analysis showed IgG antibodies directed against bands of 250-, 210-(doublet) and 190-kDa molecular weight, corresponding to desmoplakin I, envoplakin and desmoplakin II, and periplakin, respectively. Additionally, the patients serum contained IgG antibodies that recognized a 160-kDa band comigrating with the band recognized by a murine anti-Dsg1 monoclonal antibody (Clone DG3.10, Progen, Heidelberg, Germany) (Fig. 1b). It is surprising that, to date, anti-Dsg1 antibodies have never been detected in PNP sera by immunoblotting or immunoprecipitation, whereas they have recently been reported in 50% of PNP sera by an ELISA assay using baculovirus-expressed recombinant Dsg1. One possible explanation is that PNP sera, like pemphigus foliaceus (PF) sera, may recognize a conformational epitope on Dsg1 which is denatured during the immunoblotting extraction procedure. The pathogenic effect of PNP anti-Dsg1 antibodies

Traitement par rituximab d’un purpura thrombopénique immunologique au cours d’un lupus systémique

Resume Introduction Le purpura thrombopenique immunologique est une maladie auto-immune dont le traitement repose en premiere intention sur la corticotherapie generale. Le traitement peut etre difficile, en particulier en cas de contre-indication aux traitements classiques : corticoides, splenectomie ou immunosuppresseurs. Nous rapportons le cas d’une malade lupique dont le purpura thrombopenique immunologique a ete traite avec succes par rituximab (anticorps anti-CD20) du fait d’une tuberculose disseminee contre-indiquant l’utilisation des traitements classiques. Le rituximab (Mabthera®) a obtenu une AMM dans le traitement des lymphomes folliculaires chimioresistants ou en rechute. Observation Une femme de 31 ans, d’origine maghrebine, etait atteinte depuis 10 ans d’un lupus erythemateux systemique traite par prednisone, hydroxychloroquine, methotrexate et anti-inflammatoires non-steroidiens. Trois mois apres l’introduction d’une quadritherapie antituberculeuse pour une miliaire tuberculeuse disseminee survenait un purpura thrombopenique grave (plaquettes : 4G/l). La malade etait initialement traitee sans succes par trois cures d’immunoglobulines. La thrombopenie restant inferieure a 5 G/l, la malade recevait 4 perfusions hebdomadaires de rituximab (Mabthera®) : 375 mg/m2. La thrombopenie regressait apres la troisieme perfusion. Parallelement, les anticorps anti-ADN natifs initialement tres eleves se normalisaient. Aucun effet secondaire n’etait observe. La malade n’avait pas de rechute de son purpura, ni de son lupus, 29 mois apres la derniere perfusion. Commentaires Le rituximab semble representer une alternative interessante dans le traitement du purpura thrombopenique immunologique en cas d’inefficacite ou de contre-indication aux traitements conventionnels.

Recurrence of drug-induced reactions in DRESS patients.

Drug reaction with eosinophilia and systemic symptoms (DRESS) may relapse following introduction of drugs structurally unrelated to the initial culprit drug.

Anti‐desmoglein 1 antibodies in healthy related and unrelated subjects and patients with pemphigus foliaceus in endemic and non‐endemic areas from Tunisia

Background  Pemphigus foliaceus is an autoimmune blistering skin disease characterized by the production of pathogenic IgG autoantibodies directed against desmoglein 1.

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.

Extensive erosive bullous pemphigoid: an atypical and serious clinical variant

SIR, Eccrine squamous syringometaplasia, a relatively rare but benign entity, has been reported in cancer patients receiving various chemotherapeutic regimens. It is usually described as erythematous plaques, papules or vesicles, which may be limited to the extremities or may be generalized. Docetaxel (Taxotere; Rhone-Poulenc Rorer) is a synthetic taxoid prepared from a non-toxic natural precursor, 10-deacetyl baccatin III, obtained from the leaves of the ornamental yew Taxus baccata L. This drug has been investigated in various types of cancer such as breast, lung or gastric cancer, and cutaneous side-effects have been previously described with this drug. We report the first case of squamous syringometaplasia in a patient treated with docetaxel (Taxotere) for a metastatic oesophageal neoplasm. In October 1999, a 53-year-old man with a history of alcohol and tobacco abuse was diagnosed as having a squamous cell carcinoma of the oesophagus with liver metastasis. He received first-line chemotherapy with cisplatin ⁄ fluorouracil. Further to progressive disease, he received docetaxel (Taxotere) as palliative second-line chemotherapy every 21 days, in association with 4 days of corticosteroids. Ten days after starting the fourth course of this regimen, he presented with acral oedematous erythema with sensitive erythematous infiltrated macules symmetrically distributed on the lower third of the legs and on both hands (Fig. 1a). Histopathology of a deep biopsy including the hypodermis showed keratinocyte necrosis associated with squamous syringometaplasia of the sweat ducts. The squamous syringometaplasia was associated with necrosis in the coiled secretory glands (Fig. 1b). The dermis was infiltrated by inflammation-associated lymphocytes, neutrophils and eosinophils, without any vasculitis. With symptomatic treatment, i.e. cold compresses and paracetamol, the eruption resolved progressively and disappeared within 7 days with intense desquamation, but without scarring. Squamous syringometaplasia is histologically defined as the transformation of the normal epithelial eccrine duct (i.e. double layer of cuboidal cells and the luminal eosinophilic cuticle) into two or more layers of squamous epithelial cells with intercellular bridges similar to the stratum spinosum. It has been reported in association with ingestion of benoxaprofen, exposure to tetrachloro-dibenzo-p-dioxin, chronic cutaneous ulcers and scars, squamous cell carcinoma, keratoacanthoma, lobular panniculitis and pyoderma gangrenosum. Patients undergoing chemotherapy develop acral epidermal erythema, a macular rash or papulovesicles of squamous syringometaplasia. Squamous syringometaplasia has been described in association with the chemotherapeutic agents cytarabine, mitoxantrone, fluorouracil, cisplatin, doxorubicin, cyclophosphamide, etoposide, methotrexate, bisulfan, melphalan, carmustine and thiotepa. Trials of docetaxel have been conducted in patients with cutaneous malignant melanoma and in human immunodeficiency virus-positive patients with Kaposi’s sarcoma. According to Bedikian et al. when docetaxel was used as first-line chemotherapy, 12Æ5% of the patients responded and 75% showed skin toxicities. Brownish discoloration of nails and a maculopapular rash with desquamation were the most common manifestations. In 1995, Zimmerman et al. reported cutaneous reactions that had occurred over the first three courses of therapy in 12 patients enrolled for phase I chemotherapy. The most common cutaneous reaction seen in these patients was characterized by discrete erythematous to violaceous patches or oedematous plaques. Figure 1. (a) Acral oedematous erythema with sensitive erythematous infiltrated macules on the hand; (b) photomicrograph showing squamous syringometaplasia associated with necrosis in the coiled secretory glands. British Journal of Dermatology 2002; 146: 524–540.

Treatment of scabies with oral ivermectin in 15 infants: a retrospective study on tolerance and efficacy

The incidence of scabies is increasing in Europe, and it often affects children and infants. Although numerous topical treatments have been approved for treatment of scabies in adults, they are often poorly tolerated in infants. One treatment, ivermectin, remains off label for infants weighing < 15 kg.