S. Lourari

Bullous and mucous membrane pemphigoid show a mixed response to rituximab: experience in seven patients.

Editor Rituximab, a chimeric monoclonal antibody directed against the cell-surface glycoprotein CD20, was originally developed to treat B-cell malignancies. Recently, rituximab, alone or in combination with intravenous immune globulins, has been shown to induce remission in up to 86% of patients with pemphigus refractory to oral steroids. However, there is limited information regarding the efficacy and safety of rituximab in auto-immune bullous disorders other than pemphigus. Herein, we report on a retrospective study of seven patients with refractory bullous pemphigoid (BP) or mucous membrane pemphigoid (MMP) who underwent treatment with rituximab. We performed a retrospective study on patients treated with rituximab for an auto-immune bullous disease other than pemphigus. Patients were selected between August 2007 and August 2009 at Toulouse and Limoges University Hospitals. During this period, seven patients (four men and three women) had received rituximab treatment. Five had BP and two had MMP (Table 1). The decision to initiate rituximab treatment was a multidisciplinary therapeutic decision. The median age at diagnosis was 70 years (range 33–85). Most patients had a history of comorbidities, including cardiac disease (four), pulmonary disease (one), renal disorder (one) and cutaneous cancers (two). All patients had previously not responded to topical corticosteroids or to at least one systemic immunosuppressive regimen (systemic corticosteroids, methotrexate, mycophenolate mofetil, cyclophosphamide, dapsone, azathioprine, etanercept). On physical examination, all patients had cutaneous lesions and four of the seven patients had erosions of the mucous membranes: oral (three patients), genital (three patients), ocular (two patients) and nasal (one). Direct immunofluorescence showed linear IgG and complement C3 deposits at the dermoepidermal junction of perilesional skin in six patients. Using indirect immunofluorescence analysis, antibasement membrane zone antibodies were detected in the serum of five and anti-BP-180 autoantibodies were detected by ELISA (Euroimmun, Lubeck, Germany) analysis in six patients. Six patients received four infusions of rituximab at weekly intervals at a dose of 375 mg ⁄ m. In one patient with BP, four additional rituximab infusions were given 11 months after the first dose, due to relapse of the disease. All patients received concomitant immunosuppressive medications. Four patients experienced complete remission on therapy, while two patients had partial remission. The median time to improvement in skin lesions was 4 months. Four patients are still in maintained remission, but one patient relapsed after 4 months of complete remission. The average duration of follow-up was 8 months (0.25; 27). Concerning clinical adverse events, one 85year-old patient with BP suddenly died 10 days after introduction of the first infusion of rituximab. The patient had a previous history of cardiac disease (ischaemic cardiopathy, atrial fibrillation and abdominal aortic aneurysm). In this retrospective review, rituximab appears to be an interesting therapeutic option, alone or in association with other systemic immunosuppressants, to treat BP and MMP that is resistant to conventional immunosuppressive treatments. Rituximab has shown promise in several case reports and cohort studies in treating paraneoplastic pemphigus, refractory cases of pemphigus vulgaris and foliaceus. There are also case reports for other autoimmune bullous skin disorders, where rituximab therapy successfully treated four patients with MMP and nine with refractory BP (Table 2). At present, rituximab treatment may be proposed in patients with autoimmune bullous diseases who are resistant to at least two conventional treatment regimens, including systemic glucocorticosteroids and immunosuppressants. However, further studies are needed to assess the role of rituximab in autoimmune bullous diseases other than pemphigus.

Cutaneous T-cell lymphoma following treatment of rheumatoid arthritis with tumour necrosis factor-α blocking agents: two cases

Editor Biological agents blocking tumour necrosis factor-alpha (TNF-α) have been in use for the treatment of autoimmune and inflammatory diseases since 1998. The development of lymphoma and exceptionally cutaneous T-cell lymphomas (CTCL) has been associated with the use of these agents.1 However, the level of risk remains controversial. We describe two patients with long-standing rheumatoid arthritis (RA) who developed CTCL 2 and 29 months after the initiation of etanercept and infliximab, respectively. The first case was a 74-year-old woman with a long history of destructive RA who developed a localized alopecia and an infiltrated, pruritic and erythemato-squamous eruption on the trunk, buttocks, and thighs 2 months after starting etanercept therapy 25 mg twice a week. The histological examination (Fig. 1), immunohistochemical and T-cell receptor gene rearrangement studies revealed pilotropic mycosis fungoides with follicular mucinosis. In situ hybridization for Epstein–Barr virus (EBV) using an EBER probe (Ventana, Tucson, AR) was negative. Etanercept was stopped, and no systemic disease modifying therapy was given for 6 months. Because of persistence of skin lesions, PUVA therapy was started, with excellent clinical response. The second case was a 62-year-old woman who had RA for 23 years. She received a treatment with infliximab for 29 months, associated with methotrexate during the last 12 months. She developed after the 16th infusion of infliximab an erythematous plaque on her left flank. A diagnosis of mycosis fungoides was made on histological examination (Fig. 2). T-cell receptor gene rearrangement studies showed clonal T-cell rearrangement in the skin. In situ hybridization for EBV using an EBER probe (Ventana) was negative. Infliximab therapy was stopped, and a spontaneous regression of skin lesions was observed within weeks. The patient remained cleared with a follow-up of 15 months. We report two patients who developed CTCL during treatment with TNF-α-blocking agents. RA is known to be associated with an increased risk of both Hodgkin and non-Hodgkin’s lymphoma.1 However, there is no indication of an increased risk of CTCL in RA. Only one prospective study focusing on dermatological conditions during TNF-α-blocking therapy has been published. It showed that dermatological conditions are a clinically important problem in RA patients receiving TNF-α-blocking therapy.2 The events recorded most frequently were skin infections, eczema, and drug-related eruptions. Other events with a possible relation to TNF-α-blocking therapy included vasculitis, psoriasis, drug-induced systemic lupus erythematosus, dermatomyositis, and a lymphomatoidpapulosis-like eruption. Five cases of skin carcinoma were recorded in this study. In the literature, seven cases of cutaneous lymphoma have been reported in patients treated with anti-TNF agents.3–8 These were mycosis fungoides (n = 2), anaplastic large cell lymphoma (n = 1), CD30+ T-cell lymphoma (n = 1), CD8+ T-cell lymphoma (n = 2) and Sezary syndrome (n = 1). The issue of a potential increased risk of lymphoma with TNF-αblocking agents remains controversial. In 2002, scientists from the Conflict of Interest: Carle Paul has received grants, honoraria and has been investigator for Wyett and Schering Plough. Cristina Livideanu has been investigator for Schering Plough. Figure 1 Lymphocytic dermal infiltrate with mucinous degeneration localized around hair follicle (haematoxylin–eosin ×50).

Sentinel lymph node biopsy for melanoma is becoming a consensus: a national survey of French centres involved in melanoma care in 2008

Background  The role of sentinel lymph node (SLN) biopsy in melanoma care remains controversial and is not included in most guidelines for the management of melanoma in Europe.

High-frequency ultrasonography but not 930-nm optical coherence tomography reliably evaluates melanoma thickness in vivo: a prospective validation study

Early diagnosis and rapid surgical excision are essential for improving the prognosis of patients with melanoma. Reflectance confocal microscopy has been validated as a feasible procedure for in vivo diagnosis of melanoma but cannot be used to measure tumour thickness. However, ultrasonography and optical coherence tomography may allow melanoma thickness to be measured in vivo.

Photoletter to the editor: Blue nevus with satellitosis mimicking melanoma. Contribution of dermoscopy and reflectance confocal microscopy.

Blue nevus is an acquired benign melanocytic nevus that can undergo malignant transformation. We report a 70-year-old man who presented with a recently enlarged long-term blue nodule on his scalp. He reported onset of new satellitosis around the lesion. Although clinically thought to be a malignant melanoma, histopathological, dermoscopic and reflectance confocal-microscopy examinations did not confirm this diagnosis.

Traitements non chirurgicaux des carcinomes cutanés et de leurs précurseurs

The skin carcinomas are the most common skin cancers and adult cancers. Risk factors for skin cancer are known. Surgery is the treatment of choice for skin carcinomas. There are several alternative therapies for the treatment of skin cancer and precancerous lesions: radiotherapy, cryosurgery, curettage, electrocautery, photodynamic therapy, topical imiquimod, and topical 5-fluorouracil. The management of skin cancer and precancerous lesions has been the subject of recommendations for good practice in diagnosis and therapy.