Background: Mucous membrane pemphigoid (MMP) still represents a potentially life-and sight-threatening disease. In a subset of patients with severe MMP, conventional immunosuppressants are ineffective or contraindicated.Observations: Twenty-five patients with severe refractory MMP, including 5 with mucous membranedominant epidermolysis bullosa acquisita, received 1 or 2 cycles of rituximab (375 mg/m 2 weekly for 4 weeks). Twenty-one of the patients were receiving concomitant therapy with dapsone and/or sulfasalazine therapy, which was maintained during rituximab cycles. Complete responses in all affected sites (ocular and/or extraocular) were obtained in 17 patients (68%) by a median time of 12 weeks after the first cycle, and 5 additional patients responded completely after a second cycle, yielding an 88% complete response rate. In all but 1 of the 10 patients with ocular lesions, their eyes became noninflammatory within a mean of 10 weeks. Among the 3 patients (12%) who developed severe infectious complications, 2 (8%) died; they had been receiving concomitant conventional immunosuppressants and high-dose corticosteroids and were hypogammaglobulinemic. Treatment with immunosuppressants was discontinued for all other patients, and no other infection was observed. Ten patients experienced relapse after a mean of 4 (range, 1-16) months after achieving complete responses.Conclusions: Rituximab appears to have rapid and dramatic efficacy in patients with severe, refractory MMP. The occurrence of severe infections in patients receiving concomitant conventional immunosuppressants supports using rituximab without other immunosuppressants. Controlled prospective studies are warranted to define an optimal treatment protocol.

We conducted a prospective study between 1995 and 2002 to investigate nose and throat (NT) manifestations of mucous membrane pemphigoid (MMP). One hundred ten consecutive patients with clinical, histologic, and immunologic criteria of MMP were seen in 2 referral centers for bullous diseases. They were systematically asked about the existence of persistent NT symptoms. Patients who had any were examined with a flexible nasopharyngolaryngoscope by the same otorhinolaryngologist. When possible, NT mucous membrane (MM) biopsies were taken for direct immunofluorescence (IF) assays to determine lesion specificity. Thirty-eight (35%) patients (23 F/15 M; mean age, 58.5 yr) had the following NT symptoms: 35 (92%) nasal, 19 (50%) pharyngeal, and 10 (26%) laryngeal. Five (13%) had acute dyspnea. Thirty-three (87%) of the 38 symptomatic patients had lesions at physical examination: 30 (79%) nasal, 6 (16%) pharyngeal, and 19 (50%) laryngeal. Laryngeal involvement was asymptomatic in 11 patients. Lesions were mainly atrophic rhinitis and oropharyngeal and epiglottal erosions. Nasal valves, choanae, pharynx, and/or larynx were severely scarred in 7 (18%) patients, causing the death of 3. Direct IF showed malpighian epithelium associated with linear immune deposits (IgG, IgA, or C3) along the chorioepithelial junction in all 18 biopsies performed, including those of 4 symptomatic patients without lesions at physical examination. The presence of severe ophthalmologic lesions (p = 0.02) and > or =3 sites involved other than NT (p = 0.02) were predictive of laryngeal involvement. In contrast, laryngeal symptoms, disease duration, HLA DQB1*0301, and smoking were not significantly associated with laryngeal lesions. In conclusion, at least 35% of MMP patients had NT involvement. Atrophic rhinitis was the most frequent lesion. The most severe were the laryngeal lesions that were significantly associated with severe ocular involvement and disseminated disease, and could be fatal. Our results highlight the necessity of a multidisciplinary approach to MMP management to assure early diagnosis of NT involvement, to guide therapeutic choices, and to improve patient survival and functional outcomes.

Epidermolysis bullosa acquisita (EBA) is a rare autoimmune bullous disease (AIBD). However, higher EBA incidence and predisposing genetic factor(s) involving an HLA haplotype have been suspected in some populations. This retrospective study assessed the overrepresentation of black patients with EBA, its link with HLA-DRB1*15:03, and their clinical and immunological characteristics. Between 2005 and 2009, 7/13 (54%) EBA and 6/183 (3%) other-AIBD patients seen consecutively in our department were black (P=10(-6)); moreover 7/13 (54%) black patients and 6/183 (3%) white patients had EBA (P=10(-6)). In addition, between 1983 and 2005, 12 black patients had EBA. Finally, among the 19 black EBA patients, most of them had very atypical clinical presentations, 9 were natives of sub-Saharan Africa, 1 from Reunion Island, 7 from the West Indies, and 2 were of mixed ancestry. HLA-DRB1*15:03 allelic frequencies were 50% for African patients, significantly higher than the control population (P<10(-3)), and 21% for the West Indians (nonsignificant). High EBA frequencies have already been reported in American blacks significantly associated with the HLA-DR2. In conclusion, black-skinned patients developing EBA seem to have a genetic predisposition, and EBA should be suspected systematically for every AIBD seen in this population.