Rituximab combined with conventional therapy versus conventional therapy alone for the treatment of mucous membrane pemphigoid (MMP).

BACKGROUND: The use of rituximab for refractory autoimmune blistering diseases is increasing. Data related to rituximab for the treatment of mucous membrane pemphigoid (MMP) are limited. OBJECTIVE: We sought to compare the efficacy of adding rituximab with traditional immunosuppressive therapies in the treatment of MMP. The primary outcome was achievement and time to disease control. METHODS: Patients with a diagnosis of MMP from August 2001 to June 2015 who had greater than 6 months of follow-up after the initiation of therapy were reviewed. RESULTS: In all, 24 patients were treated with rituximab and 25 were treated with conventional immunosuppression. Of patients, 100% in the rituximab group achieved disease control compared with 40% in the conventional group (P < .01), with a mean time to disease control of 10.17 months and 37.7 months (P = .02). Adverse events were seen in 33% of patients after rituximab, compared with 48% of patients in the conventional group (P = .2). LIMITATIONS: Rituximab dosing was not uniform and the 2 groups were not matched in terms of disease severity, nor were they randomized. CONCLUSIONS: Our study indicates that the addition of rituximab to conventional therapy in patients with MMP results in more rapid and sustained disease control with potentially fewer adverse events.

Super-Resolution Microscopy Reveals Altered Desmosomal Protein Organization in Tissue from Patients with Pemphigus Vulgaris.

Pemphigus vulgaris (PV) is an autoimmune epidermal blistering disease in which autoantibodies (IgG) are directed against the desmosomal cadherin desmoglein 3. To better understand how PV IgG alters desmosome morphology and function in vivo, biopsies from patients with PV were analyzed by structured illumination microscopy, a form of superresolution fluorescence microscopy. In patient tissue, desmosomal proteins were aberrantly clustered and patient IgG colocalized with markers for lipid rafts and endosomes. Additionally, steady-state levels of desmoglein 3 were decreased and desmosomes were reduced in size in patient tissue. Desmosomes at blister sites were occasionally split, with PV IgG decorating the extracellular faces of split desmosomes. Desmosome splitting was recapitulated in vitro by exposing cultured keratinocytes both to PV IgG and to mechanical stress, demonstrating that splitting at the blister interface in patient tissue is due to compromised desmosomal adhesive function. These findings indicate that desmoglein 3 clustering and endocytosis are associated with reduced desmosome size and adhesion defects in tissue of patients with PV. Further, this study reveals that superresolution optical imaging is a powerful approach for studying epidermal adhesion structures in normal and diseased skin.