By Gary M. White, MD
Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease that predominately involves mucous membranes with resultant scar formation. The targets of the autoimmune attack include the bullous pemphigoid antigens BP180 and BP230, laminin-332 (formerly laminin-5-epiligrin), laminin-6, type VII collagen, and integrin beta42.
The eye may be affected by a chronic conjunctivitis, burning, and excessive tearing. Later, conjunctival shrinkage, entropion, corneal opacities, and trichiasis may occur. If untreated, fibrous adhesions may attach both lids to the eye and ultimately blindness can develop. The oral mucosa is also commonly involved, causing oral ulceration and/or a desquamating gingivitis. The nasal, pharyngeal, laryngeal, esophageal, and/or anogenital regions may be affected as well. The skin may be affected in 10-25% of patients. The most common pattern is that of a localized form where recurrent blisters localized to the head and neck heal with scarring. This form has been termed Brunsting-Perry pemphigoid. Disseminated blistering that heals with scarring is a rare manifestation. Transitions among these forms may occur. One case of paraneoplastic cicatricial pemphigoid (non-small cell lung carcinoma) has been reported [BJD 1999;141;127].
In one study of 477 patients [BJD 2017;177;1074], 5.4% had symptomatic esophageal involvement. Dysphagia was the most frequent complaint.
MMP may be subdivided based upon the target antigen, e.g., laminin-332, the BP antigens, the sublamina densa region, or unidentified BM constituents. Those patients found to target the BP antigens may actually have a form of BP in which mucosal lesions predominate. Immunoelectron microscopy shows the level of separation above the lamina densa within the lamina lucida.
DIF of the conjunctiva may show IgG or IgA. IIF may be positive and may be more sensitive if done in BMZ split-skin. A circulating IgA detected in one study bound a 45 kD BMZ antigen. It may be that the predominant circulation Ag is IgA, especially in patients with ocular disease only. Negative DIF in cases clinically suggest of MMP should prompt repeated biopsies as false negatives are not uncommon [JAAD 2017;77;700].
Dapsone should be prescribed initially. It is often helpful to start at 100 mg/day (check CBC frequently initially) and then increase as needed or taper if possible. Topical steroids applied inside the mouth are often helpful adjuncts. One of my patients does well on fluocinonide gel daily to the gums and dapsone 75 mg/day. I see him now every 2-3 months maintenance, checking a CBC and SGPT and asking about tingling in the toes.
Rituximab seems to be very helpful as an adjunct to conventional therapy. In a study of 24 patients, 100% on rituximab and conventional therapy achieved disease control vs. 40% on conventional therapy alone [JAAD 2016;74;835]. Both regimens of 4 weekly infusions of 375 mg/m2 and 2 infusions of 1000 mg given 15 days apart were used. Rituximab has also been used for isolated refractory desquamative gingivitis due to MMP [JAMA Derm 2016;152;1396].
Prednisone may be added if needed. For ocular disease, subconjunctival injection may be done. Azathioprine has also been used and may be combined with prednisone. Cyclophosphamide may be necessary (e.g., 75-100 mg/day) alone or in conjunction with prednisone. Minocycline 50-100 mg/day was very effective in one study (BJD 1995;132;784). Patients experienced a marked diminution in orodynia. Many were able to decrease or even stop steroid therapy. One report found benefit with a combination of prednisone, low-dose oral cyclophosphamide, and high-dose pulse intravenous cyclophosphamide. Another report found mycophenolate mofetil (e.g., 2 gms/day) as an effective steroid-sparing agent [JAAD 2001;45;256].
Etanercept was very effective in one case [JAAD 2002;46;113]. IVIG has been used [JAAD 2002;46;116].
A small bulla on the forehead in a patient with the Brunsting-Perry type.
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