Mucous membrane pemphigoid (MMP)

Mucous membrane pemphigoid (MMP), formerly known as cicatricial pemphigoid, benign mucosal pemphigoid, or benign mucous membrane pemphigoid, is a rare group of chronic autoimmune blistering diseases that primarily affect the mucous membranes. The immune system mistakenly produces autoantibodies against proteins within the basement membrane that anchor the outer layer of tissue to the underlying connective tissue, leading to painful blisters, erosions, inflammation, and progressive scarring. Although the mouth is the most commonly affected site, MMP may also involve the eyes, nose, throat, larynx, esophagus, genitals, and, less commonly, the skin.

Unlike bullous pemphigoid, which primarily affects the skin, MMP predominantly affects mucosal tissues and has a much greater tendency to heal with permanent scarring. In severe cases, scarring can result in vision loss, airway narrowing, difficulty swallowing, or genital adhesions if left untreated.

When MMP predominantly affects the eyes, it is known as ocular mucous membrane pemphigoid, also commonly called ocular cicatricial pemphigoid (OCP). This form causes chronic inflammation and scarring of the conjunctiva that can progressively damage the eyelids, tear ducts, and cornea, potentially leading to irreversible vision loss or blindness.

The historical term benign mucosal pemphigoid is no longer recommended because even mild disease can progress and cause serious complications. MMP includes several related disease subtypes that differ according to the proteins targeted by the immune system. Autoantibodies most commonly target BP180 (type XVII collagen), but may also target laminin 332, BP230, type VII collagen, or α6β4 integrin.

Symptoms vary depending on which mucous membranes are affected and may include:

• Painful blisters, erosions, or ulcers in the mouth
• Bleeding or peeling gums (desquamative gingivitis)
• Pain or difficulty eating, drinking, or speaking
• Eye redness, irritation, burning, tearing, dry eyes, or blurred vision
• Progressive scarring of the conjunctiva that may lead to vision loss or blindness
• Chronic nasal crusting, nosebleeds, or nasal obstruction
• Hoarseness or voice changes
• Difficulty swallowing (dysphagia)
• Sore throat or painful swallowing
• Shortness of breath or airway narrowing in severe cases
• Painful genital blisters, erosions, itching, or scarring
• Mild skin blisters or erosions in some individuals

MMP can occur alongside other autoimmune diseases, including Hashimoto’s thyroiditis, Graves’ disease, rheumatoid arthritis, systemic lupus erythematosus (SLE), Sjögren disease, inflammatory bowel disease (Crohn’s disease, ulcerative colitis), type 1 diabetes,  autoimmune blistering diseases (e.g., Bullous Pemphigoid, Pemphigus Vulgaris).

People with ocular involvement may also develop complications such as dry eye disease, inward-turning eyelashes (trichiasis), inward-turning of the eyelid (entropion), adhesions between the eyelid and eye (symblepharon), corneal scarring, and vision loss.

MMP is a rare disease with an estimated incidence of approximately 1 to 2 new cases per million people each year, although the true prevalence is likely higher because diagnosis is frequently delayed or missed.

The disease most commonly develops between 60 and 80 years of age and affects women somewhat more often than men, although it can occur at any age.

Researchers believe MMP develops through a combination of genetic susceptibility and immune dysregulation. Certain human leukocyte antigen (HLA) gene variants, including HLA-DQB1*0301 and HLA-DRB1*11, have been associated with increased disease risk.

Although the exact cause remains unknown, certain medications have been reported to trigger MMP in susceptible individuals, including some dipeptidyl peptidase-4 (DPP-4) inhibitors used to treat type 2 diabetes and, rarely, immune checkpoint inhibitors used in cancer therapy.

Because early symptoms often resemble more common eye, oral, or ear, nose, and throat disorders, diagnosis may be delayed by months or even years.