Mucous membrane pemphigoid

Mucous membrane pemphigoid is a rare autoimmune condition that causes painful blisters primarily in the mouth and eyes, and can lead to serious complications including vision loss if not treated early.

Cicatricial pemphigoid, Benign mucosal pemphigoid, Benign mucous membrane pemphigoid, Mucosynechia atrophic bullous dermatitis, Scarring pemphigoid, Ocular pemphigoid, Oral pemphigoid

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Table of contents

• What is mucous membrane pemphigoid?
• Who gets this condition?
• What causes mucous membrane pemphigoid?
• What are the symptoms?
• How is it diagnosed?
• How is it treated?
• What is the outlook?

What is mucous membrane pemphigoid?

Mucous membrane pemphigoid is an uncommon blistering condition that most frequently affects the lining of the mouth and gums. Other moist surfaces of the body, known as mucous membranes (the thin, protective layers that line internal body cavities and passages), can also be affected^[1]. These include the surface layers of the eyes and inside of the eyelids, the inside of the nose, the throat, food pipe (esophagus), and the genital area^[2].

The skin is sometimes affected by a few scattered blisters, particularly on areas such as the face, neck and scalp. When blisters heal, they may leave scars in the affected areas^[1]. This scarring is what gives the condition one of its alternative names—cicatricial pemphigoid, where “cicatricial” means relating to scars.

• Oral cavity (mouth and gums)
• Eyes and conjunctiva
• Nasal cavity
• Throat and larynx
• Esophagus
• Anogenital region
• Skin (particularly head, neck, and scalp)

Who gets this condition?

Mucous membrane pemphigoid is a rare disease with a reported incidence of approximately 1.3 to 2.0 cases per million people per year^[2]. It is predominantly a disease of older adults, with most cases occurring around the age of 70, although some cases have been reported in childhood^[2]. Women are more likely to develop this condition than men^[3].

What causes mucous membrane pemphigoid?

The exact cause of mucous membrane pemphigoid is unknown. It is considered an autoimmune disease, which means the body’s defense system mistakenly attacks its own tissues instead of protecting against harmful invaders like bacteria and viruses^[4].

In this condition, the immune system produces special proteins called antibodies that mistakenly target and attack the basement membrane zone—the layer that connects the outer surface lining to the tissue underneath^[2]. When these antibodies attack, they cause the basement membrane to break down, which leads to the formation of blisters. Once the connection between these layers is disrupted, fluid gathers between them and creates the characteristic blisters that burst and leave painful open sores^[6].

Researchers believe that a combination of genetic and environmental factors may play a role in who develops this condition. The disease has been associated with certain genetic markers, particularly a specific immune system gene called HLA-DQB1*0301^[3]. In rare cases, mucous membrane pemphigoid may be triggered by certain medications such as methyldopa, clonidine, and D-penicillamine^[3].

What are the symptoms?

The symptoms of mucous membrane pemphigoid vary depending on which parts of the body are affected. The severity of disease depends on the site and extent of involvement^[2].

In the mouth (affecting more than 85% of patients): The condition typically appears as red, blistered or damaged patches on the inner cheeks, gums or roof of the mouth. The gums may feel sore, particularly when brushing teeth. Blisters are usually painless until they burst and form ulcers, which can cause burning or stinging, especially when eating spicy foods, citrus fruits, drinking hot beverages or alcohol, or using mouthwashes that contain alcohol^[1][2]. People may have difficulty eating due to pain.

In the eyes (affecting 65% of patients): Eye involvement can be particularly serious. Eyes may appear red and feel dry, gritty, or sore. There may be a burning or stinging sensation, discharge from the eyes, or inflammation of the conjunctiva (the clear membrane covering the white part of the eye)^[2]. If not treated urgently, the condition may cause the eyelid to stick to the surface of the eye (a condition called symblepharon), the eyelid to turn inward (called entropion), or scarring of the cornea^[2]. In severe cases, these complications can lead to impaired vision or complete blindness^[4].

In the nose (affecting 20-40% of patients): Some people may get a stuffy or blocked nose, have blood-tinged mucus, or experience nosebleeds. There may also be crusting, discharge, or erosion inside the nasal cavity^[1][2].

In the throat and esophagus (affecting 5-15% of patients): People may notice a change in their voice or experience difficulty swallowing. Scarring in the food pipe can cause it to become narrow, making swallowing difficult^[1][2].

In the genital area (affecting 20% of patients): Painful blisters, erosions, and swelling may appear on the genitals and around the anus. There may be bleeding, urinary difficulty, or pain during urination. Sexual function may be affected. In severe cases, scarring can result in cosmetic changes or narrowing of the vaginal opening^[2].

On the skin (affecting 25-30% of patients): When the skin is affected, blisters tend to appear on the scalp, face, trunk, or limbs. The blisters may be itchy. Once they heal, they typically leave superficial scars. Some blisters may form blood-crusted plaques^[2][5].

The disease can be classified based on risk level. Low-risk disease involves oral lesions with or without involvement of the nasal cavity or skin. High-risk disease involves the conjunctiva, larynx, esophagus, trachea, or genital mucous membranes^[2].

How is it diagnosed?

Mucous membrane pemphigoid cannot be diagnosed solely by its appearance, as other conditions can look very similar^[1]. Doctors usually recognize the condition by its characteristic appearance, but definite diagnosis requires laboratory testing.

The diagnosis is confirmed by taking one or two small samples of tissue, called a biopsy, usually from inside the mouth under local anesthetic^[1]. These samples are then examined under a microscope. Doctors use special chemical stains that allow antibody deposits to be seen under the microscope, a technique called an immunofluorescence assay^[4].

In this test, doctors look for linear deposition of certain antibodies (IgG, IgA) or a protein called C3 along the basement membrane zone^[3]. A blood test may also be used to detect these antibodies, although autoantibodies are usually present in low amounts and may not always be revealed on testing^[2].

Because the condition can affect multiple body sites, a referral to specialists may be needed for early diagnosis. This may include an eye specialist (ophthalmologist) to check for early signs involving the eyes, an ear, nose and throat specialist for symptoms affecting those areas, and a dermatologist or oral medicine specialist for the skin and mouth^[1].

How is it treated?

The management of mucous membrane pemphigoid depends on the severity of the condition and which areas of the body are affected^[5]. A multidisciplinary approach involving different specialists is essential^[8].

For mild cases affecting mainly the mouth: Simple measures can help, including avoiding hard, sharp or rough foods and taking care when eating. Good oral hygiene is important, including professional dental care such as scaling^[6][5]. Treatments may include corticosteroids applied directly to the affected area or injected into the sores. A combination of doxycycline (an antibiotic) and nicotinamide (a form of vitamin B3) taken by mouth may also be used^[4].

For more severe disease or rapid progression: People may need drugs that suppress the immune system, called immunosuppressants. Systemic corticosteroids (taken as pills or injected) are often the first choice for initial treatment. These are typically combined with steroid-sparing agents for long-term maintenance to reduce side effects^[8]. Other medications that may be used include dapsone or prednisone^[4].

For eye involvement: Eye involvement requires urgent treatment to prevent scarring and vision loss. Regular monitoring by an ophthalmologist is essential^[1].

Due to the rarity of this disease, large controlled studies comparing the effectiveness of various treatments are lacking^[8]. Treatment choices are based on the sites involved, clinical severity, and how the disease progresses. Early recognition and treatment may decrease disease-related complications^[8].

What is the outlook?

Mucous membrane pemphigoid is usually brought under control with treatment, although this may take time. Most people will need long-term treatment to keep the condition under control^[1]. The disease severity and distribution is highly variable, from mild cases involving only the oral mucosa to severe cases involving multiple sites.

The most serious complications occur when the eyes, throat, or esophagus are involved. Eye involvement is potentially serious as it may cause scarring and affect eyesight, with severe cases potentially leading to blindness^[1][5]. Involvement of the larynx or esophagus can give rise to narrowing (strictures), which may be life-threatening^[3].

Since the consequences of this disease can be severe and limited treatment options are available once scarring develops, early diagnosis is critical^[3]. Care from a multidisciplinary team involving different specialists is very important to optimize outcomes and improve quality of life for people affected by this condition.