Information on the following diseases can be found in the Related Disorders section of this report:

• Intermittent Mucosal Pemphigoid
• Gingivitis
• Bullous Pemphigoid
• Epidermolysis Bullosa Acquisita
• Pemphigus Vulgaris

Mucous membrane pemphigoid is characterized by the development of recurring blistering skin lesions affecting the mucous membranes of the body. These lesions may result in scarring of the affected area. Specific symptoms and severity vary from case to case depending upon the specific site(s) involved. It is important to note that affected individuals will not have all of the symptoms listed below.

The mucous membranes lining the mouth and eyes are most commonly affected. In some cases, the initial sign of MMP is a red and blistered mouth. The gums (gingivae), roof of the mouth (palate), and the mucous membrane lining the inner cheek (buccal mucosa) may be affected. Involvement of the gums usually results in very red, tender gums that bleed easily and tend to slough off in shreds or sheets. Blistering lesions may spread to affect the tube that carries food from the mouth to the stomach (esophagus) as well as the voice box (larynx) potentially resulting in difficulty swallowing (dysphagia) and hoarseness. After these lesions heal, progressive scarring may occur resulting in serious complications including narrowing (stenosis) of the esophagus and/or the larynx. In addition, the opening between the vocal cords (supraglottic region) may also narrow (supraglottic stenosis). In rare severe cases, such symptoms can ultimately result in life-threatening complications such as asphyxiation.

In many cases of MMP, the mucous membranes lining the eyes (conjunctiva) may be involved. Inflammation of conjunctiva (conjunctivitis) or erosions forming on the conjunctiva may be the initial signs of ocular involvement in MMP. In most cases, one eye is involved first and the second eye becomes involved later, usually with two years. Ocular symptoms may include pain or grittiness of the eye, increased pressure within the eye (glaucoma), abnormal inward turning of the eyelid (entropion), and abnormal inward turning of the eyelashes (trichiasis) potentially causing irritation of the eyeball. In some cases, MMP may progress to cause clouding (opacity) of the corneas, loss of vision and, potentially, blindness.

In some cases, affected individuals may only develop blistering lesions affecting the eyes or the mouth with no involvement of other mucosal sites. Scarring occurs with less frequency in cases of MMP that only involve the mucous membranes of the mouth (oral mucosa). Additional sites where lesions may form include mucous membranes of the nose, genitalia, and anus. Pain, bleeding and scarring may occur at these sites. Urinary and sexual dysfunction may result secondary to genital involvement.

In approximately 20-30 percent of cases, the skin may become involved. In most cases, skin of the head and neck may be affected. Skin lesions may bleed, itch and eventually scar upon healing. Scarring may result in areas of discoloration of the skin (known as hyperpigmentation when it is darkened patches and hypopigmentation when it is light patches). Skin lesions may be either fluid-filled blisters (bullous) or reddish (erythematous) plaques. Involvement of the scalp may lead to patchy areas of hair loss (alopecia).

MMP usually has a long duration with frequent remissions and recurrence.
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The exact cause of mucous membrane pemphigoid is unknown. MMP is an autoimmune disorder. Autoimmune disorders are caused when the body's natural defenses (antibodies or immunoglobulins) against "foreign" or invading organisms (antigens) begin to attack healthy tissue for unknown reasons. The term autoantibody is used to describe antibodies that are created to attack healthy tissue. The term autoantigen (self antigen) is used to describe the normal tissues and cells of the body that are targeted by the autoantibodies.

In patients who have MMP, autoantibodies are being produced that attack the basement membrane zone (BMZ) of the epithelium. The BMZ can be thought of as a sort of "glue" that holds the outer layer of skin (epidermis or oral epithelium) onto the underlying tissues. Once this glue is attacked and destroyed by the autoantibodies, the skin is no longer tacked down, allowing it to lift off and produce blisters.

Researchers believe that in some cases affected individuals may have a genetic susceptibility to developing some forms of MMP. In these cases several factors may contribute to the development of the disorder including immunological, genetic, environmental, and/or other factors.

In some cases, MMP may be triggered secondary to the use of certain drugs. Skin lesions associated with some cases of MMP may appear following trauma to the affected area. Some cases of MMP affecting the eyes may become apparent after eye (ocular) surgery such as cataract removal.
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Mucous membrane pemphigoid is a rare group of autoimmune blistering disorders that affects females twice as often than males. The average age of onset of MMP is during the seventh decade. However, the disorder can occur at any age. The exact incidence of MMP is unknown. Because the disorder is difficult to identify, many researchers believe it is under-diagnosed.
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Symptoms of the following disorders can be similar to those of mucous membrane pemphigoid. Comparisons may be useful for a differential diagnosis:

Bullous pemphigoid (BP) is a chronic skin disease usually affecting the elderly that is characterized by firm, large blisters that develop on normal-appearing or reddened skin usually around cuts or scars. Within weeks, blisters spread to skin of the flexor (muscles that contract or flex) areas, groin, armpit, and the abdomen. Mucous membranes seldom are affected and tend to heal quickly. The blisters have little tendency to spread, but heal quickly when they do. There is, however, severe irritation. Bullous pemphigoid is an autoimmune disorder. (For more information on this disorder, choose "Bullous Pemphigoid" as your search term in the Rare Disease Database.)

Epidermolysis bullosa acquista (EBA) is a rare autoimmune disorder of the skin that typically affects middle-aged and elderly people. Trauma to the skin can cause blisters on the elbows, knees, pelvis, buttocks, and/or scalp. Increased levels of IgG (an immunoglobulin) are usually found around the blisters. After the blisters heal, scars usually remain. In some cases, mucous membrane involvement may be present. (For more information on this disorder, choose "Epidermolysis Bullosa Acquista" as your search term in the Rare Disease Database.)

Pemphigus vulgaris (PV) is an autoimmune disorder that usually affects the middle-aged and elderly. Blisters usually start as in the mouth (oral lesions). The blisters may persist for several months before appearing in other mucous membranes such as the esophagus, nose, eyelids (conjunctiva), and rectum. In some cases, the skin may not become involved for one to three years after oral lesions are noticed. The blisters are soft, break easily, and heal poorly. Pressure on the border of the blisters causes them to spread. Pressure on normal-looking skin can cause a blister to form (Nikolsky's sign) in patients with pemphigus vulgaris. (For more information on this disorder, choose "Pemphigus" as your search term in the Rare Disease Database.)

Lichen planus (LP) is a relatively common disorder of the skin that usually presents first as a network of interlacing fine white lines affecting the mucosa of the mouth (buccal mucosa). The cause remains unknown. There is an erosive form of oral lichen planus that can produce red, sore, bleeding, gums and sores on the lining of the cheeks similar to MMP. When the skin is involved, small, angular eruptions are the more obvious signs and these may coalesce into rough scaly patches. The disorder affects women more frequently than men. (For more information on this disorder, choose "Lichen Planus" as your search term in the Rare Disease Database.)

Brunsting-Perry syndrome is an old medical term used to describe a form of localized cicatricial pemphigoid in which blistering lesions affect the skin, usually of the head and neck, but do not affect any of the mucous membranes of the body. The skin lesions usually leave scars upon healing. The blisters associated with Brunsting-Perry syndrome may occur due to trauma.

Additional disorders may involve lesions affecting the mucous membranes. These disorders include Stevens-Johnson syndrome, erythema multiforme minor, paraneoplastic pemphigus, and linear IgA bullous dermatosis. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database).
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Diagnosis
A diagnosis of mucous membrane pemphigoid is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic findings and certain tests known as a biopsy and direct immunoflourescence. During a biopsy, a small sample of skin tissue is removed (biopsy) and microscopically examined. During direct immunoflourescence, the biopsied skin sample is tested to detect the presence of specific antibodies (e.g., IgA, IgG, and C3).

Treatment
The treatment of MMP is directed toward the specific symptoms that are apparent in each individual. Treatment depends upon the specific area(s) of the body affected, the severity of the disease, and its rate of progression. Treatment may require the coordinated efforts of a team of specialists. Dental specialists (oral pathologists), specialists who assess and treat skin problems (dermatologists), specialists who assess and treat eye problems (ophthalmologists), specialists who assess and treat ear and throat problems (otolaryngologists), and other healthcare professionals may need to systematically and comprehensively plan an affected individual's treatment.

No large-scale, multi-center studies have been done regarding the treatment of MMP. The usual treatment for MMP is certain drugs, used either singly or in various combinations. Corticosteroid drugs are often prescribed for affected individuals. Topical corticosteroids such as fluocinonide can relieve inflammation and itching in mild cases such as those that affect oral cavity only or the oral cavity and the skin. Other more potent gel preparations involving betamethasone dipropionate or clobetasol may also be used.

Individuals with widespread MMP may be treated with systemic corticosteroids such as prednisone and/or immunosuppressive drugs such as cyclophosphamide or azathioprine. Individuals with severe or rapidly progressing MMP may be treated with a combination of prednisone and cyclophosphamide.

Antibiotic drugs such as dapsone may also be used to relieve inflammation in mild cases of MMP. If dapsone is unsuccessful, a combination of prednisone and cycophosphamide may be necessary. All of the above mentioned drugs must be carefully monitored by a dermatologist or physician familiar with their use to guard because of potential side effects.

In rare cases, surgical procedures such as a tracheostomy may become necessary. A tracheostomy is a procedure in which a tube is inserted through a surgical opening in the windpipe (trachea) to assist breathing. A procedure to widen (dilate) a narrowed or obstructed esophagus may also be necessary. Surgical removal (ablation) of ingrown eyelashes may be performed.

Other treatment is symptomatic and supportive.
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Researchers are studying cornea epithelial stem-cell transplantation for the treatment of severe ocular-surface disorders including ocular MMP. Initial studies have demonstrated that transplantation of corneal epithelial stem cells can restore useful vision in some cases. More research is necessary to determine the long-term safety and effectiveness of this procedure as a treatment option for individuals with severe ocular symptoms of MMP.

Intravenous immunoglobulin (IVIg) therapy is being studied as a potential treatment option for individuals with MMP. Initial findings demonstrated that IVIg therapy was effective in achieving remission of symptoms associated with MMP. More research is necessary to determine the long-term safety and effectiveness of this potential treatment for individuals with MMP.

In the past few years, several people with MMP have been treated with a combination of the antibiotic drug tetracycline and a nicotinamide (vitamin B3). Affected individuals have shown rapid improvement of multiple mucocutaneous lesions under this regimen. More research is necessary to determine the long-term safety and effectiveness of tetracycline/nicotinamide combination therapy for individuals with MMP.

One individual with MMP was treated with the drug leflunomide, which is normally used to treat individuals with rheumatoid arthritis. Leflunomide was effective in relieving the symptoms of MMP and eight months after treatment there had been no relapse. More research is necessary to determine the long-term safety and effectiveness of this potential treatment for individuals with MMP.
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TEXTBOOKS
Champion RH, et al., eds. Textbook of Dermatology. 5th ed. Cambridge, MA: Blackwell Scientific Publications; 1992:1652-4.

REVIEW ARTICLES
Boedeker CC, et al. Cicatricial pemphigoid in the upper aerodigestive tract: diagnosis and management in severe laryngeal stenosis. Ann Otol Rhinol Laryngol. 2003;112:271-5.

Parisi E, et al. Modification to the approach of the diagnosis of mucous membrane pemphigoid: a case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003;95:182-6.

Chan LS, et al. The first international consensus on mucous membrane pemphigoid: definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators. Arch Dermatol. 2002;138:370-9.

Miziara ID, et al. Cicatricial pemphigoid: report of five cases. Ear Nose Throat J. 2002;81:442-8.

Kirtschig G, et al. Interventions for mucous membrane pemphigoid/cicatricial pemphigoid and epidermolysis bullosa acquista: a systematic review of the literature. Arch Dermatol. 2002;47:S193-5.

Fleming TE, Korman NJ. Cicatricial pemphigoid. J Am Acad Dermatol. 2000;43:571-91.

Ahmed AR, et al. Cicatricial pemphigoid. J Am Acad Dermatol. 1991;24:987-1001.

Leenutaphong V, et al. Localized cicatricial pemphigoid (Brunsting-Perry): electron microscopic study. J Am Acad Dermatol. 1989;21:1089-93.

JOURNAL ARTICLES
Sami N, et al. Intravenous immunoglobulin therapy in patients with multiple mucosal involvement in mucous membrane pemphigoid. Clin Immunol. 2002;102:59-67.

Miserocchi E, et al. The effect of treatment and its related side effects in patients with severe ocular cicatricial pemphigoid. Ophthalmology. 2002;109:111-8.

Carrozzo M, et al. HLA-DQB1 alleles in Italian patients with mucous membrane pemphigoid predominantly affecting the oral cavity. Br J Dermatol. 2001;145:805-8.

Kreyden OP, et al. Successful therapy with tetracycline and nicotinamide in cicatricial pemphigoid. Hautarzt. 2001;52:247-50

Tsubota K, et al. Treatment of severe ocular-surface disorders with corneal epithelial stem-cell transplantation. N Engl J Med. 1999;340:1697-703.

Chan LS. Human skin basement membrane in health and in autoimmune disease. Front Biosci. 1997;2:343-52.

Chan LS, et al. Laminin-6 and laminin-5 are recognized by autoantibodies in a subset of cicatricial pemphigoid. J Invest Dermatol. 1997;108:6486-53.

FROM THE INTERNET
Rico MJ. Cicatricial Pemphigoid. eMedicine Journal. 2001;3:11pp.

Foster CS. Cicatricial Pemphigoid. eMedicine Journal. 2001;3:11pp.