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Mucous Membrane Pemphigoid

NORD is very grateful to Carl M. Allen, DDS, MSD, Professor and Chair, Division of Oral and Maxillofacial Pathology and Radiology, The Ohio State University College of Dentistry, for assistance in the preparation of this report.

Synonyms of Mucous Membrane Pemphigoid

  • cicatricial pemphigoid
  • CP
  • MMP
  • mucous membrane pemphigoid

Disorder Subdivisions

  • Brunsting-Perry syndrome
  • localized cicatricial pemphigoid
  • vegetating cicatricial pemphigoid

General Discussion

Mucous membrane pemphigoid (MMP) is a group of rare chronic autoimmune disorders characterized by blistering lesions that primarily affect the various mucous membranes of the body. The mucous membranes of the mouth and eyes are most often affected. The mucous membranes of the nose, throat, genitalia, and anus may also be affected. The symptoms of MMP vary among affected individuals depending upon the specific site(s) involved and the progression of the disease. Blistering lesions eventually heal, sometimes with scarring. Progressive scarring may potentially lead to serious complications affecting the eyes and throat. In some cases, blistering lesions also form on the skin, especially in the head and neck area. The exact cause of MMP is unknown.

MMP has been known by many different names within the medical literature including benign mucous membrane pemphigoid, cicatricial (scarring) pemphigoid, and ocular cicatricial pemphigoid. In March of 2002, a consensus group of researchers determined that mucous membrane pemphigoid was the best designation for this group of disorders. The term "benign" mucous membrane pemphigoid was deemed inappropriate because of the potential for serious complications in some cases. The term "cicatricial" pemphigoid excluded affected individuals who do not develop scarring. Site-specific terms such as "ocular" cicatricial pemphigoid excluded individuals with multiple site involvement.

Symptoms

MMP 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, in most cases, 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 first 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 (breathing is cut off).

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. Involvement of the eyes may not be obvious at first, however, and only a special examination by an eye doctor (ophthalmologist) can detect the earliest scarring that develops just beneath the conjunctiva. 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. Adhesions may form between the eyelids (symblepharon) or between the eyelid and the eye itself. 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 develop blistering lesions affecting only 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 these patients, the skin of the head and neck is usually affected. Skin lesions may be either fluid-filled blisters (bullous) or reddish (erythematous) plaques, which may bleed or itch. Eventually they 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). Involvement of the scalp may lead to patchy areas of hair loss (alopecia).

MMP usually has a long duration with frequent remissions and recurrence.

Causes

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.

Affected Populations

Mucous membrane pemphigoid is a rare group of autoimmune blistering disorders that affects females twice as often as 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.

Related Disorders

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 "autoimmune blistering diseases" 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 in the mouth (oral lesions) but they may not be recognized as blisters because they break easily, soon after they are formed. Lesions will heal, but new blisters occur as the older ones are healing. The blisters may persist for several months before affecting other mucous membranes such as the esophagus, nose, eyelids (conjunctiva), and rectum. In some cases, the skin blisters may not develop for one to three years after oral lesions are noticed. Pressure on the border of the blisters causes them to spread. Pressure on normal-looking skin also 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 may present 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, purplish, angular bumps develop most commonly on the skin of the wrists, the ankles and the lower back. 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).

Standard Therapies

Diagnosis
A diagnosis of MMP 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 immunofluorescence. During a biopsy, a small sample of skin tissue is removed (biopsy) and microscopically examined. During direct immunofluorescence, the biopsied skin sample is tested to detect the presence of specific autoantibodies (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. If the patient has not seen an ophthalmologist, then an appointment should be made right away to have the eyes evaluated because treatment often depends on whether or not there is eye involvement. The earliest changes of scarring just underneath the lining of the eye (subepithelial fibrosis) are often asymptomatic and can only be detected by slit-lamp microscopic evaluation by an ophthalmologist. Such scarring interferes with the glands that produce the tear film, and this results in dryness of the eye. Affected patients may need to use artificial tears frequently to reduce damage to the eye.

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.

Some antibiotic drugs can affect the inflammatory process. One such drug is dapsone, a sulfa-type medication that may be used to treat mild cases of MMP. Special blood tests are needed before this drug is used, however. A combination of the antibiotic drug tetracycline and nicotinamide (vitamin B3) can also be helpful in some cases of MMP. Rapid improvement of the lesions of MMP have been seen with this regimen.

Individuals with widespread or severe MMP may be treated with systemic corticosteroids such as prednisone and/or immunosuppressive drugs such as mycophenolate mofetil, cyclophosphamide or azathioprine. Individuals with eye involvement, severe or rapidly progressing MMP may be treated with prednisone combined with cyclophosphamide, mycophenolate mofetil, or azathioprine. Patients who are taking the above mentioned drugs must be carefully monitored by a dermatologist or physician familiar with their use because of potentially significant side effects.

In rare cases, surgical procedures such as a tracheostomy may become necessary if scarring narrows the airway and breathing becomes difficult. 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 if the esophagus is involved. Surgical removal (ablation) of ingrown eyelashes may be performed if the eyes are affected.

Other treatment is symptomatic and supportive.

Investigational Therapies

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.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/

Mucous Membrane Pemphigoid Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)

Other Organizations:

References

TEXTBOOKS
Neville B, Damm DD, Allen CM, and Bouquot J, eds. Oral and Maxillofacial Pathology, 3rd ed. Philadelphia, PA: Saunders Co.: 2009.

Bolognia JL, Jorizzo JL, and Schaffer JV, eds. Dermatology, 3rd ed. Philadelphia, PA: Saunders Co.: 2012

JOURNAL ARTICLES
Schmidt E and Zillikens D: Pemphigoid diseases. Lancet 2013;381:320-332.

Chan LS: Ocular and oral mucous membrane pemphigoid (cicatricial pemphigoid). Clin Dermatol 2012;30:34-37.

Knudson RM, et al: The management of mucous membrane pemphigoid and pemphigus. Dermatol Ther 2010;23:268-280.

Saw VPJ and Dart JKG: Ocular mucous membrane pemphigoid. Ocular Surface 2008;6:128-142.

Scully C and Lo Muzio L: Oral mucosal diseases: Mucous membrane pemphigoid. Br J Oral Maxillofac Surg 2008;46:358-366.

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.

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.

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.

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

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

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

INTERNET
Frieman A. Cicatricial Pemphigoid. eMedicine Journal. Last Update:January 24, 2013 http://emedicine.medscape.com/article/1062534-overview Accessed: March 12, 2013.

Foster CS and Hamam R. Cicatricial Pemphigoid. eMedicine Journal. Last Update:August 23, 2011: http://emedicine.medscape.com/article/1191261-overview Accessed:March 12, 2013.

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2013/03/19 00:00:00 GMT+0

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