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

• Urticaria Pigmentosa
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Skin is the most common site of involvement. Urticaria pigmentosa lesions are small, brownish, flat or elevated spots that may be surrounded by reddened, itchy skin when stroked. These lesions tend to be more apparent on the areas of skin exposed to pressure or rubbing. When cases begin during childhood, the skin tends to be affected more than the other organs. Blistering of the skin lesions is seen exclusively in children younger than two years of age. Diffuse cutaneous mastocytosis is another form of mastocytosis seen in children. The skin is diffusely thickened and discolored, generally without individual distinct lesions in this form of mastocytosis.

Flushing and gastric acid hypersecretion due to mast cell-associated histamine are common complaints. Heartburn, stomach aches and diarrhea may occur. The liver, spleen and lymph nodes may become enlarged in a subset of patients. Bones affected by mastocytosis may become softened and deteriorate, although some new bone growth may occur with thickening of the outer portions or spongy inner areas of the bones. Massive mast cell degranulation may lead to life-threatening episodes of anaphylaxis. The most common triggers include, but are not limited to, certain medications like aspirin and other non-steroidal anti-inflammatory drugs, narcotics, radiocontrast material, and insect stings. These are similar in nature to severe allergic reactions and may involve hypotension, increased heart rate and loss of consciousness. Patients with an associated hematologic disorder may have symptoms of that disorder such as fatigue and weight loss.
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A genetic alteration (mutation) resulting in the overactivation of the receptor for mast cell growth factor (c-kit) has been identified in the abnormal mast cells in adult-onset mastocytosis. This mutation is believed to cause the abnormal accumulation of mast cells in certain tissues. The release of mediators produced by mast cells, such as histamine, heparin and prostaglandin D2, results in symptomatic episodes. Histamine is a natural chemical normally released during an allergic event that causes itching, wheezing, dilation of blood vessels, and hypersecretion of stomach acid.
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Mastocytosis affects males and females in equal numbers. It can begin during childhood or adulthood. Childhood-onset disease most commonly starts in the first two years of life.

Symptoms of the following disorder can be similar to those of Mastocytosis. Comparison may be useful for a differential diagnosis:

Urticaria Pigmentosa is a form of mast cell disease limited to the upper skin layer. A chronic eruption occurs characterized by brownish elevated spots (papules) which may be surrounded by reddened itchy skin when stroked. On the other hand, Mastocytosis is characterized by involvement of various organs with or without the skin symptoms. (For more information on this disorder, choose "Urticaria Pigmentosa" as your search term in the Rare Disease Database.)
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In October 2006, the FDA granted expanded approval to treat aggressive systemic mastocytosis with the cancer drug imatinib mesylate (Gleevec). For information on Gleevec, contact the drug’s manufacturer, Novartis, at:

Novartis International AG
CH-4002
Basel, Switzerland
www.novartis.com

Treatment of mastocytosis is directed at controlling the symptoms caused by mast cell mediators. H1 and H2 antihistamines are therefore cornerstones of the treatment. Cromolyn sodium can be especially effective for the treatment of some gastrointestinal symptoms. PUVA treatment may cause temporary attenuation of the urticaria pigmentosa lesions. Steroids may be necessary in selected patients unresponsive to standard therapy.

Subcutaneous injections of epinephrine can be self-administered by the patient in cases of severe anaphylactic episodes. This therapy should always be followed by evaluation of the patient in a medical facility.

Associated hematologic disorders should be treated by a blood specialist (hematologist).

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 website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

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

The MD Anderson Cancer Center in Houston, Texas, is currently (2006) recruiting patients with mastocytosis for a clinical trial of the drug, Gleevec. Interested parties should contact the principal investigator, Jorge E. Cortes, MD, at the Department of Leukemia, MD Anderson Cancer Center. His contact information is:

Jorge E. Cortes, MD
Phone: (713) 794-5783
Email: jcortes@mdanderson.org

To contact the MD Anderson Cancer Center:
Phone: 800-392-1611 (inside the US); 713-792-6161 (outside the U.S.)

More than 10 other clinical trials are currently underway (2006) to study the cause and treatment of mastocytosis. Interested persons may use the NIH information listed previously to access information about these studies. They include:

1. A clinical trial of stem cell transplantation sponsored by the National Heart, Lung, and Blood Institute (NHLBI) to treat systemic mastocytosis. The study will investigate the safety and efficacy of an experimental stem cell transplant procedure for treating this disease.

2. The National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health is sponsoring two studies to help determine growth factors that promote or inhibit mast cell proliferation in an effort to improve therapy. The reason for the proliferation of mast cells remains a mystery. These studies are aimed at providing some clues.

3. The NIAID is also sponsoring two other studies: One is an evaluation of children with mastocytosis to identify the cause of the disease and describe its course. The other is concerned with identifying bone marrow mast cells in patients with unexplained anaphylaxis, flushing or mastocytosis, and determining whether mastocytosis may be the underlying cause of unexplained anaphylaxis in some patients. Anaphylaxis is a hypersensitivity reaction in which patients may have flushing; hives; stuffy nose; red, itchy eyes; difficulty breathing; swelling of the tongue, throat, palms and soles; abdominal cramping; lightheadedness; decreased blood pressure and loss of consciousness.

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 154800; Last Update: 12/6/99.

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REVIEW ARTICLES
Tharp MD, Longley BJ Jr. Mastocytosis. Dermatol Clin. 2001;19:679-96, viii-ix.

Valent P, Horny HP, Escribano L, et al. Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res. 2001;25:603-25.

Marone G, Spadaro G, Granata F, et al. Treatment of mastocytosis: pharmacologic basis and current concepts. Leuk Res. 2001;25:583-94.

Longley BJ, Reguera MJ, Ma Y. Classes of c-KIT activating mutations: proposed mechanisms of action and implications for disease classification and therapy. Leuk Res. 2001;25:571-76.

Austen KF, Boyce JA. Mast cell lineage development and phenotypic regulation. Leuk Res. 2001;25:511-18.

Hartmann K, Henz BM. Mastocytosis: recent advances in defining the disease. Br J Dermatol. 2001;144:682-95.

Valent P, Schernthaner GH, Sperr WR, et al. Variable expression of activation-linked surface antigens on human mast cells in health and disease. Immunol Rev. 2001;179:74-84
Krishnaswamy G, Youngberg G. Acute and chronic urticaria. Challenges and considerations for primary care physicians. Postgrad Med. 2001;109:107-08, 111-14, 119-23.

Kumar S, Moody P. Mastocytosis. Pediatr Rev. 2001;22:33-34.

Worobec AS. Treatment of systemic mast cell disorders. Hematol Oncol Clin North Am. 2000;14:659-87, vii.

Hartmann K, Metcalfe DD. Pediatric mastocytosis. Hematol Oncol Clin North Am. 2000;14:579-623, vii.

Parker RI. Hematologic aspects of systemic mastocytosis. Hematol Oncol Clin North Am. 2000;14:557-68.

Soter NA. Mastocytosis and the skin. Hematol Oncol Clin North Am. 2000;14:537-55.

Taylor ML, Metcalfe DD. Kit signal transduction. Hematol Oncol Clin North Am. 2000;14:517-35.