Mastocytosis
In medicine, mastocytosis is a group of rare disorders of both children and adults caused by the presence of too many mast cells (mastocytes) in a person's body.
Symptoms
Chemicals released by mast cells cause changes in the immune system leading to typical allergy symptoms such as itching, abdominal cramping, and even anaphylaxis (shock from allergic or immune causes).
When too many mast cells exist in a person's body, the additional chemicals can cause
- bone or muscle pain;
- Abdominal discomfort;
- Nausea and vomiting;
- Stomach ulcers;
- Diarrhea;
- Skin lesions;
- Episodes of very low blood pressure and faintness;
- Shock.
Diagnosis
Doctors can diagnose urticaria pigmentosa (cutaneous mastocytosis, see below) by seeing the characteristic lesions which are dark-brown and fixed. A small skin sample (biopsy) may help confirm the diagnosis.
By taking a biopsy from a different organ, such as the bone marrow, the doctor can diagnose systemic mastocytosis. Using special techniques on a bone marrow sample, the doctor looks for an increase in mast cells. Another sign of this disorder is high levels of certain mast-cell chemicals and proteins in a person's blood and sometimes in the urine.
Classification
The presence of too many mast cells, or mastocytosis, can occur in a variety of forms. Most cases are cutaneous (confined to the skin only).
There are two types of cutaneous mastocytosis. The most common is called urticaria pigmentosa (UP). It mostly affects children. Telangiectasia Macularis Eruptiva Perstans (TMEP) is a much rarer form of cutaneous mastocytosis that affects adults.
Systemic mastocytosis involves the internal organs, usually in addition to involving the skin. Mast cells collect in various tissues and can affect organs such as the liver, spleen, lymph nodes, and bone marrow.
Pathophysiology
Mast cells are located in connective tissue, including the skin, the linings of the stomach and intestine, and other sites. They may play an important role in helping defend these tissues from disease. By releasing chemical "alarms" such as histamine, mast cells attract other key players of the immune defense system to areas of the body where they are needed.
Mast cells seem to have other roles as well. Because they gather together around wounds, mast cells may play a part in wound healing. For example, the typical itching you feel around a healing scab may be caused by histamine released by mast cells. Researchers also think mast cells may have a role in the growth of blood vessels (angiogenesis). No one with too few or no mast cells has been found, which indicates to some scientists that we may not be able to survive with too few mast cells.
Mast cells express a cell surface receptor termed c-kit (CD117), which is the receptor for scf (stem cell factor). In laboratory studies, scf appears to be important for the proliferation of mast cells, and inhibiting the tyrosine kinase receptor with imatinib (see below) may reduce the symptoms of mastocytosis.
History
Scientists first described urticaria pigmentosa in 1869. Systemic mastocytosis was first reported by scientists in 1936.
Epidemiology
No one is sure how many people have either type of mastocytosis, but mastocytosis generally has been considered to be an "orphan disease" (orphan diseases affect 200,000 or fewer people in the United States). Mastocytosis, however, often may be misdiagnosed, and occur more frequently than assumed.
Treatment
There are a number of medicines to help treat the symptoms of mastocytosis:
- Antihistamines block receptors targeted by histamine released from mast cells. Both H1 and H2 blockers may be helpful.
- Leukotriene Antagonists block receptors targeted by leukotrienes released from mast cells.
- Mast Cell Stabilizers help prevent mast cells from releasing their chemical contents. Cromolyn Sodium Oral Solution (Gatrocrom, Registered Trademark) is the only medicine specifically approved by the FDA for the treatment of mastocytosis.
- Proton Pump Inhibitors help protect the stomach and small intestine from increased gastric acid production, which often results from elevated histamine levels in patients with mastocytosis.
- Epinephrine constricts blood vessels and opens airways to maintain adequate circulation and ventilation when excessive mast cell degranulation has caused Anaphylaxis.
- Albuterol and other beta-2 agonists open airways which can constrict in the presence of histamine
- Antidepressants are an important and often overlooked tool in the treatment of mastocytosis. The stress and physical discomfort of any chronic disease may increase the likelihood of a patient developing depression. Additionally, increased numbers of mast cells and increased levels of histamine in the brains of patients with mastocytosis may further promote depression. Some antidepressants such as Doxepin are themselves potent antihistamines and may help relieve physical as well cognitive symptoms.
In rare cases in which mastocytosis is cancerous or associated with a blood disorder, the patient may have to use steroids and/or chemotherapy. The novel agent imatinib (Glivec® or Gleevec®) has been found to be effective in certain types of mastocytosis.
Research
National Institute of Allergy and Infectious Diseases (NIAID) scientists have been studying and treating patients with mastocytosis for several years at the National Institutes of Health (NIH) Clinical Center.
Some of the most important research advances for this rare disorder include improved diagnosis of mast cell disease and identification of growth factors and genetic mechanisms responsible for increased mast cell production. Researchers are currently evaluating approaches to improve ways to treat mastocytosis.
Scientists also are focusing on identifying disease-associated mutations (changes in genes). NIH scientists have identified some mutations, which may help researchers understand the causes of mastocytosis, improve diagnosis, and develop better treatments.
Sources
- Based on an informative page by the National Institute of Allergy and Infectious Diseases (NIAID).