The Mastocytosis Society,Inc. Information Sheet for Patients and Caregivers
This is a brief introduction for new patients and doctors who are unfamiliar with the management of mastocytosis. The information presented here, combined with that available in the cited references, provides a starting point from which to approach understanding, treating, and living with this rare disorder.
Mast cell disease, or mastocytosis, is characterized by the proliferation and accumulation of mast cells in a variety of tissues and can affect either sex at any age. Definite diagnosis is made by demonstrating an abnormal accumulation of mast cells in a biopsy, usually of the skin and/or bone marrow. Other causes for symptoms should be ruled out, and blood and urine testing for mast cell products may be suggestive of the diagnosis. When performed properly by experienced personnel with access to current information on recommended protocols the results of these tests will be useful in diagnosing and evaluating mastocytosis.
Mast cells are widely distributed in nearly every organ of the body, mainly close to blood and lymph vessels, nerve endings, and skin and mucous membrane surfaces. They develop from immature cells produced in the bone marrow, which migrate to the tissues where they mature.
Mast cells produce various chemicals which normally serve protective, inflammatory and regulatory functions as they interact with white blood cells and tissues. In mastocytosis these chemicals, or mediators, are abnormally abundant and cause symptoms.
Mast cell products (mediators)
Some mast cell products are stored in granules within the cell, and others are produced in response to stimulation by the immune system or by drugs, chemicals, or physical factors. Below is a table of some factors which can cause mast cells to release their products. Stress, strong emotions and estrogen can increase their effect.
The products present in granules and ready for immediate release on stimulation include histamine, heparin, tryptase, and chymase. These chemicals cause, and to some extent regulate, allergic and inflammatory changes, and are involved in tissue building or repair. In response to immune system activation of the mast cell, arachidonic acid within the cell is converted into prostaglandin D2 and leukotriene C4, which restrict air flow in the lungs, stimulate mucous formation, and attract some kinds of white blood cells.
Mast cells also generate several cytokines, which are proteins that interact with white blood cells and tissue cells to continue the allergic or inflammatory response.
Symptoms
The symptoms of mastocytosis vary from person to person and may occur as "attacks" or as simply fatigue and a feeling of ill health. Over time, symptoms may become more frequent and more severe. The rate of progression differs from person to person, and there may be an improvement in symptoms for long periods of time. The type and severity of symptoms can also vary greatly from person to person or from one episode to the next. Often, seemingly unrelated symptoms comprise an individual's personal pattern of mastocytosis. These may (or may not) include: flushing (temporary skin redness), itching, hives,bruising, and skin sensations such as tingling. Other symptoms experienced by many of the people with mastocytosis are nausea,vomiting, abdominal cramping, occasional or frequent diarrhea, and excess stomach acid or ulcers. The person may experience unexplained fractures, mild to severe pain in bones, joints, or muscles, enlargement of liver or spleen, bladder pain, heart palpitations or rapid heart beat, chest discomfort, shortness of breath, light-headedness, fatigue,weakness, weight loss, respiratory symptoms including asthma. There may be depression, poor memory or irritability; also intolerance to heat or cold or to a change in temperature. Other symptoms include headaches,fainting or near fainting, and recurrent anaphylaxis.
Treatment
Because there is not yet a cure for mastocytosis, treatment is aimed at reducing the frequency and severity of the release of mast cell products and at countering the effects of mast cell products which are inevitably released. Most patients will achieve relief of symptoms only by employing measures in both areas.
Avoidance of the factors which are known to cause a reaction for the individual patient, and cautious evaluation of other factors, such as those listed in the Table below, are important in the management of mastocytosis.
In using drugs to counter the effects of mast cell products,treatment must be tailored to the individual patient. Most commonly, H1 antihistamines such as chlorpheniramine or hydroxyzine are used to decrease the skin symptoms, vasodilation and mucous secreting actions of histamine. Stomach symptoms generally respond well to H2 antihistamines, such as cimetadine or ranitidine, which can also help reduce skin symptoms.
Aspirin or other non-steroidal anti-inflammatory drugs, if tolerated by the patient, provide relief from flushing and lightheadedness by blocking the body's production of prostaglandin D2. These drugs can cause unexpected severe reactions, though, and their use must be instituted cautiously under careful medical supervision.
Cromolyn (disodium cromoglycate) is a mast cell stabilizing drug which is frequently effective in reducing skin and gastrointestinal symptoms as well as mental and other systemic systems.
For severe diarrhea or malabsorption, collection of fluid in the abdominal cavity, and continued anaphylaxis which fails to respond to other measures, systemic corticosteroids may be required.
People with mastocytosis should carry injectable epinephrine, and they should know how to inject themselves if necessary to treat anaphylaxis.
There are other medications which may provide symptomatic relief if the ones mentioned above are ineffective or undesirable for a particular patient. No new medication or remedy should be started without careful consideration and close supervision, in case of an unexpected reaction.
Prognosis
It is not yet possible to predict the course of mastocytosis in any individual person. When involvement is limited to the skin, symptoms may improve or clear entirely, but it is also possible for the disease to progress to the systemic form. In about half the young children affected, symptoms disappear as they reach adulthood.
When the mast cell infiltration is systemic, symptoms may progress slowly over many years or may suddenly increase temporarily or permanently. The patient may even progress to the more serious categories of disease.
For the small percentage of patients who develop an associated hematological disorder, the course varies, and the prognosis depends on the associated hematological disease. ( 2 )
It is very important for the patient and the doctor to maintain good communication and to work cooperatively to achieve the best possible symptom control. Communication with other doctors caring for mastocytosis patients, and with other persons who have the disease, is important in order to maintain a support and information network. The affected person, or the child's parents, should strive to become educated about mastocytosis and to be aware of their individual needs and responses to triggering factors. A recognized medical warning device, such as a MedicAlert bracelet, should be worn, and extra caution is needed when undergoing dental work or surgery.
The Mastocytosis Society provides education and support to people with all forms of mast cell disease and their doctors, encourages research, and hopes to help find a cure for the disease. The Society also maintains a list of consultants who are available to advise professionals caring for a mastocytosis patient. Because of the rare nature of mast cell disease, we encourage doctors and patients to register with the Society in order to facilitate the communication and information exchange which will hasten the achievement of a cure.
Classification (adapted from (1) )
The following is a useful classification of the kinds of mastocytosis.
Cutaneous mastocytosis: Skin involvement only. This may include:
Urticaria pigmentosa: The typical rash of mastocytosis in the skin.
Solitary mastocytoma - a clump of mast cells restricted to a small area of the skin.
Diffuse cutaneous mastocytosis - skin involvement without urticaria pigmentosa or telangiectasia macularis eruptiva perstans (distinctive patches of discolored skin with small blood vessels on a reddened background. If the skin is heavily infiltrated with mast cells, the release of large amounts of mast cell products may cause systemic symptoms.
Systemic mastocytosis with or without skin involvement: Mast cell infiltration of at least one internal organ (like bone marrow or gastrointestinal tract). (2)
Mastocytosis in association with hematological disorder, with or without skin involvement: For example: leukemia, lymphoma, and myelodysplastic or myeloproliferative disorders.
Lymphadenopathic mastocytosis with eosinophilia, with or without skin involvement: Enlarged spleen and lymph nodes, infiltrated with mast cells, along with a blood count high in eosinophils.
Mast cell leukemia: This is rare but is the most serious form of masocytosis. The treatment and course of the disease is dictated by the leukemia.
Table of mast cell degranulators (adapted from (3) )
Allergens and other immunologic stimuli
Exercise
Physical stimuli (heat, cold, sunlight, friction, pressure, vibration)
Bacterial toxins
Venoms (snake and insect, especially bee and wasp stings)
Biologic polypeptides (released by intestinal roundworms, jellyfish,crayfish, and lobster)
Polymers (Compound 48/80, dextran)
Drugs: Aspirin, alcohol, narcotics (codeine, morphine), polymyxin B,amphotericin B, D-tubocurarine, quinine, iodine-containing radiographic dyes, scopolamine, gallamine,decamethonium, reserpine.
References:
1. Dean D. Metcalfe. Classification and Diagnosis of Mastocytosis:Current Status. J Invest Dermatol 96: 2S-4S, 1991.
2. Linda Golkar, Jeffrey D Bernhard. Seminar: Mastocytosis. Lancet 1997; 349:1379-85
3. Jack Longley, Thomas P. Duffy, Steven Kohn. Continuing Medical Education: The mast cell and mast cell disease. J Am Acad Dermatol 1995;32:545-61
Last update 6th December,2004