Mastocytosis
Encyclopedia
Mastocytosis is a group of rare
disorders of both children and adults caused by the presence of too many mast cell
s (mastocytes) and CD34
+ mast cell precursors in a person's body.
, the additional chemicals can cause a number of symptoms which can vary over time and can range in intensity from mild to severe. Because mast cells play a role in allergic reactions, the symptoms of mastocytosis often are similar to the symptoms of an allergic reaction. They may include, but are not limited to:
s are located in connective tissue
, including the skin
, the linings of the stomach and intestine, and other sites. They 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 wound
s, mast cells may play a part in wound healing. For example, the typical itching felt 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 vessel
s (angiogenesis
). No one with too few or no mast cells has been found, which indicates to some scientists we may not be able to survive with too few mast cells.
Mast cells express a cell surface receptor, c-kit (CD117
), which is the receptor for stem cell factor (scf). In laboratory studies, scf appears to be important for the proliferation of mast cells. Mutations of the c-kit receptor, leading to uncontrolled stimulation of the receptor, is a cause for the disease. Inhibiting the tyrosine kinase
receptor with imatinib
(see below) may reduce the symptoms of mastocytosis.
(cutaneous mastocytosis, see above) by seeing the characteristic lesions that 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
.
In rare cases in which mastocytosis is cancerous or associated with a blood disorder, the patient may have to use steroid
s and/or chemotherapy
. The novel agent imatinib
(Glivec or Gleevec) has been found to be effective in certain types of mastocytosis.
There are clinical trials currently underway testing stem cell transplants as a form of treatment.
There are support groups for persons suffering from mastocytosis. Involvement can be emotionally therapeutic for some patients.
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.
Rare disease
A rare disease, also referred to as an orphan disease, is any disease that affects a small percentage of the population.Most rare diseases are genetic, and thus are present throughout the person's entire life, even if symptoms do not immediately appear...
disorders of both children and adults caused by the presence of too many mast cell
Mast cell
A mast cell is a resident cell of several types of tissues and contains many granules rich in histamine and heparin...
s (mastocytes) and CD34
CD34
CD34 molecule is a cluster of differentiation molecule present on certain cells within the human body. It is a cell surface glycoprotein and functions as a cell-cell adhesion factor. It may also mediate the attachment of stem cells to bone marrow extracellular matrix or directly to stromal cells...
+ mast cell precursors in a person's body.
Classification
Mastocytosis can occur in a variety of forms:- Most cases are cutaneous (confined to the skin only), and there are several forms. The most common cutaneous mastocytosis is urticaria pigmentosaUrticaria pigmentosaUrticaria pigmentosa is the most common form of cutaneous mastocytosis...
(UP), more common in children. Telangiectasia macularis eruptiva perstansTelangiectasia macularis eruptiva perstansTelangiectasia macularis eruptiva perstans is persistent, pigmented, asymptomatic eruption of macules usually less than 0.5cm in diameter with a slightly reddish-brown tinge.-References:...
(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 liverLiverThe liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, spleenSpleenThe spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
, lymph nodeLymph nodeA lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...
s, and bone marrowBone marrowBone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
. - Other types of mast cell disease include:
- Mast cell leukemiaMast cell leukemiaMast cell leukemia is an extremely aggressive subtype of acute myeloid leukemia that usually occurs de novo but can, rarely, evolve from transformation of chronic myeloid leukemia into the more aggressive acute myeloid leukemia. In a small proportion of cases, acute mast cell leukemia may evolve...
- Mast cell sarcoma
- Mast cell leukemia
Signs and symptoms
When too many mast cells exist in a person's body and undergo degranulationDegranulation
Degranulation is a cellular process that releases antimicrobial cytotoxic molecules from secretory vesicles called granules found inside some cells...
, the additional chemicals can cause a number of symptoms which can vary over time and can range in intensity from mild to severe. Because mast cells play a role in allergic reactions, the symptoms of mastocytosis often are similar to the symptoms of an allergic reaction. They may include, but are not limited to:
- Fatigue
- Skin lesions (urticaria pigmentosaUrticaria pigmentosaUrticaria pigmentosa is the most common form of cutaneous mastocytosis...
) and itchItchItch is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to classify it as any one type of sensory experience. Modern science has shown that itch has many similarities to pain, and while both are unpleasant sensory experiences, their behavioral response...
ing - Abdominal discomfortAbdominal painAbdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
- NauseaNauseaNausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and vomitingVomitingVomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose... - DiarrheaDiarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
- Food and drug intolerance
- Olfactive intolerance
- Infections (bronchitis, rhinitis, and conjunctivitis)
- Ear/nose/throat inflammation
- AnaphylaxisAnaphylaxisAnaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
(shock from allergic or immune causes) - Episodes of very low blood pressureHypotensionIn physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
(including shock) and faintnessSyncope (medicine)Syncope , the medical term for fainting, is precisely defined as a transient loss of consciousness and postural tone characterized by rapid onset, short duration, and spontaneous recovery due to global cerebral hypoperfusion that most often results from hypotension.Many forms of syncope are... - BoneBone painBone pain is a debilitating form of pain emanating from the bone tissue. It occurs as a result of a wide range of diseases and/or physical conditions and may severely impair the quality of life for patients who suffer from it...
or muscle pain - Decreased bone density
- Headache
- Ocular discomfort
- Malabsorption
Pathophysiology
Mast cellMast cell
A mast cell is a resident cell of several types of tissues and contains many granules rich in histamine and heparin...
s are located in connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
, including the skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
, the linings of the stomach and intestine, and other sites. They play an important role in helping defend these tissues from disease. By releasing chemical "alarms" such as histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
, mast cells attract other key players of the immune defense system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
to areas of the body where they are needed.
Mast cells seem to have other roles as well. Because they gather together around wound
Wound
A wound is a type of injury in which skin is torn, cut or punctured , or where blunt force trauma causes a contusion . In pathology, it specifically refers to a sharp injury which damages the dermis of the skin.-Open:...
s, mast cells may play a part in wound healing. For example, the typical itching felt around a healing scab may be caused by histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
released by mast cells. Researchers also think mast cells may have a role in the growth of blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s (angiogenesis
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
). No one with too few or no mast cells has been found, which indicates to some scientists we may not be able to survive with too few mast cells.
Mast cells express a cell surface receptor, c-kit (CD117
Cluster of differentiation
The cluster of differentiation is a protocol used for the identification and investigation of cell surface molecules present on white blood cells, providing targets for immunophenotyping of cells...
), which is the receptor for stem cell factor (scf). In laboratory studies, scf appears to be important for the proliferation of mast cells. Mutations of the c-kit receptor, leading to uncontrolled stimulation of the receptor, is a cause for the disease. Inhibiting the tyrosine kinase
Tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....
receptor with imatinib
Imatinib
Imatinib is a drug used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec or Glivec as its mesylate salt, imatinib mesilate . It is used in treating chronic myelogenous leukemia , gastrointestinal stromal tumors and some other diseases...
(see below) may reduce the symptoms of mastocytosis.
Diagnosis
Doctors can diagnose urticaria pigmentosaUrticaria pigmentosa
Urticaria pigmentosa is the most common form of cutaneous mastocytosis...
(cutaneous mastocytosis, see above) by seeing the characteristic lesions that are dark-brown and fixed. A small skin sample (biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
) may help confirm the diagnosis.
By taking a biopsy from a different organ, such as the bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
, 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
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
and sometimes in the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
.
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, especially because it typically occurs secondary to another condition, and thus may occur more frequently than assumed.Treatment
There is currently no cure for mastocytosis, but there are a number of medicines to help treat the symptoms:- AntihistamineAntihistamineAn H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...
s 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 stabilizerMast cell stabilizerMast cell stabilizers are cromone medications used to prevent or control certain allergic disorders. They block a calcium channel essential for mast cell degranulation, stabilizing the cell and thereby preventing the release of histamine and related mediators. One suspected pharmacodynamic...
s help prevent mast cells from releasing their chemical contents. Cromolyn sodium oral solution (Gastrocrom / CromoglicateCromoglicateCromoglicic acid is traditionally described as a mast cell stabilizer, and is commonly marketed as the sodium salt sodium cromoglicate or cromolyn sodium...
) is the only medicine specifically approved by the U.S. FDA for the treatment of mastocytosis. KetotifenKetotifenKetotifen is a second-generation H1-antihistamine and mast cell stabilizer. It is most commonly sold in as a salt of Fumaric Acid, Ketotifen fumarate, and is available in two forms. In its ophthalmic form, it is used to treat allergic conjunctivitis, or the itchy red eyes caused by allergies. In...
is available in Canada and Europe, but is only available in the U.S. as eye drops (Zaditor). - Proton pump inhibitorProton pump inhibitorProton-pump inhibitors are a group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today. The group followed and has largely superseded another group of pharmaceuticals with similar...
s help reduce production of gastric acid, which is often increased in patients with mastocytosis. Excess gastric acid can harm the stomach, esophagus and small intestine. - EpinephrineEpinephrineEpinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
constricts blood vessels and opens airways to maintain adequate circulation and ventilation when excessive mast cell degranulation has caused anaphylaxisAnaphylaxisAnaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
. - SalbutamolSalbutamolSalbutamol or albuterol is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease. It is marketed as Ventolin among other brand names....
and other beta-2 agonists open airways that can constrict in the presence of histamine. - Corticosteroids can be used topically, inhaled, or systemically to reduce inflammation associated with mastocytosis.
- AntidepressantAntidepressantAn antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
s are an important and often overlooked tool in the treatment of mastocytosis. Depression and other neurological symptoms have been noted in mastocytosis. Some antidepressants, such as doxepinDoxepinDoxepin is a psychotropic agent with tricyclic antidepressant and anxiolytic properties, known under many brand-names such as Aponal, the original preparation by Boehringer-Mannheim, now part of the Roche group; Adapine, Doxal , Deptran, Sinquan and Sinequan...
, are themselves potent antihistamines and can help relieve physical as well as cognitive symptoms.
- DihydropyridinesDihydropyridinesDihydropyridine is a molecule based upon pyridine, and the parent of a class of molecules that have been semi-saturated with two substituents replacing one double bond. They are particularly well known in pharmacology as L-type calcium channel blockers....
, calcium channel blockerCalcium channel blockerA calcium channel blocker is a chemical that disrupts the movement of calcium through calcium channels.CCB drugs devised to target neurons are used as antiepileptics. However, the most widespread clinical usage of calcium channel blockers is to decrease blood pressure in patients with...
s, are sometimes used to treat high blood pressureHypertensionHypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
. At least one clinical study suggested nifedipineNifedipineNifedipine is a dihydropyridine calcium channel blocker...
, one of the dihydropyridines, may reduce mast cell degranulation in patients who exhibit urticaria pigmentosaUrticaria pigmentosaUrticaria pigmentosa is the most common form of cutaneous mastocytosis...
. A 1984 study by Fairly et al. included a patient with symptomatic urticaria pigmentosa who responded to nifedipine at dose of 10 mg po tid. However, nifedipine has not been approved by the FDA for treatment of mastocytosis.
In rare cases in which mastocytosis is cancerous or associated with a blood disorder, the patient may have to use steroid
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
s and/or chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
. The novel agent imatinib
Imatinib
Imatinib is a drug used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec or Glivec as its mesylate salt, imatinib mesilate . It is used in treating chronic myelogenous leukemia , gastrointestinal stromal tumors and some other diseases...
(Glivec or Gleevec) has been found to be effective in certain types of mastocytosis.
There are clinical trials currently underway testing stem cell transplants as a form of treatment.
There are support groups for persons suffering from mastocytosis. Involvement can be emotionally therapeutic for some patients.
Research
National Institute of Allergy and Infectious DiseasesNational Institute of Allergy and Infectious Diseases
The National Institute of Allergy and Infectious Diseases is one of the 27 institutes and centers that make up the National Institutes of Health , an agency of the United States Department of Health and Human Services...
scientists have been studying and treating patients with mastocytosis for several years at the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
(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.