Mastocytosis is a disorder found in both children and adults which results from too many mast cells in the body. Found most commonly in the skin, stomach lining, intestine, bones and connective tissue they play an important role in helping the immune system to fight disease and infection. There are several types of mastocytosis recognized in the skin (cutaneous) while those that also involve the internal organs are called systemic. Maculopapular Cutaneous Mastocytosis (MPCM) (formerly known as Urticaria Pigmentosa (UP)) is the most common cutaneous mastocytosis pattern and involves pink or brown marks on the skin. In children the spots can be small or large, where in adults they are most commonly small and are sometimes thought to be freckles.
Mastocytosis is caused in most adult patients by a genetic change in a protein called KIT on the mast cell which results in too many accumulating in different parts of the body. Increased numbers of mast cells show as pink or dark marks that may itch. There are different patterns of this rare disease and all types can cause anaphylactic reactions. The condition is estimated to affect one person per 10,000-30,000 people.
Diagnosis of Mastocytosis
Mastocytosis can be diagnosed by a doctor from a range of specialties, depending on which symptoms the patient has when the condition is first suspected. Most common is a dermatologist, but a gastroenterologist, allergist or haematologist may be the first consultant to get involved.
Skin lesions are generally diagnosed via punch biopsy (a small skin sample stained for mast cells and inspected under the microscope) to confirm the presence of an abnormal number of mast cells, which may also have an unusual shape. Experienced dermatologists may feel confident diagnosing a child by inspecting the skin lesions, and perhaps rubbing a lesion to see if it because raised and irritated from the friction. This is called Darier’s sign. Most, but not all mastocytosis skin lesions will become raised with rubbing, so a negative Darier’s sign (no response) does not rule out mastocytosis. In children with very reactive skin lesions, testing for Darier’s sign can cause a whole-body (systemic) reaction, so this should be approached with caution in those circumstances.
Tryptase, a protein released by some mast cells, can be tested via blood test. In adult mastocytosis patients it is often (but not always) elevated. It significantly raised tryptase is one criteria doctors might use in identifying patients in whom the further step of a bone marrow biopsy is warranted. A level of greater than 20 ng/ml is suggestive of bone marrow involvement. A normal tryptase level is possible even in systemic mastocytosis. Tryptase should be tracked over time for trends and to decide when further bone marrow biopsies are needed.
A bone marrow biopsy may be recommended if there are signs that point to systemic mastocytosis. Bone marrow biopsies are rarely done in children. A bone marrow biopsy takes a sample from inside the bone so that a pathologist can see how many mast cells are present, how they are distributed in the bone marrow and how the mast cells are shaped. This procedure is always done under the care of a haematologist.
Scans check for enlargement of the liver or spleen if systemic disease is suspected. All adult patients should have periodic bone (DEXA) scans to assess bone manifestations and consider treatments to prevent osteoporosis and fractures.
Bone Marrow Biopsies are performed to confirm a diagnosis of systemic mastocytosis, and to understand which form of the disease is present and track progression.
Cutaneous Mastocytosis (CM)
Not all mastocytosis patients have skin involvement, but many do.
Urticaria Pigmentosa is the most common pattern in both adults and children, with many small pink/brown marks that occur on the body but usually spare the face. They can become raised and red when irritated and resolve back to flat and less vibrant. In adults the lesions are freckle-sized or slightly larger, whereas in children they are often larger. Also known as Maculo-Papular Cutaneous Mastocytosis.
Diffuse Cutaneous Mastocytosis is seen in children. DCM often presents at birth or within the first few months. The skin is thickened and can blister extensively. (Occasionally patients are incorrectly diagnosed as having been scalded.) Children with DCM are likely to suffer from symptoms of mast cell mediator release. Rare
Mastocytoma is usually seen in infancy – often a one or several swellings larger than urticaria pigmentosa that can blister. Rare
Telangiectasia Macularis Eruptiva Perstans (TMEP) Persistent pink patches on the body in adults. Flushing and itching with fine blood vessels seen. Rare
Indolent Systemic Mastocytosis (ISM) is the most common form, with perhaps 90% of adults having this type. ISM may remain unchanged through life or, very uncommonly (1-3%), progress to one of the other types mentioned below. Skin lesions are common. Life expectancy is similar to others of same age and gender in the general population. Most patients need treatment for symptoms of mast cell mediators. At present they are rarely treated with cytoreductive agents.
Smouldering Mastocytosis is a recently agreed upon diagnosis, made when there is higher burden of mast cells (mast cell infiltration of greater than 30% in the bone marrow, serum tryptase over 200 ng/ml and liver or spleen enlarged). These patients may be offered more aggressive treatment and are monitored more frequently.
Aggressive Mastocytosis is a rare and more serious variant that may also present with swelling of the lymph nodes, liver or spleen. These patients are less likely to have skin involvement. Cytoreductive treatments are standard.
Mast Cell Leukaemia is an exceptionally rare and aggressive condition. Skin lesions are not usually present. Cytoreductive treatment is standard.
Systemic Mastocytosis with an Associated Haematologic Neoplasm (SM-AHN) is diagnosed (via blood and bone marrow testing) when a patients has an associated blood disorder against a background of systemic mastocytosis. The blood disorder would be subject to standard treatments for that condition. Prognosis usually depends on the prognosis for the associated disorder.
Evolving diagnoses include MMA (Monoclonal Mast Cell Activation Syndrome) where patients meet some but not all criteria for a mastocytosis diagnosis (and often experience anaphylaxis); and Familial Hypertryptasemia in which multiple family members have high tryptase and symptoms of mast cell activation without increased mast cell numbers.
Treating ASM, SSM, SM-AHNMD and MCL
Patients with more advanced forms of mastocytosis may need treatment for mast cell mediator symptoms (as above), but the focus of their treatment will be decreasing the number of mast cells. They should receive that treatment from a haematologist with experience treating mastocytosis. There are several promising treatments in clinical trials in addition to medications already available. Please contact us for help in referring to an appropriate centre.