Author: Dr Anthony Yung, Dermatologist, Hamilton, New Zealand; Copy Editor: Clare Morrison; Chief Editor: Dr Amanda Oakley, Dermatologist, Hamilton, New Zealand, March 2014.

What is mastocytosis?

Mastocytosis is the term for a diverse group of conditions where a single (or clonal) population of mast cells accumulates in one or more tissues, for example skin, bone marrow, liver, spleen, gastrointestinal tract and lymph nodes.

The severity of symptoms depend on the number of mast cells in the tissues. A high load of mast cells leads to more severe symptoms. Cutaneous mastocytosis causes itching, swelling and blistering of the affected skin, particularly when it is rubbed or scratched.

What is the cause of mastocytosis?

Most forms of mastocytosis are caused by a mutation of the KIT gene on the 4q12 chromosome – a mutation that increases cellular reproduction. The c-KIT gene mutation creates an overgrowth of one cell line of mast cells. This is also called a “clonal expansion” of mast cells and leads to areas of abnormal skin that easily reddens, swells and itches. The c-KIT mutation can also lead to proliferation of mast cells within the bone marrow, resulting in systemic mastocytosis.

In some cases, the genetic disorder is inherited but in most cases it is spontaneous and there is no family history of mastocytosis.

What are mast cells?

Mast cells are normal cells in the body, usually found in the skin and other tissues. Mast cells have a role in the early steps of the body’s coordination of healing responses to an injury. Granules within the mast cells contain histamine and other chemicals.

Mast cell chemicals
histamine leukotriene C4 prostaglandin D2 carboxypeptidase
heparin cathespin G-like protease tryptase tumour necrosis factor-A
chymase interleukin-8 others  

When a mast cell is activated, these chemicals are released into the surrounding skin. Mast cell chemicals are mediators of inflammation, and cause the blood vessels to leak, resulting in localised itching, swelling, redness and sometimes blistering. This is what happens normally in insect bites and is thought to be a protective mechanism. For example, a mosquito injects saliva when it bites. The saliva triggers mast cell activation to a varying degree, depending on the individual's hypersensitivity to the saliva. The unpleasant itch soon persuades the person to try to avoid getting bitten again.

Rubbing an area of skin affected by mastocytosis may also activate the mast cells. The rubbed skin becomes reddened, swollen and itchy within a few minutes (Darier sign). In young children, the rubbed area may later blister.

How is mastocytosis diagnosed?

Cutaneous mastocytosis is usually diagnosed by its clinical appearance and positive Darier sign. However, skin biopsy may be helpful for confirmation.

Mast cells may be difficult to see on standard histology with haematoxylin and eosin staining (H&E). They can be identified with special stains, eg Giemsa, toluidine blue, Astra blue or immuno-histochemical stains like tryptase and CD117 (this stains for c-KIT membrane receptor on the surface of mast cells).

A blood test showing high levels of tryptase suggests systemic involvement.

What are the different types of mastocytosis?

Mastocytosis can be broadly characterised into two groups:

The World Health Organisation (WHO) classifies mastocytosis as:

Cutaneous mastocytosis

All forms of cutaneous mastocytosis are characterised by a positive Darier sign.

Approximately two-thirds of cases of cutaneous mastocytosis occur in children.

Cutaneous mastocytosis is classified as follows:

Solitary mastocytoma and maculopapular mastocytoma are the most common forms of mastocytosis in children.

Solitary mastocytoma

A solitary mastocytoma present in infancy as an itchy area of reddish or yellowish-brown thickened patch of skin. Mastocytomas generally completely or largely resolve in time.

Maculopapular cutaneous mastocytosis

Maculopapular cutaneous mastocytosis was previously called urticaria pigmentosa. It is the most common form of mastocytosis in adults and children.

Maculopapular mastocytosis in adults is unlikely to resolve with time. It may rarely lead to systemic involvement, where the mastocytosis spreads to more than one tissue (see below).

Diffuse cutaneous mastocytosis

Diffuse cutaneous mastocytosis presenting in infancy usually presents as diffuse redness of the skin (erythroderma), sometimes with widespread blistering of the skin. Adults and adolescents with diffuse cutaneous mastocytosis often have a generalised thickening leathery appearance and texture to most or all of their skin, with a positive Darier sign.

Telangiectatic cutaneous mastocytosis

Telangiectatic cutaneous mastocytosis is also known as telangiectasia macularis eruptiva perstans (TMEP). Telangietatic cutaneous mastocytosis is very persistent and may sometimes lead to systemic involvement. The name relates to extensive telangiectases.

Systemic mastocytosis

This includes:

Systemic mastocytosis is diagnosed by the presence of a certain number of features: 1 major criteria and 1 or more minor criteria or, alternatively, the presence of 3 minor criteria. Diagnosis requires tissue biopsy and use of special stains.

Major criteria

Minor criteria

Systemic mastocytosis occurs more commonly in adults than children (it is extremely rare in children).

Indolent systemic mastocytosis

Indolent systemic mastocytosis is the most common and least serious presentation of systemic mastocytosis in adults – it is characterised by a low mast cell burden (<30%), the presence of mediator-related symptoms such as flushing and diarrhoea, and skin involvement (usually maculopapular cutaneous mastocytosis, see above).

Rarer subsets of indolent systemic mastocystosis

Systemic mastocytosis with associated clonal haematological non-mast cell lineage disease

SM-AHNMD accounts for one third of all systemic mastocytosis cases. It is assocated with concurrent myeloproliferative neoplasms (in which there is increased bone marrow production of blood cells) and myelodysplasia (in which the bone marrow produces too few blood cells).

Aggressive systemic mastocytosis

Aggressive systemic mastocytosis is due to uncontrolled neoplastic cell proliferation and leads to impaired organ function. It results in flushing, itching, low blood pressure, anaphylaxis, diarrhoea and bleeding from the gastrointestinal tract. These patients may have high serum tryptase levels.

Complications may include:

Other forms of mast cell proliferation

Mast cell leukaemia

Mast cell leukaemia is a rare disease of circulating malignant mast cells with a very poor prognosis.

Mast cell sarcoma

Mast cell sarcoma is a solid tumour of malignant mast cells.

Extracutaneous mastocytoma

Extracutaneous mastocytoma is a benign mast cell tumour where a localised area of mast cell proliferation is not in the skin.

How is mastocytosis investigated?

Patients with solitary mastocytoma generally require no work up. However, a full history should be taken, and skin, lymph nodes, liver and spleen should be examined to check for diffuse or systemic mastocytosis.

In these cases the following investigations may be undertaken:

How is mastocytosis treated?

Most localised forms of cutaneous mastocytosis without symptoms require no treatment.

General measures

Treatment for symptomatic patients with mastocytosis includes general measures to avoid triggers for histamine release. Special care should be taken with patients with systemic mastocytosis or diffuse cutaneous mastocytosis, especially if they have elevated serum tryptase, when under anaesthetic or having imaging requiring radio-contrast.

Triggering agents in mastocytosis
Physical agents
  • Heat and cold
  • Sunlight
  • Sudden changes of temperature
  • Rubbing of/pressure on skin lesions
Emotional factors
  • Stress/anxiety
  • Sleep deprivation
  • Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs)
  • Morphine, codeine and derivatives (narcotics)
  • Cough medications
  • Alcohol
  • Local anaesthetics
  • Beta-blockers
  • Anticholinergic medications (eg scopolamine)
  • Vancomycin
  • Amphotericin B
  • Thiamine (Vitamin B1)
Infectious diseases with fever
  • Dental and endoscopic procedures
  • Vaccines
  • Surgery
  • Contrast media (particularly those containing iodine)

Specific treatments

Antihistamines may also be helpful for control/suppression of histamine-related symptoms in mastocytosis. Both H1 and H2 blockers are useful.

Phototherapy (usually narrowband UVB or PUVA) has been used for localised cutaneous mastocytosis in some cases.

Patients with gastrointestinal symptoms from systemic mastocytosis may be treated with H2 histamine antagonists (cimetidine and ranitidine are some examples), proton pump inhibitors (eg omeprazole, lansoprazole, pantoprazole), or oral sodium cromoglycate.

Subcutaneous adrenaline/epinephrine (EpiPen®) may be used for anaphylactic reactions.

Oral steroids may be used in some cases of systemic mastocytosis. They act as mast cell stabilisers.

In severe cases of systemic mastocytosis or aggressive forms of mastocytosis the following treatments alone or in combination have been used:

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