Mastocytosis

What mast cells do

Mast cells live in the skin, gut, airways and around blood vessels. They release histamine, tryptase, prostaglandins and other chemicals that drive allergic reactions and inflammation. In mastocytosis, a gene change, most often KIT D816V, makes mast cells multiply and survive longer, so there are too many and they release their chemicals more easily.

Types of mastocytosis

Cutaneous mastocytosis

Limited to the skin, usually starting in the first 2 years of life.

• Maculopapular cutaneous mastocytosis (urticaria pigmentosa): multiple small brown or reddish spots
• Mastocytoma: a single larger lesion, often on a limb or trunk
• Diffuse cutaneous mastocytosis: rare, widespread thickened skin with blistering

Many children improve significantly or clear by adolescence.

Systemic mastocytosis

Mast cells accumulate in the bone marrow and other organs, mainly in adults:

Symptoms

Skin

• brown, red or tan spots or bumps
• Darier sign: rubbing a spot causes it to swell, redden and itch within minutes
• itching and flushing, sometimes with hives

Mast cell mediator symptoms

• flushing of the face and chest
• abdominal cramps, diarrhea, nausea, reflux and peptic ulcers
• dizziness, low blood pressure and fainting
• anaphylaxis, often triggered by insect stings
• headache, fatigue, brain fog
• bone pain

Organ involvement (advanced disease)

• enlarged liver or spleen
• low blood counts
• weight loss and malabsorption
• osteoporosis and fractures

Triggers

Mast cells can be triggered by:

• insect stings (bees, wasps, fire ants)
• heat, cold or sudden temperature changes
• friction or pressure on the skin
• alcohol and spicy foods
• certain medicines: NSAIDs and aspirin in some people, opioids, some anesthetic agents, and contrast dyes
• exercise, stress, infections and fever

Diagnosis

• skin examination, with Darier sign
• serum tryptase: a persistently raised baseline (over 20 ng/mL is a key criterion) suggests systemic disease
• bone marrow biopsy: shows clusters of abnormal mast cells, the main criterion for systemic mastocytosis
• KIT D816V mutation testing, often with a sensitive blood test
• skin biopsy for cutaneous forms
• bone density scan, abdominal ultrasound and blood counts to assess involvement

Mastocytosis is often first mistaken for an ordinary allergy. Hereditary alpha-tryptasemia, a common inherited trait that raises tryptase, can mimic or coexist with mastocytosis.

Treatment

For all types

• trigger avoidance
• H1 antihistamines (cetirizine, fexofenadine) for itching and flushing
• H2 blockers (famotidine) for stomach symptoms
• cromolyn sodium by mouth for gut symptoms
• leukotriene blockers (montelukast)
• epinephrine auto-injectors: two should be carried by anyone with systemic mastocytosis or a history of anaphylaxis
• venom immunotherapy after insect sting anaphylaxis, often continued lifelong
• bone protection: calcium, vitamin D and bisphosphonates for osteoporosis
• pre-medication plans before surgery, procedures and contrast scans

For skin lesions

Topical steroids and, in some cases, light therapy. Avoid rubbing lesions.

For systemic disease

• avapritinib: a targeted KIT inhibitor approved for advanced SM and for indolent SM with moderate to severe symptoms
• midostaurin: for advanced SM
• cladribine or interferon in selected cases
• stem cell transplant for some people with advanced disease

Outlook

Children with cutaneous mastocytosis usually improve, and many clear by adolescence. Adults with indolent systemic mastocytosis have a normal life expectancy, with symptoms managed by medicines and trigger avoidance. Advanced systemic mastocytosis is serious, but targeted drugs have improved outcomes.

Frequently asked questions

What is mastocytosis?

Mastocytosis is a rare condition in which too many mast cells accumulate in the skin or internal organs. These cells release histamine and other chemicals, causing itching, flushing, digestive symptoms and sometimes severe allergic reactions.

What are the symptoms of systemic mastocytosis?

Symptoms include flushing, itching, abdominal cramps, diarrhea, dizziness or fainting, anaphylaxis (especially after insect stings), fatigue, bone pain and osteoporosis. Some people have brown skin spots that itch when rubbed.

Is mastocytosis a cancer?

Mastocytosis is classified as a myeloid neoplasm, a disorder of blood-forming cells. Most adults have indolent systemic mastocytosis, which behaves benignly with a normal life expectancy. Advanced forms behave more like cancer and need specialist treatment.

Does mastocytosis in children go away?

Often, yes. Cutaneous mastocytosis that starts in early childhood commonly improves significantly or disappears by adolescence. Children with persistent or widespread disease are monitored for systemic involvement.