Mastocytosis

Mastocytosis is a rare group of conditions characterized by an abnormal buildup of mast cells in various parts of the body. Mast cells are a type of immune cell that plays a crucial role in allergic reactions and inflammation. Normally, mast cells help protect your body from infections, but in mastocytosis, these cells become overactive and accumulate in tissues and organs, causing a wide range of symptoms.

What are the symptoms of mastocytosis?

Symptoms of mastocytosis can vary greatly depending on the type and severity of the disease.

Common symptoms may include:

• Skin rash or lesions, often itchy and reddish-brown.
• Flushing or redness of the skin.
• Abdominal pain, diarrhea, or nausea.
• Bone pain and osteoporosis (weakening of bones).
• Anaphylactic reactions, severe allergic reactions, can cause breathing difficulties.
• Fatigue and general discomfort.

The severity of symptoms can range from mild to life-threatening, depending on individual factors and the specific type of mastocytosis.

What causes mastocytosis?

Genetic mutations in the KIT gene are primarily responsible for causing mastocytosis. This gene normally controls the growth and function of mast cells. When mutated, particularly at a site known as codon D816, it can lead to uncontrolled growth and accumulation of mast cells. More than 80% of patients with systemic mastocytosis have the KIT D816V mutation. Other rare mutations in different regions of the KIT gene may also cause mastocytosis. In advanced cases, additional mutations in other genes, such as TET2, SRSF2, ASXL1, RUNX1, and JAK2, may also occur.

Types of mastocytosis

Mastocytosis is classified based on the specific organs involved and the disease’s behavior, ranging from mild and localized forms to more aggressive systemic forms that affect multiple organs.

Cutaneous mastocytosis (involves the skin)

• Maculopapular cutaneous mastocytosis: Characterized by multiple small, itchy, reddish-brown spots. This type is subdivided into monomorphic and polymorphic subtypes.
• Diffuse cutaneous mastocytosis: Skin appears thickened, red, and leathery.
• Cutaneous mastocytoma: A single lump or nodule on the skin.

Systemic mastocytosis (involves organs beyond the skin)

• Bone marrow mastocytosis: Mast cells primarily accumulate in bone marrow.
• Indolent systemic mastocytosis: Mild form with a generally good prognosis.
• Smouldering systemic mastocytosis: Intermediate severity between indolent and aggressive forms.
• Aggressive systemic mastocytosis: Severe form that can cause organ damage.
• Systemic mastocytosis with an associated haematological neoplasm: Occurs alongside another blood disorder.
• Mast cell leukaemia: A rare, severe form characterized by large numbers of mast cells in the blood.

Other rare forms

• Mast cell sarcoma: A highly aggressive tumor of mast cells.
• Extracutaneous mastocytoma: Solitary tumors in organs other than the skin.

What is the prognosis for someone diagnosed with mastocytosis?

The prognosis depends significantly on the type of mastocytosis. Individuals with cutaneous mastocytosis or indolent systemic mastocytosis typically have a normal or near-normal life expectancy. However, people diagnosed with advanced forms, such as aggressive systemic mastocytosis or mast cell leukemia, often have a poor prognosis and reduced survival time. Regardless of the type, managing symptoms and related conditions is crucial. Effective management typically involves a multidisciplinary team that tailors treatment strategies to individual needs, addresses symptoms, and monitors for potential complications.

Questions to ask your doctor

• What type of mastocytosis do I have?
• What tests will I need to monitor my condition?
• What treatments are available, and what do you recommend?
• Are there any lifestyle changes or precautions I should take?
• What symptoms should I watch for and report immediately?
• Could participation in a clinical trial benefit my treatment?