Mastocytosis

Mastocytosis is a group of rare disorders characterized by abnormal mast cell proliferation and accumulation in tissues. It is associated with mutations in the KIT gene. Systemic mastocytosis is a group of disorders that affect organs such as the bone marrow, GI tract, and/or bone, with or without skin involvement. Systemic mastocytosis predominantly occurs in adults. Diagnosis is usually confirmed by typical histopathological findings on, e.g., a bone marrow biopsy sample. Treatment is focused on prevention of anaphylaxis, symptomatic therapy, and management of osteopenia and osteoporosis. In advanced disease, treatment also involves targeted therapy (e.g., avapritinib or imatinib), and, in selected cases, allogeneic bone marrow transplantation. Cutaneous mastocytosis is a group of disorders that are limited to the skin and most commonly affect children. Maculopapular cutaneous mastocytosis (urticaria pigmentosa) is the most common type of cutaneous mastocytosis and manifests with red-brown papules or macules; other types include mastocytoma (a single raised lesion) and diffuse cutaneous mastocytosis, which is rare and most commonly occurs in early infancy. Diagnosis is based on the presence of typical skin lesions, skin biopsy findings, and exclusion of systemic mastocytosis. Treatment is primarily supportive, and most cases resolve before adolescence.

Mastocytosis is a group of rare disorders associated with mutations in the KIT gene → abnormal; monoclonal mast cell proliferation and accumulation in tissues; with end-organ damage (e.g., skin, bone marrow, GI tract) → ↑ serum tryptase, ↑ histamine, and ↑ leukotriene levels ^[1]

Definition ^[2]

Systemic mastocytosis is a group of disorders of mast cell proliferation and organ involvement (e.g., bone marrow, GI tract), with or without skin manifestations.

Epidemiology ^[2]

Systemic mastocytosis mainly affects adults.

Clinical features ^[2]

• Features of increased mast cell mediators ; , e.g., ↑ histamine (can also occur in cutaneous mastocytosis)
  • Anaphylaxis (may be recurrent) in response to triggers (e.g., Hymenoptera stings, medications, food)
  • Neurological: headache, depression, sleep disturbances
  • Cutaneous: hives, pruritus, flushing
  • Gastrointestinal: abdominal pain, diarrhea, gastric ulcers (due to increased gastric acid secretion)
  • Cardiovascular: hypotension, palpitations, syncope
  • Bone: osteopenia or osteoporosis, pathologic fractures
• Features of organ infiltration: e.g., lymphadenopathy, hepatomegaly, splenomegaly, osteolytic bone lesions
• Constitutional symptoms: e.g., weakness, myalgia, arthralgia

Diagnosis ^[2]

• Diagnostic confirmation: presence of mast cell aggregates in the bone marrow and/or extracutaneous organs on histopathology
• Additional supportive findings ^[2]
  • Serum tryptase levels persistently > 20 ng/mL
  • Mast cell CD25, CD2, and/or CD30 expression
  • Activating KIT mutations
  • > 25% of mast cells with atypical morphology

Treatment ^[2]

Treatment is specialist-guided and includes:

• Prevention of anaphylaxis: e.g., H1 antihistamines and avoidance of triggers of mast cell degranulation (e.g., alcohol consumption, aspirin)
• Symptomatic therapy
  • Pruritus and flushing: e.g., H1 antihistamines, leukotriene antagonists, aspirin (off-label)
  • GI symptoms: e.g., H2 antihistamines such as famotidine, PPIs
• Treatment of osteopenia and osteoporosis: e.g., bisphosphonates
• Additional therapy for advanced disease (i.e., mast cell leukemia , aggressive systemic mastocytosis , or manifesting with an associated hematologic neoplasm )
  • Targeted therapy: e.g., avapritinib (first line) or imatinib
  • Allogeneic bone marrow transplantation

Definition ^[3]

Cutaneous mastocytosis is a group of disorders of mast cell proliferation that are limited to the skin.

Epidemiology ^[3]

Cutaneous mastocytosis most commonly affects children.

Clinical features ^[3]

• Features of increased mast cell mediators: See “Clinical features” in “Systemic mastocytosis.”
• Cutaneous features vary based on the type.
  • Maculopapular cutaneous mastocytosis (urticaria pigmentosa)
    • Most common type
    • Red-brown papules or macules (rarely, plaques, nodules, or bullae), usually on the extremities and/or trunk
  • Mastocytoma: a single raised brown or yellow plaque or nodule, typically on the limbs ^[3]
  • Diffuse cutaneous mastocytosis
    • Rare type that typically manifests at birth or in early infancy
    • Diffuse erythema, pachyderma, dermographism ^[3]

Diagnosis ^[3]

Diagnosis is based on the following:

• Clinical features
  • Typical skin lesions (vary based on the type)
  • Darier sign: erythema and urticaria after mechanical irritation (e.g., rubbing, scratching) of the skin or skin lesions ^[3]
• Skin biopsy with ↑ mast cells on histopathology; KIT mutation may be present
• Exclusion of systemic mastocytosis and other hematologic conditions, e.g., normal CBC, PBS, and bone marrow studies: See “Systemic mastocytosis.” ^[3]

Use caution when examining the skin of patients with diffuse cutaneous mastocytosis to prevent a massive release of mast cell mediators (Darier sign). ^[3]

Cutaneous mastocytosis is diagnosed based on the presence of typical skin lesions (e.g., papules with positive Darier sign), skin biopsy findings, and exclusion of systemic mastocytosis. ^[3]

Treatment ^[3]

Treatment is supportive only; there are no curative treatments available. Cutaneous mastocytosis often spontaneously resolves.

• Avoidance of triggers of mast cell degranulation
• Antihistamines and corticosteroids to control histamine-related symptoms
• Single lesion: intralesional corticosteroids
• Extensive lesions: PUVA, imatinib (off-label), or omalizumab (off-label)

Prognosis

• Low risk of progression to systemic mastocytosis ^[3]
• In children, lesions often resolve spontaneously before adolescence. ^[1]