What is mastocytosis and what are its symptoms?

Mastocytosis: Definition and Symptoms

Mastocytosis is a rare and heterogeneous disease characterized by the abnormal accumulation of clonal mast cells in one or multiple organs, presenting with symptoms ranging from skin lesions to life-threatening anaphylaxis depending on the subtype and extent of involvement. 1

Types of Mastocytosis

Mastocytosis is classified into several major categories:

1. Cutaneous Mastocytosis (CM)

   • Primarily affects children
   • Limited to skin involvement
   • Often regresses spontaneously by puberty
   • Subtypes include:
     • Urticaria Pigmentosa (UP)/Maculopapular CM (most common)
     • Solitary mastocytoma
     • Diffuse Cutaneous Mastocytosis (DCM)
     • Telangiectasia Macularis Eruptiva Persistans (TMEP, rare in children) 1

2. Systemic Mastocytosis (SM)

   • More common in adults
   • Involves bone marrow and other extracutaneous organs
   • Subtypes include:
     • Indolent SM (ISM, most common)
     • Aggressive SM (ASM)
     • SM with Associated Hematologic Non-Mast Cell Lineage Disease (SM-AHNMD)
     • Mast Cell Leukemia (MCL) 1

3. Mast Cell Sarcoma

   • Extremely rare malignant form presenting as a destructive mass 1

Common Symptoms

Skin Manifestations

• Urticaria pigmentosa: Red-brown maculopapular lesions that urticate when rubbed (Darier's sign)
• Flushing: Occurs in 20-65% of patients
• Pruritus: Common and can be severe
• Dermatographism: Skin writing phenomenon
• Blistering/bullae: Especially in DCM, can be hemorrhagic 1

Systemic Symptoms (Due to Mast Cell Mediator Release)

• Gastrointestinal: Abdominal pain, diarrhea (up to 40% of children), nausea, vomiting
• Cardiovascular: Hypotension, tachycardia, syncope
• Respiratory: Wheezing, shortness of breath
• Neurological: Headache, irritability, poor concentration
• Anaphylaxis: Can be triggered by various stimuli including Hymenoptera stings, foods, medications, and physical factors 1, 2

Advanced Disease Symptoms (In ASM, MCL)

• Organomegaly: Hepatomegaly, splenomegaly, lymphadenopathy
• Bone involvement: Osteoporosis, pathological fractures
• Cytopenias: Due to bone marrow infiltration
• Constitutional symptoms: Weight loss, fatigue, fever 1

Diagnostic Features

The diagnosis of mastocytosis is based on:

1. Clinical presentation: Characteristic skin lesions or systemic symptoms
2. Histopathology: Abnormal mast cell infiltration in affected tissues
3. Laboratory findings:
   • Elevated serum tryptase (>20 ng/mL in systemic disease)
   • KIT D816V mutation (present in >80% of adult cases)
   • Abnormal mast cell immunophenotype (CD2 and/or CD25 expression) 1

Important Clinical Considerations

• Symptom triggers: Temperature changes, physical exertion, emotional stress, alcohol, certain foods, medications, and insect stings
• Anaphylaxis risk: Higher in mastocytosis patients, especially with Hymenoptera stings
• Disease course: Generally favorable in pediatric CM with spontaneous regression; more chronic in adult SM 1, 2
• Management approach: Requires multidisciplinary care involving dermatologists, hematologists, allergists, and other specialists 1

Pitfalls in Diagnosis

• Mastocytosis can be missed in patients without skin lesions
• Serum tryptase may not be elevated in all cases, particularly in purely cutaneous disease
• Symptoms may mimic other conditions like chronic urticaria, irritable bowel syndrome, or idiopathic anaphylaxis
• The extent of skin involvement does not necessarily correlate with systemic involvement or symptom severity 1

For patients with suspected mastocytosis, evaluation should include skin examination, serum tryptase measurement, bone marrow biopsy (in adults or if systemic involvement is suspected), and molecular testing for KIT mutations to establish the diagnosis and determine appropriate management.