Mastocytosis (urticaria pigmentosa)

Synonyms: Urticaria pigmentosa

By Dr. Pascal Bafteh · last updated 09/2026

Overview & Classification (WHO 2022)

• Mastocytosis = clonal proliferation of morphologically / immunophenotypically atypical mast cells in the skin and/or organs.
• Cutaneous Mastocytosis (CM): Maculopapular CM (= Urticaria pigmentosa), diffuse cutaneous mastocytosis, solitary mastocytoma.
• Systemic Mastocytosis (SM): ISM + SSM + advanced SM (ISM > 90% of SM cases).

Pathomechanism

• Driver Mutation: KIT-D816V in KIT Exon 17 (> 80%) → constitutive activation → uncontrolled mast cell proliferation.
• Patients: cutaneous form common in children, systemic form common in adults (women > men).
• Mediator release causes clinical symptoms:
• Histamine: Vasodilation, permeability ↑, pruritus, GI symptoms
• Heparin: Anticoagulant → bleeding tendency
• Proteases (Tryptase, Chymase): Tissue degradation, inflammation
• Cytokines / Chemokines: Recruitment of further inflammatory cells
• Prostaglandins + Leukotrienes: Inflammation, bronchial hyperreactivity

Clinical Presentation

Skin Manifestations

• Urticaria pigmentosa (UP): brown macules + Darier's sign on the trunk + proximal extremities, sparing the face/palmoplantar areas.
• Diffuse cutaneous mastocytosis: generalized thickened, leathery skin in infants.
• Solitary mastocytoma: single brown papule, often in children, spontaneous regression common.
• Flush: paroxysmal redness + feeling of warmth, often face + décolleté after triggers (heat, stress, NSAIDs, alcohol).

Gastrointestinal Symptoms

• Nausea, vomiting, diarrhea, abdominal pain, seizures — due to histamine + other mediators affecting motility + acid secretion.
• Gastric ulcers due to increased acid production.

Systemic Symptoms

• Anaphylactoid reactions with hypotension, tachycardia, dyspnea — typical with insect stings, surgical anesthetics, X-ray contrast media.
• Bone marrow involvement: Anemia, thrombocytopenia, leukopenia.
• Neuropsychiatric: Headaches, concentration difficulties, fatigue, depression.
• Skeletal system: Osteoporosis + bone pain due to mediator release; DXA bone density obligatory for every SM!
• Hepatosplenomegaly in systemic form (WHO B-findings).

Diagnostics

Anamnesis & Clinical Presentation

• Skin changes + Darier's sign + trigger anamnesis + B symptoms.

Laboratory

• Basal serum tryptase: > 20 ng/ml (WHO-Minor) with acute anaphylaxis marker +20% + 2 ng/ml.
• Exclude hereditary α-tryptasemia (HαT): TPSAB1 gene duplication can explain chronically ↑ basal tryptase without mastocytosis.
• 24-h urine N-methylhistamine as a mediator marker, additionally prostaglandin D2.
• CBC + Diff for bone marrow involvement assessment.

Skin Biopsy

• Increased mast cell density (> 5 × normal value) in the dermis.
• Special stains: Giemsa + Toluidine blue + Tryptase + CD117 with aberrant CD25/CD2/CD30.
• Aberrant CD25 expression as an indication of clonality.

Bone Marrow Biopsy (in case of suspected SM, tryptase > 20 ng/ml, B symptoms)

• WHO Major Criterion: Multifocal dense mast cell infiltrates (≥ 15 mast cells/aggregate) in BM or other extracutaneous organs.
• WHO Minor Criteria: atypical spindle-shaped morphology, CD25 / CD2 / CD30 aberrantly expressed, KIT-D816V mutation, serum tryptase > 20 ng/ml.
• Diagnosis SM: 1 Major + 1 Minor OR 3 Minor.

Imaging

• Abdominal ultrasound / CT / MRI for B-/C-symptoms (hepatosplenomegaly, lymphadenopathy).
• DXA bone density measurement obligatory for osteoporosis detection.

Differential diagnoses

• Urticaria
• Atopic dermatitis (atopic eczema)
• Pityriasis rosea
• Mastocytoma
• Mycosis fungoides
• Granuloma annulare
• Urticaria papulosa
• Giant urticaria

Sources (selection)

1. Valent 2017 Mastocytosis Classification

More allergies and eczemas

• Angioedema
• Atopic dermatitis (atopic eczema)
• Seborrhoeic dermatitis
• Urticaria

Note: This page is intended for medical education and does not replace diagnosis or treatment decisions in individual cases. Treatment and follow-up content is available in the app.