What are the signs and symptoms of mastocytosis?

Signs and Symptoms of Mastocytosis

Mastocytosis presents with two distinct clinical patterns: symptoms from mast cell mediator release (flushing, pruritus, anaphylaxis) and, in advanced disease, symptoms from organ infiltration (cytopenias, hepatosplenomegaly, pathologic fractures).

Clinical Presentation by Disease Burden

Symptoms from Mast Cell Mediator Release

The most common manifestations result from histamine and other inflammatory mediators released by abnormal mast cells 1:

• Cutaneous symptoms: Pruritus, flushing, urticaria pigmentosa (tan to red-brown macules typically appearing on trunk and spreading symmetrically) 1, 2
• Cardiovascular symptoms: Hypotension, tachycardia, syncope, and potentially life-threatening anaphylaxis requiring immediate epinephrine 1
• Gastrointestinal symptoms: Abdominal cramping, diarrhea, nausea, vomiting, and malabsorption 1
• Neuropsychiatric symptoms: Headache, cognitive dysfunction, anxiety, and depression 1
• Respiratory symptoms: Wheezing, dyspnea, and bronchospasm 1

Anaphylaxis represents the most dangerous manifestation and can occur from various triggers including Hymenoptera stings (most common in adults), foods, drugs, temperature extremes, physical trauma, and psychological stress 1, 3.

Cutaneous Manifestations by Disease Subtype

Skin involvement varies dramatically by age and disease subtype 1:

• Indolent systemic mastocytosis (ISM): 85% have skin lesions, 78% have cutaneous symptoms 1
• Bone marrow mastocytosis (BMM): No skin lesions by definition, but 86% have mediator release symptoms 1
• Smoldering systemic mastocytosis (SSM): 50% have mediator release symptoms 1
• Aggressive systemic mastocytosis (ASM): Skin lesions less common than in ISM 1
• Pediatric cutaneous mastocytosis: Skin-only disease with tendency toward spontaneous regression 1

WHO Classification: B-Findings and C-Findings

B-Findings (Higher Disease Burden Without Organ Damage)

B-findings indicate substantial mast cell burden but preserved organ function 1:

1. High mast cell burden: >30% bone marrow infiltration by focal, dense mast cell aggregates AND serum tryptase >200 ng/mL 1
2. Organomegaly without dysfunction: Hepatomegaly without impaired liver function, palpable splenomegaly without hypersplenism, or lymphadenopathy on examination or imaging 1
3. Dysplasia in non-mast cell lineages: Signs of myeloproliferation or dysplasia without meeting criteria for associated hematologic neoplasm, with normal or minimally abnormal blood counts 1

C-Findings (Organ Damage from Mast Cell Infiltration)

C-findings define advanced disease with organ dysfunction 1:

• Cytopenias: Absolute neutrophil count <1 × 10⁹/L, hemoglobin <10 g/dL, or platelet count <100 × 10⁹/L due to bone marrow dysfunction 1
• Hepatic dysfunction: Palpable hepatomegaly with impaired liver function, ascites, or portal hypertension 1
• Skeletal involvement: Large osteolytic lesions with or without pathologic fractures 1
• Splenic dysfunction: Palpable splenomegaly with hypersplenism 1
• Gastrointestinal malabsorption: Hypoalbuminemia with weight loss from gastrointestinal mast cell infiltrates 1

Constitutional Symptoms by Disease Subtype

The frequency of constitutional symptoms correlates with disease aggressiveness 1:

• ISM: 15% have constitutional symptoms 1
• SSM: 45% have constitutional symptoms 1
• ASM: Higher frequency of constitutional symptoms and less common skin involvement 1

Symptom Assessment Tools

Validated questionnaires should be used for baseline assessment and monitoring 1:

• Mastocytosis Quality-of-Life Questionnaire (MQLQ) 1
• Mastocytosis Symptom Assessment Form (MSAF) 1

Critical Clinical Pitfalls

Several presentations can be easily missed 4:

• Absence of skin lesions does not exclude systemic mastocytosis—bone marrow mastocytosis has no cutaneous involvement but high mediator symptom burden 1
• Recurrent unexplained anaphylaxis, particularly from Hymenoptera stings, should prompt evaluation for mastocytosis even without skin lesions 3, 4
• Unexplained osteoporosis with elevated baseline serum tryptase may be the presenting feature 4
• Patients often have prolonged histories of chronic symptoms misattributed to other conditions before diagnosis 2, 4

Prognostic Implications of Symptoms

Symptom patterns predict survival 1:

• ISM: Median survival 301 months, similar to age-matched general population 1
• BMM: Median survival not reached (superior to ISM) 1
• SSM: Median survival 120 months with 18% risk of transformation to acute myeloid leukemia or aggressive SM 1
• ASM: Median survival 41 months 1