What is the difference between mast cell activation syndrome (MCAS) and mastocytosis?

Differences Between Mast Cell Activation Syndrome and Mastocytosis

Mast cell activation syndrome (MCAS) and mastocytosis are distinct mast cell disorders with different diagnostic criteria, clinical presentations, and treatment approaches, with mastocytosis characterized by abnormal mast cell accumulation in tissues while MCAS involves episodic mast cell mediator release without abnormal accumulation. 1

Diagnostic Criteria

Mastocytosis

• Definition: Abnormal accumulation of mast cells in tissues
• Major diagnostic criteria:
  • Multifocal dense infiltrates of mast cells in bone marrow or other extracutaneous organs 1
  • KIT D816V mutation (common in systemic mastocytosis) 2
• Classification:
  • Cutaneous mastocytosis (CM): Mast cell infiltration limited to the skin 2
  • Systemic mastocytosis (SM): Mast cell infiltration in bone marrow or other extracutaneous organs 2
• Laboratory findings:
  • Persistently elevated baseline serum tryptase (typically >20 ng/mL) 1
  • Aberrant CD25 expression on mast cells 2, 1

Mast Cell Activation Syndrome (MCAS)

• Definition: Recurrent episodes of mast cell mediator release without abnormal mast cell accumulation
• Diagnostic criteria (all three required):
  • Recurrent episodes of symptoms affecting ≥2 organ systems
  • Documented increase in validated mast cell mediators during symptomatic episodes
  • Response to medications targeting mast cell mediators 1
• Laboratory findings:
  • Normal baseline serum tryptase or only transiently elevated during attacks 1
  • No aberrant mast cell morphology or clonal markers unless primary/monoclonal MCAS 1

Clinical Presentation

Mastocytosis

• Skin lesions (e.g., urticaria pigmentosa) are common, especially in cutaneous mastocytosis 1
• Persistent symptoms due to ongoing mast cell mediator release 1
• Organ dysfunction due to mast cell infiltration in advanced forms 2
• Higher risk of severe anaphylaxis 1

MCAS

• No specific skin lesions 1
• Episodic symptoms with normal baseline between attacks 1
• Symptoms result from mediator release without tissue infiltration 1
• Multiple organ systems affected during episodes (gastrointestinal, cardiovascular, respiratory, neurological) 3

Subtypes and Classification

Mastocytosis

• Cutaneous mastocytosis (skin-limited) 2
• Systemic mastocytosis subtypes:
  • Indolent SM (ISM)
  • Smoldering SM (SSM)
  • Aggressive SM (ASM)
  • SM with associated hematological neoplasm (SM-AHN)
  • Mast cell leukemia (MCL) 2

MCAS

• Primary MCAS: Monoclonal/clonal mast cells (KIT mutation) without meeting criteria for mastocytosis 1, 4
• Secondary MCAS: Underlying inflammatory disease (often IgE-dependent allergy) 4
• Idiopathic MCAS: No detectable underlying disease or clonal mast cells 4

Treatment Approaches

Mastocytosis

• May require cytoreductive therapy in advanced forms 1
• Long-term monitoring for disease progression 1
• Treatment of mediator-related symptoms similar to MCAS 2
• Referral to specialized centers strongly recommended 2

MCAS

• Focus on symptom control with antimediator drugs 1, 3:
  • H1 and H2 antihistamines (can be increased to 2-4 times standard dose if needed)
  • Mast cell stabilizers (e.g., oral cromolyn sodium)
  • Emergency medications for acute reactions (epinephrine autoinjectors)
• Trigger avoidance (temperature extremes, mechanical irritation, alcohol, certain medications) 3

Prognosis

Mastocytosis

• Variable prognosis depending on subtype 1
• Indolent SM: Normal life expectancy
• Advanced forms (ASM, SM-AHN, MCL): Worse outcomes 1

MCAS

• Generally good prognosis with appropriate symptom management 1
• Some clonal MCAS cases may progress to SM 1
• No specific studies evaluating long-term prognosis 3

Common Pitfalls and Considerations

• Mastocytosis and MCAS can coexist in the same patient 5, 6
• Hereditary alpha-tryptasemia can be associated with both conditions 2, 1
• Serum tryptase should be measured within 30-120 minutes of symptom onset during acute reactions 3
• Many patients believe they have MCAS but may have a less severe form of mast cell activation or another underlying disease 7
• Both conditions require multidisciplinary management, especially for special situations like pregnancy, surgery, or anesthesia 3

Key Distinguishing Features

Feature	Mastocytosis	MCAS
Mast cell accumulation	Present	Absent
KIT D816V mutation	Common	Rare (except in primary MCAS)
Baseline serum tryptase	Often persistently elevated	Usually normal between episodes
Skin lesions	Common	Absent
Disease course	Persistent	Episodic
Risk of progression	Present in advanced forms	Low

Understanding these differences is crucial for accurate diagnosis and appropriate management of patients with mast cell disorders.