What are the tryptase (enzyme) levels for different types of mastocytosis (mast cell disorder)?

Tryptase Levels in Different Types of Mastocytosis

Serum tryptase levels vary significantly across mastocytosis subtypes, with cutaneous mastocytosis typically showing normal or near-normal levels (median 10 ng/mL), indolent systemic mastocytosis showing moderately elevated levels (median 67 ng/mL), and advanced forms including mast cell leukemia showing markedly elevated levels (>900 ng/mL). 1, 2

Cutaneous Mastocytosis (CM)

Normal to Minimally Elevated Levels:

• Most patients with cutaneous mastocytosis have normal or near-normal serum tryptase levels with a median of 10 ng/mL (range 2-23 ng/mL), defined by the absence of dense compact mast cell infiltrates in bone marrow. 2
• In pediatric cutaneous mastocytosis, serum tryptase is significantly elevated only in children with systemic disease, not in those with isolated skin involvement. 1
• Among children with urticaria pigmentosa, 8 out of 20 had elevated tryptase, but none had bone marrow findings compatible with systemic mastocytosis. 1
• In mastocytomas, only 1 out of 6 children had elevated tryptase. 1

Systemic Mastocytosis (SM) - General

Elevated Across All Subtypes:

• Serum tryptase is elevated in the vast majority of patients with SM across all subtypes, with persistently elevated serum total tryptase >20 ng/mL serving as one of the minor diagnostic criteria. 1
• A strong correlation exists between the grade of bone marrow infiltration by neoplastic mast cells and tryptase levels (r = 0.8) in systemic mastocytosis patients. 2
• The measurement of serum tryptase is a reliable noninvasive diagnostic approach to estimate the burden of mast cells in patients with mastocytosis and to distinguish between categories of disease. 2

Indolent Systemic Mastocytosis (ISM)

Moderately Elevated Levels:

• Patients with indolent systemic mastocytosis show a median tryptase level of 67 ng/mL. 2
• Three patients with isolated bone marrow mastocytosis (no skin lesions and no signs of multiorgan involvement) had serum tryptase levels <20 ng/mL. 2
• Monitoring reveals that 65% of ISM patients show increasing tryptase levels over time, 22% show decreasing levels, and 13% show fluctuating patterns. 3

Smoldering Systemic Mastocytosis

Markedly Elevated Levels:

• Two patients with slowly progressing SM and high mast cell burden (smoldering SM) had tryptase levels >900 ng/mL, among the highest levels observed. 2

Aggressive Systemic Mastocytosis (ASM) and SM with Associated Hematologic Neoplasm (SM-AHN)

Variable but Generally High Levels:

• Enzyme levels differ significantly among the groups of patients with different types of SM, with advanced forms showing higher levels. 2
• The presence of an associated hematologic neoplasm (AHN) may confound tryptase correlations, as the AHN itself may contribute to elevation of serum tryptase levels. 1
• AHNs are diagnosed in 71% of patients with mast cell leukemia, affecting tryptase interpretation. 1

Mast Cell Leukemia (MCL)

Extremely Elevated Levels:

• The highest tryptase levels (>900 ng/mL) were detected in the patient with mast cell leukemia. 2
• This represents the most aggressive form with the greatest mast cell burden. 2

Clinical Interpretation and Diagnostic Thresholds

Key Diagnostic Cut-Points:

• Tryptase >20 ng/mL meets a minor diagnostic criterion for systemic mastocytosis and mandates bone marrow evaluation. 1, 4
• Tryptase >200 ng/mL indicates high mast cell burden requiring urgent hematology referral and possible hospitalization. 4
• A bone marrow tryptase cut-off of 50 μg/L identifies systemic mastocytosis with 93% sensitivity and 90% specificity. 5

Important Caveats

Alpha vs. Beta Tryptase Distinction:

• The alpha form of tryptase is the predominant type present in blood at baseline in normal subjects and is elevated in systemic mastocytosis. 6
• Most mastocytosis patients with systemic disease have B12-measured tryptase levels (measuring both alpha and beta) that are at least 10-fold greater than G5-measured tryptase levels (measuring primarily beta). 6
• The ratio of total tryptase to beta-tryptase can distinguish mastocytosis from acute anaphylaxis, with a ratio ≥20 suggesting systemic mastocytosis. 4

Confounding Factors:

• A minority of patients with SM have normal tryptase levels, possibly related to the lack of alpha tryptase genes described in Caucasian populations. 1
• Elevated serum tryptase may also occur transiently during anaphylaxis or in other myeloid malignancies and hereditary alpha-tryptasemia. 1, 7

Prognostic Significance

Disease Progression Monitoring:

• Patients with significantly increasing tryptase (slope ≥0.15) after 48 months show greater rates of diffuse bone sclerosis (13% vs. 2%) and hepatosplenomegaly (16% vs. 5%). 3
• Progressively increasing tryptase values are associated with multilineage KIT mutation, progression to smoldering or aggressive SM, and shorter progression-free survival. 3
• Total tryptase levels generally reflect the increased burden of mast cells in all forms of systemic mastocytosis and the decreased burden associated with cytoreductive therapies. 7