Assessment of clinical findings, tryptase levels, and bone marrow histopathology in the management of pediatric mastocytosis

Abstract

Background: The management of children with pediatric mastocytosis poses a challenge. This is because there is limited information as to the application of clinical and laboratory findings and bone marrow histopathology as they relate to medical intervention and communication.

Objective: We sought to examine clinical aspects of pediatric mastocytosis in relationship to serum tryptase levels and bone marrow pathology to provide practical guidance for management.

Methods: Between 1986 and 2012, 105 children were evaluated at the National Institutes of Health. Organomegaly was confirmed by means of ultrasound. Baseline tryptase levels and at least 1 subsequent tryptase measurement was available in 84 and 37 of these children, respectively. Fifty-three children underwent a bone marrow examination. These data were used to examine relationships between clinical findings, tryptase levels, and marrow histopathology.

Results: In patients with high tryptase levels and severe mediator symptoms, all with organomegaly had systemic disease, and none without organomegaly had systemic disease. Serum tryptase levels differed significantly between patients with urticaria pigmentosa and those with diffuse cutaneous (P < .0001) and systemic mastocytosis (P < .0001) and in all 3 categories versus control subjects (P < .0001). Tryptase levels and symptoms decreased over time in most patients, and tryptase levels correlated with bone marrow mast cell burden in patients with systemic mastocytosis (P < .0001). There was a significant relationship between clinical resolution and the percentage decrease in tryptase levels (P = .0014).

Conclusions: The majority of children experienced major or complete disease resolution (57%), whereas the remainder exhibited partial improvement. Organomegaly was a strong indicator of systemic disease. Serum tryptase levels furthered classification and reflected clinicopathologic findings, while sequential tryptase measurements were useful in supplementing clinical judgment as to disease course.

Keywords: Mast cells; bone marrow examination; cutaneous mastocytosis; diffuse cutaneous mastocytosis; mastocytosis; tryptase; urticaria pigmentosa.

FIG 1

Baseline serum tryptase levels in children with mastocytosis and control subjects. Age-matched control subjects include atopic and nonatopic children. Symbols represent mastocytosis variants (control subjects, n = 199; patients with UP, n = 48; patients with DCM, n = 13; patients with SM, n = 18). Median bars and 25th and 75th percentiles are shown. Two patients with the nodular UP form are included within the UP graph (values of 63.9 and 86.2 ng/mL). One patient each with ISM and DCM who had marrow biopsies performed did not have tryptase measurements. Patients with mastocytomas are not shown. The shaded area represents normal tryptase range (<11.4 mg/mL). ***P < .0001.

FIG 2

Mast cell mediator symptom prevalence by age category. A, Blistering. B, Pruritus. C, Flushing. D, Diarrhea. Within each panel, each dot represents the prevalence for specific age categories (0-1, 1-2, 2-3, 3-4, 4-6, 6-8, 10-12, 12-14, 14-18, and ≥ 18 years), and the red bar is the 95% CI for that prevalence. The blue loess curves illustrate prevalence across age categories when all mastocytosis variants are analyzed collectively. Symptoms were scored as present (1) or not present (0).

FIG 3

Serum tryptase levels over time. Sequential serum tryptase levels in patients with UP (n = 18; nodular maculopapular cutaneous mastocytosis, n = 1; A), DCM (n = 7; B), or ISM (n = 11; C) with at least 18 months of follow-up. Linear regression lines are presented for each patient, along with each observation. Blue lines denote values from patients with complete disease resolution, purple lines denote major resolution, and red lines denote partial resolution. Serum tryptase levels decreased or remained stable over time for all variants. The shaded area represents the tryptase normal range (<11.4 mg/mL).

FIG 4

Percentage of mast cell cellularity observed on bone marrow biopsy specimens correlated with serum tryptase levels for ISM. Data shown are for bone marrow biopsy specimens in which there was a tryptase level obtained at the time of biopsy (n = 32). Green circles indicate UP (n = 6), filled squares indicate DCM (n = 7), open squares indicate mastocytomas (n = 2), and triangles indicate ISM (n = 17). The 2 children with a nodular subtype did not have a bone marrow biopsy performed. Note that some data points superimpose. Correlation coefficient Spearman rho = 0.84 (P < .0001) for SM and Spearman rho = 0.41 (P = .363) for DCM. UP values are all 1% or less, with no correlation.