Assessment of clinical findings, tryptase levels, and bone marrow histopathology in the management of pediatric mastocytosis Melody C. Carter, MD, Sarah.

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Presentation transcript:

Assessment of clinical findings, tryptase levels, and bone marrow histopathology in the management of pediatric mastocytosis Melody C. Carter, MD, Sarah T. Clayton, BS, Hirsh D. Komarow, MD, Erica H. Brittain, PhD, Linda M. Scott, NP, Daly Cantave, MSN, Donna M. Gaskins, BSN, Irina Maric, MD, Dean D. Metcalfe, MD Journal of Allergy and Clinical Immunology Volume 136, Issue 6, Pages 1673-1679.e3 (December 2015) DOI: 10.1016/j.jaci.2015.04.024 Copyright © 2015 Terms and Conditions

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. Journal of Allergy and Clinical Immunology 2015 136, 1673-1679.e3DOI: (10.1016/j.jaci.2015.04.024) Copyright © 2015 Terms and Conditions

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). Journal of Allergy and Clinical Immunology 2015 136, 1673-1679.e3DOI: (10.1016/j.jaci.2015.04.024) Copyright © 2015 Terms and Conditions

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). Journal of Allergy and Clinical Immunology 2015 136, 1673-1679.e3DOI: (10.1016/j.jaci.2015.04.024) Copyright © 2015 Terms and Conditions

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. Journal of Allergy and Clinical Immunology 2015 136, 1673-1679.e3DOI: (10.1016/j.jaci.2015.04.024) Copyright © 2015 Terms and Conditions

Fig E1 Serum tryptase levels (in nanograms per milliliter) versus serum IgE levels (in international units per milliliter) are shown. Patients with UP are represented by green dots, patients with DCM are represented by blue squares, and patients with ISM are represented by red triangles (Spearman rho = 0.517, P < .0001). Journal of Allergy and Clinical Immunology 2015 136, 1673-1679.e3DOI: (10.1016/j.jaci.2015.04.024) Copyright © 2015 Terms and Conditions

Fig E2 Appearance of skin lesions over time with concurrent serum tryptase levels. Regression of skin lesions in patients with UP, predominately maculopapular cutaneous mastocytosis lesions with some nodular lesions that evolve into a strictly maculopapular cutaneous mastocytosis (ages 2 and 7 years; tryptase level, 20 and 6.6 ng/mL, respectively; A); DCM (ages 17 months and 9 years; tryptase levels, 17.4 and 4.9 ng/mL, respectively; B); and ISM with a typical maculopapular cutaneous mastocytosis pattern (ages 3 and 9 years; tryptase levels, 32.9 and 12.6 ng/mL, respectively; C) are shown and are consistent with decreases in serum tryptase levels. Journal of Allergy and Clinical Immunology 2015 136, 1673-1679.e3DOI: (10.1016/j.jaci.2015.04.024) Copyright © 2015 Terms and Conditions

Fig E3 Skin appearance, bone marrow pathology, and serum tryptase levels in a patient with UP (tryptase level, 6.1 ng/mL; A), DCM (tryptase level, 26.0 ng/mL; B), and ISM (C: tryptase level, 53.7 ng/mL; D: tryptase level, 238.0 ng/mL). Immunohistochemistry staining for tryptase (dark brown) shows that greater than 25% of mast cells within the marrow were spindle shaped. All mast cells were CD25+, and the D816V mutation was present. Magnification is ×200 for all bone marrow biopsy specimens. Journal of Allergy and Clinical Immunology 2015 136, 1673-1679.e3DOI: (10.1016/j.jaci.2015.04.024) Copyright © 2015 Terms and Conditions