The Recurrent Flush: A Case and Review of Systemic Mastocytosis
Main Article Content
Keywords
Systemic Mastocytosis, Histamine, Mast Cells, Myeloproliferative Disorder, Anaphylaxis
Abstract
Systemic Mastocytosis (SM) is a hematologic neoplasm characterized by an abnormal proliferation of mast cells, which have the potential to infiltrate one or more visceral organs. Patients can present with a wide constellation of symptoms making it a challenging diagnosis for clinicians. Non-specific symptoms such as fatigue, headache, and weight loss may predominate; however, some patients may present with acute onset of urticaria, flushing, and diarrhea. Due to its rarity, clinicians often face a challenge in evaluating, diagnosing and effectively treating systemic mastocytosis. Identification during the indolent phase is important as SM can progress to aggressive leukemias or myeloproliferative disorders. In this article, we present a case of SM, and discuss current practices in diagnosis, evaluation and management. We conclude with future directions for treatments and diagnosis
References
REFERENCES
1. Valent P, Sperr WR, Schwartz LB, et al. Diagnosis and classification of mast cell proliferative disorders: delineation from immunologic diseases and non-mast cell hematopoietic neoplasms. J Allergy Clin Immunol 2004; 114:3-11.
2. 21. Cohen SS, Skovbo S, Vestergaard H, et al. Epidemiology of systemic mastocytosis in Denmark. Br J Haematol 2014; 166:521-8.
3. Soter NA. Mastocytosis and the skin. Hematol Oncol Clin North Am 2000; 14:537-55, vi.
4. Moura DS. Neuropsychological features of adult mastocytosis. Immunol Allergy Clin North Am 2014; 34:407-22.
5. Soter NA. Mastocytosis and the skin. Hematol Oncol Clin North Am 2000; 14: 537-55, vi.
6. Lim KH, Tefferi A, Lasho TL, et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood 2009; 113:5727-36.
7. Horny HP, Ruck M, Wehrmann M, et al. Blood findings in generalized mastocytosis: evidence of frequent simultaneous occurrence of myeloproliferative disorders. Br J Haematol 1990; 76:186-93.
8. Lim KH, Tefferi A, Lasho TL, et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood 2009; 113:5727-36.
9. Barete S, Assous N, de Gennes C, et al. Systemic mastocytosis and bone involvement in a cohort of 75 patients. Ann Rheum Dis 2010; 69:1838-41.
10. Van Der Veer E, Van Der Goot W, De Monchy JGR, et al. High prevalence of fractures and osteoporosis in patients with indolent systemic mastocytosis. Allergy 2012; 67:431-8.
11. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391-2405.
12. Horny H, Metcalfe D, Bennet J, et al. Mastocytosis. In: Swerdlow S, Campo E, Harris N, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: World Health Organization; 2008:54-63.
13. Wang SA, Hutchinson L, Tang G, et al. Systemic mastocytosis with associated clonal hematological non-mast cell lineage disease: clinical significance and comparison of chromosomal abnormalities in SM and AHNMD components. Am J Hematol 2013; 88:219-24.
14. Valent P, Arock M, Akin C, et al. The classification of systemic mastocytosis should include mast cell leukemia (MCL) and systemic mastocytosis with a clonal hematologic non-mast cell lineage disease (SM-AHNMD). Blood 2010; 116:850-1.
15. Akin C, Metcalfe DD. Surrogate markers of disease in mastocytosis. Int Arch Allergy Immunol 2002; 127:133-6.
16. Valent P, Horny HP, Escribano L, et al. Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res 2001; 25:603-25.
17. Valent P, Sotlar K, Sperr WR, et al. Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal. Ann Oncol 2014; 25:1691-700.
18. Pardanani A, Lim KH, Lasho TL, et al. WHO subvariants of indolent mastocytosis: clinical details and prognostic evaluation in 159 consecutive adults. Blood 2010; 115:150-1.
19. Brockow K, Jofer C, Behrendt H, et al. Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk factors in 120 patients. Allergy 2008; 63:226-32.
20. Butterfield JH, Weiler CR. Prevention of mast cell activation disorder associated clinical sequelae of excessive prostaglandin D2 production. Int Arch Allergy Immunol 2008; 147:338-43.
21. Horan RF, Sheffer AL, Austen KF. Cromolyn sodium in the management of systemic mastocytosis. J Allergy Clin Immunol 1990; 85:852-5.
22. Carter MC, Robyn JA, Bressler PB, et al. Omalizumab for the treatment of unprovoked anaphylaxis in patients with systemic mastocytosis. J Allergy Clin Immunol 2007; 119:1550-1.
23. Lim KH, Pardanani A, Butterfield JH, et al. Cytoreductive therapy in 108 adults with systemic mastocytosis: outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine. Am J Hematol 2009; 84:790-4.
24. Escribano L, Álvarez-Twose I, Sánchez-Muñoz L, et al. Prognosis in adult indolent systemic mastocytosis: a long-term study of the Spanish Network on Mastocytosis in a series of 145 patients. J Allergy Clin Immunol 2009; 124:514-21.
25. Paul C, Sans B, Suarez F, et al. Masitinib for the treatment of systemic and cutaneous mastocytosis with handicap: a phase 2a study. Am J Hematol 2010; 85:921-5.
26. Georgin-Lavialle S, Lhermitte L, Dubreuil P, et al. Mast cell leukemia. Blood 2013; 121:1285-95.
27. Ustun C, Reiter A, Scott BL, et al. Hematopoietic stem-cell transplantation for advanced systemic mastocytosis. J Clin Oncol 2014; 32:3264-74.
28. Cherner JA, Jensen RT, Dubois A, O’Dorisio TM, Gardner JD, Metcalfe DD. Gastrointestinal dysfunction in systemic mastocytosis. A prospective study. Gastroenterology 1988; 95:657–667.
29. Lim KH, Tefferi A, Lasho TL, et al; Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood. 2009;113(23):572736.
30. Theoharides TC, Valent P, Akin C. Mast cells, mastocytosis, and related disorders. N Engl J Med 2015;373:163-72
1. Valent P, Sperr WR, Schwartz LB, et al. Diagnosis and classification of mast cell proliferative disorders: delineation from immunologic diseases and non-mast cell hematopoietic neoplasms. J Allergy Clin Immunol 2004; 114:3-11.
2. 21. Cohen SS, Skovbo S, Vestergaard H, et al. Epidemiology of systemic mastocytosis in Denmark. Br J Haematol 2014; 166:521-8.
3. Soter NA. Mastocytosis and the skin. Hematol Oncol Clin North Am 2000; 14:537-55, vi.
4. Moura DS. Neuropsychological features of adult mastocytosis. Immunol Allergy Clin North Am 2014; 34:407-22.
5. Soter NA. Mastocytosis and the skin. Hematol Oncol Clin North Am 2000; 14: 537-55, vi.
6. Lim KH, Tefferi A, Lasho TL, et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood 2009; 113:5727-36.
7. Horny HP, Ruck M, Wehrmann M, et al. Blood findings in generalized mastocytosis: evidence of frequent simultaneous occurrence of myeloproliferative disorders. Br J Haematol 1990; 76:186-93.
8. Lim KH, Tefferi A, Lasho TL, et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood 2009; 113:5727-36.
9. Barete S, Assous N, de Gennes C, et al. Systemic mastocytosis and bone involvement in a cohort of 75 patients. Ann Rheum Dis 2010; 69:1838-41.
10. Van Der Veer E, Van Der Goot W, De Monchy JGR, et al. High prevalence of fractures and osteoporosis in patients with indolent systemic mastocytosis. Allergy 2012; 67:431-8.
11. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391-2405.
12. Horny H, Metcalfe D, Bennet J, et al. Mastocytosis. In: Swerdlow S, Campo E, Harris N, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: World Health Organization; 2008:54-63.
13. Wang SA, Hutchinson L, Tang G, et al. Systemic mastocytosis with associated clonal hematological non-mast cell lineage disease: clinical significance and comparison of chromosomal abnormalities in SM and AHNMD components. Am J Hematol 2013; 88:219-24.
14. Valent P, Arock M, Akin C, et al. The classification of systemic mastocytosis should include mast cell leukemia (MCL) and systemic mastocytosis with a clonal hematologic non-mast cell lineage disease (SM-AHNMD). Blood 2010; 116:850-1.
15. Akin C, Metcalfe DD. Surrogate markers of disease in mastocytosis. Int Arch Allergy Immunol 2002; 127:133-6.
16. Valent P, Horny HP, Escribano L, et al. Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res 2001; 25:603-25.
17. Valent P, Sotlar K, Sperr WR, et al. Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal. Ann Oncol 2014; 25:1691-700.
18. Pardanani A, Lim KH, Lasho TL, et al. WHO subvariants of indolent mastocytosis: clinical details and prognostic evaluation in 159 consecutive adults. Blood 2010; 115:150-1.
19. Brockow K, Jofer C, Behrendt H, et al. Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk factors in 120 patients. Allergy 2008; 63:226-32.
20. Butterfield JH, Weiler CR. Prevention of mast cell activation disorder associated clinical sequelae of excessive prostaglandin D2 production. Int Arch Allergy Immunol 2008; 147:338-43.
21. Horan RF, Sheffer AL, Austen KF. Cromolyn sodium in the management of systemic mastocytosis. J Allergy Clin Immunol 1990; 85:852-5.
22. Carter MC, Robyn JA, Bressler PB, et al. Omalizumab for the treatment of unprovoked anaphylaxis in patients with systemic mastocytosis. J Allergy Clin Immunol 2007; 119:1550-1.
23. Lim KH, Pardanani A, Butterfield JH, et al. Cytoreductive therapy in 108 adults with systemic mastocytosis: outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine. Am J Hematol 2009; 84:790-4.
24. Escribano L, Álvarez-Twose I, Sánchez-Muñoz L, et al. Prognosis in adult indolent systemic mastocytosis: a long-term study of the Spanish Network on Mastocytosis in a series of 145 patients. J Allergy Clin Immunol 2009; 124:514-21.
25. Paul C, Sans B, Suarez F, et al. Masitinib for the treatment of systemic and cutaneous mastocytosis with handicap: a phase 2a study. Am J Hematol 2010; 85:921-5.
26. Georgin-Lavialle S, Lhermitte L, Dubreuil P, et al. Mast cell leukemia. Blood 2013; 121:1285-95.
27. Ustun C, Reiter A, Scott BL, et al. Hematopoietic stem-cell transplantation for advanced systemic mastocytosis. J Clin Oncol 2014; 32:3264-74.
28. Cherner JA, Jensen RT, Dubois A, O’Dorisio TM, Gardner JD, Metcalfe DD. Gastrointestinal dysfunction in systemic mastocytosis. A prospective study. Gastroenterology 1988; 95:657–667.
29. Lim KH, Tefferi A, Lasho TL, et al; Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood. 2009;113(23):572736.
30. Theoharides TC, Valent P, Akin C. Mast cells, mastocytosis, and related disorders. N Engl J Med 2015;373:163-72