Pediatric Mastocytosis: An Update

Abstract

Mastocytosis is a rare clonal disorder, characterized by excessive proliferation and accumulation of mast cells (MC) in various organs and tissues. Cutaneous mastocytosis (CM), the most common form in children, is defined when MC infiltration is limited to the skin. Systemic mastocytosis (SM), the most common form in adults, is characterized by MC proliferation and accumulation in organs, such as bone marrow, lymph nodes, liver and spleen (1). Genetic aberrations, mainly the KIT D816V mutation, play a crucial role in the pathogenesis of mastocytosis, resulting in enhancing MC survival and subsequent accumulation in organs and tissues (2,3). CM includes 3 forms: solitary mastocytoma, maculopapular cutaneous mastocytosis (MPCM) and diffuse cutaneous mastocytosis (DCM). In the majority of children with CM, skin lesions regress spontaneously around puberty; unfortunately, in a few cases, it is not a self-limiting disease (4). Even if SM occurs occasionally, all children with mastocytosis require planned follow-up over time. Children with mastocytosis often suffer from MC mediator-related symptoms, the most common of which is itching, often triggered by rubbing the lesions. Management of pediatric mastocytosis is mainly based on strict avoidance of triggers. Treatment with H1 and H2 histamine receptor blockers on demand, and the availability of epinephrine auto-injectors for the patients to use in case of severe anaphylactic reactions are recommended.

Itchy Red-Brown Spots on a Child

“…Cutaneous mastocytosis, the skin-restricted variant, is by far the most common form of childhood mastocytosis (90% of mastocytosis cases in children) 1 and generally appears within the first 2 years of life. [1][2][3][4][5][6][7] Pediatric CM usually is a benign and transient disease with an excellent prognosis and a negligible risk for systemic involvement. 2,3,5 The pathogenesis of CM in children is obscure 1 ; however, somatic or germline gain-of-function mutations of the c-KIT proto-oncogene, which encodes KIT (ie, a tyrosine kinase membrane receptor for stem cell factor), may account for most pediatric CM phenotypes.…”

“…2,3,5 The pathogenesis of CM in children is obscure 1 ; however, somatic or germline gain-of-function mutations of the c-KIT proto-oncogene, which encodes KIT (ie, a tyrosine kinase membrane receptor for stem cell factor), may account for most pediatric CM phenotypes. 1,3,6 Activating c-KIT mutations leads to constitutive activation of the KIT receptor (expressed on the surface membrane of mast cells) and instigates autonomous (stem cell factorindependent) clonal proliferation, enhanced survival, and accumulation of mast cells. 2 Maculopapular CM is the most common clinical form of CM.…”

“…2 Darier sign typically is positive, with a wheal and flare developing upon stroking or rubbing 1 or several lesions. [1][2][3][4][5][6] The lesions gradually involute and often spontaneously regress at the time of puberty. [1][2][3][5][6][7] The clinical signs and symptoms of mastocytosis are not only related to mast cell infiltration but also to mast cell activation within the tissues.…”

“…[1][2][3][4][5][6] The lesions gradually involute and often spontaneously regress at the time of puberty. [1][2][3][5][6][7] The clinical signs and symptoms of mastocytosis are not only related to mast cell infiltration but also to mast cell activation within the tissues. The release of intracellular mediators from activated mast cells may have local and/or systemic consequences.…”

“…[2][3][4]7 Systemic symptoms are rare in childhood CM and consist of wheezing, shortness of breath, nausea, vomiting, reflux, abdominal cramping, diarrhea, tachycardia, hypotension, syncope, anaphylaxis, and cyanotic spells. [1][2][3][4][5][6][7] An elevated serum tryptase level is an indicator of both mast cell burden and risk for mast cell activation in the skin. 4,7 Treatment of pediatric CM is conservative and symptomatic.…”