Fig. 3

Biological factors and cutaneous symptoms. Cutaneous mastocytosis is characterized by abnormal mast cell (MC) proliferation and degranulation in the skin leading to symptoms such as itchy, brown patches (see photograph). In many cases, mutations in the coding kit gene (c-kit) are responsible for intensification of mast cell proliferation, infiltration, and mediator release in the skin. In the case of this patient, several factors could contribute to the extension of cutaneous symptoms. When the coping strategies of the patient are surpassed, life events induce emotional stress (red flash), implicating the cerebral limbic system and triggering activation of the sympathetic nervous system and the hypothalamic–pituitary–adrenal axis. Heat and sun radiation (yellow flash) can reinforce the activation of mast cells, which locally release several substances such as histamine, tryptase, and corticotropin-releasing factor (CRF), inducing a melanogenic effect. Cutaneous sensory nerve endings, in close contact with mast cells, can also be activated and induce neurogenic inflammation. They mediate the orthodromically itchy reflex associated with prurit (blue flashes). The following antidromic stimulation (violet flash) induces the release of mediators from sensory endings (substance P, calcitonin gene-related peptide CGRP). These neuropeptides cause further mast cell degranulation. All these processes extend and exacerbate cutaneous mastocytosis symptoms