A 39-year-old man with a 10-year history of pruritus, chronic watery diarrhea, and diffuse, hyperpigmented skin papules underwent skin biopsy, which showed numerous superficial mast cells by CD117⁺ immunohistochemistry. A serum tryptase level was 417 ng/mL (reference range, 2-10 ng/mL), and referral was made to Hematology. Bone marrow biopsy revealed abundant aggregates of mast cells (panel A, CD117⁺), and random colonic biopsies revealed subepithelial sheets and aggregates of mast cells. The diagnosis of systemic mastocytosis was made. Histamine receptor blockade with cetirizine and ranitidine provided symptomatic relief, as did the mast cell–stabilizing agents cromolyn and monteleukast.

Six months later, this patient demonstrated clinical improvement but extensive urticaria pigmentosa (UP) lesions persist on the trunk and extremities. Darier's sign remains positive, wherein gentle friction is sufficient to degranulate mast cells associated with the UP lesions (panel B, after the examiner traced a vertical line on the patient’s forearm). Unlike other forms of dermatographism, Darier’s sign refers to urtication that is limited to the UP involved areas and, as in this case, spares the skin unaffected by UP.