A 28-year-old male developed urticaria pigmentosa confirmed by skin biopsy in 2008. The number of skin lesions had been gradually increasing over the course of 6 years. A bone marrow biopsy confirmed the presence of ISM with c-kit D816V mutation and serum tryptase of 134 ng/ml. He complained of nausea, palpitations, and presyncope, which recurred every 2–4 weeks []. More severe multisystem reactions occurred approximately twice per year, usually triggered by respiratory tract infections, resulting in itchy skin, flushing, nausea, lightheadedness, severe joint pain, and mild throat constriction with no loss of consciousness. Symptoms were poorly controlled in spite of sodium cromoglycate, ketotifen, and cetirizine. In late 2014, treatment with omalizumab 150 mg at 4-week intervals was started (). In early 2015, due to a suboptimal response to therapy, his omalizumab dosage was increased to 300 mg every four weeks. Four months later, tryptase levels had fallen from 134 ng/ml to 84 ng/ml (), with complete control of all symptoms by seven months. A trial of dose reduction of omalizumab back to 150 mg every 4 weeks resulted in a return of episodic flushing, nausea, bone pain, palpitations, and diarrhea as well as 2 anaphylactic reactions, both requiring hospitalization within a span of 6 weeks. Basal tryptase levels had increased to 100 ng/ml. Omalizumab dosage was increased to 300 mg at 2-week intervals and later maintained at 4-weeks intervals. By early 2017, he had experienced only one reported flare of symptoms with facial flushing, dizziness, and diarrhea. In April 2018, the patient reported his first anaphylactic reaction in nearly two years, 3 months after omalizumab injections had been discontinued. The number of skin lesions of urticaria pigmentosa was not controlled by omalizumab, and later, he required ultraviolet therapy with a good clinical response.
A 51-year-old female with c-kit-positive ISM and tryptase 31.8 ng/ml () reported intermittent episodes of shortness of breath, chest tightness, abdominal pain, and diarrhea. She had generalized lesions of urticaria pigmentosa involving her entire body, although numerous on her lower extremities. Ketotifen and ranitidine failed to control the symptoms. Omalizumab injections were started at 300 mg every two weeks (). At follow-up, her shortness of breath and chest tightness were controlled and GI symptoms had improved. Furthermore, her urticaria pigmentosa had improved and was now only observed on the lower abdomen and upper thighs. After the fourth cycle of omalizumab, she experienced an immediate multisystem reaction with respiratory distress and tongue swelling. A fifth cycle was attempted but again resulted in a similar reaction, leading to discontinuation of omalizumab therapy. At follow-up, she reported a worsening respiratory and functional status as well as 3-4 loose bowel movements per day. Basal tryptase levels had increased up to 41.2 ng/ml ().