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 40-year-old female with c-kit-positive ISM had daily flushing, nausea, abdominal discomfort, and loose stools 3-4 times per day. She had cutaneous lesions of telangiectasia macularis eruptiva perstans and tryptase 55.2 ng/ml (). She complained of debilitating bone pain, episodic presyncope, shortness of breath, and frequent palpitations. Ongoing medications included cetirizine, ranitidine, ketotifen, and cromolyn. Treatment with omalizumab 300 mg every 4 weeks was started (). After 3 injections, bone pain and GI symptoms had subsided. After 6 cycles of omalizumab, cutaneous lesions had decreased in number, daily palpitations and syncopal episodes had subsided, and tryptase had increased to 61.7 ng/ml (). She was subsequently able to discontinue both ketotifen and cromolyn with ongoing treatment with omalizumab.