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 32-year-old male with lesions of urticaria pigmentosa was diagnosed with c-kit-positive ISM. During the summer of 2015, while working outside, he experienced 3 Hymenoptera stings resulting in immediate onset of flushing and presyncope (). In spite of administration of epinephrine, he developed nausea and vomiting, generalized hives, and worsening presyncope. He was resuscitated in an emergency department but continued to experience daily diarrhea, numbness, and tingling sensation in his extremities, night sweats, severe headaches, and flushing upon strenuous physical activity. Because the symptoms were refractory to a combination of cetirizine, ranitidine, montelukast, and cromolyn, he was started on omalizumab 300 mg at 4-week intervals (). A follow-up 8 months later revealed improved symptomatic control and a fall in tryptase from 42.2 to 34 ng/ml (). However, he has continued to experience intermittent itching, flushing, and diarrhea. A follow-up in late 2018 revealed that he had chosen to discontinue omalizumab, with continued control of disease.