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.
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 ().