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 49-year-old male patient was referred to our clinic with a history of severe anaphylaxis (urticaria, angioedema, dyspnea, and hypotension) after a honeybee sting. Sensitization to apis mellifera was confirmed with both skin prick test and serum specific IgE and conventional IT for apis mellifera (Alutard SQ, ALK-Abelló, Hørsholm, Denmark) was initiated. Five minutes after the injection of 0.4-mL dose of the 4th vial (100,000 SQ units/mL) in the buildup phase, he developed anaphylaxis (flushing, itching, shortness of breath, and nausea). One week later, IT was continued with 0.1 mL of the 4th vial. An anaphylaxis episode similar to the previous one developed 5 minutes after the dose of 0.4 mL of the 4th vial in the patient whose IT dose was being increased 0.1 mL every week. This time the 3rd vial was started 1 week later by decreasing it by 0.6 mL. A systemic reaction similar to the previous one developed again at a dose of 0.4 mL of the 4th vial in our case who was continued IT at doses increased by 0.1 mL every week. We decided to combine IT with omalizumab 150 mg/2-week treatment due to these reactions. The omalizumab dosing scheme with b-VIT is not standardized and various dosing schedules have been used []. The scheme administered to our case is shown in . With IT + omalizumab combination, he was able to tolerate the buildup doses with which he had experienced anaphylaxis previously, and the maintenance dose (1 mL of the 4th vial) was reached. Omalizumab was discontinued and no reaction was observed with the maintenance dose administered 1 month later. However, after the maintenance dose of the 2nd month symptoms of itching, urticaria, cough, and dyspnea developed within 15 minutes. Adrenaline 0.5 mg intramuscular (IM) twice with an interval of 5 minutes, diphenhydramine 45.5 mg (Avil, Sandoz Ilac Sanayii A.S., Istanbul, Turkey) IM and methylprednisolone 40 mg (Prednol, Mustafa Nevzat Ilac Sanayii A.S., Istanbul, Turkey) intravenous were administered. Two weeks later, 150 mg of omalizumab was administered first and IT was administered 4 hours later by decreasing the dose to 0.4 mL of 4th vial. A reaction similar to the previous one occurred about half an hour after this dose. Patients who experienced significant bee anaphylaxis and have recurrent anaphylaxis episodes with b-VIT, must be evaluated regarding basal serum tryptase levels and mastocytosis []. The basal serum tryptase level was 63 ng/mL in our case (reference range < 11.5 ng/mL). The case had no mastocytosis skin findings and no history of chronic itching or urticaria. He did not describe a history of anaphylaxis with another allergen. The patient refused to be undergone bone marrow biopsy. Both IT and omalizumab treatments were terminated. Protection measures and how to use an epinephrine auto-injector were explained again.