The patient was a 27-year-old man with a history of recurrent episodes of angioedema. The episodes begun when he was 19 years old, and their frequency and severity had been rising over the previous six months. There was a history of urticaria following penicillin administration in early childhood, but there were no other known allergies.\nInitially, the episodes were manifested by mild urticaria which resolved spontaneously. But the severity and frequency of attacks increased over the years. In the last few months, the attacks became more frequent, at least twice a month, and included autonomic dysfunction: one episode of syncope and a few presyncopal episodes associated with scrotal and neck swelling and abdominal pain. Two of the episodes were considered “life threatening” due to imminent airway obstruction and were treated with subcutaneous epinephrine and intravenous steroids, which were tapered down gradually after each episode. Due to the severity of the episodes, the patient was instructed to carry epinephrine 0.3 mg autoinjector (EpiPen) at all times.\nExtensive search for possible etiology was carried out. Ancillary studies were nonproductive. Blood tests included a complete blood count, full chemistry panel, serum levels of thyroid stimulating hormone, antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, C-1 inhibitor activity, tryptase, and chromogranin. Urinary vanillylmandelic acid and 5-hydroxyindoleacetic acid were also negative, as were urine and stool tests for OVA and parasites. Imaging studies (chest roentgenograms, abdominal ultrasound) did not show evidence of echinococcal infection, and endoscopically obtained biopsies from the GI tract did not show eosinophils or mast cells. Skin biopsy was negative for C-KIT, and bone marrow aspiration showed no evidence of increased mast cell count and was negative for tryptase and C-KIT. While the workup was in progress, the patient was placed on prophylactic antihistamines, using several preparations, but the attacks persisted, and periodically supplemental steroids were necessary.\nThe patient disclosed that from time to time he was using marijuana socially and that it seemed to him that the attacks were less frequent when he did. The patient declared that he did not prepare the cigarette himself, so we presumed he did not have a significant skin contact with cannabis. The history was consistent with the known effect of cannabis on the immune system as described in the introduction, so we conjectured that marijuana may have had a modulatory effect facing failure of other treatment modalities. We suggested that the patient should try medical grade marijuana inhalations (cannabis products for medical indications may be legally used in Israel, but authorization by the Ministry of Health is required for each individual patient and prescription must be renewed monthly). The patient was informed that there was no supporting evidence in the medical literature for this treatment in his condition but that the potential risk for side effects was minimal and he consented to try. He was instructed not to drive or engage in other potentially risky activities during treatment.\nWe prescribe a total of 20 grams of medical grade marijuana per month, inhaled two to three times a week, which in Israel is the minimal accepted dosage for medical indications. The patient stayed on this dose for two years during which the patient did not have a single attack and no adverse effects were observed. After two years, the patient tried to stop treatment, on his own initiative, but developed a recurrent severe attack a week later. After resuming the treatment no further attacks were observed over the next 4 months of close followup (the regulations for legal use of medical marijuana stipulate that the prescription must be renewed monthly). The timeline of the course of the disease is depicted in .
A 67-year-old white female with a 3-year history of recurrent, twice-weekly angioedemas of the lips, tongue and larynx. The clinical response of the angioedemas to the intake of antihistamines (AH) of doses up to three times higher than that normally recommended was not sufficient. Thus, glococorticosteroids (GCS) on a weekly basis were often necessary to control the symptoms. Omalizumab 150 mg was administered subcutaneously in 4-week intervals. After the first injection of omalizumab, facial swellings improved markedly. Treatment with AH and GCS were discontinued after 8 weeks. Omalizumab was paused after the fourth injection. Eleven weeks after stopping therapy, facial angioedemas reoccurred (Fig. ). Omalizumab 150 mg was resumed and the angioedema disappeared after 1 week. The patient stayed symptom-free. The interval between injections was stretched to every 2 months and the patient stayed symptom-free with only intermittent discrete eyelid swellings.