Idiopathic Angioedema due to NSAID use with discovery due to Montelukast use

Hess S
LECOM/ Larkin Community Hospital, South Miami, FL, USA

Nonsteroidal Anti- Inflammatory medications have been found to cause “Pseudoallergic reactions” in which symptoms mimic an IgE mediated allergic reaction. The common symptoms are bronchospasm, urticaria, rhinoconjuncitivitis and occasionally anaphylaxis. The symptoms occur within minutes to hours after the medication is taken. Pseudoallergic reactions differ from IgE mediated reactions in that they can occur on the first dose without any previous sensitization. Pseudoallergic reactions occur as a direct result of the pharmacological action of the medication and are dose dependent.

Case Report
A 5 year old African American male with no past medical history presents with repeated episodes of facial angioedema that started 4 weeks prior. The mother reports the episodes occur with swollen lips and eyes lasting 12-48 hours. The mother has taken her son to the ED and urgent care with treatment consisting of steroids and an antihistamine. While being examined in the office, the patient develops sudden lip swelling. The child denies any itchy skin, urticaria or abdomen pain.
C4 and C1 esterase inhibitor levels returned normal values. Total IgE returned at 40 and serum specific IgE failed to return any positive values. The mother reports the patient had 3 similar episodes of angioedema after the initial visit but no episodes for the last 2 weeks. The mother reports the pediatrician started Montelukast daily and since then the child has not had any episodes. Further history was taken and the mother stated that the child has taken Ibuprofen daily for musculoskeletal pain for the past 2 months. She reports that within an hour of giving it, the patient would have nasal congestion and watery eyes which usually subsided in 1-2 hours. The child was diagnosed with a Pseudoallergy to NSAIDs. They were instructed to avoid all NSAIDs and continue Montelukast.

The precise mechanism of Pseudoallergic reactions has not been established however it likely involves inhibition of the Cyclooxygenase enzyme. Cyclooxygenase inhibition causes a shift in the arachidonic acid metabolism toward the 5-lipoxygenase pathway and increased production of leukotrienes. Ibuprofen is a non -selective Cyclooxygenase inhibitor affecting both COX-1 and COX-2. The patient’s mother in the initial visit did not state that the patient was taking Ibuprofen when asked about the child’s medications. After the patient began taking Montelukast and the symptoms improved, the clinician asked specifically about Aspirin or NSAID use which the mother stated she gave daily Ibuprofen to the patient. The significant improvement with the Montelukast as a leukotriene receptor antagonist provided the vital clue of the Pseudoallergy diagnosis.

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