Dysregulation of Arachodonic Acid Metabolism resulting from Aminosalicylate administration may cause Asthma Exacerbation in atopic patients with Inflammatory Bowel Disease

Abstract

INTRODUCTION: Aminosalicylates have been reported to be associated with respiratory side effects. Dyspnea, cough and pneumonitis have been well documented. Asthma has been speculated to be a potential adverse reaction of aminosalicylates because of the molecular similarity with aspirin. However, there have been no reported cases of asthma exacerbations occurring as a result of aminosalicylate administration. We report two cases of documented asthma occurrences, confirmed with medication rechallenge, resulting from mesalamine. CASE SERIES Case 1: MO is a 28 year old woman with a history of asthma, not requiring chronic medications, and newly diagnosed terminal ileal and colonic Crohn's disease. She initially presented with a fever, abdominal pain and leukocytosis. Abdominal CT revealed an abscess adjacent to the ileum. Laparoscopic drainage and antibiotics resulted in abscess resolution and white count normalization. One week following mesalamine administration, MO reported dyspnea and wheezing similar to previous asthma exacerbations. Chest radiograph was normal. Self-discontinuation of mesalamine and albuterol resolved her symptoms. Two weeks later, mesalamine was restarted. The patient developed recurrent dyspnea and wheezing which resolved following mesalamine discontinuation. Case 2: CL is a 47 year old woman with a history of asthma not requiring chronic medications and colonic Crohn's disease. Initial presentation and subsequent exacerbations resulted in frequent hospitalizations and recurrent steroid administration. Treatment with mesalamine was reported to result in dyspnea and wheezing attributed to an asthma exacerbation. Chest radiograph was normal. Her respiratory symptoms were treated with albuterol and she self-discontinued her mesalamine. She subsequently transferred her care to our institution. She was restarted on mesalamine with development of dyspnea and wheezing which was attributed to an asthma exacerbation by her pulmonologist. Mesalamine was discontinued with resolution of her dyspnea. DISCUSSION: Asthma has been speculated to be an adverse reaction to aminosalicylates. However, there have been no documented cases of asthma occurring as a result of aminosalicylates. Given the similar molecular structures of aspirin and aminosalicylates, an imbalance in arachidonic acid metabolism can be a possible mechanism for asthma. The direct inhibition of the cyclooxygenase (COX1) pathway by aspirin leads to decreased prostaglandin E2 synthesis and uninhibited 5-lipoxygenase pathway resulting in increased leukotrienes. The presence of pro-inflammatory mediators may trigger bronchospasm in sensitive individuals. While aminosalicylates have been shown to inhibit prostaglandin and leukotriene formation, it can be speculated that they may stimulate prostaglandin production in certain concentrations which may rarely promote dysregulation of normal arachidonic acid metabolism. These cases illustrate that asthma exacerbation is a potential adverse reaction to mesalamine. Both patients had a history of asthma and in both cases the bronchospasm improved with discontinuation of mesalamine. Rechallenge with mesalamine resulted in recurrence of dyspnea and wheezing. The clinical evidence combined with the above proposed pathophysiology suggests that the previously speculated, but unreported complication of asthma from aminosalicylate treatment, can occur in predisposed individuals. Physicians should be aware of this potential adverse reaction to aminosalicylates to ensure optimal care.