Immunoglobulin E-mediated anaphylaxis with inhaled cromolyn sodium

Adverse reactions to cromolyn sodium inhalation are rare and evidence to document IgE mediation is meager. We report a case of a 7-yr-old, timothy-sensitive, asthmatic girl with severe anaphylaxis after inhaled cromolyn sodium. After 1 wk of attempted cromolyn sodium inhalation, a demonstration dose was administered in the physician's office. Within 1 min of a single inhalation, the patient became cyanotic, hypotensive, and suffered cardiopulmonary arrest. Resuscitation successfully revived the patient, who remained in status asthmaticus requiring intravenous therapy for 36 hr. Sera obtained at anaphylaxis and 3 mo later were negative for IgG anti-cromolyn sodium antibodies by the Farr technique. IgE involvement was investigated by passive transfer of the patient's 2-mo serum to the mother; 48 hr after transfer, both passively sensitized and nonsensitized skin sites were challenged intradermally with 0.02 ml of 1% aqueous cromolyn sodium, 1% lactose solution, and 100 PNU/ml timothy extract. Markedly positive reactions occurred to cromolyn sodium (44/110 mm², wheal/flare area) and timothy (44/80 mm²) at sensitized sites, with negative reactions in nonsensitized areas. Challenge with 1% cromolyn sodium solution at a site sensitized with heat-inactivated patient serum (56° C, 3 hr) produced mild induration (5 mm²), and lactose induced a small area of induration without flare. In vitro studies with the patient's basophils, obtained 11 mo after the systemic reaction, failed to demonstrate enhanced histamine release in the presence of cromolyn sodium. This case represents the worst reported adverse reaction to cromolyn and suggests that the mechanism was the result of IgE-mediated anaphylaxis. Physicians using this medication should be aware that clinically significant immune sensitization to cromolyn can occur.