Anaphylaxis Treatment or Trigger? A Case Report of Reaction to Diphenhydramine and Steroids as Premedications

The following case study was authored by J Freeman, C Reynolds, W Soong, and J Anderson, and presented at the American College of Asthma, Allergy and Immunology (ACAAI) ) annual meeting in Seattle, Washington.

Introduction: Anaphylaxis affects 1.6%-5.1% of adults. Treatment with epinephrine is generally effective, and supplementary medications can be used for prevention/treatment of anaphylactoid symptoms. Common adjuncts include corticosteroids and antihistamines. Radiocontrast is necessary for evaluation of certain conditions and cannot always be avoided even with history of reaction. While underlying mechanisms of contrast reactions are not well understood, premedication with corticosteroids/antihistamines can often be used for prevention of reactions.

Case Description: 64-year-old male with DM2, hemodialysis-dependent ESRD, and known contrast reactions presented for routine fistulogram and experienced severe anaphylaxis 10 minutes postadministration of IV premedications (methylprednisolone/diphenhydramine), prior to contrast administration. Anaphylaxis resolved after epinephrine, albuterol, and fluids, and he was referred to Allergy for identification of offending agents. Prick/intradermal testing to various steroids/antihistamines was performed. Testing was positive to IV methylprednisolone succinate, IV hydrocorticone succinate, and IV diphenhydramine. Patient has since tolerated PO prednisone, loratadine, and fexofenadine.

Discussion: Our patient may have anaphylaxed to steroid, succinate, and/or diphenhydramine. Negative testing to prednisolone and prednisone-tolerance make succinate a more likely culprit than steroid, but further testing/challenge is needed to elucidate. Regarding antihistamines, this is one of few reports of reaction/positive testing to diphenhydramine with concurrent negative

testing/tolerance to loratadine and fexofenadine. Adjunct therapies for prevention/treatment of allergic reactions can occasionally trigger anaphylaxis. These medications should therefore be included in anaphylaxis workup. Allergy testing may help predict tolerability of alternative agents when similar medications are needed. Given limited reports in the literature, further studies are needed to better determine reliability of testing for these agents and cross-reactivity between them.

In August, the US Food and Drug Administration approved the first generic version of both EpiPen and EpiPen Jr (epinephrine) auto-injector for the emergency treatment of allergic reactions in adults and pediatric patients who weight more than 33 pounds.

The approval, granted to Teva Pharmaceuticals USA, indicates a generic version of the 0.3 mg- and 0.15 mg-strength injectors. The marketing is approved to include patients with life-threatening allergic reactions (anaphylaxis).

According to the FDA, anaphylaxis occurs in approximately 2% of all Americans, with those who have experienced a previous episode being at risk for another one. The epinephrine injector has been approved under several various product names over the years, and are intended for emergency patient use at the time of an event.

Scott Gottlieb, MD, commissioner of the FDA, said in a statement that the approval is part of the FDA’s commitment to progress patient access to less costly, safe, effective therapy options.

“This approval means patients living with severe allergies who require constant access to life-saving epinephrine should have a lower-cost option, as well as another approved product to help protect against potential drug shortages,” Gottlieb said. “The path to developing generic drug-device combination products like this one is challenging.”