Delayed drug reaction to trimetoprim/sulfamethoxazole or cephalexin
Question:
3/31/2016
I recently saw a patient for drug fever. 62 year-old who had cellulitis/abscess on his arm. He was started on Bactrim on 12/31/15 and Keflex was added on 1/4/16 with improvement in the infection. On 1/13/16, he developed chills/rigors and had a fever of 102.6 F. Also had diffuse erythema/flushing and some pruritus on the torso but no clear hives, angioedema or respiratory symptoms. Since his infection was improved and his blood cultures were negative, this was thought to be a hypersensitivity reaction from the antibiotics. Antibiotics were discontinued, and he improved. What would you recommend regarding administering these antibiotics in the future? Are Penicillin and other Cephalosporins ok? Would it be worthwhile to do skin testing or a challenge?
Answer:
Adverse drug reaction issues are a challenge as there are limited definitive tests and thus most recommendations are based upon probabilities and experience. Your patient experienced a delayed reaction, 13 days after trimethoprim/sulfamethoxazole and 9 days after initiation of the cephalothin. Thus, IgE mechanism is not relevant to this reaction so immediate wheal and flare skin tests are not of much value other than from a medicolegal perspective. The two most likely mechanisms would be a cellular mediated immune response or an immune complex reaction. No additional information was provided, but it may have been helpful to have complement studies and a urinalysis to assess the likelihood of a serum sickness reaction during the acute symptoms. Patch testing with the suspected culprits is a consideration but the methodology and techniques for patch testing are debated. The 2015 Practice Parameters on Drug Allergy made the following statement:
“In recent years there have been reports concerning the diagnostic utility of patch tests with systemically administered drugs in non–IgE-mediated cutaneous drug reactions. 11 Drug patch testing may be useful for certain types of cutaneous drug reactions, including maculopapular exanthems, acute generalized exanthematous pustulosis, and fixed drug eruptions,12-14 but generally is not helpful for SJS or urticarial eruptions.12-15”
I would not be comfortable with challenging with trimethoprim/sulfamethoxazole or cephalexin. However, I would be comfortable with challenging with other cephalosporins or penicillins. My concern with trimethoprim/sulfamethoxazole is the potential for severe, life-threatening, delayed drug reactions. The antigens responsible for delayed reactions are not usually known but I do not think the risk of a life threatening reaction to a beta lactam antibiotic is sufficient to disallow all use of these agents.
In summary, I do not think immediate wheal and flare testing for IgE mediated drug allergy is relevant in your patient. Patch testing to detect T cell mediated responses is a consideration but I would not perform do the lack of consensus on how to perform such testing. I would consider an oral challenge with alternative beta lactams, but not cephalexin, and I would avoid trimethorprim/sulfamethoxazole.
Wolkenstein P, Chosidow O, Flechet ML, et al. Patch testing in severe cutaneous adverse drug reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. Contact Dermatitis. 1996;35: 234–236. III.
Romano A, Viola M, Mondino C, et al. Diagnosing nonimmediate reactions to penicillins by in vivo tests. Int Arch Allergy Immunol. 2002;129:169 –174. III.
I hope this information is of help to you and your patient.
All my best.
Dennis K. Ledford, MD, FAAAAI