Serum sickness-like reaction to cefuroxime: a case report and review of the literature

Journal of Drugs in Dermatology, July, 2007 by Rajani Katta, Vijayalaxmi Anusuri

Cefaclor is a second-generation oral cephalosporin and is one of the major causes of SSLR, as supported by retrospective and prospective studies. Levine reported the results of a prospective trial to determine the incidence and character of adverse events in children treated with either cefaclor or amoxicillin. The incidence rates of SSLR, EM, and urticaria were 3.4% in children treated with cefaclor and 0.79% in children treated with amoxicillin. No children in the amoxicillin group described SSLR or EM. (6) The study found that these reactions were significantly more likely to occur during or after the second or third course of therapy. (6)

The US FDA spontaneous reporting system of adverse drug reactions contain many more reports of SSLR after cefaclor than after other antibiotics including amoxicillin, cephalexin, and trimethoprim/sulfamethoxazole. (1)

Ibia et al performed a review of private pediatric practices and noted that significantly more rashes were documented for cefaclor as compared with penicillins, sulfonamides, and other cephalosporins. Of the patients receiving cefaclor, 12.3% developed various rashes, including 1.9% diagnosed with definite or probable SSLRs. Other rashes were described as urticaria, EM, or indistinct. (7) Heckbert et al studied occurrences of SSLR in a population of children who had been prescribed cefaclor or amoxicillin, and found that the risk of serum sickness was significantly elevated after cefaclor compared with amoxicillin. (5) In order to explain the increased incidence of SSLR in patients receiving cefaclor, Kearns et al studied 19 patients with this reaction. They compared these patients to others with immediate hypersensitivity to cefaclor, to controls who had tolerated cefaclor therapy well, and to immediate family members of those with cefaclor-associated SSLR. Using an in vitro lymphocyte-based cytotoxicity assay, they found positive results in patients with SSLR and their mothers who had never received cefaclor. They concluded that SSLR to cefaclor required biotransformation of the parent drug. This transformation may have resulted from inherited defects in the metabolism of reactive intermediates. (8)

It remains unclear why cefaclor, more so than other antibiotics or cephalosporins, triggers SSLR. Kearns et al found a lack of in vitro cross-reactivity between cefaclor and cephalexin in patients with SSLR. (8) A later study examined patients with SSLR to cefaclor, and found no in vitro cross-reactivity with loracarbef, another second-generation cephalosporin. These patients were also able to tolerate a full course of therapy of loracarbef without adverse reactions. (9) However, there have been reports of SSLR induced by other cephalosporins, including first-generation cephalosporins such as cephalexin (1) and cephazolin. (10) Lowery et al described 4 cases of SSLR to cefprozil, another second-generation cephalosporin, in addition to other cases reported to the US FDA. (11) In our case, cefuroxime, also another second-generation cephalosporin, was implicated as the causative agent.