Serum sickness-like reaction (SSLR) is a drug reaction that manifests with fevers, an urticarial or exanthematous rash, arthralgias, myalgias, and occasionally lymphadenopathy. As opposed to true serum sickness, it is not secondary to heterologous or chimeric therapeutic proteins and it usually lacks immune complex formation characteristic of serum sickness. The theorized pathogenesis for SSLR includes aberrant inflammation secondary to abnormal metabolism of medication byproducts. Most reactions occur within 1-3 weeks after drug initiation.

Eosinophilia may be present, but unlike true serum sickness, immune complexes, hypocomplementemia, and vasculitis are not found. Most reactions are mild and self-limited and resolve within several days to weeks after drug withdrawal.

Antibiotics, particularly cefaclor, penicillins, and sulfonamides, nonsteroidal anti-inflammatory drugs (NSAIDs), allopurinol, propranolol, and carbamazepine are among the most frequent offenders.