Serum Sickness-Like Reactions Clinical Characteristics and Management: A Systematic Review

J Allergy Clin Immunol Pract. 2025 May;13(5):1068-1074. doi: 10.1016/j.jaip.2025.02.027. Epub 2025 Mar 1.

Abstract

Background: Serum sickness-like reaction (SSLR) is an adverse reaction mainly to drugs, infectious agents, or vaccines, characterized by the presence of rash, arthralgia, or arthritis and occasionally fever.

Objective: This systematic review aimed to analyze the clinical characteristics, implicated agents, symptomatology, and management of SSLR.

Methods: We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Case reports and case series were included owing to the paucity of data in the literature on SSLR. We performed a comprehensive search of Embase and MEDLINE. Data extracted included age, comorbidities, medication exposure, time to reaction, symptoms, diagnostic criteria, and treatment modalities. Descriptive statistics were employed to summarize the data. We used χ2 test was used to compare categorical variables between adults and children.

Results: A total of 44 studies involving 468 patients were included. Antibiotics were more associated with SSLR in children than in adults (P < .01). β-Lactam antibiotics, particularly amoxicillin (72.1%), were the leading implicated agents. Dermatologic manifestations, primarily maculopapular rashes, were present in 100.0% of cases whereas joint symptoms occurred in 78.7%. Corticosteroids were effective in resolving symptoms in most cases.

Conclusions: Serum sickness-like reaction presents diagnostic challenges owing to overlapping symptoms with other drug reactions. β-Lactams are the most common implicated agents, particularly in pediatric populations. Systemic corticosteroids may provide relief, but standardized guidelines for diagnosis and management are needed. Further research is essential to clarify the pathophysiology and optimize treatment strategies for SSLR.

Keywords: Corticosteroids; Hypersensitivity; Maculopapular rash; Pediatric drug reactions; Serum sickness-like reaction; β-Lactams.

Publication types

  • Systematic Review

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Anti-Bacterial Agents* / adverse effects
  • Child
  • Humans
  • Serum Sickness* / diagnosis
  • Serum Sickness* / drug therapy
  • Serum Sickness* / therapy

Substances

  • Anti-Bacterial Agents
  • Adrenal Cortex Hormones