Serum sickness
A type III hypersensitivity reaction to animal-derived antiserum.
Serum sickness is a type III hypersensitivity reaction caused by immune complexes that form when the human immune system mistakes proteins in animal-derived antiserum for harmful antigens.[1] Symptoms classically include fever, rash, and polyarthritis or polyarthralgias, appearing an average of 12 days after exposure.[2][3] It is a rare but important cause of fever, arthritis, and rash in both children and adults.[2]
Quick Facts
- Field
- Hematology
- Symptoms
- rash
- joint pain
- fever
- lymphadenopathy (swelling of lymph nodes)
- Causes
- antiserum, some drugs
- Diagnosis
- symptoms, blood test (low cell counts and complement protein counts), urine test
- Differential
- lupus
- erythema multiforme
- hives
- Prevention
- not using non-human antitoxins, prophylactic antihistamines or corticosteroids
- Treatment
- resolves spontaneously
- Medication
- corticosteroids
- antihistamines
- analgesics
- prednisone
Facts from the source article.
Key facts and history
Von Pirquet and Schick provided a pathogenic description based on clinical observations of patients treated with horse serum containing diphtheria antitoxin.[4] They observed a clinical syndrome of fever, lymphadenopathy, cutaneous eruptions, and arthralgias 8 to 12 days after subcutaneous injections of horse serum.[4] Serum sickness is becoming less common over time because many animal-serum-based drugs have been replaced with artificial drugs.[5] Clemens von Pirquet and Béla Schick provided the first description of serum sickness in 1905, based on clinical observations of patients treated with horse serum containing diphtheria antitoxin.[6][4]
Exposure to animal-derived antibodies, typically administered to combat infections or venomous bites, is the usual cause of serum sickness.[7] These immune complexes then settle, penetrate blood vessel walls, and trigger the complement cascade, which sparks an inflammatory response and depletes complement component 3 (C3).[1] This process leads to leukocytoclastic vasculitis and hypocomplementemia, characterized by reduced serum C3 levels.[8] As of 2012, the Johns Hopkins Bloomberg School of Public Health reported that routinely recommended vaccinations for the general U.S. population have not been demonstrated to cause serum sickness.[9]
What the research sources say
The same source notes that medications containing heterologous antigens are the most common cause, including vaccinations, immune modulating agents, and anti-venoms.[2] De Silva's review reports that serum sickness after antivenom has a delayed onset between 5 and 14 days after its administration.[4] The Rixe account explains that laboratory results may show elevated serum creatinine, which typically returns to baseline within days to weeks of discontinuing the offending agent.[2] De Silva's review states that laboratory analyses show elevated erythrocyte sedimentation rate, leukocytosis, haematuria, proteinuria, and a decrease in complement components.[4]
The Rixe account emphasizes that serum sickness is a self-limited entity that usually resolves upon discontinuation of the offending agent, with or without additional treatment.[2] Serum sickness is defined as a type III hypersensitivity reaction mediated by immune complexes, with a classic presentation including fever, rash, and polyarthritis or polyarthralgias.[2]
References
- Wikipedia, "Serum sickness" (CC BY-SA 4.0), which cites: Paizis, "Encyclopedia of Immunology", Academic Press, 1998, p. 2168–2170 (we also read that source) en.wikipedia.org
- Rixe, "Serum Sickness", StatPearls [Internet], 2023-08-28. facts only, no text reused. ncbi.nlm.nih.gov
- Wikipedia, "Serum sickness" (CC BY-SA 4.0), which cites: Khalaf, "Serum Sickness-Like Reactions Clinical Characteristics and Management: A Systematic Review", The Journal of Allergy and Clinical Immunology: In Practice, 2025-05-01, p. 1068–1074 (original not read by us) en.wikipedia.org
- De Silva, "Adverse reactions to snake antivenom, and their prevention and treatment", British Journal of Clinical Pharmacology, 2016-09-16. facts only, no text reused. pmc.ncbi.nlm.nih.gov
- Wikipedia, "Serum sickness" (CC BY-SA 4.0), which cites: Paizis, "Encyclopedia of Immunology", Academic Press, 1998, p. 2168–2170; Paizis, "Encyclopedia of Immunology", Academic Press, 1998, p. 2168–2170; Benjamin, "Pediatric Emergency Medicine", Saunders, 2008, p. 741–743 (we also read that source) en.wikipedia.org
- Wikipedia, "Serum sickness" (CC BY-SA 4.0), which cites: Paizis, "Encyclopedia of Immunology", Academic Press, 1998, p. 2168–2170; Jackson R, "Serum sickness", J Cutan Med Surg, October 2000, p. 223–5 (we also read that source) en.wikipedia.org
- Wikipedia, "Serum sickness" (CC BY-SA 4.0), which cites: Paizis, "Encyclopedia of Immunology", Academic Press, 1998, p. 2168–2170; Copenhaven, "Pediatric Clinical Advisor - Instant Diagnosis and Treatment", Mosby, 2007, p. 518; Paizis, "Encyclopedia of Immunology", Academic Press, 1998, p. 2168–2170 (we also read that source) en.wikipedia.org
- Wikipedia, "Serum sickness" (CC BY-SA 4.0), which cites: Benjamin, "Pediatric Emergency Medicine", Saunders, 2008, p. 741–743; Paizis, "Encyclopedia of Immunology", Academic Press, 1998, p. 2168–2170; Paizis, "Encyclopedia of Immunology", Academic Press, 1998, p. 2168–2170 (we also read that source) en.wikipedia.org
- Wikipedia, "Serum sickness" (CC BY-SA 4.0), which cites: "Institute for Vaccine Safety || do Vaccines Cause Serum Sickness?" (original not read by us) en.wikipedia.org
Each numbered sentence above was checked against the source it cites before publication. Sentences citing Wikipedia adapt text from the English Wikipedia article Serum sickness (contributors), used under CC BY-SA 4.0; this entry is available under the same licence. Other sources were used for facts only; no text or images are copied from them.
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