|Symptoms||Fever, rash, joint pain|
|Causes||Certain vaccines (such as rabies), antivenom, immunomodulators (such as rituximab or thymoglobulin)|
|Diagnostic method||Blood tests, skin biopsy|
|Differential diagnosis||Serum sickness–like reaction (SSLR), acute rheumatic fever, Kawasaki disease, Dengue, Stevens-Johnson syndrome, IgA vasculitis|
|Treatment||Stopping the cause, antihistamines, NSAIDs, steroids, plasma exchange|
Serum sickness is a type of allergic reaction to non-human proteins. Symptoms commonly include fever, rash, and joint pain. It generally occurs 7 to 14 days after exposure and symptoms can last for a few weeks. Complications are rare, though repeated episodes of serum sickness may potentially result in kidney failure.
It most commonly occurs as a result of certain vaccines (such as rabies), antivenom, and immunomodulators (such as rituximab and thymoglobulin). The underlying mechanism involves hypersensitivity, specifically immune complex hypersensitivity (type III). Diagnosis may be supported by urine tests, blood tests, and a skin biopsy.
Treatment often simple involves stopping whatever is causing the condition. Antihistamines and NSAIDs may be used to improve symptoms. For more severe symptoms steroids may be used. If this is not effective plasma exchange may be an option. Outcomes are generally excellent.
Serum sickness is rare. It; however, may occur in up to 27% of people treated with thymoglobulin post kidney transplant. It was first described in detail by Clemens von Pirquet and Béla Schick in 1905.
Signs and symptoms
Signs and symptoms can take as long as 14 days after exposure to appear, and may include signs and symptoms commonly associated with hypersensitivity or infections.
- joint pain (arthralgia), especially finger and toe joints
- fever, as high as 40 °C and usually appears before rash
- lymphadenopathy (swelling of lymph nodes), particularly near the site of injection, head and neck
- hypotension (decreased blood pressure)
- splenomegaly (enlarged spleen)
- protein in the urine
- blood in the urine
When an antiserum is given, the human immune system can mistake the proteins present for harmful antigens. The body produces antibodies, which combine with these proteins to form immune complexes. These complexes precipitate, enter the walls of blood vessels, and activate the complement cascade, initiating an inflammatory response and consuming much of the available complement component 3 (C3). The result is a leukocytoclastic vasculitis. This results in hypocomplementemia, a low C3 level in serum. They can also cause more reactions resulting in typical symptoms of serum sickness.
Antitoxins and antisera
Some of the drugs associated with serum sickness are:
Allergenic extracts, hormones and vaccines can also cause serum sickness. However, according to the Johns Hopkins Bloomberg School of Public Health, currently routinely recommended vaccinations to the general population in the U.S have not been shown to cause serum sickness. 
Diagnosis is based on history given by patient, including recent medications.
Avoidance of antitoxins that may cause serum sickness is the best way to prevent serum sickness. Although, sometimes, the benefits outweigh the risks in the case of a life-threatening bite or sting. Prophylactic antihistamines or corticosteroids may be used concomitant with the antitoxin. Skin testing may be done beforehand in order to identify individuals who may be at risk of a reaction. Physicians should make their patients aware of the drugs or antitoxins to which they are allergic if there is a reaction. The physician will then choose an alternate antitoxin if it's appropriate or continue with prophylactic measures.
With discontinuation of the offending agent(s), symptoms usually disappear within 4–5 days.
Corticosteroids, antihistamines, and analgesics are the main line of treatment. The choice depends on the severity of the reaction.
- Rixe, N; Tavarez, MM (January 2020). "Serum Sickness". PMID 30855896. Cite journal requires
- "Serum sickness". dermnetnz.org. DermNet NZ. Retrieved 14 February 2021.
- Jackson R (October 2000). "Serum sickness". J Cutan Med Surg. 4 (4): 223–5. doi:10.1177/120347540000400411. PMID 11231202.
- Brucculeri M, Charlton M, Serur D (2006). "Serum sickness-like reaction associated with cefazolin". BMC Clin Pharmacol. 6: 3. doi:10.1186/1472-6904-6-3. PMC 1397863. PMID 16504095.
- Lundquist AL, Chari RS, Wood JH, et al. (May 2007). "Serum sickness following rabbit antithymocyte-globulin induction in a liver transplant recipient: case report and literature review". Liver Transpl. 13 (5): 647–50. doi:10.1002/lt.21098. PMID 17377915.