Serum sickness in humans is a reaction to proteins in antiserum derived from a non-human animal source, occurring 5–10 days after exposure. It is a type of hypersensitivity, specifically immune complex hypersensitivity (type III). The term serum sickness–like reaction (SSLR) is occasionally used to refer to similar illnesses that arise from the introduction of certain non-protein substances, such as penicillin. It was first characterized by Clemens von Pirquet and Béla Schick in 1906.
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.  Needs update due to SARS-CoV-2 see: https://www.nejm.org/covid-vaccine
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.
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