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Serum sickness and serum sickness-like reactions

Mark H Wener, MD
Section Editor
N Franklin Adkinson, Jr, MD
Deputy Editor
Anna M Feldweg, MD


The cardinal features of serum sickness are rash, fever, and polyarthralgias or polyarthritis, which begin one to two weeks after the first exposure to the responsible agent and resolve within a few weeks of discontinuation. Although patients may appear very ill and uncomfortable during the acute febrile stage, the disease is self-limited and prognosis is excellent once the responsible drug is stopped.

This topic review will discuss serum sickness and serum sickness-like reactions, with an emphasis upon the biology and clinical features of serum sickness. A detailed discussion of hypersensitivity vasculitis, which has features similar to serum sickness, is presented separately. (See "Overview of cutaneous small vessel vasculitis" and "Hypersensitivity vasculitis in children".)


The term "serum sickness" was introduced by von Pirquet and Schick, who published a book with that title (Die Serumkrankheit) in 1905 [1]. The authors described an illness that developed in some patients after administration of horse serum that had been given as an anti-toxin for the treatment of diphtheria and scarlet fever. They noted that there was a delay between administration of the horse serum and the development of the symptoms of serum sickness, and the delay was shorter if horse serum was administered again at a later time.


Lack of clarity about the meaning of the term "serum sickness" arose because it has been used to describe a variety of different, although related, syndromes. The classic clinical syndrome is caused by immunization of the host (human) by heterologous (nonhuman) serum proteins and subsequent illness caused by formation of immune complexes. However, the term also has been used to describe syndromes of rash, arthritis, and fever, with onset several days to weeks following administration of a drug or in association with some infectious diseases.

Serum sickness — Serum sickness is the prototypic example of the Gell and Coombs "type III" or immune complex-mediated hypersensitivity disease (table 1) [2]. The reaction requires the presence of the antigen, coincident with antibodies directed against the antigen, leading to the formation of antigen-antibody or immune complexes. These should normally be cleared by the mononuclear phagocyte system, although if this system is not functioning well or is saturated by the immune complex load, then excess immune complexes may form in the circulation and deposit in tissues or form directly in the involved tissues. Immune complexes may deposit preferentially in joints because the synovial endothelium is fenestrated (with more permeable pores or slits) and thus is more accessible to proteins and protein complexes, although the reason that immune complexes target specific tissues is not well-understood. Once deposited, the presence of immune complexes in parenchymal tissues triggers an inflammatory response.

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Literature review current through: Nov 2017. | This topic last updated: Oct 19, 2015.
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