Serum Sickness

Last Updated: January 21, 2002

Synonyms and related keywords: hypersensitivity reaction
Author: Susan M Chen, MD, Clinical Assistant Professor, Department of Emergency Medicine, University of Pennsylvania Health System, Presbyterian Medical Center
Susan M Chen, MD, is a member of the following medical societies: American Academy of Emergency Medicine, and Society for Academic Emergency Medicine

Background: Serum sickness is a type III hypersensitivity reaction that results from the injection of heterologous or foreign protein or serum. Reactions secondary to the administration of nonprotein drugs are clinically similar to serum sickness reactions.

Pathophysiology: Not all substances that are recognized as foreign by the immune system elicit an immune response. The antigen must be of characteristic size or have specific antigenic determinants and physiological properties to be an effective stimulator of the immune system. After an appropriate antigen is introduced, an individual's immune system responds by synthesizing antibodies after 4-10 days. The antibody reacts with the antigen, forming soluble circulating immune complexes that may diffuse into the vascular walls, where they may initiate fixation and activation of complement. Complement-containing immune complexes generate an influx of polymorphonuclear leukocytes into the vessel wall, where proteolytic enzymes that can mediate tissue damage are released. Immune complex deposition and the subsequent inflammatory response are responsible for the widespread vasculitic lesions seen in serum sickness.


Mortality/Morbidity: Symptoms usually last 1-2 weeks before spontaneously subsiding. Long-lasting sequelae generally do not occur. Fatalities are rare and usually are due to continued administration of the antigen.

Age: Individuals older than 15 years may experience more frequent and more severe disease because they receive larger volumes of antitoxin.

History: Primary serum sickness occurs 6-21 days after the administration of the inciting antigen. The onset may be more rapid with subsequent exposures to the same antigen, with symptoms occurring 1-4 days after exposure.

Physical: Physical examination may reveal cutaneous symptoms; fever; lymphadenopathy; arthritis or arthralgias; edema; and renal, cardiovascular, neurologic, or pulmonary manifestations.

Causes: Drugs that have been implicated in the development of serum sickness–like reactions include the following: allopurinol (Zyloprim), arsenicals and mercurial derivatives, barbiturates, captopril (Capoten), cephalosporins, furazolidone (Furoxone), gold salts, griseofulvin (Fulvicin, Grifulvin), halothane, hydralazine (Apresoline), iodides, methyldopa, para-aminosalicylic acid, penicillamine, penicillins, phenytoin (Dilantin), piperazine, procainamide (Procan SR, Procanbid, Pronestyl-SR), quinidine (Quinaglute, Quinalan, Quinidex, Quinora), streptokinase (Streptase, Kabikinase), sulfonamides, and thiouracils.

Other causes of serum sickness may include the following: