serum sickness

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Serum Sickness



Serum sickness is a type of delayed allergic response, appearing four to 10 days after exposure to some antibiotics or antiserum, the portion of serum that contains antibodies, such as gamma globulin, which may be given to provide immunization against some diseases.


Serum sickness is very similar to an allergic reaction. The patient's immune system recognizes the proteins in the drug or antiserum as foreign proteins, and produces its own antibodies to protect against the foreign proteins. The newly formed antibodies bind with the foreign protein to form immune complexes. These immune complexes may enter the walls of blood vessels where they set off an inflammatory reaction.
While other types of allergic reactions may produce a rapid response, the serum sickness reaction is delayed because it takes time for the body to produce antibodies to the new protein.

Causes and symptoms

The usual symptoms are severe skin reactions, often on the palms of the hands and soles of the feet. Fever, sometimes as high as 104o F, is always present and usually appears before the skin rash.
Joint pain may be reported in up to 50% of cases. This is usually seen in the larger joints, but occasionally the finger and toe joints may also be involved.
Swelling of lymph nodes, particularly around the site of the injection, is seen in 10-20% of cases. There may also be swelling of the head and neck.
Urine analysis may show traces of blood and protein in the urine.
Other symptoms may involve the heart and central nervous system. These may include changes in vision, and difficulty in movement. Breathing difficulty may occur.
Traditionally, antitoxins were the most common cause of serum sickness, but those reports date from a time when most antitoxins were made from horse serum. As many as 16% of the people who received antirabies serum derived from horses developed serum sickness. The risk of a reaction to antitoxins has dropped dramatically since manufacturers have started using human serum instead of horse serum to make their products.
Although antitoxins are the most common cause of serum sickness, a number of drugs have been reported to cause a serum sickness reaction. The following list is not complete, but indicates some of the drugs that have been associated with this type of reaction:
  • allopurinol (Zyloprim)
  • barbiturates
  • captopril (Capoten)
  • cephalosporin antibiotics
  • griseofulvin (Fulvicin, Grifulvin)
  • penicillins
  • pehnytoin (Dilantin)
  • procainamide (Procan SR, Procanbid, Pronestyl-SR)
  • quinidine (Quinaglute, Quinidex, Quinora)
  • streptokinase (Streptase, Kabikinase)
  • sulfonamide antibacterial drugs
Of cases of serum sickness reported to the United States Food and Drug Administration, the drugs most commonly associated with the reaction have been the cephalosporin antibiotics, including cefaclor (Ceclor) and cefalexin (Keflex) and the sulfonamide combination trimethoprim-sulfamethoxazole (Bactrim, Septra.) This does not mean that these are high-risk drugs, since these drugs are very widely used, so that there are many people exposed to them.
In addition to these substances, allergenic extracts used for testing and immunization, hormones, and vaccines have been known to cause serum sickness.


Diagnosis is made by observing the symptoms and reviewing the patient's medical and medication history. Although the symptoms of serum sickness may be similar to other conditions, patients who present with symptoms of serum sickness and who have a recent history of exposure to a drug or other product which may cause this type of reaction should be suspected of having serum sickness.


The first step in treatment of serum sickness is always to discontinue the drug or other substance which is suspected of causing the reaction. After that, all treatment is symptomatic. Antihistamines, pain relievers, and corticosteroids may be given to relieve the symptoms. The choice of treatment depends on the severity of the reaction.


Most serum sickness reactions are mild, and disappear on their own after one or two weeks as long as the cause is removed. Sometimes, symptoms of pain and discomfort may continue for several weeks, even after all the observable reactions such as skin rash and protein in the urine have disappeared. In very rare cases, however, there can be severe reactions and permanent damage. In very rare but extreme cases, serum sickness can lead to shock, permanent kidney damage, and even death.

Key terms

Allergy — Altered body reaction, usually hypersensitivity, as a response to exposure to a specific substance.
Antibody — Any of a large number of proteins that are produced after stimulation by an antigen and act specifically against the antigen in an immune response.
Antihistamine — A drug that inhibits the actions of histamine. Histamine causes dilatation of capillaries, contraction of smooth muscle, and stimulation of gastric acid secretion.
Antitoxin — An antibody that is capable of neutralizing the specific toxin (a specific cause of disease) that stimulated its production in the body and is produced in animals for medical purposes by injection of a toxin or toxoid with the resulting serum being used to counteract the toxin in other individuals.
Serum — The clear yellowish fluid that remains from blood plasma after fibrinogen, prothrombin, and other clotting factors have been removed by clot formation—called also blood serum.
Sulfonamide — A sulfa drug, one of a large group of drugs used to treat bacterial infections.


The most effective method of prevention is simple avoidance of antitoxins that may cause serum sickness. If patients have had a reaction in the past, particularly if the reaction was to a commonly used drug, they should be made aware of it, and be advised to alert physicians and hospitals in the future. Patients who have had particularly severe reactions may be advised to wear identification bracelets, or use other means to alert health care providers.
When it is necessary to administer an antitoxin, skin tests may be used to identify people who are at risk of a reaction. If the situation does not allow enough time for skin testing, the antitoxin should be given along with an intravenous antihistamine. Other drugs, such as epinephrine, which may be needed for an emergency, should be available.



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Action Against Allergy (AAA). PO Box 278, Twickenham Middlesex, Greater London TW1 4QQ, England.
American Allergy Association (AAA). 3104 E Camelback, Ste. 459 Phoenix, AZ 85016.
Gale Encyclopedia of Medicine. Copyright 2008 The Gale Group, Inc. All rights reserved.


 [se´rum] (pl. serums, se´ra) (L.)
the clear portion of any animal or plant fluid that remains after the solid elements have been separated out. The term usually refers to blood serum, the clear, straw-colored, liquid portion of the plasma that does not contain fibrinogen or blood cells, and remains fluid after clotting of blood. Blood serum from persons or animals whose bodies have built up antibodies is called antiserum or immune serum. Inoculation with such an antiserum provides temporary, or passive, immunity against the disease, and is used when a person has already been exposed to or has contracted the disease. Diseases in which passive immunization is sometimes used include diphtheria, tetanus, botulism, and gas gangrene.
antilymphocyte serum (ALS) antiserum derived from animals that have been immunized against human lymphocytes, a powerful nonspecific immunosuppressive agent that causes destruction of circulating lymphocytes.
antirabies serum antiserum obtained from the blood serum or plasma of animals immunized with rabies vaccine; used for postexposure prophylaxis against rabies if rabies immune globulin is unavailable.
blood grouping s's preparations containing particular antibodies against red cell antigens, used for blood typing. Those most commonly used are the anti-A and anti-B blood grouping serums used to determine ABO blood types and the anti-Rh blood grouping serums (anti-D, anti-C, anti-E, anti-c, and anti-e) used to determine Rh blood types.
serum glutamic-oxaloacetic transaminase (SGOT) see aspartate transaminase.
serum glutamic-pyruvic transaminase (SGPT) see alanine transaminase.
immune serum antiserum.
pooled serum the mixed serum from a number of individuals.
serum sickness a hypersensitivity reaction following the administration of foreign serum or other antigens; it is marked by urticarial rashes, edema, adenitis, joint pains, high fever, and prostration. Reactions to tetanus antitoxin derived from horse serum were especially common but are now rare owing to refinement of the antigenic components.
serum sickness syndrome a serum sickness–like hypersensitivity reaction occurring after the administration of certain drugs. It is marked clinically by low-grade fever, urticaria, facial edema, pain and swelling of the joints, and lymphadenopathy, and occasionally may be associated with neuritis of the brachial plexus, guillain-barré syndrome, periarteritis nodosa, and nephritis.
Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. © 2003 by Saunders, an imprint of Elsevier, Inc. All rights reserved.

se·rum sick·ness

an immune complex disease appearing some days (usually 1-2 weeks) after injection of a foreign serum or serum protein, with local and systemic reactions such as urticaria, fever, general lymphadenopathy, edema, arthritis, and occasionally albuminuria or severe nephritis; originally described in patients receiving serotherapy. The term is sometimes used for clinically similar allergic reactions to drugs.
See also: immune complex disease.
Farlex Partner Medical Dictionary © Farlex 2012

serum sickness

A hypersensitive reaction to the administration of a foreign serum, characterized by fever, swelling, skin rash, and enlargement of the lymph nodes.
The American Heritage® Medical Dictionary Copyright © 2007, 2004 by Houghton Mifflin Company. Published by Houghton Mifflin Company. All rights reserved.

serum sickness

An immune response that follows re-exposure to an antigen to which an organism had been previously sensitised. Immediately after exposure, there is antigen excess; from days 5–14, small antigen-antibody complexes accumulate in vessels, causing lesions of serum sickness; by week 2, antibodies predominate, forming larger antigen-antibody complexes catabolised by the reticuloendothelial system.
Clinical findings
Urticaria, fever, lymphadenopathy, ±arthritis, glomerulonephritis.
Segen's Medical Dictionary. © 2012 Farlex, Inc. All rights reserved.

serum sickness

Immunology An immune response to re-exposure to an antigen to which an organism had been previously sensitized Clinical Urticaria, fever, lymphadenopathy, ±arthritis, glomerulonephritis. See Immune complex disease, Zone of equivalence.
McGraw-Hill Concise Dictionary of Modern Medicine. © 2002 by The McGraw-Hill Companies, Inc.

se·rum sick·ness

(sēr'ŭm sik'nĕs)
An immune complex disease appearing 1-2 weeks after injection of a foreign serum or serum protein, with local and systemic reactions such as urticaria, fever, general lymphadenopathy, edema, arthritis, and occasionally albuminuria or severe nephritis.
Synonym(s): serum disease, serum reaction.
Medical Dictionary for the Health Professions and Nursing © Farlex 2012

serum sickness

A brief allergic reaction that may develop after an injection of an antiserum of animal origin. In serum sickness, the immune system produces antibodies to substances in the serum and these may form IMMUNE COMPLEXES which cause inflammation in various tissues.
Collins Dictionary of Medicine © Robert M. Youngson 2004, 2005

se·rum sick·ness

(sēr'ŭm sik'nĕs)
Immune complex disease appearing some days (usually 7-14) after injection of foreign serum or serum protein, with local and systemic reactions such as urticaria, fever, general lymphadenopathy, edema, and arthritis.
Medical Dictionary for the Dental Professions © Farlex 2012
References in periodicals archive ?
In addition, serum sickness was suspected from day 10 in patient A and day 13 in patient B on the basis of clinical and biological signs (consumption of complement factors).
Recognizing the proteins as foreign, the vast majority of people develop over a period of days or weeks some degree of the generalized immune frenzy called serum sickness. Common symptoms include fever, rashes, nausea and muscle weakness.
Pathogenically, true serum sickness represents a type III arthus hypersensitivity reaction to proteins in toxins or drugs, mediated by circulating antigen-antibody complexes.
Minocycline has fewer GI effects and less photosensitivity, but tends to be more expensive and is associated with vertigo and serum sickness (Arch.
Although the heterophile antibody test may occasionally be false positive in patients with autoimmune diseases, serum sickness, pregnancy, or HIV infection, false negatives are far more frequent (about 15% overall), particularly in children who are under 4 years of age (approximately 45%).