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Table of Contents > Conditions > Serum Sickness
Serum Sickness
Signs and Symptoms
What Causes It?
Who's Most At Risk?
What to Expect at Your Provider's Office
Treatment Options
Drug Therapies
Complementary and Alternative Therapies
Prognosis/Possible Complications
Following Up
Supporting Research

Serum sickness results from a reaction to an antigen, a protein that the body recognizes as foreign. The classic example of a cause of serum sickness is an antiserum administered following a snakebite to counter the poisonous venom. Today, the most common cause of serum sickness is the antibiotic penicillin. Serum sickness will usually develop within 7 to 10 days after initial exposure to the antigen; at times, however, the reaction does not develop until as long as three weeks later. With subsequent exposures, serum sickness tends to develop more rapidly (within one to four days) and only a very small amount of the substance may cause an intense response.

Signs and Symptoms

The first signs of serum sickness are redness and itching at the injection site. Other signs and symptoms include:

  • Skin lesions, possibly including bruise-like patches from bleeding into the skin; a faint red discoloration over the hands, fingers, feet, and toes before other lesions or a brighter rash erupt; hives
  • Joint pain
  • Fever
  • Malaise (feeling unwell)
  • Swollen lymph nodes
  • Swelling, especially around the face and neck
  • Wheezing
  • Flushing
  • Runny nose
  • Rarely, low blood pressure, as with anaphylaxis (a severe, total body allergic reaction)
  • Muscle pain
  • Diarrhea, nausea, abdominal cramping

What Causes It?

Antigens, the proteins described earlier, stimulate the body to produce antibodies. These antibodies form complexes with the antigens and, in the case of serum sickness, become trapped on endothelial surfaces—layers of cells that line the heart, blood vessels, lymph vessels, and other body cavities. This leads to a series of immune-system reactions that cause the symptoms of serum sickness.

Penicillins are the most common cause of serum sickness. Other causes include:

  • Other antibiotics; fluoxetine used for depression; barbiturates; a class of diuretics called thiazides; aspirin-containing products; propylthiouracil used for overactive thyroid; and hydantoins used for seizures.
  • Influenza vaccine
  • Snake venom antiserum
  • Diphtheria and tetanus antisera; no longer happens generally because these are now prepared from human origin as opposed to foreign species as was done years ago
  • Bee or wasp sting - not common

Who's Most At Risk?

You are more likely to suffer from serum sickness if

  • A drug or antitoxin known to cause serum sickness is delivered by injection
  • High quantities of snake venom antiserum are required
  • If there has been past exposure to a drug or antitoxin known to cause serum sickness

What to Expect at Your Provider's Office

A healthcare provider will look for typical signs and symptoms and ask about recent exposure to any antiserum. Blood and urine tests and tests of skin with lesions may aid the diagnosis.

Treatment Options
  • If you are aware of a hypersensitivity to a particular drug or other agent, you should tell your healthcare provider before you get any kind of injection.
  • A healthcare provider can perform skin tests to check for serum sensitivity before giving antiserum.
  • Once a hypersensitivity is identified, your healthcare provider may use a method that desensitizes you to the antiserum, at least temporarily.
  • Because of their potential to cause serum sickness, serum from animals should be avoided unless there is no other treatment option.

Drug Therapies

Doctors will typically prescribe antihistamines or analgesics for serum sickness. If symptoms don't respond to this treatment, they may prescribe corticosteroids, such as prednisone. Normally, there is no need for hospitalization. In severe cases providers may resort to plasmapheresis—a procedure for removing blood, separating plasma from the blood, then replacing the blood along with plasma substitutes.

Complementary and Alternative Therapies

Serum sickness requires immediate conventional medical attention. Scientific studies have not yet evaluated the effectiveness of CAM therapies in treating serum sickness. However, nutritional and herbal treatments may support conventional treatment by helping to reduce inflammation and stabilize the immune system. Although certain CAM measures may help relieve symptoms of serum sickness, others may worsen serum sickness by increasing the number of circulating immune complexes (see section entitled What Causes It? for description of immune complexes).


Certain nutrients used in clinical practice can stabilize immune function and may lessen reactions such as serum sickness. These include:

  • Vitamin C
  • L-methionine (an amino acid or protein building block obtained from dietary sources)
  • Choline (considered part of the vitamin B complex; found in meat and some vegetables)
  • Inositol (considered part of the vitamin B complex; found in fruits, vegetables, whole grains, and organ meats)

The use of these substances for serum sickness is theoretical and has not been tested scientifically.

Omega-3 fatty acids, found in fish oil, are generally used to reduce inflammation; however, these substances along with eicosapentanoic acid (EPA), should be avoided in the case of serum sickness because of a recent animal study showing increased levels of antigen-antibody immune complexes following ingestion of fish oil. Increased circulation of immune complexes may worsen serum sickness.


Anti-inflammatory herbs may, theoretically, lessen some of the symptoms of serum sickness:

  • Eleuthro root (Eleutherococcus senticosis), frequently marketed as Siberian ginseng—used for inflammatory conditions
  • Ginkgo (Ginkgo biloba)—may decrease swelling
  • Licorice root (Glycyrrhiza glabra)—may decrease inflammation
  • Milk thistle (Silybum marianum)—may decrease inflammation
  • Peppermint oil (Menthae piperitae aetheroleum)—approved in Germany to treat hives
  • Turmeric (Curcuma longa)—may decrease inflammation and swelling, particularly when used in conjunction with a supplement called bromelain; rarely, though, bromelain may cause an allergic reaction.

Toki-shakuyaku-san (TSS), a Japanese (Kampo) formula that contains six herbs, was found to decrease circulating immune complexes in animals. The main active ingredient to help clear the complexes was thought to be:

  • Angelica root (Angelica archangelica)

Herbs that may cause allergic hypersensitivity reactions, such as cayenne pepper (Capsicum spp.,used to treat forms of arthritis), should be avoided in the case of serum sickness.


To date, no scientific studies have investigated the value of homeopathic remedies in treating serum sickness. However, homeopaths commonly use the following for hives and other symptoms related to serum sickness:

  • Apis for hives with intense burning as well as for swelling; people for whom this treatment is appropriate describe a stinging relieved by cool compresses
  • Rhus toxicodendron for hives that are very itchy and relieved by warm compresses; a person for whom this is appropriate tends to be restless and must change positions frequently
  • Urtica urens for hives and other red, raised rashes that are painful, burning, and stinging but relieved by rubbing

An experienced homeopath considers each individual case and may recommend treatments to address both the underlying condition and any current symptoms.


Massage should not be used in cases of serum sickness as it may promote inflammation as well as lower blood pressure.

Prognosis/Possible Complications

Serum sickness usually resolves in 7 to 10 days, with full recovery in 2 to 3 weeks. However, it may lead to nervous system disorders as well as a life-threatening allergic reaction called anaphylaxis.

Following Up

Healthcare providers should monitor acutely ill persons for rare instances of myocarditis (inflammation of the heart muscle) and peripheral neuritis (nerve inflammation).

Supporting Research

Behrman RE, ed. Nelson Textbook of Pediatrics. 15th ed. Philadelphia, Pa: W.B. Saunders Co; 1996.

Blumenthal M, Goldberg A, Brinckmann J, eds. Herbal Medicine: Expanded Commission E Monographs. Newton, Mass: Integrative Medicine Communications; 2000:3-6, 33-35, 52-54, 106-109, 160-169, 233-239, 257-263, 300-303, 379-384.

Boyer LV, Seifert SA, Clark RF, et al. Recurrent and persistent coagulopathy following pit viper envenomation. Arch Intern Med. 1999;159(7):706-710.

Brenner BM, Rector FC. The Kidney. Philadelphia, Pa: W.B. Saunders Co; 1996.

Canale ST. Campbell's Operative Orthopaedics. 9th ed. St. Louis, Mo: Mosby Inc; 1998.

Cecil RI, Plum F, Bennett JC, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, Pa: W.B. Saunders Co; 1996.

Dambro MR, ed. Griffith's 5 Minute Clinical Consult. Baltimore, Md: Lippincott Williams & Wilkins; 1999.

Fauci AS, Braunwald E, Isselbacher KJ, et al., eds. Harrison's Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill Book Co; 1998.

Feigen GA, Smith BH, Dix CE, et al. Enhancement of antibody production and protection against systemic anaphylaxis by large doses of vitamin C. Res Commun Chem Pathol Pharmacol. 1982;38(2):313-333.

Iijima K, Tanaka M, Toriizuka K, Cyong JC. Effects of Kampo medicines on the clearance of circulating immune complexes in mice. J Ethnopharmacol. 1994;41(1-2):77-83.

Middleton E, ed. Allergy: Principles and Practice. 5th ed. St. Louis, Mo: Mosby-Year Book; 1998.

Proctor BD,Murray PG, Joondeph BC. Bilateral anterior uveitis: a feature of streptokinase-induced serum sickness. N Engl J Med. 1994;330(8):576-577.

Rakel RE, ed. Conn's Current Therapy. 51st ed. Philadelphia, Pa: W.B. Saunders Co; 1999.

Tateno S, Kobayashi Y, Robinson DR. Dietary fish oil supplementation exacerbates serum sickness nephritis in mice. Nephron. 1997;77(1):86-92.

Wilde JA, McMillan JA, Serwint J, Butta J, O'Riordan MA, Steinhoff MC. Effectiveness of influenza vaccine in health care professionals: a randomized trial. JAMA. 1999;281(10):908-913.

Review Date: December 2000
Reviewed By: Participants in the review process include: Amy Atar, MD, Infectious Disease Specialist and HIV Consultant, Cambridge City Hospital, Cambridge, MA; Jacqueline A. Hart, MD, Department of Internal Medicine, Newton-Wellesley Hospital, Harvard University and Senior Medical Editor Integrative Medicine, Boston, MA; David Winston, Herbalist, Herbalist and Alchemist, Inc., Washington, NJ; Leonard Wisneski, MD, FACP, George Washington University, Rockville, MD.

Copyright © 2004 A.D.A.M., Inc

The publisher does not accept any responsibility for the accuracy of the information or the consequences arising from the application, use, or misuse of any of the information contained herein, including any injury and/or damage to any person or property as a matter of product liability, negligence, or otherwise. No warranty, expressed or implied, is made in regard to the contents of this material. No claims or endorsements are made for any drugs or compounds currently marketed or in investigative use. This material is not intended as a guide to self-medication. The reader is advised to discuss the information provided here with a doctor, pharmacist, nurse, or other authorized healthcare practitioner and to check product information (including package inserts) regarding dosage, precautions, warnings, interactions, and contraindications before administering any drug, herb, or supplement discussed herein.

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