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Serum sickness

Serum sickness describes a delayed immune system response, either to certain kinds of medications or to antiserum (given after a person has been bitten by a snake or to counter exposure to rabies, for example). Serum is the clear fluid part of blood. Serum sickness is similar to an allergy, in that the body mistakenly identifies a protein from the antiserum or medication as harmful and activates the immune system to fight it off. 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, but sometimes it can take as long as 3 weeks. If you are exposed again to the substance, serum sickness tends to develop faster (within 1 to 4 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 rash, hives
  • Joint pain
  • Fever
  • Malaise (feeling unwell)
  • Swollen lymph nodes
  • Itching
  • Wheezing
  • Flushing
  • Diarrhea, nausea, and abdominal cramping

What Causes It?

Antigens, proteins the body mistakenly identifies as harmful, cause your immune system to produce antibodies. These antibodies bind with the antigens and build up on the layers of cells that line the heart, blood vessels, lymph vessels, and other body cavities. This causes inflammation and other symptoms of serum sickness.

Penicillin is the most common cause of serum sickness. Other causes include:

  • Other antibiotics, including cephalosporins
  • Fluoxetine (Prozac) used for depression
  • Barbiturates
  • A class of diuretics called thiazides
  • Products that contain aspirin
  • Many other medications
  • Snake venom antiserum
  • Bee or wasp sting (rare)

Who is Most At Risk?

You are more likely to suffer from serum sickness if:

  • You are injected with one of the drugs or antitoxin known to cause serum sickness.
  • You need a large amount of snake venom antiserum.
  • You have previously been exposed to a drug or antitoxin known to cause serum sickness.

What to Expect at Your Provider's Office

Your doctor will look for typical symptoms and ask if you have been recently exposed to any antiserum. Your doctor may order blood and urine tests.

Treatment Options


  • If you know you are sensitive to a particular drug or antiserum, you should tell your health care provider before you get any kind of injection.
  • A provider can perform skin tests to check for serum sensitivity before giving antiserum.
  • If you are sensitive to an antiserum, your provider may use a method that desensitizes you to the antiserum, at least temporarily.

Drug Therapies

Treatment for serum sickness is aimed at reducing symptoms. Your doctor may prescribe antihistamines or analgesics (NSAIDs), along with topical medications to relieve itching or rash. In serious cases, your doctor may prescribe corticosteroids, such as prednisone. Normally, there is no need for hospitalization. Fever typically gets better within 48 to 72 hours of treatment.

Complementary and Alternative Therapies

If you suspect you have serum sickness, you should see a doctor immediately and receive conventional medical treatment. Some complementary and alternative therapies (CAM) may support conventional treatment by helping to reduce inflammation and stabilize your immune system, but no scientific studies have been done on the effectiveness of CAM therapies for serum sickness. Although certain CAM therapies may help relieve symptoms, others could make them worse. Take any herb, supplement, or medication only under your doctor's supervision.

Nutrition and Supplements

The following nutrients may help support your immune system and reduce allergic reactions, though there is no scientific evidence they will be effective for serum sickness. As noted, some may make serum sickness worse. Talk to your doctor before taking any of these supplements.

Following these nutritional tips may help reduce risks and symptoms:

  • Eliminate all suspected food allergens, including dairy, wheat (gluten), soy, corn, preservatives, and chemical food additives. Your health care provider may want to test you for food allergies.
  • Eat foods high in B-vitamins and iron, such as whole grains (if no allergy), dark leafy greens (such as spinach and kale), and sea vegetables.
  • Eat antioxidant-rich foods, including fruits (such as blueberries, cherries, and tomatoes), and vegetables (such as squash and bell pepper).
  • Avoid refined foods, such as white breads, pastas, and sugar.
  • Eat fewer red meats and more lean meats, cold-water fish, tofu (soy, if no allergy), or beans for protein.
  • Use healthy oils for cooking, such as olive oil or vegetable oil.
  • Reduce significantly or eliminate trans-fatty acids, found in commercially-baked goods such as cookies, crackers, cakes, and donuts. Also avoid French fries, onion rings, processed foods, and margarine.
  • Avoid coffee and other stimulants, alcohol, and tobacco.
  • Drink 6 to 8 glasses of filtered water daily.
  • Exercise moderately for 30 minutes daily, 5 days a week.

Traditional Chinese Medicine and acupuncture can help lessen the body's tendency toward allergic hypersensitivity reactions.


DO NOT use massage to treat serum sickness as it may promote inflammation and lower blood pressure.

Prognosis/Possible Complications

Serum sickness usually improves in 7 to 10 days, with full recovery in 2 to 4 weeks. However, it may lead to nervous system disorders and a life-threatening allergic reaction called anaphylaxis, so it is important to get medical treatment.

Following Up

Health care providers should monitor seriously ill people for rare instances of myocarditis (inflammation of the heart muscle) and peripheral neuritis (nerve inflammation).

Supporting Research

Bhat KPL, Kosmeder JW 2nd, Pezzuto JM. Biological effects of resveratrol. Antioxid Redox Signal . 2001;3(6):1041-64.

Bonds RS, Kelly BC. Severe serum sickness after H1N1 influenza vaccination. Am J Med Sci . 2013;345(5):412-3.

Bope and Kellerman: Conn's Current Therapy, 2012 . 1st. ed. Philadelphia, PA: Elsevier Saunders; 2011.

Cabrera C, Artacho R, Gimenez R. Beneficial effects of green tea -- a review. J Am Coll Nutr . 2006;25(2):79-99.

Jacob A, Chaves L, Eadon MT, Chang A, Quigg RJ, Alexander JJ. Curcumin alleviates immune-complex-mediated glomerulonephritis in factor-H-deficient mice. Immunology . 2013;139(3):328-37.

Maheshwari RK, Singh AK, Gaddipati J, Srimal RC. Multiple biological activities of curcumin: a short review. Life Sci . 2006;78(18):2081-7.

Marx: Rosen's Emergency Medicine . 7th ed. St. Louis, MO: Elsevier Mosby; 2009.

Rotsein OD. Oxidants and antioxidant therapy. Crit Care Clin. 2001;17(1):239-47. Shi J, Yu J, Pohorly JE, Kakuda Y. Polyphenolics in grape seeds-biochemistry and functionality . J Med Food . 2003;6(4):291-9.

Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases . J Am Coll Nutr. 2002;21(6):495-505.

Williams JE. Review of antiviral and immunomodulating properties of plants of the Peruvian rainforest with a particular emphasis on Una de Gato and Sangre de Grado. Altern Med Rev . 2001;6(6):567-79.

Wolverton. Comprehensive Dermatologic Drug Therapy . 2nd ed. Philadelphia, PA: Elsevier Saunders; 2007.

Yoon JH, Baek SJ. Molecular targets of dietary polyphenols with anti-inflammatory properties. Yonsei Med J . 2005;46(5):585-96.

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          Review Date: 3/24/2015  

          Reviewed By: Steven D. Ehrlich, NMD, Solutions Acupuncture, a private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

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