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Serum Sickness

Last updated Dec. 22, 2018

Approved by: Maulik P. Purohit MD, MPH

Serum Sickness is an allergic reaction to the presence of foreign proteins in blood. It usually occurs after exposure to certain medications or antiserums, usually following treatments for snake bites, rabies, or tetanus.


What are other Names for this Condition? (Also known as/Synonyms)

  • Immune Complex Disease
  • Serum Reaction
  • Type III Hypersensitivity Reaction

What is Serum Sickness? (Definition/Background Information)

  • Serum Sickness is an allergic reaction to the presence of foreign proteins in blood. It usually occurs after exposure to certain medications or antiserums, usually following treatments for snake bites, rabies, or tetanus
  • Serum, or plasma, is a clear component of blood. It does not contain blood cells, but is rich in antibodies, a type of protein. Antiserum is derived from the serum of a human or animal, which is immune to a specific infection or poison
  • It is administered to an individual to aid in the development of antibodies against the infection or component. Antiserum is typically administered as a form of passive immunization in which the body produces antibodies, in response to the administered serum
  • Serum Sickness can develop in any individual who receives a form of antiserum. It is most commonly seen in individuals injected with proteins to help prevent organ transplant rejection (antithymocyte globulin) and to treat immune disorders (rituximab)
  • Serum Sickness occurs when the body mistakes the protein present within the antiserum as being harmful or dangerous to the body, and its immune system attacks these introduced foreign proteins
  • Symptoms usually develop within 1-3 weeks after receiving the antiserum and are recognized by fever, swollen, joints, and a rash in most cases. A medical history, physical examination, and simple blood and urine tests are used to diagnose Serum Sickness
  • The standard treatment for Serum Sickness is with antihistamines and NSAIDs, which can help reduce symptoms
  • The prognosis of Serum Sickness is very good, and most individuals can expect a full recovery within a few weeks. While complications are generally uncommon, individuals may develop anaphylaxis, swelling of the face, and nerve inflammation
  • Serum Sickness cannot be prevented if the allergy remains unidentified. If there is a history of a specific allergy, then avoidance of the triggering antiserum, can help prevent Serum Sickness

Who gets Serum Sickness? (Age and Sex Distribution)

  • Serum Sickness can affect any individual regardless of age, sex, race, or ethnicity
  • Any individual who has been administered an antiserum can be at risk

What are the Risk Factors for Serum Sickness? (Predisposing Factors)

The following individuals are at risk for Serum Sickness:

  • Individuals injected with an animal-derived serum are more likely to develop Serum Sickness
  • Those injected with large amounts of antiserum (such as in the case of serious snake bites) are also at a high risk for developing Serum Sickness
  • Individuals treated with thymoglobulin serum after an organ transplant
  • Individuals, who have previously developed Serum Sickness, after exposure to serum or antiserum
  • Those having a history of frequent exposure to horses or rabbits
  • In rare cases, individuals may develop Serum Sickness after a bee sting or a wasp sting

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider. 

What are the Causes of Serum Sickness? (Etiology)

Serum Sickness is an immune system response to foreign proteins present within an administered antiserum. The body’s immune system mistakes the proteins that comprise the antiserum as antigens, causing it to attack the foreign substance.

  • It leads to the formation of immune complexes due to the combination of antibodies present in blood and antigens present in the administered antiserum
  • Once formed, these immune complexes deposit on the blood vessel walls triggering the activation of certain complements
  • The activation of these complements is what causes the associated symptoms of Serum Sickness

What are the Signs and Symptoms of Serum Sickness?

The symptoms of Serum Sickness may occur within 1-3 weeks after administering antiserum; it is not known to develop immediately following treatment with antiserum. The signs and symptoms of Serum Sickness can vary according to the severity of the reaction and may include:  

  • Continuous high fever
  • Continuous joint pain/swelling
  • Development of itchy skin rash/hives
  • General ill feeling
  • Swollen and/or tender lymph nodes
  • Abdominal pain usually coupled with diarrhea and nausea

How is Serum Sickness Diagnosed?

Accurate diagnosis of Serum Sickness may include one or more of the following procedures:

  • A physical examination may reveal swollen lymph nodes that are tender to the touch
  • Medical history evaluation
  • Blood tests may be used to determine the presence of immune complexes, antibodies against the foreign protein, unusual complement levels, or vasculitis (inflamed blood vessels)
  • A urine test may be used to determine the presence of protein or blood
  • If a rash occurs, a skin biopsy can help confirm vasculitis (inflamed blood vessels) and the presence of complements

Many clinical conditions have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis. 

What are possible Complications of Serum Sickness?

Possible complications of Serum Sickness, depending upon the severity of the reaction may include:

  • Anaphylaxis (severe allergic reaction)
  • Swelling of the face and limbs due to vasculitis
  • Peripheral neuritis (nerve inflammation), which could lead to encephalitis (inflammation of the brain)
  • Sometimes, individuals treated with thymoglobulin, a rabbit-derived serum, are at risk of acute kidney failure
  • Myocarditis (inflammation of the heart)

How is Serum Sickness Treated?

Once the individual begins to show signs and symptoms of Serum Sickness, an immediate halt in the usage of the serum should be employed if possible. Treatment of Serum Sickness varies depending on the severity of the symptoms. Nevertheless, the symptoms are typically resolved within 1-4 weeks. The following treatment methods are typically used to alleviate the sign and symptoms.

Treatment measures for mild cases include:

  • Antihistamines (diphenhydramine HCL) and topical steroids may be used to relieve itchiness
  • Non-steroidal anti-inflammatory drugs (NSAIDs) may be used to reduce fever and lower inflammation
  • Corticosteroids may also be used over short periods to reduce inflammation

Treatment measures for individuals with severe symptoms may include:

  • Plasma exchange may be utilized to remove immune complexes, antibodies, and proteins, if symptoms are not resolving
  • Hospitalization and strict monitoring may be necessary in case of anaphylaxis
  • High dosage IV corticosteroids may be utilized for a few days to immediately relieve symptoms, in case of severe reactions

How can be Serum Sickness be Prevented?

There is no known method to prevent Serum Sickness, if the type of allergy is unknown. However, after an initial reaction, the following preventative methods can be enforced:

  • Individuals with a past history of reaction to antiserum should notify their healthcare provider and avoid future exposure to the antiserum
  • If an individual with a previous history of Serum Sickness needs to receive an antiserum, the signs and symptoms can be reduced by pre-medication with anti-allergy drugs
  • An allergy test can be performed to check for sensitivity to the specific antiserums
  • For individuals receiving antibodies as part of cancer treatment, a healthcare professional may use desensitization to help reduce the severity of the symptoms
  • In cases of risk of severe allergic reactions, a medic alert bracelet should be worn on the arm

What is the Prognosis of Serum Sickness? (Outcomes/Resolutions)

  • The prognosis of individuals with Serum Sickness is very good with treatment, especially if medical treatment is provided after the symptoms arise
  • Most individuals with Serum Sickness recover within 1-4 weeks after treatment, with no adverse effects being observed
  • In more serious reactions, individuals may develop nervous system disorders if immediate medical attention is not provided

Additional Relevant and Useful Information for Serum Sickness:

Certain diet changes may help in boosting the immune system to reduce the severity of allergic reactions, but it is important to work with a nutritionist or a healthcare provider to make the best decisions.

What are some Useful Resources for Additional Information?


References and Information Sources used for the Article:


Helpful Peer-Reviewed Medical Articles:


Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: July 22, 2016
Last updated: Dec. 22, 2018