Serum sickness

BACKGROUND

Antiserum refers to a sample of serum from either a person or animal that has developed immunity to particular foreign substances (antigens). Antiserum contains antibodies against that particular antigen.

If an individual is exposed to a potentially dangerous foreign substance that he is not immune to, an injection of antiserum may be administered. This treatment provides temporary, but immediate protection until the person develops his or her own immune response against the antigen. For instance, antiserums for tetanus and rabies exposure are commonly used.

Serum sickness is a hypersensitive reaction, which occurs in response to certain antiserums. The body's immune system mistakes a protein in the antiserum as an antigen, and white blood cells attack it. The body then develops an immune response against the antiserum.

Allergic reactions can be classified into four immunopathologic categories. These classifications are based on the immune system's response to the allergen, not on the severity of the reaction. Serum sickness is a Type III allergic reaction, which involves the formation of an antigen-antibody immune complex that deposits on blood vessel walls and activates cell components known as complements. In most cases of serum sickness, immunoglobulin G (IgG) antibodies mediate the response. Immunoglobulin M (IgM) complexes are less common and elicit immune complexes more readily removed by the reticuloendothelial system. Immunoglobulin E-mediated vasoactive amines (substance containing amino groups that alters blood vessels' permeability or causes vasodilation) may cause hives and may further initiate complement activation.

Patients who have serum sickness usually recover completely within 7-28 days. Fatalities are rare and usually are the result of continued exposure to the antigen.

The frequency of serum sickness appears to be dose related. In one study, 10% of patients who received 10mL of tetanus antitoxin developed serum sickness, while nearly all patients who received 80mL or more developed serum sickness. All of the patients were successfully treated.

CAUSES

Serum sickness is a hypersensitivity reaction, similar to an allergic reaction, which occurs in response to a certain antiserum. The body's immune system mistakes a protein in the antiserum as a potentially harmful substance (antigen). The body then develops an immune response against the antiserum.

Antibodies bind with the antiserum protein to create larger particles (immune complexes). The immune complexes are deposited in various tissues, causing inflammation and other symptoms like skin rash, itching, hives, joint pain, arthritis, peripheral neuritis (inflamed peripheral nerve), optic neuritis (inflamed optical nerve), myelitis (inflamed spinal cord), fever, shock, muscle pain, diarrhea, abdominal pain, nausea, vomiting, decreased blood pressure, malaise and enlarged lymph nodes.

Antiserum derived from horse serum and administered as antitoxins or antivenoms are the most common cause of serum sickness. These products are used to treat or prevent rabies, tetanus, botulism and snakebites.

Antiserums derived from horse, rabbit or mouse serum (like antithymocyte globulin, OKT-3) may also cause serum sickness. These preparations are used to treat graft rejection, malignancies (cancerous tumors) or autoimmune diseases.

Other heterologous proteins (derived from more than one animal) may cause serum sickness in some people.

Stings from insects of the order Hymenoptera such as, bees and mosquitoes, as well as tick bites may cause serum sickness.

Exposure to certain medications (especially penicillin) can result in a similar reaction. However, unlike other drug allergies, which occur very soon after receiving the medication for the second (or subsequent) time, serum sickness can develop one to three weeks after the first exposure to a medication. The following drugs may cause serum sickness-like reactions: antibiotics (like cephalosporins, ciprofloxacin, metronidazole, penicillin, rifampicin, streptomycin or tetracycline), antifungals (like itraconazole), antineoplastic agents (like mercaptopurine, procarbazine or thiouracil), anticonvulsants (like carbamazepine or phenytoin), antidepressants (like bupropion or fluoxetine), antidysrhythmics (like procainamide or quinidine), antihypertensives (like captopril, hydralazine, methyldopa or propranolol), anti-inflammatories (like gold salts, indomethacin, naproxen, penicillamine, phenylbutazone, sulindac) and others (like, allopurinol, barbiturates, dextrans, halothane, iodides or methimazole).

SYMPTOMS

Symptoms usually do not develop until one to three weeks after the initial exposure to the antiserum because the body has to produce antibodies to the antigen. However, patients who have been exposed to the offending antigen previously may develop symptoms in one to three days. Symptoms usually last one to two weeks before spontaneously subsiding. Fatalities are rare and usually are the result of continued exposure to the antigen.

Common symptoms include skin rash, itching, hives, joint pain, arthritis, peripheral neuritis (inflamed peripheral nerve), optic neuritis (inflamed optical nerve), myelitis (inflamed spinal cord), fever, shock, muscle pain, diarrhea, abdominal pain, nausea, vomiting, decreased blood pressure, malaise (general feeling of discomfort) and enlarged lymph nodes.

Rare symptoms include: chest pain or breathlessness (resulting from pleuritis, pericarditis, or myocarditis) and encephalitis (inflammation of the brain).

DIAGNOSIS

General: In general, laboratory studies are not always helpful in establishing a diagnosis. Symptoms of serum sickness are often similar to other conditions. However, patients who present symptoms of serum sickness and who have recently been exposed to a drug or other product that may cause the reaction should be suspected of having serum sickness. Certain laboratory findings have been reported in patients who have serum sickness, including enlarged lymph nodes, protein or blood in the urine and vasculitis.

Physical examination: If symptoms of serum sickness arise after exposure to antiserum, a qualified healthcare provider should be consulted. During a physical examination a qualified healthcare provider may observe large lymph nodes that are tender to the touch in the patient.

Urine sample: A urine sample may contain blood or proteins.

Blood test: A blood test may indicate vasculitis (inflamed blood vessels).

TREATMENT

The patient should stop taking the offending antiserum immediately. Treatment thereafter focuses on relieving the symptoms. Patients usually recover completely within 7-28 days. Patients should avoid using the offending antiserum in the future.

Antihistamines: Antihistamines like diphenhydramine HCL (Benadryl©) may be used to relieve itching that is associated with serum sickness.

Corticosteroids: Corticosteroids like prednisone (like Deltasone©, Orasone© or Sterapred©) have been used to reduce inflammation associated with serum sickness. Treatment usually lasts about two weeks. Doses should gradually decrease as symptoms clear up. Symptoms may reappear in severe cases if steroids are stopped too quickly.

Nonsteroidal anti-inflammatory drugs (NSAIDs): NSAIDs like ibuprofen (Motrin© or Advil©) may be used to decrease inflammation and reduce fever.

INTEGRATIVE THERAPIES

Note : Currently, there is insufficient evidence available on the safety and effectiveness of integrative therapies for the prevention or treatment of serum sickness.

PREVENTION

Avoid exposure to medication or antiserum that has caused sickness in the past.

Patients should inform their healthcare providers, including dentists, about any reactions they have had to medication or antiserum.

A healthcare provider can perform an allergy test to check for serum sensitivity before administering antiserum.

Consider wearing a Medic-Alert bracelet or ID to inform others of serious allergies.

AUTHOR INFORMATION

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

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• Natural Standard: The Authority on Integrative Medicine. http://www.naturalstandard.com. Copyright © 2009. Accessed May 25, 2009.
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• University of Maryland Medical Center. Serum Sickness. http://www.umm.edu. Accessed May 25, 2009.
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