Serum Sickness

How serum sickness happens

When the body encounters a large amount of foreign protein, it makes antibodies over 1 to 2 weeks. These antibodies bind to the remaining protein, forming immune complexes that circulate and deposit in small blood vessels, joints and kidneys. There they activate complement, an inflammatory pathway, causing fever, rash, joint inflammation and sometimes kidney or vessel damage. This is a type III hypersensitivity reaction.

The name comes from the early 1900s, when it followed injections of horse serum used to treat diphtheria and other infections.

Causes

True serum sickness

• antivenoms for snake or scorpion bites
• antithymocyte globulin used in transplant and aplastic anemia
• rabies immune globulin from animal sources
• monoclonal antibodies, particularly chimeric ones such as rituximab and infliximab

Serum sickness-like reaction

Similar symptoms, usually without the immune complexes or kidney involvement, follow some ordinary medicines:

• cefaclor (classically in children), amoxicillin and other beta-lactam antibiotics
• sulfonamide antibiotics
• bupropion, minocycline, propranolol and some others

Symptoms

Symptoms usually start 7 to 14 days after first exposure, or within 1 to 4 days if previously exposed:

• fever and feeling unwell
• rash: hives or a red, raised rash. In serum sickness proper, a distinctive rash may appear along the sides of the hands and feet. See hives
• joint pain and swelling, often in the knees, wrists, ankles and fingers
• swollen lymph nodes
• muscle aches
• swelling of the face, hands or feet
• kidney inflammation (protein or blood in urine) in some cases
• rarely, nerve inflammation or vasculitis

Diagnosis

Serum sickness is diagnosed from the timing of symptoms after exposure to a likely trigger. Tests help exclude other causes and assess severity:

• urinalysis for protein and blood
• blood tests: raised inflammation markers (ESR, CRP), low complement levels (C3, C4), kidney function
• skin biopsy occasionally
• ruling out infections, such as viral rashes, and other drug reactions such as DRESS or Stevens-Johnson syndrome

Treatment

• Stop the trigger. This is the most important step
• Antihistamines for itching and hives
• NSAIDs for joint pain and fever, if appropriate. Follow the label dose
• Corticosteroids for severe symptoms, such as marked joint swelling, high fever or kidney involvement, usually a short course tapered over 1 to 2 weeks
• plasmapheresis in rare, severe cases

Prevention and future treatment

• record the reaction as an allergy or adverse reaction in your medical records
• avoid the specific drug in the future, and discuss related drugs with your doctor. Children who had a reaction to cefaclor often tolerate other antibiotics
• when antivenom or antithymocyte globulin is essential, doctors may give steroids or antihistamines alongside to reduce the risk
• humanized antibody drugs cause fewer reactions than older animal-derived products

Outlook

Serum sickness and serum sickness-like reactions usually resolve completely within 1 to 3 weeks after the trigger is stopped, without lasting damage. Re-exposure can trigger a faster and stronger reaction.

Frequently asked questions

What is serum sickness?

Serum sickness is a delayed immune reaction to certain medicines or foreign proteins, such as antivenoms. Immune complexes form and deposit in tissues, causing fever, rash, joint pain and swollen lymph nodes about 1 to 2 weeks after exposure.

What medicines cause serum sickness-like reactions?

Common triggers include antibiotics such as cefaclor, amoxicillin and other penicillins and cephalosporins, sulfonamides, bupropion and minocycline. Children taking antibiotics for ear infections are a commonly affected group.

How long does serum sickness last?

Most cases resolve within 1 to 3 weeks after stopping the trigger. Antihistamines, anti-inflammatory medicines and sometimes steroids help symptoms settle faster.

Is serum sickness dangerous?

It is usually self-limiting and not dangerous, though it can be very uncomfortable. Rarely, it affects the kidneys or blood vessels. Symptoms such as breathing difficulty, widespread blistering or reduced urine need urgent care.

Can I take the same medicine again after serum sickness?

Generally no. Re-exposure can trigger a faster and stronger reaction. Your doctor will record the reaction and choose alternative medicines. Related drugs may be safe, but discuss them with your doctor or an allergist.