Serum Sickness Treatment & Management

Updated: Jul 19, 2022
  • Author: Hassan M Alissa, MD; Chief Editor: Herbert S Diamond, MD  more...
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Approach Considerations

Withdrawal of the offending agent is the mainstay of treatment in serum sickness. Nonsteroidal anti-inflammatory drugs and antihistamines provide symptomatic relief.

Severe cases (multisystem involvement with significant symptoms) may warrant a 7- to 10-day course of corticosteroids. [4] In some cases, plasmapheresis can attenuate serum sickness. [5]

Hospitalize the patient if any significant comorbidities are present (eg, advanced or very young age, immunocompromise), if any severe symptoms or hemodynamic instability/hypotension is present, or if the diagnosis is unclear.

The presenting features of fever, rash, and joint pain may be observed in numerous infectious and autoimmune diseases. Consider a consultation with an allergist or a rheumatologist.


Deterrence, Prevention, and Long-Term Monitoring

Avoidance of the offending agent is the best way to prevent serum sickness. However, in some circumstances, avoidance is not possible.

Skin tests are indicated before antiserum administration, particularly in patients with a history of allergy to horse dander or in those who have previously received the substance. Skin tests reveal the presence of immunoglobulin E antibodies and, thus, help to identify individuals at risk of anaphylaxis. However, these tests are not reliable in the identification of individuals with an increased risk for serum sickness.

If rapid administration of antiserum is necessary, establish intravenous access in each arm (one site for the infusion of antiserum and the other for the treatment of complications) and premedicate the patient with 50-100 mg of diphenhydramine. If a reaction occurs, temporarily discontinue the infusion, and administer epinephrine and other necessary medications. Once the adverse reaction is halted, resume slow infusion.

Premedication with steroids is not protective.


Fajt and Petrov reported the first case of successful drug desensitization in a patient with rituximab-induced serum sickness. Although drug desensitization has traditionally been used to treat type I IgE-mediated hypersensitivity reactions, a rapid 12-step intravenous rituximab desensitization protocol allowed resumption of treatment in a 37-year-old woman who had developed serum sickness 72 hours following rituximab infusion for a gastric mucosa-associated lymphoid tissue lymphoma (MALToma). [29]

The patient’s MALToma, which had progressed after stopping rituximab, went into remission after the completion of four rituximab desensitizations. She received 25 maintenance rituximab doses using this desensitization protocol quarterly without complications. [29]

Dilley et al report on the successful use of a new patient weight–based protocol in two children who had experienced hypersensitivity reactions to rituximab. The authors conclude that desensitization to rituximab is a safe and effective procedure in the pediatric population. [30]

Long-term monitoring

Reconsider the diagnosis of serum sickness if symptoms persist beyond 3-4 weeks. Symptoms may reappear in severe cases if steroids are tapered too quickly; this recurrence is usually responsive to another course of treatment. After identifying the causative agent, inform the patient and advise that future exposure may cause a similar or more severe response.