What is serum sickness?

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Last updated: May 4, 2025View editorial policy

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From the Guidelines

Serum sickness is a rare side effect of rituximab treatment, occurring in about 1% of patients, and can be managed with pre-medication and careful monitoring 1. When considering the management of serum sickness in patients treated with rituximab, it is essential to prioritize morbidity, mortality, and quality of life. The evidence suggests that serum sickness is a rare but potential side effect of rituximab treatment, with an incidence of about 1% 1.

Key Considerations

  • Pre-medication with 100 mg of methylprednisolone, anti-histamine drugs, and paracetamol may reduce the risk of serum sickness reactions 1.
  • Patients should be carefully monitored, particularly when high cryocrit levels are present 1.
  • The administration of rituximab can be modified to reduce the risk of serum sickness, such as administering half a dose per day on two consecutive days and/or prolonging the administration of each infusion 1.

Management of Serum Sickness

  • Treatment of serum sickness involves immediately discontinuing the offending agent and providing supportive care with antihistamines and NSAIDs for mild cases.
  • For moderate to severe cases, prednisone at 0.5-1 mg/kg/day for 5-7 days with a gradual taper is recommended.
  • In severe cases with significant organ involvement, methylprednisolone 1-2 mg/kg/day may be necessary.

Prevention

  • Prevention involves avoiding known triggering agents in patients with previous reactions and considering premedication with antihistamines and corticosteroids when administering potentially reactive substances.
  • Patients should be educated about the importance of avoiding the triggering agent in the future and carrying medical alert information about their reaction. Overall, while serum sickness is a potential side effect of rituximab treatment, it can be managed effectively with pre-medication, careful monitoring, and prompt treatment.

From the Research

Definition and Characteristics of Serum Sickness

  • Serum sickness is an adverse reaction mainly to drugs, infectious agents, or vaccines, characterized by the presence of rash, arthralgia/arthritis, and occasionally fever 2.
  • Serum sickness-like reaction (SSLR) presents diagnostic challenges due to overlapping symptoms with other drug reactions 2.

Implicated Agents and Symptomatology

  • Beta-lactam antibiotics, particularly amoxicillin, are the leading implicated agents in SSLR, especially in pediatric populations 2.
  • Dermatological manifestations, primarily maculopapular rashes, are present in 100.0% of cases, while joint symptoms occur in 78.7% 2.
  • Symptoms of serum sickness can also include fever, urticaria, edema, lymphadenopathy, splenomegaly, abdominal pain, proteinuria, and neurologic manifestations 3.

Management and Treatment

  • Corticosteroids are effective in resolving symptoms in most cases of SSLR 2.
  • Systemic corticosteroids may provide relief, but standardized guidelines for diagnosis and management are needed 2.
  • Early and aggressive treatment of anaphylaxis during immunotherapy may prevent the occurrence of immune complex disease, including serum sickness 3.

Historical Context and Understanding

  • The concept of serum sickness was first studied in the late 19th and early 20th century in relation to reactions to diphtheria antitoxin and horse serum 4.
  • Pirquet and Schick's work on these reactions led to the understanding of the concept of "allergy" as a change in the reaction of the human organism to the re-introduction of the same substance 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Serum sickness-like reactions clinical characteristics and management: A systematic review.

The journal of allergy and clinical immunology. In practice, 2025

Research

Serum sickness triggered by anaphylaxis: a complication of immunotherapy.

The Journal of allergy and clinical immunology, 1985

Research

Serum sickness.

Journal of cutaneous medicine and surgery, 2000

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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