Serum disease T80.61

Authors: Prof. Dr. med. Peter Altmeyer, Alexandros Zarotis

All authors of this article

Last updated on: 23.12.2020

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Rituximab induced serum sickness; serum sickness

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by Pirquet and Schick, 1905

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Acute systemic clinical picture due to deposition of circulating immune complexes (predominantly antigen-specific IgG, more rarely IgM antibodies) in the tissue, which probably occurs after antigen-induced activation of the complement cascade.

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Incidences vary and depend on the type of therapeutic agent applied (see below).

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Type III allergy. Deposition of antigen-antibody-containing immune complexes leads to complement fixation and consecutive granulocyte chemotaxis and leukocytoclasia. Complication of serum therapy, e.g. with repeated use of antithymocyte globulin (rabbit serum), antidiphtheria serum (horse serum), anti-mosquito sera, streptokinase, rituximab, etc.

Clinical features
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7-14 days after primary and 2-4 days after re-exposure to a foreign serum, also after streptokinase or after administration of immunoglobulins (see IVIG below), occurrence of fever, arthralgias, arthritides, swelling of lymph nodes and a usually extensive, very itchy, maculo-papular exanthema, palpable purpura.

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BSG↑↑, leukocytosis, C3a↑, eosinophilia, hematuria, and proteinuria possible.

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Picture of the leukocytoclastic vasculitis. DIF: Deposition of IgG, IgM, IgA, C3 on the dermal vessels.

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Clinical picture and medical history!

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Measures depending on the acuteity of the clinical symptoms. For mild to moderate symptoms, systemic glucocorticoids such as prednisolone (e.g. Solu-Decortin H) 50-80 mg i.v., after the acute symptoms have subsided, peroral glucocorticoid therapy in slowly decreasing doses. Also non-steroidal anti-inflammatory drugs such as diclofenac.


In case of severe symptoms (possibly shock symptoms) immediate intensive care is required!

Case report(s)
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Ryan NM et al. (2019) Of 100 follow-up patients who received an antivenom serum, 29% showed signs of serum disease (fever, urticaria or urticarial exanthema, myalgia, arthalgia, headache, general malaise and nausea). After an antivenom serum against tiger mosquitoes, these symptoms occurred in 41% of patients. A relationship between the amount of the antivenome and the extent of the clinical symptoms could not be proven.

Bayer G et al (2019) reported the occurrence of serum disease after rituximab (RISS). Symptoms occurred on average 12 days after the first injections. In a larger group the following symptoms were detectable: rheumatoid symptoms (92%), fever (87%), exanthema (78%). The incidence was significantly higher in a group that received rituximab for autoimmune diseases and less frequently for underlying haematological diseases.

After application of "Varicella/zoster immunoglobulin" a serum disease was detected in 0.2% of cases (Levin MJ et al. 2019).

Less frequently a serum disease is observed after biologics (Sala-Cunill A et al. 2019).

Tawanwongsri W et al. (2019) reported the occurrence of rabbit serum-induced serum disease in twins.

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  1. Bayer G et al (2019) Rituximab-induced serum sickness is more frequent in autoimmune diseases than compared to hematological malignancies: A French nationwide study. Eur J Intern Med pii: S0953-6205(19)30192-X.
  2. Levin MJ et al (2019) Varicella zoster immune globulin (VARIZIG) administration up to 10 days after varicella exposure in pregnant women, immunocompromised participants, and infants: Varicella outcomes and safety results from a large, open-label, expanded-access program. PLoS One 14:e0217749.
  3. Ryan NM et al (2019) Incidence of serum sickness after the administration of Australian snake antivenom (ASP-22). Clin Toxicol (Phila) 54:27-33.
  4. Sala-Cunill A et al (2019) Biologics and anaphylaxis.Curr Opin Allergy Clin Immunol doi: 10.1097/ACI.
  5. Tawanwongsri W et al (2019) Serum Sickness after Equine Rabies Immunoglobulin in Identical Male Twins: TwoCase Reports.Case Rep Dermatol 11:40-47.
  6. Williams PhD MV, Cox B, Lafuse PhD WP, Ariza ME. Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Clin Ther 41:848-863.
  7. Ratushny V et al (2017) Presumed serum sickness following thymoglobulin treatment of acute cellular rejection of a cardiac allograft. Cutis 100:186-188.
  8. by Pirquet C, Schick B (1905) Serum sickness. Franz Denticke, Leipzig


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Last updated on: 23.12.2020