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Pediatric Serum Sickness Workup

  • Author: Tova Ronis, MD; Chief Editor: Harumi Jyonouchi, MD  more...
Updated: Apr 25, 2016

Approach Considerations




Laboratory Studies

The following studies are indicated in patients with serum sickness:

  • CBC with differential - Leukocytosis or leukopenia, eosinophilia, or mild thrombocytopenia
  • Erythrocyte sedimentation rate and C-reactive protein levels - Usually slightly elevated
  • Urinalysis - Proteinuria, hematuria, active sediment
  • Blood urea nitrogen (BUN) and creatinine levels - May be transiently elevated
  • C3, C4, CH50 - Depressed complement levels due to complement consumption
  • Quantitative immunoglobulins - Hypergammaglobulinemia that results from prolonged course of antithymocyte globulin (ATG)
  • Immune complexes - C1q binding or Raji cell assays for elevated levels of immune complexes (These test can be confirmatory but are not essential for diagnosis.)


Skin biopsy is usually not indicated for serum sickness but may be considered to further evaluate for vasculitis if the etiology is unclear.


Histologic Findings

Biopsy of serum sickness skin lesions reveals a perivascular lymphohistiocytic infiltrate and may show edema of perivascular stroma.[13] Immune deposits (IgM, IgE, C3, and IgA) are found in superficial small blood vessels and renal glomeruli with direct immunofluorescence (DIF).

Results from biopsy of skin lesions in serum sickness–like reactions have noted interstitial inflammatory infiltrate with neutrophils and eosinophils, perivascular lymphocytic, eosinophilic, histiocytic, or neutrophilic infiltrate, typically consistent with urticaria without evidence of vasculitis.[47]

Because of the high rate of blood flow and the filtration effect at the renal glomeruli, the immune complexes with serum sickness are deposited at the glomerular basement membrane. These deposits can be visualized with electron microscopy in the subendothelial and mesangial areas. These deposits lead to the activation of the complement system and the recruitment of neutrophils. Inflammatory mediators are released, resulting in a histologic picture of glomerulonephritis.[48]

Contributor Information and Disclosures

Tova Ronis, MD Attending Rheumatologist, Division of Rheumatology, Children's National Medical Center; Clinical Assistant Professor of Pediatrics, George Washington University Medical Center

Tova Ronis, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Rheumatology, Childhood Arthritis and Rheumatology Research Alliance

Disclosure: Nothing to disclose.


Lawrence K Jung, MD Chief, Division of Pediatric Rheumatology, Children's National Medical Center

Lawrence K Jung, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Rheumatology, Clinical Immunology Society, New York Academy of Sciences

Disclosure: Nothing to disclose.

Philip J Cohen, MD Chief, Section of Dermatology, New Jersey Veterans Affairs Medical Center

Disclosure: Nothing to disclose.

Hanna Kim, MD, MS Pediatric Rheumatology Fellow, AI Dupont Hospital for Children, Thomas Jefferson University, National Institutes of Health (NIH), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Hanna Kim, MD, MS is a member of the following medical societies: American Academy of Pediatrics, American College of Rheumatology, American Medical Association, Childhood Arthritis and Rheumatology Research Alliance, Rheumatism Society of the District of Columbia

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD Faculty, Division of Allergy/Immunology and Infectious Diseases, Department of Pediatrics, Saint Peter's University Hospital

Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Pediatric Research, Society for Mucosal Immunology

Disclosure: Nothing to disclose.


Robyn Siperstein, MD Staff Physician, Department of Dermatology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School

Robyn Siperstein, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society for MOHS Surgery, and Sigma Xi

Disclosure: Nothing to disclose.

David J Valacer, MD Consulting Staff, Hoffman La Roche Pharmaceuticals

David J Valacer, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American Thoracic Society, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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Urticarial rash in a child 10 days after cefaclor was administered for sore throat. Associated findings included fever, arthralgia of knees and ankles, and eosinophilia.
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