eMedicine Specialties > Rheumatology > Vasculitis

Serum Sickness: Differential Diagnoses & Workup

Author: Hassan M Alissa, MD, Fellow in Rheumatology, Department of Internal Medicine, Loyola University Medical Center
Coauthor(s): Elaine Adams, MD, Chief of Medical Service, Chief of Rheumatology Section, Hines Veterans Affairs Hospital; Associate Chief, Associate Professor, Department of Internal Medicine, Loyola University School of Medicine; Rochella Abaygar Ostrowski, MD, Assistant Professor, Department of Medicine, Division of Rheumatology, Loyola University Medical Center; Staff Physician, Department of Medicine, Division of Rheumatology, Edward Hines Jr Veterans Affairs Hospital; Richard Hariman, MD, Fellow, Department of Rheumatology, Loyola University Medical Center
Contributor Information and Disclosures

Updated: Jun 22, 2009

Differential Diagnoses

Cryoglobulinemia
Kawasaki Disease
Glomerulonephritis, Poststreptococcal
Leukocytoclastic Vasculitis
Hepatitis, Viral
Sickle Cell Anemia
Hypersensitivity Reactions, Immediate
Systemic Lupus Erythematosus
Infectious Mononucleosis
Infective Endocarditis

Other Problems to Be Considered

Dermatitis herpetiformis
Guillain-Barré syndrome
Henoch-Schönlein purpura
Microscopic polyangiitis
Shunt nephritis
Still disease

Workup

Laboratory Studies

  • Patients with serum sickness may have leukopenia or mild leukocytosis, with or without eosinophilia. Plasma cells may be observed on a peripheral blood smear.2
  • The erythrocyte sedimentation rate is usually elevated.2
  • Patients may have polyclonal gammopathy or a transient monoclonal immunoglobulin G (IgG) spike.5
  • Urinalysis may reveal mild proteinuria or hematuria, and serum creatinine levels may be transiently elevated.
  • Complement levels (C3, C4) are often decreased.2
  • Cryoglobulins, often of the mixed (IgM-IgG) type, may be present.

Histologic Findings

Numerous histological changes may be found in serum sickness, depending on the organ involved and, possibly, the nature of the antigen. The tissues most commonly involved include those of the heart, arteries, joints, and kidneys. Arteritic lesions are focal, necrotizing, and inflammatory processes usually involving all layers of the artery. Acute inflammatory exudate, necrosis of the arterial wall, fibrinoid material, or primarily a mononuclear reaction may be observed. Joints may have focal mononuclear infiltrates with edema and fibrinoid formation in the synovial tissues. Kidneys develop endothelial proliferation of the glomerular capillaries with slight basement membrane thickenings.3

More on Serum Sickness

Overview: Serum Sickness
Differential Diagnoses & Workup: Serum Sickness
Treatment & Medication: Serum Sickness
Follow-up: Serum Sickness
References
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References

  1. Pichler, WJ. Drug hypersensitivity. In: Rich RR, ed. Clinical Immunology Principles and Practice. 3rd ed. St Louis, Mo: Mosby/Elsevier; 2008:714.

  2. Mannik M. Serum sickness and pathophysiology of immune complexes. In: Rich RR, ed. Clinical Immunology Principles and Practice. St. Louis, Mo: Mosby; 1996:1062-71.

  3. Dixon FJ, Cochrane CC. Immune complex injury. In: Samter M, ed. Immunological Diseases. 4th ed. New York, NY: Little, Brown and Company; 1988:233.

  4. Sicherer SH, Leung DYM. Serum sickness. In: Kliegman, ed. Nelson Textbook of Pediatrics. 18th ed. Online Edition, Chapter 149.

  5. Erffmeyer JE. Serum sickness. Ann Allergy. Feb 1986;56(2):105-9. [Medline].

  6. King BA, Geelhoed GC. Adverse skin and joint reactions associated with oral antibiotics in children: the role of cefaclor in serum sickness-like reactions. J Paediatr Child Health. Dec 2003;39(9):677-81. [Medline].

  7. Abraham E, Wunderink R, Silverman H, et al. Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. A randomized, controlled, double-blind, multicenter clinical trial. TNF-alpha MAb Sepsis Study Group. JAMA. Mar 22-29 1995;273(12):934-41. [Medline].

  8. Karliner JS, Belaval GS. Incidence of reactions following administration of antirabies serum; study of 526 cases. JAMA. Aug 2 1965;193:359-62. [Medline].

  9. Frank, MM, Lawley TJ. Immune complexes and allergic disease. In: Middleton E Jr, ed. Allergy Principles and Practice. 5th ed. St Louis, Mo: Mosby; 1998:704-6.

  10. Lawley TJ, Frank MM. Immune complexes and allergic diseases. In: Middleton E Jr, ed. Allergy Principles and Practice. 4th ed. St. Louis, Mo: Mosby; 1993:990.

  11. Lawley TJ, Bielory L, Gascon P, Yancey KB, Young NS, Frank MM. A prospective clinical and immunologic analysis of patients with serum sickness. N Engl J Med. Nov 29 1984;311(22):1407-13. [Medline].

  12. Pilette C, Coppens N, Houssiau FA, Rodenstein DO. Severe serum sickness-like syndrome after omalizumab therapy for asthma. J Allergy Clin Immunol. Oct 2007;120(4):972-3. [Medline].

  13. Disperati P, Hicks LK, Buckstein R. Rituximab-induced serum sickness in a patient with follicular lymphoma. Leuk Lymphoma. Aug 2007;48(8):1633-5. [Medline].

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Further Reading

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Keywords

serum sickness, hypersensitivity vasculitis, drug-induced vasculitis, immune complex disease, foreign serum, serum protein, serum disease, serum reaction, foreign proteins, haptens, antigens, leukocytoclastic vasculitis, secondary serum sickness, antirabies serum, tetanus antitoxin

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Contributor Information and Disclosures

Author

Hassan M Alissa, MD, Fellow in Rheumatology, Department of Internal Medicine, Loyola University Medical Center
Hassan M Alissa, MD is a member of the following medical societies: American College of Physicians
Disclosure: Nothing to disclose.

Coauthor(s)

Elaine Adams, MD, Chief of Medical Service, Chief of Rheumatology Section, Hines Veterans Affairs Hospital; Associate Chief, Associate Professor, Department of Internal Medicine, Loyola University School of Medicine
Elaine Adams, MD is a member of the following medical societies: American College of Physicians and American College of Rheumatology
Disclosure: Nothing to disclose.

Rochella Abaygar Ostrowski, MD, Assistant Professor, Department of Medicine, Division of Rheumatology, Loyola University Medical Center; Staff Physician, Department of Medicine, Division of Rheumatology, Edward Hines Jr Veterans Affairs Hospital
Rochella Abaygar Ostrowski, MD is a member of the following medical societies: American College of Physicians and American College of Rheumatology
Disclosure: Nothing to disclose.

Richard Hariman, MD, Fellow, Department of Rheumatology, Loyola University Medical Center
Richard Hariman, MD is a member of the following medical societies: American College of Rheumatology
Disclosure: Nothing to disclose.

Medical Editor

John Varga, MD, Professor, Department of Internal Medicine, Division of Rheumatology, Northwestern University
John Varga, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, Central Society for Clinical Research, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Elliot Goldberg, MD, Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine
Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD, Professor of Medicine, Temple University School of Medicine; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital
Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, and Phi Beta Kappa
Disclosure: medifocus Honoraria Review panel membership; health dialogs Honoraria Consulting; West Penn Allegheny Health System None Board membership

 
 
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