Serum Sickness Clinical Presentation

  • Author: Hassan M Alissa, MD; Chief Editor: Herbert S Diamond, MD   more...
 
Updated: Aug 30, 2011
 

History

Serum sickness develops 1-3 weeks after initial administration of the causative agent (in many cases a medication) but can occur within 12-36 hours in individuals who have been previously sensitized through an antecedent exposure.[5]

Symptoms described in serum sickness include the following[19] :

  • Fever/malaise - 100%
  • Cutaneous eruptions - 93%
  • Arthralgias - 77%
  • Gastrointestinal complaints - 67%
  • Headaches - 57%
  • Myalgias - 37%
  • Blurred vision - 37%
  • Dyspnea/wheezing - 20%
  • Lymphadenopathy - 17%

Specific GI symptoms may include abdominal pain, nausea, vomiting, or diarrhea.[2] Chest pain or breathlessness due to pleuritis, pericarditis, or myocarditis is possible but rare.

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Physical Examination

Fever develops in almost all patients with serum sickness, preceding skin rash in 10-20% of cases. The fever is characterized by high spikes that normalize within the same day.[4]

Most rashes associated with serum sickness are urticarial (92%) and/or serpiginous.[2] They typically start on the anterior lower trunk or the periumbilical or axillary regions and spread to the back, upper trunk, and extremities.[4] In the extremities, eruptions occur at the junction of the palmar or plantar skin with the dorsolateral surface of the hands, feet, fingers, and toes.

Morbilliform or scarlatiniform rash, palpable purpura, erythema simplex, or erythema multiforme are less common. Pruritus and erythema are possible at injection sites. Edema can be limited to site of injection but can also be observed in the face.[2]

Lymphadenopathy (10-20%) may be generalized or may involve tenderness in the nodes that drain the injection site; splenomegaly may occur.

Arthritis (10%-50%) is usually in the metacarpophalangeal and knee joints and usually symmetrical.[15] Occasionally, small joints, joints of the spine, and the temporomandibular joint may be inflamed. Myalgias or myositis also may occur.

Edema may occur, particularly about the face and neck.

Renal manifestations include proteinuria, microscopic hematuria, and oliguria; however, significant disease usually does not result.

Cardiovascular findings may include myocardial and pericardial inflammation. Generalized vasculitis occurs rarely.

Neurologic manifestations include the following[2, 15] :

Pulmonary manifestations, such as pleurisy, are rare. However, dyspnea and cyanosis are not uncommon.

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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 Rheumatology

Disclosure: Nothing to disclose.

Coauthor(s)

Susan M Chen, MD  Clinical Assistant Professor, Department of Emergency Medicine, University of Pennsylvania Health System, Penn Presbyterian Medical Center

Susan M Chen, MD is a member of the following medical societies: American Academy of Emergency Medicine

Disclosure: Nothing to disclose.

Francis Counselman, MD, FACEP  Chair, Professor, Department of Emergency Medicine, Eastern Virginia Medical School

Francis Counselman, MD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians, Association of Academic Chairs of Emergency Medicine (AACEM), Norfolk Academy of Medicine, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Elaine Adams, MD  Associate Chief of Staff, Chief of Rheumatology Section, Hines Veterans Affairs Hospital; Professor of 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  Assistant Professor, Division of Rheumatology, Medical College of Wisconsin

Richard Hariman, MD is a member of the following medical societies: American College of Rheumatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Matthew M Rice, MD, JD, FACEP  Senior Vice President, Chief Medical Officer, Northwest Emergency Physicians of TeamHealth; Assistant Clinical Professor of Medicine, University of Washington School of Medicine

Matthew M Rice, MD, JD, FACEP is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, National Association of EMS Physicians, Society for Academic Emergency Medicine, and Washington State Medical Association

Disclosure: Team Health Salary Employment

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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.

Erik D Schraga, MD  Staff Physician, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD  Adjunct Professor of Medicine, Division of Rheumatology, University of Pittsburgh 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: Merck Ownership interest Other; Smith Kline Ownership interest Other; Zimmer Ownership interest Other

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. 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.

  6. 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].

  7. Benson E. Bupropion-induced hypersensitivity reactions. Med J Aust. Jun 18 2001;174(12):650-1. [Medline].

  8. Wooltorton E. Bupropion (Zyban, Wellbutrin SR): reports of deaths, seizures, serum sickness. CMAJ. Jan 8 2002;166(1):68. [Medline]. [Full Text].

  9. Gamarra RM, McGraw SD, Drelichman VS, Maas LC. Serum sickness-like reactions in patients receiving intravenous infliximab. J Emerg Med. Jan 2006;30(1):41-4. [Medline].

  10. Vermeire S, Van Assche G, Rutgeerts P. Serum sickness, encephalitis and other complications of anti-cytokine therapy. Best Pract Res Clin Gastroenterol. 2009;23(1):101-12. [Medline].

  11. 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].

  12. 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].

  13. Meijer JM, Pijpe J, Vissink A, Kallenberg CG, Bootsma H. Treatment of primary Sjogren syndrome with rituximab: extended follow-up, safety and efficacy of retreatment. Ann Rheum Dis. Feb 2009;68(2):284-5. [Medline].

  14. Lazoglu AH, Boglioli LR, Taff ML, Rosenbluth M, Macris NT. Serum sickness reaction following multiple insect stings. Ann Allergy Asthma Immunol. Dec 1995;75(6 Pt 1):522-4. [Medline].

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

  16. 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].

  17. 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].

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

  19. 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.

 
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