Serum Sickness

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Serum Sickness

• Jill Tichy, M.D. PGY III

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Serum SicknessWhat is it?

• Immunization of host (human) by heterologous
  (non-human) serum proteins caused by formation of
  immune complexes
• A diagnosis made clinically and one of exclusion

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Definition continued

• Cardinal symptoms include rash, fever,
  polyarthralgias or polyarthritis
• Malaise
• Occurs one to two weeks after first exposure to
  responsible agent
• Resolves within a few weeks of discontinuing the
  drug

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Type III or Immune Complex Mediated
Hypersensitivity

• Antigens combine with host immunoglobulins
  specific to those antigens
• Resultant immune complexes are in excess of
  phagocyte system
• Deposit in tissues and trigger the inflammatory
  response

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Blame the heterologous proteins

• Equine or Rabbit Antithymocyte Globulin (ATG)
• Rituximab
• Inflimixab
• Venom Anti-toxins
• Rabies Vaccine
• Streptokinase
• Penicillin
• Cefaclor
• Amoxicillin
• Bactrim

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Supportive Physical Exam Findings

• Pruritic Rash sparing the mucous membranes
• Rash can be serpiginous and macular which starts
  at the trunk and spreads distally
• Skin changes at the junction of the lateral
  aspect of palms and soles

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Supportive Physical Exam Findings
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Supportive Physical Exam Findings

• Joints commonly involved are MCP, knees, wrists,
  ankles and shoulders
• Spine and TMJ involvement is also reported
• Joint pain typically occurs after rash has
  started
• Myalgias also seen
• Trismus

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Supportive Laboratory Data

• Neutropenia with reactive lymphocytes
• Mild Thrombocytopenia
• Eosinophilia
• Elevated CRP and ESR
• Proteinuria (50 of patients)
• Elevations in creatinine

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Supportive Laboratory DataDermatopathology

• Histology varies
• Typical is mild peri-vascular infiltrates with
  lymphocytes and histiocytes without vessel
  necrosis

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Differential Diagnosis

• Acute Rheumatic Fever
• Disseminated gonococcemia and meningococcemia
• Reactive Arthritis (Reiters Syndrome)
• Rickettsial Diseases
• Disseminated EBV/CMV
• Stevens-Johnson Syndrome
• Stills Disease
• Kawasakis Disease
• Viral Exanthems

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TreatmentStop offending agent

• Mild symptoms self-limiting
• Anti-histamines NSAIDs
• Severe symptoms (fever gt 38.5 extensive rash,
  severe arthritis) give steroids
• Avoid responsible drug in the future
• Not clear if similar drugs should be avoided

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References

• Lawley, TJ, Bielory, L, Gascon, P, et al. A
  prospective clinical and immunologic analysis of
  patients with serum sickness. N Engl J Med 1984
  3111407
• Bielory, L, Yancey, KB, Young, NS, et al.
  Cutaneous Manifestations of serum sickness in
  patients receiving antithymocyte globulin. J AM
  Acad Dermatol 1985 13411
• Snow, M, Cannella, A, Stevens, RB, Presumptive
  Serum Sickness as a Complication of
  Rabbit-Derived Antithymocyte Globulin
  Immunosuppression
• Harrisons Textbook of Internal Medicine
• Uptodate photography