Serum Sickness
Jill Tichy, M.D. PGY III
Serum Sickness
What 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
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
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
Blame the heterologous proteins










Equine or Rabbit Antithymocyte Globulin (ATG)
Rituximab
Inflimixab
Venom Anti-toxins
Rabies Vaccine
Streptokinase
Penicillin
Cefaclor
Amoxicillin
Bactrim
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
Supportive Physical Exam Findings
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
Supportive Laboratory Data






Neutropenia with reactive lymphocytes
Mild Thrombocytopenia
Eosinophilia
Elevated CRP and ESR
Proteinuria (50% of patients)
Elevations in creatinine
Supportive Laboratory Data
Dermatopathology


Histology varies
Typical is mild peri-vascular infiltrates with
lymphocytes and histiocytes without
vessel necrosis
Differential Diagnosis









Acute Rheumatic Fever
Disseminated gonococcemia and meningococcemia
Reactive Arthritis (Reiter’s Syndrome)
Rickettsial Diseases
Disseminated EBV/CMV
Stevens-Johnson Syndrome
Still’s Disease
Kawasaki’s Disease
Viral Exanthems
Treatment
Stop offending agent





Mild symptoms self-limiting
Anti-histamines; NSAIDs
Severe symptoms (fever > 38.5; extensive
rash, severe arthritis) give steroids
Avoid responsible drug in the future
Not clear if similar drugs should be
avoided
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; 311:1407
Bielory, L, Yancey, KB, Young, NS, et al. Cutaneous
Manifestations of serum sickness in patients receiving
antithymocyte globulin. J AM Acad Dermatol 1985;
13:411
Snow, M, Cannella, A, Stevens, RB, Presumptive Serum
Sickness as a Complication of Rabbit-Derived
Antithymocyte Globulin Immunosuppression
Harrison’s Textbook of Internal Medicine
Uptodate photography