1. Serum Sickness Jill Tichy, M.D. PGY III

2. Serum Sickness What is it? Immunization of host (human) by heterologous (non-human) serum proteins caused by formation of immune complexes Immunization of host (human) by heterologous (non-human) serum proteins caused by formation of immune complexes A diagnosis made clinically and one of exclusion A diagnosis made clinically and one of exclusion

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

4. Type III or Immune Complex Mediated Hypersensitivity Antigens combine with host immunoglobulins specific to those antigens Antigens combine with host immunoglobulins specific to those antigens Resultant immune complexes are in excess of phagocyte system Resultant immune complexes are in excess of phagocyte system Deposit in tissues and trigger the inflammatory response Deposit in tissues and trigger the inflammatory response

5. Blame the heterologous proteins Equine or Rabbit Antithymocyte Globulin (ATG) Equine or Rabbit Antithymocyte Globulin (ATG) Rituximab Rituximab Inflimixab Inflimixab Venom Anti-toxins Venom Anti-toxins Rabies Vaccine Rabies Vaccine Streptokinase Streptokinase Penicillin Penicillin Cefaclor Cefaclor Amoxicillin Amoxicillin Bactrim Bactrim

6. Supportive Physical Exam Findings Pruritic Rash sparing the mucous membranes Pruritic Rash sparing the mucous membranes Rash can be serpiginous and macular which starts at the trunk and spreads distally 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 *Skin changes at the junction of the lateral aspect of palms and soles

7. Supportive Physical Exam Findings

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

9. Supportive Laboratory Data Neutropenia with reactive lymphocytes Neutropenia with reactive lymphocytes Mild Thrombocytopenia Mild Thrombocytopenia Eosinophilia Eosinophilia Elevated CRP and ESR Elevated CRP and ESR Proteinuria (50% of patients) Proteinuria (50% of patients) Elevations in creatinine Elevations in creatinine

10. Supportive Laboratory Data Dermatopathology Histology varies Histology varies Typical is mild peri-vascular infiltrates with lymphocytes and histiocytes without vessel necrosis Typical is mild peri-vascular infiltrates with lymphocytes and histiocytes without vessel necrosis

11. Differential Diagnosis Acute Rheumatic Fever Acute Rheumatic Fever Disseminated gonococcemia and meningococcemia Disseminated gonococcemia and meningococcemia Reactive Arthritis (Reiter’s Syndrome) Reactive Arthritis (Reiter’s Syndrome) Rickettsial Diseases Rickettsial Diseases Disseminated EBV/CMV Disseminated EBV/CMV Stevens-Johnson Syndrome Stevens-Johnson Syndrome Still’s Disease Still’s Disease Kawasaki’s Disease Kawasaki’s Disease Viral Exanthems Viral Exanthems

12. Treatment Stop offending agent Mild symptoms self-limiting Mild symptoms self-limiting Anti-histamines; NSAIDs Anti-histamines; NSAIDs Severe symptoms (fever > 38.5; extensive rash, severe arthritis) give steroids Severe symptoms (fever > 38.5; extensive rash, severe arthritis) give steroids Avoid responsible drug in the future Avoid responsible drug in the future Not clear if similar drugs should be avoided Not clear if similar drugs should be avoided

13. 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 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 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 Snow, M, Cannella, A, Stevens, RB, Presumptive Serum Sickness as a Complication of Rabbit-Derived Antithymocyte Globulin Immunosuppression Harrison’s Textbook of Internal Medicine Harrison’s Textbook of Internal Medicine Uptodate photography Uptodate photography