Human serum sickness: a prospective analysis of 35 patients treated with equine anti-thymocyte globulin for bone marrow failure.

We have prospectively evaluated the clinical and immunological features of serum sickness in 35 patients treated for bone marrow failure with anti-thymocyte globulin (ATG 15 mg/kg/day) and methylprednisolone (1 to 1.5 mg/kg/day). Twenty-one patients were treated for 10 days and 14 were treated for 28 days. Clinical evidence of serum sickness developed in 30 patients (86%) and included fever and malaise (100%), cutaneous eruptions (93%), arthralgias (67%), gastrointestinal complaints (67%), cephalgia (57%), blurring of vision (37%), arthritis, (30%) and lymphadenopathy (13%). Clinical serum sickness began on day 7 +/- 1 (X +/- S.E.M.) and lasted for 10 +/- 2 days in the 18 affected patients receiving the shorter course of ATG. In the 12 affected patients receiving the longer course of ATG, serum sickness began on day 9 +/- 1. The earliest manifestations of serum sickness were fever, malaise, and cutaneous eruptions. Cutaneous findings consisted of morbilliform eruptions (n = 19) and urticaria (n = 1) or a combination (n = 8) that lasted 10 to 14 days. Twenty-one patients (75%) developed a highly characteristic serpiginous band of erythema and purpura along the sides of the fingers, toes, palms and soles 12 to 48 hours before other symptoms of serum sickness. Biopsies of lesional skin during the course of serum sickness revealed immune deposits (IgM, IgE, IgA and C3) in dermal vasculature in 7 of 9 patients. Immunological changes that occurred during the course of serum sickness included increased serum levels of IgG, IgM, IgA, and IgE. Circulating immune complexes, as measured by the C1q-binding assay, increased from a mean value of 12% to 45% on day 13 +/- 1. Complement levels (C3, C4, and CH50) decreased 50 to 80% from their baseline levels on day 10 +/- 2. Acute phase reactants increased: erythrocyte sedimentation rate, C-reactive protein and beta-2 microglobulin. Abnormal urinalysis developed in 17 patients (57%) over the course of serum sickness and included proteinuria, hematuria and hemoglobinuria on day 10 +/- 3. Hematopoietic response occurred in 43%. All 5 patients who did not develop serum sickness recovered from bone marrow failure. Our data document the clinical and immunopathological findings in human serum sickness and suggest that the principles of antigen-antibody interaction, complement activation, and resultant inflammatory response as seen in the previous animal studies are directly applicable to studies of patients with serum sickness.