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Human serum sickness: a prospective analysis of 35 patients treated with equine anti-thymocyte globulin for bone
L Bielory1, P Gascon, T J Lawley
1Clinical Hematology Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland.
Abstract:
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.
Insights
Serum sickness is common in patients treated for bone marrow failure with anti-thymocyte globulin (ATG) and methylprednisolone, presenting with fever, rash, and immune complex deposition. Understanding these clinical and immunological features is crucial for patient management.
Area of Science:
- Immunology
- Hematology
- Dermatology
Background:
- Bone marrow failure treatments often involve immunosuppressive agents.
- Anti-thymocyte globulin (ATG) is used to manage bone marrow failure.
- Serum sickness is a known immune-mediated adverse reaction.
Purpose of the Study:
- To prospectively evaluate the clinical and immunological characteristics of serum sickness in patients receiving ATG for bone marrow failure.
- To correlate treatment duration with serum sickness development and severity.
- To elucidate the immunopathological mechanisms underlying serum sickness in this context.
Main Methods:
- Prospective evaluation of 35 patients with bone marrow failure treated with ATG and methylprednisolone.
- Clinical assessment for serum sickness symptoms and duration.
- Immunological assays including serum immunoglobulin levels, circulating immune complexes, complement levels, and acute phase reactants.
- Skin biopsies for immunofluorescence studies.
- Urinalysis to detect renal involvement.
Main Results:
- 86% of patients developed clinical serum sickness, characterized by fever, malaise, and cutaneous eruptions.
- A distinct serpiginous band of erythema and purpura on extremities preceded other symptoms in 75% of affected patients.
- Skin biopsies showed immune deposits in dermal vasculature; immunological changes included increased immunoglobulins, elevated immune complexes, decreased complement, and increased acute phase reactants.
- Abnormal urinalysis was observed in 57% of patients.
Conclusions:
- Serum sickness is a frequent complication of ATG treatment for bone marrow failure, with predictable clinical and immunological manifestations.
- The findings support the applicability of animal models of serum sickness to human disease, highlighting antigen-antibody interactions and complement activation.
- Early recognition of serum sickness symptoms and understanding its immunopathology are essential for effective patient care.