Cutaneous manifestations of serum sickness in patients receiving antithymocyte globulin

We have prospectively evaluated the cutaneous manifestations of serum sickness in thirty-five patients treated with horse antithymocyte globulin for bone marrow failure. Twenty-one patients (21/35) were treated with antithymocyte globulin (15 mg/kg/day) for 10 days, and fourteen of thirty-five patients were treated with antithymocyte globulin (15 mg/kg/day) for 14 days and then every other day for an additional 14 days. Clinical evidence of serum sickness developed in thirty patients and included fever and malaise (100%), cutaneous eruptions (93%), arthralgias and myalgias (67%), gastrointestinal complaints (67%), and lymphadenopathy (13%). Cutaneous findings consisted of morbilliform eruptions (n = 19), urticaria (n = 1), or a combination of these two reaction patterns (n = 8). Cutaneous manifestations of serum sickness began on day 7 +/- 1 and lasted for 12 +/- 2 days for the group as a whole. Biopsies of lesional skin revealed mild perivascular lymphohistiocytic infiltrates by light microscopy in these leukopenic patients. Direct immunofluorescence microscopy of lesional skin from patients with serum sickness demonstrated immunoreactants in seven of nine subjects (78%). Immunoreactants were confined to the walls of dermal blood vessels and consisted of IgM (7/9), C3 (6/9), IgE (5/9), and IgA (4/9). IgG (horse or human) was not identified in any of these specimens. Twenty-one patients (21/28) also developed an erythematous eruption on the sides of the fingers, toes, palms, and soles 12 to 48 hours prior to their morbilliform eruption. This study describes the cutaneous manifestations of human serum sickness occurring during therapy with horse antithymocyte globulin, documents a cutaneous sign of serum sickness, and suggests that the cutaneous eruptions associated with human serum sickness are immunologically mediated.