Procainamide-induced agranulocytosis differs serologically and clinically from procainamide-induced lupus.
Agranulocytosis is a well recognized but uncommon complication of procainamide (PA) therapy, whereas a lupus-like syndrome occurs in approximately 20% of patients treated chronically with PA. In order to gain insight into the immunopathogenic relationships among these conditions, we compared the humoral immune abnormalities in these patient groups as well as in asymptomatic PA-treated patients. A relatively uniform profile of IgM but not IgG autoantibody reactivity with a set of chromatin-related antigens was observed in eight elderly men who developed agranulocytosis after treatment with PA. In contrast PA-induced lupus patients had predominant reactivity with [(H2A-H2B)-DNA] in both IgM and IgG classes. Five of eight patients with agranulocytosis had elevated levels of neutrophil-reactive IgG which appeared to be due to immune complexes based on Fc gamma receptor blocking studies. However, 12 of 15 patients with PA-induced lupus, none of whom had neutropenia, had similar levels of neutrophil-reactive IgG, suggesting that this reactivity was not causally related to agranulocytosis. Agranulocytosis developed after less than 3 months treatment with PA in six of eight patients. This time course was similar to that seen in 77 PA-induced agranulocytosis patients reported in the literature plus 127 patients reported to the U.S. Food and Drug Administration in whom 90% developed agranulocytosis within 3 months of starting PA. In contrast, the mode duration of treatment with PA before lupus-like symptoms develop is 10-12 months. These findings, together with the different profiles of autoantibodies and clinical presentations, suggest that agranulocytosis arises from a different mechanism than that underlying PA-induced lupus.
Starkebaum
G
G
Division of Rheumatology, Department of Medicine, University of Washington School of Medicine, Seattle 98108, USA.
Kenyon
C M
CM
Simrell
C R
CR
Creamer
J I
JI
Rubin
R L
RL
D000368:Aged; D000369:Aged, 80 and over; D000380:Agranulocytosis / Q000097:blood* / Q000139:chemically induced / Q000276:immunology*; D019268:Antibodies, Antineutrophil Cytoplasmic; D000974:Antibodies, Antinuclear / Q000097:blood; D001323:Autoantibodies / Q000097:blood; D004247:DNA / Q000276:immunology; D006657:Histones / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011342:Procainamide / Q000009:adverse effects*
D019268:Antibodies, Antineutrophil Cytoplasmic; D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D006657:Histones; D004247:DNA; D011342:Procainamide