To report 2 patients who presented with agranulocytosis that was found to be immune-mediated and associated with occult primary Sjögren's syndrome (primary SS) and to identify and study similar cases reported in the literature.
Two patients encountered in 2 large medical centers over a period of 5 years were studied in detail. All reported cases of agranulocytosis in primary SS identified through a MEDLINE search were reviewed.
Two patients presented with marked systemic symptoms alone or associated with recurrent infections. Agranulocytosis with either a pattern of maturation arrest or a hypercellular reactive bone marrow was found and was associated with "acute phase" markers, hypergammaglobulinemia, a small paraprotein peak, and high rheumatoid factor titers. A diagnosis of immune-mediated agranulocytosis associated with an occult primary SS was established and was successfully treated with intravenous immunoglobulins or prednisone. Both patients subsequently developed skin vasculitis. This rare association of agranulocytosis and Sjögren's syndrome was identified in 11 other cases and was the presenting manifestation of primary SS in 10 of 13 (77%) patients.
Agranulocytosis should be recognized as a rare but well-established association of primary SS. Bone marrow neutrophil production may be affected, or neutrophils may be destroyed in the circulation, by both humoral and cellular immune-mediated mechanisms. Agranulocytosis or neutropenia should be added to the varied hematologic manifestations of primary SS and may be its presenting feature and an important clue to diagnosis.