Human cyclic neutropenia: clinical review and long-term follow-up of patients

Abstract

Human cyclic neutropenia is a distinctive disorder of unknown cause characterized by regularly recurrent episodes of profound neutropenia, which have a periodicity of about 3 weeks. This periodicity remains constant and is remarkably consistent among patients. Although blood elements other than neutrophils are nt depleted, essentially all patients experience a cycling of monocyte counts with monocyte cycles of the same length as but reciprocal to neutrophil cycles. Cycling of platelet and reticulocyte numbers also may occur. Patients experience a clinical syndrome of recurrent illness characterized by malaise, fever, aphthous stomatitis, and cervical adenopathy. Incidental infections may occur with neutropenia but respond readily to antibiotics. The clinical course is benign compared with others conditions in which similar degrees of neutropenia occur. The only life-threatening complication encountered during long-term follow-up of patients was the occurrence of spontaneous peritonitis, segmental bowel necrosis, and septicemia which required surgical intervention. Most patients develop the disease in childhood, but a significant number of patients develop the disease in adulthood as an apparently acquired condition. The disease occurs equally in both sexes and is familial in some. Studies of marrow morphology, myelopoiesis, and neotrophil kinetics have shown that cyclic neutropenia is primarily a disease of abnormally regulated neutrophil production. The judicious use of antibiotics, careful oral and dental care, and patient education are the mainstays of management. Alternate-day corticosteroids have been used successfully to abate the recurrent signs and symptoms, and in one patient the disease was gradually corrected by alternate day prednisolone. Human cyclic neutropenia is of special investigative interest because clarification of this disease may contribute greatly to an understanding of the normal control of myelopoiesis.