Familial Cyclical Neutropenia

Abstract

CYCLICAL neutropenia is a disorder of unknown cause characterized by episodes of neutropenia occurring at more or less regular intervals. Although it is rare, it may prove to be of particular importance, for its study may provide insight into the normal control of granulopoiesis and into the genesis of biological rhythms. The first case to be recognized was described by Leale ( I~I O ) , who noted an abnormal blood picture in a patient suffering from recurrent furunculosis. In I949 Reimann and deBerardinis collected 16 cases, published and unpublished, and described an additional case of their own. They suggested that cyclical neutropenia was a distinct entity, that only the more severely affected patients were recognized, and that specific search for the disease, especially amongst relatives of known sufferers, might disclose otherwise unsuspected cases. By 1963 Reimann was able to collect and review in his monograph Periodic Diseases a total of 42 cases. He emphasized their strikingly similar clinical and haematological features. The numbers of circulating neutrophils fell regularly, often at intervals of 20-21 days, and during the intervening periods were normal or moderately reduced. The cyclical changes in the peripheral blood followed cyclical changes in the bone marrow. Clinical manifestations nearly always appeared before the age of 10 years and tended to recur regularly thereafter. The commonest were fever, buccal ulceration and skin infections. The disease usually ran a benign course, although death due to infection occurred in four of his cases. Reimann found that splenectomy or administration of adrenal corticosteroids produced slight improvement in some cases, but no form of therapy ever resulted in a cure. More recently, Brodsky, Reimann and Dennis (1965) described one patient in whom clinical and haematological improvement followed therapy with testosterone.The aetiology of cyclical neutropenia remains unknown. Most studies in female patients have failed to show a relationship between the episodes of neutropenia and the menstrual cycle, which is the only well-understood long-term human physiological cycle (Reimann, 1963). A relationship between cyclical neutropenia and other periodic syndromes was suggested by Reimann and deBerardinis (1949). Occasional cases of the disease have been found in association with non-periodic diseases such as haemolytic anaemia (Doan, 1932), diabetes insipidus (Thompson, 1934), lymphosarcoma (Sandella, 1951 ;Natelson, 1953) and agammaglobulinaemia (Laski, Sass-Korstak and Hillman, 1954;Good and Varco, 1955). In a few cases the disease appears to have been genetically determined since studies of relatives of patients have revealed various forms of neutropenia. Thus Hahneman and Alt (1958), Gorlin and Chaudhry (1960) and Videbaek (1962) found cyclical neutropenia in a parent and child, and Good and Varco (1955) described two brothers, one suffering from cyclical neutropenia and the other from neutropenia which was apparently non-cyclical. In addition Vahlquist (1946),...

How we evaluate and treat neutropenia in adults

“…20,21 The cycles are of varying length but are very consistent within each patient. The syndrome is usually of mild severity, although some patients can develop infections or oral ulcers during their neutrophil nadir.…”

Childhood Cancer and Congenital Defects A Study of U.S. Death Certificates During the Period 1960–1966

“…To our knowledge, neither anomaly has been reported previously in persons with neoplasia, but myelogenous leukemia has been described twice in siblings of persons with hereditary neutropenia [lo, 561. Lymphosarcoma has been reported in three persons with cyclical neutropenia [41]. These inborn blood dyscrasias may mimic leukemia [8], or leukemia may induce a hematologic disorder that mimics them.…”

Neutrophil Dysfunction and Host Susceptibility to Periodontal Inflammation: Current State of Knowledge

“…Benign chronic neutropenia characterized by prolonged noncyclic neutropenia is associated with hyperplastic, edematous, fiery-red gingiva, and in some cases with periodontitis [38,39]. Cyclic neutropenia characterized by periodic oscillations in production and release of mature PMN including a 21-day cycle with severe neutropenia persisting for 3-10 days is consistently associated with gingivitis and periodontitis [40]. Treatment includes human recombinant granulocyte colony stimulating factor (hrG-CSF) three times per week with successful increase in PMN numbers.…”