Diagnosis and Clinical Course of Autoimmune Neutropenia in Infancy: Analysis of 240 Cases

Abstract

Primary autoimmune neutropenia (AIN) is caused by granulocyte-specific autoantibodies and occurs predominantly in infancy. Clinical presentation and diagnosis have not been well established, resulting in burdening diagnostic investigations and unnecessary treatment with granulocyte colony-stimulating factor (G-CSF). In the present study, clinical, laboratory, and immunologic data of 240 infants with primary AIN were evaluated. Suspected association with parvovirus B19 infection was investigated using serologic and DNA-based methods. Primary AIN was mainly diagnosed at the age of 5 to 15 months but was observed as early as day 33 of life. In 90% of the cases, AIN was associated with benign infections despite severe neutropenia. Spontaneous remission, shown by 95% of the patients, usually occurred within 7 to 24 months. Autoantibodies in the patient's sera were not always present, and screening had to be repeated several times until antibody detection succeeded. About 35% of the autoantibodies showed preferential binding to granulocytes from NA1 and NA2 homozygous donors. Bone marrow was typically normocellular or hypercellular, with a variably diminished number of segmented granulocytes. A significant association with parvovirus B19 infection was not found. Symptomatic treatment with antibiotics was sufficient in most patients. Eighty-nine percent of the patients received antibiotics (cotrimoxazole) for prophylaxis of infections. For severe infections or for surgical preparation, G-CSF, corticosteroids, and intravenous IgG were administered, resulting in increased neutrophil counts in 100%, 75%, and 50% of the patients treated, respectively. In combination with the detection of granulocyte-specific antibodies, the typical clinical picture allowed diagnosis of AIN without burdening investigations. Treatment with G-CSF was found to be a reliable alternative to temporarily increase the neutrophil count.

Autoimmune neutropenia in children: analysis of 116 cases

“…They were less likely to have an ENT infection than group II patients (20% vs. 45%). The age at diagnosis and the severity of neutropenia were more similar in group I with data previously published by others, respectively 8 months and <500 neutrophils by microliter (2,3).…”

Severe chronic neutropenia in Chinese children in Hong Kong

“…11,13 Bux et al reported a group of infants with autoimmune neutropenia who were all infants at the time of diagnosis and whose neutropenia recovered within 3 years from presentation. 12 These findings were similar to some patients in our cohort. However, bone marrow studies in a large proportion of our patients showed granulocytic maturation arrest at the level of promyelocytes and myelocytes that is more compatible with the Kostmann type of congenital SCN.…”

“…It can be subclassified into congenital, cyclic, autoimmune and idiopathic neutropenias. 1,8,11,12 The estimated frequencies of these types of SCN range from 0.5 to four cases per million population. 11,13 Bux et al reported a group of infants with autoimmune neutropenia who were all infants at the time of diagnosis and whose neutropenia recovered within 3 years from presentation.…”

Serum G‐CSF levels are not increased in patients with antibody‐induced neutropenia unless they are suffering from infectious diseases

“…Thus, in patients with immune neutropenia, G-CSF may be primarily produced as an emergency signal due to of infectious diseases and not to maintain a normal number of neutrophils. This mechanism of regulation would also explain the frequent observation of an increased absolute neutrophil count during the course of severe bacterial infections in infants with primary autoimmune neutropenia (Bux et al, 1998). The hypothesis is not contradictory to the elevated G-CSF levels observed in SCN patients, since it is known that bacteria colonize in higher numbers patients with SCN than controls, resulting in increased G-CSF production.…”

“…Although recombinant granulocyte-colony stimulating factor (G-CSF) has been successfully used for treatment of severe cases of autoimmune neutropenia (Bux et al, 1998), little is known about the serum G-CSF levels in patients with immune neutropenia. Recently, it has been shown that in contrast to thrombocytopenia due to megakaryocyte deficiency, in immune thrombocytopenia thrombopoietin serum levels are not elevated despite severe thrombocytopenia (Emmons et al, 1996).…”