An update on the diagnosis and treatment of chronic idiopathic neutropenia

Abstract

Purpose of Review Neutropenia lasting for at least for 3 months and not attributable to drugs or a specific genetic, infectious, inflammatory, autoimmune or malignant cause is called chronic idiopathic neutropenia. (CIN) CIN and autoimmune neutropenia (AIN) are very similar and overlapping conditions. The clinical consequences depend upon the severity of neutropenia, but it is not considered a premalignant condition. Recent findings Long-term observational studies in children indicate that the disease often lasts for 3 to 5 years in children, then spontaneously remits, but it rarely remits in adult cases. The value of anti-neutrophil antibody testing in both children and adults is uncertain. Most recent data suggest that CIN and AIN are immune mediated diseases, but there are no new clinical or genetic tests to aid in diagnosis. Treatment with granulocyte colony stimulating factor (G-CSF) is effective to increase blood neutrophils in almost all cases; this treatment is reserved, however for patients with both neutropenia and evidence of recurrent fevers, inflammatory symptoms and infections. There is little or no evidence to indicate that G-CSF treatment predisposes to myeloid malignancies in this population. Summary It is important to recognize CIN and AIN, the most common causes of chronic neutropenia in both children and adults. If the neutropenia is not severe, i.e. > 0.5 × 109/L, most patients can be observed and not treated prophylactically with antibiotics or a growth factor. When neutropenia is severe treatment with G-CSF is often beneficial.

Idiopathic neutropenia of infancy: Data from the Italian Neutropenia Registry

“…Furthermore a series of studies from Crete investigated local adult patients, originally defined as affected by nonimmune chronic IN of adults , for whom, actually, the term idiopathic could be misleading since some evidence about an immune mediate pathogenesis impairing the granulocytopoiesis have been reported: it is not clear how much this pathogenic mechanism can be considered valid also in pediatric IN and/or INs of other ethnic groups. In our opinion and accordingly to other authors it should be better to more simply address every type of neutropenia eluding any specific diagnosis as “idiopathic”. Since it is probable that, in childhood as in adulthood, a high percentage of these cases were autoimmune neutropenias in which, due to the low sensitivity of current tests, it is not possible to reach a firm diagnosis, we suggested, in case of first negativity, to repeat the searching of indirect antineutrophil antibodies several times (at least 4) with the possible association of the other best techniques currently available.…”

“…Furthermore after having examined a large number of key features our analysis shows that AIN and IN cohorts have very comparable clinical presentation, infection load (type and number), prognostic factors, outcome including time and modalities of resolution and use of G‐CSF. All these features, plus the correlation, in our INs as in AIN pediatric patients, between younger age at appearance of neutropenia and absence of monocytosis with earlier recovery, the awareness that the detection of anti‐neutrophil autoantibodies is depending on methods and contexts, the reported evidence that no correlation can be found in AIN patients between disappearance of autoantibodies and time of recovery from neutropenia, lead us, according to many other authors to be firmly convinced that a vast percentage of INs, both in adulthood and in childhood, were AINs impossible to diagnose, probably for different antibody titers or avidity for the target antigen: this aspect poses the needs to make efforts to find effective disease specific diagnostic tests preferentially performed by highly specialized laboratories. In any case, even though the outcomes in both groups is pretty the same, we continue to suggest the searching of the anti‐neutrophil autoantibodies in any case of suspected AIN since it is better for parents to receive a formal diagnosis for their child, and to be informed, in the light of the earlier recovery from an AIN than from an IN shown by the present analysis, that the neutropenia will probably disappear in few months.…”

“…In literature there is an evident discrepancy of terminology about IN since patients who do not display any known cause of neutropenia are classified as affected from time to time not only by IN or chronic IN , but also by chronic IN syndrome , chronic‐acquired IN or idiopathic chronic benign neutropenia . Furthermore a series of studies from Crete investigated local adult patients, originally defined as affected by nonimmune chronic IN of adults , for whom, actually, the term idiopathic could be misleading since some evidence about an immune mediate pathogenesis impairing the granulocytopoiesis have been reported: it is not clear how much this pathogenic mechanism can be considered valid also in pediatric IN and/or INs of other ethnic groups.…”

The cost of a “benign” condition: Healthcare utilization and infectious outcomes in young children with primary autoimmune neutropenia

“…Previous publications have attempted to differentiate AIN from a chronic benign neutropenia of childhood or chronic idiopathic neutropenia (CIN) based on the presence of positive anti‐neutrophil antibodies (AIN patients) versus their absence (CIN patients). Given that both conditions are clinically indistinguishable in terms of presentation, management, and prognosis, for the purposes of this article, both of these entities will be referred to as AIN …”

“…Given that both conditions are clinically indistinguishable in terms of presentation, management, and prognosis, for the purposes of this article, both of these entities will be referred to as AIN. 10,11 Despite the expectation of this relatively benign clinical course, many patients presenting with isolated neutropenia consistent with AIN undergo extensive evaluation to rule out a more clinically significant form of neutropenia, such as severe congenital neutropenia or malignant disease. Institutions may follow patients within a subspecialty hematology clinic until resolution.…”