Background

Autoimmune cytopenias are a heterogeneous group of non-malignant disorders characterized by immune-mediated destruction of peripheral blood cells. They can affect one or multiple cell lineages (autoimmune hemolytic anemia, AIHA; immune thrombocytopenia, ITP; autoimmune neutropenia, AIN; or Evans snydrome, ES, respectively). Despite their similar pathogenesis, these entities differ in terms of epidemiology and clinical presentation. Newly diagnosed ITP and AIN appear to have a benign course, whereas chronic ITP (cITP), AIHA, and ES impose substantial health risks and may represent a substantial therapeutic challenge.

 

Due to the insufficient diagnostic value of antibody detection in suspected immune-mediated cytopenias, the diagnosis can often be established only after exclusion of a large variety of relevant conditions. The broad spectrum of the latter and the potential risk of misdiagnosis provide grounds for inadequate management and treatment failure.

 

A French cohort study of 2016 reported an extremely increased risk (120-fold) to develop an autoimmune cytopenia of patients suffering from a PID compared to the unaffected population (Fischer et al., 2017). The evidence for a strong association between these conditions is supported by another French study detecting PIDs in 13% of cases with isolated AIHA (Aladjidi et al. 2011). Along with the generally underestimated prevalence of PIDs, this data suggests the diagnostic workup of clinically relevant immune cytopenias needs to be extended towards detection of underlying PIDs in order to enable disease-specific treatment (Mahlaoui et al., 2017).

 

Inborn errors that predispose to single- or multilineage cytopenia due to bone marrow failure, and additional factors such as persisting/chronic infections should also be taken into consideration in the differential diagnosis of childhood cytopenias.

The present study aims to standardize the diagnostic approach based on existing international guidelines, facilitate patient stratification with regard to their underlying disease or distinct phenotype into different therapeutic groups according to established recommendations, and to prospectively observe their clinical course.