Pediatric Autoimmune and Chronic Benign Neutropenia Workup

Neutropenia is usually discovered during the workup of a febrile illness. However, leukopenia and neutropenia are often discovered incidentally, as a result of a routine CBC or a CBC performed for an unrelated reason.

The clinical severity and frequency of infections, rather than the severity of neutropenia, should dictate the extent of laboratory workup, since finding a periodic drop in the neutrophil count to zero is not uncommon in chronic benign neutropenia.

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A CBC demonstrates a white blood cell (WBC) count that is either decreased or within the reference range and a neutrophil count of less than 1000/µL (absolute neutropenia).

Performing sequential CBCs with differential to document chronicity is important, because most neutropenia in infants resolves with recovery from an acute infection. In individuals with autoimmune neutropenia, the absolute neutrophil count often remains less than 500.

Monocytosis and eosinophilia may occur, although significant eosinophilia is rare, unlike in severe congenital neutropenia. In individuals with primary autoimmune neutropenia, hemoglobin and platelet counts are normal. In patients with secondary autoimmune neutropenia, associated anemia, an increased reticulocyte count due to hemolysis, and thrombocytopenia may be present.

Antinuclear antibodies may be positive in patients with secondary autoimmune neutropenia, although only rarely in infants. Direct antiglobulin test (DAT) or direct Coombs test results may be positive in individuals with secondary autoimmune neutropenia; perform this study when evidence of hemolysis or thrombocytopenia (Evan syndrome) is present.

Documentation of neutrophil antibodies is not always necessary for patients with a benign course of autoimmune neutropenia. In addition, an absence of demonstrable antineutrophil antibodies does not exclude the diagnosis. The age of onset (most commonly 5-15 mo), a benign clinical course, and normal bone marrow findings are sufficient to make a diagnosis of chronic benign neutropenia of childhood or primary autoimmune neutropenia. However, from the point of prognostication, documenting the presence of antibodies is reassuring.

In addition, research has indicated that, in some patients, antibodies detected at the onset are not detectable on retesting before the patient has recovered. Thus, antibody test findings may not always be positive, depending on the timing. Also, sensitivity for antibody detection varies depending on the test. The indirect granulocyte immunofluorescence test (GIFT) is more sensitive than monoclonal antibody-specific immobilization of granulocyte antigens (MAIGA).

Lalezali and colleagues demonstrated antibodies in 119 of 121 infants and children with chronic neutropenia, whereas Jonsson and Buchanan demonstrated a positive result in only 13 of 28 patients studied.^{[1, 10]}

Bone marrow examination is often necessary to exclude other diagnoses, although bone marrow findings alone are not diagnostic.

The bone marrow may be hypercellular or normocellular with myeloid hyperplasia. However, it can be completely normal, including physiologic lymphoid hyperplasia.

In clinically severe instances of autoimmune neutropenia, "maturation arrest" may be observed, in that there is a paucity or absence of mature neutrophils. However, a preponderance of myelocytes, metamyelocytes, and bands may be present.

Serum immunoglobulin quantitation helps to exclude neutropenia associated with hypogammaglobulinemia.

In most instances, bone marrow findings are normal. Maturation arrest at promyelocyte or myelocyte stage typically seen in severe congenital neutropenia is absent.

Often, an increased number of mature lymphocytes consistent with the patient's age are present.