Autoimmune neutropenia (AIN) in adults is most commonly secondary to autoimmune diseases, malignancies, infections, or drug exposure. Primary AIN is rare in adults and differs significantly from its pediatric counterpart. In children, AIN typically follows a benign and self-limited course, and resolves spontaneously within two years. In contrast, adult primary AIN tends to have a chronic, relapsing course, with rare spontaneous remissions. Clinical presentations range from asymptomatic neutropenia to severe infections in both populations. Diagnosis is challenging due to the rarity of the condition and the limited availability of specialized assays to detect anti-human neutrophil antigen (HNA) autoantibodies, which are essential for confirming immune-mediated neutropenia. Treatment responses in adults are often variable and transient, requiring individualized management strategies.

A 45-year-old woman with hypertension, treated with losartan and hydrochlorothiazide, and a history of two pregnancies, presented with persistent neutropenia over four years. She had a previous COVID-19 infection complicated by otitis media but no other infectious episodes. Initial labs showed absolute neutrophil count (ANC) of 0.05 × 10³/µL, with normal vitamin B12, folate, copper levels, and negative infectious screening. Autoimmune testing revealed positive cytoplasmic ANCA (C-ANCA) at 1:320 and strong anti-PR3 positivity, though without clinical or radiologic evidence of vasculitis. Bone marrow biopsy demonstrated hypercellularity with a maturation arrest of the myeloid lineage. Flow cytometry of peripheral blood and bone marrow was unremarkable. Abdominal imaging revealed splenomegaly measuring 15.6 cm. A diagnostic splenectomy was performed leading to transient improvement of ANC to 1.46 × 10³/µL, with relapse within four months. Two short courses of G-CSF were attempted, but discontinued due to diffuse musculoskeletal pain and systemic flu-like symptoms; no blood samples were obtained during therapy, preventing assessment of hematologic response. Anti-HNA assays performed at UNIFESP identified anti-HNA-1b antibodies through granulocyte immunofluorescence (GIFT) and agglutination (GAT) tests. HNA genotyping confirmed the antibody targeted a self-antigen, establishing the diagnosis of primary autoimmune neutropenia. High-dose prednisone (1 mg/kg/day) led to hematological response (ANC 1.02 × 10³/µL), but neutropenia recurred after tapering. Despite persistent severe neutropenia, the patient remains asymptomatic, off-treatment, and without infectious complications to date.

Primary autoimmune neutropenia in adults is a rare and underdiagnosed condition that requires high clinical suspicion and access to specialized laboratory testing for anti-HNA antibodies. Responses to splenectomy, G-CSF, and corticosteroids are often incomplete or transient. Management should be individualized, balancing the severity of neutropenia with clinical symptoms and infection risk. As this case illustrates, profound neutropenia does not always correlate with clinical infections, and observation may be appropriate in asymptomatic patients. This case underscores the need for targeted diagnostics and tailored therapeutic strategies in adult AIN.