25-year trends in autoimmune neutropenia-related mortality in the United States: A national CDC wonder analysis (1999-2023)

Abstract Background: Autoimmune neutropenia (AIN) is a rare immune-mediated hematologic disorder characterized by peripheral destruction of neutrophils through antineutrophil antibodies targeting Fcγ receptors. AIN significantly increases vulnerability to infections and sepsis, leading to hospitalizations, prolonged immunosuppression, and mortality. Although clinical outcomes of AIN have been described in small cohorts, national trends in mortality remain poorly characterized. This study evaluates the long-term epidemiology and demographic disparities in AIN-related mortality across the United States over a 25-year period. Methods: We extracted data from the CDC WONDER Multiple Cause of Death database from 1999 to 2023, including adults aged ≥25 years with autoimmune neutropenia (ICD-10: D70) listed as a contributing cause of death. Age-adjusted mortality rates (AAMRs) per 100,000 were calculated using U.S. census population estimates. Trends were stratified by sex, race/ethnicity, age group, region, state, and urbanization level. Joinpoint regression was used to identify inflection points and estimate annual percent change (APC) and average annual percent change (AAPC) with 95% confidence intervals (CIs). Results: A total of 72,005 deaths were associated with autoimmune neutropenia during the study period. Nationally, the AAMR decreased from 1.49 in 1999 to 1.18 in 2017, followed by a reversal and increase to 1.36 by 2023. Three Joinpoint segments were identified: * 1999–2005: significant decline [APC –2.75; 95% CI: –4.19 to –1.27] * 2005–2017: plateau with mild decline [APC –0.24; 95% CI: –0.69 to 0.21] * 2017–2023: resurgence [APC 2.36; 95% CI: 1.28 to 3.46] Sex-specific trends: Mortality was consistently higher in males, with AAMRs declining from 1.90 (1999) to 1.37 (2013), then increasing to 1.54 (2023). In females, AAMRs fell from 1.22 to 1.00 (2010), rising slightly to 1.21 by 2023. Racial disparities: Non-Hispanic (NH) Black adults had the highest AAMRs across the period (1.85 to 1.34), followed by NH White (1.47 to 1.36) and Hispanic adults (1.38 to 1.06). While AAMRs decreased over time for all groups, NH Black individuals experienced persistently elevated mortality. Age group analysis: Adults ≥65 years exhibited the highest burden, with AAMRs peaking at 4.58 in 1999, plateauing near 3.91 (2004–2017), and rising again to 4.46 in 2023. Adults aged 45–64 showed smaller fluctuations, while younger age groups had relatively stable low rates. Geographic variation: States above the 90th percentile in AAMRs included Vermont (2.28), Rhode Island (2.01), and North Dakota (1.86). Non-metropolitan areas demonstrated slightly higher average AAMRs than urban areas, suggesting disparities in access to hematology services and infection control. Conclusion: This is the first national study to comprehensively assess 25-year mortality trends in autoimmune neutropenia. After initial improvement, mortality rates have recently increased, particularly among older adults, males, and NH Black populations. The rising trend since 2017 highlights the need for renewed clinical attention to immune cytopenias, improved access to specialized hematologic care, and proactive infection prevention strategies. Public health interventions should prioritize high-risk groups and underserved regions to reduce avoidable deaths from this rare but serious condition. Keywords: Autoimmune Neutropenia, Immune Cytopenia, Agranulocytosis, Hematologic Disparities, Mortality Trends, CDC WONDER, Age-Adjusted Mortality, Joinpoint Regression, Public Health Equity, Immune-Mediated Cytopenias