Trends in sepsis-related mortality due to dermatologic infections in the United States: Demographic and geographic patterns from 1999 to 2023

Abstract

Background

Dermatologic infections complicated by sepsis represent a significant yet understudied cause of mortality in the United States, with evolving epidemiological patterns that warrant investigation.

Objective

To examine nationwide trends in sepsis-related mortality due to dermatologic infections from 1999 to 2023, with focus on demographic and geographic disparities.

Methods

This population-based retrospective study analyzed CDC WONDER mortality data using ICD-10 codes for dermatologic infections with sepsis. Joinpoint regression analysis calculated annual percentage changes (APCs) in age-adjusted mortality rates, stratified by gender, age, race/ethnicity, and geographic region.

Results

Among 119,837 deaths, overall mortality showed statistically significant rise during 1999-2004 (APC: 9.05%, p<0.001) and 2012-2023 (APC: 4.72%, p<0.001), with a plateau during 2004-2012. Males showed steeper recent increases (2019-2023: APC: 6.64%, p<0.001) than females. The South region experienced the highest sustained increase (2012-2023: APC: 5.19%, p<0.001). Among racial/ethnic groups, Hispanic populations showed the most pronounced variations, with the highest initial increase followed by a statistically significant decline before rising again.

Limitations

Reliance on death certificate data may introduce coding inconsistencies and underreporting.

Conclusion

Sepsis-related mortality due to dermatologic infections shows concerning upward trends across most demographic groups and regions, highlighting the need for enhanced prevention strategies and targeted interventions for vulnerable populations.

Introduction

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, and it remains one of the leading causes of morbidity and mortality worldwide. While much of the clinical and epidemiological research on sepsis has focused on pulmonary, abdominal, and urinary sources of infection, dermatologic infections—such as cellulitis, erysipelas, necrotizing fasciitis, and impetigo—also represent significant contributors, particularly when complicated by systemic involvement.^1,2

Skin and soft tissue infections (SSTIs) are common and can rapidly progress to sepsis, especially among vulnerable populations, including the elderly, immunocompromised individuals, and those with chronic illnesses such as diabetes.^3,4 These infections, while often initially localized, can evolve into invasive disease through hematogenous spread or deep tissue extension. Necrotizing fasciitis and gas gangrene, in particular, are aggressive and frequently fatal if not treated promptly. ⁵

Dermatologic infections warrant particular focus in sepsis mortality research for several reasons. First, while respiratory and urinary sources of sepsis have been extensively studied, skin and soft tissue infections represent a uniquely preventable and recognizable source, yet account for approximately 10% of all sepsis cases. ² Second, dermatologic infections often present with visible early warning signs that, if recognized promptly, offer opportunities for intervention before progression to sepsis. Third, the epidemiology of skin infections has been uniquely affected by the emergence of community-acquired MRSA, the opioid epidemic, and changes in immunosuppressive therapies, making temporal trend analysis particularly valuable. Finally, dermatologic sources of sepsis disproportionately affect specific demographic groups and may be more sensitive to healthcare access disparities than other infection sources, providing insights into broader health equity issues.

Over the past two decades, various initiatives have aimed to reduce sepsis-related mortality through early recognition and treatment protocols, including the implementation of the Surviving Sepsis Campaign. ⁶ Despite these efforts, the burden of sepsis remains high in the United States, with mortality rates showing variable trends across different infection sources and demographic subgroups.^7,8

Previous studies have examined temporal trends in overall sepsis mortality and disparities by race, sex, and region,^9–11 yet there is limited literature specifically addressing sepsis mortality originating from dermatologic infections. Understanding the epidemiologic patterns of these infections is crucial for informing targeted public health interventions and improving clinical outcomes.

This study uses national mortality data from the Centers for Disease Control and Prevention (CDC) Wide-ranging Online Data for Epidemiologic Research (WONDER) platform to evaluate trends in sepsis-related mortality associated with dermatologic infections from 1999 to 2023 in the United States. Rates were stratified by gender (male, female), age groups (<15, 15-24, 25-44, 45-64, ≥65 years, and a simplified dichotomous categorization of <45 vs ≥45 years for trend analysis), race/ethnicity (non-Hispanic White, non-Hispanic Black or African American, non-Hispanic Asian or Pacific Islander, non-Hispanic American Indian or Alaska Native, and Hispanic or Latino), and geographic region (Northeast, Midwest, South, and West) according to U.S. Census Bureau definitions. The age 45 cutoff was selected based on epidemiological evidence suggesting increased susceptibility to severe skin and soft tissue infections and sepsis-related complications in middle-aged and older adults due to age-related immune dysfunction and higher prevalence of comorbidities such as diabetes mellitus.

A distinguishing feature of dermatologic infections, compared with pulmonary or intra-abdominal sources, is their external visibility — cutaneous signs of early infection are often identifiable in community or outpatient settings before systemic deterioration occurs. The evolution from a localized skin infection to life-threatening sepsis may therefore represent not only a function of microbial virulence, but also a consequence of delayed care-seeking, structural barriers to timely treatment, and inequities in access to early medical evaluation. Characterizing mortality trends arising from this specific infection source may thus illuminate actionable gaps in early infection management and highlight health equity dimensions not captured in aggregate sepsis analyses.

Existing literature on sepsis mortality has largely examined sepsis as a composite, undifferentiated outcome, without stratifying by the primary infectious source. Skin and soft tissue infections are clinically distinct in that they are frequently managed initially in outpatient settings and may present opportunities for early intervention that are not available with internal sources of infection. Yet national-level mortality data specifically attributable to sepsis arising from dermatologic infections have not been previously reported. Focusing on this distinct etiology allows for the identification of demographic and geographic mortality patterns that may support the development of more precisely targeted public health strategies aimed at reducing preventable sepsis-related deaths.

Methods

Study design and data source

This retrospective, population-based study utilized publicly available mortality data from the Centers for Disease Control and Prevention (CDC) Wide-ranging Online Data for Epidemiologic Research (WONDER) platform. ¹² Specifically, the Multiple Cause of Death database was accessed to obtain information on deaths occurring in the United States between January 1, 1999, and December 31, 2023. CDC WONDER is a comprehensive online database that provides access to national mortality data compiled from death certificates for all U.S. residents. The platform offers standardized, population-based mortality statistics with demographic and geographic stratification capabilities, making it particularly suitable for epidemiological trend analyses. However, limitations include reliance on death certificate accuracy, potential underreporting of certain conditions, and lack of clinical detail beyond coded diagnoses.

Study population

This nationwide mortality study included all decedents in the United States from 1999 to 2023 whose death certificates listed both a dermatologic infection and sepsis as underlying or contributing causes of death. The ICD-10 codes were selected based on the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) official guidelines for coding dermatologic infections and sepsis. ¹³ Dermatologic infections were defined using the following ICD-10 codes: A46 (Erysipelas); A48.0 (Gas gangrene); L00 (Staphylococcal scalded skin syndrome); L01.0-L01.1 (Impetigo and impetiginization of other dermatoses); L02.0-L02.9 (Cutaneous abscess, furuncle, and carbuncle); L03.0-L03.9 (Cellulitis); L08.0-L08.9 (Other specified local infections of skin and subcutaneous tissue); and M72.6 (Necrotizing fasciitis).

Sepsis was identified using ICD-10 codes: A40.0-A40.9 (Streptococcal septicemia); A41.0-A41.9 (Other septicemia); and A48.3 (Toxic shock syndrome). Deaths were included when both a dermatologic infection code and a sepsis code were listed as underlying or contributing causes of death. Inclusion criteria were as follows: (1) death occurring within the United States between January 1, 1999, and December 31, 2023; (2) death certificate listing at least one qualifying dermatologic infection ICD-10 code (as specified above); and (3) death certificate listing at least one qualifying sepsis ICD-10 code concurrently as an underlying or contributing cause of death. Exclusion criteria included: (1) deaths without any listed dermatologic infection code; (2) deaths without any listed sepsis code; and (3) records with suppressed or unreliable data per CDC WONDER reporting thresholds (i.e., counts fewer than 10 deaths per stratum, which are suppressed in the database to protect privacy). No age restriction was applied; all age groups were included in the overall analysis.

Statistical analysis

We calculated annual age-adjusted mortality rates per 100,000 population, standardized to the 2000 U.S. standard population. ¹⁴ Rates were stratified by gender (male, female), age (<45, ≥45 years), race/ethnicity (non-Hispanic White, non-Hispanic Black or African American, non-Hispanic Asian or Pacific Islander, non-Hispanic American Indian or Alaska Native, and Hispanic or Latino), and geographic region (Northeast, Midwest, South, and West) according to U.S. Census Bureau definitions.

Joinpoint regression analysis was performed to identify significant changes in mortality trends over time. This method identifies points (joinpoints) where the linear slope of the trend changes significantly and calculates the annual percentage change (APC) with 95% confidence intervals for each identified segment. Joinpoint regression was conducted using a log-linear model to estimate the Annual Percent Change (APC) in mortality rates, assuming constant percentage change on a logarithmic scale. The permutation test (Monte Carlo method) with 4,499 permutations was used to determine the optimal number of joinpoints (0–3) at a significance level of p < 0.05, as recommended by the National Cancer Institute’s Joinpoint Regression Program guidelines. ¹⁵

All analyses were performed using the Joinpoint Regression Program (version 4.9.0.0) from the National Cancer Institute and SAS software (version 9.4, SAS Institute Inc., Cary, NC). This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines for observational studies. The STROBE checklist is available as a supplementary file submitted with this manuscript.

Ethical considerations

This study analyzed publicly available, de-identified mortality data obtained from the CDC WONDER platform, which compiles aggregate national death certificate records. Because the data are fully de-identified, publicly accessible, and involve no direct interaction with human subjects, this research is not considered human subjects research and does not require institutional review board (IRB) review or approval, in accordance with the federal exemption criteria outlined in 45 CFR §46.102(e)(1) and 45 CFR §46.104(d)(4). No individual-level patient data, protected health information, or identifiable records were accessed at any stage of this study.

Results

Overall, gender-specific, and age-specific trends

From 1999 to 2023, there were 119,837 sepsis-related deaths attributable to dermatologic infections in the United States. Sepsis-related mortality due to dermatologic infections demonstrated significant variations over the study period (1999-2023). Three distinct periods were identified: an initial period of significant increase from 1999 to 2004 (APC: 9.05%, 95% CI: 4.68 to 13.49, p<0.001), followed by a plateau phase from 2004 to 2012 (APC: 0.87%, 95% CI: -0.94 to 2.77, p=0.323), and a subsequent significant increase from 2012 to 2023 (APC: 4.72%, 95% CI: 4.01 to 5.42, p<0.001) (Figure 1).

Figure 1.

Overall trends in sepsis-related mortality attributable to dermatologic infections in the United States 1999–2023. Annual Percent Change (APC) reported; * denotes statistically significant APC at α = 0.05.

Female mortality rates showed a pattern similar to the overall trend, with a significant increase from 1999 to 2004 (APC: 8.76%, 95% CI: 5.23 to 12.41, p<0.001), followed by a stable period from 2004 to 2013 (APC: 0.82%, 95% CI: -0.66 to 2.33, p=0.259), and another significant increase from 2013 to 2023 (APC: 4.68%, 95% CI: 3.86 to 5.51, p<0.001) (Figure 2).

Figure 2.

Trends in sepsis-related mortality attributable to dermatologic infections in the United States by gender 1999–2023. Annual Percent Change (APC) reported; * denotes statistically significant APC at α = 0.05.

Male mortality trends demonstrated a more complex pattern with four joinpoints: no significant change from 1999 to 2001 (APC: -0.01%, 95% CI: -11.55 to 12.76, p=0.994), followed by a sharp increase from 2001 to 2004 (APC: 13.82%, 95% CI: 1.55 to 27.57, p=0.03), a stable period from 2004 to 2009 (APC: 0.20%, 95% CI: -3.02 to 3.52, p=0.897), a moderate increase from 2009 to 2019 (APC: 3.69%, 95% CI: 2.88 to 4.51, p<0.001), and a steeper increase from 2019 to 2023 (APC: 6.64%, 95% CI: 4.35 to 8.98, p<0.001) (Figure 2).

For individuals aged 45 years and older, mortality rates showed no significant change from 1999 to 2001 (APC: 0.51%, 95% CI: -9.20 to 11.25, p=0.915), followed by a significant increase from 2001 to 2004 (APC: 12.94%, 95% CI: 3.58 to 23.14, p=0.01), a stable period from 2004 to 2010 (APC: 0.00%, 95% CI: -1.59 to 1.60, p=0.985), a moderate increase from 2010 to 2019 (APC: 3.63%, 95% CI: 2.92 to 4.35, p<0.001), and a steeper increase from 2019 to 2023 (APC: 6.10%, 95% CI: 4.33 to 7.91, p<0.001) (Figure 3).

Figure 3.

Trends in sepsis-related mortality attributable to dermatologic infections in the United States by age group, 1999–2023. Annual Percent Change (APC) reported; * denotes statistically significant APC at α = 0.05.

For those under 45 years, a consistent increase was observed throughout the study period from 1999 to 2021 (APC: 5.10%, 95% CI: 4.35 to 5.87, p<0.001) (Figure 3).

Geographic variations

The Northeast region showed a steady increase from 1999 to 2021 (APC: 2.66%, 95% CI: 2.16 to 3.15, p<0.001), followed by a more pronounced but non-significant increase from 2021 to 2023 (APC: 11.11%, 95% CI: -4.27 to 28.97, p=0.156) (Figure 4).

Figure 4.

Trends in sepsis-related mortality attributable to dermatologic infections in the United States by U.S. census region, 1999–2023. Annual Percent Change (APC) reported; * denotes statistically significant APC at α = 0.05.

The Midwest region demonstrated three distinct periods: a significant increase from 1999 to 2005 (APC: 8.63%, 95% CI: 5.26 to 12.11, p<0.001), a stable period from 2005 to 2010 (APC: -0.81%, 95% CI: -4.91 to 5.15, p=0.998), and a significant increase from 2010 to 2023 (APC: 4.79%, 95% CI: 4.07 to 5.51, p<0.001) (Figure 4).

The South region showed an initial significant increase from 1999 to 2004 (APC: 10.55%, 95% CI: 5.57 to 15.76, p<0.001), followed by a stable period from 2004 to 2012 (APC: 0.22%, 95% CI: -2.06 to 2.54, p=0.845), and a subsequent significant increase from 2012 to 2023 (APC: 5.19%, 95% CI: 4.23 to 6.16, p<0.001) (Figure 4).

The West region demonstrated three distinct periods: a significant increase from 1999 to 2004 (APC: 9.44%, 95% CI: 4.48 to 14.64, p<0.001), a non-significant decrease from 2004 to 2009 (APC: -1.47%, 95% CI: -6.88 to 4.26, p=0.588), and a significant increase from 2009 to 2023 (APC: 3.89%, 95% CI: 3.18 to 4.60, p<0.001) (Figure 4).

Race/ethnicity patterns

Non-Hispanic American Indian or Alaska Native population showed a consistent significant increase throughout the study period from 1999 to 2023 (APC: 3.53%, 95% CI: 2.60 to 4.47, p<0.001) (Figure 3).

Non-Hispanic Asian or Pacific Islander population demonstrated an initial significant increase from 1999 to 2007 (APC: 5.66%, 95% CI: 1.25 to 10.26, p=0.014), followed by a non-significant decrease from 2007 to 2023 (APC: -0.78%, 95% CI: -1.65 to 0.11, p=0.083) (Figure 5).

Figure 5.

Trends in sepsis-related mortality attributable to dermatologic infections in the United States by race/ethnicity, 1999–2023. Annual Percent Change (APC) reported; * denotes statistically significant APC at α = 0.05.

Non-Hispanic Black or African American population showed an initial significant increase from 1999 to 2005 (APC: 8.55%, 95% CI: 3.77 to 13.55, p=0.001), followed by a stable period from 2005 to 2012 (APC: -0.33%, 95% CI: -1.36 to 0.70, p=0.997), and a subsequent significant increase from 2012 to 2023 (APC: 5.19%, 95% CI: 3.89 to 6.51, p<0.001) (Figure 5).

Non-Hispanic White population demonstrated three distinct periods: a significant increase from 1999 to 2004 (APC: 9.12%, 95% CI: 4.90 to 13.50, p<0.001), a stable period from 2004 to 2010 (APC: 0.53%, 95% CI: -2.57 to 3.72, p=0.728), and a significant increase from 2010 to 2023 (APC: 4.54%, 95% CI: 3.93 to 5.16, p<0.001) (Figure 5).

Hispanic or Latino population showed the most pronounced changes, with a significant increase from 1999 to 2004 (APC: 12.15%, 95% CI: 5.44 to 19.30, p=0.001), followed by a significant decrease from 2004 to 2011 (APC: -3.92%, 95% CI: -7.37 to -0.33, p=0.034), and a subsequent significant increase from 2011 to 2023 (APC: 4.65%, 95% CI: 3.70 to 5.60, p<0.001) (Figure 5).

Although socioeconomic data were unavailable in CDC WONDER, prior research indicates that lower-income and uninsured individuals experience higher rates of delayed care for skin infections, which could amplify racial disparities. Future analyses incorporating socioeconomic gradients could clarify these interactions.

Discussion

This comprehensive analysis of sepsis-related mortality due to dermatologic infections in the United States from 1999 to 2023 reveals significant temporal trends and demographic variations. The overall pattern shows an initial period of significant increase (1999-2004), followed by a plateau (2004-2012), and a subsequent sustained increase (2012-2023). This pattern, with some variations, is generally consistent across different demographic groups and geographic regions.

The initial increase in mortality rates during 1999-2004 coincides with the emergence and spread of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) in the United States^16–19 CA-MRSA, particularly the USA300 clone, became a dominant cause of skin and soft tissue infections during this period and has been associated with increased virulence factors that may contribute to more severe infections and complications. ²⁰ The stabilization observed from 2004 to 2012 might reflect improved awareness, earlier diagnosis, and implementation of appropriate treatment guidelines for MRSA infections. ²¹

A critical consideration in interpreting these trends is distinguishing between actual increases in sepsis-related mortality due to dermatologic infections versus changes in coding practices and clinical awareness. Several factors support the likelihood that our findings reflect genuine epidemiological changes rather than solely coding artifacts. First, the biphasic pattern observed—with increases in 1999-2004, stabilization in 2004-2012, and renewed increases after 2012—does not align with gradual coding improvements, which would be expected to show more linear changes. Second, the demographic and geographic variations we observed are consistent with known risk factor distributions and healthcare access patterns, suggesting biological rather than administrative explanations. However, we cannot entirely exclude the influence of improved sepsis recognition following the Sepsis-3 consensus definitions in 2016 ¹ and increased clinical awareness through initiatives like the Centers for Medicare & Medicaid Services SEP-1 sepsis quality measure implemented in 2015. The acceleration in recent years (2019-2023) may reflect both true epidemiological changes and enhanced diagnostic sensitivity. Future studies incorporating clinical data beyond death certificates would help clarify this important distinction.

The concerning upward trend observed since 2012 warrants further investigation. Several factors may contribute to this recent increase, including the aging population with increased comorbidities, ²² rising prevalence of immunosuppressive conditions and treatments, ²³ increasing antibiotic resistance among skin pathogens, ²⁴ and changes in ICD coding practices and sepsis recognition. ²⁵ Additionally, the opioid epidemic in the United States has been associated with an increase in skin and soft tissue infections among people who inject drugs, potentially contributing to the observed trends. ²⁶

The gender-specific analysis reveals that males experienced a more complex trend pattern than females, with a particularly steep increase in recent years (2019-2023). The observed gender disparity, with males experiencing steeper recent increases in mortality (2019-2023: APC 6.64% vs females’ more gradual trend), may be attributed to several biological and behavioral factors. Men typically exhibit delayed healthcare-seeking behavior, potentially leading to more advanced infections at presentation.^27,28 Occupational and recreational exposures may also contribute, as men are more likely to engage in activities associated with skin trauma and bacterial exposure. ²⁹ Additionally, biological differences in immune response, with some studies suggesting that testosterone may impair certain aspects of immune function, could contribute to more severe outcomes.^30,31 The interaction between these factors and age-related immunosenescence may explain why the gender difference is most pronounced in older age groups. ³²

The pronounced increase in mortality rates during 2019-2023, particularly among males (APC: 6.64%) and those aged ≥45 years (APC: 6.10%), warrants special consideration of the COVID-19 pandemic’s impact. The pandemic may have contributed to increased sepsis-related mortality through multiple mechanisms: delayed healthcare seeking due to lockdowns and fear of hospital exposure, healthcare system strain leading to delayed recognition and treatment of non-COVID conditions, and potential immunological effects of SARS-CoV-2 infection that may predispose to secondary bacterial infections. Additionally, disruptions in routine care for chronic conditions such as diabetes—a major risk factor for skin and soft tissue infections—may have indirectly contributed to increased severity of dermatologic infections during this period. Similar observations were reported in other population-level studies showing increases in sepsis-related mortality during and after the COVID-19 pandemic, likely linked to healthcare disruptions, delayed diagnosis, and post-infectious immune dysregulation. ³³ These findings suggest that pandemic-era healthcare system strain may have exacerbated outcomes for non-COVID infections such as dermatologic sepsis. ³⁴

The regional analysis demonstrates that all four census regions experienced significant increases in mortality rates during the most recent segments, with the Midwest and South showing the highest recent APCs. These geographic disparities may reflect regional variations in population demographics, healthcare access, antibiotic prescribing practices, and prevalence of risk factors such as diabetes and obesity..^35–37 Regional variations in mortality trends may also reflect differences in healthcare infrastructure and accessibility, with rural areas—particularly prevalent in the South and Midwest regions—potentially experiencing challenges in timely access to emergency care and specialized infection management, contributing to the higher mortality rates observed in these regions.

The race/ethnicity-specific analysis reveals important disparities. The Hispanic or Latino population experienced the most pronounced variations, with the highest initial increase (1999-2004: APC: 12.15%), followed by a significant decrease (2004-2011: APC: -3.92%), and a subsequent increase (2011-2023: APC: 4.65%). This pattern may reflect changes in healthcare access, socioeconomic factors, and potentially changing demographics within this population group. ³⁸ The non-Hispanic American Indian or Alaska Native population showed a consistent increase throughout the study period, highlighting persistent disparities that require targeted interventions. ³⁹

The non-Hispanic Asian or Pacific Islander population was the only group to show a non-significant decrease in recent years, suggesting potential protective factors or more effective healthcare utilization patterns that merit further investigation. The significant increases observed in both non-Hispanic Black or African American and non-Hispanic White populations in recent years indicate that this public health challenge affects diverse racial and ethnic groups.

Implications and public health relevance

These findings underscore the evolving and persistent burden of sepsis-related mortality due to dermatologic infections. Despite medical advances in sepsis recognition and management, certain populations remain at elevated risk. The upward trends, particularly in the post-2010 period, suggest that dermatologic sources of sepsis are an underrecognized contributor to national mortality patterns. Public health responses must prioritize early detection, timely antimicrobial therapy, and equitable access to healthcare services. Culturally tailored outreach and community-based prevention strategies may be especially effective in mitigating risk among minority populations.

Additionally, the geographic and demographic patterns identified in this study could inform region-specific guidelines and targeted interventions. For example, increased clinician education about early dermatologic sepsis signs in high-burden regions or among high-risk age groups may improve outcomes. More granular studies into specific pathogens, such as MRSA, and their resistance patterns in skin infections may also help shape clinical practice.

At the policy level, these findings underscore the importance of expanding existing federal initiatives such as the Sepsis Alliance “It’s About TIME” campaign and CDC’s National Sepsis Program to include dermatologic infection awareness and prevention.^40,41 Integrating targeted sepsis education into primary care and dermatology practices, especially in high-burden regions like the South, could substantially reduce preventable deaths.

Dermatologic sepsis as a preventable public health target

Among the various sources of sepsis, cutaneous infections hold a clinically unique position: they manifest externally and are frequently first encountered in ambulatory or community settings, where early intervention remains feasible. The visible nature of skin infections means that warning signs may be detectable before the onset of systemic compromise, offering a potential window for prevention that does not exist with visceral infection sources. The continued upward mortality trends documented in this study therefore imply that sepsis originating from dermatologic infections may not be driven solely by pathogen characteristics, but may also reflect missed opportunities for timely recognition, suboptimal care escalation, and persistent inequities in access to healthcare.

The demographic and regional disparities documented in this study lend further support to this interpretation. Areas with accelerating mortality rates may reflect deficiencies in primary care infrastructure, insufficient access to urgent medical evaluation, or inadequate pathways for escalating care in patients with severe skin infections. Racial and ethnic differences in mortality trajectories may similarly reflect underlying structural inequities, including disparities in insurance coverage, socioeconomic resources, and the social determinants that shape the timing and location of care-seeking for cutaneous infections. Taken together, these findings suggest that sepsis mortality attributable to dermatologic infections may serve as an indicator of broader deficiencies in early infection management at the population level.

From a preventive perspective, the findings of this study suggest several underutilized intervention targets. Enhancing the capacity of community and primary care providers to identify high-risk skin infections at an early stage, expanding equitable access to timely antimicrobial therapy, and promoting public awareness of the signs and symptoms that herald severe soft tissue infections may collectively offer meaningful opportunities to interrupt the progression from localized dermatologic disease to fatal sepsis.

Strengths

This study has several notable strengths. First, it utilizes a large, nationally representative dataset spanning 25 years (1999–2023), providing robust statistical power for the identification of long-term mortality trends across demographic and geographic subgroups. Second, the exclusive focus on dermatologic infection-associated sepsis mortality fills a clear gap in the existing literature, as prior studies have not characterized this specific etiology at the national level. Third, joinpoint regression analysis was employed to detect statistically significant inflection points in temporal trends, enabling a more precise and methodologically rigorous characterization of trend patterns than simple linear regression approaches. Fourth, the use of CDC WONDER mortality data, which is compiled from standardized death certificates across all U.S. states, ensures consistency and comparability of data across the entire study period. Fifth, the comprehensive stratification by gender, age group, race/ethnicity, and geographic region allows for the identification of high-risk subpopulations and may inform targeted public health and clinical interventions. Finally, the use of age-adjusted mortality rates standardized to the 2000 U.S. standard population enables valid comparisons across time periods and demographic groups, minimizing confounding due to population aging.

Limitations

Several limitations must be acknowledged. First, the use of death certificate data from CDC WONDER relies on accurate coding of both sepsis and dermatologic infections, which may lead to underreporting or misclassification. While joinpoint regression allows for detection of statistically significant inflections, it does not directly account for underlying healthcare access or comorbidity data, which could further explain observed trends. Finally, regional analyses may obscure within-region heterogeneity, especially in large states with diverse populations.

An important limitation is the potential impact of evolving ICD-10 coding practices and clinical awareness on our findings. The implementation of ICD-10-CM in October 2015 (replacing ICD-9-CM) may have influenced coding accuracy and specificity for both dermatologic infections and sepsis. Additionally, increased clinical awareness of sepsis through national quality improvement initiatives, including the Surviving Sepsis Campaign and CMS SEP-1 measures, may have improved recognition and documentation of sepsis cases. However, our study period spans both ICD-9 and ICD-10 eras, and the observed trends show patterns that predate these major coding changes, suggesting that clinical factors beyond coding practices contribute to the observed mortality patterns.

Despite these limitations, this study provides valuable insights into the evolving epidemiology of sepsis-related mortality due to dermatologic infections in the United States. The comprehensive analysis of demographic and geographic patterns enhances our understanding of this important public health issue and identifies populations and regions that may benefit from targeted interventions.

Additionally, the use of death certificate data introduces potential misclassification bias due to variability in sepsis and infection coding accuracy. ²⁵ The absence of clinical variables—such as comorbidities, microbiological confirmation, and socioeconomic factors—limits causal inference and may underestimate the contribution of access-to-care barriers to mortality patterns.

Conclusion

This study documents a pattern of rising sepsis-related mortality attributable to dermatologic infections across diverse demographic groups and geographic regions of the United States over a 25-year period. By examining this specific infectious etiology in isolation, the analysis reveals a previously undercharacterized and potentially preventable contributor to the national burden of sepsis mortality. The consistent disparities observed across racial, ethnic, gender, age, and regional strata indicate that deficiencies in early recognition, timely access to care, and effective outpatient management of skin and soft tissue infections likely play an important role in shaping these trends. Strengthening early detection and treatment of high-risk dermatologic infections — particularly in vulnerable populations and underserved regions — may represent an actionable strategy for reducing sepsis-related mortality. Future research should further investigate the clinical, healthcare access, and socioeconomic factors driving these patterns to inform targeted prevention efforts.