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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Immunol.</journal-id>
<journal-title>Frontiers in Immunology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Immunol.</abbrev-journal-title>
<issn pub-type="epub">1664-3224</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fimmu.2025.1610499</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Immunology</subject>
<subj-group>
<subject>Systematic Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>All-cause and cause-specific mortality in psoriasis patients: a systematic review and meta-analysis</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Yang</surname>
<given-names>Yi</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/3031868/overview"/>
<role content-type="https://credit.niso.org/contributor-roles/conceptualization/"/>
<role content-type="https://credit.niso.org/contributor-roles/data-curation/"/>
<role content-type="https://credit.niso.org/contributor-roles/formal-analysis/"/>
<role content-type="https://credit.niso.org/contributor-roles/project-administration/"/>
<role content-type="https://credit.niso.org/contributor-roles/supervision/"/>
<role content-type="https://credit.niso.org/contributor-roles/validation/"/>
<role content-type="https://credit.niso.org/contributor-roles/visualization/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zhang</surname>
<given-names>Qin</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/data-curation/"/>
<role content-type="https://credit.niso.org/contributor-roles/formal-analysis/"/>
<role content-type="https://credit.niso.org/contributor-roles/investigation/"/>
<role content-type="https://credit.niso.org/contributor-roles/visualization/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Huang</surname>
<given-names>Anning</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/investigation/"/>
<role content-type="https://credit.niso.org/contributor-roles/methodology/"/>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Zhao</surname>
<given-names>Jinpeng</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Yang</surname>
<given-names>Jianren</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wang</surname>
<given-names>Lulu</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Xu</surname>
<given-names>Guomei</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="author-notes" rid="fn001">
<sup>*</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/funding-acquisition/"/>
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</contrib-group>
<aff id="aff1">
<sup>1</sup>
<institution>Graduate School of Beijing University of Chinese Medicine, Beijing University of Chinese Medicine</institution>, <addr-line>Beijing</addr-line>,&#xa0;<country>China</country>
</aff>
<aff id="aff2">
<sup>2</sup>
<institution>Department of Dermatology, Beijing University of Chinese Medicine Third Affiliated Hospital</institution>, <addr-line>Beijing</addr-line>,&#xa0;<country>China</country>
</aff>
<author-notes>
<fn fn-type="edited-by">
<p>Edited by: Durga Prasanna Misra, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI), India</p>
</fn>
<fn fn-type="edited-by">
<p>Reviewed by: Saumya Panda, Belle Vue Clinic, India</p>
<p>Omar Graciano Machuca, University of Guadalajara, Mexico</p>
</fn>
<fn fn-type="corresp" id="fn001">
<p>*Correspondence: Guomei Xu, <email xlink:href="mailto:C9302@bucm.edu.cn">C9302@bucm.edu.cn</email>
</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>24</day>
<month>07</month>
<year>2025</year>
</pub-date>
<pub-date pub-type="collection">
<year>2025</year>
</pub-date>
<volume>16</volume>
<elocation-id>1610499</elocation-id>
<history>
<date date-type="received">
<day>12</day>
<month>04</month>
<year>2025</year>
</date>
<date date-type="accepted">
<day>04</day>
<month>07</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2025 Yang, Zhang, Huang, Zhao, Yang, Wang and Xu</copyright-statement>
<copyright-year>2025</copyright-year>
<copyright-holder>Yang, Zhang, Huang, Zhao, Yang, Wang and Xu</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<sec>
<title>Objective</title>
<p>The objective of this meta-analysis is to assess the all-cause and cause-specific mortality in patients with psoriasis.</p>
</sec>
<sec>
<title>Method</title>
<p>In accordance with PRISMA guidelines, a systematic search of PubMed, EMBASE, and the Cochrane Library (from inception to March 2025) was conducted. Eligible studies comprised English-language cohort studies comparing mortality risk (HR/OR/RR) in adults with psoriasis versus healthy/non-psoriasis controls. Two reviewers independently screened studies, extracted data, and assessed study quality using the Newcastle-Ottawa Scale. Hazard ratios (HRs) were synthesized using random-effects models in Stata 14.0. Sensitivity analyses, subgroup analyses, and assessments of publication bias (via funnel plots and Egger&#x2019;s test) were also performed.</p>
</sec>
<sec>
<title>Result</title>
<p>A total of 20 studies involving 8825989 participants were included. Psoriasis patients demonstrated significantly increased risks of all-cause mortality [HR=1.19, 95% CI (1.11&#x2013;1.28), P=0.000], cardiovascular mortality [HR = 1.32, 95% CI (1.11&#x2013;1.58), P = 0.002], infection-related mortality [HR=1.24, 95% CI (1.13&#x2013;1.36), P=0.000], and suicide mortality [HR=1.50, 95% CI (1.03&#x2013;2.19), P=0.034]. The risk of mortality due to neoplasms was marginally elevated but not statistically significant [HR=1.05, 95% CI (0.98&#x2013;1.12), P=0.151]. No significant associations were found for neurological disease mortality [HR=0.96, 95%CI (0.83&#x2013;1.11), P=0.976] or accident-related mortality [HR=0.91, 95% CI (0.81&#x2013;1.02), P=0.629]. Sensitivity analysis supports the findings. Subgroup analyses revealed higher all-cause mortality risks in Europe (HR=1.11) and Asia (HR=1.23), as well as an increased risk with greater disease severity (moderate-to-severe: HR=1.44; severe: HR=1.54). No publication bias was detected.</p>
</sec>
<sec>
<title>Conclusion</title>
<p>Psoriasis is associated with an increased risk of all-cause, cardiovascular, infection-related, and suicide mortality, highlighting the need for enhanced monitoring and targeted interventions to prevent adverse outcomes particularly for individuals with severe psoriasis.</p>
</sec>
<sec>
<title>Systematic review registration</title>
<p>
<uri xlink:href="https://www.crd.york.ac.uk/PROSPERO/view/CRD420251017192">https://www.crd.york.ac.uk/PROSPERO/view/CRD420251017192</uri>, identifier CRD420251017192.</p>
</sec>
</abstract>
<kwd-group>
<kwd>psoriasis</kwd>
<kwd>mortality</kwd>
<kwd>cardiovascular</kwd>
<kwd>infection</kwd>
<kwd>suicide</kwd>
<kwd>meta-analysis</kwd>
<kwd>hazard ratio</kwd>
</kwd-group>
<counts>
<fig-count count="9"/>
<table-count count="3"/>
<equation-count count="0"/>
<ref-count count="38"/>
<page-count count="14"/>
<word-count count="4436"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-in-acceptance</meta-name>
<meta-value>Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec id="s1" sec-type="intro">
<label>1</label>
<title>Introduction</title>
<p>Psoriasis is a chronic, immune-mediated, relapsing inflammatory disorder characterized by erythematous plaques with silvery scales, it can present at any age, affecting approximately 125 million global population (<xref ref-type="bibr" rid="B1">1</xref>). Psoriasis is commonly associated with a range of systemic comorbidities, including cardiovascular diseases, malignancies, and infections, and imposes a substantial psychological burden due to its chronic and recurrent nature (<xref ref-type="bibr" rid="B2">2</xref>). Current therapeutic approaches include topical treatments, conventional systemic therapies, biologics targeting specific cytokines, and phototherapy (<xref ref-type="bibr" rid="B3">3</xref>). However, significant clinical gaps remain, as these therapies often exhibit high recurrence rates and suboptimal long-term efficacy (<xref ref-type="bibr" rid="B4">4</xref>).</p>
<p>Recent evidence underscores an elevated risk of all-cause and cause-specific mortality in psoriasis patients, largely driven by chronic inflammation and immune dysregulation (<xref ref-type="bibr" rid="B5">5</xref>, <xref ref-type="bibr" rid="B6">6</xref>). Proinflammatory cytokines, such as TNF-&#x3b1; and IL-17, contribute to the acceleration of atherosclerosis, thereby increasing cardiovascular risk, while systemic immunosuppression enhances susceptibility to severe infections (<xref ref-type="bibr" rid="B7">7</xref>). Additionally, psychosocial stressors associated with visible skin lesions substantially elevate the incidence of anxiety, depression and suicides (<xref ref-type="bibr" rid="B8">8</xref>). These findings highlight the urgent need for integrated management strategies that address both the cutaneous manifestations and systemic complications of psoriasis.</p>
<p>To more accurately assess the all-cause and cause-specific mortality risks associated with psoriasis, we conducted a systematic review and meta-analysis integrating cohort studies that evaluated the impact of psoriasis on mortality outcomes, with the aim of informing targeted interventions and improving clinical monitoring of high-risk subgroups.</p>
</sec>
<sec id="s2">
<label>2</label>
<title>Method</title>
<p>This study adhered to the Meta-analysis of Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) (<xref ref-type="bibr" rid="B9">9</xref>) guidelines and followed a pre-registered protocol on the International Prospective Register of Systematic Reviews (PROSPERO) platform, under approval number CRD420251017192.</p>
<sec id="s2_1">
<label>2.1</label>
<title>Data sources</title>
<p>A comprehensive systematic search was conducted across the PubMed, EMBASE, and Cochrane Library databases using relevant Medical Subject Heading (MeSH) terms for PubMed, along with appropriate keywords. The search covered articles published from the inception of each database up to March 2025. Key search terms included &#x201c;Psoriasis,&#x201d; &#x201c;Mortality,&#x201d; &#x201c;Risk,&#x201d; and their relevant synonyms. The complete search strategy is outlined in <xref ref-type="supplementary-material" rid="SM1">
<bold>Supplementary Material Table&#xa0;1</bold>
</xref>.</p>
</sec>
<sec id="s2_2">
<label>2.2</label>
<title>Inclusion criteria</title>
<p>Studies were included based on the following criteria: (1) prospective or retrospective cohort study design; (2) patients diagnosed with psoriasis, aged 18 years or older, regardless of disease duration or nationality; (3) a control group consisting of healthy individuals or non-psoriasis patients; (4) the primary outcome of mortality risk, reported as hazard ratio (HR), or odds ratio (OR), relative risk (RR) during the follow-up period; (5) studies published in English.</p>
</sec>
<sec id="s2_3">
<label>2.3</label>
<title>Exclusion criteria</title>
<p>The following studies were excluded: (1) duplicate publications; (2) reviews, clinical case reports, meeting abstracts, letters, or comments; (3) incomplete data or studies lacking outcomes of interest; (4) studies focused on hospitalized patients; (5) studies investigating alcohol-related mortality.</p>
</sec>
<sec id="s2_4">
<label>2.4</label>
<title>Study selection</title>
<p>Two authors (Yi Yang and Qin Zhang) independently screened all identified studies, and the results were compared. If the results were consistent, the final analysis was conducted. In cases of disagreement, the full-text articles were reviewed to ensure the studies met the eligibility criteria. Any discrepancies were resolved through group discussions.</p>
</sec>
<sec id="s2_5">
<label>2.5</label>
<title>Data extraction</title>
<p>A data extraction table was created using Microsoft Excel. Both authors (Yi Yang and Qin Zhang) independently extracted relevant data from the eligible studies, including the first author, publication year, country, study type, number of events, and confounding factors. The extracted data were cross-checked for accuracy, and discrepancies were resolved through group discussions to ensure consistency.</p>
</sec>
<sec id="s2_6">
<label>2.6</label>
<title>Quality assessment</title>
<p>The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS) (<xref ref-type="bibr" rid="B10">10</xref>), which evaluates studies based on three domains: selection, comparability, and outcome. The NOS score ranges from 0 to 9, with higher scores indicating better study quality. The criteria include participant selection (4 points), comparability between groups (2 points), and assessment of exposure factors (3 points). Studies were classified as high quality (NOS &#x2265; 7), medium quality (NOS 4&#x2013;6), or low quality (NOS 0&#x2013;3).</p>
</sec>
<sec id="s2_7">
<label>2.7</label>
<title>Data analysis</title>
<p>Data analysis was performed using Stata software (version 14). Mortality risk was reported as HR with corresponding 95% confidence intervals (CIs). Depending on the results of the heterogeneity test, either a random-effects or fixed-effects model was used. A P-value &lt; 0.1 or I&#xb2; &gt; 50% indicated high heterogeneity. Given the potential for clinical, methodological, and statistical heterogeneity, a random-effects model was typically applied for the meta-analysis (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B12">12</xref>). Sensitivity analysis was conducted to assess the robustness of the results, with a one-by-one elimination method used to explore sources of heterogeneity. Subgroup analyses were performed based on cohort study type, study region, and the severity of psoriasis. Publication bias was assessed using funnel plots and Egger&#x2019;s regression tests.</p>
</sec>
</sec>
<sec id="s3" sec-type="results">
<label>3</label>
<title>Results</title>
<sec id="s3_1">
<label>3.1</label>
<title>Literature search</title>
<p>A preliminary literature search identified a total of 3,315 relevant records, including 701 articles from PubMed, 2,460 from EMBASE, and 154 from the Cochrane Library. These records were imported into EndNote reference management software. After removing duplicates, 2,623 records remained. Following a review of the titles and abstracts, irrelevant records were excluded, leaving 44 articles for full-text review. Any uncertain records were assessed by reading the full text to verify their eligibility for inclusion in the study. A total of 20 cohort studies (<xref ref-type="bibr" rid="B5">5</xref>, <xref ref-type="bibr" rid="B6">6</xref>, <xref ref-type="bibr" rid="B13">13</xref>&#x2013;<xref ref-type="bibr" rid="B30">30</xref>) were deemed eligible after this screening process, and the flow of literature screening is illustrated in <xref ref-type="fig" rid="f1">
<bold>Figure&#xa0;1</bold>
</xref>.</p>
<fig id="f1" position="float">
<label>Figure&#xa0;1</label>
<caption>
<p>Literature screening.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fimmu-16-1610499-g001.tif">
<alt-text content-type="machine-generated">Flowchart of the study identification process. Initially, 3,315 records from PubMed, Embase, and Cochrane Library were identified. After removing 692 duplicates and 183 other records, 2,440 records were screened. By title and abstract, 2,396 were excluded. Of the remaining 44, none were unretrieved. After assessing 44 reports, 24 were excluded for reasons like meeting abstracts and repeating data. Ultimately, 20 studies were included in the review.</alt-text>
</graphic>
</fig>
</sec>
<sec id="s3_2">
<label>3.2</label>
<title>Basic characteristics</title>
<p>The 20 cohort studies included a total sample size of 8825989 participants, comprising 851942 psoriasis patients and 7974047 controls. The baseline characteristics of the included participants are summarized in <xref ref-type="table" rid="T1">
<bold>Table&#xa0;1</bold>
</xref>. Among the studies, 15 (<xref ref-type="bibr" rid="B5">5</xref>, <xref ref-type="bibr" rid="B6">6</xref>, <xref ref-type="bibr" rid="B13">13</xref>&#x2013;<xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B17">17</xref>&#x2013;<xref ref-type="bibr" rid="B19">19</xref>, <xref ref-type="bibr" rid="B21">21</xref>&#x2013;<xref ref-type="bibr" rid="B25">25</xref>, <xref ref-type="bibr" rid="B29">29</xref>, <xref ref-type="bibr" rid="B30">30</xref>) focused on the risk of all-cause mortality in psoriasis patients, and 7 (<xref ref-type="bibr" rid="B5">5</xref>, <xref ref-type="bibr" rid="B14">14</xref>&#x2013;<xref ref-type="bibr" rid="B16">16</xref>, <xref ref-type="bibr" rid="B20">20</xref>, <xref ref-type="bibr" rid="B22">22</xref>, <xref ref-type="bibr" rid="B28">28</xref>) studies evaluated the risk of cardiovascular mortality. Mortality related to infection, neoplasms, and suicide was assessed in 4 studies (<xref ref-type="bibr" rid="B14">14</xref>&#x2013;<xref ref-type="bibr" rid="B16">16</xref>, <xref ref-type="bibr" rid="B21">21</xref>, <xref ref-type="bibr" rid="B26">26</xref>, <xref ref-type="bibr" rid="B28">28</xref>) each. Additionally, 3 studies (<xref ref-type="bibr" rid="B14">14</xref>, <xref ref-type="bibr" rid="B16">16</xref>, <xref ref-type="bibr" rid="B21">21</xref>) examined mortality due to neurological diseases, and 3 (<xref ref-type="bibr" rid="B14">14</xref>, <xref ref-type="bibr" rid="B21">21</xref>, <xref ref-type="bibr" rid="B28">28</xref>) others explored accident-related mortality. The studies included were published between 2007 and 2024. The adjusted confounding factors varied across studies, with age, gender, and hypertension being the most commonly controlled variables. Of the 20 studies, 10 were conducted in Europe, 7 in America, and 4 in Asia. <xref ref-type="table" rid="T1">
<bold>Table&#xa0;1</bold>
</xref> presents the detailed characteristics of the cohort studies.</p>
<table-wrap id="T1" position="float">
<label>Table&#xa0;1</label>
<caption>
<p>Characteristics of studies included in the meta-analysis.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="middle" align="center">Author</th>
<th valign="middle" align="center">Year</th>
<th valign="middle" align="center">Region</th>
<th valign="middle" align="center">Study type</th>
<th valign="middle" align="center">Sample size</th>
<th valign="middle" align="center">Cause of mortality</th>
<th valign="middle" align="center">Confounders adjusted</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="middle" align="center">Si, Z (<xref ref-type="bibr" rid="B6">6</xref>).</td>
<td valign="middle" align="center">2024</td>
<td valign="middle" align="center">America</td>
<td valign="middle" align="center">Retrospective cohort study</td>
<td valign="middle" align="center">Total:14021, psoriasis:13664, no psoriasis:357</td>
<td valign="middle" align="center">All-cause mortality</td>
<td valign="middle" align="center">Sex, age group, race, education, marital status, BMI category, smoking status, drinking status, hypertension and diabetes</td>
</tr>
<tr>
<td valign="middle" align="center">Abuabara, K (<xref ref-type="bibr" rid="B28">28</xref>).</td>
<td valign="middle" align="center">2010</td>
<td valign="middle" align="center">Europe</td>
<td valign="middle" align="center">Retrospective cohort study</td>
<td valign="middle" align="center">Total:17933, psoriasis:14330, no psoriasis:3603</td>
<td valign="middle" align="center">Accidents, cardiovascular disease, chronic lower respiratory disease, dementia, diabetes, infection, kidney disease, liver disease, malignant neoplasms, other, suicide, unknown/missing</td>
<td valign="middle" align="center">Age, sex</td>
</tr>
<tr>
<td valign="middle" align="center">Ahlehoff, O (<xref ref-type="bibr" rid="B27">27</xref>).</td>
<td valign="middle" align="center">2011</td>
<td valign="middle" align="center">Europe</td>
<td valign="middle" align="center">Retrospective cohort study</td>
<td valign="middle" align="center">Total:4040257, psoriasis:4003265, no psoriasis:36992</td>
<td valign="middle" align="center">All-cause mortality, cardiovascular disease, composite endpoint: stroke, myocardial infarction and cardiovascular death</td>
<td valign="middle" align="center">/</td>
</tr>
<tr>
<td valign="middle" align="center">Chen, T. C (<xref ref-type="bibr" rid="B26">26</xref>).</td>
<td valign="middle" align="center">2024</td>
<td valign="middle" align="center">Asia</td>
<td valign="middle" align="center">Retrospective cohort study</td>
<td valign="middle" align="center">Total:1298015, psoriasis:1112581, no psoriasis:185434</td>
<td valign="middle" align="center">Any infection, respiratory infections, sepsis, skin/soft-tissue infections, urinary tract infections, infectious arthropathies, endocarditis, tuberculosis, hepatitis B, hepatitis C</td>
<td valign="middle" align="center">Age, sex and comorbidities which are related to lifestyle factors, including chronic obstructive pulmonary disease, hyperlipidemia, hypertension, alcohol-related conditions, ischemic heart disease, hospital-diagnosed obesity, and type 2 diabetes and other covariates, including cancer, rheumatoid arthritis, psoriatic arthritis, dermatological immune-mediated inflammatory diseases, inflammatory bowel disease, multiple sclerosis, spondylopathies, systemic connective tissue disorders and inflammatory polyarthritis</td>
</tr>
<tr>
<td valign="middle" align="center">Dai, Y. X (<xref ref-type="bibr" rid="B25">25</xref>).</td>
<td valign="middle" align="center">2018</td>
<td valign="middle" align="center">Asia</td>
<td valign="middle" align="center">Retrospective cohort study</td>
<td valign="middle" align="center">Total:213402, psoriasis:106701, no psoriasis:106701</td>
<td valign="middle" align="center">All-cause mortality</td>
<td valign="middle" align="center">Age, sex, socioeconomic status, residence, hypertension, diabetes mellitus, dyslipidemia, coronary artery disease, stroke, connective tissue disease, renal diseases, chronic liver diseases and cirrhosis and hepatitis, chronic obstructive pulmonary disease, and cancer</td>
</tr>
<tr>
<td valign="middle" align="center">Gelfand, J. M (<xref ref-type="bibr" rid="B24">24</xref>).</td>
<td valign="middle" align="center">2007</td>
<td valign="middle" align="center">Europe</td>
<td valign="middle" align="center">Retrospective cohort study</td>
<td valign="middle" align="center">Total:712952, psoriasis:575433, no psoriasis:137519</td>
<td valign="middle" align="center">All-cause mortality</td>
<td valign="middle" align="center">Age, sex</td>
</tr>
<tr>
<td valign="middle" align="center">Iskandar, I. Y. K (<xref ref-type="bibr" rid="B23">23</xref>).</td>
<td valign="middle" align="center">2022</td>
<td valign="middle" align="center">Asia</td>
<td valign="middle" align="center">Retrospective cohort study</td>
<td valign="middle" align="center">Total:1356020, psoriasis:1232717, no psoriasis:123303</td>
<td valign="middle" align="center">All-cause mortality</td>
<td valign="middle" align="center">Index year, age and sex</td>
</tr>
<tr>
<td valign="middle" align="center">Kan, J (<xref ref-type="bibr" rid="B5">5</xref>).</td>
<td valign="middle" align="center">2024</td>
<td valign="middle" align="center">America</td>
<td valign="middle" align="center">Prospective cohort study</td>
<td valign="middle" align="center">Total:19741, psoriasis:19199, no psoriasis:542</td>
<td valign="middle" align="center">All-cause mortality, CVD</td>
<td valign="middle" align="center">Sex, age, race, education, marital<break/>status, family PIR, smoking and drinking</td>
</tr>
<tr>
<td valign="middle" align="center">Kong, X. and W. Wang (<xref ref-type="bibr" rid="B22">22</xref>)</td>
<td valign="middle" align="center">2024</td>
<td valign="middle" align="center">America</td>
<td valign="middle" align="center">Prospective cohort study</td>
<td valign="middle" align="center">Total:11155, psoriasis:10865, no psoriasis:290</td>
<td valign="middle" align="center">All-cause mortality, CVD</td>
<td valign="middle" align="center">Age, sex, race/ethnicity, marital status, educational level, poverty-income ratio, smoking, drinking, physical activity, estimated glomerular filtration rate and urinary albumin/creatinine ratio</td>
</tr>
<tr>
<td valign="middle" align="center">Lee, M. S (<xref ref-type="bibr" rid="B21">21</xref>).</td>
<td valign="middle" align="center">2017</td>
<td valign="middle" align="center">Asia</td>
<td valign="middle" align="center">Prospective cohort study</td>
<td valign="middle" align="center">Total:160414, psoriasis:80207, no psoriasis:80207</td>
<td valign="middle" align="center">All-cause mortality, circulatory system diseases, malignancies, respiratory system diseases, infectious diseases, digestive system diseases, urogenital diseases, endocrine, nutritional and metabolic diseases, mental and behavioral disorders, diseases of the nervous system and sense organs, intentional self-harm or suicide, accidents and unintentional injuries, others</td>
<td valign="middle" align="center">/</td>
</tr>
<tr>
<td valign="middle" align="center">Mehta, N. N (<xref ref-type="bibr" rid="B20">20</xref>).</td>
<td valign="middle" align="center">2010</td>
<td valign="middle" align="center">Europe</td>
<td valign="middle" align="center">Retrospective cohort study</td>
<td valign="middle" align="center">Total:17933, psoriasis:14330, no psoriasis:3603</td>
<td valign="middle" align="center">Cardiovascular disease</td>
<td valign="middle" align="center">Age, sex, hyperlipidemia, hypertension, smoking, diabetes</td>
</tr>
<tr>
<td valign="middle" align="center">Pezzolo, E (<xref ref-type="bibr" rid="B19">19</xref>).</td>
<td valign="middle" align="center">2021</td>
<td valign="middle" align="center">Europe</td>
<td valign="middle" align="center">Retrospective cohort study</td>
<td valign="middle" align="center">Total:61758, psoriasis:49065, no psoriasis:12693</td>
<td valign="middle" align="center">All-cause mortality</td>
<td valign="middle" align="center">/</td>
</tr>
<tr>
<td valign="middle" align="center">Prodanovich, S (<xref ref-type="bibr" rid="B18">18</xref>).</td>
<td valign="middle" align="center">2009</td>
<td valign="middle" align="center">America</td>
<td valign="middle" align="center">Retrospective cohort study</td>
<td valign="middle" align="center">Total:5736, psoriasis:3236, no psoriasis:2500</td>
<td valign="middle" align="center">All-cause mortality</td>
<td valign="middle" align="center">Age, sex, hypertension, diabetes mellitus, dyslipidemia, tobacco, any vascular disease.</td>
</tr>
<tr>
<td valign="middle" align="center">Semenov, Y. R (<xref ref-type="bibr" rid="B17">17</xref>).</td>
<td valign="middle" align="center">2021</td>
<td valign="middle" align="center">America</td>
<td valign="middle" align="center">Retrospective cohort study</td>
<td valign="middle" align="center">Total:13031, psoriasis:12684, no psoriasis:347</td>
<td valign="middle" align="center">All-cause mortality</td>
<td valign="middle" align="center">Age</td>
</tr>
<tr>
<td valign="middle" align="center">Skov, L (<xref ref-type="bibr" rid="B16">16</xref>).</td>
<td valign="middle" align="center">2019</td>
<td valign="middle" align="center">Europe</td>
<td valign="middle" align="center">Retrospective cohort study</td>
<td valign="middle" align="center">Total:42096, psoriasis:29936, no psoriasis:12160</td>
<td valign="middle" align="center">Immune mechanism, endocrine, nutritional and metabolic diseases, mental and behavioral disorders, diseases of the nervous system, diseases of the circulatory system (heart disease), other diseases of the circulatory system, diseases of the respiratory system, diseases of the digestive system, diseases of the musculoskeletal system and connective tissue, diseases of the genitourinary system, symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified, Injury, poisoning and certain other consequences of external causes, external causes of morbidity and mortality: intentional self-harm, unknown causes</td>
<td valign="middle" align="center">Age, sex</td>
</tr>
<tr>
<td valign="middle" align="center">Springate, D. A (<xref ref-type="bibr" rid="B30">30</xref>).</td>
<td valign="middle" align="center">2017</td>
<td valign="middle" align="center">Europe</td>
<td valign="middle" align="center">Retrospective cohort study</td>
<td valign="middle" align="center">Total:612898, psoriasis:508457, no psoriasis:104441</td>
<td valign="middle" align="center">All-cause mortality</td>
<td valign="middle" align="center">/</td>
</tr>
<tr>
<td valign="middle" align="center">Stern, R. S. and A. Huibregtse (<xref ref-type="bibr" rid="B15">15</xref>).</td>
<td valign="middle" align="center">2011</td>
<td valign="middle" align="center">Europe</td>
<td valign="middle" align="center">prospective cohort study</td>
<td valign="middle" align="center">Total:2752, psoriasis:1376, no psoriasis:1376</td>
<td valign="middle" align="center">All-cause mortality, major cardiovascular, diseases, neoplasms, other causes</td>
<td valign="middle" align="center">Age, sex</td>
</tr>
<tr>
<td valign="middle" align="center">Svedbom, A (<xref ref-type="bibr" rid="B14">14</xref>).</td>
<td valign="middle" align="center">2015</td>
<td valign="middle" align="center">Europe</td>
<td valign="middle" align="center">Retrospective cohort study</td>
<td valign="middle" align="center">Total:193849, psoriasis:154775, no psoriasis:39074</td>
<td valign="middle" align="center">All-cause mortality, liver disease, missing, other causes, diabetes mellitus, kidney disease, cardiovascular disease, neoplasm, accidents, severe infection, suicide, CLRD, neurological disease</td>
<td valign="middle" align="center">/</td>
</tr>
<tr>
<td valign="middle" align="center">Zhao, H (<xref ref-type="bibr" rid="B13">13</xref>).</td>
<td valign="middle" align="center">2024</td>
<td valign="middle" align="center">America</td>
<td valign="middle" align="center">prospective cohort study</td>
<td valign="middle" align="center">Total:12107, psoriasis:11829, no psoriasis:278</td>
<td valign="middle" align="center">All-cause mortality</td>
<td valign="middle" align="center">Sex, age group, race, education, marital status, BMI category, smoking status, drinking status and diabetes</td>
</tr>
<tr>
<td valign="middle" align="center">Zhou, T (<xref ref-type="bibr" rid="B29">29</xref>).</td>
<td valign="middle" align="center">2025</td>
<td valign="middle" align="center">America</td>
<td valign="middle" align="center">prospective cohort study</td>
<td valign="middle" align="center">Total:19919, psoriasis:19397, no psoriasis:522</td>
<td valign="middle" align="center">All-cause mortality</td>
<td valign="middle" align="center">Age, gender, race, education level, marital status, PIR, drinking, smoking, moderate activity, diabetes, hypertension, cardiovascular disease, LDL-C and total cholesterol</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="s3_3">
<label>3.3</label>
<title>Quality assessment</title>
<p>The quality of all included studies was assessed using the Newcastle-Ottawa Scale (NOS), which evaluates sample selection, comparability, and exposure factors, as shown in <xref ref-type="table" rid="T2">
<bold>Table&#xa0;2</bold>
</xref>. The average NOS score for the studies was 7.6, with scores ranging from 6 to 9. Specifically, 3 studies scored 6 points, 6 studies scored 7 points, 8 studies scored 8 points, and 3 studies scored 9 points. This indicates that the overall quality of the studies included in this meta-analysis is high.</p>
<table-wrap id="T2" position="float">
<label>Table&#xa0;2</label>
<caption>
<p>Newcastle-Ottawa quality of cohort studies.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="middle" align="center">Study</th>
<th valign="middle" align="center">Year</th>
<th valign="middle" align="center">Selection</th>
<th valign="middle" align="center">Comparability</th>
<th valign="middle" align="center">Outcome</th>
<th valign="middle" align="center">Total</th>
</tr>
</thead>
<tbody>
<tr>
<th valign="middle" colspan="6" align="left">Cohort studies (n=20)</th>
</tr>
<tr>
<td valign="middle" align="left">Si, Z (<xref ref-type="bibr" rid="B6">6</xref>).</td>
<td valign="middle" align="center">2024</td>
<td valign="middle" align="center">****</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">***</td>
<td valign="middle" align="center">9</td>
</tr>
<tr>
<td valign="middle" align="left">Abuabara, K (<xref ref-type="bibr" rid="B28">28</xref>).</td>
<td valign="middle" align="center">2010</td>
<td valign="middle" align="center">***</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">7</td>
</tr>
<tr>
<td valign="middle" align="left">Ahlehoff, O (<xref ref-type="bibr" rid="B27">27</xref>).</td>
<td valign="middle" align="center">2011</td>
<td valign="middle" align="center">****</td>
<td valign="middle" align="center">*</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">7</td>
</tr>
<tr>
<td valign="middle" align="left">Chen, T. C (<xref ref-type="bibr" rid="B26">26</xref>).</td>
<td valign="middle" align="center">2024</td>
<td valign="middle" align="center">****</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">8</td>
</tr>
<tr>
<td valign="middle" align="left">Dai, Y. X (<xref ref-type="bibr" rid="B25">25</xref>).</td>
<td valign="middle" align="center">2018</td>
<td valign="middle" align="center">***</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">7</td>
</tr>
<tr>
<td valign="middle" align="left">Gelfand, J. M (<xref ref-type="bibr" rid="B24">24</xref>).</td>
<td valign="middle" align="center">2007</td>
<td valign="middle" align="center">****</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">***</td>
<td valign="middle" align="center">9</td>
</tr>
<tr>
<td valign="middle" align="left">Iskandar, I. Y. K (<xref ref-type="bibr" rid="B23">23</xref>).</td>
<td valign="middle" align="center">2022</td>
<td valign="middle" align="center">****</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">8</td>
</tr>
<tr>
<td valign="middle" align="left">Kan, J (<xref ref-type="bibr" rid="B5">5</xref>).</td>
<td valign="middle" align="center">2024</td>
<td valign="middle" align="center">***</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">*</td>
<td valign="middle" align="center">6</td>
</tr>
<tr>
<td valign="middle" align="left">Kong, X. and W. Wang (<xref ref-type="bibr" rid="B22">22</xref>)</td>
<td valign="middle" align="center">2024</td>
<td valign="middle" align="center">****</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">8</td>
</tr>
<tr>
<td valign="middle" align="left">Lee, M. S (<xref ref-type="bibr" rid="B21">21</xref>).</td>
<td valign="middle" align="center">2017</td>
<td valign="middle" align="center">***</td>
<td valign="middle" align="center">*</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">6</td>
</tr>
<tr>
<td valign="middle" align="left">Mehta, N. N (<xref ref-type="bibr" rid="B20">20</xref>).</td>
<td valign="middle" align="center">2010</td>
<td valign="middle" align="center">****</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">8</td>
</tr>
<tr>
<td valign="middle" align="left">Pezzolo, E (<xref ref-type="bibr" rid="B19">19</xref>).</td>
<td valign="middle" align="center">2021</td>
<td valign="middle" align="center">****</td>
<td valign="middle" align="center">*</td>
<td valign="middle" align="center">*</td>
<td valign="middle" align="center">6</td>
</tr>
<tr>
<td valign="middle" align="left">Prodanovich, S (<xref ref-type="bibr" rid="B18">18</xref>).</td>
<td valign="middle" align="center">2009</td>
<td valign="middle" align="center">****</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">8</td>
</tr>
<tr>
<td valign="middle" align="left">Semenov, Y. R (<xref ref-type="bibr" rid="B17">17</xref>).</td>
<td valign="middle" align="center">2021</td>
<td valign="middle" align="center">****</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">***</td>
<td valign="middle" align="center">9</td>
</tr>
<tr>
<td valign="middle" align="left">Skov, L (<xref ref-type="bibr" rid="B16">16</xref>).</td>
<td valign="middle" align="center">2019</td>
<td valign="middle" align="center">****</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">*</td>
<td valign="middle" align="center">7</td>
</tr>
<tr>
<td valign="middle" align="left">Springate, D. A (<xref ref-type="bibr" rid="B30">30</xref>).</td>
<td valign="middle" align="center">2017</td>
<td valign="middle" align="center">****</td>
<td valign="middle" align="center">*</td>
<td valign="middle" align="center">***</td>
<td valign="middle" align="center">8</td>
</tr>
<tr>
<td valign="middle" align="left">Stern, R. S. and A. Huibregtse (<xref ref-type="bibr" rid="B15">15</xref>).</td>
<td valign="middle" align="center">2011</td>
<td valign="middle" align="center">****</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">*</td>
<td valign="middle" align="center">7</td>
</tr>
<tr>
<td valign="middle" align="left">Svedbom, A (<xref ref-type="bibr" rid="B14">14</xref>).</td>
<td valign="middle" align="center">2015</td>
<td valign="middle" align="center">****</td>
<td valign="middle" align="center">*</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">7</td>
</tr>
<tr>
<td valign="middle" align="left">Zhao, H (<xref ref-type="bibr" rid="B13">13</xref>).</td>
<td valign="middle" align="center">2024</td>
<td valign="middle" align="center">****</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">8</td>
</tr>
<tr>
<td valign="middle" align="left">Zhou, T (<xref ref-type="bibr" rid="B29">29</xref>).</td>
<td valign="middle" align="center">2025</td>
<td valign="middle" align="center">****</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">**</td>
<td valign="middle" align="center">8</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="s3_4">
<label>3.4</label>
<title>Risk of all-cause mortality</title>
<p>Of the 20 studies included, 15 (<xref ref-type="bibr" rid="B5">5</xref>, <xref ref-type="bibr" rid="B6">6</xref>, <xref ref-type="bibr" rid="B13">13</xref>&#x2013;<xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B17">17</xref>&#x2013;<xref ref-type="bibr" rid="B19">19</xref>, <xref ref-type="bibr" rid="B21">21</xref>&#x2013;<xref ref-type="bibr" rid="B25">25</xref>, <xref ref-type="bibr" rid="B29">29</xref>, <xref ref-type="bibr" rid="B30">30</xref>) reported the risk of all-cause mortality in psoriasis patients. The meta-analysis revealed that psoriasis patients had a significantly increased risk of all-cause mortality [HR = 1.19, 95% CI (1.11&#x2013;1.28), I&#xb2; = 95.2%, P = 0.000], with substantial heterogeneity (<xref ref-type="fig" rid="f2">
<bold>Figure&#xa0;2</bold>
</xref>). Further investigation into the sources of heterogeneity is warranted. Sensitivity analysis demonstrated the robustness of the results, as the exclusion of any individual study did not alter the overall findings (<xref ref-type="supplementary-material" rid="SM1">
<bold>Supplementary Material Figure&#xa0;1</bold>
</xref>).</p>
<fig id="f2" position="float">
<label>Figure&#xa0;2</label>
<caption>
<p>Forest plot for the risk of all-cause mortality in psoriasis.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fimmu-16-1610499-g002.tif">
<alt-text content-type="machine-generated">Forest plot showing hazard ratios (HR) and 95% confidence intervals (CI) for various studies. Each study is represented by a point and a line, indicating the HR and CI. The vertical line at HR = 1 denotes no effect. The overall effect estimate is shown at the bottom, with an HR of 1.19 and CI of 1.11 to 1.28, indicating statistical significance. Studies include authors like Si, Z. (2024), Dai, Y. X. (2018), and others, each with varying weights and HRs. The plot notes a high heterogeneity with I-squared of 95.2% and p-value of 0.000.</alt-text>
</graphic>
</fig>
</sec>
<sec id="s3_5">
<label>3.5</label>
<title>Risk of cardiovascular mortality</title>
<p>Seven studies (<xref ref-type="bibr" rid="B5">5</xref>, <xref ref-type="bibr" rid="B14">14</xref>&#x2013;<xref ref-type="bibr" rid="B16">16</xref>, <xref ref-type="bibr" rid="B20">20</xref>, <xref ref-type="bibr" rid="B22">22</xref>, <xref ref-type="bibr" rid="B28">28</xref>) reported the risk of cardiovascular mortality in psoriasis patients. The meta-analysis showed that psoriasis was associated with a higher risk of cardiovascular mortality [HR = 1.32, 95% CI (1.11&#x2013;1.58), I&#xb2; = 83%, P = 0.002, <xref ref-type="fig" rid="f3">
<bold>Figure&#xa0;3</bold>
</xref>]. Although sensitivity analysis confirmed the stability of the results, the high I&#xb2; value (83%) and significant P-value (P = 0.000) from the Q-test indicate considerable heterogeneity. Both clinical and methodological heterogeneity were considered as potential sources, while statistical heterogeneity was ruled out. The results of the sensitivity analysis are presented in the <xref ref-type="supplementary-material" rid="SM1">
<bold>Supplementary Material Figure&#xa0;2</bold>
</xref>.</p>
<fig id="f3" position="float">
<label>Figure&#xa0;3</label>
<caption>
<p>Forest plot for the risk of cardiovascular mortality in psoriasis.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fimmu-16-1610499-g003.tif">
<alt-text content-type="machine-generated">Forest plot displaying hazard ratios (HR) with 95% confidence intervals (CI) for various studies. Each study is represented by a box and a horizontal line, indicating the HR and CI. Weights from a random effects analysis are shown in percentages. An arrow indicates a wide range for one study, and an overall diamond represents the combined HR of 1.32 (95% CI: 1.11, 1.58).</alt-text>
</graphic>
</fig>
</sec>
<sec id="s3_6">
<label>3.6</label>
<title>Risk of infection mortality</title>
<p>Four studies (<xref ref-type="bibr" rid="B14">14</xref>, <xref ref-type="bibr" rid="B21">21</xref>, <xref ref-type="bibr" rid="B26">26</xref>, <xref ref-type="bibr" rid="B28">28</xref>) assessed the risk of infection-related mortality in psoriasis patients. The meta-analysis revealed an increased risk of infection mortality among psoriasis patients [HR = 1.24, 95% CI (1.13&#x2013;1.36), I&#xb2; = 71.5%, P = 0.000, <xref ref-type="fig" rid="f4">
<bold>Figure&#xa0;4</bold>
</xref>]. Sensitivity analysis indicated that none of the studies reversed the pooled effect, supporting the reliability of the findings regarding infection mortality in psoriasis patients (<xref ref-type="supplementary-material" rid="SM1">
<bold>Supplementary Material Figure&#xa0;3</bold>
</xref>).</p>
<fig id="f4" position="float">
<label>Figure&#xa0;4</label>
<caption>
<p>Forest plot for the risk of infection mortality in psoriasis.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fimmu-16-1610499-g004.tif">
<alt-text content-type="machine-generated">Forest plot showing hazard ratios (HR) with 95% confidence intervals (CI) for four studies. Abuabara (2010) HR: 1.65, CI: 1.25-2.17, weight: 9.17%. Chen (2024) HR: 1.15, CI: 1.12-1.19, weight: 43.23%. Lee (2017) HR: 1.22, CI: 1.14-1.31, weight: 36.05%. Svedbom (2015) HR: 1.38, CI: 1.09-1.75, weight: 11.55%. Overall HR: 1.24, CI: 1.13-1.36, I-squared: 71.5%, p: 0.015. Weights are from a random effects analysis.</alt-text>
</graphic>
</fig>
</sec>
<sec id="s3_7">
<label>3.7</label>
<title>Risk of neoplasm mortality</title>
<p>The risk of neoplasm-related mortality was analyzed in four studies (<xref ref-type="bibr" rid="B14">14</xref>, <xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B21">21</xref>, <xref ref-type="bibr" rid="B28">28</xref>). The summary analysis showed a slight increase in the risk of mortality due to neoplasms [HR = 1.05, 95% CI (0.98&#x2013;1.12), I&#xb2; = 38.3%, P = 0.151, <xref ref-type="fig" rid="f5">
<bold>Figure&#xa0;5</bold>
</xref>]. Sensitivity analysis confirmed the stability of these results (<xref ref-type="supplementary-material" rid="SM1">
<bold>Supplementary Material Figure&#xa0;4</bold>
</xref>).</p>
<fig id="f5" position="float">
<label>Figure&#xa0;5</label>
<caption>
<p>Forest plot for the risk of neoplasm mortality in psoriasis.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fimmu-16-1610499-g005.tif">
<alt-text content-type="machine-generated">Forest plot showing hazard ratios (HR) and confidence intervals (CI) for four studies: Abuabara (2010), Lee (2017), Stern and Huibregtse (2011), Svedbom (2015). Overall HR is 1.05 (0.98, 1.12), with random effects analysis weights noted. Horizontal lines represent CI, and diamonds represent HRs.</alt-text>
</graphic>
</fig>
</sec>
<sec id="s3_8">
<label>3.8</label>
<title>Risk of suicide mortality</title>
<p>Four studies (<xref ref-type="bibr" rid="B14">14</xref>, <xref ref-type="bibr" rid="B16">16</xref>, <xref ref-type="bibr" rid="B21">21</xref>, <xref ref-type="bibr" rid="B28">28</xref>) reported on the risk of suicide-related mortality in psoriasis patients. The meta-analysis found an increased risk of suicide mortality [HR = 1.50, 95% CI (1.03&#x2013;2.19), I&#xb2; = 69.7%, P = 0.034, <xref ref-type="fig" rid="f6">
<bold>Figure&#xa0;6</bold>
</xref>]. Sensitivity analysis confirmed that the results remained consistent and reliable (<xref ref-type="supplementary-material" rid="SM1">
<bold>Supplementary Material Figure&#xa0;5</bold>
</xref>).</p>
<fig id="f6" position="float">
<label>Figure&#xa0;6</label>
<caption>
<p>Forest plot for the risk of suicide mortality in psoriasis.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fimmu-16-1610499-g006.tif">
<alt-text content-type="machine-generated">Forest plot depicting hazard ratios (HR) and 95% confidence intervals (CI) for four studies: Abuabara, K., Lee, M. S., Skov, L., and Svedbom, A. The overall HR is 1.50 with weights shown from a random effects analysis.</alt-text>
</graphic>
</fig>
</sec>
<sec id="s3_9">
<label>3.9</label>
<title>Risk of neurological disease mortality</title>
<p>Three studies (<xref ref-type="bibr" rid="B14">14</xref>, <xref ref-type="bibr" rid="B16">16</xref>, <xref ref-type="bibr" rid="B21">21</xref>) evaluated the mortality risk from neurological diseases in psoriasis patients. The meta-analysis showed no significant increase in the risk of neurological disease-related mortality [HR = 0.96, 95% CI (0.83&#x2013;1.11), I&#xb2; = 89.0%, P = 0.976, <xref ref-type="fig" rid="f7">
<bold>Figure&#xa0;7</bold>
</xref>].</p>
<fig id="f7" position="float">
<label>Figure&#xa0;7</label>
<caption>
<p>Forest plot for the risk of neurological disease mortality in psoriasis.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fimmu-16-1610499-g007.tif">
<alt-text content-type="machine-generated">Forest plot depicting hazard ratios with 95% confidence intervals from three studies. Lee (2017) shows 1.08, Skov (2019) shows 1.48, and Svedbom (2015) shows 0.63. The overall effect is 0.99. Weights range from 31.43% to 34.79%. The analysis notes an I-squared value of 89.0%, indicating significant heterogeneity.</alt-text>
</graphic>
</fig>
</sec>
<sec id="s3_10">
<label>3.10</label>
<title>Risk of accident mortality</title>
<p>Three studies (<xref ref-type="bibr" rid="B14">14</xref>, <xref ref-type="bibr" rid="B21">21</xref>, <xref ref-type="bibr" rid="B28">28</xref>) examined the risk of accident-related mortality in psoriasis patients. The meta-analysis found a slight increase in accident-related mortality risk [HR = 0.91, 95% CI (0.81&#x2013;1.02), I&#xb2; = 21.9%, P = 0.629, <xref ref-type="fig" rid="f8">
<bold>Figure&#xa0;8</bold>
</xref>].</p>
<fig id="f8" position="float">
<label>Figure&#xa0;8</label>
<caption>
<p>Forest plot for the risk of accident mortality in psoriasis.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fimmu-16-1610499-g008.tif">
<alt-text content-type="machine-generated">Forest plot showing hazard ratios (HR) with 95% confidence intervals for three studies: Abuabara (2010) HR 1.03, Lee (2017) HR 0.88, Svedbom (2015) HR 1.21. Overall HR 0.95 with I-squared 21.9%, p-value 0.278. Weights are from random effects analysis.</alt-text>
</graphic>
</fig>
</sec>
<sec id="s3_11">
<label>3.11</label>
<title>Subgroup analysis</title>
<p>Subgroup analyses were conducted to investigate the risk of all-cause mortality based on study type, region, and psoriasis severity. The results indicated that the risk of all-cause mortality was significantly higher in studies conducted in Europe [HR = 1.107, 95% CI (1.006&#x2013;1.217), I&#xb2; = 92.9%, P = 0.036] and Asia [HR = 1.230, 95% CI (1.097&#x2013;1.379), I&#xb2; = 98.1%, P = 0.000], but not in studies from America. Additionally, psoriasis severity was found to be positively associated with an increased risk of all-cause mortality. Specifically, moderate-to-severe psoriasis [HR = 1.435, 95% CI (1.174&#x2013;1.755), I&#xb2; = 0.0%, P = 0.000] and severe psoriasis [HR = 1.543, 95% CI (1.441&#x2013;1.652), I&#xb2; = 67.6%, P = 0.000] were associated with higher mortality risk, whereas mild psoriasis did not show a significant association. The detailed findings are shown in <xref ref-type="table" rid="T3">
<bold>Table&#xa0;3</bold>
</xref>.</p>
<table-wrap id="T3" position="float">
<label>Table&#xa0;3</label>
<caption>
<p>Results of subgroup analysis.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="middle" rowspan="2" align="center">Subgroup</th>
<th valign="middle" colspan="2" align="center">All-Cause Mortality</th>
</tr>
<tr>
<th valign="middle" align="center">Pooled hazard ratio (95% CI)</th>
<th valign="middle" align="left">
<italic>P</italic>
</th>
</tr>
</thead>
<tbody>
<tr>
<th valign="middle" colspan="3" align="left">Study type</th>
</tr>
<tr>
<td valign="middle" align="left">Retrospective</td>
<td valign="middle" align="center">1.240 (1.114-1.381)</td>
<td valign="middle" align="center">0.000</td>
</tr>
<tr>
<td valign="middle" align="left">Prospective</td>
<td valign="middle" align="center">1.121 (1.055-1.192)</td>
<td valign="middle" align="center">0.000</td>
</tr>
<tr>
<td valign="middle" align="left">
<italic>Region</italic>
</td>
<td valign="middle" align="left"/>
<td valign="middle" align="left"/>
</tr>
<tr>
<td valign="middle" align="left">America</td>
<td valign="middle" align="center">1.276 (0.938-1.736)</td>
<td valign="middle" align="center">0.120</td>
</tr>
<tr>
<td valign="middle" align="left">Europe</td>
<td valign="middle" align="center">1.107 (1.006-1.217)</td>
<td valign="middle" align="center">0.036</td>
</tr>
<tr>
<td valign="middle" align="left">Asia</td>
<td valign="middle" align="center">1.230 (1.097-1.379)</td>
<td valign="middle" align="center">0.000</td>
</tr>
<tr>
<th valign="middle" colspan="3" align="left" style="">Disease severity</th>
</tr>
<tr>
<td valign="middle" align="left">Mild</td>
<td valign="middle" align="center">1.086 (0.957-1.233)</td>
<td valign="middle" align="center">0.200</td>
</tr>
<tr>
<td valign="middle" align="left">Moderate to severe</td>
<td valign="middle" align="center">1.435 (1.174-1.755)</td>
<td valign="middle" align="center">0.000</td>
</tr>
<tr>
<td valign="middle" align="left">Severe</td>
<td valign="middle" align="center">1.543 (1.441-1.652)</td>
<td valign="middle" align="center">0.000</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="s3_12">
<label>3.12</label>
<title>Publication bias</title>
<p>Publication bias was assessed for the 15 studies on overall mortality risk using a funnel plot. The subsequent bias test revealed no significant publication bias (P = 0.518 &gt; 0.1, <xref ref-type="fig" rid="f9">
<bold>Figure&#xa0;9</bold>
</xref>), and the funnel plot exhibited a roughly symmetrical distribution, suggesting that the results are less likely to be influenced by publication bias.</p>
<fig id="f9" position="float">
<label>Figure&#xa0;9</label>
<caption>
<p>Funnel plot for all-cause mortality in psoriasis patients.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fimmu-16-1610499-g009.tif">
<alt-text content-type="machine-generated">Funnel plot depicting log hazard ratio (LNHR) on the x-axis and log standard error (LNSE) on the y-axis. Data points are scattered within pseudo ninety-five percent confidence limits marked by dashed lines forming a triangle, with a vertical line at the center.</alt-text>
</graphic>
</fig>
</sec>
</sec>
<sec id="s4" sec-type="discussion">
<label>4</label>
<title>Discussion</title>
<sec id="s4_1">
<label>4.1</label>
<title>Main findings</title>
<p>This meta-analysis, which includes 20 cohort studies with a total of 8,825,989 participants, reveals a significant association between psoriasis and an increased risk of all-cause mortality (HR=1.19, 95% CI: 1.11&#x2013;1.28) as well as cause-specific mortality. The latter includes heightened risks for cardiovascular (HR=1.32), infection-related (HR=1.24), and suicide-related mortality (HR=1.50). However, no significant associations were found for mortality related to neurological diseases, or accidents. Notably, the risk of all-cause mortality escalates with disease severity, with moderate-to-severe psoriasis showing an HR of 1.44 and severe psoriasis an HR of 1.54, indicating a potential dose-response relationship. Subgroup analysis revealed significant regional disparities in all-cause mortality risk, with HR of 1.107 (Europe) and 1.230 (Asia). These findings support the notion that the systemic inflammatory burden of psoriasis may exacerbate comorbid conditions and contribute to elevated mortality risks.</p>
</sec>
<sec id="s4_2">
<label>4.2</label>
<title>Interpretation of findings</title>
<p>Previous studies have demonstrated that psoriasis increases the risk of all-cause mortality, with subgroup analyses revealing a particularly elevated risk in patients with severe psoriasis (<xref ref-type="bibr" rid="B31">31</xref>). However, the association between psoriasis and all-cause mortality has not been systematically examined. In contrast, our analysis incorporates recent cohort studies and conducts subgroup analyses stratified by study design (retrospective/prospective) and geographic region (America/Europe/Asia), significantly enhancing the reliability of findings regarding psoriasis-associated all-cause mortality. Earlier systematic reviews identified elevated risks of mortality from cardiovascular, hepatic, renal, infectious, neoplastic, and lower respiratory diseases in psoriasis patients but failed to detect an increased risk of suicide-related mortality, likely due to limited statistical power from small sample sizes with only 12 relevant studies included (<xref ref-type="bibr" rid="B31">31</xref>). Notably, the present study analyzed more recent and larger-scale cohorts and revealed a significantly elevated suicide mortality risk, underscoring the critical role of psychosocial burden in psoriasis-related mortality.</p>
</sec>
<sec id="s4_3">
<label>4.3</label>
<title>Underlying mechanisms</title>
<p>The elevated mortality risks observed in psoriasis patients are driven by multifaceted pathophysiological mechanisms. Chronic inflammation mediated by the Th17/IL-23/IL-17 axis promotes endothelial dysfunction and accelerates atherosclerosis through elevated levels of TNF-&#x3b1;, IL-17, and IL-6, which enhance vascular endothelial activation and plaque instability (<xref ref-type="bibr" rid="B32">32</xref>). Concurrently, for patients with psoriasis, systemic immunosuppression from biologics and inherent immune dysregulation heightening susceptibility to severe infections such as sepsis and respiratory infections (<xref ref-type="bibr" rid="B33">33</xref>, <xref ref-type="bibr" rid="B34">34</xref>). Psychosocial burdens arise from visible skin lesions, which induce social stigmatization and chronic stress. Proinflammatory cytokines cross the blood-brain barrier, disrupting serotonin and dopamine pathways via microglial activation and synaptic dysfunction, thereby amplifying suicide risk (<xref ref-type="bibr" rid="B35">35</xref>). The regional disparities in all-cause mortality risk may reflect interactions between environmental factors and genetic susceptibility (<xref ref-type="bibr" rid="B36">36</xref>).</p>
</sec>
<sec id="s4_4">
<label>4.4</label>
<title>Clinical and preventive implications</title>
<p>This meta-analysis revealed that patients with psoriasis face an increased risk of all-cause mortality and elevated cause-specific mortality risks, including cardiovascular diseases, infections, and suicide. These findings underscore the necessity of prioritizing daily management and prevention of comorbidities in psoriasis patients to mitigate mortality risks. For preventive strategies, regular screening for hypertension, dyslipidemia, atherosclerosis, and infection susceptibility is recommended to address cardiovascular and infectious risks (<xref ref-type="bibr" rid="B7">7</xref>). Additionally, routine psychological assessments and targeted mental health interventions are critical for patients exhibiting suicidal ideation, particularly given the psychosocial burden associated with visible skin lesions (<xref ref-type="bibr" rid="B37">37</xref>). Subgroup analysis demonstrated that patients with severe psoriasis faced significantly higher mortality risks. This highlights the imperative for stratified management based on disease severity, including tailored interventions such as intensified cardiovascular monitoring, optimized biologic dosing, and multidisciplinary mental health support for high-risk subgroups (<xref ref-type="bibr" rid="B38">38</xref>).</p>
</sec>
<sec id="s4_5">
<label>4.5</label>
<title>Implications and limitations</title>
<p>This study possesses several strengths, including a large sample size, rigorous adherence to PRISMA guidelines, evaluation of bias risk, sensitivity analyses, and subgroup analyses stratified by study type, region, and disease severity. However, some limitations must be acknowledged. First, only cohort studies were included, which controlled for confounding factors to some extent; however, certain subgroups had a limited number of studies, which reduced statistical power. Future research could broaden the inclusion criteria to incorporate additional study designs. Second, significant heterogeneity was observed across studies, including variations in the definition of severe psoriasis, classification of specific causes of death, follow-up duration, and adjustment for confounding factors. To account for potential heterogeneity, a random-effects model was applied. These limitations should be considered when interpreting the findings of this study.</p>
</sec>
</sec>
<sec id="s5" sec-type="conclusions">
<label>5</label>
<title>Conclusions</title>
<p>This meta-analysis revealed that psoriasis is associated with an elevated risk of all-cause mortality, as well as increased mortality attributable to cardiovascular diseases, infections, suicide, and other factors. Our findings underscore the necessity of multidisciplinary interventions, particularly in severe cases. Future studies should further elucidate the underlying pathophysiological mechanisms to facilitate the development of more effective preventive strategies and therapeutic approaches for patients with psoriasis.</p>
</sec>
</body>
<back>
<sec id="s6" sec-type="data-availability">
<title>Data availability statement</title>
<p>The original contributions presented in the study are included in the article/<xref ref-type="supplementary-material" rid="SM1">
<bold>Supplementary Material</bold>
</xref>. Further inquiries can be directed to the corresponding author.</p>
</sec>
<sec id="s7" sec-type="author-contributions">
<title>Author contributions</title>
<p>YY: Conceptualization, Data curation, Formal analysis, Project administration, Supervision, Validation, Visualization, Writing &#x2013; original draft, Writing &#x2013; review &amp; editing. QZ: Data curation, Formal analysis, Investigation, Visualization, Writing &#x2013; original draft. AH: Investigation, Methodology, Validation, Writing &#x2013; review &amp; editing. JZ: Writing &#x2013; original draft, Writing &#x2013; review &amp; editing. JY: Writing &#x2013; review &amp; editing. LW: Writing &#x2013; review &amp; editing. GX: Funding acquisition, Project administration, Supervision, Validation, Writing &#x2013; original draft, Writing &#x2013; review &amp; editing.</p>
</sec>
<sec id="s8" sec-type="funding-information">
<title>Funding</title>
<p>The author(s) declare that financial support was received for the research and/or publication of this article. This study is funded by Collaborative Research Project of the Third Affiliated Hospital, Beijing University of Chinese Medicine (303&#x2013;02&#x2013;227).</p>
</sec>
<sec id="s9" sec-type="COI-statement">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="s10" sec-type="ai-statement">
<title>Generative AI statement</title>
<p>The author(s) declare that no Generative AI was used in the creation of this manuscript.</p>
</sec>
<sec id="s11" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<sec id="s12" sec-type="supplementary-material">
<title>Supplementary material</title>
<p>The Supplementary Material for this article can be found online at: <ext-link ext-link-type="uri" xlink:href="https://www.frontiersin.org/articles/10.3389/fimmu.2025.1610499/full#supplementary-material">https://www.frontiersin.org/articles/10.3389/fimmu.2025.1610499/full#supplementary-material</ext-link>
</p>
<supplementary-material xlink:href="DataSheet1.docx" id="SM1" mimetype="application/vnd.openxmlformats-officedocument.wordprocessingml.document"/>
<supplementary-material xlink:href="Table1.docx" id="SM2" mimetype="application/vnd.openxmlformats-officedocument.wordprocessingml.document"/>
</sec>
<fn-group>
<title>Abbreviations</title>
<fn fn-type="abbr" id="abbrev1">
<p>HR, hazard ratio; OR, odds ratio; RR, relative risk; CI, confidence intervals; MeSH, medical subject headings; NOS, Newcastle-Ottawa scale; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PROSPERO, international prospective register of systematic reviews; ICD, international classification of diseases.</p>
</fn>
</fn-group>
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