{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T05:36:14Z","timestamp":1782970574617,"version":"3.54.5"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Rare inflammatory rheumatic diseases are often characterized by heterogeneous, multisystemic symptom patterns, complicating early diagnostic differentiation. This study aimed to model a structured, symptom- and laboratory-based decision approach for risk stratification of rheumatologic diagnoses in patients referred to a tertiary Center for Rare Diseases (CRD) with unclear systemic complaints.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective cross-sectional analysis of 173 patients evaluated at a CRD. Patients were classified into rheumatologic (RHEUMA) and non-rheumatologic (OTHER) diagnostic groups based on final diagnostic outcomes. A standardized questionnaire capturing 52 symptoms was aggregated into domain-specific and composite scores. Laboratory data were summarized into predefined indices. Group differences were analyzed descriptively using inferential statistics. A decision tree model based on Chi-Square Automatic Interaction Detection (CHAID) was constructed to support structured risk stratification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A confirmed rheumatologic diagnosis was established in 52.0% of patients. Symptom and comorbidity patterns were broadly similar across diagnostic groups, with fatigue and generalized pain being the most prevalent complaints. The RHEUMA group showed significantly higher scores in selected symptom domains and in an immunoserological laboratory index (all\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05). The CHAID-based decision model, integrating symptom scores, laboratory markers, and autoimmune history, showed an apparent classification of 81.5% (AUC\u202f=\u202f0.893), compared to 76.3% (AUC\u202f=\u202f0.823) for logistic regression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The proposed decision tree model provides a transparent framework for structured risk stratification in a highly preselected tertiary referral population. Given the monocentric, retrospective, and exploratory study design, the findings should be interpreted as hypothesis-generating. External validation in independent cohorts is required to assess model generalizability, calibration, and robustness before clinical implementation can be considered. Within these constraints, the approach illustrates the potential of transparent, rule-based symptom aggregation to support structured clinical reasoning and prioritization in complex multisystem presentations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1734483","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:23:57Z","timestamp":1782966237000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A decision tree-based algorithm for structured risk stratification of rare rheumatic diseases in a tertiary referral setting"],"prefix":"10.3389","volume":"13","author":[{"given":"Christine","family":"Babka","sequence":"first","affiliation":[{"name":"Medizinische Hochschule Hannover (MHH), Zentrum f\u00fcr seltene Erkrankungen","place":["Hannover, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Storck","sequence":"additional","affiliation":[{"name":"Ostfalia Hochschule f\u00fcr Angewandte Wissenschaften \u2013 Hochschule Braunschweig\/Wolfenb\u00fcttel, Fakult\u00e4t Handel und soziale Arbeit","place":["Suderburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Witte","sequence":"additional","affiliation":[{"name":"Medizinische Hochschule Hannover (MHH), Klinik f\u00fcr Rheumatologie und Immunologie","place":["Hannover, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vega","family":"G\u00f6decke","sequence":"additional","affiliation":[{"name":"Medizinische Hochschule Hannover (MHH), Zentrum f\u00fcr seltene Erkrankungen","place":["Hannover, Germany"]},{"name":"Medizinische Hochschule Hannover (MHH), Klinik f\u00fcr Nieren- und Hochdruckerkrankungen","place":["Hannover, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.3390\/diagnostics11071300","article-title":"Statistical methods to support difficult diagnoses","volume":"11","author":"Pilz","year":"2021","journal-title":"Diagnostics"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1002\/art.41610","article-title":"Integrative analysis reveals a molecular stratification of systemic autoimmune diseases","volume":"73","author":"Barturen","year":"2021","journal-title":"Arthritis Rheumatol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1007\/s11926-023-01099-5","article-title":"Undifferentiated connective tissue disease: comprehensive review","volume":"25","author":"Rubio","year":"2023","journal-title":"Curr Rheumatol Rep"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e85","DOI":"10.1016\/S2665-9913(19)30042-6","article-title":"Symptom-based stratification of patients with primary Sj\u00f6gren\u2019s syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials","volume":"1","author":"Tarn","year":"2019","journal-title":"Lancet Rheumatol"},{"key":"ref5","article-title":"Integrative Versorgungskonzepte bei seltenen Erkrankungen: Der Ansatz von Shared Care","author":"von Bandemer","year":"2010","journal-title":"Forschung Aktuell"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.eclinm.2023.102260","article-title":"Effect of the addition of a mental health specialist for evaluation of undiagnosed patients in centres for rare diseases (ZSE-DUO): a prospective, controlled trial with a two-phase cohort design","author":"Hebestreit","year":"2023","journal-title":"EClinicalMedicine"},{"key":"ref7","article-title":"Die gesundheitliche Situation von Menschen mit Seltenen Erkrankungen in Deutschland","author":"Aichinger","year":"2023","journal-title":"Endbericht"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"469","DOI":"10.3238\/arztebl.m2022.0219","article-title":"The interdisciplinary diagnosis of rare diseases: results of the translate-NAMSE project","volume":"119","author":"Rillig","year":"2022","journal-title":"Dtsch \u00c4rztebl Int"},{"key":"ref9","first-page":"7","article-title":"Rare diseases in Germany - developments in the status of medical care","volume-title":"J Health Monit","author":"Schlangen","year":"2023"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s13023-022-02176-1","article-title":"Dual guidance structure for evaluation of patients with unclear diagnosis in centers for rare diseases (ZSE-DUO): study protocol for a controlled multi-center cohort study","volume":"17","author":"Hebestreit","year":"2022","journal-title":"Orphanet J Rare Dis"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1007\/s00103-014-2040-2","article-title":"Measures to improve the health situation of patients with rare diseases in Germany. 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