{"paper_id":"3d40bb9a-8f58-4985-a9db-7ce4c8323fcb","body_text":"Cutaneous adverse drug reactions in patients with congenital heart disease: a systematic review with focus on perioperative outcomes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Cutaneous adverse drug reactions in patients with congenital heart disease: a systematic review with focus on perioperative outcomes R. Mohamad Javier¹˒², Savira Salsabila³, Errini Sabilla Lilhawa Ditsi, and 21 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8317443/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Mar, 2026 Read the published version in BMC Cardiovascular Disorders → Version 1 posted 10 You are reading this latest preprint version Abstract Background: Cutaneous adverse drug reactions (CADRs) are uncommon but clinically significant complications among patients with congenital heart disease (CHD), particularly those with pulmonary arterial hypertension (PAH) or perioperative hemodynamic instability. The complex pharmacologic regimens required in CHD—often involving prostaglandins, vasodilators, antibiotics, and antiepileptics—predispose patients to idiosyncratic and immune-mediated reactions. Despite increasing recognition of CADRs in cardiovascular medicine, systematic evidence focusing on CHD populations remains limited. Methods: A systematic search of MEDLINE (PubMed), Embase, Web of Science, and CENTRAL was conducted from database inception to October 31, 2024, covering all types of congenital heart disease, both cyanotic and acyanotic, isolated and syndromic forms. Eligible studies included randomized controlled trials, observational studies, and case reports that reported CADRs in patients with structural CHD, regardless of age or surgical status. Extracted outcomes included type of CADR, implicated drug, temporal association, histopathology, management, and clinical outcome. Study quality was assessed using the Joanna Briggs Institute (JBI) checklist for case reports and case series. Results: Thirteen studies encompassing 27 patients met the inclusion criteria. Most patients (61%) were neonates or infants with duct-dependent CHD receiving prostaglandin E1 (alprostadil) for lesions such as transposition of the great arteries, hypoplastic left heart syndrome, and Taussig–Bing anomaly. The predominant CADRs included migratory urticaria and erythematous eruptions linked to prostaglandin E1 (n=8, 30%) and radiographically detected brown fat necrosis following prolonged infusion (n=5, 19%). Severe hypersensitivity reactions—including drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens–Johnson syndrome (SJS)—occurred in patients receiving vancomycin, carbamazepine, or levetiracetam (n=3, 11%), typically postoperatively or in intensive care. Other reports included bosentan-induced indurated erythema in an adult with repaired tetralogy of Fallot and amoxicillin-associated exanthema in pediatric post-repair patients. All studies scored low on JBI quality assessment due to descriptive designs and limited follow-up. The most frequently implicated drug classes were prostaglandin analogs (63%), antiepileptics (15%), and antibiotics (15%), with reaction patterns ranging from transient vasomotor erythema to immune-mediated hypersensitivity Conclusions: CADRs, though infrequently reported, occur across the therapeutic continuum of CHD management—from neonatal prostaglandin therapy to adult antimicrobial and antiepileptic use. The predominance of prostaglandin-associated reactions underscores the importance of dermatologic and metabolic surveillance during infusion therapy, while severe whereas severe hypersensitivity reactions underscore the interface between cardiology and dermatology. Larger multicenter studies are warranted to clarify incidence, risk factors, and outcomes, guiding safer pharmacologic management in congenital cardiology. Congenital heart disease pulmonary arterial hypertension prostaglandin E1 drug eruption cutaneous adverse drug reaction DRESS Stevens–Johnson syndrome Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 24 Mar, 2026 Read the published version in BMC Cardiovascular Disorders → Version 1 posted Editorial decision: Revision requested 23 Feb, 2026 Reviews received at journal 15 Jan, 2026 Reviewers agreed at journal 11 Jan, 2026 Reviews received at journal 26 Dec, 2025 Reviewers agreed at journal 21 Dec, 2025 Reviewers invited by journal 19 Dec, 2025 Editor invited by journal 16 Dec, 2025 Editor assigned by journal 13 Dec, 2025 Submission checks completed at journal 13 Dec, 2025 First submitted to journal 09 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-8317443\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":563764051,\"identity\":\"bb5e1603-9156-4845-b18a-1af465a4f304\",\"order_by\":0,\"name\":\"R. 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Disorders\",\"twitterHandle\":\"BMC_series\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Congenital heart disease, pulmonary arterial hypertension, prostaglandin E1, drug eruption, cutaneous adverse drug reaction, DRESS, Stevens–Johnson syndrome\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-8317443/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-8317443/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground:\\u003c/strong\\u003e Cutaneous adverse drug reactions (CADRs) are uncommon but clinically significant complications among patients with congenital heart disease (CHD), particularly those with pulmonary arterial hypertension (PAH) or perioperative hemodynamic instability. The complex pharmacologic regimens required in CHD—often involving prostaglandins, vasodilators, antibiotics, and antiepileptics—predispose patients to idiosyncratic and immune-mediated reactions. Despite increasing recognition of CADRs in cardiovascular medicine, systematic evidence focusing on CHD populations remains limited.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMethods:\\u003c/strong\\u003e A systematic search of MEDLINE (PubMed), Embase, Web of Science, and CENTRAL was conducted from database inception to October 31, 2024, covering all types of congenital heart disease, both cyanotic and acyanotic, isolated and syndromic forms. Eligible studies included randomized controlled trials, observational studies, and case reports that reported CADRs in patients with structural CHD, regardless of age or surgical status. Extracted outcomes included type of CADR, implicated drug, temporal association, histopathology, management, and clinical outcome. Study quality was assessed using the Joanna Briggs Institute (JBI) checklist for case reports and case series.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResults:\\u003c/strong\\u003e Thirteen studies encompassing 27 patients met the inclusion criteria. Most patients (61%) were neonates or infants with duct-dependent CHD receiving prostaglandin E1 (alprostadil) for lesions such as transposition of the great arteries, hypoplastic left heart syndrome, and Taussig–Bing anomaly. The predominant CADRs included migratory urticaria and erythematous eruptions linked to prostaglandin E1 (n=8, 30%) and radiographically detected brown fat necrosis following prolonged infusion (n=5, 19%). Severe hypersensitivity reactions—including drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens–Johnson syndrome (SJS)—occurred in patients receiving vancomycin, carbamazepine, or levetiracetam (n=3, 11%), typically postoperatively or in intensive care. Other reports included bosentan-induced indurated erythema in an adult with repaired tetralogy of Fallot and amoxicillin-associated exanthema in pediatric post-repair patients. All studies scored low on JBI quality assessment due to descriptive designs and limited follow-up. The most frequently implicated drug classes were prostaglandin analogs (63%), antiepileptics (15%), and antibiotics (15%), with reaction patterns ranging from transient vasomotor erythema to immune-mediated hypersensitivity\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusions:\\u003c/strong\\u003e CADRs, though infrequently reported, occur across the therapeutic continuum of CHD management—from neonatal prostaglandin therapy to adult antimicrobial and antiepileptic use. The predominance of prostaglandin-associated reactions underscores the importance of dermatologic and metabolic surveillance during infusion therapy, while severe whereas severe hypersensitivity reactions underscore the interface between cardiology and dermatology. Larger multicenter studies are warranted to clarify incidence, risk factors, and outcomes, guiding safer pharmacologic management in congenital cardiology.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Cutaneous adverse drug reactions in patients with congenital heart disease: a systematic review with focus on perioperative outcomes\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-12-23 18:13:32\",\"doi\":\"10.21203/rs.3.rs-8317443/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Revision requested\",\"date\":\"2026-02-23T10:33:01+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2026-01-15T07:29:33+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"247256478103775469292221120507957673236\",\"date\":\"2026-01-12T01:28:48+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2025-12-27T02:42:46+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"256454744889307295742654644355566957951\",\"date\":\"2025-12-21T23:41:35+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2025-12-19T19:34:07+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvited\",\"content\":\"\",\"date\":\"2025-12-16T05:00:58+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2025-12-13T09:13:15+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2025-12-13T09:13:09+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"BMC Cardiovascular Disorders\",\"date\":\"2025-12-09T11:52:51+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"bmc-cardiovascular-disorders\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"bcar\",\"sideBox\":\"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/bcar/default.aspx\",\"title\":\"BMC Cardiovascular Disorders\",\"twitterHandle\":\"BMC_series\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"7ca5166f-1e2c-4be9-9f02-27ec19c86721\",\"owner\":[],\"postedDate\":\"December 23rd, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"published-in-journal\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2026-03-30T16:16:17+00:00\",\"versionOfRecord\":{\"articleIdentity\":\"rs-8317443\",\"link\":\"https://doi.org/10.1186/s12872-026-05774-0\",\"journal\":{\"identity\":\"bmc-cardiovascular-disorders\",\"isVorOnly\":false,\"title\":\"BMC Cardiovascular Disorders\"},\"publishedOn\":\"2026-03-24 16:08:59\",\"publishedOnDateReadable\":\"March 24th, 2026\"},\"versionCreatedAt\":\"2025-12-23 18:13:32\",\"video\":\"\",\"vorDoi\":\"10.1186/s12872-026-05774-0\",\"vorDoiUrl\":\"https://doi.org/10.1186/s12872-026-05774-0\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-8317443\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-8317443\",\"identity\":\"rs-8317443\",\"version\":[\"v1\"]},\"buildId\":\"8U1c8b4HqxoKbykW_rLl7\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}