Non-selective Beta-Blockers and Retroperitoneal Fibrosis: A Potential Factor in Symptomatic Exacerbation a case report.

Non-selective Beta-Blockers and Retroperitoneal Fibrosis: A Potential Factor in Symptomatic Exacerbation a case report. | 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 Case Report Non-selective Beta-Blockers and Retroperitoneal Fibrosis: A Potential Factor in Symptomatic Exacerbation a case report. Diletta Vittoria Carla Settimi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7651729/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Retroperitoneal fibrosis is a rare fibro-inflammatory disorder characterized by progressive deposition of dense collagenous tissue within the retroperitoneal space, enveloping vascular and visceral structures. Although most cases are idiopathic, certain pharmacological agents have been implicated in symptom exacerbation. This case report describes an acute deterioration of gastrointestinal function following initiation of a non-selective beta-adrenergic blocker in stable disease. A 45-year-old Caucasian woman with dyslipidaemia and chronic sinus tachycardia underwent exploratory laparotomy for suspected peritoneal malignancy. Histopathology confirmed extensive fibrotic deposition with chronic inflammatory infiltrates and excluded neoplasia, establishing a diagnosis of retroperitoneal fibrosis. During three years of surveillance with serial laboratory assays and magnetic resonance imaging, the disease remained quiescent. To optimize heart-rate control, therapy with a beta-1-selective antagonist was replaced by propranolol 40 mg twice daily, a non-selective beta-adrenergic blocker. Within days, severe crampy abdominal pain, marked distension and altered bowel habits developed despite stable imaging. The close temporal relationship and the established role of beta-2 receptors in intestinal smooth muscle relaxation implicated non-selective blockade in aggravating colonic dysmotility on a background of fibrotic compression. Dietary modifications and low-dose antispasmodics provided only marginal relief. This case illustrates that non-selective beta-blockers may exacerbate gastrointestinal symptoms in retroperitoneal fibrosis by impairing smooth muscle relaxation. In patients with colonic involvement, beta-1-selective agents should be preferred, with careful consideration of cardiovascular benefits versus gastrointestinal risks. Beta blocker Introduction The association between retroperitoneal fibrosis and beta-blocker therapy has been reported only once in the literature, and no robust scientific studies currently support this correlation. However, in the present case, a patient diagnosed with retroperitoneal fibrosis experienced a marked exacerbation of previously latent symptoms following the administration of a non-selective beta-blocker. Case A 45-year-old woman with a history of dyslipidemia and tachycardia, initially managed with bisoprolol (Cardicor®) 1.25 mg once daily, underwent urgent exploratory laparotomy in 2013 due to imaging findings suspicious for multiple metastatic lesions involving the abdominal viscera. The patient presented with non-specific abdominal discomfort, bloating, and unintentional weight loss. Intraoperatively, a bilateral salpingectomy and peritoneal inspection were performed. Multiple fibrotic masses and dense adhesions were noted, particularly in the retroperitoneal area and around the intestines. Histopathological examination of the biopsied tissue revealed chronic inflammatory infiltrate and dense fibrosis, consistent with a diagnosis of idiopathic retroperitoneal fibrosis (RPF), excluding the initial suspicion of peritoneal carcinomatosis. Complete surgical excision was not feasible due to extensive involvement of the abdominal viscera and retroperitoneal structures, resulting in residual disease. Over the following years, the patient underwent serial follow-up including laboratory tests (inflammatory markers, autoimmune panel, and serum IgG4), genetic evaluations, and imaging with magnetic resonance imaging (MRI). These confirmed the diagnosis of idiopathic RPF with stable residual disease. During the most recent year, the patient experienced increased episodes of symptomatic tachycardia. A cardiologic workup excluded structural heart disease and identified inappropriate sinus tachycardia as the likely cause. As a result, her treatment was modified from bisoprolol to a non-selective beta-blocker (propranolol 40 mg twice daily), which led to partial symptom control. In the same period, she presented to the emergency department on three separate occasions for crampy abdominal pain. These episodes were attributed to persistent fibrotic involvement of the colon, as confirmed by imaging, which demonstrated stable but extensive disease with no evidence of progression or malignancy. Symptom exacerbations were managed conservatively with analgesics and supportive therapy. Discussion Retroperitoneal fibrosis (RPF) is a rare but clinically significant disease characterized by the proliferation of fibro-inflammatory tissue within the retroperitoneal space. This pathological tissue commonly encases the abdominal aorta, iliac vessels, and adjacent structures such as the ureters, lymphatics, and, less frequently but notably, segments of the gastrointestinal tract including the colon. The condition can be idiopathic or secondary to drugs, infections, malignancies, or surgical interventions. Idiopathic RPF is increasingly considered an immune-mediated disease and, in a subset of patients, part of the spectrum of IgG4-related disease, with TGF-β, IL-6, and other pro-inflammatory cytokines playing pivotal roles in disease propagation and tissue fibrosis [ 1 – 3 ]. While most attention in the clinical management of RPF is focused on urinary tract obstruction due to ureteral involvement, compression or functional alteration of the colon is an underrecognized but important contributor to patient morbidity. Anatomically, the descending and sigmoid colon lie within the potential field of fibrotic encasement. When fibrosis extends laterally and posteriorly, these colonic segments may become partially compressed, displaced, or inflamed, which can lead to symptoms such as abdominal bloating, pain, altered bowel habits, and in some cases, pseudo-obstruction [ 4 ]. In this context, the pharmacological use of non-selective β-blockers (NSBBs) such as propranolol or carvedilol deserves closer scrutiny. NSBBs block both β₁- and β₂-adrenergic receptors. While β₁-receptors are primarily located in the heart, β₂-receptors are widely expressed in gastrointestinal smooth muscle and are responsible for promoting relaxation and peristalsis. Their blockade can lead to increased smooth muscle tone, reduced motility, and slowed colonic transit time. This effect, typically negligible in healthy individuals, can become clinically relevant in patients with RPF, where mechanical and inflammatory impairment of the colon already limits normal motility [ 5 – 6 ]. Indeed, the combination of extrinsic fibrotic compression and intrinsic pharmacologic inhibition of colonic relaxation can create a compounding effect, worsening symptoms such as constipation, cramping, and postprandial bloating. This may mimic or exacerbate features of colonic pseudo-obstruction, especially in cases where fibrosis is extensive or where vascular encasement leads to subtle mesenteric ischemia. Additionally, β₂-blockade may reduce mucosal perfusion by impairing vasodilation in the splanchnic circulation, theoretically increasing the risk of localized ischemic injury in compromised bowel segments [ 7 ]. Paradoxically, preclinical studies suggest that some NSBBs, particularly carvedilol, may have anti-fibrotic and anti-inflammatory properties. In models of chemically induced colitis, carvedilol has been shown to inhibit TGF-β1 expression, suppress NF-κB activation, and downregulate α-smooth muscle actin (α-SMA), key factors in intestinal fibrosis and myofibroblast activation [ 8 ]. These data raise the intriguing possibility that NSBBs could attenuate fibrotic progression in chronic inflammatory conditions. However, the translation of these effects to retroperitoneal tissues remains speculative, especially considering the differing embryological origins and tissue environments of the colon and retroperitoneum. Given these complex and sometimes contradictory effects, the role of NSBBs in patients with RPF and gastrointestinal involvement must be carefully individualized. While their cardiovascular and hepatic indications remain valid, clinicians should consider β₁-selective alternatives (e.g., bisoprolol, atenolol) in patients who report gastrointestinal symptoms, particularly those consistent with hypomotility or mechanical bowel dysfunction. Conclusion The use of non-selective β-blockers in patients with retroperitoneal fibrosis warrants critical evaluation, especially in cases with colonic involvement. Their ability to inhibit β₂-mediated smooth muscle relaxation may amplify symptoms related to colonic dysmotility, adding a functional burden to the already present mechanical and inflammatory disruption caused by fibrosis. While experimental data point to potential anti-fibrotic effects of NSBBs, these benefits may not be clinically relevant—or may even be outweighed—by their adverse impact on gastrointestinal smooth muscle tone. Further studies are needed to better understand this interaction and guide pharmacologic choices in the management of RPF patients presenting with prominent abdominal symptoms. Declarations Ethics approval and consent to participate: Not applicable. Consent for publication: Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Availability of data and materials: Not applicable. Competing interests: The author declares that they have no competing interests. Funding: None. Author ’ s contributions: The author conceived the study, collected and analyzed the data, drafted the manuscript and approved the final version. Acknowledgements: Not applicable. References Vaglio A, Salvarani C, Buzio C. Retroperitoneal fibrosis. Lancet. 2006;367(9506):241–251. Zen Y, Nakanuma Y. IgG4-related disease: a cross-organ perspective. Mod Pathol. 2011;24(4):489–501. Coarradi D et al. Immunopathology of idiopathic retroperitoneal fibrosis: role of dendritic cells and T lymphocytes. Am J Surg Pathol. 2007;31(4):494–503. Koep L, Zuidema GD. The clinical significance of idiopathic retroperitoneal fibrosis. Surgery. 1977;81(3):250–257. Browning KN, Travagli RA. Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions. Compr Physiol. 2014;4(4):1339–1368. Salpeter SR et al. Cardiopulmonary effects of beta-blockers in patients with reactive airway or gastrointestinal conditions: a systematic review. Ann Intern Med. 2002;137(9):715–725. Chang CH et al. Beta-blockers and intestinal barrier function: mechanisms of anti-inflammatory action. Biochem Pharmacol. 2013;85(9):1228–1236. Bayoumi A, El-Bakly WM, Ali MA. Carvedilol attenuates colonic fibrosis and epithelial damage in murine colitis via inhibition of TGF-β1 and NF-κB pathways. Front Pharmacol. 2021;12:635488. Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted 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-7651729","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":517223820,"identity":"c3dd09aa-1b87-47bf-a507-6983c33f4515","order_by":0,"name":"Diletta Vittoria Carla Settimi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA00lEQVRIiWNgGAWjYDCCAxCKh4GZGcSUkCFSS4IBUAtbAkgLD9FaQBYZQKwjBPhuJD/+8PHHHxnddp7Pr27UWPAwsB8+ugGfFskbaWaSM4AOMzvMu8065xjQYTxpaTfwaTE4c4aNmQeqxTiHDahFgseMkBbmz3/AWnieGef8I0bL8R4GaQaIFubHuW1EaJE83mYm2ZNmDNTCZsac2yfBw0bIL3yHmR9/+GEjZ292/vDjzznf6uT42Q8fw6sFGbBJgElilYMA8wdSVI+CUTAKRsHIAQCImkPXeCD0DQAAAABJRU5ErkJggg==","orcid":"","institution":"","correspondingAuthor":true,"prefix":"","firstName":"Diletta","middleName":"Vittoria Carla","lastName":"Settimi","suffix":""}],"badges":[],"createdAt":"2025-09-18 16:43:45","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7651729/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7651729/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":91829288,"identity":"5f8f94f5-d80f-4327-9f48-aa55e1c611ab","added_by":"auto","created_at":"2025-09-22 08:55:00","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":34809,"visible":true,"origin":"","legend":"","description":"","filename":"acasereport..docx","url":"https://assets-eu.researchsquare.com/files/rs-7651729/v1/add3ebf346088a157ed243ef.docx"},{"id":91829286,"identity":"793395fc-362f-46c2-8360-9340ed9bc1d2","added_by":"auto","created_at":"2025-09-22 08:55:00","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":342,"visible":true,"origin":"","legend":"","description":"","filename":"rs7651729.json","url":"https://assets-eu.researchsquare.com/files/rs-7651729/v1/252931cbb5bc78fac5e9503c.json"},{"id":91829287,"identity":"4935cf7b-c86a-4a1c-af72-4addb0bffea4","added_by":"auto","created_at":"2025-09-22 08:55:00","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":21967,"visible":true,"origin":"","legend":"","description":"","filename":"rs76517290enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7651729/v1/f9113860cc18bbe2401c056f.xml"},{"id":91829290,"identity":"89c7f942-2f3e-451f-b747-ad48ba7052c2","added_by":"auto","created_at":"2025-09-22 08:55:00","extension":"xml","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":20724,"visible":true,"origin":"","legend":"","description":"","filename":"rs76517290structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7651729/v1/dd66d09ba1be7c13a332ccf5.xml"},{"id":91829289,"identity":"75697359-a539-43e5-ac97-46ad14a1c7c5","added_by":"auto","created_at":"2025-09-22 08:55:00","extension":"html","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":24282,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7651729/v1/37aa9c442d68ec61af67089f.html"},{"id":91829295,"identity":"25a3b490-f61d-476b-9e96-b45071cee277","added_by":"auto","created_at":"2025-09-22 08:55:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":222056,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7651729/v1/cf86904b-9f8a-4ea6-98ed-9e4c97d6e322.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eNon-selective Beta-Blockers and Retroperitoneal Fibrosis: A Potential Factor in Symptomatic Exacerbation a case report.\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe association between retroperitoneal fibrosis and beta-blocker therapy has been reported only once in the literature, and no robust scientific studies currently support this correlation. However, in the present case, a patient diagnosed with retroperitoneal fibrosis experienced a marked exacerbation of previously latent symptoms following the administration of a non-selective beta-blocker.\u003c/p\u003e"},{"header":"Case","content":"\u003cp\u003eA 45-year-old woman with a history of dyslipidemia and tachycardia, initially managed with bisoprolol (Cardicor®) 1.25 mg once daily, underwent urgent exploratory laparotomy in 2013 due to imaging findings suspicious for multiple metastatic lesions involving the abdominal viscera. The patient presented with non-specific abdominal discomfort, bloating, and unintentional weight loss. Intraoperatively, a bilateral salpingectomy and peritoneal inspection were performed. Multiple fibrotic masses and dense adhesions were noted, particularly in the retroperitoneal area and around the intestines.\u003c/p\u003e\u003cp\u003eHistopathological examination of the biopsied tissue revealed chronic inflammatory infiltrate and dense fibrosis, consistent with a diagnosis of idiopathic retroperitoneal fibrosis (RPF), excluding the initial suspicion of peritoneal carcinomatosis. Complete surgical excision was not feasible due to extensive involvement of the abdominal viscera and retroperitoneal structures, resulting in residual disease.\u003c/p\u003e\u003cp\u003eOver the following years, the patient underwent serial follow-up including laboratory tests (inflammatory markers, autoimmune panel, and serum IgG4), genetic evaluations, and imaging with magnetic resonance imaging (MRI). These confirmed the diagnosis of idiopathic RPF with stable residual disease.\u003c/p\u003e\u003cp\u003eDuring the most recent year, the patient experienced increased episodes of symptomatic tachycardia. A cardiologic workup excluded structural heart disease and identified inappropriate sinus tachycardia as the likely cause. As a result, her treatment was modified from bisoprolol to a non-selective beta-blocker (propranolol 40 mg twice daily), which led to partial symptom control.\u003c/p\u003e\u003cp\u003eIn the same period, she presented to the emergency department on three separate occasions for crampy abdominal pain. These episodes were attributed to persistent fibrotic involvement of the colon, as confirmed by imaging, which demonstrated stable but extensive disease with no evidence of progression or malignancy. Symptom exacerbations were managed conservatively with analgesics and supportive therapy.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eRetroperitoneal fibrosis (RPF) is a rare but clinically significant disease characterized by the proliferation of fibro-inflammatory tissue within the retroperitoneal space. This pathological tissue commonly encases the abdominal aorta, iliac vessels, and adjacent structures such as the ureters, lymphatics, and, less frequently but notably, segments of the gastrointestinal tract including the colon. The condition can be idiopathic or secondary to drugs, infections, malignancies, or surgical interventions. Idiopathic RPF is increasingly considered an immune-mediated disease and, in a subset of patients, part of the spectrum of IgG4-related disease, with TGF-β, IL-6, and other pro-inflammatory cytokines playing pivotal roles in disease propagation and tissue fibrosis [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e–\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eWhile most attention in the clinical management of RPF is focused on urinary tract obstruction due to ureteral involvement, compression or functional alteration of the colon is an underrecognized but important contributor to patient morbidity. Anatomically, the descending and sigmoid colon lie within the potential field of fibrotic encasement. When fibrosis extends laterally and posteriorly, these colonic segments may become partially compressed, displaced, or inflamed, which can lead to symptoms such as abdominal bloating, pain, altered bowel habits, and in some cases, pseudo-obstruction [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn this context, the pharmacological use of non-selective β-blockers (NSBBs) such as propranolol or carvedilol deserves closer scrutiny. NSBBs block both β₁- and β₂-adrenergic receptors. While β₁-receptors are primarily located in the heart, β₂-receptors are widely expressed in gastrointestinal smooth muscle and are responsible for promoting relaxation and peristalsis. Their blockade can lead to increased smooth muscle tone, reduced motility, and slowed colonic transit time. This effect, typically negligible in healthy individuals, can become clinically relevant in patients with RPF, where mechanical and inflammatory impairment of the colon already limits normal motility [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e–\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIndeed, the combination of extrinsic fibrotic compression and intrinsic pharmacologic inhibition of colonic relaxation can create a compounding effect, worsening symptoms such as constipation, cramping, and postprandial bloating. This may mimic or exacerbate features of colonic pseudo-obstruction, especially in cases where fibrosis is extensive or where vascular encasement leads to subtle mesenteric ischemia. Additionally, β₂-blockade may reduce mucosal perfusion by impairing vasodilation in the splanchnic circulation, theoretically increasing the risk of localized ischemic injury in compromised bowel segments [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eParadoxically, preclinical studies suggest that some NSBBs, particularly carvedilol, may have anti-fibrotic and anti-inflammatory properties. In models of chemically induced colitis, carvedilol has been shown to inhibit TGF-β1 expression, suppress NF-κB activation, and downregulate α-smooth muscle actin (α-SMA), key factors in intestinal fibrosis and myofibroblast activation [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. These data raise the intriguing possibility that NSBBs could attenuate fibrotic progression in chronic inflammatory conditions. However, the translation of these effects to retroperitoneal tissues remains speculative, especially considering the differing embryological origins and tissue environments of the colon and retroperitoneum.\u003c/p\u003e\u003cp\u003eGiven these complex and sometimes contradictory effects, the role of NSBBs in patients with RPF and gastrointestinal involvement must be carefully individualized. While their cardiovascular and hepatic indications remain valid, clinicians should consider β₁-selective alternatives (e.g., bisoprolol, atenolol) in patients who report gastrointestinal symptoms, particularly those consistent with hypomotility or mechanical bowel dysfunction.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe use of non-selective β-blockers in patients with retroperitoneal fibrosis warrants critical evaluation, especially in cases with colonic involvement. Their ability to inhibit β₂-mediated smooth muscle relaxation may amplify symptoms related to colonic dysmotility, adding a functional burden to the already present mechanical and inflammatory disruption caused by fibrosis. While experimental data point to potential anti-fibrotic effects of NSBBs, these benefits may not be clinically relevant—or may even be outweighed—by their adverse impact on gastrointestinal smooth muscle tone. Further studies are needed to better understand this interaction and guide pharmacologic choices in the management of RPF patients presenting with prominent abdominal symptoms.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate:\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConsent for publication:\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials:\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCompeting interests:\u003c/p\u003e\n\u003cp\u003eThe author declares that they have no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFunding:\u003c/p\u003e\n\u003cp\u003eNone.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAuthor\u003cspan dir=\"RTL\"\u003e\u0026rsquo;\u003c/span\u003es contributions:\u003c/p\u003e\n\u003cp\u003eThe author conceived the study, collected and analyzed the data, drafted the manuscript and approved the final version.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAcknowledgements:\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eVaglio A, Salvarani C, Buzio C. Retroperitoneal fibrosis. Lancet. 2006;367(9506):241\u0026ndash;251.\u003c/li\u003e\n\u003cli\u003eZen Y, Nakanuma Y. IgG4-related disease: a cross-organ perspective. Mod Pathol. 2011;24(4):489\u0026ndash;501.\u003c/li\u003e\n\u003cli\u003eCoarradi D et al. Immunopathology of idiopathic retroperitoneal fibrosis: role of dendritic cells and T lymphocytes. Am J Surg Pathol. 2007;31(4):494\u0026ndash;503.\u003c/li\u003e\n\u003cli\u003eKoep L, Zuidema GD. The clinical significance of idiopathic retroperitoneal fibrosis. Surgery. 1977;81(3):250\u0026ndash;257.\u003c/li\u003e\n\u003cli\u003eBrowning KN, Travagli RA. Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions. Compr Physiol. 2014;4(4):1339\u0026ndash;1368.\u003c/li\u003e\n\u003cli\u003eSalpeter SR et al. Cardiopulmonary effects of beta-blockers in patients with reactive airway or gastrointestinal conditions: a systematic review. Ann Intern Med. 2002;137(9):715\u0026ndash;725.\u003c/li\u003e\n\u003cli\u003eChang CH et al. Beta-blockers and intestinal barrier function: mechanisms of anti-inflammatory action. Biochem Pharmacol. 2013;85(9):1228\u0026ndash;1236.\u003c/li\u003e\n\u003cli\u003eBayoumi A, El-Bakly WM, Ali MA. Carvedilol attenuates colonic fibrosis and epithelial damage in murine colitis via inhibition of TGF-\u0026beta;1 and NF-\u0026kappa;B pathways. Front Pharmacol. 2021;12:635488.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Beta blocker","lastPublishedDoi":"10.21203/rs.3.rs-7651729/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7651729/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eRetroperitoneal fibrosis is a rare fibro-inflammatory disorder characterized by progressive deposition of dense collagenous tissue within the retroperitoneal space, enveloping vascular and visceral structures. Although most cases are idiopathic, certain pharmacological agents have been implicated in symptom exacerbation. This case report describes an acute deterioration of gastrointestinal function following initiation of a non-selective beta-adrenergic blocker in stable disease.\u003c/p\u003e\u003cp\u003eA 45-year-old Caucasian woman with dyslipidaemia and chronic sinus tachycardia underwent exploratory laparotomy for suspected peritoneal malignancy. Histopathology confirmed extensive fibrotic deposition with chronic inflammatory infiltrates and excluded neoplasia, establishing a diagnosis of retroperitoneal fibrosis. During three years of surveillance with serial laboratory assays and magnetic resonance imaging, the disease remained quiescent. To optimize heart-rate control, therapy with a beta-1-selective antagonist was replaced by propranolol 40 mg twice daily, a non-selective beta-adrenergic blocker. Within days, severe crampy abdominal pain, marked distension and altered bowel habits developed despite stable imaging. The close temporal relationship and the established role of beta-2 receptors in intestinal smooth muscle relaxation implicated non-selective blockade in aggravating colonic dysmotility on a background of fibrotic compression. Dietary modifications and low-dose antispasmodics provided only marginal relief.\u003c/p\u003e\u003cp\u003eThis case illustrates that non-selective beta-blockers may exacerbate gastrointestinal symptoms in retroperitoneal fibrosis by impairing smooth muscle relaxation. In patients with colonic involvement, beta-1-selective agents should be preferred, with careful consideration of cardiovascular benefits versus gastrointestinal risks.\u003c/p\u003e","manuscriptTitle":"Non-selective Beta-Blockers and Retroperitoneal Fibrosis: A Potential Factor in Symptomatic Exacerbation a case report.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-22 08:54:55","doi":"10.21203/rs.3.rs-7651729/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"17559030-f259-4a5c-a0c2-a39c4dda4485","owner":[],"postedDate":"September 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-22T08:54:55+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-22 08:54:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7651729","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7651729","identity":"rs-7651729","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}