Current Understanding and Future Perspectives of Interstitial Cystitis/Bladder Pain Syndrome

Abstract

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic disease characterized by suprapubic pain and lower urinary tract symptoms. Perhaps because of the heterogeneous nature of this disease and its multifactorial etiology, clinical trials in allinclusive populations of IC/BPS patients without phenotyping in the last decade have mainly failed to discover new therapeutic modalities of IC/BPS. Thus, phenotyping IC/BPS, aimed at identifying bladder-centric and/or bladder-beyond pathologies, including cystoscopic observation of Hunner or non-Hunner lesions of the bladder mucosa, is particularly important for the future of IC/BPS management. Based on recent discussions at international conferences, including the International Consultation on IC, Japan, it has been proposed that Hunner-lesion IC should be separated from other non-Hunner IC/BPS because of its distinct inflammatory profiles and epithelial denudation compared with non-Hunner IC/BPS. However, there are still no standard criteria for the diagnosis of Hunner lesions other than typical lesions, while conventional cystoscopic observations may miss atypical or small Hunner lesions. Furthermore, diagnosis of the bladder-centric phenotype of IC/BPS requires confirmation that identified mucosal lesions are truly a cause of bladder pain in IC/BPS patients. This review article discusses the current status of IC/BPS pathophysiology and diagnosis, as well as future directions of the proper diagnosis of bladder-centric IC/BPS, in which pathophysiological mechanisms other than those in inflammatory pathways, such as angiogenic and immunogenic abnormalities, could also be involved in both Hunner-lesion IC and non-Hunner IC/BPS. It is hoped that this new paradigm in the pathophysiological evaluation and diagnosis of IC/BPS could lead to pathology-based phenotyping and new treatments for this heterogeneous disease.

The O'Leary‐Sant Interstitial Cystitis Symptom Index is a clinically useful indicator of treatment outcome in patients with interstitial cystitis/bladder pain syndrome with Hunner lesions: A post hoc analysis of the Japanese phase III trial of KRP‐116D, 50% dimethyl sulfoxide solution

“…18 Furthermore, neovascularization with overexpression of angiogenic factors such as platelet-derived endothelial cell growth factor or vascular endothelial growth factor in the bladder mucosa has been identified as an important mechanism leading to glomerulations in non-Hunner-type IC/BPS. [19][20][21] Therefore, further phenotyping based on mucosal pathologies including angiogenic changes would be necessary to identify those bladdercentric IC patients suitable for intravesical DMSO treatment in the non-Hunner-type IC population. Moderate correlations between GRA and IC symptom variables including ICSI, ICPI, and NRS for bladder pain were observed.…”

“…However, a recent study reported that Hunner‐type IC bladders and a proportion of non‐Hunner‐type IC bladders with severe (grade 3) glomerulations exhibited similarities in terms of decreased urothelial cytoskeleton and cell proliferation protein expression in the bladder epithelium, suggesting a common pathophysiological process in Hunner‐type IC and a subgroup of non‐Hunner‐type IC 18 . Furthermore, neovascularization with overexpression of angiogenic factors such as platelet‐derived endothelial cell growth factor or vascular endothelial growth factor in the bladder mucosa has been identified as an important mechanism leading to glomerulations in non‐Hunner‐type IC/BPS 19–21 . Therefore, further phenotyping based on mucosal pathologies including angiogenic changes would be necessary to identify those bladder‐centric IC patients suitable for intravesical DMSO treatment in the non‐Hunner‐type IC population.…”

Components of the Endogenous Cannabinoid System as Potential Biomarkers for Interstitial Cystitis/Bladder Pain Syndrome

“…Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition causing pelvic pain, pressure, or discomfort that is perceived to be related to the urinary bladder, often accompanied by various other urinary symptoms, such as increased urinary urgency and frequency [ 1 , 2 ]. These symptoms present in the absence of infection or other identifiable causes, reflecting the idiopathic nature of the disorder [ 3 , 4 ].…”

Interstitielle Zystitis: Interventionelle und operative Therapie – mehr als eine Ultima Ratio

“…Typisch sind neben chronischen Beckenschmerzen, Druck-oder Missempfinden bis hin zu starken Schmerzen im Bereich der Blase auch irritative Beschwerden wie Pollakisurie, Nykturie oder imperativer Harndrang [1]. Neben den offensichtlichen Symptomen können bei einigen IC/BPS-Patienten zusätzlich zystoskopisch und/oder histologisch nachweisbare Veränderungen der Harnblase, die ulzerösen Hunner-Läsionen, auftreten [2,3]. Bis heute ist die Pathogenese weitestgehend ungeklärt und eine Vielzahl an verwechselbaren Erkrankungen machen die interstitielle Zystitis zu einer Ausschlussdiagnose.…”