Etiology of Hunner Lesions: Linking Immune Dysregulation and Chronic Inflammation in Interstitial Cystitis/Bladder Pain Syndrome
- 1Department of Urology, Wake Forest University School of Medicine, Winston-Salem, NC USA
- 2Wake Forest Institute for Regenerative Medicine, 391 Technology Way NE, Winston-Salem, NC 27101 USA
Abstract
Introduction and Hypothesis: Hunner lesions (HL) are distinctive ulcerative bladder lesions characterized by a central scar and surrounding erythema. Traditionally, HL has been used as a clinical diagnostic tool for a subset of patients with interstitial cystitis/bladder pain syndrome (IC/BPS); however, emerging evidence supports a unique pathophysiology for IC/BPS with HL (HIC) that is distinct from IC/BPS without HL (NHIC). This review is aimed at synthesizing current literature on the etiology of HL/HIC and evaluate whether HIC and NHIC warrant classification as separate clinical conditions with distinct management strategies.
Methods: A comprehensive literature review using PubMed was conducted to identify literature surrounding HL etiology and pathophysiology. Case–control studies, cohort studies, experimental studies, case reports, and animal studies were included; editorial comments and literature reviews were excluded from this review.
Results: Emerging data suggest that a subset of patients might be predisposed to HIC, including alteration in major histocompatibility complex (MHC) molecules, HLA amino acid positions, and additional protein expression alterations detected by RNA sequencing. Hypoxia-inducible factor activation and chronic ischemia have also been shown to play a role in HL development. Both local and systemic inflammation are seen in HIC, with clonal B-cell expansion influencing the upregulation of inflammatory cytokines, chemokines, and lymphoplasmacytic cells. With additional validation these biomarkers have the potential to serve as a diagnostic tool.
Conclusion: Hunner lesion with IC/BPS is a chronic condition likely caused by an upregulation of humoral immunity leading to an overexpression of inflammatory markers within the urothelium, suggesting an autoimmune-mediated pathology for this patient subgroup.
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BibTeX
@article{acoff2026etiology,
title = {{Etiology of Hunner Lesions: Linking Immune Dysregulation and Chronic Inflammation in Interstitial Cystitis/Bladder Pain Syndrome}},
author = {Eboni T. Acoff and Kaylee Ferrara and Hannah Ruetten and Gopal Badlani and Robert J. Evans and Amr El Haraki and Stephen J. Walker},
journal = {International Urogynecology Journal},
year = {2026},
month = jun,
doi = {10.1007/s00192-026-06739-9},
url = {https://doi.org/10.1007/s00192-026-06739-9},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Etiology of Hunner Lesions: Linking Immune Dysregulation and Chronic Inflammation in Interstitial Cystitis/Bladder Pain Syndrome
AU - Eboni T. Acoff
AU - Kaylee Ferrara
AU - Hannah Ruetten
AU - Gopal Badlani
AU - Robert J. Evans
AU - Amr El Haraki
AU - Stephen J. Walker
PY - 2026
DA - 2026/06/20
JO - International Urogynecology Journal
DO - 10.1007/s00192-026-06739-9
UR - https://doi.org/10.1007/s00192-026-06739-9
AB - Introduction and Hypothesis: Hunner lesions (HL) are distinctive ulcerative bladder lesions characterized by a central scar and surrounding erythema. Traditionally, HL has been used as a clinical diagnostic tool for a subset of patients with interstitial cystitis/bladder pain syndrome (IC/BPS); however, emerging evidence supports a unique pathophysiology for IC/BPS with HL (HIC) that is distinct from IC/BPS without HL (NHIC). This review is aimed at synthesizing current literature on the etiology of HL/HIC and evaluate whether HIC and NHIC warrant classification as separate clinical conditions with distinct management strategies. Methods: A comprehensive literature review using PubMed was conducted to identify literature surrounding HL etiology and pathophysiology. Case–control studies, cohort studies, experimental studies, case reports, and animal studies were included; editorial comments and literature reviews were excluded from this review. Results: Emerging data suggest that a subset of patients might be predisposed to HIC, including alteration in major histocompatibility complex (MHC) molecules, HLA amino acid positions, and additional protein expression alterations detected by RNA sequencing. Hypoxia-inducible factor activation and chronic ischemia have also been shown to play a role in HL development. Both local and systemic inflammation are seen in HIC, with clonal B-cell expansion influencing the upregulation of inflammatory cytokines, chemokines, and lymphoplasmacytic cells. With additional validation these biomarkers have the potential to serve as a diagnostic tool. Conclusion: Hunner lesion with IC/BPS is a chronic condition likely caused by an upregulation of humoral immunity leading to an overexpression of inflammatory markers within the urothelium, suggesting an autoimmune-mediated pathology for this patient subgroup.
SN - 0937-3462
SN - 1433-3023
ER -