Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and highly heterogenous condition of uncertain etiology. In previous work we characterized two phenotypic subgroups within IC/BPS: bladder-centric and non-bladder-centric. The goal of this study was to characterize the disease status and/or progression in these clinical subgroups.
Methods: 47 females (32 IC/BPS patients; 15 non-IC/BPS controls) were selected for this study and IC/BPS patients were further divided into two groups based on anesthetic bladder capacity (BC) = 400 cc (low; N=16) or > 400 cc (non-low; N=16). Within each BC subgroup, one-half of the patients were Hunner’s lesion positive (HL+) and the other half were HL-. Bladder biopsy tissue slides were stained with hematoxylin-eosin (for inflammation) and picrosirius red (for collagen content/architecture). CT-Fire software was used to quantify collagen density. Acute and chronic inflammation were graded as either minimal (1), moderate (2), or severe (3). HL and BC groups were independently compared to the control group (3-way). Continuous variables were evaluated by Kruskal Wallis tests, and categorical variables were evaluated with Fisher's exact test; p<0.05 was considered significant.
Results: HL+ patients had a lower overall collagen density (181.99 vs 232.72; p=0.026). Interestingly, HL+ patients showed more acute inflammation (56.3% vs 6.7%; p=0.010), and chronic inflammation (p=0.024) compared to controls. More importantly, while the overall collagen density was lower in HL+ patients, the peri-detrusor fiber deposition was significantly higher (50.0% vs 6.7%; p=0.017). Peri-inflammatory collagen thinning approached but did not reach significance (75% vs 33%; p=0.069). These observations were present in all HL+ patients, independent of BC. The HL- patients did not differ significantly from controls.
Conclusions: The presence of Hunner’s lesions, regardless of BC, is associated with a unique bladder mucosa in which collagen density is diminished while peri-detrusor collagen increases, along with a concomitant increase in inflammation. These findings suggest a dynamic collagen fiber destruction and redistribution process induced by inflammation, which may be the underlying pathophysiology of Hunner’s lesions.
Source of Funding: 1R01DK124599-01, R21DK106554-01
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