Phenotyping Interstitial Cystitis/Bladder Pain Syndrome: Clinical and Mechanistic Evidence, Candidate Biomarkers, and Implications for Management

Interstitial cystitis and bladder pain syndrome are clinically overlapping conditions that should be distinguished according to Hunner lesion status. IC with Hunner lesions is a distinct inflammatory bladder disease characterized by urothelial denudation, lymphoplasmacytic infiltration, adaptive immune activation, and progressive structural impairment. The intensity and distribution of these inflammatory and structural abnormalities may vary among patients with IC, but the underlying pathological pattern is comparatively coherent. BPS without Hunner lesions is substantially more heterogeneous. Urothelial barrier dysfunction, mast cell and sensory nerve signaling, pelvic floor dysfunction, peripheral sensitization, and central or nociplastic pain mechanisms may contribute to symptoms in different combinations. Candidate urine and blood-based biomarkers, including cytokines, chemokines, neurotrophic factors, immune cell indices, and multiomics signatures, may support phenotyping, assessment of disease activity, or prediction of treatment response. However, most remain exploratory because their intended clinical use, analytical standardization, diagnostic thresholds, and external validity have not been established. This narrative review compares the clinical and histopathological features of IC and BPS, evaluates the evidence for proposed immune and neuroregulatory mechanisms, examines the translational status of candidate biomarkers, and discusses disease-specific and phenotype-guided management. These findings support a primary distinction between IC and BPS. Additional phenotyping is useful after this distinction to characterize heterogeneity within BPS and clinically relevant coexisting mechanisms.