Hunner Lesion Phenotype in Interstitial Cystitis/Bladder Pain Syndrome: A Systematic Review and Meta-Analysis

Purpose: We compared demographics, clinical presentation, comorbidities, urinary profiles, and treatment responses between patients with interstitial cystitis/bladder pain syndrome with and without Hunner lesions. Materials and Methods: We performed a systematic review of the literature in PubMed (R) in February 2019. Publications were included if they compared data between patients with interstitial cystitis/bladder pain syndrome with and without Hunner lesions, yielding 59 articles. Meta-analysis was performed on a subset of clinical characteristics. Results: Meta-analysis showed that patients with interstitial cystitis/bladder pain syndrome with Hunner lesions were significantly older (MD 6.7 years, 95% CI 2.0-11.3, p = 0.005), reported higher urinary frequency (MD 3.2 per day, 95% CI 1.1-5.4, p = 0.003), nocturia (MD 1.0 per night, 95% CI 0.1-2.0, p < 0.034) and Interstitial Cystitis Symptom Index (MD 2.2, 95% CI 1.4-3.0, p < 0.001), but lower cystometric bladder capacity (MD -113 ml, 95% CI -164 to -61 ml, p < 0.001) compared to those with interstitial cystitis/bladder pain syndrome without Hunner lesions. There were no differences in pain scores (p = 0.105), symptom duration (p = 0.2) or sex (p = 0.83) between the 2 groups. While some studies reported higher rates of comorbid pain syndromes (eg fibromyalgia) among patients without Hunner lesions, overall results were conflicting. Patients with Hunner lesions had higher urinary levels of pro-inflammatory cytokines/chemokines (CXCL10, NGF, IL-6, IL-8, MIF), luminal nitric oxide and responded well to endoscopic treatment of the Hunner lesions (eg fulguration or triamcinolone injection). In comparative studies patients with interstitial cystitis/bladder pain syndrome with Hunner lesions responded better to oral cyclosporine A than those without Hunner lesions. Conclusions: Systematic review and meta-analysis demonstrated significant differences in demographics, clinical presentation, urinary marker profiles, and treatment responses between patients with and without Hunner lesions, suggesting that they may represent 2 distinct clinical phenotypes. Studies are needed to investigate their mechanistic differences.