Among the interstitial cystitis/bladder pain syndrome (IC/BPS) population, a minor subset of patients presents with Hunner’s lesions (HL). Lesion fulguration or intralesional triamcinolone injections are the recommended treatments for this distinct cystoscopic finding. However, symptom relapse often requires repeated procedures. Cyclosporine A (CyA) is a fifth-line treatment for IC/BPS due to the limited number of studies reporting its efficiency and potential adverse events [1]. The objectives of our study were to assess the clinical outcomes of refractory IC/BPS patients with HL treated with lesion fulguration in association with CyA as a maintenance therapy and to assess CyA safety profile. We hypothesized that low-dose CyA could allow sustained symptom alleviation while limiting adverse events, therefore decreasing the need for repeated procedures.

This was a retrospective observational study of refractory IC/BPS patients with HL treated with daily 1.5 mg/kg of CyA from April 2015 to March 2021. Lesion fulguration was performed on all patients prior to CyA introduction. Dose reduction was conducted in stable patients with prolonged treatment duration or in the occurrence of adverse events. Unsatisfied patients were allowed to undergo further procedures at any point in their follow-up while maintaining their CyA treatment. Data at the last follow-up was used to assess long-term treatment efficiency. Treatment response was defined as a Subjective improvement rate (SIR) of ≥ 50%. Patient Global Impression of Improvement (PGI-I) was also collected throughout follow-ups.

Among our cohort of 22 patients, the median follow-up under CyA treatment was 27 months (interquartile range: 13.0-45.3). Half of the patients had already received fulgurations in the past. At the last follow-up, patients reported sustained significant pain reduction with a median pain score of 0/10 compared to 8/10 prior to CyA introduction (P < 0.001). Urinary frequency per 24 hours significantly decreased to 9.5 compared to 20.8 pre-treatment (P < 0.001) and nocturia also decreased to 2.3 episodes per night in contrast to 6 pre-treatment (P < 0.001). SIR and PGI-I were of 90% and 1 respectively, including four patients who considered themselves cured (SIR 100%). All patients but one were considered treatment responders (SIR ≥ 50%). Three patients needed one additional treatment with either triamcinolone injections or fulguration due to pain relapse at their follow-up of 3, 13 and 33 months. Detailed clinical outcomes are shown in table 1. 

CyA dose was decreased to 1.2 mg/kg daily or less in 12 patients who remained relieved subsequently. Reasons for dose decrease were long-term symptom alleviation (6), increased creatinine measurements (5) or decrease in platelets or leucocytes (1). Significant overall decrease in renal function was observed, however remained clinically not significant and improvement in renal function was observed following CyA dose reductions. De novo arterial hypertension or worsening in chronic hypertension was diagnosed in 3 patients and was well-controlled with the introduction or adjustment of antihypertensive medication. One patient discontinued CyA due to abdominal pain. Adverse events are reported in table 2.

Our results demonstrated statistically and clinically significant sustained improvement in pain and urinary symptoms, as well as an important subjective improvement in patients treated with CyA for a median of 27 months following fulguration. The time interval before symptom resurgence following fulguration reported in the literature is approximately 12 months in the majority of patients [2]. In our cohort, only three patients required additional procedures after 3, 13 and 33 months. Moreover, our population was composed of refractory patients, many of whom did not improved with numerous medical treatments and had already received previous fulgurations. This may suggest that our population was characterized by an important bladder inflammation enabling symptom relapse. Considering that long-term benefits were obtained, CyA might be responsible for effective suppression of bladder inflammatory condition following the baseline fulguration and therefore preventing relapses. Previous studies have reported hypertension and nephrotoxicity as main significant adverse events with daily CyA doses of 2 or 3 mg/kg [3]. The low dose of 1.5 mg/kg or less may have limited adverse events while still providing symptom relief.

Oral CyA seems to allow a sustained long-term response following HL fulguration by alleviating pain, decreasing urinary symptoms and procuring great subjective improvement. The low dose of 1.5 mg/kg appears to have limited adverse events while preventing the need for repeated procedures.

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