MAPP Research Network Confirms Clear Differences in Patients With Hunner’s Lesions
In an effort to support the proposition that Hunner’s lesions represent a distinct patient group, the MAPP Research team conducted a deep phenotypic study. They analyzed 193 men and 385 women with chronic pelvic pain of whom 28 out of 223 patients had confirmed Hunner’s lesions. Those with lesions were sig- nificantly older, had more nighttime urination and higher symptom scores than those without. But, interestingly, they had less widespread body pain, fewer chronic overlapping pain con- ditions and lower fibromyalgia scores than those without. Hunner’s patients also had less anxiety, perceived stress and catastrophizing. The authors concluded “The deep phenotyping studies from MAPP provided strong evi- dence that Hunner lesion is a distinct clinical phenotype different from non- Hunner lesion.”
Source: AUA 2020 Abstract MP07- 03 - COMPARISON OF DEEP PHENOTYPING FEATURES OF UCPPS PATIENTS WITH AND WITHOUT HUNNER LESION- A MAPP RESEARCH NETWORK STUDY
Hunner’s Lesion Biopsies Show Intense Inflammation
Researchers in Japan conducted Next Generation RNA sequencing to look for any disease specific genes associated with Hunner’s Lesions. This study revealed an adaptive and innate immune-mediated inflamma- tory nature of Hunner’s lesions, accompanying epithelial dysfunction. They identified CXCR3, CXCL9/10/11, IL-17A/F, TLR6/7/8, NOD2, FOXP3 and PD-L1/2 for the first time, as potential pathognomonic genes. Local dynamic changes of Th17/Treg axis, in association with PD-1/PD-L1 pathway, may be responsible for HIC pathophysiology.
Source: AUA 2020 Poster MP07-02 COMPARATIVE TRANSCRIPTOME ANALYSIS OF IC/BPS WITH HUNNER LESIONS AND BACILLUS CALMETTE-GUERIN RELATED CYS- TITIS BY NEXT-GENERATION RNA- SEQUENCING: DISCOVERY OF DISEASE-SPECIFIC GENES AND ASSOCIATED BIOLOGICAL PATH- WAYS
Best Therapy for Hunner’s Lesions
Researchers in Canada sought to determine if cyclosporine A (Cya) added effectiveness to the treatment of Hunner’s Lesions if used in con- junction with steroid injections or fulguration. This was a retrospective observational study of 20 refractory IC-HL patients treated with daily 1.5 mg/kg of CyA following fulguration (n[16) or triamcinolone injection (n[4) between 2007 and 2019. Among the 20 patients, the median pain score was 0/10 (8/10 pre-treatment) and only 2 patients still reported flares. Median SIR and PGI- I were 82.5% and 1/7 respectively, including 6 patients who considered themselves cured (SIR 100%). Post- treatment urgency, frequency and nocturia also significantly improved. Following the procedure, 4 patients experienced symptoms relapse and required additional procedures while continuing CyA medication for adequate symptom relief. All other 16 patients maintained symptom alleviation at the last follow-up. No patient presented elevated blood pressure or clinically significant elevation in creatinine levels. They concluded that cyclosporine A appears to be an efficient treatment following HL fulguration or triamcinolone injection by allowing sustained pain alleviation, great subjective improvement and a decrease in UF and nocturia. The low dose of 1.5 mg/kg limits adverse events while still preventing symptom recurrence.
Source: AUA 2020 Abstract MP07- 05 - DESCRIPTIVE ANALYSIS OF PATIENTS WITH HUNNER LESION TREATED WITH FULGURATION OR INTRALESIONAL TRIAMCINOLONE INJECTIONS IN ASSOCIATION WITH CYCLOSPORINE A
Hunner’s Lesions Respond Well To Early, Conservative Treatment
This study describes a stepwise management of patients with Hunner lesions and presents patient out- comes from a single institution from January 2005 to January of 2015. Fifty-five patients with Hunner’s lesions were included. Mean age was 65 years, 76% were female, and median symptom duration was 2 years. All patients had a biopsy to rule out malignancy with therapeutic fulguration which resulted in subjective symptom improvement in 82% and median time to repeat proce- dures was 12 months. Triamcinolone injection into the lesion was done in 35 patients and 91% reported subjective improvement. Repeat injections were done for 74% and median time between injections was 8 months. AUA symptom scores and quality of life improved significantly with both treatment modalities. Additional treatment with cyclosporine was used in 47% and only 7% (4 out of 55) went on to have their bladder removed. The authors found that patients with Hunner lesions benefitted from early, conservative treatments to endo- scopic management. They stated that excellent symptom control can be achieved with biopsy/fulguration and triamcinolone injections but recur- rence is common and repeat treat- ments are needed for most patients.
Source: Crescenze IM, et al. HUNNER LESION DISEASE ADVANCED MANAGEMENT OF PATIENTS WITH ULCERATIVE INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME. Urology. 2019 Aug 20
New Urine Test Shows High Confidence in Correctly Diagnosing IC
Researchers continue to seek new ways to diagnose Hunner’s lesions without resorting to painful hydrodistention and/or biopsy. The search for a new, accurate urine test, has been the goal for many research teams over the years. In the IP4IC study, researchers at Beaumont Hospital measured urinary cytokine levels 146 IC patients and 262 asymptomatic controls. A separate smaller dataset, P3, was collected in the clinic with physician documented diagnosis. This method correctly classified 146 of 146 (100%) IC participants, both with and without Hunner’s lesions, and 262 of 262 (100%) control participants in the training set. For the validation set, 100% (N=26/26) IC patients and 96.3% (N=26/27) controls were cor- rectly identified. A combination of both non-invasive urinary cytokines as well as pain and symptom scores was required for a classifier with strong validity. This may be the holy grail of new diagnostic testing for IC. It is high confidence urine test that could drive a personalized medical diagnosis of patients with suspicion of IC based on inflammation and pain and symptoms.
Source: Lamb L, et al. MP39-11 TOWARD PERSONALIZED MEDICINE FOR AN INTERSTITIAL CYSTITIS INDIVIDUALIZED DIAGNOSIS USING A NEW BLADDER INFLAMMATION SCORE
Epstein-Barr Virus Implicated In Hunner’s Lesions
Researchers in Taiwan suspected that the Epstein Barr virus could play a role in chronic IC/BPS and long- term, persistent bladder inflammation. They studied 16 patients with Hunner’s lesions, 23 with non- Hunner’s IC/BPS and ten patient controls. Their results were stunning. They discovered that 87.5% of patients with Hunner’s lesions in their study had active Epstein Barr
infection. A total of 46.2% of patients with IC/BPS had evidence of EBV infection in the bladder. Those with EBV infection had more severe clinical symptoms, more severe bladder pain and a smaller bladder capacity.
Source: Jia-Fong J, et al. MP39-07 THE ROLE OF EPSTEIN-BARR VIRUS INFECTION IN BLADDER OF INTER- STITIAL CYSTITIS/BLADDER PAIN SYNDROME
Next Generation Sequencing Reveals Distinct Genomic Profiles in IC/BPS
Bladder pain syndrome/interstitial cystitis (BPS/IC) comprises a diverse variety of clinical subtypes/pheno- types. Among them, BPS/IC with Hunner’s lesions has been implied to be a distinct entity, histologically characterized by inflammatory infil- trates and urothelial denudation. In this study, researchers performed sequencing-based whole transcrip- tome analysis to identify differentially expressed genes (DEGs) and charac- terize the genomic landscape in BPS/IC.
A total of 54 urinary bladder biopsy samples were taken from 33 patients with BPS/IC with (12) (one each from the lesion and a non- lesion area; n = 24 in total) or without (21) Hunner lesions, and 9 non-IC patients without bladder symptoms and pathology, and sub- jected to whole RNA-sequencing. A total of 17,363 DEGs were identified among the groups. Two clusters emerged. Cluster 1: BPS/IC with Hunner lesions. Cluster 2: BPS/IC without Hunner lesions and non-IC control (Fig. 1).
DEGs upregulated in BPS/IC with Hunner lesions were significantly enriched in the T/B cell receptor sig- naling, chemokine signaling, Th17 cell differentiation, VEGF signaling, NF-κB signaling, NOD-like receptor signaling, Toll-like receptor signaling, inflammatory mediator regulation of TRP channels, and GAG degradation pathways, while those downregulated in BPS/IC with Hunner lesions were significantly related to the adher- ence/tight junction and estrogen sig- naling pathways (all P<0.05). On the other hand, DEGs in BPS without Hunner lesions were only 104 genes, which analysis could not find any significant biological pathways.
The results demonstrated a distinct genomic profile of BPS/IC with Hunner lesions. Urothelial deficiency, inflammatory/immune responses, aberrant vascularization, and abnor- mal estrogen signaling pathway may
be involved in the pathophysiology of BPS/IC with Hunner lesions.
Source: Yoshiyuki, A. MP39-02
WHOLE-TRANSCRIPTOME PROFILING IN BLADDER PAIN SYNDROME/INTERSTITIAL CYSTITIS BY NEXT-GENERATION SEQUENCING: A DISTINCT GENOMIC LANDSCAPE BY THE PHENOTYPES