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Clinical Phenotyping of Interstitial Cystitis/Bladder Pain Syndrome

By: H. Henry Lai, MD | Posted on: 01 Sep 2022

Interstitial cystitis/bladder pain syndrome (IC/BPS) is one of the most challenging clinical syndromes that urologists manage. Despite presenting with similar symptoms of chronic pelvic/bladder pain, the patient population is heterogeneous and consists of distinct subgroups or “phenotypes” that may have different underlying pathophysiology. Management of IC/BPS can be optimized if these phenotypes can be recognized in the office, and targeted treatments are offered. Here we will highlight what we have learned about clinical phenotyping of IC/BPS, and how to identify these phenotypes in office.

The first phenotype of IC/BPS is “Hunner lesion” (previously known as Hunner ulcers or ulcerative IC). A recent systematic review and meta-analysis showed that patients with Hunner lesion were significantly older (by 6.7 years), had higher urinary frequency and nocturia (mean differences 3.2/day and 1.0/night), lower rates of chronic overlapping pain syndromes (eg fibromyalgia), and higher urinary levels of pro-inflammatory cytokines/chemokines (CXCL10, NGF, IL-6, IL-8, MIF) than patients without Hunner lesions.1 These results suggested that IC/BPS patients with Hunner lesion have bladder-centric phenotype, since they have visible inflammatory lesions in the bladder, worse urinary symptoms, and fewer systemic (nonurological) symptoms.

“Management of IC/BPS can be optimized if these phenotypes can be recognized in the office, and targeted treatments are offered.”

Diagnosis of Hunner Lesion: Cystoscopy remains the only reliable way to diagnose Hunner lesions. In the majority of cases, Hunner lesion can be identified with office flexible cystoscopy without formal distention of the bladder under general anesthesia. Flexible cystoscopy is well tolerated, and can identify patients for targeted treatments with fulguration and/or triamcinolone injection. A visual atlas is available to facilitate the recognition of Hunner lesion in office.2 Early diagnosis by cystoscopy is recommended in patients suspected to have Hunner lesion, without requiring them to fail other behavioral, oral, or intravesical treatments first. The updated AUA Guideline states that 1) men and women over the age of 50 years, 2) those who have failed conventional IC/BPS therapies but have never had cystoscopy, and 3) those who have reported “abnormal cystoscopic findings” should undergo cystoscopy.3 The odds of identifying Hunner lesion are significantly higher in patients over 50, so it is reasonable to offer cystoscopy to this age group. However, performing cystoscopy in every single IC/BPS patient is not advisable. Hunner lesion may be found in both men and women. Men with chronic pelvic pain (eg chronic prostatitis) should also be asked about IC/BPS symptoms such as increased pain with bladder filling or painful urinary urge. Many men thought to have chronic prostatitis may also have IC/BPS,4 and may benefit from cystoscopic evaluation.

Treatment of Hunner Lesion: Fulguration with electrocautery and/or injection of triamcinolone under general anesthesia should be performed. Oral cyclosporine A may be offered to Hunner patients who are refractory to fulguration and/or triamcinolone.3

The second phenotype of IC/BPS includes patients with associated pelvic floor tenderness.5 About 80% of female and male IC/BPS patients had some degree of pelvic floor tenderness on pelvic examination. The higher the numbers of levator muscle groups involved with tenderness, the worse their urinary and pain symptoms and quality of life.

Diagnosis of Pelvic Floor Tenderness: A systematic pelvic examination can be performed in females (in the lithotomy position) and in males (in the standing prone position) to assess for the presence or absence of pelvic floor tenderness on the left and right levator ani muscles anteriorly and posteriorly, and the left and right obturator internus muscles laterally. A standardized pelvic examination protocol may be adopted for clinic use.5

Treatment of Pelvic Floor Tenderness: There is level 1 evidence based on a randomized controlled trial showing that IC/BPS patients with pelvic floor tenderness on pelvic examination had a significantly higher global assessment response rate when they were randomized to receive myofascial physical therapy versus global therapeutic massage (59% vs 26%, p=0.0012).6 The AUA Guideline states that myofascial manual physical therapy (if appropriately trained clinicians are available) should be offered to IC/BPS patients who present with pelvic floor tenderness on pelvic examination.3 However, pelvic floor strengthening exercises (Kegel exercises) should be avoided.

Figure. Clinical phenotypes of IC/BPS and their targeted treatments. PT, physical therapy. tx, therapy.

A third IC/BPS phenotype that has emerged from recent studies are patients who present with widespread pain beyond the pelvis.7 Among men and women with IC/BPS, only about 25% (1 in 4) reported pain in the pelvic region only. The majority (3 of 4) also reported pain outside of the pelvis in addition to pelvic pain. About 33% (1 in 3) reported widespread pain (nonurological pain) involving multiple body regions outside the pelvis (eg upper and lower extremity, head, and neck) in addition to the pelvic pain. IC/BPS patients with widespread pain may also present with additional chronic pain diagnoses such as irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, or migraine headache. It is believed that IC/BPS patients with widespread pain have different, “top-down” etiology of their systemic pain, involving central sensitization (enhanced amplification of their afferent signals in the central nervous system resulting in increased perceived pain), decreased descending inhibition from the higher brain centers to the spinal pain gate, and systemic processes (eg pro-inflammatory state) perpetuating their pain. These patients have centralized pain. Their bladder or pelvis may simply be a “bystander” or pelvic manifestation of their systemic pain. This is supported by functional MRI studies that showed different brain functional connectivity patterns between IC/BPS patients with versus without widespread pain.8 The extent of widespread pain also correlated to greater sensitivity to pressure pain.9 The extent of widespread pain, amount of nonurological somatic symptoms, and poorer overall health were predictive of worsening pain and urinary outcomes over 12 months of followup.10

Diagnosis of Widespread Pain: Widespread pain can be diagnosed using a simple body map as described previously.7 The body map can be completed in less than a minute.

Treatment of Widespread Pain: Conceptually, IC/BPS patients with widespread pain or centralized pain phenotype should benefit more from systemic therapies (eg tricyclic and neuroleptic medications) and interdisciplinary pain management (eg cognitive behavioral modification) addressing their systemic pain and psychosocial issues than from local therapies that target the bladder (eg intravesical instillation, pentosan polysulfate) or the pelvic floor (myofascial physical therapy). However, the optimal strategies to manage these patients remain poorly defined (as opposed to Hunner lesion patients who truly have “IC” with inflammation in the interstitium).

In summary, IC/BPS patients may be classified into 3 major phenotypes in the clinic: 1) Hunner lesion (bladder-centric), 2) pelvic floor tenderness (pelvic floor), and 3) widespread pain (centralized pain). Specific treatments may be offered to target these clinical phenotypes to optimize the management of IC/BPS (see Figure).

  1. Lai HH, Pickersgill NA, Vetter JM. Hunner lesion phenotype in interstitial cystitis/bladder pain syndrome: a systematic review and meta-analysis. J Urol. 2020;204(3):518-523.
  2. Ronstrom C, Lai HH. Presenting an atlas of Hunner lesions in interstitial cystitis which can be identified with office cystoscopy. Neurourol Urodyn. 2020;39(8):2394-2400.
  3. Clemens JQ, Erickson DR, Varela NP, Lai HH. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2022;208(1):34-42.
  4. Lai HH, Krieger JN, Pontari MA, Buchwald D, Hou X, Landis JR. Painful bladder filling and painful urgency are distinct characteristics in men and women with urological chronic pelvic pain syndromes: a MAPP Research Network study. J Urol. 2015;194(6):1634-1641.
  5. Gupta P, Gallop R, Spitznagle T, et al. Is pelvic floor muscle tenderness a distinct urologic chronic pelvic pain syndrome phenotype? Findings from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Symptom Pattern Study. J Urol. 2022;208(2):341-349.
  6. FitzGerald MP, Payne CK, Lukacz ES, et al. Randomized multicenter clinical trial of myofascial physical therapy in women with interstitial cystitis/painful bladder syndrome and pelvic floor tenderness. J Urol. 2012;187(6):2113-2118.
  7. Lai HH, Jemielita T, Sutcliffe S, et al. Characterization of whole body pain in urological chronic pelvic pain syndrome at baseline: a MAPP Research Network study. J Urol. 2017;198(3):622-631.
  8. Kutch JJ, Ichesco E, Hampson JP, et al. Brain signature and functional impact of centralized pain: a Multidisciplinary Approach to the study of chronic Pelvic Pain (MAPP) Network study. Pain. 2017;158(10):1979-1991.
  9. Harte SE, Schrepf A, Gallop R, et al. Quantitative assessment of nonpelvic pressure pain sensitivity in urologic chronic pelvic pain syndrome: a MAPP Research Network study. Pain. 2019;160(6):1270-1280.
  10. Naliboff BD, Stephens AJ, Lai HH, et al. Clinical and psychosocial predictors of urological chronic pelvic pain symptom change in 1 year: a prospective study from the MAPP Research Network. J Urol. 2017;198(4):848-857.