Interstitial cystitis/bladder pain syndrome





Introduction


Interstitial cystitis/bladder pain syndrome (IC/BPS) is a heterogeneous and symptom-based condition marked by bladder or urethral pain and associated lower urinary tract symptoms, especially urinary frequency and urgency, in the absence of infection and other demonstrated pathology. Tremendous efforts have been made to gain an understanding of this disease, but the etiology remains unclear. This chapter will present current understanding and controversies surrounding nomenclature and definition of the disorder, pathogenesis, and diagnostic approach. Finally, management options, from conservative to surgical, are presented incorporating the latest clinical evidence and consensus guideline recommendations.


Nomenclature


Efforts to improve the clinical outcomes of women with IC/BPS have been complicated by a lack of international consensus on the definition of and diagnostic criteria for this challenging condition. In 1987, for research purposes, the National Institutes of Health (NIH) established standardized diagnostic criteria for IC ( ; Box 35.1 ). However, these expert consensus–based research criteria were quite restrictive and were found to be less useful for clinical purposes. In fact, among 269 women followed for 1 year as part of the National Interstitial Cystitis Database study, 60% of those thought very likely to have IC would not be diagnosed based on these criteria ( ).



Box 35.1

(From Gillenwater JY, Wein AJ. Summary of the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases Workshop on Interstitial Cystitis , Bethesda, MD, August 28–29, 1987, National Institutes of Health. J Urol . 1988;140:203.)

The 1987 National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Diagnostic Criteria for Interstitial Cystitis


Category A: At least one of the following findings on cystoscopy:





  • Diffuse glomerulations (≤10 per quadrant) in at least three quadrants of the bladder



  • A classic Hunner ulcer



Category B: At least one of the following symptoms:





  • Pain associated with the bladder



  • Urinary urgency



Exclusion criteria:





  • Age <18 years a



  • Urinary frequency while awake <8 times per day



  • Nocturia fewer than two times per night



  • Maximal bladder capacity >350 mL while patient is awake



  • Absence of an intense urge to void with bladder filled to 150 mL of water with medium filling rate (30–100 mL/min) during cystometry



  • Involuntary bladder contractions on cystometry using medium filling rate



  • Duration of symptoms <9 months a



  • Symptoms relieved by antimicrobial agents (antibiotics, urinary antiseptics), anticholinergics, or antispasmodics a



  • Urinary tract infection in the past 3 months a



  • Active genital herpes



  • Vaginitis a



  • Uterine, cervical, vaginal, or urethral cancer within the past 5 years a



  • Bladder or ureteral calculi a



  • Urethral diverticulum a



  • History of cyclophosphamide or chemical cystitis or tuberculosis or radiation cystitis



  • Benign or malignant bladder tumors




Relative exclusion criteria.




Over the last 20 years, various professional organizations have proposed different nomenclature for painful bladder conditions, with differing diagnostic recommendations. In 2002, the International Continence Society focused on bladder pain and introduced the term painful bladder syndrome (PBS). PBS was defined as the complaint of suprapubic pain related to bladder filling accompanied by other symptoms, such as increased daytime and nighttime frequency, in the absence of proven urinary infection or other obvious pathology ( ).


In 2008, the European Society for the Study of Interstitial Cystitis (ESSIC) reached a consensus to rename IC and PBS to BPS ( ). BPS would be diagnosed on the basis of chronic pelvic pain, pressure, or discomfort perceived to be related to the urinary bladder accompanied by at least one other urinary symptom, such as persistent urge to void or urinary frequency for greater than 6 months. In a departure from other contemporaneous guidelines, ESSIC recommended that classification of BPS types might be performed according to findings at cystoscopy with hydrodistention, as well as histologic findings in bladder biopsies ( Box 35.2 ). Confusable diseases as the cause of the symptoms must be excluded ( Table 35.1 ). The presence of other organ symptoms, as well as cognitive, behavioral, emotional, and sexual symptoms, should be addressed.



Box 35.2

(From van de Merwe JP, Nordling J, Bouchelouche P, et al. Diagnostic criteria, classification, and nomenclature for painful bladder syndrome/interstitial cystitis: an ESSIC proposal. Eur Urol . 2008;53:60. With permission.)

Schematic Representation of the ESSIC Approach for Diagnosis of Interstitial Cystitis/Bladder Pain Syndrome (2008)







BPS , Bladder pain syndrome; ESSIC , European Society for the Study of Interstitial Cystitis; IC , interstitial cystitis.



TABLE 35.1

Confusable Diseases for Bladder Pain Syndrome in Women

(Modified from van de Merwe JP, Nordling J, Bouchelouche P, et al. Diagnostic criteria, classification, and nomenclature for painful bladder syndrome/interstitial cystitis: an ESSIC proposal. Eur Urol . 2008;53:60.)






































































Confusable Disease Excluded or Diagnosed by



  • Carcinoma and carcinoma in situ




  • Cystoscopy and biopsy




  • Infection with







    • Common intestinal bacteria





  • Routine bacterial culture







    • Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium, Corynebacterium urealyticum, Candida species





  • Special cultures







    • Mycobacterium tuberculosis





  • Dipstick, if sterile pyuria, culture for M. tuberculosis







    • Herpes simplex virus or human papillomavirus





  • Physical examination, culture




  • Radiation




  • Medical history




  • Chemotherapy, including immunotherapy with cyclophosphamide




  • Medical history




  • Antiinflammatory therapy with tiaprofenic acid




  • Medical history




  • Bladder neck obstruction or neurogenic outlet obstruction




  • Uroflowmetry and ultrasound




  • Bladder stone




  • Imaging or cystoscopy




  • Lower ureteric stone




  • Medical history and/or hematuria: upper urinary tract imaging such as CT or IVP




  • Urethral diverticulum




  • Medical history, physical examination, MRI or ultrasound




  • Urogenital prolapse




  • Medical history, physical examination




  • Endometriosis




  • Medical history, physical examination




  • Vaginal candidiasis




  • Medical history, physical examination




  • Cervical, uterine, or ovarian cancer




  • Physical examination, biopsies




  • Incomplete bladder emptying (retention)




  • Postvoid residual urine volume measured by ultrasound scanning




  • Overactive bladder




  • Medical history




  • Pudendal nerve entrapment




  • Medical history, physical examination, nerve block may help confirm diagnosis




  • Pelvic floor muscle–related pain




  • Medical history, physical examination


The diagnosis of a confusable disease does not necessarily exclude a diagnosis of bladder pain syndrome.

CT , Computed tomography; IVP , intravenous pyelogram; MRI , magnetic resonance imaging.


The terminology most widely used clinically in the United States is IC/BPS, defined by the Society for Urodynamics and Female Urology as “[a]n unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than six weeks duration, in the absence of infection or other identifiable causes” ( ). This definition allows treatment to begin after a relatively short symptomatic period (6 weeks rather than 6 months, as in the ESSIC definition) and was used by the American Urological Association (AUA) in their IC/BPS guidelines published in 2011 and amended in 2015 ( ).


Recently, international IC/BPS experts have called for the development of more consistent nomenclature and guidelines for IC/BPS ( ; ). It has long been recognized that some patients with IC/BPS have erosive bladder lesions (“Hunner lesions”), and increasing evidence supports different treatment outcomes in patients with such lesions. Given this, interest has grown in classifying and defining IC/BPS based on the presence or absence of these lesions, sometimes called Hunner lesion disease versus non–Hunner lesion disease, or ulcerative IC and nonulcerative IC (Whitmore et al.). We anticipate that future diagnostic classifications for IC/BPS are likely to include this categorization.


Epidemiology


First described over a century ago by , , and , IC/BPS was not studied from an epidemiologic standpoint until the last several decades. Likely related to changing definitions of IC, reported prevalence rates varied substantially among early population-based studies, ranging widely from 18 to 865 women per 100,000 (0.02%–0.9% prevalence; ). Use of more modern definitions and varying study methodology led to subsequent prevalence estimates ranging from 0.45% ( ) to as high as 12.6% ( ).


Given the lack of objective tests available to diagnose the condition, epidemiologic studies generally fall into three categories: self-report studies, symptom assessments, and review of billing data/diagnosis codes ( ). These varied methods likely contribute to the wide range of estimates regarding burden of disease. In a population-based, cross-sectional survey of individuals in the Boston area, reported the prevalence of PBS as 0.83% to 2.71% of women, depending on the definition used. Perhaps the most rigorous large-scale estimate of disease prevalence is provided by the RAND Interstitial Cystitis Epidemiology (RICE) study, a US population-based telephone survey. RICE investigators estimated the prevalence of IC/BPS in women 18 years of age and older to range from 2.7% to 6.5%, which translated to 3.3 to 7.9 million adult US women ( ). Prevalence estimates in female populations are consistently higher than in male populations, with investigations based on diagnosis in clinical practice suggesting a female-to-male ratio of 5:1 ( ), whereas population-based studies find a lower ratio (2–3:1; ). In population-based studies, IC/BPS is not consistently associated with any racial/ethnic background but is most common in middle-aged groups (40–59 years range) and those with lower socioeconomic status ( ; ).


Regardless of the exact prevalence of IC/BPS, this condition has been shown to overlap with many other pain syndromes and has a significant impact on patients’ quality of life. Many IC/BPS patients suffer from fibromyalgia, irritable bowel syndrome, anxiety, and depression ( ; ; ). As many as 85% of patients with IC/BPS will be diagnosed with high-tone pelvic floor dysfunction or levator ani pain, which often manifests as general pelvic pain, dyspareunia, urinary hesitancy, and difficulty with defecation ( ). Epidemiologic studies confirm that women with IC/BPS symptoms have poorer self-reported physical and mental health than the general US population ( ).


Etiology


The etiology of IC/BPS is currently unknown and likely to be multifactorial. A comprehensive review of this broad topic is beyond the scope of this chapter; therefore, we briefly review several potential IC/BPS etiologies, including both peripheral and central causes, with a focus on recent research results.


Epithelial alterations


Increasing evidence suggests that alterations of the urothelium (specialized transitional epithelium lining the renal pelvis, ureters, and bladder) play an important role in IC/BPS. Both molecular and structural uroepithelial changes have been observed in patients with IC/BPS and in animal models of the disease ( ). The urothelium forms an efficient barrier against potentially harmful urine components. Also, activation of urothelial cells by chemical, thermal, or mechanical stimuli can cause the release of various mediators or neurotransmitters, which may influence nerve activity, detrusor cell contraction, and ultimately bladder function ( ). Thus, a wide variety of epithelial dysfunctions, such as altered expression or sensitivity of molecular targets, channels, or receptors, might lead to abnormal sensation and function such as that seen in IC/BPS.


Histologic examination of the bladder in IC/BPS differs based on the presence or absence of Hunner lesions identified during cystoscopy (see Diagnostic Cystoscopy ). The bladder mucosa of patients with Hunner lesion disease is characterized by chronic inflammatory changes, including lymphocytes, plasma cells, macrophages, neutrophils, and mast cells, particularly between the urothelium and lamina propria (suburothelium) ( ). Similar inflammation is not seen in non–Hunner lesion IC/BPS. Others have reported that findings of pancystitis, clonal B-cell expansion, and epithelial denudation are unique to Hunner lesion disease ( ). These differences suggest that different disease mechanisms are involved in IC/BPS patients with and without Hunner lesions, supporting proponents of new IC/BPS diagnostic classifications that separate Hunner lesion disease from other types of IC/BPS ( ).


Other mucosal abnormalities do not clearly differ in IC/BPS patients with or without Hunner lesions. Immunohistological studies of bladder mucosa from bladder biopsies of IC/BPS patients with and without Hunner lesions have demonstrated differences in markers related to inflammation, angiogenesis, fibrosis, and denudation compared with controls. In some cases, the changes correlate with symptom outcomes. reported increased TNF-α, VEGF, CD31, and TGF-β in IC/BPS patients with and without Hunner lesions compared with controls, whereas increased mast cell tryptase and collagen were observed in Hunner lesion patients only (compared with non–Hunner lesion patients and controls). The increased expression of CD31, a protein marker related to angiogenesis, in IC/BPS patients had the highest correlations with pain and urinary symptoms.


Gene expression studies in RNA taken from bladder biopsies also suggest that disease mechanisms may differ in IC/BPS patients with and without Hunner lesions. In one study, patients with Hunner lesions had a distinct gene expression profile, with upregulation of genes involved in biological pathways related to cell proliferation, the immune system, and infectious processes ( ). The RNA sequence analysis from IC/BPS patients without Hunner lesions did not differ from controls.


An elevated mast cell count in the bladder muscularis was long promoted as a diagnostic histopathologic feature of IC/BPS, and different values for mast cell counts in the detrusor layer were proposed as a diagnostic marker. studied 69 patients with IC/PBS (diagnosed based on the 1987 NIH criteria and including both ESSIC types 2 and 3) and 37 controls (with and without non-IC/BPS chronic cystitis) and demonstrated that the presence of mast cells correlated with the level of background lymphoplasmacytic infiltrate, but not with the diagnosis of IC. This suggests that mast cell counts are not of value in diagnosing IC/BPS.


The urothelium’s surface coat of glycosaminoglycans (GAG) has been proposed to be deficient in some patients with IC/BPS. When the GAG layer is damaged, the urothelium has increased permeability to urine components, which may result in local inflammation, neural sensitization, and subsequent pain, frequency, and urgency. Important components of the GAG layer include chondroitin sulfate, hyaluronic acid, heparin sulfate, dermatan sulfate, and keratin sulfate ( ), and early research identified a lack of chondroitin sulfate in the GAG layer of IC/BPS patients ( ). Several agents with GAG-like properties, such as sodium hyaluronate, heparin, and pentosan polysulfate, are administered intravesically as treatment for IC/BPS, based on the hypothesis that replenishing the GAG layer might lead to urothelial layer recovery. Indeed, intravesical instillation of chondroitin sulphate into the rat bladder was shown to restore a damaged epithelial permeability barrier ( ).


Alternatively, dysfunction in other components of the urothelium may also be related to increased permeability. considered electron microscopy characteristics of the urothelium and demonstrated defects in umbrella cells (denudation, increased pleomorphism, and decreased microplicae of the cell membrane) in patients with IC/BPS (diagnosed using ESSIC 2008 criteria) compared with controls. Importantly, the severity of these defects correlated with symptom severity and bladder capacity.


Neurogenic inflammation


Neurogenic inflammation involves the enhanced release of proinflammatory neuropeptides (such as substance P) from sensory and/or sympathetic nerves, which can lead to persistent afferent nerve sensitization and local inflammatory changes. This process is mediated by mast cells, as the neurotransmitters released by peripheral neurons induce mast cell degranulation and the release of additional proinflammatory mediators. It is proposed that the inflammatory mediators’ actions on afferent neurons create a positive feedback loop, resulting in altered neural plasticity and central nervous sensitization in the dorsal root ganglia and the upper spinal cord and contributing to symptom persistence in IC/BPS ( ). This process, mediated by mast cells, has been proposed to be a nidus for induction, establishment, and chronicity of the various tissue changes seen in IC/BPS. Other conditions in which neurogenic inflammation may be implicated include irritable bowel syndrome, vulvodynia, migraines, and fibromyalgia, conditions that frequently overlap with IC/BPS.


Infectious agents


Extensive efforts have been made, with limited success, to establish an infectious agent as the cause of IC. first suggested a hematogenously disseminated bacterial cystitis as the cause. Most patients with IC/BPS report a history of urinary tract infection and have received several courses of antibiotics based on their symptoms, not on positive urine cultures. To date, no single bacterium, virus, fungus, or fastidious microorganism has been isolated as an etiologic factor in IC/BPS.


More recently, molecular methods such as 16S rRNA rapid next-generation gene sequencing and expanded quantitative urine culture techniques have been employed to demonstrate that the lower urinary tract is not sterile, and alterations in the bladder microbiome (“dysbiosis”) have been identified that are associated with other chronic urinary tract conditions, such as urgency urinary incontinence ( ). In the largest study to date focused on the bladder microbiome in women with IC/BPS, compared microbiota in voided urine specimens obtained from 181 female IC/BPS and 182 female control participants. IC/BPS participants had a clinical diagnosis of IC/BPS, as well as current bladder pain or discomfort and associated urologic symptoms. A total of 92 bacterial species (41 genera) were identified, with similar mean species counts in IC/BPS and control participants (2.49 ± 1.48 vs. 2.30 ± 1.28). The species composition did not significantly differ between IC/BPS and control participants. Testing of individual genera showed a lower prevalence ( P = .002) and relative abundance ( P = .001) of Corynebacterium among IC/BPS participants compared with controls. Overall, this and smaller studies have reported differing and inconclusive results related to dysbiosis and IC/BPS, and more research is needed ( ; ).


Centralized pain processing


Women with IC/BPS frequently have other concurrent functional pain syndromes, including fibromyalgia, irritable bowel syndrome, and vulvodynia. A key component of these conditions is diffuse hyperalgesia (increased pain to normally painful stimuli) and/or allodynia (pain to normally nonpainful stimuli), suggesting a fundamental problem with pain and/or sensory processing in the central nervous system (CNS), rather than a peripheral abnormality originating from the location of experienced pain ( ). Some studies suggest that patients with non–Hunner lesion IC/BPS are more likely to have such concurrent disorders, although results are conflicting ( ; ). This potential difference has led experts to suggest that IC/BPS without Hunner lesions might share a neurophysiologic dysfunction affecting the CNS with the other functional pain syndromes. Regardless of the presence or absence of Hunner lesions, IC/BPS patients who have other concurrent pain syndromes are likely to have dysfunction in central pain pathways and increased pain perception. The mechanism(s) underlying central pain amplification and sensitization remains unclear. Increasing evidence suggests this may include altered processing of afferent signals in the brain (see below). Central visceral hypersensitivity/pain may also involve the persistent activation of dorsal horn neurons, resulting in changes within the spinal cord that can mediate pain long after resolution of inflammation or other pelvic insult.


Altered brain structure and function


Neuroimaging research in chronic pain syndromes other than IC/BPS has demonstrated that brain structure and function are important factors related to chronic pain, creating the rationale for recent neuroimaging research in IC/BPS patients. The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network, an NIH program funded since 2008, developed a standardized protocol for functional magnetic resonance imaging (MRI) across sites ( ). This protocol was implemented in a 1-year observational cohort study of IC/BPS patients and in healthy control participants. IC/BPS participants in this MAPP study had a clinical diagnosis of IC/BPS and reported current bladder pain or discomfort with associated urologic symptoms on enrollment.


Several studies from this MAPP cohort have demonstrated differences in the brains of women with IC/BPS compared with healthy, age-matched control participants ( Fig. 35.1 ). Differences were particularly apparent in medial areas of the motor and sensory cortex, the right posterior insula, and the periaqueductal grey area of the brainstem, areas consistent with the sensorimotor representation of the pelvis ( ; ; ), and previously implicated in viscerosensory bladder function, urinary continence, and descending modulation of nociceptive signals ( ; ; ). Also, grey and white matter structure alterations and resting-state function were convergent in the supplementary motor area, a region with a role in providing corticospinal input to active pelvic floor muscles ( ; ; ). These findings led to the investigators’ conclusion that painful bladder conditions involve disturbances in brain-level sensorimotor systems that regulate urine storage and produce differences in brain structure and function ( ).




Fig. 35.1


Neuroimaging findings in urologic chronic pelvic pain syndrome. Locations in the brain of altered function ( green ; assessed using resting-state functional MRI), grey matter structure ( red ; assessed using T1-weighted MRI), and white matter structure ( blue ; assessed using diffusion tensor MRI) in participants with urologic chronic pelvic pain syndrome compared with matched healthy control individuals. There is overlap in the right posterior insula (A), the medial sensorimotor areas (B), and the brainstem and PAG (C). MRI , Magnetic resonance imaging; PAG , periaqueductal grey.

(From Clemens JQ, Mullins C, Ackerman AL, et al. Urologic chronic pelvic pain syndrome: insights from the MAPP Research Network. Nat Rev Urol . 2019;16:187. With permission.)


A subset of 52 MAPP participants with urologic chronic pelvic pain syndrome (including 34 women with IC/BPS) was imaged longitudinally. In these participants, brain functional connectivity (a measure of functional interaction among brain regions during rest) could predict short-term (3-month) pain reduction with 73.1% accuracy. Participants whose pain symptoms improved had stronger functional connectivity in the left frontoparietal brain network than those whose pain symptoms remained constant or worsened, possibly reflecting neural systems that regulate a patient’s attention to her symptoms ( ). These findings suggest that differences in CNS pain processing may have a fundamental role in IC/BPS, in addition to dysfunction identified in the bladder and urinary tract.


Clinical phenotyping


Most experts now agree that the IC/BPS diagnosis includes heterogeneous patients with varying pathologic etiologies. Given this, there are increasing efforts to phenotype or classify patients based on clinical factors to better target treatments to each patient ( ; ). Many phenotyping approaches in IC/BPS have been proposed, and important clinical differences have been found between phenotypic groups. However, few data exist that demonstrate different treatment outcomes in phenotypically defined patients, with the exception of cystoscopic treatment of Hunner lesions (see Management of Interstitial Cystitis/Bladder Pain Syndrome ).


The ESSIC guidelines emphasize use of cystoscopic findings and bladder biopsy results to classify IC/BPS patients ( ). Supporting this approach, IC/BPS patients with Hunner lesions have been found to differ from those without Hunner lesions, with more severe urinary frequency and smaller bladder capacity ( ). studied IC/BPS patients with Hunner lesions and abnormal bladder biopsy results (including histopathologic findings of inflammatory infiltrates, granulation tissue, overexpression of mast cells, and/or intrafascicular fibrotic changes), also called ESSIC type 3C disease ( Box 35.2 ), and compared them to IC/BPS patients with normal cystoscopy and biopsy results. Those with type 3C disease had a lower average maximal voided volume and lower average bladder capacity under anesthesia. Others have reported that IC/BPS patients with Hunner lesions are older and more likely to have other comorbid pain syndromes, and that those patients without Hunner lesions more likely to have pelvic floor dysfunction and myofascial pain ( ; ).


used the U-POINT system to classify 100 IC/BPS patients into six clinically identifiable domains, including Urinary, Psychosocial, Organ-Specific, Infection, Neurological/Systemic, and Tenderness (muscle). Most female IC/BPS patients were categorized into multiple domains (87% into three or more), and the identification of impacted domains outside the bladder (e.g., psychosocial and muscle tenderness) was associated with more severe pain and urinary symptoms. Based on known mechanisms of action, treatments can be targeted to each U-POINT domain, as illustrated in Table 35.2 ( ). Future research is needed to identify if treatment outcomes are improved using U-POINT or other phenotyping systems.



TABLE 35.2

The U-POINT Classification and Proposed Treatment Options Based on the Predominant Clinical Phenotype of Interstitial Cystitis/Bladder Pain Syndrome Patients

(From Khullar V, Chermansky C, Tarcan T, et al. How can we improve the diagnosis and management of bladder pain syndrome? Part 1: ICI-RS 2018. Neurourol Urodyn . 2019;38:S66. With permission.)































Clinical Phenotype Treatment Options
Urinary Behavioral treatments, antimuscarinic drugs, intravesical treatment (heparin, DMSO, HA, CS, PPS), HD, onabotulinum toxin A, sacral neuromodulation, radical surgery
Psychosocial Stress management and psychosocial support
Organ-specific
Hunner lesion (−) Amitriptyline, cimetidine, hydroxyzine, PPS, quercetin, intravesical treatment (DMSO, heparin, HA, CS, alkalinized lidocaine, PPS), HD, onabotulinum toxin A, radical surgery
Hunner lesion (+) Cyclosporin A, endoscopic treatment (fulguration, laser ablation, resection, steroid injection), hyperbaric oxygen, radical surgery
Infectious Antibiotics
Neurological/systemic Gabapentanoids, cimetidine, hydroxyzine, sacral neuromodulation
Tenderness Pelvic floor physiotherapy, massage therapy, acupuncture, trigger point injections

DMSO , Dimethylsulfoxide; HA , hyaluronic acid; CS , chondroitin sulfate; PPS , pentosan polysulfate; HD , hydrodistension.


The clinical phenotyping of patients with urologic chronic pelvic pain disorders (including women with IC/BPS) is a major goal of the MAPP Research Network ( ). MAPP investigators performed a 1-year observational cohort study of over 200 women with IC/BPS and identified important clinical factors associated with quality-of-life outcomes and with symptom trajectories over time, including the presence of pain outside the pelvis, the presence of concurrent nonurological chronic pain conditions (such as fibromyalgia and irritable bowel syndrome), and the severity of bladder-focused symptoms ( ; ; ). Based on multiple MAPP studies, suggest that IC/BPS patients who have concurrent nonurological chronic pain conditions or widespread pain have a more systemic condition and may be more likely to experience symptom progression and decreased quality of life than those with bladder-focused symptoms. Future MAPP research will validate such phenotypic profiles with longer-term outcomes in this patient population and will identify potential phenotypes based on both biological factors (for example urine biomarker, immune assay, and neuroimaging results) and clinical characteristics.


Flares


Traditionally, the natural history of symptoms in IC/BPS has included periods of symptom exacerbation or “flares.” The majority of IC/BPS patients report a history of symptom flares, and flare frequency is associated with symptom severity, bother, and disruption to normal activities ( ). Although flares are an important part of the IC/BPS patient experience, little research has focused on flares. explored flares from the patient perspective by conducting focus groups of IC/BPS patients. In this study, the most commonly described flares were painful increases in symptoms lasting days, but the patient experience of flares varied widely, including in symptom type, severity, and duration (from minutes to weeks). Many factors have been reported to trigger symptom flares, including foods and drinks (e.g., citrus fruits, tomatoes, spicy food, alcoholic and caffeinated beverages), urinary tract infections, stress, and wearing tight clothing ( ). One large case-crossover study conducted in the MAPP network found that, among many tested potential triggers, including dietary factors and stress, only recent sexual activity was associated with flare onset ( ). However, in a subset of participants who identified dietary factors as causing flares, consumption of tomatoes, yogurt, spicy foods, alcohol, caffeinated beverages, and carbonated beverages was associated with flares. These results suggest that flare triggers may be specific to certain patients, and that implementing recommendations for prevention strategies in all patients may be too restrictive.


Almost no studies to date have tested treatments aimed specifically at flares, but many have reported patient self-management strategies, most commonly increased fluid intake, increased rest, dietary changes, heat or cold therapy, and relaxation techniques such as meditation and visualization ( ). Research in this area is clearly needed.


Evaluation


IC/BPS is a diagnosis of exclusion. The AUA established an evidence-based clinical framework for diagnosis and overall management of IC/BPS, last updated in 2015 ( Fig. 35.2 ; ). The guideline states that insufficient literature was identified to constitute an evidence base for diagnosis of IC/BPS in clinical practice. For this reason, diagnosis statements are largely based on clinical principles or expert opinion. The basic assessment should include a careful history, physical examination, and laboratory examination to document symptoms and signs that characterize IC/BPS and exclude other disorders commonly associated with IC/BPS in the differential diagnosis ( ). Cystoscopy and urodynamic testing may be considered but are not necessary for making the diagnosis in uncomplicated presentations. The following sections generally follow the AUA recommendations except where specifically noted.




Fig. 35.2


American Urologic Association Guideline Amendment: Interstitial Cystitis/Bladder Pain Syndrome Diagnosis and Treatment Algorithm. IC/BPS , Interstitial cystitis/bladder pain syndrome; hx , history; Dx , diagnosis; PPS , pentosan polysulfate sodium; DMSO , dimethylsulfoxide; OAB , overactive bladder; GI, gastrointestinal; Tx , treatment; BTX , botulinum toxin A.

(From Hanno PM, Erickson D, Moldwin R, Faraday MM, American Urological Association. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment. J Urol. 2015;193:1545. With permission.)


History


The history should elucidate symptoms, their duration, and exacerbating and alleviating factors. Symptoms should be chronic in nature and present for at least 6 weeks. The number of voids per day, sensation of constant urge to void, and the location, character, and severity of pain, pressure, or discomfort should be documented. The patient should be queried regarding specific foods or drinks that worsen pain and whether pain worsens with bladder filling and/or improves with bladder emptying. Dyspareunia, dysuria and relationship of pain to menses should also be noted.


Confusable diagnoses must be excluded (see Table 35.1 ). Patients cannot have evidence of cystitis caused by infection, use of cyclophosphamide or other chemical agents, radiation, or tuberculosis. Other infections, such as vaginitis, urethritis, urethral ureaplasma, or genital herpes, cannot be present. Also, urethral diverticulum, bladder carcinoma, and carcinoma in situ must be excluded.


Although not mandatory for diagnosis, a voiding diary (an example is shown in Fig. 14.1 ) may be beneficial for documenting baseline symptoms and providing a benchmark for tracking changes in symptoms with treatment. Frequent low-volume voids are suggestive of IC/BPS. Validated symptom questionnaires, such as the Interstitial Cystitis (O’Leary–Sant) Symptom and Problem Indices (ICSI and ICPI), the Genitourinary Pain Index, and the Bladder Pain/Interstitial Cystitis Symptom Score may also be used to document baseline symptoms and their impact on quality of life ( ; ; ).


A comprehensive history should also include menstrual and sexual history, medical history with emphasis on other chronic pain disorders (i.e., fibromyalgia, irritable bowel syndrome, migraines, endometriosis, vulvodynia, etc.), surgical history, medication use and allergies, and use of tobacco, alcohol, and drugs. Given the known relationship between sexual abuse and/or traumatic life events and pain syndromes including IC/BPS, it is also important to obtain this history as part of the evaluation ( ; ).


Physical examination


A comprehensive physical examination should include an abdominal examination to detect tenderness, masses, hernias, and the presence of prior surgical incisions. A back examination to elicit costovertebral angle tenderness may be helpful if there is concern for infection. A focused neurologic examination to elicit the bulbocavernosus reflex and assess perineal sensation is recommended to help rule out an underlying neurologic condition.


The pelvic examination should begin with evaluation of the external genitalia for signs of infection, masses, dermatologic conditions, and vulvar pain disorders (i.e., vestibulitis or vulvodynia). The pelvic examination includes assessment for vaginitis with vaginal microscopy and/or cultures, if appropriate, and evaluation for signs of vulvovaginal atrophy, urethral caruncle, and cervical cancer screening if indicated. Evaluation for pelvic organ prolapse should be documented. Prolapse is not commonly associated with pain. However, anterior vaginal wall prolapse may be associated with frequency, urgency, incontinence, or obstructive urinary symptoms, and treatment of prolapse may be considered in select IC/BPS patients. The posterior bladder wall and urethra should be palpated to check for tenderness and masses. A bimanual examination should be performed to detect pelvic masses and uterine tenderness. A rectovaginal examination is performed to evaluate for tenderness and masses.


Lastly, the pelvic floor muscles should be palpated to determine tenderness, tone, strength, and ability to appropriately contract and relax. recently developed a standardized and reproducible pelvic floor muscle examination protocol intended to screen for the presence of pelvic floor myofascial pain. In addition to palpation of three external sites (bilateral sacroiliac joints, medial edge of the anterior superior iliac spine, and cephalad edge of the pubic symphysis) to screen for the presence or absence of self-reported pain, the examination includes internal vaginal palpation of the pelvic floor muscles. The internal examination calls for palpation of each muscle group in the center of the muscle belly, then along the length of the muscle, proceeding counter-clockwise: right obturator internus, right levator ani, left levator ani, and left obturator internus (with pain rated by the patient on a scale of 0–10 at each site; Fig. 35.3 ).


Nov 27, 2021 | Posted by in GYNECOLOGY | Comments Off on Interstitial cystitis/bladder pain syndrome
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