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Interstitial Cystitis

Interstitial cystitis (IC) is a chronic inflammatory disorder of the urinary bladder.


Presentation

Clinically, interstitial cystitis is often divided into 2 distinct subgroups based on findings at cystoscopy and bladder over distention. These categories are the ulcerative (i.e., classic) and non-ulcerative (i.e., Messing-Stamey) types [2]. Ulcerative patient have higher urinary frequency and lower bladder capacity whereas, non-ulcerative patients present with more diffuse pain syndrome and other systemic complaints.

The most common symptoms include suprapubic pain, increased urine frequency that can be as often as every 10 mins, nocturia and painful sexual intercourse. Suprapubic pain is notably worse on filling and better on urinating. Also, it is aggravated with certain foods or drinks. Dysuria, urinary hesitancy, discomfort and difficulty on driving, travelling and riding are other symptoms of interstitial cystitis.

Lymphadenopathy
  • Interstitial cystitis, vaginismus Rectal spasms or pain with digital rectal examination Pelvic inflammatory disease, interstitial cystitis, endometriosis Suprapubic tenderness Interstitial cystitis, trigonitis, UTI Tenderness in groin Femoral hernia, lymphadenopathy[aafp.org]
Abdominal Pain
  • However, symptoms of low abdominal pain and urinary retention (1 patient) persisted, and cystectomy was performed in both patients after 14 and 20 months, respectively.[ncbi.nlm.nih.gov]
Suprapubic Pain
  • A 20-year-old woman with systemic lupus erythematosus presented with dysuria, urinary frequency and suprapubic pain and was found to have a chronic interstitial cystitis, a chronic inflammation of the bladder wall, mostly affecting middle-aged women.[ncbi.nlm.nih.gov]
Mitral Valve Prolapse
  • valve prolapse. [13] Diagnosis [ edit ] A diagnosis of IC/BPS is one of exclusion, as well as a review of clinical symptoms. [7] The AUA Guidelines recommend starting with a careful patient history, physical examination and laboratory tests to assess[en.wikipedia.org]
Morning Stiffness
  • She had noticed exudative erythema, swelling and sclerosis on the bilateral fingers and dorsal aspects of the hands since 1993, and Raynaud's phenomenon and morning stiffness of the fingers from November, 1998.[ncbi.nlm.nih.gov]
Radiculopathy
  • Since pelvic pains could represent compressive radiculopathy of sacral roots, a cautious trial of minimally invasive caudal epidural steroid injections was performed.[ncbi.nlm.nih.gov]
Pelvic Pain
  • PURPOSE: We performed pooled analyses from 3 small, clinical trials of tanezumab in patients with urological chronic pelvic pain, including chronic prostatitis/chronic pelvic pain syndrome and interstitial cystitis/bladder pain syndrome, to identify patient[ncbi.nlm.nih.gov]
Urinary Urgency
  • BCG- and PPS-treated patients had elevated urinary urgency treatment effects compared with placebo groups.[ncbi.nlm.nih.gov]
  • urgency and frequency associated with pelvic pain that varies with bladder filling. 1 Unlike bladder inflammation caused by bacterial infection, the condition occurs in the absence of urinary tract infection or other obvious pathology.[dx.doi.org]
Nocturia
  • Daytime frequency in the absence of nocturia is not characteristic of interstitial cystitis. The absence of significant nocturia may suggest an alternative diagnosis (eg, sensory urgency).[web.archive.org]
  • Overactive bladder (OAB) and interstitial cystitis (IC) have similar symptoms, including urinary urgency/frequency and nocturia, making them difficult to differentiate on the basis of clinical presentation alone.[ncbi.nlm.nih.gov]
Urinary Incontinence
  • We report on a patient with a 2-year history of severe interstitial cystitis with disabling symptoms of painful urgency and urinary incontinence.[ncbi.nlm.nih.gov]
  • . , help women deal with all types of urology conditions, both common and complex, including bladder problems and urinary incontinence.[hackensackumc.org]
Dysuria
  • The GI symptoms and dysuria regressed with initial therapy of SLE by steroid but persistent obstructive uropathy (OU) and renal insufficiency required bilateral nephrostomy.[ncbi.nlm.nih.gov]

Workup

The exclusion of other clinical entities remains the foremost goal of the workup and evaluation of patients thought to have interstitial cystitis. A complete, careful history and a thorough physical examination are ‘MUST’. The patient must have pain with frequency and urgency to confirm the diagnosis. Thus patient with just frequency and urgency are excluded from the diagnosis. It is easily confused with other infectious, inflammatory, gynecological, urological and neurological problems and it should be excluded using various tests like dipstick urine analysis, urine cultures, serum PSA in men over 40 years, ultrasound scanning and cystoscopy.

The diagnosis of interstitial cystitis should be confirmed using cystoscope on hydrodistended bladder followed by biopsy. A clinician should consider other alternative diagnosis before confirming interstitial cystitis. When the symptoms of long standing urine frequency, urgency and pelvic pain are present without any identifiable etiology, then one must think of interstitial cystitis.

Urine analysis and culture are mandatory to rule out other causes. Also, necessary are cystoscopy and biopsy. Diagnostic hydrodistention (ie, overdistention) is performed by placing the irrigation fluid at 80-100cm water above the patient's bladder. Manual compression of the urethra around the cystoscope sheath should be performed as the bladder fills to help prevent the escape of fluid and to ascertain the true bladder capacity.

Continuous intravesical observation of the bladder wall is necessary to note perforation and extravasation as the bladder is filled. A seemingly large bladder capacity or exceedingly prolonged filling time without deceleration of the filling rate may indicate bladder perforation. The diagnostic distention is typically held for 1-2 minutes, and then the bladder is drained. The amount of drainage (bladder capacity under anesthesia) and the color of the effluent are recorded. Characteristically, the last 50-100mL of effluent may be blood tinged (terminal pinking) in patients with interstitial cystitis. The bladder capacity may be reduced in patients with the ulcerative variety of interstitial cystitis, whereas the bladder capacity is normal or only slightly reduced in patients with the nonulcerative form of interstitial cystitis. Biopsy is performed to rule out malignant lesion.

GP51 is considered as a possible biomarker for interstitial Cystitis as there is significant variation in the level of GP51 in the patients with interstitial cystitis as compared with normal individuals [9]. This is still under research and we need significant proof in believing it.

Ulcerations in Cystoscopy
  • […] during cystoscopy IC has been found to be common in patients with endometriosis and other pelvic pain disorders, and for this reason, is often referred to as the “evil twin” of endometriosis.[vitalhealth.com]
  • Currently, the most common stratification is based on presence/absence of visible ulcers on cystoscopy. This is a useful distinction because visible ulcers can be fulgurated ( 56 ).[doi.org]
  • An absence of glomerulations or Hunner's ulcers on cystoscopy does not exclude a diagnosis of IC; a minority of individuals with IC (10%) will not have either of these medical signs.[web.archive.org]

Treatment

Treatment of patients with interstitial cystitis is often delayed due to delay in diagnosis. Patient’s education regarding the condition and its chronicity are an integral part of treatment. Ongoing reassurance and physical and emotional support are necessary. Referral to interstitial cystitis support group or to a local chapter of Interstitial Cystitis Association is helpful in providing support to the patient.

Treatment includes diet and fluid management, stress management and behavioral modification along with pharmacological, surgical and alternative therapies. Behavioral therapy includes pelvic floor rehabilitation and bladder training programs along with counseling regarding interstitial cystitis. Food items that can aggravate the symptoms are coffee, alcohol, soda, monosodium glutamate, tomatoes, citrus and spicy food, vinegar, chocolates, cranberry juice. Avoiding these food items or substituting them is advisable, as it is thought that the disrupted urothelium barrier is sensitive to the metabolites of these foods.

The pharmacological treatment is symptom dependant and is largely dependent on the predominance of either pain or voiding symptoms [10]. If there is pain and minimal voiding symptoms, it is a challenge as one does not know where it comes from. However, if voiding symptoms are significant then one goes for all the conservative therapies mentioned above. If there is no improvement, then oral therapy of anti spasmodic/antimuscarinics [11], non-narcotic analgesics is tried along with amitriptyline for 8 weeks. If it fails, a trial of hydroxyzine for 8 weeks is suggested. If no response is observed, then follow hydroxyzine with pentosan polysulphate sodium. If conservative and pharmacological treatment fails to give relief then surgery like neuro modulation should be considered. In rare patient in whom Hunner ulcer is seen instillation therapy with DMSO (dimethyl sulfoxide) is used.

Prognosis

Prognosis is fair. The patients lead a long life with symptomatic treatment.

Etiology

The cause of interstitial cystitis is not clearly known and it is proposed to be multifactorial. Various etiologies include inflammation, infection, hypoxia related, autoimmune and neurological. There is pathogenic role of mast cells in mucosal and/or detrussor layers of bladder, production of toxic substances in urine, manifestation of pelvic floor muscle dysfunction or dysfunctional voiding. Many have linked it with stress, anxiety, hyper responsiveness and panic [1].

Epidemiology

Interstitial cystitis affects men and women of all culture, socio economic background and of all ages. 2.7-6.5 million women and 4.2 million men in USA are affected with this condition. It is slightly more common in Jewish women. Median age of presentation is 40 years. However, it also occurs in children.

Sex distribution
Age distribution

Pathophysiology

The pathophysiology is not clearly understood. There are various theories that have been put forward like autoimmune theory, nerve theory, mast cell theory, leaky lining theory, infection theory and the theory of toxic substance in the urine.

Recent studies show that interstitial cystitis patients have substances in their urine which inhibit the growth of cells in the bladder epithelium. Current evidence also shows that mast cells release histamine and cause pain, swelling, scarring and interfere with healing [2]. There are also studies which show proliferation of nerve fibers in the bladder of the patients while they are absent in other individuals [3]. Thus, one thing is clear that whatever may be the reason, the surface bladder lining of the patient with interstitial cystitis is damaged.

The transitional cell apical membrane of bladder is coated with GAGS and proteoglycans. Disruption of this layer can lead to transmigration of urinary solutes across the mucosal surface, affecting nerves and muscles and potentially leading to pain. Thus, restoration of this layer remains a mainstay in treatment if interstitial cystitis [4]. Up-regulation of histaminergic [5] and muscarinic neurotransmitter receptors has been shown to be present in patients with Interstitial Cystitis, which may contribute to the inflammatory symptoms present [6] [7]. Additionally, up-regulation of neural afferent pathways has been shown in interstitial cystitis [8] along with central hyperresponsiveness.

Interstitial cystitis is often divided into 2 distinct subgroups. These are the ulcerative (i.e., classic) and non-ulcerative (i.e., Messing-Stamey) types. On cystoscopy, ulcerative type presents with diffusely reddened appearance on the bladder surface epithelium with one or more ulcerative patches surrounded by mucosal congestion (Hunner ulcer) on the dome or lateral walls of bladder. Biopsy findings reveal the ulcerative lesions which can sometimes be transmural, and associated with significant inflammatory change, presence of granulation tissue, infiltration by mast cells and, occasionally even fibrosis. It progressively leads to smaller bladder capacity.

Non ulcerative type presents with the same symptoms as that of ulcerative, but the cystoscopic findings are different. After overdistension of bladder, there are glomerulations that are discrete, tiny, lesions appearing like raspeberries along the dome and/or the lateral walls of the urinary bladder. There are tiny mucosal tears and submucosal hemorrhages. Bladder biopsy findings are unremarkable. There are number of undefined pathologies related to interstitial cystitis but finally it remains a syndrome which is recognized by urine frequency, urgency and pelvic pain.

Prevention

There is no known etiology to prevent the condition itself. However, one should avoid consuming those food items which aggravate the symptoms.

Summary

Interstitial cystitis (IC) is a chronic inflammatory condition of the mucosal and submucosal lining of the bladder. The term was first coined by Dr. Alexander Skene in 1887 to describe the disease. It is also called Bladder Pain Syndrome (BPS) characterized by daytime and night time urinary frequency, urgency and pelvic pain of unknown etiology. It is a diagnosis of exclusion and is usually confused with many other bladder disorders.

Patient Information

Interstitial cystitis (IC) also called as Bladder Pain Syndrome (BPS) is a clinical syndrome consisting of increased urinary frequency, urgency and pelvic pain. It is a diagnosis of exclusion as it is easily confused with other urological conditions like urinary tract infection or inflammatory disease. It may also be confused with benign prostate hypertrophy (BPH). Various gynecological conditions also have such symptoms. Thus, a thorough clinical history and examination is required. It is usually diagnosed using cystoscope and biopsy to rule out other major diseases.                       

Biomarker for Interstitial cystitis is under research. As regards treatment, counseling and imparting knowledge about the condition to the patient is a must. Pelvic floor rehabilitation and bladder training programs are necessary to be considered. One needs to be made aware of the chronicity of the disease. There are certain food items which aggravate the symptoms and one should refrain from eating those. Pharmacological therapy is considered mutually by the physician and patient if there is no improvement with the conservative therapy. It is based on giving symptomatic relief.

References

Article

  1. Berry SH, Elliott MN, Suttorp M, Bogart LM, et al. Prevalence of symptoms of bladder pain syndrome/interstitial cystitis among adult females in the United States. J Urol. 2011 Aug;186 (2): 540-4.
  2. Persu C, Cauni V, Gutue S, Blaj I, et al. From interstitial cystitis to chronic pelvic pain. J Med Life. 2010 Apr-Jun;3(2):167-74..
  3. Moutzouris DA, Falagas ME. Interstitial Cystitis: An Unsolved Enigma. Clin J Am Soc Nephrol. 2009 Nov;4(11):1844-57
  4. Hunner GL. A rare type of bladder ulcer in women: Report of cases. J Boston Med Surg. 1915;172:660-5.
  5. Dimitrakov J, Guthrie D. Genetics and Phenotyping of Urological Chronic Pelvic Pain Syndrome. J Urol. Apr 2009; 181(4): 1550–1557..
  6. Dyer AJ, Twiss CO. Painful bladder syndrome: an update and review of current management strategies. Curr Urol Rep. Feb 2014;15(2):384.
  7. Hurst RE, Zebrowski R. Identification of proteoglycans present at high density on bovine and human bladder luminal surface. J Urol. Nov 1994;152(5 Pt 1):1641-5.
  8. Meares EM Jr. Interstitial cystitis--1987. Urology. Apr 1987;29(4 Suppl):46-8.
  9. Rosenberg MT, Newman DK, Page SA). Interstitial cystitis/painful bladder syndrome: symptom recognition is key to early identification, treatment. Cleve Clin J Med. 2007 May; 74 Suppl 3: S54–62.
  10. Twiss C, Kilpatrick L, Craske M, Buffington CA, Ornitz E, Rodríguez LV. Increased startle responses in interstitial cystitis: evidence for central hyperresponsiveness to visceral related threat. J Urol. May 2009;181(5):2127-33.
  11. Mukerji G, Yiangou Y, Grogono J, Underwood J, Agarwal SK, Khullar V. Localization of M2 and M3 muscarinic receptors in human bladder disorders and their clinical correlations. J Urol. Jul 2006;176(1):367-73.

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Last updated: 2019-07-11 21:01