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.

• Collapse

  The authors attributed these findings to circulatory collapse. They cited evidence that experimental shock in dogs resulted in intestinal infarction. [annals.org]

  Studies using treatments not available in the U.S., herbal or supplement treatments, or studies that reported outcomes information collapsed across multiple interventions also were excluded. [web.archive.org]

  Studies using treatments not available in the US, herbal or supplement treatments, or studies that reported outcomes information collapsed across multiple interventions also were excluded. [auanet.org]

• Infertility

  He specialises in both male and female urinary incontinence, overactive bladder, male infertility, and kidney stones, and is well-versed in both andrology and female urology. [topdoctors.co.uk]

  La Vignera, Male accessory gland inflammation, infertility, and sexual dysfunctions: a practical approach to diagnosis and therapy, Andrology, 5, 6, (1064-1072), (2017). [doi.org]

  Loan Repayment Programs: NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities [web.archive.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]

• Dyspepsia

  Side effects of sodium pentosan polysulfate include headache, rash, dizziness, diarrhea, dyspepsia, abdominal pain, hair loss (which is reversible), and liver function abnormalities. [emedicinehealth.com]

  […] sodium 300mg/day in 2 or 3 divided doses, 600mg/day* in 3 divided doses for males in some cases† Possibly aids in repairing or restoring the mucous layer of the bladder Diarrhea, nausea, localized alopecia (reversible upon discont.), headache, rash, dyspepsia [practicalpainmanagement.com]

  […] in dyspepsia: a six-country study. [dx.doi.org]

• Liver Dysfunction

  These should be used short term, as long-term use may cause renal or liver dysfunction. Intravesical lidocaine with heparin and/or sodium bicarbonate may be used for those who have acute episodes of severe bladder pain. [uspharmacist.com]

  Rarely, more severe symptoms, such as gastrointestinal bleeding, seizures, metabolic acidosis, high blood levels of potassium, low blood pressure, slow heart rate, fast heart rate, atrial fibrillation, coma, liver dysfunction, acute kidney failure, cyanosis [en.wikipedia.org]

• Vascular Disease

  Other studies have suggested that vascular disease leading to poor blood supply to the bladder may play a role. Further research is needed before we have any definite answers. [healthengine.com.au]

  Vascular diseases of the gastrointestinal tract. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine. 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 143. Roline CE, Reardon RF. Disorders of the small intestine. [medlineplus.gov]

  A patient with acute arterial thrombosis typically has a known cardiovascular or peripheral vascular disease and/or symptoms of chronic mesenteric ischemia in addition to acute symptoms! [amboss.com]

• Heart Disease

  RESULTS: A conditional logistic regression analysis showed that the OR of prior statin users for cases was 1.52 (95% confidence interval (CI): 1.19-1.94) compared to controls after adjusting for diabetes, hypertension, coronary heart disease, obesity, [ncbi.nlm.nih.gov]

  See also acute abdomen Prognosis References:[1][5][6][4] Acute mesenteric ischemia Etiology Acute arterial embolism; (∼ 50% of cases): generally resulting from atrial fibrillation, myocardial infarction, valvular heart disease, or endocarditis Arterial [amboss.com]

  Chronic obstructive pulmonary disease. Emphysema and other smoking-related lung diseases increase your risk of intestinal ischemia. Heart problems. [mayoclinic.org]

  Smoking cessation will also decrease the incidence of heart disease, hypertension, stroke, peripheral vascular disease, and lung cancer. Exercise Many people with IC have reported that gentle stretching exercises help alleviate the symptoms of IC. [emedicinehealth.com]

• Muscle Spasm

  Pelvic floor rehabilitation, or bladder retraining Pelvic floor rehabilitation with physical therapists that are specifically trained to manage pelvic floor spasm can be very beneficial in managing the muscle spasm often associated with interstitial cystitis [beaumont.org]

  Jill Peters: "Pelvic floor dysfunction is basically a muscle spasm of the pelvic muscles that kind of are the floor of the pelvis in which the bladder sits. [web.archive.org]

  Pain occurring after urination may relate to pelvic floor tension and/or muscle spasms. Pain may also radiate to the lower back, upper legs, vulva and penis. [washington.edu]

  Related to pelvic floor muscles spasm, stress is believed to contribute to both muscle spasms and an overall decrease in quality of life. [glowm.com]

• Alopecia

  Alopecia (1–5% incidence) was reported in three studies. In addition, the incidence of rectal haemorrhage was 4% in one dose-ranging study. Pentosan polysulfate treatment generally had no significant effect on laboratory parameters. [doi.org]

  Purpose Most Common Adverse Events Pentosan polysulfate sodium 300mg/day in 2 or 3 divided doses, 600mg/day* in 3 divided doses for males in some cases† Possibly aids in repairing or restoring the mucous layer of the bladder Diarrhea, nausea, localized alopecia [practicalpainmanagement.com]

  Adverse reactions to pentosan polysulfate include diarrhea, dyspepsia, reversible alopecia, headache, rash, dizziness, abdominal pain and uncommon liver function abnormalities (1 to 4 percent). [aafp.org]

  The most commonly reported side effects include nausea, diarrhea, headache, and alopecia ( 62 ). Although evidence is limited, hydroxyzine is considered by many urologists as a first-line treatment. [dx.doi.org]

• Eruptions

  "Clinical study of cutaneous drug eruptions in 200 patients". Indian J Dermatol Venereol Leprol. 74 (1): 80. doi:10.4103/0378-6323.38431. PMID 18193504. ^ Ward, KE; Archambault, R; Mersfelder, TL (1 February 2010). [en.wikipedia.org]

• Suggestibility

  This suggests that a controlled method to determine dietary sensitivities, such as an elimination diet, may play an important role in patient management. [ncbi.nlm.nih.gov]

  Some research suggests that more than half of patients improve after six weeks of once-a-week treatments. [health.harvard.edu]

  Current questionnaire‐based literature suggests that citrus fruits, tomatoes, vitamin C, artificial sweeteners, coffee, tea, carbonated and alcoholic beverages, and spicy foods tend to exacerbate symptoms, while calcium glycerophosphate and sodium bicarbonate [onlinelibrary.wiley.com]

• Distractibility

  Bladder training for interstitial cystitisis a therapeutic technique in which patients void at designated times and use relaxation techniques and distractions to help keep to the schedule. [columbiaurology.org]

  […] bladder distension: a procedure aimed at increasing bladder capacity and interfering with pain signals that are being transmitted by the nerve cells in the bladder bladder training: patient voids at designated times and uses relaxation techniques and distractions [beaumont.org]

  You urinate at specific times and use relaxation techniques and distractions to help keep to the schedule. Over time, you try to lengthen the time between the scheduled voids. Surgery. [hopkinsmedicine.org]

• Dizziness

  Side effects from medications, including fatigue and dizziness, may also impact your ability to perform physically at work. [disabilitysecrets.com]

  /d during allergy season Controls allergies that can provoke symptom flares Drowsiness, dry mouth, and twitches Amitriptyline or imipramine‡ 25mg daily at bedtime; increase to 50mg after one to two months Aids in control of severe pain or depression Dizziness [practicalpainmanagement.com]

  Side effects of sodium pentosan polysulfate include headache, rash, dizziness, diarrhea, dyspepsia, abdominal pain, hair loss (which is reversible), and liver function abnormalities. [emedicinehealth.com]

• Burning Sensation

  It may cause a burning sensation during and after instillation and can cause a garlicky odor on the skin and breath for up to three days following treatment. DMSO is sometimes combined with other medications. [health.harvard.edu]

  Its symptoms are a constant urge to pee; a painful, burning sensation when urinating; dark, cloudy or smelly urine; pain in the lower abdomen; and generally feeling unwell. It’s a common problem and easily cured with antibiotics. [irishexaminer.com]

  It may cause a burning sensation during and after instillation and can cause a garlicky odor on the skin and breath for up to three days following treatment. DMSO is sometimes combined with other medications.. Bacillus Calmette-Guerin (BCG). [web.archive.org]

  Experts aren’t sure why the burning sensation occurs, though some say issues with the pelvic floor muscles could irritate the muscles and nerves controlling how urine passes. [rd.com]

  A burning sensation when urinating. Abdominal pain, pelvic pressure and/or lower back pain. You may experience lower abdominal discomfort, bloating and/or feel pressure in the lower pelvic area, especially when urinating. Blood in the urine. [chesapeakeurology.com]

• Pelvic Pain

  How is chronic pelvic pain diagnosed? Because pelvic pain symptoms are similar to those of other disorders, doctors must first rule out other conditions before diagnosing interstitial cystitis. [urologyaustin.com]

  Although not approved for pelvic pain, there are many publications including our own from Beaumont demonstrating improvement in interstitial cystitis and pelvic pain symptoms. Beaumont urologists helped developed pudendal neuromodulation. [beaumont.org]

  […] tends to occur as their entire chronic pelvic muscle tension releases Reduced interest in sex is common with pelvic pain In muscle related pelvic pain, there is typically no pathology of the physical structures involved in sexually activity Our view [pelvicpainhelp.com]

  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

  Reports show decrease in urinary urgency and urinary frequency, as well as decreased need for medications. [beaumont.org]

  BCG treatment also significantly increases the incidence of GRA and improves the symptoms of urinary urgency. PPS can significantly improve urinary frequency and urgency symptoms in IC/PBS patients. [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

  Secondary parameters were mean 24-hours frequency and nocturia on a 3-day micturition dairy, changes from baseline in O'Leary-Sant questionnaire score and visual analog scale (VAS) for suprapubic pain. [ncbi.nlm.nih.gov]

  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]

• 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]

  The limited cutaneous form of systemic sclerosis (SSc) is associated with urinary incontinence (UI): an international multicentre study. [sclero.org]

  A Patient Page on urinary tract infection was published in the May 2, 2012, issue, one on urinary incontinence in older women was published in the June 2, 2010, issue; and one on bladder cancer was published in the February 16, 2005, issue. [jamanetwork.com]

  […] tract: implications for the treatment of stress urinary incontinence and bladder reconstruction. 8. [stemcellrevolution.com]

• 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]

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

  ulcers (lesions or sores on the lining of the bladder) may be observed (Hunner’s ulcers affect approximately 5-10% of patients who have IC). [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 ). [dx.doi.org]

  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). [cjasn.asnjournals.org]

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

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].

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.

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.

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

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.

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.

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.