Interstitial cystitis
Interstitial cystitis, a type of bladder pain syndrome, is chronic pain in the bladder and pelvic floor of unknown cause. Symptoms include feeling the need to urinate right away, needing to urinate often, bladder pain and pain with sex. IC/BPS is associated with depression and lower quality of life. Some of those affected also have irritable bowel syndrome and fibromyalgia.
The cause of interstitial cystitis is unknown. While it can, it does not typically run in a family. The diagnosis is usually based on the symptoms after ruling out other conditions. Typically the urine culture is negative. Ulceration or inflammation may be seen on cystoscopy. Other conditions which can produce similar symptoms include overactive bladder, urinary tract infection, sexually transmitted infections, prostatitis, endometriosis in females, and bladder cancer.
There is no cure for interstitial cystitis and management of this condition can be challenging. Treatments that may improve symptoms include lifestyle changes, medications, or procedures. Lifestyle changes may include stopping smoking, dietary changes, reducing stress, and receiving psychological support. Medications may include paracetamol with ibuprofen and gastric protection, amitriptyline, pentosan polysulfate, or histamine. Procedures may include bladder distention, nerve stimulation, or surgery. Kegel exercises and long term antibiotics are not recommended.
In the United States and Europe, it is estimated that around 0.5% of people are affected. Women are affected about five times as often as men. Onset is typically in middle age. The term "interstitial cystitis" first came into use in 1887.
Signs and symptoms
The most common symptoms of IC are suprapubic pain, urinary frequency, painful sexual intercourse, and waking up from sleep to urinate.In general, symptoms may include painful urination described as a burning sensation in the urethra during urination, pelvic pain that is worsened with the consumption of certain foods or drinks, urinary urgency, and pressure in the bladder or pelvis. Other described symptoms are urinary hesitancy, and pain and difficulty driving, working, exercising, or traveling. Pelvic pain experienced by those with IC typically worsens with filling of the urinary bladder and may improve with urination. Other, more severe symptoms include chronic inflammation, ulcuration, fybrotic scar tissue and stiffness of the bladder.
During cystoscopy, 5–10% of people with IC are found to have Hunner's ulcers. A person with IC may have discomfort only in the urethra, while another might struggle with pain in the entire pelvis. Interstitial cystitis symptoms usually fall into one of two patterns: significant suprapubic pain with little frequency or a lesser amount of suprapubic pain but with increased urinary frequency.
Association with other conditions
Some people with IC/BPS have been diagnosed with other conditions such as irritable bowel syndrome, fibromyalgia, myalgic encephalomyelitis/chronic fatigue syndrome, allergies, Sjögren syndrome, which raises the possibility that interstitial cystitis may be caused by mechanisms that cause these other conditions. There is also some evidence of an association between urologic pain syndromes, such as IC/BPS and CP/CPPS, with non-celiac gluten sensitivity in some people.In addition, men with IC/PBS are frequently diagnosed as having chronic nonbacterial prostatitis, and there is an extensive overlap of symptoms and treatment between the two conditions, leading researchers to posit that the conditions may share the same cause and pathology.
Causes
The cause of IC/BPS is not known. However, several explanations have been proposed and include the following: autoimmune theory, nerve theory, mast cell theory, leaky lining theory, infection theory, and a theory of production of a toxic substance in the urine. Other suggested etiological causes are neurologic, allergic, genetic, and stress-psychological including exposure to abuse in childhood or adulthood. In addition, recent research shows that those with IC may have a substance in the urine that inhibits the growth of cells in the bladder epithelium. An infection may then predispose those people to develop IC. Evidence from clinical and laboratory studies confirms that mast cells play a central role in IC/BPS possibly due to their ability to release histamine and cause pain, swelling, scarring, and interfere with healing. Research has shown a proliferation of nerve fibers is present in the bladders of people with IC which is absent in the bladders of people who have not been diagnosed with IC.Regardless of the origin, most people with IC struggle with a damaged urothelium, or bladder lining. When the surface glycosaminoglycan layer is damaged, urinary chemicals can "leak" into surrounding tissues, causing pain, inflammation, and urinary symptoms. Oral medications like pentosan polysulfate and medications placed directly into the bladder via a catheter sometimes work to repair and rebuild this damaged/wounded lining, allowing for a reduction in symptoms. Most literature supports the belief that IC's symptoms are associated with a defect in the bladder epithelium lining, allowing irritating substances in the urine to penetrate into the bladder—a breakdown of the bladder lining. Deficiency in this glycosaminoglycan layer on the surface of the bladder results in increased permeability of the underlying submucosal tissues.
GP51 has been identified as a possible urinary biomarker for IC with significant variations in GP51 levels in those with IC when compared to individuals without interstitial cystitis.
A proposed mechanism for interstitial cystitis is the autoimmune mechanism. Some studies have noted the link between IC, anxiety, stress, hyper-responsiveness, panic, and abuse. Biopsies on the bladder walls of people with IC may contain larger counts of mast cells than healthy bladder walls. Mast cells, which contain histamine granules, respond to allergic stimuli. In this theory, Mast cells are activated in response to antigen detection in the bladder wall. The activation of mast cells triggers the release of histamine, amongst other inflammatory mediators. Additionally, another proposed mechanism is increased activity of unspecified nerves in the bladder wall. An unknown toxin or stimuli may activate nerves within the bladder wall, causing the release of neuropeptides. These neuropeptides can induce a secondary cascade which stimulates pain in the bladder wall.
Genes
Some genetic subtypes, in some people, have been linked to the disorder.- An antiproliferative factor is secreted by the bladders of people with IC/BPS which inhibits bladder cell proliferation, thus possibly causing the missing bladder lining.
- PAND, at gene map locus 13q22–q32, is associated with a constellation of disorders including IC/BPS and other bladder and kidney problems, thyroid diseases, serious headaches/migraines, panic disorder, and mitral valve prolapse.
Diagnosis
The KCl test, also known as the potassium sensitivity test, is no longer recommended. The test uses a mild potassium solution to evaluate the integrity of the bladder wall. Though the latter is not specific for IC/BPS, it has been determined to be helpful in predicting the use of compounds, such as pentosan polysulphate, which are designed to help repair the GAG layer.
For complicated cases, the use of hydrodistention with cystoscopy may be helpful. Researchers, however, determined that this visual examination of the bladder wall after stretching the bladder was not specific for IC and that the test, itself, can contribute to the development of small glomerulations often found in IC. Thus, a diagnosis of IC is one of exclusion, as well as a review of clinical symptoms.
In 2006, the ESSIC society proposed more rigorous and demanding diagnostic methods with specific classification criteria so that it cannot be confused with other, similar conditions. Specifically, they require that a person must have pain associated with the bladder, accompanied by one other urinary symptom. Thus, a person with just frequency or urgency would be excluded from a diagnosis. Secondly, they strongly encourage the exclusion of confusable diseases through an extensive and expensive series of tests including a medical history and physical exam, a dipstick urinalysis, various urine cultures, and a serum PSA in men over 40, flowmetry and post-void residual urine volume by ultrasound scanning and cystoscopy. A diagnosis of IC would be confirmed with a hydrodistention during cystoscopy with biopsy.
They also propose a ranking system based upon the physical findings in the bladder. People would receive a numeric and letter based score based upon the severity of their disease as found during the hydrodistention. A score of 1–3 would relate to the severity of the disease and a rating of A–C represents biopsy findings. Thus, a person with 1A would have very mild symptoms and disease while a person with 3C would have the worst possible symptoms. Widely recognized scoring systems such as the O'Leary Sant symptom and problem score have emerged to evaluate the severity of IC symptoms such as pain and urinary symptoms.