Interstitial cystitis - This is a chronic progressive inflammation of the bladder of non-infectious origin. It is manifested by pelvic pain, pollakiuria, nocturia, peremptory urination, dyspareunia. Diagnosed with cystometry, cystoscopy with hydrobrushing, potassium test, taking into account the results of a general urinalysis. For treatment, antihistamines, tricyclic antidepressants, synthetic mucopolysaccharides, intravesical instillations of cytoprotectors, anesthetics, corticosteroids, botulinum toxin injections, cystoscopic bougienage, reconstructive plasty are used.
The term "interstitial cystitis" was first proposed by the American gynecologist A. Skin in 1887 to describe inflammation spreading beyond the epithelial layer. In 1915, an American obstetrician-gynecologist Guy Gunner revealed a characteristic ulcerative lesion of the mucosa, later named after him and recognized as a pathognomonic symptom of the disease.
Diagnostic criteria for interstitial forms of cystitis were developed in 1988. Currently, the disorder is also called the syndrome of a painful or hypersensitive bladder (SBMP, SGMP). The prevalence of pathology in the population, according to various sources, ranges from 2.7 to 8%. Up to 90% of cases of painful bladder syndrome are detected in women. The average age of patients is 45 years. Representatives of the white race are more often affected.
Despite numerous studies, the etiology of the disease has not been conclusively established. Specialists in the field of modern urology have identified a number of factors that increase the risk of interstitial inflammation of the urinary bladder wall, as well as several theories of its origin. Presumptive causes of the pathology may be:
- Glycosaminoglycan layer defect. In patients with an interstitial form of cystitis, structural disturbances in the barrier glycosaminoglycans, which protect the levelical mucosa, are often detected. Violation of the integrity of urothelial mucus is associated with the action of aggressive factors of urine on intramural nerve receptors. Increased secretion of the antiproliferative factor causing epithelial dysfunction can play a role.
- Autoimmune reaction. The frequent association of the interstitial variant of organ inflammation with autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, Hashimoto's thyroiditis) has become the basis for the development of the corresponding theory. In addition, autoantibodies are revealed in the blood of patients, the role and origin of which is still unclear. An indirect confirmation of the autoimmune genesis of cystitis is an increase in the number of mast cells in the bladder.
- Bacterial agent. Although the causative agent of the disease was not found, the role of the infectious factor cannot be ruled out. In the course of bacteriological studies, conditionally pathogenic flora, forming films on urothelium, was detected in the biomaterials of patients. The most commonly defined corynebacteria are Lipophiloflavium jikeium, which produce exotoxins and the enzyme neuraminidase, which can actively destroy urothelial mucus by cleavage of sialic acids.
Among the possible causes of cystitis are also called neuropathy, lymphatic congestion, impaired metabolism of nitrogen oxides, the damaging effects of urine, psychological disorders that lead to a decrease in the threshold of pain sensitivity. The main risk factors are obstetric and gynecological operations, abdominal cavity interventions, the presence of fibromyalgia, vulvodynia, anorectal dyskinesia, spastic colitis, irritable bowel syndrome, bronchial asthma, drug allergies, rheumatoid arthritis, Sjogren's syndrome, and other autoimmune diseases.
A key element in the development of interstitial cystitis is the facilitation of the access of potassium and other active components of urine to the submucosal and muscle layers of the levelical wall. With possible urothelial dysfunction, congenital insufficiency of the components of the glycosaminoglycan barrier, its damage by pathogenic factors of microorganisms, toxic substances, autoantibodies, and immune complexes, the urine comes in direct contact with uncovered interstitial and muscle cells, which leads to their damage, destruction, and the onset of an inflammatory reaction.
Mast cell degranulation and histamine release cause a hyperergic response with local edema, impaired microcirculation, ischemia of the bladder membranes. At the same time, inflammatory mediators have an irritating effect on the endings of sensitive nerve fibers. Enhanced afferentation in the spinal cord and brain is accompanied by the onset of pain, stimulation of smooth muscle contraction, and increased urination. With significant destruction of tissues against the background of stretching of the levelical wall, rupture of the mucosa, submucosal layer is possible. The outcome of the inflammatory reaction in conditions of insufficient blood supply is an increase in fibrogenesis and sclerotic processes.
The main criterion for the systematization of clinical variants of interstitial cystitis is the anatomical integrity of the mucous membrane. This approach is based on the key diagnostic value of visible tissue destruction and provides the opportunity to choose differentiated tactics of patient management. Modern urologists distinguish two forms of the disease:
- Interstitial ulcerative cystitis. A classic variant of inflammation in which a Gunner ulcer forms in the area of the apex of the bladder is a specific damage to the epithelial and submucosal layer in the form of a deep rupture due to organ stretching and tissue destruction. It is characterized by a more severe course, it is diagnosed in 10-20% of patients. In the presence of a peptic ulcer, the diagnosis of interstitial bladder inflammation is unquestionable.
- Interstitial non-ulcer cystitis. The most common and difficult to diagnose form of the disorder with less severe clinical symptoms. Changes in the mucosa are minimal, the inflammatory process is localized mainly in the deep layers of the urinary bladder wall. The diagnosis of non-ulcer cystitis is usually established by exclusion, most patients are first treated for a long time and to no avail for other diseases.
Symptoms of interstitial cystitis
The disease is asymptomatic for a long time, clinical symptoms gradually increase as the morphological changes in the organ worsen. The disorder is usually manifested by pain in the supraclonal area, sacrum, perineum, external opening of the urethral canal, and vagina. Painful sensations intensify when the bladder is full, stop or noticeably weaken after urination. Possible irradiation of pain on the inner surface of the thigh. Up to 98-99% of patients complain of frequent urination, dysuria, the prevalence of nocturnal diuresis.
With the development of irreversible changes in the interstitial layer of the body, there is an increase in urination up to 50-60 and more times a day, imperative urges, the appearance of blood in the urine are disturbed by patients. The disease is characterized by a chronic cyclically progressive course with periods of remissions and exacerbations. In women, the symptoms of cystitis are enhanced during ovulation, before menstruation. Deterioration can be observed against the background of physical and mental stresses, after smoking, drinking alcohol, spicy spices, potassium-containing products (chocolate, coffee, tomatoes, citrus fruits).
With a long course of the disease, a wrinkled bladder forms due to the replacement of the organ wall with scar tissue. Due to urinary stagnation with interstitial cystitis, vesicoureteral reflux and hydroureteronephrosis may develop. Violation of natural urination provokes the deposition of salts, which eventually leads to the formation of calculi in the organ.
Complications of cystitis are also stenosis of the ureters, chronic bleeding that provokes the occurrence of hypochromic anemia. If untreated, the risk of impaired filtration capacity of the kidneys increases, which in severe cases results in chronic renal failure. Often there are sexual disorders - decreased libido, orgasmic dysfunction.
As a rule, the diagnosis of interstitial cystitis is established by excluding diseases with similar clinical manifestations. Specialists have developed a number of clinical and instrumental criteria that facilitate diagnostic search. The likelihood of diagnosing interstitial inflammation of the urinary membranes increases in patients over 18 years old without any other urological, gynecological, andrological pathology, presenting for six months or longer complaints of characteristic pelvic pain, urination from 5 or more times per hour, nocturia more than 2 times per night.
An important diagnostic criterion is the ineffectiveness of previous treatment with uroantiseptics, antibiotics, antispasmodics, anticholinergics. Recommended examination methods are:
- General urine analysis. Erythrocyturia is often observed, leukocyturia is possible. The specific gravity of urine is within the normal range; the collected portion often has a small volume. Bacterial contamination of biological material is usually absent, less often with bacterial culture of urine saprophytes are determined.
- Cystometry. According to cystometry, the capacity of a filled bladder is less than 350 ml. For the interstitial variant of the inflammatory process, the appearance of imperative urges to urinate after retrograde administration of up to 150 ml of liquid or up to 100 ml of gas is characteristic. There are no involuntary detrusor contractions.
- Hydroburst cystoscopy. With cystoscopy, Gunner's ulcers or glomerulation of the II-III degree are visually determined in the form of extensive mucous hemorrhages that arose after hydraulic stretching. In 94% of patients, a histological examination of the biopsy reveals degranulated mast cells, neutrophils, macrophages, and fibrosis.
- Potassium test. The method involves the alternate introduction of sterile water and a solution of potassium chloride into the bladder cavity. The occurrence of more intense pain during the installation of potassium chloride indicates a possible interstitial inflammation. The test is used limitedly due to low specificity.
To exclude other pathological conditions with a similar clinical picture, ultrasound, CT, MRI of the pelvic organs, inoculation of the prostate secretion, smear from the urethra and vagina, PCR diagnostics of urogenital infections, review and excretory urography, cystography, uroflowmetry can be additionally prescribed. Differential diagnosis is carried out with infectious diseases of the urinary tract (nonspecific urethritis, cystitis, ureteritis), inflammatory processes in the pelvic organs (colpitis, endocervicitis, endometritis, adnexitis, adhesions), diverticulitis, in men - with prostatodynia, chronic prostatitis, chronic prostatitis.
In accordance with the recommendations of relevant international organizations, urolithiasis with the presence of stones in the distal ureter or bladder, active genital herpes, cancer of the urethra, neck and body of the uterus, urethral diverticulum, tuberculous, post-radiation and chemical cystitis, and bladder neoplasia are excluded. , skineitis, leukoplakia, malakoplakiya, overactive bladder. If there are indications, the urologist appoints consultations of a gynecologist, andrologist, nephrologist, infectious disease specialist, venereologist, TB specialist, and oncologist.
Treatment of interstitial cystitis
Given the uncertainty of etiopathogenesis, the treatment of the disease is mainly empirical. Experts from international urological associations have developed a three-stage algorithm for managing patients with interstitial levelical inflammation. The duration of each stage is determined by the characteristics of the course of cystitis in a particular patient and the effectiveness of the measures taken.
At stage I, non-pharmacological methods and oral pharmacotherapy are used. For patients with newly diagnosed interstitial cystitis, diet and lifestyle correction are recommended: quitting smoking, reducing the amount of spices, salt, alcohol, carbonated drinks, coffee, increasing the daily fluid intake to 1.5-2 liters. Bladder training, massage, acupuncture, detrusor electrical stimulation are shown. Drug therapy includes:
- Antihistamines. Prescribing medications presumably reduces the hyperergic inflammatory response. In randomized trials, the therapeutic effect of selective H2-histamine receptor blockers has been proven, although significant morphological changes in the tissues are usually not observed when taken.
- Tricyclic antidepressants. Despite a slight increase in bladder capacity, patients experience a subjective improvement already in the first week after taking the drugs. At the recommended dosage, antidepressants have a pronounced analgesic effect, which persists even after they are canceled.
- Synthetic mucopolysaccharides. Due to the restoration of defects in the glycosaminoglycan layer, the contact of urine with cells of the deep layers of the urinary bladder decreases. As a result, pain decreases, urination becomes more rare, their imperativeness decreases. Mucopolysaccharide funds practically do not affect nocturia.
At the second stage, non-destructive intravesical pharmacotherapy is carried out. For levelical instillation, cytoprotectors are used that restore the protective layer of glycosaminoglycans, dimethyl sulfoxide (as monotherapy or followed by heparin), anesthetics in combination with glucocorticoids, which reduce inflammation and relax the muscle membrane. Intra-detrusor administration of botulinum toxin allows you to relax muscle fibers, reduce pain and urination, and increase the cystometric capacity of the bladder by more than 2 times. At this stage, endovascular iontophoresis of drugs is performed.
Stage III methods are recommended in the absence of the effect of non-destructive methods of treatment. Cystoscopic bladder hydroboughening leads to ischemic necrosis of the intravesical sensory receptors and restores microvascularization of the organ. When revealing Gunner's ulcers, transurethral resection, electrocoagulation, and laser therapy of the damaged mucosa are additionally performed. For patients with severe sclerosis of the wall, significant loss of organ capacity, painful pelvic pain and severe dysuria, reconstructive plastic interventions (augmentation cystoplasty, intestinal bladder plastic surgery) are recommended.
Prognosis and prevention
The outlook is relatively favorable. As a result of a comprehensive medication and non-medication (diet, physiotherapy) treatment, most patients experience a regression of symptoms, but complete recovery is rare. The effectiveness of oral therapy reaches 27-30%, intravesical techniques - from 25 to 73%. Initial measures for the prevention of interstitial cystitis have not been developed due to the uncertainty of etiopathogenesis.
To prevent exacerbations, it is necessary to promptly identify and treat inflammatory diseases of the genitourinary system, avoid risk factors (emotional stress, hard physical work, eating foods rich in potassium, smoking, large doses of alcohol), and control seasonal allergies.
Interstitial cystitis can exist in several different forms:
- ulcerative - when there is an inflamed rupture of not only the mucous membrane, but also the submucous layer,
- non-ulcer - no defects are observed on the mucosa.
The typical clinical manifestation of interstitial cystitis is not fully established. But the main signs of the disease are:
- chronic pain in the pelvic area - it is considered such with prolonged expression (more than one year). The spread of soreness is observed in the vagina and anus. In men, an expression of pain in the scrotum is noted. It is characterized by an effort with a full bladder and a decrease in pain after urination,
- the occurrence of discomfort during a sexual act. In men, pain during orgasm,
- frequent urge to emit urine not only during the day, but also at night.
Symptoms of interstitial cystitis may be practically not expressed at the initial stages of the development of the disease, but as the disease progresses, the symptoms appear more clearly. In addition, the course of this ailment may worsen with a change in the hormonal background, the course of menstruation, the use of spicy foods, alcohol, coffee or chocolate, as well as due to intense physical exertion.
Epidemiology: Facts and Figures
By interstitial cystitis (IC) is meant a clinical syndrome, which is characterized by frequent day and night urination and pelvic pain.
The figures indicate that in 90% of cases, the pathology falls on the female share. Previously, this disease was considered quite rare: it was assumed that it develops with only a probability of no more than 5.1: 1000. However, less encouraging data have been obtained in recent years. Thus, epidemiological studies have shown that in American women, IC is detected with a probability of 60–70: 100,000. At the same time, in Europe, the prevalence of the disease does not exceed 18 cases per 100,000. Such a significant difference in the epidemiological indicators of the Old and New Worlds can be explained by differences in diagnostic approaches, as well as significant differences in lifestyle, nutrition, etc. In the Russian Federation, unfortunately, there are no statistics on the prevalence of IC, and domestic experts rely on as a rule, to the information of Western colleagues.
It should be noted that neither the marital status, nor the number of sexual partners, nor the level of education affect the likelihood of developing IC. The average age of onset of the disease is 40 years, but cases of the development of pathology in young patients, including children, are not excluded.
Causes of interstitial cystitis and risk factors
It is sad, but the etiology of IC is still not fully understood. A deficiency of glycosaminoglycans in the epithelial layer of the bladder can play a certain pathogenetic role in the development of the disease, which leads to increased permeability of adjacent submucosal tissues for toxic substances contained in urine.
The infectious aspect may be important, however, it has not yet been possible to accurately identify the causative agent of the disease and even definitely assess its role in the pathogenesis of IC. Some experts believe that the pathology may be associated with infection with some still undiscovered slowly growing virus or an extremely whimsical bacterium.
According to other sources, pelvic muscle dysfunction or impaired urination, as well as autoimmune diseases, are associated with IC.
Previously, scientists excluded the possibility of inheriting a tendency to IC, but in 2005 the results of a study evaluating the occurrence of a disease in monozygotic and dizygotic twins were obtained. They suggest that chronic interstitial cystitis is characterized by at least a partial genetic predisposition.
It is known that IC often occurs against the background of some chronic diseases, including inflammatory bowel diseases, systemic lupus erythematosus, irritable bowel syndrome, fibromyalgia, and atopic allergies. In addition, IC is often associated with mental disorders, in particular depression.
Risk factors predisposing to the occurrence of IC include:
- Floor. As already mentioned, in 90% of cystitis is observed in women. It is important to note that in men, the symptoms of this disease are most often associated with concomitant prostatitis.
- Skin and hair color. Fair-skinned red-haired women are at higher risk of developing IC.
- Age. In most cases, the diagnosis is first established for patients 30 years of age or older.
- Chronic pain syndrome, for example, irritable bowel syndrome or fibromyalgia.
How is IC?
The disease usually begins acutely when the patient suddenly, in a certain period of time, discovers problems with urination. Often, patients associate the onset of symptoms of IC with a urinary tract infection.
First of all, the pathology is characterized by frequent and painful urges to urinate, which are accompanied by a feeling of pressure, discomfort and pain in the pelvic area, as well as a feeling of incomplete emptying of the bladder. In addition, sexual disorders appear, including pain during intercourse, decreased libido and orgasm frequency.
Chronic cystitis is characterized by alternating periods of exacerbation and partial or even complete remissions, during which there are no symptoms. The duration of acute periods can vary significantly: from several days to months or even years. On average, 8 months after the manifestation of the disease, 50% of patients expect spontaneous remission of various lengths. In women, the symptoms of interstitial cystitis sometimes vary in severity depending on the phase of the menstrual cycle.
Unlike infectious diseases of the urinary tract, interstitial cystitis cannot be diagnosed with a routine urinalysis or culture. The fact of the presence of IC is confirmed on the basis of a characteristic clinical picture, but only after the exclusion of other possible diseases, including genitourinary infections, urolithiasis, bladder cancer, kidney pathologies, multiple sclerosis, endometriosis and others. A key step in the diagnosis of IC - cystoscopy - endoscopic diagnosis of the bladder using an urethrocystoscope. During the procedure, fluid may be injected into the bladder cavity in order to assess the functional state of the organ.
In some cases, during a cystoscopy, a bladder biopsy is performed to exclude malignant processes and other rare causes of the pain syndrome.
IC treatment principles
IC therapy has two main tasks: stopping pain and reducing the severity of the inflammatory process. Unfortunately, achieving these goals is not easy. In most cases, the treatment of interstitial cystitis in women and men is a serious problem in restoring patients to a normal quality of life. There is no clearly defined, standard method of treatment that would alleviate the suffering of most patients. As a rule, the technique is selected based on the individual response of the patient. At the same time, given the likelihood of spontaneous remission, expensive or aggressive treatment is prescribed with caution.
An integral part of therapy is the formation in patients of an idea about, alas, the chronic course of the disease, its prognosis and difficulties with treatment. An important role in the successful control of IC is played by diet therapy.
Some studies have shown that in almost 90% of patients, exacerbation of the disease is associated with the intake of certain products. The list of “hazardous” products includes:
- Monosodium glutamate
- Spicy food
- Cranberry juice
Many experts recommend either avoiding the consumption of triggers altogether, or adding them to the diet occasionally. In order to reflect the connection between the introduction of various foods into food and exacerbation of symptoms of IC, it is advisable to keep a nutrition diary. Next, we will consider how it is customary to treat interstitial cystitis.
The most common mistake in the medical treatment of IC is associated with the incorrect prescription of antibiotics, which are absolutely ineffective in such cases. The roots of this error lie in the initially incorrect diagnosis, which, as a rule, is found to be empirically established, based on exclusively clinical symptoms, bacterial inflammation of the bladder. We can say that the key to effective treatment of interstitial cystitis is the correct determination of the causes of symptoms.
Drug therapy of interstitial cystitis involves the administration of oral drugs and intravesical instillations of drugs.
Among the preparations for internal use should be highlighted:
- Tricyclic antidepressants (amitriptyline). The drugs prescribed in low doses of this group help to relax the bladder, and also prevent the release of substances that can provoke pain and inflammation. In addition, tricyclic antidepressants improve sleep quality. According to a randomized, double-blind, placebo-controlled study, amitriptyline provides a statistically significant improvement in IC.
- Antihistamines, in particular, hydroxyzine, which in the Russian Federation belongs to the pharmacological group of anxiolytics (tranquilizers).
Antiallergic drugs block the release of histamine from mast cells located in the walls of the bladder, which helps to reduce pain, the severity of inflammation, as well as reduce the number of urges to urinate, including nightly. It should be borne in mind that hydroxyzine can have a sedative effect, so it is preferred to prescribe it before bedtime.
For intravesical instillations, the local anti-inflammatory drug dimethyl sulfoxide is widely used, it is the only drug approved for use for this purpose by the American Food and Drug Administration FDA. Against the background of the introduction of dimethyl sulfoxide, the walls of the bladder relax, pain and the severity of inflammation decrease. The standard course of treatment includes six instillations (one per week for six weeks).
In addition, physiotherapy procedures (endovascular iontophoresis, laser photoirradiation of the bladder, UHF, inductotherapy, balneotherapy, etc.), as well as surgical treatment, which is performed only in severe persistent cases, can be used in IC. During the surgery, they try to achieve an increase in the bladder, optimize the outflow of urine and perform a resection of ulcerative lesions of the mucosa (if any).
Prognosis of interstitial cystitis
Despite the fact that most often the disease has an alternating course, which is characterized by alternating exacerbations and remissions, severe cases are not excluded, in which there is a gradual and persistent progression of symptoms of IC that cannot be stopped. Sometimes it is possible to alleviate the clinical picture of the disease with the help of self-control measures, such as quitting smoking, increasing physical activity, reducing the influence of stress factors, choosing free underwear and clothes, and, of course, following a diet.
The disease seriously reduces the quality of life, and so much so that in the United States, for example, this diagnosis gives rise to disability. The work, presented by American scientists led by Kimberly Hepner in 2012, showed that in a group of adult women with symptoms of IC, 11% of respondents considered suicide as a way to relieve the pain associated with their illness. Studies show that the impact of IC on quality of life can be compared with the suffering experienced by patients at the terminal stage of renal failure or rheumatoid arthritis 9, 10.
All this disappointing information says that modern scientists are faced with the difficult task of finding new means and methods of treating chronic cystitis - a serious disease that remains one of the most difficult and unsolved riddles in world medicine.
- Rovner E. S., Kim E. D. Interstitial cystitis // Medscape Reference. May - 2011.
- Konkle KS, Berry SH, Elliott MN, Hilton L, Suttorp MJ, Clauw DJ, et al. Comparison of an interstitial cystitis / bladder pain syndrome clinical cohort with symptomatic community women from the RAND Interstitial Cystitis Epidemiology study. J Urol. 2012 Feb. 187 (2): 508–12.
- Curhan G. C., Speizer F. E., Hunter D. J. Epidemiology of interstitial cystitis: a population based study // The journal of urology. - 1999. - Vol. 161. - P. 549–552.
- Parsons CL, Boychuk D, Jones S, et al. Bladder surface glycosaminoglycans: an epithelial permeability barrier. J Urol. 1990 Jan. 143 (1): 139–42.
- Warren JW, Keay SK, Meyers D, Xu J. Concordance of interstitial cystitis in monozygotic and dizygotic twin pairs. Urology. 2001 Jun. 57 (6 Suppl 1): 22–5.
- Hsieh, CH, Chang, WC, Huang, MC, Su, TH, Li, YT, Chiang, HS (December 2012). "Treatment of interstitial cystitis in women." Taiwan Journal of Obstetrics & Gynecology. 51 (4): 526-532.
- van Ophoven A, Pokupic S, Heinecke A, Hertle L. A prospective, randomized, placebo controlled, double-blind study of amitriptyline for the treatment of interstitial cystitis. J Urol. 2004 Aug. 172 (2): 533–6.
- Hepner, Kimberly A., Watkins, Katherine E., Elliott, Marc, Clemens, J. Quentin, Hilton, Lara, Berry, Sandra H. (June 2012). "Suicidal ideation among patients with bladder pain syndrome / interstitial cystitis." Urology. 80 (2): 280–285.
- American Urological Association Guideline: Diagnosis and Treatment of Interstitial Cystitis. Bladder Pain Syndrome January 2011 "(PDF). American Urological Association. Retrieved 1 April 2011.
- Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA. Ho N, Koziol J, Parsons CL. Epidemiology of Interstitial Cystitis, in G. Sant (Ed.), Interstitial Cystitis. Philadelphia: Lippincott-Raven Publishers, 1997, 9-15.
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In order for a person to never have problems with interstitial cystitis, it is necessary to adhere to simple rules of prevention, which consist of:
- timely elimination of any inflammatory processes of the bladder,
- control over allergic reactions,
- Compliance with the nutrition prescribed by the doctor - limiting the use of fatty foods and foods with protein content. In addition, it is necessary to reduce salt intake to two grams per day,
- complete elimination of stressful situations,
- passing a full preventive examination in a medical institution at least twice a year.
It is also necessary to perform moderate physical activity, maintain a healthy lifestyle and wear loose clothing.