Interstitial cystitis is a chronic progressive inflammation of the bladder of non—infectious origin. It is manifested by pelvic pain, pollakiuria, nocturia, imperative urge to urinate, dyspareunia. It is diagnosed using cystometry, cystoscopy with hydrobugging, potassium test taking into account the results of a general urine analysis. Antihistamines, tricyclic antidepressants, synthetic mucopolysaccharides, intravesical instillations of cytoprotectors, anesthetics, corticosteroids, botulinum toxin injections, cystoscopic augmentation, reconstructive plastic surgery are used for treatment.
ICD 10
N30.1 Interstitial cystitis (chronic)
Meaning
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, the American obstetrician-gynecologist Guy Gunner revealed a characteristic ulcerative lesion of the mucous membrane, subsequently 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 painful or hypersensitive bladder syndrome. The prevalence of pathology in the population, according to various data, ranges from 2.7 to 8%. Up to 90% of cases of painful bladder syndrome have been detected in women. The average age of the patients is 45 years. The disorder is more often affected by representatives of the white race.
Causes
Despite numerous studies, the etiology of the disease has not been definitively established. Specialists in the field of modern urology have identified a number of factors that increase the risk of interstitial inflammation of the urogenital wall, and several theories of its origin have been proposed. The possible causes of pathology may be:
- Defect of the glycosaminoglycan layer. In patients with interstitial cystitis, violations of the structure of barrier glycosaminoglycans, which provide protection of the vesical mucosa, are often detected. Violation of the integrity of urothelial mucus is associated with the effect of aggressive urine factors on intramural nerve receptors. An increased secretion of an antiproliferative factor that causes epithelial dysfunction may play a certain role.
- Autoimmune reaction. Frequent association of interstitial variant of organ inflammation with autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, Hashimoto’s thyroiditis) it became the basis for the development of an appropriate theory. In addition, autoantibodies are detected in the blood of patients, the role and origin of which are 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 has not been detected, the role of the infectious factor cannot be excluded. During bacteriological studies, conditionally pathogenic flora forming films on the urothelium was detected in the biomaterials of patients. The most commonly identified corynebacteria are Lipophiloflavium jikeium, which produce exotoxins and the enzyme neuraminidase, capable of actively destroying urothelial mucus due to the cleavage of sialic acids.
Among the probable causes of cystitis are also called neuropathy, lymphatic stagnation, impaired metabolism of nitrogen oxides, 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.
Pathogenesis
The key link in the development of interstitial cystitis is considered to facilitate the access of potassium and other active components of urine to the submucosal and muscular layers of the vesical wall. With possible dysfunction of the urothelium, congenital insufficiency of the components of the glycosaminoglycan barrier, its damage by pathogenic factors of microorganisms, toxic substances, autoantibodies, immune complexes, urine directly contacts uncovered interstitial and muscle cells, which leads to their damage, destruction, and the onset of an inflammatory reaction.
The degranulation of mast cells and the release of histamine causes a hyperergic response with local edema, impaired microcirculation, and ischemia of the urogenital membranes. At the same time, inflammatory mediators have an irritating effect on the endings of sensitive nerve fibers. Increased afferentation to the spinal cord and brain is accompanied by pain, stimulation of contraction of smooth muscle fibers, increased urination. With significant destruction of tissues against the background of stretching of the vesical wall, a rupture of the mucous, submucosal layer is possible. The outcome of an inflammatory reaction in conditions of insufficient blood supply is an increase in fibrogenesis and sclerotic processes.
Classification
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 an opportunity to choose differentiated patient management tactics. Modern urologists distinguish two forms of the disease:
- Interstitial ulcerative cystitis. The classic variant of inflammation, in which a Gunner’s ulcer forms in the area of the tip of the bladder, is a specific damage to the epithelial and submucosal layer in the form of a deep rupture due to stretching of the organ and destruction of tissues. It is characterized by a more severe course, it is diagnosed in 10-20% of patients. In the presence of an ulcerative defect, the diagnosis of interstitial urogenital inflammation is undoubted.
- Interstitial non-ulcerative cystitis. The most common and difficult to diagnose form of the disorder with less pronounced clinical symptoms. Mucosal changes are minimal, the inflammatory process is localized mainly in the deep layers of the urogenital wall. The diagnosis of non-ulcerative cystitis is usually established by the exclusion method, most patients are first treated for a long time and to no avail for other diseases.
Interstitial cystitis symptoms
The disease has been asymptomatic for a long time, the clinical symptoms increase gradually as the morphological changes of the organ worsen. The disorder is usually manifested by pain in the supraplonic region, sacrum, perineum, external opening of the urethral canal, vagina. Painful sensations increase when the bladder is filled, 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 urge to urinate, dysuria, predominance of nocturnal diuresis.
With the development of irreversible changes in the interstitial layer of the organ, there is an increase in urination up to 50-60 or more times a day, patients are concerned about imperative urges, the appearance of blood in the urine. The disease is characterized by a chronic cyclically progressive course with periods of remissions and exacerbations. In women, the symptoms of cystitis increase during ovulation, before menstruation. Deterioration of the condition can be observed against the background of physical and mental stress, after smoking, drinking alcoholic beverages, spicy spices, potassium-containing products (chocolate, coffee, tomatoes, citrus fruits).
Complications
With a prolonged course of the disease, a wrinkled bladder is formed due to the replacement of the organ wall with scar tissue. Due to the resulting stagnation of urine in interstitial cystitis, vesicoureteral reflux, hydroureteronephrosis may develop. Violation of natural urination provokes the deposition of salts, which eventually leads to the formation of concretions in the organ.
Complications of cystitis are also ureteral stenosis, chronic bleeding, provoking the occurrence of hypochromic anemia. In the absence of treatment, the risk of violations of the filtration capacity of the kidneys increases, which in severe cases ends in chronic renal failure. Sexual disorders are often observed — decreased libido, orgasmic dysfunction.
Diagnostics
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 probability of diagnosing interstitial inflammation of the urinary membranes increases in patients older than 18 years without other urological, gynecological, andrological pathology, presenting complaints of characteristic pelvic pain for six months or longer, urination from 5 or more times within an hour, nocturia more than 2 times per night.
An important diagnostic criterion is the ineffectiveness of previously conducted treatment with uroantiseptics, antibiotics, antispasmodics, anticholinergic drugs. The recommended methods of examination are:
- Urinalysis. Erythrocyturia is often observed, leukocyturia is possible. The specific gravity of urine is within the norm, the collected portion often has a small volume. Bacterial contamination of biological material is usually absent, less often with bacterial urine culture, saprophytes are detected.
- Cystometry. According to cystometry, the capacity of the filled bladder is less than 350 ml. The interstitial variant of the inflammatory process is characterized by the appearance of imperative urge to urinate after retrograde administration of up to 150 ml of liquid or up to 100 ml of gas. There are no involuntary contractions of detrusor.
- Cystoscopy with hydrobugging. During cystoscopy, Gunner’s ulcers or grade II-III glomerulation are visually determined in the form of extensive mucous hemorrhages that have arisen after hydraulic stretching. In 94% of patients, histological examination of the biopsy reveals degranulated mast cells, neutrophils, macrophages, fibrosis.
- Potassium test. The method involves alternately introducing sterile water and a solution of potassium chloride into the bladder cavity. Possible interstitial inflammation is indicated by the occurrence of more intense pain during the installation of potassium chloride. The test is used only to a limited extent due to its low specificity.
To exclude other pathological conditions with a similar clinical picture, ultrasound, CT, MRI of the pelvic organs, inoculation of prostate secretions, smear from the urethra and vagina, PCR diagnostics of urogenital infections, overview 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, adhesive disease), diverticulitis; in men – with prostatodynia, chronic prostatitis, vesiculitis.
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, cervix and uterine body, urethral diverticula, tuberculosis, radiation and chemical cystitis, neoplasia of the bladder, skineitis, leukoplakia, malacoplakia, hyperactive bladder are necessarily excluded. If there are indications, the urologist prescribes consultations of a gynecologist, andrologist, nephrologist, infectious disease specialist, venereologist, phthisiologist, oncologist.
Treatment for interstitial cystitis
Taking into account the ambiguity of etiopathogenesis, the therapy of the disease is mainly empirical. Experts of international urological associations have developed a three-stage algorithm for the management of patients with interstitial vesical inflammation. The duration of each stage is determined by the peculiarities of the course of cystitis in a particular patient and the effectiveness of the measures taken.
At the first stage, non-drug methods and oral pharmacotherapy are used. Patients with newly diagnosed interstitial cystitis are recommended to correct their diet and lifestyle: quitting smoking, reducing the amount of spices, salt, alcohol, carbonated drinks, coffee, increasing daily fluid intake to 1.5-2 liters. Bladder training, massage, acupuncture, electrical stimulation of detrusor are shown. Drug therapy includes:
- Antihistamines. Prescribing medications presumably reduces the hyperergic inflammatory reaction. In randomized studies, the therapeutic effect of selective H2-histaminoreceptor blockers has been proven, although significant morphological changes in tissues are usually not observed when they are taken.
- Tricyclic antidepressants. Despite a slight increase in the capacity of the bladder, patients feel a subjective improvement in the first week after starting taking medications. In the recommended dosage, antidepressants have a pronounced analgesic effect, which persists even after their withdrawal.
- Synthetic mucopolysaccharides. Due to the restoration of defects in the glycosaminoglycan layer, the contact of urine with the cells of the deep layers of the urogenital wall is reduced. As a result, pain is weakened, urination becomes more rare, and their imperativeness decreases. Mucopolysaccharide agents have practically no effect on nocturia.
At stage II, non-destructive intravesical pharmacotherapy is performed. Cytoprotectors that restore the protective layer of glycosaminoglycans, dimethyl sulfoxide (as monotherapy or with the subsequent appointment of heparin), anesthetics in combination with glucocorticoids that reduce inflammation and relax the muscle membrane are used for level instillation. Intradetrusory administration of botulinum toxin allows you to relax muscle fibers, reduce pain and frequency of urination, more than 2 times increase the cystometric capacity of the bladder. At this stage, endovesical iontophoresis of drugs is carried out.
Stage III methods are recommended in the absence of the effect of non-destructive methods of treatment. Cystoscopic hydrobugging of the bladder leads to ischemic necrosis of intravesical sensory receptors and restores microvascularization of the organ. When Gunner’s ulcers are detected, transurethral resection, electrocoagulation, and laser therapy of the damaged mucosa are additionally performed. Reconstructive plastic interventions (augmentation cystoplasty, intestinal bladder plastic surgery) are recommended for patients with severe wall sclerosis, significant loss of organ capacity, excruciating pelvic pain and severe dysuria.
Prognosis and prevention
The forecast is relatively favorable. As a result of complex drug and non-drug (diet, physiotherapy) treatment, most patients experience a regression of symptoms, but full recovery rarely occurs. The effectiveness of oral therapy reaches 27-30%, intravesical techniques — from 25 to 73%. Measures for the primary prevention of interstitial cystitis have not been developed due to the ambiguity of etiopathogenesis.
To prevent exacerbations, it is necessary to timely identify and treat inflammatory diseases of the genitourinary system, avoid risk factors (emotional stress, heavy physical work, eating foods rich in potassium, smoking, high doses of alcohol), and control seasonal allergies.