Hemorrhagic cystitis is an inflammatory process of the bladder, which is accompanied by micro– or macrohematuria, of various etiologies. It occurs more often in women. It proceeds with frequent and urgent urges, pain during infection, the presence of bloody impurities (including in the form of clots) in the urine. The diagnosis is confirmed clinically and laboratory (general analysis, backposev, urine PCR), ultrasound, cystoscopy with biopsy is also indicated. Depending on the etiology, treatment is carried out with the help of antiviral drugs, antibiotics, uroseptics, hemostatic agents, intravesical instillations.
ICD 10
N30.4 N30.8
Meaning
Hemorrhagic cystitis (HC) is a clinical and morphological type of cystitis, the hallmark of which is hematuria caused by bleeding from the bladder of varying severity. In the general structure of cystitis is 5-10% with a tendency to increase the incidence rate. It is statistically more common among women. Hemorrhagic cystitis requires urgent hospitalization of the patient in the department of urology to prevent complications and exclude severe pathologies of the urinary tract: urolithiasis, tumor processes, etc.
Causes
Hemorrhagic cystitis can have an infectious (viral, microbial, fungal) and non-infectious (chemical and radiation exposure) etiology. As the frequency of occurrence decreases , these factors are arranged in the following order:
- Bacterial infection. Among microbial agents, the most frequent pathogens of HC are E. coli (70-95%), saprophytic Staphylococcus (5-10%). Other Enterobacteria are less frequently detected: klebsiella, proteus.
- Viral infection. Children and immunocompromised adults are most predisposed to the development of hemorrhagic cystitis of viral etiology. Etiological significance is represented by human polyomaviruses 1 and 2, adenoviruses 7, 11, 34, 35 types, cytomegaloviruses, herpesviruses 1 and 2 types, Epstein-Barr virus. Sometimes a mixed infection is detected (HSV + CMV, HSV + EBV).
- Radiation therapy. Radiation cystitis develops in 5-25% of patients undergoing remote or intracavitary irradiation (brachytherapy) for pelvic organ tumors. This complication is more susceptible to patients with cancer of the prostate, cervix, rectum, etc.
- Drug therapy. Hemorrhagic cystitis is provoked by antitumor drugs (busulfan, cyclophosphamide, temozolomide, doxorubicin, etc.), antibiotics (penicillin and its derivatives), hormones (danazol), vaccines. Pathology can develop both with intravenous and intravesical administration of medicinal agents.
Risk factors
The following categories are among the risk groups, among which hemorrhagic cystitis occurs significantly more often:
- recipients of bone marrow and parenchymal organs;
- cancer patients with pelvic tumors;
- patients with autoimmune diseases (SLE, RA, Wegener’s granulomatosis);
- patients with recurrent infectious cystitis;
- women with vaginal dysbiosis, HPV-associated cervical erosion and other chronic gynecological pathologies;
- men suffering from prostatitis;
- patients undergoing repeated invasive manipulations on the genitourinary tract;
- patients with congenital immunodeficiency, AIDS.
Behavioral factors that increase the likelihood of HC incidence include early initiation of sexual relations, multiple changes of sexual partners, neglect of the rules of intimate hygiene.
Pathogenesis
With various etiological forms of hemorrhagic cystitis, the mechanism of damage to the bladder has its own differences. The pathogenesis of viral cystitis is based on the tropism of some viruses to the epithelium of the urinary tract with the development of microcirculatory disorders in the urea wall. Pathological changes are represented by hyperplasia of the urothelium, inflammatory infiltration of the mucosa, vascular fullness, multiple petechial hemorrhages. Viral inflammation creates a favorable background for bacterial invasion.
In radiation cystitis, free radicals are formed under the influence of ionizing radiation, causing deep damage or death of bladder cells (BC). The protective barrier formed by the glycosaminoglycan layer and urothelium is destroyed first. Due to the irritating effect of urine, inflammation, swelling and vasodilation of the BC wall occur. Microscopic obliterating endarteritis of the urea vessels, ischemia and ulceration of the mucous membrane develops and progresses.
In the areas of damage, new vessels grow (neovascularization), which are characterized by greater fragility and light bleeding with slight stretching or injury to the BC wall. Hematuria occurs. Hemorrhages in the submucosal layer entail a decrease in the number of smooth muscle cells, collagen deposition, infiltration of fibroblasts, followed by loss of normal contractile properties of BC.
Classification
According to the etiology, hemorrhagic cystitis is divided into medicinal, radiation, infectious. According to the terms of development, radiation- and chemically-induced HZ can be:
- early (develops in the first 48-72 hours after CT and RT);
- late (develops a few weeks or months after the end of treatment).
Taking into account the severity of hematuria, 4 degrees of hemorrhagic cystitis are distinguished in clinical urology:
I. Mild – microhematuria detected by laboratory methods is noted;
II. Moderate severity – macrohematuria visible to the eye is noted in the urine;
III. Severe – accompanied by macrohematuria with small blood clots;
IV. Complicated – massive macrohematuria, blood clots cause obstruction of the urinary tract and require instrumental extraction.
Symptoms
The clinic of acute HC practically does not differ from ordinary cystitis, except for the presence of hematuria. At the onset of the disease, pollakiuria, urgent urges to empty the bladder are noted. At the same time, little urine is released during the injection process, and attempts to urinate are extremely painful, accompanied by a pain in the lower abdomen. With microhematuria, urine visually looks normal, but more often it is colored reddish, sometimes blood clots are detected with the naked eye.
In an acute infectious process, the patient is worried about chills, fever, weakness, headache. Hemorrhagic cystitis usually has a recurrent type of course. Outside of exacerbation, patients complain of discomfort in the urethra and suprapubic region, moderate burning sensation when urinating, dyspareunia, general asthenia. Exacerbations of hemorrhagic cystitis are usually provoked by acute respiratory viral infections, coincide with exacerbation of genital herpes and other STDs.
Complications
Massive macrohematuria develops in 0.6-15% of cases of hemorrhagic cystitis. It can lead to tamponade of the bladder, which is fraught with difficulty in the outflow of urine. Against the background of tamponade, urosepsis, renal failure may develop, a rupture of the BC may occur. Recurrent inflammation leads to sclerosis and shrinking of the bladder (microcystis).
Persistent viral infection (especially combined) causes urothelial dysplasia. Periodically occurring hematuria causes iron deficiency anemia and its manifestations. For pregnant women, untreated hemorrhagic cystitis of infectious etiology is a dangerous risk of intrauterine infection of the fetus.
Diagnostics
The algorithm of examination of patients with hematuria includes consultation of a urologist, thorough collection of anamnesis with analysis of risk factors, laboratory tests, examination for infections, ultrasound and endoscopic examination of the genitourinary tract. To differentiate the ethological variant of hemorrhagic cystitis:
- Gynecological examination. All women additionally need a gynecologist’s consultation with an examination on a chair, setting up an O’Donnell-Hirshhorn test. At the same time, concomitant gynecological diseases are detected, smears are taken for flora, bac. sowing, PCR.
- Laboratory examination. First of all, an urine analysis and a Nechiporenko analysis are performed, on the basis of which the fact and degree of hematuria are established. To identify infectious pathogens, microbiological examination of urine with sensitivity to antibiotics, examination of urethral and vaginal smears for STIs, Femoflor test, blood ELISA for the presence of antiviral antibodies to HSV, CMV, HPV, EBV and other viruses is performed. Additionally, the blood test, coagulogram, urine for atypical cells are examined.
- Echography. Ultrasound of the bladder with hemorrhagic cystitis reveals thickening of the walls and blurred contours, hypervascularization, the presence of additional inclusions (clots) in the organ cavity. To detect other pathological processes in the pelvic organs, ultrasound of the kidneys, uterus and ovaries, prostate gland is performed. It is recommended to supplement seroscale echography with Dopplerography.
- Cystoscopy with biopsy. During an examination cystoscopy, an increase in the vascular pattern, hyperemia and looseness of the mucosa, which bleeds easily when in contact with the instrument, is determined. Pathomorphological features of hemorrhagic cystitis are the presence in the biopsy of pronounced inflammatory infiltration, coilocytosis, cells in the form of “mulberry berries”.
- Other studies. In order to exclude ICD and tumor processes, MRI urography, ureteropyeloscopy are indicated.
Differential diagnosis
During the examination, other urological, oncological, infectious, systemic pathologies accompanied by hematuria are excluded:
- glomerulonephritis;
- encrusting cystitis;
- tuberculosis of the bladder;
- urolithiasis;
- schistosomiasis;
- oncological processes: bladder cancer, breast cancer, prostate cancer;
- complications from taking anticoagulants, etc.
Treatment
Therapy in uncomplicated cases
Treatment is carried out in a urological hospital. Medications are selected taking into account the etiology of hemorrhagic cystitis, the presence of concomitant diseases and complications. If the cause of HC was LT or HT, a revision of the treatment regimen is performed with the replacement of drugs, adjustment of the dose and method of irradiation. The standard approach for uncomplicated hemorrhagic cystitis includes the following areas:
- Antiviral therapy. It is indicated for virus-associated hemorrhagic cystitis. Synthetic nucleoside analogues, DNA polymerase pyrophosphate inhibitors, dCMP nucleotide analogues, etc. are used for etiotropic therapy.
- Antimicrobial therapy. It is prescribed for bacterial cystitis, as well as for other forms with a high risk of microbial complications. More often, cephalosporins, penicillins, fluoroquinolones, phosphonic acid derivatives are used in antibacterial courses.
- Uroseptics. They include nitrofurans, herbal preparations, and herbal diuretics. They are used as an adjunct to antimicrobial therapy, especially for antibiotic resistance.
- Other medications. To relieve pain, antispasmodics, NSAIDs are used, with severe hematuria, hemostatic agents are prescribed. With symptoms of general intoxication, copious drinking and infusion therapy are indicated. Intravesical instillations of antiseptics, astringents, hemostatics, sodium hyaluronate are produced.
Treatment of complicated forms
In severe hemorrhagic cystitis, procedures aimed at relieving complications are added to the listed measures. With severe hematuria, accompanied by anemia and thrombocytopenia, hemotransfusion of erythrocyte and platelet mass is performed. In the treatment of post-radiation cystitis, forced diuresis and hyperbaric oxygenation are used.
Tamponade elimination is performed by washing the BC through a urethral catheter or cystostomy. Sometimes irrigation urethrocystoscopy is performed for controlled removal of blood clots. With continued bleeding, selective embolization of the arteries is resorted to. With the development of acute renal failure, hemodialysis is indicated.
Prognosis and prevention
The prognosis and quality of later life largely depend on the cause that caused hemorrhagic cystitis. Infectious cystitis responds well to treatment, but may recur with the persistence of infection and the persistence of risk factors. Behavioral factors play a significant role in the prevention of hemorrhagic cystitis: an orderly sex life, the use of barrier contraception during casual sexual contacts, taking drugs under the supervision of a doctor. During radiotherapy of the pelvic organs, the prevention of hemorrhagic cystitis should be carried out in parallel with the main treatment.