Overview.
A chronic pelvic pain syndrome, is a special type of bladder pain syndrome manifested as pelvic pain and discomfort, accompanied by frequent urination, urinary urgency onset of infection, autoimmune, inflammation, neurological, psychosocial and other factors related to personalized treatment plan, conservative treatment, severe surgical treatment
Definition
Interstitial cystitis is a class of pelvic pain syndromes, which refers to the main clinical manifestations of varying degrees of pain, urinary frequency and urgency in the bladder and peripelvic region that lasts for more than 6 weeks, provided that infection or other diseases are excluded [1].
According to the recommendation of the standardization committee of the International Continence Society (ICS), the term “interstitial cystitis/bladder pain syndrome (IC/BPS)” is now used.
Classification
Interstitial cystitis is categorized into ulcerative and non-ulcerative types depending on the cystoscopic pathology.
Ulcerative type of interstitial cystitis
Interstitial cystitis is typically characterized by Hunner’s ulcers, which are most commonly found at the junction between the bladder apex and the posterior and lateral walls, areas of ectopic red mucosa with small blood vessels radiating to a central scar, and fibrin deposits or clots attached. As the bladder swells, blood oozes from the lesion in a cascade over the mucosal margins.
It is seen in only 5% to 10% of patients.
Non-ulcerative interstitial cystitis
Non-ulcerative interstitial cystitis with hemorrhagic spots in the mucosa following watery bladder distension accounts for more than 90% of interstitial cystitis.
Pathogenesis
Interstitial cystitis varies in incidence statistics due to unclear etiology and inconsistent definitions and diagnostic criteria. The incidence of interstitial cystitis in the United States is (52-67)/100,000 in women and 8/100,000 in men. The prevalence of females in Fuzhou, China, in 2009 was 100/100,000 per 100,000 population.
It is less common in males, and the prevalence in females is two to five times higher than that in males.
The peak age of onset in women is young adults, i.e., middle-aged women between 30 and 50 years old, and it is rare under 18 years old.
Causes
Causes
The cause of interstitial cystitis remains unclear and may be related to infection, autoimmunity, inflammation, neurologic, psychosomatic and other factors.
Infection
Although the presentation of urinary tract infections is similar to that of interstitial cystitis, the exact relationship between microbial infections and interstitial cystitis is not well established.
It is generally believed that microbial infection is not a direct cause of the development of interstitial cystitis, but infection is usually a factor that induces or aggravates interstitial cystitis.
Inflammation.
Some patients show diffuse inflammation in the bladder.
Histologic analysis of the bladder often shows mast cell infiltration, high levels of proinflammatory cytokines and chemokines detectable in the serum, bulbous hemorrhagic spots on cystoscopy after water dilatation, and erosion and thinning of the bladder wall suggest a role for inflammation in the pathogenesis of interstitial cystitis.
Immunologic factors
Autoimmune antibodies are present in patients with interstitial cystitis.
The autoantibodies initially detected in patients with interstitial cystitis are antinuclear antibodies, which are similar to the autoantibody profile of systemic autoimmune diseases such as dry syndrome.
Studies have found that 41.2% of patients with interstitial cystitis also have autoimmune diseases.
Neurologic factors
Increased sympathetic nerve activity in the bladder, upregulation of peripheral and central sensory innervation, increased nerve fiber density, and the presence of neuroinflammation are all factors, which suggest a neurological abnormality in interstitial cystitis.
Psychosomatic factors
Psychosomatic abnormalities are often present in patients and have a marked impact on their psychosocial functioning and quality of life. Patients have significantly more pain, sleep disturbances, depression, anxiety, stress, social dysfunction and sexual dysfunction than patients with non-interstitial cystitis.
Predisposing factors
Interstitial cystitis has more onset or exacerbation factors, including sex, menstruation, dieting, mental stress, seasonal weather changes, sudden strenuous activities, wearing tight pants, pushing/lifting heavy objects, standing for long periods of time, and holding urine.
Symptoms
Interstitial cystitis presents with prolonged (6 months or more) pain of varying degrees in the bladder and peripelvic area, as well as urinary urgency and frequency.
Main Symptoms
Pain
It may manifest as pain in the lower abdomen and suprapubic region (including cramping and discomfort), pain in the urethra, vagina, and perineum. Some patients have pain and discomfort in the vagina, urethra, perineum, pubic bone and its surrounding areas.
The pain is worse with a full bladder and is relieved by urination.
The pain may be mild or progressive.
The degree of pain is susceptible to diet, mental stress, physical state and environmental factors. Painful symptoms are aggravated before menstruation or during ovulation.
Bladder irritation sign
There are severe symptoms of urinary frequency, urgency and pain.
Frequent urination: It means urinating more often (more than ten times or even dozens of times a day) but the amount of urine is very small. Sometimes it is necessary to urinate once in a few minutes, but the volume of urine is only a few drops.
Urgency of urination: Once the urge to urinate is hard to control, you must go to urinate, and sometimes you will wet your pants.
Painful urination: can occur after frequent and urgent urination.
Other symptoms
May manifest with lower abdominal cramping and pressure sensation.
Pressure, burning sensation and urinary discomfort during urination.
Vulvar itching and burning sensation, pain during intercourse, ejaculation pain and fidgeting etc. 60% of patients have pain during intercourse.
Consultation
Department of Medicine
Urology
If you have unexplained suprapubic pain, accompanied by urinary frequency, urgency and pain, it is recommended to consult the urology department promptly.
Preparation
Consultation: Registration, Preparation of Documents, Frequently Asked Questions
Tips for medical consultation
Record the symptoms, duration and other relevant information, so as to give the doctor more reference.
Special tips: It is recommended not to take painkillers when in pain to prevent masking the condition.
Preparation Checklist
Symptom list
Especially focus on the time of symptom onset, special manifestations, etc.
Is there pain in the lower abdomen?
Are there symptoms such as frequent urination, urgent urination, painful urination, etc.?
How long have the symptoms lasted?
Medical history list
Are there any relatives with similar symptoms in the family?
Are there any asthma, autoimmune diseases, rheumatoid, inflammatory bowel disease, other urologic conditions?
Checklist
Test results from the last 6 months, which can be brought to the doctor’s office
Imaging tests: cystoscopy.
Laboratory tests: urine routine, urine culture, GP51, AFP marker test.
Pathological examination: Histologic examination of bladder mucosa.
Other tests: PST (potassium ion sensitivity test) test.
Medication list
Medication used in the last 3 months, if available in a box or package, carry it to the doctor’s office
Alpha-blockers: tamsulosin, cyclobenzaprine, naftalidil
Antihistamines: hydroxyzine, cetirizine
Antidepressants: amitriptyline, promethazine
Diagnosis
Diagnostic basis
The diagnosis of interstitial cystitis is an exclusive one. It requires a history taking, physical examination and laboratory tests to exclude other conditions that can cause pelvic pain before interstitial cystitis can be considered.
Medical History.
There may be a history of asthma, autoimmune disease, rheumatoid, or inflammatory bowel disease.
There may be a history of depression or panic attacks, functional somatic complaints.
Clinical manifestations
There is pain in the lower abdominal bladder area that is painful when the bladder is full and relieved by urination.
Accompanied by urinary frequency, urgency, and dysuria.
Symptom scales
There are five commonly used scales that can be used to assess a patient’s symptoms and assist in diagnosis.
These include the Interstitial Cystitis Symptom Score ICSI, the Interstitial Cystitis Problem Score ICPI, the Wisconsin Interstitial Cystitis Inventory (UW-IC), the Pain, Urinary Frequency, Urgency Score PUF, and the Bladder Pain Interstitial Cystitis Symptom Score BPIC-SS.
Symptom scales are important tools for assessing symptom severity and treatment outcomes in patients with IC.
Voiding diary
A continuous record of urination for 72 hours, including the time of each drink, the amount of water consumed, the time of urination, the amount of urine, and accompanying symptoms.
A voiding diary helps to differentiate simple polyuria from interstitial cystitis because interstitial cystitis has a lower than normal volume of urine per voiding, but the total urine volume is usually normal.
The average volume of urine in patients with interstitial cystitis is less than 100 ml per voiding, and the average volume of urine in a single voiding is 84 to 174 ml. Also, female patients with interstitial cystitis urinate 17 to 25 times per day, compared with just 6 times in normal women.
A voiding diary is also helpful in assessing the severity of symptoms in female patients and can also be used to evaluate the effectiveness of treatment.
Laboratory Tests
Urine routine
Purpose: To find out the changes in red blood cells, white blood cells, etc. in the urine.
Significance: Routine urine results are usually normal and can be used to rule out urinary tract infections and can aid in the diagnosis of interstitial cystitis.
Urine culture
Purpose: To find out whether there are germs in the urine and whether there is infection.
Significance: Urine culture results suggesting negative urine culture can be used to rule out bacterial cystitis, tuberculous cystitis, vaginitis, etc., and can assist in the diagnosis of interstitial cystitis. In women, testing for ureaplasma and chlamydia should also be performed, especially in patients with negative urine cultures and purulent urine.
Markers
Purpose: To find out the changes in GP51 and AFP.
Significance: A significant decrease in glycoprotein 51 (GP51), a significant increase in prostaglandin E2 (PGE2), and an increase in the value of AFP may indicate interstitial cystitis.
Imaging
Cystoscopy
Purpose
Used to rule out bladder cancer/carcinoma in situ, even if Hunner ulcer is found it is only a reflection of the severity of the disease and does not exclude the possibility of other diseases;
For determining the effect of bladder filling and emptying on pelvic pain;
Objective evaluation of functional bladder capacity.
SIGNIFICANCE: Cystoscopy can be used not only for the diagnosis of interstitial cystitis, but also to aid in its treatment. This is because cystoscopy distinguishes ulcerative from non-ulcerative forms of interstitial cystitis, which respond differently to treatment.
Tissue biopsy
Purpose: To learn about lesions in the bladder mucosa.
Significance: Histologic findings show bladder mucosal epithelial exfoliation or ulcer formation, fracture defects in the mucosal layer, and mast cell infiltration as a nonspecific inflammatory manifestation.
Routine bladder biopsy is not recommended for the diagnosis of interstitial cystitis but can be used to rule out other specific diagnoses such as carcinoma in situ of the bladder.
Bladder water dilatation
Bladder water dilatation is the dilation of the bladder by the pressure of water.
It is usually performed under general anesthesia or lumbar epidural anesthesia (therapeutic water dilation).
The presence of terminal hematuria when the bladder is emptied of fluid after water dilatation, as well as submucosal hemorrhage are thought to be characteristic of interstitial cystitis.
Diagnostic criteria
The NIADDK’s diagnostic criteria for interstitial cystitis are listed below.
Prerequisites
Pain in the bladder area or lower abdomen or suprapubic with dysuria.
Submucosal punctate hemorrhage or Hunner’s ulcer seen after water dilatation under anesthesia.
Cystoscopy is performed after water injection into the bladder under general anesthesia or epidural anesthesia to a pressure of 80-100 cmH2O held for 1-2 minutes, twice in total.
Diffuse submucosal punctate hemorrhage should be found, extending over 3 quadrants with more than 10 in each quadrant, and not at the site of cystoscopic passage.
The following conditions are excluded
Bladder volume greater than 350 ml in the awake state.
No urge to urinate when filling with water at 30-100 ml/min to 150 ml.
Periodic involuntary contractions during bladder irrigation.
Symptoms not more than 9 months old.
No increase in nocturia.
Treatment with antibiotics, anti-microbial agents, anticholinergic or antispasmodic agents is effective.
Urination less than 8 times per day when awake.
Prostatitis or bacterial cystitis within 3 months.
Bladder or lower urinary tract stones.
Active genital herpes.
Tumors of the uterus, vagina, or urethra.
Urethral diverticulum.
Cyclophosphamide or other chemical cystitis.
Tuberculous cystitis.
Radiation cystitis.
Benign and malignant bladder tumors.
Vaginitis.
Age less than 18 years.
Differential diagnosis
The diagnosis of mesenchymal cystitis requires the exclusion of other conditions such as tuberculous cystitis, radiation cystitis, adenoid cystitis, bacterial cystitis, and eosinophilic cystitis.
Tuberculous cystitis
Similarities: Both may present with symptoms such as frequent urination, urgency, and painful urination, as well as urine bacterial cultures that are often negative.
Differences: Tuberculous cystitis is often preceded by renal tuberculosis, and the clinical manifestations include bladder irritation, hematuria, pyuria, low-grade fever, night sweats, and malaise; antacid bacilli can be found in the urinary sediment, and cystoscopy reveals the formation of typical tuberculous nodules in the bladder wall or dark-red ulcerated surfaces of varying sizes.
Radiation cystitis
Similarity: Both may present with symptoms such as frequent urination, urgency, and painful urination.
Differences: In addition to bladder irritation signs, the clinical manifestations of radiation cystitis include sudden, continuous or recurrent painless hematuria with blood clots of varying sizes in the urine; antacids can be found in the urinary sediment, and cystoscopy can show mucosal congestion and edema, or even ulceration and perforation.
Bacterial cystitis
Similarity: both may present with symptoms such as frequent urination, urgency and painful urination.
Differences: Bacterial cystitis, caused by bacterial infection, clinical manifestations, in addition to signs of urinary tract irritation, there are symptoms such as hematuria, pus, and fever; urine culture can show positive bacteria, cystoscopy shows that the mucous membrane of the bladder is congested and edematous with exudate.
Glandular cystitis
Similarities: Both occur in women, both may have symptoms such as frequent urination, urgency, dysuria, pain in the perineal area, and both may have pressure pain in the suprapubic bladder area.
Differences: adenohydrocystitis is mostly secondary to lower urinary tract infection or obstruction, functional abnormalities; in addition to bladder irritation signs, there are also hematuria and dysuria; cystoscopy shows rough and uneven bladder mucosa, congestion and edema, thickening, and multiple papillary projections.
Eosinophilic cystitis
Similarities: Both may present with symptoms of urinary frequency, urgency, dysuria, and pain in the perineal area.
Differences: eosinophilic cystitis, mostly urinary tract allergic diseases, past history of allergy or asthma; in addition to bladder irritation signs, there are hematuria, pus; cystoscopy shows bladder mucosal edema, ulceration, erythema formation. Pathologic examination shows eosinophilic infiltration.
Treatment
Aim of treatment: to control pain, reduce symptoms and improve quality of life.
Treatment principle
On the premise of ensuring symptom control, non-surgical treatment is preferred;
When the effect of single treatment is not good, a combination of multiple treatments should be combined;
Focus on the degree of improvement of pain and take it as an important index to evaluate the treatment effect.
General treatment
Dietary treatment
Eat a light diet, avoiding stimulating foods and beverages such as acidic drinks, coffee, alcohol, tea, soda, and avoiding chocolate, spicy foods, and artificial sweeteners.
The dietary regimen is individualized to provide dietary therapy depending on the patient.
Bladder training
Frequent urination can leave the bladder in a low volume state for long periods of time, resulting in reduced bladder capacity.
Bladder training with regular and delayed urination can expand bladder capacity and reduce bladder sensitivity, resulting in relief of frequent and urgent urination symptoms.
Medication
Oral medications
M-receptor antagonists
M receptor antagonists can improve the symptoms of lower urinary tract symptoms in the storage phase by blocking bladder muscarinic receptors, relieving overcontraction of the urethral muscle, reducing bladder sensitivity.
They are mainly used alone and in combination with a-blockers.
Adverse reactions: dry mouth, dizziness, constipation, dysuria and blurred vision. It is generally not recommended for patients with residual urine > 50 ml or in the presence of forced urinary muscle weakness or with urinary retention.
M-receptor antagonists may be added to patients whose storage phase symptoms do not improve significantly or persist with alpha-blockers.
Alpha Receptor Blockers
Relieve outlet power obstruction by blocking adrenergic receptors in bladder neck smooth muscle and relaxing the smooth muscle.
Commonly used drugs: tamsulosin, selodosin, naftopidil, and so on.
Adverse effects mainly include dizziness, headache, fatigue, drowsiness, upright hypotension, increased incidence of iris relaxation syndrome after cataract surgery and sexual dysfunction.
Analgesics.
The goal of pharmacotherapy for pain is to find drugs or treatment regimens that are effective in relieving pain with minimal adverse effects.
Non-selective, low-potency nonsteroidal anti-inflammatory drugs (NSAIDs) are preferred as first-line analgesics; if they are not effective, high-potency, selective NSAIDs are then chosen. opioids should be used with caution as a second-line drug.
Antidepressants
Mechanism of action: relax bladder smooth muscle, reduce bladder tension.
Common drugs: amitriptyline, promethazine, clomipramine and so on.
Adverse reactions: excessive sweating, dry mouth, blurred vision, dysuria, constipation, etc.; caution should be exercised in patients with hepatic impairment.
Antihistamines
Mechanism of action: the drug acts on the mast cells on the bladder wall to inhibit their release of inflammatory substances causing pain.
Common drugs: hydroxyzine, cetirizine, cimetidine and so on.
Adverse reactions: drowsiness, low mental activity, dizziness and dry mouth. Suspension of breastfeeding in breastfeeding women.
Precautions: The drug is used in the initial or severe acute phase of the disease and is prone to relapse after discontinuation; it is recommended to continue the maintenance dose.
Bladder Drug Infusion
Bladder water dilatation
Bladder water dilatation is both a screening method and a treatment that can relieve symptoms or even make them disappear, but its efficacy lasts for a shorter period of time, with an average maintenance time of about 6 months.
Complications are rare and include severe bleeding after water dilatation, worsening of symptoms and bladder rupture.
Multiple repetitions are usually not possible.
Dimethyl sulfoxide and heparin
Mechanism of action: Dimethyl sulfoxide has anti-inflammatory, analgesic, and bacteriostatic effects. Heparin enhances the protective layer of the bladder wall and also has anti-inflammatory and anti-adhesive effects.
Adverse reactions: there are gastrointestinal reactions, alopecia. It is contraindicated in patients with bleeding tendency and anticoagulant therapy.
Precautions: urinary catheter insertion is required for instillation; patients’ body fluids have a garlic-like odor after instillation.
Hydroxychlorosan sodium
Mechanism of action: Hydroxychlorosan sodium can cause healing of the bladder surface, which in turn reduces the patient’s symptoms.
Adverse reactions: there are allergic reactions, etc.
Precautions: There are few studies on this drug and its contraindications are unclear.
Hyaluronic acid
Mechanism of action: temporary repair of defective epithelial mucosa, effective in relieving symptoms.
Adverse reactions: edema, redness, heat sensation, localized heavy pressure sensation.
Precautions: For mild to moderate patients; urinary catheter is required for instillation.
Surgical treatment
Transurethral surgery
Limited to patients with definite Hunner ulcers. And after surgery, the symptoms are easy to recur with the passage of time, and most of them need to be treated again.
Surgical modalities: transurethral electrolysis/electrocoagulation, laser cauterization.
Urethral reconstruction surgery
For patients with refractory interstitial cystitis with severe symptoms, reconstructive urologic surgery may be used as a last resort to improve pain and quality of life if other treatment options have failed to control symptoms.
Reconstructive urologic surgery is usually performed in large, experienced hospitals, and may include urinary diversion (with or without cystectomy) and bladder enlargement plasty.
Other treatments
Traditional Chinese Medicine (TCM)
This syndrome belongs to the categories of heat drench, blood drench, qi drench, cream drench and labor drench in TCM. It needs to be diagnosed and typed, and standardized treatment should be carried out after consultation with a Chinese medicine practitioner.
Prognosis
Cure
Interstitial cystitis is difficult to cure.
Several treatment modalities are often used in combination, with pain control and symptomatic relief being the main goals of treatment.
Harmfulness
Patients experience long-term pelvic pain and urinary frequency and urgency, which affects their daily life.
Patients with interstitial cystitis often suffer from mental anxiety and depression, and need to recognize the disease correctly and face it positively and optimistically.
Daily
Daily Management
Dietary management
Diet should be based on light and easily digestible food. Increase protein intake appropriately, such as milk and lean meat.
Certain foods may cause worsening of symptoms, including coffee, tea, citrus fruits, carbonated and alcoholic beverages, bananas, tomatoes, spicy foods, artificial sweeteners, vitamin C, and wheat products. Patients avoid as many of these foods as possible for 1 week to 3 months, then find those patients with sensitive dietary triggers and avoid them by adding a particular food, one by one, for 3 consecutive days, and observing whether it causes an exacerbation of symptoms.
Life management
Smoking cessation.
Live a regular life, pay attention to rest and avoid exertion. Keep emotional stability, avoid emotional excitement.
Urine care: For patients with frequent urination, wash the perineum after going to the toilet; adult diapers can be used, but be careful to change them in time and wash the perineum.
Behavioral management
Bladder training, achieved by relaxing the pelvic floor muscles, with the goal of decreasing the frequency of urination and potentially increasing bladder capacity.
Control of fluid intake, regular urination and conscious prolongation of intervals between urination.
Hot or cold compresses to the suprapubic or perineal area are likely to reduce symptoms.
Avoid behaviors that can aggravate interstitial cystitis, such as tight clothing and constipation.
The following ways may relieve stress: more exercise, proper bathing, reduced working hours, meditation, yoga, etc.
Psychological support
Interstitial cystitis patients tend to have varying degrees of anxiety due to the presence of pain and urgency and frequency of urination. Stress originating from family, work, or previous traumatic experiences can also trigger or exacerbate pelvic pain.
If anxiety or depression is present, one should take the initiative to communicate with family members for understanding and support. You can also communicate with your doctor about your condition, learn about the disease and discuss reasonable treatment options. If necessary, you can consult a psychiatrist to alleviate psychosomatic problems and face such a chronic disease with a positive mindset.
Prevention
The cause of interstitial cystitis is not clear and there are no effective preventive measures. Good behavioral habits may reduce the incidence.
Adopt good habits, do not smoke or drink alcohol.
Regularize your routine, get enough sleep and keep your mind optimistic.