CC may manifest differently. Very mild forms of CC may not even cause symptoms and an infection of the urinary bladder is only an incidental finding obtained during analyses carried out for any other reason.

Some patients may report fatigue, lethargy, malaise and weakness or present with fever. Nausea and vomiting may be observed, too. These systemic symptoms are not necessarily accompanied by micturition problems and thus require a very thorough workup to realize that the source of disease is located within the urinary tract.

Micturition disorders, if present, usually consist in dysuria, pollakiuria with very small amounts of urine passed and possibly hematuria. Most patients report persistent lower abdominal pain and a burning sensation upon micturition rather than acute abdominal pain while urinating. Pollakiuria may turn into incontinence. Of note, incontinence may also be the only symptom pointing at an infection of the urinary tract. Incontinence is not dependent on the presence of pain while passing urine.

Urine properties may be visibly altered. Urine may appear cloudy, contain traces of blood and may be malodorous.

• Chronic Infection

  Treatment of chronically infected mice with the same FimH inhibitor lowered their bladder bacterial burden by >1000-fold. [ncbi.nlm.nih.gov]

  Further, proteomics identified bladder epithelial remodeling consequent to chronic infection that enhances sensitivity to neutrophil damage. [zora.uzh.ch]

  in an experimental mouse model of chronic bladder infection with uropatogenic E. coli infection (causative agent of 80% of UTI), injury to the bladder mucosal lining due to severe inflammation preceded chronic cystitis Immunodeficient mice, lacking [pathologyoutlines.com]

  […] negative Chronic cystitis w hematuria Chronic infective cystitis Chronic nonspecific cystitis Cystitis, chronic Hematuria due to chronic cystitis Subacute cystitis 595.2 Excludes Applies To Chronic cystitis NOS Subacute cystitis ICD-9-CM Volume 2 Index [icd9data.com]

  The underlying causes include: chronic bladder outlet obstruction pelvic lipomatosis benign prostatic hypertrophy bladder TCC chronic infection bladder calculi Chronic irritation from infection, calculi or even tumors results in metaplasia of the urothelium [radiopaedia.org]

• Suprapubic Pain

  Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain. [icd10data.com]

  Patients may be asymptomatic, or may experience dysuria, frequency, urgency and suprapubic pain .Urine may be grossly cloudy. [medigoo.com]

  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. [12] Association with other conditions [ edit ] Some people [en.wikipedia.org]

  Excessive urgency and frequency of urination, suprapubic pain, dyspareunia, chronic pelvic pain and negative urine cultures are characteristic of interstitial cystitis. The course of the disease is usually marked by flare-ups and remissions. [aafp.org]

• Back Pain

  […] or pressure in the lower abdomen or lower back When bladder infections spread, they can also cause mid-back pain. [healthline.com]

  Typical symptoms are a burning pain during and immediately after urination, unusually urgent or frequent urinations, low-grade fever, and lower back pain. [britannica.com]

  […] in the urine, and often pelvic and back pain. [dawnscarzellamd.com]

  They may have pins and needles or shooting pains down their legs or chronic back pain. All of these things are potentially coming from the bladder.” [todaysdietitian.com]

  Some or all of the pain that is diagnosed as bladder pain syndrome may be caused by spasm in the pelvic floor, lower abdomen, or back muscles. [womenshealth.gov]

• Anger

  Stress, anxiety, anger, depression, and frustration may worsen IC. As with any chronic pain disorder, psychosocial support is essential to treatment. Provide support to help the patient deal with these problems as well as the disorder itself. [americannursetoday.com]

  Ackerman AL, Lai HH, Parameshwar PS, Eilber KS, Anger JT. Symptomatic overlap in overactive bladder and interstitial cystitis/bladder pain syndrome: development of a new algorithm. BJU Int. 2018 Sep 25. [Medline]. [emedicine.medscape.com]

• Pelvic Pain

  Chronic Pelvic Pain Syndrome (CPPS) is just what it sounds like — pain that may occur anywhere the pelvis. This type of pain may occur in several places at once or move around within the pelvis from one day to the next. [choicespc.net]

  […] floor treatments [ edit ] Urologic pelvic pain syndromes, such as IC/BPS and CP/CPPS, are characterized by pelvic muscle tenderness, and symptoms may be reduced with pelvic myofascial physical therapy. [40] This may leave the pelvic area in a sensitized [en.wikipedia.org]

  Patients also may be asked to answer a short questionnaire called the Pelvic Pain Urgency/Frequency (PUF) survey to help the physician identify if the pelvic pain is coming from the bladder. [nmihi.com]

  Another line that provides many different options for heat/cold therapy is Pelvic Pain Solutions. [wellnessmama.com]

• Urinary Urgency

  Patients experience symptoms of urinary frequency, urinary urgency or pain in the areas between the navel and the inside of the thighs that can be mild or severe and occasional or constant. [tucc.com]

  The device generates low-amplitude stimulation that decreases urinary urgency. The procedure is FDA-approved to treat urinary urgency and frequency, although not specifically IC. [americannursetoday.com]

  The symptoms of IC/PBS are pelvic or bladder pain, frequent urination, and urinary urgency. IC/PBS has a variable course, meaning that symptoms can appear and disappear over time. [medicinenet.com]

  This family of related conditions includes the following: Women & Men Chronic Pelvic Pain Hernias Interstitial Cystitis Overactive Bladder Pelvic Floor Dysfunction Pudendal Nerve Neuralgia Recurrent Urinary Tract Infections Urinary Urgency (urgent need [choicespc.net]

• Dysuria

  Micturition disorders, if present, usually consist in dysuria, pollakiuria with very small amounts of urine passed and possibly hematuria. [symptoma.com]

  Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain. [icd10data.com]

  Patients may be asymptomatic, or may experience dysuria, frequency, urgency and suprapubic pain .Urine may be grossly cloudy. [medigoo.com]

  The early symptoms of cystitis in women are dysuria, or pain on urination; urgency, or a sudden strong desire to urinate; and increased frequency of urination. [medical-dictionary.thefreedictionary.com]

  In case of interstitial cystitis, changes of phases of the course of inflammatory processes occur, thus leading to a severe pain syndrome and a decrease in bladder capacity with increasing dysuria. [uf.ua]

• Urinary Incontinence

  Some common ones are Cystitis - inflammation of the bladder, often from an infection Urinary incontinence - loss of bladder control Overactive bladder - a condition in which the bladder squeezes urine out at the wrong time Interstitial cystitis - a chronic [icdlist.com]

  The limited cutaneous form of systemic sclerosis (SSc) is associated with urinary incontinence (UI): an international multicentre study. [sclero.org]

  SYMPTOMS: Trigonitis and chronic cystitis can cause severe bladder pain and burning, pelvic pain and pressure, reduced bladder capacity, an increase in the frequency and urge to urinate, particularly at night, blood in the urine and urinary incontinence [dawnscarzellamd.com]

  Sacral Nerve Stimulation Implant: This surgically implanted device was recently approved by the FDA for treating a type of urinary incontinence. It is currently undergoing tests for use in IC. [kidney.org]

  Denies urinary incontinence. On physical examination, you find Ms. Cranford in no apparent distress. Her lungs are clear; her heart rate is regular with no murmur. Her extremities show no cyanosis, clubbing, or edema. [americannursetoday.com]

• Nocturia

  Common cystitis symptoms can include; frequent and painful urination, blood in the urine, nocturia, or night-time urination, strong-smelling urine, feeling of pressure in the bladder and sometimes fever. [vitatree.ca]

  The three characteristic features of cystitis include: Increased frequency of urination, especially during night (technically referred to as nocturia). Pain or burning sensation while passing urine (technically referred to as dysuria). [phaa.com]

  IC always causes pain associated with bladder filling or emptying, usually accompanied by urinary frequency, urgency, and nocturia. The pain, which originates from the bladder, usually is felt suprapubically. [americannursetoday.com]

  Animal models have shown decreased bladder sensitivity to potassium chloride, [85] and small human studies have shown promising results in reduction of frequency, nocturia, pain, urgency, and O'Leary-Sant scores. [86] While these results are initially [emedicine.medscape.com]

Anamnesis, clinical examination and urine analysis are the mainstays of CC diagnosis.

Urine analysis may reveal proteinuria, hematuria and, most importantly, bacteriuria. Obtained samples should be used to prepare bacterial cultures and to establish an antibiogram. Any decision for an antibiotic treatment of CC should be based on an antibiogram. If bacteria cannot be detected in urine samples of different days, less common causes for CC and differential diagnoses should be considered.

Although gynecological and urological examination is usually not required to diagnose uncomplicated urinary tract infections, it may be recommendable if patients suffer from recurrent cystitis. Anatomic anomalies may predispose patients for urinary tract infections. Also, sexually transmitted diseases constitute important differential diagnoses and may have been overlooked initially [12].

Additionally, diagnostic imaging may be helpful to rule out other pathologies, e.g., urolithiasis, malformations, restriction or compression of the urinary tract, urinary retention and neoplasms. In order to visualize the urinary tract, urography should be performed, either by means of plain radiography, magnetic resonance imaging or computed tomography.

• Pyuria

  The majority of patients with cystitis will have pyuria (≥10 WBCs per mm3) on microscopy; however, pyuria without symptoms and signs is not sufficient to make the diagnosis. [clinicaladvisor.com]

  Current emphasis in the diagnosis of UTI rests with the detection of pyuria, as follows: A positive leukocyte esterase dipstick test suffices in most instances In females with clinical findings suggestive of UTI, urine microscopy may be indicated even [emedicine.medscape.com]

  Nonbacteriuric patients with pyuria should be tested or empirically treated for Chlamydia infection. 20 A careful pelvic examination is needed to rule out vaginitis, vulvar lesions and urethral diverticula. [aafp.org]

In general, CC is treated exactly as uncomplicated cystitis. However, the decision for an antimicrobial agent should be strictly based on previous testing of sensibility. While fluoroquinolones, trimethoprim and sulfonamides, nitrofurantoin as well as fosfomycin are frequently used as an initial treatment for urinary tract infections which are not based on an antibiogram, bacteria may develop resistances against these compounds and in fact, multiresistant bacteria are the main cause for persistent cystitis.

Antiviral compounds or antiparasitic drugs should be administered to treat non-bacterial cystitis if the respective etiology is proven.

Patients may additionally benefit from parasympatholytics that counteract abdominal pain due to spasms of the smooth musculature of the urinary bladder. Butylscopolamine may be used to this end.

Prognosis is good if an adequate treatment can be provided and patients comply with instructions regarding drug intake. To date, even multiresistant pathogens are generally susceptible to one or more antibiotics and thus, causative therapy is possible. Permanent functional impairment and rupture of the urinary bladder are rare events [11]. This may change with continuous, irresponsible administration of antimicrobials, namely of reserve antibiotics.

Bacterial infection is the most common cause of CC. Distinct bacterial species are able to colonize and replicate within the urinary bladder. They are well adapted, resist the constant flow of urine and avoid killing by the host's immune system. In detail, the following species have been related to CC:

• Enterobacteriaceae like Enterobacter spp., Escherichia coli, Klebsiella spp., Proteus spp.,
• Pseudomonas aeruginosa
• Enterococcus faecalis
• Staphylococcus spp.
• Streptococcus spp.

Less frequently, viral infections or infestation with parasites may account for cystitis. In this line, adenovirus, BK virus, cytomegalovirus, human papilloma virus as well as Schistosoma haematobium and Toxocara spp., respectively, shall be mentioned [1] [2] [3] [4].

Escherichia coli is by far the most common trigger of CC. It is also a very good example to explain how most urinary tract infections take place. The patient's behavior as well as preferred clothing, e.g., wiping from back to front after going to the toilet, sexual intercourse, particularly anal intercourse, and wearing of tight, non-breathable underwear all increase the risk of fecal bacteria to reach the ostium urethrae externum.

An urinary catheter may serve as a guide for bacteria to ascend to the urinary bladder and should therefore be changed in short intervals.

Immunodeficiency, possibly iatrogenic or due to comorbidities like diabetes mellitus or HIV infection, increases the general risk of urinary tract infection and therefore of CC. Furthermore, some women may be more prone to urinary tract infections because their vaginal mucosa may be more susceptible to bacterial colonization. Genetic predisposition seems to account for that [5]. Postmenopausal alterations of the vaginal flora may also serve as an explanation for the increased incidence of recurrent cystitis in elder women [6].

Urinary retention is another risk factor for CC and may result from anatomical anomalies or from prostatic hyperplasia or neoplasms.

Urinary tract infections are very common, particularly in women. Presumably, anatomical differences mainly account for this phenomenon observable across all age groups: Women have a much shorter urethra and its external opening is in close proximity to the main source of infection, the anus.

With regards to young, sexually active adults, annual incidence rates of approximately 1 per 100 men and more than 50 per 100 women have been reported [7]. Middle aged adults are less frequently affected, but incidence rises again in older individuals. Due to the high incidence of prostate enlargement in elder men, consequent urinary retention and an elevated risk of cystitis, the male-to-female ratio increases in this age group. However, even elder women are much more often affected than elder men. Postmenopausal hormonal changes render elder women more susceptible to cystitis than middle aged females [6].

As has been stated above, Enterobacteriaceae like Escherichia coli account for the majority of CC cases. These pathogens are fecal bacteria, they may reach the external opening of the urethra, ascend through this organ and get to the urinary bladder. Other microorganisms may ascend by means of a catheter or even reach the urinary bladder during bacteremia. Pathogens may also spread from adjacent sources of infections, e.g., from the gastrointestinal tract.

Distinct bacterial species have different pathogenicity and virulence factors that assure its survival within the bladder and harm the host. Escherichia coli, for instance, express fimbriae and other adhesins that permit irreversible attachment to the bladder's wall. Otherwise, the constant flow of urine would rapidly rinse these pathogens from the urinary bladder [8]. Escherichia coli also produce hemolysin, which is of importance for nutrient acquisition, and cytotoxic necrotizing factor 1, which induces host cell remodeling. Recently, it has been shown that administration of antibodies against these toxins may reduce cystitis [9]. Some strains are able to invade urothelial cells and replicate intracellularly [10]. Consequently, these strains have a mechanism to evade host defense that differ from those bacteria that merely attach to the mucosal layer of the bladder.

Antibiotic prophylaxis is sometimes recommended as the preventive measure of choice but poses significant risks of induction of resistances and side effects. If this approach is chosen, antibiotics should be selected based on an antibiogram, should be administered continuously and never below the dosage necessary to reach the minimally inhibitory concentration. Proper use of antibiotics may, however, significantly reduce the frequency of relapses in CC patients [13].

More importantly, patients should be advised to avoid behaviors that are associated with an increased risk of urinary tract infections. Women should be instructed to wipe from front to back after using the toilet, anal intercourse should not be combined with vaginal intercourse, and underwear should be loose and breathable.

Postmenopausal women may benefit from topical administration of estrogens, but benefits and possible complications should be considered carefully.

Recently, scientific evidence has been provided for the effectivity of cranberry products [14].

The urinary bladder is a hollow organ whose main function is to collect, store and release urine according to nervous input. Its wall is composed of mucosa, submucosa, tunica muscularis and adventitia. Similar to other organs forming the urinary tract, the bladder's inner layer, the mucosa, is called urothelium. This specific form of epithelium is well adapted to fluctuating volumes.

The general medical term for an inflammation of the urinary bladder is cystitis. According to etiology, pathogenesis and clinical presentation, different forms of cystitis can be distinguished. Acute cystitis usually subsides within a few days, whereas chronic forms of cystitis either persist for longer periods of time or follow a pattern of remission and recurrence. One the one hand, such pathologies may result from persistence of microorganisms that are attached to the bladder's mucosal layer. Here, infection and inflammation rarely comprise submucosa or tunica muscularis. On the other hand, autoimmune or vascular disturbances may trigger permanent inflammation of deeper layers of the bladder's wall. The former is generally referred to as chronic cystitis (CC) and shall be discussed in this article; the latter etiologic factors have been proposed to account for chronic interstitial cystitis, an entity that is described elsewhere.

Partial or complete remission and relapses are characteristic for CC. Patients present repeatedly with symptoms similar to those experienced during acute cystitis, e.g., dysuria, pollakiuria and possibly hematuria as well as abdominal pain. Also, they frequently suffer from immunosuppressive comorbidities such as diabetes mellitus. Urine properties are altered. The vast majority of CC cases is provoked by bacterial infection with Enterobacteriaceae, particularly with Escherichia coli. These pathogens enter the lower urinary tract through the ostium urethrae externum, ascend to the urinary bladder and may even pass the ureters and reach the kidneys. This should be avoided by early initiation of an adequate treatment. Therefore, bacterial cultures should be prepared, tested against a variety of antibiotics and appropriate medication should be chosen based on this antibiogram. Patients should be strongly advised to continue drug therapy although symptoms may resolve earlier.

Cystitis is the medical term that describes an inflammation of the urinary bladder. If such an inflammation persists for prolonged periods of time or follows a pattern of remission and recurrence, chronic cystitis (CC) may be diagnosed.

Causes
Bacterial infections account for the vast majority of bladder infections. Fecal pathogens like Escherichia coli may easily reach the external opening of the urethra and ascend to the urinary bladder. Behavior and decisions regarding underwear may facilitate infection with fecal bacteria, e.g., the female habit to wipe from back to front after using the toilet, anal intercourse and wearing of tight, non-breathable underwear.

In rare cases, viral infection or parasitic infestation causes cystitis.

Bladder infection is usually diagnosed within days after symptom onset. However, resistance to antibiotic drugs or other compounds applied to eliminate pathogens from the urinary tract may render the initial therapy ineffective. Resistance may also develop during initial therapy if patients don't comply with given instructions regarding medication, particularly if single doses are lowered or if the whole treatment is terminated early. In these cases, a small population of pathogens remains inside the bladder and causes infection and inflammation to flare up again. The patient may then develop CC.

Symptoms
While CC may be asymptomatic, most patients suffer from recurrent episodes of abdominal pain, burning sensations during micturition and a frequent, urgent need to urinate, although only small amounts of urine can be passed. Incontinence may be experienced. Systemic symptoms may be observed and may consist in fatigue, lethargy, fever and weakness. Of note, systemic symptoms are not necessarily associated with micturition disturbances.

Diagnosis
Anamnesis, clinical examination and laboratory analysis of urine samples are the mainstays of CC diagnosis. The latter also aims at identifying the causative agent. It is very important to test the pathogen's sensibility to distinct antimicrobial drugs before deciding on a therapeutic approach.
Additional exams, e.g., gynecological or urological examination as well as diagnostic imaging, may be carried out to rule out differential diagnoses like sexually transmitted diseases, calculi and urinary retention.

Treatment
Causative therapy is based on antimicrobial drugs that are selected according to the previously established antibiogram. Antibiotics as well as any other prescribed drugs should be taken exactly as recommended by the physician. Non-compliance with therapeutic schemes is one of the main reasons for relapses.

Additionally, analgesics and spasmolytics may be applied to relieve abdominal pain and bladder spasms.

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