Cystitis overview

# Overview
Cystitis is defined as inflammation of the urinary bladder. When caused by an infection, cystitis is classified as a type of the lower UTI. Cystitis results mostly from ascending infections from the urethra but can also result from descending infections from the blood or the lymphatic system. The condition more often affects women, but can affect either gender and all age groups. Urinary tract infections have been described since 1550 BC. In 1836 the earliest record of interstitial cystitis without the presence of a bladder stone were published. Cystitis may be classified according to the etiology and therapeutic approach into various subtypes including: traumatic, interstitial, eosinophilic, hemorrhagic cystitis, and cystitis cystica. For the purpose of treatment, cystitis may also be classified into acute uncomplicated, complicated, and recurrent cystitis. Cystitis occurs when the normally sterile lower urinary tract (urethra and bladder) is infected by bacteria, which leads to irritation and inflammation. Females are more prone to the development of cystitis because of their relatively shorter urethra. Complicated cystitis is due to the obstruction and stasis of urine flow. More than 85% of cases of cystitis are caused by escherichia coli (E. coli), a bacterium found in the lower gastrointestinal tract. Other causes of cystitis include certain medications, diabetes, crohn's disease, iatrogenic causes, endometriosis, pelvic inflammatory disease, urinary obstruction, and bladder incontinence. Cystitis must be differentiated from other causes of dysuria. Approximately 50% of patients with acute uncomplicated cystitis will recover without treatment within a few days or weeks. If left untreated, some patients with cystitis may progress to develop recurrent infection, pyelonephritis, hematuria, and rarely renal failure. Prognosis is generally good. The majority of patients with cystitis do not have recurrence or complications after treatment. Patients with cystitis are usually well-appearing. Common physical examination findings of cystitis include fever and suprapubic tenderness. Antimicrobial therapy is indicated in cystitis.  The treatment of cystitis depends on the disease course (acute uncomplicated vs. complicated) and the rates of resistance in the community.  Preventative measures to avoid cystitis include abstinence from sexual activity, use of barrier contraception during sexual intercourse, increasing fluid intake and frequency of urination, and use of estrogen (among postmenopausal women).

# Historical Perspective
Urinary tract infections have been described since ancient times with the first documented description in the Ebers Papyrus dated to 1550 BC. In 1836, Joseph Parrish published about interstitial cystitis by describing three cases of severe lower urinary tract symptoms without the presence of a bladder stone. Dr. Alexander Skene in 1887 used the term "interstitial cystitis" to describe the disease.

# Classification
Cystitis may be classified according to the etiology and therapeutic approach into various subtypes such as traumatic, interstitial, eosinophilic, hemorrhagic cystitis, foreign body, emphysematous, and cystitis cystica. Cystitis can also be classified as acute or chronic depending on the duration of the infection. For the purpose of treatment, cystitis may also be classified into acute uncomplicated, complicated, and recurrent cystitis. It can be classified as bacterial, viral, fungal or parasitic depending on the causative pathogen.

# Pathophysiology
Urine is normally sterile due to the low pH and unidirectional flow of urine that does not allow bacteria to grow and invade the urinary tract. Cystitis occurs when the normally sterile lower urinary tract (urethra and bladder) is either infected by bacteria or rarely a fungus, which leads to irritation and inflammation. Irritation followed by inflammation can also occur in response to trauma, chemicals or foreign bodies. Females are more prone to the development of cystitis because of their relatively shorter and straighter urethra. Bacteria does not have to travel as far to enter the bladder, which is in part due to the relatively short distance between the opening of the urethra and the anus. The pathogenesis of complicated cystitis include obstruction and stasis of urine flow. Normal flow of urine washes away the pathogens and clears the tract. Obstruction leads to overdistension and bacterial growth is facilitated by the residual urine. Stasis of urine flow allows entry of pathogens into the urinary tract.

# Causes
Infections are the most common cause of cystitis. More than 80% of cases of cystitis are caused by Escherichia coli (E. Coli), a bacterium found in the lower gastrointestinal tract. Some viruses, fungi and parasites can rarely cause cystitis. Other causes of cystitis include certain medications, iatrogenic causes, pelvic inflammatory disease, trauma, and radiation therapy.

# Differential Diagnosis
Cystitis must be differentiated from other causes of dysuria such as acute pyelonephritis, urethritis, prostatitis, vulvovaginitis, urethral strictures or diverticula, benign prostatic hyperplasia and neoplasms such as renal cell carcinoma and cancers of the bladder, prostate, and penis.

# Epidemiology and Demographics
Urinary tract infections are found more frequently in women than in men. It is estimated that more than 30% of women will experience at least one episode of cystitis. Of these 30%, 20% women will have recurrent cystitis. The case-fatality rate/mortality rate of uncomplicated cystitis is approximately zero. Females are more commonly affected with cystitis than males. The female to male ratio is 4 to 1. Acute uncomplicated cystitis commonly affects women ages 18-39 years. There is no racial predilection to cystitis. Cystitis is a common disease that affect everyone, mostly women, worldwide.

# Risk Factors
Common risk factors in the development of cystitis include female gender, sexual intercourse, diabetes, pregnancy, catheterization, fecal incontinence, old age, and immobility. Some foods are thought to have a role in increasing the risk of cystitis such as vitamin C, coffee or tea, carbonated and alcoholic drinks, citrus fruit, or spicy foods.

# Screening
Screening is not recommended for cystitis in a general population. However, pregnancy is an indication for screening for the presence of bacteria in the urine, as this may require aggressive treatment unlike other settings. Other situations that require screening for asymptomatic bacteriuria are prior to urologic surgery or for the research purposes.

# Natural History, Complications, and Prognosis
Approximately 50% of patients with acute uncomplicated cystitis will recover without treatment within a few days or weeks. If left untreated, some patients with cystitis may progress to develop recurrent infection, pyelonephritis, hematuria, and rarely renal failure. Prognosis is generally good. The majority of patients with cystitis do not have recurrence or complications after treatment.

# Diagnosis

## Diagnostic Study of Choice
Acute uncomplicated typical cystitis is mainly diagnosed based on clinical presentation. Patients with classic symptoms including dysuria, frequency, urgency, and/or suprapubic pain may not need any diagnostic studies. Patients with atypical symptoms might require urinalysis and urine culture to confirm cystitis.

## History and Symptoms
A detailed and thorough medical history from the patient is necessary. Specific areas of focus when obtaining a history from the patient include use of urinary catheters,pregnancy, sexual history, diabetes, recent antibiotic use, history of renal disease, urinary incontinence, and urinary retention. Symptoms of cystitis include painful urination, abnormal urine color (cloudy), blood in the urine, frequent urination or urgent need to urinate, or pressure in the lower pelvis.

## Physical Examination
Patients with cystitis are usually well-appearing. Common physical examination finding of cystitis includes suprapubic tenderness. A focused physical examination is helpful in confirming the suspicion of cystitis and in ruling out alternate pathology.

## Laboratory Findings
Presence of signs and symptoms of cystitis like dysuria, nocturia, frequency and urgency increase the probability of confirmation of cystitis as the diagnosis. Laboratory tests used in the diagnosis and confirmation of cystitis include urinalysis and urine culture. Laboratory findings consistent with the diagnosis of cystitis include pyuria and either white blood cells (WBCs) or red blood cells (RBCs) on urinalysis and a positive urine culture.

## Electrocardiogram
There are no ECG findings associated with cystitis.

## X-ray
X ray is not usually done to diagnose cystitis. An x ray of KUB (Kidneys, ureters, and bladder) is done to probe the suspicion for emphysematous cystitis. In case of emphysematous cystitis, it can show presence of gas in the bladder wall. Sometimes, an x ray that is taken for another reason, might reveal gas in the urinary bladder and thus lead to the diagnosis of emphysematous cystitis.

## Echocardiography and Ultrasound
There are no echocardiography findings associated with cystitis. Ultrasonography is not done routinely to diagnose cystitis. Ultrasonography is sometimes done to diagnose the suspicion of emphysematous cystitis and for detecting the presence of tumors or stones. Imaging findings for chronic hemorrhagic cystitis due to radiation or chemotherapyinclude a small fibrosed bladder with a thick wall and resultant hydronephrosis. Calcification is only rarely seen.

## CT scan
In case of emphysematous cystitis, a CT scan of the abdomen can show presence of gas in the bladder wall. CT scan done while looking for other causes of abdominal pain, sometimes reveal gas directing the bladder wall and thus the diagnosis of emphysematous cystitis. CT scan may not be that useful in other causes of cystitis.

## MRI
MRI is not used in the routine diagnosis of cystitis. An MRI can help diagnose a tumor or a stone in the bladder that is leading to stasis and thus to the inflammation and infection of the bladder. Inflammation and edema can also be noticed by the help of an MRI. MRI is sometimes used to diagnose cystitis glandularis. Imaging findings for chronic hemorrhagic cystitis due to radiation include a fibrosed bladder with a thick wall, hydronephrosis and rarely, calcifications.

## Other Imaging Findings
There are no other imaging findings associated with cystitis.

## Other Diagnostic Studies
Cystoscopy is not usually done to diagnose cystitis. Cystoscopy is recommended in recurrent cystitis, emphysematous cystitis, cystitis in children less than 2 years or in any kind of cystitis with normal routine tests. Hunter lesions can be identified using cystoscopy in patient with interstitial cystitis or bladder pain syndrome. Cystoscopy may sometime require the administration of local anaesthesia to facilitate the process. Mass spectrometry based metabolomic analysis is useful in detecting urinary metabolites in Interstitial cystitis.

# Treatment

## Medical Therapy
A major proportion of the urinary tract infections resolves on its own if left untreated. Complications can occur but not very frequently. Cystitis can though increase morbidity and the goal of therapy is early resolution of infectious symptoms. Antimicrobial therapy is indicated in cystitis. The treatment of cystitis depends on the disease course (acute uncomplicated vs complicated) and the rates of resistance in the community. Due to the risk of the infection spreading to the kidneys (complicated UTI) and the high complication rate in diabetics and the elderly population, prompt treatment is almost always recommended. The increasing resistance to various drugs is a growing challenge. One aspect of increasing drug resistance is the gram negative bacteria population that produces extended spectrum beta lactamase. Hyperbaric oxygen is used to treat hemorrhagic cystitis associated with exposure to radiation and emphysematous cystitis, as presence of gas in the bladder wall interferes with the tissue oxygenation. Proper oxygenation may help to curtail the associated damage.

## Interventions
There are no recommended therapeutic interventions for the management of cystitis.

## Surgery
Surgery is not the primary treatment for cystitis and is not required most of the times. Surgery can be done for associated pathologies leading to cystitis like a tumor or a stone leading to obstruction of the bladder and thus encouraging growth of pathogens and thus cystitis.

## Primary Prevention
Preventative measures to avoid cystitis include the measures for preventing a urinary tract infection which include voiding after intercourse, use of barrier contraception, increasing fluid intake and frequency of urination, and use of estrogen (among postmenopausal women). Single-dose prophylactic antimicrobial therapy prior to sexual intercourse may be administered to patients who have recurrent episodes of cystitis that are associated with sexual activity. Cleaning the urethral meatus after intercourse has also shown to be effective in preventive recurrent cystitis.

## Secondary Prevention
Secondary prophylaxis of cystitis is useful to prevent recurrent cystitis. It is more beneficial in patients in which cystitis is associated with sexual intercourse, a structural defect or a disease like diabetes that can lead to recurrent infections.