Hemorrhagic cystitis
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# Overview
Hemorrhagic cystitis or Haemorrhagic cystitis is a diffuse inflammatory condition of the urinary bladder due to an infectious or noninfectious etiology, resulting in bleeding from the bladder mucosa. This is seen most often in female cancer patients as a complication of therapy, however it is can also be seen in children as a result of a viral infection.

# Causes
Causes of hemorrhagic cystitis include chemotherapy, radiation, infections, and exposure to certain chemicals and dyes. Adenovirus (particularly serotypes 11 and 21 of subgroup B) is the most common cause of acute viral hemorrhagic cystitis in children, though it can result from BK virus as well.

## Drugs
- Cyclophosphamide
- Ifosfamide
- Methotrexate
- Mitotane
- Busulfan
- Doxorubicin
- Ketamine
- Metabolites of chemotherapeutic drugs
- Penicillin G

## Infectious
- Viral: Adenovirus, BK virus, Herpes simplex virus, Cytomegalovirus
- Bacterial: E.coli, Proteus mirabilis, Klebsiella
- Fungal: Cryptococcus neoformans, Aspergillus fumigatus, Candida albicans
- Parasite: Toxoplasma Gondii

## Environmental Toxins
- Aniline dyes
- Pesticides

## Radiation
- Usually due to radiation therapy for pelvic malignancies

# Pathophysiology

## Drugs
Chemotherapeutic drugs such as cyclophosphamide and ifosfamide may cause hemorrhagic cystitis. Acrolein, a urinary  metabolite of cyclophosphamide and ifosfamide, is responsible for causing damage to the urinary bladder.

## Chemical
A chemical hemorrhagic cystitis can develop when vaginal products are
inadvertently placed in the urethra.  Gentian violet douching to treat
candidiasis has resulted in hemorrhagic cystitis when the drug was misplaced
in the urethra, but this hemorrhagic cystitis resolved spontaneously with
cessation of treatment.  Accidental urethral placement of contraceptive
suppositories has also caused hemorrhagic cystitis in several patients.  The
bladder irritation was thought to be caused by contact of the acidic compound
nonoxynol-9 (pH, with the bladder.  In the acute setting, the bladder can be
copiously irrigated with alkalinized normal saline to minimize bladder
irritation.

## Radiation
In the acute phase of radiation and chemotherapy cystitis, there is a hemorrhagic cystitis secondary to denudation of the urothelium. The most severe radiation injuries cause bladder necrosis, incontinence, and fistula formation. At histologic analysis, there is cellular atypia, with mild to moderate nuclear pleomorphism. The epithelial proliferation may be so marked as to be confused with invasive cancer in the lamina propria.
Chronic radiation effects result from an obliterative endarteritis in the lamina propria, followed by ischemic changes and interstitial fibrosis

# Diagnosis

## History and Symptoms
Common symptoms of hemorrhagic cystitis include pain during urination, hematuria, and urinary urgency. Droller et al. has proposed a grading system for the severity of hemorrhagic cystitis:
- Grade I: Non-visible hematuria
- Grade II: Macroscopic hematuria
- Grade III: Macroscopic hematuria with small clots
- Grade IV: Gross hematuria with clots, urinary obstruction. Instrumentation needed for clot evacuation.

## Laboratory Findings
In immunocompromised patients, pus is present in the urine but often no organism can be cultured. In children, polymerase chain reaction sequencing of urine can detect fragments of the infectious agent.
The procedure differs somewhat for women and men.  Laboratory testing of urine
samples now can be performed with dipsticks that indicate immune system
responses to infection, as well as with microscopic analysis of samples.
Normal human urine is sterile.  The presence of bacteria or pus in the urine
usually indicates infection.  The presence of hematuria, or blood in the
urine, may indicate acute UTIs, kidney disease, kidney stones, inflammation of
the prostate (in men), endometriosis (in women), or cancer of the urinary
tract.  In some cases, blood in the urine results from athletic training,
particularly in runners.

## Imaging Findings
Imaging findings for acute hemorrhagic cystitis due to radiation or chemotherapy include:
- Abnormal bladder wall with focal or diffuse irregular thickening, spasticity, and decreased distensibility
- Hypervascularity in the wall and bleeding vessels result in intraluminal clot
MR imaging may show inflammation and edema as high signal intensity with T2-weighted sequences and can enable the bladder wall to be distinguished from clot.
Imaging findings for chronic hemorrhagic cystitis due to radiation or chemotherapy include a small fibrosed bladder with a thick wall and resultant hydronephrosis. Calcification is only rarely seen.

# Treatment
In the case of hemorrhagic cystitis from cyclophosphamide, this can be prevented through aggressive hydration and the use of mesna, which neutralizes the toxicity of acrolein, a metabolite of cyclophosphamide. Viral hemorrhagic cystitis in children generally spontaneously resolves within a few days.
The first step in the treatment of HC should be directed toward clot
evacuation.  Bladder outlet obstruction from clots can lead to urosepsis,
bladder rupture, and renal failure.  Clot evacuation can be performed by
placing a wide-lumen bladder catheter at bedside.  The bladder can be
irrigated with water or sodium chloride solution.  The use of water is
preferable because water can help with clot lysis.  Care must be taken to not
-verdistend the bladder and cause a perforation.