Hemorrhagic cystitis
Encyclopedia
Hemorrhagic cystitis or Haemorrhagic cystitis is diffuse inflammation of the bladder
Bladder
Bladder usually refers to an anatomical hollow organBladder may also refer to:-Biology:* Urinary bladder in humans** Urinary bladder ** Bladder control; see Urinary incontinence** Artificial urinary bladder, in humans...

 leading to dysuria
Dysuria
In medicine, specifically urology, dysuria refers to painful urination.Difficult urination is also sometimes described as dysuria.It is one of a constellation of irritative bladder symptoms, which includes urinary frequency and haematuria....

, hematuria
Hematuria
In medicine, hematuria, or haematuria, is the presence of red blood cells in the urine. It may be idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the urinary tract , ranging from trivial to lethal...

, and hemorrhage. The disease can occur as a complication of cyclophosphamide, ifosfamide and radiation therapy. In addition to hemorrhagic cystitis, temporary hematuria
Hematuria
In medicine, hematuria, or haematuria, is the presence of red blood cells in the urine. It may be idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the urinary tract , ranging from trivial to lethal...

 can also be seen in bladder infection or in children as a result of viral infection and can be treated with antibiotics.

Causes

Causes of hemorrhagic cystitis include chemotherapy (e.g. cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....

, Ifosfamide
Ifosfamide
Ifosfamide is a nitrogen mustard alkylating agent used in the treatment of cancer.It is sometimes abbreviated "IFO".-Uses:It is given as a treatment for a variety of cancers, including:...

), radiation, or infection. Ifosfamide is the most common cause of hemorrhagic cystitis. Radiation-induced hemorrhagic cystitis develops in similar or smaller patient numbers when compared to cyclophosphamide-induced cases .

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
BK virus
The BK virus is a member of the polyomavirus family. Past infection with the BK virus is widespread, but significant consequences of infection are uncommon, with the exception of the immunocompromised and the immunosuppressed.-History:...

 as well.
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 the spermicidal detergent
nonoxynol-9
Nonoxynol-9
Nonoxynol-9, sometimes abbreviated as N-9, is an organic compound that is used as a surfactant. It is a member of the nonoxynol family of nonionic surfactants. N-9 and related compounds are ingredients in various cleaning and cosmetic products. It is widely used in contraceptives for its...

. In the acute setting, the bladder can be
copiously irrigated with alkalinized normal saline to minimize bladder
irritation.

Although hemorrhagic cystitis post-transplantation/bone marrow transplantation is not technically infectious, a short discussion is in order for completeness. Patients
undergoing therapy to suppress the immune system are at risk for hemorrhagic
cystitis due to either the direct effects of chemotherapy or activation of
dormant viruses in the kidney, ureter, or bladder.

Diagnosis

Diagnosis is made by history and examination.

In immunocompromised patients, pus is present in the urine but often no organism can be cultured. In children, polymerase chain reaction
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....

 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.

Symptoms

The frequency of bladder infections in humans varies significantly according
to age and sex. The male/female ratio of UTIs in children younger than 12
months is four to one because of the high rate of birth defects in the urinary
tract of male infants. Urinary tract infections are fairly common in young
girls. In adult life, the male/female ratio of UTIs is one to 50. After age
50, however, the incidence among males increases due to prostate disorders.

Treatment

In the case of preventing hemorrhagic cystitis from cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....

, the use of aggressive hydration and the use of mesna
Mesna
Mesna is an organosulfur compound. It is used in cancer chemotherapy involving cyclophosphamide and ifosfamide as an adjuvant. It is marketed by Baxter as Uromitexan and Mesnex...

, which neutralizes the toxicity of the cyclophosphamide-metabolite acrolein
Acrolein
Acrolein is the simplest unsaturated aldehyde. It is produced widely but is most often immediately reacted with other products due to its instability and toxicity...

, may reduce the likelihood of developing hemorrhagic cystitis. Unfortunately mesna is ineffective as a treatment once hemorrhagic cystitis has developed. Although rare, once a case of radiation-induced hemmorrhagic cystitis is diagnosed there is no empirically-proven treatments to heal this type of condition, which can severely degrade a patient's quality of life and might possibly lead to renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...

with risk of death.

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
overdistend the bladder and cause a perforation.
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