Hemorrhagic cystitis: Difference between revisions
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{{SI}} {{CMG}} {{AE}} {{Maliha}} | {{SI}} {{CMG}} {{AE}} {{Maliha}} | ||
'''To review more details about cystitis, [[Cystitis|click here]]. | |||
==Overview== | ==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.<ref name=radio> Haemorrhagic cystitis. Radiopaedia.http://radiopaedia.org/cases/haemorrhagic-cystitis Accessed on February 17, 2016</ref> 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 | '''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.<ref name=radio> Haemorrhagic cystitis. Radiopaedia.http://radiopaedia.org/cases/haemorrhagic-cystitis Accessed on February 17, 2016</ref> 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== | ||
Causes of hemorrhagic cystitis include chemotherapy | Causes of hemorrhagic cystitis include chemotherapy, radiation, infections, and exposure to certain chemicals and dyes.<ref name=gov> NCI Dictionary of Cancer Terms. NIH.http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=695987 Accessed on February 17, 2016</ref> [[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]]<ref name="pmid24000900">{{cite journal| author=Payne H, Adamson A, Bahl A, Borwell J, Dodds D, Heath C et al.| title=Chemical- and radiation-induced haemorrhagic cystitis: current treatments and challenges. | journal=BJU Int | year= 2013 | volume= 112 | issue= 7 | pages= 885-97 | pmid=24000900 | doi=10.1111/bju.12291 | pmc=PMC4155867 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24000900 }} </ref> | *[[Cyclophosphamide]]<ref name="pmid24000900">{{cite journal| author=Payne H, Adamson A, Bahl A, Borwell J, Dodds D, Heath C et al.| title=Chemical- and radiation-induced haemorrhagic cystitis: current treatments and challenges. | journal=BJU Int | year= 2013 | volume= 112 | issue= 7 | pages= 885-97 | pmid=24000900 | doi=10.1111/bju.12291 | pmc=PMC4155867 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24000900 }} </ref> | ||
*[[Ifosfamide]] | *[[Ifosfamide]] | ||
| Line 19: | Line 15: | ||
*[[Busulfan]] | *[[Busulfan]] | ||
*[[Doxorubicin]] | *[[Doxorubicin]] | ||
*[[Ketamine]] | |||
*Metabolites of chemotherapeutic drugs | |||
*[[Penicillin G]] | |||
===Infectious=== | |||
*Viral: ''[[Adenovirus]]''<ref name="pmid12113867">{{cite journal| author=Ronald A| title=The etiology of urinary tract infection: traditional and emerging pathogens. | journal=Am J Med | year= 2002 | volume= 113 Suppl 1A | issue= | pages= 14S-19S | pmid=12113867 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12113867 }} </ref>, BK virus, [[Herpes simplex virus]], [[Cytomegalovirus]]<ref name=ppp> Hemorrhagic cystitis. Pathology Outlines.http://www.pathologyoutlines.com/topic/bladderhemorrhagiccystitis.html Accessed on February 17, 2016</ref> | |||
*Bacterial: [[E.coli]], ''[[Proteus mirabilis]]'', [[Klebsiella]]<ref name="pmid20877590">{{cite journal| author=Manikandan R, Kumar S, Dorairajan LN| title=Hemorrhagic cystitis: A challenge to the urologist. | journal=Indian J Urol | year= 2010 | volume= 26 | issue= 2 | pages= 159-66 | pmid=20877590 | doi=10.4103/0970-1591.65380 | pmc=PMC2938536 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20877590 }} </ref> | |||
*Fungal: ''[[Cryptococcus neoformans]]'', ''[[Aspergillus fumigatus]]'', ''[[Candida albicans]]'' | |||
*Parasite: ''[[Toxoplasma]] Gondii''<ref name="pmid21349389">{{cite journal| author=Ples R, Méchaï F, Champiat B, Droupy S, Huerre M, Guettier C et al.| title=[Pseudotumoral toxoplasmic cystitis revealing acquired immunodeficiency syndrome]. | journal=Ann Pathol | year= 2011 | volume= 31 | issue= 1 | pages= 46-9 | pmid=21349389 | doi=10.1016/j.annpat.2010.11.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21349389 }} </ref> | |||
===Environmental Toxins=== | |||
*Aniline dyes<ref name="pmid20877590">{{cite journal| author=Manikandan R, Kumar S, Dorairajan LN| title=Hemorrhagic cystitis: A challenge to the urologist. | journal=Indian J Urol | year= 2010 | volume= 26 | issue= 2 | pages= 159-66 | pmid=20877590 | doi=10.4103/0970-1591.65380 | pmc=PMC2938536 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20877590 }} </ref> | |||
*Pesticides | |||
===Radiation=== | |||
*Usually due to radiation therapy for pelvic malignancies<ref name="pmid24000900">{{cite journal| author=Payne H, Adamson A, Bahl A, Borwell J, Dodds D, Heath C et al.| title=Chemical- and radiation-induced haemorrhagic cystitis: current treatments and challenges. | journal=BJU Int | year= 2013 | volume= 112 | issue= 7 | pages= 885-97 | pmid=24000900 | doi=10.1111/bju.12291 | pmc=PMC4155867 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24000900 }} </ref><ref name="pmid27919130">{{cite journal| author=Wakamiya T, Kuramoto T, Inagaki T| title=[Two Cases of Spontaneous Rupture of the Urinary Bladder Associated with Radiation Cystitis, Repaired with Omentum Covering]. | journal=Hinyokika Kiyo | year= 2016 | volume= 62 | issue= 10 | pages= 545-548 | pmid=27919130 | doi=10.14989/ActaUrolJap_62_10_545 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27919130 }} </ref> | |||
==Pathophysiology== | ==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]].<ref name="pmid24000900">{{cite journal| author=Payne H, Adamson A, Bahl A, Borwell J, Dodds D, Heath C et al.| title=Chemical- and radiation-induced haemorrhagic cystitis: current treatments and challenges. | journal=BJU Int | year= 2013 | volume= 112 | issue= 7 | pages= 885-97 | pmid=24000900 | doi=10.1111/bju.12291 | pmc=PMC4155867 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24000900 }} </ref> | |||
===Chemical=== | ===Chemical=== | ||
A chemical hemorrhagic cystitis can develop when vaginal products are | A chemical hemorrhagic cystitis can develop when vaginal products are | ||
inadvertently placed in the urethra. Gentian violet douching to treat | inadvertently placed in the [[urethra]]. Gentian violet douching to treat | ||
candidiasis has resulted in hemorrhagic cystitis when the drug was misplaced | candidiasis has resulted in hemorrhagic cystitis when the drug was misplaced | ||
in the urethra, but this hemorrhagic cystitis resolved spontaneously with | in the urethra, but this hemorrhagic cystitis resolved spontaneously with | ||
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copiously irrigated with alkalinized normal saline to minimize bladder | copiously irrigated with alkalinized normal saline to minimize bladder | ||
irritation. | 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== | ==Diagnosis== | ||
===History and Symptoms=== | |||
Common symptoms of hemorrhagic cystitis include pain during urination, [[hematuria]], and urinary urgency.<ref name=gov> NCI Dictionary of Cancer Terms. NIH.http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=695987 Accessed on February 17, 2016</ref><ref name=www> Hemorrhagic Cystitis. Wikipedia.https://en.wikipedia.org/wiki/Hemorrhagic_cystitis Accessed on February 22, 2016</ref> Droller et al. has proposed a grading system for the severity of hemorrhagic cystitis:<ref name="pmid24000900">{{cite journal| author=Payne H, Adamson A, Bahl A, Borwell J, Dodds D, Heath C et al.| title=Chemical- and radiation-induced haemorrhagic cystitis: current treatments and challenges. | journal=BJU Int | year= 2013 | volume= 112 | issue= 7 | pages= 885-97 | pmid=24000900 | doi=10.1111/bju.12291 | pmc=PMC4155867 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24000900 }} </ref> | |||
*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. | 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. | ||
| Line 47: | Line 69: | ||
the prostate (in men), endometriosis (in women), or cancer of the urinary | the prostate (in men), endometriosis (in women), or cancer of the urinary | ||
tract. In some cases, blood in the urine results from athletic training, | tract. In some cases, blood in the urine results from athletic training, | ||
particularly in runners. | particularly in runners. | ||
== | ===Imaging Findings=== | ||
Imaging findings for acute hemorrhagic cystitis due to [[radiation]] or [[chemotherapy]] include:<ref name=rrr> Radiation and Chemotherapy cystitis. Radiopaedia.http://radiopaedia.org/articles/radiation-and-chemotherapy-induced-cystitis Accessed on February 23, 2016</ref> | |||
*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.<ref name=rrr> Radiation and Chemotherapy cystitis. Radiopaedia.http://radiopaedia.org/articles/radiation-and-chemotherapy-induced-cystitis Accessed on February 23, 2016</ref> | |||
<ref> | |||
==Treatment== | ==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. | 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. | ||
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 | The first step in the treatment of HC should be directed toward clot | ||
evacuation. Bladder outlet obstruction from clots can lead to urosepsis, | evacuation. Bladder outlet obstruction from clots can lead to urosepsis, | ||
bladder rupture, and renal failure. Clot evacuation can be performed by | bladder rupture, and [[renal failure]]. Clot evacuation can be performed by | ||
placing a wide-lumen bladder catheter at bedside. The bladder can be | placing a wide-lumen bladder catheter at bedside. The bladder can be | ||
irrigated with water or sodium chloride solution. The use of water is | 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 | preferable because water can help with clot lysis. Care must be taken to not | ||
overdistend the bladder and cause a perforation. <ref> | overdistend the bladder and cause a perforation.<ref name=www> Hemorrhagic Cystitis. Wikipedia.https://en.wikipedia.org/wiki/Hemorrhagic_cystitis Accessed on February 22, 2016</ref> | ||
==References== | ==References== | ||
Latest revision as of 13:29, 22 October 2017
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maliha Shakil, M.D. [2]
To review more details about cystitis, click here.
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.[1] 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.[2] 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[3]
- Ifosfamide
- Methotrexate
- Mitotane
- Busulfan
- Doxorubicin
- Ketamine
- Metabolites of chemotherapeutic drugs
- Penicillin G
Infectious
- Viral: Adenovirus[4], BK virus, Herpes simplex virus, Cytomegalovirus[5]
- Bacterial: E.coli, Proteus mirabilis, Klebsiella[6]
- Fungal: Cryptococcus neoformans, Aspergillus fumigatus, Candida albicans
- Parasite: Toxoplasma Gondii[7]
Environmental Toxins
- Aniline dyes[6]
- Pesticides
Radiation
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.[3]
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.[2][9] Droller et al. has proposed a grading system for the severity of hemorrhagic cystitis:[3]
- 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:[10]
- 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.[10]
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 overdistend the bladder and cause a perforation.[9]
References
- ↑ Haemorrhagic cystitis. Radiopaedia.http://radiopaedia.org/cases/haemorrhagic-cystitis Accessed on February 17, 2016
- ↑ 2.0 2.1 NCI Dictionary of Cancer Terms. NIH.http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=695987 Accessed on February 17, 2016
- ↑ 3.0 3.1 3.2 3.3 Payne H, Adamson A, Bahl A, Borwell J, Dodds D, Heath C; et al. (2013). "Chemical- and radiation-induced haemorrhagic cystitis: current treatments and challenges". BJU Int. 112 (7): 885–97. doi:10.1111/bju.12291. PMC 4155867. PMID 24000900.
- ↑ Ronald A (2002). "The etiology of urinary tract infection: traditional and emerging pathogens". Am J Med. 113 Suppl 1A: 14S–19S. PMID 12113867.
- ↑ Hemorrhagic cystitis. Pathology Outlines.http://www.pathologyoutlines.com/topic/bladderhemorrhagiccystitis.html Accessed on February 17, 2016
- ↑ 6.0 6.1 Manikandan R, Kumar S, Dorairajan LN (2010). "Hemorrhagic cystitis: A challenge to the urologist". Indian J Urol. 26 (2): 159–66. doi:10.4103/0970-1591.65380. PMC 2938536. PMID 20877590.
- ↑ Ples R, Méchaï F, Champiat B, Droupy S, Huerre M, Guettier C; et al. (2011). "[Pseudotumoral toxoplasmic cystitis revealing acquired immunodeficiency syndrome]". Ann Pathol. 31 (1): 46–9. doi:10.1016/j.annpat.2010.11.001. PMID 21349389.
- ↑ Wakamiya T, Kuramoto T, Inagaki T (2016). "[Two Cases of Spontaneous Rupture of the Urinary Bladder Associated with Radiation Cystitis, Repaired with Omentum Covering]". Hinyokika Kiyo. 62 (10): 545–548. doi:10.14989/ActaUrolJap_62_10_545. PMID 27919130.
- ↑ 9.0 9.1 Hemorrhagic Cystitis. Wikipedia.https://en.wikipedia.org/wiki/Hemorrhagic_cystitis Accessed on February 22, 2016
- ↑ 10.0 10.1 Radiation and Chemotherapy cystitis. Radiopaedia.http://radiopaedia.org/articles/radiation-and-chemotherapy-induced-cystitis Accessed on February 23, 2016