Epidemiology and etiology

Numerous etiologies have been linked to hemorrhagic cystitis (Table 99-11) 45 Of these, the oxazaphosphorine alkylating agents (cyclophosphamide and ifosfamide) are most frequently implicated. Incidence rates vary considerably, but generally range between 18% and 40% with ifosfamide and 0.5% to 40% with high-dose cyclophosphamide in the absence of prophylactic measures.46 Chronic, low-dose oral cyclophos-

phamide as typically used in autoimmune disorders and chronic lymphocytic leukemia is also infrequently associated with hemorrhagic cystitis.

Table 99-11 Primary Causes of Hemorrhagic Cystitis

Pharmacologic

Nonpharmacologic

Cyclophosphamide Chronic low doses High doses used in BMT Ifosfamide

Intravesicularthiotepa Chronic: oral busulfan

Pelvic irradiation Viral infection Cytomegalovirus Pa po va virus Herpes simplex virus Adenovirus

Anabolic steroids

B.MT, bone marrow Transplantation From Ref. 45.

Twenty percent of patients receiving pelvic irradiation may experience hemorrhagic cystitis, especially with concurrent cyclophosphamide. Viral infections commonly associated with this condition most frequently occur in bone marrow transplant recipients who may also receive cyclophosphamide.

Cyclophosphamide or ifosfamide induced damage to the bladder wall is primarily caused by their shared metabolite known as acrolein. Acrolein causes sloughing and inflammation of the bladder lining, leading to bleeding and hemorrhage. This is most common when urine output is low since higher concentrations of acrolein come into contact with the bladder urothelium for longer periods of time.

Patients with hemorrhagic cystitis from treatment may present with dysuria, anuria, or hematuria. Diagnosis is made based on symptoms and urinalysis which shows presence of red blood cells in the urine.

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