Diseases of the Bladder



Diseases of the Bladder





3.1 Bacterial Cystitis


N Engl J Med 2003; 349: 259


3.2 Emphysematous Cystitis



3.3 Candidal Urinary Tract Infections



3.4 Tuberculosis of the Bladder, Urethra



3.5 Schistosomiasis



3.6 Hemorrhagic Cystitis

Cause: In children, may be secondary to adenovirus type 11 and 21 (Am J Dis Child 1973; 26: 605). Immunocompromised pts and pts undergoing bone marrow transplant (BMT) may be secondary to BK virus (a polyoma virus). Other causes: acrolein, the



urotoxic metabolite of cyclophosphamide and ifosfamide, radiation therapy to the pelvis and bladder, and an allergic reaction. May be secondary to medications, including penicillin, NSAIDs, allopurinol, danazol, risperidone (J Urol 1998;160:159; 1990;143: 1; BJU 1997;79:3).








Table 3.1 Diseases of the Bladder














































Bacterial Cystitis


Emphysematous Cystitis


Candidal UTI


TB


Schistosomiasis


Cause


E. coli accounts for 75-90% of acute uncomplicated cystitis in women, staph saprophyticus in 5-15%. Enterococci and aerobic gram-neg rods other than E. coli account for remainder


Complication of UTI with gas formation in the bladder wall or lumen


Fungal infection of urinary tract


Mycobacterium tuberculosis; virtually always secondary to renal TB


Infection with the parasite trematode Schistosoma hematobium


Epidemiology


Uncomplicated UTI is a UTI in setting of functionally and structurally normal urinary tract. Complicated UTI: Pyelonephritis and/or structural or functional abnormality that decreases efficacy of antibiotic rx


E. coli most common organism. Other organisms: Proteus mirabilis, Nocardia, Candida, Enterobacter, Klebsiella, Streptococcus, Clostridium perfringens


Risk factors include female; elderly age; debilitated with predisposing factors, such as glycosuria, particularly from DM; urinary stasis from lower urinary tract obstruction or neurogenic bladder, recent UTIs, an immunocompromised state, or steroid therapy. Associated with enterovesical fistula, diverticulitis, Crohn’s disease, carcinoma of rectum/sigmoid


Candida albicans most common (51%), C. tropicalis (25%), C. parapsilosis (12%), Torulopsis glabrata (9%), others (3%)


Usually starts at or around one or both ureteral orifices


Transmission occurs throughout African continent and Far East and Middle East. Freeswimming cercariae penetrate skin or are ingested, become schistosomula in blood, and mature into adults in blood vessels. Oviposition occurs primarily in pelvic lower urinary tract, bladder most frequently affected, but can affect distal ureter and kidney


Sx


Dysuria, frequency, urgency, urge incontinence, hematuria


Frequency, urgency, nocturia, dysuria, suprapubic tenderness, pneumaturia


Dysuria, flank pain, nausea, frequency, stranguria, pyuria, hematuria, pneumaturia, vomiting, oliguria, anuria


Dysuria, urgency, frequency


Pruritic, macular rash at site of penetration 3-18 h after exposure; Katayama fever at onset of oviposition; active schistosomiasis may be associated with hematuria and terminal dysuria


Dx


UA and culture c + s of midstream urine with > 105 orgs, or > 102 orgs if symptomatic


Imaging: not indicated in most pts. May be indicated if suspect obstruction, UTI fails to respond to appropriate antibiotics, unusual organism


UA and culture


KUB: thin radiolucent streaks or gas bubbles outlining bladder wall; air within bladder lumen with air-fluid level in upright position


US: bladder wall thickening with gas appearing as small echogenic foci within bladder wall and lumen


CT: gas within bladder wall or lumen; may reveal other pathology such as diverticulitis Cystoscopy: gas bubbles within shaggy, erythematous bladder wall Urine microscopic: candidal fungi with budding forms or pseudohyphae. Urinary casts containing fungi diagnostic for renal infection. > 10,000 on clean catch or catheterized specimen. PCR rapidly and accurately identifies Candida.


Imaging: US may identify fungal material in collecting sx; CT scan demonstrates fungal accretions as mass with density lower than stone


Same as for renal TB



Rx


Tailor antibiotics to urine culture results. Uncomplicated UTI rx for 3 days, > 7 d in women with sx that persist, hx recent UTI, DM, or pregnancy. Complicated UTI treat for 10-21 d. Young men with uncomplicated UTI rx for 7 d. Older men rx as if complicated UTI. Bladder anesthetics: phenazopyridine 100-200 mg tid for 2 d or Uristat (Ortho-McNeil) 2 tabs po tid for 1-2 d


Antibiotics, bladder drainage, control blood sugar if elevated


Candidal cystitis: Fluconazole (oral or IV): 400-mg loading dose, then 200 mg/day for 14 d


Amphotericin bladder irrigations (50 mg amphotericin B in 1 L water or D5W admin at 42 mL/h) successful in 82-90% pts


Significant fungal accretions in kidney may require placement of percutaneous nephrostomy tube for drainage.


Gold standard for disseminated or invasive disease is IV amphotericin, although similar results with fluconazole in non-neutropenic pts


Rx same as for renal TB. If ureterovesical junction obstruction occurs, may require surgery


Systemic amphotericin B: 0.5 mg/kg body wt IV × 2 wk total of 35-40 mg/kg/body weight initial crs. Ketoconazole 400 mg qd × 6 mo cures 85%



Epidem: Hemorrhagic cystitis (HC) related to acrolein occurs in 4-40% of pts, mortality rate up to 75% (J Urol 1989; 141: 1063). About 5-11.5% of pts rx with pelvic radiation therapy have bladder cmplc, including HC (J Urol 1993;150:332; S Afr Med J 1986; 70: 727). HC after pelvic radiation therapy occurs 6 mo to 10 yr or more following rx (J Urol 1978; 119: 64) High-dose busulfan also appears to be a risk factor for HC (Bone Marrow Transplant 2003; 32: 903).

Pathophys: Cyclophosphamide-related HC is believed to be related to bladder damage caused by acrolein. Induced edema, ulceration, neovascularization, hemorrhage, and necrosis (Biochem Pharmacol 1979; 28: 2945). The effect may be dose related; a minimal accumulative dose of 2.8 g has been reported to cause HC (Lancet 1983; 1: 1213), and incidence is higher with IV as opposed to oral administration (Cancer 1988; 61: 451).

Sx: Grossly bloody urine, clots, suprapubic pain

Lab: CBC, coags, UA and culture

Crs: Variable. Ranges from self-limiting to life-threatening hemorrhage

Cmplc: Secondary bladder cancer with cyclophosphamide therapy and pelvic radiation therapy

Diff Dx: R/o bacterial UTI, malignancy

Xray: Imaging for suspected obstruction; evaluate upper tracts with US or CT.

Rx: Preventive: hyperhydration using 5% dextrose 0.9% saline at a rate of 250 mL/hr and furosemide to maintain urine output; 150 mL/hr in pts receiving cyclophosphamide for BMT associated with 7% incidence HC and is less costly than MESNA (Oncology 1999; 57:
287). Rx: Ribavirin has been reported to be successful in rx of pediatric BMT recipients with HC (J Urol 1993; 149:565; Bone Marrow Transplant 1991; 7: 247). BK virus: hyperhydration and, for refractory cases, laser vaporization of papulous tumors (Eur Urol 1999;36:257) and parenteral vidarabine have been used (Bone Marrow Transplant 2000; 25: 319). Radiation therapy and acrolein-related: (1) continuous bladder irrigation (CBI); (2) intravesical alum, silver nitrate, carboprost, tromethamine, and formalin; (3) systemic therapy with epsilon aminocaproic acid and sodium pentosan polysulphate (J Urol 1986;136:813; 2005;173:103); (4) electrocauterization; (5) neodymium YAG laser; (6) hydrostatic dilation; (7) hyperbaric oxygen (Urology 1986; 27: 271); (8) urinary diversion; and (9) hypogastric artery embolization (J Urol 1999;161:1747; 1997;154:2301; J Urol 1993;150:332; 1990;143:1; Lancet 1995;346:803).


3.7 Interstitial Cystitis

Cause: Exact cause unknown. Proposed etiologies include infections (N Engl J Med 1994; 331: 1212), bladder mastocytosis, mast cell activation (Urol Clin North Am 1994; 21: 41), and defect in epithelial permeability barrier of bladder surface GAG (J Urol 1993; 150: 845), urine abnormalities that may be toxic (Urol Clin North Am 1994; 21: 153), alterations in sensory nervous system (Neuroscience 1992; 48: 187), and autoimmune-related causes (Eur Urol 1980; 6: 10).

Epidem: Reported incidence of 500,000-1,000,000 cases in United States (Urology 1997; 49: 2), but may be at least 20 times higher incidence (Clin Obstet Gynecol 2002; 45: 242). Rare in childhood. Median age of onset is 40 yr; 25% of pts are < 25 yr (Urol Clin North Am 1994; 2: 1). Occurs more often in females (female-to-male ratio: 9: 1). Increased incidence in Jews (Neurourol Urodynam 1990; 9: 241) is 100%. Up to 50% of affected people experience spontaneous remissions, probably unrelated to rx, that last for 1-80 mo (AUA Update 1999; 2: 10). Associated
diseases include allergies, allergic si, fibromyalgia, vulvodynia, migraine headaches, endometriosis, chronic fatigue syndrome, incontinence, asthma, systemic lupus erythematosus, inflammatory bowel disease, and Sjögren’s syndrome (Urology 1997; 49: 52; Urol Clin North Am 1994; 21: 20; J Musculoskel Pain 1993; 1: 295).

Pathophys: No pathognomonic histopathologic features. Histopathology used to r/o other possible diseases, such as carcinoma, eosinophilic cystitis, and tuberculosis (TB) cystitis. Hunner’s ulcers visible during hydrodistention in 20% of affected pts (Urol Clin North Am 1994; 21: 20). Refer to NIADDK Research definition of interstitial cystitis (IC) (Table 3.2).








Table 3.2 NIADDK Research Definition of Interstitial Cystitis











Required Criteria




  • Glomerulations or Hunner’s ulcers on cystoscopic examination



  • Pain associated with bladder or urinary urgency



  • Cystoscopy and hydrodistention: Glomerulations in 3 quadrants of bladder and 10 per quadrant; bladder distended under anesthesia to 80-100 cm H2O for 1-2 min 1-2 times for evaluation of glomerulations


Exclusion Criteria




  • Bladder capacity > 350 mL on awake cystometry



  • Absence of intense urge to void at 150 mL H2O during cystometry (fill rate: 30-100 mL/min)



  • Presence of phasic involuntary bladder contractions during cystometry



  • Duration of symptoms < 9 mo



  • No nocturia



  • Symptomatic relief with antibiotics, anticholinergics, antispasmodics, urinary antiseptics



  • Awake daytime frequency < 8 times/d



  • Dx of bacterial cystitis or prostatitis within 3 mo



  • Bladder or lower ureteral calculi



  • Active genital herpes



  • Uterine, cervical, vaginal, or urethral cancer



  • Urethral diverticulum



  • Chemical (cyclophosphamide), tuberculous or radiation cystitis



  • Benign or malignant bladder tumors



  • Vaginitis



  • Age < 18 yr


Source: NIADDK—National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases.



Sx: Most (93.6%) classic IC pts report various degrees of pain. Of those pts with pain, 80.4%, 73.8%, 65.7%, and 52.5% reported pain in lower abdomen, urethra, lower back, and vaginal area, respectively (Urology 1997; 49[suppl 5A]:64). Other sx include urgency, frequency, pelvic pressure, bladder spasm, dyspareunia, burning, awakening at night with pain, and pain that persists for many days after intercourse (Urol Clin North Am 1994; 21: 7). Many sx are aggravated by menstrual cycle, and 75% pts report that sexual intercourse exacerbates the sx.

Si: Severe urinary frequency and urgency, voiding at least 8 times a day, tender bladder base during pelvic examination, nocturia

Crs: No sure cure for interstitial cystitis. Severity and frequency of sx vary.

Cmplc: May have significant adverse affect on quality of life

Diff Dx: Other forms of cystitis, DI, bladder cancer, voiding dysfunction

Lab: UA, c + s, urine cytology

Xray: Not routinely indicated

Intravesical potassium sensitivity test (PST)—based on theory that most pts with IC have urothelial defects that allow cations to penetrate the mucosa and thus depolarize the sensory nerve fibers and subsequently create lower urinary tract sx. Most (80%) IC pts tested are pos for PST, whereas only 2% of healthy volunteers are pos.

Other Eval: Urodynamic evaluation helpful to assess bladder capacity and r/o disorder. Cystoscopy under anesthesia with hydrodistention of the bladder and bladder bxs can be performed to look for glomerulations (> 10 glomerulations in 3 quadrants of bladder using double-fill hydrodistention technique (Urol Clin North Am 1994; 21: 63) and Hunner’s ulcers and to assess bladder capacity. Hydrodistention is also therapeutic.

Rx: Variety of therapies used to manage IC. Therapies targeting the urothelium are very important, especially in those pts with strongly pos PST.


Oral therapy: Pentosan polysulfate sodium 100 mg po tid. Pain relief requires rx of 2-4 mo and up to 1 yr. Nearly half (42%) response rate compared to 18% with PBO. May add tricyclic to increase response rate (J Urol 2001; 165 [suppl5]:67). Calcium glycerophosphate has been shown to be beneficial in prevention of food-related exacerbation of IC sx with 79% pts reporting decreased pain (Abstract Urol 2001; 57: 119). Hydroxyzine (H-1) antagonist: 25 mg po qhs to start and increase to 50 mg qhs and 25 mg qam. Improves sx in 40-55% pts (Urology 1997; 49: 108). Amitriptyline—starting dose of 10-25 mg qhs; may increase to 75-100 mg qhs. Success rates of 64-90% at a f/u of 2-14 mo (Urol Clin North Am 1994; 21: 63; J Urol 1990; 143: 279). Dietary changes—between 51% and 62% pts with IC note increase in sx with acidic foods, carbonated drinks, alcoholic beverages, and caffeine (Urol Clin North Am 1994; 21: 121).

Intravesical therapy: DMSO is primary intravesical therapy for IC (Urol Clin North Am 1994; 21: 73; Urology 1987; 29: 17); may be used alone or in combination with steroids, heparin, bicarbonate. Rx varies from 1-2 instillations per week for 4-8 wk. Efficacy of 50-90%, 35-40% relapse rate, and only 50% of these pts reported to respond to re-rx with DMSO (Urology 1997; 49[suppl 5A]:105). Hypochlorous acid: a 0.4% solution is administered under anesthesia. Average success rate 72% with an average 6-mo duration of response. Contraindicated if VUR is present (Urology 1979; 13: 389). Other possible intravesical agents include capsaicin, silver nitrate, lidocaine, doxorubicin, hyaluronic acid, BCG, and cromolyn sodium.

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