Updated: Dec 27, 2007
The genitourinary system is a common site of extrapulmonary tuberculosis (TB). Genitourinary tuberculosis (GUTB) may involve the kidneys, ureter, bladder, or genital organs. Clinical symptoms usually develop 10-15 years after the primary infection. Only about a quarter of patients with GUTB have a known history of TB; about half of these patients have normal chest radiography findings.
Mycobacterium tuberculosis bacilli are inhaled through the lungs to the alveoli, where they are phagocytosed by polymorphonuclear leukocytes and macrophages. Although most bacilli are initially contained, some are carried to the region's lymph nodes. Eventually, the thoracic duct may deliver mycobacteria to the venous blood; this may result in seeding of different organs, including the kidneys.
Multiple granuloma form at the site of metastatic foci. In the kidneys, they are typically bilateral, cortical, and adjacent to the glomeruli and may remain inactive for decades.
Although both kidneys are seeded, clinically significant disease, which is caused by capillary rupture and delivery of proliferating bacilli into the proximal tubules, usually develops in only one kidney. The medullary hypertonic environment impairs the phagocytic function.
Growing granuloma may erode into the calyceal system, spreading the bacilli to the renal pelvis, ureters, bladder, and other genitourinary organs. Depending on the status of the patient's defense mechanisms, fibrosis and strictures may develop with chronic abscess formation. Extensive lesions can result in nonfunctioning kidneys. Hypertension in persons with renal TB is twice as common as it is in the general population.
Ureteral TB is an extension of the disease from the kidneys, generally to the ureterovesical junction. It only rarely affects the middle third of the ureter. Ureteral TB often causes ureteral strictures and, sometimes, hydronephrosis. Occasionally, severe cases can cause stricture of virtually the entire ureter. Ureteral TB develops in about half of all patients with renal TB.
Bladder TB is secondary to renal TB and usually starts at the ureteral orifice. It initially manifests as superficial inflammation with bullous edema and granulation. Fibrosis of the ureteral orifice can lead to stricture formation with hydronephrosis or scarification (ie, golf-hole appearance) with vesicoureteral reflux. Severe cases involve the entire bladder wall, where deep layers of muscle are eventually replaced by fibrous tissue, thus producing a thick fibrous bladder. Tubercles are rare in the bladder; if present, they usually appear at the ureteral orifice. Malignancy should be considered with any isolated tubercles away from the ureteral orifices.
The higher frequency of isolated epididymal TB lesions in children favors the possibility of hematological spread of infection, while adults seem to develop tuberculous epididymoorchitis caused by direct spread from the urinary tract.1 The formation of a draining sinus is uncommon in developed countries, but epididymal induration and beading of the vas are common.
Involvement of the testis is usually due to direct extension. Infertility may result from bilateral vasal obstruction. Nodular beading of the vas is a characteristic physical finding. Orchitis and the resulting testicular swelling can be difficult to differentiate from other mass lesions of the testes.
Prostatic TB is also spread hematogenously, but involvement is rare. The affected prostate is nodular and not tender to palpation. Eighty-five percent of patients also have renal TB. Severe cases may cavitate and form a perineal sinus, although this development is rare. Decreased semen volume may indicate extensive prostatic disease or ejaculatory duct obstruction.2
Patients with genital and urethral TB present with a superficial tuberculous ulcer on the penis or in the female genital tract secondary to mycobacteria exposure during intercourse. The penile ulcer may cause cavernositis that extends to the urethra. This form of TB may involve the uterus and fallopian tubes, causing strictures. Consider malignancy if genital ulcers are present. Urethral TB is secondary to genital TB. Acute urethritis manifests as mycobacterial discharge and often results in chronic stricture formation.
GUTB comprises approximately 6% of extrapulmonary cases of TB (217 of 3438 cases in 1999). Individuals infected with HIV account for about 50% of the total population with TB, and 70% of patients with AIDS and TB had extrapulmonary disease, accounting for an overall incidence of 2.3%.
GUTB in developing countries comprises approximately 15-20% of extrapulmonary cases of TB.
The presentation is often vague, and physicians must have a high degree of awareness to make the diagnosis.
Renal Cell Carcinoma
Schistosomiasis
Renal malacoplakia
Medullary sponge kidney
Cholesteatoma
Pyonephrosis
Renal echinococcosis
Fungal infection
Bladder cancer
Psoas abscess with calcification
Calyceal diverticula
Findings include granuloma with central Langerhans cells surrounded by lymphocytes, fibrocytes, and epithelioid cells, which later progress to central caseous formation and varying degrees of fibrosis and calcification.
Genitourinary tuberculosis (GUTB) responds better to a short course of treatment than pulmonary TB because GUTB carries a lower mycobacterial load. Also, isonicotinic acid hydrazide (INH) and rifampin penetrate well into the cavitary lesions associated with GUTB. A high concentration of INH, rifampin, and pyrazinamide are maintained in urine.
Although chemotherapy is the mainstay of treatment, surgical intervention, either as ablation or reconstruction, is often required during the course of GUTB. Generally, at least 4-6 weeks of chemotherapy with appropriate agents is first tried if immediate surgery is not necessary. In a recent European series, the overall frequency of surgical management in GUTB in the past 20 years was 0.5% of total urological surgical procedures.
The goals of pharmacotherapy are to reduce morbidity, to eradicate infection, and to prevent complications.
These agents are used to treat susceptible tuberculosis (TB) infections.
First-line agent for susceptible mycobacteria. Bactericidal or bacteriostatic, depending on concentration and susceptibility. More effective, less toxic, and less expensive. Inhibits mycolic acid synthesis necessary for mycobacterial cell wall formation. Affects mycobacterial MAO and diamine oxidase. Adverse effects include peripheral neuropathy, optic neuritis, encephalopathy, hepatitis, interstitial nephritis, gynecomastia, lupuslike syndromes, anemia (eg, aplastic, sideroblastic, hemolytic), pancytopenia, maculopapular or acneiform rash, exfoliative dermatitis, hyperglycemia, metabolic acidosis, and xerostomia.
5 mg/kg/d PO/IM (usual dose is 300 mg/d)
10-20 mg/kg/d PO/IM; not to exceed 300 mg/d
Increases serum level of drugs metabolized by hepatic cytochrome P-450 system, including anticonvulsants, warfarin, benzodiazepines, haloperidol, theophylline, and ketoconazole; antacids decrease absorption
Documented hypersensitivity; hepatic disease; renal impairment; alcoholism; diabetes; pregnancy; seizure; malnutrition
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Obtain baseline LFT, stop if aminotransferase level triples; in lactating mother, watch for neurotoxicity or hepatotoxicity in child; supplement pyridoxine to avoid neurotoxicity; toxic dose >20 mg/kg/d; take on empty stomach; studies show that even in anuric patient, dosage of 300 mg (5 mg/kg) is well tolerated
First-line treatment. Bactericidal and bacteriostatic, depending on concentration and susceptibility. Binds to beta subunit of DNA-dependent RNA polymerase and inhibits bacterial RNA synthesis. Effective against both slowly and actively dividing bacteria in both cavitary and caseous lesions. Adverse effects include hepatitis, interstitial nephritis, hemolysis, glomerulonephritis, nephrotic syndrome, pancreatitis, pseudomembranous colitis, myopathy, pruritus, and discoloration of body fluids.
10 mg/kg/d PO/IV; not to exceed 600 mg/d
10-20 mg/kg/d PO/IV; not to exceed 600 mg/d
Decreases serum level of digoxin, verapamil, diltiazem, thyroid hormones, warfarin, sulfonylureas, progestins, corticosteroids, theophylline, diazepam, quinine, and methadone
Documented hypersensitivity; hepatic disease; alcoholism; dental disease; pregnancy; contact lenses
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Take on empty stomach; in renal insufficiency, no need to lower dose below 600 mg/d (leads to significant reduction in effectiveness); in hepatic impairment, dose should not exceed 8 mg/kg/d; obtain periodic LFT; decreases effectiveness of oral contraceptives and additional measures should be used for at least 1 cycle after course of rifampin; lowers serum concentration of protease inhibitors and nonnucleoside reverse transcriptase inhibitors
First-line treatment. Bactericidal or bacteriostatic, depending on concentration and susceptibility, possibly by decreasing intracellular pH of macrophages. Less toxic, more effective. Effective against only M tuberculosis. Adverse effects include hepatitis, hyperuricemia, photosensitivity, sideroblastic anemia, thrombocytopenia, fever, and arthralgia (also nongouty).
15-30 mg/kg/d PO; not to exceed 2 g/d
7.5-20 mg/kg PO bid or 15-40 mg/kg/d PO; not to exceed 2 g/d
Pharmacodynamic, antigout agents must be altered because of increase in uric acid level
Documented hypersensitivity; hepatic disease; gout; alcoholism
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Use only in combination with other effective antituberculous agents; inhibits renal excretion of urates; may result in hyperuricemia (usually asymptomatic); perform baseline serum uric acid determinations; discontinue if signs of hyperuricemia with acute gouty arthritis appear; perform baseline LFTs (closely monitor in liver disease); discontinue pyrazinamide if signs of hepatocellular damage appear; caution in history of diabetes mellitus; in renal impairment, adjust dose as follows:
CrCl >50 mL/min: No dosage adjustment
CrCl 10-50 mL/min: Extend dosing interval to 48-72 h
CrCl <10 mL/min: Extend dosing interval to 72 h
Dialysis: Administer dose 24 h before dialysis
Monitor serum uric acid level
Second-line treatment. Bactericidal and bacteriostatic, depending on concentration. Inhibits RNA synthesis. Adverse effects include ocular neuritis, peripheral neuropathy, hyperuricemia, fever, thrombocytopenia, proteinuria, interstitial nephritis, arthralgia, and toxic epidermal necrolysis.
15-25 mg/kg/d PO; not to exceed 1600 mg/d
<12 years: Not recommended
>12 years: 15-25 mg/kg/d PO; not to exceed 1600 mg/d
Aluminum salts may delay and reduce absorption (administer several hours before or after ethambutol dose)
Documented hypersensitivity; ocular disease; gout; renal disease
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Reduce dose in impaired renal function
May cause reversible visual adverse effects if promptly discontinued
Second- or third-line treatment. Bactericidal by inhibiting protein synthesis through irreversible binding to 30S ribosomal subunit in susceptible bacteria. Adverse effects include ototoxicity, renal tubular acidosis, renal tubular necrosis, myasthenia, exfoliative dermatitis, and agranulocytosis.
15 mg/kg/d IM (deep); not to exceed 1 g/d; alternatively, 25-30 mg/dose 3 times/wk IM (deep)
20-40 mg/kg/d IM (deep) or 3 times/wk IM (deep); not to exceed 1 g/d
Additive nephrotoxicity with acyclovir, cisplatin, vancomycin, cyclosporin, NSAIDs; additive ototoxicity with IV loop diuretic; additive myasthenic effect with neuromuscular blockers and general anesthetics
Documented hypersensitivity; hepatic or renal impairment; advanced age; hearing disorder; myasthenia gravis; parkinsonism
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Narrow therapeutic index; not intended for long-term therapy; caution in renal failure not on dialysis; caution with myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; in renal impairment, adjust dose as follows:
CrCl >80 mL/min: No dose adjustment
CrCl 50-80 mL/min: Reduce dose to 7.5 mg/kg/d
CrCl 10-49 mL/min: Reduce dose to 7.5 mg/kg/q1-3d
CrCl <10 mL/min: Reduce dose to 7.5 mg/kg/q3-4d
Serum peak 40-50 mcg/mL, trough 5 mcg/mL; with dialysis, administer dose 6-8 h before dialysis
Second- or third-line treatment. Inhibits cell wall synthesis by competing with d-alanine. Adverse CNS effects include drowsiness, anxiety, depression, psychosis, seizure, memory loss, tremor, vertigo, and paraesthesia. Other adverse effect is hepatic toxicity.
15 mg/kg/d PO in divided doses; not to exceed 1 g/d
10-20 mg/kg/d PO in divided doses; not to exceed 1 g/d
Incompatible with alcohol consumption because may increase possibility and risk of epileptic episodes; isoniazid in combination with cycloserine may result in increased cycloserine CNS adverse effects such as dizziness
Documented hypersensitivity; alcoholism; severe renal or hepatic failure; seizure disorder; severe anxiety; depression or psychosis
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Discontinue drug or reduce dosage if allergic dermatitis or symptoms of CNS toxicity, such as convulsions, headache, tremor, depression, confusion, psychosis, somnolence, hyperreflexia, vertigo, paresis or dysarthria develop; risk of convulsions is increased in patients with chronic alcoholism; administration has been associated with vitamin B-12 and folic acid deficiency, megaloblastic anemia, and sideroblastic anemia; monitor blood levels weekly in reduced renal function, patients receiving more than 500 mg/d, and those with symptoms of toxicity; periodic serum level (<30 mcg/mL); pyridoxin (50-100 mg/d) to avoid CNS adverse effects; monitor renal and hepatic function
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tuberculosis, genitourinary tuberculosis, urinogenital tuberculosis, urinogenital TB, TB, genitourinary TB, GUTB, renal tuberculosis, renal TB, urethral tuberculosis, urethral TB, bladder tuberculosis, bladder TB, thimble bladder, prostatic tuberculosis, prostatic TB, fallopian tuberculosis, penile tuberculosis, sterile pyuria, Mycobacterium tuberculosis, M tuberculosis, high-resolution transrectal ultrasonography, TRUS, sexually transmitted disease, STD, sexually transmitted infection, STI, ureteral tuberculosis, ureteral TB, epididymal TB, epididymal tuberculosis, tuberculous epididymoorchitis, tuberculous ulcer, endometrial TB, endometrial tuberculosis
Mohamed S Soliman, MD, Consulting Staff, Integral Healthcare of Cheraw
Mohamed S Soliman, MD is a member of the following medical societies: American College of Chest Physicians and American Thoracic Society
Disclosure: Nothing to disclose.
Klaus-Dieter Lessnau, MD, FCCP, Clinical Assistant Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory, Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital
Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Artificial Internal Organs, American Thoracic Society, Physicians for Social Responsibility, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.
Aizid Hashmat, MD, Chairman, Department of Urology, Brooklyn Hospital Center
Aizid Hashmat, MD is a member of the following medical societies: American Urological Association
Disclosure: Nothing to disclose.
Allen Donald Seftel, MD, Department of Urology, Associate Professor, Case Western Reserve University
Allen Donald Seftel, MD is a member of the following medical societies: Ohio State Medical Association
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.
Shlomo Raz, MD, Professor, Department of Surgery, Division of Urology, University of California at Los Angeles School of Medicine
Shlomo Raz, MD is a member of the following medical societies: American College of Surgeons, American Medical Association, American Urological Association, and California Medical Association
Disclosure: Nothing to disclose.
J Stuart Wolf, Jr, MD, FACS, David A Bloom Professor of Urology, Director, Division of Minimally Invasive Urology, Department of Urology, University of Michigan Medical Center
J Stuart Wolf, Jr, MD, FACS is a member of the following medical societies: American College of Surgeons, American Medical Association, American Urological Association, Catholic Medical Association, Endourological Society, Society for Urology and Engineering, Society of Laparoendoscopic Surgeons, and Society of University Urologists
Disclosure: Terumo Corporation Consulting fee Consulting; Omeros Corporation Consulting fee Consulting
Edward David Kim, MD, FACS, Professor of Surgery, Division of Urology, University of Tennessee Graduate School of Medicine; Consulting Staff, University of Tennessee Medical Center
Edward David Kim, MD, FACS is a member of the following medical societies: American College of Surgeons, American Society for Reproductive Medicine, American Society of Andrology, American Urological Association, and Tennessee Medical Association
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