AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

Section 2 of 11  

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Background

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.

Pathophysiology

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.

Frequency

United States

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%.

International

GUTB in developing countries comprises approximately 15-20% of extrapulmonary cases of TB.

Mortality/Morbidity

• Worldwide, 10 million people per year contract TB, and 3 million per year die from TB.

Race

• The incidence is highest in persons emigrating from Mexico or from Asian, Middle Eastern, African, and South American countries.

Sex

• The male-to-female ratio is 5:3.

Age

• The most common age at presentation is 30-45 years.
• Recently, the frequency of TB notably increased among persons aged 45-55 years and in those older than 70 years. This increase is primarily in developed countries.
• Rare but documented cases in the 5- to 12-year-old age group have been reported.

CLINICAL

Section 3 of 11  

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• Clinical
• Differentials
• Workup
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• Follow-up
• Miscellaneous
• Multimedia
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History

The presentation is often vague, and physicians must have a high degree of awareness to make the diagnosis.

• Symptoms are generally chronic, intermittent, and nonspecific. Genitourinary tuberculosis (GUTB) often manifests as repeated urinary tract infections that do not respond to the usual antibiotics.
• Persons with GUTB rarely display the typical symptoms of TB.
• • The most common symptoms of GUTB, in descending order of frequency, include increased frequency of urination (during the day initially but at night later in the disease course), dysuria, frank pain, suprapubic pain, blood or pus in the urine, and fever.
  • Urinary urgency is relatively uncommon unless the bladder is extensively involved.
  • Patients with GUTB may present with a painful testicular swelling, perianal sinus, or genital ulcer.
  • Asymptomatic patients are not uncommon. Unexplained infertility in both men and women is sometimes attributable to GUTB.³ Also, physicians have diagnosed endometrial TB while seeking the cause of congenital TB in the newborn.

Physical

• While the hallmark of GUTB is sterile pyuria, up to 20% of patients develop a secondary coliform infection.
• Gross hematuria occurs in 10% of cases and is usually total and painless. Microscopic hematuria is present in 50% of cases.
• Tender testicular or epididymal swelling, beading of the spermatic cord, and epididymocutaneous sinus formations may develop.

Causes

• The most common pathogen associated with TB is M tuberculosis.
• Uncommonly implicated pathogens include the following:
• • Mycobacterium kansasii
  • Mycobacterium fortuitum
  • Mycobacterium bovis
  • Mycobacterium avium-intracellulare
  • Mycobacterium xenopi
  • Mycobacterium celatum

DIFFERENTIALS

Section 4 of 11  

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Other Problems to be Considered

Renal malacoplakia
Medullary sponge kidney
Cholesteatoma
Pyonephrosis
Renal echinococcosis
Fungal infection
Bladder cancer
Psoas abscess with calcification
Calyceal diverticula

WORKUP

Section 5 of 11  

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• Follow-up
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Lab Studies

• Tuberculin skin test results are positive in about 90% of patients, but this finding denotes only prior inhalation of mycobacteria rather than active disease.
• Complete blood cell count, sedimentation rate, serum chemistry, and C-reactive protein studies are helpful to assess the severity of disease, renal function, and response to treatment.
• Serial early-morning urine collection for acid-fast smear (at least 3) is a specific (89-96%) but less sensitive (approximately 52%) tool.  
• Serial urine cultures are still considered the criterion standard for evidence of active disease, with sensitivity of 65% and specificity of 100%. Every effort should be made to process the samples immediately after collection. Sending cultures before starting antituberculosis treatment and adjusting therapy according to sensitivity in case of resistance is always recommended. The following methods are available:
• • Solid media: The Lowenstein-Jensen medium yields results in more than 4 weeks.
  • Radiometric media: The BACTEC 460 medium yields results in 2-3 days.
• The polymerase chain reaction (PCR) test has been extensively studied and has been proven highly sensitive, specific, and rapid.
• • In various studies, data show sensitivity ranging from 87-100% (usually >90%) and specificity from 92-99.8% (usually >95%). Compare this with cultures (37%), bladder biopsies (47%), and intravenous pyelography (IVP) examinations (88%).⁴
  • Along with an accurate clinical assessment, PCR is the best tool available for avoiding a treatment delay because results are available in only about 6 hours.
  • The following PCR tests are available with near-equivalent quality:
  • • Genus-specific 16S rRNA PCR test
    • Species-specific IS6110 PCR test
    • Roche Amplicor MTB PCR test^{5, 6, 7}
    • Amplified Mycobacterium tuberculosis Direct Detection Test (AMDT)
• Although not widely used, the following tests are also available:
• • Luciferase and fluorescent techniques: Staining with auramine or rhodamine and examining via fluorescence microscopy can be used to detect low numbers of mycobacteria.
  • High-performance liquid chromatography (HPLC) test: HPLC quickly reveals qualitative and quantitative differences in mycolic acid in cell walls.
  • DNA probe: This probe provides species specification in a few hours.

Imaging Studies

• Radiography
• • Chest and spine radiographs may show old or active lesions. In 50% of patients, chest radiographic findings are negative.
  • Kidney, ureter, and bladder (KUB) radiographs reveal calcifications in the kidney and ureter in approximately 50% of patients. Calcifications are intraluminal, as opposed to schistosomiasis, which produces intramural calcifications. Calcifications in the bladder are uncommon.
• Intravenous pyelography and voiding cystography
• • These tests are the standard diagnostic imaging studies for renal TB and have 88-95% sensitivity. They also help define the extent and severity of disease.
  • The earliest radiographically detectable changes are cavitary lesions that progress to the papilla and invade the collecting system, causing calyceal disruption. Findings of infundibular stenosis and multiple ureteral strictures are highly suggestive of renal TB. Later findings may include cortical necrosis, calcifications, and coalesced cavitary lesions with scarring, stricture, sinus, or abscess formation. A small contracted bladder suggests extensive bladder TB.
• Sonograms may reveal cystic or cavitary lesions, cortical scarring, hydronephrosis, and abscess in kidneys; ultrasonography is very sensitive in testicular TB. Adnexal mass, thickened omentum or peritoneum, peritoneal tubercles, loculated or free fluid in the pelvic cavity, and adhesions are common ultrasonographic findings of female genital TB.
• In recent years, high-resolution transrectal ultrasonography (TRUS) has become a very useful noninvasive technique in the evaluation of the subfertile man who has severe oligospermia or azoospermia associated with a low-volume ejaculate.⁸ TRUS can reveal abnormalities in the seminal vesicles and ejaculatory duct and can help assess the status of the prostate. It may show dilatation or fibrosis of epididymis, atrophy, thickening or calcification of seminal vesicles, or prostatitis.
• Retrograde pyelography is rarely indicated except in patients with renal failure in whom the kidneys cannot excrete contrast and to evaluate stricture in the upper urinary tract. It also helps for sampling urine from individual kidneys for microbiology.
• CT scanning with contrast
• • This imaging test is a useful adjunct to IVP and is helpful in late or advanced disease for assessing the extent of disease and the indirect functional status of the affected kidney compared with the normal opposite kidney. This study is very sensitive for detecting calcification and thickened walls of the ureter and bladder.
  • Nonvisualization of the affected kidney via excretory urography indicates advanced disease.
• Angiography is useful when focal lesions mimic a primary renal mass or when partial nephrectomy is planned. Angiography also shows obliterated interlobar arteries and avascular lesions.
• Renal nuclear scan findings are nonspecific but can be used to assess kidney function and to monitor the effects of therapy.
• MRI, hysterosalpingography, and image-intensifier endoscopy are sometimes useful to reveal radiographic changes in genitourinary tuberculosis (GUTB).

Other Tests

• Vasography in association with TRUS may demonstrate mechanical obstruction of the vas deferens.

Procedures

• Laparoscopy: The discovery of peritoneal tubercles during tubal ligation is not uncommon in developing countries.
• Consider biopsies of genital ulcers; tubercles in the bladder, especially if scattered away from the ureteric orifice (an uncommon feature of bladder TB); and any lesion with even a slight possibility of malignancy. The yield of biopsy for TB is about 45%.
• Fine-needle aspiration (FNA) as a minimally invasive technique plays a prime role in the diagnosis of tubercular epididymitis and epididymoorchitis.⁹ Acid-fast bacilli (AFB) may be detected on FNA smears in up to 60% of these patients.

Histologic Findings

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.

TREATMENT

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Medical Care

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.

• The primary aims of treatment are to preserve renal parenchyma and function, to make the patient noninfectious, and to manage comorbid conditions.
• Monitor culture and sensitivity reports and change the regimen if necessary.
• Standard treatment is rifampin, INH, pyrazinamide, and ethambutol for 2 months, then rifampin and INH for 4 more months unless resistance to either agent exists; if so, obtain a follow-up sensitivity report.
• In patients who are HIV-positive, continue treatment for a total of 9 months.
• Special considerations apply to patients with impaired renal function. Rifampicin, isoniazid, pyrazinamide, ethionamide, and prothionamide may be given in normal doses because they are either eliminated in the bile or broken down to metabolites that are not excreted by the kidney. Ethambutol causes optic neuritis, which may be irreversible, and reduced doses should be given according to the glomerular filtration rate (GFR). Streptomycin and other aminoglycosides are ototoxic and nephrotoxic and should be avoided if possible in patients with impaired renal function.
• Examples of short course therapy are as follows:
• • Prescribe 2 months of daily therapy with INH, rifampin, and pyrazinamide, then 2 months at 3 times per week with INH and rifampin.
  • Prescribe 4 months of therapy at 3 times per week with INH, rifampin, and pyrazinamide. This course is cost-effective in developing countries if compliance is ensured, although it may promote multidrug resistance.
  • Prescribe 2 months of daily therapy with INH, rifampin, pyrazinamide, and streptomycin or ethambutol, then 2 months at 3 times per week with INH and rifampin. Add streptomycin or ethambutol if resistance to INH or rifampin is a possibility.
• Indications for prescribing steroids include the following: 
• • Severe bladder symptoms
  • Tubular structure involvement (eg, ureter, fallopian tubes, spermatic cord)
• High-dose prednisone (ie, at least 20 mg tid) for 4-6 weeks is recommended because rifampicin reduces effectiveness and bioavailability of prednisone by 66%.

Surgical Care

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.

• Indications
• • Hydronephrosis
  • Progressive renal insufficiency secondary to obstruction
  • Nonfunctioning or poorly functioning kidneys
  • Stricture of fallopian tube or vas deferens that is causing infertility
  • Persistent pain
  • Severe, persistent, or recurrent uterine bleeding
  • Possible neoplasm
  • Recurrence of endometrial TB
• Ablative surgery
• • Partial or total nephrectomy
  • Epididymectomy
  • Salpingectomy
  • Other procedures
• Reconstructive surgery
• • Ureteric or urethral dilatation
  • Stent
  • Resection
  • Replacement or reimplant
  • Urinary diversion
  • Augmentation cystoplasty

Consultations

• A urologist should provide constant follow-up care to prevent further irreversible parenchymal damage.

Diet

• Institute a high-nutrition diet in malnourished patients.

Activity

• GUTB can be sexually transmitted until mycobacterial excretion ceases.

MEDICATION

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The goals of pharmacotherapy are to reduce morbidity, to eradicate infection, and to prevent complications.

Drug Category: Antitubercular agents

These agents are used to treat susceptible tuberculosis (TB) infections.

FOLLOW-UP

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Further Inpatient Care

• Use surgical intervention as needed.
• Treat comorbid conditions.

Further Outpatient Care

• If the patient is not complying with therapy, use direct observation therapy 2-3 times a week.

Deterrence/Prevention

• Maintain a high degree of clinical awareness for genitourinary tuberculosis (GUTB).
• Screen emigrants from endemic areas. If an emigrant from a TB-endemic area has intermittent recurrent urinary tract infections after several courses of antibiotics, obtain a purified protein derivative (PPD) skin test and serial early-morning urine samples to test for acid-fast bacilli to evaluate for GUTB.
• Screen sex partners and family members.
• Before starting medications, investigate regional drug-resistance data.
• Researchers now question the use of Bacille Calmette-Guérin (BCG) vaccine, even in developing countries, because TB is diagnosed in vaccinated persons. Additionally, the BCG vaccine is not cost-effective in developing countries.
• The chemoprophylaxis protocol for unconfirmed clinical disease is INH for 6 months (9 mo in patients who are HIV positive), INH and rifampin for 3 months, or rifampin and pyrazinamide for 2 months.

Complications

• Stricture
• Obstruction
• Superinfection
• Abscess
• Sinus formation
• Renal hypertension
• Scarring of renal parenchyma, loss of renal function, and, eventually, end-stage renal disease
• Stricture and obstruction of ejaculatory duct or vas deferens may cause azoospermia and sterility. Similarly, involvement of fallopian tubes or endometrium may lead to infertility, which is common in developing countries.
• Congenital TB: Culture-positive pulmonary TB in newborns and endometrial TB in mothers have been documented.

Prognosis

• Good
• • Early detection of disease
  • Young age
  • Sensitivity to first-line medications
  • Absence of comorbid conditions
  • Compliance with medications and follow-up care
  • Good social support system
• Poor
• • Late detection with complications
  • Low socioeconomic group
  • Old age
  • Other immunocompromising conditions

Patient Education

• Crucial education issues include long-term compliance, preventive measures, and early detection in other persons.
• GUTB can be sexually transmitted until treatment clears mycobacteria from semen, urine, or other genital secretions. Mycobacteria usually clear approximately 4 weeks after appropriate medications are started.
• For excellent patient education resources, visit eMedicine's Men's Health Center, Women's Health Center and Bacterial and Viral Infections Center. Also, see eMedicine's patient education article Tuberculosis.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Failure to consider renal tuberculosis (TB) in any nondiscrete renal calcification
• Failure to offer HIV testing to all patients with TB
• Failure to perform a full workup for malignancies if tubercles or ulcers are present away from ureteric orifices, if genital ulcers are present, or with suspicious renal lesions
• Failure to recognize, prevent, and treat adverse medication effects
• Failure to inform patients that genitourinary tuberculosis (GUTB) may cause sterility in females
• Failure to consider genital TB in a male sex partner if the female has persistent, swollen, painful inguinal lymph nodes and no obvious source of infection

Special Concerns

• In developed countries, the incidence of TB is decreasing at rate of 12%, which means the disease will take 30 more years to eradicate. No noticeable decrease is occurring in developing countries.

MULTIMEDIA

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Media file 1:  Genitourinary tuberculosis. Graph reporting cases of tuberculosis by disease form.
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Media type:  Graph

REFERENCES

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Article Last Updated: Dec 27, 2007