Continuing Education Activity
Genitourinary tuberculosis (GUTB), most commonly caused by Mycobacterium tuberculosis, is the infection of the urinary tract or genital organs due to hematogenous spread of chronic latent pulmonary tuberculosis. Diagnosis GUTB is difficult and is delayed due to symptoms often getting masked by another disease, including urinary tract infection (UTI). Resistant or recurrent urinary tract infections should be tested for GUTB without delay. This activity outlines the evaluation and treatment of genitourinary tuberculosis and highlights the role of the interprofessional team members to improve outcomes for patients affected by GUTB.
- Outline the bacteria involved in genitourinary tuberculosis.
- Review the presentations of genitourinary tuberculosis.
- Identify the antibiotics used to treat genitourinary tuberculosis.
- Describe how the team members and the close coordination and collaboration of the interprofessional team are very important for the better outcomes of the patients if genitourinary tuberculosis.
Genitourinary tuberculosis (GUTB) is defined as the infection of the urinary tract or genitalia most commonly caused by Mycobacterium tuberculosis. GUTB term was coined by Hans Wildbolz in 1937. GUTB comprises 20% of all extrapulmonary tuberculosis. Following pulmonary tuberculosis, 2 to 20% of individuals can develop genitourinary tuberculosis after 5 to 25 years.
An estimated 10 million people got infected with tuberculosis worldwide, out of which 1.5 million people died in 2018, according to the World Health Organization. About one-quarter of the world's population has latent TB. Tuberculosis is curable and preventable. Tuberculosis spreads from person to person through the air droplets.
Renal and Urologic Tuberculosis
Most commonly involves the urinary collecting system (renal pelvis, calyces, ureter, and bladder) and less commonly involves renal parenchyma.
Involves epididymis, testis, urethra, and prostate in the male and Fallopian tube, endometrium, and ovaries in the female.
Renal and prostatic TB is due to hematogenous spread of mycobacterium from a chronic latent pulmonary infection. Other genitourinary organs are affected by the local spread of infection.
The most common cause of GUTB is infection with M. tuberculosis. Other less common causes are infection with M. kansasii, M. fortuitum, M. bovis, M. avium-intracellulare (MAI), M. xenopi, and M. celatum.
Few cases of prostatic TB have been reported as a complication of Bacillus Calmette-Guerin (BCG) intravesical instillation therapy for the treatment of superficial bladder tumors. The most common organism isolated was M. bovis.
It is transmitted sexually as the bacteria clears from the body secretions like semen, urine, and genital secretions.
There are cases that reported male to female transmission of GUTB. Infection with Human immunodeficiency virus (HIV), prolonged use of steroids, and other immunosuppressive therapies increase the risk of active TB and may indicate the risk of reactivation of dormant foci of infection. In sexually active young men, epididymal TB is most common.
Hematogenous spread of M. tuberculosis from the primary focus may result in TB prostatitis. 10 to 12% of men with primary foci of TB showed the presence of prostatic TB on autopsy in some research studies.
Risk Factors for GUTB
- Primary infection - pulmonary or extrapulmonary TB
- Previous infection - The presence of dormant bacilli and deterioration of the immune system may lead to the occurrence of GUTB.
- Immune system suppression - drugs, infections (HIV), diseases (congenital immune disorders)
- Geographical residence: More in developing countries like Asia and Africa as compared to the United States, United Kingdom, Australia, etc.
- Living conditions: crowded, unhygienic places, migrants, prisoners.
Genitourinary tuberculosis is the second most common form (20 to 40%) of extrapulmonary tuberculosis in developed countries and the third most common in developing countries (2019). Extrapulmonary TB accounts for 15% of the total incidence of 7.0 million cases of TB as of 2018. It is estimated by the Health Organization (WHO) that approximately 9 million people get infected by TB every year, out of which 95% are from developing countries. 2 to 3 million people face mortality due to TB each year. Miliary TB is the main culprit form of TB, which leads to spreads the infection to the genital tract in 25 to 60% of cases (2017).
It can affect people of all ages but is predominant in males in their fourth and fifth decades. The most common organ affected is the kidney, followed by epididymis, testis, bladder, ureter, and prostate gland. An increased incidence of GUTB is found in people suffering from immunodeficiency like HIV/AIDS.
In GUTB, the kidney is the organ that is most commonly (74%) affected, followed by other organs like testes, epididymis, bladder, ureter, and prostate glands. Isolated organs involvement may also be seen in 5% to 30% of cases.
Inhalation of aerosolized Mycobacterium tuberculosis bacteria results in tuberculosis. The active cases of TB may cough, sneeze, spit or expel while they spit, infectious aerosols of diameter 0.5 to 5 micrometers and can sneeze up to 40,000 droplets.
The mycobacteria replicate in alveolar macrophages and form a Ghon's focus, which remains latent in lung granulomas and lymph nodes.
Genitourinary tuberculosis results from the spread of mycobacterium at the time of primary pulmonary infection or reactivation of old pulmonary infection. Reactivation is common in people suffering from immunodeficiency or those taking steroids. In the case of HIV, the occurrence of GUTB is usually the manifestation of disseminated disease. The infection spreads hematogenously involving kidney forming granulomas (typically bilateral, cortical, and adjacent to the glomeruli), which may either heal forming fibrosis, remain inactive for decades, or break down and rupture into the tubular lumen with excretion of bacilli into the urinary tract. The environment of the medullary region of the kidney is hypertonic, and it impairs the phagocytic functions of the kidney. Descending infection involves the ureter and bladder, leading to stricture and fibrosis with subsequent urinary tract obstruction and hydronephrosis. This may also make hypertension in patients with renal TB twice as common as in the general population.
Genital TB may result from hematogenous spread of infection from the kidney or lungs to the prostate and epididymis in the male and fallopian tubes in the female or directly from the local spread of infection through the urinary tract. The female genital tract is affected secondary to intercourse. Testicular involvement is usually due to the direct spread and leads to infertility due to bilateral vasal occlusion. Isolated epididymis involvement due to hematogenous spread is seen in children, while in the case of adults, the direct spread leads to epi-didymo orchitis development. Acute urethritis manifests as a bacterial (mycobacterial)discharge and often results in chronic stricture formation.
Secondary amyloidosis involving a kidney due to TB should be suspected if a patient with tuberculosis develops heavy proteinuria in the nephrotic range. Some pay present with glomerular ischemia and related findings.
Tuberculous interstitial nephritis seems to have idiopathic or immunological epiphenomenon pathophysiology may be indicated if the patient presents with active urine sediment with rapidly progressive renal failure, high leucocyte count in urine sediment, other primary foci of TB elsewhere in the body.
The histopathological finding may depend on the organs involved. The most common findings are:
- Multiple epithelioid granulomas with neutrophils and central caseating necrosis along with lymphocytes, mononuclear cells, and plasma cells found in an early stage. Necrosis results due to the release of cytokines, such as tumor necrosis factor and interleukin-1.
- In the chronic stage, extensive fibrosis and calcifications are seen.
- Renal biopsies may show tuberculous interstitial nephritis, interstitial inflammation with eosinophilia with granuloma, and caseating granulomas in some and non-specific IgG deposition in the mesangium.
History and Physical
The clinical presentation of the patient with genitourinary tuberculosis may vary from asymptomatic to non-specific symptoms related to the organ involved. The patient may be from an endemic region or have a prior history of pulmonary tuberculosis.
Patient with GUTB may present with the following symptoms:
- Recurrent or resistant urinary tract infection
- Irritative urinary symptoms like frequency, dysuria, and urgency
- Flank pain, the renal mass may be present in the case of renal TB.
- Testicular mass, perineal pain, and urethral discharge may be seen in genital TB.
- Menstrual irregularity, abdominal pain, infertility, or pelvic inflammatory disease in case of female genital involvement
- Unexplained infertility in both sexes
- Non-specific symptoms like fever, weight loss, and backache
Tender scrotal swelling, irregular/nodular prostate, genital ulcer, and perineal sinus/ fistula.
- Ureteral involvement is usually seen at the ureterovesical junction and may lead to ureteral strictures, and severe cases may cause hydronephrosis.
- Bladder TB usually starts at the ureteral orifice, in the form of superficial inflammation with bullous edema and granulation, which may also lead to ureteral strictures and complications. The complication may manifest as fibrosis and involvement of the muscle layers leading to the thick fibrous bladder. Tubercles may be seen, but mainly at the ureteric orifices; if not, suspect malignancy.
- The typical appearance is epididymal induration and beading of vas deferens and rarely draining sinus.
- Testicular beading and nodular appearance are characteristic of TB and help differentiate it from other mass lesions of the testis.
- The affected prostate is nodular in appearance and non-tender on palpation. In severe cases, it may lead to cavitation & perineal sinus formation. Decreased semen volume may be observed.
- Urethral involvement and genial area TB - penis presents with the superficial TB ulcer. Carvernositis occurs due to penile ulcers extending to the urethra with time. It may also involve the uterus and Fallopian tubes, leading to strictures.
Evaluation of the patient with genitourinary tuberculosis requires a detailed history, physical examination, and a combination of laboratory and radiographic studies. The workup plan and findings are explained below.
- Tuberculin skin test/Mantoux test: 0.1 ml of purified protein derivative (PPD) injected in the forearm and skin induration measured after 48 to 72 hours. In healthy, nonhealthcare workers, skin induration greater than 10 mm in diameter is considered positive, and greater than 15 mm in diameter indicates active disease.
- Interferon-gamma release assay: It is an in-vitro test for quantifying the interferon-gamma response to M. tuberculosis antigens.
- Urine studies: Urinalysis may show sterile pyuria (presence of white cells in the urine, but negative bacterial culture) and hematuria. 3 to 6 early-morning urine samples, preferably on consecutive days, are collected for acid-fast stain (Ziehl-Neelsen stain), mycobacterial culture (Lowenstein-Jensen medium), and polymerase chain reaction (PCR) to detect M. tuberculosis. Culture has a specificity of 100%, and PCR has a specificity of 93% to 98%. Mycobacterial culture is the gold standard test, while urine PCR is the ideal diagnostic test because it gives a result within 24-48 hours.
- Radiographic imaging: Chest and spine X-ray may show active or healed TB lesions. Plain X-ray abdomen and pelvis may show calcification of the organ affected by GUTB. Intravenous pyelography (IVP) and voiding cystography are the standard studies for renal TB, which may show findings like strictures throughout the collecting system, calcifications, and hydronephrosis. Other imaging techniques like CT scans and ultrasonography can be done for advanced disease.
- Biopsy: Biopsies from genital ulcers and tubercles in the bladder should be sent for histopathological examination, which may show epithelioid granuloma and caseous necrosis.
- Supportive tests: All patients should be tested for HIV. Renal function tests and complete blood count should be done to check the status of the kidney.
Treatment / Management
- GUTB, in general, is treated like pulmonary TB with a four-drug regimen for 6 months (rifampin, isoniazid, pyrazinamide, and ethambutol for the first 2 months, then isoniazid and rifampin for 4 months).
- Patients that may need longer treatment include HIV coinfection and kidney abscess or malfunction.
- Patients with multidrug-resistant TB (MDR-TB) require treatment with fluoroquinolones, aminoglycosides, and other drugs for 18 to 24 months.
- Patients with GUTB complicated with ureteral stricture and hydronephrosis should be treated with early stenting or percutaneous nephrostomy.
- Nephrectomy is considered in patients with nonfunctioning kidney, coexisting renal cell carcinoma, and extensive disease involving the whole kidney.
- Urinary tract infection
- Malignancy (renal cell carcinoma, testicular tumor)
- Chronic pyelonephritis
- Urethral stricture
- Bacillus Calmette Guerin (BCG) cystitis
Toxicity and Side Effect Management
Common Side Effects of Antitubercular Drugs
- Isoniazid: hepatitis, toxic neuropathy, headache
- Rifampicin: red/orange colored urine, arthralgias
- Pyrazinamide: painful joints due to hyperuricemia
- Ethambutol: optic neuropathy
Side Effect Management
- Hepatotoxicity occurs with isoniazid, rifampicin, and pyrazinamide. The risk factor for hepatotoxicity includes old age, malnutrition, and alcoholic liver disease. So the liver function test should be done every 2 months. Drugs should be stopped immediately if the liver function test is abnormal.
- Peripheral neuropathy results from isoniazid and ethambutol which can be prevented by giving pyridoxine.
- Allergic reactions can occur with any antitubercular drugs. Desensitization should be done to reintroduce the drug.
The prognosis of genitourinary tuberculosis is excellent in young patients, early detected cases, a patient without comorbid conditions, and patients with good medication compliance. Patients with testicular and epididymal TB may require surgery. Early detection and treatment with antitubercular drugs reduce mortality by 2.2%.
Relapse can occur in cases of GUTB after initial urine sterilization. The relapse rate for GUTB without nephrectomy is 6%, while the relapse rate for GUTB with nephrectomy is less than 1%. Therefore, urine mycobacterial culture/PCR should be done every 6 to 12 months for 10 years after the completion of antituberculous therapy in a patient with GUTB without nephrectomy.
- Renal hypertension
- Chronic renal failure
- Prostatic abscess
- Reduced bladder capacity
- Tuberculous interstitial nephritis
- Vaginal TB ulcer
- Infectious disease specialist
- Urologist and urologic surgeon in case of any complications related to urinary tract
- Gynecologist if the patient complains of infertility
Deterrence and Patient Education
The main goal in the treatment of GUTB is early detection and treatment with antitubercular drugs. Patients should strictly follow medication adherence, along with a balanced diet. For non-compliant patients, directly observed therapy (DOT) should be used where patients are given medications under the direct care of health care workers.
Patients should be given appropriate knowledge about the side effects of antitubercular drugs and should return immediately if any side effects develop.
Mycobacteria usually clear approximately 4 weeks after appropriate medications are started. Inform patients that genitourinary tuberculosis (GUTB) may cause sterility in females, and consider genital TB in a male sex partner if the female has persistent, swollen, painful inguinal lymph nodes and no obvious source of infection.
Pearls and Other Issues
It is important to review regional drug resistance before starting medications.
- Urine generally clears of infectious organisms within 2 weeks in case of testicular TB after initiation of treatment.
- Periodic checks for semen cultures are required in prostatic TB, and if results turn out to be positive after 3 months, suspect either bacterial resistance to the current regimen of drugs or non-compliance. Also, to ensure the efficacy of treatment, follow-up with repeat transrectal ultrasound-guided prostatic biopsies should be done.
- Special care is to be taken in the case of patients with impaired renal function. Streptomycin and similar aminoglycosides should be avoided in patients with decreased renal function as they cause ototoxicity and nephrotoxicity. Also, ethambutol may cause irreversible optic neuritis, which makes its dose reduction a need according to the glomerular filtration rate (GFR). Rifampicin, isoniazid, pyrazinamide, prothionamide, and ethionamide may be given in patients with impaired renal function since they are excreted in bile and metabolites do not get excreted by the kidney.
- Patients with severe bladder involvement and the presence of tubular strictures may need to be prescribed steroids. If the patient is on rifampicin, a high dose of prednisolone is recommended since rifampicin decreases the bioavailability and effectiveness of the prednisolone to approximately 66%.
- Ruling out malignancy is a must if genital ulcers are present.
- Genitourinary tuberculosis can be prevented by BCG vaccination, screening patients from an endemic region with symptoms of tuberculosis, and the use of condoms if one partner is affected with GUTB.
Enhancing Healthcare Team Outcomes
Genitourinary tuberculosis is becoming a major public health problem in the developing world. Patients from the endemic region with clinical symptoms of GUTB should be tested without delay. Early detection, patient education, and long-term monitoring are key to eradicate GUTB. Managing cases of GUTB involves multiple interprofessional team approach that includes an infectious disease expert, a urologist, a gynecologist, radiologist, public health nurse or clinician, and a pharmacist. The role of clinicians is important in early detection and patient education about medication compliance and side effects. They also have an important role to play in patients who develop complications. The pharmacist has a key role to give medication under supervision to non-compliant patients.