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Genitourinary Tuberculosis

Author: Ellis H. Tobin Author: Kristina Roddy Author: Suman K. Jha Author: Stephen W. Leslie Editor: Balram Rathish Updated: 8/16/2024 11:21:18 PM

Introduction

Tuberculosis is ranked as the 13th overall cause of death worldwide and the most frequent single infectious disease, accounting for an estimated 1.3 million annual mortalities according to the World Health Organization (WHO).[1] While pulmonary tuberculosis is by far the most frequent manifestation of the disease, extrapulmonary tuberculosis is found in about 20% of all cases but constitutes about 50% of tuberculosis cases in those with human immunodeficiency virus coinfection.[2][3]

The lymph nodes, pleura, urogenital tract, abdominal, bones/joints, and meninges are the most commonly affected extrapulmonary tuberculosis sites.[4] Urogenital tuberculosis encompasses infection of the urinary tract (kidneys, bladder, ureters) and genitals, with urinary tuberculosis being more common than the genital variety. The nonspecific symptomatology, long indolent course of the infection, lack of suspicion for tuberculosis, increasing multidrug resistance, and diagnostic difficulties, serious and irreversible complications specific to the genitourinary tract can result, including renal damage, urinary strictures, and infertility.

Etiology

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Etiology

Tuberculosis is caused by a family of closely related bacterial organisms classified as the Mycobacterium tuberculosis complex.[5] These organisms are aerobic, non-spore-forming bacteria with a large lipid concentration within their cell wall.[5] The lipids confer the acid-fast staining property characteristic of the family of mycobacteria.[5] In addition, the lipid content of their cell wall likely confers unique immunologic properties that play a key role in host-pathogen interactions.[5] For more information, see the companion StatPearls' reference review on "Tuberculosis."[5]

Genitourinary tuberculosis starts as a lung infection, which then spreads hematogenously to the kidneys, prostate, and epididymis.[6] In patients with miliary tuberculosis, the urogenital tract is involved in up to 62% of cases through hematogenous spread.[6] Lymphatic involvement of regional lymph nodes leads to bacterial spread through the thoracic duct into the bloodstream, ultimately infecting the kidneys—the urogenital organs affected most often by tuberculosis. From the kidneys, the infection can involve the ureters, bladder, urethra, and genital organs in men via the ejaculatory ducts.[6]

Epidemiology

Exact estimates of urogenital tuberculosis are lacking, but the medical literature reports much higher incidence rates in developing countries of Africa and Southeast Asia.[3][6][7][8][9][10] According to the WHO's Global Tuberculosis Report, the highest incidence of tuberculosis cases per 100,000 population is found in the following countries:

  • Lesotho (661)
  • Philippines (638)
  • Central African Republic (540)
  • North Korea (518)
  • Gabon (509)
  • East Timor (498)
  • Marshall Islands (483)
  • Myanmar (475)
  • South Africa (468)
  • Mongolia (452)
  • Namibia (450)
  • Papua New Guinea (432)
  • Indonesia (385)
  • Congo (369)
  • Mozambique (361)
  • Pakistan (258)
  • Bangladesh (221)
  • India (199)
  • China (52)
  • United States (2.9)

The United States (US) Center for Disease Control and Prevention (CDC) reports that the US continues to have a very low rate of tuberculosis, at 2.9 cases per 100,000 population, but this represents a 22% increase from 2022, with most of these cases found in residents not born in the US. California has the largest number of reported cases, but Alaska has the highest rate adjusted for population.[11] Genitourinary tuberculosis is the second most common (40%) extrapulmonary manifestation of the disease (after lymphatic involvement (50%), followed by pleural effusions (24%).[6][10] While the overall incidence of worldwide tuberculosis is declining, the percentage of patients with extrapulmonary disease is increasing.[12] Genitourinary involvement is most commonly seen in men in their 40s and 50s.[6][13] In autopsy studies, only half of the patients with renal involvement had symptoms related to a kidney infection.[14] 

In general, extrapulmonary tuberculosis most commonly affects persons with immunocompromising conditions, including human immunodeficiency virus (HIV) and diabetes, children (younger than 15), female sex, older adults (65 and older), living in or migrating from a region with a high tuberculosis incidence, or a prior history of the disease.[12][15][16][17][18][19] In some parts of the world, such as sub-Saharan Africa, up to 50% of patients with pulmonary tuberculosis and 60% to 90% of those with extrapulmonary disease will test positive for HIV.[20] 

Globally, about 12% of all individuals with tuberculosis are also coinfected with HIV.[21] Worldwide, the presence of HIV increases the risk of active tuberculosis 30-fold, and 25% of the mortalities in those who are HIV-positive are due to tuberculosis. Genital tuberculosis is most commonly seen in women between 15 and 45 years and in men at around 30 years.[22][23][24][25] The reported incidence of genital tract tuberculosis in women at infertility clinics varies geographically, from less than 1% in the US to 6% to 21% in South Africa and 3% to 28% in India.[26][27][28] Despite reported extrapulmonary tuberculosis being generally linked to older age, genital tract tuberculosis in women commonly presents in those of reproductive age and much less frequently in those who are postmenopausal—likely as many people are asymptomatic and are only diagnosed after evaluation for infertility.[26]

Pathophysiology

Understanding the pathophysiology of genitourinary tuberculosis is crucial for recognizing its varied clinical manifestations and guiding effective treatment strategies. 

Route of Exposure

The primary route of infection is inhalation of aerosols containing Mycobacterium tuberculosis (Mtb). Other routes include ingestion of Mycobacterium bovis in dairy products or direct entrance via intravesicular instillation of Bacillus Calmetterin in high-grade or in-situ bladder cancer cases.[29][30][31] Penile tuberculosis has been reported after ritual circumcision, and rare cases of genital tuberculosis in women have been linked to partners who are men with active disease.[7] 

Sexual transmission is a route specific to genital (penile) tuberculosis. Sexual transmission, via infected semen or potentially via sputum as a sexual lubricant, has been further suggested by studies, including results from a retrospective study showing that 3% to 5% of women with active genital tuberculosis had partners who were men with active urogenital tuberculosis.[26] Case study results found sexual partners affected by urogenital tuberculosis to have molecularly identical strains.[26] 

Progression of Disease

While most individuals (up to 95%) with a primary Mtb infection are able to eliminate or contain the mycobacteria (in the form of a latent tuberculosis infection), up to 27% will have disease progression to other sites via hematogenous or lymphatic spread.[7] In the case of urogenital tuberculosis, there is often a latent period of up to 20 years or more between the initial primary infection and evidence of genitourinary disease.[32] Immunosuppression that reduces cell-mediated immunity can lead to the proliferation of the organism, more rapid disease progression, and a higher risk for severe or serious complications.[7] 

Mycobacteria tuberculosis can survive inside leukocytes and other immune cells after phagocytosis; this organism reproduces slowly, dividing only once every 24 hours. This very slow rate of bacterial reproduction explains the disease's slow, indolent, and insidious nature.[14] The infection is resistant to most commonly used antibiotics as these typically work only during the late stages of bacterial cell division.[14] Reactivation of the disease is common, with a lifetime risk of 15%.[21][33] 

Organ-Specific Pathogenesis

Renal: The kidneys are highly vascularized and can be seeded with Mtb hematogenously, through the lymphatics, or direct spread after primary infection from the lungs or intestines.[7] Renal involvement can occur in all forms of tuberculosis. Results from an autopsy study found asymptomatic renal cortical foci in 73% of cases of pulmonary tuberculosis, most often bilateral.[34] Initial radiographic signs may show multiple, faint, tiny parenchymal calcifications. Reactivating isolated renal foci can allow the infection to progress, likely accounting for the reported greater frequency of unilateral renal tuberculosis.[14] Granulomatous inflammation and disease progression lead to chronic tubulointerstitial nephritis, papillary necrosis, ulcers, and fibrosis with extensive caseous destruction of the renal parenchyma and formation of lobules, dilated calices, cavities, and calcifications.[7] 

Untreated progressive renal disease can lead to the destruction of the renal parenchyma and obstructive nephropathy. End-stage chronic renal failure will develop in 5.7% of all patients diagnosed with renal tuberculosis.[14] The kidney may become small, calcified, and nonfunctional in some severe cases. These shrunken, nonfunctioning, calcified renal units are sometimes called "putty" or" cement kidneys" and represent a form of autonephrectomy.[35][36][37][38]

The renal medulla is generally spared after initial exposure as small granulomas typically start developing in the peritubular capillaries or the periglomerular renal cortex.[7] Over time, these lesions merge and form larger granulomas, usually in the upper and lower renal poles.[39] The rupture of any of these granulomas can expose the entire ipsilateral collecting system to the infection. More diffuse renal involvement is seen in immunocompromised individuals.[7]

Tuberculosis bacilli in the nephron tend to sequester and multiply primarily in the loop of Henle. This is due to the unique conditions in this part of the nephron (high ammonia levels, hypertonicity, and relatively poor blood flow) that limit the effectiveness of the immune response and foster the formation of medullary granulomas, papillary necrosis, scarring, abscess formation, chronic tubulointerstitial nephritis, and characteristic caseous necrosis and renal parenchymal damage.[7][39] Renal tuberculosis can also cause amyloidosis of the kidney, ultimately resulting in renal failure.[40][41][42][43] Hypertension is twice as common in patients with renal tuberculosis compared to the general population.

Bladder/ureter: Bladder and ureteral infections are typically due to the descent of Mtb microbes from renal medullary lesions through the lower urinary tract.[7] Up to 50% of patients with renal tuberculosis have ureteric involvement, with the lower third of the ureter being affected most often, followed by the ureteropelvic junction.[7] In severe cases, the entire ureter can be involved. Ureteric involvement without renal tuberculosis has not been described.[7] In addition to a descending renal infection, bladder involvement has also been shown to occur via the retrograde spread of tuberculosis from the prostate or testes.[7] Despite regular contact with Mtb-infected urine, urethral tuberculosis is uncommon, found in only 1.9% to 4.5% of all cases of urogenital tuberculosis and never as an isolated entity.[14]

Genitalia, women: Genital tuberculosis in women typically begins with a hematogenously spread focus in the endosalpinx, which may then infect, in descending order of frequency, the endometrium, ovaries, cervix, and vagina.[26] Lymphatic spread from involved abdominal organs is also possible but less common.[44][45] This condition may also develop from sexual intercourse with a man with genitourinary tuberculosis.[6]

Both fallopian tubes are involved in most women (greater than 90%) with genital tuberculosis, and the involvement could be tuberculosis endosalpingitis, exosalpingitis, interstitial tuberculosis salpingitis, or salpingitis isthmica nodosa.[46][47][48] The uterine endometrium is affected in 70% and the ovaries in 25% of cases, but the myometrium is usually spared.[8][46] Infection most often spreads from the fallopian tubes to the endometrium through direct drainage (50% to 80% of cases), commonly manifesting as distortion of the uterine cavity and intrauterine adhesions with menstrual dysfunction and infertility in women.[26] Involvement of the ovaries (20% to 30%) can cause adhesions, caseation, adnexal cysts, tubo-ovarian masses, and defective ovarian reserves.[26][49] Genital tuberculosis in women accounts for about 5% of all pelvic infections, and the global incidence of these infections in young women is increasing.[50][51]

Genitalia, men: Tuberculosis of the genitalia in men occurs either through hematogenous spread directly to the prostate and/or the epididymis, from sexual contact with an infected individual, or through the urinary tract with retrograde spread to the scrotal contents or prostate.[14] Due to its vascularity, the first genital organ affected is usually the epididymis.[52] Initial symptoms may be a testicular or scrotal mass, hematospermia, a penile ulcer, or unexplained infertility, often due to bilateral obstruction of the vas deferens. Renal lesions often accompany genital tuberculosis, but genital involvement may also present in isolation.[53] Up to about 10% of men with genital tuberculosis will develop infertility.[14][54][55]

Special Situations

HIV infection increases the occurrence, incidence, and morbidity of urogenital tuberculosis, which tends to be more widely disseminated in the body and is more likely to demonstrate bilateral renal involvement and lymphadenopathy. However, due to the reduced inflammatory response in these patients, there is less fibrosis, caseation, scarring, and stricture formation. The combination of genitourinary tuberculosis and HIV is associated with a high mortality risk.[56][57] Treatment of both infections is necessary, but drug interactions can make this complicated.[56][57]

Urogenital tuberculosis in those with renal transplants has been reported but is quite rare.[58][59][60][61] In areas with high rates of endemic tuberculosis, the prevalence of active tuberculosis in patients who received transplanted kidneys is reported as high as 15%.[61] In such patients, over 55% will face transplant rejection, and the overall mortality rate is reported to be as high as 60%.[61]

Diagnosis is difficult, and drug interactions, as well as renal failure, complicate treatment. For example, rifampin should generally be avoided in renal transplant recipients due to cytochrome P450 activity, which decreases serum levels of cyclosporine and prednisolone.[62] Treatment duration is usually at least 18 months, and extended prophylaxis is often required.[62] Unfortunately, the diagnosis is often made only after removal and examination of the transplanted kidney.[58][59][60] 

History and Physical

When symptomatic, dysuria, urinary hesitancy, and urinary frequency are common complaints in genitourinary tuberculosis. Lower urinary tract symptoms are often misdiagnosed as acute urinary tract infections, as secondary bacterial infections can occur in up to 50% of patients with urogenital tuberculosis, further confounding the issue. Gross hematuria will be found in about 10% of patients and microhematuria in about 50%. Nonspecific constitutional symptoms of tuberculosis, such as fever, weight loss, and night sweats, are uncommon and often indicative of concomitant tuberculosis outside the urogenital tract.[7] Genital tuberculosis most commonly presents as ulcers on the genitalia. Clinical manifestations of urogenital tuberculosis tend to have very long latency times, which average over 20 years.[32] Isolated genitourinary organ involvement with tuberculosis is uncommon without pulmonary disease but is more commonly found in global areas where the disease is endemic.[63]

Bladder tuberculosis can present as cystitis with symptoms of dysuria, nocturia, frequent and urgent need to urinate, with evidence of chronic inflammation at the ureterovesical junction—which can lead to progressive fibrosis, narrowing, stenosis, stricture formation, vesicoureteral reflux, and hydroureteronephrosis.[7] Chronic bladder wall and detrusor muscle inflammation (typically for at least 1 year) can significantly reduce functional bladder capacity.[64] Lower urinary tract symptoms of frequency, urgency, and dysuria generally appear once the bladder capacity reaches 100 mL or less. Rare complications of bladder tuberculosis include vesicovaginal, vesicocolic, and enterovesical fistulae and bladder perforation.[7][65] Once tuberculosis has advanced sufficiently to infect the bladder, urinary symptoms of frequency, dysuria, urgency, and nocturia develop in about half the cases, with gross hematuria and low back pain in about a third.[6][32][66][67]

Genital tuberculosis in women often presents as an indolent disease and is usually diagnosed during an evaluation for infertility.[44][68][69][70] Tuberculosis should be considered in infertile women in endemic countries, and screening should always be performed before consideration of in-vitro fertilization.[47] When symptomatic, women with urogenital tuberculosis may present with menstrual irregularities, lower abdominal or pelvic pain, an adnexal mass, ascites, abdominal distension, abnormal vaginal discharge, dyspareunia, and unexplained vaginal bleeding.[26][44][68][69][70][71][72][73][74][75] In postmenopausal women, genital involvement is characterized by postmenopausal bleeding, leukorrhea, and pyometra.[76] 

Ovarian involvement may demonstrate elevated Ca-125 levels, mimicking ovarian cancer.[70][71][72][73][74][75]  Genital tuberculosis in women is also commonly misdiagnosed as chronic pelvic inflammatory disease (PID). The lack of clinical response to broad-spectrum antibiotics for PID in a patient at epidemiologic risk should raise concern for genital tuberculosis.[22] Complications include genital fistulas to surrounding structures and unexplained infertility.[7] 

Penile tuberculosis is extremely rare and can be associated with various lesions of the penis, including subcutaneous erythematous nodules that can ulcerate, developing after direct sexual contact or secondary to another urogenital focus.[77][78] Inguinal lymphadenopathy may be palpable as it progresses.[77] Penile tuberculosis can mimic penile carcinoma and sexually transmitted infections, which means it should be considered in the differential diagnoses of persistent genital ulcers unresponsive to conventional treatment.[77][78]

Prostatic tuberculosis is often asymptomatic. Many cases remain undetected, diagnosed incidentally by biopsy to rule out malignancy, following transurethral resection, or at autopsy.[77][79] Common symptoms, when present, include urinary frequency and nocturia, dysuria without urgency, hematuria, perineal pain, and azoospermia may be present.[77] Up to about 50% of men with genitourinary tuberculosis may be affected.[63] Renal tuberculosis will be present in 85% of men with prostatic tuberculosis, and an elevated prostate-specific antigen will be found in about a third of men. Prostatic abscesses are rare but can occur among immunocompromised patients or neglected cases; abscesses can drain into surrounding tissues with fistula formation to the perineum, urethra, or scrotum.[7][77] Prostatic tuberculosis will only be found in 2.6% of all men with genitourinary tuberculosis, but at autopsy, between 10% and 12% of men with tuberculosis have demonstrated histological evidence of prostatic involvement.[80]

Renal tuberculosis in patients with renal tuberculosis is often asymptomatic, and the initial presentation might be an incidental abnormal urinalysis, often sterile pyuria. However, given acute and chronic bacterial infections concomitant with tuberculosis are common, suspicion of tuberculosis should arise in patients with appropriate risk factors when no response to antibiotic therapy is observed.[7] With advancing renal tuberculosis, nonspecific symptoms and signs such as flank pain and hematuria may be present. While both kidneys may be affected, unilateral clinical involvement is more common.[32][81]

Hypertension is not generally a feature of renal tuberculosis, and renal function is typically preserved other than in the case of tuberculosis-related interstitial nephritis, characterized by normal-sized kidneys, interstitial granulomas, and active extrarenal tuberculosis.[82] Renal tuberculosis has been associated with fistula formation, rapidly progressive and crescentic glomerulonephritis, and membranous nephropathy.[7][83][84][85] Chronic inflammation of the kidneys related to tuberculosis can also lead to carcinoma.[7][86]

Scrotal (including the testes, epididymis, and vas deferens): Epididymo-testicular tuberculosis can present as acute or chronic, with single or multiple nodules, skin ulcers, scrotal fistulas, and varying degrees of scrotal swellings, usually painless. Common findings include induration of the epididymis and beading of the vas deferens. About one-third of cases will have bilateral findings; half will demonstrate scrotal fistulas and a firm nodule or epididymal thickening will be found in up to 50% of cases. Advanced cases may show abscess formation and scrotal wall sinuses. Seminal vesicle and ejaculatory duct involvement with fibrosis may cause infertility in men.[87] Tuberculous orchitis with no epididymal involvement is rare and can mimic a testicular tumor. Urinary symptoms are typically absent in patients with isolated epididymal-testicular tuberculosis and are seen only when there is a concomitant renal and/or prostatic involvement.[77]

Ureteric involvement can lead to chronic inflammation, irregular ureteric strictures, ureteral obstruction with hydronephrosis, and vesicoureteral reflux.

Urethral involvement is relatively uncommon (seen in less than 5% of patients with genitourinary tuberculosis) but is found much more often in men and is associated with prostatic involvement; this is suggested by long urethral strictures, sometimes with multiple perineal fistulas called a "watering can" perineum.[3][88] This is best visualized with a retrograde or voiding urethrogram and is more commonly associated with gonorrhea.[88]

Evaluation

Urogenital tuberculosis is often missed clinically because of the lack of suspicion among clinicians, its insidious indolent onset, and unreliable clinical manifestations. Even when suspected, the gold standard for a tuberculosis diagnosis is to identify Mtb in a clinical sample. At this time, a range of microbiological, molecular, histopathological, and imaging tests are available to help make the diagnosis of urogenital tuberculosis. Multiple modalities are usually suggested. A delay in diagnosis is common and allows more advanced disease progression, contributes to worsening renal failure, increases the risk of infertility, and often results in some degree of irreversible organ damage and tissue injury. 

Identifying Mycobacterium tuberculosis 

Histology: Histological examination of biopsies and fine-needle aspirates is an important adjunct to culture and maximizes identification of Mtb. Histological examination of biological specimens sent from biopsies and fine-needle aspirates can identify granulomas and acid-fast Mtb bacilli via Ziehl–Neelsen or Kinyoun acid-fast stains.[7] 

Lipoarabinomannan assay: Lipoarabinomannan (LAM) is a glycolipid part of the cell wall of Mtb and can be detected in the urine of patients with active tuberculosis.[89] The lateral flow urine LAM assay is an immunochromatographic assay comprising nano-gold-labeled antibodies attached to LAM, which are captured by immobilized LAM antibodies further along the test strip, forming a visual band.[7] Patients with significant immunosuppression are at the highest risk of disseminated Mtb infection and resultant renal involvement, thereby releasing Mtb LAM glycolipid into the urine.[90] The utility of this assay for diagnosing urogenital tuberculosis has not yet been fully evaluated.[7]       

Microscopic urinalysis: Microscopic analysis of the urinary sediment from a 24-hour specimen for acid-fast bacilli testing yields positive results in up to 90% of cases of renal tuberculosis but is not considered diagnostic for genitourinary tuberculosis as it will also appear positive for non-tuberculous mycobacteria.[3][39][67][91] However, if adequate numbers of bacteria are present (at least 5000/mL), it has a reported specificity of 97% with a sensitivity of 42% to 52%.[92]

Molecular testing: Given the limitations and delays inherent to culturing mycobacteria, polymerase chain reaction (PCR) testing for Mtb identification was developed and has been widely adopted.[93][94][95][96] The World Health Organization approved PCR testing for use in sputum samples for initial diagnosis of pulmonary tuberculosis and suspected cases of multidrug-resistant Mtb in sputum samples in 2010, followed by nonrespiratory samples in the diagnosis of extrapulmonary tuberculosis in 2013.[97] 

PCR testing has several benefits. This testing can detect Mtb even when there are very few bacilli, provides results in less than 2 hours, has minimal carry-over contamination, is relatively affordable, and can detect the presence of gene mutations indicative of rifampin resistance.[94] PCR testing also has an improved sensitivity compared to microscopy, estimated (depending on endemicity and sample tested) between 80% to 95%.[98] 

Compared with cultures, PCR testing was 95.6% sensitive and 98.1% specific;[99] compared with bacteriologic, histologic, or clinicoradiologic methods, PCR testing was 94.3% sensitive and 85.7% specific.[7][14] However, results from a study of men and women with urogenital tuberculosis found PCR testing of urine samples to have a sensitivity of 63%, while results from another study of premenstrual endometrial biopsies in infertile women showed a sensitivity of just 46.6%.[100][101] PCR testing is an excellent diagnostic aid when positive, but a negative reading does not necessarily rule out urogenital tuberculosis.[102] 

Mycobacterium tuberculosis culture: The culture of clinical specimens for Mycobacterium tuberculosis is the gold-standard method for the diagnosis of active tuberculosis, with an overall sensitivity of 65% and specificity of 100%.[103] Solid Lowenstein–Jensen culture medium typically takes 6 weeks to rule out Mtb growth but has largely been phased out by automated liquid media mycobacteria growth indicator tube culture systems. The advantages of a liquid culture include its sensitivity, identification of specific Mycobacterium species, the ability to perform phenotypic drug susceptibility tests, and genotyping for further molecular epidemiology studies. The disadvantage of cultures is the time needed for the growth of mycobacteria. Nevertheless, the culture of at least 3 (or up to 5) separate consecutive morning urine specimens for mycobacteria establishes the diagnosis of urinary tuberculosis in 80% to 93% of cases.[5][104] Liquid cultures require at least 9 to 10 days for positive results, and at least 6 weeks before they can be conclusively considered negative.[21] A well-equipped laboratory is also required. The false-negative rate is reported as 10% to 20%.[105] 

Nucleic acid amplification testing: Several nucleic acid amplification tests are now available for Mycobacterium tuberculosis, and the World Health Organization has conditionally recommended their use for the initial diagnosis of tuberculosis, but the evidence supporting this for genitourinary tuberculosis is weak and of low quality.[21] A negative nucleic acid amplification test cannot rule out genitourinary tuberculosis and it cannot be used for disease tracking.[106] For now, patients with evidence of genitourinary tuberculosis are better served by using a PCR test along with additional Mtb identification modalities such as cultures.[21]

Smear microscopy: Smear microscopy refers to the microscopic examination of sputum, urine, discharge, prostatic massage fluid, and biopsy tissue for acid-fast bacilli performed using Ziehl–Neelsen or auramine staining. Like cultures and molecular testing, this may be performed on clinical samples, including, in the case of urogenital tuberculosis, urine, semen, prostatic massage fluid, tissue from bladder/prostate/endometrial biopsy, pus from prostatic/epididymal/tubo-ovarian abscess, discharge from a draining scrotal or perineal fistula or penile ulcer.[77] Smear microscopy diagnostic yields using urine are less than 40% and mycobacterial culture/molecular testing must also be performed.[7]

Smear microscopy's advantages include that it is a simple, quick, inexpensive, and highly specific test that is readily available globally, even in areas with low socio-economic levels.[107] This test's reliability depends on a bacterial load of more than 10,000 organisms/mL and is subject to observer error. Unfortunately, smear microscopy requires serial examinations and has a poor record of detecting extrapulmonary tuberculosis.[107][108]

Transrectal prostatic biopsy: As prostatic tuberculosis can be difficult to diagnose, a transrectal prostate biopsy may be a useful diagnostic tool, particularly to exclude an underlying adenocarcinoma. Such biopsies must be performed cautiously, given the possibility of widespread dissemination of the bacteria in untreated patients with active genital tuberculosis.[77]

Whole-genome sequencing and targeted next-generation sequencing: Whole-genome sequencing (WGS) and targeted next-generation sequencing (NGS) show promise for further improvements in rapid molecular diagnosis, including identifying drug resistance and characterizing transmission patterns. WGS (as opposed to NGS) is currently limited to strains grown in culture as it requires a high quantity of good-quality deoxyribonucleic acid, limiting its diagnostic rapidity. Both modalities are currently limited for various reasons, including their relatively high cost and the need for specialized, well-trained laboratory technologists.[7]                                                                                                   

Adjunctive Testing

Imaging techniques are up to 91.4% sensitive for a radiological diagnosis of urogenital tuberculosis.[3][14] 

Chest radiographs can identify concurrent or past pulmonary tuberculosis infections and should be performed in all patients with suspected tuberculosis. One study of 37 men and women with urogenital tuberculosis had results showing that 13.5% of the participants had concurrent pulmonary tuberculosis.[26][109] Results from other reports found abnormal chest x-ray findings consistent with pulmonary tuberculosis in 8% to 27% of women with genital tuberculosis.[26] In general, 50% of patients with genitourinary tuberculosis or more will have negative chest x-rays. 

Computed tomography/urography imaging is widely used for imaging of suspected abdominal, flank, and genitourinary disorders as it provides more detail than intravenous pyelograms, especially in late cases of suspected urogenital tuberculosis.[3] Cortical masses and granulomas can be detected, and calcifications throughout the urinary tract, and urinary strictures can be seen—which are present in more than 50% of patients with renal or genitourinary tuberculosis.[3][7][110] Further, adrenal involvement would be demonstrated by bilateral enlargement together with peripheral enhancement.[3] Addison disease will often accompany bilateral adrenal involvement. 

Bladder involvement is suggested by wall thickening with calcifications in a small, contracted, fibrous bladder (sometimes called a "thimble" bladder if the capacity is 20 mL or less).[3] Mucosal ulcers (visible on cystoscopy) and trabeculations are commonly present. The simultaneous finding of characteristic kidney and bladder lesions is suggestive of genitourinary tuberculosis.[14]  

End-stage kidney disease would be suggested by a small, nonfunctional kidney with peripheral renal lobar calcifications secondary to papillary necrosis, a "cement" or "putty" kidney," sometimes also referred to as an autonephrectomy.[3][35][36][37][38][111]  A "putty" kidney may rarely occur without any history or evidence of pulmonary tuberculosis, making the diagnosis even more challenging.[112][113] Renal tuberculosis is suggested by the finding of 3 characteristic imaging features even without pulmonary involvement; such features include the following:

  • Lesions characteristic of both renal and bladder involvement simultaneously 
  • Infundibular intrarenal strictures
  • Low-attenuation lesions in the renal cortex
  • Papillary necrosis
    • These may appear as triangular or circular calcifications along the periphery of the renal collecting system.
  • Renal calcifications contiguous with the collecting system
    • Schistosomiasis tends to create more focal calcifications, primarily in the bladder.
  • Renal parenchymal scarring and fibrosis
  • Variable caliectasis with thickening of the urothelium (where the renal pelvis is not dilated)[3][14]

Ureteral tuberculosis imaging signs would include “pipe stem” changes (short, rigid ureter), “corkscrewing or beaded corkscrew” (segmental ureteral dilatations), “beading” (alternating areas of ureteral strictures and dilatations, a "sawtooth" appearance, and intraluminal calcifications.[3][114] These radiographic features of ureteric involvement may be best imaged with retrograde pyelography performed during cystoscopy.[3] The lower third of the ureter is involved most often, but the entire ureter may become involved.[3] Ureteral calcifications from tuberculosis tend to be inside the lumen, appearing almost as a ureteral cast, while schistosomiasis causes intramural calcifications.[3]

F18-fluorodeoxyglucose positron emission tomography imaging can help identify sites of active urogenital tuberculosis and track its progress, but distinguishing tuberculosis from cancer and other disorders is not possible, limiting its utility.[115][116][117][118]

Hysterosalpingography is used to evaluate the uterine endometrium, tubal lumen, and cervix.[119] Contrast is injected directly into the uterine cavity, and x-rays are used to examine the uterus and fallopian tubes.[119] As it is the gold standard for determining tubal infertility, hysterosalpingography has been recognized as the most accurate method for detecting isolated genital tuberculosis in women.[3][51][119] Findings include intrauterine adhesions and a distorted or obliterated uterine cavity, beaded or rigid fallopian tubes, calcified adnexal lymph nodes or nodules, and a stenosed cervical canal.[3][26] For more information, see the companion StatPearls' reference review on "Hysterosalpingogram."[119] 

Intravenous pyelograms/urography: While previously used more widely and usually abnormal in renal tuberculosis, computed tomography urography, magnetic resonance imaging, and ultrasonography have largely replaced intravenous urography.[3][21][120][121][122] Nevertheless, intravenous urography is still the "gold standard" radiographic modality, particularly for early genitourinary tuberculosis, although the radiographic features of ureteric involvement may be best visualized with retrograde pyelography performed during cystoscopy.[3][21][123][124] Voiding cystourethrography and retrograde urethrograms can be used to better visualize urethral strictures and lower urinary/perineal fistulas.                                        

Magnetic resonance imaging is particularly useful when prostate malignancy is suspected.[125][126][127] Renal lesions tend to be hypointense on T1 and T2-weighted imaging. Prostatic tuberculosis is suggested by streaky diffuse and radiating areas of low signal intensity on T2-weighed imaging, known as the "watermelon skin" sign.[3][83][128][129][130][131][132] Fibrosis is suggested by a decreased apparent diffusion coefficient.[3]

Magnetic resonance imaging is also useful for defining the extent of tuberculosis, particularly in the prostate, and evaluating the seminal vesicles and ejaculatory ducts.[3][7][26][87][133] This imaging is also useful for detecting sinuses, fistulas, peritonitis, and adnexal abdominal masses.[3][7][26][87] Testicular tuberculosis would show hypointense T2-weighted lesions with variable calcifications on a magnetic resonance imaging examination, but ultrasonography is generally preferred for initial imaging of the epididymis, scrotum testes, or vas deferens.[3][21]

Ultrasound: A urinary tract ultrasound is recommended in all patients presenting with urogenital inflammation.[3][77][134] Ultrasound is best suited for epididymal, testicular, and vas deferens involvement but may also help with renal, ureteral, and bladder disease.[3][21][121][134] Ultrasound is also useful in tracking the progress of hydronephrosis from genitourinary tuberculosis and its response to medical treatment.[134] Ultrasound may also be preferred in children and pregnant patients. Characteristic findings in genitourinary tuberculosis on ultrasound may include the following: 

  • Adnexal tubo-ovarian masses, peritoneal thickening, and endometrial involvement are common findings on ultrasonography in women with genital tuberculosis.
  • Bladder ultrasonography might show a low-capacity bladder with a thickened wall and may be associated with vesicoureteric reflux.
  • Early urogenital tuberculosis may only demonstrate normal ultrasonographic findings.
  • Fluid in the pelvic cavity (free or loculated) is a characteristic finding.
  • Pelvic scarring and adhesions are characteristic of genitourinary tuberculosis.
  • Renal findings may include granulomas (small hypoechoic masses), calyceal stenosis, hypoechoic cystic lesions, calcifications, and hydroureteronephrosis.
  • Scrotal ultrasonography can show scrotal wall thickening, an enlarged heterogeneous and hypoechoic epididymis, or it may show a nodular epididymal tail. 
  • Testicular involvement presents as a miliary pattern of lesions, 1 or more nodules, or general diffuse enlargement; testicular disease is secondary to epididymal tuberculosis.
  • Transrectal ultrasound of the prostate may show hypoechoic areas and irregular peripheral patterns or dilated seminal vesicles suggestive of ejaculatory duct obstruction.
    • The prostate may appear to show prostatic cancer or prostatitis.
    • The seminal vesicles may have thickened walls and/or calcifications.[3][7][21][77][79][87][134][135]

Cystoscopy and ureteroscopy: Diagnostic cystoscopy will typically show only non-specific findings of localized erythema, urothelial erosions, ulcers, small granulomas, and distortion of the ureteral orifices. When the ureteral orifice is affected by fibrosis from tuberculosis, it becomes short and straight, giving it a "golf hole" or gaping appearance that may result in vesicoureteral reflux. A golf hole-shaped ureteral orifice is suggestive of tuberculosis, and an examination of the upper urinary tracts by imaging or ureteroscopy is recommended. 

Biopsies of the affected area for pathological examination are often necessary to confirm a diagnosis of urogenital tuberculosis. However, while histopathologic sampling should be done whenever possible, a tuberculosis culture is more sensitive and should always accompany it.[26] Histopathological examination of specimens from biopsies and fine-needle aspiration cytology can identify epithelioid granuloma tissue or caseous necrosis and are often considered diagnostic for tuberculosis, but only the presence of Mtb on culture or tissue-based molecular testing can provide definitive proof.[77] 

Cystoscopy with a bladder biopsy is a low-morbidity procedure that may be performed when there is clinical suspicion of genitourinary tuberculosis and bacillus-negative urine, being most useful in the acute phase.[136] The most frequent findings are local hyperemia, mucosal erosion and ulceration, tubercle formation, and irregularity of the ureteral meatus.[136] Retrograde pyelograms may be performed at the same time but are rarely necessary.[137] A bladder biopsy performed during a cystoscopy is 18.5% to 52% sensitive for tuberculosis.[14]

Laboratory Testing

Routine urinalysis/bacterial urine culture: Urinalyses are abnormal in over 90% of patients with urogenital tuberculosis.[67] The majority have pyuria with or without hematuria, but heavy proteinuria and cellular casts are not generally observed.[138] Persistent sterile pyuria, pyuria in acidic urine without bacterial culture growth, and a symptomatic urinary tract infection unresponsive to conventional antibiotic therapy (especially in those with risk factors for tuberculosis exposure) should prompt suspicion of urogenital tuberculosis.[7][138] Chronic epididymitis or chronic prostatitis that does not resolve with standard antibiotics should also raise the suspicion of genital tuberculosis.[7] 

Routine laboratory tests: The most common laboratory abnormalities among patients with urogenital tuberculosis are nonspecific. In one study, the results showed the most common laboratory abnormalities were anemia (83.04%), hypoalbuminemia (58.10%), electrolyte abnormalities including hyponatremia (50.93%), leukocytosis (41.96%), azotemia (36.94%), and thrombocytosis (26.79%).[138] A raised C-reactive protein can be a useful biomarker of disease activity but is non-specific.[7] The US Centers for Disease Control and Prevention also recommends HIV testing in all patients with a positive screening for Mtb. Appropriate hepatitis testing is also suggested.

The interferon-gamma release blood assay: This assay mixes the test blood sample with simulated tuberculosis bacterial antigen peptides and controls.[106][139][140] The antigens used will test positive for Mycobacterium tuberculosis and Mycobacterium bovis but negative for other Mycobacteria, such as Bacillus Calmette-Guérin (BCG), and the test results are typically available within a few days.[106][139][140] Specific immunity to tuberculosis typically develops within 6 to 8 weeks of infection.

In one study, results showed the interferon-gamma release blood assay (IGRA) in the peripheral blood of both individuals with urogenital tuberculosis was found to have a sensitivity of 52.6%.[77][102] Another study had results that found the sensitivity and specificity of IGRA in peripheral blood from women with confirmed genital tuberculosis were 86% to 94% and 70% to 75%, respectively, compared to a composite reference standard.[26] 

In short, IGRA testing can be helpful as an initial screening in the evaluation of patients with possible tuberculosis infections, especially in BCG-vaccinated individuals, but negative results do not reliably rule out active tuberculosis, while positive results do not necessarily indicate active disease.[140][141][142][143] See the companion StatPearls' article on the "Interferon Test" for more information and details.[140]

Tuberculin skin testing: This common skin test uses a standardized solution made with a purified protein derivative (PPD) where a measured amount is injected under the skin.[144] In patients with an Mtb infection, this will produce a T-cell-mediated delayed-type hypersensitivity skin reaction.[144] The test requires 2 patient visits and will be positive in patients with previous BCG infection or treatment.[143][144] See the companion StatPearls' article on the "PPD Skin Test" for more information and details.[144]

Neither tuberculin skin testing nor IGRA are recommended for diagnosing active tuberculosis, but they are indicated for the initial screening and diagnosis of all other tuberculosis infections.[140][144] Patients with positive results on either modality should undergo a chest x-ray examination and additional testing for possible genitourinary tuberculosis as appropriate.[144] See the companion StatPearls' article on "Tuberculosis Screening" for more information and details.[145]

Selecting Specific Diagnostic Testing for Genitourinary Tuberculosis

The selection of diagnostic methods depends on their availability, cost, the degree of clinical suspicion, renal function, and the patient's clinical presentation. Contact your local hospital laboratory or reference lab to determine which tests are available. At least 1 or more Mycobacterium tuberculosis identification tests are typically used, with a positive culture being considered the gold standard. Adjunctive testing is used as needed.

  • Angiography can be helpful in evaluating focal lesions that simulate a renal mass or if a partial nephrectomy is planned; this will demonstrate that interlobar arterial obstructions are avascular areas.[146]
  • Biopsies are suggested in highly suspicious cases (such as characteristic clinical and radiological signs, or unexplained genital ulcers) where cultures and polymerase chain reaction testing are negative or the diagnosis otherwise remains in doubt.[147]
  • Intravenous urography is still useful in genitourinary tuberculosis, especially in early cases. 
  • Microscopic examination of urine samples with acid-fast stains can be useful with experienced laboratory technicians but may positively stain non-tuberculous mycobacteria.[92]
  • Mycobacterium tuberculosis culture is considered definitive, but a final test result can take from 6 to 8 weeks; this is best used together with other, quicker testing modalities, such as polymerase chain reaction.[21] At least 3 consecutive morning samples are recommended.
  • Nucleic acid amplification testing is useful for pulmonary tuberculosis, but its specific role in genitourinary tuberculosis remains unclear.[21][106]
  • Polymerase chain reaction testing is fast and sensitive for genitourinary tuberculosis but may have false positives; this is best used together with a confirmatory culture or similar test.[21]
  • Renal nuclear scans are useful in determining kidney function and monitoring the effects of therapy but are very nonspecific.
  • Retrograde pyelograms may optimally visualize ureteral abnormalities and strictures but are rarely needed except in cases of minimal urine output or renal failure.
  • Tuberculin skin testing and IGRA are simple and readily available but can only identify latent tuberculosis and are best used for initial screening.[21][145]
  • Smear microscopy is simple and available but has a low sensitivity of <40% and an Mtb culture must also be performed.[7][21] 
  • Ultrasonography is useful as an initial imaging test, particularly for genital infections. However, inflammatory findings may often be non-specific.
  • Vasography can be used to visualize obstructions in the vas deferens.[148][149]

Treatment / Management

Medical Treatment: Antituberculous Therapy

Medical treatment for urogenital tuberculosis is the same as recommended for pulmonary tuberculosis. Initial therapy consists of a combination of ethambutol, isoniazid, pyrazinamide, and rifampin for 6 to 9 months.[5][21][150][151] After the first 2 months, ethambutol and/or pyrazinamide may be discontinued in selected patients depending on studies showing sensitivity to isoniazid and rifampin.[5][150] Patients who are also infected with HIV should receive 8 months (European Guidelines) or 9 months (US CDC Guidelines) of anti-tuberculosis therapy.[21] Extending the treatment to 24 months may be considered for selected cases demonstrating multidrug resistance.[46] (A1)

Alternate anti-tuberculosis drug regimens using rifapentine and moxifloxacin have been suggested but have not been adequately studied in extrapulmonary tuberculosis.[152] Second-line medications used for drug-resistant cases include amikacin, bedaquiline, carbapenems with clavulanic acid, clofazimine, cycloserine, ethionamide,  kanamycin, levofloxacin, linezolid, moxifloxacin, para-aminosalicylate, pretomanid, and pyrazinamide.[21][153] The CDC recommends an initial treatment consisting of a 5-drug combination for about 6  months in such cases, followed by a continuation phase of at least 4 drugs for an additional 9 to 12 months. Drug selection should be based on patient preferences, side effects, clinical conditions, comorbidities, medication tolerability, and bacterial antibiotic sensitivity studies.

Streptomycin is no longer generally used in the treatment of tuberculosis due to its high rate of adverse events and growing global resistance, but it may be considered in selected drug-resistant cases.[154] See the companion StatPearls' reference reviews, "Tuberculosis," "Antitubercular Medications," and "Streptomycin" for more information and details on the medical therapy of genitourinary tuberculosis.[5][95][99][154]

The benefit of steroids for genitourinary tuberculosis is still unclear, although there is some evidence they may help if there is evidence of progressive fibrosis, strictures (ureteral, fallopian tubes, or vas deferens), or severe bladder symptoms.[155] For patients taking rifampin, high-dose prednisone (at least 20 mg, 3 times daily) for 4 to 6 weeks is recommended. This is because rifampin reduces the bioavailability and activity of prednisone by two-thirds while increasing its renal excretion by 45%.[156][157][158][159] Rapid progression of genitourinary tuberculosis with extensive scarring and tissue damage has been reported immediately after the initiation of medical antituberculous therapy, and clinicians should be aware of this and monitor patients appropriately.[160] 

Surgical Treatment

Immediate surgical therapy is necessary and required in cases of obstructive uropathy with hydronephrosis, sepsis, or renal failure, which would typically require double J stenting (preferred) or percutaneous nephrostomies.[161] In some cases, these temporary measures may become permanent. Surgery is not considered a curative treatment for genitourinary tuberculosis but is an important and necessary adjunct to medical therapy in obtaining biopsies and correcting or minimizing the complications of the disease, such as abscess formation, strictures, fistulas, ureteral obstruction, and infertility.[21][162] Surgery may also be used selectively in cases of medical treatment failures. Biopsies and/or fine needle aspiration may be performed to obtain tissue for examination in cases of initial treatment failures, but such procedures should generally not be performed if there is suspicion of an underlying malignancy. Given the delays inherent in making the diagnosis, disease-related complications are often present. Surgical treatment as an adjunct to anti-tuberculosis drugs is required in about 55% of patients during or even after medical therapy.[6][7][14](B3)

Specific indications for surgery include the following:

  • Abscess formation
  • Hydronephrosis
  • Hypertension associated with renal tuberculosis
  • Infertility due to stricture formation of the fallopian tubes or vas deferens
  • Intractable urinary symptoms such as "thimble" bladder
  • Need for a tissue sample (biopsy) for diagnostic purposes
  • Kidney failure with obstructive uropathy, especially if progressive and unresponsive to pharmacotherapy
  • Nonfunctioning kidneys with symptoms not relieved by medical therapy
  • Persistent symptoms unresponsive to medical treatment, such as pain or bleeding
  • Recurrent endometrial tuberculosis or uterine bleeding resistant to medical therapy
  • Strictures of the urethra resulting in voiding dysfunction
  • Suspicion of an underlying malignancy

Endoscopic surgeries and balloon dilation procedures to relieve tuberculous ureteral strictures are less successful than other indications, with a high relapse rate and a need for repeated treatments. Steroid use has been suggested in these cases to improve outcomes. Bladder neck and urethral strictures are best managed endoscopically, but relapses and repeated surgeries are common.

Medical therapy for genitourinary tuberculosis is generally recommended before considering surgery. Even in cases of a non-functioning autonephrectomy or "putty" kidney, antituberculous drug therapy is recommended as the initial treatment, with surgery indicated when there is no response to medications, persistent symptoms such as pain, abscess formation, hypertension, recurrent urinary tract infections, suspicion of a malignancy in the affected renal unit, or other complications.[112][113] Hypertension is relieved in 65% of such cases after a nephrectomy.[163](B3)

In cases of a badly infected, unilateral, nonfunctioning kidney, a nephrectomy without ureterectomy may also be recommended to decrease the risk of relapse, eliminate bladder and lower urinary tract seeding, treat hypertension, and avoid abscess formation as antituberculous medical therapy may not sterilize all renal foci of infection, resulting in delayed complications.[14][21]  When performing a nephrectomy in a tuberculous kidney, abnormal or affected perinephric fat should be removed together with the kidney; the ureters are typically not resected, and it is recommended that the renal hilar vessels be ligated individually. The overall incidence of nephrectomy in genitourinary tuberculosis has been reported as 27%.[14](B3)

The optimal timing of surgery remains controversial. The benefits of a delay to allow for the resolution of all active disease and inflammation need to be balanced with the potential for additional tissue harm and organ damage if surgical procedures are overly delayed.[21] Surgery should generally be delayed for at least 4 to 6 weeks after the start of antituberculous medical therapy.

Surgical procedures include draining an obstructed pelvicalyceal system (internal or external diversion), incision and drainage of abscesses, reconstruction or ileal replacement of the ureters, renal auto-transplantation, dismembered pyeloplasties, ureterocalicostomy, ureteral reimplantation with a psoas hitch or Boari flap, the release of pelvic adhesions, relief of hydrosalpinx and pyosalpinx, bladder procedures such as bladder augmentation, urinary diversion, and the occasional orchiectomy or nephrectomy.[21][162] Lower ureteral strictures are best managed with complete resection and a ureteroneocystostomy. Every case must be considered and evaluated individually based on each patient's clinical situation, preferences, comorbidities, surgical tolerance, and circumstances.

Reconstructive surgery and nephrectomies in patients with genitourinary tuberculosis frequently pose significant technical challenges, as sutures will often pull out from weakened tissue and extensive adhesions with scarring of the affected organ and surrounding structures obliterate tissue planes.[21] This makes dissection by laparoscopic/robotic surgery and even open procedures extremely difficult and dangerous to perform in some patients.[7][21] When facing particularly complex or challenging cases, consideration should be given to referring the patient to a high-volume tertiary care center. 

Fertility Considerations

Women: Early antituberculous therapy in genital tuberculosis in women improves menstrual cycle regularity and endometrial thickness while reducing the incidence of adhesions.[164] However, this condition can cause irreversible damage to genital organs, and the prognosis for fertility, even after treatment, is low if there is any significant damage to the fallopian tubes or endometrium.[165] 

The overall posttreatment conception rates vary from 12% to 23%, and results from a study reported a live birth rate of only 7%.[26][27] Another study reported a 19.2% conception rate, 16.6% pregnancy rate, and 7.2% live birth rate.[27][22] The high rate of pregnancy loss was related to residual structural uterine damage.[68] The overall effect of anti-tuberculosis treatment on fertility in women remains uncertain, according to a 2023 systematic review.[166](A1)

An examination of 149 fertile women with genital tuberculosis and no evidence of endometrial or tubal involvement demonstrated that early treatment with anti-tuberculosis medications together with assisted reproductive techniques could produce an overall pregnancy rate of 60%.[167] Still, according to a 2023 systematic review, the overall effect of anti-tuberculosis treatment on fertility in women remains uncertain.[166] For women who are unable to conceive spontaneously following treatment, salpingectomy or tubal clipping may be considered to improve pregnancy outcomes.[47] In-vitro fertilization is recommended in cases where the fallopian tubes are damaged, but only if the endometrium remains intact or is minimally scarred, though the prognosis and overall pregnancy rate remain relatively poor.[164][168] In cases where the endometrium is destroyed but the ovaries remain undamaged, gestational surrogacy has been suggested and used.[26] (A1)

Men: Patients with genitourinary tuberculosis and infertility will often have multifocal obstruction involving the epididymides, ejaculatory duct, or vas deferens that cannot be surgically reconstructed, leaving assisted reproduction with testicular sperm extraction techniques as their only realistic chance of conception.[169][170][171] In men, up to about 10% of infertile men with idiopathic obstructive azoospermia are estimated to have genital tuberculosis and bilateral vasal or epididymal blockages from Mtb.[14][54][55][171] (B2)

Such cases are generally not amenable to a surgical correction but assisted reproductive techniques using microsurgical testicular sperm extraction and in-vitro fertilization with intracytoplasmic sperm injections are possible with relatively good outcomes.[169][170] A few cases may be amenable to surgical intervention, such as ejaculatory duct obstruction with evidence of dilated seminal vesicles.[172] Rare cases may have normal sperm counts.[173] See the companion StatPearls' reference reviews on "Male Infertility," "Azoospermia," and "Assisted Reproductive Technology (ART) Techniques" for more information and details."[54][55][170]

Differential Diagnosis

Due to its nonspecific symptoms, it is essential to consider a range of differential diagnoses when diagnosing genitourinary tuberculosis. Conditions that may present similarly to urogenital tuberculosis include the following:

  • Azoospermia
  • Bladder disorders
  • Crohn disease
  • Epididymitis/urethritis
  • Fallopian tubal obstruction
  • Gonorrheal infections
  • Idiopathic infertility 
  • Infertility from other causes
  • Malignancies such as urothelial and renal cell  tumors (testicular, prostate, and penile cancers in men, ovarian and endometrial malignancies in women)
  • Papillary necrosis
  • Prostate cancer
  • Prostatitis
  • Renal scarring and calcifications
  • Schistosomiasis
  • Sexually transmitted diseases
  • Spermatoceles (epididymal cysts)
  • Staghorn renal calculi
  • Urethral strictures from other etiologies, such as trauma or non-tuberculosis infections
  • Urinary tract infections (especially if partially or recently treated)
  • Xanthogranulomatous pyelonephritis

Prognosis

The prognosis of genitourinary tuberculosis is excellent when prompt diagnosis and active antibiotic therapy are initiated. Depending on the extent of the disease, bacterial antibiotic resistance, and the degree of tissue/organ damage at the time of disease-specific antibiotic initiation, about 55% (8% to 95%) of patients with genitourinary tuberculosis will require adjunctive surgery.[6][7][14] Drug-resistant strains of Mycobacterium tuberculosis account for 3.3% of newly diagnosed cases (and 20% of relapses) and require 5 or even 6 drugs for extended durations of 18 months or longer. According to the CDC, cure rates are typically only 50% to 60% for multi-drug-resistant cases compared to about 95% for drug-susceptible diseases. For some extremely drug-resistant strains, the cure rate drops to just 30% to 50%.

Approximately 6% of patients with genitourinary tuberculosis will relapse within 5 years after completing a complete course of therapy, and the lifetime risk of relapse has been reported as high as 22%, which is higher than for pulmonary Mtb disease.[6][14][178] Therefore, long-term monitoring and follow-up of these patients for 10 years is recommended.[14][178][179] Relapse rates after nephrectomy are markedly reduced to less than 1%.[8] Specific data on the rate of infertility due to genital tuberculosis in women depend on the use of anti-tuberculosis medications and the degree of damage to the fallopian tubes and endometrium.[47] The CDC recommends that patients with tuberculosis requiring treatment who have end-stage renal disease necessitating hemodialysis should have their dosages of antitubercular medications adjusted (usually higher) and administered immediately after dialysis therapy. Close consultation with nephrology is recommended.

Complications

Genitourinary tuberculosis can lead to significant morbidity if not promptly diagnosed and treated. Potential complications that may arise include the following:

  • End-stage renal failure
  • Epididymitis
  • Hydroureteronephrosis
  • Infertility (men and women)
    • Scarring of the vas and/or epididymides
    • Tubal obstruction
    • Tubo-ovarian abscess
    • Uterine adhesions
  • Penile ulcers
  • Prostatic abscess
  • Renal injury, scarring, granulomas, and abscesses
  • Scrotal abscesses and fistulae
  • Small, contracted bladder
  • Ureteral strictures, "beading," obstruction, or stone-pipe changes
  • Vesicoureteral reflux

Consultations

The advice of a clinician with expertise in treating tuberculosis is suggested to avoid acquired multidrug resistance and optimize medical treatment.

Deterrence and Patient Education

Deterrence and patient education are critical in managing and preventing genitourinary tuberculosis. Genitourinary tuberculosis often has an insidious and nonspecific onset that is overlooked by patients and clinicians alike. Physicians should remain highly suspicious of possible tuberculosis whenever encountering unexplained symptoms with otherwise negative test results. Patients should be informed about the importance of early and prolonged treatment to prevent relapses and complications such as strictures, organ damage, and infertility. Educating patients on recognizing symptoms (such as persistent urinary tract infections, sterile pyuria, or unexplained genital ulcers) can prompt timely and appropriate medical interventions. Additionally, awareness of the risk factors, including a history of tuberculosis or immunocompromised states, is essential.

Antituberculous regimens require the administration of multiple antibiotics over extended periods. They may be associated with unpleasant adverse effects, making long-term patient compliance a challenge. Encouraging patients to complete their full course of antituberculous therapy and attend regular follow-ups can significantly reduce the risk of recurrence and transmission, ultimately improving outcomes. 

Pearls and Other Issues

Pearls and other important information regarding genitourinary tuberculosis include the following:

  • A characteristic sign of genital tuberculosis in men is nodular beading of the vas deferens. 
  • A negative smear for acid-fast bacilli, a lack of granulomas on histopathology, negative chest imaging studies, and a failure to culture Mycobacterium tuberculosis do not definitively exclude the diagnosis.[9]
  • Any patient with unexplained, persistent sterile pyuria should be screened for possible genitourinary tuberculosis, especially in global regions where the disease is endemic.
  • Consider tuberculosis whenever a genitourinary disorder or lesion fails to respond to standard treatment. For example, a case of chronic prostatitis that does not respond to standard antibiotic therapy could indicate prostatic tuberculosis. Fluoroquinolones used to treat prostatitis may be effective for both diseases, but the duration of treatment for prostatitis is markedly insufficient for tuberculosis.
  • If there is a strong clinical suspicion of genitourinary tuberculosis, medical therapy may be started without waiting for confirmatory cultures.
  • Intravenous pyelography is the preferred imaging modality for genitourinary tuberculosis, especially in the earlier stages. CT urography may be preferred for late-stage disease.
  • Isolated genitourinary tuberculosis may occur, although the majority will have a history or other evidence of pulmonary disease.
  • Patients with a high risk of tuberculosis with positive PCR tests and negative cultures should generally be treated with 6 months of standard anti-tuberculosis therapy.
  • Persistent, painful, swollen inguinal lymph nodes with no obvious cause or infectious source should be considered suspicious for genitourinary tuberculosis.
  • Semen cultures can be used to monitor the efficacy of medical therapy in patients with prostatic tuberculosis. If there are still positive results after 3 months, consider bacterial resistance to antibiotics or patient non-compliance with treatment.
  • The prevalence of genital tuberculosis in infertile women is quite low in the US, Canada, and Europe, but it is still a significantly underdiagnosed cause of infertility.[49][180] Suggestions have been made that all women with unexplained infertility be screened for latent tuberculosis.[45][69][181] Before starting other infertility treatments, women who initially test positive for tuberculosis should undergo an endometrial biopsy for histological evaluation, PCR testing, and Mtb cultures.[49][180]
  • Tuberculin skin testing will be positive in patients with a history of BCG infections or therapy.[143][144] Use of the IGRA is recommended instead.[143]
  • Tuberculosis is a reportable disease in the United States.

Enhancing Healthcare Team Outcomes

The diagnosis and management of genitourinary tuberculosis requires a coordinated effort by healthcare teams consisting of primary care clinicians, public health officials, infectious disease specialists, nephrologists, urologists, general surgeons, gynecologists, pharmacists, nurses, and advanced care practitioners.[5] The indolent nature of the disease, the lack of specific symptoms or signs, and the low incidence of genitourinary tuberculosis in North America and Europe mean that many Western physicians will not include Mtb in their differential diagnosis and will be unfamiliar with its diagnosis and treatment. Efforts to identify at-risk patients, knowledge of diagnostic modalities, treatment options, pharmacologic interventions, as well as their potential adverse reactions, and appropriate surgical strategies are all required to optimally manage this common form of extrapulmonary tuberculosis. 

Responsibilities within the interprofessional team should be clearly defined, with each member contributing their specialized knowledge and skills to optimize patient care. Effective interprofessional communication fosters a collaborative environment where information is shared, questions are encouraged, concerns are addressed promptly, and problems are treated expeditiously. Care coordination plays a pivotal role in ensuring that the patient's journey from diagnosis to treatment and follow-up is well-managed, minimizing errors and enhancing patient safety. By embracing these principles of skill, strategy, ethics, responsibility, interprofessional communication, and care coordination, healthcare professionals can deliver patient-centered care, ultimately improving outcomes and enhancing team performance in the diagnosis and management of patients with genitourinary tuberculosis.

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