Tuberculosis (TB) is a disease dating back to antiquity and has continued to thrive to the present time. Signs of TB have been found in Egyptian mummies dating back to 3000 to 2400 BCE,¹ and scholars have postulated that TB may have led to the deaths of Egyptian pharaoh Akhenaton (1353-1336 BCE) and his wife Nefertiti. TB, then known as “the consumption,” reached epidemic proportion in Europe in the 1700s, and was responsible for one in four deaths in England. The causative bacillus, Mycobacterium tuberculosis, and the mode of transmission were described by Robert Koch on March 24, 1882, which is now designated annually as World Tuberculosis Day.²

In 2013, the World Health Organization estimated an annual rate of 9 million new TB cases, and it is second only to human immunodeficiency virus (HIV) and AIDS as a single infectious agent killer. TB is also a major cause of death in HIV-related mortalities. Globally, the incidence is declining, albeit slowly.³

In the United States, the incidence of TB showed a resurgent increase, peaking in 1992 after decades of steady decline due to the emergence of HIV/ AIDS; subsequently, the incidence of TB has continuously declined at the rate of 3% to 4% per year, with 9588 new cases reported in 2013. The majority of cases represent reactivation of latent TB acquired previously in foreign-born individuals, and reflects TB incidence in their countries of origin.⁴

Extrapulmonary sites account for 10% of all TB cases; genitourinary TB accounts for 30% to 40% of all extrapulmonary cases, second to lymph nodal affection. Peak occurrence for urogenital TB is between the ages of 20 and 40 years, with a 2:1 ratio of men to women; it is more prevalent in developing countries.⁵

Urogenital TB arises from hematogenous dissemination from the lungs; the kidney, epididymis, and prostate are the primary landing sites. The bacillus then gains access to other organs via direct or lymphatic means. Affected individuals are often free of any pulmonary symptoms or involvement.

Signs and symptoms for urogenital TB are typically nonspecific and usually mimic a wide range of more commonly occurring urologic conditions. Lower urinary tract symptoms (LUTS), pyuria, hematuria, and pain are among the usual presenting symptoms; they are usually refractory to standard treatment regimens and are easily missed unless a high index of suspicion is exercised.

Case Report 1: TB Prostatitis

A 42-year-old Malaysian man presented with a 6-month period of mild LUTS and an elevated prostate-specific antigen (PSA) level of 4.1 ng/mL. Prior treatment included tamsulosin and one course each of ciprofloxacin, 500 mg, and double-strength trimethoprim and sulfamethoxazole. Physical examination results were unremarkable except for a slightly firm prostate estimated at 20 g and trace erythrocytes and leukocytes in his urine. Routine urine culture results were negative and repeat PSA measurement remained in the range of 4 ng/mL. Transrectal ultrasound and biopsy results revealed granulomatous prostatitis. Acid-fast bacilli (AFB) culture submitted subsequent to the biopsy returned positive for drug-susceptible M tuberculosis. Chest radiograph and intravenous pyelogram results were normal and the patient was treated with isonicotinylhydrazine (INH), rifampin, and pyrazinamide for 6 months. On digital rectal examination the prostate remained slightly firm and PSA level normalized at 0.7 ng/mL.

Case Report 2: TB Epididymitis

A 40-year-old recent immigrant from Mexico presented initially to his primary care physician with persistent right scrotal pain of several months’ duration. Results from urinalysis, urine culture, and sexually transmitted disease were negative; his physical examination and scrotal ultrasound were unremarkable. He was treated with doxycycline and a nonsteroidal anti-inflammatory drug with no significant relief. He returned 4 months later with clinical right epididymitis-orchitis confirmed with scrotal ultrasound; again routine bacteriologic testing and urinalysis results were normal. AFB culture returned positive for drug-susceptible M tuberculosis. Computed tomography urogram and chest radiograph results were normal. The patient was treated for 1 year with INH, rifampin, pyrazinamide, and ethambutol. Compliance with his medication regimen was an issue and the patient was lost to follow-up shortly after completion of treatment.

Discussion

Several features of our two cases warrant additional comment. The nonspecific presentations of urogenital TB and its attributes as a potential imitator should be duly noted. Neither patient had pulmonary manifestation or symptoms elsewhere to suggest TB; both had normal chest radiograph results. Sterile pyuria, absent in both cases, is more common with bladder and kidney involvement (ie, urinary rather than genital TB). The country of origin is entirely consistent with the known demographic of TB in the United States: in 2013, 54.2% of TB reported in foreign-born persons originated from Mexico, India, Southeast Asia, and China. The racial-ethnic disparity among various subgroups is especially impressive if one considers that the TB incidence of foreign-born Asians is 26 times that of US-born whites.⁴

Traditional diagnosis of urogenital TB relies on the identification of M tuberculosis via urine culture. In contrast to sputum, staining of concentrated urine for AFB is usually negative, as was the case in the individual with TB prostatitis. Three to five early-morning urine samples should be cultured shortly after collection because prolonged exposure to urinary acidity may retard mycobacterial growth.⁴ AFB culture may take up to 6 weeks and is 80% to 90% sensitive. Alternatively, nuclear acid amplification/polymerase chain reaction (PCR) provides a rapid means of diagnosis, but is not a substitute for culture confirmation and drug susceptibility testing, given the emergence of multidrug-resistant (MDR) TB (480,000 cases of MDR TB worldwide, 86 cases the United States in 2013). MDR TB represents a significant escalation in management and containment protocol, and usually requires 2 years of treatment (vs 6 mo), with costly medications and a high proportion of patients requiring hospitalization.⁶

PCR testing is a rapid and highly sensitive means of diagnosis, especially when organism discharge is intermittent and in small amounts, as with urogenital TB. Multiple sampling is also required. Numerous commercial kits are available. PCR testing is not suited as a follow-up to treatment because it is capable of amplifying dead organisms as well.² PCR testing allows for much quicker diagnosis, initiation of treatment, and containment of the index case, which limits additional infections.

The M tuberculosis bacillus, with all of its attributes as an infectious agent, has continued to flourish despite our best efforts to combat it, and will likely live among us for millennia to come. It is likely that most practicing urologists will encounter it at varying frequency, and it is reasonable to surmise that many among us may have also missed the opportunity to diagnose the occasional case of urogenital TB, given its often nonspecific and ill-defined presenting manner and our propensity to resort to descriptive diagnoses such as interstitial cystitis/bladder pain syndrome, chronic pelvic pain syndrome, or orchialgia, among others, when confronted with such complaints.

The readily available PCR testing, with its high sensitivity and rapid return, combined with a high index of suspicion on the part of the urologist, will serve our patients well. Even if test results are negative, it is an invaluable negative, as we have eliminated an easily treatable yet potentially morbid entity and can confidently move forward along the appropriate treatment algorithm.

The relatively infrequent cases of advanced urinary TB highlighted by renal and infundibular scarring, hydronephrosis, segmental distal ureteral strictures, and late bladder involvement—complete with sterile pyuria or chronic scrotal draining sinus—should pose no great challenge to our ability to diagnose. Conversely, those who present with LUTS, vague pelvic complaints, hematuria, or scrotal discomfort are easily missed among crowds of patients with similar complaints who are free of TB. The usually refractory nature of these complaints, combined with the knowledge of the patient's racial-ethnic background in the appropriate setting, should prompt urologists to entertain TB as a potential offending cause and initiate investigation. 

References

1. Zink AR, Sola C, Reischl U, et al. Characterization of Mycobacterium tuberculosis complex DNAs from Egyptian mummies by spoligotyping. J Clin Microbiol. 2003;41:359-367.
2. Morey AF, Dugi DD III. Genital and lower urinary tract trauma. In: McDougal WS, Wein AJ, Kavoussi LR, et al, eds. Campbell-Walsh Urology. 10th ed. Philadelphia, PA: WB Saunders; 2011:468-479.
3. Tuberculosis. Fact sheet No. 104. Reviewed March 2015. World Health Organization website. http://www.who.int/mediacentre/factsheets/fs104/en/. Accessed May 18, 2015.
4. Alami NN, Yuen CM, Miramontes R, et al; Centers for Disease Control and Prevention (CDC). Trends in tuberculosis—United States, 2013. MMWR Morb Mortal Wkly Rep. 2014;63:229-233.
5. Gomella LG, ed. The 5 Minute Urology Consult. Philadelphia, PA: Lippincott Williams & Wilkins; 2010:544-545.
6. Marks SM, Flood J, Seaworth B, et al. Treatment practices, outcomes, and costs of multidrug-resistant and extensively drug-resistant tuberculosis, United States, 2005-2007. Emerg Infect Dis [Internet]. 2014 May.http://dx.doi.org/10.3201/eid2005.131037