Best practice in the diagnosis and management of urogenital tuberculosis

Abstract

Tuberculosis (TB) is a current public health problem, remaining the most common worldwide cause of mortality from infectious diseases. Urogenital tuberculosis (UGTB) is the second most common form of extrapulmonary TB in countries with severe epidemic situations and the third most common form in regions with a low incidence of TB. In this article we present the terminology, epidemiology and classification of UGTB, as well as describing the laboratory findings and clinical features and approaches to chemotherapy as well as surgery.

Introduction

Tuberculosis (TB) is a current public health problem, remaining the most common worldwide cause of mortality from infectious disease. TB (both pulmonary [PTB] and extrapulmonary [EPTB]) leads to male and female infertility [Khanna and Agrawal, 2011; Kulshrestha et al. 2011; Wise and Marella, 2003; Tzvetkov and Tzvetkova, 2006; Lenk and Schroeder, 2001; Scherban et al. 2008; Wise and Shteynshlyuger, 2008]. It is a sexually transmitted disease [Scherban and Kulchavenya, 2008] which explains why it is not only a medical, but also a big social problem.

Urogenital tuberculosis (UGTB) is ancient but remains an unsolved problem. Clinical features are flexible and variable and UGTB mimics numerous other diseases, which results in delayed diagnosis. Despite about 7000 articles available in the literature with the keywords ‘urogenital / genitourinary tuberculosis’, there are no good multicenter studies with a high level of evidence on this problem. UGTB is an embodiment of contradictions: from terms and classification to therapy and management. Nevertheless we have to overcome this quagmire to best understand this eternally enigmatic and potentially fatal dangerous disease.

Terminology

The first note of UGTB was made by Porter in 1894 [Porter, 1894]. Later, in 1937, Wildbolz suggested the term genitourinary TB [Wildbolz, 1937]. We prefer the term UGTB, because kidney TB (KTB), which is usually primary, is diagnosed more often than genital TB. Only 53% of patients with KTB have genital lesions, but in 61.9% patients with epididymorchitis and in 79.3% patients with TB of the prostate, a renal lesion can be diagnosed [Kulchavenya, 2009; Gómez García et al. 2010], although some authors believe that TB often affects the lower genitourinary system rather than the kidney. TB of the lower genitourinary tract most commonly affects the epididymis and the testis, followed by bladder, ureter, prostate and penis [Wise and Shteynshlyuger, 2008].

Actually the term UGTB is incorrect too, because it includes KTB and male genital tuberculosis (MGTB), with different clinical features and approaches to management. However, as this term is usually used in the literature, we shall use it here too.

Epidemiology

More than 95% of patients diagnosed with PTB live in developing countries, where the incidence is as great as 600/100,000 annually. It has been well described that the urogenital system is a common site of EPTB in adults, but the true incidence of UGTB is less clear, and reports have varied from 4% to 73% [Zarrabi and Heyns, 2009]. About 2 billion people are infected with Mycobacterium tuberculosis (MBT); they are carriers of latent infection, forming a large reservoir for reactivation of TB [Barry et al. 2009]. Thus, any contemporary person has a risk to be infected with MBT and, in unfavorable conditions, to get sick with UGTB.

In 1984 EPTB remained a major health problem in Australia, where 24.3% of all new TB notifications were of extrapulmonary origin. The most common sites of disease were the lymph nodes, urogenital tract, pleura and bone [Dwyer et al. 1987]. By the 1980s, the availability of anti-TB chemotherapy reduced the incidence and prevalence of TB. Changing patterns of population migration and the development of large pools of immune-compromised individuals reversed the downward trend of TB [Wise and Marella, 2003].

In 2009 almost one-fifth of United States TB cases were extrapulmonary; unexplained slower annual case count decreases have occurred in EPTB, compared with annual case count decreases in PTB cases. Among 253,299 cases, 73.6% were PTB and 18.7% were EPTB, including lymphatic (40.4%), pleural (19.8%), bone and/or joint (11.3%), genitourinary (6.5%), meningeal (5.4%), peritoneal (4.9%) and unclassified EPTB (11.8%) cases [Peto et al. 2009].

UGTB usually results from the reactivation of old, dormant tuberculous diseases by pathogens of the MTB complex [Lenk, 2011] and is the second most common form of EPTB in countries with severe epidemic situations and the third most common form in regions with a low incidence of TB [Colbert et al. 2012; Kulchavenya et al. 2012b; Lima et al. 2012].

Predisposition

Factors leading to the increased incidence of TB include the high incidence of TB among the AIDS population and the emergence of drug-resistant strains of TB [Gusmão et al. 1998; Fekak et al. 2003]. TB with AIDS tends to occur in a younger population and is often extrapulmonary or with atypical lung involvement. Drug resistance is similar in patients with and without AIDS [Cremades Romero et al. 1998].

In Japan, because of the progress in chemotherapy for MTB, it has become quite rare to diagnose patients with UGTB; however, the incidence of TB remains comparatively high, particularly in older patients, in advanced countries [Miyake and Fujisawa, 2011]. Furthermore, infectious adverse events associated with intravesical instillation therapy with bacille Calmette–Guérin (BCG), which is one of the most useful agents against non-muscle-invasive bladder cancer, are frequently developed [Wise and Marella, 2003; Drechsler and Kirch, 2010; Miyake and Fujisawa, 2011; Kulchavenya et al. 2012a]. Congenital anomalies of the urogenital tract, renal cysts, kidney transplantation and urolithiasis significantly increase the risk of developing UGTB. The incidence of TB has been estimated to be as much as 10-fold higher among renal failure patients than among the general population [Chan et al. 1996; Gusmão et al. 1998; Kulchavenya and Muzyko, 2007; Korzeniewska et al. 2009; Rabbani et al. 2011; Takeshita et al. 2012].

Classification

UGBT is an infectious disease of the kidneys, urinary tract and male genitals, caused by MTB. A clear definition and classification are necessary for correct therapy. The following classification of UGTB is recommended [Kulchavenya, 2009, 2010]:

• I. KTB:

• Level 1 – nondestructive form, TB of parenchyma;

• Level 2 – small destructive form, TB papillitis;

• Level 3 – destructive form with one or two caverns (cavernous kidney TB);

• Level 4 – widespread destructive form with more than two caverns (polycavernous kidney TB).

Complications of KTB: TB of urinary tract (TB of ureter, bladder grades 1–4, urethra), strictures, fistula and renal failure.

• II. MGTB:

• – Orchiepididymitis (monolateral and bilateral);

•  Prostate TB (infiltrative or cavernous forms);

• – TB of seminal vesicles;

• – TB of penis.

Complications of MGTB: strictures, fistula, infertility, sexual dysfunction.

KTB levels 1–2 should be treated with chemotherapy, KTB level 3 may require partial nephrectomy, KTB level 4 is indicated for nephrectomy, by open surgery or laparoscopically. Stricture of the ureter is indicated for reconstructive surgery only in KTB levels 1–3, KTB level 4 with stricture of the ureter is indicated for nephroureterectomy. Bladder TB grades 1–2 should be treated by chemotherapy, bladder TB grade 3 requires additional prescription of trospium chloride, bladder TB grade 4 is indicated for cystectomy and reconstructive enteroplastic operation. MGTB should be treated with chemotherapy; scrotal fistula is indicated for surgery.

Clinical features

Diagnosis is often difficult because TB has a variety of clinical findings. It can mimic numerous other disease entities. A high level of clinical suspicion allows early diagnosis and timely initiation of proper management [Teo and Wee, 2011; Muttarak et al. 2005]. The nonspecific clinical features of UGTB make the early and accurate diagnosis of this disease difficult. Hematuria, lower urinary tract symptoms, flank pain and scrotal swelling are the most common presenting features. Chronic epididymitis associated with a draining scrotal sinus is often associated with UGTB [Zarrabi and Heyns, 2009]. The most common presenting symptoms are polyuria, dysuria and acidic urinary pH with pyuria. A total of 80% of patients have abnormal imaging studies of the urinary system, with hydronephrosis being the most frequently found condition [Tanthanuch et al. 2010]. In a review of 8961 cases from the world literature there was shown a great difference between clinical features of UGTB in different regions depending on epidemic situation, economic state of the country, etc. [Figueiredo and Lucon, 2008].

Patients usually exhibit local symptoms. Fever, weight loss and anorexia are uncommon. A total of 89% of the patients have abnormal urinalysis (hematuria and/or pyuria) [Kao et al. 1996] Patients can present with unusual complaints not immediately suspicious for TB [Colbert et al. 2012] and this infection is easily overlooked unless clinicians maintain a strong awareness of its possibility [Patterson et al. 2012]. In Moscow, UGTB manifested with chronic cystitis in 13.1%, subacute orchiepididymitis in 13.1%, anatomofunctional alterations of the kidneys (hydronephrotic transformation, nonfunctioning kidney, ureteritis, etc.) in 28.5% of patients [Batyrov et al. 2004]. The diagnosis of renal tuberculosis (RTB) can be hypothesized in a nonspecific bacterial cystitis associated with a therapeutic failure or a urinalysis with a persistent leukocyturia in the absence of bacteriuria [Lima et al. 2012]. Nonoptimal empiric therapy for urogenital tract infections (UTIs) resulted in a high level of comorbidity UGTB and UTIs, and the old symptom of ‘sterile pyuria’ has now lost its significance [Kulchavenya, 2010].

Laboratory diagnosis

A delay in diagnosing UGTB is common and results in significant morbidity. Patients who are diagnosed at a late stage often have complications such as ureteral stricture with hydronephrosis, a shrunken bladder, autonephrectomy or destruction of the testis by a cold abscess. This is unfortunate, because effective medical therapy is readily available [Zarrabi and Heyns, 2009].

There remain four pillars to the diagnosis of UGTB: bacteriology, pathomorphology, radiology and provocative test with therapy ex juvantibus; however, some simple and cheap tests may also be useful.

Urinalysis in the diagnosis of UGTB

Urinalysis is the least invasive method of diagnosing UGTB. The classically described ‘sterile pyuria’ is not very sensitive or specific for UGTB, but persisting sterile pyuria in an individual at risk should increase the clinician’s index of suspicion [Zarrabi and Heyns, 2009].

The introduction of the four-glass test in 1968 by Meares and Stamey (M&S) was a great step forward to diagnose chronic prostatitis not only by symptoms, but also by investigation of segmented urine and prostatic secretion specimens to localize the inflammation/infection to the urethra, bladder or prostate (or any of these combinations) [Meares and Stamey, 1968]. Thus, for many generations the Meares and Stamey four-glass test was considered as the ‘gold standard’ and recommended not only for research but also for the general practicing urologist as a routine test for diagnosing chronic prostatitis [Nickel, 2003]. Unfortunately, one had to realize that these recommendations were not followed for several reasons, because the test is (i) time consuming, (ii) difficult to perform, (iii) costly and (iv) bothersome for the patient [McNauhgton-Collins et al. 2000]

These were the main reasons why the premassage and postmassage two-glass test (PPMT) was developed [Nickel, 2000; Nickel et al. 2006]. However, by the PPMT only the laboratory burden (cost) is reduced by reducing the number of specimens, but the discomfort for the patient remains the same, because the patient has to produce a midstream urine sample, interrupt micturition not to empty the bladder completely, because after the following prostatic massage by digital rectal examination (DRE) he is supposed to produce another urine specimen again during the same visit. First, not every patient can interrupt micturition before the bladder becomes empty. Second, voluntary stop of micturition converts laminar flow of urine in a turbulent one and thus provokes reflux of urine into the prostatic ducts, which is fraught with the risk of develop chemical burns, inflammation and prostatolithiasis. Another aspect of using the M&S four-glass test is probably even more serious. Patients assigned to the M&S four-glass test are usually not informed that between VB1 and VB2 (see below) and thereafter continuous urination without interruption is necessary to produce a true midstream urine specimen which is necessary to (i) diagnose concomitant cystitis and (ii) serve also as a basic comparative parameter by which localization of inflammation/infection to the urethra or prostate can be made possible. Interruption of urine flow between VB1 and VB2 and at the end of VB2 will lead to contraction of the prostate and thus contamination of urine with prostatic secretion.

In our previous work [Kul’chavenia et al. 2011], we developed a three-glass test for screening of patients with clinical signs and symptoms of chronic prostatitis with the option of further tests for final diagnosis only in those patients where additional investigations are needed. This KE three-glass test comprises three urine samples taken from only one continuous urine stream: VB1 comprises the first 10 ml, VB2 the midstream portion of a noninterrupted stream and VB3 the final portion at the very end of the stream. As the prostate is part of the external sphincter of the bladder, it contracts at the end of a micturition. Therefore, the urine sample at the end of the micturition (VB3) corresponds practically to the urine sample after prostatic massage. However, the discomfort of prostatic massage by DRE can be avoided. Leukocyturia in the first portion (VB1) indicates inflammation in the urethra, in the second portion (VB2) indicates general inflammation in the urinary bladder and/or upper urinary tract and in the third portion (VB3) indicates inflammation in the prostate. Leukocyturia in all three portions may mirror inflammation of the total urinary system.

Therefore the three-glass test (i) allows DRE for diagnosis of chronic prostatitis to be avoided and (ii) facilitates the use of total leukocyturia as a measure as highly suspicious of UGTB. Nonspecific bacterial prostatitis as well as nonspecific epididymitis very rarely are accompanied by pyelonephritis. In contrast, MGTB combines with KTB in up to 80% of cases. So for patients with epididymitis and/or prostatitis, having pyuria in all three portions of urine is highly suspicious of UGTB, as long as it is real pyuria, not contamination of urine by prostatic secretion, as is inevitable in the four-glass test. In our study UGTB was revealed in patients with chronic prostatitis using the three-glass test in 1.8% of patients [Kul’chavenia et al. 2011].

Bacteriology

At least six, but preferably nine or more, specimens of urine, expressed prostatic secretion and ejaculate should be cultured, each onto at least three slants (Lowenstein–Jensen, Finn–II, Middlebrook 7H9-12) [Lenk, 2011]. Nevertheless, the standard technique is positive in 36–57% of UGTB patients only [Kulchavenya, 2009; Batyrov et al. 2004; Lee et al. 2011; Tanthanuch et al. 2010]. Positive cultures were 15% higher if sowing was performed three times in 1 day [Zhuravlev et al. 2012]. For MGTB, to investigate prostatic secretion, then postmassage urine, then ejaculate and postejaculate urine in 1 day, by microscopy, culture and real-time polymerase chain reaction (PCR), each probe is recommended. It is very important to keep the shortest time between the collection of urine, prostatic secretion and ejaculate and their sowing; the optimal time should be no more than 40 min [Kulchavenya, 2010]. In order to identify mycobacteria and to perform anti-TB susceptibility tests, direct preparations stained with Ziehl–Nielsen (ZN) method to evaluate a smear microscopically or PCR method are insufficient; cultivation of mycobacteria is necessary [Aslan et al. 2007]. PCR has been found to be useful in diagnosing early disease as well as confirming diagnosis in clinically suspected cases. False-negative PCR is an important limitation of this technique [Thangappah et al. 2011].

TB is an anthropozoonotic disease; this is the reason for possible cross-contamination between humans and animals [Dumonceaux et al. 2011]. The presence of Mycobacterium bovis in urine accounted for 4.2–12.5% of all UGTB cases [BlagodarnyĬ et al. 1990; Berta et al. 2011; Singh et al. 2011a].

To overcome the limitations of current urine-based diagnostic assays of UGTB, isothermal microcalorimetry has been used to detect the metabolic activity of MTB and other commonly neglected pathogenic mycobacteria in urine and accurately determine their growth parameters [Kumar et al. 2012].

Pathomorphology

One more problem in the diagnosis of UGTB is the loss of pathomorphological signs of TB, especially in comorbidity with HIV infection. For identification of MBT biopsies and operation tissue should be investigated also using the ZN method. Histopathological examination (HPE) for the tissues obtained gives inconclusive diagnosis in the absence of caseous necrosis or stained acid-fast bacilli. A total of 78 tissue specimens (renal, prostate, epididymis, penile and soft tissue) from patients with clinically suspected UGTB were processed for both PCR and histopathology. In 87.1% samples, results for both PCR and HPE were in agreement. False positivity and false negativity was observed in 5.1% and 7.6% samples, respectively. With HPE as the gold standard, PCR has shown sensitivity of 87.5% and specificity of 86.7% and positive agreement between the two tests was observed as significant. PCR results were obtained within a mean period of 3.4 days while those of HPE were obtained in 7.2 days. The authors concluded that tissue PCR is a sensitive and specific method for obtaining early and timely diagnosis of UGTB. Application of tissue PCR results can augment the diagnostic accuracy to pathologically labeled granulomatous inflammations [Chawla et al. 2012]. In another study the possibility of the early rapid diagnosis of RTB by PCR on renal biopsy specimens was estimated. It was found that the sensitivity and specificity of real-time PCR were 93.3% and 56.7%, respectively. The sensitivity and specificity of the urine MTB culture were 23.3% and 100%, respectively [Sun et al. 2010].

There was no correlation between the histological findings and the mycobacteriological investigations. The investigation of tissue specimens on the presence of mycobacteria also from other organs of the urogenital tract is a suitable method to find bacteriological proof of TB, especially in the absence of positive bacteriological findings from the urine or accessory gland secretion for the estimation of species and resistance of these bacteria [Lenk et al. 1986].

It is necessary to keep in mind that biopsy for confirming UGTB by histology may have serious complications [Kulchavenya, 2010; Silva et al. 2011] until generalization of TB in untreated patient. Miliary TB has been diagnosed in a patient resulting from the hematogenous spread following transurethral ultrasound (TRUS)-guided prostate biopsy [Kim et al. 2011]. Biopsy may sometimes be useful in diagnostic UGTB [Shenoy et al. 2012], and histologic follow-up was estimated as a good method for monitoring the efficacy of treatment. Transrectal prostate biopsy may be an important tool for the diagnosis and follow-up of prostatic TB [Lee et al. 2001].

Radiology

Radiology is good method for diagnosis of UGTB, both prostate and kidney. Unfortunately this method is useful only for late cavernous forms, but our aim is early diagnosis. Pyelograms disclosed abnormalities in 94% and most revealed late changes [Kao et al. 1996] Caverns of prostate and/or kidney are absolutely pathognomonic symptom, but caverns mean late-diagnosed complicated form, cavernous UGTB cannot be cured by chemotherapy [Kulchavenya, 2010].

Provocation test

In many cases provocation test with injection of 20, 50 or 100 units of tuberculin subcutaneously may be useful. All laboratory investigations including body temperature are repeated 24 and 48 hours after tuberculin injection. The test is positive if leukocytosis, lymphocytopenia, leukocyturia, leukocytospermia and body temperature have increased by more than 1°C. Also local reaction (hyperemia, induration in place of injection tuberculin) is to be taken into account. After provocative subcutaneous tuberculin test, identification of MBT by culture or PCR increased by 16%. On the whole, this test improved the diagnosis of UGTB, especially the obscure, latent forms, to 63% [Kulchavenya and Kim, 2010; Kulchavenya and Krasnov, 2010].

Therapy ex juvantibus

Therapy ex juvantibus may be of first type, when patients receive antibiotics which do not inhibit MBT, and of second type, when patients receive antibiotics which inhibit only MBT. For therapy ex juvantibus first type, phosphomycin, cephalosporins and nitrofurantoin are suitable. For therapy ex juvantibus second type we can use isoniazid, PAS, protionamide, ethionamide, ethambutol and pyrazinamide. For good results of the therapy ex juvantibus, pathognomonic therapy is also indicated: phytotherapy with canefron, nonsteroidal anti-inflammatory drugs, etc. [Kulchavenya and Kim, 2010].

Therapy

Drugs that can cure most TB patients have been available since the 1950s, yet TB remains the world’s first highest cause of death among adults by infectious diseases. Unfortunately, during the last half a century no new drugs were developed. At the same time, resistance of MBT has increased enormously. Mono-, poly- and multi-drug-resistant MBT to the basic anti-TB drugs was found in up to 52.2% of EPTB patients and up to 78.7% of PTB patients [Kao et al. 1996]. Anti-TB drug treatment is based on an initial 2-month intensive phase with three or four drugs daily followed by a 4-month continuation phase with only two drugs [Lenk, 2011].

Medical treatment of genital TB is somewhat different from that of other TB, because prostatotropic drugs have to be preferred. In countries with a low incidence of TB three anti-TB drugs with bactericidal activity may be sufficient for bacterial eradication and prevention of resistance. In epidemic regions patients with MGTB should be treated with four or five anti-TB drugs: isoniazid 10 mg/kg + rifampicin 10 mg/kg + pyrazinamide 20 mg/kg + streptomycin 15 mg/kg + PAS 150 mg/kg (or ofloxacin 800 mg or levofloxacin 500 mg daily) simultaneously for 2-4 months, followed by 6–8 months of chemotherapy with isoniazid and rifampicin only [Kulchavenya, 2010].

The World Health Organization (WHO) recommended a reduction in the treatment time to 9 or 6 months with four drugs (isoniazid, rifampicin, pyrazinamide and streptomycin or ethambutol); in complicated or combined cases the length of the therapy may be 12–14 months. In cases of retreatment, immunosuppression and HIV/AIDS, the treatment time increases to 9 or 12 months [World Health Organization, 2004, 2008].

Chemotherapy for late-diagnosed complicated forms of UGTB is not effective enough, so surgery is indicated [Viswaroop et al. 2006]. The organ-removing operations were conducted in 73% of patients [Batyrov et al. 2004]. Surgery, whether in the acute setting (orchiectomy, nephrostomy) or after medical treatment (nephrectomy, cystoplasty), still plays an important role in the treatment of patients with UGTB [Zarrabi and Heyns, 2009].

To improve the chemotherapy complicated form of UGTB with bladder involvement, a modified scheme was developed [Kulchavenya, 2010]. The ‘modified’ tetrad included isoniazid 10 mg/kg + rifampicin 10 mg/kg + pyrazinamide 20 mg/kg + ofloxacin 800 mg for 2 months. This was followed by a 6-10 months treatment with isoniazid and rifampicin only. In addition from the first day of the therapy all patients received trospium chloride 15 mg b.i.d. for 3 months as pathogenetic treatment. The efficiency of the modified tetrad was compared with results of the standard chemotherapy (isoniazid 10 mg/kg + rifampicin 10 mg/kg + pyrazinamide 20 mg/kg + streptomycin 15 mg/kg). The outcome analysis showed that standard therapy was insufficient in more than a half of the cases: only 42.1% could be cured, 57.9% developed complications such as posttuberculous cystalgia (36.8%) and microcystitis (21.1%). Patients treated with the modified tetrad responded in a favorable manner: urinary frequency reduced by about 75%, bladder capacity increased an average of 4.7-fold. Recovery was reached in 84.3%. Posttuberculous cystalgia developed in 15.7% only. None of the patients developed microcystitis after the combined treatment. Tolerance to the treatment was good: only one patient had a mild side effect (mouth dryness).

Surgery

Unfortunately, mostly due to late diagnosis, medical treatment may not result in the resolution of symptoms. Thus, surgical intervention and reconstruction of the urinary tract are frequently indicated [Viswaroop et al. 2006; Wise and Shteynshlyuger, 2008]. The organ-removing operations have been conducted in 73% of UGTB patients. Preoperative tuberculostatic therapy reduces the frequency of postoperative complications. In early diagnosis, the organ has been saved in only 9.4% of operations [Batyrov et al. 2004]. It was found that eradicative techniques such as nephrectomy and nephroureterectomy still prevail. Early drainage of the kidney for its decompression allows preservation of the kidney and following reconstructive surgery in 70.6% of cases. The number of early and later complications have decreased considerably [Zuban’ et al. 2008].

Bladder TB grade 4 (microcystitis) is indicated for cystectomy followed by enteroplasty [Kulchavenya and Krasnov, 2012]. Urinary bladder rehabilitation either by augmentation cystoplasty or orthotopic neobladder reconstruction increases the bladder capacity and storage time and also preserves the upper tracts [Singh et al. 2011b]. Bladder and ureter reconstruction with ileum is a good option in difficult cases of lack of or irreversible damage to the urinary way. Vesico-ureteral reconstruction letting urethral miction improves quality of life [Resina et al. 2009; Singh et al. 2011b]. Following the full course of the therapy and, if it was indicated, surgery, patients should be under surveillance for 3–5 years with an annual check-up and antirelapse therapy, if necessary.

Conclusion

UGTB is a frequently occurring but mostly overlooked disease. The main reasons for late diagnosis are a lack of alertness on UGTB among urologists and general practitioners relative to patients with UTIs, kidney anomalies, renal cysts, etc., the nonspecific variable clinical features and decreasing positive cultures of MBT due to nonoptimal empiric therapy for UTIs following the prescribing of fluoroquinolones and amikacin. Standard chemotherapy is effective only for early diagnosed form of UGTB; in a complicated form, a modified scheme with five anti-TB drugs in combination with pathogenetic therapy is indicated. Destructive forms of KTB and MGTB cannot be cured by chemotherapy, so surgery is necessary.