Clinical characteristics and outcome of genitourinary tuberculosis in Sri Lanka: an observational study

We report our 21-year experience in the management of GUTB in a resource limited setting. Although we suspected TB in a larger cohort, only a subset was confirmed to have TB based on the microbiological and histological criteria. Although granulomata with Langhans giant cells were seen in histology, caseation was rare. This may be due to the effect of quinolones that are used liberally for patients with urinary symptoms. All ureteric strictures were treated with stenting and prednisolone. However, most ureteral strictures needed reconstruction with ureteric reimplantation. Drug toxicity was more common among females. Few patients developed thimble bladder syndrome and progressive deterioration of renal function.

In our cohort, kidney, ureter, bladder, and testis/epididymis are the common organs involved. A study from India by Bansal et al., found that among 60 cases, the commonest organ affected was the kidney (n = 34) followed by the bladder (n = 25) and the ureter (n = 20) [12]. Another retrospective study from India by Krishnamoorthy et al. showed that among 110 cases, renal, ureter and bladder involvement was seen among 70, 30 and 18 respectively similar to our study [13]. Interestingly, urethral and prostate involvement was extremely rare in our cohort. Although many urethral fistulae and masses were evaluated with biopsies and microbiological investigations for TB during the study period, none became positive for TB. Although prostate gland involvement is less common, a few incidental prostate TB cases were identified in chippings after trans-urethral resection in our neighbouring country—India [13, 14]. However, we were able to detect only one patient during the last two decades. The reason for this regional variation seems unclear. In our cohort, around 15% of GUTB presented with scrotal manifestations such as a lump or rarely a sinus. In these patients, the positivity of ESR and Mantoux were significantly lower than those with abdominal manifestations. Therefore, high degree of suspicion and obtaining a tissue sample for further evaluation is mandatory to clinch the diagnosis.

Diagnosis of GUTB is a challenge due to the rarity of the disease and varying clinical presentation [15]. Furthermore, basic imaging such as X-rays and ultrasonography are not reliable. X-ray KUB may show ill-defined or diffuse calcifications, but this is becoming rare and in our cohort, such features were seen in 7.3% only [4]. Features in ultrasonography are also non-specific and may show calyceal dilatation, parenchymal destruction, calcification, hydronephrosis or collections [4, 16]. However, it is not useful in most patients except in those with scrotal manifestations [17]. CT-urogram was a useful investigation to detect anatomical abnormalities that are characteristic of TB such as ureteric stricture, unusual parenchymal calcification, renal/peri-renal abscesses and non-functioning kidney [4, 18, 19]. Cystoscopy and bladder biopsy was very useful in clinching the diagnosis in those with haematuria and lower urinary tract symptoms [20]. Presence of inflammation, small capacity bladder, inflammatory masses and golf hole ureteric orifices were characteristic.

It is important to note that microbiological or histopathological confirmation is mandatory to start ATT due to the rarity of the disease and the potential side effects of ATT [21, 22]. Starting ATT on clinical grounds without proper microbiological or histological confirmation should be discouraged as it may cause more harm. In our cohort, 7 patients developed serious adverse effects due to ATT and one patient died of liver failure. It is important to note that urine for AFB, Mantoux and granulomata are notorious to give rise to false positive results thus, use in isolation is not recommended by the experts [21]. Nevertheless, combination of these investigations is very useful to detect GUTB as TB culture or PCR may become negative with widespread use of quinolones. Thus a combined effort of surgeons, radiologists, pathologists, microbiologists and chest physicians are required for the diagnosis of GUTB [23].

Many patients required some form of intervention in addition to ATT for 6 months. However, 6 months of ATT may not be adequate in patients with a high burden of diseased tissue [21]. Unlike in pulmonary TB, surgery in GUTB is an important adjunct [18]. Surgical procedures should be done after 4–6 weeks of anti TB therapy. Pus should be drained either through open or minimally invasive approach. Sinus formation after drainage of tuberculous abscess was not problematic and all healed with ATT. Extirpative/excision surgery such as nephrectomy or orchidectomy is required in extensive disease not responding to ATT or when there is a suspicion of malignancy [18]. A reconstructive procedure was necessary for almost all our patients with ureteric stricture as they did not respond to ATT and steroids. Although TB causes bladder fibrosis, ureteric reimplantation or Boari flap were technically feasible with satisfactory healing as opposed to bladder fibrosis after radiotherapy. Bladder augmentation procedures are required for thimble bladder with disabling storage symptoms [18]. However, all five patients refused augmentation procedure as they did not prefer clean intermittent catheterization post-surgery. Finally, complex fistulae such as colovesical fistulae would need anatomical delineation followed by excision and reconstruction [18].

Prognosis of GUTB is satisfactory in general and in most patients, there was no evidence of impaired renal function at the time of diagnosis. Even those with renal dysfunction had their serum creatinine level stabilised or recovered towards normal with ATT. However, a minority developed end-stage disease especially in those with thimble bladder and bilateral renal involvement. We had three patients with ESRD and two died while on haemodialysis and one underwent successful renal transplant. Therefore, long term follow up is essential in patients with GUTB to identify those with progressive fibrosis and renal impairment. Relapses were uncommon after successful treatment completion.

We noticed several changes in the pattern of GUTB in Sri Lanka over the recent years. The number of cases is increasing in Sri Lanka as evident by the 4 cases reported in 2007 and 59 cases in 2019 [4, 5]. This may be due to increased awareness, detection and reporting. Furthermore, advancements in the facilities such as better availability of reagents for TB detection, availability of tests giving rapid results such as PCR and advanced nucleic acid replication tests—GeneXpert also would have contributed [21]. Since GeneXpert test is not recommended for urine, detection of acid-fast bacilli in urine smears was useful in our resource-limited setting [21]. Increased cases may be a reflection of increased prevalence of immunocompromising conditions such as diabetes mellitus and malignancies in the Sri Lankan population [24‐26]. Multi drug resistance is becoming an emerging problem although it was not seen among our GUTB patients [21]. In Sri Lanka, an average of 16 patients with multi drug resistant TB per year has been reported during the period of 2018 to 2020 [5]. Fortunately, isolated GUTB is not contagious unlike active pulmonary TB and therefore, precautions such as social distancing are not required during the initial phase of treatment [21]. The World Health Organization (WHO) has proposed the “End TB Strategy” to eliminate TB with a target of reduction of TB mortality by 95% and incidence by 90% by 2035 [27]. To achieve this goal, a high degree of suspicion and early case detection with prompt treatment is the way forward. In Sri Lanka, directly Observed Treatment (DOT) with polypills rather than individual drugs are implemented to enhance compliance and minimise default rate [21].

There are several limitations in this study. This is an observational study based on patients that were diagnosed and treated by a single urological surgeon in two consecutive centres. However, we believe that our study is generalizable to most part of Sri Lanka as the urology units of the two institutions cater to a large catchment population throughout the island. Although many were referred with non-sinister symptoms, some had radiological evidence of urinary tract obstruction. This may have added some bias of picking up more severe disease; however this should have been minimal. As this is a resource limited setting, certain investigations were not carried out at times due to non-availability of facilities and reagents uninterruptedly. Certain important data like presence of comorbidities like diabetes mellitus and other risk factors has not been recorded. Follow-up data is incomplete as information from patients who attended routine follow-up visits only have been collected. Nevertheless, this is a comprehensive report of two decades of experience and the first report of GUTB from Sri Lanka.