Stesura Seveso Archivio Italiano di Urologia e Andrologia 2014; 86, 3224 CASE REPORT Treatment of tuberculous ureteritis. What is the appropriate time for invasive treatment? A case report and review of literature Özgür Haki Yüksel, Ahmet Ürkmez, Ayhan Verit Fatih Sultan Mehmet Research & Training Hospital, Dept. of Urology, Istanbul, Turkey. We report a case of isolated distal ureter tuberculosis who presented with irritative voiding symptoms treated with sole medical therapy and discuss the clinical, imaging, diagnostic and therapeutical features. In case of irritative voiding symptoms and radiological presentation of ureteral pathologies, genitourinary tuberculosis should be con- sidered in the differential diagnosis. We believe that medical therapy should be the main option before the invasive procedures. KEY WORDS: Ureter tuberculosis; Medical therapy; Invasive treatment. Submitted 14 June 2014; Accepted 1 August 2014 Summary No conflict of interest declared. INTRODUCTION Nearly one third of the world’s population is estimated to be infected with Mycobacterium tuberculosis. Genitourinary tuberculosis is not very common but it is considered as a severe form of extra pulmonary tubercu- losis. Extra pulmonary tuberculosis accounts for approx- imately 20% of cases of active tuberculosis. Only 20 to 30% of the patients with genitourinary tuberculosis have a history of lung infection (1). Urogenital tuberculosis is characterized by clinical polymorphism. However, the isolated ureteric form is very rare (2). We report a case of isolated distal ureter tuberculosis who presented with irritative voiding symptoms treated with sole medical therapy and discuss the clinical, imaging, diagnostic and therapeutical features. CASE REPORT Our case was a 55-year-old woman without significant medical history. The patient consulted us for urinary fre- quency and microscopic hematuria for the past eight months. The physical examination revealed an exhausted patient. The patient presented with weight loss as 10 kg in eight months. Laboratory investigations showed appropri- ate kidney function with a creatinine of 0.97 mg/dl, an inflammatory syndrome with an erythrocyte sedimen- tation rate of 54 mm/hour and C-reactive protein of DOI: 10.4081/aiua.2014.3.224 2.69 mg/L, whereas the remaining laboratory investiga- tions were unremarkable. The patient then underwent a renal and pelvic ultrasound which showed left hydro - nephrosis and hydroureter. This examination was com- pleted by a magnetic resonance urography that revealed a left ureterohydronephrosis in the left distal ureter second- ary to focal wall thickening (Figure 1). Furthermore, con- sidering the irritative voiding symptoms, we suggested a Koch’s bacillus assessment of the patient’s urine which resulted strongly positive. The treatment consisted of antituberculous antibiotics. After 6 months of treatment was observed a decline of hydroureteronephrosis (Fıgure 2). Mycobacterial culture came to be negative. DISCUSSION The incidence of tuberculosis is estimated as 26 per 100.000 in Turkey. According to the WHO 2006, extra- pulmonary tuberculosis rate is 15-25%. In 2005, surveil- lance of Ministry of Health in Turkey resulted in 20535 cases suffering from tuberculosis, out of them 91.3% were new cases, 73% and 27% were pulmonary and extrapul- monary tuberculosis, respectively. Extrapulmonary tuber- culosis cases were genitourinary locations in 4.5%, gas- troıntestinal and peritoneal locations in 4.5%; intratho- racic lymphadenitis in 5.5%, extrathoracic lymphadenitis in 26% and pleuric locations in 37%. More rarely bone and central nervous system were affected. Risk factors for extrapulmonary tuberculosis are HIV infection, tumour necrosis factor-! antagonists (e.g. Infliximab), corticos- teroids, malignancy, female gender. Being female gender is the unique risk factor for our patient. Urogenital tubercolosis comprises renal disease, ureteric disease and genital infection. The diagnosis of renal dis- ease is easily missed, as back or flank pain, dysuria or general symptoms occur in only 30% of patients. Renal tubercolosis is usually unilateral and rarely causes renal failure; the exception is tuberculous interstitial nephritis, which may affect both kidneys. Renal abscesses may destroy the entire renal parenchyma. Pelvo-calyceal involvement may result in thickening of the collecting system; more distally, ureteric fibrosis and stricture for- mation may cause hydronephrosis, whereas tubercolosis YukselCR_Stesura Seveso 08/10/14 12:17 Pagina 224 225Archivio Italiano di Urologia e Andrologia 2014; 86, 3 Treatment of tuberculous ureteritis. What is the appropriate time for invasive treatment? A case report and review of literature of the bladder wall may lead to fibrosis. Renal biopsy may show granulomatous interstitial nephritis, often with multifocal caseous necrosis. Cystoscopy with biopsies of bladder, ureteric or prostate tissue may also be helpful. The CT/MRG urography and intravenous urography with micturition examinations are designed to make an extended assessment of the urogenital tuberculosis lesions. Imaging or the renal tract may show a character- istically ‘beaded’ ureter (ureteritis cystica) (3). This is probably due to an extending fibro-inflammatory process with thickening of the ureteral wall that could be con- fused with a ureteral tumor in evaluation of imaging (4). Urogenital tuberculosis is characterized by varied clinical symptoms (5). Ureteral localization was always described as secondary to renal disease because it represents the extension of mucosal lesions from the kidney (6). The case reported here did not reveal any visible renal impairment by imaging exploration except hydrourete - ronephrosis. Endoscopy must always be performed with the patient under general anesthesia with a muscle relaxant to reduce the risk of hemorrhage. The phase of bladder filling should be performed under direct vision. Bladder biopsy is contraindicated in the presence of acute tuber- culous cystitis (7). Indications for ureteroscopy are rare but renal tuberculosis should be included in the differ- ential diagnosis of lateralizing hematuria, especially in the absence of an obvious cause for the bleeding. In this case direct culture of urine from the renal pelvis may have more sensitivity than culture of voided urine (8). The confirmation of the diagnosis is based on assessing microscopically the presence Koch’s bacilli in the urine by direct testing for alcohol-acid-resistant bacillus. The Koch’s bacillus culture requires a long time for obtaining the final results as long as eight weeks. The identification of Koch’s bacillus using polymerase chain reaction is faster and takes 24 to 48 hours, but with a sensitivity reduced to 48.5% (9). According to the WHO, the antituberculous drug treat- ment is based on an initial 2 months intensive phase of treatment with three or four drugs (rıfampicın, isoniazid, pyrazinamide, etambutol or streptomycin) to destroy almost all tuberculous bacilli. This is followed by a 4 months manteinance phase with only two drug mostly rıfampicin and ısoniazid (10). The most common site for tuberculous stricture is the ureterovesical junction. Uretheral strictures may develop in more than 50% of patients with renal involvement (11). Strictures of the lower end of the ureter, which can either be managed medically or surgically, occur in approximately 9% of patients. If obstruction at the lower end of the ureter is present at the start of chemotherapy careful observation is required. These strictures may result from edema and they respond to chemotherapy. The patient should receive chemotherapy and should be monitored by intravenous urograms at weekly intervals. Corticosteroids can be added to chemotherapy if there is deterioration or no improvement after 3 weeks. If there is still deterioration or no improvement after a 6 week period, surgical reimplantation should be carried out if an initial attempt of dilatation has failed. Double J ureter- al catheter drainage may be used during this period for assessing the efficacy of medical therapy. Early ureteral stenting or PCN (percutaneous nephrostomy) in patients with tuberculous ureteral strictures may increase the opportunity for later reconstructive surgery and decrease the likelihood of renal loss (12). In all other situations, patients should have at least 4 weeks of extensive chemotherapy before surgery (7). The overall incidence of surgical management of geni- tourinary tuberculosis in the past 20 years was reported to be about 0.5% of all urological surgical procedures (13). Although chemotherapy is the mainstay of treat- ment, ablative surgery as a first-line management may be unavoidable for sepsis or abscesses (14). Medical treat- ment is the first-line therapy in genitourinary tuberculo- sis. Both radical and reconstructive surgery should be carried out in the first 2 months of intensive chemother- apy (15). The duration of medical therapy has been Figure 2. Magnetic resonanse urography: At the lower end of the left ureter was observed a significant decrease in contrast enhancement (marked by the arrow). Figure 1. Magnetic resonanse urography: the left distal ureter secondary to focal wall thickening (marked by the arrow). YukselCR_Stesura Seveso 08/10/14 12:17 Pagina 225 Archivio Italiano di Urologia e Andrologia 2014; 86, 3 Ö. Haki Yüksel, A. Ürkmez, A. Verit 226 reduced to 6 months in uncomplicated cases. Only in complicated cases (recurrences of tuberculosis, immuno- suppression and HIV/AIDS) a 9 to 12 month therapy is necessary (6). In conclusion, in the presence of irritative voiding symp- toms and radiological imaging showing a pathological ureter, genitourinary tuberculosis should be considered in the differential diagnosis. We believe that medical therapy should be the main option before the invasive procedures. REFERENCES 1. World Health Organization (WHO) (2010) Global Tuberculosis Control 2010: Epidemiology, Strategy, Financing. WHO/HTM/TB 2010. 7. 2. Matos MJ, Bacelar MT, Pinto P, Ramos I. Genitourinary tubercu- losis. Euro J Radiol. 2005; 55:181. 3. Figueiredo AA, Lucon AM, Arvellos AN, et al. A better under- standing of urogenital tuberculosis pathophysiology based on radio- logical findings. Eur J Radiol. 2010; 76:246. 4. Dhar NB, Angermeier KW. Idiopathic ureteral strictures without evidence of malignancy. 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Genito-urinary tuberculosis–experience with 52 urology in patients. S Afr Med J. 1993; 83:903. 12. Shin KY, Park HJ, Lee JJ, et al. Role of early endourologic man- agement of tuberculous ureteral strictures. J Endourol. 2002; 16:755. 13. Rizzo M, Ponchietti R, Di Loro F, et al. Twenty-years experience on genitourinary tuberculosis. Arch Ital Urol Androl. 2004; 76:83. 14. Carl P, Stark L. Indications for surgical management of geni- tourinary tuberculosis. World J Surg. 1997; 21:505. 15. Gow JG. Tuberculosis: genitourinary tuberculosis. Br J Hosp Med. 1979; 22:556. Correspondence Özgür Haki Yüksel, MD (Corresponding Author) ozgurhaki@gmail.com Ahmet Ürkmez, MD Ayhan Verit, MD, Prof Fatih Sultan Mehmet Research and Training Hospital, Dept. of Urology, Icerenkoy/Atasehir Tr- 3 4752 Istanbul, Turkey YukselCR_Stesura Seveso 08/10/14 12:17 Pagina 226