Q. A 53-year-old Bangladeshi woman has been referred to you with a few months history of frequency, nocturia and malaise. Urine cultures with the GP have been negative. How will you investigate this patient?
A. I would first take a general and focused urological history. However, given the ethnic background, the chronicity of the symptoms and the associated malaise I am concerned that there may be an underlying history of urinary tuberculosis (TB). However, recurrent UTI, stones and interstitial cystitis should be considered in the differential.
I would specifically ask about previous exposure to TB, loss of appetite, fever, night sweats, loin pain, haematuria and suprapubic pain. I would then ask about a past history of pulmonary TB and renal stones. I would want to exclude any underlying conditions which may result in an immunocompromised state such as diabetes mellitus, steroid use and HIV status.
In the examination, I would specifically record the temperature and the presence or absence of any lymphadenopathy. A general examination of the chest and abdomen is mandatory as well as a specific examination of the genitalia. I would then perform a dipstick urinalysis and send the urine off for formal microscopy and culture and sensitivities (C&S) if required. I would also request baseline blood tests (including full blood count [FBC], urea and electrolytes [U&Es], erythrocyte sedimentation rate [ESR], liver function tests [LFTs]). I would then ask for radiological tests including a chest x-ray, a plain x-ray KUB, and then a renal tract USS with a formal post-void residual.
Q. The dipstick urinalysis shows blood and WBCs, but no nitrites. What would be your next step in the investigation process?
A. I would send the urine for cytology and arrange for three early morning urine (EMU) samples to be sent for acid-fast staining and TB culture.
Q. Why would you send three samples and why early morning?
A. The organism causing TB is excreted only intermittently in the urine and There fore, sending multiple samples of urine that has been standing in the bladder overnight gives us the best chance of a positive yield.
Q. How are EMU samples processed? Why is Gram stain not used?
A. The smear made of the urine sample is stained using the Ziehl-Neelsen stain to look for acid-fast bacilli and the specimen is also cultured using the Lowenstein-Jensen culture medium. The causative organism of TB, Mycobacterium tuberculosis (an obligate aerobic rod, is not suitable for Gram staining due to high lipid content of the cell wall), is a slow growing organism and cultures may take 6-8 weeks to grow.
Q. How is acid-fast staining performed? What is the basis behind this stain?
A. Acid-fast staining may be performed in the following way. First, a fixed smear of the bacteria is covered on a slide with a piece of blotting paper. This is then stained with carbol fuchsin for 2 minutes. The blotting paper is then removed and the stain is decolourised with a mixture of HCl and ethanol for 10-15 seconds and rinsed. The stain is then restained with crystal violet for 1 minute and rinsed again.
When viewed under oil immersion, acid-fast cells appear pink, whereas non-acid-fast cells appear purple.
Q. Are there any other investigations to potentially confirm the presence of TB?
A. Yes, a molecular biologic technique called polymerase chain reaction (PCR) using pooled urine samples to amplify M. tuberculosis species-specific DNA by in vitro enzymatic replication is also available.
Q. Does the tuberculin test have a role in the diagnosis of urinary TB?
A. This is a skin test involving an intradermal injection of a purified protein derivative of M. tuberculosis. A positive result suggests an exposure to TB, not necessarily an active infection. The importance is that in a patient with suspected TB, a positive tuberculin test is consistent with the diagnosis, a negative test excludes it.
Q. How is TB acquired?
A. Primary TB is usually acquired in childhood by inhalation of infected droplets causing deposition of bacilli in the lungs. In immunocompetent individuals, this primary infection is self-limiting or subclinical. Clinical features may later develop as post-primary manifestations at times of reduced immunity. The spread of infection from lungs to the urinary system is haematogenous and starts in the kidney, from where it spreads by direct extension to the ureters and bladder. In the genital tract, the primary site of involvement by haematogenous spread is the epididymis in males and fallopian tubes in females, from where it may spread by direct extension to adjacent organs such as the testes, prostate, and uterus.
Q. What are the pathological manifestations of urinary TB?
A. The pathognomonic lesion of TB is a caseating granuloma, which comprises Langhans giant cells surrounded by lymphocytes and fibroblasts. The healing of these lesions results in fibrosis and calcification. That is the reason for the scarring, calcification and parenchymal destruction and distortion seen with healed TB. The kidney classically becomes small, shrunken and distorted, resulting, in extreme cases, in ‘autonephrectomy’. The calyceal necks as well as the ureters may develop strictures most commonly in the region of vesico- uretric junction (VUJ). ttere may be distortion of ureteric orifices (golf-hole appearance) leading to reflux (VUR). In the bladder, active lesions show bullous oedema, ulceration and haemorrhage. Chronic lesions in the bladder may take the form of discrete stellate appearance or the whole bladder may become small and fibrotic (thimble bladder).
Q. What is this investigation in Figure 9.1 and what does it show?
Figure 9.1 Coronal CT scan of the abdomen.
A. Figure 9.1 is a coronal reconstruction of a computed tomography (CT) scan of the abdomen showing right renal upper pole cortical atrophy, linear calcification in the upper pole calyx with infundibular stenosis, lower pole hydronephrosis and dilated proximal ureter with a long distal ureteric stricture.
Q. What is your radiological investigation of choice?
A. I would ideally request a CT urogram or an intravenous urography (IVU) to assess the anatomy, the presence of calcification, parenchymal destruction or areas of narrowing.
Q. How would you manage this patient?
A. In my experience, genito-urinary TB is still rare and may be complicated. In accordance with National Institute for Health and Care Excellence (NICE) TB guidelines (2016), the clinician responsible for care should refer the person with TB to a clinician with training in, and experience of, the specialised care of people with TB. Thus I believe the patient is best managed in a multidisciplinary team setting involving shared care between urologists, microbiologists and respiratory physicians. The mainstay of management is usually medical treatment with multidrug antituberculous therapy with isoniazid (with pyridoxine), rifampicin, pyrazinamide and ethambutol for 2 months then isoniazid (with pyridoxine) and rifampicin for a further 4 months.
Q. Why is TB treated with three or four drugs?
A. Multidrug anti-TB regimens are used to achieve prompt bacterial eradication, to decrease the duration of therapy and to decrease the likelihood of development of drug-resistant organisms.
Q. Can you describe the names, dosages and common side effects of anti-tuberculous drugs?
A. The names, dosages and common side effects of anti-tuberculous drugs are listed in Table 9.2.
Table 9.2 Names, dosages and common side effects of anti-TB medication
|
Drug |
Dose (mg/kg) |
Associated side effects |
|
Isoniazid (INH) |
5 |
Hepatotoxicity, peripheral neuropathy |
|
Rifampicin |
10 |
Hepatotoxicity, orange discoloration of urine |
|
Pyrazinamide |
20 |
Hepatotoxicity, arthralgia |
|
Ethambutol |
20 |
Retrobulbar neuritis, reduced visual acuity, altered colour vision with reduced red-green discrimination |
Q. Is there a role for the use of steroids n the management of urinary TB?
A. Steroids are indicated in cases of ureteric stricture not responding to anti-tuberculous therapy alone in 4-6 weeks on serial IVU or CT urogram.
Q. Which patients are high risk for multi-drug-resistant TB and what should you do?
A. Patients with a history of previous TB drug treatment, especially with a known poor adherence to treatment, contact with a known case of multi-drug-resistant TB and birth or residence in a country in which the World Health Organization (WHO) reports that a high proportion (5% or more) of new TB cases are multidrug resistant.
For people with clinically suspected multi-drug-resistant TB, a TB specialist should request rapid diagnostic nucleic acid amplification tests for rifampicin resistance on primary specimens.
Q. What are the radiological manifestations of genito-urinary TB?
A. Radiologically the following may be seen: small shrunken kidneys, calyceal distortion, infundibular stenosis, cavitation, calcification, ureteric dilatation proximal to a VUJ stricture, multiple ureteric strictures or a contracted and calcified bladder. There may be the presence of pelvic calcification secondary to calcification of vas, seminal vesicle or prostate.
Q. What is the radiological investigation of choice?
A. I would ideally request a CT urogram or an IVU.