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Tuberculosis

Overview

  • WHO estimates one quarter of world infected with latent TB
  • 2016 – 10 million new cases, 1.7 million deaths
    • Mainly 8 countries – India, China, Indonesia, Philippines, Pakistan, Nigeria, Bangladesh and South Africa
  • Slow global decline since the 90s with BCG vaccine
  • Emerging problems with HIV/TB and multi-drug resistance
  • Affects men > women 2:1

 

Tuberculosis is a condition caused by a group of closely related acid-fast bacilli together called the mycobacterium tuberculosis complex

  • Mycobacterium tuberculosis
  • Mycobacterium bovis
  • Mycobacterium africanum
    etc

There organisms have similar clinical features regarding the infection they cause, but drug susceptibilities may differ

 

Pathology of TB and urogenital TB

  • Initial mode of entry is via lungs – usually from cough generated infectious aerosols
  • Bacilli reach the alveoli – phagocytosed by alveolar macrophages
    • In a minority of cases – the infection is immediately cleared
    • 90 % of cases – this primary infection triggers an inflammatory response and cytokine cascade -> formation of granulomas responsible for latent TB
    • 5 – 10 % of cases – immediate active disease, usually locally in the lungs but can be extra-pulmonary
  • Therefore 5 – 10 % of those infected progress to active disease, and 90 % develop latent disease or immediately clear it
  • In active TB it can take 12 – 24 months to develops signs or symptoms
  • Lifetime risk of “reactivation TB” from latent disease is 5 – 15 %, higher in those with risk factors

 

Urogenital TB

  • Direct haematogenous or lymphatic spread of the mycobacterium from the lungs results in seeding of the urogenital tract
    • Primarily the kidney and epididymis – then ascending or descending spread to other organs
  • 15 % of cases of TB are extra-pulmonary
    • 15 – 40 % of extra-pulmonary cases will involve the urogenital organs
    • Urogenital organs second more common extra-pulmonary site, after lymphatic system
  • Symptoms and signs of TB are specific to the affected organ – but can be general in nature (“the great mimicker”)
  • Other rarer mechanisms of development of genitourinary TB are from BCG, contiguous spread from other organs, or very rarely direct inoculation

 

  • TB causes its pathology through a combination of caseation and cavitation, and subsequent healing by fibrosis and scarring

 

Risk factors

These are risk factors for both primary infection and latent re-activation:

  • Living in endemic location for primary infection
  • Malnutrition
  • HIV infection
  • Diabetes
  • Immunosuppression
  • Chronic renal and liver disease
  • Alcohol and substance abuse
  • Smoking
  • Homelessness or poor housing/overcrowding

 

Clinical manifestations of urogenital TB

Symptoms and signs are often non-specific and the diagnosis is often made late.

 

Renal – most commonly involved – 80 % of urogenital TB affects the kidney

  • Slowly progressive and often minimal symptoms over years of damage
  • Usually bilateral
  • May be minimally evident on imaging, but granulomatous interstitial nephritis may cause renal failure
  • Calcification and fibrosis
  • Parenchymal abscesses and scarring
  • Papillary necrosis (“moth eaten calyces”)
  • Infundibular stenosis with calyceal dilation – dilated calyces filled with caseous material (“putty kidney”)
  • Nephrocutaneous fistulae are rare
  • End stage = auto-nephrectomy – up to one third of renal TB

 

Ureter – TB in the ureter descends from the kidney as bacilli pass in the urine

  • Typically distal third, then proximal/PUJ next most commonly affected
  • Urothelial thickening including in renal pelvis
  • Ureteric stricture most common finding
  • Granulomas form in the ureteric wall
  • Fibrosis and stricturing (“beaded” ureter, “corkscrew” ureter)
  • Rigid fibrosis can inhibit peristalsis – “pipe stem” ureter
  • -> reflux and obstruction -> renal failure

 

Bladder – descending infection from renal TB (or rarely from intravesical BCG)

  • Early signs just mucosal irritation and oedema
  • Granulomas form in the urothelium
  • Chronic inflammation of the trigone and UO -> golf hole UO -> reflux and stricturing
  • Progressive fibrosis and thickening of bladder wall -> significantly reduced bladder capacity (“thimble bladder”)
    • Frequency, urgency, dysuria and pain
  • Rarely can fistulate to other organs

 

Prostate – rare, developing from either haematogenous spread or urinary spread

  • Chronic inflammation – granulomatous prostatitis
  • Caseating necrosis
  • Abscesses
  • Calcification
  • Perineal fistula
  • Tracking to seminal vesicles -> calcification and infertility

 

Scrotal contents – epididymis is the second most commonly affected organ after the kidney

  • Often bilateral epididymo-orchitis
  • Progresses to draining scrotal sinus
  • May also just be a non tender very enlarged epididymis
  • Testicular involvement occurs later, with direct invasion from the epididymis
  • Classic “beaded” vas due to fusiform swellings
  • Scarring and stricturing of the vas deferens -> obstructive azoospermia infertility

 

Other organs:

  • Urethral involvement is rare – usually manifesting as urethral stricture
  • Female pelvic organs can be involved – uterine tubes most commonly, then endometrium, ovaries and cervix -> significant contributor to female infertility in affected areas
  • Adrenals – TB may invade and cause adrenal necrosis and calcification, may present as Addison’s

Classic things which may raise suspicion of TB (esp in those from endemic areas)

  • Sterile pyuria
  • Chronic cystitis not responding to usual treatment
  • Haematuria
  • Non tender enlarged epididymis
  • Scrotal sinus or urethrocutaneous fistula
  • Unexplained parenchymal calcification

 

 

Assessment and work-up for TB

History:

  • Flank pain
  • Haematuria
  • Urinary symptoms
  • Fevers, night sweats, systemic symptoms
  • Travel history
  • History of personal TB or close contacts
  • Medical history / immunosuppression / medications
  • Previous surgery

Examination:

  • General examination
  • Abdominal masses
  • Flank tenderness
  • Genital exam – epididymal masses, beaded vas, sinuses/fistulae
  • Prostate exam

 

Investigation as appropriate – CT IVP, ultrasound, cystoscopy, RPGs, urine cytology, urine culture, bloods incl renal function, special diagnostic tests to confirm TB diagnosis + chest imaging to establish concurrent pulmonary TB

 

Diagnosis of urogenital TB

There is no single easy confirmatory test for diagnosing urogenital tuberculosis – the diagnosis is made with a combination of history, imaging, examination, biopsies and cultures.

The gold standard is culture of urine or tissue for mycobacterium

  • Traditional Lowenstein-Jensen culture media takes up to 6 weeks
  • 3 consecutive early morning first void samples increases sensitivity
  • Tissue biopsies should be sent fresh in saline, not in formalin
  • Culture also allows determination of drug susceptibilities

Urine microscopy for acid fast bacilli (AFB) can provide interim support for the diagnosis.

  • Uses Ziehl-Neelsen staining
  • Sensitivity increases with multiple samples – recommended 3 continuous early morning first void samples

Tissue histology may not demonstrate mycobacterium but if showing caseating granulomas in the right clinical context will support the diagnosis of TB.

Gene Xpert (nucleic acid amplification test NAAT) is a real time quantitative PCR assay which amplifies M.tuberculosis DNA

  • Higher sensitivity cf. urine microscopy for AFB and as specific
  • Results in < 1 day
  • Does not replace culture as the gold standard for diagnosis

Quantiferon gold and the tuberculin skin test has no role in the diagnosis of active TB – it cannot be used to rule in or rule out infection. It is used as screening for latent TB.

 

Management of urogenital TB

  1. Treat any emergencies such as obstruction
  2. Establish the diagnosis
  3. Medical management, in conjunction with ID
  4. Surgical management

 

Medical management is multi-disciplinary, generally led by infectious disease specialists.

  • 6 months of isoniazid and rifampicin
  • With addition of ethambutol and pyrazinamide in the first two months
  • May need longer treatments if resistance, or immunosuppressed
  • 90 % cure rate
  • Consider directly observed treatment if concerns over compliance
  • Requires monitoring with bloods, risk of liver dysfunction, risk of optic neuritis with ethambutol, give pyridoxine with avoid peripheral neuropathy with isoniazid, rifampicin causes red urine

 

Medical management may not obviate the need for surgical treatments, as the affected organs heal with fibrosis which can cause complications.

 

Surgical management is case by case and often diagnostic and therapeutic procedures are concurrent.

  • Relieve obstruction
  • Drain infection and abscesses
  • Nephrectomy indicated if non functioning kidney harbouring ongoing TB despite treatment, or in resistant hypertension (65 % hypertension improves)
    • Often difficult due to surrounding fibrosis
  • Ureteric reconstruction (anastomotic or substitution, avoid TUU)
  • Bladder reconstruction or diversion

 

  • Ideally – 6 weeks of anti-TB treatment prior to surgery