Tuberculous Cystitis

Tuberculous cystitis is infection of the bladder by Mycobacterium tuberculosis, almost always secondary to renal tuberculosis, with spread by infected urine from the kidney.

Genitourinary disease makes up about 5 to 10% of extrapulmonary tuberculosis and may appear years after the primary infection. Risk is increased by HIV infection, diabetes, immunosuppression, kidney disease and endemic exposure.

Untreated, it progresses to ulceration, fibrosis, a contracted thimble sized bladder, vesicoureteric reflux and ureteric stricture.

Pathophysiology. Mycobacteria shed from renal lesions seed the bladder mucosa near the ureteric orifices, forming tubercles and ulcers. Healing leads to fibrosis and calcification.

The ureteric orifice becomes rigid and patulous (golf hole orifice), allowing reflux, while fibrosis of the intramural ureter causes obstruction and hydronephrosis.

Frequency, nocturia, dysuria and urgency that persist despite antibiotics, haematuria, suprapubic pain and sterile pyuria on routine culture. Loin pain, fever, weight loss and night sweats suggest renal or systemic disease. Late disease gives a small capacity bladder with incontinence. Ask about previous tuberculosis, contacts, HIV and immunosuppression.

• Three early morning urine samples for acid fast smear, culture on solid and liquid media, and a nucleic acid amplification test with rifampicin resistance detection. Culture remains necessary for drug susceptibility.
• Routine urine culture is usually negative (sterile pyuria), with secondary bacterial infection in some.
• Chest radiograph, HIV test, blood glucose, creatinine, liver function tests. A tuberculin skin test or interferon gamma release assay supports but cannot confirm active disease.
• CT urography: renal calcification and scarring, caliceal destruction, ureteric strictures, hydronephrosis, calcified or contracted bladder.
• Cystoscopy: oedema, tubercles, ulcers, golf hole ureteric orifice, and reduced capacity. Biopsy for histology (caseating granulomas) and culture, with care in an acutely inflamed bladder.

Differential diagnosis.

• Bacterial cystitis
• Interstitial cystitis or bladder pain syndrome
• Schistosomal cystitis
• BCG cystitis after intravesical therapy
• Carcinoma in situ
• Eosinophilic or radiation cystitis
• Encrusted cystitis

• Usual six month regimen: 2 months of isoniazid, rifampicin, pyrazinamide and ethambutol, then 4 months of isoniazid and rifampicin, adjusted to susceptibility. Adult daily doses:
  • Isoniazid 5 mg/kg (usual maximum 300 mg).
  • Rifampicin 10 mg/kg (usual maximum 600 mg).
  • Pyrazinamide 25 mg/kg (range 20 to 30 mg/kg).
  • Ethambutol 15 mg/kg (range 15 to 20 mg/kg).
  • Pyridoxine 10 to 25 mg once daily with isoniazid.
• Fixed dose combinations aid adherence. Take on an empty stomach where tolerated.
• Renal impairment: when eGFR is under 30, give pyrazinamide and ethambutol three times weekly rather than daily, and monitor drug exposure.
• Hepatotoxicity: stop the hepatotoxic drugs if ALT is over 5 times the upper limit of normal, or over 3 times with symptoms or jaundice, then reintroduce sequentially under specialist care.
• Ethambutol: check visual acuity and colour vision before and during treatment, and avoid it where acuity cannot be monitored.
• Rifampicin induces many enzymes, reducing exposure to hormonal contraception, warfarin, tacrolimus, ciclosporin and many antiretrovirals. With dolutegravir, give 50 mg twice daily during rifampicin and for 2 weeks after.
• Corticosteroid to reduce ureteric fibrosis is used by some in early stricture disease, with weak evidence.
• Surgery after drug therapy has begun: ureteric stent or nephrostomy for obstruction, ureteric reimplantation or reconstruction for stricture after 4 to 6 weeks of treatment with stable disease, augmentation cystoplasty for a contracted bladder after treatment is complete, and nephrectomy for a non-functioning, calcified kidney.
• Drug resistant disease needs a specialist regimen directed by susceptibility results.

Special groups. HIV infection needs coordination of antiretroviral therapy and rifampicin dosing. In pregnancy, the usual four drug regimen is used without streptomycin. Children use weight based dosing.

Monitoring. Liver tests at baseline and at 2 and 4 weeks, then as needed. Urine culture at 2 months and end of treatment. Ultrasound at 3 and 6 months for hydronephrosis, then at 12 months, since strictures can form after cure. Bladder capacity and symptoms at the end of treatment.

Referral and escalation. Refer to infectious disease or chest medicine for treatment and to urology for obstruction and reconstruction. Urgent referral for hydronephrosis with renal impairment, sepsis or suspected drug resistant disease.