Malakoplakia of the Bladder

Malakoplakia is a chronic granulomatous inflammatory condition caused by defective intracellular killing of bacteria by macrophages, so that partly digested bacteria collect as characteristic calcified inclusions.

The urinary tract, and especially the bladder, is the commonest site.

It occurs mostly in middle aged and older women, and in immunosuppressed patients: kidney transplant recipients, those on corticosteroids or chemotherapy, HIV infection, diabetes, autoimmune disease and malignancy.

Escherichia coli is the organism in most cases, with Proteus, Klebsiella and Enterococcus reported less often.

Pathophysiology. Reduced macrophage cyclic guanosine monophosphate and lysosomal enzyme activity impair bacterial degradation. Undigested bacterial fragments become coated with calcium and iron within phagolysosomes, forming Michaelis-Gutmann bodies.

Lesions are soft yellow brown plaques or nodules in the mucosa that enlarge and can ulcerate, obstruct the ureters or involve the kidney.

Recurrent urinary tract infection, dysuria, frequency, haematuria, suprapubic pain, and sometimes a pelvic mass. Ureteric involvement causes hydronephrosis and rising creatinine. Bilateral renal involvement presents as renal failure and fever. Ask about immunosuppression, transplantation, diabetes and chronic infection.

• Urine culture, which is usually positive for a Gram negative organism, plus creatinine, blood glucose and HIV test.
• Renal and bladder ultrasound, and CT or MRI for mass lesions, hydronephrosis and renal involvement.
• Cystoscopy: soft yellow or brown plaques or nodules about 1 to 4 cm across, with a surrounding erythematous rim, sometimes ulcerated or polypoid. The picture mimics carcinoma.
• Biopsy is diagnostic: sheets of foamy macrophages with granular eosinophilic cytoplasm (von Hansemann cells) containing Michaelis-Gutmann bodies, which stain with periodic acid-Schiff, von Kossa and iron stains. Send tissue for culture.

Differential diagnosis.

• Urothelial carcinoma
• Tuberculous cystitis
• Xanthogranulomatous inflammation
• Cystitis glandularis
• Eosinophilic cystitis
• Encrusted cystitis
• BCG granulomatous cystitis
• Schistosomal cystitis

• Antibiotics with good intracellular penetration for at least 3 to 6 months, continued until the lesions resolve at cystoscopy. Use culture sensitivity to choose:
  • Ciprofloxacin 500 mg orally every 12 hours, with the dose and interval reduced when eGFR is under 30.
  • Co-trimoxazole 960 mg orally every 12 hours, halved when eGFR is 15 to 30 and avoided when under 15.
  • Doxycycline 100 mg orally every 12 hours, or rifampicin 600 mg orally once daily, as alternatives, with attention to the interactions of rifampicin with immunosuppressants.
• Fluoroquinolone cautions: tendon rupture (greater with corticosteroids, transplant and age over 60), QT prolongation, dysglycaemia, aortic aneurysm and neuropsychiatric effects. Use only when alternatives are unsuitable.
• Bethanechol 25 mg orally three times daily with ascorbic acid 500 mg orally once daily has been used in small series to correct the macrophage defect. It must not be used with outlet obstruction. Evidence is weak.
• Reduce immunosuppression and treat diabetes where this is clinically possible.
• Transurethral resection of lesions for diagnosis and for large or obstructing plaques. Relieve ureteric obstruction by stent or nephrostomy.
• Cystectomy or nephrectomy is rare, for destroyed organs or refractory disease. Relapse after treatment is not uncommon.

Monitoring. Creatinine at each visit, and ultrasound at 3 months. Cystoscopy with repeat biopsy at 3 to 6 months, and again 3 months after stopping antibiotics. Review for relapse for at least 2 years.

Referral and escalation. Refer to urology and infectious disease, and to nephrology in transplant recipients. Urgent referral for hydronephrosis, rising creatinine or sepsis.