Eosinophilic Cystitis

Eosinophilic cystitis is a rare inflammatory disease of the bladder in which eosinophils infiltrate the mucosa and muscle, sometimes with muscle necrosis and fibrosis.

It is seen in children, where it is usually allergic and self-limiting, and in adults, where it is more often linked to bladder trauma, instrumentation or a tumour.

Reported triggers are atopy and food allergy, drugs (penicillins, cyclophosphamide and other chemotherapy, non-steroidal anti-inflammatory drugs, tranilast), intravesical therapy (BCG, mitomycin C, thiotepa), previous transurethral resection, parasitic infection (Schistosoma, Toxocara, Echinococcus), bacterial infection, systemic eosinophilia and eosinophilic gastroenteritis.

No cause is found in a large share of cases.

Pathophysiology. Antigen exposure or urothelial injury draws eosinophils into the bladder wall, where degranulation releases major basic protein and other toxic mediators that injure the urothelium and muscle.

Repeated injury leads to ulceration, oedema, fibrosis and reduced capacity.

Frequency, urgency, dysuria, suprapubic pain, haematuria, nocturia and occasionally retention. Some have hydronephrosis from ureteric orifice involvement or a bladder mass. Ask about allergy, asthma, eczema, previous instrumentation, intravesical drugs, travel or water contact in endemic areas, and bowel symptoms. Peripheral eosinophilia is present in a minority, roughly 20 to 40%.

• Urinalysis, culture, urine cytology, full blood count with eosinophil count, creatinine and electrolytes.
• Stool and urine microscopy for ova, and serology for Schistosoma and Toxocara where exposure is possible.
• Renal and bladder ultrasound, and CT or MRI when a mass or hydronephrosis is present. Findings include wall thickening and a mass that can mimic cancer.
• Cystoscopy with deep biopsy including muscle: erythema, oedema, ulceration, or polypoid and papillary lesions.
• Histology: dense eosinophilic infiltrate, oedema, and in later disease muscle necrosis and fibrosis. Exclude carcinoma, which can coexist.

Differential diagnosis.

• Urothelial carcinoma including carcinoma in situ
• Schistosomal cystitis
• Tuberculous cystitis
• Interstitial cystitis or bladder pain syndrome
• Malakoplakia
• Inflammatory pseudotumour
• Radiation or drug induced cystitis
• Bacterial cystitis
• Eosinophilic granulomatosis with polyangiitis

• Remove the trigger: stop the suspected drug, treat any infection with culture directed antibiotics, and avoid known allergens.
• Parasitic cause: praziquantel 40 mg/kg orally in two divided doses on one day for Schistosoma. Other parasites need the specific antiparasitic agent.
• Transurethral resection of papillary or mass lesions serves for diagnosis, and bleeding can be controlled at the same time.
• Antihistamine: cetirizine 10 mg orally once daily for adults, reduced to 5 mg once daily when eGFR is under 30. Use in mild disease and in children.
• Corticosteroid for moderate to severe or persistent disease: prednisolone 0.5 to 1 mg/kg orally once daily (maximum 60 mg) for 2 to 4 weeks, then taper over 4 to 8 weeks. Children: 1 mg/kg once daily. Evidence is from case series only.
• Refractory disease: azathioprine 1 to 2 mg/kg orally once daily, after testing thiopurine methyltransferase activity, with monthly blood count and liver tests for the first 3 months.
• Children: most resolve with trigger removal and antihistamine over weeks to months.
• Surgery (augmentation cystoplasty or cystectomy) is rare, for a fibrotic small capacity bladder or failure of medical treatment.

Special groups. Children need weight based dosing and a search for food and drug allergy. In adults, a persisting mass needs repeat biopsy because carcinoma can coexist.

Monitoring. Symptom review at 4 weeks. Repeat eosinophil count and ultrasound at 3 months. Repeat cystoscopy at 3 months, or earlier if haematuria persists.

Referral and escalation. Refer to urology for biopsy. Urgent referral for clot retention, hydronephrosis or a mass of uncertain nature.