Eosinophilic cystitis: Review and report of two cases
Luis F. Ebel Sepulveda*, A. Foneron**, L. Troncoso*, R. Cañoles*, C Carrasco**, A. Hornig*, G. Gil*, D. Corti*
ACTAS UROLÓGICAS ESPAÑOLAS 2009;33(4):443-446
Abstract
Eosinophilic cystitis is a low frequency disease, with less than 200 reported cases in the world. It is characterized by bladder wall inflammation, mainly by eosinophils, with fibrosis and muscle necrosis areas. Its origin seems to be immunological, although the triggering factors are not well known. Several predisposing factor have been described such as allergic diseases, bladder injuries, drugs, infections, etc. It affects patients of all ages, mainly adults. It presents with frequency, hematuria and suprapubic pain. Other less frequent symptoms are dysuria, urinary retention, nicturia, and enuresis. Laboratory (urine sediment, urine culture and complete blood count) and radiological (ultrasound, intravenous pyelography, computed tomography and nuclear magnetic resonance) findings are nonspecific. The lesions observed in cystoscopy may mimic other diseases, which is why definitive diagnosis is histological. Management can be observation or antihistamine, antiinflammatory and corticosteroid treatment. In refractory cases, surgery is an alternative.
We report the cases of two male patients with their symptoms, studies and management.
Keywords: Cystitis. Eosinophilic cystitis. Eosinophilia. Bladder
Eosinophilic cystitis (EC) is a rare disease characterized by transmural inflammation of the bladder predominantly by eosinophils, which causes mucosal thickening and fibrosis, with or without muscle necrosis. It was first described by Brown1 and Palubinskas2 in 1960, and since then fewer than 200 cases have been reported worldwide3,4.
The importance of its knowledge lies in that its clinical symptoms mimic other more common diseases (interstitial cystitis, urinary infections, bladder neoplasms), but its management is completely different.
Epidemiology
The incidence of EC is extremely low. It affects patients of all ages, but mainly adults (83%)5. It is equally distributed between men and women, but in children boys are affected more often than girls3,4.
Although risk factors have not been defined, it has been associated with other diseases such as bronchial asthma, atopy, eosinophilia, parasite infections6, bladder neoplasms1,7,8, bladder trauma9, eosinophilic enteritis10, and urinary infections11. There are reports of EC related to the use of certain drugs such as cyclophosphamide, coumarin, tranilast, penicillin, and mitomycin C12-16.
Pathophysiology
It is thought that the origin of the disease is immunological. It would be initiated with the arrival of an antigen to the bladder, which binds to an antibody (predominantly IgE) forming an antigen-antibody complex that it deposited on the bladder wall and activates mast cells and eosinophils. These release enzymes and interleukins triggering inflammation. Interleukin-5 is an important factor because it attract a larger amount of eosinophils and macrophages, which in turn release more IL-5, perpetuating the disease17-20.
Clinical Presentation
The most common presenting symptoms are frequency, hematuria and suprapubic pain, but these lack specificity3,4. Other less common symptoms are dysuria, urinary retention, nicturia, enuresis, urinary incontinence and abdominal mass6,21. In 63% of children, EC presents with an intravesical tumor21. Of patients who present with urinary retention, 79% are women or children3,4.
The course of the disease varies depending on age at presentation. It tends to be self-limiting in children, while in adults it usually has a chronic course with periodic recurrences22,23.
Studies
Urine sediment can reveal hematuria, pyuria and proteinuria. Eosinophiluria is rare and nonspecific. Urine cultures are usually negative3.
Eosinophilia (>1500 eosinophils/ml) is present in few cases, especially in patients with associated allergic diseases. It is correlated with higher disease activity24.
Renal function is normal, except in cases of bladder or ureteral obstruction by fibrosis20,23,25,26.
Echotomography is usually normal, but may show thickening of the bladder wall and dilatation of the urinary excretory system. On excretion pyelography, bladder filling defects, ureterohydronephrosis or renal exclusion can be observed in advanced cases. The findings on axial computed tomography are similar, often mimicking other neoplastic processes3,4.
On cystoscopy, edematous, erythematous, polypoid lesions can be observed that are difficult to differentiate from those caused by bladder tuberculosis, interstitial cystitis, transitional cell carcinoma, carcinoma in situ and sarcomas27,28. There are no bladder areas that are more frequently affected.
Definitive diagnosis is histopathological, revealing transmural inflammation of the bladder predominantly by eosinophils, more marked in the lamina propria. There may be muscle necrosis with variable degrees of fibrosis, especially in chronic processes (Fig. 1 and 2)29. It should not be confused with the presence of eosinophils in the bladder, which can be due to trauma, infections, tumors, etc.
Eosinophilic infiltration of the bladder has been reported in 2% of patients with bladder cancer. These have a lower recurrence rate (28% vs 43%)34.
FIGURE 1. A dense inflammatory infiltrate compromising the submucosa can be seen. There is loss of urothelium with fibrin deposits. Hematoxylin-eosin, 10x.
FIGURE 2. Same case as before. The inflammatory infiltrate is mixed with predominance of eosinophils. Hematoxylin-eosin, 40x.
Treatment
Conservative management is recommended, especially in asymptomatic patients. Children should be initially observed given the high possibility of spontaneous remission21,22. Adults usually require medication.
When a drug reaction is suspected, the suspect drugs should be discontinued. Initial treatment should include antihistamines and nonsteroidal anti-inflammatory drugs. It is recommended to start with hydroxyzine 20 mg every 8 hours. If somnolence occurs, the patient should be changed to another antihistamine (eg, cetirizine). In refractory or severe cases presenting with ureteral infiltration, corticosteroids should be added3,4,32. The success rate of this therapy is almost 80% and 100% when corticosteroids are added3.
When intravesical polypoid lesions are present, given the suspicion of bladder cancer, they should be completely resected. This permits correct diagnosis and may sometimes be therapeutic33.
Associated urinary infections should be treated according to urine culture and antibiotic susceptibility testing.
Other drug treatments described are the use of dimethylsulfoxide34, cyclosporine A35, azathioprine, silver nitrate, and montelukast24.
Approximately 7% of cases show an aggressive course with progressive destruction of the upper urinary tract, recurrent hematuria and impaired bladder function, which are unresponsive to medical treatment23. In these cases, nephroureterectomies, partial or total cystectomy36 and augmentation cystoplasties37 have been performed.
Case Report
Case 1:
A 34-year-old man seen for suprapubic pain, frequency and nicturia. Laboratory findings were unremarkable. Cystoscopy showed glomerulations on bladder distention. Random bladder biopsy revealed a bladder mucosa with perivascular infiltrate and multiple eosinophils. Eosinophilic cystitis was diagnosed. The patient was initially treated with intravesical instillations of heparin and corticosteroids, but urinary frequency of 20/6 persisted. Amitriptyline, oxybutynin and tolteridone were subsequently used with no response. The urodynamic study revealed an sensitive unstable bladder during the continence phase. A repeat cystoscopy was performed without significant findings. A repeat biopsy revealed nonspecific inflammation. Treatment was started with hydroxyzine 20 mg every 8 hours and sodium diclofenac 50 mg every 8 hours, with a good response. Pain remitted and urinary frequency decreased to 6/0, with increased voiding volume. The antihistamine was changed to cetirizine because of somnolence, with an identical response.
Case 2:
A 43-year-old man who was seen for an elevated urinary frequency of 8/4, with gross hematuria. His history included a recent bladder biopsy revealing chronic cystitis. An excretion pyelography and computed tomography of abdomen and pelvis were performed, which were normal. On cystoscopy, the bladder appeared erythematous with a papillary lesion in the bladder floor. The biopsy taken reported eosinophilic cystitis. Treatment was started with hydroxyzine 20 mg every 12 hours and sodium diclofenac 50 mg every 8 hours. There was a partial response, with remission of hematuria, but urinary frequency of 5/3 persisted. When prednisone 20 mg/day was added, all pain/discomfort disappeared and urinary frequency returned to normal.
CONCLUSIONS
Eosinophilic cystitis is an unusual disease whose improvement depends on an exact diagnosis. The reports in the literature reveal that it is diagnosed incidentally in most cases.
Treatment should be specific for this type of cystitis, and when the diagnosis is not available, empirical treatment is not indicated.
A complete study including bladder biopsy is required for its diagnosis.
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Source: Servicio de Urología – Hospital Regional de Valdivia y Departamento de Urología – Universidad Austral de Chile
**Servicio de Anatomía Patológica – Hospital Regional de Valdivia .Universidad Austral de Chile Chile.
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