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
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.
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.
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.
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.
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.
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.
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.
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.
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.
1. Brown EW. Eosinophilic granuloma of the bladder. J Urol 1960;83:665–668. [PubMed]
2. Palubinskas AJ. Eosinophilic cystitis: case report of eosinophilic infiltration of the urinary bladder. Radiology 1960;75: 589–591.[PubMed]
3. Van den Ouden D. Diagnosis and management of eosinophilic cystitis: a pooled analysis of 135 cases. Eur Urol 2000;37(4):386-394.[PubMed]
4. Teegavarapu P, Sahai A, Chandra A, Dasqupta P, Khan MS. Eosinophilic Cistitis and its management. Int J clin Pract 2005;59(3):356-360. [PubMed]
5. Thompson H, Dicks D, Kramer S. Clinical Manifestations and funtional outcomes in children with eosinophilic cystitis. J Urol 2005;174(6):2347-49.[PubMed]
6. Perlmutter AD, Edlow JB, Kevy SV. Toxocara antibodies in eosinophilic cystitis. J Pediatr 1968;73(3): 340-344.[PubMed]
7. Constantides C, Gavras P, Stinios J, Apostolaki C, Dimopoulos C. Eosinophilic cystitis: a rare case which presented as an invasive bladder tumour. Acta Urol Belg 1994;62(4):71-73.[PubMed]
8. Kilic S, Erguvan R, Ipek D, Gokce H, Gunes A, Aydin NE et al. Eosinophilic cystitis: a rare inflammatory pathology mimicking bladder neoplasms. Urol Int 2003;71(3):285-289.[PubMed]
9. Hellstrom HR, Davis BK, Shonnard JW. Eosinophilic cystitis: A Study of 16 cases. Am J Clin Pathol 1979;72(5):777-784. [PubMed]
10. Gregg JA, Utz DC. Eosinophilic cystitis associated with eosinophilic gastroenteritis. Mayo Clin Proc 1974;49(3):185-7.[PubMed]
11. Goldstein M. Eosinophilic cystitis. J Urol 1971;106(6):854-857.[PubMed]
12. Inglis JA, Tolley DA, Grigor KM. Allergy to mitomycin-C complicating topical administration for urothelial cancer. Br J Urol 1987;59(6):547–549.[PubMed]
13. Nakada T, Ishikawa S, Sakamota M, Katayama T, Iqarashi T, Mizimura Y et al. N-(3´, 4´-dimethoxycinnamoyl) anthrallic acid, an anti allergic compound, induced eosinophilic cystitis. Urol Int 1986;41(6):457–464.[PubMed]
14. Okada H, Minayoshi K, Goto A. Two cases of eosinophilic cystitis induced by tranilast. J Urol 1992;147(5):1366-1368.[PubMed]
15. Ulker V, Apaydin E, Gursan A, Ozyurt C, Kandiloglu G. Eosinophilic cystitis induced by mitomycin-C. Int Urol Nephrol 1996;28:755-759.[PubMed]
16. Clark T, Chang SS, Cookson MS. Eosinophilic cystitis presenting as a recurrent symptomatic bladder mass following intravesical mitomycin C therapy. J Urol 2002;167(4):1795.[PubMed]
17. Frensilli FJ, Sacher EC, Keegan GT. Eosinophilic cystitis: observations on etiology. J Urol 1972; 107(4): 595–596.[PubMed]
18. Rubin L, Pincus MB. Eosinophilic cystitis: the relationship of allergy in the urinary tract to eosinophilic cystitis and the pathophysiology of eosinophilia. J Urol 1974;112:(4) 457-60.[PubMed]
19. Dubucquoi S, Janin A, Desreumaux P, Rigot JM, Copin MC, Francois M et al. Evidence for eosinophil activation in eosinophilic cystitis. Eur Urol 1994; 25(3):254-258.[PubMed]
20. Dubucquoi S, Desreumaux P, Janin A et al. Interleukin 5 synthesis by eosinophils: association with granules and immunoglobulin-dependent secretion. J Exp Med 1994;179(2):703-708.[PubMed]
21. Van den Ouden D, Van Kaam N, Eland D. Eosinophilic cystitis presenting as urinary retention. Urol Int 2001;66(1): 22–26. [PubMed]
22. Baquedano P, Nardiello A, Monje M. Cistitis Eosinofílica: Reporte de un caso. Rev Chil Urol 2003; 68 (2): 207-210
23. Itano NM, Malek RS. Eosinophilic cystitis in adults. J Urol 2001;165: 805–807. [PubMed]
24. Sterrett S, Morton J, Perry D, Donovan J. Eosinophilic Cystitis: Successful long-term treatment with MonteluKast Sodium. Urology 2006;67(2);423.e19-423.e21[PubMed]
25. Mitas JA, Thompson T. Ureteral involvement complicating eosinophilic cystitis. Urology 1985;26(1):67-70.[PubMed]
26. Hellstrom HR, Davis BK, Shonnard JW, MacPherson TA. Eosinophilic pyeloureteritis: report of a case. J Urol 1979;122(6): 833-834.[PubMed]
27. Kayigil O, Ozbagi T, Cakar S, Martin A. Contracted bladder secondary to eosinophilic cystitis. Int Urol Nephrol 2001;33(2):341.-342. [PubMed]
28. Medina Perez M, Valero Puerta J, Sanchez Gonzalez M, Valpuesta Fernandez EI: Polypoid eosinophilic cystitis mimicking bladder carcinoma. Arch Esp Urol. 1999;52(3):272-273. [PubMed]
29. Eosinophilic cystitis, in Urologic surgical pathology, chapter four. Bostwick D, Eble J. Mosby 1997, pp 186-187.
30. Flamm J. Tumor-associated tissue inflammatory reaction and eosinophilia in primary superficial bladder cancer. Urology 1992;40(2):180-185.[PubMed]
31. Romero Tenorio M, Flores Ortiz J, Arroyo Maestre JM, Ramirez Chamorro F, Perez Requena J, Lerida Vaca L, Flores Gines J : Eosinophilic cystitis in children. Study of 4 cases. Arch Esp Urol. 1997;50(7):750-754.[PubMed]
32. Motzkin D. Nonsteroidal anti-inflammatory drugs in the treatment of eosinophilic cystitis. J Urol 1990;144(6):1464-1466.[PubMed]
33. Ferrero Doria R, Ortuno Pacheco G, Guzman Martinez-Valls PL, Morga Egea JP, Tomas Ros M, Rico Galiano JL, Sempere Gutierrez A, Fontana Compiano LO: Eosinophilic cistitis. Actas Urol Esp. 1997;21(4):385-390.[PubMed]
34. Sibert L, Khalaf A, Bugel H, Sfaxi M, Grise P. Intravesical dimethyl sulfoxide instillations can be useful in the symptomatic treatment of profuse hematuria due to eosinophilic cystitis. J Urol 2000;164(2):446.[PubMed]
35. Pomeranz A, Eliakim A, Uziel Y, Gottesman G, Rathaus V, Zehavi T et al. Eosinophilic cystitis in a 4 year old boy: successful treatment with cyclosporin A. Pediatrics 2001;108(6):E113..[PubMed]
36. Sidh SM, Smith SP, Siber SB, Young JD. Eosinophilic cystitis: advanced disease requiring surgical intervention. Urology 1980;15:23-26.[PubMed]
37. Cardini S, Smulevich E, Salvadori A, Lombardi M. Augmentation ileocystoplasty in a case of eosinophilic cystitis. Minerva Urol Nefrol 1997;49(4):219-23.[PubMed]
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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