Eosinophilic cystitis with disease - conservative or invasive?
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https://www.eduzhai.net Clinical M edicine and Diagnostics 2013, 3(5): 108-110 DOI: 10.5923/j.cmd.20130305.02 Eosinophilic Cystitis with Co-morbid Condition – Conservative or Aggressive? Azhar Amir Hamzah1,*, Wong MPK1, Mohammad Nor Gohar Rahman1, Azreen Syazril Adnan2, Amer Hayat Khan3 1Urology Unit, Department of Surgery, Hospital University of M alaysia, Kubang Kerian, Kelantan, M alaysia 2CKD Resource Centre, Hospital Universiti Sains M alaysia, Kubang Kerian, Kelantan, 16150, M alaysia 3Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains M alaysia, Penang, 11800, M alaysia Abstract Eosinophilic cystitis is a rare clin ical entity and there are no distinct features clinically to differentiate it fro m a malignancy. Its pathogenesis is poorly understood, however, it has been closely allied with local immune response to antigen-antibody complexes. Current patient is a a 52 years old female presented with recurrent Urinary tract infection, haematuria, and past medical h istory of pulmonary tuberculosis. Patient was referred to Hospital Universit i Sains Malaysia for dysuria with frank haematuria. It was due to heparinizat ion, as patient was heparinized and started on anti-platetet therapy for acute coronary syndrome. Her symptoms resolved spontaneously after withholding the heparin infusion. Patient was re-ad mitted for acute coronary syndrome and urinary tract infection. Urinalysis and culture test shows present of pus cell and mixed growth on the culture, which were resolved. With six months interval Patient was readmitting (3rd episode of admission) due to septic shock and of right loin pain with renal punch positive. Currently, her Urinalysis shows significant amount of leucocytes as well as blood. Moreover, patient presented with right infected diabetic foot ulcer. Nevertheless, her symptoms and total white cell counts improved with Co -amo xiclav. There are also no biochemical parameters suggesting of acute renal failure. Histopathological examination of previous bladder lesion biopsy was traced and consistent with Eosinophilic cystitis. The modality of treat ment is primarily conservative but some advocated combined surgical and medical therapy to improve the outcome of the disease. Keywords Eosinophilic Cystitis, EC, Pseudotumour of Bladder 1. Introduction Eosinophilic Cystitis is a rare clinica l condition which the pathogenesis of the disease has not been fully understood. The clinical presentations of such condition is challengeable, while so me reported symptoms are usually irritative urinary symptoms such as dysuria, suprapubic pain, urgency and frequency with also occasional alarming sympto ms of gross haematuria, pyuria and also urinary retention. The clinical presentations may varies mimic those of infection to malignancy. In a large pooled analysis from the Netherlands, among the 135 patients with eosinophilic cystitis, the most common presenting symptoms were frequency (67%), dysuria (62%), gross/microscopic hematuria (68%), suprapubic pain (49%) and urinary retention (10%). Eosinophilic cystitis was first described in 1960, wh ile researcher described the cond it ion as the eos inophilic gra nulomas of the bladder wall.  Although the pathogenesis * Corresponding author: firstname.lastname@example.org (Azhar Amir Hamzah ) Published online at https://www.eduzhai.net Copyright © 2013 Scientific & Academic Publishing. All Rights Reserved is not fully understood, it has been postulated that the occurrence of the disease is closely related to immunological inflammatory response secondary to the Antigen-Antibody Co mplexes. Literature revealed that the mean age of presentation is 41.6 years old with an equal d istribution existed between males and females. Furthermore, in the pediatrics group, boys were found more often affected than girls of a ratio of 2:1. We are reporting the rarity of the disease and also to embark on the management of the disease. 2. Case Presentation A Malay lady with age of 52 years comes to hospital Universiti Sains Malaysia (HUSM), with co-morb id condition of ischemic heart d isease, uncontrolled diabetes mellitus, and dyslipidaemia. Patient has history of pulmonary tuberculosis with 6 months completion of anti-tuberculosis regimen in 2005. With three years interval, patient referred to HUSM for dysuria with fran k haematuria. It was her first encounter of haematuria but it was due to heparinization, as patient was heparinized and started on Clinical M edicine and Diagnostics 2013, 3(5): 108-110 109 anti-platetet therapy for acute coronary syndrome. Her symptoms resolved spontaneously after withholding the heparin infusion. Ultrasound of the kidney, ureter and bladder (US-KUB) was performed and found normal. Patient was discharged and found defaulter on upcoming appointment. In March 2010, Patient was re-ad mitted for acute coronary syndrome and u rinary tract infection. Urinalysis and culture test shows present of pus cell 11-100cells/µL, red blood cells >100cells/µL, epithelial cell <10 cells/µL and mixed growth on the culture. She was d ischarged with antibiotics after her condition stable. Next year, read mitted with complains of left loin to groin pain associated with frank haematuria with visib le blood clots in the urine. An urgent Ultrasound KUB was performed which again showed no abnormality detected; no ultrasonography evidence of urolithiasis, however, it was an inco mplete examination as the urinary bladder was empty. In view of the repeated history of UTI and haematuria, patient counseling were conducted regarding repeat cystoendoscopic examination (July 2011) which revealed mu ltip le nodular lesions with haemorrhagic spot seen at the posterior aspect of the bladder wall; however, there were no active bleeding or oozing noted. Bladder wall b iopsy were taken at the nodular lesions and sent for histopathological examination. The haematuria resolved after b ladder irrigation, and she was discharged with urology clin ic appointment to review the histopathological examination res u lts . Again, her repeated urine cu ltures show mixed gro wth. Histopathological examination of previous bladder lesion biopsy was traced and consistent with Eosinophilic cystitis. Patient counseling were conducted and explained the modality of treat ments and suggested for another surveillance cystoendoscopy examination with possible transurethral resection of the bladder lesion. Figure 2. High-power microscopic views showing heavy infiltration of the specimen by Eosinophils Figure 3. High-power microscopic views showing heavy infiltration of the specimen by Eosinophils 3. Discussion Figure 1. Low power microscopic view of three fragments of bladder wall (nodule) biopsied specimens with H&E stains Six months later, patient was read mitting due to septic shock. She co mplains of right lo in pain with renal punch positive, whereas deny history of fran k haematuria prior to admission. Currently, her Urinalysis shows significant amount of leucocytes as well as blood. Total white cell counts were raised ranging fro m 10-26 x 103/µL. Furthermore, patient presented with right infected diabetic foot ulcer. Nevertheless, her symptoms and total white cell counts improved with Co-amo xiclav. There are also no biochemical parameters suggesting of acute renal failure. Eosinophilic Cystitis is a rare clin icopathology condition presented commonly at the mean age of 41 years old with an equal distribution between both the genders. It is often described as a rare inflammatory d isorder with a close relationship with immunological hypersensitivity reactions. The condition was first described in the literature by Brown in 1960 whereby he described the features of eosinophilic granulomas of the bladder. It has been postulated that the antigen enters the bladder and form an antigen-antibody complexes wh ich attracts eosinophils to the wall. The predo minant antibody is Immunoglobulin E whereby format ion of the co mp lex will lead to degranulation of mast cells and activation of 110 Azhar Amir Hamzah et al.: Eosinophilic Cystitis with Co-morbid Condition – Conservative or Aggr essive? eosinophils. This will leads to sequelae of responses secondary to the activation of eosinophils that causes significant tissue damage and repair. There is a significant increase in numbers of activated Eosinophils producing and secreting interleukin -5 (IL-5) which in return enhances further activation of the Eosinophils and promoting the cytotoxic reaction towards the bladder wall tissues. It is through this vicious cycle, the chronicity of the lesions in Eosinophilic cystitis is thought to be formed, which lead to a friable raised mass appearance on the bladder wall during the cystoendoscopic examinations. There had been a number of published case reports on the associated aetiological factors of Eosinophilic Cystitis, namely, transitional cell carcino ma, transurethral resection of prostate, intravesical mitocycin-C, tran ilast med ication, parasitic infections, eosinophilic enteritis, recurrent urinary tract infections, vesicoureteric reflu x, ovarian teratoma, chronic granulomatous disease, sutures, and some food products such as tomatoes, coffee and carrots. In present patient, she had previous tuberculosis and also history of recurrent urinary tract infections. This may have predisposed her to develop these chronic lesions. Ho wever, she does not have any previous history of atopy. The modality of treat ment ranges fro m conservative med ical therapy to surgical resection of the bladder lesion. Cystoendoscopic examinations may reveal a great range of abnormalities in d ifferent degrees of severity; they may range fro m just a mucosal erythema to raised polypoidal, edematous and fungating with invasive-appearing lesions.[3,5] It is a great challenge to distinguish eosinophilic cystitis fro m other co mmon types of benign inflammatory or malignant bladder disease through cystoendoscopic examination. Therefore, mult iple b iopsy of the lesions is needed. Furthermo re, there has been reported that the eosinophilic cystitis may occur metachronously in a previously transitional cell tu mor bearing bladder in 25% of cases or synchronously with carcino ma in situ of the bladder. As mentioned above, the inflammatory nodules caused by the eosinophilic may be d ifficu lt to be d istinct fro m infective or malignant changes, hence, most surgeons instilled that the resection is mandatory fo llo wed by corticosteroid or antihistamine treat ment. As discussed by Salman et. al. in their experience in dealing with eosinophilic cystitis; the lesion mimic those of a invasive bladder cancer, hence, transurethral resection of bladder lesion was proceeded. In a centre where h istopathological report can be obtained in days, there may still a leeway for conservative medical therapy with closed appropriate monitoring of these lesions. As being postulated immune reaction as the pathogenesis of this chronic lesion, it usually resolved spontaneously after removal of the offending antigen. Therefore, it would be a great importance to gain detail history of the possible causative agent which resulting in the eosinophilic cystitis including a full immunological wo rk up. So far, as up to date with the current literatures, it was advised to combine both resection and medical therapy as it provides a good curative outcome. In more resistant cases where it recur despite of the above management, a more rad ical surgical intervention was advised which involved partial or total cystectomy or augmentation ileocystoplasty.[3,7] 4. Conclusions Eosinophilic cystitis is a rare disease which is commonly related to immune react ion. The pathogenesis has not been fully understood. Therefore, the management of the disease should be tailored to each indiv idual. In our case, due to her non compliant to our follow-up, it would be mo re appropriate that she is subjected to a cystoendoscopic examination with transurethral resection of the bladder lesion in co mbination with oral medical therapy of corticosteroid and antihistaminic drugs. REFERENCES  van den Ouden, D.. Diagnosis and management of eosinophilic cystitis: a pooled analysis of 135 cases. Eur Urol. 2000; 37 (4): 386-94.  Verhagen, P. C., Nikkels, P. G. & de Jong, T. P. Eosinophilic cystitis. Arch Dis Child. 2001; 84 (4): 344-6.  Teegavarapu, P. S., Sahai, A., Chandra, A., Das gupta, P. & Khan, M . S.Eosinophilic cystitis and its management. Int J Clin Pract, 2005; 59 (3): 356-60.  Dubucquoi, S., Janin, A., Desreumaux, P., Rigot, J. M ., Copin, M . C., Francois, M ., Torpier, G., Capron, M . & Gosselin, B. Evidence for eosinophil activation in eosinophilic cystitis. Eur Urol, 1994; 25 (3): 254-8.  Itano, N. M . & M alek, R. S. Eosinophilic cystitis in adults. J Urol,2001; 165 (3): 805-7.  Salman, M ., Al-Ansari, A. A., Talib, R. A., El M alik el, F., Al-Bozaom, I. A. & Shokeir, A. A. Eosinophilic cystitis simulating invasive bladder cancer: a real diagnostic challenge. Int Urol Nephrol,2006; 38 (3-4): 545-8.  Popert, R. J., Ramsay, J. W., Owen, R. A., Fisher, C. & Hendry, W. F. Eosinophilic cystitis mimicking invasive bladder tumour: discussion paper. J R Soc Med, 1990; 83 (12): 776-8.
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