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Encrusted cystitis and pyelitis in children: An unusual condition with potentially severe consequences
PEDIATRIC UROLOGY
ENCRUSTED CYSTITIS AND PYELITIS IN CHILDREN: AN UNUSUAL CONDITION WITH POTENTIALLY SEVERE CONSEQUENCES PAUL MERIA, MARGAR MARGARYAN, ELIE HADDAD, BERTRAND DORE, HENRI B. LOTTMANN
AND
ABSTRACT Objectives. To report our experience with the management of encrusted cystitis and pyelitis (EC and EP) in the pediatric population. EC and EP are well-known entities in adults but are rarely identified in children. They consist of mucosal encrustations and are due to specific microorganisms. Methods. Between 1996 and 2001, 4 children with a mean age of 9 years (range 4 to 13) were treated for EC (n ⫽ 2), EP (n ⫽ 1), and EC and EP (n ⫽ 1). The latter was a kidney transplant recipient. We retrospectively evaluated the clinical characteristics of the patients and the results of conservative management. Results. The delay between the beginning of the symptoms and the diagnosis was longer than 1 month in all cases. The diagnosis of EC was not evoked and was made during cystoscopy in all cases. EP was diagnosed during pyelotomy in 1 patient because it was evoked and confirmed by computed tomography scan in the kidney transplant recipient. Corynebacterium urealyticum was identified in the urine of all patients. EC was treated by antibiotics and endoscopic debulking, and EP was treated by antibiotics and local acidification. The duration of antibiotic therapy was between 1 and 6 months. The tolerance to local acidification of the kidneys was poor. Cure was achieved in 3 cases, but the treatment of EP failed in the kidney transplant recipient and graft removal was decided after 6 months of failed management because intractable febrile urinary tract infections became life threatening for the patient. Conclusions. EC and EP are uncommon in children; however, these diseases must be considered. They must be diagnosed rapidly and require, if possible, conservative management. Nevertheless, kidney loss can occur in transplant recipients with EP. UROLOGY 64: 569–573, 2004. © 2004 Elsevier Inc.
E
ncrusted cystitis (EC) and encrusted pyelitis (EP) were initially described in adults, and many cases have been reported since the first descriptions in the early 20th century.1–5 They can occur in the same patient and are characterized by mucosal inflammation and encrustations of the bladder and/or upper urinary tract.4 – 6 Such encrustations consist of deposits of ammonium magnesium phosphate and struvite.4,6 The role of ureasplitting microorganisms was demonstrated in the pathophysiology of EC and EP, and Corynebacterium urealyticum (CU), a gram-positive bacillus From the Department of Urology, St. Louis Hospital; Department of Pediatric Urology, St. Joseph Hospital; Department of Pediatric Nephrology, Robert Debre´ Hospital, Paris; and Department of Urology, Jean Bernard Hospital, Poitiers, France Reprint requests: Paul Meria, M.D., Department of Urology, St. Louis Hospital, 1 Avenue C Vellefaux, Paris F-75475, France Submitted: February 23, 2004, accepted (with revisions): April 14, 2004 © 2004 ELSEVIER INC. ALL RIGHTS RESERVED
initially called CGD2, was identified as the most frequent causative agent.4,5,7 CU is frequently selected by repeated broad-spectrum antibiotic therapy and is nosocomially acquired. Other risk factors are involved in the development of EC and EP, including previous urologic procedures or urologic disease, the presence of urinary catheters, immunodepression, and debilitating diseases.4,8,9 Most of the clinical reports have described adults and have demonstrated that EC and EP can be severe conditions with a potentially fatal outcome.6,10 Children can also be affected. To the best of our knowledge, only 1 case of EC has been reported in such a population.2 In the present study, we report our experience with the management of such diseases in children. MATERIAL AND METHODS Between 1996 and 2001, 4 children were treated at our institutions for encrusted diseases of the urinary tract. One 0090-4295/04/$30.00 doi:10.1016/j.urology.2004.04.013 569
TABLE I. Patient characteristics Patient 1/EP (n)/disease Sex/age (yr) M/4 History, previous Nephrostomy for recurrent operations UPJ stricture and acute pyelonephritis
2/EC
3/EC
M/9 Bladder exstrophy, bladder neck operation, endoscopic injection of bulking agent for persistent incontinence
F/12 Voiding dysfunction; Hinman syndrome, repeat UTI, cystoscopy and trigonal biopsy
Incontinence, pollakiuria, repeat UTI, encrustations expelled, low bladder capacity (50 mL) Cystoscopy Cystoscopy, CT scan
Clinical features
Pain, hematuria, fever
Incontinence, pollakiuria, repeat UTI, encrustations expelled
Diagnosis
Incidental during pyeloplasty Alkaline pH, pyuria, hematuria CU (urine, encrustations)
Cystoscopy
Treatment
Teicoplanin (32 days), local acidification by nephrostomy tube (21 days)
Endoscopic removal of encrustations, teicoplanin (60 days)
Outcome
No residual encrustation, kidney function normal
No residual encrustation
Urinalysis Microorganism
Follow-up (mo)
60
4/EC and EP
Alkaline pH, pyuria, hematuria CU (urine)
48
Alkaline pH, pyuria, hematuria CU (urine, encrustations) Endoscopic removal of encrustations (twice), teicoplanin (30 days), then rifampicin (90 days), biofeedback, alphablockers No residual encrustation; bladder capacity 300 mL 72
M/13 Posterior ureteral valves with acontractile bladder; clean intermittent catheterization through Mitrofanoff channel; renal failure and kidney transplantation with double-J stent Encrustations expelled, fever 40 days after kidney transplantation
Alkaline pH, pyuria, hematuria CU (urine, encrustations) Teicoplanin (6 mo), local acidification by nephrostomy tube (poor tolerance)
Persistent encrustations, major septic episodes, graft removal 36
KEY: EP ⫽ encrusted pyelitis; EC ⫽ encrusted cystitis; M ⫽ male; F ⫽ female; UPJ ⫽ ureteropelvic junction; UTI ⫽ urinary tract infection; CT ⫽ computed tomography; CU ⫽ Corynebacterium urealyticum.
4-year-old boy presented with EP, one 9-year-old boy presented with EC, one 12-year-old girl presented with EC, and one 13-year-old boy, with a kidney graft, presented with EC and EP of the transplant. Table I shows the clinical characteristics of the patients. We retrospectively assessed the clinical features of EC and EP in children, and the value of conservative management in such patients. The research of specific microorganisms such as CU was made on specific enriched media, as previously described, using urine and, if possible, encrustations and/or mucosal cultures.2,4 Cultures were made aerobically on blood agar supplemented with antibiotics at 37°C for more than 48 hours.2,4 Conservative management, as previously described in adults,4,9 consisted in the association of antibiotics, local acidification of kidneys for EP, and endoscopic removal of encrustations for EC. Thomas’ solution was used for local acidification (sodium gluconate 27 g, citric acid 27 g, malic acid 27 g, and distilled water 1000 mL). The mean follow-up was 54 months (range 36 to 72). Patients underwent repeat computed tomography (CT) scans for EP and repeat cystoscopy for EC at regular intervals. Urine cultures were also performed during follow-up. 570
RESULTS The clinical characteristics of the diseases were not specific, and the delay between the beginning of the symptoms and diagnosis was greater than 1 month in all cases. In patients 1 through 3, the diagnosis was incidental during pyeloplasty (patient 1) or during cystoscopy (patients 2 and 3). The presence of typical encrustations involving the renal pelvis or bladder mucosa led us to the diagnosis. In patient 4, the diagnosis was clearly evoked by the clinical features and was confirmed by plain abdominal radiography (Fig. 1) and CT (Fig. 2). All patients were negative for human immunodeficiency virus 1 and 2 assays. All of the patients had at least one risk factor for EC and/or EP. Patient 1 had a nephrostomy tube. Patient 2 had received an endoscopic injection of a bulking UROLOGY 64 (3), 2004
FIGURE 1. Plain abdominal film showing encrustation of left iliac fossa corresponding to EP in kidney graft (arrows indicate caliceal encrustations).
displayed poor tolerance, requiring intermittent treatment. Despite an intensive conservative management, the patient with a kidney transplant had a poor outcome. First, peritoneal extravasation of Thomas’ solution occurred, and he developed severe metabolic disorders requiring emergency treatment in the intensive care unit. Subsequently, the nephrostomy tube and double-J stent were replaced. Acidification and antibiotic therapy were inefficient, and he developed febrile septic complications. At the last stage, CU was no longer identified in the urine, but a multiresistant Pseudomonas aeruginosa was identified. Septic complications, associated with immunosuppressive therapy, became life threatening, and, after 6 months of struggle, removal of the otherwise normally functioning kidney was performed. Diffuse pelvicaliceal encrustations were found on the graft specimen (Fig. 3). With a mean follow-up of 54 months, the results were good in the 3 other cases with no residual encrustations and sterile urine cultures. Patient 1 had normal CT findings and patients 2 and 3 recovered normal bladder mucosa and bladder function. COMMENT
FIGURE 2. CT scan showing encrustations of upper calix within kidney transplant.
agent for incontinence 3 months before presentation. Patient 3 had undergone cystoscopy and biopsy 1 year previously. Patient 4 had an acontractile bladder valve and had performed clean intermittent catheterization through a Mitrofanoff channel for many years. He developed end-stage renal failure and had received a kidney transplant with routine insertion of a double-J stent that had been in place for 1 month. He had received immunosuppressive therapy. Thus, previous mucosal trauma was present in all 3 patients with EC and EP occurred in the patients with previous surgery and a remaining drain. CU was identified in the urine and/or encrustations or mucosa of all patients and was always sensitive to glycopeptides. EC was treated by endoscopic soft debulking using a cold loop in association with antibiotics. The 2 boys with EP received antibiotics and kidneydirect acidification with Thomas’ solution. They UROLOGY 64 (3), 2004
To the best of our knowledge, only 1 case of EC had been reported previously, in a 9-year-old child.2 We describe the first series of EC and EP in children, including the first case of EC and EP in a child with a kidney graft. The diagnosis was not evoked immediately in 3 of our 4 patients, because it was unexpected in this population. Nevertheless, the retrospective analysis of symptoms showed that they were comparable to those described in the adult population.2–5 The risk factors for the development of EC and EP in children are also identical to those for adults. The presence of voiding dysfunction with a postvoid residual urine volume in our patients with EC is probably a co-factor of urinary tract infection: repeated antibiotic therapy for infections contributed to the selection of CU. The development of EC occurred in inflammatory bladders with previous mucosal traumas, as has also been demonstrated in adults.2–5 Kidney transplantation, which associates urologic procedures with immunodepression, represents a major risk factor.8,9 Our 13-year-old patient who developed EC and EP also had had a Mitrofanoff channel and performed clean intermittent catheterization. The presence of a cutaneous urostomy and clean intermittent catheterization allows the penetration of skin microorganisms within the urinary tract, increasing the risk of EC in the case of urea-splitting bacteria.9 The penetration of CU within the bladder of our patient probably occurred through 571
FIGURE 3. Graft removal showing upper calix residual encrustations (instrument tip and arrow indicate involved calix).
the Mitrofanoff urostomy, and the presence of a double-J stent allowed the microorganism to contaminate the transplant. The presence of a urinary stent has been demonstrated as a risk factor for EP in kidney transplant recipients. The stent plays a facilitating role in the ascension of microorganisms from the bladder to the kidney, leading to EP after the development of EC.8 The other patient with EP had a nephrostomy stent in place to which the penetration of CU within the upper urinary tract can be attributed. Many urea-splitting microorganisms are responsible for encrusted diseases of the urinary tract, but CU is presently the most frequent causative agent of such diseases and was present in all patients in our series.9 CU is a commensal of the skin, with a marked tropism for urothelial cells and urinary catheters.11–13 Its penetration within the urinary tract is facilitated by endourologic procedures and, in some cases, by a urostomy.9 CU is strongly adherent to urinary tract mucosa, especially if inflammatory and/or traumatic lesions are present.2–5 The development of encrusted diseases is due to the specific properties of CU, and its bacteriologic diagnosis remains difficult. This fastidious and opportunistic slow-growing microorganism can be missed in routine cultures and requires enriched media and prolonged cultures for longer than 48 hours.14 Recent developments in molecular biology, using polymerase chain reaction, have led to an improvement in the detection of CU after negative cultures in patients who had received previously many antibiotics.14 This is a promising tool, complementary with conventional microbiology, for the bacteriologic diagnosis of EC and EP. The presence of alkaline urine, associated with struvite crystals, should lead to a search for CU and other urea-splitting microorganisms, even in children. Cultures of encrustations can also be performed to 572
look for causative agents.7,9 Imaging techniques are also required, and unenhanced CT is presently the best technique for the diagnosis of EP. Linear calcifications of pelvicaliceal urothelium are observed in the case of EP.15 The diagnosis of EC is easily confirmed by cystoscopy even in children. The major risk of EP is graft loss in kidney transplant recipients. This complication was described by Aguado et al.,16 who demonstrated that reoperations after kidney transplantation increased the risk of EP. In a previous report, we preserved the graft in two kidney transplant recipients, but this objective is probably more difficult in children. Graft removal was necessary in our patient because of bad tolerance and partial efficacy of the treatment.9 Ureteral strictures complicating EP have been described and were probably due to the EP itself. Such complications seem to be more frequent in transplanted kidneys but can also be observed in native kidneys.7 The treatment of ureteral strictures can require ureteral-ileoplasty in the case of endoscopic procedure failure.9,17 The tolerance to local acidification within the kidney was poor in our two children with EP, requiring intermittent treatment or interruption. Poor tolerance has also been described in adults. In a recent series, Joshi et al.18 demonstrated that more than one half of the patients had lumbar pain when treated for residual struvite stones by kidney acidification using citric acid alone. We have not had experience with other solutions, such as Suby’s G solution or Renacidin, but their tolerance has also been described as poor.4,19 One of the advantages in such solutions is the presence of citric acid, which provides citrate, which is able to form complexes with the phosphate and calcium from the stones.19 The low pH of these solutions, around 4, is effective, because the solubility of struvite components increases when the pH is less than 5.5.19 Low-irrigation flow and low-pressure instillation are required to limit pain and other complications such as acidosis.9,17,19 Straight monitoring is required, particularly in children, and treatment must be performed on an inpatient basis. Poor tolerance led us to perform graft removal in our transplant recipient, although the kidney function was satisfactory. The other risk of prolonged urine acidification is candiduria, which was not observed in our short series of children.9,19 Antibiotic therapy must be administered in conjunction with acidification and must be started a few days before. Presently, most CU strains are resistant to the usual antibiotics; glycopeptides, such as teicoplanin or vancomycin are the only antibiotics with constant effectiveness.4,9 The results obtained in our patients were satisfactory because urinalysis was negative for CU after treatment. UROLOGY 64 (3), 2004
EC was also treated by endoscopic removal of the encrustations. In children, several procedures can be necessary. As in adults, encrustations must be removed gently with a cold loop to avoid deeper penetration of the infective agent.4 In the case of voiding dysfunction, psychotherapy and rehabilitation have been proposed, because the presence of residual urine volume represents a co-factor of infection and CU development. Close follow-up is required after conservative management of EC and EP because of the risk of recurrence. Repeat CT scans and urinalysis are necessary in children, just as they are in adults. CONCLUSIONS Although uncommon in children, EC and EP must be considered in the differential diagnosis in children with risk factors and presenting with urinary symptoms. A specific search for CU must be done. The treatment is identical to that performed in adults, and the risk of kidney loss must also be considered in children. REFERENCES 1. Hager BH, and Magath TB: The etiology of encrusted cystitis with alkaline urine. JAMA 85: 1353–1355, 1925. 2. Soriano F, Ponte C, Santamaria M, et al: Corynebacterium group D2 as a cause of alkaline encrusted cystitis: report of four cases and characterization of the organisms. J Clin Microbiol 21: 788 –792, 1985. 3. Estorc JJ, de la Coussaye JA, Viel EJ, et al: Teicoplanin treatment of alkaline encrusted cystitis due to Corynebacterium group D2. Eur J Med 1: 183–184, 1992. 4. Meria P, Desgrippes A, Arfi C, et al: Encrusted cystitis and pyelitis. J Urol 160: 3–9, 1998. 5. Giannakopoulos S, Alivizatos G, Deliveliotis C, et al: Encrusted cystitis and pyelitis. Eur Urol 39: 446 –448, 2001. 6. Chung SY, Davies BJ, and O’Donnell WF: Mortality from grossly encrusted bilateral pyelitis ureteritis and cystitis by Corynebacterium group D2. Urology 61: 463, 2003.
UROLOGY 64 (3), 2004
7. Meria P, and Jungers P: Encrusted pyelitis: an underdiagnosed condition? Nephrol Dial Transplant 15: 943–945, 2000. 8. Benoit G, Blanchet P, Eschwege P, et al: Insertion of a double pigtail ureteral stent for the prevention of urological complications in renal transplantation: a prospective randomised study. J Urol 156: 881–884, 1996. 9. Meria P, Desgrippes A, Fournier R, et al: The conservative management of Corynebacterium group D2 encrusted pyelitis. BJU Int 84: 270 –275, 1999. 10. Audard V, Garrouste-Orgeas M, Misset B, et al: Fatal septic shock caused by Corynebacterium D2. Intensive Care Med 29: 1376 –1379, 2003. 11. Soriano F, and Ponte C: A case of urinary tract infection caused by Corynebacterium urealyticum and coryneform F1. Eur J Clin Microbiol Infect Dis 11: 626 –628, 1992. 12. Marty N, Agueda L, Lapchine L, et al: Adherence and hemagglutination of Corynebacterium group D2. Eur J Clin Microbiol Infect Dis 10: 20 –24, 1991. 13. Soriano F, Ponte C, and Galiano MJ: Adherence of Corynebacterium urealyticum and Corynebacterium jeikeium to intravascular and urinary catheters. Eur J Clin Microbiol Infect Dis 12: 453–456, 1993. 14. Simoons Smith AM, Savelkoul PHM, Newling DWW, et al: Chronic cystitis caused by Corynebacterium urealyticum detected by polymerase chain reaction. Eur J Clin Microbiol Infect Dis 19: 949 –952, 2000. 15. Thoumas D, Darmaillacq C, Pfister C, et al: Imaging characteristics of alkaline encrusted cystitis and pyelitis. AJR Am J Roentgenol 178: 389 –392, 2002. 16. Aguado JM, Morales M, Salto E, et al: Encrusted pyelitis and cystitis by Corynebacterium urealyticum: a new and threatening complication following renal transplant. Transplantation 56: 617–622, 1993. 17. Benoit G, Eschwege P, Paradis V, et al: Successful treatment of encrusted pyelitis in a renal transplant with local acidification and surgical ileocaliceal anastomosis. J Urol 162: 1369 –1370, 1999. 18. Joshi HB, Kumar PVS, and Timoney AG: Citric acid (solution R) irrigation in the treatment of refractory infection (struvite) stone disease: is it useful? Eur Urol 39: 586 –590, 2001. 19. Bernardo NO, and Smith AD: Chemolysis of urinary calculi. Urol Clin North Am 27: 355–364, 2000.
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ENCRUSTED CYSTITIS AND PYELITIS IN CHILDREN: AN UNUSUAL CONDITION WITH POTENTIALLY SEVERE CONSEQUENCES PAUL MERIA, MARGAR MARGARYAN, ELIE HADDAD, BERTRAND DORE, HENRI B. LOTTMANN
AND
ABSTRACT Objectives. To report our experience with the management of encrusted cystitis and pyelitis (EC and EP) in the pediatric population. EC and EP are well-known entities in adults but are rarely identified in children. They consist of mucosal encrustations and are due to specific microorganisms. Methods. Between 1996 and 2001, 4 children with a mean age of 9 years (range 4 to 13) were treated for EC (n ⫽ 2), EP (n ⫽ 1), and EC and EP (n ⫽ 1). The latter was a kidney transplant recipient. We retrospectively evaluated the clinical characteristics of the patients and the results of conservative management. Results. The delay between the beginning of the symptoms and the diagnosis was longer than 1 month in all cases. The diagnosis of EC was not evoked and was made during cystoscopy in all cases. EP was diagnosed during pyelotomy in 1 patient because it was evoked and confirmed by computed tomography scan in the kidney transplant recipient. Corynebacterium urealyticum was identified in the urine of all patients. EC was treated by antibiotics and endoscopic debulking, and EP was treated by antibiotics and local acidification. The duration of antibiotic therapy was between 1 and 6 months. The tolerance to local acidification of the kidneys was poor. Cure was achieved in 3 cases, but the treatment of EP failed in the kidney transplant recipient and graft removal was decided after 6 months of failed management because intractable febrile urinary tract infections became life threatening for the patient. Conclusions. EC and EP are uncommon in children; however, these diseases must be considered. They must be diagnosed rapidly and require, if possible, conservative management. Nevertheless, kidney loss can occur in transplant recipients with EP. UROLOGY 64: 569–573, 2004. © 2004 Elsevier Inc.
E
ncrusted cystitis (EC) and encrusted pyelitis (EP) were initially described in adults, and many cases have been reported since the first descriptions in the early 20th century.1–5 They can occur in the same patient and are characterized by mucosal inflammation and encrustations of the bladder and/or upper urinary tract.4 – 6 Such encrustations consist of deposits of ammonium magnesium phosphate and struvite.4,6 The role of ureasplitting microorganisms was demonstrated in the pathophysiology of EC and EP, and Corynebacterium urealyticum (CU), a gram-positive bacillus From the Department of Urology, St. Louis Hospital; Department of Pediatric Urology, St. Joseph Hospital; Department of Pediatric Nephrology, Robert Debre´ Hospital, Paris; and Department of Urology, Jean Bernard Hospital, Poitiers, France Reprint requests: Paul Meria, M.D., Department of Urology, St. Louis Hospital, 1 Avenue C Vellefaux, Paris F-75475, France Submitted: February 23, 2004, accepted (with revisions): April 14, 2004 © 2004 ELSEVIER INC. ALL RIGHTS RESERVED
initially called CGD2, was identified as the most frequent causative agent.4,5,7 CU is frequently selected by repeated broad-spectrum antibiotic therapy and is nosocomially acquired. Other risk factors are involved in the development of EC and EP, including previous urologic procedures or urologic disease, the presence of urinary catheters, immunodepression, and debilitating diseases.4,8,9 Most of the clinical reports have described adults and have demonstrated that EC and EP can be severe conditions with a potentially fatal outcome.6,10 Children can also be affected. To the best of our knowledge, only 1 case of EC has been reported in such a population.2 In the present study, we report our experience with the management of such diseases in children. MATERIAL AND METHODS Between 1996 and 2001, 4 children were treated at our institutions for encrusted diseases of the urinary tract. One 0090-4295/04/$30.00 doi:10.1016/j.urology.2004.04.013 569
TABLE I. Patient characteristics Patient 1/EP (n)/disease Sex/age (yr) M/4 History, previous Nephrostomy for recurrent operations UPJ stricture and acute pyelonephritis
2/EC
3/EC
M/9 Bladder exstrophy, bladder neck operation, endoscopic injection of bulking agent for persistent incontinence
F/12 Voiding dysfunction; Hinman syndrome, repeat UTI, cystoscopy and trigonal biopsy
Incontinence, pollakiuria, repeat UTI, encrustations expelled, low bladder capacity (50 mL) Cystoscopy Cystoscopy, CT scan
Clinical features
Pain, hematuria, fever
Incontinence, pollakiuria, repeat UTI, encrustations expelled
Diagnosis
Incidental during pyeloplasty Alkaline pH, pyuria, hematuria CU (urine, encrustations)
Cystoscopy
Treatment
Teicoplanin (32 days), local acidification by nephrostomy tube (21 days)
Endoscopic removal of encrustations, teicoplanin (60 days)
Outcome
No residual encrustation, kidney function normal
No residual encrustation
Urinalysis Microorganism
Follow-up (mo)
60
4/EC and EP
Alkaline pH, pyuria, hematuria CU (urine)
48
Alkaline pH, pyuria, hematuria CU (urine, encrustations) Endoscopic removal of encrustations (twice), teicoplanin (30 days), then rifampicin (90 days), biofeedback, alphablockers No residual encrustation; bladder capacity 300 mL 72
M/13 Posterior ureteral valves with acontractile bladder; clean intermittent catheterization through Mitrofanoff channel; renal failure and kidney transplantation with double-J stent Encrustations expelled, fever 40 days after kidney transplantation
Alkaline pH, pyuria, hematuria CU (urine, encrustations) Teicoplanin (6 mo), local acidification by nephrostomy tube (poor tolerance)
Persistent encrustations, major septic episodes, graft removal 36
KEY: EP ⫽ encrusted pyelitis; EC ⫽ encrusted cystitis; M ⫽ male; F ⫽ female; UPJ ⫽ ureteropelvic junction; UTI ⫽ urinary tract infection; CT ⫽ computed tomography; CU ⫽ Corynebacterium urealyticum.
4-year-old boy presented with EP, one 9-year-old boy presented with EC, one 12-year-old girl presented with EC, and one 13-year-old boy, with a kidney graft, presented with EC and EP of the transplant. Table I shows the clinical characteristics of the patients. We retrospectively assessed the clinical features of EC and EP in children, and the value of conservative management in such patients. The research of specific microorganisms such as CU was made on specific enriched media, as previously described, using urine and, if possible, encrustations and/or mucosal cultures.2,4 Cultures were made aerobically on blood agar supplemented with antibiotics at 37°C for more than 48 hours.2,4 Conservative management, as previously described in adults,4,9 consisted in the association of antibiotics, local acidification of kidneys for EP, and endoscopic removal of encrustations for EC. Thomas’ solution was used for local acidification (sodium gluconate 27 g, citric acid 27 g, malic acid 27 g, and distilled water 1000 mL). The mean follow-up was 54 months (range 36 to 72). Patients underwent repeat computed tomography (CT) scans for EP and repeat cystoscopy for EC at regular intervals. Urine cultures were also performed during follow-up. 570
RESULTS The clinical characteristics of the diseases were not specific, and the delay between the beginning of the symptoms and diagnosis was greater than 1 month in all cases. In patients 1 through 3, the diagnosis was incidental during pyeloplasty (patient 1) or during cystoscopy (patients 2 and 3). The presence of typical encrustations involving the renal pelvis or bladder mucosa led us to the diagnosis. In patient 4, the diagnosis was clearly evoked by the clinical features and was confirmed by plain abdominal radiography (Fig. 1) and CT (Fig. 2). All patients were negative for human immunodeficiency virus 1 and 2 assays. All of the patients had at least one risk factor for EC and/or EP. Patient 1 had a nephrostomy tube. Patient 2 had received an endoscopic injection of a bulking UROLOGY 64 (3), 2004
FIGURE 1. Plain abdominal film showing encrustation of left iliac fossa corresponding to EP in kidney graft (arrows indicate caliceal encrustations).
displayed poor tolerance, requiring intermittent treatment. Despite an intensive conservative management, the patient with a kidney transplant had a poor outcome. First, peritoneal extravasation of Thomas’ solution occurred, and he developed severe metabolic disorders requiring emergency treatment in the intensive care unit. Subsequently, the nephrostomy tube and double-J stent were replaced. Acidification and antibiotic therapy were inefficient, and he developed febrile septic complications. At the last stage, CU was no longer identified in the urine, but a multiresistant Pseudomonas aeruginosa was identified. Septic complications, associated with immunosuppressive therapy, became life threatening, and, after 6 months of struggle, removal of the otherwise normally functioning kidney was performed. Diffuse pelvicaliceal encrustations were found on the graft specimen (Fig. 3). With a mean follow-up of 54 months, the results were good in the 3 other cases with no residual encrustations and sterile urine cultures. Patient 1 had normal CT findings and patients 2 and 3 recovered normal bladder mucosa and bladder function. COMMENT
FIGURE 2. CT scan showing encrustations of upper calix within kidney transplant.
agent for incontinence 3 months before presentation. Patient 3 had undergone cystoscopy and biopsy 1 year previously. Patient 4 had an acontractile bladder valve and had performed clean intermittent catheterization through a Mitrofanoff channel for many years. He developed end-stage renal failure and had received a kidney transplant with routine insertion of a double-J stent that had been in place for 1 month. He had received immunosuppressive therapy. Thus, previous mucosal trauma was present in all 3 patients with EC and EP occurred in the patients with previous surgery and a remaining drain. CU was identified in the urine and/or encrustations or mucosa of all patients and was always sensitive to glycopeptides. EC was treated by endoscopic soft debulking using a cold loop in association with antibiotics. The 2 boys with EP received antibiotics and kidneydirect acidification with Thomas’ solution. They UROLOGY 64 (3), 2004
To the best of our knowledge, only 1 case of EC had been reported previously, in a 9-year-old child.2 We describe the first series of EC and EP in children, including the first case of EC and EP in a child with a kidney graft. The diagnosis was not evoked immediately in 3 of our 4 patients, because it was unexpected in this population. Nevertheless, the retrospective analysis of symptoms showed that they were comparable to those described in the adult population.2–5 The risk factors for the development of EC and EP in children are also identical to those for adults. The presence of voiding dysfunction with a postvoid residual urine volume in our patients with EC is probably a co-factor of urinary tract infection: repeated antibiotic therapy for infections contributed to the selection of CU. The development of EC occurred in inflammatory bladders with previous mucosal traumas, as has also been demonstrated in adults.2–5 Kidney transplantation, which associates urologic procedures with immunodepression, represents a major risk factor.8,9 Our 13-year-old patient who developed EC and EP also had had a Mitrofanoff channel and performed clean intermittent catheterization. The presence of a cutaneous urostomy and clean intermittent catheterization allows the penetration of skin microorganisms within the urinary tract, increasing the risk of EC in the case of urea-splitting bacteria.9 The penetration of CU within the bladder of our patient probably occurred through 571
FIGURE 3. Graft removal showing upper calix residual encrustations (instrument tip and arrow indicate involved calix).
the Mitrofanoff urostomy, and the presence of a double-J stent allowed the microorganism to contaminate the transplant. The presence of a urinary stent has been demonstrated as a risk factor for EP in kidney transplant recipients. The stent plays a facilitating role in the ascension of microorganisms from the bladder to the kidney, leading to EP after the development of EC.8 The other patient with EP had a nephrostomy stent in place to which the penetration of CU within the upper urinary tract can be attributed. Many urea-splitting microorganisms are responsible for encrusted diseases of the urinary tract, but CU is presently the most frequent causative agent of such diseases and was present in all patients in our series.9 CU is a commensal of the skin, with a marked tropism for urothelial cells and urinary catheters.11–13 Its penetration within the urinary tract is facilitated by endourologic procedures and, in some cases, by a urostomy.9 CU is strongly adherent to urinary tract mucosa, especially if inflammatory and/or traumatic lesions are present.2–5 The development of encrusted diseases is due to the specific properties of CU, and its bacteriologic diagnosis remains difficult. This fastidious and opportunistic slow-growing microorganism can be missed in routine cultures and requires enriched media and prolonged cultures for longer than 48 hours.14 Recent developments in molecular biology, using polymerase chain reaction, have led to an improvement in the detection of CU after negative cultures in patients who had received previously many antibiotics.14 This is a promising tool, complementary with conventional microbiology, for the bacteriologic diagnosis of EC and EP. The presence of alkaline urine, associated with struvite crystals, should lead to a search for CU and other urea-splitting microorganisms, even in children. Cultures of encrustations can also be performed to 572
look for causative agents.7,9 Imaging techniques are also required, and unenhanced CT is presently the best technique for the diagnosis of EP. Linear calcifications of pelvicaliceal urothelium are observed in the case of EP.15 The diagnosis of EC is easily confirmed by cystoscopy even in children. The major risk of EP is graft loss in kidney transplant recipients. This complication was described by Aguado et al.,16 who demonstrated that reoperations after kidney transplantation increased the risk of EP. In a previous report, we preserved the graft in two kidney transplant recipients, but this objective is probably more difficult in children. Graft removal was necessary in our patient because of bad tolerance and partial efficacy of the treatment.9 Ureteral strictures complicating EP have been described and were probably due to the EP itself. Such complications seem to be more frequent in transplanted kidneys but can also be observed in native kidneys.7 The treatment of ureteral strictures can require ureteral-ileoplasty in the case of endoscopic procedure failure.9,17 The tolerance to local acidification within the kidney was poor in our two children with EP, requiring intermittent treatment or interruption. Poor tolerance has also been described in adults. In a recent series, Joshi et al.18 demonstrated that more than one half of the patients had lumbar pain when treated for residual struvite stones by kidney acidification using citric acid alone. We have not had experience with other solutions, such as Suby’s G solution or Renacidin, but their tolerance has also been described as poor.4,19 One of the advantages in such solutions is the presence of citric acid, which provides citrate, which is able to form complexes with the phosphate and calcium from the stones.19 The low pH of these solutions, around 4, is effective, because the solubility of struvite components increases when the pH is less than 5.5.19 Low-irrigation flow and low-pressure instillation are required to limit pain and other complications such as acidosis.9,17,19 Straight monitoring is required, particularly in children, and treatment must be performed on an inpatient basis. Poor tolerance led us to perform graft removal in our transplant recipient, although the kidney function was satisfactory. The other risk of prolonged urine acidification is candiduria, which was not observed in our short series of children.9,19 Antibiotic therapy must be administered in conjunction with acidification and must be started a few days before. Presently, most CU strains are resistant to the usual antibiotics; glycopeptides, such as teicoplanin or vancomycin are the only antibiotics with constant effectiveness.4,9 The results obtained in our patients were satisfactory because urinalysis was negative for CU after treatment. UROLOGY 64 (3), 2004
EC was also treated by endoscopic removal of the encrustations. In children, several procedures can be necessary. As in adults, encrustations must be removed gently with a cold loop to avoid deeper penetration of the infective agent.4 In the case of voiding dysfunction, psychotherapy and rehabilitation have been proposed, because the presence of residual urine volume represents a co-factor of infection and CU development. Close follow-up is required after conservative management of EC and EP because of the risk of recurrence. Repeat CT scans and urinalysis are necessary in children, just as they are in adults. CONCLUSIONS Although uncommon in children, EC and EP must be considered in the differential diagnosis in children with risk factors and presenting with urinary symptoms. A specific search for CU must be done. The treatment is identical to that performed in adults, and the risk of kidney loss must also be considered in children. REFERENCES 1. Hager BH, and Magath TB: The etiology of encrusted cystitis with alkaline urine. JAMA 85: 1353–1355, 1925. 2. Soriano F, Ponte C, Santamaria M, et al: Corynebacterium group D2 as a cause of alkaline encrusted cystitis: report of four cases and characterization of the organisms. J Clin Microbiol 21: 788 –792, 1985. 3. Estorc JJ, de la Coussaye JA, Viel EJ, et al: Teicoplanin treatment of alkaline encrusted cystitis due to Corynebacterium group D2. Eur J Med 1: 183–184, 1992. 4. Meria P, Desgrippes A, Arfi C, et al: Encrusted cystitis and pyelitis. J Urol 160: 3–9, 1998. 5. Giannakopoulos S, Alivizatos G, Deliveliotis C, et al: Encrusted cystitis and pyelitis. Eur Urol 39: 446 –448, 2001. 6. Chung SY, Davies BJ, and O’Donnell WF: Mortality from grossly encrusted bilateral pyelitis ureteritis and cystitis by Corynebacterium group D2. Urology 61: 463, 2003.
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7. Meria P, and Jungers P: Encrusted pyelitis: an underdiagnosed condition? Nephrol Dial Transplant 15: 943–945, 2000. 8. Benoit G, Blanchet P, Eschwege P, et al: Insertion of a double pigtail ureteral stent for the prevention of urological complications in renal transplantation: a prospective randomised study. J Urol 156: 881–884, 1996. 9. Meria P, Desgrippes A, Fournier R, et al: The conservative management of Corynebacterium group D2 encrusted pyelitis. BJU Int 84: 270 –275, 1999. 10. Audard V, Garrouste-Orgeas M, Misset B, et al: Fatal septic shock caused by Corynebacterium D2. Intensive Care Med 29: 1376 –1379, 2003. 11. Soriano F, and Ponte C: A case of urinary tract infection caused by Corynebacterium urealyticum and coryneform F1. Eur J Clin Microbiol Infect Dis 11: 626 –628, 1992. 12. Marty N, Agueda L, Lapchine L, et al: Adherence and hemagglutination of Corynebacterium group D2. Eur J Clin Microbiol Infect Dis 10: 20 –24, 1991. 13. Soriano F, Ponte C, and Galiano MJ: Adherence of Corynebacterium urealyticum and Corynebacterium jeikeium to intravascular and urinary catheters. Eur J Clin Microbiol Infect Dis 12: 453–456, 1993. 14. Simoons Smith AM, Savelkoul PHM, Newling DWW, et al: Chronic cystitis caused by Corynebacterium urealyticum detected by polymerase chain reaction. Eur J Clin Microbiol Infect Dis 19: 949 –952, 2000. 15. Thoumas D, Darmaillacq C, Pfister C, et al: Imaging characteristics of alkaline encrusted cystitis and pyelitis. AJR Am J Roentgenol 178: 389 –392, 2002. 16. Aguado JM, Morales M, Salto E, et al: Encrusted pyelitis and cystitis by Corynebacterium urealyticum: a new and threatening complication following renal transplant. Transplantation 56: 617–622, 1993. 17. Benoit G, Eschwege P, Paradis V, et al: Successful treatment of encrusted pyelitis in a renal transplant with local acidification and surgical ileocaliceal anastomosis. J Urol 162: 1369 –1370, 1999. 18. Joshi HB, Kumar PVS, and Timoney AG: Citric acid (solution R) irrigation in the treatment of refractory infection (struvite) stone disease: is it useful? Eur Urol 39: 586 –590, 2001. 19. Bernardo NO, and Smith AD: Chemolysis of urinary calculi. Urol Clin North Am 27: 355–364, 2000.
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