Jemima_Mellerio(GenitourinaryAbnormalitiesinEBwithoutphotos)

Jemima_Mellerio(GenitourinaryAbnormalitiesinEBwithoutphotos)...

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Unformatted text preview: Genitourinary abnormalities in EB abnormalities Jemima Mellerio St John’s Institute of Dermatology & Great Ormond Street Hospital London UK GU abnormalities in EB GU • • • • Little in literature Mainly one-off case reports Data from NEBR Little practical guidance on Little monitoring or management monitoring GU abnormalities in EB • • Which GU problems arise? Which types of EB get which Which problems? problems? • What is the scale of GU problems? • Cases from Great Ormond Street • Can we formulate some protocols for Can screening and management? screening Which GU problems arise? Which Kidneys Renal parenchyma Ureters Collecting system Bladder Urethra Which GU problems arise? 4 main patterns seen: main • Acute or chronic glomerulonephritis • Renal amyloidosis • IgA nephropathy • Obstructive uropathy Acute or chronic glomerulonephritis glomerulonephritis • Secondary to streptococcal or other Secondary infection infection • Presentation: Haematuria BP BP renal function function • Probably need to treat infection to Probably enable resolution enable Acute or chronic Acute glomerulonephritis glomerulonephritis • Despite treatment may lead to Chronic Chronic renal renal failure Acute or chronic Acute glomerulonephritis glomerulonephritis • Described in RDEB and JEB • Most skin fragility therefore more Most likely assoiciated skin infection likely Renal amyloidosis Renal • Amyloid secondary to chronic antigen Amyloid stimulation and inflammation stimulation • Elevated serum amyloid A protein • Presentation of nephrotic syndrome: Presentation nephrotic Heavy proteinuria albumin albumin Oedema Renal amyloidosis • No specific treatment and may lead No to to Chronic Chronic renal renal failure Renal amyloidosis • Described only in RDEB • Presumably could occur in any Presumably severe (longstanding) form of EB severe IgA nephropathy IgA • Cause not fully understood • Possibly from chronic mucosal Possibly infection infection • Presentation: Haematuria Proteinuria BP BP IgA nephropathy • No specific treatment and may lead No to to Chronic Chronic renal renal failure IgA nephropathy • Described only in RDEB • Presumably could occur in any Presumably severe (longstanding) form of EB severe Obstructive uropathy Obstructive • Predominantly at vesico-ureteric Predominantly junction and urethra junction • Presentation: Infection Pain stream stream Obstructive uropathy Obstructive • If untreated leads to If Bladder distension Hydroureteronephrosis Chronic renal renal failure Obstructive uropathy Obstructive • Strictures of urethra, including Strictures meatus, in RDEB, JEB and Kindler syndrome • VUJ obstruction in JEB especially VUJ EB with pyloric atresia EB EB with pyloric atresia EB • Usually fatal in infancy • Survivors may have profound Survivors morbidity from GU tract disease morbidity • Bladder wall thickening, blistering Bladder and fibrosis and • VUJ obstruction • Congenital focal segmental Congenital gloemrulosclerosis described gloemrulosclerosis Which GU problems arise? Exacerbating factors in EB Exacerbating • Dehydration (reduced oral intake, Dehydration increased fluid loss from skin or gut) increased • Chronic skin colonisation and Chronic infections infections • Surgical intervention • Constipation The scale of GU problems in EB in • Difficult to ascertain in great detail • Largest series from National EB Largest Registry in US Registry Frequency of clinical complications (%) Frequency EBS JEB DDEB RDEB Meatal stenosis 0.3 0.24 Urinary retention 0.77 Hydronephrosis 0.12 Glomerulonephritis 0.0 4.24 5.11 2.12 2.12 0.85 Pyelonephritis 1.69 3.47 1.98 3.47 Bladder hypertrophy 0.12 Cystitis From Fine et al. 1999 0.94 3.35 1.67 0.24 0.0 0.24 0.24 0.0 1.45 2.04 7.12 0.82 4.93 Risk of death from renal failure in EB • Notable cumulative risk of death for Notable severe RDEB increasing from age 15 years (second only to SCC) years Plateaus at 12% by age 35 years • Risk for other types <2% in total Fine et al. 2004 Case 1 Case Case 1 Case • 11 year old boy with non-Herlitz JEB 11 (LAMB3 mutations) • Born with coronal hypospadias • Repaired 1999 (age 4 y) • 2000 difficulty voiding • Urethral dilatations Mar and Oct 2001 • Still pain tip of penis on voiding and Still poor stream poor Case 1 Case • Dec 2001 EUA and ventral meatotomy • 2002 suprapubic catheter - unable to 2002 clamp due to pain clamp • 2004 urethral dilatation • 2005 meatotomy • Apr 2006 midpenile urethrostomy Apr showed adhesions in posterior urethra showed Case 1 Case • Sep 2006 urethrostomy - inflammation Sep and stenoses and • Self-dilatation at home with ultrapotent Self-dilatation topical steroids topical • ? where next… Appendix Mitrofanoff? Appendix Fertility issues Fertility Case 2 Case Case 2 Case • 13 year old boy with non-Herlitz JEB 13 (laminin 5-deficient) (laminin • Dysuria and penile blisters 2002 (age Dysuria 9 y) - normal urodynamic studies y) • Sep 2005 renal USS: Sep 2 echogenic foci Rt kidney echogenic calculus distal Lt ureter calculus mild Lt ureteric dilatation mild Case 2 Case • Nov 2005 acute urinary retention for Nov 30 h • Bladder to umbilicus • Constipation treated with enema • Still no urine - suprapubic catheter • USS normal • KUB normal Case 2 Case • Clamp and release suprapubic catheter Clamp no PU for 48 h no • Antegrade cystogram: no stricture • Started to PU on clamping • 4 days after admission calculus days appeared at meatus appeared • Removed with minor meatotomy • Tests showed idiopathic hypercalciuria Case 2 Case • Had poor oral intake and no Had gastrostomy gastrostomy • Did not PU at school and only 1-2x per Did day at home day • Constipation (on opiates) • Subsequent gastrostomy and adequate Subsequent fluid and nutritional input fluid • BP, urinalysis and KUB: normal Case 3 Case Case 3 Case • 15 year old boy with severe RDEB • Jan 2005 (age 13 y) macroscopic Jan haematuria and trace protein haematuria • Jun 2005 acute renal failure 2o to acute tubular necrosis with hypernatraemic dehydration dehydration • Na 171, urea 40.2, creat 239 • Hypertensive - amlodipine Case 3 Case • ? Post-infectious: raised ASOT and Post-infectious: DNAase DNAase • ? Due to reduced fluid intake • Renal US: small Rt kidney, nil focal • Renal function recovered to baseline Renal level with rehydration level Case 3 Case • 2006 ongoing haematuria +/2006 proteinuria proteinuria • Increased gastrostomy and oral Increased fluids (3L per day) fluids • Hypertension well-controlled • Renal USS normal • Refused IV access for DMSA • Holding off renal biopsy at present Case 3 Case • Dehydration a significant contributing Dehydration factor factor • Still in diapers • Was restricting fluid intake so no need Was to PU at school to • Allowing diaper change only once a Allowing day day • Now using bottle to PU but diaper for Now BO BO Case 4 Case Case 4 Case • 8 year old boy with EB with pyloric year atresia (mild) atresia • 2001 (age 3 y) diarrhoea and 2001 vomiting on trip to Pakistan vomiting • Developed protein-losing Developed enteropathy enteropathy • Settled with parenteral nutrition and Settled prednisolone prednisolone Case 4 Case • 2002 further episode of proteinlosing enteropathy after losing campylobacter infection campylobacter • Settled with prednisolone and Settled azithromycin azithromycin • 2002-3 younger brother also with EBPA died due to severe gut PA involvement involvement Case 4 Case • Mar 2005 protein+ on urinalysis • Aug 2005 penile pain on urinating, Aug frequency, no UTI frequency, • USS: 2cm thick polypoid thickening of USS: bladder bladder • Cystoscopy: haemorrhagic, polypoid Cystoscopy: oedematous lesion in dome of bladder, rest of bladder haemorrhagic bladder, Case 4 Case • Bladder biopsy: fragmented Bladder epithelium with inflammatory cells. No tumour tumour • Started on prednisolone 30mg od for 1 Started week with improved symptoms week • When steroids weaned, symptoms When and haematuria recurred and Case 4 Case • Nov 2005: started Elmiron in addition Nov to prednisolone to • Currently continues Elmiron and pred Currently 2.5mg od 2.5mg • USS: normal kidneys, bladder wall USS: thickening thickening • DMSA: normal • 2006: further episode PLE requiring 2006: methyl prednisolone and IVIG methyl Case 4 Case • Elmiron (pentosan polysulphate Elmiron sodium): heparin-like molecule sodium): • Indication: interstitial cystitis • Anticoagulant and fibrinolytic effects • Mechanism in IC unknown – may line Mechanism bladder wall, may have an effect on cytokines cytokines Case 5 Case Case 5 Case • 15 year old boy with EB with pyloric 15 atresia (mild) with ITGB4 mutations mutations • 1993 (age 2.5 y): macroscopic 1993 haematuria and dysuria haematuria • Cystoscopy: normal urethra, Cystoscopy: haemorrhagic cystitis, urothelial debris debris • Suprapubic catheter inserted Case 5 Case • Extreme pain on clamping SP catheter • 1995 (age 5 y): vesico-ureteric reflux 1995 vesico-ureteric UTIs UTIs hydronephrosis hydronephrosis bladder outflow obstruction bladder dribbling dribbling pain on voiding pain • SP catheter still in SP Case 5 Case • 2000 (age 9 y): hypertension proteinuria proteinuria bilateral VU reflux bilateral bilateral renal calculi bilateral pyelonephritis scarring Rt kidney scarring • SP catheter still on free drainage due to SP pain when clamped pain Case 5 Case • 2002 (age 11 y): small Rt kidney Lt kidney 2 calculi Lt • Cystoscopy attempted but not possible Cystoscopy due to stricture proximal to meatus due • Percutaneous removal of calculi • SP catheter still in Case 5 Case • 2003 (age 12 y): Rt nephrectomy, 2003 ileocystoplasty and appendix Mitrofanoff ileocystoplasty • Subsequently self-catheterises Subsequently Mitrofanoff Mitrofanoff • Coping well at present Case 6 Case Case 6 Case • • • • • • 10 year old girl with severe RDEB Long-standing constipation Poor weight gain (< 0.4th centile) Gastrostomy for medication only Anaemic Compliance issues Case 6 Case • Early 2006: several UTIs, started on Early trimethoprim trimethoprim • USS: hydronephrosis • Subsequently urinary retention • USS: marked renal and ureteric dilatation • Very distended bladder and postmicturition volume 300 ml Case 6 Case • MAG3 scan: stasis of urine bilaterally in MAG3 dilated pelvicalyceal systems, no VU reflux reflux • Intermittent catheterisation by mother • Constipation treated • Gastrostomy used for feeds Case 6 Case • Bowels open most days (PEG-based Bowels laxative) laxative) • Eating better, weight increasing • Missing less school • In diapers but will try to toilet train • Occasional catheterisation with no Occasional residual residual • Repeat USS due soon Type Type GU problem 1 NH-JEB Urethral strictures 2 NH-JEB Calculi, dehydration 3 RDEB ?Post-strep GN + ATN Dehydration 4 EB-PA Bladder wall involvement 5 EB-PA Urethral and bladder involvement, obstruction, Mitrofanoff 6 RDEB Obstruction, constipation, dehydration Screening for GU disease in EB Screening RDEB Urea and electrolytes 6 monthly Urinalysis Blood pressure JEB USS renal tract If abnormal DMSA scan If scar or If discrepancy discrepancy Functional test Functional e.g. MAG3 e.g. Annually Screening for GU disease in EB Screening RDEB Urea and electrolytes Urinalysis Blood pressure JEB If abnormal Urine microscopy and culture USS renal tract DMSA scan Functional test Functional e.g. MAG3 e.g. Screening for GU disease in EB Screening Infection ? Obstruction ? Vesico-ureteric reflux Pain stream stream USS renal tract MAG3 scan Micturating cystourethrogram Management of GU disease in EB in General principles • Avoid instrumentation and surgery if Avoid possible possible • Urethral catheters tolerated short-term • Supra-pubic catheters well-tolerated Supra-pubic longer term longer • Avoid constipation and dehydration • Encourage toilet training at normal age References References • Berger TG et al. Junctional epidermolysis bullosa, pyloric atresia and Berger et Junctional genitourinary disease. Pediatr Dermatol 1986; 3: 130-4. Pediatr • Donatucci CF et al. Management of urinary tract in children with Donatucci et Management epidermolysis bullosa. Urology 1992; 40: 137-42. Urology • Fine JD. Epidemiology of urogenital problems in EB. In Clinical Fine Management of Children and Adults with Epidermolysis Bullosa, DebRA UK, 2003. DebRA • Fine JD et al. Inherited epidermolysis bullosa and the risk of death Fine et from renal disease: experience of the National Epidermolysis Bullosa Registry. Am J Kidney Dis 2004; 44: 651-60. Am • Mann JF et al. The spectrum of renal involvement in epidermolysis Mann et The bullosa dystrophica hereditaria: report of two cases. Am J Kidney Dis Am 1988; 11: 437-41. 1988; ...
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This note was uploaded on 09/13/2011 for the course ENG 101 taught by Professor Dr.hickenbottom during the Spring '10 term at West Liberty.

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