GENiTO URinary problem .in olders adults.ppt

1. Genitourinary
abnormalities in EB
Jemima Mellerio
St John’s Institute of Dermatology &
Great Ormond Street Hospital
London UK

2. GU abnormalities in EB
• Little in literature
• Mainly one-off case reports
• Data from NEBR
• Little practical guidance on
monitoring or management

3. • Which GU problems arise?
• Which types of EB get which
problems?
• What is the scale of GU problems?
• Cases from Great Ormond Street
• Can we formulate some protocols for
screening and management?
GU abnormalities in EB

4. Which GU problems arise?
Kidneys
Ureters
Bladder
Urethra
Renal parenchyma
Collecting system

5. 4 main patterns seen:
• Acute or chronic glomerulonephritis
• Renal amyloidosis
• IgA nephropathy
• Obstructive uropathy
Which GU problems arise?

6. Acute or chronic
glomerulonephritis
• Secondary to streptococcal or other
infection
• Presentation:
• Probably need to treat infection to
enable resolution
Haematuria  BP
 renal
function

7. • Despite treatment may lead to
Acute or chronic
glomerulonephritis
Chronic
renal
failure

8. • Described in RDEB and JEB
• Most skin fragility therefore more
likely assoiciated skin infection
Acute or chronic
glomerulonephritis

9. Renal amyloidosis
• Amyloid secondary to chronic antigen
stimulation and inflammation
• Elevated serum amyloid A protein
• Presentation of nephrotic syndrome:
Heavy
proteinuria  albumin Oedema

10. • No specific treatment and may lead to
Renal amyloidosis
Chronic
renal
failure

11. • Described only in RDEB
• Presumably could occur in any
severe (longstanding) form of EB
Renal amyloidosis

12. IgA nephropathy
• Cause not fully understood
• Possibly from chronic mucosal
infection
• Presentation:
Haematuria  BP
Proteinuria

13. • No specific treatment and may lead to
IgA nephropathy
Chronic
renal
failure

14. • Described only in RDEB
• Presumably could occur in any
severe (longstanding) form of EB
IgA nephropathy

15. Obstructive uropathy
• Predominantly at vesico-ureteric
junction and urethra
• Presentation:
Infection Pain  stream

16. Obstructive uropathy
• If untreated leads to
Chronic
renal
failure
Bladder
distension Hydro-
uretero-
nephrosis

17. Obstructive uropathy
• Strictures of urethra, including
meatus, in RDEB, JEB and Kindler
syndrome
• VUJ obstruction in JEB especially EB
with pyloric atresia

18. EB with pyloric atresia
• Usually fatal in infancy
• Survivors may have profound
morbidity from GU tract disease
• Bladder wall thickening, blistering
and fibrosis
• VUJ obstruction
• Congenital focal segmental
gloemrulosclerosis described

19. Exacerbating factors in EB
• Dehydration (reduced oral intake,
increased fluid loss from skin or gut)
• Chronic skin colonisation and
infections
• Surgical intervention
• Constipation
Which GU problems arise?

20. The scale of GU problems
in EB
• Difficult to ascertain in great detail
• Largest series from National EB
Registry in US

21. Frequency of clinical complications (%)
EBS JEB DDEB RDEB
Meatal stenosis 0.3 4.24 0.24 3.35
Urinary retention 0.77 5.11 0.94 1.67
Bladder hypertrophy 0.12 2.12 0.24 0.0
Hydronephrosis 0.12 2.12 0.24 0.24
Glomerulonephritis 0.0 0.85 0.0 1.45
Pyelonephritis 1.69 1.98 2.04 0.82
Cystitis 3.47 3.47 7.12 4.93
From Fine et al. 1999

22. Risk of death from renal
failure in EB
• Notable cumulative risk of death for
severe RDEB increasing from age 15
years (second only to SCC)
• Plateaus at 12% by age 35 years
• Risk for other types <2% in total
Fine et al. 2004

23. Case 1

24. Case 1
• 11 year old boy with non-Herlitz JEB
(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
poor stream

25. Case 1
• Dec 2001 EUA and ventral meatotomy
• 2002 suprapubic catheter - unable to
clamp due to pain
• 2004 urethral dilatation
• 2005 meatotomy
• Apr 2006 midpenile urethrostomy
showed adhesions in posterior urethra

26. Case 1
• Sep 2006 urethrostomy - inflammation
and stenoses
• Self-dilatation at home with ultrapotent
topical steroids
• ? where next…
Appendix Mitrofanoff?
Fertility issues

27. Case 2

28. Case 2
• 13 year old boy with non-Herlitz JEB
(laminin 5-deficient)
• Dysuria and penile blisters 2002 (age
9 y) - normal urodynamic studies
• Sep 2005 renal USS:
2 echogenic foci Rt kidney
calculus distal Lt ureter
mild Lt ureteric dilatation

29. Case 2
• Nov 2005 acute urinary retention for
30 h
• Bladder to umbilicus
• Constipation treated with enema
• Still no urine - suprapubic catheter
• USS normal
• KUB normal

30. Case 2
• Clamp and release suprapubic catheter -
no PU for 48 h
• Antegrade cystogram: no stricture
• Started to PU on clamping
• 4 days after admission calculus
appeared at meatus
• Removed with minor meatotomy
• Tests showed idiopathic hypercalciuria

31. Case 2
• Had poor oral intake and no
gastrostomy
• Did not PU at school and only 1-2x per
day at home
• Constipation (on opiates)
• Subsequent gastrostomy and adequate
fluid and nutritional input
• BP, urinalysis and KUB: normal

32. Case 3

33. Case 3
• 15 year old boy with severe RDEB
• Jan 2005 (age 13 y) macroscopic
haematuria and trace protein
• Jun 2005 acute renal failure 2o to acute
tubular necrosis with hypernatraemic
dehydration
• Na 171, urea 40.2, creat 239
• Hypertensive - amlodipine

34. Case 3
• ? Post-infectious: raised ASOT and
DNAase
• ? Due to reduced fluid intake
• Renal US: small Rt kidney, nil focal
• Renal function recovered to baseline
level with rehydration

35. Case 3
• 2006 ongoing haematuria +/-
proteinuria
• Increased gastrostomy and oral
fluids (3L per day)
• Hypertension well-controlled
• Renal USS normal
• Refused IV access for DMSA
• Holding off renal biopsy at present

36. Case 3
• Dehydration a significant contributing
factor
• Still in diapers
• Was restricting fluid intake so no need
to PU at school
• Allowing diaper change only once a
day
• Now using bottle to PU but diaper for
BO

37. Case 4

38. Case 4
• 8 year old boy with EB with pyloric
atresia (mild)
• 2001 (age 3 y) diarrhoea and
vomiting on trip to Pakistan
• Developed protein-losing
enteropathy
• Settled with parenteral nutrition and
prednisolone

39. Case 4
• 2002 further episode of protein-
losing enteropathy after
campylobacter infection
• Settled with prednisolone and
azithromycin
• 2002-3 younger brother also with EB-
PA died due to severe gut
involvement

40. Case 4
• Mar 2005 protein+ on urinalysis
• Aug 2005 penile pain on urinating,
frequency, no UTI
• USS: 2cm thick polypoid thickening of
bladder
• Cystoscopy: haemorrhagic, polypoid
oedematous lesion in dome of
bladder, rest of bladder haemorrhagic

41. Case 4
• Bladder biopsy: fragmented
epithelium with inflammatory cells. No
tumour
• Started on prednisolone 30mg od for 1
week with improved symptoms
• When steroids weaned, symptoms
and haematuria recurred

42. Case 4
• Nov 2005: started Elmiron in addition
to prednisolone
• Currently continues Elmiron and pred
2.5mg od
• USS: normal kidneys, bladder wall
thickening
• DMSA: normal
• 2006: further episode PLE requiring
methyl prednisolone and IVIG

43. Case 4
• Elmiron (pentosan polysulphate
sodium): heparin-like molecule
• Indication: interstitial cystitis
• Anticoagulant and fibrinolytic effects
• Mechanism in IC unknown – may line
bladder wall, may have an effect on
cytokines

44. Case 5

45. Case 5
• 15 year old boy with EB with pyloric
atresia (mild) with ITGB4 mutations
• 1993 (age 2.5 y): macroscopic
haematuria and dysuria
• Cystoscopy: normal urethra,
haemorrhagic cystitis, urothelial
debris
• Suprapubic catheter inserted

46. Case 5
• Extreme pain on clamping SP catheter
• 1995 (age 5 y): vesico-ureteric reflux
UTIs
hydronephrosis
bladder outflow obstruction
dribbling
pain on voiding
• SP catheter still in

47. Case 5
• 2000 (age 9 y): hypertension
proteinuria
bilateral VU reflux
bilateral renal calculi
pyelonephritis
scarring Rt kidney
• SP catheter still on free drainage due to
pain when clamped

48. Case 5
• 2002 (age 11 y): small Rt kidney
Lt kidney 2 calculi
• Cystoscopy attempted but not possible
due to stricture proximal to meatus
• Percutaneous removal of calculi
• SP catheter still in

49. Case 5
• 2003 (age 12 y): Rt nephrectomy,
ileocystoplasty and appendix Mitrofanoff
• Subsequently self-catheterises
Mitrofanoff
• Coping well at present

50. Case 6

51. Case 6
• 10 year old girl with severe RDEB
• Long-standing constipation
• Poor weight gain (< 0.4th centile)
• Gastrostomy for medication only
• Anaemic
• Compliance issues

52. Case 6
• Early 2006: several UTIs, started on
trimethoprim
• USS: hydronephrosis
• Subsequently urinary retention
• USS: marked renal and ureteric dilatation
• Very distended bladder and post-
micturition volume 300 ml

53. Case 6
• MAG3 scan: stasis of urine bilaterally in
dilated pelvicalyceal systems, no VU
reflux
• Intermittent catheterisation by mother
• Constipation treated
• Gastrostomy used for feeds

54. Case 6
• Bowels open most days (PEG-based
laxative)
• Eating better, weight increasing
• Missing less school
• In diapers but will try to toilet train
• Occasional catheterisation with no
residual
• Repeat USS due soon

55. 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

56. Screening for GU disease in EB
JEB
RDEB 6 monthly
Annually
If abnormal
If scar or
discrepancy
Urea and electrolytes
Urinalysis
Blood pressure
USS renal tract
DMSA scan
Functional test
e.g. MAG3

57. Screening for GU disease in EB
JEB
RDEB
If abnormal
Urea and electrolytes
Urinalysis
Blood pressure
USS renal tract DMSA scan Functional test
e.g. MAG3
Urine microscopy
and culture

58. Screening for GU disease in EB
Infection Pain  stream
? Obstruction
? Vesico-ureteric
reflux
USS renal tract
MAG3 scan
Micturating
cystourethrogram

59. Management of GU disease
in EB
General principles
• Avoid instrumentation and surgery if
possible
• Urethral catheters tolerated short-term
• Supra-pubic catheters well-tolerated
longer term
• Avoid constipation and dehydration
• Encourage toilet training at normal age

60. References
• Berger TG et al. Junctional epidermolysis bullosa, pyloric atresia and
genitourinary disease. Pediatr Dermatol 1986; 3: 130-4.
• Donatucci CF et al. Management of urinary tract in children with
epidermolysis bullosa. Urology 1992; 40: 137-42.
• Fine JD. Epidemiology of urogenital problems in EB. In Clinical
Management of Children and Adults with Epidermolysis Bullosa,
DebRA UK, 2003.
• Fine JD et al. Inherited epidermolysis bullosa and the risk of death
from renal disease: experience of the National Epidermolysis Bullosa
Registry. Am J Kidney Dis 2004; 44: 651-60.
• Mann JF et al. The spectrum of renal involvement in epidermolysis
bullosa dystrophica hereditaria: report of two cases. Am J Kidney Dis
1988; 11: 437-41.