Extracutaneous manifestations of Epidermolysis Bullosa

Transcription

1 Extracutaneous manifestations of Epidermolysis Bullosa DEBRA International Congress Toronto 13th September 2012 Dr Anna Martinez Great Ormond Street Hospital London

2 400

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4 EB: more than just skin deep

5 Multisystemic disease

6 Multisystem disease

7 Multidisciplinary team Anaesthetist Cardiologist Clinical geneticist Dentist Dermatologist Dietician Endocrinologist ENT surgeon Gastroenterologist General surgeon Haematologist Interventional radiologist Microbiologist Obstetrician Oncologist Ophthalmologist Orthopaedic surgeon OT/hand therapist Paediatrician Physiotherapist Plastic surgeon Play therapist Podiatrist Psychologist Social worker Specialist nurse Symptom control team Urologist

8 Review some of the extracutaneous complications

9 Gastrointestinal tract Painful and ulcerated mouth Difficulty swallowing Feeding problems Reflux Constipation

10 Painful and ulcerated mouth Analgesia Haberman feeder with lubrication

11 Painful and ulcerated mouth NSAID spray Non stinging mouthwash Gelclair-gel that coats lining mouth

12 Difficulty swallowing and narrowing of oesophagus Very common in patients with RDEB 65% Most strictures arise upper 1/3 of oesophagus

13 Difficulty swallowing and narrowing of oesophagus Parents and patients report the symptoms Can do a X-ray test-upper GI contrast study Sudden narrowing can sometimes improve with high dose steroids Strictures often need treating with an oesophageal dilatation

14 catheter guidewire 8 mm balloon

15 Difficulty swallowing and narrowing of oesophagus Re stricture rate is variable

16 Feeding problems Input from specialist dietitian important Supplements & specialist feeds

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18 Gastrostomy feeding Sometimes needed Particularly in patients with RDEB Also important role NHJEB

19 ADVANTAGES DISADVANTAGES more feed give medicines worsening of GOR leakage

20 Very common in RDEB (75%) Also common in babies with DMEBS Treat with proton pump inhibitors such as lansoprazole

21 Constipation Common problem in all children Most common GI complication in all types of EB-35% Treat increase fibre in diet & increase fluid intake regular laxative movicol paediatric-polyethylene glycol based

22 Eyes Ken Nischal Corneal abrasions superficial wound Scaring Eye lid problems

23 Corneal abrasions Any types of EB specially in JEB and DEB Very painful

24 Scaring Especially in JEB and RDEB Can lead to reduced vision

25 Treatment of Scaring Prevention Lubricants Surgery Amniotic membrane transplant

26 Amniotic membrane transplant Pre-op 3 weeks post-op 1 year post-op

27 Teeth Suzanne Kramer Enamel defects Secondary caries

28 All forms of JEB Pitting and discoloration Enamel defect

29 Secondary caries Fragile and painful mouth Small mouth opening from scarring

30 Anaemia in EB Common especially in severe types of EB

31 Anaemia in EB

32 Anaemia of inflammation

33 Inflammation When there is a wound or infection the cells in the body produce chemical messengers called cytokines to help the cells communicate and heal If there are constant wounds and infections these cytokines are persistently high in the circulation This causes many problems

34 Anaemia of inflammation Cytokines make the liver produce a protein called hepcidin Hepcidin traps the iron inside cells such as the gut so that there is not enough free in the circulation to make more haemoglobin

35 What is the best way to treat anaemia in EB? Oral iron gets trapped in cells Same with intravenous iron

36 What is the best way to treat anaemia in EB? Blood transfusion but IV access Need better studies

37 Growth & puberty Can be abnormal or delayed in children with EB due to a combination of: nutritional difficulties high levels of certain cytokines in blood because of chronic wounds

38 Cytokines GnRH Secondary hypogonadism

39 Pubertal assessment Clinically Pubertal staging scale

40 Treatment Work with endocrinologist Aim to reach puberty with peers

41 Boys Testosterone intramuscular oral capsules gel

42 Girls Oestrogen orally oestrogel

43 Growth

44 The growth hormone pathway Cytokines interfere with production of growth hormone and its derivatives as well as the transport of active growth hormone around the body

45 We know this because January-October children RDEB age 4-16 years 10 girls: 8 boys

46 Results Measured GH and its derivatives GH transport protein Found they were very low

47 Abnormal growth Likely to be due to high amounts of cytokines affecting growth hormone pathway This been proven in many other inflammatory diseases in children Even increasing amount of feed growth can be abnormal

48 Bones Osteopenia, osteoporosis and vertebral factures can occur in patients with severe EB Published literature Mary Fewtrell : Br J Dermatol (GOS) 39 children severe EB Anna Bruckner : J Am Acad Dermatol children generalised EB Children RDEB have low BMD for age

49 13 of 42 (32%) had vertebral fractures age range yrs (mean 9.6 yrs) sex 7 girls: 6 boys

50 Reduced mobility Low calcium & Vitamin D Delayed puberty High cytokines??reduced mesenchymal stem cells

51 Should we use bone strengtheners bisphosphonates in EB? These attach to bony surfaces undergoing resorption and kill the osteoclast

52 Should we use bisphosphonates? Used so far in 17 children All reported less pain Spine X-rays improved

53 Should we use bisphosphonates? Use if fractures on X-rays Use if severe bony pain Need clinical trials

54 Joint Contractures

55 Physiotherapist

56 Hydrotherapy

57 Mitten deformity

58 Hand occupational therapist

59 Hand occupational therapist

60 Hand surgeon

61 The heart

62 Cardiomyopathy & EB Can be asymptomatic initially Mostly seen in severe generalised RDEB Dilated cardiomyopathy (DCM)

63 Cardiomyopathy in EB Can happened in first year of life Likely to be caused by combination: malnutrition iron overload viral myocarditis drugs

64 Cardiomyopathy: management Avoid potentially medicines that can damage the heart Cardiac echo annually from age 2 years Treat early

65 kidney problems in EB

66 kidney problems in EB Uncommon but potentially serious Examples are blockage of urine flow chronic kidney infection chronic renal failure

67 What makes EB patients at risk of getting kidney problems? Chronic skin infection Dehydration (reduced oral intake, increased losses through skin and gut) Constipation

68 What do we do? Treat relevant infections Make sure enough fluids taken Avoid constipation Avoid unnecessary procedures and surgery Monitor the kidney function

69 Monitoring JEB and RDEB 6 monthly blood and urine tests and check blood pressure JEB Yearly ultrasound of renal tract If we find any problems we do further tests

70 Ear, nose and throat problems in EB

71 Airway involvement Mainly occurs in patients with: JEB, especially Herlitz EBS with muscular dystrophy Can present with a hoarse cry and noisy breathing

72 Airway involvement Work closely with specialist ENT surgeon Nebulised steroids or oral steroids may be helpful Sometimes a treachostomy is needed

73 Herlitz junctional EB

74 EBS with muscular dystrophy

75 Cancer and EB High incidence of squamous cell carcinoma (SCC) in RDEB Also in JEB and milder forms of DEB 80% cumulative risk by 45 years 5 year median survival from first SCC

76 Cancer in EB

77 Cancer in EB Occur mainly over bony prominences Spreads & reoccurs despite wide local excision Youngest patient reported has been age 6 We have recently 13 year old boy Start surveillance from age 10 for RDEB

78 Summary EB more than skin deep Many extracutaneous manifestations

79 Multidisciplinary team Anaesthetist Cardiologist Clinical geneticist Dentist Dermatologist Dietician Endocrinologist ENT surgeon Gastroenterologist General surgeon Haematologist Interventional radiologist Microbiologist Obstetrician Oncologist Ophthalmologist Orthopaedic surgeon OT/hand therapist Paediatrician Physiotherapist Plastic surgeon Play therapist Podiatrist Psychologist Social worker Specialist nurse Symptom control team Urologist

80 Summary Inflammation and the inflammatory cytokines play a major role in the complications If we could switch off inflammation improve many complications seen

81 Acknowledgments

82 Thank you for listening Any Questions?

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