Recomendados
Más contenido relacionado
Similar a Австрийский центр буллезного эпидермолиза (EB House Austria)
Similar a Австрийский центр буллезного эпидермолиза (EB House Austria) (10)
Último
Último (20)
Австрийский центр буллезного эпидермолиза (EB House Austria)
- 1. 1st Eurasean Conference on Rare Diseases and Orphan Products 3rd All-Russian Conference for Rare Diseases and Rarely Used Medical Technologies EB House Austria H.Hintner Department of Dermatology Paracelsus Medical University Salzburg
- 2. EPIDERMOLYSIS BULLOSA Definition A group of rare hereditary skin diseases with complications in multiple organs Mutations in the genes of structural proteins of keratinocytes or of the dermo-epidermal junction lead following minor trauma to blisters and erosions on skin and mucous membranes
- 3. electron microscopy normal human skin
- 5. PRESENT CLASSIFICATION of EB Major EB type Major EB subtype Proteins targeted for mutation EB simplex (EBS) EBS, Weber-Cockayne (EBS-WC) K5, K14 EBS, Koebner (EBS-K) K5, K14 EBS, Dowling-Meara (EBS-DM) K5, K14 EBS with muscular dystrophy (EBS-MD) plectin JEB, Herlitz (JEB-H) laminin-332 Junctional EB (JEB) JEB, non-Herlitz (JEB-nH) laminin-332; type XVII collagen JEB with pyloric atresia (JEB-PA) 6 4 integrin Dystrophic EB (DEB) dominant DEB (DDEB) type VII collagen recessive DEB, Hallopeau-Siemens type VII collagen (RDEB-HS) recessive dystrophic EB, non-Hallopeau- type VII collagen Siemens (RDEB-nHS)
- 6. IMPETIGO of the NEWBORN
- 7. Diagnostical algorithm in neonatal bullous skin disease Staining of lesion material Gram (fluid aspirate) Giemsa (scraping from base of blister) Tzanck (scraping from base of blister) KOH (preparation of blister roof) Bacterial, viral and fungal cultures Polymerase chain reactions
- 8. Diagnostical algorithm in neonatal bullous skin disease Skin biopsy Histology Direct immunofluorescence Antigen mapping Electron microscopy Blood sample Indirect immunofluorescence Mutation analysis
- 9. FOR AN EXACT DIAGNOSIS A SKIN BIOPSY IS ALWAYS NECESSARY! BIOPSY FROM CLINICALLY NORMAL APPEARING SKIN – INNER ASPECT UPPER ARM
- 10. EBS - Immunoperoxidase - type IV collagen
- 11. „subepidermal“ blistering - EBJ PAS - Stain
- 12. „subepidermal“ blistering - EBD H&E Stain
- 13. electron microscopy normal human skin
- 14. junctional eb
- 15. dystrophic eb
- 16. dystrophic eb
- 17. ANTIGEN MAPPING I - Determination of the level of split formation (junctional in lamina lucida vs. dystrophic below lamina densa) - Biopsy of a fresh blister or of clinically normal appearing skin - Immunofluorescence with, for example, anti- type IV collagen
- 18. Antigen mapping I junctional dermolytic
- 19. Antigen mapping with anti-type IV collagen Determination of the level of split formation
- 20. ANTIGEN MAPPING II - Biopsy of clinically normal appearing skin (inner aspect upper arm) - Immunofluorescence microscopy with a panel of antibodies against structural proteins of keratinocytes or the dermo- epidermal junction - Normal expression, reduction, lack of staining
- 21. antigen mapping K14 - NHS
- 22. antigen mapping K14 - EBS-K
- 23. antigen mapping laminin 5 - NHS
- 24. antigen mapping laminin 5 - EBJ-H
- 26. enzyme digestion
- 28. PRESENT CLASSIFICATION of EB Major EB type Major EB subtype Proteins targeted for mutation EB simplex (EBS) EBS, Weber-Cockayne (EBS-WC) K5, K14 EBS, Koebner (EBS-K) K5, K14 EBS, Dowling-Meara (EBS-DM) K5, K14 EBS with muscular dystrophy (EBS-MD) plectin JEB, Herlitz (JEB-H) laminin-332 Junctional EB (JEB) JEB, non-Herlitz (JEB-nH) laminin-332; type XVII collagen JEB with pyloric atresia (JEB-PA) 6 4 integrin Dystrophic EB (DEB) dominant DEB (DDEB) type VII collagen recessive DEB, Hallopeau-Siemens type VII collagen (RDEB-HS) recessive dystrophic EB, non-Hallopeau- type VII collagen Siemens (RDEB-nHS)
- 29. eb simplex - WC
- 30. eb simplex - K
- 31. eb simplex - DM
- 32. eb simplex - MD
- 33. eb simplex - MD
- 34. junctional eb - Herlitz
- 35. junctional eb - Herlitz exuberant granulation tissue
- 36. junctional eb – non Herlitz
- 37. junctional eb – non Herlitz
- 38. junctional eb – non Herlitz
- 39. junctional eb – non Herlitz
- 40. junctional eb – non Herlitz
- 41. junctional eb – non Herlitz male pattern baldness
- 44. dystrophic eb, rezessive-HS milia formation
- 45. dystrophic eb, rezessive-HS pseudosyndactyly
- 46. dystrophic eb, rezessive-HS pseudosyndactyly, contractures
- 47. dystrophic eb, rezessive-HS pseudosyndactyly, contractures
- 48. eb house austria as CENTRE OF EXPERTISE eb outpatient unit eb academy eb research
- 49. MANAGEMENT OF PATIENTS WITH EB • Centre of expertise • Support group • University Department • Hospital • Dermatologist (specialist) • Family physician • Family • PATIENT
- 50. MANAGEMENT OF PATIENTS WITH EB • 2 EB – Physicians • 2 EB – Nurses • Group of experts from all fields of medicine = INTERDISCIPLINARY MANAGEMENT • Patient training (one week, with the family) • Routine visits or visit on demand • Recreation • .....
- 52. EPIDERMOLYSIS BULLOSA Cutaneous and extracutaneous complications - Squamous cell carcinomas - Dental problems - Wound healing problems - Pseudosyndactyly and contractures - Nutrition - Strictures - EB naevi - Prentatal and preimplantation diagnosis
- 53. EPIDERMOLYSIS BULLOSA and CANCER - Early (from 2nd decade on) multiple, highly aggressive squamous cell carcinomas that rapidly metastasize - RDEB-HS: 14a (0,8%); 20a (7,5%); 35a (67,8%); 40a (73,4%); 45a (80,2%) and 55a (90,1%)
- 54. Squamous cell carcinomas in RDEB - HS
- 55. RDEB - HS Lymph node metastasis
- 56. EB and DENTAL PROBLEMS - Enamel defects: Results of the gene / protein defect odontogenesis - Caries (nutrition!) - Problematic oral hygiene
- 57. EBJ - nH dental enamel defects, caries
- 58. RDEB – HS, EBJ - nH microstomia, caries
- 59. RDEB - HS caries, microstomia
- 60. EBJ - nH cosmetically satisfiing crowns
- 61. EBJ - nH panoramic x-ray
- 62. „at the dentist“ sloughing of mucous membranes
- 64. WOUND HEALING – WOUND CARE - Wear cotton gloves - NON-ADHESIVE TAPE! (Binding, padded layers of dressing) - Place ointment in the eyes
- 65. You can not prevent sloughing!
- 66. cotton wool underneath blood pressure cuff
- 67. No adhesive tape !
- 69. electrode attached with mepiform
- 71. change of dressing after hand surgery
- 72. change of dressing after hand surgery
- 73. splints
- 74. splints
- 75. The glove is well accepted
- 76. a very special technique
- 79. RDEB - HS skin erosion around gastrostomy button
- 80. ABCD rule • A symmetry • B order irregularity • C olor variegation • D iameter > 6mm EB naevi are clinically highly suspective for melanoma!!! JEB-nHS
- 81. EB - Naevus EBJ non-H
- 82. EBS-K 1998 1999 2000
- 83. EB – Naevi Pathogenesis EBJ non-H 1992
- 84. EB - Naevi Histopathology HE S 100 Stain
- 85. Ki-67 (400x) Pathogenesis • Free floating melanocytes spread within the blister cavity HMB-45 (1000x) • Settle down at random (edge of blister) • Proliferate independently in microenvironment of regeneration
- 86. GENETIC COUNSELING Autosomal rezessiver Erbgang: Autosomal dominanter Erbgang: z.B. in junktionaler Epidermolysis z.B. in dominanter dystrophen bullosa Herlitz Epidermolysis bullosa
- 87. PRENATAL and PREIMPLANTATION Genetic Diagnosis Hiva Fassihi, John Mc Grath, St.John‘s Institute of Dermatology, London • Fetal skin biopsy (1979); HE and electron microscopy; IF • Chorionic villus sampling and amniocentesis • Preiimplantation genetic diagnosis • Non - invasive, prenatal diagnosis (fetal DNA or cells in maternal circulation); fetal loss rate ~ 1 %
- 89. EB - ACADEMY • „Library“ • Training (speakers from intern and extern) • Organization of congresses • Teledermatology: diagnosis; second opinion; training • EB Registry • .....
- 90. visiting professor J.-D. Fine
- 93. SALZBURG – BOZEN - MODENA Gene therapy for “butterfly children“
- 94. EB – CLINET
- 95. CLINET • CEs und EB – Experts in 27 (28) EU – Member states • Exchange of information • Organisation of Cross Border Health Care Directive • Basis for clinical studies
- 96. EB – CLINET
- 99. Epidermolysis bullosa is a Rare = Orphan Disease • Incidence: 1 in 2000 individuals • Often life threatening and chronically debilitating with high complexity and enormous costs • 5000 to 8000 RD = 6% to 8% of the population • 27 to 36 million patients in the EU
- 100. Rare diseases in Dermatology are mostly: GENODERMATOSES Definition: Diagnosis, prevention and therapy of hereditary skin diseases, which are caused by mutations in genes encoding components of the skin, mucous membranes, hair and nails or of factors of the biogenetic maschinery for the production of those components.
- 101. ~ 400 Monogenetic Genodermatoses • Epidermolysis bullosa hereditaria - group • Hereditary disorders of keratinisation • Hereditary connective tissue diseases • Ectodermal dysplasias • Hereditary diseases of hair and nails • Hereditary pigmentary disorders • Hereditary metabolic diseases • Genodermatoses with benign tumors • Genodermatoses with malignant tumors • Others
- 102. Cowden Syndrom Darier EKD fig.var. Mendes da Costa PTEN GENODERMATOSES ATP2A2 GJB3,GJB4 HAE PXE Cylindromas C1NH ABCC6 16q12-q13
- 103. Recklinghausen tuberous sclerosis Netherton (Pringle ) NF1 TSC1, TSC2 SPINK 5 Peutz Jeghers Ehlers-Danlos Pct STK11 Col UROD
- 104. Commission Communication 697 to the European Parliament, the Counsil, the European Economic and Social Committee and the Committee of the Regions on Rare Diseases: Europe‘s Challenges 11.11.2008 Council Recommondation for European Action in the field of Rare Diseases 08.06.2009
- 105. DIRECTIVE (EC 2011/24/EU) OF THE EUROPEAN PARLIAMENT and of the COUNCIL on the APPLICATION of PATIENT‘S RIGHTS in CROSS – BORDER HEALTH CARE 9.3.2011
- 106. EUROPEAN COMMISSION RARE DISEASE TASK FORCE ( HIGH LEVEL GROUP) EUROPEAN UNION COMMITTEE of EXPERTS on RARE DISEASES (EUCERD) Member Austria: H.Hintner
- 107. MUTATION vs. SINGLE NUCLEOTIDE POLYMORPHISM (SNP) Risk factors for diseases: $ 199.– Entire genome: 10.000.- $ (with disease) 40.000.- $ (normal persons) Company ILUMINA
- 108. Thank you!