Food allergy lecture for clinical pharmacist student

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  • DR.Dr.Ariyanto Harsono SpAK
  • DR.Dr.Ariyanto Harsono SpAK
  • Food allergy lecture for clinical pharmacist student

    1. 1. 1 Penatalaksanaan Alergi Makanan Pada Anak Prof DR Dr ARIYANTO HARSONO SpA(K) Lab/SMF Ilmu Kesehatan Anak FK Unair/RSUD Dr. Soetomo
    2. 2. 2 Pendahuluan • The American Academy of Allergy and Immunology – Alergi Makanan : Reaksi imunologi yang menyimpang terhadap makanan, sebagian besar reaksi ini melalui reaksi hipersensitifitas tipe I
    3. 3. Food Hypersensitivity: reaksi terhadap makanan dengan dasar reaksi tipe II, III, IV Food Intolerance: reaksi terhadap makanan dengan dasar reaksi non imunologi Contoh: Toksik  Metabolik  Idiosinkrasi 3Prof DR Dr Ariyanto Harsono SpA(K)
    4. 4. 4 Patofisiologi • Alergen Makanan – Protein, glikoprotein, polipeptida – BM > 18.000 dalton – tahan panas – tahan enzim proteolitik
    5. 5. Prof DR Dr Ariyanto Harsono SpA(K) 5
    6. 6. 6 patofisiologi • Pada ikan : alergen M • Pada telur : ovomucoid • Pada susu : betalaktoglobulin (BLG) alfalaktalbumin (ALA) bovin serum albumin (BSA) bovin gama globulin (BGG)
    7. 7. 7 Cow's milk -caseins Whey ασ1-Casein, ασ2-Casein β-Casein κ-Casein β-Lactoglobulin α-Lactalbumin Exposure of allergen
    8. 8. 8 patofisiologi • Pada kacang tanah : Arachin Conarachin • Pada permunian : Peanut I Glicoprotein 180.000 dalton
    9. 9. 9 patofisiologi • Pada udang : – alergen I (21.000 dalton) – alergen II (200.000 dalton) • Pada gandum : – albumin – pseudoglobulin – euglobulin
    10. 10. 10 1. Genetic: Atopy 2. Exposure 3. Mucosal Barrier Immunology Paradigm Factors Of Allergy Development
    11. 11. Prof DR Dr Ariyanto Harsono SpA(K) 11
    12. 12. a, b, c, d : HLA DR e : HLA DM f : HLA DM CIITA Genetic
    13. 13. 13 patofisiologi • Paparan awal – sel yang berperan • sel penyaji antigen • sel T • sel B
    14. 14. 14
    15. 15. 15 Macrophage are abundant in the lamina propria of the villi. Function: 1.Phagocytosis 2.Immune regulation by cytokines release 3.APC Goblet Cells
    16. 16. Aktivasi sel-sel Imuno- kompeten •Sel T •Sel B •Sel Mast •Sel Langer- hans Aktivasi sel-sel struk- tural •Sel endotel •Sel epitel Aktivasi dan Rekruitmen •Sel Mast •Eosinofil •Neutrofil •Basofil Pelepasan mediator Kerusakan epitel Stimulasi neural Dilatasi & peningkatan permeabilitas vaskulerl Bronkokonstriksi Perbaikan epitel •Proliferasi fibroblast •Deposisi kolagen •Hipertropi/hiperp lasia otot polos •Ekspansi vaskuler Penyempitan saluran nafas bawah Symptom alergi Bronkus hiper-reaktif A L E R G E N A B C D E Imunopatologi alergi Airway remodelling 16 Prof DR Dr Ariyanto Harsono SpA(K) Trigger
    17. 17. Macam Reaksi • Reaksi tipe cepat (Rapid onset reaction) • Reaksi tipe lambat (Delayed onset Reaction) • Target organ: – Mengenai 1 atau lebih organ tertentu – Contoh : • Paru : asma bronkial • Hidung : rinitis alergika • Kulit : urtikaria, dermatitis atopik • Kardiovaskuler : renjatan anafilaktik 17Prof DR Dr Ariyanto Harsono SpA(K)
    18. 18. VACCINATION ACTIVATION ANTIGEN SPECIFIC B CELL GENERATION OF MEMORY ACTIVATED CD4 + Th-2 CELL IL-4 DIFFERENTIATION & AFFINITY MATURATION ANTIBODY SECRETING PLASMA CELLS ANTIGEN PROCESSING & PRESENTATION MHC Class II B CELL IMMUNOGLOBULINE T CELL RECEPTOR ANTIGEN B CELL IL-5,IL-13 Cow’s Milk Protein Cow’s Milk epitope
    19. 19. Granule contents: Histamine,TNF-α Proteases, Heparin Lipid mediators: Prostaglandins Leukotrienes Cytokine production: Specifically IL-4, IL-13 19Prof DR Dr Ariyanto Harsono SpA(K)
    20. 20. IgGIgG mediated: Kolik, Protein loosing enteropathy, Gastro-intestinal haemorrhage Prof DR Dr Ariyanto Harsono SpA(K) 1 Unsoluble allergen
    21. 21. IgMIgM mediated: Kolik, Protein loosing enteropathy, Gastro-intestinal haemorrhage Prof DR Dr Ariyanto Harsono SpA(K) 1 Unsoluble allergen
    22. 22. Prof DR Dr Ariyanto Harsono SpA(K) 22
    23. 23. 23 paparan awal...
    24. 24. 24 patofisiologi • Patologi yang timbul disebabkan : – intereksi antar sel – mediator – sitokin
    25. 25. 26 patofisiologi • Paparan selanjutnya mulai berperan – limfosit T – netrofil – eosinofil
    26. 26. 27 Paparan selanjutnya
    27. 27. Mast Cells and basophiles involve in allergic reaction in the context of antigen-IgE complex
    28. 28. 33 Physiologic barriers Block penetration of ingested antigens: Epithelial cells Glycocalyx Intestinal microvillus membrane structure Tight junctions joining adjacent enterocytes Intestinal peristalsis Break down ingested antigens: Salivary amylases and mastication Gastric acid and pepsins Pancreatic enzymes Intestinal enzymes Intestinal epithelial cell lysozyme activity Immunologic barriers Block penetration of ingested antigens: Antigen-specific s-IgA in gut lumen Clear antigens penetrating gastrointestinal barrier: Serum antigen-specific IgA and IgG Reticuloendothelial system
    29. 29. 34 Intestinal Epithelial Cells (IECs) Central regulatory role in *Determining allergen absorption *Pattern of uptake of ingested Ag *Function as APC
    30. 30. Mucosal immunoglobulins S-IgA: Non inflammatory Mucosal protection S-IgM similar to Plasma IgM, activates complement and phagocytes IgG: Neutralization, potentially inflammatory, Activates Complement and phagocytes IgE: Adverse hypersensitivity states, parasite expulsion
    31. 31. IgA Immunological Barrier The role of B Cells
    32. 32. Component (SC) Dimeric
    33. 33. 38 mAb-IgA
    34. 34. 39 mAb-SC
    35. 35. Development of Cow’s Milk Allergy Early introduction of food antigens • stimulate production of IgE • IgE-mediated response to an allergen – result of a series of molecular & cellular interactions – Involving APC, T cells and B cells. APCs present epitope • MHC class II molecules to T cells; peptide-MHC complex. • "first signal" leads to: – T-cell proliferation, differentiation – initiation of "second"signal These cells and their products • interact with B-cells bearing appropriate antigen-specific receptors • isotype switching • generation of antigen- specific IgE.
    36. 36. IgE in Relation to Cow’s Milk Allergy • In atopic children – early antigenic exposure -> IgE production – sensitisation of mast cells • gastro-intestinal • respiratory tracts. • IgE production starts early – primary immune response to food – continue even when the allergen is avoided by an elimination diet. • Food IgE-antibody concentrations: – increase to individual peak levels and thereafter decline – sensitised through breast-milk to foods their mother have eaten This explains • infants already react to their first intake of cow's milk formula • Infants with onset of allergic to one food, also at high risk of developing allergy to other foods.
    37. 37. once IgE response to cow’s milk protein is initiated Prevention of food allergy using hypoallergenic milk formula in the first trimester of life is very important, because: it progresses throughout the infant life sensitisation to other food allergen may develop
    38. 38. 43 Immunoglobulin Other Than IgE IgG, IgM 1. Anaphylactoid 2. Malabsorption. 3. Protein Losing Enteropathy
    39. 39. Induction of Oral Tolerance T-cells regulation: 1.Intra Epithelial Lymphocytes: extrathymically derived, have limited TCR repertoir, capable of recognizing common microbiologic Ags, and demonstrate predominantly cytolytic functions 2.Lamina Propria Lymphocytes: thymicaly derived, contributes to limiting TCR/CD3-mediated signals in the mucosa .
    40. 40. M Cell Epithelial Cell Intra Epithelial Lymphocyte Lamina Propria Lymphocyte
    41. 41. 46 IEL LPL CD3 Anergy/Tolerance
    42. 42. 47 Infiltrasi eosinofil...
    43. 43. 48 Gejala klinik organ sasaran • Kulit • saluran napas • saluran cerna • Mata • telinga • kardiovaskuler
    44. 44. Target Organ IgE-mediated disorder Non IgE-mediated disorder Skin Gastro- intestinal Respiratory Tract Multi- system Urticaria and angioedema Atopic Dermatitis Oral Allergy Syndrome Gastrointestinal anaphylaxis Allergic eosinophilic gastroenteritis Asthma; Allergic Rhinitis Food-induced anaphylaxis Food associated, exercise- induced anaphylaxis Atopic Drmatitis Dermatitis Herpetiformis Proctocolitis Enterocolitis Allergic eosinophilic- gastroenteritis Enteropathy syndrome Celiac Disease Heiner Syndrome Clinical Manifestation
    45. 45. 51
    46. 46. 54
    47. 47. Target organ Unusual Clinical manifestation •Skin •ENT •Respiratory •Gastrointestinal •Multi system Vasculitis; Fixed Skin Eruption Chronic Serous Otitis Media Chronic Pulmonary disease (Heiner Syndrome) Hypersensitivity pneumonitis Constipation; Gastroesophageal reflux Irritability/Sleeplessness in infants; Arthropathy; Nephropathy; Thrombocytopenia Unusual Clinical Manifestation
    48. 48. 61
    49. 49. Diagnosis • Anamnesis • pemeriksaan fisik • laboratorium • uji eliminasi provokasi
    50. 50. diagnosis • Step 1 : eliminasi – eliminasi diet – minimal diet 1 (modified Rowe’s diet 1) – minimal diet 2 (modified Rowe’s diet 2) – egg & fish free diet – his own’s diet
    51. 51. Diagnosis... Step 2 • Provokasi :-DBPCFC -Open Challenge
    52. 52. Penatalaksanaan • “The mainstay of treatment of allergic disease is avoidance of allergen” • allergen yang ditemukan dg uji eliminasi provokasi harus disingkirkan sebaik mungkin • desensitisasi tidak dilakukan
    53. 53. Diet Eliminasi 1. Elimination Diet 2. Minimal Diet 1 3. Minimal Diet 2 4. Egg and Fish free diet 5. His own Diet Prof DR Dr Ariyanto Harsono SpA(K) 66
    54. 54. Diet Eliminasi 1. Elimination Diet 2. Minimal Diet 1 3. Minimal Diet 2 4. Egg and Fish free diet 5. His own Diet Prof DR Dr Ariyanto Harsono SpA(K) 67 Elimination Diet (BSTIK) Alergen utama yang harus dipantang selama 3 minggu Buah Susu Telur Ikan Kacang
    55. 55. Diet Eliminasi 1. Elimination Diet 2. Minimal Diet 1 3. Minimal Diet 2 4. Egg and Fish free diet 5. His own Diet Makanan hipoalergenik yang diperbolehkan:  Nasi(Beras)  Daging sapi  Kelapa  Kedelai  Sayur  Wortel  Bawang  Gula, garam Prof DR Dr Ariyanto Harsono SpA(K) 68
    56. 56. Diet Eliminasi 1. Elimination Diet 2. Minimal Diet 1 3. Minimal Diet 2 4. Egg and Fish free diet 5. His own Diet Makanan hipoalergenik lain yang diperbolehkan:  Kentang  Daging kambing  Jagung  Kacang merah  Sayur  Wortel  Bawang  Gula, garam Prof DR Dr Ariyanto Harsono SpA(K) 69
    57. 57. Diet Eliminasi 1. Elimination Diet 2. Minimal Diet 1 3. Minimal Diet 2 4. Egg and Fish free diet 5. His own Diet Diet ini digunakan untuk gejala alergi pada kulit.  Telur  Ikan dipantang selama 3 minggu Prof DR Dr Ariyanto Harsono SpA(K) 70
    58. 58. Diet Eliminasi 1. Elimination Diet 2. Minimal Diet 1 3. Minimal Diet 2 4. Egg and Fish free diet 5. His own Diet Diet ini digunakan untuk gejala alergi hirupan pada saluran nafas, pada uji kulit debu rumah dan tungau positif, anamnesa positif. Makanan yang disebutkan oleh pasien sendiri yang dipantang selama 3 minggu Prof DR Dr Ariyanto Harsono SpA(K) 71
    59. 59. Makanan Pengganti Buah Susu Telur Ikan Kacang  Sayur  Kentang  Wortel  Nasi  Teh  Susu Formula HA/Soya  Kue mangkok, lapis, bikang  Daging sapi, hati,paru, otak.  Tahu, tempe, kecap Prof DR Dr Ariyanto Harsono SpA(K) 72
    60. 60. PENATALAKSANAAN Pencegahan Primer Pencegahan Sekunder Pencegahan Tertier (Therapy) Imunoterapi Diet Pharmalogic therapy Beta-2 agonis Xanthine derivative Corticosteroid Antagonist H1 generasi IIProf DR Dr Ariyantoarsono SpA(K) 73
    61. 61. PENATALAKSANAAN Pencegahan Primer Pencegahan Sekunder Pencegahan Tertier (Therapy) Imunoterapi Diet Pharmalogic therapy Beta-2 agonis Xanthine derivative Corticosteroid Antagonist H1 generasi IIProf DR Dr Ariyantoarsono SpA(K) 74
    62. 62. Kehamilan = “Th2-disease” *Anti-oksidan *Hindari asap rokok *Probiotik trimester Pencegahan Primer: Masa Kehamilan 75 Prof DR Dr Ariyanto Harsono SpA(K)
    63. 63. • ASI Eksklusif • Diet eliminasi untuk ibu • Formula HA • Tunda makanan padat Prof DR Dr Ariyanto Harsono SpA(K) 76
    64. 64. Pencegahan Primer dengan susu Formula FORMULA H.A. Partially hydrolyzed formulas: BUBUR SUSU BISKUIT SUSU X X 77Prof DR Dr Ariyanto Harsono SpA(K) BISKUIT/BUBUR SUSU HA V
    65. 65. PENATALAKSANAANPencegahan Primer Pencegahan Sekunder Pencegahan Tertier (Therapy) Imunoterapi Diet Pharmalogic therapy Beta-2 agonis Xanthine derivative Corticosteroid Antagonist H1 generasi IIProf DR Dr Ariyantoarsono SpA(K) 78
    66. 66. Pencegahan Sekunder dengan susu Formula FORMULA E.H.A. Extensively hydrolyzed formulas: BUBUR SUSU BISKUIT SUSU X X 79 Prof DR Dr Ariyanto Harsono SpA(K) BISKUIT SUSU/Bubur susu HA X
    67. 67. Prevensi Sekunder dengan susu Formula Soy formulas: BUBUR SUSU BISKUIT SUSU X X 80Prof DR Dr Ariyanto Harsono SpA(K) BISKUIT SUSU/BUBUR SUSU HA X
    68. 68. Prevensi Sekunder dengan susu Formula Amino Acids: BUBUR SUSU BISKUIT SUSU X X 81Prof DR Dr Ariyanto Harsono SpA(K) BISKUIT SUSU/BUBUR SUSU HA X
    69. 69. PENATALAKSANAANPencegahan Primer Pencegahan Sekunder Pencegahan Tertier (Therapy) Imunoterapi Diet Pharmalogic therapy Prof DR Dr Ariyantoarsono SpA(K) 82
    70. 70. Penatalaksanaan….. • Eliminasi makanan setelah uji provokasi • Diberi petunjuk makanan pengganti – Pengganti Susu Sapi: • Susu formula hidrolisat kasein • Susu formula hidrolisat whey • Susu formula kedelai – Pengganti Buah: sayur – Pengganti telur, ikan, ayam: daging sapi/kambing • Jika diet tidak bisa dilaksanakan harus diberi pengobatan simtomatis 83Prof DR Dr Ariyanto Harsono SpA(K)
    71. 71. PENATALAKSANAANPencegahan Primer Pencegahan Sekunder Pencegahan Tertier (Therapy) Imunoterapi Diet Pharmacologic therapy Prof DR Dr Ariyantoarsono SpA(K) 84
    72. 72. penatalaksanaan • Tujuan penatalaksanaan – frekuensi serangan – intensitas serangan – penggunaan obat – hari bolos sekolah – kualitas hidup
    73. 73. 86 penatalaksanaan • Makanan pengganti (substitusi) – susu : formula hidrolisat whey formula hidrolisat kasein formula kedelai – buah : sayur – telur/ikan : daging sapi daging kambing tahu tempe
    74. 74. 87 penatalaksanaan • Makan direstoran tidak aman • Dianjurkan melakukan “label reading” • pada bayi, ibu juga harus ikut eliminasi
    75. 75. 88 penatalaksanaan • Farmakoterapi – tidak bisa menggantikan eliminasi alergen – mengurangi gejala ringan tapi menutupi gejala awal kulit
    76. 76. Obat-obatan dan yang digunakan untuk mengobati alergi dapat dibagi menjadi kelompok besar: 1. Obat yang menghambat aktivitas bahan kimia yang dilepaskan dalam tubuh selama reaksi alergi: - antihistamin dan antagonis leukotriene; 2. Obat yang mengendurkan otot di saluran udara dari paru- paru, atau mengecilkan jaringan padat, atau membalikkan efek dari bahan kimia yang dilepaskan selama reaksi alergi: - bronkodilator, dekongestan dan epinefrin; anti acetylchloline 3. Obat-obatan yang mencegah aktivasi sel yang terlibat dalam reaksi alergi: - agen anti-alergi: kromolin, ketotifen 4. Obat yang memiliki efek yang lebih umum dalam mengurangi peradangan: - kortikosteroid; 5. Terapi yang memodifikasi respon imun: - imunoterapi alergen. Prof DR Dr Ariyanto Harsono SpA(K) 89
    77. 77. 90 penatalaksanaan • Cromolin, nedocromil – penggunaan pada asma • asma ringan • asma latihan • gejala GI • dermatitis atopi
    78. 78. 91 penatalaksanaan • Glukokortikoid – digunakan pada penderita alergi makanan dengan gejala • asma • rinitis alergika • anafilaksis
    79. 79. 92 penatalaksanaan • Beta adrenergik agonis – beta 2 agonis • untuk asma – epinefrin • untuk renjatan anafilaksis
    80. 80. 93 penatalaksanaan • Metilxantin – sebagai bronkodilator • Antagonis kolinergik – untuk pengobatan tambahan pada penderita dengan gejala asma, rinitis alergika
    81. 81. 94 penatalaksanaan • Leukotrien antagonis: Montelukast, Zafirlukast – untuk gejala asma • kombinasi dengan xantin dan beta 2 agonis
    82. 82. penatalaksanaan • H1 reseptor antagonis • Generasi II – efek samping CNS ( - ) – dapat digunakan mulai 6 bulan – dapat digunakan dalam jangka lama – efektif untuk • urtikaria kronik • rinitis alergika • dermatitis atopik • asma ringan

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