Shellfish allergy
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This document provides an overview of shellfish allergy, including: - Classification of different types of shellfish such as crustaceans, mollusks, and others. - Epidemiology showing shellfish allergy prevalence is around 2% and is a common cause of anaphylaxis. - Major allergens in shellfish like tropomyosin and their heat stability and cross-reactivity. - Clinical manifestations ranging from mild oral symptoms to anaphylaxis and factors affecting reactions. - Diagnosis involving patient history, skin prick tests, food challenges and IgE antibody tests to confirm allergy.
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Shellfish allergy
- 1. Shellfish Allergy Pannipa Kittipongpattana, MD. 16 August 2019 Division of Pediatric Allergy and Immunology Department of Pediatrics, Faculty of Medicine King Chulalongkorn Memorial Hospital Shellfish Allergy
- 2. Outline ❏ Classification of shellfish ❏ Epidemiology of shellfish allergy ❏ Shellfish Allergens ❏ Cross reactivity ❏ Clinical manifestation ❏ Diagnosis & management
- 3. Outline ❏ Classification of shellfish ❏ Epidemiology of shellfish allergy ❏ Shellfish Allergens ❏ Cross reactivity ❏ Clinical manifestation ❏ Diagnosis & management
- 4. Classification of shellfish Asian Pac J Allergy Immunol 2012;30:3-10 Seafood* *“Seafood” in North America often includes freshwater organisms = “Edible aquatic life” Fish (vertebrate) Shellfish (invertebrate) Mollusca Arthropoda Chordata Crustacea Chelicerates Hexapoda Myriapoda Gastropoda Bivalvia Cephalopoda Malacostraca Xiphosura Insecta Arachnida
- 5. T. Ruethers et al. Molecular Immunology 100 (2018) 28–57 Taxonomic tree of edible seafood species and related allergen sources
- 6. Classification of crustacean and mollusk species, comprising the shellfish group EAACI Molecular Allergology User´s Guide 2016
- 7. Similarities of Decapoda 5 pairs of legs & external skeleton Sub-order Dendrobranchiata Shell Each segment overlaps Shape Curve Claws 3 pairs Gills Branching Eggs Release Sub-order Pleocyemata Shell 2nd segment on top Shape Distinct bending Claws 2 pairs Gills Plate-like Eggs Attach Family Penaeidae Family Caridae
- 8. กุ้งที่คนไทยนิยมบริโภค ชื่อไทย ชื่ออังกฤษ ชื่อวิทยาศาสตร์ Adult length ที่อยู่อาศัย เคย Krill order Euphausiacea 1.5 cm Saltwater กุ้งฝอย Riceland prawn Macrobrachium Lanchesteri 2-7 cm Freshwater กุ้งขาว Whiteleg shrimp Pacific white shrimp King prawn Litopenaeus vannamei, formerly Penaeus vannamei 23 Saltwater กุ้งแชบ๊วย Banana shrimp Fenneropenaeus merguiensis formerly Penaeus merguiensis 20-25 cm Saltwater กุ้งกุลาดา Black tiger prawn Penaeus monodon 18-25 cm Saltwater กุ้งก้ามกราม/แม่น้า กุ้งนาง (เพศเมีย) Giant river prawn Macrobrachium Rosenbergii 13-31 cm Freshwater กุ้งมังกร Spiny lobster Panulirus spp. >30 cm Saltwater ล็อบสเตอร์ Lobster Nephropidae spp. >30 cm Saltwater เครย์ฟิช Crayfish Small Lobster Freshwater lobster Family: Astacidae, Cambaridae, Parastacidae varies Freshwater
- 10. ชื่อไทย ชื่ออังกฤษ ชื่อวิทยาศาสตร์ Adult width ที่อยู่อาศัย ปูแสม Mangrove crab Sesarma mederi 3-7 cm Saltwater ปูจาก/แป้น Gren tidal crab Varuna litterata 3-7 cm Freshwater ปูนา Ricefield crab Somanniathelphusa spp. Freshwater ปูน้าตก Waterfall crab Stream crab Larnaudia larnaudii Freshwater ปูขน/ไก่/ภูเขา Hairy leg mountain crab Cardiosoma carnifex 8-20 cm Freshwater ปูม้า/ชัก Flower crab Portunus armatus formerly Portunus pelagicus 15-20 cm Saltwater ปูทะเล/ดา/ไข่/ ทองหลาง Giant mud crab Scylla serrata 24 cm Saltwater ปูจั๊กจั่น/กบ Red frog crab Ranina ranina 7-15 cm Saltwater กั้งกระดาน Slipper lobster Thenus orientalis 12-25 cm Saltwater กั้งตั๊กแตน Mantis shrimp Oratosquilla nepa 11-14 cm Saltwater ปู-กั้งที่คนไทยนิยมบริโภค
- 12. Mimickers แมงดาถ้วย/แมงดาทะเลหางกลม Carcinoscorpius rotundicauda แมงดาจาน/แมงดาทะเลหางเหลี่ยม Tachypleus gigas Horseshoe CRAB … แต่ไม่ใช่ Crustacea หอยเม่น (Sea urchin, 海胆) Echinoidea spp. *phylum Echinodermata ปูอลาสกา Alaskan king crab Paralithodes camtschaticus ปูอัด Kani Kamaboko ไข่กุ้ง (Tobiko, とびこ) ไข่ปลาบิน Exocoetidae spp.
- 13. Outline ❏ Classification of shellfish ❏ Epidemiology of shellfish allergy ❏ Shellfish Allergens ❏ Cross reactivity ❏ Clinical manifestation ❏ Diagnosis & management
- 14. * mostly data from self-report EAACI Molecular Allergology User´s Guide 2016 Asian Pac J Allergy Immunol 2012;30:3-10 Overall prevalence 2% Adult 1.1-5.2 % anaphylaxis 42% Children 0.1-1.2 % anaphylaxis 12% Shellfish allergy is common and has high rate of anaphylaxis Shellfish allergy is one of the leading causes of food-induced anaphylaxis
- 15. Lao-Araya M, Trakultivakorn M. Prevalence of food allergy among preschool children in northern Thailand. Pediatr Int. 2011.
- 16. Outline ❏ Classification of shellfish ❏ Epidemiology of shellfish allergy ❏ Shellfish Allergens ❏ Cross reactivity ❏ Clinical manifestation ❏ Diagnosis & management
- 19. # Protein kDa Heat stability Exposure Function 1 Tropomyosin ~38 Highly stable ingest inhale Muscle contraction 2 Arginine kinase ~45 stable ingest inhale ATP binding 3 Myosin light chain 2 ~23 stable ingest Muscle contraction 4 Sarcoplasmic calcium- binding protein ~25 stable ingest Calcium binding 5 Myosin light chain 1 ~17.5 stable ingest Muscle contraction 6 Troponin C ~21 unknown ingest Muscle contraction 7 Troponin I ~30 unknown ingest Muscle contraction 8 Triose phosphate isomerase ~28 labile ingest Gluconeogenesis, glycolysis
- 20. Major allergen In adult Major allergen Major allergen In children T. Ruethers et al. Molecular Immunology 100 (2018) 28–57
- 21. Middleton's Allergy: Principles and Practice, 8th Edition
- 22. Asian Pac J Allergy Immunol 2012;30:3-10
- 23. Asian Pac J Allergy Immunol 2012;30:3-10
- 24. Sources of shellfish allergen Fresh and cooked meat: Muscle EAACI Molecular Allergology User´s Guide 2016 Food additives Tail Abdomen Pincers Cooking fume
- 25. T. Ruethers et al. Molecular Immunology 100 (2018) 28–57 Similarity of major allergen (Tropomyosin)
- 26. T. Ruethers et al. Molecular Immunology 100 (2018) 28–57 Among crustaceans, tropomyosin homology 88-100 % Crustaceans vs insects & mites, tropomyosin homology 78-98 %
- 27. T. Ruethers et al. Molecular Immunology 100 (2018) 28–57 Crustaceans vs mollusks, tropomyosin homology ~60 %
- 28. T. Ruethers et al. Molecular Immunology 100 (2018) 28–57 cephalopoda bivalvia gastropoda bivalvia Among mollusks, tropomyosin homology 70-84 % cephalo poda gastrop oda
- 29. T. Ruethers et al. Molecular Immunology 100 (2018) 28–57 Vertebrates vs Invertebrates, tropomyosin homology ~60 % Animal proteins with a sequence identity greater than 63% to human homologs are rarely allergenic (Middleton 8th Edition )
- 30. T. Ruethers et al. Molecular Immunology 100 (2018) 28–57
- 31. Figure 1. Diagnostic test results. Allergy 2007;62:85-7.
- 32. Letters / Ann Allergy Asthma Immunol 113 (2014) 666e675 Anaphylaxis caused by hemocyanin contained in shrimp cephalothorax 3 patients developed anaphylaxis after shrimp ingestion - Negative specific IgE to D.pteronyssinus, shrimp, and recombinant shrimp tropomyosin (rPen a 1) - Prick to-prick testing with fresh shrimp (Litopenaeus vannamei) - Abdomen: negative - Cephalothorax: positive - IgE immunoblot with both raw and boiled shrimp abdomen and cephalothorax extracts: - 2 prominent bands of approximately 70 kDa - identified by mass spectrometry as hemocyanin - No IgE-binding bands with abdomen extract RAW Cooked RAW Cooked RAW Cooked
- 33. Hemocyanin Molecular weight: ~75 kDa Heat stability: stable? Homology: 62.5-100% among crustaceans Function: Oxygen-transport protein Found in: Crustacean hemolymph Cephalothorax contains - Heart - hepatopancreas Small amounts may be present in the veins within abdomen. But shrimp commercial extracts are made with deveined abdominal muscle. Letters / Ann Allergy Asthma Immunol 113 (2014) 666e675 Loss of IgE binding after heated at 60°C for 10 minutes in phosphate-buffered saline (1:3, wt/vol); D Guillen, 2014 Residual IgE binding after ‘boiled’ for 10 minutes; S Piboonpocanun, 2011 All patients had reaction with cooked shrimp ingestion
- 34. Outline ❏ Classification of shellfish ❏ Epidemiology of shellfish allergy ❏ Shellfish Allergens ❏ Cross reactivity ❏ Clinical manifestation ❏ Diagnosis & management
- 35. J Allergy Clin Immunol 2001;108:881-90. Tropomyosins homology - Between crustaceans : >95% - Between mollusks: 68-100% - Crustaceans & Mollusks: 56-68% - Intra-class of mollusks - Bivalve 85-97% - Gastropod 91-100% - Cephalopod 70-100% Asian Pac J Allergy Immunol 2012;30:3-10
- 36. Food allergy: A practice parameter update 2014
- 37. O. Jirapongsananuruk et al. Clinical and Experimental Allergy, 2008. 38 : 1038–1047 68 children with a history of shrimp allergy and skin tests positive to shrimp were orally challenged to both shrimp species Negative OFC 11.76% Positive OFC P.monodon 17.65% Positive OFC M.rosenbergii 23.53% Positive OFC to both 47.06%
- 38. Cross reactivity with other invertebrates - Patients with shellfish allergy are frequently allergy to mites and insects - Cross-reactivity is probably due to the high homology of tropomyosin - Primary sensitization to tropomyosin is probably due to non-crustacean source, such as house dust mites or cockroaches via inhalation, which may cause food allergy to shellfish in some patients - Clinically relevant cross-reactivity between crustacean and HDM allergens has been described as ‘Mite–Crustacean–Mollusc syndrome’ Pediatr Allergy Immunol. 2012 Nov;23(7):608-15.
- 39. EAACI Molecular Allergology User´s Guide 2016 Mites (Arachnids) Cockroach (Insects) Parasites (Nematodes) Immunological cross-reactivity among crustacean and mollusk species as well as to mites, insects, and nematodes
- 40. Middleton's Allergy: Principles and Practice, 8th Edition
- 41. Outline ❏ Classification of shellfish ❏ Epidemiology of shellfish allergy ❏ Shellfish Allergens ❏ Cross reactivity ❏ Clinical manifestation ❏ Diagnosis & management
- 42. T. Ruethers et al. Molecular Immunology 100 (2018) 28–57 - Mainly infects fish - Direct GI irritation - Allergic reaction & cross-reactivity
- 43. Clinical manifestation Asian Pac J Allergy Immunol 2012;30:3-10 Symptoms Mild oral symptoms similar to pollen-food syndrome Anaphylaxis Factors Host Exposure Shellfish Type Amount Process Part eaten Age Sensitization ingestion inhalation contact
- 44. EAACI Molecular Allergology User´s Guide 2016
- 45. EAACI Molecular Allergology User´s Guide 2016 Features and clinical pattern of three different developments of shellfish allergy
- 46. Outline ❏ Classification of shellfish ❏ Epidemiology of shellfish allergy ❏ Shellfish Allergens ❏ Cross reactivity ❏ Clinical manifestation ❏ Diagnosis & management
- 47. Diagnosis - History - Tests for sensitization (e.g. SPT, specific IgE) - Food challenges EAACI Molecular Allergology User´s Guide 2016
- 48. History Symptoms and affected organ systems Onset and course of progression Co-factors (e.g. exercise, NSAID, alcohol etc.) Shellfish containing food (highly-, mildly-, non-processed) Previous reactions to crustacean or mollusk Additional features, e.g. house dust-mite, insect allergy Atopic diseases, e.g. atopic eczema, asthma R/O seafood poisoning, e.g. - Histamine from Scombroid poisoning (fish) - Marine biotoxins from filter feeders (mussels) EAACI Molecular Allergology User´s Guide 2016
- 49. Skin prick test (SPT) Commercial shellfish extracts - Reliable for highly abundant & cross-reactive allergens (e.g tropomyosin) - False negative - heat sensitive allergens (e.g. myosin light chain) - weak- or non-cross-reactive allergens (e.g. arginine kinase) - specific shellfish species (e.g. Southern hemisphere) Prick-prick test with offending shellfish product - Specie-specific - Potentially false negative, if lowly abundant and low stability (e.g. MLC) - In case of severe anaphylactic reaction, - Titrated testing with diluted shellfish product - Specific IgE-testing before SPT EAACI Molecular Allergology User´s Guide 2016
- 50. O. Jirapongsananuruk et al. Clinical and Experimental Allergy, 2008. 38 : 1038–1047 68 children with a history of shrimp allergy and skin tests positive to shrimp were orally challenged to both shrimp species Negative OFC 11.76% Positive OFC P.monodon 17.65% Positive OFC M.rosenbergii 23.53% Positive OFC to both 47.06%
- 51. Fig. 2. Mean wheal diameter (MWD) from different skin tests in groups of patients with positive or negative challenges to Penaeus monodon or Macrobrachium rosenbergii. (a). Box plots of MWD from different skin tests in patients with positive (groups I and III) and negative (groups II and IV) challenges to P. monodon. (b) Shows MWD from different skin tests in patients with positive (groups II and III) and negative (groups I and IV) challenges to M. rosenbergii. O. Jirapongsananuruk et al. Clinical and Experimental Allergy, 2008. 38 : 1038–1047
- 52. O. Jirapongsananuruk et al. Clinical and Experimental Allergy, 2008. 38 : 1038–1047 Fair correlations ComSPT–PmSPT Fair correlations ComSPT—PmPTP Fair correlations ComSPT–MrPTP No correlations ComSPT–MrSPT Fair correlations MrSPT–MrPTP Moderate correlations PmSPT–PmPTP
- 53. Fig. 3. Predictive probabilities for mean weal diameter (MWD) from different skin tests to determine the positive food challenges. Predictive probabilities for MWD (mm) from different skin tests to determine positive food challenges are shown. (a) and (b) Demonstrate predictive probabilities of skin tests for a positive challenge to Penaeus monodon and Macrobrachium rosenbergii, respectively. Thin lines represent predicted probability and MWD. 22.5 mm 95% predictive 20 mm 95% predictive 30 mm 80% predictive 30 mm 95% predictive O. Jirapongsananuruk et al. Clinical and Experimental Allergy, 2008. 38 : 1038–1047
- 54. Allergen-specific IgE Shellfish extract - potentially false negative or low titers in case of low abundant allergens or extract do not represent the specific shellfish species consumed by the patient (e.g. Southern hemisphere) Purified allergen (tropomyosin) from shrimps, house dust-mite and anisakis - available on the allergen microchip (ISAC, Thermo Fisher Scientific) - used to quantify allergen-specific IgE EAACI Molecular Allergology User´s Guide 2016
- 55. EAACI Molecular Allergology User´s Guide 2016
- 56. ✓ ✓ ✓
- 57. Code: f24 - Latin name: - Pandalus borealis (กุ้งแดง) - Penaeus monodon (กุ้งกุลาดา/ black) - Metapenaeopsis barbata (กุ้งทราย/กุ้งตกกระ) - Metapenaus joyneri (กุ้งตะกาด) - Source material: Boiled, frozen Atlantic shrimp and raw, frozen prawns from the Indo-West-Pacific Code: f23 - Latin name: Chionocetes spp. - Source material: Boiled crab meat Code: f258 - Latin name: Loligo edulis, Loligo vulgaris - See also Pacific flying squid (Todarodes pacificus) f58 Code: f58 - Latin name: Todarodes pacificus - Source material: Squid meat http://www.phadia.com/en/Products/Allergy-testing-products/ImmunoCAP-Allergen-Information กุ้งตะกาดกุ้งทราย/กุ้งตกกระ กุ้งกุลาดากุ้งแดง หมึกทะเลญี่ปุ่น
- 58. T. Ruethers et al. Molecular Immunology 100 (2018) 28–57
- 59. EAACI Molecular Allergology User´s Guide 2016 Specific IgE sensitization SPT - skin prick test, FC - Food challenge Only Pen m 1 and Pen m 4 sensitization has been associated with clinical reactivity Ability to predict allergy sIgE to Pen m 1 better than SPT or sIgE to whole shrimp sIgE to Pen m 4 better in children very limited information about mollusk allergen
- 60. Diagnostic algorithm for shellfish allergy EAACI Molecular Allergology User´s Guide 2016
- 61. Diagnostic algorithm for shellfish allergy EAACI Molecular Allergology User´s Guide 2016
- 62. Diagnostic algorithm for shellfish allergy EAACI Molecular Allergology User´s Guide 2016
- 63. Oral food challenge In case of doubtful relationship between shellfish ingestion and allergic reaction: - Oral double-blind, placebo-controlled food challenge in patients without moderate or severe anaphylactic reactions: 1. Preparing meal with whole seafood extract or the ground boiled of the offending seafood species (masked in fruit juice, chocolate or vanilla ice cream, or in a burger) 2. Accumulated doses of up to 24 g of seafood (e.g.1-2 large prawns) EAACI Molecular Allergology User´s Guide 2016
- 64. Anna Nowak, Work Group report: Oral food challenge testing. J Allergy Clin Immunol 2009;123:S365-83. 1 portion size = 56-85 gm
- 65. Management Advices and avoidance - Strictly avoidance based on clinical reactions - Prompt recognition and treatment of acute allergic reactions - Avoidance of all members of the crustacean family is generally recommended - Avoidance of mollusks is advised if allergy to it is demonstrated - High IgE reactivity to tropomyosin might be advised to avoid all shellfish - Avoidance of vertebrate fish is unnecessary EAACI Molecular Allergology User´s Guide 2016 Immunotherapy - At present commercially available products for allergen-specific immunotherapy of shellfish protein allergy are not available Prognosis - In general, childhood-onset allergy to seafood has a poor prognosis, with the minority outgrowing their food allergies during childhood - adult-onset shellfish allergy is thought to be persistent although this has not been extensively studied
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