YHPA Immunology Symposium Anaphylaxis Urticaria & Angioedema Vincent St Aubyn Crump FRCP The Samlesbury Hotel Saturday, 21st May 2016 Nothing to declare: No conflict of Interest Anaphylaxis Vincent St Aubyn Crump FRCP YHPA Immunology Symposium 21 May2016 The perplexing conundrum of anaphylaxis Anaphylaxis is a perplexing disease, It is under-recognized & undertreated But also many conditions masquerade
& are misdiagnosed as anaphylaxis Symptoms of Anaphylaxis Skin (80-90%) Itching, flushing, urticaria, angioedema Eyes Itching, tearing, redness, swelling of the skin around the eyes Nose and mouth Sneezing, runny nose, nasal congestion, swelling of the tongue, metallic taste Lungs and throat (70%) Difficulty getting air in or out, repeated coughing, chest tightness, wheezing or other sounds of labored breathing, increased mucus production, throat swelling or itching, hoarseness, change in voice, sensation of choking Heart and circulation (70%) Dizziness, weakness, fainting, rapid, slow, or irregular heart rate, low blood pressure Digestive system Nausea, vomiting, abdominal cramps, diarrhea Nervous system Anxiety, confusion, sense of impending doom Common triggers for Anaphylaxis Foods In children, hen's eggs, cow's milk, peanuts, tree nuts, fish, wheat, and soy are the most
common food triggers. In teens and adults, peanuts, tree nuts, fish, and crustaceans (shellfish such as shrimp) are the most common triggers Any food, including fruits, vegetables, seeds, and some spices and food additives, can cause anaphylaxis. Medications, such as antibiotics (penicillins and cephalosporins) and analgesics (aspirin, ibuprofen), potentially any medication. Venom from insects, including bees, yellow jackets, wasps, hornets, and fire ants. Latex from natural rubber, found in some latex gloves, balloons, condoms, sports equipment, and medical supplies. Allergen immunotherapy ("allergy shots"), such as those given for the treatment of allergic rhinitis (hay fever). Exercise, either by itself, or after food ingestion (eg, wheat, celery, shrimp, or other food) or after medication ingestion (eg, aspirin, ibuprofen). Less common triggers include exposure to airborne allergens (such as horse dander), human seminal fluid, cold water, or cold air. Case 1: ES 31 yr-old O+ Chronic spontaneous urticaria & angioedema for 10 years Over last 6 months she has been getting more frequent & more severe attacks 1m before her referral she took Paracetamol 500mg x2 for a viral ilness and within hour of first
dose developed itching palms, generalised urticaria, angioedema of lips & tongue, difficulty breathing and tightness in throat ->A/E Rx adrenaline and discharged with adrenaline autoinjector Medications: Seretide inhaler Fexofenadine 180mg prn for urticaria Ibuprofen (OTC) prn for about 6m PMH: NSAIDs for dysmenorrhea and leading up to hospitalisation taking Ibuprofen more regularly for sprained ankle. Moderate-severe asthma Naprosyn-induced asthma 5 years ago Skin Prick Test: Allergic to house dust mite Oral Celecoxib /Celebrex (Selective NSAID) Challenge 2 weeks ago passed: Celebrex 100mg po & observe for 2 hours Advised to avoid ALL other (non-selective) NSAIDs & use Celebrex only No need for EpiPen Case 2: J Mc C
33 yr-old male History: June 2014 at 1am: Collapsed admitted to ICU on Cardiac monitor Discharge Diagnosis: Morbid Obesity & Type 2diabetes & advised to lose weight 2 episodes of anaphylaxis since life-style change: 28 June: within 30min brisk walking developed hives, diarrhoea, hospital (Systolic BP 50) Rx: adrenaline ,. Had pizza & alcohol 2nd 10 Aug: 1hr after subway -> gym collapsed after urticaria. Unconscious for 10 min. Rx: adrenaline Current medication: Metformin 500mg bd Simvastatin Past Medical History Asthma: with colds Eczema: as baby, no hay fever DIET: eats wheat daily without any adverse effects Family history : Unknown (adopted) On Examination: Morbidly Obese J Mc C: Investigations
Blood Test: ImmunoCAP RAST Skin Prick Tests: House dust mite: 0 Cat: 0mm Dog: 0 Grass: 0 Birch: 0 Alternaria:0 Milk: 0 Egg: 0 Wheat: 3mm Diagnosis? Peanut: 0 Nut Mix 1 Class 2 Nut mix 1 contains :Peanut, Hazelnut, Brazil nut, Almond and Coconut. Nut mix 2: 0 Class
Nut mix 2 contains :Pecan nut, Cashew nut, Pistachio and Walnut. Wheat: 1 Class Peanut: 0 Class Silver Birch:0 Class Molecular wheat test Omega-5-Gliadin: Class 3+ Case 3: A rare case of anaphylaxis 28 yr-old pharmacist, married for 2 years & trying to start a family Vaginal irritation for 18months. Worse after unprotected sex . Fully investigated by Gynaecologist & Derm: no infections or contact dermatitis Irritation getting worse & recently accompanied by hives all over body, on 2 occasions wheezing & light-headedness PMH: Atopic: Mild intermittent Asthma & perennial rhinitis Atopic eczema as a child Medications:
Salbutamol inhaler prn Loratidine 10mg prn Skin Prick Test: House dust mite: 12mm Grass: 0 Cat:7mm Histamine: 4mm Diagnosis: ? Rare anaphylaxis continued 2 weeks later Skin Prick Test sample of husbands semen:12mm Saline: 0 Histamine: 5mm Specific IgE semen: class 3 Diagnosis: Semen Anaphylaxis Case 4: MB,26 yr-old female
Peanut anaphylaxis since age 13 yrs-old Over last 1 year anaphylaxis to increasing number of unrelated foods (soy, sesame, some unknown foods -reactions always occur after eating. Reactions always while eating or within 1 hour Sometimes hives, sometimes bright red all over/flushing, throat closes up and she cant breathe-> Ambulance About 10 visits to A/E in last 6m & used her EpiPen x3 times in last year & Flight emergency landing: peanut Medications EpiPen X 4 Seretide inhaler Loratidine 10mg bd &Cetirizine 10mg nocte
Past Medical History Asthma since age 5yrs Atopic eczema as infant Possible Chronic spontaneous urticaria Social/ Family history Works in bank, smokes 5cgs/dy sister has asthma & Nut allergy Diet: Meticulously reads labels and strictly avoids peanuts, nuts, seeds, egg, milk, most fruits, . Investigations Specific IgE Skin Prick Test
While skin testing Diagnosis? Peanut: 0 Ara h 2: 0 ALL tree nuts: negative Milk:0 Egg: 0 Wheat: class 2 (o-5) Previous investigations: Had a blood test which said she was allergic to peanut, milk, egg, soy, wheat) Diagnosis & Management Not allergic to peanut Laryngo-pharyngeal Reflux (Silent GERD) With Hyperventilation Syndrome /panic attacks
Improved with Omeprazole Refused Oral blinded peanut Challenge Refused referral for Psychological assessment Prevalence of Anaphylaxis in UK 1 in 300 of the European population at some time in their lives suffer from anaphylaxis 20 people die from anaphylaxis each year in UK The prevalence of anaphylaxis in the UK is increasing, but deaths from anaphylaxis is stable Increase in anaphylaxis-related hospitalizations but no increase in fatalities: An analysis of United Kingdom national anaphylaxis data, 1992-2012 Paul J. Turner & Richard Pumphrey et al, Jour Aller & Clin Immunol, 135 (4); 956-963 (April 2015) Anaphylaxis admissions vs Anaphylactic fatalities
What is anaphylaxis? First coined by French doctors, Charles Richet (Nobel winner) & Dr Portier in 1902 from Greek words ana meaning against & phylaxis (protection) Anaphylaxis = Anti-protection Set of symptoms opposite of immunity that they were hoping to achieve by injecting sea anemone sting in a dog, which caused death due to anaphylaxis Majority of anaphylaxis used to be caused by horse serum, penicillin & insect stings. Foods were rarely related before the last 3 decades Symptoms of anaphylaxis Skin Itching, flushing, hives (urticaria), swelling (angioedema) 80-90% Eyes Itching, tearing, redness, swelling of the skin around the eyes Nose and mouth Sneezing, runny nose, nasal congestion, swelling of the tongue, metallic taste Lungs and throat Difficulty getting air in or out, repeated
coughing, chest tightness, wheezing or other sounds of laboured breathing, increased mucus production, throat swelling or itching, hoarseness, change in voice, sensation of choking : 70% Heart and circulation Dizziness, weakness, fainting, rapid, slow, or irregular heart rate, low blood pressure 70% Digestive system Nausea, vomiting, abdominal cramps, diarrhoea Nervous system Anxiety, confusion, sense of impending doom Definition of anaphylaxis vs systemic allergic reactions Anaphylaxis is a severe, life-threatening generalised or systemic hypersensitivity reaction which is likely when both of the following criteria are met: 1. Sudden onset and rapid progression of symptoms 2. Life-threatening airway and/or breathing and/or circulation problems Skin and/or mucosal changes (flushing, urticaria, angioedema) often also occur but are absent in a significant proportion of cases. Gastro-intestinal symptoms (vomiting, diarrhoea, abdominal pain) can also be associated with symptoms of anaphylaxis.
Skin / mucosal and gastrointestinal symptoms without airway, breathing or circulation symptoms are systemic allergic reactions, but not life threatening reactions and therefore not classified as anaphylaxis. 3 Clinical criteria for diagnosing anaphylaxis (WAO) Anaphylaxis is highly likely when any 1 of the following 3 criteria are fulfilled: 1. Acute onset of an illness (minutes to hours) Involvement of skin, mucosal tissue, or both (i.e., generalised hives, pruritus, or flushing, swollen lips-tongue-uvula) and at least 1 of the following: 1. Respiratory compromise (i.e., dyspnoea, wheeze-bronchospasm, stridor, reduced peak expiratory flow [PEF], hypoxaemia) or 2. Reduced BP or associated symptoms of end-organ dysfunction (i.e., hypotonia/collapse, syncope, incontinence) 2. Occurrence of 2 or more of the following symptoms or signs after exposure to a likely allergen (minutes or hours) 1. Involvement of skin, mucosal tissue, or both (i.e., generalised hives, pruritus, or flushing, swollen lips-tongue-uvula) 2. Respiratory compromise (i.e., dyspnoea, wheeze-bronchospasm, stridor, reduced PEF, hypoxaemia) 3. Reduced BP or associated symptoms of end-organ dysfunction (i.e., hypotonia/collapse, syncope,
incontinence) 4. Persistent GI symptoms (i.e., crampy abdominal pain, vomiting) 3. Reduced BP after exposure to a known allergen (minutes to several hours) Systolic BP of <90 mmHg or >30% decrease from baseline. Classification of Anaphylaxis Anaphylaxis Nonimmunologic Idiopathic Immunologic IgE-mediated Non-IgE mediated IgG Drugs
Physical Exercise Cold Anaphylactic deaths in UK 50 Series 1 45 40 35 30 25 Series 1 20 15 10 5 0
Stings Anaesthetics Nuts Antibiotics ?Food Fatal Anaphylaxis in UK 1992 2001. Pumphrey R Curr Opin All Clin Immunol 4 (4): 285-290, 2004 Other drugs Food Contrast Media Others
~20 deaths per year Suspected causes of anaphylactic deaths in UK Non-food:139 Drugs: 88 Anaesthetics: 35 Suxamethonium: 19 Antibiotics: 27 Cephalosporin: 12 Aminopenicillin: 10 Other drugs: 15 NSAID: 6 Gelatines: 5 ACE inhibitor: 3 Vitamin K: 2 Contrast Media: 11 Iodinated: 9 Stings: 47 29 wasp
During meal: 5 ?milk: 3 ? nuts: 3 ?Grape: 1 ?Fish: 1 ? Nectarine: 1 Anaphylactic deaths: First-Time Reactions Although most patients had been stung or exposed to the causative drug previously without a reaction, fatal reactions was thought to be the first in: 23/34 sting 17/24 antibiotics 17/20 muscle relaxants 4/6 NSAID 13/13 other drug 10/10 contrast media Risk factors for anaphylactic reactions (co-factors)
Augmenting factors Concomitant diseases Co-factors Factors which lower the reaction threshold or which make symptoms more severe by directly influencing the immunological mechanism of type 1 allergy: Exercise NASID Antacid / PPI Alcohol Infections Menstruation
= Co-existing diseases, which jeoparadize patients or which increase mortality e.g. Asthma Cardiac disease Mastocytosis = a subgroup of risk factors, not acting on an immunological basis themselves eg. Certain allergens (nuts) Adolescence ACE-inhibitors
Beta-blockers Psyche Threshold dose & co-factor-dependent anaphylaxis Up to 39% of severe anaphylactic reactions are triggered by cofactors Management of Anaphylaxis Management of Anaphylaxis in community: Postemergency After emergency treatment for a suspected anaphylactic reaction Children <16 year-old: Admission Adults >16 year-old: Observation for 6-12 hrs from onset of symptoms
Mast Cell Tryptase As soon as possible after emergency RX and the second 1-2 hours (no later than 4 hrs) after e r Refer Adrenaline Autoinjector & Patient Info & Support before discharge Specialist Allergy Service NICE pathway for Drug Allergy NICE patway for NICE pathway pt. experience for Food Allergy
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