Allergic Disorders (1) PDF

Allergic Disorders Angela Oest, MS, PA-C, MPH Center for Food Allergy & Asthma Research (CFAAR) Ann & Robert H. Lurie Children’s Hospital of Chicago Division of Allergy & Immunology Northwestern University Feinberg School of Medicine *Some slide material courtesy of Kristine Burgess  Objectives...

Allergic Disorders Angela Oest, MS, PA-C, MPH Center for Food Allergy & Asthma Research (CFAAR) Ann & Robert H. Lurie Children’s Hospital of Chicago Division of Allergy & Immunology Northwestern University Feinberg School of Medicine *Some slide material courtesy of Kristine Burgess  Objectives Identify and compare Type I versus Type IV hypersensitivity reactions. Identify the most common allergens involved in allergic disorders. List the risk factors for the development of allergies. Discuss the basic treatments for atopic dermatitis, allergic asthma, and allergic rhinitis. Discuss the different forms of allergy testing. List the indications for immunotherapy. Discuss the diagnosis and treatment of food allergies. Discuss the indications for referral to a board-certified allergist. 8/13/23 2 Type I vs Type IV Hypersensitivity Type I Hypersensitivity Type IV Hypersensitivity Immediate (within minutes-hours) Delayed (48-72 hours) IgE-mediated T cell-mediated Classic allergy, Atopy, Anaphylaxis Contact dermatitis 8/13/23 3  Mechanism of Type I Hypersensitivity Allergen (antigen) is processed by APC (macrophage) → interacts with a Th2 cell → Th2 cell stimulates B-cells to produce IgE by releasing IL-4 → IgE binds via the Fc portion to a mast cell or basophil sensitizing the cell → Subsequent exposure to antigen causes the mast cell or basophil to degranulate → releases inflammatory mediators (histamine) 8/13/23 4  Type I Hypersensitivity: Clinical Presentation Clinical examples: Allergy, Atopy, Anaphylaxis Symptoms - Increased vascular permeability (edema, swelling) - Vasodilation (hypotension) - Smooth muscle contraction (bronchospasm and congestion) - Stimulus of nerve endings (pruritus) Treatment - Antihistamine – blocks H1 or H2 receptors - Epinephrine – potent vasoconstrictor 8/13/23 5  Mechanism of Type IV Hypersensitivity Antigen-sensitized T-cells release cytokines after a second contact with antigen → cytokines released induce an inflammatory reaction 8/13/23 6  Type IV Hypersensitivity: Clinical Presentation Clinical examples: - Contact dermatitis - Tuberculin – to be discussed in Clinical Immunology lecture - Granulomatous – to be discussed in Clinical Immunology lecture - Contact Dermatitis Common triggers: poison ivy, nickel, latex, Symptoms: intensely pruritic rash, bumps/blisters, crusting/oozing, well-demarcated area of contact - Treatment: Antihistamine & topical steroid 8/13/23 7  Definition: Atopy vs Allergy Atopy - an exaggerated IgE-mediated immune response - all atopic disorders are Type I Hypersensitivity disorders Allergy - any exaggerated immune response to a foreign antigen regardless of mechanism Allergen - an antigen that produces an abnormally vigorous immune response to a perceived threat that would otherwise be harmless to the body Atopic Disease: - Atopic Dermatitis - Allergic Rhinitis - Allergic Asthma 8/13/23 8  Atopic March Atopic Dermatitis and Food Allergy Allergic Asthma Allergic Rhinitis Of those with atopic dermatitis: 75% will develop allergic rhinitis 50% will develop asthma 8/13/23 9  Risk Factors of Atopic Disease Genetics - 25-50% chance of atopy if one parent is allergic - 60-75% chance of atopy if both parents are allergic Environment - Differences in hygiene ("The Hygiene Hypothesis") - Increased antibiotic use - Decreased infections/vaccination - Mode of delivery during childbirth - Westernized diet and altered gut flora - Outdoor air pollution - Increased indoor allergen exposure 8/13/23 10  The Hygiene Hypothesis: Are we too clean? Definition: the stimulation of the immune system by microbes or microbial products protects from the development of inflammatory diseases Includes the period from in utero to school age Mechanism: an imbalance between the Th1 and Th2 subtypes of T helper cells - Early exposure to infectious agents helps direct the immune system toward a Th1 cell-predominant response - Th2 predominance is more associated with atopy - Factors such as larger families, day care, rural vs urban environments play a role 8/13/23 11 Hygiene Hypothesis 8/13/23 12  Health Disparities of Atopic Disease Race - Atopic dermatitis is slightly more common among Caucasians, but more severe disease is noted among Black & Hispanic patients - Blacks and American Indian/Alaska Natives have the highest asthma prevalence Gender & Age - In childhood asthma is more common for males (8.3%) than females (6.7%). Among adults, more common in females (9.8%) than males (5.5%) - 80% of atopic dermatitis presents before age 6 - Atopic dermatitis affects male and female children similarly, but is more prevalent in adult women - Food Allergy prevalence: 8% of children, 11% of adults 8/13/23 13 Racial and Ethnic Differences in Current Food Allergy Prevalence among US Children 16 Reported FA Convincing FA 14 % Reporting. Current Food Allergy 12 11.4% 10 8 7.6% 6 4.7% 4 2 0 White NH Black NH Asian NH Hispanic Multiple/Other NH FA impacts all racial/ethnic groups Gupta RS, Warren CM, Smith BM, Blumenstock JA, Jiang J, Davis MM, Nadeau KC. The Public Health Impact of Parent-Reported Childhood Food Allergies in the United States. Pediatrics 2018-1235  Health Disparities of Atopic Disease Socioeconomic Status - In 2018, current asthma rates were significantly higher (11.0%) among those with a family income below the poverty threshold as compared to above the poverty threshold Sociodemographic factors at play - Educational attainment - Exposure and housing characteristics - Psychological distress - Insurance coverage - Cost barriers - Unemployment 8/13/23 15  Atopic Dermatitis Epidemiology - Typically presents within first 2 months of life with 80% of cases presenting by age 6 - Adult onset is rare (consider biopsy) Symptoms - Erythematous, dry, pruritic patches "the itch that rashes" - Oozing, weeping, cracked excoriations can occur - Lichenification – thickening hardening of the skin 8/13/23 16  The Presentation of Atopic Dermatitis First 6 months: the face, cheeks, chin, forehead and scalp (spares diaper area) 6-12 months: elbows and knees — places that are easy to scratch or rub Toddlers (2-5 years): flexor surfaces of elbows and knees, or wrists/ankles and hands. Also common around the mouth and eyelids 5+: flexor surfaces (popliteal and antecubital fossae are classic), hands 8/13/23 17  Atopic Dermatitis: Exacerbating Factors Allergen exposure (inhalant, food, contact) Skin dehydration (hot showers, lack of moisturization) Emotional stress Hormonal (pregnancy, menstruation) Secondary Infection (S. aureus, Group A Strep, herpes, fungal/yeast) Season (improves in summer, flares in winter) Tight clothing (pruritus flares after taking off clothing) 8/13/23 18  Atopic Dermatitis: Diagnosis & Treatment Diagnosis is based on clinical appearance Treatment - Patient education Reduce exacerbants Lukewarm baths (bleach baths) Frequent, liberal application of moisturizers (immediately after bathing) Aquaphor, Cerave, Vanicream, Eucerin Scent-free, dye-free skin soaps, detergents, skin care products 8/13/23 19 Atopic Dermatitis: Treatment continued - Medication Antipruritic - Antihistamines stop the itch/scratch cycle – long acting (cetirizine, levocetirizine, fexofenadine, loratadine) preferred over diphenhydramine Anti-inflammatory Topical steroids (short course of oral corticosteroid for severe flare) Calcineurin inhibitors – anti-inflammatory (tacrolimus, pimicrolimus) Phosphodiesterase-4 Inhibitors (Eucrisa) Biologics – IL-4 blocker (Dupixent) - Other UV light therapy Treat secondary infection (bacterial/fungal) 8/13/23 20  Allergic Asthma Allergen-induced bronchospasm Signs & Symptoms - Shortness of breath, wheezing, cough, and/or chest tightness - End-expiratory wheezing and decreased breath sounds 8/13/23 21  Allergic Asthma Diagnosis - History & physical exam - Spirometry or pulmonary function tests provide objective data – 6+ years old Treatment - Allergen avoidance/treatment - Medication therapy SABA (short acting beta agonist) - (i.e. albuterol) ICS (inhaled corticosteroid) ICS + LABA (long acting beta agonist) Leukotriene inhibitors – montelukast, zafirlukast Biologics (Xolair – anti-IgE, Dupixent, Nucala, Fasenra - IL-4/IL-5 inhibitors) Systemic steroids (Prednisone) for exacerbation 8/13/23 22 Asthma Step Therapy 8/13/23 23  Allergic Rhinitis Epidemiology - Seasonal or perennial exposure to aeroallergens Sensitization occurs first to perennial allergens (year round exposure) - Relationship to age and seasonal pattern 8/13/23 24  Allergic Rhinitis Signs & Symptoms Itchy, runny nose Nasal mucosa boggy, pale blue or erythematous Chronic sneezing Itching of the palate and middle ear Postnasal drip → sore throat, coughing, or throat clearing Nasal polyps Adenotonsillar hypertrophy Allergic/adenoid facies Allergic salute Allergic shiners & Dennie’s lines (Dennie- Morgan fold) Allergic conjunctivitis 8/13/23 25  Allergic Rhinitis: Diagnosis & Treatment Diagnosis - Thorough history is key - Allergy testing Treatment - Environmental modification (allergen avoidance) Dust mite: allergen encasements on bedding, wash bedding regularly in hot water, eliminate carpet & upholstery, limit stuffed animals Pollen: HEPA filters, windows closed, air conditioning, change clothing/bathe after outdoor exposure, avoid peak pollination time in AM Dander: pet avoidance, eliminate from bedroom, HEPA filters Mold: Avoid raking/handling moist decaying leaves and gardening, correct flooding, dehumidifier 8/13/23 26  Allergic Rhinitis: Treatment Continued Medication therapy - Nasal corticosteroids are first line! - Second-line Oral antihistamines Leukotriene inhibitors - Other Immunotherapy (“allergy shots”) - Allergic conjunctivitis- antihistamine eyedrops - Severe untreated symptoms may trigger sinusitis or otitis media 8/13/23 27  Inhalant Allergens: Pollen Trees- late March to early June Grasses- early May to early July Weeds- August to early October Varies by geographic region 8/13/23 28  Inhalant Allergens: Pet Dander Allergens are proteins of animals’ skin, urine, hair and saliva Common trigger for allergic asthma Cats – very allergenic Dogs – no such thing as a "hypoallergenic dog" but some people not allergic to all dogs Rodent (rats, mice) 8/13/23 29  Inhalant Allergen: Dust Mites Microscopic arthropods that feed on human and animal dander (two species) Allergens are fecal material and dead bodies Found in mattresses, pillows, thick carpet Require temp 25-30o C, high humidity Perennial 8/13/23 30  Inhalant Allergen: Cockroach Big trigger for asthma, especially in inner-city children Antigenic component is debris from dead bodies Avoid food crumbs, consider exterminator 8/13/23 31  Inhalant Allergen: Mold/fungi Inhaled spores Outdoor types - Alternaria, found in soil, hay, dead leaves – most common Indoor types - Aspergillus & Penicillium, found in damp basements, showers Little cross-reactivity between species 8/13/23 32  Allergy Testing Methods Skin Testing - Patch testing Contact - Skin prick test Puncture - Intradermal testing Intradermal injection (0.2cc) Allergy Blood Testing - In vitro testing for serum immunoglobulin (IgE) Total IgE – total "allergic load" sIgE – specific allergen 8/13/23 33  Patch Testing Diagnosis of allergic contact dermatitis - Most common: chemical or irritants - Identify allergen in 50-70% of time Delayed hypersensitivity- occurs 12-72 hours after exposure to antigen - Suspected allergen is affixed to skin for 48 hours - Area is inspected at 48 & 72 hours for erythema and vesicular reactions 8/13/23 34  Skin Prick Testing Allergen introduced into the epidermis with a small needle or device - Histamine & saline controls are used (≥ 3mm considered positive) Most common skin test Used to formulate allergy immunotherapy Benefits - Rapid (results in 15 minutes) - Allows testing of multiple antigens - Low risk of systemic absorption - Reasonable sensitivity 8/13/23 35  Intradermal Testing Placement of test antigen below the epidermal layer of skin Known quantity of antigen - Volume of 0.2cc High sensitivity More frequent adverse reactions - Inhalant allergen testing - Not typical for foods 8/13/23 36  The Role of in vitro allergy testing Severe dermatographism, eczema or hives that prevents skin testing feasibility Patients on antihistamines or tricyclic antidepressants (suppress skin test results) Patients uncooperative with skin testing Patients at high risk of anaphylaxis with skin testing Used to assess ongoing risk of systemic reaction in patients with food allergy In general, panel testing is not recommended 8/13/23 37 sIgE interpretation example 8/13/23 Presentation or Section Title 38  Allergen Immunotherapy Indications Allergic symptoms of congestion, rhinorrhea, or itchy, watery eyes with a positive skin test to aeroallergens Allergic asthma with known triggers Chronic sinusitis Inability to tolerate medications (sedation from antihistamines, or nasal sores from nasal sprays) Inability to control symptoms with medications or desire to reduce medication need History of IgE-mediated anaphylactic reactions to hymenoptera venom 8/13/23 39  Allergen Immunotherapy Customized formulation based on skin test results Injections are administered ~weekly (or twice weekly) to maintenance level Once maintenance level is achieved, frequency of injections is gradually reduced to every 4 weeks Allergen concentration is increased from dilute (1:100,000) to concentrated (1:100) solutions gradually, with dose (amount) increased within a given concentration Benefits generally seen in 6-12 months Length of therapy is usually 3-5 years (provides 10-20 years of protection upon completion) Approximately 90% of patients have greatly improved symptoms following a full course of therapy - Improves quality of life - Decreased need for medications 8/13/23 40  Food Allergy Most commonly presents in childhood Hypotheses include relationship to atopic dermatitis and gut microbiome Food allergy and eczema: "chicken and the egg" - which came first? Prevalence: 8% of children, 11% of adults Early introduction of peanut in infancy can be protective - Requires prior evaluation for high-risk infants Significant psychosocial impact 8/13/23 41  Food Allergy Most common allergens - Milk - Eggs - Peanuts - Tree nuts - Fish - Shellfish - Wheat - Soy - Sesame Commonly outgrown – milk, egg, soy Typically persists throughout life – peanut, tree nut 8/13/23 42  Childhood Food Allergy Prevalence in the US 3. Convincing Food Allergy % of US Population 2.2 Convincing FA = 7.6% (95% CI: 7.1%-8.1%) 2.25 Physician-Diagnosed FA = 4.7% (95% CI: 4.3%-5.0%) 1.8 1.9 1.5 1.3 1.2 1.0 0.9 0.9 0.8 0.7 0.75 0.6 0.5 0.5 0.3 0.3 0.2 0.2 0.1 0. Peanut Milk Shellfish Tree Nut Egg Fin Fish Wheat Soy Sesame Gupta et al. The Public Health Impact of Parent-Reported Childhood Food Allergies in the United States. Pediatrics. 2018-1235  Adult Food Allergy Prevalence in the U.S. 3.75 2.9 Convincing Food Allergy % of US Population 3. Convincing FA = 10.8% (95% CI: 10.4-11.1) Physician-Diagnosed FA = 5.1% (95% CI: 4.9-5.4%) 2.25 1.9 1.8 Reported FA = 19.0% (95% CI, 18.5%-19.5%) 1.5 1.2 1.3 1.2 0.9 0.9 0.8 0.8 0.7 0.6 0.75 0.4 0.4 0.4 0.3 0.2 0.1 0. Shellfish Milk Peanut Tree Nut Fin Fish Wheat Egg Soy Sesame At least 10.8% (>26 million) of US adults are food allergic. However, nearly 19% of adults believe that they have a food allergy 44 Gupta et al. Prevalence and Severity of Food Allergies Among US Adults. JAMA Network Open. 2019;2(1):e185630. Food-Allergic Children with Top 9 Allergies by Age Milk Peanut Shellfish Tree Nut Egg Fin Fish Wheat Soy Sesame 60% % of Convincingly Food-allergic Children 50% 40% 30% 20% 10% 0% < 1 Year 1-2 Years 3-5 Years 6-10 Years 11-13 Years 14-17 Years Gupta RS, Warren CM, Smith BM, Blumenstock JA, Jiang J, Davis MM, Nadeau KC. The Public Health Impact of Parent-Reported Childhood Food Allergies in the United States. Pediatrics 2018-1235  Food Allergy: Diagnosis Diagnosis - Thorough history - IgE-mediated: immediate response (seconds – up to 2 hours) - If no history of anaphylaxis Skin prick testing low specificity so high false positives Usually followed with sIgE testing to assess risk of systemic reaction - If history of anaphylaxis sIgE in vitro blood test Oral food challenge is gold standard – not typically performed if recent reaction 8/13/23 46  Anaphylaxis Severe, rapidly progressive allergic reaction that involves 2 or more body systems Food, insect stings, medications are most common triggers Involves many body systems: - Skin – urticaria/angioedema, flushing, pruritis - Respiratory – bronchoconstriction – cough/wheeze/laryngeal edema - Gut – rapid onset of vomiting or diarrhea - Nose/Eyes - rhinorrhea, tearing "like a faucet" - Cardiovascular – hypotension and collapse - Neuropsyche – anxiety, patients describe an "impending sense of doom" If 2 or more body systems are involved – TREAT with EPINEPHRINE! 8/13/23 47  Food Allergy Symptoms Skin Oral Respiratory GI Cardiovascular Neurological Urticaria Mouth Itching Cough Nausea Hypotension Confusion Pruritus Throat closing Wheezing Emesis Tachycardia Headache Flushing Rash around Dyspnea Diarrhea Dizziness Tunnel vision Angioedema mouth Laryngeal Abdominal Syncope angioedema cramping Specific Diagnoses for following symptoms: Only GI Symptoms: May be an intolerance, FPIES, Celiac Disease, Gluten Sensitivity Only Oral Symptoms: May be Oral Allergy Syndrome/ Pollen Food Allergy Syndrome  Food Allergy Treatment Treatment Avoidance (label reading) Education about label reading Epinephrine auto-injectors Education is vital Oral desensitization (oral immunotherapy) 8/13/23 49  Oral Allergy Syndrome Cross-reactivity between inhalant and contact allergens and foods Typically, doesn't progress to systemic reaction More common in-season May choose to cook, peel or avoid cross- reactive food in-season 8/13/23 50  Indications for Referral to an Allergist Uncontrolled allergic rhinitis Asthma - 50% of patients with asthma have allergies as a factor causing or contributing to their asthmatic inflammation All food allergies Evaluation for immunotherapy or desensitization Any history of anaphylaxis Chronic urticaria (>6 weeks) Uncontrolled atopic dermatitis Contact dermatitis with the need to identify trigger (allergist or dermatologist) 8/13/23 51  Penicillin (PCN) Allergy According to the CDC, ~10% of all U.S. patients report having an allergic reaction to a penicillin class antibiotic in their past When evaluated, fewer than 1% of the population are truly allergic to penicillin ~80% of patients with IgE-mediated penicillin allergy lose their sensitivity after 10 years Prudent to rule out IgE-mediated PCN when appropriate: - use of broad-spectrum antibiotics in patients labeled “penicillin-allergic” is associated with higher healthcare costs, increased risk for antibiotic resistance, and suboptimal antibiotic therapy - Obtain thorough history – testing not appropriate in severe hypersensitivity reaction - like Stevens-Johnson syndrome, toxic epidermal necrolysis, serum sickness Testing methods - Skin test (95% negative predictive value) - Oral test dose 8/13/23 52 Questions?