8/11/16. Kevin Letz DNP, MSN, MBA, CEN, CNE, FNP-C, PCPNP-BC, ANP-BC, FAANP

Size: px

Start display at page:

Download "8/11/16. Kevin Letz DNP, MSN, MBA, CEN, CNE, FNP-C, PCPNP-BC, ANP-BC, FAANP"

Marjory Pearson
5 years ago
Views:

1 An allergic reaction is the body s immune system reacting inappropriately to a foreign substance, such as pollen. The immune system perceives the benign substance as dangerous, thereby triggering a reaction. Kevin Letz DNP, MSN, MBA, CEN, CNE, FNP-C, PCPNP-BC, ANP-BC, FAANP An allergen can be almost anything which acts as an antigen (agents eliciting an antibody response) to stimulate an immune response Allergic Rhinitis Conjunctivitis GI Disorders Atopic Dermatitis Asthma Food Molds Grasses Trees Kevin Letz, DNP Weeds Dust-Mites Animals Drugs 1

The Allergy & Asthma Crisis in America is well documented. While there may be debate on 50 causation (i.e. the clean hypothesis, increased 40 pollution) there is no debate to the facts of an ever increasing number of Americans 30 suffering from allergic disease.

3 Millions of Cases 60 0 5 6 7 10 18 55 Parkinson's Alzheimer's Stroke CHD Cancer Diabetes Allergy About 30% of patients seen in a primary care setting present with Allergy-Like Symptoms Allergies

5 million workdays and 2 million school days per year $5 billion antihistamine market and growing Approximately 60% of patients on antihistamines do not have allergies Eczema GI Disorders Otitis

2 The Allergy & Asthma Crisis in America is well documented. While there may be debate on 50 causation (i.e. the clean hypothesis, increased 40 pollution) there is no debate to the facts of an ever increasing number of Americans 30 suffering from allergic disease. At least 1 of 20 every 5 patients in a primary care setting (>55 10 million nationwide) has allergic disease. 3 Millions of Cases Parkinson's Alzheimer's Stroke CHD Cancer Diabetes Allergy About 30% of patients seen in a primary care setting present with Allergy-Like Symptoms Allergies are responsible for the loss of over 3.5 million workdays and 2 million school days per year $5 billion antihistamine market and growing Approximately 60% of patients on antihistamines do not have allergies Eczema GI Disorders Otitis Media Allergic Rhinitis Asthma Adult Asthma As many as 40% of infants with atopic dermatitis may become asthmatic by age 4 It is estimated that 79% of children with otitis media have been diagnosed with allergic rhinitis Atopic eczema: 17.1% of infants. Starts atopic march. Moore MM et al. Pediatrics Mar;113(3 Pt 1): Food allergy: 8% of children. 2.5% of adults. Sampson HA.Curr Opin Allergy Clin Immunol. 2002;2(3): Allergic rhinitis: 10-30% of adults, up to 40% of children. Berger WE. Ann Allergy Asthma Immunol. 2003;90(6 Sup3):7. Asthma: %. Mortality is highest in adolescents. Akinbami LJ et al. Pediatrics Aug;110(2 Pt 1):

3 GENETIC FACTORS: 50% of atopic risk BIOLOGICAL FACTORS: Increased serum IgE in infancy Decreased interferon (IFN) gamma production ENVIRONMENTAL FACTORS: Allergen exposure Tobacco exposure Lack of exposure to microbes Pollution Wright AL. J Allergy Clin Immunol Jan;113(1 Suppl):S2-7. Environmental factors increasing atopy: Decreased fecal-oral infections Decreased parasite infestations Decreased exposure to endotoxin Decreased respiratory infections Increased sedentary life (obesity) Increased time exposed to indoor allergens Eat Dirt The Hygiene Hypothesis and Allergic Diseases Weiss ST N Engl J Med Sep 19;347(12): ,000,000 patients with allergies 4,000 Allergists in the US Each Allergist would have to see ~14,000 patients! Other Provider Specialties ~ 80,000 Family Practice Physicians ~ 14,000 Dermatologists ~ 10,000 Pediatricians ~ 5,000 ENT Physicians ~160,000 APPs in primary care Each Provider would have to see ~ 490 patients Bach JF. N Engl J Med 2002;347(12): The demand for allergists will increase 35% by 2020, while at the same time the number of medical students choosing the specialty tumbles. The ACAAI predicts a shortfall of more than 2,100 allergists with no solution in sight. "By the year 2020, there will not be enough allergists to handle the increased amount of patients suffering from allergies." - American College of Allergy, Asthma & Immunology History & Physical exam alone often leads to an incorrect diagnosis (50/50 guessers). Negative results can be as informative as positive results, ruling out allergy as the cause of symptoms. With allergic diseases, clinicians frequently progress directly from signs and symptoms to pharmacotherapy, even when diagnostic evidence is readily available. Empiric management may result in unnecessary repeat office visits, inappropriate medication, greater costs, and unnecessary referrals. 3

As the number of medical students choosing the specialty of allergy continues to plummet it is obvious that more allergists will

The solution will be other specialists (primary care) taking a more active role in allergy evaluation and management.

Evaluation & Management Murine CDRs* (< 5% of molecule) ε-switch B lymphocyte Allergic mediators Allergic inflammation: eosinophils

4 As the number of medical students choosing the specialty of allergy continues to plummet it is obvious that more allergists will not be the solution. The solution will be other specialists (primary care) taking a more active role in allergy evaluation and management. Percutaneous skin testing Pulmonary function testing Rx injections Sublingual immunotherapy Avoidance measures / education Evaluation & Management Murine CDRs* (< 5% of molecule) ε-switch B lymphocyte Allergic mediators Allergic inflammation: eosinophils and lymphocytes Plasma cell IgG1 kappa Human framework (> 95% of molecule) Release of IgE Allergens Asthma Exacerbation *CDR = complementarity -determining region Mast cells Basophils Adapted with permission from Boushey H. J Allergy Clin Immunol. 2001;108:S77-S 83. 4

5 IgE Allergens FcεRI Immediate Release Granule contents: Histamine, TNF-α, Proteases, Heparin Sneezing Nasal congestion Itchy, runny nose Watery eyes Over Minutes Lipid mediators: Prostaglandins Leukotrienes Wheezing Bronchoconstriction Mucus production Over Hours Cytokine production: Specifically IL-4, IL-5, IL-13 Eosinophil recruitment Inflammation Before 10 Minutes After Allergen Challenge 5

Effect of Inflammation in the Upper Airways on Asthma Disease in the upper airways has been thought capable of aggravating and even causing lower airways disease Treatment of the nose with

6 Effect of Inflammation in the Upper Airways on Asthma Disease in the upper airways has been thought capable of aggravating and even causing lower airways disease Treatment of the nose with corticosteroids prevents or improves asthma symptoms or lower airway hyperresponsiveness 1. Henrikson JM, Wenzel. Am Rev Respir Dis 1984;130: Welsh PW, et al. Mayo Clin Proc 1987;62: Corren J, et al. J Allergy Clin Immunol 1992;90: Watson WTA, et al. J Allergy Clin Immunol 1993;91: Foresi A, et al. J Allergy Clin Immunol 1996;98: Aubier M, et al. Am Rev Respir Dis 192;146: Allergic rhinitis affects up to: 25% of the general population 40% of children Up to 86% of patients with asthma have allergic rhinitis Seasonal allergic rhinitis is more common among children Allergic rhinitis alone Allergic rhinitis + asthma Asthma alone Meltzer. Ann Allergy As thma Immunol. 2000;84:176-87; ARIA. J Allergy Clin Immunol. 2001;108:S148-61; Guerra et al. J Allergy Clin Immunol. 2002;109:419-25; Greisner et al. Allergy As thma Proc. 1998;19:185-8; Yawn et al. J Allergy Clin Immunol. 1999;103:54-9; Leynar et al. J Allergy Clin Immunol. 2000;106:S First step in the diagnosis is for the clinician to perform an allergy specific history and physical Type of symptoms Duration of symptoms Likely causes Environmental survey Occupation Hobbies Medical history Family history Suspected diagnosis Cold or and allergic reaction? Avoidance Symptom management with medications (allergy shots) Note: not for food allergies or drug allergies Action should be based on specific allergens which are known to be triggers. This is a good place to start The only therapy available that alters the natural course of the disease. May prevent the progression from mono- to poly-sensitization May prevent the development of asthma Decreased symptoms often persist after shots are discontinued 6

Unclear allergy Challenge required Institution of elimination diet Additional education needed Uncontrolled disease High risk medication Therapeutic Trials

formulas (Stanford) Probiotics (UCSF) Kevin Letz, DNP All Patients complaining of allergy-like symptoms, reditchy eyes, sneezing or upper respiratory infections

asthmatics in vivo Skin-Prick Test in vitro Blood Testing No risk of immediate side effects Cost is somewhat high Anti-histamines do NOT need to be discontinued

7 Unclear allergy Challenge required Institution of elimination diet Additional education needed Uncontrolled disease High risk medication Therapeutic Trials Recombinant anti-ige antibody (Stanford) Gene (naked DNA) immunization with CPG repeats (Johns Hopkins) Sublingual (Stanford) Oral (Stanford) Hypo-allergenic formulas (Stanford) Probiotics (UCSF) Kevin Letz, DNP All Patients complaining of allergy-like symptoms, reditchy eyes, sneezing or upper respiratory infections Patients who chronically use allergy medications Pediatric patients especially those with a stubborn rash, chronic ear infections or GI symptoms Persistent asthmatics in vivo Skin-Prick Test in vitro Blood Testing No risk of immediate side effects Cost is somewhat high Anti-histamines do NOT need to be discontinued Quality-controlled quantitative results Minimally invasive to the patient One blood sample multiple determinations Must wait for lab results Follow up required Less clinically sensitive/specific 7

Allerg en N Sensitivity Specificity Accu ra cy Mountain Cedar 90 88% 93% 90% Timothy Grass 96 94% 97% 90% Bermu d a Grass 87 86% 97% 91%

) 93 96% 93% 95% Cat Hair 90 96% 89% 93% Cat Rag weed Wheat Egg Wheat (food) 92 85% 93% 90% Co ws Milk 85 81% 92% 89% Egg White 83 80%

PhadiaCAPSystem specific Ig EFEIA Ced ar Current Mini-Panel Total IgE& 10 Common Alergens FDA Cleared Demo n stra ted Proficien cy (CAP)

Reactive if > 7 15 14 20 65 80 Possibly reactive (physician challenge) Unlikely reactive if < (home challenge) 30 26 0.35 0.

Risk of systemic reaction albeit low Anti-histamines must be discontinued (3-5 days) Minimally invasive Method is technique dependent

8 Allerg en N Sensitivity Specificity Accu ra cy Mountain Cedar 90 88% 93% 90% Timothy Grass 96 94% 97% 90% Bermu d a Grass 87 86% 97% 91% Total Ig E Milk Mold Timothy Grass Short Ragweed 90 90% 95% 92% Ho u sed u st Mite (pt.) 93 96% 93% 95% Cat Hair 90 96% 89% 93% Cat Rag weed Wheat Egg Wheat (food) 92 85% 93% 90% Co ws Milk 85 81% 92% 89% Egg White 83 80% 94% 92% Altern aria (Mo ld ) 82 87% 94% 90% Dust Mite Bermu d a Grass System Average 89 88% 94% 91% Mountain Co mp a riso n to PhadiaCAPSystem specific Ig EFEIA Ced ar Current Mini-Panel Total IgE& 10 Common Alergens FDA Cleared Demo n stra ted Proficien cy (CAP) Phase I: Allergy Method Comparison Recommended Interpretation of Food Allergen-Specific IgE levels (ku/l) Egg Milk Peanut Fish Soy Wheat Reactive if > Possibly reactive (physician challenge) Unlikely reactive if < (home challenge) * Sampson, H. Utility of food specific IgE in predicting symptomatic food allergy. JACI Risk of systemic reaction albeit low Anti-histamines must be discontinued (3-5 days) Minimally invasive Method is technique dependent Usually performed by trained staff Positive result means actual physical manifestation to allergen Highly sensitive and specific Cost effective Same day results Several devices available Result in various degrees of trauma to the skin 8

Off Beta-Blockers Off anti-histamines What about other meds Anaphylaxis kit available (EpiPen minimum) Placing technique Wait time Interpretation

Association Dog Molds Rhinovirus NO 2 & NO x Limited evidence of Association Formaldehyde, Fragrances, RSV, ETS (school-aged and older children)

Wash in HOT water (130 F) to kill mites. For non-encased bedding (e.g., blankets and quilts) choose items that can withstand frequent hot water washing.

Replace draperies with blinds Remove carpet from child s bedroom Remove upholstered furniture Find a new home for indoor pets Keep pet outside If

9 Off Beta-Blockers Off anti-histamines What about other meds Anaphylaxis kit available (EpiPen minimum) Placing technique Wait time Interpretation Documentation Kevin Letz, DNP Sufficient evidence of Causal Relationship Cat Cockroach ETS House dust (preschooler) mite Sufficient evidence of an Association Dog Molds Rhinovirus NO 2 & NO x Limited evidence of Association Formaldehyde, Fragrances, RSV, ETS (school-aged and older children) Encase all pillows and mattresses of the beds the child sleeps on with allergenimpermeable encasings. Wash bedding weekly to remove allergen. Wash in HOT water (130 F) to kill mites. For non-encased bedding (e.g., blankets and quilts) choose items that can withstand frequent hot water washing. Remove or wash and dry stuffed toys weekly. Very Effective Vacuum with a HEPA vacuum cleaner. Avoid humidifiers. Replace draperies with blinds Remove carpet from child s bedroom Remove upholstered furniture Find a new home for indoor pets Keep pet outside If these aren t possible Similar interventions as with dust mites: Encasings, HEPA air cleaner, HEPA vacuum, Keep pet out of bedroom Takes weeks before allergen levels reach those of non-cat households 9

Bathing cats MAY be effective at reducing allergen (n = 8 cats) The reduction was not maintained by 1 week.

Integrated pest management (IPM) Least toxic methods first Clean up food/spills Food and trash storage in closed containers Fix water leaks Clean counter tops daily Boric acid Bait stations/ gels Don

central air conditioner Do not use a humidifier Vent bathrooms/clothes dryers to outside Use exhaust fan in bathroom/ other damp areas Check faucets and pipes for leaks and repair Complete mold

10 Bathing cats MAY be effective at reducing allergen (n = 8 cats) The reduction was not maintained by 1 week. Therefore it had been recommended to bathe the cat twice a week However, a more recent study of 12 cats suggests the decrease in dander after bathing lasts about 1 day. Integrated pest management (IPM) Least toxic methods first Clean up food/spills Food and trash storage in closed containers Fix water leaks Clean counter tops daily Boric acid Bait stations/ gels Don t!! Spray liquids in house, especially play and sleep space Use industrial strength pesticide sprays that require dilution Ways to control moisture and/or decrease humidity to < 50%: Dehumidifier or central air conditioner Do not use a humidifier Vent bathrooms/clothes dryers to outside Use exhaust fan in bathroom/ other damp areas Check faucets and pipes for leaks and repair Complete mold abatement may be required using a licensed contractor Items too moldy to clean should be discarded. An area larger than 3 ft x 3 ft should be professionally cleaned. Chlorine solution 1:10 with water is acceptable for smaller areas. Don t mix chlorine with cleaners containing ammonia! Quaternary ammonium compounds are also good fungicides if bleach isn t used. Identify and stop sources of water intrusion. Keep home and car smoke free Encourage support to quit smoking Recommend aids such as nicotine gum/patch Medication from physician to assist in quitting Choose smoke-free social settings At the very least, do not smoke around your child or in the car! (This should not keep us from encouraging parents to quit!) 10

Eliminate tobacco smoke Install exhaust fan close to source of contaminants Ventilate room if fuelburning appliance used Avoid use of products emitting irritants Control dust mites and animal

11 Eliminate tobacco smoke Install exhaust fan close to source of contaminants Ventilate room if fuelburning appliance used Avoid use of products emitting irritants Control dust mites and animal allergens Avoid ozone generators and some ionic air cleaners that produce ozone Allergen Vaccine Desensitization Hyposensitization Allergy shots Exposing patients to a specific allergen in order to: promote tolerance to a specific allergen with the ultimate clinical goal of causing a sustained decrease in allergic symptoms. Allergen immunotherapy is distinct from available pharmacologic treatments. Its aim is sustained alteration in immune response beyond discontinuation of treatment. Almost 100 years Oldest continuously practiced form of medicine During immunotherapy, two primary changes in T cells have been observed: Immune deviation of allergen-specific cell responses from a Th2 pattern to a Th1 pattern The induction of regulatory cells resulting in tolerance of energy of antigen-specific effector T cells Allergy Inc. 11

12 Cytokine and/or cytokine receptor modulation Inhibition of early and late phase reactions Decrease in seasonal rise of specific IgE Production of IgG blocking antibody Desensitization (partial histamine depletion) Tolerance (low and/or high zone) Patients with allergic disease with specific IgE antibodies to clinically relevant allergens documented by in vitro or skin tests Factors to consider when prescribing immunotherapy: Effectiveness of medications and avoidance measures Side effects/costs of medications vs. immunotherapy Possible special benefit in children as preventative therapy Benefits: Reduced symptoms Reduced medication use Reduced treatment cost Clinical remission (?) Indications Allergic rhinitis Asthma Stinging insect hypersensitivity Multiple allergens studied Pollen Count (grains/m 3 ) Symptom Score Initial Placebo Trial Study group Placebo Current Trial Maintenance Dis c ontinuation None (control) May June July Aug May June July Aug May June July Aug May June July Aug Initial Placebo Trial Current Trial Initial Placebo Trial Current Trial Pollen Count (grains/m 3 ) Pollen Count (grains/m 3 ) Rescue-Medication Score Study group Placebo Maintenance Dis c ontinuation None (control) Visual-Analogue Score Study group Placebo Maintenance Dis c ontinuation None (control) May June July Aug May June July Aug May June July Aug May June July Aug May June July Aug May June July Aug May June July Aug May June July Aug

13 Randomized double-blind Significant decrease in asthma symptoms Decrease in asthma medications Decrease in mite-specific immediate and late phase reactions Double-blind, placebo controlled Decrease in specific and non-specific bronchial sensitivity Decrease prick skin test reaction Decrease eye, nasal and asthma symptoms with cat challenge/exposure Improved asthma control May prevent sensitization to new allergens Group New Allergen Sensitization No. of Patients None Cat Dog Alternaria Grass May prevent progression to asthma Control group A. Des Roches et al. JACI 1998;99: Year Follow-Up Treatment Year Total 5 Year Cost (single injection) $800 $290 $290 $290 $290 $1960 Do not develop Asthma 30 Develop Asthma 9 Medications (oral & topical) $1200 $1200 $1200 $1200 $1200 $6000 Control Number of Patients Jacobson et al. EAACI 1998 Annual Meeting Birmingham, UK. 13

14 When writing a prescription, consider: (1) cross-reactivity of allergens (2) Optimization of the dose of each allergen (3) Enzymatic degradation of allergens Build-up phase Involves administration of increasing quantities of allergen vaccine subcutaneously Types of schedules u u u u 1. Conventional / routine 2. Daily 3. Cluster 4. Rush / modified rush Allergy Inc. Conventional schedules (continued) Most commonly used Injections given 1-2 times a week Approximately doses increments until maintenance dose is achieved Average build-up phase from 3-6 months Patients with higher degree of allergen sensitivity may require longer build-up phase Continuation during pregnancy appears safe Initiation during pregnancy not recommended Continue current dose and do not increase (or only increase very slowly) If history of systemic reactions, consider holding injections Settipane, et al, in study of offspring of atopic pregnant women undergoing immunotherapy: 31% of children developed asthma or allergic rhinitis 45% of children of controls developed asthma or allergic rhinitis Standardized allergenic extracts (BAU or AU): cat, dust mite, short ragweed, grass, Hymenoptera Non-standardized allergenic extracts (weight-to-volume or PNU) Incorrect diagnosis Selection of allergen(s) was inadequate ( missing allergen ) Maintenance dosage and duration of vaccine therapy not high or frequent enough Environmental control measures inadequate Poor adherence with treatment schedule Other co-morbid medical conditions or interfering medications (hypothyroidism, hormones, beta-blockers, etc.) 14

15 Local reactions: redness, swelling and heat at injection Common occurrence If persistent large local reaction consider: Pre-medication with H1 blockers Decreasing dose or rate of build-up Signs and symptoms can include; urticaria, angioedema, increased respiratory symptoms (nasal, pulmonary or ocular), gastrointestinal and hypotension Onset usually rapid (majority occurring within 30 minutes) Low incidence (<.05% to 3.5% of injections) Factors that may increase risk of systemic reaction include: Symptomatic asthma High degree of allergen hypersensitivity Use of beta-blockers (possibly ACE inhibitors) Dosing error Injection from new vial Injection given during period of allergy symptom exacerbation Tourniquet above injection site Aqueous epinephrine 1:1,000 SQ or IM Consider IM epinephrine if serious reaction Adults: 0.3ml to 0.5ml q10 minutes up to 3 times Children: 0.01ml/kg body weight q10 minutes up to 3 times (Then consider more aggressive measures) H1 antihistamines: diphenhydramine IM or IV Adults: 25 to 50 mg Children: 1-2 mg/kg H2 blockers p.o. or IV (cimetidine, ranitidine, famotidine) for epinephrine resistant hypotension Intravenous fluids or vasopressors as needed for vascular collapse Consider glucagon if patient on beta-blocker Sublingual immunotherapy (SLIT): Drops, sprays, or dissolving tablets placed beneath the tongue have studied and used in European countries Dosing of sublingual therapy likely requires several times the concentrations used for subcutaneous immunotherapy Data from European studies suggest efficacy with a favorable safety profile Most studies of SLIT have been with single allergens and translation of these studies to treatment with multiple allergens needs to be further studied. Few FDA approved formulations in the US Low dose immunotherapy based on provocation-neutraliza tion testing Non-injective routes of immunotherapy (experimental) Allergen is effective for: Allergic asthma Allergic rhinitis and conjuctivitis Stinging insect allergy May help prevent further allergen sensitization and asthma in children Cost-effective 15

Reference List Bousquet J, Lockey RF, Malling H. WHO Position Paper. Allergen Immunothera py. Allergy 1998 V53 #44. Practice Parameters for Allergen. J Allergy Clin Immunol 1998; 1001-91.

16 Reference List Bousquet J, Lockey RF, Malling H. WHO Position Paper. Allergen Immunothera py. Allergy 1998 V53 #44. Practice Parameters for Allergen. J Allergy Clin Immunol 1998; Durham et al. Long-term clinical efficacy N Engl Med 1999; J Alvarez-Casta, Casta-Herranz, Puyana-Ruiz J, Cuesta-Herra nz C, Blanco-Quires A. Ohman JL, Findlay, Leitennan SB. in cat induced asthma. Double-blind trial Lilja G, Lowenstein H, et al. with cat and dog dander extracts J Allergy Clin Immunol 1989 Des Roches A, Paradis L, Menardo J-L, et al. Immunotherap y with a standardized dermatopha goi des extract Jacobsen L, Dreberg S, et al. as a preventive treatment (abstract) J Allergy Clin Immunol Simons F, Roberts J, Gu X, Simons K. Epinephrine absorption in children with a history of anaphylaxis. Dolz I, Martinez-Cocer a C, Bartolome JM, Cimarra M. A double-blind placebo-controll ed study of immunotherap y Creticos P, Lockey R, et al. Immunother apy, A Practical Guide to Current Procedures. Miles, Inc Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. National Institutes of Health 199 Lockey R, Bukantz S. Allergen Immunother apy. Marcel Dekker 1991 Virant FS. Immunology and allergy clinics of North America. Vol. 19, No. 1, February, W.B. Saunders. Middleton E, et al. Allergy Principles and Practice. 6th ed., Mosby % of allergy services can be provided by primary care Improved adherence and ease of treatment Evidence based disease management Reduced cost of care and improved productivity Average reimbursement $500 per patient (50 pts per month = $300,000 revenue) 16

Kevin Letz DNP, MSN, MBA, RN, CEN, CNE, FNP-C, PNP-BC, ANP-BC

Kevin Letz DNP, MSN, MBA, RN, CEN, CNE, FNP-C, PNP-BC, ANP-BC Kevin Letz, DNP An allergic reaction is the body s immune system reacting inappropriately to a foreign substance, such as pollen. The immune