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Anaphylaxis New Insights

Anaphylaxis New Insights. Anthony Montanaro M.D. Professor of Medicine Oregon Health Sciences University. Anaphylaxis. First described Portier and Richet 1902 “Without protection” Characterized by explosive release of mediators by mast cells mediated by IgE

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Anaphylaxis New Insights

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  1. Anaphylaxis New Insights Anthony Montanaro M.D. Professor of Medicine Oregon Health Sciences University

  2. Anaphylaxis • First described Portier and Richet 1902 • “Without protection” • Characterized by explosive release of mediators by mast cells mediated by IgE • Non-IgE mechanisms - “Anaphylactoid”

  3. Anaphylaxis • Clinical Presentation - Generalized Pruritis - Urticaria / Angioedema - Upper / Lower airway compromise - Hypotension / Vascular collapse / Cardiac arrest - Abdominal cramping / Vomiting - Sense of impending doom

  4. Anaphylaxis Mild forms • Itching • Nasal congestion • Metallic taste

  5. Anaphylaxis Etiology • Drugs • Venoms • Foods • Inhalant allergens (cat/grass) • Exercise ± foods • Idiopathic

  6. Anaphylaxis Differential Diagnosis • Flushing • Vasovagal • Non-IgE Drug Rxn • Hypoglycemia • Anxiety

  7. AnaphylaxisAnaphyltoxin Mediated • Human plasma and blood products • Immunoglobulin • Dialysis membranes

  8. Anaphylaxis Direct Histamine-Releasers • Opiates • Curare • Dextran • Some chemotherapeutic agents • Polymixin B • Radiocontrast media

  9. AnaphylaxisMechanism Unknown • Nonsteroidal anti-inflammatory drugs • Synthetic steroid hormones • Recombinant immunoregulatory molecules • Exercise induced • Mastocytosis • Cholinergic, cold induced • Idiopathic

  10. SUNSHINE/ANAPHYLAXIS METHODS AND RESULTS • Audit of Epi-Pen Rxs in 2004 made by state and region • 1.5 mil Rxs, 2.5 mil units, 5.71 Epi-Pens/1,000 pop. • Mass 11/1,000, Hawaii 2.7/1,000 • New England 8-12/1,000, southern 3/1,000 • Differences persist when controlled for pop. Demographics, #HCP, #Rx written Camargo, JACI 120:131-136, 2007

  11. SUNSHINE/ANAPHYLAXIS CONCLUSIONS • Data supports possible role between low vitamin D levels and allergic disease • Inconsistencies do exist, i.e., D.C. high-Virginia low, Portland. MA. high, Portland, OR low • Previous reports suggest similar observations in autoimmune diseases M.S./D.M. • More to come on why, when and how much Camargo, JACI 120:131-136, 2007

  12. AnaphylaxisPenicillin • Estimated to account for 75% of cases • 80% Hx. + Skin test - • Skin testing predicts IgE reactions only • 50% of patients lose ST reactivity after 10 years

  13. Cephalosporins for Pen Allergic Patients Background • Suspected Pen Allergy common • + ST documented 7-23% suspected • Cross reactivity cephalosporins cited to be 10% based on data from 70s! • Cephalosporins <1982 commercially made from cephalosporium mold and were contaminated with penicillin • Pen allergic pts. have 3x risk of adverse reactions to other unrelated drugs. Pegler, BMJ 2007

  14. Cephalosporins for Pen Allergic Patients Findings: metanalysis (Medline, EMBASE, Cochrane) • Limited reviews to RCT and systematic reviews • 6 studies included 2387 pts. with reported pen allergy who received a cephalosporin, 44,897 without pen allergy. • Risk of cross reactivity only with 1st generation. • OR 4.79 - 1st generation 1.13 - 2nd generation 0.45 - 3rd generation Pegler, BMJ 2007

  15. Cephalosporins for Pen Allergic Patients Conclusions: • Cited cross reactivity of 10% is an overestimate. • Cross reactivity between pen/2nd, 3rd gen. ceph. is low! • Cross reactivity pen/ceph may be lower than with unrelated antibiotics. • Anaphylaxis to cephalosporins is rare. • In lifethreatening infections it is reasonable to consider a 2nd/3rd gen. ceph. in pts. With a history of pen allergy. Pegler, BMJ 2007

  16. AnaphylaxisAntibiotic Desensitization • Rarely indicated • Undertaken in inpt. / ICU setting • Potentially life threatening • Protective only during active therapy

  17. AnaphylaxisNSAIDS • All cox-1 implicated • Case reports mild cox-2 reactions may predict more severe cox-1 reactions • In pts. With known sensitivity, high dose Acetomenophen may cross react

  18. ALTERNATIVES IN NSAID- SENSITIVE PATIENTS BACKGROUND • NSAID sensitivity increasingly recognized and frequent indication for allergy consultation • NSAID sensitivity related to degree of Cox-1 inhibition • Best Cox-2 inhibitors have been pulled from market but had been shown to be well tolerated in Cox-1 sensitive • Nabutamone (Relafen) and Meloxicam (Mobic). Preferential Cox-2 inhibitors Prieto, JACI 119:960-964, 2007

  19. ALTERNATIVES IN NSAID- SENSITIVE PATIENTS METHODS AND RESULTS • 70 pts studied NSAID sensitivity, 40-mucocutaneous/30 resp. (36 + challenge) • All underwent oral graded challenge up to 2 gm. Nabutamone and 15 mg Meloxicam in 51 pts • 94% tolerated 1 gm Nab. • 84% tolerated 2 gm Nab. • 96% tolerated Meloxicam Prieto, JACI 119:960-964, 2007

  20. ALTERNATIVES IN NSAID- SENSITIVE PATIENTS CONCLUSIONS • Nabutamone and Meloxicam are safe alternatives to Cox-1 in most NSAID-sensitive pts. • No significant differences between the two • All adverse reactions noted were easily controlled • Rare, but serious, reactions do occur and require expert controlled trials Prieto, JACI 119:1960-964, 2007

  21. ACEI / Anaphylaxis • Multiple case reports of anaphylaxis in venom sensitive patients Rx’d with ACEI and VIT or field stings. • 2 reported cases ceased with ACEI withheld for > 24 hrs. & recurred with re-introduction. • Studies have demonstrated decreased angiotensin I & II and increased risk for venom anaphylaxis and VIT failure. • ARBs appear to be tolerated in most ACEI sensitive White, Ann Allergy 101:426-230, 2008.

  22. ACEI / Anaphylaxis • 157/288 evaluated had venom sp. IgE. • 79 underwent VIT, 17/79 (21%) on ACEI average 30.9 mos. • 13/62 (21%) not on ACEI experienced systemic reaction to VIT. • 0 on ACEI experienced systemic reaction to VIT or field stings. • ACEI may be safe in patients on VIT- larger studies are needed. White, Ann Allergy 101:426-430, 2008.

  23. AnaphylaxisStinging Insect Allergy • Caused by Hymenoptera species -Apid - honey bees -Vespids - yellow jacket, wasp, hornet • Reactions - local, systemic, serum sickness • Continues to account for hundreds of deaths and significant cost and morbidity in US

  24. AnaphylaxisStinging Insect Allergy • Large local reactions not predictive of systemic anaphylaxis • Pts. With systemic reactions require skin test to determine IgE reactivity-some have toxicologic reactions • Hx +, ST + require desensitization

  25. AnaphylaxisVenom Desensitization • 95% effective in preventing life-threatening anaphylaxis • requires minimum 3-5 yrs of therapy • Patients with history of cardiovascular collapse, systemic reactions during therapy may require lifelong therapy

  26. AnaphylaxisRadiocontrast Media Reactions • Non IgE mediated • 5-8% of all contrast administrations • .1% potentially life threatening • Pts with previous reactions 15-50% risk of subsequent events • Pre-Rx with low osmolarity rcm, risk reduced to 1%

  27. AnaphylaxisRadiocontrast Media-Pre Rx • Undertaken in high risk individuals -glucocorticoids 50 mg pred 13, 7 , 1 hr pre procedure -antihistamines 50 mg benadryl 1 hr pre -ephedrine 25 mg 1 hr pre -H2 antagonists may be helpful

  28. Latex Anaphylaxis • IgE mediated latex allergy Risk Factors -Occupational exposures -Spina Bifeda / mult. GU procedures -Atopy -? Contact hypersensitivity

  29. Latex AnaphylaxisDiagnosis • Evidence of latex IgE 5-7% of blood donors • Standardized ST reagent available soon • Serologic studies approx. 75% sens/specific • Hx + specific provocation neg. 15% • Much of data generated prior to mfg. controls

  30. Latex AnaphylaxisPrevention-High Risk Pts. • No personal use dipped products i.e. gloves/condoms • Strict avoidance of environments with powdered glove use • Awareness of cross reacting foods (avocado, banana, chestnut, kiwi-50%)

  31. Exercise Induced Anaphylaxis • Clinical manifestations similar to allergen induced • Flushing, pruritis, urticaria common • Upper resp./CV collapse rare • Sxs. assoc. with incr. Histamine/tryptase following exercise • May occur with allergenic foods in some (1/3)

  32. AnaphylaxisDiagnosis • History and PE most important • Skin testing helpful for high mw proteins • Invitro IgE testing useful pollens, foods, some drugs, latex • Tryptase-stable mast cell enzyme markedly elevated in anaphylaxis, systemic mastocytosis

  33. Mast Cell Tryptase • B tryptase is a neutral serine protease found in basophils and mast cells. • Marker of mast cell activation in anaphylaxis and systemic mastocytosis. • Elevated levels may help distinguish from cardiogenic shock in ER/OR/post mortem • Peaks at 15 min. ½ life 2 hrs. may remain elevated up to 3 d. • Sensitivity – 50%, specificity > 90% levels > 10 ug in cad, hes, mds.

  34. AnaphylaxisTreatment • Epinephrine sc or im .01 cc/kg(1:1000) -Maximum dose 0.3 to 0.5 cc -IV associated with fatal arrythmia and MI (use only in CPR setting) • Standard ABCs of CPR • Third spacing, decreased pvr may require large volume fluid replacement

  35. AnaphylaxisTreatment • H1 antihistamines (ie parenteral 1 mg/kg diphenhydramine) • H2 antihistamines (ie 4mg/kg cimetidine) controversial • Glucocorticoids (120 mg, IV methylprednisolone, may prevent late phase response) • Naloxone, Glucagon refractory case reports

  36. Sublingual Epinephrine Methods / Results • SL disintegrating tablets containing 1, 10, 20 and 40 mg Epi compared to .3mg IM in rabbits – plasma conc. Measured • No difference in AUC / Cmax- 40mg SL / .33cc IM • 10/20 mg SL no different placebo • No difference Tmax SL/IM 9 vs 21 min. Simons, JACI, 2006.

  37. Anaphylaxis-Biphasic/prolonged • Estimated to occur 6-20% of all cases • May occur 1-24 hrs. following cessation of initial response • Severity/clinical course may be similar or worse • Risk factors include:delay of epi,inadequte or need for high dose epi,?corticosteroids • Provides basis for 8-24 hr observation

  38. ADEQUACY OF EPI-PENCONCLUSIONS • Distance from skin to muscle is variable and related to BMI in many • Distance genetically greater in women regardless of BMI • Epi-Pen length inadequate for I.M. therapy in over 40%! Song, Annals 2005

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