Urticaria anaphylaxis

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Urticaria anaphylaxis

  1. 1. WHAT YOU SHOULD HAVE READ BUT….2010 <ul><li>urticaria </li></ul>University of Verona, Italy Attilio Boner
  2. 2. Orticaria valutazione
  3. 3. The Urticaria Severity Score: a sensitive questionnaire/index for monitoring response to therapy in patients with chronic urticaria Jariwala Ann Allergy Asthma Immunol 2009;102:475 A novel chronic urticaria-specific questionnaire, the Urticaria Severity Score (USS).
  4. 4. The Urticaria Severity Score: a sensitive questionnaire/index for monitoring response to therapy in patients with chronic urticaria Jariwala Ann Allergy Asthma Immunol 2009;102:475
  5. 5. The Urticaria Severity Score: a sensitive questionnaire/index for monitoring response to therapy in patients with chronic urticaria Jariwala Ann Allergy Asthma Immunol 2009;102:475
  6. 6. Orticaria eziologia
  7. 7. CHRONIC URTICARIA CAUSED BY FOLIC ACID Valdivieso Ann Allergy Asthma Immunol 2009;103:81 <ul><li>A 72-year-old woman presented with an 8-month history of daily urticaria and occasional facial angioedema. </li></ul><ul><li>She received antihistamines but was free of hives only for a few hours each day. </li></ul><ul><li>Polyclonal hypergammaglobulinemia was detected. The levels of analytes were as follows: serum globulin, 4.80 g/dL (reference range, 1.5–3.0 g/dL); γ - globulins, 28.2% (reference range, 10%–19%); IgG, 3,729 mg/dL (reference range, 1,000 –2,100 mg/dL); IgA, 525 mg/dL (reference range, 100–500 mg/dL); and IgM, 273 mg/dL (reference range, 44–290 mg/dL). </li></ul><ul><li>The results of antibody tests directed against hepatitis B and C, nuclear, thyroglobulin, thyroid peroxidase, DNA, mitochondrial, and lupus anticoagulant antigens were negative. </li></ul>
  8. 8. CHRONIC URTICARIA CAUSED BY FOLIC ACID Valdivieso Ann Allergy Asthma Immunol 2009;103:81 <ul><li>We suspected that folic acid was the possible cause of the urticaria. </li></ul><ul><li>Prick and intradermal tests were performed with folic acid, 1 and 5 mg/mL, and were negative. </li></ul><ul><li>The results of single-blind oral challenge tests with increasing doses of folic acid, 1 mg/mL, administered at 30-minute intervals (0.25, 0.50, and 1 mL) were positive. </li></ul>
  9. 9. CHRONIC URTICARIA CAUSED BY FOLIC ACID Valdivieso Ann Allergy Asthma Immunol 2009;103:81 <ul><li>We suspected that folic acid was the possible cause of the urticaria. </li></ul><ul><li>Prick and intradermal tests were performed with folic acid, 1 and 5 mg/mL, and were negative. </li></ul><ul><li>The results of single-blind oral challenge tests with increasing doses of folic acid, 1 mg/mL, administered at 30-minute intervals (0.25, 0.50, and 1 mL) were positive. </li></ul>The patient was advised to discontinue folic acid treatment. Six months later, she remained free of urticaria.
  10. 10. CHRONIC URTICARIA CAUSED BY FOLIC ACID Valdivieso Ann Allergy Asthma Immunol 2009;103:81 <ul><li>We suspected that folic acid was the possible cause of the urticaria. </li></ul><ul><li>Prick and intradermal tests were performed with folic acid, 1 and 5 mg/mL, and were negative. </li></ul><ul><li>The results of single-blind oral challenge tests with increasing doses of folic acid, 1 mg/mL, administered at 30-minute intervals (0.25, 0.50, and 1 mL) were positive. </li></ul>Hypersensitivity reactions to folic acid are extremely unusual; to our knowledge, only 7 cases have been reported in the literature.
  11. 11. 32% 35 – 30 – 25 – 20 – 15 – 10 – 0 5 – 0 0 <ul><li>Hospitalized children with acute urticaria from Taiwan who did not respond to antihistamine treatment. </li></ul><ul><li>M pneumoniae infection determined by positive serologic findings. </li></ul><ul><li>Mycoplasma IgM (>20 U/L) or a positive cold agglutination test </li></ul>Association of acute urticaria with Mycoplasma pneumoniae infection in hospitalized children Wu Ann Allergy Asthma Immunol 2009;103:134 % Children with Urticaria Serologic evidence of M pneumoniae infection
  12. 12. 32% 35 – 30 – 25 – 20 – 15 – 10 – 0 5 – 0 0 <ul><li>Hospitalized children with acute urticaria from Taiwan who did not respond to antihistamine treatment. </li></ul><ul><li>M pneumoniae infection determined by positive serologic findings. </li></ul><ul><li>Mycoplasma IgM (>20 U/L) or a positive cold agglutination test </li></ul>Association of acute urticaria with Mycoplasma pneumoniae infection in hospitalized children Wu Ann Allergy Asthma Immunol 2009;103:134 % Children with Urticaria Serologic evidence of M pneumoniae infection One-third of acute childhood urticaria leading to patient hospitalization was related to M pneumoniae infection.
  13. 13. Association of acute urticaria with Mycoplasma pneumoniae infection in hospitalized children Wu Ann Allergy Asthma Immunol 2009;103:134 Effect of azithromycin treatment on the duration of urticaria. <ul><li>Hospitalized children with acute urticaria from Taiwan who did not respond to antihistamine treatment. </li></ul><ul><li>M pneumoniae infection determined by positive serologic findings. </li></ul><ul><li>Mycoplasma IgM (>20 U/L) or a positive cold agglutination test </li></ul>treated with azithromycin not treated with azithromycin
  14. 14. Association of acute urticaria with Mycoplasma pneumoniae infection in hospitalized children Wu Ann Allergy Asthma Immunol 2009;103:134 Effect of azithromycin treatment on the duration of urticaria. <ul><li>Hospitalized children with acute urticaria from Taiwan who did not respond to antihistamine treatment. </li></ul><ul><li>M pneumoniae infection determined by positive serologic findings. </li></ul><ul><li>Mycoplasma IgM (>20 U/L) or a positive cold agglutination test </li></ul>treated with azithromycin not treated with azithromycin Azithromycin treatment statistically significantly shortened the time for improvement ( P =0.01) and the time for complete resolution ( P =0.04).
  15. 15. Effect of arterial hypertension on chronic urticaria duration. Nebiolo Ann Allergy Asthma Immunol 2009;103:407 <ul><li>P rospective study of a cohort of 228 consecutive adult patients with chronic idiopathic urticaria (CIU). </li></ul><ul><li>Followed up for a 3- to 5-year period. </li></ul>Kaplan-Meier curve demonstrating the relationship between chronic urticaria duration and the presence (continuous line) or absence (dotted line) of hypertension.
  16. 16. Effect of arterial hypertension on chronic urticaria duration. Nebiolo Ann Allergy Asthma Immunol 2009;103:407 <ul><li>P rospective study of a cohort of 228 consecutive adult patients with chronic idiopathic urticaria (CIU). </li></ul><ul><li>Followed up for a 3- to 5-year period. </li></ul>Kaplan-Meier curve demonstrating the relationship between chronic urticaria duration and the presence (continuous line) or absence (dotted line) of hypertension. <ul><li>H ypertension is associated with extended duration of CIU. </li></ul><ul><li>A new approach to antihistamine-refractory CIU treatment, includes adequate treatment of hypertension. </li></ul>
  17. 17. 55% Idiopathic 45% <ul><li>Chronic urticaria is defined as the presence of urticaria (hives) for at least 6 weeks. </li></ul><ul><li>If we eliminate physical urticarias and urticarial vasculitis from consideration. </li></ul>Chronic Urticaria Autoimmune Pathogenesis of chronic urticaria Kaplan CEA 2009;39:777 60 – 50 – 40 – 30 – 20 – 10 – 0
  18. 18. 55% Idiopathic 45% <ul><li>Chronic urticaria is defined as the presence of urticaria (hives) for at least 6 weeks. </li></ul><ul><li>If we eliminate physical urticarias and urticarial vasculitis from consideration. </li></ul>Chronic Urticaria Autoimmune Pathogenesis of chronic urticaria Kaplan CEA 2009;39:777 60 – 50 – 40 – 30 – 20 – 10 – 0 Clinical severity of the disease (including accompanying angio-oedema) is more severe in the autoimmune subpopulation.
  19. 19. Orticaria terapia
  20. 20. The effectiveness of levocetirizine and desloratadine in up to 4 times conventional doses in difficult-to-treat urticaria Staevska JACI 2010;125:676 Background: H1-antihistamines are first line treatment of chronic urticaria, but many patients do not get satisfactory relief with recommended doses. European guidelines recommend increased antihistamine doses of up to 4-fold ( Zuberbier Allergy 2006;61:321 ). Objective: To provide supportive evidence for the European guidelines.
  21. 21. % patients who became symptom-free at 5 mg <ul><li>80 patients with chronic urticaria ( 19-67 years). </li></ul><ul><li>Levocetirizine or desloratadine (40/40). Treatment started at the conventional daily dose of 5 mg and then increased weekly to 10 mg, 20 mg, or 20 mg of the opposite drug if relief of symptoms was incomplete. </li></ul>9 levocetirizine 4 desloratadine The effectiveness of levocetirizine and desloratadine in up to 4 times conventional doses in difficult-to-treat urticaria Staevska JACI 2010;125:676 10 – 1 – 0
  22. 22. % patients who became symptom-free at The effectiveness of levocetirizine and desloratadine in up to 4 times conventional doses in difficult-to-treat urticaria Staevska JACI 2010;125:676 8 levocetirizine 7 desloratadine 10 – 1 – 0 5 levocetirizine 1 desloratadine 10 – 1 – 0 10 mg 20 mg
  23. 23. The effectiveness of levocetirizine and desloratadine in up to 4 times conventional doses in difficult-to-treat urticaria Staevska JACI 2010;125:676 1. Of the 28 patients nonresponsive to 20 mg desloratadine, 7 became symptom-free with 20 mg levocetirizine. 2. None of the 18 levocetirizine nonresponders benefited with 20 mg desloratadine. <ul><li>80 patients with chronic urticaria ( 19-67 years). </li></ul><ul><li>Levocetirizine or desloratadine (40/40). Treatment started at the conventional daily dose of 5 mg and then increased weekly to 10 mg, 20 mg, or 20 mg of the opposite drug if relief of symptoms was incomplete. </li></ul>
  24. 24. The effectiveness of levocetirizine and desloratadine in up to 4 times conventional doses in difficult-to-treat urticaria Staevska JACI 2010;125:676 1. Of the 28 patients nonresponsive to 20 mg desloratadine, 7 became symptom-free with 20 mg levocetirizine. 2. None of the 18 levocetirizine nonresponders benefited with 20 mg desloratadine. <ul><li>80 patients with chronic urticaria ( 19-67 years). </li></ul><ul><li>Levocetirizine or desloratadine (40/40). Treatment started at the conventional daily dose of 5 mg and then increased weekly to 10 mg, 20 mg, or 20 mg of the opposite drug if relief of symptoms was incomplete. </li></ul>Increasing antihistamine doses improved quality of life but did not increase somnolence.
  25. 25. <ul><li>Solar urticaria is divided into 2 types: type I and type II. </li></ul><ul><li>Type I defines patients who have precursors located in the serum, plasma, or cutaneous tissue fluid that become photoallergens once activated by the appropriate wavelength and bind to IgE receptors , resulting in mast cell degranulation. </li></ul><ul><li>Type II is also IgE mediated, but precursors are found in both healthy patients and patients with solar urticaria. It is hypothesized that only patients with solar urticaria have an abnormal circulating IgE autoantibody that recognizes these irradiated precursors. </li></ul>Partial improvement of solar urticaria after Omalizumab Waibel JACI 2010;125:490
  26. 26. <ul><li>We present a 16-year-old boy with solar urticaria who was refractory to oral antihistamines but improved partially with omalizumab. </li></ul><ul><li>Symptoms would occur within minutes and would progress to raised, confluent urticarial plaques only on sun-exposed skin. Once he returned indoors, his skin symptoms would completely resolve after 30 minutes without hyperpigmentation or eczematous changes. </li></ul>Partial improvement of solar urticaria after Omalizumab Waibel JACI 2010;125:490
  27. 27. <ul><li>We present a 16-year-old boy with solar urticaria who was refractory to oral antihistamines but improved partially with omalizumab. </li></ul><ul><li>Symptoms would occur within minutes and would progress to raised, confluent urticarial plaques only on sun-exposed skin. Once he returned indoors, his skin symptoms would completely resolve after 30 minutes without hyperpigmentation or eczematous changes. </li></ul>Partial improvement of solar urticaria after Omalizumab Waibel JACI 2010;125:490 He had significantly altered his social behavior because of these symptoms.
  28. 28. <ul><li>We present a 16-year-old boy with solar urticaria who was refractory to oral antihistamines but improved partially with omalizumab. </li></ul><ul><li>Symptoms would occur within minutes and would progress to raised, confluent urticarial plaques only on sun-exposed skin. Once he returned indoors, his skin symptoms would completely resolve after 30 minutes without hyperpigmentation or eczematous changes. </li></ul>Partial improvement of solar urticaria after Omalizumab Waibel JACI 2010;125:490 He had only tried over-the-counter sunscreen with minimal improvement.
  29. 29. Phototesting demonstrating a wheal and flare for the UV-A (5 and 10 J/cm 2 ) and UV-B (20, 30, 40, and 50 mJ/cm 2 ) spectrum within 1 minute of testing. The patient demonstrated significant sensitivity with erythema and flushing even in areas protected with a Tyvek Protective Wear Suit (DuPont, Wilmington, Del). No reaction occurred to the visible light spectrum. Partial improvement of solar urticaria after Omalizumab Waibel JACI 2010;125:490
  30. 30. <ul><li>The patient was unsuccessfully treated with loratadine (30 mg/d), cetirizine (20 mg/d), and diphenhydramine (up to 200 mg/d). </li></ul><ul><li>Omalizumab (Xolair). On the basis of his initial IgE level (851 IU/mL) and weight (57.7 kg), a calculated dose of 400 mg every 2 weeks for 3 months was initiated. </li></ul><ul><li>Repeat phototesting was performed 1 week after his sixth omalizumab dose. </li></ul>Partial improvement of solar urticaria after Omalizumab Waibel JACI 2010;125:490
  31. 31. <ul><li>The patient was unsuccessfully treated with loratadine (30 mg/d), cetirizine (20 mg/d), and diphenhydramine (up to 200 mg/d). </li></ul><ul><li>Omalizumab (Xolair). On the basis of his initial IgE level (851 IU/mL) and weight (57.7 kg), a calculated dose of 400 mg every 2 weeks for 3 months was initiated. </li></ul><ul><li>Repeat phototesting was performed 1 week after his sixth omalizumab dose. </li></ul>UV-A and UV-B testing sites showed improvement with no immediate reaction that was previously seen on initial testing. Partial improvement of solar urticaria after Omalizumab Waibel JACI 2010;125:490
  32. 32. <ul><li>6 patients with severe chronic spontaneous urticaria (CSU) unresponsive to other treatment; </li></ul><ul><li>high-dose IVIG (2 g/kg every 4-6 weeks). </li></ul>Effect of high-dose intravenous immunoglobulin treatment in therapy-resistant chronic spontaneous urticaria Mitzel-Kaoukhov Ann Allergy Asthma Immunol 2010;104:253–258 Relationship between treatment score and duration of treatment for each patient.
  33. 33. <ul><li>6 patients with severe chronic spontaneous urticaria (CSU) unresponsive to other treatment; </li></ul><ul><li>high-dose IVIG (2 g/kg every 4-6 weeks). </li></ul>Effect of high-dose intravenous immunoglobulin treatment in therapy-resistant chronic spontaneous urticaria Mitzel-Kaoukhov Ann Allergy Asthma Immunol 2010;104:253–258 Relationship between treatment score and duration of treatment for each patient. Patients showed an improvement in symptoms and a reduction in co-medication use just after the first cycle.
  34. 34. Effects of a pseudoallergen-free diet on chronic spontaneous urticaria: a prospective trial Magerl Allergy 2010:65:78 <ul><li>140 pts with chronic urticaria. </li></ul><ul><li>Pseudo-allergen free diet for 3 weeks. </li></ul>% PATIENTS 14% 14% PARTIAL RESPONDERS STRONG RESPONDERS 15 – 10 – 5 – 0
  35. 35. <ul><li>140 pts with chronic urticaria. </li></ul><ul><li>Pseudo-allergen free diet for 3 weeks. </li></ul>% PATIENTS 14% 14% PARTIAL RESPONDERS STRONG RESPONDERS 15 – 10 – 5 – 0 Additionally, (6%) subjects made a substantial reduction in their medication without experiencing worse symptoms or quality of life. Effects of a pseudoallergen-free diet on chronic spontaneous urticaria: a prospective trial Magerl Allergy 2010:65:78
  36. 36.   Explicitly prohibited foodstuffs Chewing gum, candy, and similar products Spices and herbs (except salt and chives) Additives: E100-E1518, preservatives or artificial colors, gelling agents, thickening matter, humectant, emulsifiers, flavor potentiators, antioxidants, separating agents, sweeteners, baking agents, modified starches,foaming agents, stabilizers, flavoring agents Breads with additional grains, herbs, or other such added ingredients Packaged bread is preferable to bakery bread, because the ingredients are on the label Alcohol Sesame Effects of a pseudoallergen-free diet on chronic spontaneous urticaria: a prospective trial Magerl Allergy 2010:65:78
  37. 37.   Explicitly prohibited foodstuffs Pasta with eggs, cake, biscuits, potato chips Margarine and mayonnaise Eggs Smoked meats Seafood Tomatoes, artichokes, peas, mushrooms, spinach, rhubarb, olives, sweet peppers Fruit, dried fruits, and fruit juices Herbal tea Any substitutions not listed as acceptable in the clinical diary's guidelines Any substance that the patient remains unsure if it is allowed or not Use only fresh foods; no preserved foods, except deep-frozen foods without any additives Effects of a pseudoallergen-free diet on chronic spontaneous urticaria: a prospective trial Magerl Allergy 2010:65:78
  38. 38. <ul><li>Esiste un questionario per la valutazione di gravità, </li></ul><ul><li>L’infezione da M pneumoniae può causare orticaria acuta che migliora con i macrolidi piuttosto che con gli anti-H1, </li></ul><ul><li>L’ipertensione può essere un fattore aggravante, </li></ul><ul><li>Si può aumentare la dose di antistaminico 4x, meglio la cetirizina della desloratadina, </li></ul><ul><li>Nelle forme antistaminico resistenti pensa all’omalizumab, alle IgG ev ad alte dosi. </li></ul><ul><li>La dieta priva di pseudoallergeni può aiutare </li></ul>Take home
  39. 39. WHAT YOU SHOULD HAVE READ BUT….2010 <ul><li>anaphylaxis </li></ul>University of Verona, Italy Attilio Boner
  40. 40. anafilassi
  41. 41. Anafilassi epidemiologia
  42. 42. Higher incidence of pediatric anaphylaxis in northern areas of the United States Sheehan JACI 2009;124:850 <ul><li>Incidence of pediatric anaphylaxis. </li></ul><ul><li>National billing database of US pediatric hospitals for all patient encounters billed as anaphylaxis. </li></ul>Rates of anaphylaxis by type of anaphylaxis.
  43. 43. Higher incidence of pediatric anaphylaxis in northern areas of the United States Sheehan JACI 2009;124:850 <ul><li>Incidence of pediatric anaphylaxis. </li></ul><ul><li>National billing database of US pediatric hospitals for all patient encounters billed as anaphylaxis. </li></ul>Rates of anaphylaxis by type of anaphylaxis. Anaphylaxis cases caused by food, immunization or serum, and “other” were all more common in the northern hospitals.
  44. 44. Regional variation in epinephrine autoinjector prescriptions in Australia: more evidence for the vitamin D-anaphylaxis hypothesis Mullins Ann Allergy Asthma Immunol 2009;103:488 <ul><li>EpiPen prescriptions (2006-2007) and anaphylaxis hospital admission rates (2002-2007) in 10 regions. </li></ul><ul><li>Average solar radiation exposure (measured in megajoules per square meter) in June (Winter). </li></ul><ul><li>Exposure is greater in northern than southern regions of Australia. </li></ul>
  45. 45. Geographic variation in epinephrine autoinjector (EpiPen) prescription rates Regional variation in epinephrine autoinjector prescriptions in Australia: more evidence for the vitamin D-anaphylaxis hypothesis Mullins Ann Allergy Asthma Immunol 2009;103:488 Patients’ age 0-4 years 5-15 years > 15 years
  46. 46. Geographic variation in epinephrine autoinjector (EpiPen) prescription rates Regional variation in epinephrine autoinjector prescriptions in Australia: more evidence for the vitamin D-anaphylaxis hypothesis Mullins Ann Allergy Asthma Immunol 2009;103:488 Patients’ age 0-4 years 5-15 years > 15 years EpiPen prescription rates were higher in southern latitudes (less sunlight) compared with northern regions ( P 0 .001).
  47. 47. Geographic variation in anaphylaxis admission rates in patients from birth to the age of 4 years. Anaphylaxis admission rates varied as a function of age and latitude, being more common in patients from birth to the age of 4 years than in other age groups and more common in southern than northern regions. Regional variation in epinephrine autoinjector prescriptions in Australia: more evidence for the vitamin D-anaphylaxis hypothesis Mullins Ann Allergy Asthma Immunol 2009;103:488
  48. 48. Anafilassi patogenesi
  49. 49. Clinical predictors for biphasic reactions in children presenting with anaphylaxis Mehr Clinical & Experimental Allergy 2009;39:1390 Background: One of the main reasons for hospital admission once a child has been stabilized following anaphylaxis is to monitor for a biphasic reaction. However, only a small percentage of anaphylactic episodes involve biphasic reactions that would benefit from admission. Identification of predictive factors for a biphasic reaction would assist in determining who may benefit from prolonged observation. Objective: To determine predictive factors for biphasic reactions in children presenting with anaphylaxis.
  50. 50. <ul><li>Retrospective study of children presenting with anaphylaxis to a major paediatric emergency department over a 5-year period. </li></ul>% REACTIONS 100 – 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 87% 11% 2% UNIPHASIC BIPHASIC PROTRACTED Clinical predictors for biphasic reactions in children presenting with anaphylaxis Mehr Clinical & Experimental Allergy 2009;39:1390
  51. 51. <ul><li>Retrospective study of children presenting with anaphylaxis to a major paediatric emergency department over a 5-year period. </li></ul>% REACTIONS 100 – 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 87% 11% 2% UNIPHASIC BIPHASIC PROTRACTED Clinical predictors for biphasic reactions in children presenting with anaphylaxis Mehr Clinical & Experimental Allergy 2009;39:1390 <ul><li>A biphasic reaction was defined as an initial anaphylactic reaction with a period of resolution for  1 h, during which there were no new symptoms or treatment administered, followed by a second phase anaphylactic. </li></ul>
  52. 52. <ul><li>Retrospective study of children presenting with anaphylaxis to a major paediatric emergency department over a 5-year period. </li></ul>% REACTIONS 100 – 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 87% 11% 2% UNIPHASIC BIPHASIC PROTRACTED Clinical predictors for biphasic reactions in children presenting with anaphylaxis Mehr Clinical & Experimental Allergy 2009;39:1390 <ul><li>A protracted reaction was defined as an anaphylactic reaction without an interval period of resolution associated with CVS symptoms or signs. </li></ul>
  53. 53. <ul><li>For the management of the primary anaphylactic reaction, children developing biphasic reactions were more likely to have received >1 dose of adrenaline (58% vs. 22%, P = 0.01) and/or a fluid bolus (42% vs. 8%, P = 0.01) than those experiencing uniphasic reactions. </li></ul>Children who received >1 dose of adrenaline and/or a fluid bolus for treatment of their primary anaphylactic reaction were at increased risk of developing a biphasic reaction Clinical predictors for biphasic reactions in children presenting with anaphylaxis Mehr Clinical & Experimental Allergy 2009;39:1390
  54. 54. Anafilassi eziologia
  55. 55. ANAPHYLACTIC REACTION TO PERMANENT TATTOO INK Lee-Wong Ann Allergy Asthma Immunol 2009;103:88 <ul><li>Delayed hypersensitivity reactions to tattoo ink are well described, but, anaphylaxis after permanent tattoos has never been reported. </li></ul><ul><li>A 30-year-old woman received her first multicolored tattoo in 1993, with no adverse reactions. </li></ul><ul><li>In June 1999, she had colored ink added to the tattoo. </li></ul><ul><li>Approximately 12 hours after the procedure, a feeling of heat began at her anus and spread rapidly over her body, followed by the development of hives over her face, chest, and upper back. She experienced acute shortness of breath and intractable abdominal pain. </li></ul>
  56. 56. ANAPHYLACTIC REACTION TO PERMANENT TATTOO INK Lee-Wong Ann Allergy Asthma Immunol 2009;103:88 <ul><li>Delayed hypersensitivity reactions to tattoo ink are well described, but, anaphylaxis after permanent tattoos has never been reported. </li></ul><ul><li>A 30-year-old woman received her first multicolored tattoo in 1993, with no adverse reactions. </li></ul><ul><li>In June 1999, she had colored ink added to the tattoo. </li></ul><ul><li>Approximately 12 hours after the procedure, a feeling of heat began at her anus and spread rapidly over her body, followed by the development of hives over her face, chest, and upper back. She experienced acute shortness of breath and intractable abdominal pain. </li></ul>Throughout this episode, the tattoo appeared normal.
  57. 57. ANAPHYLACTIC REACTION TO PERMANENT TATTOO INK Lee-Wong Ann Allergy Asthma Immunol 2009;103:88 <ul><li>Six months later , the patient returned for further coloring of her tattoo, at which time she experienced similar symptoms, occurring faster and resolving after a regimen of antihistamines and IV methylprednisolone sodium succinate (Solu-Medrol). </li></ul><ul><li>Allergy prick skin testing using samples of 13 different ink colors were a 5-mm wheal with allergen 1 (purple with carbon) then a 3-mm wheal with allergen 8 (blue). </li></ul>Allergy skin prick testing on a patient’s back
  58. 58. ANAPHYLACTIC REACTION TO PERMANENT TATTOO INK Lee-Wong Ann Allergy Asthma Immunol 2009;103:88 <ul><li>Tattoos are created by injecting ink into the dermis using a hollow needle. </li></ul><ul><li>Within 12 hours after tattooing, dermal pigmentation, dermal hemorrhage, and epidermal necrosis are evident. </li></ul><ul><li>The inks used in tattoos are composed of different pigmented compounds , such as cadmium sulfide (yellow); cobalt (blue); manganese (purple); mercuric sulfide , azo , or cadmium (red); and chromium oxide (green). </li></ul>
  59. 59. ANAPHYLACTIC REACTION TO PERMANENT TATTOO INK Lee-Wong Ann Allergy Asthma Immunol 2009;103:88 <ul><li>Delayed-hypersensitivity reactions have been described in response to tattoo ink, especially reds . </li></ul><ul><li>The most common tissue reaction is a localized lichenoid pattern , although distant lesions have been described. </li></ul><ul><li>Another well-described pattern of allergic response is granulomatous reactions . </li></ul><ul><li>Skin changes occur weeks to years after tattoo placement. </li></ul>
  60. 60. Anaphylaxis in the obstetric patient: analysis of a statewide hospital discharge database Mulla Ann Allergy Asthma Immunol 2010;104:55 <ul><li>Statewide public use hospital discharge data for 2004 and 2005 in Texas </li></ul><ul><li>A total of 19 maternal anaphylaxis cases were identified. </li></ul><ul><li>The prevalence was 2.7 cases per 100,000 deliveries . </li></ul><ul><li>Penicillins and cephalosporins were the anaphylactic trigger in 11 of the patients. </li></ul><ul><li>There were no maternal deaths. </li></ul>
  61. 61. Anaphylaxis in the obstetric patient: analysis of a statewide hospital discharge database Mulla Ann Allergy Asthma Immunol 2010;104:55 <ul><li>Statewide public use hospital discharge data for 2004 and 2005 in Texas </li></ul><ul><li>A total of 19 maternal anaphylaxis cases were identified. </li></ul><ul><li>The prevalence was 2.7 cases per 100,000 deliveries . </li></ul><ul><li>Penicillins and cephalosporins were the anaphylactic trigger in 11 of the patients. </li></ul><ul><li>There were no maternal deaths. </li></ul>Anaphylaxis during pregnancy is a rare event this β-lactam antibiotics were the most common triggers of anaphylaxis.
  62. 62. Cutaneous manifestations in Hymenoptera and Diptera anaphylaxis: relationship with basal serum tryptase Potier CEA 2009;39:717 <ul><li>140 patients with a history of a systemic reaction to venom. </li></ul><ul><li>Most patients with elevated tryptase were screened for mastocytosis: skin biopsy and a bone marrow biopsy. </li></ul><ul><li>Tryptase was elevated in 23 patients. </li></ul><ul><li>Mastocytosis was diagnosed in 7 patients with elevated tryptase: indolent systemic mastocytosis in 6 cases and cutaneous mastocytosis without systemic involvement in 1 case. </li></ul><ul><li>In 5 cases, mastocytosis was previously undiagnosed . </li></ul>
  63. 63. Cutaneous manifestations in Hymenoptera and Diptera anaphylaxis: relationship with basal serum tryptase Potier CEA 2009;39:717 <ul><li>140 patients with a history of a systemic reaction to venom. </li></ul><ul><li>Most patients with elevated tryptase were screened for mastocytosis: skin biopsy and a bone marrow biopsy. </li></ul><ul><li>Tryptase was elevated in 23 patients. </li></ul><ul><li>Mastocytosis was diagnosed in 7 patients with elevated tryptase: indolent systemic mastocytosis in 6 cases and cutaneous mastocytosis without systemic involvement in 1 case. </li></ul><ul><li>In 5 cases, mastocytosis was previously undiagnosed . </li></ul>Serum tryptase concentrations ≥13.5 ng/mL were considered to be elevated.
  64. 64. Anafilassi comorbidità
  65. 65. Exercise Food Dependent Anaphylaxis
  66. 66. Definition of an exercise intensity threshold in a challenge test to diagnose food-dependent exercise-induced anaphylaxis . Loibl Allergy 2009:64:1560 <ul><li>a 46-year-old woman with allergic rhinoconjunctivitis and a 3-year history of anaphylaxis during physical exercise after having taken a meal containing cakes and sugar. </li></ul><ul><li>Specific IgE antibodies by Immuno-CAP </li></ul><ul><li>First provocation tests with 20 min of unstandardized bicycle ergometer exercise failed to induce any symptoms. </li></ul>
  67. 67. Definition of an exercise intensity threshold in a challenge test to diagnose food-dependent exercise-induced anaphylaxis . Loibl Allergy 2009:64:1560 <ul><li>Thus, a defined supervised treadmill exercise in the sports medicine outpatient clinic was performed. On day 1, the maximal exercise intensity for the patient was identified by beginning a treadmill at a speed of 4 km/h and increasing the speed by 2 km/h for every 3 min. After 15 min and at a speed of 12 km/h, the maximal exercise intensity was reached with a heart rate of 170/min, a subjective Borg score of 17 (out of 20) and a maximal lactate level of 9.2 mmol/l . </li></ul>
  68. 68. Definition of an exercise intensity threshold in a challenge test to diagnose food-dependent exercise-induced anaphylaxis . Loibl Allergy 2009:64:1560 <ul><li>On day 2, directly after ingestion of a nutty wheat pastry containing ω5-Gliadin, the same procedure was followed. When a submaximal exercise intensity at a lactate level of 3.9 mmol/l was reached, the exercise was continued at a speed of 10 km/h until symptoms occurred. After 18 min and 3500 m (patient's heart rate 159/min), the patient reported pruritus and urticaria on her neck, décolleté and arms. </li></ul><ul><li>Tryptase increased from a baseline value of 7.25 μg/l (normal range <11.4 μg/l) to 13.1 μg/l and 27.2 μg/l, at 40 and 120 min after the test, respectively. </li></ul>
  69. 69. Definition of an exercise intensity threshold in a challenge test to diagnose food-dependent exercise-induced anaphylaxis . Loibl Allergy 2009:64:1560 <ul><li>This case shows that a submaximal intensity exercise test was needed in the diagnosis of FDEIA to induce symptoms . </li></ul><ul><li>Considering the fact that intestinal permeability and therefore allergen absorption are more pronounced during longer and tougher exercise, we conclude that the outcome of an exercise challenge test to diagnose FDEIA is substantially influenced by the test intensity and the test application. </li></ul><ul><li>Further research on the exercise intensity to elicit symptoms in different patients with FDEIA appears to be necessary. </li></ul>
  70. 70. Combined cetirizine-montelukast preventive treatment for food-dependent exercise-induced anaphylaxis Peroni, Ann Allergy Asthma Immunol 2010;104:272-273 <ul><li>17-year-old adolescent admitted for 2 episodes of anaphylaxis that occurred while jogging 60 minutes after eating; </li></ul><ul><li>Open food-exercise challenges with 2 peaches was associated with generalized urticaria, nausea, swelling, coughing, and wheezing within 3 minutes. </li></ul>Cetirizine 10 mg no protection Cetirizine 10 mg + Montelukast 10 mg Full protection
  71. 71. diagnosi differenziale
  72. 72. Familial atypical cold urticaria: Description of a new hereditary disease. Gandhi JACI 2009:124:1245 Background: Acquired cold urticaria (ACU) is usually a self-limited, sporadic , cutaneous disease diagnosed based on history and a positive cold stimulation time test (CSTT) result . We describe 3 unrelated families (A, B, and C) with lifelong atypical cold urticaria distinguished from ACU and familial cold autoinflammatory syndrome.
  73. 73. Familial atypical cold urticaria: Description of a new hereditary disease. Gandhi JACI 2009:124:1245 <ul><li>35 subjects are described with familial atypical cold urticaria displaying an autosomal dominant pattern of inheritance. </li></ul><ul><li>All tested subjects had negative CSTT results. </li></ul>Filled symbols represent affected individuals
  74. 74. Familial atypical cold urticaria: Description of a new hereditary disease. Gandhi JACI 2009:124:1245 A , Sixteen-month-old boy after a 5 minute exposure to 5°C atmosphere outdoor exposure followed by 5 minutes at room temperature.
  75. 75. Familial atypical cold urticaria: Description of a new hereditary disease. Gandhi JACI 2009:124:1245 B , Thirty-four-month-old boy at room temperature for 2 hours, crying.
  76. 76. Familial atypical cold urticaria: Description of a new hereditary disease. Gandhi JACI 2009:124:1245 C , Four-year-old girl bathing indoors at room temperature.
  77. 77. Familial atypical cold urticaria: Description of a new hereditary disease. Gandhi JACI 2009:124:1245 Cutaneous manifestations of 2 affected siblings from family B (A and B) and 1 affected child from family A (C). Fig 2, A , Sixteen-month-old boy after a 5 minute exposure to 5°C atmosphere outdoor exposure followed by 5 minutes at room temperature. Fig 2, B , Thirty-four-month-old boy at room temperature for 2 hours, crying. Fig 2, C , Four-year-old girl bathing indoors at room temperature.
  78. 78. Familial atypical cold urticaria: Description of a new hereditary disease. Gandhi JACI 2009:124:1245 Negative CSTT result and demonstration of evaporative cooling-induced symptoms . A , CSTT performed for 5 minutes with 5 minutes of rewarming without the development of a wheal. B , Water droplet after 10 minutes of occlusion without any cutaneous manifestations. C , Water droplet after being exposed to compressed air for less than 1 minute with marked erythema and pruritus. Testing with 100% ethanol yielded similar results.
  79. 79. 3.75 y 6 mo 100% 100% 5 min 5 min 100% 100% 100% 100% 23% 42% 23% 57% 7% 50% 46% 86% 100% 100% 69% 100% 54% 71% 92% 100% Data represent the means of absolute values (age of onset and cold exposure) and the prevalence (%) Family A (n = 13) Family B (n = 7) Clinical characteristics and symptom prevalence of FACU in families A and B Familial atypical cold urticaria: Description of a new hereditary disease. Gandhi JACI 2009:124:1245 Timing Mean age of onset Lifelong duration Minimum required exposure Characteristics Pruritus Erythema Angioedema Burning Numbness Syncope/near syncope Triggers Cold atmosphere Ingestion of cold food or beverage Handling cold objects Aquatic activities
  80. 80. Familial atypical cold urticaria: Description of a new hereditary disease. Gandhi JACI 2009:124:1245 Distinguishing features of FACU, ACU, and FCAS FACU ACU FCAS Inheritance pattern Known genetic mutation Onset in early childhood Lifelong duration Atmospheric cold elicitation Immediate onset after cold exposure Onset with ingestion of cold foods Pruritus Respiratory symptoms (bronchospasm) CV collapse/syncope Fever or chills Extremity pain CSTT Antihistamines effective Autosomal dominant Usually sporadic Autosomal dominant Unknown ++ +++ ++ +++ ++ +++ + + − − − ++ Unknown − − + +++ ++ +++ ++ ++ − − +++ +++ NLRP3 ++ +++ ++ − − + − − +++ +++ − + FACU : familial atypical cold urticaria; ACU acquired cold urticaria; FCAS familial cold autoinflammatory syndrome
  81. 81. Familial atypical cold urticaria: Description of a new hereditary disease. Gandhi JACI 2009:124:1245 PROPOSED DIAGNOSTIC CRITERIA FOR FACU <ul><li>Rash: Localized pruritic erythema after cold exposure with urticaria, angioedema, or both </li></ul><ul><li>Autosomal dominant pattern of disease inheritance </li></ul><ul><li>Rash resolution usually <1 h after rewarming </li></ul><ul><li>Absence of fever, chills, or joint complaints </li></ul><ul><li>Age of onset in childhood with lifelong duration of symptoms </li></ul><ul><li>Negative CSTT result (no wheal formation) </li></ul>The above diagnostic criteria are strongly suggestive of FACU and are helpful in distinguishing it from ACU and FCAS ( familial cold autoinflammatory syndrome) .
  82. 82. Anafilassi terapia
  83. 83. % SUBJECTS WITH ANAPHYLAXIS 36.2% 40 – 35 – 30 – 25 – 20 – 15 – 10 – 5 – 0 <ul><li>O nline survey to university students. </li></ul><ul><li>513 individuals. </li></ul>Food allergy and food allergy attitudes among college students. Greenhawt JACI 2009;124:323
  84. 84. Food allergy and food allergy attitudes among college students. Greenhawt JACI 2009;124:323 Avoiding Allergenic Foods 39.7% 40 – 30 – 20 – 10 – 0 % SUBJECTS WITH FOOD ALLERGY Having Self-injectable Epinephrine Always Carrying Self-injectable Epinephrine 21% 6% ONLY!
  85. 85. Food allergy and food allergy attitudes among college students. Greenhawt JACI 2009;124:323 <ul><li>O nline survey to university students. </li></ul><ul><li>513 individuals. </li></ul>Reaction locations of a food allergy. Students were allowed to select multiple venues.
  86. 86. Reasons justifying food allergy risk-taking behavior among university students Food allergy and food allergy attitudes among college students. Greenhawt JACI 2009;124:323 Reasons given ∗ Percentage (n = 173) No history of severe reaction 37.6 (n = 65) Do not have consistent symptoms 21.9 (n = 38) Do not perceive this to be a risky action 20.8 (n = 36) Belief that item does not contain enough allergen to trigger a reaction 18.5 (n = 32) Belief that I could treat any reaction that occurred 17.9 (n = 31) Belief that I can eat around the allergen 14.5 (n = 25) Indifference 12.1 (n = 21) Last reaction was in the distant past 10.4 (n = 1) ∗ Students were allowed to select multiple reasons.
  87. 87. Factors associated with repeated use of epinephrine for the treatment of anaphylaxis Manivannan Ann Allergy Asthma Immunol 2009;103:395 <ul><li>208 patients with anaphylaxis </li></ul>13% % Patients Receiving >1 Dose of Epinephrine 20 – 15 – 10 – 0 5 – 0
  88. 88. Factors associated with repeated use of epinephrine for the treatment of anaphylaxis Manivannan Ann Allergy Asthma Immunol 2009;103:395 31.1 Median Age (Years) 35 – 30 – 25 – 20 – 15 – 10 – 0 5 – 0 18.9 1 Dose >1 Dose Epinephrine
  89. 89. Factors associated with repeated use of epinephrine for the treatment of anaphylaxis Manivannan Ann Allergy Asthma Immunol 2009;103:395 31.1 Median Age (Years) 35 – 30 – 25 – 20 – 15 – 10 – 0 5 – 0 18.9 1 Dose >1 Dose Patients who received repeated doses were more likely to have wheezing ( P =0.03), cyanosis ( P =0.001), hypotension and shock ( P =0.03), stridor and laryngeal edema ( P =0.007), nausea and emesis ( P =0.04), arrhythmias ( P <0.01), and cough ( P =0.04) and less likely to have urticaria ( P =0.049). Epinephrine
  90. 90. Epinephrine treatment is infrequent and biphasic reactions are rare in food-induced reactions during oral food challenges in children Järvinen JACI 2009:124:1267 <ul><li>Reaction details of positive OFCs in children between 1999 and 2007. </li></ul><ul><li>1273 OFCs. </li></ul>% CHALLENGE WITH A REACTION 34% 35 – 30 – 25 – 20 – 15 – 10 – 5 – 0
  91. 91. SOY 40 – 30 – 20 – 10 – 0 WHEAT MILK EGG PEANUT TREE NUTS 9% % (+) CHALLENGE REQUIRING EPINEPHRINE ADMINISTRATION 3.7% 12% 16% 26% 33% Epinephrine treatment is infrequent and biphasic reactions are rare in food-induced reactions during oral food challenges in children Järvinen JACI 2009:124:1267
  92. 92. SOY 40 – 30 – 20 – 10 – 0 WHEAT MILK EGG PEANUT TREE NUTS 9% % (+) CHALLENGE REQUIRING EPINEPHRINE ADMINISTRATION 3.7% 12% 16% 26% 33% Reactions requiring epinephrine occurred in older children (median, 7.9 vs 5.8 years; P <.001) Epinephrine treatment is infrequent and biphasic reactions are rare in food-induced reactions during oral food challenges in children Järvinen JACI 2009:124:1267
  93. 93. Anaphylaxis in the community: Learning from the survivors Simons JACI 2009;124:301 <ul><li>An e-mail survey </li></ul><ul><li>1885 participants </li></ul>% SUBJECTS 73% NONUSERS USERS 27% 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 EPINEPHRINE
  94. 94. Anaphylaxis in the community: Learning from the survivors Simons JACI 2009;124:301 <ul><li>An e-mail survey </li></ul><ul><li>1885 participants </li></ul>% SUBJECTS 73% NONUSERS USERS 27% 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 The groups were similar with regard to multisystem organ involvement and many other aspects of anaphylaxis. EPINEPHRINE
  95. 95. Anaphylaxis in the community: Learning from the survivors Simons JACI 2009;124:301 <ul><li>respiratory or shock symptoms; </li></ul><ul><li>peanut, fish, or insect sting triggers; </li></ul><ul><li>to be asthmatic; and to have taken or been given asthma medication on the day of the episode. </li></ul>Epinephrine users were more likely (all P < 0.05) to report
  96. 96. Anaphylaxis in the community: Learning from the survivors Simons JACI 2009;124:301 <ul><li>whether to give the injection, </li></ul><ul><li>whether repeat the dose, </li></ul><ul><li>whether and/or go to an emergency department. </li></ul>Epinephrine users reported problems in deciding
  97. 97. Anaphylaxis in the community: Learning from the survivors Simons JACI 2009;124:301 <ul><li>use of an H1-antihistamine (38%), </li></ul><ul><li>no prescription for epinephrine (28%), and/or </li></ul><ul><li>a mild anaphylaxis episode (13%). </li></ul>Nonusers reported not injecting epinephrine for various reasons, including
  98. 98. Anaphylaxis in the community: Learning from the survivors Simons JACI 2009;124:301 Problems encountered with epinephrine autoinjector use Deciding whether to use it 32% † Deciding whether to go to emergency department 16% † Holding the autoinjector in place for 10 seconds 11% Disposing of the autoinjector 9% Choosing exact place on the thigh for the injection 8% Deciding whether to repeat the dose 8% † Deciding whether to inject through clothes 6% Remembering which end to put against thigh 3% Following the instructions 2% Remembering to pull off the safety release 2% † some of the common problems involved judgment about the severity of the reaction
  99. 99. Anaphylaxis in the community: Learning from the survivors Simons JACI 2009;124:301 Problems encountered with epinephrine autoinjector use Deciding whether to use it 32% † Deciding whether to go to emergency department 16% † Holding the autoinjector in place for 10 seconds 11% Disposing of the autoinjector 9% Choosing exact place on the thigh for the injection 8% Deciding whether to repeat the dose 8% † Deciding whether to inject through clothes 6% Remembering which end to put against thigh 3% Following the instructions 2% Remembering to pull off the safety release 2% † some of the common problems involved judgment about the severity of the reaction One or more of the problems listed above were encountered by 275 (55%) of 500 epinephrine users.
  100. 100. Anaphylaxis in the community: Learning from the survivors Simons JACI 2009;124:301 Why epinephrine autoinjectors were not used An antihistamine was used 38% Did not receive a prescription for epinephrine autoinjector 28% The allergic reaction was mild 13% An asthma puffer was used 8% Did not have epinephrine autoinjector available 8% Unsure when to give the epinephrine injection 8% In previous reaction no treatment was needed 8% Afraid to inject epinephrine 6% Quick recovery time (reaction went away fast) 4% Concern about possible side effects of epinephrine 4% Did not think autoinjector was needed because trigger was being avoided 3% Epinephrine autoinjector was past expiry date 2% Could not afford to purchase epinephrine autoinjector 1% Was given prescription for autoinjector but did not purchase it 0.1%
  101. 101. Epinephrine Auto-injectors: Is Needle Length Adequate for Delivery of Epinephrine Intramuscularly? Stecher Pediatrics 2009;124;65 <ul><li>256 children patients between the ages of 1 and 12 years </li></ul><ul><li>Ultrasound was used to determine the depth from the skin to the vastus lateralis muscle. </li></ul>% Children Who Would Not Receive Epinephrine Intramuscularly from Current Auto-injectors 30% 12% <30 kg >30 kg 30 – 20 – 10 – 0
  102. 102. Epinephrine Auto-injectors: Is Needle Length Adequate for Delivery of Epinephrine Intramuscularly? Stecher Pediatrics 2009;124;65 <ul><li>256 children patients between the ages of 1 and 12 years </li></ul><ul><li>Ultrasound was used to determine the depth from the skin to the vastus lateralis muscle. </li></ul>% Children Who Would Not Receive Epinephrine Intramuscularly from Current Auto-injectors 30% 12% <30 kg >30 kg 30 – 20 – 10 – 0 The needle on epinephrine auto-injectors is not long enough to reach the muscle in a significant number of children.
  103. 103. Voluntarily reported unintentional injections from epinephrine auto-injectors Simons JACI 2010;125:419 <ul><li>From 1994 to 2007, a total of 15,190 unintentional injections from epinephrine auto-injectors were reported to US Poison Control Centers </li></ul>Characteristics of the population (%) 60% Median age of 14 years 40% Injected in home 85% Occurred during attempts to treat allergic reactions 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0
  104. 104. Voluntarily reported unintentional injections from epinephrine auto-injectors Simons JACI 2010;125:419 <ul><li>From 1994 to 2007, a total of 15,190 unintentional injections from epinephrine auto-injectors were reported to US Poison Control Centers </li></ul>Characteristics of the population (%) 60% Median age of 14 years 40% Injected in home 85% Occurred during attempts to treat allergic reactions 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 to p revent these unintentional injections, improved epinephrine auto-injector design is needed, along with increased vigilance in training the trainers and in training and coaching the users.
  105. 105. A comparison of 4 epinephrine autoinjector delivery systems: usability and patient preference Guerlain Ann Allergy Asthma Immunol 2010;104:172 <ul><li>48 participants divided equally among 3 age groups: 7 to 10, 11 to 15, and 16 to 55 years. </li></ul><ul><li>Without training, participants performed simulated-use testing for all 4 epinephrine delivery systems. </li></ul><ul><li>Usability (ie, the ability to perform the manufacturer’s labeled instructions ). </li></ul>
  106. 106. A comparison of 4 epinephrine autoinjector delivery systems: usability and patient preference Guerlain Ann Allergy Asthma Immunol 2010;104:172 % patients correctly following the instructions 46% INT02 EpiPen 50 – 40 – 30 – 20 – 10 – 0 P<0.01 for trend 27% INT01 12% 0% TwinJect <ul><li>48 participants divided equally among 3 age groups: 7 to 10, 11 to 15, and 16 to 55 years. </li></ul><ul><li>Without training, participants performed simulated-use testing for all 4 epinephrine delivery systems. </li></ul><ul><li>Usability (ie, the ability to perform the manufacturer’s labeled instructions ). </li></ul>
  107. 107. A comparison of 4 epinephrine autoinjector delivery systems: usability and patient preference Guerlain Ann Allergy Asthma Immunol 2010;104:172 % patients correctly following the instructions 46% INT02 EpiPen 50 – 40 – 30 – 20 – 10 – 0 P<0.01 for trend 27% INT01 12% 0% TwinJect <ul><li>48 participants divided equally among 3 age groups: 7 to 10, 11 to 15, and 16 to 55 years. </li></ul><ul><li>Without training, participants performed simulated-use testing for all 4 epinephrine delivery systems. </li></ul><ul><li>Usability (ie, the ability to perform the manufacturer’s labeled instructions ). </li></ul>The user-centered device design may have a significant impact on correct epinephrine autoinjector use.
  108. 108. Long-term stability of epinephrine dispensed in unsealed syringes for the first-aid treatment of anaphylaxis Rawas-Qalaji Ann Allergy Asthma Immunol 2009;102:500 Background: When epinephrine autoinjectors are unavailable or unaffordable, patients at risk for anaphylaxis in the community are sometimes provided with an unsealed syringe containing a premeasured epinephrine dose for use in first-aid treatment of anaphylaxis episodes. Objectives: To study the stability of epinephrine solution in unsealed syringes under conditions of high ambient temperature, low vs high humidity, and light vs dark.
  109. 109. Long-term stability of epinephrine dispensed in unsealed syringes for the first-aid treatment of anaphylaxis Rawas-Qalaji Ann Allergy Asthma Immunol 2009;102:500 <ul><li>40 unsealed syringes each containing an epinephrine dose of 0.3 mg (as a 1-mg/mL epinephrine solution) were stored at 38°C for 5 months. </li></ul><ul><li>10 syringes at each of 4 different standardized storage conditions: dark and light at low (15%) humidity and dark and light at high (95%) humidity. </li></ul>* P .05 compared with control syringes containing 0.32 (0.00) mg. + Below the US Pharmacopeia compendial limits for epinephrine injections (90% to 115% of label claim). Mean (SEM) epinephrine dose remaining in the prefilled unsealed syringes stored at 38°C and at high or low humidity for 5 mo
  110. 110. Long-term stability of epinephrine dispensed in unsealed syringes for the first-aid treatment of anaphylaxis Rawas-Qalaji Ann Allergy Asthma Immunol 2009;102:500 <ul><li>40 unsealed syringes each containing an epinephrine dose of 0.3 mg (as a 1-mg/mL epinephrine solution) were stored at 38°C for 5 months. </li></ul><ul><li>10 syringes at each of 4 different standardized storage conditions: dark and light at low (15%) humidity and dark and light at high (95%) humidity. </li></ul>* P .05 compared with control syringes containing 0.32 (0.00) mg. + Below the US Pharmacopeia compendial limits for epinephrine injections (90% to 115% of label claim). Mean (SEM) epinephrine dose remaining in the prefilled unsealed syringes stored at 38°C and at high or low humidity for 5 mo Light had no significant effect.
  111. 111. Long-term stability of epinephrine dispensed in unsealed syringes for the first-aid treatment of anaphylaxis Rawas-Qalaji Ann Allergy Asthma Immunol 2009;102:500 <ul><li>40 unsealed syringes each containing an epinephrine dose of 0.3 mg (as a 1-mg/mL epinephrine solution) were stored at 38°C for 5 months. </li></ul><ul><li>10 syringes at each of 4 different standardized storage conditions: dark and light at low (15%) humidity and dark and light at high (95%) humidity. </li></ul>* P .05 compared with control syringes containing 0.32 (0.00) mg. + Below the US Pharmacopeia compendial limits for epinephrine injections (90% to 115% of label claim). Mean (SEM) epinephrine dose remaining in the prefilled unsealed syringes stored at 38°C and at high or low humidity for 5 mo In hot climates, if an unsealed syringe prefilled with an epinephrine dose is provided for the first-aid treatment of anaphylaxis, it should be replaced every few months (2-3 mo.) on a regular basis with a new syringe containing a fresh dose of epinephrine.
  112. 112. 0 0.317 (0.004) 100 0.319 (0.001) 100 1 0.313 (0.006) 99 0.315 (0.003) 99 2 0.285 (0.010) 90 0.298 (0.005) 93 3 0.190 (0.011) b 60 c 0.288 (0.005) 90 4 0.178 (0.023) b 55 c 0.265 (0.009) b 83 c 5 0.123 (0.023) b 39 c 0.260 (0.007) b 82 c a Month 0 = control doses. b P <.05 vs control syringes. c Below the US Pharmacopeia compendial limits for epinephrine injections (90%–115% of label claim). Time Mo. Low (15%) humidity High (85%) humidity Mean (SEM) % of control dose dose,mg Mean (SEM) % of control dose dose,mg Long-term stability of epinephrine dispensed in unsealed syringes for the first-aid treatment of anaphylaxis Rawas-Qalaji Ann Allergy Asthma Immunol 2009;102:500
  113. 113. <ul><li>Meno sole più anafilassi </li></ul><ul><li>Le reazioni bifasiche riguardano ~ 10% dei pazienti e sono più frequenti nei casi di reazione iniziale grave, </li></ul><ul><li>L’anafilassi (A) può comparire con i tatuaggi, durante la gravidanza, ed è particolarmente grave nei pazienti con mastocitosi, </li></ul><ul><li>L’A da sforzo richiede un test intenso per essere smascherata e può essere prevenuta con Montelukast + cet. </li></ul><ul><li>L’A. da alimenti si verifica spesso al ristorante e solo 1 pt su 5 ha con se l’adrenalina ed quasi 1 pt su 5 ha bisogno di due dosi, </li></ul><ul><li>L’ago può non essere sufficientemente lungo nel pt obeso, </li></ul><ul><li>I pt fanno parecchi errori con l’autoiniezione, è importante far fare, </li></ul><ul><li>Le preparazioni estemporanee devono essere rimpiazzate ogni 2-3 mesi. </li></ul>
  114. 114. angiedema
  115. 115. Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks Craig JACI 2009;124:801 <ul><li>Hereditary angioedema (HAE) is a rare disorder with 3 known forms (types I, II, and III). Whereas types I and II are characterized by quantitative and/or functional C1 esterase inhibitor (C1-INH) deficiency, type III is characterized by normal complement levels and may be caused by mutations in the factor XII gene and occurs only in women. </li></ul><ul><li>C1-INH is one of the control proteins that regulates vascular permeability for the complement system. By inhibiting components of the complement (specifically C1r and C1s), contact (factor XII and kallikrein), coagulation (factor XI and thrombin), and fibrinolytic (tissue-type plasminogen activator and fibrinolysin) systems, C1-INH regulates the generation of vasoactive peptides, of which bradykinin is considered the most important. </li></ul>
  116. 116. <ul><li>The regulation of bradykinin is a key step in preventing the development of angioedema. </li></ul><ul><li>In type I HAE, impaired synthesis of functionally active C1-INH and elevated turnover result in insufficient plasma concentrations of C1-INH, whereas in type II HAE, a dysfunctional C1-INH molecule is synthesized in normal amounts. </li></ul><ul><li>The clinical manifestations of type I or II HAE are episodic bouts of well circumscribed, non-itching swelling of the deep cutaneous, subcutaneous, submucosal, and subepithelial tissues. Patients may experience swelling of the abdomen, face, genitalia, and extremities, abdominal pain, nausea, vomiting, or diarrhea, as well as life-threatening swelling of the larynx. </li></ul>Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks Craig JACI 2009;124:801
  117. 117. <ul><li>Pasteurized C1 esterase inhibitor concentrate (Berinert, CSL Behring) at intravenous doses of 10 or 20 U/kg body weight with placebo in the treatment of single, acute abdominal or facial attacks in patients with hereditary angioedema. </li></ul><ul><li>125 patients with type I or II hereditary angioedema . </li></ul>2.0 – 1.5 – 1.0 – 0.5 – 0 Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks Craig JACI 2009;124:801 0.5 1.2 1.5 MEDIAN TIME TO ONSET OF RELIEF (HOURS) 20 u/k 10 u/kg C1 esterase inhibitor concentrate at a dose of placebo p=0.0025
  118. 118. Background: Hereditary angioedema caused by mutations in the factor XII gene is a recently described disease entity that occurs mainly in women . It differs from hereditary angioedema caused by C1 inhibitor deficiency. Objective: To assess the clinical symptoms, factors triggering acute attacks, and treatments of this disease. Hereditary angioedema caused by missense mutations in the factor XII gene: Clinical features, trigger factors, and therapy. Bork JACI 2009;124:129
  119. 119. <ul><li>Female patients with hereditary angioedema and the factor XII mutations. </li></ul><ul><li>Followed for 8-4 years. </li></ul>Swelling of the lips (A) and normal state (B) in a woman with HAE-FXII. Hereditary angioedema caused by missense mutations in the factor XII gene: Clinical features, trigger factors, and therapy. Bork JACI 2009;124:129
  120. 120. Hereditary angioedema caused by missense mutations in the factor XII gene: Clinical features, trigger factors, and therapy. Bork JACI 2009;124:129 <ul><li>Female patients with hereditary angioedema and the factor XII mutations. </li></ul><ul><li>Followed for 8-4 years. </li></ul>Age at onset in 35 patients with HAE-FXII
  121. 121. Diagnosis:   Diagnosis of HAE-FXII was based on personal history (recurrent angioedema attacks and no urticaria), family history revealing other affected family members, plasma examination (C1-INH activity normal or slightly decreased), and genetic tests positive for FXII mutation p.Thr309Lys or p.Thr309Arg. Samples were taken during attack-free intervals. Dewald G, Bork K. “Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor”. Biochem Biophys Res Commun. 2006;343:1286–1289 Hereditary angioedema caused by missense mutations in the factor XII gene: Clinical features, trigger factors, and therapy. Bork JACI 2009;124:129
  122. 122. Diagnosis:   Diagnosis of HAE-FXII was based on personal history (recurrent angioedema attacks and no urticaria), family history revealing other affected family members, plasma examination (C1-INH activity normal or slightly decreased), and genetic tests positive for FXII mutation p.Thr309Lys or p.Thr309Arg. Samples were taken during attack-free intervals. Dewald G, Bork K. “Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor”. Biochem Biophys Res Commun. 2006;343:1286–1289 These mutations show the same locus, 5q33-qter of the Hageman factor or coagulation factor XII (FXII) gene on chromosome 5. One mutation leads to a threonine-to-lysine substitution (p.Thr309Lys) and the other to a threonine-to-arginine substitution (p.Thr309Arg). Hereditary angioedema caused by missense mutations in the factor XII gene: Clinical features, trigger factors, and therapy. Bork JACI 2009;124:129
  123. 123. <ul><li>HAE caused by a genetic C1-INH deficiency (HAE–C1-INH; with a subtype I and subtype II, numerous mutations); </li></ul><ul><li>HAE caused by the 2 known mutations in the FXII gene (HAE-FXII); </li></ul><ul><li>HAE-unknown—that is, HAE with an unknown genetic cause (normal C1-INH activity in plasma, no causative mutation in the gene coding for C1-INH, and neither of the known FXII gene mutations [p.Thr309Lys or p.Thr309Arg]). </li></ul>We now can distinguish the following forms of HAE: Hereditary angioedema caused by missense mutations in the factor XII gene: Clinical features, trigger factors, and therapy. Bork JACI 2009;124:129
  124. 124. <ul><li>On average 12.7 ± 7.9 angioedema attacks per year. Recurrent facial swellings occurred in all patients; skin swellings other than facial, abdominal pain attacks, tongue swellings, and laryngeal edema occurred less frequently. </li></ul><ul><li>Clinical symptoms started mainly after intake of oral contraceptives or pregnancy. </li></ul>Symptoms: Hereditary angioedema caused by missense mutations in the factor XII gene: Clinical features, trigger factors, and therapy. Bork JACI 2009;124:129
  125. 125. <ul><li>Oral contraceptive use (8 women). </li></ul><ul><li>Pregnancy (7 women). </li></ul><ul><li>Hormone replacement therapy (3 women). </li></ul><ul><li>Intake of angiotensin-converting enzyme inhibitors (2 women). </li></ul><ul><li>Angiotensin 1 receptor blocker (1 woman). </li></ul>Exacerbations occurred after : Hereditary angioedema caused by missense mutations in the factor XII gene: Clinical features, trigger factors, and therapy. Bork JACI 2009;124:129
  126. 126. <ul><li>C1 inhibitor concentrate for angioedema attacks (6 women) and, for prophylaxis. </li></ul><ul><li>Progesterone (8 women). </li></ul><ul><li>Danazol (2 women). </li></ul><ul><li>Tranexamic acid (1 woman). </li></ul>Effective treatments included: Hereditary angioedema caused by missense mutations in the factor XII gene: Clinical features, trigger factors, and therapy. Bork JACI 2009;124:129
  127. 127. Treatment of acute angioedema attacks 27 patients received corticosteroids for 186 attacks, and 15 patients received antihistamines for 67 attacks; these treatments were not effective. 7 patients received C1-INH concentrate (Berinert P; CSL Behring, Marburg, Germany). One patient reported that it was not effective. In the other 6 patients, Berinert P was very or moderately effective. Hereditary angioedema caused by missense mutations in the factor XII gene: Clinical features, trigger factors, and therapy. Bork JACI 2009;124:129
  128. 128. Prophylactic treatment   Progesterone:  8 patients received a progesterone-containing and estrogen-free oral contraceptive. Seven of them took desogestrel, which is a progestagen, for 1 to 6 years. Women were symptom-free during the period of progesterone treatment. Danazol: One woman received 200 mg danazol, an attenuated androgen, daily for 12 years. During this time she was symptom-free. Tranexamic acid:  Three years ago, 1 woman started treatment with tranexamic acid, 4 g per day, and has had no attacks since then. Hereditary angioedema caused by missense mutations in the factor XII gene: Clinical features, trigger factors, and therapy. Bork JACI 2009;124:129
  129. 129. Idiopathic systemic capillary leak syndrome: Novel therapy for acute attacks Dowden JACI 2009;124:1111 <ul><li>Idiopathic systemic capillary leak syndrome (ISCLS) is a life-threatening disorder of unknown cause that should be included in the differential diagnosis of angioedema. </li></ul><ul><li>Patients typically present in the fifth and sixth decades of life with intermittent acute attacks of peripheral edema, hypotension, hypoalbuminemia, hemoconcentration, weight gain, and a monoclonal gammopathy. </li></ul>
  130. 130. Idiopathic systemic capillary leak syndrome: Novel therapy for acute attacks Dowden JACI 2009;124:1111 During an acute attack, there is an unexplained capillary hyperpermeability with a shift of plasma from the intravascular to the interstitial space. Acute attacks are followed by a resolution phase, with fluid shifts leading to intravascular volume overload and associated severe pulmonary edema. The mortality rate ranges from 30% to 76%.
  131. 131. Idiopathic systemic capillary leak syndrome: Novel therapy for acute attacks Dowden JACI 2009;124:1111 A prophylactic regimen of theophylline and terbutaline has been shown to decrease the frequency of attacks. However, there is no effective therapy for acute attacks. We report novel and effective treatments for acute attacks <ul><li>Increasing theophylline levels to 20 to 25 μg/mL </li></ul><ul><li>Treatment with the TNF-α antagonist infliximab (10 mg/kg) </li></ul>
  132. 132. Idiopathic systemic capillary leak syndrome: Novel therapy for acute attacks Dowden JACI 2009;124:1111 A prophylactic regimen of theophylline and terbutaline has been shown to decrease the frequency of attacks. However, there is no effective therapy for acute attacks. We report novel and effective treatments for acute attacks <ul><li>Increasing theophylline levels to 20 to 25 μg/mL </li></ul><ul><li>Treatment with the TNF-α antagonist infliximab (10 mg/kg) </li></ul>Although the underlying pathogenesis is unknown, our findings strongly support an immunologic basis for this syndrome. The ability of TNF-α to increase vascular permeability and increases in levels of this cytokine during acute attacks in our 3 patients lend credence to the use of TNF antagonists.
  133. 133. Allergic contact stomatitis to cinnamon in chewing gum mistaken as facial angioedema Kind Allergy 2010:65:276 Cinnamon may elicit delayed type hypersensitivity mimicking angioedema. Pathc tests are suited to identify the culprit. Right buccal mucosa with a soft white plaque with a verrucous surface and a surrounding erythema.
  134. 134. Usefulness of abdominal ultrasonography in the follow-up of patients with hereditary C1-inhibitor deficiency Pedrosa Ann Allergy Asthma Immunol 2009;102:483 In 11 cases, ultrasonography was performed during acute attacks . Ascites and intestinal wall swelling were found in 7 of these 11 cases and, thus, diagnosis was confirmed. <ul><li>59 patients with HAE. </li></ul><ul><li>Ultrasonographic findings performed routinely or in the moment of an acute abdominal attack. </li></ul>
  135. 135. Usefulness of abdominal ultrasonography in the follow-up of patients with hereditary C1-inhibitor deficiency Pedrosa Annal Allergy Asthma Immunol 2009;102:483 <ul><li>59 patients with HAE. </li></ul><ul><li>Ultrasonographic findings performed routinely or in the moment of an acute abdominal attack. </li></ul>Abdominal ultrasonographic assessments were performed routinely in 31 patients receiving androgen prophylaxis Four cases of angiomas, 4 of steatosis, and 1 each of portal hypertension, hepatic cysts, and hepatomegaly were found.
  136. 136. Usefulness of abdominal ultrasonography in the follow-up of patients with hereditary C1-inhibitor deficiency Pedrosa Annal Allergy Asthma Immunol 2009;102:483 <ul><li>59 patients with HAE. </li></ul><ul><li>Ultrasonographic findings in the assessments performed routinely or in the moment of an acute abdominal attack. </li></ul>Abdominal ultrasonographic assessments were performed routinely in 31 patients receiving androgen prophylaxis Four cases of angiomas, 4 of steatosis, and 1 each of portal hypertension, hepatic cysts, and hepatomegaly were found. No abnormalities was found in 17 patients not receiving androgen therapy.
  137. 137. Usefulness of abdominal ultrasonography in the follow-up of patients with hereditary C1-inhibitor deficiency Pedrosa Annal Allergy Asthma Immunol 2009;102:483 <ul><li>59 patients with HAE. </li></ul><ul><li>Ultrasonographic findings in the assessments performed routinely or in the moment of an acute abdominal attack. </li></ul>Abdominal ultrasonographic assessments were performed routinely in 31 patients receiving androgen prophylaxis Four cases of angiomas, 4 of steatosis, and 1 each of portal hypertension, hepatic cysts, and hepatomegaly were found. Abdominal ultrasonography has been proved useful as an early tool for diagnosing the adverse effects of therapy and for confirming diagnosis in the case of an acute abdominal attack.

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