2. Orticaria valutazione

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. 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. 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. Orticaria eziologia

19. Orticaria terapia

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.

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

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

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. 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

40. anafilassi

41. Anafilassi epidemiologia

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. 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. 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. Anafilassi patogenesi

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.

54. Anafilassi eziologia

64. Anafilassi comorbidità

65. Exercise Food Dependent Anaphylaxis

71. diagnosi differenziale

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.

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. 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. 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. 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. 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. 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. 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

82. Anafilassi terapia

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!

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.

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. 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

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. 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

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. 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. 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%

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.

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

114. angiedema

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

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. 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

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. 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

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%.

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.