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Clinical Characteristics of Anaphylaxis in Pediatric Patientsat a Tertiary-care HospitalPanitsara Sriboonnark*, Kanika Piromrat** , Sasawan Chinratanapisit***Department of Pediatrics, Bhumibol Adulyadej Hospital**Division of Allergy and Immunology, Department of Pediatrics, Bhumibol Adulyadej HospitalAbstractBackground: Anaphylaxis is an important allergic reaction because it may cause life-threatening condition. The previous clinical studies in Thailand did not categorize the severity of anaphylaxis. Besides the study in clinical characteristics, severity of anaphylaxis was graded into mild, moderate and severe in this study. The benefit of grading was to elucidate the factors that may influence severity of anaphylaxis, proper management and prevention.Objective: To investigate the incidence, clinical characteristics and anaphylaxis grading in pediatric patients at Bhumibol Adulyadej hospital and investigate the factors that related to moderate to severe anaphylaxis.Methods: A retrospective descriptive study was performed in pediatric patients, who were diagnosed as having anaphylaxis and admitted to pediatric department, Bhumibol Adulyadej hospital between January 1st, 2011 and December 31th, 2016.Results: The incidence of anaphylaxis in pediatric patients was 260 per 100,000 admitted pediatric patients per year between 2011 and 2016. The mean age was 8.61 years (range 0.25 to 15 years). The most common clinical characteristic was skin and subcutaneous symptoms (98.3%). 6.8% was graded as severe anaphylaxis. Cardiovascular symptoms were associated with moderate to severe anaphylaxis (p<0.001). 44.9% of patients had atopic diseases. Asthma was the potential factor for moderate to severe anaphylaxis (p<0.001). No death was found in this study. Recurrent of anaphylaxis was 15.3%. Biphasic anaphylaxis was 28.4%. Delayed administration of epinephrine was associated with biphasic anaphylaxis (p<0.001).Conclusion: Patients who had asthma and cardiovascular symptoms were associated with moderate to severe anaphylaxis. Delayed administration of epinephrine was associated with biphasic anaphylaxis. These patients should be closely followed after admission. 15.3% of patients had recurrent anaphylaxis. Identifying causes, avoidance of triggers and portable epinephrine carriage together with proper instruction of self-administration are very important in all anaphylactic patients.Keywords: Anaphylaxis, incidence, clinical characteristics, biphasic anaphylaxis, epinephrineCorrespondence to: Chinratanapisit S.Division of Allergy and Immunology, Department of Pediatrics, Bhumibol Adulyadej Hospital, Bangkok 10220, Thailand.????????????????????????????????????????????????????????????????????????????????????????????? ?????????, ????? ???????????, ?????? ??????????????.???????????????????: ????????????????????????????????????????????? ?????????????????????????????? ???????????????????? ???????????????????????????????????????????? ??????????????????????????? ?????? ?????????????????? ?????????????????????????????????????????????????????????????????????? ????????????? ???????????????????????????????????????????????????????? ????????????????????????? ?????????????????????????????????????: ??????????????????????????????????????????????????????????????? ?????????????????????????????????????????????????????????????????????????????????????????? ????????????????????????????????????????????????????????????????????????????????????????: ????????????????????????????????????????????????????????? ??????????????????????????????????????????????????????????????? ???????????????????????????????????????????????????????????????? 1 ?????? ?.?.2554 ??? 31 ??????? ?.?. 2559??????????: ??????????????????????????????????????????????????????????????????????????????????? ????260 ?????????????????????????????????????????????????????????100,000 ?? ??????? ?.?.2554 ??? ?.?.2559???????????????????? 8.61 ?? (3 ????????15 ??) ????????????????????????????????????????? ?????? ????????????????????????? (98.3%) ??????????????????????????? (6.8%) ????????????????????????????????????????????????????????????????????????????????????????? (p<0.001) ?????????????????????????? 44.9% ?????????????????????????????????????????????????????????????????????????????????? (p<0.001) ?????????????????????????????????????????????? ???????????????????????????? 15.3% ?? biphasic anaphylaxis 28.4% ???????????????????????????????????????????????????? biphasic anaphylaxis ????: ???????????????????????????????????????????????????????????????? ??????????????????????????????????????????????????? ?????????????????????????????????????????????????????????????????????? biphasic anaphylaxis ????????????????????????????????????????????????????????? ???????????? 15.3% ???????????????????????????? ?????????????????????????????? ?????????????????????????? ??????????????????????????????????? ??????????????????????????????????????????????????????:?????????????, ???????????, ???????????????, biphasic anaphylaxis, ??????????BackgroundAnaphylaxis is an acute systemic allergic reaction and a life threatening condition. Rapid diagnosis is very important. Diagnostic criteria were latest reviewed and published in 2006 to help clinicians recognize signs and symptoms of anaphylaxis.(1) Anaphylaxis typically occurs through an IgE dependent immunologic mechanism, most common triggered by foods, medication or stinging insects.(2) The incidence of anaphylaxis in the United Kingdom was 6.7 per 100,000 persons per year in 2001 and increased to 7.9 per 100,000 persons per year in 2005.(3) In study at Siriraj hospital, the annual occurrence of anaphylaxis increased from 9.16 per 100,000 admitted patient in 1999 to 55.45 per 100,000 admitted patients in 2004.(4) In Ramathibodi hospital study, the incidence of anaphylaxis in hospitalized pediatric patients was 451 per 100,000 pediatric admissions between 2009 to 2013.(5)Severity of anaphylaxis was graded as mild, moderate or severe anaphylaxis by Faith Huang which were published in 2012.(6) Criteria of severe anaphylaxis includes one of the following; cyanosis orSpO2 < 92% at any stage, hypotension, confusion, collapse, loss of consciousness or incontinence.(6)The studies in the United states,fatal anaphylaxis in the pediatric population has particularly been associated with known preexisting asthma(7), delayed administration of epinephrine.(8) Epinephrine is the treatment of choice for anaphylaxis.(8) Delayed administration of epinephrine has been identified as a risk factor for fatal food-induced anaphylaxis(9) and was associated with the occurrence of biphasic anaphylaxis.(10) Epinephrine should be prescribed for children who experienced anaphylaxis and may re-encounter the triggers outside of a health care setting for prevention of poor outcomes.(11)The objectives of our study were to determine the incidence of anaphylaxis in pediatric patients who were admitted to pediatric department, Bhumibol Adulyadej hospital. Furthermore, to investigate clinical characteristics of anaphylactic patients, anaphylaxis grading (mild, moderate, severe) and exploring risk factors that relate to moderate to severe anaphylaxis in order to achieve the best outcome of management and preventive measure.MethodsA retrospective, descriptive study was performed by reviewing medical chart of pediatric patients age 1 month to 15 yearsold who were admitted to pediatric department, Bhumibol Adulyadej hospital between January 1st, 2011 and December 31th, 2016. This study used The International Statistical Classification of Disease, 10th Revision (ICD-10) to search the data. The ICD-10 codes used to search the medical records were as follow: T78.0, anaphylactic shock due to adverse food reaction; T78.1, adverse reaction to food not else classified; T78.2, anaphylactic shock, unspecified; T78.3, angioneurotic edema, laryngeal edema, Quincke edema, urticarial-larynx; T80.5, anaphylactic shock due to serum; T80.9, unspecified complication following infusion, transfusion and therapeutic injection; T88.6, anaphylactic shock due to adverse effect of correct drug of medicament properly administered. A total of 231 records were recruited using the previously listed ICD 10 codes. The inclusion criteria for diagnosing anaphylaxis was published in 2006 by the National Institute of Allergy and Infectious Disease (NIAID).(1) Anaphylaxis is highly likely when any one of the following criteria are fulfilled: 1) acute onset of illness (minutes to several hours) with involvement of skin, mucosal tissue, or both (e.g. generalized hives, pruritus, or flushing, swollen lips-tongue-uvula) and at least one of the following: a) respiratory compromise (e.g. dyspnea, wheeze-bronchospasm, stridor, reduced peak expiratory flow [PEF], hypoxemia); b) reduced BP (blood pressure) or associated symptoms of end organ dysfunction (e.g. hypotonia [collapse], syncope, incontinence); 2) two or more of the following that occur rapidly after exposure to a likely allergen for that patient: a) involvement of skin or mucosal tissue (e.g. generalized hives, itch-flush, swollen lips-tongue-uvula); b) respiratory compromise (e.g. dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia); c) reduced BP or associated symptoms (e.g. hypotonia [collapse], syncope, incontinence); d) persistent gastrointestinal symptoms (e.g. crampy abdominal pain, vomiting), and 3) reduced BP after exposure to a known allergenfor that patient (minutes to several hours): a) infants and children: low BP (age specific) or greater than a 30% decrease in systolic BP; b) adults: systolic BP of less than 90 mm Hg or greater than a 30% decrease from that person’s base line. Data were collected using a case record form including (1) demographic data e.g. age, gender (2) history of previous anaphylaxis (3) history of atopic diseases (4) family history of atopic diseases (5) clinical manifestation of anaphylaxis (6) triggers of anaphylaxis (7) severity of anaphylaxis: mild, moderate or severe (8) biphasic anaphylaxis (9) place (10) treatment (11) timing from contact triggers to onset of symptoms (minutes) (12) timing from onset of symptoms to first dose of epinephrine administration (minutes) (13) number of epinephrine usage (14) prescription of prefilled epinephrine or epinephrine auto injector. The criteria for anaphylaxis severity assessment by Faith Huang which were published in 2012 were used for the anaphylaxis grading in this study as shown below.(6)Anaphylaxis gradeCriteria1. Mild (skin and subcutaneous tissue, GI, and/or mild respiratory symptoms)Flushing, urticaria, periorbital or facial angioedema; mild dyspnea, wheeze or upper respiratory tract symptoms; mild abdominal pain and/or emesis2. Moderate (mild symptoms + features suggesting moderate respiratory, cardiovascular, or GI symptoms)Marked dysphagia, hoarseness, and/or stridor; shortness of breath, wheezing, and retractions; crampy abdominal pain, recurrent vomiting, and/or diarrhea; and/or mild dizziness3. Severe (hypoxia, hypotension, or neurological compromise)Cyanosis or SpO2 < 92% at any stage, hypotension, confusion, collapse, loss of consciousness; incontinenceIn the patients with a history of previous anaphylaxis, the telephone interview were performed using a questionnaire that stressed on (1) numbers of anaphylaxis experienced by the patients (2) history of follow up at allergy clinic (3) history of epinephrine prefilled syringe or epinephrine auto injector usage (4) cause of not using epinephrine prefilled syringe or epinephrine auto injector.Statistical analysisThe Statistical Package for the Social Science version 18.0 (SPSS Inc., Chicago, IL, USA) was used for all statistical calculations. Descriptive statistics were used; the continuous data (age, onset of first dose of epinephrine) expressed as mean + SD, descriptive information (e.g. gender, history of atopic diseases, clinical manifestations, severity of anaphylaxis, biphasic anaphylaxis, triggers of anaphylaxis, treatments of anaphylaxis) were expressed as percentage. Clinical characteristics of mild anaphylaxis and moderate to severe anaphylaxis groups were compared using Chi-square test or Fisher’s exact test. To compared mean timing of onset of first dose epinephrine administration in uniphasic and biphasic anaphylaxis by independent student’s t-test or Mann-Whitney U-test. A p-value of <0.05 was considered to be statistically significant.ResultsA total of 176 episodes of anaphylaxis were identified and fulfilled the diagnostic criteria by NAIAD. The incidence of anaphylaxis in pediatric patients at Bhumibol Adulyadej hospital was 260 per 100,000 admitted pediatric patients per year between January 1st, 2011 and December 31th, 2016.Baseline characteristics of mild anaphylaxis and moderate to severe anaphylaxis (Table 1)176 episodes of anaphylaxis occurred in 160 patients. There were 98male cases (61.3%) and 62 female cases (38.8%). The mean age was 8.61+4.12 years. The minimum age was 3 months and the maximum age was 15 years. Previous anaphylaxis episodes were reported in 27 episodes that occurred in 16 patients (15.3%). Patients with atopic disease were 44.9% which classified into allergic rhinitis (30.7%), asthma (13.1%), atopic dermatitis (1%) and food allergy (26.7%). Asthma was statistically significant potential factor for moderate to severe anaphylaxis (p<0.001). There were no significant difference in mean age, gender, history of previous anaphylaxis, other atopic diseases and family history of atopic diseases between patients with mild anaphylaxis and moderate to severe anaphylaxis.Clinical characteristics of mild anaphylaxis and moderate to severe anaphylaxisPatients with cardiovascular symptoms (e.g. hypotension, faint, syncope, urinary incontinence) were significantly associated with moderate to severe anaphylaxis (p<0.001). (Table 2) Biphasic anaphylaxis occurred in 50 episodes (28.4%). Biphasic anaphylaxis was significantly associated with moderate to severe anaphylaxis (p=0.014). The mean of timing from onset of symptoms to the first dose of epinephrine administration was not significantly difference between two groups (p=0.427). (Table 3)Triggers of anaphylaxis and investigation (Table 4)Foods are the most common triggers of anaphylaxis (60.8%) including seafood 26.1% (shrimp 16.5%), fried insects 7.4%, wheat 4.5%, egg 2.8% and cow milk 2.3%. The second most common triggers were medication 19.3% including antibiotics 9.7%, NSAIDs 2.3% and chemotherapy 1.7%. There were two patients who had moderate to severe anaphylaxis from etoposide and one patient had mild anaphylaxis from L-asparaginase. Blood components which caused anaphylaxis were fresh frozen plasma in two patients and cryoprecipitate in one patient. Anaphylaxis from immunotherapy occurred in one patient. Anaphylaxis from stinging insects were found in 13 patients (7.4%). One patient has been examined by serum specific IgE for five hymenoptera and the result was positive for five hymenoptera. Exercise-induced anaphylaxis occurred in one case. His skin prick test and serum specific IgE for foods were all negative.In this study, 79/113 patients (69.9%) were examined for the causes of anaphylaxis by skin prick test and/or serum specific IgE. 81 patients were not examined; 39 patients had histories of anaphylaxis from drugs, blood components and stinging insects. 8 patients were followed up at other hospitals and 34 patients were referred by the right. After we excluded the patients who followed up at other hospital and the patients who had histories of anaphylaxis from drugs, blood components and stinging insects, 113 patients should be performed skin prick test or specific IgE. The skin prick tests were performed in 57/113 cases (50.4%). The causes of anaphylaxis were confirmed by skin prick tests in 30 cases (52.6%). Food allergens were positive in 45/57 cases (78.9%) and shrimp was the most common of food allergens 38/45 cases (84.4%). Shrimp-induced anaphylaxis were diagnosed in 29 cases. Among these 16 cases had been tested by skin prick test and 11 cases had positive results. The most prevalent allergen found positive in the skin prick test were house dust mites 54/57 cases (94.7%) and American cockroach 50/57 cases (87.7%) respectively. Serum specific IgE were examined in 26 cases. 10 cases; 2/4 cow milk, 3/3 egg white, 4/4 mixed shell-fish, 1/1 wasp, had positive results that correlated with the causes of anaphylaxis (38.5%). Idiopathic anaphylaxis was diagnosed in 4 cases. All of them were examined for the possible causes by skin prick test but the results did not correlate with histories of anaphylaxis. Treatments of anaphylaxis (Table 5)In the hospital, intramuscular epinephrine were given to 172 episodes of anaphylaxis (97.7%). H1 Antihistamine, H2 antihistamine and systemic corticosteroid were administered in every episodes (100%). The other therapies were intravascular fluid therapy 96%, beta2 agonist nebulizer 42.6%, oxygen therapy 25% and inotropic drugs 0.6% in one patient who had septic shock. Epinephrine prefilled syringe or epinephrine auto-injector were prescribed in 153 episodes (86.9%) before discharge. Patients who were treated with beta2 agonist nebulization and oxygen therapy were associated with moderate to severe anaphylaxis statistically significant (p < 0.001). 16 patients had a previous history of anaphylaxis and 27 episodes in this study. The results of telephone-interview of patients and parents revealed the usage of epinephrine prefilled syringe in 4 cases (25%). The causes of not using epinephrine prefilled syringe for self management were (1) dare not to inject epinephrine (2) did not carry epinephrine (3) expired medicine (4) anaphylaxis occurred near the hospital. 7 cases were followed up at allergy clinic (43.7%), 9 cases were not followed up because they did not realize the benefit of regular visit. Clinical characteristics of uniphasic and biphasic anaphylaxis (Table 6)Age, gender, history of atopic disease and clinical manifestation of anaphylaxis were not associated with biphasic anaphylaxis. Timing from onset of symptoms to the first dose epinephrine administration were recorded in 103 cases (58.5%). Delayed epinephrine administration was statistically significant associated with biphasic anaphylaxis (p<0.001).DiscussionThe incidence of anaphylaxis in pediatric patients at Bhumibol Adulyadej hospital was 260 per 100,000 admitted pediatric patients per year between January 1st, 2011 and December 31th, 2016. In comparison to Ramathibodi hospital,the incidence of anaphylaxis in hospitalized pediatric patients was 451 per 100,000 pediatric admissions between 2009 to 2013.(5) The incidence of anaphylaxis in hospitalized pediatric patients at Bhumibol Adulyadej hospital was lower than at Ramathibodi hospital. In 2005 to 2006, the incidence of anaphylaxis in emergency department at Bhumibol Adulyadej hospital was 52.5 per 100,000 patients per year but this study included patients in all age groups.(12) Severity of anaphylaxis in this study was graded as mild, moderate and severe. The study of Faith Huang in 2004 to 2008 found 55% mild anaphylaxis, 37% moderate anaphylaxis and 5% severe anaphylaxis(6) which was similar to our study; 65.9% mild anaphylaxis, 27.3% moderate anaphylaxis and 6.8% severe anaphylaxis. We summed up moderate and severe anaphylaxis into one group because clinical characteristics were similar, need intensive management and close observation and for practical statistical analysis. The studies in the United state, Sampson HA, et al. found that fatal anaphylaxis in the pediatric population was particularly associated with known preexisting asthma(7) and delayed administration of epinephrine.(8) No death was found in patients with asthma in this study. We found that patients with asthma, cardiovascular symptoms, biphasic anaphylaxis, initial treatment with beta2 agonist nebulization and oxygen therapy were associated with moderate to severe anaphylaxis. The study at Ramathibodi hospital in Thai adult patients found that rapid respiratory rate and abdominal pain were significantly associated with biphasic anaphylaxis.(13) The study at Thammasat university hospital showed that delayed administration of epinephrine was associated with biphasic anaphylaxis.(10) No clinical characteristics in this study was associated with biphasic anaphylaxis but we also found that delayed administration of epinephrine was significantly associated with biphasic anaphylaxis. Treatment with beta2 agonist nebulization and oxygen therapy were associated with biphasic anaphylaxis. The cause of association between initial beta2 agonist nebulization and oxygen therapy with biphasic anaphylaxis might be the consequence of underlying diseases and severity of the patients.Food was the most common trigger of anaphylaxis in this study. No fatal food-induced anaphylaxis had been reported in the studies in Thailand. In the United states, Atkins D, et al. found that delayed administration of epinephrine was associated with fatal food-induced anaphylaxis.(9) Drug-induced anaphylaxis was the second most common trigger of anaphylaxisin this study beside antibiotics, NSAIDs, chemotherapeutic agents were becoming more prevalence. Chemotherapeutic agents were reported in Siriraj study including; vincristine, L-asparaginase, mesna, cyclosporine, carboplatin and cyclophosphamide. The anaphylactic reaction induced by chemotherapeutic agents were variable severity and unpredictable. Symptoms could be mild, moderate or severe reactions.(14) In this study, there were two patients who had moderate to severe anaphylaxis from etoposide and one patient had mild anaphylaxis from L-asparaginase. Food-dependent, exercise-induced anaphylaxis was diagnosed in a 13-year-old boy who developed urticarial rash with chest tightness after running for 5 minutes. He had rice with omelet 30 minutes before running. His skin prick test and serum specific IgE yield negative results. He was not examined by exercise challenge test. In Thai children, a three-day wheat and exercise challenge protocol were performed in 4 cases at Siriraj hospital. Anaphylaxis occurred in 2 cases, both of them receivedhigh dose of wheat 100 and 130 grams.(15)Delayed administration of epinephrine was significantly associated with biphasic anaphylaxis but no association with the severity of anaphylaxis. Since the study was the retrospective study so we had limitation in data collection. In the future, prospective studyshould be performed to solve the conflicting aspect.ConclusionThe incidence of anaphylaxis in pediatric patients at Bhumibol Adulyadej hospital was 260 per 100,000 admitted pediatric patients per year. Moderate to severe anaphylaxis was associated with patients with underlying asthma, cardiovascular symptoms, biphasic anaphylaxis, initial treatment with beta2 agonist nebulization and oxygen therapy. Delayed administration of epinephrine was significantly associated withbiphasic anaphylaxis. These patients should be closely followed after admitted to the hospital. Identifying causes, avoidance of triggers and portable epinephrine carriage together with proper instruction of self-administration are very important in all anaphylactic patients.AcknowledgementThis study was supported by the Kumklao Foundation, Bhumibol Adulyadej Hospital. ReferenceSampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, et al. Second symposium on the definition and management of anaphylaxis: summary report -Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol 2006;117:391-7. Simons FE, Ardusso LR, Bilo MB, ElGamal YM, Ledford DK, Ring J, et al. World Allergy Organization anaphylaxis guidelines: summary. J Allergy Clin Immunol 2011;127:587-93, e22. Sheikh A, Hippisley-Cox J, Newton J, Fenty J. Trends in national incidence, lifetime prevalence and adrenaline prescribing for anaphylaxis in England. J R Soc Med 2008;101:139-43.?Jirapongsananuruk O, Bunsawansong W, Piyaphanee N, Visitsuthorn N, Thongngarm T, Vichyanond P. Features of patients with anaphylaxis admitted to a university hospital. Ann Allergy Asthma Immunol 2007;98:157-62. Manuyakorn W, Benjaponpitak S, Kamchaisatian W. Pediatric anaphylaxis: triggers, clinical features, and treatment in a tertiary-care hospital. Asian Pac J Allergy Immunol 2015;33. Huang F, Chawla K, Kirsi M. Anaphylaxis in a New York City pediatric emergency department: Triggers, treatments, and outcomes. J Allergy Clin Immunol 2012;129:162-8. Bock SA, Mu?oz-Furlong A, Sampson HA. Fatalities due to anaphylactic reactions to foods.?J Allergy Clin Immunol 2001;107:191–193.Sampson HA, Mendelson LM, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and adolescents.?N Eng J Med 1992;327:380–384.Atkins D, Bock SA. Fatal anaphylaxis to foods: epidemiology, recognition, and prevention. Curr Allergy Asthma Rep 2009;9:179-85. Lertnawapanand R, Maekanantawat W. Anaphylaxis and biphasic phase in Thailand: 4-year observation. Allergology International 2011;60:283-289.Scott H, Sicherer?F, Estelle R, Simons FE. Self-injectable epinephrine for first-aid management of anaphylaxis. Pediatrics 2007;119:638.Piromrat K, Chinratanapisit S, Trathong S. Anaphylaxis in an emergency department: a 2-year study in a tertiary-care hospital. Asian Pac J Allergy Immunol. 2008; 26:121-8.Sricharoen P, Sittichanbuncha Y, Wibulpolprasert A, Srabongkosh E, Sawanyawisuth K. What clinical factors are associated with biphasic anaphylaxis in Thai adult patients? Asian Pac J Allergy Immunol 2015;33:8-13.Visitsunthorn N, Utsawapreechawong W, Pacharn P, Jirapongsananurak O, Vichayanond P. Immediate type hypersensitivity to chemotherapeutic agents in pediatric patients. Asian Pac J Allergy Immunol 2009;27:191-197.Pacharn P, Jirapongsananurak O,Daengsuwan T, Vichayanond P, Visitsunthorn N. Wheat-dependent, exercise-induced anaphylaxis in Thai children: a report of 5 cases. Asian Pac J Allergy Immunol 2009;27:115-120. Table 1. Baseline characteristics of mild anaphylaxis and moderate to severe anaphylaxisCharacteristicsTotal episodesn=176Mild anaphylaxisn=116Moderate to severe anaphylaxis n=60P-valueAge mean+SD8.61+4.128.45+4.028.92+4.320.483Gender n (%)Male Female107 (60.8)69 (39.2)67 (57.8) 49 (42.2)40(66.7)20 (33.3)0.251Previous anaphylaxis n(%)27 (15.3)18 (15.5)9 (15)0.928Atopic disease n(%)Allergic rhinitisAsthmaAtopic dermatitisFood allergy79 (44.9)54 (30.7)23 (13.1)2 (1.1)47 (26.7)45 (38.8)30 (25.9)6 (5.2)1 (0.9)30 (25.9)34 (56.7)24 (40)17 (28.3)1 (1.7)17 (28.3)0.0240.054<0.00110.725Family history of atopic disease n (%)Allergic rhinitisAsthma31 (17.6)13 (7.4)25 (21.6)9 (7.8)6 (10)4 (6.7)0.0571Table 2. Clinical characteristic of mild anaphylaxis and moderate to severe anaphylaxisClinical characteristicTotal episodesn=176Mild anaphylaxisn=116Moderate to severe anaphylaxis n=60P-valueClinical manifestation n(%) Skin & cutaneous system Respiratory system Gastrointestinal system Cardiovascular system Neurological system173 (98.3)129 (73.3)70 (39.8)15 (8.5)1 (0.6)114 (98.3)85 (73.3)48 (41.4)2 (1.7)059 (98.3)44 (73.3)22 (36.7)13 (21.7)1 (1.7)10.9930.545<0.0010.341Table 3. Characteristic of mild anaphylaxis and moderate to severe anaphylaxisClinical characteristicTotal episodesMild anaphylaxisModerate to severe anaphylaxis P-valueBiphasic anaphylaxis n(%)50 (28.4)(n=176)26 (22.4)(n=116)24 (40)(n=60)0.014Onset of first doses of epinephrine mean+SD129.56+115.09(n=103)126.41+117.90(n=64)134.74+111.64(n=39)0.723Multiple doses of epinephrine injection n(%)41 (23.8)(n=176)20 (17.2)(n=116)21 (35)(n=60)0.012Table 4. Triggers of anaphylaxisTriggersTotal episodesn=176Mild anaphylaxisn=116Moderate to severe anaphylaxis n=60P-valueFoods n (%)107 (60.8)76 (65.5)31 (51.7)0.07Drugs n (%)34 (19.3)20 (17.2)14 (23.3)0.332Blood components n (%)3 (1.7)1 (0.9)2 (3.3)0.268Stinging insects n (%)13 (7.4)7 (6)6 (10)0.371Unknown n (%)19 (10.8)12 (10.3)7 (11.7)0.789Table 4.1. FoodTriggersTotal episodesn=176Mild anaphylaxisn=116Moderate to severe anaphylaxis n=60P-valueFoods n (%) Seafood Shrimp Wheat Fried insects Egg Cow’s milk Other foods107 (60.8)46 (26.1)27 (15.3)8 (4.5)13 (7.4)5 (2.8)4 (2.3)31 (17.6)76 (65.5)31 (26.7)17 (14.7)5 (4.3)10 (8.6)4 (3.4)3 (2.6)24 (20.7)31 (51.7)15 (25)10 (16.7)3 (5)3 (5)1 (1.7)1 (1.7)7 (11.7)0.07Table 5. Treatments of anaphylaxisTreatmentTotal episodes n=176Mild anaphylaxisn=116Moderate to severe anaphylaxisn=60P-valueIntramuscular epinephrine n (%)172 (97.7)112 (96.6)60 (100)0.301H1 Antihistamine n (%)176 (100)116 (100)60 (100)-H2 Antihistamine n (%)176 (100)116 (100)60 (100)-Systemic corticosteroid n (%)176 (100)116 (100)60 (100)-Intravenous fluid n (%)169 (96)110 (94.8)59 (98.3)0.425Beta2 agonist nebulization n (%)75 (42.6)37 (31.9)38 (63.3)<0.001Oxygen therapy n (%)44 (25)16 (13.8)28 (46.7)<0.001Inotropic drug n (%)1 (56.8)01 (1.7)0.341Table 6. Clinical characteristics of uniphasic and biphasic anaphylaxis CharacteristicsTotal episodesn=176Uniphasic anaphylaxisn=126Biphasic anaphylaxis n=50P-valueAge mean+SD8.61+4.128.60+3.998.63+4.480.965Gender n (%) Male Female107 (60.8)69 (39.2)76 (60.3)50 (39.7)31 (62)19 (38)0.837Previous anaphylaxis n (%)27 (15.3)16 (12.7)11 (22)0.123Atopic disease n (%) Allergic rhinitis Asthma Atopic dermatitis Food allergy79 (44.9)54 (30.7)23 (13.1)2 (1.1)47 (26.7)55 (43.7)40 (31.7)15 (11.9)1 (0.8)33 (26.2)24 (48)14 (28)8 (16)1 (2)14 (28)0.6010.6270.4670.4890.807Clinical manifestation n (%) Skin & cutaneous system Respiratory system Gastrointestinal system Cardiovascular system Neurological system173 (98.3)129 (73.3)70 (39.8)15 (8.5)1 (0.6)124 (98.4)91 (72.2)10 (7.9)53 (42.1)049 (98)38 (76)5 (10)17 (34)1 (2)10.6090.6580.3240.284Triggers n (%) Foods Drugs Blood componentsStinging insects107 (60.8)34 (19.3)3 (1.7)13 (7.4)76 (60.3)23 (18.3)3 (2.4)10(7.9)31 (62)11 (22)03 (6)0.8370.5700.5590.761Onset of first doses of epinephrine mean+SD129.56+115.09 n=10390.38+58.23n=66199.46+153.52n=37<0.001 ................
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