1. Drug Allergy Prevalence in the Adult Population Group 13 Faculty of Medicine of the University of Porto Faculty of Medicine of the University of Porto Department of Biostatistics and Medical Informatics 2005/06

2. 2 Table of contents  Introduction –Aim  Participants and Methods  Results and Discussion  Limitations  Website  Manuscript

3. 3 Introduction Adverse reactions to drugs include all non therapeutic consequences of the drug with the exception of treatment failures, intentional or accidental poisoning, and drug abuse 1. World Health Organization 1 - Joint Task Force on Practice Parameters, the American Academy of Allergy, Asthma and Immunology, and the Joint Council of Allergy, Asthma and Immunology. Executive summary of disease management of drug hypersensitivity: a practice parameter. Ann Allergy Asthma Immunol. 1999 Dec;83(6 Pt 3):665-700.

4. 4 Introduction  The terms "drug allergy“, "drug hypersensitivity" and "drug reaction" are often used interchangeably 2. –Drug reactions encompass all adverse events related to drug administration, regardless of etiology. –Drug hypersensitivity is defined as an immune- mediated response to a drug agent in a sensitized patient. –Drug allergy is restricted specifically to a reaction mediated by IgE. 2 - Riedl MA, Casillas AM. Adverse drug reactions: types and treatment options. Am Fam Physician. 2003 Nov 1;68(9):1781-90.

5. 5 Introduction 2 - Riedl MA, Casillas AM. Adverse drug reactions: types and treatment options. Am Fam Physician. 2003 Nov 1;68(9):1781-90. 3 - Vervloet D, Durham S. Adverse reactions to drugs. BMJ. 1998 May 16;316(7143):1511-4. 4 - Gruchalla RS. Drug metabolism, danger signals, and drug-induced hypersensitivity. J Allergy Clin Immunol. 2001 Oct;108(4):475-88. 5 - Gruchalla R. Understanding drug allergies. J Allergy Clin Immunol. 2000 Jun;105(6 Pt 2):S637-44. Adverse Drug Reactions Type A (predictable) 2,3 Type B (unpredictable) 2,3  Overdosage  Side effects  Secondary effects  Drug-drug interactions Dose independent, not related with the pharmacologic actions of the drug, often serious and can cause death 4,5  Drug hypersensitivity  Pseudoallergic  Idiosyncrasy  Intolerance

6. 6 Introduction  Drug hypersensitivity reactions are thought to represent 25% of adverse drug reactions 1 1 - Joint Task Force on Practice Parameters, the American Academy of Allergy, Asthma and Immunology, and the Joint Council of Allergy, Asthma and Immunology. Executive summary of disease management of drug hypersensitivity: a practice parameter. Ann Allergy Asthma Immunol. 1999 Dec;83(6 Pt 3):665-700.

7. 7 Introduction Drug hypersensitivity is a common and complicated problem in clinical practice 3,6 Multiple mechanisms of drug-host interaction, many of which are poorly understood 2 Diagnosis of drug hypersensitivity is difficult 2,6 Drug-allergic reactions are underdiagnosed 6 2 - Riedl MA, Casillas AM. Adverse drug reactions: types and treatment options. Am Fam Physician. 2003 Nov 1;68(9):1781-90. 3 - Vervloet D, Durham S. Adverse reactions to drugs. BMJ. 1998 May 16;316(7143):1511-4. 6 - Demoly P, Kropf R, Bircher A, Pichler WJ. Drug hypersensitivity: questionnaire. EAACI interest group on drug hypersensitivity. Allergy. 1999 Sep;54(9):999-1003.

8. 8 Introduction  They are the most common iatrogenic illness, complicating 5 to 15 % of therapeutic drug courses. 2  In the USA, more than 100,000 deaths are attributed annually to serious adverse drug reactions. 2  3 to 6 % of all hospital admissions are because of adverse drug reactions. 2  6 to 15 % of hospitalized patients in USA experience a serious adverse drug 2 reaction, being the 4 th and 6 th leading cause of death of that patients 5 2 - Riedl MA, Casillas AM. Adverse drug reactions: types and treatment options. Am Fam Physician. 2003 Nov 1;68(9):1781-90. 5 - Gruchalla R. Understanding drug allergies. J Allergy Clin Immunol. 2000 Jun;105(6 Pt 2):S637-44.

9. 9 Introduction  The main drugs implicated are antibiotics and non-steroidal anti-inflammatory drugs 3 3 - Vervloet D, Durham S. Adverse reactions to drugs. BMJ. 1998 May 16;316(7143):1511-4.

10. 10 Introduction  Clinical manifestations of drug allergy 3 : 3– Vervloet D, Durham S. Adverse reactions to drugs. BMJ. 1998 May 16;316(7143):1511-4. © Dermatology database of Institute for Biomedical Informatics, Faculty of Medicine, Ljubljana, Slovenia Anaphylaxis Urticaria, rhinitis, asthma Pulmonary Interstitial pneumonitis, asthma Hepatic Acute or chronic hepatitis Haematological Haemolytic anaemia, neutropenia Renal Interstitial nephritis, nephrotic syndrome Cardiac Eosinophilic myocarditis Other Serum sickness, drug fever

11. 11 Introduction Other studies  The prevalence of self-reported drug allergy study in a Portuguese population was 7.8% 7  A French study of 2067 adults aged 20-67 years reported that 14.7% gave reliable histories of systemic adverse drug reactions 3 3– Vervloet D, Durham S. Adverse reactions to drugs. BMJ. 1998 May 16;316(7143):1511-4. Gomes E, Cardoso MF, Praca F, Gomes L, Marino E, Demoly P. Self-reported drug allergy in a general adult Portuguese population. Clin Exp Allergy. 2004 Oct;34(10):1597-601.

12. 12 Aim To determine the lifetime prevalence of drug allergy in the adult population

13. 13 Secondary Aims  Identify the drugs that are most frequently associated to allergic reactions, (classifying them using the same system of INFARMED database – ATC system)  Describe the different types of allergic expression  Relate the allergic reactions already described with the presence of some diseases

14. 14 Study participants  Target population - all adult people (above 18 years old) living in Porto region  Available population - all adult people living in Porto region with telephone in their household  Unit of Analysis – single person  Inclusion Criteria – be an adult, have phone in their household, live in Porto and have capacities to answer the questionnaire properly  Exclusion Criteria – see flowchart

15. 15 Flowchart

16. 16 Study design  Observational, cross-sectional and descriptive study, executed via phone interviews.  Data collection method – Phone interviews, filling up a questionnaire previously designed  Sample selection method – two stages random digit dialling  Frequency measurement – lifetime prevalence

17. 17 Random Digit Dialling 8  Two Stages RDD Sampling Methods  Was used relative to the telephone numbers of Porto region.  Software randomly selected digits of the type 22xxxxx and generated prefix numbers  Software randomly selected two digits and generated suffix numbers 8 - Groves RM, Biemer PP, Lyberg LE, Massey JT, Nicholls WLII, Waksberg J, editors. Telephone Survey Methodology. New York: John Wiley & Sons, Inc; 2001.

18. 18 Random Digit Dialling

19. 19 Data collection methods  Telephone interview  Questionnaire Questionnaire

20. 20 Main variables description  Presence of drug allergies in a life time period  Reaction type (skin, respiratory, digestive, others)  Suspected drug  Presence of allergic diseases  Other diseases  Age  Sex

21. 21 Statistical Analysis  Descriptive analysis for all the variables.  To determine prevalence proportions graphs and tables were used.  Qui-square or Fisher’s tests to find associations between the main nominal variables  Wald test was used to determine an approximated confidence interval for the principal proportions of nominal variables.  For all the statistical tests we used a significance level of 5% (  =0,05), thus a confidence level of 95%  We used the SPSS ® 13.0 software

22. 22 Results & Discussion  All phone calls were made between the 2nd March and 26th April;  The time-table included the period between 9 a.m. and 6.30 pm;  Response rate: 75%

23. 23 Results

24. 24 Sample characterization

25. 25 Next to celebrate birthday? Amongst the inquired that were asked about if they were the next to celebrate birthday, only 40% answered negatively. This results may be due to the fact that a significant part of the inquired were old people living alone.

26. 26 Felt sick due to drug’s intake? 95% confidence interval: 13% - 26% 19.7% of the inquired mentioned feeling sick after taking a drug at least once during his/her life.

27. 27 We found no association between being (or not) the next to celebrate birthday and having felt sick due to drug’s intake.

28. 28 Reported allergies & Age groups We found no association between the occurence of allergy and the different age groups.

29. 29 Medical confirmation of drug allergy 95% Confidence interval: 6% - 16%

30. 30 Reported allergies & medical confirmation

31. 31 There is an association between the group that have felt sick due to drug’s intake and the group that have medical confirmation of drug allergy

32. 32 Allergic reactions confirmed by doctor

33. 33 Thinks that is allergic to drugs? 95% Confidence interval: 11% - 24%

34. 34 There is an association between the group that have felt sick due to drug’s intake and the group that thinks they have allergy to drugs

35. 35 Drugs that people think they are allergic

36. 36 Analysis confirmation? 16,4% of the inquired did some test or analysis to confirm drug allergy 23,3% of the people who have felt sick after taking a drug did some test or analysis

37. 37 Allergic diseases

38. 38 Allergy to drugs & Allergic diseases 17,8 % of the inquired answered they had an allergy disease However, we couldn’t establish an association between the occurrence of allergic disease and having felt sick due to drug’s intake.

39. 39 Other allergies?  21,7% stated they had other kinds of allergy such as allergy to pollen, food, dust, animals.

40. 40 Allergic to how many drugs?  Majority of the inquired was allergic to one or two drugs

41. 41 Frequency of allergy symptoms according to type of reaction

42. 42 Looked for medical assistance? 67% of those who have felt sick after taking a drug stated that they looked for medical assistance.

43. 43 Need medical assistance?

44. 44 Need medical treatment? 30% of those who have felt sick after taking a drug stated that they needed medical treatment.

45. 45 Need medical treatment?

46. 46 Prevalences 95% Confidence interval: 13% - 26%95% Confidence interval: 11% - 24%95% Confidence interval: 6% - 16% The prevalence of self-reported drug allergy study in a Portuguese population was 7.8% 7 whereas a French study reported that 14.7% gave reliable histories of systemic adverse reactions to one or more drugs 3. Whether these results reflect population differences or study bias we can’t precise with the present data. The elaboration of studies in what matters to this theme seems therefore appropriate and necessary. 3– Vervloet D, Durham S. Adverse reactions to drugs. BMJ. 1998 May 16;316(7143):1511-4. 7 - Gomes E, Cardoso MF, Praca F, Gomes L, Marino E, Demoly P. Self-reported drug allergy in a general adult Portuguese population. Clin Exp Allergy. 2004 Oct;34(10):1597-601.

47. 47 Main limitations  Telephone interviews may not be accurate enough to determine whether a reaction were really of hypersensitivity or not  People living in Porto, without a telephone at home are excluded  Interviews were done in a restricted period of time  Very low household rate

48. 48 Discussion - difficulties  Questionnaire problems: –excessive extension; –complexity of phrasal structure and lexicon; –too many similar questions led to some confusion.  Cooperation of the inquired population: –difficulties to understand what was being said (advanced age); –lack of time (active class); –people were afraid.  Slanting of the inquired population due to the impossibility of making phone calls during all day: –phone calls made only in the morning and afternoon; –many of the population inquired was of advanced age; –active population excluded.

49. 49 Discussion - difficulties  Difficulties to contact the resident: –the person who answered the phone didn’t live in that domicile and was incapable to inform about the best hour to further contacts; –Most of the times, the person who was next to celebrate birthday was impossible to reach; Random Digit Dialling disadvantages:  Lots of unfruitful phone calls: –most of the numbers dialled were not valid (non- attributed/commercial); –phone numbers were valid not residences; –this lead to a waste of precious time;  Even when the first combination of prefix and suffix was a residence, the many of next ones weren’t: –we had to make dozens of phone calls with the same prefix to obtain five residences.

50. 50 Conclusions  Our results showed a prevalence of adverse drug reactions in the adult population of 13%-26%.  However, only 6%-16% were confirmed as an allergy by a doctor.

51. 51  The drugs that were most frequently associated to allergic reactions were mainly the antiinfectious drugs, such as Penicillin.  The most frequent type of allergic expression was cutaneous reaction.

52. 52 Gantt chart  Microsoft Project Microsoft Project

53. 53 Website

54. 54 Manuscript

55. 55 References 1 - Joint Task Force on Practice Parameters, the American Academy of Allergy, Asthma and Immunology, and the Joint Council of Allergy, Asthma and Immunology. Executive summary of disease management of drug hypersensitivity: a practice parameter. Ann Allergy Asthma Immunol. 1999 Dec;83(6 Pt 3):665-700. 2 - Riedl MA, Casillas AM. Adverse drug reactions: types and treatment options. Am Fam Physician. 2003 Nov 1;68(9):1781-90. 3 - Vervloet D, Durham S. Adverse reactions to drugs. BMJ. 1998 May 16;316(7143):1511-4. 4 - Gruchalla RS. Drug metabolism, danger signals, and drug-induced hypersensitivity. J Allergy Clin Immunol. 2001 Oct;108(4):475-88. 5 - Gruchalla R. Understanding drug allergies. J Allergy Clin Immunol. 2000 Jun;105(6 Pt 2):S637-44. 6 - Demoly P, Kropf R, Bircher A, Pichler WJ. Drug hypersensitivity: questionnaire. EAACI interest group on drug hypersensitivity. Allergy. 1999 Sep;54(9):999-1003. 7 - Gomes E, Cardoso MF, Praca F, Gomes L, Marino E, Demoly P. Self-reported drug allergy in a general adult Portuguese population. Clin Exp Allergy. 2004 Oct;34(10):1597-601. 8 - Groves RM, Biemer PP, Lyberg LE, Massey JT, Nicholls WLII, Waksberg J, editors. Telephone Survey Methodology. New York: John Wiley & Sons, Inc; 2001.

56. The End