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

Drug Allergy Prevalence in the Adult Population

Group 13

Faculty of Medicine of the University of PortoFaculty of Medicine of the University of Porto

Department of Biostatistics and Medical InformaticsDepartment of Biostatistics and Medical Informatics2005/062005/06

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Table of contents

Introduction– Aim

Participants and Methods Results and Discussion Limitations Website Manuscript

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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 abuse1.

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.

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Introduction The terms "drug allergy“, "drug

hypersensitivity" and "drug reaction" are often used interchangeably2.– 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.

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Introduction


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 ReactionsType 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 death4,5

Drug hypersensitivity Pseudoallergic Idiosyncrasy Intolerance

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Introduction

Drug hypersensitivity reactions are thought to represent 25% of adverse drug reactions1

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.

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Introduction

Drug hypersensitivity is a common and complicated problem in clinical practice3,6

Multiple mechanisms of drug-host interaction, many of which are poorly understood2

Diagnosis of drug hypersensitivity is difficult2,6

Drug-allergic reactions are underdiagnosed6



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.

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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 drug2 reaction, being the 4th and 6th leading cause of death of that patients5

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.

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Introduction

The main drugs implicated are antibiotics and non-steroidal anti-inflammatory drugs3


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Introduction

Clinical manifestations of drug allergy3:

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

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IntroductionOther 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 reactions3


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.

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Aim

To determine the lifetime prevalence of drug allergy in the adult population

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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

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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

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Flowchart

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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

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Random Digit Dialling8

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.

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Random Digit Dialling

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Data collection methods

Telephone interview Questionnaire

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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

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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

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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%

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Results

24

Sample characterization

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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.

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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.

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Chi-Square Tests

,302b 1 ,583

,008 1 ,927

,297 1 ,586

,664 ,456

,293 1 ,588

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Pearson Chi-Square

Continuity Correctiona

Likelihood Ratio

Fisher's Exact Test

Linear-by-LinearAssociation

N of Valid Cases

Value dfAsymp. Sig.

(2-sided)Exact Sig.(2-sided)

Exact Sig.(1-sided)

Computed only for a 2x2 tablea.

2 cells (50,0%) have expected count less than 5. The minimum expected count is2,40.

b.

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

The interviwed was the next adult to have birthday * Felt sick throughout his/her life after taking adrug Crosstabulation

11 3 14

78,6% 21,4% 100,0%

37,9% 50,0% 40,0%

18 3 21

85,7% 14,3% 100,0%

62,1% 50,0% 60,0%

29 6 35

82,9% 17,1% 100,0%

100,0% 100,0% 100,0%

Count

% within The interviwedwas the next adult tohave birthday

% within Felt sickthroughout his/her lifeafter taking a drug

Count



Count



No

Yes

The interviwed was thenext adult to have birthday

Total

No Yes

Felt sick throughouthis/her life after taking

a drug

Total

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Reported allergies & Age groups

We found no association between the occurence of allergy and the different age groups.

Chi-Square Tests

1,391a 3 ,708

1,424 3 ,700

,315 1 ,575

150

Pearson Chi-Square

Likelihood Ratio


N of Valid Cases

Value dfAsymp. Sig.

(2-sided)

2 cells (25,0%) have expected count less than 5. Theminimum expected count is 1,20.

a.

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Medical confirmation of drug allergy

95% Confidence interval: 6% - 16%

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Reported allergies & medical confirmation

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Drug allergy confirmed by a doctor * Felt sick throughout his/her life after taking a drugCrosstabulation

115 19 134

85,8% 14,2% 100,0%

95,0% 63,3% 88,7%

6 11 17

35,3% 64,7% 100,0%

5,0% 36,7% 11,3%

121 30 151

80,1% 19,9% 100,0%

100,0% 100,0% 100,0%

Count

% within Drug allergyconfirmed by a doctor


Count



Count



No

Yes

Drug allergy confirmedby a doctor

Total

No Yes


a drug

Total

Chi-Square Tests

24,192b 1 ,000

21,122 1 ,000

19,093 1 ,000

,000 ,000

24,032 1 ,000

151

Pearson Chi-Square


Likelihood Ratio

Fisher's Exact Test


N of Valid Cases

Value dfAsymp. Sig.


Exact Sig.(1-sided)


1 cells (25,0%) have expected count less than 5. The minimum expected count is3,38.

b.

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

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Allergic reactions confirmed by doctor$group_confirmed Frequencies

6 75,0% 75,0%

1 12,5% 12,5%

1 12,5% 12,5%

8 100,0% 100,0%

Antiinfectious

CNS

Musculoskeletal system

Drug group- confirmedby doctor

a

Total

N Percent

Responses Percent ofCases

Groupa.

$subgroup_confirmed Frequencies

6 75,0% 75,0%

1 12,5% 12,5%

1 12,5% 12,5%

8 100,0% 100,0%

Antibacterial/penicillin

Gout medications

Psycodrugs / Ansiolitics,sedatifs and hipnotics

Drug subgroup- confirmed bydoctor

a

Total

N Percent


Groupa.

$principle_confirmed Frequencies

5 62,5% 62,5%

1 12,5% 12,5%

1 12,5% 12,5%

1 12,5% 12,5%

8 100,0% 100,0%

Penicillin

Amoxicillin

Allopurinol

Alprazolam

Chemical substance- confirmed by doctor

a

Total

N Percent


Groupa.

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Thinks that is allergic to drugs?

95% Confidence interval: 11% - 24%

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Chi-Square Tests

35,454b 1 ,000

32,274 1 ,000

29,464 1 ,000

,000 ,000

35,204 1 ,000

142

Pearson Chi-Square


Likelihood Ratio

Fisher's Exact Test


N of Valid Cases

Value dfAsymp. Sig.


Exact Sig.(1-sided)


0 cells (,0%) have expected count less than 5. The minimum expected count is5,11.

b.

Do you think you're alergic to drugs * Felt sick throughout his/her life after taking a drugCrosstabulation

104 13 117

88,9% 11,1% 100,0%

92,0% 44,8% 82,4%

9 16 25

36,0% 64,0% 100,0%

8,0% 55,2% 17,6%

113 29 142

79,6% 20,4% 100,0%

100,0% 100,0% 100,0%

Count

% within Do you thinkyou're alergic to drugs


Count



Count



No

Yes

Do you think you'realergic to drugs

Total

No Yes


a drug

Total

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

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$group_thinkallergic Frequencies

7 46,7% 50,0%

2 13,3% 14,3%

4 26,7% 28,6%

1 6,7% 7,1%

1 6,7% 7,1%

15 100,0% 107,1%

Antiinfectious

Blood

CNS

Anti-allergic

Musculoskeletal system

Drug group- Thinksallergic

a

Total

N Percent


Groupa.

$subgroup_thinkallergic Frequencies

7 46,7% 50,0%

2 13,3% 14,3%

2 13,3% 14,3%

1 6,7% 7,1%

1 6,7% 7,1%

1 6,7% 7,1%

1 6,7% 7,1%

15 100,0% 107,1%

Antibacterial/penicillin

Anticoagulant/Antithrombotics-Anticoagulant

Analgesic/Antipiretic

Antihistaminics-Nonsedantig antihistaminics

Psycodrugs-Antidepressives

Gout medications

Psycodrugs / Ansiolitics,sedatifs and hipnotics

drugsubgroup- Thinksallergic

a

Total

N Percent


Groupa.

$principle_thinkallergic Frequencies

6 40,0% 42,9%

2 13,3% 14,3%

1 6,7% 7,1%

1 6,7% 7,1%

1 6,7% 7,1%

1 6,7% 7,1%

1 6,7% 7,1%

1 6,7% 7,1%

1 6,7% 7,1%

15 100,0% 107,1%

Penicillin

Acetylsalicylic acid

Metamizol magnesium

Paracetamol

Amoxicillin

Cetirizine

Maprotiline

Allopurinol

Alprazolam

Chemicalsubstance- Thinksallergic

a

Total

N Percent


Groupa.

Drugs that people think they are allergic

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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

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Allergic diseases

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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.

Chi-Square Tests

,254b 1 ,614

,054 1 ,817

,246 1 ,620

,594 ,395

,253 1 ,615

149

Pearson Chi-Square


Likelihood Ratio

Fisher's Exact Test


N of Valid Cases

Value dfAsymp. Sig.


Exact Sig.(1-sided)


0 cells (,0%) have expected count less than 5. The minimum expected count is5,07.

b.

Existence of allergy disease * Felt sick throughout his/her life after taking a drugCrosstabulation

100 22 122

82,0% 18,0% 100,0%

82,6% 78,6% 81,9%

21 6 27

77,8% 22,2% 100,0%

17,4% 21,4% 18,1%

121 28 149

81,2% 18,8% 100,0%

100,0% 100,0% 100,0%

Count

% within Existence ofallergy disease


Count



Count



No

Yes

Existence of allergydisease

Total

No Yes


a drug

Total

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Other allergies?

21,7% stated they had other kinds of allergy such as allergy to pollen, food, dust, animals.

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Allergic to how many drugs?

Majority of the inquired was allergic to one or two drugs

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Frequency of allergy symptoms according to type of reaction

42

Looked for medical assistance?

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

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Need medical assistance?

44

Need medical treatment?

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

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Need medical treatment?

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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 drugs3. 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.


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

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

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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.

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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.

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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.

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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.

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Gantt chart

Microsoft Project

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Website

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Manuscript

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References1 - 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 - 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.

The End

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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