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Prevalence of Hypersensitivity to Non-Steroidal Anti-Inflammatory Drugs

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Prevalence of Hypersensitivity to Non-Steroidal Anti-Inflammatory Drugs ORIGINAL ARTICLE Łukasz Kasper, Krzysztof Sładek, Grażyna Bochenek, Mariusz Duplaga, Andrzej Szczeklik Department of Medicine, Jagiellonian University Medical College, Krakow, Poland Head of the unit: Prof. J. Musiał Prevalence of hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) in the population of adult asthmatics in Poland based on an epidemiological questionnaire Abstract Introduction: Hypersensitivity reactions to drugs account for 25% of all side effects related to drugs, affecting more than 7% of the population. One in four such reactions is caused by acetylic acid and other non-steroidal anti-inflammatory drugs. Material and methods: Between 1998 and 2000 epidemiological research was carried out in various centers, with the aim of estimating the frequency of allergy-based diseases in Poland. The objective of the study was to evaluate the frequency of hypersensi- tivity to non-steroidal anti-inflammatory drugs (NSAIDs), based on an epidemiological questionnaire, in the Polish adult population. Results: Bronchial asthma was diagnosed in 582 patients (5.4%). Of that group, 75 patients (12.9%) additionally reported symptoms of hypersensitivity to NSAIDs. Aspirin-induced asthma was diagnosed in 11 patients (14.7%) with clinical manifestations of hypersensitivity responses. Frequency of aspirin-induced asthma with clinical symptoms amounted to 1.9% of asthmatics. In the assessment of severity of the disease, aspirin intolerance was the only statistically significant factor (p = 0.0003; odds ratio 28.6 with assumed 95% confidence interval). Conclusions: In the population of adults in Poland, the frequency of aspirin-induced asthma amounted to 0.1%. Hypersensi- tivity to NSAIDs was observed in 12.9% of asthmatics. In asthmatics with symptoms of hypersensitivity to non-steroidal anti-inflammatory drugs, which takes the course of clinically demonstrable aspirin-induced asthma, the risk of severe asthma is 30-fold higher. Key words: asthma, prevalence, aspirin induced asthma, non-steroidal anti-inflammatory drugs, hypersensitivity Pneumonol. Alergol. Pol. 2009; 77: 431–439 Introduction pean Academy of Allergology and Clinical Im- munology published the clinical classification of Hypersensitivity reactions to drugs account for hypersensitivity reactions to aspirin and NSAIDs. about 25% of all side effects related to drugs, af- Eight reaction types were distinguished, the first fecting more than 7% of the population [1]. It has four being related to the suppression of the activi- been discovered that one in four of such reactions ty of cyclooxygenase (an important enzyme in the is caused by acetylic acid and other non-steroidal metabolism of arachidonic acid) by aspirin and anti-inflammatory drugs [2]. other non-steroidal anti-inflammatory drugs. The Like many other drugs, aspirin and non-ste- other four reactions are peculiar and characteristic roidal anti-inflammatory drugs may lead to hyper- of a given drug substance. They probably occur in sensitivity reactions, which can be either related the immunological pathway, regardless of cyclo- or unrelated to the mechanism of immunological oxygenase inhibition. The first two reaction types response [3]. In 2001 Stevenson [4] and the Euro- are most common in clinical practice. Addres for correspondence: Łukasz Kasper, Department of Medicine, Jagiellonian University Medical College, Skawinska 8, 31–066 Krakow, Poland, tel.: (012) 430 52 66, ext. 277, fax: (012) 430 51 47, mobile: 601 771 511, e-mail: [email protected] Received: 18.11.2008 Copyright © 2009 Via Medica ISSN 0867–7077 www.pneumonologia.viamedica.pl 431 Pneumonologia i Alergologia Polska 2009, vol. 77, no 5, pages 431–439 The first one relates only to asthma patients, took into consideration the assessment of drug who may often be affected by chronic sinusitis and hypersensitivity symptoms, based on a question- nasal polyps. Following the administration of aspi- naire prepared by the Department of Medicine, rin and other non-steroidal anti-inflammatory Jagiellonian University Medical College in Krakow. drugs, these patients experience attacks of asthma, The study aimed at a retrospective analysis of chronic inflammation of the nasal mucosa, redde- epidemiological data on the occurrence frequency ning of the eyes and face, and oedema of soft tis- of non-steroidal anti-inflammatory drugs hyper- sue around the eyes. Some patients may only have sensitivity in asthma patients. The data was gathe- symptoms in the lower airways, while in others the red in the period 1998–2000. symptoms may affect the upper airways, i.e. the nose, sinuses and eyes. Such a clinical form of the Material and methods condition is referred to as aspirin-induced asthma [5–8]. In some cases patients may also suffer from The epidemiological study related to the oc- ailments in the gastrointestinal tract and have skin currence of asthma, seasonal and perennial rhini- problems. The reaction of the first type is brought tis, as well as atopic and contact dermatitis, was about by aspirin as well as other non-steroidal anti- carried out in 11 Polish research centers (in Bialy- inflammatory drugs that are capable of inhibiting stok, Bydgoszcz, Krakow, Gdansk, Lublin, Lodz, cyclooxygenase. The reaction of the second type Poznan, Rabka, Warsaw, Wroclaw and Zabrze). It concerns the skin. From 15 minutes to two hours utilised a questionnaire on hypersensitivity to aspi- after taking aspirin, and/or other NSAIDs, some rin and other non-steroidal anti-inflammatory patients with chronic idiopathic urticaria develop drugs. The document was drafted on the initiative urticaric wheals on the face, the hairy parts of the of the Department of Medicine, Jagiellonian Uni- head, neck and upper chest. It is often accompa- versity Medical College, which also contributed nied by angioedema. These reactions depend on greatly to its development. The detailed question- the drug dose taken by the patient and also on the naire contained five questions on hypersensitivi- intensity of chronic urticaria symptoms. The more ty to aspirin and other non-steroidal anti-inflam- aggravated the symptoms, the greater the likeliho- matory drugs. If the respondents confirmed the od that aspirin-induced symptoms will appear and occurrence of any post-drug symptoms, they were that they will be more bothersome to the patient. asked to specify the medicine by choosing from the This problem affects about 20–40% of patients suf- 15 commonest drugs on the market, and to optio- fering from idiopathic urticaria. It is often referred nally give its name. Further questions detailed the to as the urticaria/angioedema-type of aspirin hy- symptoms which followed taking the medication: persensitivity [9, 10]. The pathomechanism of aspi- dyspnea, whizzing, blocked nose with watery na- rin hypersensitivity that affects the skin is similar sal secretion, skin symptoms, gastrointestinal tract to its bronchial form. It consists in the inhibition symptoms and anaphylactic shock symptoms. Then of COX by aspirin and an increased synthesis of the respondents were asked about the time of the cysteinyl leukotrienes [11, 12]. symptoms’ occurrence and whether they took the Very few reliable studies have been carried out same drug again later on and experienced a similar so far with regard to NSAIDs hypersensitivity in sequence of symptoms. By collecting data from patients with bronchial asthma [13, 14]. In the 16 238 people, including 12 970 adults, the centers European surveys ECRHS and ISAAC [15–22] the reached 98% of the planned number of respondents. symptoms of drugs hypersensitivity, in particular After obtaining consent from the Main Pro- intolerance to NSAIDs, are not taken into account. ject Coordinator in Wroclaw center, and from all Our knowledge about the frequency of aspirin-in- the researchers working in the other ten centers, duced asthma occurrence is based upon studies 104 questionnaires were taken from the database. conducted on select populations, e.g. groups of This data concerned patients whom experts found patients with heavy asthma and disease exacerba- to be suffering from bronchial asthma and who tion requiring hospital treatment and/or mechani- gave a positive answer to at least one question cal ventilation [23–25]. on hypersensitivity to aspirin and non-steroidal Between 1998 and 2000 a multicenter epide- anti-inflammatory drugs. miological survey was carried out which focused Then a full epidemiological questionnaire stu- on the occurrence of allergic disease in Poland [26, dy was conducted, focusing on patients suspected 27]. The survey estimated the occurrence frequen- of intolerance to anti-inflammatory drugs. The stu- cy of asthma, seasonal and perennial allergic rhi- dy covered nine of the 11 research centers partici- nitis as well as atopic dermatitis. The project also pating in the project (one center did not obtain 432 www.pneumonologia.viamedica.pl Łukasz Kasper et al., Hypersensitivity to NSAIDs in Poland consent for using the survey materials, while in the skin. Skin manifestation of hypersensitivity another one the questionnaires were by accident was the only symptom reported in 25 patients, unavailable). Eventually, 75 questionnaires were i.e. 33.3% of the studied group. In the remaining included in the analysis. Due to the fact that many 50 patients, skin manifestations were accompa- patients living in distant parts of Poland could not nied by other symptoms such as dyspnea, na- and/or did not want to visit the Department of sal and abdominal reactions, and general
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