Clinical Features of Drug Allergy and Factors Affecting Drug-Related Anaphylaxis: Single-center Experience of the Tertiary University Hospital
Abstract
Background-Aims: Drug hypersensitivity is defined as any unfavorable reaction that occurs after the administration of any drug. We aim to determine the frequency, etiology, and clinical features of drug hypersensitivity reactions (DHRs), and to evaluate the factors affecting drug-related anaphylaxis among the patients admitted to the outpatient allergy clinic of the tertiary university hospital.
Materials-methods: In this cross-sectional study, medical records of the 8295 patients who visited the allergy outpatient clinic of Sivas Cumhuriyet University Hospital from 2nd July 2018 to 10th December 2019 were retrospectively reviewed by the hospital data system using the ICD-code Y57.4. The frequency, etiologies, demographic and clinical features of the DHRs were evaluated.
Results: Among the 8295 patients who visited the allergy outpatient clinic of Sivas Cumhuriyet University Hospital, 159 patients with a mean age of 40,52± 14,85 years (129 female, 30 male) were evaluated with the diagnosis of DHRs. The frequency of DHRs among admissions was found to be approximately 2%. Accompanying allergic diseases included respiratory (17%), cutaneous (10%), venom (n=3), drug (7%), and food hypersensitivity (n=2). Multiple allergic diseases were detected in 20%. Eighty-six % (n=138) could recognize the culprit drug. The causes of drug allergy were non-steroidal anti-inflammatory drugs (NSAIDs) (27%), beta-lactams (16%), co-sensitization to beta-lactams and NSAIDs (8%), antimicrobials except beta-lactams (8%), and other kinds of drugs (39%). Type 1 reaction occurred in 80%, type 4 in 21%, non-immune mediated in 7, and mixed type composed of type 1 and 4 in 9 patients. Anaphylaxis occurred in 46,5%. Fifteen% had grade 2, 22% had grade 3, and 4 had grade 4 anaphylactic reactions. According to systematical assessment, cutaneous symptoms were observed in 93%, respiratory in 38%, cardiovascular in 29,5%, neurologic in 25%, and gastrointestinal in 11%. Allergy to NSAIDs (88,6 %) and beta-lactams (82,5%) were more frequent in type 1 reactions than in type 4 and mixed type reactions (p<0,001).
Discussion-conclusions: Drug-related anaphylaxis was commonly grade 3, occurred by NSAIDs and beta-lactams, and presented with cutaneous symptoms. Although drug-induced HSRs generally occurred by NSAII and/or beta-lactams, drugs such as proton pump inhibitors and vitamins were the culprits in up to 40% of the cases. Particular attention should be paid to this group in the evaluation of drug-related anaphylaxis. Healthcare providers and patients need to be informed more in order not to neglect the diagnosis of anaphylaxis and to increase the frequency of adrenaline administration when necessary.
References
- 1. Wilkerson RG. Drug Hypersensitivity Reactions. Immunol Allergy Clin North Am. 2023 Aug;43(3):473-489.
- 2. Suh DC, Woodall BS, Shin SK, Hermes-De Santis ER. The clinical and economic impact of adverse drug reactions in hospitalized patients. Ann Pharmacother. 2000 Dec;34(12):1373-9.
- 3. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998 Apr 15;279(15):1200-5
- 4. Kalyoncu AF, Karakoca Y, Demir AU, Alpar R, Shehu V, Cöplü L, Sahin AA, Baris YI. Prevalence of asthma and allergic diseases in Turkish university students in Ankara. Allergol Immunopathol (Madr). 1996 Jul-Aug;24(4):152-7.
- 5. Bavbek S, Erkekol FÖ, Celik GE, Gönüllü I, Misirligil Z. Self-reported prevalence of hypersensitivity reactions against drugs among medical students: does awareness cause any difference? Pharmacoepidemiol Drug Saf. 2011 Feb;20(2):154-61.
- 6. Kurt E, Demir AU, Cadirci O. Immediate type drug hypersensitivity reactions and associated risk factors in an adult Turkish men population. Iran J Allergy Asthma Immunol. 2010 Dec;9(4):245-50.
- 7. Çelik GE, Karakaya G, Öztürk AB, Gelincik A, Abadoğlu O, Sin A, Damadoğlu E, Yılmaz İ, Demirtürk M, Dursun B, Özdemir SK, Çelikel S, Değirmenci P, Bozkurt B, Göksel Ö, Erkekol FÖ, Aydın Ö, Kavut AB, Kırmaz C, Kalpaklıoğlu F, Büyüköztürk S, Kalyoncu F. Drug allergy in tertiary care in Turkey: results of a national survey. The ADAPT study: adult drug allergy perception in Turkey. Allergol Immunopathol (Madr). 2014 Nov-Dec;42(6):573-9.
- 8. Mueller HL. Diagnosis and treatment of insect sensitivity. J Asthma Res. 1966 Jun;3(4):331-3.
- 9. Aberer W, Bircher A, Romano A, Blanca M, Campi P, Fernandez J, Brockow K, Pichler WJ, Demoly P; European Network for Drug Allergy (ENDA); EAACI interest group on drug hypersensitivity. Drug provocation testing in the diagnosis of drug hypersensitivity reactions: general considerations. Allergy. 2003 Sep;58(9):854-63.
- 10. Demoly P, Gomes ER. Drug hypersensitivities: definition, epidemiology, and risk factors. Eur Ann Allergy Clin Immunol. 2005 Jun;37(6):202-6.
- 11. Gomes E, Cardoso MF, Praça F, Gomes L, Mariño E, Demoly P. Self-reported drug allergy in a general adult Portuguese population. Clin Exp Allergy. 2004 Oct;34(10):1597-601.
- 12. Dorner T, Lawrence K, Rieder A, Kunze M. Epidemiology of allergies in Austria. Results of the first Austrian allergy report. Wien Med Wochenschr. 2007;157(11-12):235-42.
- 13. Muraro A, Worm M, Alviani C, Cardona V, DunnGalvin A, Garvey LH, Riggioni C, de Silva D, Angier E, Arasi S, Bellou A, Beyer K, Bijlhout D, Bilò MB, Bindslev-Jensen C, Brockow K, Fernandez-Rivas M, Halken S, Jensen B, Khaleva E, Michaelis LJ, Oude Elberink HNG, Regent L, Sanchez A, Vlieg-Boerstra BJ, Roberts G; European Academy of Allergy and Clinical Immunology, Food Allergy, Anaphylaxis Guidelines Group. EAACI guidelines: Anaphylaxis (2021 update). Allergy. 2022 Feb;77(2):357-377.
- 14. Knowles SR, Drucker AM, Weber EA, Shear NH. Management options for patients with aspirin and nonsteroidal antiinflammatory drug sensitivity. Ann Pharmacother. 2007 Jul;41(7):1191-200.
- 15. Kowalski ML, Makowska J. Use of nonsteroidal anti-inflammatory drugs in patients with aspirin hypersensitivity: safety of cyclo-oxygenase-2 inhibitors. Treat Respir Med. 2006;5(6):399-406.
- 16. Kowalski ML, Makowska JS, Blanca M, Bavbek S, Bochenek G, Bousquet J, Bousquet P, Celik G, Demoly P, Gomes ER, Niżankowska-Mogilnicka E, Romano A, Sanchez-Borges M, Sanz M, Torres MJ, De Weck A, Szczeklik A, Brockow K. Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs)- classification, diagnosis and management: review of the EAACI/ENDA(#) and GA2LEN/HANNA*. Allergy. 2011 Jul;66(7):818-29.
- 17. Çelik GE, Erkekol FÖ, Aydın Ö, Demirel YS, Mısırlıgil Z. Are drug provocation tests still necessary to test the safety of COX-2 inhibitors in patients with cross-reactive NSAID hypersensitivity? Allergol Immunopathol (Madr). 2013 May-Jun;41(3):181-8.
- 18. Messaad D, Sahla H, Benahmed S, Godard P, Bousquet J, Demoly P. Drug provocation tests in patients with a history suggesting an immediate drug hypersensitivity reaction. Ann Intern Med. 2004 Jun 15;140(12):1001-6. 19. Na HR, Lee JM, Jung JW, Lee SY. The usefulness of drug provocation tests in children with a history of adverse drug reaction. Korean J Pediatr. 2011 Jul;54(7):304-9.
- 20. Aun MV, Bisaccioni C, Garro LS, Rodrigues AT, Tanno LK, Ensina LF, Kalil J, Motta AA, Giavina-Bianchi P. Outcomes and safety of drug provocation tests. Allergy Asthma Proc. 2011 Jul-Aug;32(4):301-6.
İlaç Alerjisinin Klinik Özellikleri ve İlaca Bağlı Anafilaksiyi Etkileyen Faktörler: Üçüncü Basamak Üniversite Hastanesi Tek Merkez Deneyimi
Abstract
Giriş- amaç: İlaç aşırı duyarlılığı, herhangi bir ilacın uygulanmasından sonra meydana gelen herhangi bir olumsuz reaksiyon olarak tanımlanır. Amacımız, üçüncü basamak bir üniversite hastanesi alerji polikliniğine başvuran hastalarda ilaç aşırı duyarlılığının sıklığını, etiyolojisini ve klinik özelliklerini belirlemek ve ilaca bağlı anafilaksiyi etkileyen faktörleri değerlendirmektir.
Materyal-metodlar: Bu kesitsel çalışmada, Sivas Cumhuriyet Üniversitesi Hastanesi alerji polikliniğine 2 Temmuz 2018 - 10 Aralık 2019 tarihleri arasında başvuran 8295 hastanın tıbbi kayıtları geriye dönük olarak hastane veri sistemi tarafından ICD kodu Y57.4 kullanılarak incelendi. İlaç aşırı duyarlılık reaksiyonlarının (ADR) sıklığı, etiyolojileri, demografik ve klinik özellikleri değerlendirildi.
Bulgular: Sivas Cumhuriyet Üniversitesi Hastanesi alerji polikliniğine başvuran 8295 hastadan yaş ortalaması 40,52± 14,85 olan 159 hasta (129 kadın, 30 erkek) ilaca bağlı aşırı duyarlılık reaksiyonu (İAR) tanısı ile değerlendirildi. Başvurular arasında IAR sıklığı yaklaşık %2 saptanmıştır. Eşlik eden alerjik hastalıklar arasında solunum (%17), deri (%10), venom (n=3), ilaç (%7) ve gıda (n=2) aşırı duyarlılığı yer almıştır. Çoklu alerjik hastalık tanısı %20’sinde saptandı. %86'sı (n=138) sorumlu ilacı tanıyabildi. İlaç alerjisinin nedenleri non-steroid anti-inflamatuar ilaçlar (NSAII'ler) (%27), beta-laktam antibiyotikler (%16), beta-laktamlara ve NSAII'lere eş zamanlı duyarlılık varlığı (%8), beta-laktamlar dışındaki antimikrobiyaller (%8) ve diğer tür ilaçlardı (%39). Hastaların %80'inde tip 1, %21'inde tip 4, 7'sinde non-immun aracılı ve 9'unda tip 1 ve 4'ten oluşan mikst tip reaksiyon görüldü. Anafilaksi %46,5 oranında meydana geldi. %15'inde derece 2, %22'sinde derece 3 ve 4'ünde derece 4 anafilaktik reaksiyon vardı. Sistematik değerlendirmeye göre %93 deri, %38 solunum, %29,5 kardiyovasküler, %25 nörolojik ve %11 gastrointestinal semptomlar gözlendi. NSAII'lere (% 88,6) ve beta-laktamlara (% 82,5) alerji, tip 1 reaksiyonlarda, tip 4 ve karma tip reaksiyonlara göre daha sıktı (p<0,001).
Tartışma ve sonuçlar: İlaca bağlı anafilaksi genellikle 3. Derece idi, NSAII'ler ve beta-laktamlar tarafından meydana geliyordu ve kutanöz semptomlarla kendini göstermekteydi. İlaca bağlı ADR'ler genellikle NSAII ve/veya beta-laktamlar tarafından meydana gelse de, vakaların %40'e varan kısmında proton pompası inhibitörleri ve vitaminler gibi ilaçlar suçludur. İlaca bağlı anafilaksinin değerlendirilmesinde bu gruba özel dikkat gösterilmelidir. Anafilaksi tanısını ihmal etmemek ve gerektiğinde adrenalin uygulama sıklığını artırmak için sağlık çalışanları ve hastaların daha fazla bilgilendirilmesi gerekmektedir.
References
- 1. Wilkerson RG. Drug Hypersensitivity Reactions. Immunol Allergy Clin North Am. 2023 Aug;43(3):473-489.
- 2. Suh DC, Woodall BS, Shin SK, Hermes-De Santis ER. The clinical and economic impact of adverse drug reactions in hospitalized patients. Ann Pharmacother. 2000 Dec;34(12):1373-9.
- 3. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998 Apr 15;279(15):1200-5
- 4. Kalyoncu AF, Karakoca Y, Demir AU, Alpar R, Shehu V, Cöplü L, Sahin AA, Baris YI. Prevalence of asthma and allergic diseases in Turkish university students in Ankara. Allergol Immunopathol (Madr). 1996 Jul-Aug;24(4):152-7.
- 5. Bavbek S, Erkekol FÖ, Celik GE, Gönüllü I, Misirligil Z. Self-reported prevalence of hypersensitivity reactions against drugs among medical students: does awareness cause any difference? Pharmacoepidemiol Drug Saf. 2011 Feb;20(2):154-61.
- 6. Kurt E, Demir AU, Cadirci O. Immediate type drug hypersensitivity reactions and associated risk factors in an adult Turkish men population. Iran J Allergy Asthma Immunol. 2010 Dec;9(4):245-50.
- 7. Çelik GE, Karakaya G, Öztürk AB, Gelincik A, Abadoğlu O, Sin A, Damadoğlu E, Yılmaz İ, Demirtürk M, Dursun B, Özdemir SK, Çelikel S, Değirmenci P, Bozkurt B, Göksel Ö, Erkekol FÖ, Aydın Ö, Kavut AB, Kırmaz C, Kalpaklıoğlu F, Büyüköztürk S, Kalyoncu F. Drug allergy in tertiary care in Turkey: results of a national survey. The ADAPT study: adult drug allergy perception in Turkey. Allergol Immunopathol (Madr). 2014 Nov-Dec;42(6):573-9.
- 8. Mueller HL. Diagnosis and treatment of insect sensitivity. J Asthma Res. 1966 Jun;3(4):331-3.
- 9. Aberer W, Bircher A, Romano A, Blanca M, Campi P, Fernandez J, Brockow K, Pichler WJ, Demoly P; European Network for Drug Allergy (ENDA); EAACI interest group on drug hypersensitivity. Drug provocation testing in the diagnosis of drug hypersensitivity reactions: general considerations. Allergy. 2003 Sep;58(9):854-63.
- 10. Demoly P, Gomes ER. Drug hypersensitivities: definition, epidemiology, and risk factors. Eur Ann Allergy Clin Immunol. 2005 Jun;37(6):202-6.
- 11. Gomes E, Cardoso MF, Praça F, Gomes L, Mariño E, Demoly P. Self-reported drug allergy in a general adult Portuguese population. Clin Exp Allergy. 2004 Oct;34(10):1597-601.
- 12. Dorner T, Lawrence K, Rieder A, Kunze M. Epidemiology of allergies in Austria. Results of the first Austrian allergy report. Wien Med Wochenschr. 2007;157(11-12):235-42.
- 13. Muraro A, Worm M, Alviani C, Cardona V, DunnGalvin A, Garvey LH, Riggioni C, de Silva D, Angier E, Arasi S, Bellou A, Beyer K, Bijlhout D, Bilò MB, Bindslev-Jensen C, Brockow K, Fernandez-Rivas M, Halken S, Jensen B, Khaleva E, Michaelis LJ, Oude Elberink HNG, Regent L, Sanchez A, Vlieg-Boerstra BJ, Roberts G; European Academy of Allergy and Clinical Immunology, Food Allergy, Anaphylaxis Guidelines Group. EAACI guidelines: Anaphylaxis (2021 update). Allergy. 2022 Feb;77(2):357-377.
- 14. Knowles SR, Drucker AM, Weber EA, Shear NH. Management options for patients with aspirin and nonsteroidal antiinflammatory drug sensitivity. Ann Pharmacother. 2007 Jul;41(7):1191-200.
- 15. Kowalski ML, Makowska J. Use of nonsteroidal anti-inflammatory drugs in patients with aspirin hypersensitivity: safety of cyclo-oxygenase-2 inhibitors. Treat Respir Med. 2006;5(6):399-406.
- 16. Kowalski ML, Makowska JS, Blanca M, Bavbek S, Bochenek G, Bousquet J, Bousquet P, Celik G, Demoly P, Gomes ER, Niżankowska-Mogilnicka E, Romano A, Sanchez-Borges M, Sanz M, Torres MJ, De Weck A, Szczeklik A, Brockow K. Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs)- classification, diagnosis and management: review of the EAACI/ENDA(#) and GA2LEN/HANNA*. Allergy. 2011 Jul;66(7):818-29.
- 17. Çelik GE, Erkekol FÖ, Aydın Ö, Demirel YS, Mısırlıgil Z. Are drug provocation tests still necessary to test the safety of COX-2 inhibitors in patients with cross-reactive NSAID hypersensitivity? Allergol Immunopathol (Madr). 2013 May-Jun;41(3):181-8.
- 18. Messaad D, Sahla H, Benahmed S, Godard P, Bousquet J, Demoly P. Drug provocation tests in patients with a history suggesting an immediate drug hypersensitivity reaction. Ann Intern Med. 2004 Jun 15;140(12):1001-6. 19. Na HR, Lee JM, Jung JW, Lee SY. The usefulness of drug provocation tests in children with a history of adverse drug reaction. Korean J Pediatr. 2011 Jul;54(7):304-9.
- 20. Aun MV, Bisaccioni C, Garro LS, Rodrigues AT, Tanno LK, Ensina LF, Kalil J, Motta AA, Giavina-Bianchi P. Outcomes and safety of drug provocation tests. Allergy Asthma Proc. 2011 Jul-Aug;32(4):301-6.
Details
| Primary Language | English |
|---|---|
| Subjects | Health and Community Services |
| Journal Section | Medical Science Research Articles |
| Authors | |
| Publication Date | September 30, 2023 |
| Acceptance Date | September 25, 2023 |
| Published in Issue | Year 2023 |