Phenotypes and Natural Evolution of Drug Hypersensitivity

  • Inmaculada DoñaEmail author
  • María Salas
  • Natalia Isabel Pérez-Sánchez
  • Carmen Moreno-Aguilar
  • María José Torres
Drug Allergy (L Mayorga, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Drug Allergy


Purpose of review

Drug hypersensitivity reactions (DHRs) are adverse effects that clinically resemble allergy. They belong to type B adverse drug reactions, which are dose-independent and unpredictable. Misclassification of DHR may lead to under and/or overdiagnosis, which affects the management of patients, leading to higher risk of suffering an allergic reaction or the use of alternative more-expensive and potentially less-effective drugs. A precise phenotype of DHR is required for a better evaluation and proper management of patients experiencing DHR. The purpose of this review is to summarise the different phenotypes of DHR basing on different criterions.

Recent findings

The phenotyping of DHRs is challenging as clinical presentations are heterogeneous, the underlying mechanism is poorly understood and terminology varies among different studies. Moreover, natural evolution may be different depending on the phenotype.


This review summarises the complexity of DHR phenotyping, which can be based on different criterions as chronology, mechanism and clinical symptoms as well as natural evolution. A precise phenotyping of DHR is needed to determine the adequate evaluation and management of patients.


Anaphylaxis Exanthema Hypersensitivity Immediate Non-immediate Urticaria 


Funding Information

I Doña holds a Juan Rodes research contract (JR15/00036) and NI Pérez-Sánchez holds a Rio Hortega contract (CM17/00141), both from the Carlos III National Health Institute, Spanish Ministry of Economy and Competitiveness (grants cofounded by European Social Fund, ESF).

Compliance with Ethical Standards

Conflict of Interest

Inmaculada Doña, María Salas, Natalia Isabel Pérez-Sánchez, Carmen Moreno-Aguilar and María José Torres declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    International drug monitoring. The role of national centres Report of a WHO meeting. World Health Organ Tech Rep Ser. 1972;498:1–25.Google Scholar
  2. 2.
    Kongkaew C, Noyce PR, Ashcroft DM. Hospital admissions associated with adverse drug reactions: a systematic review of prospective observational studies. Ann Pharmacother. 2008;42(7):1017–25.PubMedGoogle Scholar
  3. 3.
    Gomes ER, Demoly P. Epidemiology of hypersensitivity drug reactions. Curr Opin Allergy Clin Immunol. 2005;5(4):309–16.PubMedGoogle Scholar
  4. 4.
    Hakkarainen KM, Hedna K, Petzold M, Hägg S. Percentage of patients with preventable adverse drug reactions and preventability of adverse drug reactions--a meta-analysis. PLoS One. 2012;7(3):e33236.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Rawlins MD, T.J., Pathogenesis of adverse drug reactions, in Textbook of adverse drug reactions, D. DM, Editor. 1977, Oxford University Press: Oxford. p. 10.Google Scholar
  6. 6.
    Bernstein JA. Nonimmunologic adverse drug reactions. How to recognize and categorize some common reactions. Postgrad Med. 1995;98(1):120–2 125-6.Google Scholar
  7. 7.
    •• Demoly P, et al. International consensus on drug allergy. Allergy. 2014;69(4):420–37 In this position paper, the International Collaboration in Asthma, Allergy and Immunology (iCAALL) critically reviewed guidelines and consensus documents on DHR and compiled an International CONsensus (ICON) providing recommendations on drug allergy.PubMedGoogle Scholar
  8. 8.
    Joint Task Force on Practice, P, et al. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010;105(4):259–73.Google Scholar
  9. 9.
    Bernstein JA. Allergic drug reactions. How to minimize the risks. Postgrad Med. 1995;98(2):159–60 163-6.Google Scholar
  10. 10.
    deShazo RD, Kemp SF. Allergic reactions to drugs and biologic agents. JAMA. 1997;278(22):1895–906.PubMedGoogle Scholar
  11. 11.
    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;34(10):1597–601.PubMedGoogle Scholar
  12. 12.
    Johansson SG, et al. Revised nomenclature for allergy for global use: report of the nomenclature review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol. 2004;113(5):832–6.PubMedGoogle Scholar
  13. 13.
    Coombs PR, G.P., Classification of allergic reactions responsible for clinical hypersensitivity and disease. . In: Gell RR, editor. Clinical aspects of immunology. Oxford (UK): Oxford University Pess;, 1968: p. 575–96.Google Scholar
  14. 14.
    •• Pichler WJ. Delayed drug hypersensitivity reactions. Ann Intern Med. 2003;139(8):683–93 In this review, concepts of the role of T-cells in various drug-induced hypersensitivity diseases are described.PubMedGoogle Scholar
  15. 15.
    Doña I, Blanca-López N, Cornejo-García JA, Torres MJ, Laguna JJ, Fernández J, et al. Characteristics of subjects experiencing hypersensitivity to non-steroidal anti-inflammatory drugs: patterns of response. Clin Exp Allergy. 2011;41(1):86–95.PubMedGoogle Scholar
  16. 16.
    •• Kowalski ML, et al. Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs. Allergy. 2013;68(10):1219–32 This position paper provides a classification of reactions induced by NSAIDs based on clinical manifestations and suspected mechanism.PubMedGoogle Scholar
  17. 17.
    Pichler WJ, Beeler A, Keller M, Lerch M, Posadas S, Schmid D, et al. Pharmacological interaction of drugs with immune receptors: the p-i concept. Allergol Int. 2006;55(1):17–25.PubMedGoogle Scholar
  18. 18.
    Blanca M, Romano A, Torres MJ, Férnandez J, Mayorga C, Rodriguez J, et al. Update on the evaluation of hypersensitivity reactions to betalactams. Allergy. 2009;64(2):183–93.PubMedGoogle Scholar
  19. 19.
    Torres MJ, Blanca M, Fernandez J, Romano A, Weck A, Aberer W, et al. Diagnosis of immediate allergic reactions to beta-lactam antibiotics. Allergy. 2003;58(10):961–72.PubMedGoogle Scholar
  20. 20.
    Romano A, Blanca M, Torres MJ, Bircher A, Aberer W, Brockow K, et al. Diagnosis of nonimmediate reactions to beta-lactam antibiotics. Allergy. 2004;59(11):1153–60.PubMedGoogle Scholar
  21. 21.
    Limsuwan T, Demoly P. Acute symptoms of drug hypersensitivity (urticaria, angioedema, anaphylaxis, anaphylactic shock). Med Clin North Am. 2010;94(4):691–710 x.Google Scholar
  22. 22.
    • Blanca-Lopez N, et al. Allergic reactions to Metamizole: immediate and delayed responses. Int Arch Allergy Immunol. 2016;169(4):223–30 In this paper, a clinical characterization of allergic reactions to metamizol is performed, describing the symptoms induced by the drug. In this paper, the authors also discuss about the time interval between the drug intake and the onset of the reaction.PubMedGoogle Scholar
  23. 23.
    Ariza A, García-Martín E, Salas M, Montañez MI, Mayorga C, Blanca-Lopez N, et al. Pyrazolones metabolites are relevant for identifying selective anaphylaxis to metamizole. Sci Rep. 2016;6:23845.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Bircher AJ, Scherer Hofmeier K. Drug hypersensitivity reactions: inconsistency in the use of the classification of immediate and nonimmediate reactions. J Allergy Clin Immunol. 2012;129(1):263–4 author reply 265-6.Google Scholar
  25. 25.
    Mockenhaupt M. Severe drug-induced skin reactions: clinical pattern, diagnostics and therapy. J Dtsch Dermatol Ges. 2009;7(2):142–60 quiz 161-2.Google Scholar
  26. 26.
    Bircher AJ, Scherer K. Delayed cutaneous manifestations of drug hypersensitivity. Med Clin North Am. 2010;94(4):711–25 x.Google Scholar
  27. 27.
    Bircher AJ. Uncomplicated drug-induced disseminated exanthemas. Chem Immunol Allergy. 2012;97:79–97.PubMedGoogle Scholar
  28. 28.
    •• Zalewska-Janowska A, Spiewak R, Kowalski ML. Cutaneous manifestation of drug allergy and hypersensitivity. Immunol Allergy Clin N Am. 2017;37(1):165–81 In this review, the clinical characteristic and mechanisms involved in allergic and non-allergic hypersensitivity reactions to drugs are summarized.Google Scholar
  29. 29.
    Schnyder B. Approach to the patient with drug allergy. Med Clin North Am. 2010;94(4):665–79 xv.Google Scholar
  30. 30.
    Roujeau JC. Clinical heterogeneity of drug hypersensitivity. Toxicology. 2005;209(2):123–9.PubMedGoogle Scholar
  31. 31.
    • Setkowicz M, et al. Clinical course and urinary eicosanoids in patients with aspirin-induced urticaria followed up for 4 years. J Allergy Clin Immunol. 2009;123(1):174–8 In this study, it is analyzed the natural evolution of aspirin hypersensitivity in patients with NSAIDs-induced urticaria and underlying chronic spontaneous urticaria (NECD).PubMedGoogle Scholar
  32. 32.
    Khan DA, Solensky R. Drug allergy. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S126–37.PubMedGoogle Scholar
  33. 33.
    Fisher MM, Baldo BA. The incidence and clinical features of anaphylactic reactions during anesthesia in Australia. Ann Fr Anesth Reanim. 1993;12(2):97–104.PubMedGoogle Scholar
  34. 34.
    Mertes PM, et al. Perioperative anaphylaxis. Med Clin North Am. 2010;94(4):761–89 xi.Google Scholar
  35. 35.
    Laguna JJ, Archilla J, Doña I, Corominas M, Gastaminza G, Mayorga C, et al. Practical guidelines for perioperative hypersensitivity reactions. J Investig Allergol Clin Immunol. 2018;28(4):216–32.PubMedGoogle Scholar
  36. 36.
    •• Montanez MI, et al. Epidemiology, mechanisms, and diagnosis of drug-induced anaphylaxis. Front Immunol. 2017;8:614 This review focuses in mechanisms involved and management of anaphylaxis induced by drugs.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Ewan PW, Dugué P, Mirakian R, Dixon TA, Harper JN, Nasser SM, et al. BSACI guidelines for the investigation of suspected anaphylaxis during general anaesthesia. Clin Exp Allergy. 2010;40(1):15–31.PubMedGoogle Scholar
  38. 38.
    Bonadonna P, Lombardo C, Bortolami O, Bircher A, Scherer K, Barbaud A, et al. Hypersensitivity to proton pump inhibitors: diagnostic accuracy of skin tests compared to oral provocation test. J Allergy Clin Immunol. 2012;130(2):547–9.PubMedGoogle Scholar
  39. 39.
    Blanca-Lopez N, et al. Hypersensitivity reactions to fluoroquinolones: analysis of the factors involved. Clin Exp Allergy. 2013;43(5):560–7.PubMedGoogle Scholar
  40. 40.
    Doña I, et al. Trends in hypersensitivity drug reactions: more drugs, more response patterns more heterogeneity. J Investig Allergol Clin Immunol. 2014;24(3):143–53 quiz 1 p following 153.Google Scholar
  41. 41.
    Caubet JC, Kaiser L, Lemaître B, Fellay B, Gervaix A, Eigenmann PA. The role of penicillin in benign skin rashes in childhood: a prospective study based on drug rechallenge. J Allergy Clin Immunol. 2011;127(1):218–22.PubMedGoogle Scholar
  42. 42.
    Dona I, et al. NSAIDs-hypersensitivity often induces a blended reaction pattern involving multiple organs. Sci Rep. 2018;8(1):16710.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Yoshimine F, et al. Contribution of aspirin-intolerant asthma to near fatal asthma based on a questionnaire survey in Niigata prefecture, Japan. Respirology. 2005;10(4):477–84.PubMedGoogle Scholar
  44. 44.
    Fiszenson-Albala F, Auzerie V, Mahe E, Farinotti R, Durand-Stocco C, Crickx B, et al. A 6-month prospective survey of cutaneous drug reactions in a hospital setting. Br J Dermatol. 2003;149(5):1018–22.PubMedGoogle Scholar
  45. 45.
    •• Peter JG, et al. Severe delayed cutaneous and systemic reactions to drugs: a global perspective on the science and art of current practice. J Allergy Clin Immunol Pract. 2017;5(3):547–63 In this review, the clinical features, underlying mechanisms and management of severe delayed reactions to drugs are described.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Hausermann P, Bircher AJ. SDRIFE - another acronym for a distinct cutaneous drug exanthema: do we really need it? Dermatology. 2007;214(1):1–2.PubMedGoogle Scholar
  47. 47.
    Hausermann P, Harr T, Bircher AJ. Baboon syndrome resulting from systemic drugs: is there strife between SDRIFE and allergic contact dermatitis syndrome? Contact Dermatitis. 2004;51(5–6):297–310.PubMedGoogle Scholar
  48. 48.
    Thyssen JP, Maibach HI. Drug-elicited systemic allergic (contact) dermatitis--update and possible pathomechanisms. Contact Dermatitis. 2008;59(4):195–202.PubMedGoogle Scholar
  49. 49.
    • Paulmann M, Mockenhaupt M. Severe drug-induced skin reactions: clinical features, diagnosis, etiology, and therapy. J Dtsch Dermatol Ges. 2015;13(7):625–45 In this review, clinical features and drug involved in severe drug-induced skin reactions are described.PubMedGoogle Scholar
  50. 50.
    Sidoroff A, Dunant A, Viboud C, Halevy S, Bavinck JNB, Naldi L, et al. Risk factors for acute generalized exanthematous pustulosis (AGEP)-results of a multinational case-control study (EuroSCAR). Br J Dermatol. 2007;157(5):989–96.PubMedGoogle Scholar
  51. 51.
    Halevy S. Acute generalized exanthematous pustulosis. Curr Opin Allergy Clin Immunol. 2009;9(4):322–8.PubMedGoogle Scholar
  52. 52.
    Momin SB, del Rosso J, Michaels B, Mobini N. Acute generalized exanthematous pustulosis: an enigmatic drug-induced reaction. Cutis. 2009;83(6):291–8.PubMedGoogle Scholar
  53. 53.
    Roujeau JC, et al. Acute generalized exanthematous pustulosis. Analysis of 63 cases. Arch Dermatol. 1991;127(9):1333–8.PubMedGoogle Scholar
  54. 54.
    Britschgi M, Steiner UC, Schmid S, Depta JPH, Senti G, Bircher A, et al. T-cell involvement in drug-induced acute generalized exanthematous pustulosis. J Clin Invest. 2001;107(11):1433–41.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Schmid S, Kuechler PC, Britschgi M, Steiner UC, Yawalkar N, Limat A, et al. Acute generalized exanthematous pustulosis: role of cytotoxic T cells in pustule formation. Am J Pathol. 2002;161(6):2079–86.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau JC. Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol. 1993;129(1):92–6.PubMedGoogle Scholar
  57. 57.
    Chan HL, Stern RS, Arndt KA, Langlois J, Jick SS, Jick H, et al. The incidence of erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. A population-based study with particular reference to reactions caused by drugs among outpatients. Arch Dermatol. 1990;126(1):43–7.PubMedGoogle Scholar
  58. 58.
    Mittmann N, Knowles SR, Koo M, Shear NH, Rachlis A, Rourke SB. Incidence of toxic epidermal necrolysis and Stevens-Johnson syndrome in an HIV cohort: an observational, retrospective case series study. Am J Clin Dermatol. 2012;13(1):49–54.PubMedGoogle Scholar
  59. 59.
    Roujeau JC. Stevens-Johnson syndrome and toxic epidermal necrolysis are severity variants of the same disease which differs from erythema multiforme. J Dermatol. 1997;24(11):726–9.PubMedGoogle Scholar
  60. 60.
    Mockenhaupt M, Viboud C, Dunant A, Naldi L, Halevy S, Bavinck JNB, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Invest Dermatol. 2008;128(1):35–44.PubMedGoogle Scholar
  61. 61.
    Halevy S, Ghislain PD, Mockenhaupt M, Fagot JP, Bouwes Bavinck JN, Sidoroff A, et al. Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel. J Am Acad Dermatol. 2008;58(1):25–32.PubMedGoogle Scholar
  62. 62.
    Kardaun SH, Sekula P, Valeyrie-Allanore L, Liss Y, Chu CY, Creamer D, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol. 2013;169(5):1071–80.PubMedGoogle Scholar
  63. 63.
    Kardaun SH, Sidoroff A, Valeyrie-Allanore L, Halevy S, Davidovici BB, Mockenhaupt M, et al. Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS syndrome really exist? Br J Dermatol. 2007;156(3):609–11.PubMedGoogle Scholar
  64. 64.
    Kano Y, Hiraharas K, Sakuma K, Shiohara T. Several herpesviruses can reactivate in a severe drug-induced multiorgan reaction in the same sequential order as in graft-versus-host disease. Br J Dermatol. 2006;155(2):301–6.PubMedGoogle Scholar
  65. 65.
    Tennis P, Stern RS. Risk of serious cutaneous disorders after initiation of use of phenytoin, carbamazepine, or sodium valproate: a record linkage study. Neurology. 1997;49(2):542–6.PubMedGoogle Scholar
  66. 66.
    Guberman AH, Besag FMC, Brodie MJ, Dooley JM, Duchowny MS, Pellock JM, et al. Lamotrigine-associated rash: risk/benefit considerations in adults and children. Epilepsia. 1999;40(7):985–91.PubMedGoogle Scholar
  67. 67.
    Brahimi N, Routier E, Raison-Peyron N, Tronquoy AF, Pouget-Jasson C, Amarger S, et al. A three-year-analysis of fixed drug eruptions in hospital settings in France. Eur J Dermatol. 2010;20(4):461–4.PubMedGoogle Scholar
  68. 68.
    Khaled A, Kharfi M, Ben Hamida M, el Fekih N, el Aidli S, Zeglaoui F, et al. Cutaneous adverse drug reactions in children. A series of 90 cases. Tunis Med. 2012;90(1):45–50.PubMedGoogle Scholar
  69. 69.
    Lipowicz S, Sekula P, Ingen-Housz-Oro S, Liss Y, Sassolas B, Dunant A, et al. Prognosis of generalized bullous fixed drug eruption: comparison with Stevens-Johnson syndrome and toxic epidermal necrolysis. Br J Dermatol. 2013;168(4):726–32.PubMedGoogle Scholar
  70. 70.
    Calabrese LH, Duna GF. Drug-induced vasculitis. Curr Opin Rheumatol. 1996;8(1):34–40.PubMedGoogle Scholar
  71. 71.
    Martinez-Taboada VM, et al. Clinical features and outcome of 95 patients with hypersensitivity vasculitis. Am J Med. 1997;102(2):186–91.PubMedGoogle Scholar
  72. 72.
    Johnson DH, Cunha BA. Drug fever. Infect Dis Clin N Am. 1996;10(1):85–91.Google Scholar
  73. 73.
    Podevin P, Biour M. Drug-induced "allergic hepatitis". Clin Rev Allergy Immunol. 1995;13(3):223–44.PubMedGoogle Scholar
  74. 74.
    Parra FM, Igea JM, Martin JA, Alonso MD, Lezaun A, Sainz T. Serum sickness-like syndrome associated with cefaclor therapy. Allergy. 1992;47(4 Pt 2):439–40.PubMedGoogle Scholar
  75. 75.
    Rubin RL. Drug-induced lupus. Expert Opin Drug Saf. 2015;14(3):361–78.PubMedGoogle Scholar
  76. 76.
    Lowe GC, Henderson CL, Grau RH, Hansen CB, Sontheimer RD. A systematic review of drug-induced subacute cutaneous lupus erythematosus. Br J Dermatol. 2011;164(3):465–72.PubMedGoogle Scholar
  77. 77.
    •• Fernandez TD, et al. Negativization rates of IgE radioimmunoassay and basophil activation test in immediate reactions to penicillins. Allergy. 2009;64(2):242–8 In this study, it is analyzed the loss of sensitivity of radioimmunoassay and BAT in patients reporting immediate allergic reactions to penicillin.PubMedGoogle Scholar
  78. 78.
    •• Gomez E, et al. Immunoglobulin E-mediated immediate allergic reactions to dipyrone: value of basophil activation test in the identification of patients. Clin Exp Allergy. 2009;39(8):1217–24 In this study, it is analyzed the negativization rate of BAT in patients reporting immediate allergic reactions to dipyrone.PubMedGoogle Scholar
  79. 79.
    Torres MJ, Padial A, Mayorga C, Fernandez T, Sanchez-Sabate E, Cornejo-Garcia JA, et al. The diagnostic interpretation of basophil activation test in immediate allergic reactions to betalactams. Clin Exp Allergy. 2004;34(11):1768–75.PubMedGoogle Scholar
  80. 80.
    Garvey LH, Krøigaard M, Poulsen LK, Skov PS, Mosbech H, Venemalm L, et al. IgE-mediated allergy to chlorhexidine. J Allergy Clin Immunol. 2007;120(2):409–15.PubMedGoogle Scholar
  81. 81.
    •• Kvedariene V, et al. Diagnosis of neuromuscular blocking agent hypersensitivity reactions using cytofluorimetric analysis of basophils. Allergy. 2006;61(3):311–5 In this study, it is analyzed the role of BAT in the diagnosis of immediate allergic reactions to NMBA, including the negativization rate over time.PubMedGoogle Scholar
  82. 82.
    Antunez C, Fernandez T, Blanca-Lopez N, Torres MJ, Mayorga C, Canto G, et al. IgE antibodies to betalactams: relationship between the triggering hapten and the specificity of the immune response. Allergy. 2006;61(8):940–6.PubMedGoogle Scholar
  83. 83.
    Fernandez T, Torres MJ, R-Pena R, Fuentes MS, Robles S, Mayorga C, et al. Decrease of selective immunoglobulin E response to amoxicillin despite repeated administration of benzylpenicillin and penicillin V. Clin Exp Allergy. 2005;35(12):1645–50.PubMedGoogle Scholar
  84. 84.
    Romano A, et al. Evaluation of adverse cutaneous reactions to aminopenicillins with emphasis on those manifested by maculopapular rashes. Allergy. 1995;50(2):113–8.PubMedGoogle Scholar
  85. 85.
    Romano A, Quaratino D, di Fonso M, Papa G, Venuti A, Gasbarrini G. A diagnostic protocol for evaluating nonimmediate reactions to aminopenicillins. J Allergy Clin Immunol. 1999;103(6):1186–90.PubMedGoogle Scholar
  86. 86.
    Romano A, Viola M, Mondino C, Pettinato R, di Fonso M, Papa G, et al. Diagnosing nonimmediate reactions to penicillins by in vivo tests. Int Arch Allergy Immunol. 2002;129(2):169–74.PubMedGoogle Scholar
  87. 87.
    Barbaud A, Collet E, Milpied B, Assier H, Staumont D, Avenel-Audran M, et al. A multicentre study to determine the value and safety of drug patch tests for the three main classes of severe cutaneous adverse drug reactions. Br J Dermatol. 2013;168(3):555–62.PubMedGoogle Scholar
  88. 88.
    Asero R. Intolerance to nonsteroidal anti-inflammatory drugs might precede by years the onset of chronic urticaria. J Allergy Clin Immunol. 2003;111(5):1095–8.PubMedGoogle Scholar
  89. 89.
    Doña I, Blanca-López N, Torres MJ, Gómez F, Fernández J, Zambonino MA, et al. NSAID-induced urticaria/angioedema does not evolve into chronic urticaria: a 12-year follow-up study. Allergy. 2014;69(4):438–44.PubMedGoogle Scholar
  90. 90.
    •• Doña I, et al. Natural evolution in patients with nonsteroidal anti-inflammatory drug-induced urticaria/angioedema. Allergy. 2017;72(9):1346–55 In this study, it is analyzed the natural evolution of cross-hypersensitivity to NSAIDs manifested as urtiaria/angioedema (NIUA).PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Inmaculada Doña
    • 1
    • 2
    Email author
  • María Salas
    • 1
    • 3
  • Natalia Isabel Pérez-Sánchez
    • 1
  • Carmen Moreno-Aguilar
    • 4
    • 5
  • María José Torres
    • 1
    • 2
  1. 1.Allergy Unit, IBIMA-Regional University Hospital of Malaga-UMAMalaga Regional University Hospital (Pavillion C, Hospital Civil)MalagaSpain
  2. 2.ARADyAL network RD16/0006/0001MadridSpain
  3. 3.ARADyAL network RD16/0006/0021MadridSpain
  4. 4.Allergy UnitIMIBIC-Reina Sofia University HospitalCórdobaSpain
  5. 5.ARADyAL network RD16/0006/0018MadridSpain

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