Arquivos de Asma, Alergia e Imunologia
https://aaai-asbai.org.br/article/doi/10.5935/2526-5393.20190011
Arquivos de Asma, Alergia e Imunologia
Original Article

Hipersensibilidade a drogas: um alerta em pacientes portadores de doenças autoimunes

Drug hypersensitivity: an alert in patients with autoimmune diseases

Mateus Rios; Luiz Rocha; Gladys Queiroz; Filipe W. Sarinho; Renata Vasconcelos; Almerinda Maria Rego; Emanuel Sarinho

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Resumo

Objetivo: Avaliar a hipersensibilidade a medicamentos em pacientes com o diagnóstico de doenças autoimunes. Métodos: Estudo clínico, analítico, do tipo caso-controle. Foram selecionadas 35 mulheres com doenças autoimunes e 35 sem esse diagnóstico que participaram do protocolo de pesquisa sobre antecedentes de hipersensibilidade a drogas. Resultados: As pacientes apresentavam idade variando de 16 a 66 anos, com a mediana semelhante nos dois grupos. A doença autoimune mais prevalente foi o lupus eritematoso sistêmico, 24/35 (68,5%). A proporção de hipersensibilidade a medicamentos, nas pacientes com doenças autoimunes, foi de 14/35 (40%), e apenas 2/35 (5,7%) no grupo controle (p = 0,0029). As reações de hipersensibilidade do tipo tardia foram as mais frequentes, e na maioria dos casos precederam o diagnóstico de doença autoimune em um total de cinco pacientes, sendo que destas cinco, duas apresentaram síndrome de Stevens Johnson, duas exantema maculopapular, e uma eritema fixo pigmentar. O grupo de drogas mais envolvido foi os anti-inflamatórios não esteroides, seguidos pelos anticonvulsivantes. Conclusão: Hipersensibilidade a medicamentos foi mais frequente em pacientes portadoras de doenças autoimunes, e pode preceder o diagnóstico, especialmente se for do tipo tardia. Estudos adicionais multicêntricos para verificar uma eventual associação de hipersensibilidade a medicamentos e doenças autoimunes são necessários.

Palavras-chave

Autoimunidade, hipersensibilidade a drogas, lúpus eritematoso sistêmico.

Abstract

Objective: To evaluate drug hypersensitivity in patients with autoimmune diseases. Methods: In this clinical, analytical, casecontrol study, we selected 35 women with autoimmune diseases and 35 women without this diagnosis to participate in this research protocol on history of drug hypersensitivity. Results: Patients’ age ranged from 16 to 66 years with similar median in both groups. The most prevalent autoimmune disease was systemic lupus erythematosus, in 24/35 (68.5%) patients. The proportion of drug hypersensitivity was 14/35 (40%) in the autoimmune disease group and only 2/35 (5.7%) in the control group (p = 0.0029). Delayed hypersensitivity reactions were most frequent and preceded the diagnosis of autoimmune disease in five patients, including two with Stevens-Johnson syndrome, two with maculopapular rash and one with fixed pigmented erythema. The most frequently involved group of drugs was nonsteroidal anti-inflammatory drugs, followed by anticonvulsants. Conclusion: Drug hypersensitivity was more common in patients with autoimmune diseases and may precede the diagnosis, especially in delayed-type. Additional multicenter studies are required to evaluate a possible association of drug hypersensitivity to autoimmune diseases.

Keywords

Autoimmunity, drug hypersensitivity, systemic lupus erythematosus.

References

1. Ensina LF, Fernandes FR, Gesu GD, Malaman MF, Chavarria ML, Bernd LAG. Reações de hipersensibilidade a medicamentos. Rev Bras Alerg Imunopatol. 2009;32:42-6.

2. Kowalski ML, Makowska JS, Blanca M, Bavbek S, Bochenek G, Bousquet J, et al. Hypersensitivity to nonsteroidal anti-inflammatory drugs(NSAIDs) – classification, diagnosis and management: review of the EAACI\ENDA and GA2LEN\HANNA. Allergy. 2011;66:818‑29.

3. Demoly P, Adkinson NF, Brockow K, Castells M, Chiriac AM, Greenberger PA, et al. International Consensus on drug allergy. Allergy. 2014;69:420-37.

4. Aota N, Shiohara T. Viral connection between drug rashe and autoimmune diseases: How autoimmune responses are generated after resolution of drug rashes. Autoimmun Rev. 2008; 8:488-94.

5. Moroni L, Bianchi I, Lleo A. Geoepidemiology, gender and autoimmune disease. Autoimmun Rev. 2012;11:386-92.

6. Chiou C, Chumg WH, Hung SI, Hong HS. Pulminant type I diabetes mellitus caused by drug hypersensitivity syndrome with humam herpesvirus 6 infection. J Am Acad Dermatol. 2006;54:14-7.

7. Shiohara T, Inaoka M, Kano Y. Drug-induced hypersensitivity syndrome (DIHS): a reactivation induced by a complex interplay among herpesviruses and antiviral and antidrug immune responses. Allergol Int. 2006;55(1):1-8.

8. Kano Y, Hirahara 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;155:301-6.

9. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725.

10. Fries JF, Hunder GG, Bloch DA, Michel BA, Arend WP, Colabrese LH, et al. The American College of Rheumatology 1990 criteria for the classification of vasculitis. Summary. Arthritis Rheum. 1990;33:1135‑6.

11. Van Den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum. 2013;65(11):2737-47.

12. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010 Sep;62(9):2569-81.

13. Lichtenstein GR, Hanauer SB, Sandborn WJ. Manegement of Crohn`s diseases in adults. Am J Gastroenterol. 2009;104(2):465‑83.

14. Chiou CC, Chung WH, Hung SI, Yang LC, Hong HS, et al. Fulminant type 1 diabetes mellitus caused by drug hypersensitivity syndrome with human herpesvirus 6 infection. J Am Acad Dermatol. 2006;54(2):S14-17.

15. Aota N, Hirahara K, Kano Y, Fukuoka T, Yamada A, Shiohara T. Systemic lupus erythematosus presenting with Kikuchi-Fujimoto's disease as a long-term sequel of drug-induced hypersensitivity syndrome. A possible role of Epstein-Barr virus reactivation. Dermatology. 2009;218(3):275-7.

16. Kano Y, Sakuma K, Shiohara T. Sclerodermoid graft-versus-host disease-like lesions occurring after drug-induced hypersensitivity syndrome. Br J Dermatol. 2007;156(5):1083-4.

17. Shiohara T, Kano Y. A complex interaction between drug allergy and viral infection. Clin Rev Allergy Immunol. 2007;33(1-2):124‑33.

18. Saraya T , Mikoshiba M, Kamiyama H, Yoshizumi M, Tsuchida S, Tsukagoshi H, et al. Evidence for reactivation of human herpesvirus 6 in generalized lymphadenopathy in a patient with drug-induced hypersensitivity syndrome. J Clin Microbiol. 2013; 51(6):1979‑82.

19. Yagami A, Yoshikawa T, Asano Y, Kote S, Shiohara T, Matsunaga K. Drug-induced hypersensitivity syndrome due to mexiletine hydrochloride associated with reactivation of human herpesvirus 7. Dermatology. 2006;213(4):341-4.

20. Asano Y, Kagawa H, Shiohara T. Cytomegalovirus disease during severe drug eruptions: report of 2 cases and retrospective study of 18 patients with drug-induced hypersensitivity syndrome. Arch Dermatol. 2009;145(9):1030-6.

21. Kano T, Horie C, Inaoka M, Tadashi I, Mizukawa Y, Shiohara T. Herpes Zoster in patients with drug-induced hypersensitivity syndrome DRESS. Acta Derm Venereol. 2012;92:193-220.

22. Hirahara K, Kano Y, Ishida T, Shiohara T. Diffuse large B-cell lymphoma as a sequela of Stevens-Johnson syndrome associated with an increased Epstein-Barr virus load. Eur J Dermatol. 2012;22(1):144-5.

23. Kanetaka Y, Kano Y, Hirahara K, Kurata M, Shiohara T. Relationship between cytomegalovirus reactivation and dermatomyositis. Eur J Dermatol. 2011;21(2):248-53.

24. Sabatini A, Bombardueri S, Miqliorini P. Autoantibodies from patients with systemic lupus erythematous bind a shared sequence of Smd and Epstein-Barr vírus encoded nuclear antigen EBNA 1. Eur J Immunol. 1993;23:1146-52.

25. James JA, Kaufman KM, Farris AD, Taylor-Albert E, Lehman TJA, Harley JB. An increased prevalence of Epstein Barr virus infection in young patients suggests a possible etiology for systemic lupus erythematosus. J Clin Invest. 1997;100:3019-26.

26. Sundar K, Jacques S, Gottlieb P, Villars R, Benito ME, Taylor DK, Spatz LA. Expression of the Epstein-Barr virus nuclear antigen-1 (EBNA-1) in the mouse can elicit the production of anti-dsDNA and anti-Sm antibodies. J Autoimmun. 2004;23:127-40.

27. Kukreja A, Cost G, Marker J, Zhang C, Sun Z, Lin-Su K, et al. Multiple immuneregulatory defects in type 1 diabetes. J Clin Invest. 2002;109:131-40.

28. Balandina A, Lecart S, Dartevelle P, Saoudi A, Berrih-Aknin. Functional defect of regulatory CD4CD25 T cells in the thymus of patients whith autoimmune myasthenia gravis. Blood. 2005;105:735‑41.

29. Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA. Loss of functional suppression by CD4CD25 regulatory T cells in patients with multiple sclerosis. J Exp Med. 2004;199:971-9.

30. Takahashi R, Kano Y, Yamazaki Y, Kimishima M, Mizukawa Y, Shiohara T. Defective T cells in patients with severe drug eruptions: timing of the dysfunction is associated with the pathological phenotype and outcome. J Immunol. 2009;182:8071-9.


Submitted date:
05/26/2018

Accepted date:
04/08/2019

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