Коморбидные инфекции у больных системной красной волчанкой: современное состояние проблемы

В современной ревматологии коморбидные инфекции (КИ) оказывают значительное влияние на морбидность и летальность у больных системной красной волчанкой (СКВ). Повышенная восприимчивость больных СКВ к инфекциям связана с разнообразными расстройствами иммунной системы. Выделен ряд факторов риска развития КИ при СКВ, имеющих отношение как к самому заболеванию, так и к его лечению. Однако, несмотря на достаточное количество этих факторов, вклад каждого из них весьма разнится в зависимости от когорты наблюдаемых больных СКВ. Рассмотрены эпидемиологические и клинико-лабораторные характеристики некоторых бактериальных и вирусных КИ у больных СКВ в современной клинической практике. Подчеркивается значимость иммунизации, в первую очередь противогриппозной и пневмококковой вакцинами, больных СКВ, поскольку среди них риск летальных исходов от инфекций нижних дыхательных путей достаточно высок. Намечены пути дальнейших исследований в рамках рассматриваемой проблемы. 

1. Малеев ВВ, Покровский ВИ. Инфекционные болезни в России: проблемы и пути их решения. Терапевтический архив. 2004;(4):5-9 [Maleev VV, Pokrovskiy VI. Infectious diseases in Russia: Problems and Solutions. Terapevticheskiy arkhiv. 2004;(4):5-9 (In Russ.)].

2. Duffy KN, Duffy CM, Gladman DD. Infection and disease activity in systemic lupus erythematosus: a review of hospitalized patients. J Rheumatol. 1991;18(8):1180-4.

3. Edwards CJ, Lian TY, Badsha H, et al. Hospitalization of individuals with systemic lupus erythematosus: characteristics and predictors of outcome. Lupus. 2003;12(9):672-6. doi: 10.1191/0961203303lu452oa

4. Namendys-Silva SA, Baltazar-Torres JA, Rivero-Sigarroa E, et al. Prognostic factors in patients with systemic lupus erythematosus admitted to the intensive care unit. Lupus. 2009;18(14):1252-8. doi: 10.1177/0961203309345720

5. Suh CH, Jeong YS, Park HC, et al. Risk factors for infection and role of C-reactive protein in Korean patients with systemic lupus erythematosus. Clin Exp Rheumatol. 2001;19(2):191-4.

6. Costa-Reis P, Nativ S, Isgro J, et al. Major infections in a cohort of 120 patients with juvenile-onset systemic lupus erythematosus. Clin Immunol. 2013;149(3):442-9. doi: 10.1016/j.clim.2013.08.009

7. Bosch X, Guilabert A, Pallares L, et al. Infections in systemic lupus erythematosus: a prospective and controlled study of 110 patients. Lupus. 2006;15(9):584-9. doi: 10.1177/0961203306071919

8. Dubula T, Mody GM. Spectrum of infections and outcome among hospitalized South Africans with systemic lupus erythematosus. Clin Rheumatol. 2015 Mar;34(3):479-88. doi: 10.1007/s10067-014- 2847-0. Epub 2014 Dec 23.

9. Zonana-Nacach A, Camargo-Coronel A, Yanez P, et al. Infections in outpatients with systemic lupus erythematosus: a prospective study. Lupus. 2001;10(7):505-10. doi: 10.1191/096120301678416088

10. Noel V, Lortholary O, Casassus P, et al. Risk factors and prognostic influence of infection in a single cohort of 87 adults with systemic lupus erythematosus. Ann Rheum Dis. 2001;60(12):1141-4. doi: 10.1136/ard.60.12.1141

11. Сороцкая ВН. Распространенность и причины летальных исходов ревматических заболеваний на модели Тульской области. Автореф. дисс. … докт. мед. наук. Тула; 2005. 48 с. [Sorotskaya VN. Rasprostranennost' i prichiny letal'nykh iskhodov revmaticheskikh zabolevaniy na modeli Tul’skoy oblasti. Avtoref. diss. …dokt. med. nauk [The incidence and causes of deaths revmaticheskih diseases on the model of the Tula area. Author. diss. ... Doct. Med. Sci.]. Tula; 2005. 48 p.].

12. Gonzalez Leon R, Castillo Palma MJ, Garcia Hernandez FJ, et al. [Severe infections in a cohort of patients with systemic lupus ery￾thematosus]. Med Clin (Barc). 2010;135(8):365-7. doi: 10.1016/j.medcli.2010.03.026

13. Al-Rayes H, Al-Swailem R, Arfin M, et al. Systemic lupus erythematosus and infections: a retrospective study in Saudis. Lupus. 2007;16(9):755-63. doi: 10.1177/0961203307079943

14. Bultink IEM, Dijkmans BAC, Voskuyl AE. Infections in patients with systemic lupus erythematosus: prevalence, spectrum and associated risk factors. Ann Rheum Dis. 2005;64 Suppl. III:235.

15. Chen D, Zhan Z. Clinical features and risk factors of infection in patients with systemic lupus erythematosus: experience from a single institute of Southern China. Ann Rheum Dis. 2014;73 Suppl 2:599. doi: 10.1136/annrheumdis-2014- eular.3052

16. Jeong SJ, Choi H, Lee HS, et al. Incidence and risk factors of infection in a single cohort of 110 adults with systemic lupus erythematosus. Scand J Infect Dis. 2009;41(4):268-74. doi: 10.1080/00365540902744741

17. Faco MM, Leone C, Campos LM, et al. Risk factors associated with the death of patients hospitalized for juvenile systemic lupus erythematosus. Braz J Med Biol Res. 2007;40(7):993-1002. doi: 10.1590/S0100-879X2006005000110

18. Cervera R, Khamashta MA, Font J, et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore). 2003;82(5):299-308. doi: 10.1097/01.md.0000091181.93122.55

19. Mok CC, To CH, Ho LY, Yu KL. Incidence and mortality of systemic lupus erythematosus in a southern Chinese population, 2000–2006. J Rheumatol. 2008;35(10):1978-82.

20. Goldblatt F, Chambers S, Rahman A, Isenberg DA. Serious infections in British patients with systemic lupus erythematosus: hospitalisations and mortality. Lupus. 2009;18(8): 682-9. doi: 10.1177/0961203308101019

21. Gulay CB, Dans LF. Clinical presentations and outcomes of Filipino juvenile systemic lupus erythematosus. Pediatr Rheumatol Online J. 2011;9:7. doi: 10.1186/1546-0096-9-7

22. Лучихина ЕЛ. Анализ структуры летальных исходов при системной красной волчанке: Автореф. дисс. … канд. мед. наук. Москва;1998. 24 с. [Luchikhina EL. Analiz struktury letal’nykh iskhodov pri sistemnoi krasnoi volchanke: Avtoref. diss. … kand. med. nauk [Analysis of the structure of deaths in systemic lupus erythematosus: Author. diss. ... Cand. Med. Sci.]. Moscow; 1998. 24 p.].

23. Клюквина НГ.Системная красная волчанка у мужчин: клиника, течение, исходы. Автореф. дисс. … докт. мед. наук. Москва; 2010. 52 с. [Klyukvina NG. Sistemnaya krasnaya volchanka u muzhchin: klinika, techenie, ishody. Avtoref. diss. … dokt. med. nauk [Systemic lupus erythematosus in men: clinical, during, outcomes. Author. diss. ... Doctor. Med. Sci.]. Moscow; 2010. 52 p.].

24. Nossent J, Cikes N, Kiss E, et al. Current causes of death in systemic lupus erythematosus in Europe, 2000–2004: relation to dis￾ease activity and damage accrual. Lupus. 2007;16(5):309-17. doi: 10.1177/0961203307077987

25. Garred P, Voss A, Madsen HO, Junker P. Association of mannosebinding lectin gene variation with disease severity and infections in a population-based cohort of systemic lupus erythematosus patients. Genes Immun. 2001;2(8):442-50. doi: 10.1038/sj.gene.6363804

26. Dias AM, do Couto MC, Duarte CC, et al. White blood cell count abnormalities and infections in one-year follow-up of 124 patients with SLE. Ann N Y Acad Sci. 2009;1173:103-7. doi: 10.1111/j.1749-6632.2009.04872.x

27. Ng WL, Chu CM, Wu AK, et al. Lymphopenia at presentation is associated with increased risk of infections in patients with systemic lupus erythematosus. QJM. 2006;99(1):37-47. doi: 10.1093/qjmed/hci155

28. James JA, Sestak AL, Vista ES. SLE and Infections. In: Wallace DJ, Hahn BH, editors. Dubois’ Lupus Erythematosus and Related Syndroms. 8th ed. Philadelphia: Saunders Elsevier; 2013. P. 555-63.

29. Ruiz-Irastorza G, Olivares N, Ruiz-Arruza I, et al. Predictors of major infections in systemic lupus erythematosus. Arthritis Res Ther. 2009;11(4):R109. doi: 10.1186/ar2764

30. Иванова ММ. Патогенетическая терапия, реабилитация и прогноз больных системной красной волчанкой с преимущественным поражением почек. Автореф. дисс. … докт. мед. наук. Москва; 1985. 48 с. [Ivanova MM. Patogeneticheskaya terapiya, reabilitatsiya i prognoz bol’nykh sistemnoi krasnoi volchankoi s preimushchestvennym porazheniem pochek. Avtoref. diss. … dokt. med. nauk [Pathogenetic therapy, rehabilitation and prognosis bolnyh systemic lupus erythematosus with pri￾mary renal disease. Author. diss. ... Doct. Med. Sci.]. Moscow; 1985. 48 p.].

31. Соловьев СК. Эффективность интенсивной терапии у больных системной красной волчанкой с неблагоприятным жизненным прогнозом. Автореф. дисс. … докт. мед. наук. Москва; 2000. 58 с. [Solov’ev SK. Effektivnost’ intensivnoi terapii u bol’nykh sistemnoi krasnoi volchankoi s neblagopriyatnym zhiznennym prognozom. Avtoref. diss. … dokt. med. nauk [The effectiveness of intensive therapy in patients with systemic lupus erythematosus with a poor vital prognosis. Author. diss. ... Doct. Med. Sci.]. Moscow; 2000. 58 p.].

32. Левицки А, Линдер С, ван Волленховен РФ. Ритуксимаб в терапии системной красной волчанки. Научно- практическая ревматология. 2013;51(3):223-39 [Levitsky A, Linder S, van Vollenhoven RF. Rituximab in the management of systemic lupus erythematosus. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2013;51(3):223-39 (In Russ.)]. doi: 10.14412/1995-4484-2013- 1494

33. Diaz-Lagares C, Perez-Alvarez R, Garcia-Hernandez FJ, et al. Rates of, and risk factors for, severe infections in patients with systemic autoimmune diseases receiving biological agents off-label. Arthritis Res Ther. 2011;13(4):R112. doi: 10.1186/ar3397

34. Fernandez-Nebro A, de la Fuente JL, Carreno L, et al. Multicenter longitudinal study of B-lymphocyte depletion in refractory systemic lupus erythematosus: the LESIMAB study. Lupus. 2012;21(10):1063-76. doi: 10.1177/0961203312446627

35. Ананьева ЛП, Соловьев СК, Бекетова ТВ и др. Анти-В- клеточная терапия при иммуновоспалительных ревматических заболеваниях: эффективность и переносимость у 229 больных. Научно-практическая ревматология. 2014;52(5):495-506 [Ananieva LP, Soloviyov SK, Beketova TV, et al. Anti-B-cell therapy at immune inflammatory rheumatic diseases: efficacy and tolerability in 229 patients. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2014;52(5):495-506 (In Russ.)]. doi: 10.14412/1995- 4484-2014-495-506

36. Merrill J, Buyon J, Furie R, et al. Assessment of flares in lupus patients enrolled in a phase II/III study of rituximab (EXPLORER). Lupus. 2011;20(7):709-16. doi: 10.1177/0961203310395802

37. Rovin BH, Furie R, Latinis K, et al. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum. 2012;64(4):1215-26. doi: 10.1002/art.34359

38. Navarra SV, Guzman RM, Gallacher AE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9767):721-31. doi: 10.1016/S0140- 6736(10)61354-2

39. Furie R, Petri M, Zamani O, et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 2011;63(12):3918-30. doi: 10.1002/art.30613

40. Merrill JT, Ginzler EM, Wallace DJ, et al. Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus. Arthritis Rheum. 2012 Oct;64(10):3364-73. doi: 10.1002/art.34564

41. Luijten RK, Cuppen BV, Bijlsma JW, Derksen RH. Serious infections in systemic lupus erythematosus with a focus on pneumococcal infections. Lupus. 2014;23(14):1512-6. doi: 10.1177/0961203314543918

42. Narata R, Wangkaew S, Kasitanon N, Louthrenoo W. Community-acquired pneumonia in Thai patients with systemic lupus erythematosus. South Asian J Trop Med Public Health. 2007;38(3):528-36.

43. Kinder BW, Freemer MM, King TE, et al. Clinical and genetic risk factors for pneumonia in systemic lupus erythematosus. Arthritis Rheum. 2007;56(8):2679-86. doi: 10.1002/art.22804

44. Полянская МВ. Пневмония у пациентов с ревматическими заболеваниями: частота встречаемости, клиническая картина, факторы риска. Автореф. дисc. … канд. мед. наук. Москва; 2009. 24 с. [Polyanskaya MV. Pnevmoniya u pacientov s revmaticheskimi zabolevaniyami: chastota vstrechaemosti, klinicheskaya kartina, faktory riska. Avtoref. diss. … kand. med. nauk [Pneumonia in patients with rheumatic diseases: incidence, clinical presentation, risk factors. Author. disc. ... Cand. Med. Sci.]. Moscow; 2009. 24 p.].

45. Ward MM, Donald F. Pneumocystis carinii pneumonia in patients with connective tissue diseases: the role of hospital experience in diagnosis and mortality. Arthritis Rheum. 1999;42(4):780-9. doi: 10.1002/1529- 0131(199904)42:43.0.CO;2-M

46. Tsai MJ, Chou CW, Lin FC, Chang SC. Pneumocystis jiroveci pneumonia in patients with systemic lupus erythematosus after rituximab therapy. Lupus. 2012;21(8):914-8. doi: 10.1177/0961203312436855

47. Bonilla-Abadia F, Betancurt JF, Pineda JC, et al. Pneumocystis jirovecii pneumonia in two patients with systemic lupus erythematosus after rituximab therapy. Clin Rheumatol. 2014;33(3):415- 8. doi: 10.1007/s10067-013-2475-0

48. Stamp LK, Hurst M. Is there a role for consensus guidelines for P. jiroveci pneumonia prophylaxis in immunosuppressed patients with rheumatic diseases? J Rheumatol. 2010;37(4):686-8. doi: 10.3899/jrheum.091426

49. Mohamed DF, Habeeb RA, Hosny SM, Ebrahim SE. Incidence and risk of infection in egyptian patients with systemic lupus erythematosus. Clin Med Insights Arthritis Musculoskelet Disord. 2014;7:41-8. doi: 10.4137/CMAMD.S15346

50. Hidalgo-Tenorio C, Jimenez-Alonso J, de Dios Luna J, et al. Urinary tract infections and lupus erythematosus. Ann Rheum Dis. 2004;63(4):431-7. doi: 10.1136/ard.2003.006346

51. Duran-Barragan S, Ruvalcaba-Naranjo H, Rodriguez-Gutierrez L. Recurrent urinary tract infections and bladder dysfunction in systemic lupus erythematosus. Lupus. 2008;17(12):1117-21. doi: 10.1177/0961203308093458

52. Tsai YC, Hou CL, Yao TC, et al. Risk factors and bacterial profiles of urinary tract infections in patients with systemic lupus erythematosus. Asian Pac J Allergy Immunol. 2007;25(2- 3):155-61.

53. Wang LR, Barber CE, Johnson AS, Barnabe C. Invasive fungal disease in systemic lupus erythematosus: A systematic review of disease characteristics, risk factors, and prognosis. Semin Arthritis Rheum. 2014;44(3):325-30. doi: 10.1016/j.semarthrit.2014.06.001

54. Erdozain JG, Ruiz-Irastorza G, Egurbide MV, et al. High risk of tuberculosis in systemic lupus erythematosus? Lupus. 2006;15(4):232-5. doi: 10.1191/0961203306lu2289xx

55. Sayarlioglu M, Inanc M, Kamali S, et al. Tuberculosis in Turkish patients with systemic lupus erythematosus: increased frequency of extrapulmonary localization. Lupus. 2004;13(4):274-8. doi: 10.1191/0961203303lu529xx

56. Mosca M, Tani C, Aringer M, et al. European League Against Rheumatism recommendations for monitoring patients with systemic lupus erythematosus in clinical practice and in observational studies. Ann Rheum Dis. 2010;69(7):1269-74. doi: 10.1136/ard.2009.117200

57. Arenas Miras Mdel M, Hidalgo-Tenorio C, Jimenez-Gamiz P, Jimenez-Alonso J. Diagnosis of latent tuberculosis in patients with systemic lupus erythematosus: T.SPOT.TB versus tuberculin skin test. Biomed Res Int. 2014;2014:291031. doi: 10.1155/2014/291031

58. Kadavath S, Zapantis E, Henriquez W, et al. Effectiveness of combining tuberculin skin test and interferon gamma release assays as a screening strategy for detecting latent tuberculosis infection in high risk patients with systemic lupus erythematosus. Ann Rheum Dis. 2013;72 Suppl 3:A478. doi: 10.1136/annrheumdis-2013- eular.1435

59. Mok MY, Wong SS, Chan TM, et al. Non-tuberculous mycobacterial infection in patients with systemic lupus erythematosus. Rheumatology (Oxford). 2007;46(2):280-4. doi: 10.1093/rheuma￾tology/kel206

60. Cuchacovich R, Gedalia A. Pathophysiology and clinical spectrum of infections in systemic lupus erythematosus. Rheum Dis Clin North Am. 2009;35(1):75-93. doi: 10.1016/j.rdc.2009.03.003

61. Ramos-Casals M, Cuadrado MJ, Alba P, et al. Acute viral infections in patients with systemic lupus erythematosus: description of 23 cases and review of the literature. Medicine (Baltimore). 2008;87(6):311-8. doi: 10.1097/MD.0b013e31818ec711

62. Klumb EM, Pinto AC, Jesus GR, et al. Are women with lupus at higher risk of HPV infection? Lupus. 2010;19(13):1485-91. doi: 10.1177/0961203310372952

63. Lyrio LD, Grassi MF, Santana IU, et al. Prevalence of cervical human papillomavirus infection in women with systemic lupus erythematosus. Rheumatol Int. 2013;33(2):335-40. doi: 10.1007/s00296-012-2426-0

64. Santana IU, do Nascimento Gomes A, D’Cirqueira Lyrio L, et al. Systemic lupus erythematosus, human papillomavirus infection, cervical pre-malignant and malignant lesions: a systematic review. Clin Rheumatol. 2011;30(5):665-72. doi: 10.1007/s10067-010- 1606-0

65. Mendoza-Pinto C, Garcia-Carrasco M, Vallejo-Ruiz V, et al. The impact of glucocorticoids and anti-CD20 therapy on cervical human papillomavirus infection risk in women with systemic lupus erythematosus. Clinics (Sao Paulo). 2013 Dec;68(12):1475-80. doi: 10.6061/clinics/2013(12)01

66. Molloy E, Calabrese LH. Progressive multifocal leucoencephalopaty associated with biological therapy in rheumatic dis￾eases. Arthritis Rheum. 2014;66 Suppl 10:abstr.837.

67. Письмо Федеральной службы по надзору в сфере здравоохранения от 7 февраля 2014 г. №02И-110/14 «О новых данных по безопасности лекарственного препарата Бенлиста». Доступно по ссылке: http://www.garant.ru/products/ipo/prime/doc/70485650/#ixzz3 OWJlGxDT. Дата обращения 10 января 2015 г. [Pis’mo Federal’noi sluzhby po nadzoru v sfere zdravookhraneniya ot 7 fevralya 2014 g. №02I-110/14 «O novykh dannykh po bezopasnosti lekarstvennogo preparata Benlista» [The letter of Federal service on supervision in sphere of public health from February 7, 2014 №02I-110/14, "On the new drug for safety data Benlista"]. Available from: http://www.garant.ru/products/ipo/prime/doc/70485650/#ixzz3 OWJlGxDT. Treatment Date January 10, 2015].

68. Toussirot E, Bereau M. The risk of progressive multifocal leukoencephalopathy under biological agents used in the treatment of chronic inflammatory diseases. Inflamm Allergy Drug Targets. 2014;13(2):121-7. doi: 10.2174/1871528113666140224103712

69. Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host. Clin Infect Dis. 2014;58(3):44-100. doi: 10.1093/cid/cit684

70. Baranda L, Alvarez-Quiroga C, Gonzalez-Amaro R, et al. Immune effects of human papilloma virus (HPV) immunization in patients with systemic lupus erythematosus (SLE). Ann Rheum Dis. 2014;73 Suppl 2:539. doi: 10.1136/annrheumdis-2014-eular.5934

71. Hua C, Barnetche T, Combe B, Morel J. Effect of methotrexate, anti-tumor necrosis factor α, and rituximab on the immune response to influenza and pneumococcal vaccines in patients with rheumatoid arthritis: a systematic review and meta-analysis. Arthritis Care Res (Hoboken). 2014 Jul;66(7):1016-26. doi: 10.1002/acr.22246

72. Kapetanovic MC, Kristensen LE, Saxne T, et al. Impact of anti￾rheumatic treatment on immunogenicity of pandemic H1N1 influenza vaccine in patients with arthritis. Arthritis Res Ther. 2014 Jan 2;16(1):R2. doi: 10.1186/ar4427