Gizem VARKAL, İpek TÜRK, Özlem DOĞAN AĞBUGA, Mehmet Ali AŞIK, Şerife Şeyda ZENGİN ACEMOĞLU, Kaniye AYDIN, Didem ARSLAN, Hüseyin Turgut Elbek ÖZER

ANCA ile ilişkili vasküliti olan hastalarda görülen enfeksiyonlar ve neden olan mikroorganizmalar

Amaç: Bu çalışmada ANCA ilişkili vasküliti (AİV) olan hastalarda hastaneye yatış gerektiren enfeksiyonlarının saptanması amaçlanmıştır. Gereç ve Yöntem: AİV’li Türk hastalarda yapılmış tek merkezli, retrospektif bir çalışmadır. Hastanede yatış gerektiren enfeksiyon atakları, üreyen patojenler, laboratuvar bulguları, vaskülit tedavisi için verilen immünsüpresif tedaviler ve enfeksiyon ile ilişkisi değerlendirildi. Bulgular: AİV tanısı alan 74 hasta çalışmaya dahil edildi. Hastaların 36’sında enfeksiyon nedeniyle hastaneye yatış görüldü. Enfekte hasta grubunda diabetes mellitus (DM) birlikteliği anlamlı olarak yüksek bulundu. Siklofosfamid (SP) tedavisinin enfeksiyon riskini artırdığı bulundu. Enfekte hasta grubunun %80'den fazlası böbrek tutulumu ile başvurdu (%80,6). Otuz altı hastada toplam 68 enfeksiyon epizodu görüldü. En sık enfeksiyon tutulumu %70,6 ile solunum yolu idi. Gram-negatif bakteriler, özellikle Pseudomonas aeruginosa olmak üzere en yaygın patojendi. Pandeminin de etkisiyle viral enfeksiyonlar arasında SARS-CoV-2 ön plana çıktı. Aspergilloz, mantar enfeksiyonları arasında en sık saptanandı. Ayrıca aspergilloz, mantar enfeksiyonlarının %85,7'sinin (6 atak) nedeniydi. Enfeksiyon ataklarının %76,5'inde lenfopeni gözlendi. Enfeksiyonların %57,4'ü indüksiyon tedavisinin ilk yılında gelişmiştir. Enfeksiyöz ataklarda vaskülit tedavisinde en sık kullanılan immünsüpresif tedavi SP (%41,2) idi. Sonuç Vaskülit tedavisi sırasında enfeksiyonları yönetmek çok önemlidir. Lenfopeni, böbrek tutulumu, DM ve immünsüpresif tedavi enfeksiyon riskini artıran faktörlerdir. Klinisyenler patojen olarak özellikle solunum yolu enfeksiyonları ve gram negatif bakteriler için önleyici tedbirler almalıdır.

Anahtar Kelimeler:

ANCA ile ilişkili vaskülit, enfeksiyon, immünsüpresyon, lenfopeni

Infections and causative microorganisms in patients with ANCA-associated vasculitis

Purpose: The aim of this study was to detect infections requiring hospitalization in patients with ANCA-associated vasculitis (AAV). Materials and Methods: This is a single-center, retrospective study conducted in Turkish patients with AAV. Infection episodes requiring hospitalization, reproducing pathogens, laboratory findings, immunosuppressive treatments given for the treatment of vasculitis, and the relationship with the infection were evaluated. Results: Seventy-four patients diagnosed with AAV were included in the study. Hospitalization due to infection was observed in 36 of the patients. The coexistence of diabetes mellitus (DM) was found to be significantly higher in the infected patient group. Cyclophosphamide (CYC) treatment found to increase risk of infection. More than 80% of the infected patient group presented with renal involvement (80.6%). A total of 68 infectious episodes were seen in 36 patients. The most common involvement of infection was the respiratory tract with a rate of 70.6%. Gram-negative bacteria were the most common pathogen, especially Pseudomonas aeruginosa. With the effect of the pandemic, SARS-CoV-2 has come to the fore among viral infections. Aspergillosis was the most frequently detected among fungal infections. Besides, aspergillosis was the cause of 85.7% (6 episodes) of fungal infections. Lymphopenia was observed in 76.5% of the infection episodes. 57.4% of infections developed in the first year of the induction therapy. The most frequently used immunosuppressive therapy for the treatment of vasculitis in infectious episodes was CYC (41.2%). Conclusion: Managing infections during the vasculitis treatment is crucially important. Lymphopenia, kidney involvement, DM and immunosuppressive therapy are factors that increase the risk of infection. Clinicians should take preventive measure especially for respiratory tract infections and gram-negative bacteria as pathogens.

Keywords:

ANCA-associated vasculitis, infection, immunosuppression, lymphopenia,

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Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F et al. 2012 revised international Chapel Hill consensus conference nomenclature of vasculitides. Arthritis Rheum. 2013;65:1–11.
Yates M, Watts RA, Bajema IM, Cid MJ, Crestani B, Hauser T et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis. 2016;75:1583-94.
Flossmann O, Berden A, de Groot K, Hagen C, Harper L, Heijl C et al. Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis. 2011;70:488-94.
Rathmann J, Jayne D, Segelmark M, Jönsson G, Mohammad AJ. Incidence and predictors of severe infections in ANCA-associated vasculitis: a population-based cohort study. Rheumatology (Oxford). 2021;60:2745-54.
Speer C, Altenmüller-Walther C, Splitthoff J, Nusshag C, Kälble F, Reichel P. et al. Glucocorticoid maintenance therapy and severe infectious complications in ANCA associated vasculitis: a retrospective analysis. Rheumatol Int. 2021;41:431-8.
Khan I, Watts RA. Classification of ANCA-associated vasculitis. Curr Rheumatol Rep. 2013;15:383.
Little MA, Nightingale P, Verburgh CA, Hauser T, De Groot K, Savage C et al. Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis. Ann Rheum Dis. 2010;69:1036-43.
Zhang Y, Guo J, Zhang P, Zhang L, Duan X, Shi X et al. Predictors of mortality in critically ill patients with antineutrophil cytoplasmic antibody-associated vasculitis. Front Med (Lausanne). 2021;8:762004.
Reinhold-Keller E, Moosig F. Development of morbidity and mortality in ANCA-associated vasculitis. Z Rheumatol. 2011;70:486-92.
Ofer-Shiber S, Molad Y. Association of the Charlson comorbidity index with renal outcome and all-cause mortality in antineutrophil cytoplasmatic antibody-associated vasculitis. Medicine (Baltimore). 2014;93:152.
Sakai R, Tanaka E, Nishina H, Suzuki M, Yamanaka H, Harigai M. Risk of opportunistic infections in patients with antineutrophil cytoplasmic antibody‐associated vasculitis, using a Japanese health insurance database. Int J Rheum Dis. 2019;22:1978–84.
Haris Á, Polner K, Arányi J, Braunitzer H, Kaszás I. Incidence and clinical predictors of infections in patients treated with severe systemic ANCA-associated vasculitis. Physiol Int. 2021;108:66-79.
Weidanz F, Day CJ, Hewins P, Savage CO, Harper L. Recurrences and infections during continuous immunosuppressive therapy after beginning dialysis in ANCA-associated vasculitis. Am J Kidney Dis. 2007;50:36-46.
Garcia-Vives E, Segarra-Medrano A, Martinez-Valle F, Agraz I, Solans-Laque R. Prevalence and risk factors for major infections in patients with antineutrophil cytoplasmic antibody–associated vasculitis: influence on the disease outcome. J Rheumatol. 2020;47:407-14.
Betjes MG, Meijers RW, Litjens NH. Loss of renal function causes premature aging of the immune system. Blood Purif. 2013;36:173-8.
Vaziri ND, Pahl MV, Crum A, Norris K. Effect of uremia on structure and function of immune system. J Ren Nutr. 2012;22:149-56.
Lao M, Huang M, Li C, Li H, Qiu Q, Zhan Z et al. Infectious profile in inpatients with ANCA-associated vasculitis: a single-center retrospective study from Southern China. Clin Rheumatol. 2020;39:499-507.
Murosaki T, Sato T, Nagatani K, Sato K, Minota S. Risk factors correlated with immunosuppressant discontinuation in antineutrophil cytoplasmic antibodyassociated vasculitis patients. Int. J. Rheum. Dis. 2020;00:1–7.
Harada M, Ishii W, Masubuchi T, Ichikawa T, Kobayashi M. Relationship between immunosuppressive therapy and the development of infectious complications among patients with anti-neutrophil cytoplasmic antibody-associated vasculitis: a single-center, retrospective observational study. Cureus. 2019;11:5676.
20.Thomas K, Vasilopoulos D. Infections and vasculitis. Curr Opin Rheumatol. 2017;29:17-23.
Xu T, Chen Z, Jiang M, Ma H, Jin K, Wang Z et al. Association between different infection profiles and one-year outcomes in ANCA-associated vasculitis: a retrospective study with monthly infection screening. RMD Open. 2022;8:002424.
Waki D, Nishimura K, Tokumasu H, Kadoba K, Mukoyama H, Saito R et al. Initial high-dose corticosteroids and renal impairment are risk factors for early severe infections in elderly patients with antineutrophil cytoplasmic autoantibody-associated vasculitis: A retrospective observational study. Medicine (Baltimore). 2020;99:19173.
Goupil R, Brachemi S, Nadeau-Fredette AC, Déziel C, Troyanov Y, Lavergne V et al. Lymphopenia and treatment-related infectious complications in ANCA-associated vasculitis. Clin J Am Soc Nephrol. 2013;8:416-23.
Kronbichler A, Jayne DR, Mayer G. Frequency, risk factors and prophylaxis of infection in ANCA-associated vasculitis. Eur J Clin Invest. 2015;45:346-68.
Ognibene FP, Shelhamer JH, Hoffman GS, Kerr GS, Reda D, Fauci AS et al. Pneumocystis carinii pneumonia: a major complication of immunosuppressive therapy in patients with Wegener's granulomatosis. Am J Respir Crit Care Med. 1995;151:795–9