Invasive aspergillosis in patients with systemic lupus erythematosus: a retrospective study on clinical characteristics and risk factors for mortality

Abstract

Objective

The objective of this paper is to analyze the clinical features, outcomes, mortality risk factors, and all-cause mortalities of invasive aspergillosis (IA) in patients with systemic lupus erythematosus (SLE).

Methods

Medical records were reviewed to identify SLE patients with IA from January 2006 to June 2017, at Taipei Veterans General Hospital, Taiwan. A total of 6714 SLE patients were included. Clinical/laboratory parameters and treatment outcomes were analyzed.

Results

Four patients (19.0%) had definite and 17 had probable (81.0%) IA. Seven patients (33.3%) survived and 14 died (66.7%). Concurrently, there were 19 pneumonias (90.5%), 17 cases of other infections (81.0%), eight bacteremia (38.1%), nine cytomegalovirus (CMV, 42.7%) and six Candida (28.6%) infections. In all 55 blood cultures, 38 (69.1%) yielded gram-negative bacilli, of which carbapenem-resistant A. baumannii accounted for eight (21.1%); 17 (30.9%) yielded gram-positive cocci, of which methicillin-resistant S. aureus accounted for six (35.3%); and vancomycin-resistant Enterococcus accounted for four (23.5%). Daily steroid dose ≥ 20 mg (hazard ratio (HR) 2.00), recent pulse steroid therapy (HR 2.80), azathioprine (HR 2.00), rituximab (HR 2.00), plasmapheresis (HR 2.00), acute respiratory distress syndrome (HR 2.00), concurrent infections (HR 5.667) and CMV viremia (HR 1.75) were higher in the fatality group. All p values were less than 0.05. Septic shock (n = 7, 50% in the fatality group) is the most common cause of mortality.

Conclusions

High daily steroid dosing, recent pulse steroid therapy, azathioprine, rituximab, concurrent infections, and CMV viremia were mortality risk factors for IA in SLE.

Keywords

Aspergillosis SLE mortality

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References

Patterson

Thompson

3rd Denning

et al.

Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2016; 63: e1–e60.

Chen

et al.

Invasive pulmonary aspergillosis in patients with antineutrophil cytoplasmic antibody associated vasculitis. J Clin Rheumatol 2009; 15: 380–382.

Patterson

. Approaches to fungal diagnosis in transplantation. Transpl Infect Dis 1999; 1: 262–272.

Tan

Cohen

Fries

et al.

The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271–1277.

Hochberg

. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725–1725.

Petri

Orbai

Alarcón

et al.

Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 2012; 64: 2677–2686.

De Pauw

Walsh

Donnelly

et al.

Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008; 46: 1813–1821.

Mok

. Rituximab for the treatment of rheumatoid arthritis: An update. Drug Des Devel Ther 2013; 8: 87–100.

Gladman

Ibañez

Urowitz

. Systemic Lupus Erythematosus Disease Activity Index 2000. J Rheumatol 2002; 29: 288–291.

10.

Katz

Ehrenfeld

Livneh

et al.

Aspergillosis in systemic lupus erythematosus. Semin Arthritis Rheum 1996; 26: 635–640.

11.

Hauggaard

Ellis

Ekelund

. Early chest radiography and CT in the diagnosis, management and outcome of invasive pulmonary aspergillosis. Acta Radiol 2002; 43: 292–298.

12.

Becker

Lugtenburg

Cornelissen

Van Der Schee

Hoogsteden

De Marie

. Galactomannan detection in computerized tomography-based broncho-alveolar lavage fluid and serum in haematological patients at risk for invasive pulmonary aspergillosis. Br J Haematol 2003; 121: 448–457.

13.

Busca

Locatelli

Barbui

et al.

Usefulness of sequential Aspergillus galactomannan antigen detection combined with early radiologic evaluation for diagnosis of invasive pulmonary aspergillosis in patients undergoing allogeneic stem cell transplantation. Transplant Proc 2006; 38: 1610–1613.

14.

Weisser

Rausch

Droll

et al.

Galactomannan does not precede major signs on a pulmonary computerized tomographic scan suggestive of invasive aspergillosis in patients with hematological malignancies. Clin Infect Dis 2005; 41: 1143–1149.

15.

Caillot

Casasnovas

Bernard

et al.

Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery. J Clin Oncol 1997; 15: 139–147.

16.

Wang

Barber

Johnson

Barnabe

. Invasive fungal disease in systemic lupus erythematosus: A systematic review of disease characteristics, risk factors, and prognosis. Semin Arthritis Rheum 2014; 44: 325–330.

17.

Pamuk

Barutcu

Celik

. The development of pulmonary aspergillosis and pneumothorax in a patient with neutropenic systemic lupus erythematosus and successful treatment of the first case. BMJ Case Rep 2014, pp. 2014. DOI: 10.1136/bcr-2013-200818.

18.

Alderson

Van Dinter

Jr Opatowsky

Burton

. Disseminated aspergillosis following infliximab therapy in an immunosuppressed patient with Crohn’s disease and chronic hepatitis C: A case study and review of the literature. MedGenMed 2005; 7: 7–7.

19.

Yang

Liu

Wan

Wang

. Cyclophosphamide reduces dectin-1 expression in the lungs of naïve and Aspergillus fumigatus-infected mice. Med Mycol 2010; 48: 303–309.

20.

Tracy

Mark

Cornfield

. Invasive pulmonary aspergillosis as the presenting sign in a child with systemic lupus erythematosus. Am J Resp Crit Care Med 2016; 193: A7245–A7245.

21.

Mylonakis

Barlam

Flanigan

Rich

. Pulmonary aspergillosis and invasive disease in AIDS: Review of 342 cases. Chest 1998; 114: 251–262.

22.

Wallace

Lim

Browdy

et al.

Risk factors and outcomes associated with identification of Aspergillus in respiratory specimens from persons with HIV disease. Pulmonary Complications of HIV Infection Study Group. Chest 1998; 114: 131–137.

23.

Pappas

Alexander

Andes

et al.

Invasive fungal infections among organ transplant recipients: Results of the Transplant‐Associated Infection Surveillance Network (TRANSNET). Clin Infect Dis 2010; 50: 1101–1111.

24.

Doligalski

Benedict

Cleveland

et al.

Epidemiology of invasive mold infections in lung transplant recipients. Am J Transplant 2014; 14: 1328–1333.

25.

Neofytos

Fishman

Horn

et al.

Epidemiology and outcome of invasive fungal infections in solid organ transplant recipients. Transpl Infect Dis 2010; 12: 220–229.

26.

Singh

Husain

. AST Infectious Diseases Community of Practice. Aspergillosis in solid organ transplantation. Am J Transplant 2013; 13(Suppl 4): 228–241.

27.

Herbrecht

Letscher-Bru

Oprea

et al.

Aspergillus galactomannan detection in the diagnosis of invasive aspergillosis in cancer patients. J Clin Oncol 2002; 20: 1898–1906.

28.

Marr

Balajee

McLaughlin

Tabouret

Bentsen

Walsh

. Detection of galactomannan antigenemia by enzyme immunoassay for the diagnosis of invasive aspergillosis: Variables that affect performance. J Infect Dis 2004; 190: 641–649.

29.

Maertens

Glasmacher

Selleslag

et al.

Evaluation of serum sandwich enzyme-linked immunosorbent assay for circulating galactomannan during caspofungin therapy: Results from the caspofungin invasive aspergillosis study. Clin Infect Dis 2005; 41: e9–e14.

30.

Maertens

Van Eldere

Verhaegen

Verbeken

Verschakelen

Boogaerts

. Use of circulating galactomannan screening for early diagnosis of invasive aspergillosis in allogeneic stem cell transplant recipients. J Infect Dis 2002; 186: 1297–1306.

31.

Maertens

Klont

Masson

et al.

Optimization of the cutoff value for the Aspergillus double-sandwich enzyme immunoassay. Clin Infect Dis 2007; 44: 1329–1336.

32.

Pfeiffer

Fine

Safdar

. Diagnosis of invasive aspergillosis using a galactomannan assay: A meta-analysis. Clin Infect Dis 2006; 42: 1417–1727.

33.

Verweij

Weemaes

Curfs

Bretagne

Meis

. Failure to detect circulating Aspergillus markers in a patient with chronic granulomatous disease and invasive aspergillosis. J Clin Microbiol 2000; 38: 3900–3901.

34.

Mortensen

Knudsen

Jensen-Fangel

Stausbøl-Grøn

Arendrup

Petersen

. Successful management of invasive aspergillosis presenting as pericarditis in an adult patient with chronic granulomatous disease. Mycoses 2009; 54: e233–e236.

35.

Kuderer

Dale

Crawford

Lyman

. Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: A systematic review. J Clin Oncol 2007; 25: 3158–3167.

36.

Lyman

Dale

Wolff

et al.

Acute myeloid leukemia or myelodysplastic syndrome in randomized controlled clinical trials of cancer chemotherapy with granulocyte colony-stimulating factor: A systematic review. J Clin Oncol 2010; 28: 2914–2924.

37.

Brummer

Maqbool

Stevens

. In vivo GM-CSF prevents dexamethasone suppression of killing of Aspergillus fumigatus conidia by bronchoalveolar macrophages. J Leuk Biol 2001; 70: 868–872.

38.

Sionov

Segal

. Polyene and cytokine treatment of experimental aspergillosis. FEMS Immunol Med Microbiol 2003; 39: 221–227.

39.

Sionov

. Experimental systemic murine aspergillosis: Treatment with polyene and caspofungin combination and G-CSF. J Antimicrob Chemother 2005; 56: 594–597.

40.

Quezada

Koshkina

Zweidler-McKay

Zhou

Kontoyiannis

Kleinerman

. Intranasal granulocyte-macrophage colony-stimulating factor reduces the Aspergillus burden in an immunosuppressed murine model of pulmonary aspergillosis. Antimicrob Agents Chemother 2008; 52: 716–718.

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