1814 The Journal of Rheumatology 2012; 39:9; doi:10.3899/jrheum.111498
Personal non-commercial use only. The Journal of Rheumatology Copyright © 2012. All rights reserved.
Invasive Fungal Infections in Patients with Systemic
Lupus Erythematosus
MARCO ULISES MARTÍNEZ-MARTÍNEZ, DAVID HERRERA-VAN OOSTDAM, SUSANA ROMÁN-ACOSTA,
MARTÍN MAGAÑA-AQUINO, LOURDES BARANDA-CÁNDIDO, and CARLOS ABUD-MENDOZA
ABSTRACT. Objective. Invasive fungal infections (IFI) are catastrophic diseases associated with a high mortality.
Relatively few cases of IFI have been described in systemic lupus erythematosus (SLE) and their relat-
ed factors have not been completely explored. We evaluated factors associated with IFI in patients with
SLE.
Methods. All patients with both IFI and SLE admitted to our hospital in the last 7 years were evaluat-
ed and each was compared with 5 hospitalized patients with SLE (controls). Demographic factors, dura-
tion of SLE, and treatment in the previous month were compared.
Results. Sixty patients with SLE were evaluated (10 with IFI and 50 controls). Median age was 29
years. High C-reactive protein levels were associated with IFI, along with other factors such as high dis-
ease activity, mechanical ventilation, treatment with antibiotics, hemodialysis, high doses of glucocor-
ticoids (GC), and treatment with mycophenolate mofetil. Mortality was 4 times more frequent in
patients with IFI than in SLE patients without the deep fungal infection.
Conclusion. IFI is a rare infection observed in patients with rheumatic diseases. We describe factors
associated with IFI in patients with SLE. IFI is associated with elevated morbidity and mortality. Early
diagnosis and treatment are desirable. (First Release June 15 2012; J Rheumatol 2012;39:1814–18;
doi:10.3899/jrheum.111498)
Key Indexing Terms:
SYSTEMIC LUPUS ERYTHEMATOSUS INFECTIONS INVASIVE FUNGAL INFECTIONS
From the Regional Unit of Rheumatology and Osteoporosis, Central
Hospital “Dr. Ignacio Morones Prieto” and Faculty of Medicine,
Universidad Autónoma de San Luis Potosí, San Luis Potosí, México.
M.U. Martínez-Martínez, MD; D. Herrera-van Oostdam, MD;
S. Román-Acosta, MD; M. Magaña-Aquino, MD; L. Baranda-Cándido,
MD; C. Abud-Mendoza, MD, Regional Unit of Rheumatology and
Osteoporosis, Central Hospital “Dr. Ignacio Morones Prieto” and
Faculty of Medicine, Universidad Autónoma de San Luis Potosí.
Address correspondence to Dr. C. Abud-Mendoza, Regional Unit of
Rheumatology and Osteoporosis, Central Hospital “Dr. Ignacio Morones
Prieto,” Av. V. Carranza 2395, San Luis Potosí, S.L.P., México, 78240.
E-mail: c_abud@hotmail.com
Accepted for publication April 26, 2012.
Infection is a frequent cause of morbidity and mortality in
patients with systemic lupus erythematosus (SLE)
1
.
Predisposing risk factors for infections in patients with SLE
are diverse; they include genetic or acquired immune defi-
ciencies such as defects in phagocytic cell function, lym-
phopenia, and decreases in the production of some cytokines,
immunoglobulins, and in complement levels
2
. Moreover, SLE
therapy may increase the risk of infectious processes
1
.
Invasive fungal infection (IFI) is a life-threatening condi-
tion occurring most often in patients with hematological
malignancy, hematopoietic stem cell transplant recipients, and
solid organ transplant recipients
3
. Although predisposing risk
factors have been described in these diseases, the character of
SLE and its complications related to IFI are not completely
understood. We retrospectively analyzed associated factors
for the development of deep fungal infections in patients with
SLE in our institution over a 7-year period.
MATERIALS AND METHODS
Selection of patients and collection of clinical data. From the hospital’s cen-
tral discharge register, we identified all patients discharged with a diagnosis
of SLE
4
from January 2004 to May 2011. By linking with the register we
identified 10 cases of IFI/fungemia among 309 patients admitted with SLE.
Fungemia confirmation was based on a positive blood culture for fungi. IFI
was deemed a fungal infection at sites other than skin, urine, or mucous mem-
branes (histological diagnosis through biopsy or necropsy)
5
. We included
fungemia with IFI because it is included as an invasive fungal disease by the
European Organization for Research and Treatment of Cancer/Invasive
Fungal Infections Cooperative Group and the US National Institute of Allergy
and Infectious Diseases Mycoses Study Group Consensus Group.
To identify factors associated with IFI, we performed a case-control study.
For each case in which SLE and IFI were confirmed, 5 controls from our SLE
cohort were selected. The next 5 hospital admissions with the diagnosis of
SLE after 1 case (IFI and SLE) were matched as controls. The clinical data
were reviewed and evaluated regarding the 1997 American College of
Rheumatology (ACR) revised criteria for the classification of SLE
4,6
and
IFI
5
. Cases and controls included men and women; pediatric cases as well as
adults were included to evaluate age as a factor related to IFI. Patients were
excluded if they did not fulfill the ACR criteria or if they had incorrect diag-
nosis registrations. Data retrieved from the medical records included age, sex,
disease duration, laboratory test results [hematology, creatinine, albumin,
C-reactive protein (CRP)], medical events (requiring hemodialysis and
mechanical ventilation), disease activity (measured by SELENA-SLEDAI —
Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic
Lupus Erythematosus Disease Activity Index
7
), and treatment, particularly 1
month prior to fungal infection. These data were obtained at diagnosis of IFI
for the cases. Data for the controls were obtained at admission (treatment and
medical events included all medications and events received during the
selected admission).
Statistical analysis. Nonparametric statistical analyses were performed;
descriptive data are reported as median and interquartile range. Categorical
measurements were compared using chi-squared or Fisher’s exact test. All
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