JRD Journal of Rheumatic Diseases J Rheum Dis 2093-940X 2233-4718 The Korean College of Rheumatology 10.4078/jrd.2017.24.4.203 jrd-24-203 Original Article Prevalence and Risk Factors Associated with Neutropenia in Hospitalized Patients with Systemic Lupus Erythematosus ChungMin Kyung KimIn Je LeeJisoo Division of Rheumatology, Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea Corresponding to: Jisoo Lee, Division of Rheumatology, Department of Internal Medicine, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Korea. E-mail: leejisoo@ewha.ac.kr 10 2017 31 10 2017 24 4 203 210 04042017 04052017 15052017 Copyright © 2017 The Korean College of Rheumatology 2017 This is a Open Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Objective

This study estimated the prevalence and explored possible risk factors associated with neutropenia in hospitalized patients with systemic lupus erythematosus (SLE).

 Methods

This review included 160 admissions of 85 SLE patients between 2006 and 2013. Neutropenia was defined as absolute neutrophil count (ANC) below 1,500/mm3. The baseline characteristics of the patients were compared between patients who experienced neutropenia and those who did not. Clinical and serological factors related to neutropenia episodes during admission were analyzed.

 Results

Thirty-five (21.9%) neutropenic episodes were found among the 160 admissions. Most of the neutropenic episodes were mild to moderate. Severe neutropenia of ANC ＜500/mm3 occurred in 3.1% of the cases. Patients with neutropenia had higher frequencies of ANA (100.0% vs. 86.8%, p=0.042) and anti-double stranded DNA (87.5% vs. 60.4%, p=0.008), and satisfied more SLE classification criteria at the time of diagnosis than those without (5.1 vs. 4.6, p=0.009). Anemia, leukopenia, thrombocytopenia and low complement levels were frequently accompanied with neutropenia. Chronic kidney disease (odds ratio, 11.17; 95% confidence interval, 1.46∼85.27; p=0.020) was associated with neutropenia.

 Conclusion

This study demonstrates that neutropenia is frequent in hospitalized patients with SLE, and patients with neutropenia have more hematologic and immunologic abnormalities. Renal damage was more frequent among those presenting with neutropenia.

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Initial characteristics of SLE patients at the time of SLE diagnosis according to the presence of neutropenia during hospitalization (n=85)

Variable With neutropenia (n=32) Without neutropenia (n=53) p-value
Female 31 (96.9) 47 (88.7) 0.247
Age at diagnosis (yr) 32.8±11.7 31.1±11.7 0.253
SLE criteria satisfaction 5.1±1.1 4.6±1.3 0.009∗
Manifestation at diagnosis      
 Malar rash 11 (34.4) 19 (35.8) 0.890
 Discoid rash 6 (18.8) 11 (20.8) 0.050
 Photosensitivity 9 (28.1) 11 (20.8) 0.602
 Oral ulcer 12 (37.5) 13 (24.5) 0.203
 Arthritis 14 (43.8) 31 (58.5) 0.187
 Serositis 5 (15.6) 6 (11.3) 0.740
 Hematologic 23 (71.9) 29 (54.7) 0.116
 Renal 10 (31.3) 9 (17.0) 0.126
 Neuropsychiatric 2 (6.3) 2 (3.8) 0.630
Autoantibody†      
 ANA 32 (100) 46 (86.8) 0.042∗
 Anti-dsDNA 28 (87.5) 32 (60.4) 0.008∗
 Anti-Sm 7 (21.9) 10 (18.9) 0.737
 Anti-RNP 11 (34.4) 11 (20.8) 0.165
 Anti-SSA/Ro 15 (46.9) 15 (28.3) 0.083
 Anti-SSB/La 6 (18.8) 9 (17.0) 0.836
 Lupus anticoagulant 16 (50.0) 20 (37.7) 0.268
 Anticardiolipin antibody 14 (43.8) 22 (41.5) 0.839

Values are presented as number (%) or mean±standard deviation. SLE: systemic lupus erythematosus, ANA: antinuclear antibodies, Anti-dsDNA: anti-double stranded deoxyribonucleic acid, Anti-Sm: anti-Smith, Anti-RNP: anti-ribonucleoprotein.

Represents statistical significance of p＜0.05.

Autoantibody positivity at diagnosis.

Characteristics of admissions with neutropenia in patients with SLE

Variable Total (n=35) Neutropenia
Mild* (n=17) Moderate† (n=13) Severe‡ (n=5)
Cause of admission        
Infection 5 (14.3) 1 (5.9) 2 (15.4) 2 (40.0)
SLE flare § 27 (77.1) 13 (76.5) 11 (84.6) 3 (60.0)
Others§ 3 (8.6) 3 (17.6) 0 (0.0) 0 (0.0)
Neutropenia duration (d) 7.9±4.4 7.5±4.6 7.0±2.4 12.4±5.8
Use of G-CSF 2 (5.7) 0 (0) 0 (0) 2 (40.0)
Neutropenic fever 10 (28.6) 0 (0) 6 (46.2) 4 (80.0)

Values are presented as number (%) or mean±standard deviation. SLE: systemic lupus erythematosus, G-CSF: granulocyte-colony stimulating factor, ANC: absolute neutrophil count.

ANC≥1,000/mm3∼＜1,500/mm3

ANC≥500/mm3∼＜1,000/mm3

ANC＜500/mm3.

Peripheral neuropathy, allergic rhinitis, deep vein thrombosis.

Comparison of clinical characteristics of admissions with and without neutropenia in patients with SLE

Variable With neutropenia (n=35) Without neutropenia (n=125) p-value
Age at admission (yr) 36.7±11.8 36.9±11.2 0.971
Disease duration (yr) 5.3±8.1 4.9±5.0 0.690
Cause of admission      
Infection 5 (14.3) 21 (16.8) 0.714
SLE 27 (77.1) 95 (76.0) 0.741
Others† 3 (8.6) 9 (7.2) 0.978
Comorbidities      
DM 1 (2.9) 3 (2.4) 0.839
Hypertension 4 (11.4) 13 (10.4) 0.904
Chronic kidney disease 7 (20.0) 2 (1.6) 0.004∗
Sjögren's syndrome 3 (8.6) 4 (3.2) 0.234
Medication in use      
Glucocorticoid 20 (57.1) 95 (76.0) 0.050
Dose of glucocorticoid (mg) 6.79±8.03 8.32±9.01 0.319
Hydroxychloroquine 13 (37.1) 60 (48.0) 0.153
Cyclophosphamide 2 (5.7) 1 (0.8) 0.104
Azathioprine 6 (17.1) 20 (16.0) 0.827
MMF 1 (2.9) 5 (4.0) 0.763
Mizoribine 3 (8.6) 7 (5.6) 0.383
SLEDAI 11.3±6.4 10.2±7.5 0.576
Hemoglobin (mg/dL) 10.3±1.9 11.2±2.1 0.029∗
Leukocyte (/mm3) 2,029.4±6,668.2 6,534.2±3,337.1 0.001∗
Platelet (×103/mm3) 149.0±71.9 190.9±93.1 0.029∗
ESR (mm/h) 21.23±16.81 24.47±19.92 0.250
CRP (mg/dL) 2.13±5.62 2.95±4.77 0.535
Decreased C3 29 (82.9) 68 (54.4) 0.005∗
Decreased C4 19 (54.3) 35 (28.0) 0.012∗
Rise in anti-dsDNA titer 27 (77.1) 79 (63.2) 0.207
Presence of proteinuria‡ 9 (25.7) 28 (22.4) 0.766

Values are presented as number (%) or mean±standard deviation. SLE: systemic lupus erythematosus, DM: diabetes mellitus, MMF: mycophenolate mofetil, SLEDAI: systemic lupus erythematosus disease activity index, ESR: erythrocyte sediment rate, CRP: C-reactive protein, C: complement, Anti-dsDNA: anti-double stranded deoxyribonucleic acid.

Represents statistical significance of p＜0.05, using generalized estimating equation analysis.

Myocardial infarction, peripheral neuropathy, allergic rhinitis, drug fever, hemarthrosis, compression fracture, deep vein thrombosis, gastrointestinal bleeding, gastric spasm.

Proteinuria＞0.5 g/d.

Risk factors associated with neutropenia during hospitalization in patients with SLE in univariate and multivariate analysis

Variable Univariate
 Multivariate
Odds ratio 95% CI p-value Odds ratio 95% CI p-value
Age at admission 0.99 0.96∼1.04 0.971 - - -
Disease duration 1.02 0.94∼1.09 0.690 - - -
Cause of admission            
Infection 0.84 0.32∼2.18 0.714 - - -
SLE 1.16 0.49∼2.71 0.741 - - -
Others† 0.98 0.27∼3.63 0.978 - - -
Comorbidities            
DM 1.27 0.12∼13.04 0.839 - - -
Hypertension 0.91 0.21∼4.02 0.904 - - -
Chronic kidney disease 16.38 2.44∼109.85 0.004∗ 11.17 1.46∼85.27 0.020∗
Sjögren's syndrome 3.14 0.48∼20.67 0.234 - - -
Medication in use            
Glucocorticoid 0.44 0.19∼1.00 0.050 0.51 0.18∼1.48 0.217
Dose of glucocorticoid 0.98 0.93∼1.03 0.319 - - -
Hydroxychloroquine 0.56 0.25∼1.24 0.153 0.70 0.22∼2.24 0.543
Cyclophosphamide 5.76 0.70∼47.72 0.104 5.57 0.89∼34.96 0.067
Azathioprine 1.12 0.41∼3.09 0.827 - - -
MMF 0.78 0.16∼3.90 0.763 - - -
Mizoribine 1.61 0.55∼4.73 0.383 - - -
SLEDAI 1.01 0.97∼1.06 0.576 - - -
Hemoglobin 0.82 0.68∼0.98 0.029∗ 1.00 0.82∼1.22 0.995
Leukocyte 0.99 0.995∼0.998 0.001∗ - - -
Platelet 0.82 0.68∼0.98 0.029∗ 1.00 0.99∼1.00 0.183
ESR 0.99 0.97∼1.01 0.250 - - -
CRP 0.97 0.86∼1.08 0.535 - - -
Decreased C3 3.70 1.49∼9.18 0.005∗ 2.130 0.69∼6.60 0.190
Decreased C4 2.90 1.26∼6.65 0.012∗ 1.635 0.52∼5.17 0.402
Increased anti-dsDNA 1.75 0.73∼4.15 0.207 - - -
Presence of proteinuria‡ 1.14 0.48∼2.69 0.766 - - -

SLE: systemic lupus erythematosus, CI: confidence interval, DM: diabetes mellitus, MMF: mycophenolate mofetil, SLEDAI: systemic lupus erythematosus disease activity index, ESR: erythrocyte sediment rate, CRP: C-reactive protein, C: complement, Anti-dsDNA: anti-double stranded deoxyribonucleic acid, −: not applicable.

Represents statistical significance of p＜0.05, using generalized estimating equation analysis.

Myocardial infarction, peripheral neuropathy, allergic rhinitis, drug fever, hemarthrosis, compression fracture, deep vein thrombosis, gastrointestinal bleeding, gastric spasm.

Proteinuria＞0.5 g/d.