Lupus (2015) 0,
1–8
http://lup.sagepub.com
LUPUS AROUND THE WORLD
Comparison of clinical and serological differences among juvenile-, adult-, and late-onset systemic lupus erythematosus in Korean patients JH Choi1, DJ Park1, JH Kang1, YR Yim1, KE Lee1, JW Lee1, L Wen1, TJ Kim1, YW Park1, JK Lee2 and SS Lee1 1
Division of Rheumatology, Department of Internal Medicine, Chonnam National University Medical School & Hospital, Gwangju, Korea; and 2 Department of Neurosurgery, Chonnam National University Medical School & Hospital, Gwangju, Korea
Objectives: We investigated whether systemic lupus erythematosus (SLE) patients could be distinguished based on the time of disease onset and, if so, whether the groups differed in their clinical and laboratory features in ethnically homogeneous Korean patients. Methods: We enrolled 201 SLE patients with available clinical data at the time of onset of SLE from the lupus cohort at Chonnam National University Hospital. Sociodemographic, clinical, and laboratory data, including autoantibodies, and concomitant diseases were found at the time of diagnosis of SLE by reviewing patient charts. We divided SLE patients according to age at SLE diagnosis into three groups: juvenile-onset SLE (JSLE, diagnosed at 18 years), adultonset SLE (ASLE, diagnosed at 19–50 years), and late-onset SLE (LSLE, diagnosed at >50 years), and compared baseline demographic, clinical, and relevant laboratory findings. Results: Of the 201 patients, 27 (14.4%), 149 (74.1%), and 25 (12.4%) were JSLE, ASLE, and LSLE patients, respectively. Fever, oral ulcers, nephritis, anemia, and thrombocytopenia were more common in JSLE patients than ASLE or LSLE patients (p < 0.05, < 0.05, 0.001, < 0.05, and < 0.05, respectively). However, Sjo¨gren’s syndrome was more frequent in LSLE patients than JSLE or ASLE patients (p < 0.05). Disease activity was significantly higher in JSLE patients than in ASLE or LSLE patients (p < 0.001). Anti-dsDNA and antinucleosome antibodies were found more frequently in JSLE patients and less frequently in LSLE patients (p < 0.05 and 0.005, respectively) and decreased complement levels were more common in JSLE patients and less common in LSLE patients (p < 0.001, 0.001, and < 0.05, respectively). Conclusions: Our results indicate that SLE patients present with different clinical and serological manifestations according to age at disease onset. JSLE patients have more severe disease activity and more frequent renal involvement and LSLE patients have milder disease activity, more commonly accompanied by Sjo¨gren’s syndrome, at disease onset. Lupus (2015) 0, 1–8. Key words: Systemic lupus erythematosus; onset; age
Introduction Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a highly variable presentation and course. It can affect virtually every organ of the body and many symptoms may be observed. Skin, musculoskeletal, Correspondence to: Shin-Seok Lee, Division of Rheumatology, Department of Internal Medicine, Chonnam National University Medical School & Hospital, 42 Jebong-ro, Dong-gu, Gwangju 501-757, Korea. Email: [email protected] J.H.C. and D.J.P. contributed equally to this work. Received 4 June 2014; accepted 12 May 2015
hematologic, and serological involvement are most commonly observed.1 Some patients show predominately hematologic, renal, or central nervous system manifestations.2,3 The clinical course of SLE may be characterized by periods of remission and by chronic or acute relapses. Several factors, including age and ethnicity, can affect the nature and severity of SLE, and response to treatment also varies by race, ethnicity, and age. Non-Caucasians tend to exhibit acute disease onset, more severe and numerous clinical manifestations, and higher disease activity.4–10 Hispanics, African descendants and Asians exhibit more frequent renal, hematological, serosal, neuropsychiatric
! The Author(s), 2015. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav
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10.1177/0961203315591024
Clinical differences among JSEL, ASLE, and LSLE JH Choi et al.
2
and immunological abnormalities.5,7,11–14 Furthermore, response to treatment for lupus nephritis varies according to race and ethnicity.15 Similarly, ethnicity can affect the nature and severity of SLE and its response to treatment: Age of onset also influences the clinical manifestations and severity of SLE. Approximately 15–20% of SLE patients experience disease onset prior to adulthood, and about 2–20% of all patients with SLE experience onset of SLE after the age of 50.16–18 Studies have reported that juvenile-onset SLE patients tend to have more aggressive presentation and course, with higher rates of organ involvement and lower life expectancy than adult-onset SLE patients.19–24 Late-onset SLE patients tend to have more insidious onset of disease and tend to have less major organ involvement and more benign disease course.25 However, they have a poorer prognosis than patients who developed SLE before the age of 50 years, because of the generally higher frequency of comorbid diseases and higher organ damage, due to aging and longer exposure to ‘‘classical’’ vascular risk factors.17,26,27 Several studies have reported differences of onset of the disease. However, there are few studies that have investigated differences in clinical manifestations with disease onset in Asian lupus patients. Thus, we investigated whether SLE patients could be distinguished according to clinical manifestations, especially organ involvement and laboratory findings (including autoantibodies), based on the time of disease onset and, if so, whether different groups could be distinguished among ethnically homogeneous Korean patients, in terms of their clinical and laboratory features.
Methods Population and study design We evaluated 201 SLE patients from January 2005 to January 2013, with available clinical data at the time of onset of SLE, followed at the Department of Rheumatology at Chonnam National University Hospital, a tertiary and academic center in Korea. All patients satisfied at least four of the American College of Rheumatology (ACR) criteria for the classification of SLE.28,29 We divided SLE patients according to age at SLE diagnosis into three groups (juvenile-onset SLE (JSLE), adult-onset SLE (ASLE), and late-onset SLE (LSLE)) and compared baseline demographic, clinical, and relevant laboratory findings. JSLE was defined as diagnosis below 18 years
of age, while those diagnosed between 19 and 50 years of age were classified as ASLE, and LSLE was defined as diagnosis at more than 50 years of age. Patients were excluded if they had other autoimmune diseases, such as rheumatoid arthritis, systemic sclerosis, or primary Sjo¨gren’s syndrome, but not secondary Sjo¨gren’s syndrome or secondary antiphospholipid syndrome. We diagnosed secondary Sjo¨gren’s syndrome according to the 2002 revised international classification criteria, in which symptoms of oral or ocular dryness exist in addition to ocular sign, oral sign, or positive minor salivary gland biopsy findings. We defined secondary antiphospholipid syndrome as a diagnosis of antiphospholipid syndrome after a diagnosis of SLE based on the Sapporo classification criteria.30 We also excluded patients if their medical records were incomplete or insufficient for the diagnosis of SLE at the supposed time of diagnosis. The study was approved by our institutional review board. Patient data collection Sociodemographic data, such as gender, age at diagnosis, duration of disease and clinical manifestations, and serological profiles, including autoantibodies, were identified by reviewing hospital records. The disease duration of SLE was determined from the date of initial diagnosis. Clinical manifestations at the time of onset included symptoms listed in the ACR criteria (malar rash, discoid rash, alopecia, photosensitivity, oral ulcer, arthritis and arthralgia, serositis, renal involvement, central nervous system (CNS) involvement, and hematological disorders) and Raynaud’s phenomenon, fever, dry eyes, and dry mouth. The clinical manifestations were defined as follows: alopecia, increased hair loss due to SLE that was clearly visible to the physician; Raynaud’s phenomenon, blanching of fingers and/or toes induced by exposure to cold, stress, or both with definite two-phase color change; fever, body temperature of >38 C in the absence of suspected or proven infection; dry eye, confirmed by an abnormal Schirmer’s test and not attributable to medications; and dry mouth, confirmed by salivary scintigraphy or a positive minor salivary gland biopsy. Information about concomitant diseases, including diabetes mellitus (DM), hypertension, antiphospholipid syndrome, Sjo¨gren’s syndrome, thyroid disease, and history of cancer, was also collected. DM was defined according to the American Diabetes Association criteria for the diagnosis of
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Clinical differences among JSEL, ASLE, and LSLE JH Choi et al.
3
diabetes (2012) or as a history of the use of insulin or oral hypoglycemic agents.31 Hypertension was defined as a systolic blood pressure of 140 mmHg and/or diastolic blood pressure of 90 mmHg on two or more occasions and/or patient self-reported intake of antihypertensive medications. Antiphospholipid syndrome was diagnosed according to the revised Sapporo classification criteria.30 Sjo¨gren’s syndrome was diagnosed according to the revised international classification criteria for Sjo¨gren’s syndrome.32 The SLE Disease Activity Index (SLEDAI)-2000 score was also calculated for assessing lupus activity and flare at the time of the enrollment in this study.33 Antinuclear antibodies (ANA) were detected by indirect fluorescent antibody (IFA) assay. Anti-double-stranded DNA (anti-dsDNA) antibodies were detected by radioimmunoassays. Autoantibodies, such as anti-Sm, Ro, La, and ribonucleoprotein (RNP), were assessed by enzyme-linked immunosorbent assays (ELISAs). Anti-nucleosome and anti-ribosomal P antibodies were assessed using immunoblot technique. Statistical analyses Statistical analyses were performed using the SPSS software (version 18.0 for Windows; SPSS Inc, Chicago, IL, USA). P values of
1–8
http://lup.sagepub.com
LUPUS AROUND THE WORLD
Comparison of clinical and serological differences among juvenile-, adult-, and late-onset systemic lupus erythematosus in Korean patients JH Choi1, DJ Park1, JH Kang1, YR Yim1, KE Lee1, JW Lee1, L Wen1, TJ Kim1, YW Park1, JK Lee2 and SS Lee1 1
Division of Rheumatology, Department of Internal Medicine, Chonnam National University Medical School & Hospital, Gwangju, Korea; and 2 Department of Neurosurgery, Chonnam National University Medical School & Hospital, Gwangju, Korea
Objectives: We investigated whether systemic lupus erythematosus (SLE) patients could be distinguished based on the time of disease onset and, if so, whether the groups differed in their clinical and laboratory features in ethnically homogeneous Korean patients. Methods: We enrolled 201 SLE patients with available clinical data at the time of onset of SLE from the lupus cohort at Chonnam National University Hospital. Sociodemographic, clinical, and laboratory data, including autoantibodies, and concomitant diseases were found at the time of diagnosis of SLE by reviewing patient charts. We divided SLE patients according to age at SLE diagnosis into three groups: juvenile-onset SLE (JSLE, diagnosed at 18 years), adultonset SLE (ASLE, diagnosed at 19–50 years), and late-onset SLE (LSLE, diagnosed at >50 years), and compared baseline demographic, clinical, and relevant laboratory findings. Results: Of the 201 patients, 27 (14.4%), 149 (74.1%), and 25 (12.4%) were JSLE, ASLE, and LSLE patients, respectively. Fever, oral ulcers, nephritis, anemia, and thrombocytopenia were more common in JSLE patients than ASLE or LSLE patients (p < 0.05, < 0.05, 0.001, < 0.05, and < 0.05, respectively). However, Sjo¨gren’s syndrome was more frequent in LSLE patients than JSLE or ASLE patients (p < 0.05). Disease activity was significantly higher in JSLE patients than in ASLE or LSLE patients (p < 0.001). Anti-dsDNA and antinucleosome antibodies were found more frequently in JSLE patients and less frequently in LSLE patients (p < 0.05 and 0.005, respectively) and decreased complement levels were more common in JSLE patients and less common in LSLE patients (p < 0.001, 0.001, and < 0.05, respectively). Conclusions: Our results indicate that SLE patients present with different clinical and serological manifestations according to age at disease onset. JSLE patients have more severe disease activity and more frequent renal involvement and LSLE patients have milder disease activity, more commonly accompanied by Sjo¨gren’s syndrome, at disease onset. Lupus (2015) 0, 1–8. Key words: Systemic lupus erythematosus; onset; age
Introduction Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a highly variable presentation and course. It can affect virtually every organ of the body and many symptoms may be observed. Skin, musculoskeletal, Correspondence to: Shin-Seok Lee, Division of Rheumatology, Department of Internal Medicine, Chonnam National University Medical School & Hospital, 42 Jebong-ro, Dong-gu, Gwangju 501-757, Korea. Email: [email protected] J.H.C. and D.J.P. contributed equally to this work. Received 4 June 2014; accepted 12 May 2015
hematologic, and serological involvement are most commonly observed.1 Some patients show predominately hematologic, renal, or central nervous system manifestations.2,3 The clinical course of SLE may be characterized by periods of remission and by chronic or acute relapses. Several factors, including age and ethnicity, can affect the nature and severity of SLE, and response to treatment also varies by race, ethnicity, and age. Non-Caucasians tend to exhibit acute disease onset, more severe and numerous clinical manifestations, and higher disease activity.4–10 Hispanics, African descendants and Asians exhibit more frequent renal, hematological, serosal, neuropsychiatric
! The Author(s), 2015. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav
Downloaded from lup.sagepub.com at UNIVERSITE LAVAL on July 6, 2015
10.1177/0961203315591024
Clinical differences among JSEL, ASLE, and LSLE JH Choi et al.
2
and immunological abnormalities.5,7,11–14 Furthermore, response to treatment for lupus nephritis varies according to race and ethnicity.15 Similarly, ethnicity can affect the nature and severity of SLE and its response to treatment: Age of onset also influences the clinical manifestations and severity of SLE. Approximately 15–20% of SLE patients experience disease onset prior to adulthood, and about 2–20% of all patients with SLE experience onset of SLE after the age of 50.16–18 Studies have reported that juvenile-onset SLE patients tend to have more aggressive presentation and course, with higher rates of organ involvement and lower life expectancy than adult-onset SLE patients.19–24 Late-onset SLE patients tend to have more insidious onset of disease and tend to have less major organ involvement and more benign disease course.25 However, they have a poorer prognosis than patients who developed SLE before the age of 50 years, because of the generally higher frequency of comorbid diseases and higher organ damage, due to aging and longer exposure to ‘‘classical’’ vascular risk factors.17,26,27 Several studies have reported differences of onset of the disease. However, there are few studies that have investigated differences in clinical manifestations with disease onset in Asian lupus patients. Thus, we investigated whether SLE patients could be distinguished according to clinical manifestations, especially organ involvement and laboratory findings (including autoantibodies), based on the time of disease onset and, if so, whether different groups could be distinguished among ethnically homogeneous Korean patients, in terms of their clinical and laboratory features.
Methods Population and study design We evaluated 201 SLE patients from January 2005 to January 2013, with available clinical data at the time of onset of SLE, followed at the Department of Rheumatology at Chonnam National University Hospital, a tertiary and academic center in Korea. All patients satisfied at least four of the American College of Rheumatology (ACR) criteria for the classification of SLE.28,29 We divided SLE patients according to age at SLE diagnosis into three groups (juvenile-onset SLE (JSLE), adult-onset SLE (ASLE), and late-onset SLE (LSLE)) and compared baseline demographic, clinical, and relevant laboratory findings. JSLE was defined as diagnosis below 18 years
of age, while those diagnosed between 19 and 50 years of age were classified as ASLE, and LSLE was defined as diagnosis at more than 50 years of age. Patients were excluded if they had other autoimmune diseases, such as rheumatoid arthritis, systemic sclerosis, or primary Sjo¨gren’s syndrome, but not secondary Sjo¨gren’s syndrome or secondary antiphospholipid syndrome. We diagnosed secondary Sjo¨gren’s syndrome according to the 2002 revised international classification criteria, in which symptoms of oral or ocular dryness exist in addition to ocular sign, oral sign, or positive minor salivary gland biopsy findings. We defined secondary antiphospholipid syndrome as a diagnosis of antiphospholipid syndrome after a diagnosis of SLE based on the Sapporo classification criteria.30 We also excluded patients if their medical records were incomplete or insufficient for the diagnosis of SLE at the supposed time of diagnosis. The study was approved by our institutional review board. Patient data collection Sociodemographic data, such as gender, age at diagnosis, duration of disease and clinical manifestations, and serological profiles, including autoantibodies, were identified by reviewing hospital records. The disease duration of SLE was determined from the date of initial diagnosis. Clinical manifestations at the time of onset included symptoms listed in the ACR criteria (malar rash, discoid rash, alopecia, photosensitivity, oral ulcer, arthritis and arthralgia, serositis, renal involvement, central nervous system (CNS) involvement, and hematological disorders) and Raynaud’s phenomenon, fever, dry eyes, and dry mouth. The clinical manifestations were defined as follows: alopecia, increased hair loss due to SLE that was clearly visible to the physician; Raynaud’s phenomenon, blanching of fingers and/or toes induced by exposure to cold, stress, or both with definite two-phase color change; fever, body temperature of >38 C in the absence of suspected or proven infection; dry eye, confirmed by an abnormal Schirmer’s test and not attributable to medications; and dry mouth, confirmed by salivary scintigraphy or a positive minor salivary gland biopsy. Information about concomitant diseases, including diabetes mellitus (DM), hypertension, antiphospholipid syndrome, Sjo¨gren’s syndrome, thyroid disease, and history of cancer, was also collected. DM was defined according to the American Diabetes Association criteria for the diagnosis of
Lupus Downloaded from lup.sagepub.com at UNIVERSITE LAVAL on July 6, 2015
Clinical differences among JSEL, ASLE, and LSLE JH Choi et al.
3
diabetes (2012) or as a history of the use of insulin or oral hypoglycemic agents.31 Hypertension was defined as a systolic blood pressure of 140 mmHg and/or diastolic blood pressure of 90 mmHg on two or more occasions and/or patient self-reported intake of antihypertensive medications. Antiphospholipid syndrome was diagnosed according to the revised Sapporo classification criteria.30 Sjo¨gren’s syndrome was diagnosed according to the revised international classification criteria for Sjo¨gren’s syndrome.32 The SLE Disease Activity Index (SLEDAI)-2000 score was also calculated for assessing lupus activity and flare at the time of the enrollment in this study.33 Antinuclear antibodies (ANA) were detected by indirect fluorescent antibody (IFA) assay. Anti-double-stranded DNA (anti-dsDNA) antibodies were detected by radioimmunoassays. Autoantibodies, such as anti-Sm, Ro, La, and ribonucleoprotein (RNP), were assessed by enzyme-linked immunosorbent assays (ELISAs). Anti-nucleosome and anti-ribosomal P antibodies were assessed using immunoblot technique. Statistical analyses Statistical analyses were performed using the SPSS software (version 18.0 for Windows; SPSS Inc, Chicago, IL, USA). P values of
