Impact of follow-up visits on disease outcome in Chinese systemic lupus erythematosus

The objective of this study is to determine whether the frequency of visits would affect disease activity and disease damage in patients with systemic lupus erythematosus (SLE). We recruited 147 patients who met the 1997 American College of Rheumatology (ACR) criteria for SLE. Patients were divided into three groups based on follow-up frequency: ≤ 6 visits/year (group 1), 6–12 visits/year (group 2), and > 12 visits/year (group 3). Disease activity and organ damage were evaluated using the SLE disease activity index (SLEDAI) and Systemic Lupus International Collaborative Clinics (SLICC)/ACR criteria, respectively. Data on disease features, patient characteristics, and treatment were retrospectively reviewed. We found that the SLICC score was significantly lower in patients with > 12 visits/year (P = 0.008), while the SLEDAI score showed no significant difference. The age at symptom onset (32.68 ± 13.53) and the age at SLE diagnosis (33.32 ± 13.81) in group 3 were significantly older than those in the other two groups. In univariate regression analysis, the frequency of visits, the age at symptom onset, and the age at SLE diagnosis were found to be associated with the SLICC scores. Visit frequency has no impact on SLE disease activity, but may be associated with less disease damage, an important outcome.     

Kawasaki disease and juvenile systemic lupus erythematosus

Kawasaki disease (KD) is a common vasculitis in childhood. To the authors' knowledge, only one case of juvenile systemic lupus erythematosus (JSLE)-like onset mimicking KD and another case of KD and JSLE association have previously been described. However, the prevalence of this association of the two diseases was not reported. Therefore, over 27 consecutive years, 5419 patients were followed at the Pediatric Rheumatology Unit and 271 (5%) of them met the ACR classification criteria for JSLE. Two (0.7%) of them were female. These also had KD according to European League against Rheumatism / Paediatric Rheumatology European Society (EULAR/PReS) consensus criteria and are described in this report. One case was a 13-year-old who presented all six KD criteria. Echocardiogram showed pericardial effusion, dilatation and tortuosity of right and left coronary, and her symptoms promptly improved after treatment with intravenous immunoglobulin (IVIG). Lupus diagnosis was established a few days later. Another case was a 4-year-old who had also met all six KD criteria, with improvement after IVIG, and lupus diagnosis was made 1 year later. In conclusion, the frequency of the association between these two autoimmune diseases was rare. The occurrence of a second autoimmune systemic disease in a patient with a history of KD should also be considered. Furthermore, the initial presentation of lupus may mimic KD.     

Impact of C1q deficiency on the severity and outcome of childhood systemic lupus erythematosus

Objective: To delineate the clinical and laboratory features of systemic lupus erythematosus (SLE) in C1q‐deficient Saudi children and to compare them with sporadic SLE patients with respect to their clinical and laboratory features and disease outcome. Methods: The C1q‐deficient SLE patient group comprised 14 patients, while the comparative group comprised 11 patients selected by systemic sampling from our pediatric lupus clinic database. The two groups were compared with respect to: demographic, clinical and laboratory variables and outcome. Results: The C1q‐deficient SLE patients had an earlier age of onset of disease (P = 0.003); 43% had familial SLE and none of the comparative group had family histories of SLE. The two groups were comparable with respect to gender, disease duration and follow‐up. Scarring alopecia, discoid rash and nail changes were more frequent in the C1q‐deficient SLE patient group. However, there were no significant differences. The mean white blood cell count was lower (P = 0.04) and the level of anti‐Sm and anti‐phospholipid antibodies were higher (P = 0.04) in the C1q‐deficient SLE patients. Other variables did not show significant differences. Two patients from the C1q‐deficient SLE patient group died due to infection. All patients from the control group are alive. Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index mean was higher in the C1q‐deficient SLE patients group but was not statistically significant. Conclusion: C1q‐deficient SLE patients tend to be younger and more likely to have familial disease with severe cutaneous manifestations. The mortality among them is more frequent, which may reflect disease severity.     

Serum-soluble CXCL16 in juvenile systemic lupus erythematosus: a promising predictor of disease severity and lupus nephritis

Juvenile systemic lupus erythematosus (jSLE) is a multisystem autoimmune disease of unpredicted course and prognosis. Rates of organ involvement in SLE are higher in children, and overt lupus nephropathy is more often a presenting manifestation of SLE in children than adults. Inflammatory soluble chemokine CXC motif-ligand 16 (sCXCL16) is an important pathogenic mediator in inflammatory diseases as SLE. Herein, we aimed to evaluate serum level of sCXCL16 in jSLE patients in comparison to healthy controls and to correlate it with disease activity and extent of cutaneous and renal affection, to detect its possible role in disease pathogenesis. Serum level of sCXCL16 was determined by ELISA in 27 patients with jSLE (mean age 12.35 years ±?2.26 SD) in addition to 30 age- and sex-matched healthy controls and correlated with clinical and laboratory parameters in lupus group. Serum sCXCL16 was significantly higher in jSLE patients than controls (P ≤?0.001), and it correlated positively with SLE disease activity, severity of lupus nephritis, 24-h urinary protein, anti-dsDNA titre, blood pressure, and ESR, while it correlated negatively with serum C3 levels. Serum sCXCL16 was higher in jSLE patients with alopecia and malar erythema. Serum sCXCL16 might play a role in inflammatory pathogenesis of jSLE particularly in periods of disease activity. It might serve as a future useful laboratory test for detection of jSLE activity, renal insult, and its severity which might limit the need for invasive renal biopsies in such a delicate patient population.     

Pattern of neuropsychiatric manifestations and outcome in juvenile systemic lupus erythematosus

The aim of this study was to study the neuropsychiatric (NP) manifestations, diagnostic evaluation, treatment and outcome in juvenile systemic lupus erythematosus (SLE). We reviewed the charts of all children with SLE and evidence of NP manifestations as defined by the presence of at least one of the following: headache, cerebrovascular accident (CVA), chorea, seizure, papilledema, and psychiatric or spinal cord manifestations. Out of 90 children with SLE, 20 (16 female) had NP manifestations. The mean age at onset was 8.8 years. The mean period between onset of SLE and NP manifestations was 10.2 months. NP manifestations were the presenting feature in 3 patients. Eleven patients had headache, 10 had psychiatric manifestations, 10 had seizure and 6 had CVA. Coma was seen in 5 patients, chorea in 4, transverse myelitis in 2 and papilledema in 2. Anticardolipin antibodies were high in 12 patients. Five patients had an abnormal CSF study. Nine patients had EEG abnormalities and 13 showed MRI abnormalities. All patients received oral prednisone and 17 were treated with IVMP and immunosuppressive therapy (cyclophosphamide or azathioprine); 85% of our patients recovered completely, but 15% had persistent NP sequelae; 10% died from severe infection. In conclusion, NP involvement in juvenile SLE is common. However, early diagnosis and early treatment with adjunctive intravenous pulse cyclophosphamide may improve the outcome.Abbreviations CVA Cerebrovascular accident - IVMP Intravenous methylprednisolone - NP Neuropsychiatric - SLE Systemic lupus erythematosus     

Impact of antiphospholipid syndrome on disease characteristics and outcome in patients with systemic lupus erythematosus

Aim of the workTo assess the impact of antiphospholipid syndrome (APS) on systemic lupus erythematosus (SLE) clinical characteristics and disease outcome.Patients and methods216 SLE patients were classified according to the presence of APS into: SLE group (n = 109) and SLE-APS (n = 107). Evaluation of clinical, laboratory tests, immunological tests, SLE disease activity index 2000 (SLEDAI-2 K) and SLE damage index (SDI) were done.ResultsThe 216 patients mean age was 32.1 ± 8.4 years and the F:M was 8.4:1. There was a significantly higher frequency of abortion, neurological and cardiac manifestations (p < 0.001, p = 0.008, p = 0.016 respectively) in SLE-APS group. The SDI was significantly higher in SLE-APS patients (p < 0.001) with special attention to the presence of cerebrovascular accident (CVA) (p = 0.01), pulmonary hypertension (p = 0.04), cardiomyopathy (p = 0.034) and venous thrombosis (p < 0.0001). The frequency of thrombosis and active SLEDAI-2 K visits were significantly related to higher damage in SLE-APS (p < 0.001 and p < 0.001 respectively). Damage in SLE group was associated with hypocomplementemia (p = 0.015) and thrombosis (p = 0.049). Factors associated with damage in all SLE patients were male gender (p = 0.024), serositis (p = 0.02), neurological involvement (p < 0.001), thrombotic events (p < 0.001), cumulative doses of oral (p = 0.02) and pulse (p = 0.004) steroids and frequency of cyclophosphamide (CYC) use (p = 0.003). Predictors of damage included male gender, APS, neurological manifestations, use of steroids and CYC (p = 0.045, OR = 8.5; p < 0.0001, OR = 4.3; p = 0.001, OR = 6.3; p = 0.047, OR = 1.03; p = 0.005, OR = 2.96, respectively).ConclusionAPS adversely affect SLE disease course with prominent impact on end organ damage especially cerebral, cardiopulmonary and vascular events denoting the need for strict control of disease activity and early diagnosis.     

Superoxide release in juvenile systemic lupus erythematosus

The objective of this study was to analyze the un-stimulated and stimulated release of superoxide anion (O₂ ^?) by granulocytes and monocytes in juvenile systemic lupus erythematosus (jSLE). The un-stimulated and phorbol myristate acetate (PMA, 30 nM)-induced O₂ ^?by granulocytes and monocytes were determined in six different times of incubation in patients with 23 jSLE and 28 controls. The analysis compared the jSLE group, which was classified into two subgroups by SLEDAI in one inactive subgroup (score <3) (n?=?13 patients) and one active subgroup (score ≥3) (n?=?10 patients) to the same control group. At time of blood withdrawal, 13 (56.52%) had inactive and 10 (43.47%) patients had active SLE. jSLE patients’ granulocytes and monocytes had always a lower un-stimulated O₂ ^? production when compared to controls. Stimulated granulocytes had an increased O₂ ^? production at baseline followed by a significant lower production at 60?min in jSLE when compared to controls. Stimulated monocytes had a similar O₂ ^? production among patients with jSLE and controls. The results suggest a defect in phagocytic function in jSLE. The significant higher release of O₂ ^? in the assays of the stimulated granulocytes, in the initial instances, the so-called respiratory burst, could be attributed to the inflammatory state of phagocytes.     

Bone status in juvenile systemic lupus erythematosus

Osteoporosis is a well-recognized major health problem in adult patients with systemic lupus erythematosus (SLE). Children and adolescents with SLE, however are at even higher risk of developing osteoporosis later in life, since they develop the disease before achieving peak bone mass, which serves as a 'bone bank' for the rest of life. There is still a paucity of studies on bone mass in pediatric SLE, but those studies available provide evidence of reduced bone mass in this age group. A frequency of osteopenia of 40% measured by dual energy X-ray absorptiometry at one or more skeletal sites has been reported, and the lumbar spine is most seriously affected. Peak bone mass seems to be lower in childhood-onset SLE patients compared to healthy controls, and there are no signs of catch-up of bone mass in young adult patients with a history of pediatric SLE. Glucocorticoid therapy has been found to have a major negative effect on bone mass in these patients, thus the importance of keeping corticosteroid doses down to the lowest possible dose whenever possible. Interestingly, studies of oral alendronate therapy in children with rheumatic childhood diseases have shown promising results with increases of 15-33% during one year of treatment with no major side effects reported. Finally, there is a hope that new biologic therapies, which are more specific and steroid-sparing, will also have a beneficial effect on bone health in SLE in the future.     

Musculoskeletal sonography in juvenile systemic lupus erythematosus

Objective

To demonstrate the role of sonography in depicting periarticular changes in juvenile systemic lupus erythematosus (SLE) and to find out whether certain tendons in juvenile SLE patients were different from those of healthy controls.

Methods

Thirty juvenile SLE patients (27 female, 3 male) were recruited for this study. Sonographic evaluations were performed in the knee, ankle, elbow, wrist, and metacarpophalangeal (MCP) joints on the nondominant sides of the individuals. For comparison, 32 healthy volunteers were included as a control group.

Results

Knee effusion was observed more frequently in the juvenile SLE group compared with the control group (P = 0.00). When tendon thickness measurements were compared between the groups, flexor and extensor tendons of the third finger (at MCP joint level) of juvenile SLE patients were found to be thinner (P = 0.04 and P = 0.03, respectively). Tendon thickness values did not correlate with disease duration or SLE disease activity index scores (P > 0.05).

Conclusion

The main findings of our study were relevant with 1) increased involvement of the knee, ankle, hand extensor tendons, wrist, elbow, and hand flexor tendons (in decreasing order of frequencies) in juvenile SLE, and 2) decreased extensor/flexor tendon thicknesses in the hands of juvenile SLE patients. Physicians should be aware of the potentially disabling scenario of tendon pathologies. Defining the extent of joint and tendon pathologies in juvenile SLE may guide us in the management of the disease.     

Outcome in juvenile onset systemic lupus erythematosus

PURPOSE OF REVIEW: Over the past 2 decades, there has been a marked improvement in survival among patients with juvenile-onset systemic lupus erythematosus. As a result of the increased life expectancy, children and adolescents with systemic lupus erythematosus are now faced with considerable morbidity resulting from sequelae of disease activity, side effects of medications, and comorbid conditions. This morbidity affects physical and psychosocial well-being. Therefore, the need is increasing for monitoring the development of irreversible organ damage and the effect of the disease and its treatment on daily life. This review summarizes the recent advances in the investigation on survival, accumulated damage, and health-related quality of life in patients with juvenile-onset systemic lupus erythematosus. RECENT FINDINGS: The 5-year survival rate of patients with juvenile-onset systemic lupus erythematosus approaches 100%, and the 10-year survival rate is close to 90%. The development of cumulative organ damage has been observed in 50-60% of patients. Children and adolescents with systemic lupus erythematosus have been found to have poorer health-related quality of life, particularly in the physical domain, and lower socioeconomic achievements than their healthy peers. SUMMARY: The prolongation of the life span of patients with juvenile-onset systemic lupus erythematosus has been accompanied by a substantial risk of damage accumulation and has not been paralleled by an improvement in health-related quality of life. This problem highlights the need of measuring cumulative organ damage and health-related quality of life in the long-term follow-up of patients with juvenile-onset systemic lupus erythematosus and of designing new treatments and treatment strategies that are aimed not only at improving control of disease activity but also at minimizing the development of nonreversible damage.     

Preliminary core sets of measures for disease activity and damage assessment in juvenile systemic lupus erythematosus and juvenile dermatomyositis

OBJECTIVE: To identify preliminary core sets of outcome variables for disease activity and damage assessment in juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM). METHODS: Two questionnaire surveys were mailed to 267 physicians from 46 different countries asking each member to select and rank the response variables used when assessing clinical response in patients with JSLE or JDM. Next, 40 paediatric rheumatologists from 34 countries met and, using the nominal group technique, selected the domains to be included in the disease activity and damage core sets for JSLE and JDM. RESULTS: A total of 41 response variables for JSLE and 37 response variables for JDM were selected and ranked through the questionnaire surveys. In the consensus conference, domains selected for both JSLE and JDM activity or damage core sets included the physician and parent/patient subjective assessments and a global score tool. Domains specific for JSLE activity were the immunological tests and the kidney function parameters. Concerning JDM, functional ability and muscle strength assessments were indicated for both activity and damage core sets, whereas serum muscle enzymes were included only in the activity core set. A specific paediatric domain called 'growth and development' was introduced in the disease damage core set for both diseases and the evaluation of health-related quality of life was advised in order to capture the influence of the disease on the patient lifestyle. CONCLUSIONS: We developed preliminary core sets of measures for disease activity and damage assessment in JSLE and JDM. The prospective validation of the core sets is in progress.     

Cardio-pulmonary involvement in juvenile systemic lupus erythematosus

Cardio-pulmonary manifestations of systemic lupus erythematosus (SLE) are well recognized in adults. We report the occurrence of clinically significant cardio-pulmonary disease in a cohort of predominantly Caucasian children with SLE. All children with SLE attending the Royal Liverpool Children's NHS Trust between 1995 and 2003 were reviewed. Of 29 children with SLE, 27 (93%) were Caucasian. Nine (31%) had cardio-respiratory complications: cardiac only (n = 1); respiratory only (n = 4); both cardiac and respiratory manifestations (n = 4). Median (range) duration of follow-up of affected children: four years (six months to 11 years). Six out of eight (75%) presented with respiratory complications before SLE was diagnosed. Three children had pericardial effusions, one requiring pericardiocentesis for tamponade. One had cardiac conduction defects and another significant pulmonary hypertension. Respiratory complications comprised: interstitial lung disease (n = 4), with two showing evidence of pulmonary fibrosis; pleural effusions (n = 2), pulmonary haemorrhage (n = 1) and lupus pneumonitis (n = 1). Disease course was complicated by CMV infection in one child. Lung biopsy was performed in five cases. Seven were treated with cyclophosphamide with significant improvement in symptoms/lung function. Of this predominantly Caucasian paediatric cohort with SLE, 31% had significant cardio-pulmonary involvement. All children with SLE should have regular monitoring of their cardio-respiratory status.     

Anti-nucleosome antibodies may predict lupus nephritis and severity of disease in systemic lupus erythematosus

Background/ObjectiveDetection of anti-nucleosome antibodies in patients with systemic lupus erythematosus (SLE) has been well established and it is claimed that their presence is associated with disease activity. The objective of this study is to determine the diagnostic value of anti-nucleosome antibodies in the assessment of lupus nephritis and clinically active SLE.MethodsThe anti-nucleosome antibodies were evaluated in the serum of 200 Tunisian SLE patients at disease onset by a sensitive immunodot assay. Serum samples from each patient were also tested for ANA and anti-ds DNA antibody by IIF on Hep 2 cells and Crithidia luciliae respectively. During the follow-up, the patients were regularly monitored for clinical parameters. Global SLE activity was measured by the European Consensus Lupus Activity Measurement (ECLAM).ResultsThe prevalence of anti-nucleosome and anti-dsDNA antibodies was 69% and 63.5% respectively. Anti-nucleosome antibodies were found to be 30.1% positive in SLE patients lacking anti-dsDNA antibody. 79.5% patients had active SLE at the first clinical examination. Anti-nucleosome antibodies were more sensitive than anti-dsDNA antibodies to detect active SLE (78% vs. 71.7%, P =0.19). 52.5% of SLE patients had renal involvement. Among these patients, the rate of anti-nucleosome positivity and anti-dsDNA were 77.1% and 67.6% respectively. The positivity of anti-nucleosome antibodies was significantly higher in patients with renal disease than the subjects without renal disease (P = 0.009). Anti-nucleosome and anti-ds DNA antibodies were significantly correlated with disease activity (P < 0.001 and P < 0.001 respectively).ConclusionAnti-nucleosome antibody reactivity may be a useful marker in the diagnosis and assessment of active SLE.     

Gastrointestinal system manifestations in juvenile systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease which may involve gastrointestinal system (GIS). The aim of this study was to present GIS manifestations of pediatric SLE patients. The medical files of 69 children with SLE followed between January 2011 and January 2016 were reviewed. All fulfilled the Systemic Lupus International Collaborating Clinics criteria. All patients (≤18 years of age) with GIS manifestations were included. GIS manifestations were observed in 19 (27.5%) out of 69 SLE patients and present at the time of SLE diagnosis in 13 (68.4%). The GIS manifestations due to SLE were autoimmune hepatitis (AIH) (n = 8) and lupus enteritis (n = 1). Manifestations associated with SLE were hepatomegaly and hypertransaminasemia due to macrophage activation syndrome (MAS) (n = 3) and hepatic steatosis (n = 1). GIS manifestations as a result of the adverse events of drugs were as follows: toxic hepatitis (n = 3; associated with methotrexate and nonsteroidal anti-inflammatory drugs in one, methotrexate in another, and azathioprine in another patient), azathioprine-induced cholestatic hepatitis (n = 1), and gastritis associated with corticosteroid (n = 1). In one patient, acute appendicitis occurred as a coincidence. In this study, one of every five pediatric SLE patients had GIS-related manifestations. GIS involvement may occur as an initial manifestation of the disease.