Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus

OBJECTIVE: To investigate potential differences between childhood-onset and adult-onset systemic lupus erythematosus (SLE). METHODS: An inception cohort with childhood-onset SLE (n = 67) was compared with an inception cohort with adult-onset SLE (n = 131), each of whom was diagnosed between 1990 and 1998 and followed up until February 1999. Prospective information included data on medications, laboratory markers, and disease activity and damage as measured by the SLE Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), respectively. RESULTS: Eighty-five percent of patients with childhood-onset SLE and 88% of patients with adult-onset SLE were female; the mean duration of followup was 3.2 and 3.5 years, respectively. On average, the children had more-active disease than did the adults at the time of diagnosis and during followup. There was a higher incidence of renal disease in those with childhood-onset SLE (78% versus 52% in adults; P = 0.0005), and the adjusted mean SLEDAI renal score was higher in the children than in the adults (2.37 versus 0.82; P < 0.0001). Treatment with steroids (97% versus 72%; P < 0.0001) and immunosuppressive drugs (66% versus 37%; P = 0.0001) was used significantly more often in children with SLE. Four adult patients with SLE, but none of the children, died during the followup. At the end of the followup, the mean SDI scores in those with childhood-onset SLE were higher than those with adult-onset SLE (1.70 versus 0.76; P = 0.008). CONCLUSION: Children with childhood-onset SLE have more active disease at presentation and over time than do adults with SLE, especially active renal disease. Compared with adults with SLE, children receive more intensive drug therapy and accrue more damage, often related to steroid toxicity.     

Antiribonucleoprotein antibodies in children with HIV infection: a comparative study with childhood-onset systemic lupus erythematosus

A number of clinical and laboratory features of HIV infection are found in systemic lupus erythematosus (SLE). The objective of this study was to analyze the presence of circulating antibodies to small nuclear ribonucleoproteins (snRNP) in both diseases. Sera from 44 HIV-infected children, from 22 patients with childhood-onset SLE, and from 50 healthy children were studied. Anti-snRNP antibodies were detected by ELISA using recombinant and affinity-purified nuclear antigens, by counterimmunoelectrophoresis (CIE), and by immunoblotting using extractable nuclear antigens. Results included the detection of anti-snRNP antibodies by ELISA in 30 HIV-infected patients (68.1%) and 19 SLE patients (86.3%). These antibodies were directed against U1-RNP (61.3% and 77.2%, respectively), Sm (29.5% and 54.5%, respectively), 60 kDa Ro/SS-A (47.7% and 50%, respectively), and La/SS-B proteins (18.1% and 9%, respectively). None of the HIV-infected children and 11 SLE patients (50%) showed anti-snRNP antibodies by CIE. None of the HIV-infected patients showed anti-70 kDa U1-RNP or anti-D-Sm antibodies by immunoblotting. No differences between the two groups were noted on the presence of nonprecipitating anti-snRNP antibodies. No such reactivities were observed among the normal sera tested. The authors concluded that nonprecipitating anti-snRNP antibodies in HIV-infected children are as frequent as in childhood-onset SLE. The significance of these antibodies is not clear at present. Although polyreactive and low-affinity antibodies and a mechanism of molecular mimicry may explain these results, a specific stimulation of B cells by nuclear antigens could not be excluded.     

Disease outcomes and ovarian function of childhood-onset systemic lupus erythematosus

The objective of this study was to determine the medical outcomes including the ovarian function childhood-onset SLE (cSLE). The medical records of all patients diagnosed with cSLE in the Greater Cincinnati area between 1981 and 2002 were reviewed. Patient interviews were performed to obtain additional information on current medication regimens, disease activity [SLE Disease Activity Index (SLEDAI-2k)], and damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)]. The occurence of premature ovarian failure (POF) and reduction of the ovarian reserve was assessed by timed gonadotropin levels. There were 77 patients (F : M = 70 : 7, 53% Caucasian, 45% African-American and 2% Asian) with a mean age at diagnosis of 14.6 years. Nine patients died (88.3% survival) during the mean follow-up of 7.1 years (standard deviation [SD] 5.6) and 88% of the patients continued to have active disease (SLEDAI-2k mean/SD: 6.6/6.7), with 42% of them having disease damage (SDI mean/SD: 1.62/2.1); Non-Caucasian patients had higher disease activity (mean SLEDAI-2k: 10 versus 3.4; P < 0.0001) and more disease damage (mean SDI : 2.1 versus 1.2; P < 0.02) than Caucasian patients. Cyclophosphamide was given to 47% of the patients during the course of their disease and associated with the presence of significantly reduced ovarian reserve (RR = 2.8; 95% CI: 1.7-4.8; P = 0.026). Patient mortality and disease damage with cSLE continue to be high. Although overt POF with cyclophosphamide exposure is rare, it is a risk factor for significantly decreased ovarian reserve cSLE.     

Headaches in patients with systemic lupus erythematosus: a comparative study

The incidence and nature of headaches in 85 systemic lupus erythematosus (SLE) patients attending an outpatient clinic were studied and compared to those experienced by 61 nurses. The two groups were similar in age, sex and ethnicity. Test-retest assessment of reliability gave both groups 95% confidence limits of 0.09-0.21. Thirty-two (38%) patients developed migrainous headaches and nine (10%) stress headaches with the onset of lupus. In the control group, four (6%) developed migraine and 40 (66%) developed stress headaches on commencing work. We could not document any association of headaches with flares of systemic disease, the ACA syndrome, Raynaud's phenomenon or increased SLEDAI score. We conclude that migrainous headaches are more common in lupus patients than healthy controls, but in an outpatient setting are not statistically associated with flares of systemic disease.     

Pulmonary involvement in patients with childhood-onset systemic lupus erythematosus

OBJECTIVE: Pulmonary involvement is a common finding in adults with systemic lupus erythematosus (SLE). The aim of this study was to investigate the frequency of pulmonary abnormalities in patients with childhood-onset SLE, with particular reference to interstitial lung disease (ILD), and to examine any association between pulmonary abnormalities and other disease-related variables. METHODS: A cohort of 60 Norwegian patients with childhood-onset SLE was examined in a cross-sectional study by high-resolution computed chest tomography (HRCT) and pulmonary function tests (PFT). Median disease duration was 11.2 years. Disease activity, cumulative organ damage and immunological markers were also assessed. RESULTS: Five patients (8%) had abnormal HRCT findings, including micronodules in four patients and bronchiectasis in one. None of the patients had radiographic evidence of ILD. PFT results were impaired in 37% of the patients, the most frequent pulmonary dysfunction was reduced carbon monoxide diffusing capacity (26%). HRCT findings, disease activity or serology did not correlate with PFTs. Reduced diffusion capacity was associated with smoking (p-value < 0.05). CONCLUSION: Lung function was moderately impaired, while the frequency of pulmonary parenchymal involvement was low. There was no radiographic evidence of ILD, which is an unexpected finding given the high frequencies reported in adult SLE patients assessed with HRCT. The results suggests that PFT values are often abnormal, but these are infrequently associated with development of ILD or other substantial parenchymal alterations in childhood-onset SLE, and do not require further HRCT investigation in asymptomatic patients.     

Uveitis in childhood-onset systemic lupus erythematosus patients: a multicenter survey

The aim of this study is to assess uveitis prevalence in a large cohort of childhood-onset systemic lupus erythematosus (cSLE) patients. A retrospective multicenter cohort study including 852 cSLE patients was performed in ten pediatric rheumatology centers (Brazilian cSLE group). An investigator meeting was held and all participants received database training. Uveitis was diagnosed through clinical assessment by the uveitis expert ophthalmologist of each center. Patients with and without uveitis were assessed for lupus clinical/laboratory features and treatments. Uveitis was observed in 7/852 cSLE patients (0.8%). Two of them had ocular complications: cataract and irreversible blindness in one patient and retinal ischemia with subsequent neovascularization and unilateral blindness in another. Uveitis was identified within the first 6 months of cSLE diagnosis in 6/7 patients (86%). Comparison of a subgroup of cSLE patients with (n = 7) and without uveitis (n = 73) and similar length of disease duration showed that patients with uveitis had increased SLEDAI-2K score (19 vs. 6; p < 0.01). In addition, fever (71 vs. 12%; p < 0.01), lymphadenopathy (29 vs. 1.4%; p = 0.02), arthritis (43 vs. 7%; p = 0.02), and use of intravenous methylprednisolone (71 vs. 22%; p = 0.01) were higher in cSLE patients with uveitis, as compared to those without this manifestation, respectively. Presence of fever was significantly associated with uveitis, independently of SLEDAI scores or use of intravenous methylprednisolone pulses, as shown by adjusted regression analysis (adjusted prevalence ratio 35.7, 95% CI 2.4–519.6; p < 0.01). Uveitis was a rare and initial manifestation of active cSLE patients. Early recognition is essential due to the possibility of irreversible blindness.     

Pregnancy in systemic lupus erythematosus

Issues concerning contraception, fertility, and pregnancy usually arise during a typical lupus patient's disease course. Pregnancy superimposed on established lupus may alter the course of the disease, and, conversely, lupus may affect the natural history of pregnancy. Two recently described autoantibody markers, anti-SSA (Ro) and anticardiolipin, have provided new insights concerning fetal risks in these patients. Furthermore, they should lead to improved understanding of mechanisms of tissue injury and to new ideas about therapeutic interventions and/or prevention of pregnancy complications.     

Pregnancy and systemic lupus erythematosus

Pregnancy is widely authorized in systemic lupus erythematosus (SLE). Fertility is similar in SLE and in the general population although the age of menarche seems higher. Some cases of sterility might be attributed to SLE because of autoimmune ovaritis or antiphospholipid antibodies (aPL). These antibodies might lead to endothelial activation and thrombosis by influencing homeostasis, complement activation, inhibition of protein C and annexin V. They might have a deleterious effect on embryonic implantation by adhesion to the trophoblast, inhibition of invasion and placentation and decreased hCG production. The most important part of sterility seems secondary to the use of cyclophosphamide and might be prevented by acetate leuprolide administration. Maternal morbidity seems correlated to SLE activity (controlled by pregnancy planning), hypertension, preeclampsia, Hemolysis, Elevated Liver Enzymes, Low Platelets (HELLP) syndrome, therapy and aPL. Hydroxychloroquine (HCQ) should be maintained throughout pregnancy. Aspirin is prescribed alone in patients with asymptomatic aPL and in addition to heparin if there is a history of thrombosis or fetal loss with aspirin. Fetal and neonatal morbidity correlate with prematurity, adverse effects or maternal steroid therapy and maternal anti-SSA antibodies with 1 to 2% risk of congenital atrioventricular block. Abnormal obstetrical echography-doppler examination is the best predictor of pregnancy outcome. Abnormal ombilical artery flow on the second trimester echodoppler examination and history of thrombophlebitis predict fetal or neonatal death. Abnormal uterine notch on the second trimester echodoppler examination predicts adverse pregnancy outcome. Except for the preventive therapy of congenital atrioventricular block, modalities of SLE pregnancy monitoring and therapy are now well established.     

Inactive disease and remission in childhood-onset systemic lupus erythematosus

Objective

To define inactive disease (ID) and clinical remission (CR) and to delineate variables that can be used to measure ID/CR in childhood‐onset systemic lupus erythematosus (cSLE).

Methods

Delphi questionnaires were sent to an international group of pediatric rheumatologists. Respondents provided information about variables to be used in future algorithms to measure ID/CR. The usefulness of these variables was assessed in 35 children with ID and 31 children with minimally active lupus (MAL).

Results

While ID reflects cSLE status at a specific point in time, CR requires the presence of ID for >6 months and considers treatment. There was consensus that patients in ID/CR can have <2 mild nonlimiting symptoms (i.e., fatigue, arthralgia, headaches, or myalgia) but not Raynaud's phenomenon, chest pain, or objective physical signs of cSLE; antinuclear antibody positivity and erythrocyte sedimentation rate elevation can be present. Complete blood count, renal function testing, and complement C3 all must be within the normal range. Based on consensus, only damage‐related laboratory or clinical findings of cSLE are permissible with ID. The above parameters were suitable to differentiate children with ID/CR from those with MAL (area under the receiver operating characteristic curve >0.85). Disease activity scores with or without the physician global assessment of disease activity and patient symptoms were well suited to differentiate children with ID from those with MAL.

Conclusion

Consensus has been reached on common definitions of ID/CR with cSLE and relevant patient characteristics with ID/CR. Further studies must assess the usefulness of the data‐driven candidate criteria for ID in cSLE.     

Long-term remission in three patients with childhood-onset systemic lupus erythematosus

Abstract

Three cases of childhood-onset systemic lupus erythematosus (childhood SLE) with long-term remission are reported. These cases were not complicated with collagen diseases and had no SLE disease activity index scores either 3 or 5 years after onset. We suggest that some patients with childhood SLE may be able to abandon the maintenance therapy, and that careful observation is needed for each individual case. Uniform remission criteria based on clinical trials are needed.     

Long-term remission in three patients with childhood-onset systemic lupus erythematosus

Three cases of childhood-onset systemic lupus erythematosus (childhood SLE) with long-term remission are reported. These cases were not complicated with collagen diseases and had no SLE disease activity index scores either 3 or 5 years after onset. We suggest that some patients with childhood SLE may be able to abandon the maintenance therapy, and that careful observation is needed for each individual case. Uniform remission criteria based on clinical trials are needed.     

Cost of treatment of childhood-onset systemic lupus erythematosus

OBJECTIVE: To determine the direct cost of care of children with childhood-onset systemic lupus erythematosus (cSLE), and to determine the direct cost per quality-adjusted life year (QALY) with cSLE. METHODS: Administrative databases from 2 large tertiary pediatric rheumatology centers in the United States were reviewed for all patients with cSLE (n = 119) diagnosed and regularly treated in these centers between January 2001 and April 2004. Health-related quality of life estimates for patients with cSLE (n = 297) reported in the literature were used to calculate QALYs based on global health ratings of the Child Health Questionnaire (range 0-100). RESULTS: Information on 3,184 patient-months of followup was included in the analysis. During a mean +/- SD followup of 27 +/- 11.8 months, the direct cost of care for the cohort amounted to $3,965,048, excluding outpatient medications. Irrespective of patient sex, the mean +/- SD cost of cSLE per month was $1,245 +/- $2,352, or approximately $14,944 per year. Inpatient and day hospital care accounted for 28% of the cost, laboratory testing accounted for 21%, inpatient/day-patient medication costs accounted for 13%, and dialysis accounted for 11%. Visits to the rheumatology clinic only contributed 9% to the direct cost of care. When including an estimated outpatient medication cost of $1,190, the direct cost of cSLE per QALY was $30,908. CONCLUSION: Children diagnosed with cSLE were found to have a considerable direct cost of care. The treatment of cSLE appears to be far more costly than that of adult SLE and juvenile idiopathic arthritis reported in the literature.     

Pregnancy in systemic lupus erythematosus: a retrospective study from a developing community

Little data exists from the developing world on pregnancy in systemic lupus erythematosus (SLE). A 10-year review of pregnancies in lupus patients was conducted at a tertiary hospital in a developing country. Forty-seven pregnancies in 31 patients were identified. Eleven (23%) booked after 20 weeks gestation. There were no maternal deaths; six (13%) mothers experienced flares—all mild. Twelve women developed preeclampsia of which one experienced an intrauterine death. One patient was diagnosed with lupus and nephritis during pregnancy. She required an abortion to control the disease. Another with active nephritis delivered a normal but premature infant despite cyclophosphamide therapy. There was only minor deterioration in renal function. There were 36 (77%) live births, 8 first trimester abortions, 2 elective abortions and 1 still birth. Fourteen (39%) of live births were premature, and five (14%) experienced intrauterine growth retardation (IUGR). Two live-born babies experienced neonatal heartblock, and one, a neonatal lupus rash. We discuss these finding in relation to risk factors and to results from the developed world.