Roberto Marini

Risk factors for amenorrhea in juvenile systemic lupus erythematosus (JSLE): a Brazilian multicentre cohort study

We evaluated the prevalence and clinical associations of amenorrhea in 298 female juvenile systemic lupus erythematosus (JSLE) patients (ACR criteria) followed in 12 Brazilian Paediatric Rheumatology centres. Amenorrhea was observed in 35 patients (11.7%) with a mean duration of 7.2 ± 3.6 months. The hormones were performed in 32/35 patients and none of them had FSH and LH levels above and estradiol below the normal range according to pubertal changes. JSLE patients with amenorrhea were younger (15.04 ± 2.5 versus 17.8 ± 3.1 years; P = 0.001), and had a shorter period of time between menarche and current age (3.4 ± 2.9 versus 6.7 ± 5.4 years; P = 0.001). Interestingly, the frequency, cumulative dose, number of pulses and duration of intravenous cyclophosphamide treatment were alike in patients with and without amenorrhea (P > 0.05). In contrast, patients with amenorrhea had significantly higher SLEDAI (P = 0.01) and SLICC/ACR-DI (P = 0.024) scores compared to those without this condition. Independent risk factors identified by multivariate analysis were higher SLEDAI (OR = 1.059; CI = 1.004—1.116; P = 0.034) and SLICC/ACR-DI (OR = 2.125; IC = 1.373—3.291; P = 0.001) scores. Our data suggest that in spite of immunosuppressive therapy, JSLE patients have an adequate ovarian follicular reserve and amenorrhea is particularly associated with disease activity and damage. Lupus (2007) 16, 531—536.

Focal transient lesions of the corpus callosum in systemic lupus erythematosus.

Focal lesions limited to the splenium of the corpus callosum are rare and little is known about their etiology. We describe three patients with systemic lupus erythematosus (SLE) that presented transient lesions of the corpus callosum. We reviewed three patients with SLE whose magnetic resonance imaging (MRI) results revealed focal lesions in the splenum of corpus callosum. The medical records, including clinical, serological, and treatment features, were reviewed to determine the etiology of these lesions. Of 115 patients who had MRI for research purposes, three patients with focal nonhemorrhagic lesions of the corpus callosum were identified. All patients had active SLE at the time of MRI. One patient had other findings on MRI, including cerebral venous thrombosis. On follow-up MRI, patients had an inactive disease and the corpus callosum lesions disappeared. A transient lesion in the splenium of corpus callosum seems to be a nonspecific endpoint of different disease processes leading to vasogenic edema. The complete and rapid reversibility in all cases with disease control is emphasized and any invasive diagnostic or therapeutic approach is discouraged.

Th1/Th2 cytokine profile in childhood-onset systemic lupus erythematosus

OBJECTIVE To determine the serum levels of Th1 (IL-12, IFN-γ,TNF-α) and Th2 (IL-5, IL-6 and IL-10) cytokines in childhood-onset SLE, first-degree relatives and healthy controls. To elucidate their association with disease activity, laboratory and treatment features. METHODS We included 60 consecutive childhood-onset SLE patients [median age 18 years (range 10-37)], 64 first-degree relatives [median 40 (range 28-52)] and 57 healthy [median age 19 years (range 6-30 years)] controls. Controls were age and sex-matched to SLE patients. SLE patients were assessed for clinical and laboratory SLE manifestations, disease activity (SLEDAI), damage (SDI) and current drug exposures. Mood and anxiety disorders were determined through Becks Depression (BDI) and Anxiety Inventory (BAI). Th1 (IL-12, IFN-γ,TNF-α) and Th2 (IL-5, IL-6 and IL-10) cytokines levels were measured by ELISA and compared by non-parametric tests. RESULTS Serum TNF-α (p=0.004), IL-6 (p=0.007) and IL-10 (p=0.03) levels were increased in childhood-onset SLE patients when compared to first-degree relatives and healthy controls. TNF-α levels were significantly increased in patients with active disease (p=0.014) and correlated directly with SLEDAI scores (r=0.39; p=0.002). IL-12 (p=0.042) and TNF-α (p=0.009) levels were significantly increased in patients with nephritis and TNF-α in patients with depression (p=0.001). No association between cytokine levels and SDI scores or medication was observed. CONCLUSION Th1 cytokines may play a role in the pathogenesis of neuropsychiatric and renal manifestations in childhood-onset SLE. The correlation with SLEDAI suggests that TNF-α may be a useful biomarker for disease activity in childhood-onset SLE, however longitudinal studies are necessary to determine if increase of this cytokine may predict flares in childhood-onset SLE.

Obesity and Cytokines in Childhood-Onset Systemic Lupus Erythematosus

Background. In systemic lupus erythematosus (SLE), atherosclerosis is attributed to traditional and lupus related risk factors, including metabolic syndrome (MetS), obesity, and inflammation. Objective. To evaluate the association between obesity, measures of body fat content, serum tumor necrosis factor alpha (TNF-α), and interleukin (IL)-6 and -10 levels in childhood-onset SLE (cSLE). Methods. We screened consecutive cSLE patients followed up in the Pediatric Rheumatology Outpatient Clinic of the State University of Campinas. cSLE patients were assessed for disease and damage. Obesity was definite as body mass index (BMI) ≥30 kg/m2. Serum TNF-α, IL-6, and IL-10 levels were measured by ELISA. Dual-energy X-ray absorptiometry was used to determine total fat mass, lean mass, and percent of body fat. Results. We included 52 cSLE patients and 52 controls. cSLE patients had higher serum TNF-α  (P = 0.004), IL-6 (P = 0.002), and IL-10 (P < 0.001) levels compared to controls. We observed higher serum TNF-α  (P = 0.036) levels in cSLE patients with obesity. An association between serum TNF-α levels and body fat percent (P = 0.046) and total fat mass on trunk region (P = 0.035) was observed. Conclusion. Serum TNF-α levels were associated with obesity and body fat content in cSLE. Our finding suggests that obesity may contribute to the increase of serum TNF-α levels in cSLE.

Prevalence and clinical significance of anti-ribosomal P antibody in childhood-onset systemic lupus erythematosus.

Objective: To investigate the prevalence of the anti-ribosomal P (anti-P) antibodies in childhood-onset systemic lupus erythematosus patients (cSLE), healthy controls and first degree relatives. To elucidate the association between anti-P and disease activity, laboratory and treatment features in cSLE patients. Methods: We included consecutive SLE patients with disease onset before 16 years. Controls were age- and sex-matched. SLE patients were assessed for clinical and laboratory SLE manifestations, disease activity (SLE Disease Activity Index (SLEDAI)), damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)) and current drug exposures. Mood disorders were determined through Becks Depression and Becks Anxiety Inventory. Anti-P measured by enzyme-linked immunosorbent assay. Results: We included 50 consecutive cSLE patients (mean age of 16.82 ± 3.46 years), 35 first degree relatives (mean age of 38.73 ± 3.89 years) and 20 health control (mean age of 18.3 ± 4.97 years). Anti-P was observed in 13 (26%) cSLE patients and in no first-degree relative (p < 0.01) or control (p < 0.01). Anti-P was more frequently observed in patients with anxiety (p < 0.002). No other clinical, laboratory or treatment features, including SLEDAI and SDI scores were associated with the presence of anti-P in cSLE patients. Conclusion: Anti-P is frequently observed in cSLE patients and was associated with the presence of anxiety in this cohort of cSLE.

Clinical and serological manifestations associated with interferon-α levels in childhood-onset systemic lupus erythematosus

OBJECTIVE: To determine the serum levels of interferon alpha in childhood-onset systemic lupus erythematosus patients, their first-degree relatives and healthy controls and to evaluate the associations between serum interferon alpha and disease activity, laboratory findings and treatment features. METHODS: We screened consecutive childhood-onset systemic lupus erythematosus patients in a longitudinal cohort at the pediatric rheumatology unit of the State University of Campinas between 2009 and 2010. All patients demonstrated disease onset before the age of 16. Disease status was assessed according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Interferon alpha levels were measured using an enzyme-linked immunoabsorbent assay. RESULTS: We included 57 childhood-onset systemic lupus erythematosus patients (mean age 17.33±4.50), 64 first-degree relatives (mean age 39.95±5.66), and 57 healthy (mean age 19.30±4.97) controls. Serum interferon alpha levels were significantly increased in childhood-onset systemic lupus erythematosus patients compared to their first-degree relatives and healthy controls. Interferon alpha levels were significantly increased in patients with positive dsDNA antibodies, patients with cutaneous vasculitis, patients with new malar rash and patients who were not receiving medication. Interferon alpha levels correlated with C3 levels and systemic lupus erythematosus Disease Activity Index scores. In addition, we observed an inverse correlation between patient age and interferon alpha levels. CONCLUSION: Interferon alpha may play a role in the pathogenesis of childhood-onset systemic lupus erythematosus, especially in cutaneous manifestations and dsDNA antibody formation. The observation that interferon alpha levels are increased in patients who are not taking medication should be investigated in longitudinal studies to determine whether elevated interferon alpha levels may predict systemic lupus erythematosus flares.

Features of 847 Childhood-Onset Systemic Lupus Erythematosus Patients in Three Age Groups at Diagnosis: A Brazilian Multicenter Study

To evaluate demographic data and clinical and laboratory features at disease diagnosis in 3 different age groups of childhood‐onset systemic lupus erythematosus (SLE): group A, early‐onset (<6 years); group B, school age (≥6 to <12 years); and group C, adolescent (≥12 to <18 years).

Prática de vacinação em crianças com doenças reumáticas

INTRODUCAO/OBJETIVOS: Avaliar a pratica clinica com relacao a verificacao do cartao vacinal e a indicacao de vacinas especificas em pacientes com doencas reumaticas pediatricas em uso de diferentes drogas, e evidenciar a possivel associacao entre frequencia de vacinacao e tempo de pratica clinica dos reumatologistas pediatricos do estado de Sao Paulo. MATERIAL E METODOS: Um questionario foi enviado para os reumatologistas pediatricos do Departamento de Reumatologia da Sociedade de Pediatra de Sao Paulo. Esse instrumento incluiu questoes sobre tempo de pratica em Reumatologia Pediatrica, vacinacao de pacientes com Lupus Eritematoso Sistemico Juvenil (LESJ), artrite idiopatica juvenil (AIJ), dermatomiosite juvenil (DMJ) e imunizacao de acordo com os tratamentos utilizados. RESULTADOS: Cartao de vacinacao foi visto por 100% dos profissionais na primeira consulta e por 36% anualmente. Vacinas de agentes vivos nao foram recomendadas para pacientes com LESJ, AIJ e DMJ em 44%, 64% e 48%, respectivamente. Os profissionais foram divididos em dois grupos: A ( 16 anos, n = 13). Nenhuma diferenca estatistica foi observada no uso de vacinas de agentes vivos e vacinas de agentes inativos ou componentes proteicos em relacao ao tratamento nos dois grupos (P > 0,05). Alem disso, os grupos foram similares em relacao a opiniao sobre a gravidade de imunossupressao em pacientes com LESJ, AIJ e DMJ com ou sem atividade e a terapeutica utilizada (P > 0,05). CONCLUSOES: A frequencia de vacinacao por reumatologistas pediatricos de Sao Paulo e baixa, especialmente apos a primeira consulta, e nao e influenciada pelo tempo de pratica profissional.

Anti-RO/SSA and anti-La/SSB antibodies: Association with mild lupus manifestations in 645 childhood-onset systemic lupus erythematosus

BACKGROUND To our knowledge there are no studies assessing anti-Ro/SSA and anti-La/SSB autoantibodies in a large population of childhood-systemic lupus erythematosus (cSLE) patients. METHODS This was a retrospective multicenter cohort study performed in 10 Pediatric Rheumatology services, São Paulo state, Brazil. Anti-Ro/SSA and anti-La/SSB antibodies were measured by enzyme linked immunosorbent assay (ELISA) in 645 cSLE patients. RESULTS Anti-Ro/SSA and anti-La/SSB antibodies were evidenced in 209/645 (32%) and 102/645 (16%) of cSLE patients, respectively. Analysis of cSLE patients with and without anti-Ro/SSA antibodies revealed higher frequencies of malar rash (79% vs. 71%, p=0.032), photosensitivity (73% vs. 65%, p=0.035), cutaneous vasculitis (43% vs. 35%, p=0.046) and musculoskeletal involvement (82% vs. 75%, p=0.046) in spite of long and comparable disease duration in both groups (4.25 vs. 4.58years, p=0.973). Secondary Sjögren syndrome was observed in only five patients with this antibody (2.5% vs. 0%, p=0.0035), two of them with concomitant anti-La/SSB. The presence of associated autoantibodies: anti-Sm (50% vs. 30%, p<0.0001), anti-RNP (39% vs. 21%, p<0.0001) and anti-ribossomal P protein (46% vs. 21%, p=0.002) was also significantly higher in patients with anti-Ro/SAA antibodies. Further evaluation of cSLE patients with the presence of anti-La/SSB antibodies compared to those without these autoantibodies showed that the frequency of alopecia (70% vs. 51%, p=0.0005), anti-Sm (59% vs. 31%, p<0.0001) and anti-RNP (42% vs. 23%, p<0.0001) were significantly higher in the former group. CONCLUSIONS Our large multicenter cohort study provided novel evidence in cSLE that anti-Ro/SSA and/or anti-La/SSB antibodies were associated with mild manifestations, particularly cutaneous and musculoskeletal. Secondary Sjögren syndrome was rarely observed in these patients, in spite of comparable frequencies of anti-Ro/SSA and/or anti-La/SSB reported for adult SLE.

Reduction of Cerebral and Corpus Callosum Volumes in Childhood-Onset Systemic Lupus Erythematosus: A Volumetric Magnetic Resonance Imaging Analysis.

There have been few studies in which the prevalence of cerebral atrophy in childhood‐onset systemic lupus erythematosus (SLE) was evaluated using magnetic resonance imaging (MRI) volumetric measurements. This study was undertaken to determine the prevalence of cerebral and corpus callosum atrophy in childhood‐onset SLE and to determine the possible relationships between atrophy and clinical, laboratory, and treatment features of the disease.