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The objective is to perform a multimodal ophthalmological evaluation, including optical coherence angiography (OCTA), asymptomatic APS secondary to SLE (APS/SLE), and compare to SLE patients and control group (CG). We performed a complete structural/functional ophthalmological evaluation using OCTA/microperimetry exam in all participants. One hundred fifty eyes/75 asymptomatic subjects [APS/SLE (n = 25), SLE (n = 25), and CG (n = 25)] were included. Ophthalmologic abnormalities occurred in 9 (36%) APS/SLE, 11 (44%) SLE, and none of CG (p < 0.001). The most common retinal finding was Drusen-like deposits (DLDs) exclusively in APS/SLE and SLE (16% vs. 24%, p = 0.75) whereas severe changes occurred solely in APS/SLE [2 paracentral acute middle maculopathy (PAMM) and 1 homonymous quadrantanopsia]. A trend of higher frequency of antiphospholipid antibody (aPL) triple positivity (100% vs. 16%, p = 0.05) and higher mean values of adjusted Global Antiphospholipid Syndrome Score (aGAPSS) (14 ± 0 vs. 9.69 ± 3.44, p = 0.09) was observed in APS/SLE with PAMM vs. those without this complication. We identified that ophthalmologic retinal abnormalities occurred in more than 1/4 of asymptomatic APS/SLE and SLE. DLDs are the most frequent with similar frequencies in both conditions whereas PAMM occurred exclusively in APS/SLE patients. The possible association of the latter condition with aPL triple positivity and high aGAPSS suggests these two conditions may underlie the retinal maculopathy. Our findings in asymptomatic patients reinforce the need for early surveillance in these patients. Key Points • Retinal abnormalities occur in more than 1/4 of asymptomatic APS/SLE and SLE patients. • The occurrence of PAMM is possibly associated with APS and DLDs with SLE. • Presence of aPL triple positivity and high aGAPSS seem to be risk factors for PAMM., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

To assess the rheumatologists' knowledge and willingness to prescribe physical activity, we conducted a nationwide survey. All adult and paediatric rheumatologist members of the Brazilian Rheumatology Society were invited to fulfil a questionnaire on their knowledge and willingness to promote physical activity. Four hundred twenty-eight rheumatologists participated in the survey, representing approximately 25% of the society's members. Forty-five percent of the rheumatologists reported having had training to prescribe physical activity, and 68% believe that physical activity is a part of patients' treatment. Most reported assessing physical activity levels (86%) and recommending physical activity (98%) always or most of the time. However, 48% do not know the minimum physical activity recommendations for health maintenance, nor do they know how much vigorous activity should be done in replacement of moderate activity. In addition, only 20% are aware of physical activity recommendation for paediatric patients, whereas 31% know that very light-intensity physical activity promotes health-related beneficial effects. Year of graduation, having been trained on physical activity prescription, and regularly recommending physical activity to patients did not associate with the overall score of correct answers (OR: 1.00 [0.99, 1.02], p = 0.391; OR: 0.99 [0.69, 1.44], p = 983; OR: 0.90 [0.61, 1.32], p = 0.576; respectively). Rheumatologists are highly willing to promote physical activity, but major gaps in their knowledge were identified. Given the widespread recognition of physical activity as a key element on the management of rheumatic patients, these data hint to the need of incorporating physical activity in the rheumatologist' training. Key Points • This survey showed that rheumatologists are highly prone to promote physical activity. • However, rheumatologists have major gaps in knowledge of physical activity. • Adding physical activity to rheumatologist's training programs is key to improve physical activity promotion.

Objective: To evaluate the influence of ethnicity in presentation of childhood-onset systemic lupus erythematosus (cSLE) patients., Methods: This multicenter study included cSLE patients (American College of Rheumatology criteria) followed in 27 Pediatric Rheumatology services of Brazil. Ethnicities were classified in four groups according to the parents' and all four grandparents' self-reported ethnicity. The statistical analysis was performed using the Bonferroni's correction (p < 0.0027)., Results: According to ethnic groups, 1537 cSLE patients were classified in Caucasian (n = 786), African-Latin American (n = 526), Asian (n = 8), and others/unknown (n = 217). Comparisons between 1312 African-Latin American and Caucasian revealed similar median age at cSLE diagnosis [12.2(2.6-18) vs. 12.1(0.3-18) years, p = 0.234], time interval to diagnosis [0.25(0-12) vs. 0.3(0-10) years, p = 0.034], and SLEDAI-2K score [14(0-55) vs. 14(0-63), p = 0.781] in both groups. The mean number of diagnostic criteria according to SLICC (6.47 ± 1.911 vs. 5.81 ± 1.631, p < 0.0001) and frequencies of maculopapular lupus rash (8% vs. 3%, p < 0.0001), palate oral ulcers (17% vs. 11%, p = 0.001), tongue oral ulcers (4% vs. 1%, p = 0.001), and nonscarring alopecia (29% vs. 16%, p < 0.0001) were significantly higher in African-Latin American, whereas malar rash (45% vs. 58%, p < 0.0001) was more frequent in Caucasian. The presence of anti-phospholipid antibody (23% vs. 12%, p < 0.0001), low complement levels (58% vs. 41%, p < 0.0001), and isolated direct Coombs test (10% vs. 5%, p = 0.001) was also significantly higher in the former group., Conclusions: Our study demonstrated that disease presentation severity of African-Latin American cSLE patients is comparable with Caucasian. Mucocutaneous manifestations and autoantibodies profile were the only distinctive features of the former group. The unique mixed background of Brazilian patients probably minimized race diversity spectrum of these patients. Key Points • Our study demonstrated that disease presentation severity of African-Latin American cSLE patients is comparable with Caucasian. • Mucocutaneous manifestations and autoantibodies profile were the only distinctive features of African-Latin American cSLE patients. • African-Latin American cSLE patients had more often anti-phospholipid antibodies and hypocomplementemia. • The unique mixed background of Brazilian patients probably minimized race diversity spectrum of these patients.

Background/objective: Recent studies observed an association between increased serum uric acid (SUA) levels and renal damage in lupus. However, the predictive value of UA for the development of long-term renal dysfunction in lupus nephritis (LN) is still unknown. The aim of this study was to evaluate if SUA may be a predictor of long-term renal outcome in LN., Methods: Eighty biopsy-proven LN patients > 7 years of follow-up were selected. SUA levels were measured in sera stored at - 70 °C. All patients had serum stored from LN baseline, and 32 also had stored serum from 6 and 12 months after LN. Renal outcome was addressed after 7 years of follow-up to determine if SUA could be a predictor of long-term renal outcome. A good long-term renal outcome in 7 years was defined as a creatinine clearance (CrCl) ≥ 90.0 mL/min/1.73 m 2 , and poor if CrCl < 90 mL/min/1.73 m 2 . Patients were divided in two groups according to the renal outcome to assess whether SUA levels at different time points of follow-up could differentiate such groups. An ROC curve was plotted to assess accuracy., Results: SUA levels at baseline and 6 months were not able to differentiate good from poor long-term renal outcomes in LN (respectively p = 0.37, p = 0.28), but at 12 months (p = 0.02), they could clearly differentiate the two groups. ROC curve (12 months) accuracy was 0.76. SUA cutoff was 6.05 mg/dL (sensitivity = 0.67, specificity = 0.89, positive predictive value = 0.85, negative predictive value = 0.73)., Conclusion: SUA levels < 6.05 mg/dL at 12 months of follow-up is a predictor of good long-term renal outcome in lupus nephritis., Key Points: • Previous studies reported an association between increased serum uric acid level and short-term renal damage in lupus patients. • The predictive value of serum uric acid for the development of long-term renal dysfunction in lupus nephritis was never assessed. • At 12 months of follow-up serum uric acid clearly differentiated good from poor long-term renal outcome in lupus nephritis. • SUA level < 6.05 mg/dL at 12 months of follow-up was a predictor of good long-term renal outcome in lupus nephritis.

To assess epidemiology and management practices of Latin America Pediatric Rheumatologists (LAPR) about childhood-onset systemic lupus erythematosus (cSLE). A cross-sectional study was performed in 288 LAPR PANLAR members based on online survey about cSLE practices. The response rate of web-based survey by LAPR was 170/288(59%) and the majority worked in university hospitals (63%). The ACR and/or SLICC classification criteria (99%) and disease activity tools (97%) were almost universally used by LAPR, whereas damage index (70%) and CHAQ (58%) instruments were less frequently used. Laboratory exams, diagnostic imaging, and biopsies were generally available (> 75%), however low availability for densitometry (66%). Drug access was excellent for the most common prescribed medications (> 75%), except for belimumab (11%). Emerging mosquito-borne diseases were also reported: dengue (20%), chikungunya (11%), and Zika (8%). Groups were further divided in two, according to the median number of cSLE patients followed by LAPR in the last year: groups A and B (≥ 25 and < 25, respectively). Frequencies of condom in combination with other contraceptive methods were significantly higher in group A than B (p = 0.01). The frequencies of reported pregnancy (p < 0.001) and non-adherence to therapy were significantly higher in group A (p = 0.023). Alcohol intake (p = 0.004) and illicit drug use (p = 0.007) were also reported more frequently by LAPR of group A in at least one cSLE patient. This first large web-based survey demonstrated an overall excellent access for diagnosis and therapy by LAPR, probably related to their high rate of practices in tertiary care of university hospitals. Adherence to therapy, pregnancy, and substance abuse was identified as major challenges in this population, particularly in larger centers.

To assess prospectively luteinized unruptured follicle (LUF) syndrome in juvenile idiopathic arthritis (JIA) patients with and without non-steroidal anti-inflammatory drugs (NSAIDs) and healthy controls. Twenty-three adolescent and young adult female JIA patients (ILAR criteria) and 11 female healthy subjects were studied by pelvic ultrasound monitoring for follicular development and ovulation in one menstrual cycle. LUF syndrome was prospectively investigated by pelvic ultrasound with a dominant ovarian follicle without signs of follicular rupture, with elevation of serum progesterone in the luteal phase of the menstrual cycle and luteinizing hormone (LH) detected in the urine. Comparison between JIA patients with (n = 8) vs. without NSAIDs (n = 15) and healthy controls (n = 11) revealed that LUF syndrome was significantly higher in the former group (2 (25%) vs. 0% vs. 0%, p = 0.049). These two patients with LUF syndrome had normal menstrual cycles without reduced ovarian reserve, and they were under naproxen 500 mg bid during the menstrual cycle. Disease duration was comparable in JIA with and without NSAIDs [19.8 (4.4-25) vs. 13 (3.1-33) years, p = 0.232]. Further comparison between JIA patients with and without NSAIDs and healthy controls showed similar mean anti-Müllerian hormone levels (p = 0.909), estradiol (p = 0.436), FSH (p = 0.662), LH (p = 0.686), and mean antral follicle count (p = 0.240) and ovarian volume (p = 0.363). No differences were evidenced in three groups regarding Caucasian race, body mass index, duration, and length of menstrual cycles (p > 0.05). This is the first study to identify that JIA patients have a high frequency of LUF without impaired ovarian reserve. Future prospective studies are necessary to determine if chronic/continuous use of NSAIDs in JIA will have an impact in these patients' fertility.

Uric acid has been recognised as a potential marker of endothelial dysfunction and kidney disease but there are scarce data about its importance in systemic lupus erythematosus (SLE) nephritis. This study aimed to evaluate serum uric acid (UA) levels in lupus nephritis (LN), by comparing SLE patients with normal renal function, with and without nephritis. Forty-six female SLE patients were consecutively selected and divided in two groups according to renal activity at the evaluation: presence of a recently diagnosed lupus nephritis (LN+, n = 18) and absence of lupus nephritis (LN-, n = 28). Age-matched healthy women were selected (CONTROL, n = 28). Patients with gout, creatinine clearance lower than 80 ml/min and use of drugs that interfere in UA were excluded. Laboratory and clinical data were analysed by appropriate tests. A multivariate analysis was performed, and a receiver operating characteristic (ROC) curve was plotted, and the area under the curve was calculated to assess the diagnostic strength of UA in LN. The mean age was similar among LN+, LN- and CONTROL groups (32.44 ± 6.09 vs. 30.68 ± 5.36 vs. 30.86 ± 5.00 years, p = 0.52). UA was significantly higher in LN+ compared to LN- (5.54 ± 1.67 vs. 3.65 ± 1.090 mg/dL, p < 0.001) and CONTROL (5.54 ± 1.67 vs. 3.92 ± 0.95 mg/dL p < 0.001). Multivariate analysis confirmed that high UA was an independent variable related to LN (p < 0.001). The cut-off value for UA using the ROC curve was 4.47 mg/dL (AUC 0.86, p = 0.00004, CI 95% 0.75-0.96). Lupus nephritis was associated with higher UA. Hyperuricemia as a predictor of renal damage in SLE needs to be evaluated in further studies.

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.

The impact of juvenile idiopathic arthritis (JIA) in periodontal diseases is controversial probably due to gender and age heterogeneity. We therefore evaluated a homogeneous female post-pubertal JIA population for these conditions. Thirty-five JIA patients and 35 gender/age comparable healthy controls were evaluated according to demographic data, complete periodontal evaluation, fasting lipoproteins, and anti-lipoprotein lipase antibodies. JIA scores, laboratorial tests, X-rays, and treatment were also assessed. Current age was similar in JIA patients and controls (11.90 ± 2.0 vs. 12.50 ± 3.0 years, p = 0.289). Complete periodontal assessments revealed that gingival index, dental plaque, gingival bleeding, and clinical dental attachment indices were alike in JIA patients and controls (p > 0.05), except for gingival enlargement in former group (p < 0.0001). Further analysis of patients with and without gingivitis revealed that cyclosporine use was more often observed in JIA patients with gingivitis (37 vs. 0%, p = 0.01), whereas no differences were evidenced in demographic, JIA scores, inflammatory markers, and lipid profile in both groups. Of note, two parameters of periodontal assessment were correlated with JIA scores [gingival index (GI) and Childhood Health Assessment Questionnaire (CHAQ) (r s  = +0.402, p = 0.020)] and plaque index (PI) and visual analog scale (VAS) physician (r s  = +0.430, p = 0.013). In addition, evaluation of dental assessment demonstrated that JIA activity scores had positive correlation with decayed, missing, and filled teeth (DMF-T) and junvenile athritis disease activity score (JADAS) (r s  = +0.364,p = 0.037), VAS physician (r s  = +0.401,p = 0.021) and VAS patient (r s  = +0.364,p = 0.037). We demonstrated, using rigorous criteria, that periodontal and dental condition in JIA is similar to controls. In spite of that, the finding of a correlation with disease parameters provides additional evidence that increased activity and reduced functional ability underlies the deleterious effect of JIA in oral health.

The objectives of this study are to assess the frequency of chronic arthritis and compare the clinical and laboratory features in a large population of childhood-onset systemic lupus erythematosus (cSLE) and adult-onset (aSLE) patients. This historical study evaluated 336 cSLE and 1830 aSLE patients. Chronic arthritis was defined as synovitis of at least 6 weeks of duration. Rhupus was characterised as the association of SLE and chronic inflammatory arthritis with erosion and positive rheumatoid factor. Jaccoud's arthropathy is a non-erosive subluxation leading to severe deformity of the hands and feet. Data were compared using Student's t test or the Mann-Whitney test for continuous variables. For categorical variables, differences were assessed by Fisher's exact test and Pearson chi-square. Frequencies of chronic arthritis were similar in cSLE and aSLE (2.4 vs. 3.8%, p = 0.261). The median time from disease onset to appearance of chronic arthritis was shorter in cSLE (0 vs. 10 years, p < 0.001), and the median of age at chronic arthritis diagnosis was [10.8 (4.2-14.6) vs. 40 (21-67), p < 0.001]. The children presented with more chronic polyarthritis than the adults (75 vs. 32%, p = 0.024), a higher median number of joints with arthritis [8.5 (1-18) vs. 3 (1-9), p = 0.017] and a higher number of joints with limitation [1.5(0-24) vs. 0(0-4), p = 0.004]. The chronic arthritis diagnosis frequencies of hepatomegaly (25 vs. 0%, p = 0.009), splenomegaly (25 vs. 0%, p = 0.009), pericarditis (25 vs. 0%, p = 0.009), nephritis (37 vs. 3% , p = 0.006), haematuria (37 vs. 1.4%, p = 0.002), lupus anticoagulant (40 vs. 1.6%, p = 0.012), anticardiolipin IgM (40 vs. 1.5%, p = 0.012) and median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) [10.5(1-20) vs. 6(4-16), p = 0.029] were higher in cSLE. Frequency of rhupus, (12 vs. 17%, p = 1.0), Jaccoud's arthropathy (0 vs. 17%, p = 0.343) and treatments were similar in cSLE and aSLE. We determined that chronic arthritis in SLE has distinct features in children, with very early onset, polyarticular involvement and association with active disease. We further demonstrated in this series that a proportion of chronic arthritis involvement in SLE is manifested as rhupus and Jaccoud's arthropathy.

Polymyositis (PM) affects female gender during reproductive age; however, there is no study assessing ovarian reserve in these patients to evaluate ovarian reserve markers in PM. Eight female patients with PM (Bohan and Peter criteria, 1975) with aged 18-40 years, followed at our tertiary centre from March 2011 to May 2014, were invited to participate. They were age-matched with 16 healthy individuals (control group). All were evaluated at early follicular phase of menstrual cycle. Follicle stimulating hormone (FSH), estradiol, inhibin B, anti-Müllerian hormone (AMH) serum levels (ELISA) and sonographic antral follicle count (AFC) were determined. PM patients and controls had comparable mean age (31.4 ± 6.5 vs. 30.7 ± 6.2 years, P = 0.946), ethnicity and socioeconomic class (P > 0.05). PM mean age of onset was 27.3 ± 6.5 years and disease duration of 6.5 ± 4.1 years. Menstrual cycles were alike in both groups with a similar frequency of age at menarche, gynaecological age, duration and length of menstrual cycle (P > 0.05). The median serum level of AMH was significantly lower in PM compared to controls [0.7(0.3-3.4) vs. 3.1(1.4-4.0), P = 0.021]. AMH levels ≤1 ng/mL (50 vs. 6.3 %, P = 0.024) and very low AFC (37.5 vs. 6.3 %, P = 0.037) were significantly in PM patients versus controls. The other hormones (FSH, inhibin B and estradiol levels) were similar between both groups (P > 0.05). The present study was the first to identify subclinical ovarian dysfunction in PM patients during reproductive ages. Further study is necessary to assess the possible role of PM-related factors that may influence the ovarian function of these patients.

This study aims to assess ovarian reserve markers in Behçet's disease (BD) patients. Ten BD and 22 healthy controls were evaluated for ovarian reserve by examining the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, inhibin B, total morning testosterone, prolactin, thyroid-stimulating hormone (TSH), and antral follicle count. Anti-Müllerian hormone (AMH) was measured using two different enzyme-linked immunosorbent assay (ELISA) kits. Demographic data, menstrual abnormalities, disease parameters, and treatments were also analyzed. The median current age was similar in BD patients and controls (34 (20-40) vs. 31.3 (20-42) years, p = 0.33). A positive correlation was observed between the AMH Gen II ELISA and AMH/MISAnshLabs ELISA assays in the BD patients (r = +0.98; p < 0.0001) and healthy controls (r = +0.93; p < 0.0001). The mean AMH by Gen II (0.93 ± 0.8 vs. 2.59 ± 1.8 ng/mL, p = 0.01) and AMH/MIS AnshLabs ELISA (1.07 ± 0.86 vs. 2.51 ± 1.8 ng/mL, p = 0.02) were significantly reduced in the BD patients versus controls. A trend of decreased AMH (<1.0 ng/mL) was observed in BD patients compared to that in the controls (50 vs. 19 %, p = 0.09) using either kits. The mean FSH was significantly higher in the BD patients compared to that in the controls (9.1 ± 3.6 vs. 6.5 ± 2.7, p = 0.04). No differences were found for the other ovarian parameters in both groups (p > 0.05). Current disease activity was only observed in BD patients with a low AMH level; however, there was no statistical significance (40 vs. 0 %, p = 0.44). Cyclophosphamide use was reported in only one patient with a low AMH and high FSH level. The present study was the first to suggest that BD patients may have diminished ovarian reserve. The contribution of disease activity remains to be determined.

Periodontal disease (POD) may affect rheumatic diseases severity, but there are no data regarding the effect of its treatment on disease activity in SLE patients under immunosuppressive therapy. Forty-nine consecutive SLE patients (SLEDAI ≥ 2) with POD and under corticosteroid and cyclophosphamide pulse therapy (IVCYC) were selected. Periodontal assessment included bleeding gingival index (BGI), probing depth (PD), and probing attachment level (PAL). At entry, POD was defined as BGI > 1 and patients were assigned to groups according to the availability of odontological intervention in TREATED (n = 32) and NOT TREATED (n = 17). SLEDAI and POD parameters were determined at entry and after 3 months. Age, female gender, and race were alike among TREATED and NOT TREATED (p > 0.05). Both groups had also comparable disease duration (10.7 ± 6.8 vs. 11.0 ± 6.6, p = 0.83), IVCYC number (5.8 ± 4.8 vs. 4.5 ± 4.8, p = 0.17), and SLEDAI (5.9 ± 4.2 vs. 6.3 ± 4.3, p = 0.73) as well as POD parameters [BGI (40.8 ± 31.0 vs. 40.7 ± 36.2 %, p = 0.89), PD (1.7 ± 1.8 vs. 1.5 ± 0.60 mm, p = 0.80), and PAL (2.5 ± 1.9 vs. 1.9 ± 1.1 mm, p = 0.18)]. At the end of the study, TREATED group had a significant improvement in SLEDAI (5.9 ± 4.2 vs. 3.4 ± 3.3, p = 0.04) with a paralleled reduction in BGI (40.8 ± 31.0 vs. 15.2 ± 17.2 %, p < 0.01), PD (1.7 ± 1.8 vs. 1.1 ± 0.3 mm, p < 0.01), and PAL (2.5 ± 1.9 vs. 1.7 ± 0.9 mm, p < 0.01). In contrast, SLEDAI (6.3 ± 4.3 vs. 6.0 ± 5.5, p = 0.40) and POD parameters [BGI (p = 0.33), PD (p = 0.91), and PAL (p = 0.39)] remained largely unchanged in NOT TREATED group. Periodontal disease treatment seems to have a beneficial effect in controlling disease activity in SLE patients under immunosuppressive therapy. Therefore, management of this modifiable risk factor is recommended.

We have performed a retrospective study to determine if patients with antiphospholipid syndrome that developed systemic lupus erythematosus (APS/SLE) had distinct clinical and/or serological features. All 80 primary APS (PAPS) patients followed up at our APS unit were included in the study and divided into two groups: 14 APS/SLE and 66 PAPS. Prior or at onset of lupus manifestations, six patients were uniformly negative for lupus and Sjögren autoantibodies, and the other eight patients had persistent positive. In the first year after diagnosis of SLE, three patients remained with negative antibodies, the other seven patients maintained the same antibodies, and four patients developed other antibodies. APS/SLE group had a significant lower mean age at PAPS diagnosis (26.0 ± 8.0 vs. 34.2 ± 11.9 years, p = 0.03) and a longer disease duration (14.0 ± 7.0 vs. 6.0 ± 5.0 years, p < 0.0001). The mean time for PAPS to develop SLE was 5.2 ± 4.3 years. The typical clinical and laboratorial findings of APS did not discriminate both groups of patients. At lupus onset, antinuclear antibodies were more frequently observed in those who evolved to SLE (100 vs. 51.5%, p = 0.0005). Anti-double-stranded DNA (dsDNA), anti-ribosomal P, anti-Ro/SS-A, anti-La/SS-B, and anti-U1RNP antibodies were exclusively found in the APS/SLE patients, whereas anti-Smith (Sm) antibodies were not detected in both groups. The detection of a distinct subgroup of lupus-associated autoantibody in PAPS patients seems to be a hint to overt SLE disease, particularly in those patients with young age at diagnosis.

To assess the testicular Sertoli cell function according to inhibin B levels in ankylosing spondylitis (AS) patients and the possible effect of anti-TNF therapy on this hormone production, 20 consecutive AS patients and 24 healthy controls were evaluated. At study entry, AS patients were not receiving sulfasalazine/methotrexate and never have used biological/cytotoxic agents. They were assessed by serum inhibin B levels, hormone profile, urological examination, testicular ultrasound, seminal parameters, and clinical features. Ten of these patients received anti-TNF treatment and they were reevaluated for Sertoli function and disease parameters at 6 months. Four of them agreed to repeat sperm analysis. At study entry, the median of inhibin B (68 vs. 112.9 pg/mL, p = 0.111), follicle-stimulating hormone levels (3.45 vs. 3.65 IU/L, p = 0.795), and the other hormones was comparable in AS patients and controls (p > 0.05). Sperm analysis was similar in AS patients and controls (p > 0.05) with one AS patient presenting borderline low inhibin B levels. Further analysis at 6 months of the 10 patients referred for anti-TNF therapy, including one with borderline inhibin B, revealed that median inhibin B levels remained stable (116.5 vs. 126.5 pg/mL, p = 0.431) with a significant improvement in C-reactive protein (27.8 vs. 2.27 mg/L, p = 0.039). Sperm motility and concentration were preserved in the four patients who repeated this analysis after TNF blockage. In conclusion, this was the first study to report, using a specific marker, a normal testicular Sertoli cell function in AS patients with mild to moderate disease activity.

N-terminal pro-brain natriuretic peptide (NT-proBNP) is a strong marker of cardiovascular disease with recent evidence that inflammation may also influence its levels; discrimination of this confounding variable is of particular interest in rheumatic diseases. Therefore, we evaluated NT-proBNP in ankylosing spondylitis (AS) patients pre- and post-TNF blocker to determine the possible association between NT-proBNP levels and inflammatory parameters. Forty-five consecutive AS patients without previous/current cardiovascular disease or systolic myocardial dysfunction, who were eligible to anti-TNF therapy, were prospectively enrolled. All patients received TNF blockers and they were evaluated for circulating NT-proBNP levels, clinical and laboratory parameters of disease activity, traditional cardiovascular risk factors, and conventional and tissue Doppler imaging echocardiography at baseline (BL) and 6 months after (6M) treatment. At BL, all patients had active AS, NT-proBNP levels had a median of 36 (20-72) pg/mL and 11 % were high in spite of no systolic alteration. Multiple linear regression analysis revealed that this peptide, at BL, was independently correlated with erythrocyte sedimentation rate (ESR) (p < 0.001), age (p = 0.01), and pulse pressure (p = 0.01). After 6M, all disease parameters improved and NT-proBNP levels were significantly reduced [24 (16-47) pg/mL, p = 0.037] compared to BL. Changes in NT-proBNP were positively correlated with ESR changes (r = 0.41, p = 0.006). Cardiovascular risk factors remained stable during follow-up. In conclusion, our data suggest that elevations of NT-proBNP should be interpreted with caution in active AS patients with no other evidence of cardiovascular disease. The short-term reduction of NT-proBNP levels in these patients receiving anti-TNF therapy appears to reflect an improvement in inflammatory status.

This study aims to perform global gonadal and sexual function assessments in systemic lupus erythematosus-related antiphospholipid syndrome (SLE-APS) patients. A cross-sectional study was conducted in ten SLE-APS male patients and 20 healthy controls. They were assessed by demographic data, clinical features, urological examination, sexual function, testicular ultrasound, seminal parameters, sperm antibodies, and hormone profile. The median of current age was similar in SLE-APS patients and controls with a higher frequency of erectile dysfunction in the former group (30 vs. 0 %, p = 0.029). The median penis circumference was significantly reduced in SLE-APS patients with erectile dysfunction compared to patients without this complication (8.17 vs. 9.14 cm, p = 0.0397). SLE-APS patients with previous arterial thrombosis had a significantly reduced median penis circumference compared to those without this complication (7.5 vs. 9.18 cm, p = 0.039). Comparing SLE-APS patients and controls, the former had a significant lower median of sperm concentration (41.1 vs. 120.06 × 10(6)/mL, p = 0.003), percentages of sperm motility (47.25 vs. 65.42 %, p = 0.047), normal sperm forms by WHO guidelines (11 vs. 23.95 %, p = 0.002), and Kruger criteria (2.65 vs. 7.65 %, p = 0.02). Regarding seminal analysis, the medians of sperm concentration and total sperm count were significantly lower in SLE-APS patients treated with intravenous cyclophosphamide vs. those untreated with this drug (p < 0.05). Therefore, we have observed a novel association of reduced penile size with erectile dysfunction and previous arterial thrombosis in SLE-APS patients. Penis assessment should be routinely done in SLE-APS patients with fertility problems. We also identified that intravenous cyclophosphamide underlies severe sperm alterations in these patients.

The objective of this study was to analyze the clinical, laboratorial, and therapeutical response of polymyalgia rheumatica (PMR) to anti-tumor necrosis factor (anti-TNF) treatment. We systematically searched English articles on the subjects of PMR who were treated with TNF blockers in Pubmed from 1994 to 2010. In addition, we reported on two patients with PMR who were treated by the Rheumatology Division of the Hospital das Clínicas da Faculdade de Medicina da Universidade in São Paulo, Brazil. Ninety-nine cases of patients with PMR treated with anti-TNF were reviewed. The age of these patients ranged from 63 to 84 years, and 70.7% of them were female. Disease duration varied from 10.5 weeks to 95 months, and time of follow-up varied from 2 weeks to 21 months. Infliximab was the anti-TNF of choice in three studies, while etanercept was in five. Time to response varied from 2 to 8 weeks. After anti-TNF treatment, prednisone reduction was observed in all studies. Clinical improvement was found in 7/7 studies, and laboratory improvement of at least 50% of inflammatory markers was observed in 6/7 studies. This study demonstrated a good clinical and laboratory response to anti-TNF therapy in patients with PMR, with or without glucocorticoid.

Still's disease (SD) is a rare chronic inflammatory disease characterized by polyarthritis, systemic symptoms, and elevated inflammatory markers. Of note, 74 SD cases were reported with anti-tumoral necrosis factor (TNF) therapy and the experience of switching is limited to five patients. During a 3-year period, SD cases were 1.9% of 319 rheumatic patients that received anti-TNF agents in the infusion center of our University Hospital. In this manuscript, the authors add six new cases of refractory SD who had clinical and laboratory response to TNF blockers and report the outcome of switching in five of them. Partial or complete response was achieved by four of six (66.7%) patients and three of four (75%) required switching. Regarding safety, five of six (83.3%) had adverse events. Anti-TNF treatment with switching seems to be a valid approach for refractory SD patients.

Unlabelled: The association of cyclophosphamide (CYC) and prednisone (PRED) for the treatment of lung fibrosis in systemic sclerosis (SSc) was only evaluated in uncontrolled studies, although in idiopathic interstitial lung disease (ILD) this association seems to be beneficial in patients with non-specific interstitial pneumonia (NSIP)., Objectives: To treat SSc-ILD in a prospective open-label controlled study based on lung pattern during 12 months of treatment., Methods: A 3-year analysis was also performed. Twenty-four consecutive patients with SSc and ILD were submitted to an open lung biopsy. Eighteen patients (NSIP) were randomized in two groups: CYC versus CYC + PRED during 12 months. Lung function tests (diffusion lung capacity of monoxide carbone corrected for hemoglobin concentration (DLCO-Hb), forced vital capacity (FVC), total lung capacity) and Modified Rodnan Skin Score (MRSS) were performed before, after one of treatment and after 3 years from the end of the treatment., Results: Pulmonary function tests were similar in both groups on baseline. After 1 year of treatment, FVC% was comparable between CYC groups (p = 0.72) and in CYC + PRED (p = 0.40). Three years after the end of treatment, FVC% values (p = 0.39 in group CYC and p = 0.61 in CYC + PRED and p = 0.22 in CYC + PRED) and DLCO-Hb (p = 0.54 in CYC and p = 0.28 in CYC + PRED) were similar compared to 1 year of treatment. We observed a reduction of the MRSS in the CYC + PRED group after 1 year of treatment (p = 0.02); although after 3 years, MRSS values remained stable in both groups., Conclusions: CYC was effective to stabilize lung function parameters in NSIP lung pattern of SSc disease for 3 years after the end of a 1-year therapy.

Ninety-one consecutive systemic lupus erythematosus (SLE) patients (American College of Rheumatology criteria) with a history of cutaneous vasculitis were compared to 163 SLE controls without this clinical manifestation from July to December 2007 in order to determine the possible clinical and serological association of this manifestation. Data were obtained in an ongoing electronic database protocol and autoantibodies to anti-double-stranded DNA, anti-Sm, anti-RNP, anti-Ro/SS-A, anti-La/SS-B, and anticardiolipin and ribosomal P protein antibody (anti-P) were detected by standard techniques. Exclusion criteria were the presence of anti-phospholipid syndrome or antibodies, Sjögren syndrome, and a history of thrombosis. The mean age (38.5 ± 11.5 vs. 37.8 ± 11.6 years, p = 0.635), disease duration (12.5 ± 7.8 vs. 11.8 ± 7.9 years, p = 0.501), and frequency of white race (71.4% vs. 70.5%, p = 0.872) and female sex (96.8% vs. 93.7%, p = 0.272) were comparable in both groups. The vasculitis group had a higher frequency of malar rash (97.9% vs. 87.4%, p = 0.004), photosensitivity (91.4% vs. 81.6%, p = 0.030), and Raynaud phenomenon (RP; 27.7% vs. 7.5%, p < 0.001), whereas all other clinical manifestation including renal and central nervous system involvements were similar to the control group. Laboratorial data revealed that only anti-P (35.1% vs. 12.1%, p < 0.001) was more frequent in patients with vasculitis. In a multivariate logistic regression model, cutaneous vasculitis was associated to the presence of RP (OR = 3.70; 95% confidence interval [CI] = 1.73-8.00) and anti-P (OR = 3.42; 95% CI = 1.76-6.66). In summary, SLE cutaneous vasculitis characterizes a subgroup of patients with more RP and anti-P antibodies but not accompanied by a higher frequency of renal and central nervous system involvements.

The objective of this study is to characterize the lipoprotein risk levels in Takayasu arteritis (TA) patients and its possible association with disease activity and glucocorticoid use. Twenty-five female TA patients were consecutively included and compared with 30 age-, gender-, and body mass index-matched healthy controls. Demographic features and the lipid profile were determined and cardiovascular risk levels were evaluated according to NCEP/ATPIII. Total cholesterol (TC), LDL-c, HDL-c, and triglycerides were determined after a 12-h overnight fast. Exclusion criteria were conditions that interfere in the lipid profile. The disease duration was 6.6 +/- 7.4 years; 30% had clinical activity and 80% had laboratory activity. Regarding NCEP/ATPIII risk levels, TA patients presented higher frequency of lipid risk compared to controls: high TC (48% vs. 20%, p = 0.04), low HDL-c (20% vs. 0%, p = 0.015), and high triglycerides (36% vs. 10%, p = 0.026). No difference was observed related to LDL-c risk levels between both groups (40% vs. 20%, p = 0.14). Remarkably, 60% of the patients had at least one lipid risk factor for cardiovascular disease. No difference in the lipids was observed between patients with and without clinical activity; however, those with laboratory activity showed lower levels of HDL-c (1.37 +/- 0.42 vs. 2.00 +/- 0.63 mmol/L, p = 0.012) than patients without this activity. A negative correlation was found between HDL-c and CRP levels (r = -0.42, p = 0.04). Lipids were similar in patients under glucocorticoid compared to those without this therapy. This is the first study to identify that TA, an inflammatory disease, has a proatherogenic lipid profile which is associated to laboratory disease activity.

The antichromatin antibody (aCT) has been described as a useful marker for lupus nephropathy. The relevance of its nephritogenic potential may be appropriately evaluated in the context of renal histopathology. Therefore, the present study investigated the relationship of aCT with a particular histopathologic class of lupus nephritis (LN). Seventy-eight consecutive patients with systemic lupus erythematosus (ACR criteria) and active nephritis who underwent renal biopsy from 1999 to 2004 and with available frozen serum sample obtained at the time of biopsy were selected. aCT was measured by ELISA, and anti-dsDNA was measured by indirect immunofluorescence (IIF) and by ELISA. All renal biopsies were revised in a blinded manner by the same expert renal pathologist. Charts were extensively reviewed for demographic and renal features obtained at the time of biopsy. The prevalence of aCT (>or=20 U) was 59% with a mean titer of 74.3 +/- 38.7 U. Both aCT-positive and aCT-negative groups of patients had similar age, gender distribution, duration of lupus, and duration of renal disease. Anti-dsDNA was detected by IIF in 29.5% and by ELISA in 42.3% of the patients. Concomitant presence of both antibodies was observed in 63% (29/46) [anti-dsDNA by ELISA] and 45.6% (21/46) [anti-dsDNA by IIF] of the patients. Lower serum levels of C3 (73% vs. 40%, P = 0.0058) and C4 (82% vs. 46.7%, P = 0.0021) were more commonly observed in aCT >or= 20 U patients compared to the aCT-negative group. It is important to note that the use of a higher cut-off value (>or=40 U) for aCT test revealed a predominance of class IV LN (58% vs. 33%, P = 0.039) in aCT >or= 40 U compared to aCT < 40 U group. The mean levels of proteinuria, serum albumin, and creatinine were markedly altered but were comparable in both groups (P >or= 0.05). One fourth (26.3%) of the 19 patients with class IV LN and aCT >or= 40 U had no detectable anti-dsDNA (ELISA). These data suggest that high-titer aCT seems to be a valuable biomarker for proliferative class IV of LN.