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1.
Clin Rheumatol ; 2021 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-33486596

RESUMO

INTRODUCTION: The American Academy of Ophthalmology (2016-AAO) recommended hydroxychloroquine (HCQ) dose not to exceed 5 mg/kg/day (real body weight). Recently, it was reported that prescribed 2016-AAO dose provided adequate HCQ levels for most lupus nephritis (LN) patients, with low flare risk. However, the minimum HCQ dose required to keep adequate levels is unknown. OBJECTIVES: To evaluate if a further reduction in 2016-AAO dose (2-3 mg/kg/day) would sustain 12-month HCQ levels in LN patients with stable inactive disease. METHODS: Seventy-three stable LN patients under prescribed full HCQ 2016-AAO dose for ≥6 months and adequate baseline HCQ levels (≥613.5 ng/mL) were divided in two groups: reduced 2016-AAO dose (2-3 mg/kg/day), n = 32, and full 2016-AAO dose (5 mg/kg/day), n = 41. All patients were assessed at baseline, 3, 6, and 12 months. HCQ levels were measured by liquid chromatography-tandem mass spectrometry. Flare was defined as augment ≥ 3 in SLE Disease Activity Index-2000 and/or change in treatment. Rigorous clinical/laboratorial surveillance was performed. RESULTS: Prospective evaluation revealed for reduced 2016-AAO dose group a decrease of HCQ levels from baseline to 3 months (1,404.9 ± 492.0 vs. 731.6 ± 385.0 ng/mL, p < 0.01), and sustained levels at 6 months (p = 0.273) and 12 months (p = 0.091) compared to 3 months. For the full 2016-AAO dose group, a decrease occurred only from baseline to 12 months (1343.5 ± 521.5 vs. 991.6 ± 576.3 ng/mL, p < 0.001). Frequencies of patients with inadequate levels at 6 months was higher in reduced 2016-AAO group than full 2016-AAO dose (59% vs. 24%, p = 0.005), as well as at 12 months (66% vs. 32%, p = 0.002). Six-month and 12-month flare frequencies were comparable for both groups (p > 0.05). CONCLUSIONS: Prescribed HCQ low-dose regimen (2-3 mg/kg/day) does not sustain, for most patients, 6- and 12-month adequate HCQ levels. Full 2016-AAO dose maintained HCQ levels way above this limit. TRAIL REGISTRATION: ClinicalTrials.gov : NCT03122431, registered on April 20, 2017 Key Points • Reduced American Academy of Ophthalmology (2016-AAO) hydroxychloroquine (HCQ) dose (2-3 mg/kg/day, real body weight) is unable to sustain HCQ blood levels within the safe cut-off defined for flare risk. • Full 2016-AAO dose (5 mg/kg/day) maintains a safe pattern of HCQ levels up to 12 months.

2.
Clin Rheumatol ; 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33438081

RESUMO

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.

3.
Lupus ; : 961203320985214, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402039

RESUMO

INTRODUCTION: In 2016 the American Academy of Ophthalmology(2016-AAO) recommended a maximum daily HCQ use of 5.0 mg/kg real body weight(RBW) taking into consideration minimizing eye toxicity. Retinopathy in systemic lupus erythematosus(SLE) patients was recently associated with obesity and this condition is progressively more common in these patients. However, the impact of obesity in HCQ blood levels remains controversial. OBJECTIVE: To determine if the 2016-AAO recommendation based on RBW with and without maximum daily dose restriction results in adequate and safe blood levels in obese lupus nephritis(LN) patients. METHODS: A cross-sectional study was performed with 108 LN patients under the prescribed 2016-AAO dose for at least 3 months. LN patients were assessed for demographic characteristics, body mass index(BMI), disease parameters, HCQ dose, concomitant treatment and HCQ blood levels measured by liquid chromatography-tandem mass spectrometry. Obesity was defined as BMI ≥30kg/m2. RESULTS: Obesity was identified in 35/108(32%) LN patients. The calculation of HCQ daily dosage revealed that obese patients were under a lower prescribed daily dose according to the real body weight (RBW) [4.4(2.9-5.4) vs. 4.9(4-5.5)mg/Kg/day, p < 0.001] due to the maximum limit used. Regardless of that the median of HCQ blood levels was significantly higher in obese compared to non-obese patients (1562 ± 548.6 vs. 1208 ± 448.9 ng/mL, p = 0.002). Further analysis of patients under the 20016-AAO recommendation by RBW without the restriction of maximum daily dose confirmed that in spite of comparable daily dose in 14 obese patients and 61 non-obese patients [4.8 (4.5-5.4) vs. 5.0(4.5-5.5) mg/kg, p = 0.312], the median of HCQ blood levels was significantly higher in obese patients than in non-obese (1734 ± 457.3 vs. 1189 ± 449.4 ng/mL, p < 0.001). CONCLUSION: Obese patients under the 2016-AAO prescribed dose of HCQ based on RBW with and without maximum daily dose restriction have a very high HCQ blood levels compared to non-obese patients, with a potential increased risk of ocular toxicity. The use of 2016-AAO dose of HCQ according to the ideal body weight for this group of patients should be considered.Clinicaltrials.gov #NCT0312243.

4.
RMD Open ; 6(3)2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33310863

RESUMO

AIM: A decrease in proteinuria has been considered protective from renal damage in lupus nephritis (LN), but a cut-off point has yet to be established. The aim of this study was to identify the predictors of renal damage in patients with LN and to determine the best cut-off point for a decrease in proteinuria. METHODS: We included patients with LN defined clinically or histologically. Possible predictors of renal damage at the time of LN diagnosis were examined: proteinuria, low complement, anti-double-stranded DNA antibodies, red cell casts, creatinine level, hypertension, renal activity (assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)), prednisone dose, immunosuppressive drugs and antimalarial use. Sociodemographic variables were included at baseline. Proteinuria was assessed at baseline and at 12 months, to determine if early response (proteinuria <0.8 g/day within 12 months since LN diagnosis) is protective of renal damage occurrence. Renal damage was defined as an increase of one or more points in the renal domain of The Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI). Cox regression models using a backward selection method were performed. RESULTS: Five hundred and two patients with systemic lupus erythematosus patients were included; 120 patients (23.9%) accrued renal damage during their follow-up. Early response to treatment (HR=0.58), antimalarial use (HR=0.54) and a high SES (HR=0.25) were protective of renal damage occurrence, whereas male gender (HR=1.83), hypertension (HR=1.86) and the renal component of the SLEDAI (HR=2.02) were risk factors for its occurrence. CONCLUSIONS: Early response, antimalarial use and high SES were protective of renal damage, while male gender, hypertension and higher renal activity were risk factors for its occurrence in patients with LN.

6.
Clinics (Sao Paulo) ; 75: e1870, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33206754

RESUMO

OBJECTIVES: To retrospectively evaluate the performance and distinctive pattern of latent tuberculosis (TB) infection (LTBI) screening and treatment in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) under anti-tumor necrosis factor (TNF) therapy and determine the relevance of re-exposure and other risk factors for TB development. METHODS: A total of 135 and 83 patients with AS and PsA, respectively, were evaluated for LTBI treatment before receiving anti-TNF drugs via the tuberculin skin test (TST), chest radiography, and TB exposure history assessment. All subjects were evaluated for TB infection at 3-month intervals. RESULTS: The patients with AS were more often treated for LTBI than were those with PsA (42% versus 30%, p=0.043). The former also presented a higher frequency of TST positivity (93% versus 64%, p=0.002), although they had a lower frequency of exposure history (18% versus 52%, p=0.027) and previous TB (0.7% versus 6%, p=0.03). During follow-up [median, 5.8 years; interquartile range (1QR), 2.2-9.0 years], 11/218 (5%) patients developed active TB (AS, n=7; PsA, n=4). TB re-exposure was the main cause in seven patients (64%) after 12 months of therapy (median, 21.9 months; IQR, 14.2-42.8 months) and five LTBI-negative patients. TB was identified within the first year in four patients (36.3%) (median, 5.3 months; IQR, 1.2-8.8 months), two of whom were LTBI-positive. There was no difference in the TB-free survival according to the anti-TNF drug type/class; neither synthetic drug nor prednisone use was related to TB occurrence (p>0.05). CONCLUSION: Known re-exposure is the most critical factor for incident TB cases in spondyloarthritis. There are also some distinct features in AS and PsA LTBI screening, considering the higher frequency of LTBI and TST positivities in patients with AS. Annual risk reassessment taking into consideration these peculiar features and including the TST should be recommended for patients in endemic countries.

7.
Nat Rev Rheumatol ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33139947

RESUMO

The emergence of COVID-19 in early 2020 led to unprecedented changes to rheumatology clinical practice worldwide, including the closure of research laboratories, the restructuring of hospitals and the rapid transition to virtual care. As governments sought to slow and contain the spread of the disease, rheumatologists were presented with the difficult task of managing risks, to their patients as well as to themselves, while learning and implementing new systems for remote health care. Consequently, the COVID-19 pandemic led to a transformation in health infrastructures and telemedicine that could become powerful tools for rheumatologists, despite having some limitations. In this Viewpoint, five experts from different regions discuss their experiences of the pandemic, including the most challenging aspects of this unexpected transition, the advantages and limitations of virtual visits, and potential opportunities going forward.

8.
Clinics (Sao Paulo) ; 75: e1870, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33146355

RESUMO

OBJECTIVES: To retrospectively evaluate the performance and distinctive pattern of latent tuberculosis (TB) infection (LTBI) screening and treatment in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) under anti-tumor necrosis factor (TNF) therapy and determine the relevance of re-exposure and other risk factors for TB development. METHODS: A total of 135 and 83 patients with AS and PsA, respectively, were evaluated for LTBI treatment before receiving anti-TNF drugs via the tuberculin skin test (TST), chest radiography, and TB exposure history assessment. All subjects were evaluated for TB infection at 3-month intervals. RESULTS: The patients with AS were more often treated for LTBI than were those with PsA (42% versus 30%, p=0.043). The former also presented a higher frequency of TST positivity (93% versus 64%, p=0.002), although they had a lower frequency of exposure history (18% versus 52%, p=0.027) and previous TB (0.7% versus 6%, p=0.03). During follow-up [median, 5.8 years; interquartile range (1QR), 2.2-9.0 years], 11/218 (5%) patients developed active TB (AS, n=7; PsA, n=4). TB re-exposure was the main cause in seven patients (64%) after 12 months of therapy (median, 21.9 months; IQR, 14.2-42.8 months) and five LTBI-negative patients. TB was identified within the first year in four patients (36.3%) (median, 5.3 months; IQR, 1.2-8.8 months), two of whom were LTBI-positive. There was no difference in the TB-free survival according to the anti-TNF drug type/class; neither synthetic drug nor prednisone use was related to TB occurrence (p>0.05). CONCLUSION: Known re-exposure is the most critical factor for incident TB cases in spondyloarthritis. There are also some distinct features in AS and PsA LTBI screening, considering the higher frequency of LTBI and TST positivities in patients with AS. Annual risk reassessment taking into consideration these peculiar features and including the TST should be recommended for patients in endemic countries.

9.
Autoimmun Rev ; 19(12): 102693, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33164791

RESUMO

OBJECTIVE: To assess childhood-onset systemic lupus erythematosus-related antiphospholipid syndrome(cSLE-APS) in a large Brazilian population. METHODS: A retrospective observational cohort study was carried-out in 27 Pediatric Rheumatology university centers, including 1519 cSLE patients. RESULTS: cSLE-APS was observed in 67/1519 (4%) and was diagnosed at disease onset in 39/67 (58%). The median disease duration was 4.9 (0-17) years. Thrombosis recurrences were evidenced in 18/67 (27%) cSLE-APS patients. The most frequent thrombosis sites in cSLE-APS patients were: venous thrombosis in 40/67 (60%), especially deep vein thrombosis in 29/40 (72%); arterial thrombosis in 35/67 (52%), particularly stroke; small vessels thrombosis in 9/67 (13%) and mixed thrombosis in 3/67 (4%). Pregnancy morbidity was observed in 1/67 (1%). Non-thrombotic manifestation associated to cSLE-APS occurred in 21/67 (31%), mainly livedo reticularis in 14/67 (21%), valvar thickening in 4/67 (6%) and valvar vegetations not related to infections in 2/67 (3%). None of them had catastrophic APS. Further analysis demonstrated that the median of SLICC/ACR-DI [1(0-5) vs. 0(0-7),p < 0.0001] was significantly higher in cSLE-APS patients compared to cSLE without APS. The frequencies of cerebrovascular disease (40% vs. 1%,p < 0.0001), polyneuropathy (9% vs. 1%,p < 0.0001), SLICC/ACR-DI ≥1 (57% vs. 27%, p < 0.0001) and intravenous cyclophosphamide use (59% vs. 37%, p < 0.0001) were significantly higher in the former group. CONCLUSIONS: Our large multicenter study demonstrated that cSLE-APS was a rare condition, occurring during disease course with a high accrual damage. Central and peripheral neuropsychiatric involvements were distinctive features of this autoimmune thrombosis.

12.
Sci Rep ; 10(1): 14054, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32820183

RESUMO

Dry eye disease (DED) is common in Rheumatoid Arthritis (RA) patients. The application of conjunctival goblet cell count as a clinical biomarker to diagnose and respond to treatment can take place in rheumatoid arthritis patients under TNF-inhibitors (TNFi) therapy. This study aimed to investigate the ocular surface parameters and the long-term effects of TNFi therapy on ocular surface features and goblet cell count of rheumatoid arthritis patients. At baseline, rheumatoid arthritis patients eligible to TNFi were compared to healthy controls (similar age/gender), regarding Ocular Surface Disease Index (OSDI) questionnaire, Schirmer I test, tear break-up time test, vital dye staining of the ocular surface, and conjunctival impression cytology. DED severity grade, impression cytology score, and goblet cell count were analyzed. Rheumatoid arthritis patients were followed after three (3 M) and 12 months (12 M), during TNFi treatment. Sixteen rheumatoid arthritis patients and 24 controls were compared: a higher frequency of abnormal OSDI (68.8% vs. 16.7%, p = 0.002), Schirmer's test < 10 mm (37.5% vs. 8.3%, p = 0.042), meibomian gland dysfunction (50% vs. 8.3%, p = 0.007), abnormal impression cytology (75% vs. 8.3%, p < 0.001), and mild to moderate DED (81.3% vs. 4.2%, p < 0.001) were observed in rheumatoid arthritis patients, who also had lower goblet cell count [325 (274-707) cells/mm2 vs. 742 (562-863) cells/mm2, p = 0.004]. The presence of Meibomian gland dysfunction was associated with higher disease activity scores (p < 0.05). The prospective early observation of these patients at 3 M showed an increase improvement in tear production by Schirmer's test [13 (7.5-17.5) vs. 23.5 (16-35); p = 0.001], and an improvement in impression cytology score [1 (0.5-2) vs. 1 (0-1), p = 0.031] and in goblet cell count [325 (274-707) vs. 931 (656-1,244), p < 0.001]. Eight RA responders to TNFi were also re-evaluated at 12 M with further improvement in goblet cell count [393 (275-827) vs. 872 (502-1,185) vs. 1,079 (867-1,244), p = 0.047]. Multifactorial DED is frequent in RA patients, comprising aqueous, lipid, and mucin components. TNFi prompt improves tear production and recovers the goblet cells, which can be a biomarker of the pathological process and response to therapy in this population.

15.
Lupus ; 29(9): 1140-1145, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32605527

RESUMO

OBJECTIVES: This study aimed to compare the clinical features, damage accrual, and survival of patients with familial and sporadic systemic lupus erythematosus (SLE). METHODS: A multi-ethnic, multinational Latin American SLE cohort was studied. Familial lupus was defined as patients with a first-degree SLE relative; these relatives were interviewed in person or by telephone. Clinical variables, disease activity, damage, and mortality were compared. Odds ratios (OR) and 95% confidence intervals (CI) were estimated. Hazard ratios (HR) were calculated using Cox proportional hazard adjusted for potential confounders for time to damage and mortality. RESULTS: A total of 66 (5.6%) patients had familial lupus, and 1110 (94.4%) had sporadic lupus. Both groups were predominantly female, of comparable age, and of similar ethnic distribution. Discoid lupus (OR = 1.97; 95% CI 1.08-3.60) and neurologic disorder (OR = 1.65; 95% CI 1.00-2.73) were significantly associated with familial SLE; pericarditis was negatively associated (OR = 0.35; 95% CI 0.14-0.87). The SLE Disease Activity Index and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) were similar in both groups, although the neuropsychiatric (45.4% vs. 33.5%; p = 0.04) and musculoskeletal (6.1% vs. 1.9%; p = 0.02) domains of the SDI were more frequent in familial lupus. They were not retained in the Cox models (by domains). Familial lupus was not significantly associated with damage accrual (HR = 0.69; 95% CI 0.30-1.55) or mortality (HR = 1.23; 95% CI 0.26-4.81). CONCLUSION: Familial SLE is not characterized by a more severe form of disease than sporadic lupus. We also observed that familial SLE has a higher frequency of discoid lupus and neurologic manifestations and a lower frequency of pericarditis.

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