II Brazilian Society of Rheumatology consensus for lupus nephritis diagnosis and treatment.

OBJECTIVE: To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN). METHODS: Two methodologists and 20 rheumatologists from Lupus Comittee of Brazilian Society of Rheumatology participate in the development of this guideline. Fourteen PICO questions were defined and a systematic review was performed. Eligible randomized controlled trials were analyzed regarding complete renal remission, partial renal remission, serum creatinine, proteinuria, serum creatinine doubling, progression to end-stage renal disease, renal relapse, and severe adverse events (infections and mortality). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to develop these recommendations. Recommendations required ≥82% of agreement among the voting members and were classified as strongly in favor, weakly in favor, conditional, weakly against or strongly against a particular intervention. Other aspects of LN management (diagnosis, general principles of treatment, treatment of comorbidities and refractory cases) were evaluated through literature review and expert opinion. RESULTS: All SLE patients should undergo creatinine and urinalysis tests to assess renal involvement. Kidney biopsy is considered the gold standard for diagnosing LN but, if it is not available or there is a contraindication to the procedure, therapeutic decisions should be based on clinical and laboratory parameters. Fourteen recommendations were developed. Target Renal response (TRR) was defined as improvement or maintenance of renal function (±10% at baseline of treatment) combined with a decrease in 24-h proteinuria or 24-h UPCR of 25% at 3 months, a decrease of 50% at 6 months, and proteinuria < 0.8 g/24 h at 12 months. Hydroxychloroquine should be prescribed to all SLE patients, except in cases of contraindication. Glucocorticoids should be used at the lowest dose and for the minimal necessary period. In class III or IV (±V), mycophenolate (MMF), cyclophosphamide, MMF plus tacrolimus (TAC), MMF plus belimumab or TAC can be used as induction therapy. For maintenance therapy, MMF or azathioprine (AZA) are the first choice and TAC or cyclosporin or leflunomide can be used in patients who cannot use MMF or AZA. Rituximab can be prescribed in cases of refractory disease. In cases of failure in achieving TRR, it is important to assess adherence, immunosuppressant dosage, adjuvant therapy, comorbidities, and consider biopsy/rebiopsy. CONCLUSION: This consensus provides evidence-based data to guide LN diagnosis and treatment, supporting the development of public and supplementary health policies in Brazil.

Immunogenicity, safety, and antiphospholipid antibodies after SARS-CoV-2 vaccine in patients with primary antiphospholipid syndrome.

OBJECTIVE: Coronavirus disease 19 (COVID-19) has an increased risk of coagulopathy with high frequency of antiphospholipid antibodies (aPL). Recent reports of thrombosis associated with adenovirus-based vaccines raised concern that SARS-CoV-2 immunization in primary antiphospholipid syndrome (PAPS) patients may trigger clotting complications. Our objectives were to assess immunogenicity, safety, and aPL production in PAPS patients, after vaccinating with Sinovac-CoronaVac, an inactivated virus vaccine against COVID-19. METHODS: This prospective controlled phase-4 study of PAPS patients and a control group (CG) consisted of a two-dose Sinovac-CoronaVac (D0/D28) and blood collection before vaccination (D0), at D28 and 6 weeks after second dose (D69) for immunogenicity/aPL levels. Outcomes were seroconversion (SC) rates of anti-SARS-CoV-2 S1/S2 IgG and/or neutralizing antibodies (NAb) at D28/D69 in naïve participants. Safety and aPL production were also assessed. RESULTS: We included 44 PAPS patients (31 naïve) and 132 CG (108 naïve) with comparable age (p=0.982) and sex (p>0.999). At D69, both groups had high and comparable SC (83.9% vs. 93.5%, p=0.092), as well as NAb positivity (77.4% vs. 78.7%, p=0.440), and NAb-activity (64.3% vs. 60.9%, p=0.689). Thrombotic events up to 6 months or other moderate/severe side effects were not observed. PAPS patients remained with stable aPL levels throughout the study at D0 vs. D28 vs. D69: anticardiolipin (aCL) IgG (p=0.058) and IgM (p=0.091); anti-beta-2 glycoprotein I (aß2GPI) IgG (p=0.513) and IgM (p=0.468). CONCLUSION: We provided novel evidence that Sinovac-CoronaVac has high immunogenicity and safety profile in PAPS. Furthermore, Sinovac-CoronaVac did not trigger thrombosis nor induced changes in aPL production.

Intramastoid Phosphaturic Mesenchymal Tumor Causing Hypophosphatemic Osteomalacia Detected on 68Ga-DOTATATE PET/CT But Not on 99mTc-Sestamibi and 18F-FDG Scans.

68Ga-DOTATATE uptake in mesenchymal tumors causing hypophosphatemic osteomalacia has been recently described. Herein, we present a case of 68Ga-DOTATATE uptake in an intramastoid phosphaturic mesenchymal tumor that had not been depicted in previous 99mTc-Sestamibi and 18F-FDG scans. The lesion was surgically removed and the phosphorus level increased to the normal range.

ABO blood group in primary antiphospholipid syndrome: influence in the site of thrombosis?

Antiphospholipid syndrome (APS) is characterized by vascular thrombosis and/or obstetric complications associated with presence of antiphospholipid antibodies (aPL) but additional factors would also induce thrombosis. ABO (H) blood groups are known to be closely related to thrombosis, especially non-O blood type with venous events. The aim of this study was to investigate possible role of ABO (H) blood types in the thrombotic events in primary APS (PAPS). Seventy PAPS patients were selected for the study and were divided according to ABO blood group in: O PAPS (n = 26) and non-O PAPS (n = 44). ABO blood group phenotyping was performed by indirect technique. aPL anticardiolipin (aCL) and anti-ßeta2 glycoprotein-1 (aß2GPI) and the concentrations and activities of von Willebrand factor (VWF) were measured with ELISA. Lupus anticoagulant (LA) was detected by coagulation assays. A significant higher frequency of venous events was observed in non-O PAPS group (72.7 vs. 46.2 %, p = 0.040). In contrast, the frequency of arterial events was significantly higher in the O PAPS compared to the non-O PAPS group (69.2 vs. 36.4 %, respectively; p = 0.013). Frequencies of aCL, LA, aß2GPI and triple aPL positivity were similar in both groups (p > 0.05). VWF antigen (75.54 ± 8.68 vs. 79.51 ± 7.07 IU/dl, p = 0.041) and activity (70.23 ± 11.96 vs. 77.92 ± 13.67 %, p = 0.020) were decreased in O PAPS compared to non-O blood group. VWF:CB/VWF:Ag ratio was similar among groups (p > 0.05). This is the first report that confirms the role of ABO blood system in thrombosis of PAPS and suggests that non-O blood group was related with venous events and O blood group with arterial thrombosis.

Spondyloptosis in athlete.

The adolescent athletes are at greater risk of low back pain and structural spine injuries. Spondylolysis is responsible for the majority of back pain cases in young athletes, rarely occurring in adults. We report a case of a 13-year-old judo female athlete, who came to our service with 5 months of progressive low back pain during training which was initially attributed to mechanical causes, without any further investigation by imaging methods. At admission, the patient had lumbar deformity, antalgic posture and bilaterally positive unipodalic lumbar hyperextension maneuver. After a research which showed spondyloptosis, the patient underwent surgery. In this article, we discuss, based on this case report, the diagnostic approach to low back pain in young athletes, since the complaint of chronic back pain can be a marker of a structural lesion that may be permanent and bring irreversible functional loss.

Espondiloptose em atleta / Spondyloptosis in athlete

Os atletas adolescentes estão sob maior risco de lombalgia e lesões estruturais da coluna. A espondilólise é responsável pela maioria das lombalgias em jovens esportistas e raramente ocorre em adultos. Relatamos o caso de uma paciente de 13 anos, atleta de judô, que chegou a nosso serviço com quadro de cinco meses de lombalgia progressiva durante os treinos, sendo inicialmente atribuída a causas mecânicas, sem que houvesse uma investigação mais detalhada por métodos de imagem. Na admissão já apresentava deformidade lombar, postura antálgica e manobra de hiperextensão lombar em unipodálico positiva bilateralmente. Realizou-se investigação, que evidenciou espondiloptose, sendo, então, submetida a tratamento cirúrgico. Com base neste relato de caso, discutimos a abordagem diagnóstica de lombalgia em atletas jovens, uma vez que a queixa de lombalgia crônica pode ser marcador de uma lesão estrutural, a qual pode ser definitiva e trazer perda funcional irreversível.

The adolescent athletes are at greater risk of low back pain and structural spine injuries. Spondylolysis is responsible for the majority of back pain cases in young athletes, rarely occurring in adults. We report a case of a 13-year-old judo female athlete, who came to our service with 5 months of progressive low back pain during training which was initially attributed to mechanical causes, without any further investigation by imaging methods. At admission, the patient had lumbar deformity, antalgic posture and bilaterally positive unipodalic lumbar hyperextension maneuver. After a research which showed spondyloptosis, the patient underwent surgery. In this article, we discuss, based on this case report, the diagnostic approach to low back pain in young athletes, since the complaint of chronic back pain can be a marker of a structural lesion that may be permanent and bring irreversible functional loss.

Acute physical exercise is safe in patients with primary antiphospholipid syndrome with exclusive venous thrombosis and under oral anticoagulation with warfarin.

The purpose of present study was to evaluate the effects of maximal acute physical exercise on prothrombin time/international normalized ratio (PT/INR) in patients with primary antiphospholipid syndrome (PAPS) under oral anticoagulation with warfarin and the safety of acute exercise in regard to thrombosis and bleeding risk. Eighteen physically inactive women with PAPS (Sydney criteria) with exclusive venous events and without thrombocytopenia were included. All patients were under stable warfarin therapy (PT/INR target: 2.0-3.0). Eighteen age-matched healthy sedentary women without thrombosis/bleeding disorders were selected as controls. All subjects performed a maximal exercise test, and capillary blood samples were obtained pre-, post- and at 1-h post-exercise (recovery time) for PT/INR analysis using a portable CoaguCheck. PAPS patients and controls had similar mean age (31.50 ± 8.06 vs. 29.61 ± 7.05 years, p = 0.46) and body mass index (24.16 ± 3.67 vs. 24.66 ± 2.71 kg/m(2), p = 0.65). PAPS had a mild but significant increase in PT/INR value at 1-h post-exercise (recovery) compared with pre- (2.33 ± 0.34 vs. 2.26 ± 0.29, p = 0.001) and post-exercise (2.33 ± 0.34 vs. 2.26 ± 0.32, p = 0.001) that was observed in 61.11 % of these patients. None of the subjects had thrombotic or bleeding complications related to the acute exercise. Acute exercise in patients with PAPS with exclusive venous thrombosis was safe with a minor increase in PT/INR. This is an important step to introduce regular exercise training as a therapeutic tool in the management of these patients.

Baixo valor sérico de P1NP: preditor de perda de massa óssea em mulheres na pré-menopausa com Lúpus Eritematoso Sistêmico / Lower P1NP serum levels: a predictive marker of bone loss in premenopausal SLE patients

Objetivos: Determinar a incidência de perda de massa óssea em um ano em pacientes com lúpus na pré-menopausa e o valor preditor dos marcadores do metabolismo ósseo para essa complicação. Métodos: Sessenta e três pacientes foram avaliadas à entrada no estudo e após um ano de seguimento. Variações na densidade mineral óssea (DXA) acima da mínima variação significativa (MVS) foram consideradas significativas, como recomendado pela Sociedade Internacional de Densitometria Clínica (International Society for Clinical Densitometry). Os níveis séricos dos marcadores do metabolismo ósseo foram determinados no início do estudo: propeptídeo N-terminal do pro-colágeno tipo 1 (P1NP) e telopeptídeo C-terminal do colágeno tipo 1 (CTX) por eletroquimioluminescência; osteoprotegerina (OPG) e ligante do receptor ativador do fator nuclear kB (RANKL) por ELISA. Resultados: 36,5% dos pacientes apresentaram perda de massa óssea e 17,5% ganho de massa óssea na coluna lombar e/ou fêmur. Os pacientes foram divididos em três grupos: perda de massa óssea (P), massa óssea estável (E) e ganho de massa óssea (G). Pacientes com P e E tomaram doses cumulativa, média e máxima de glicocorticoide semelhantes durante o estudo, mas pacientes com G receberam doses menores (G vs. P e G vs. E, p < 0,05). Os níveis séricos basais de P1NP foram diferentes nos três grupos (P: 36,95 ± 23,37 vs. E: 54,63 ± 30,82 vs. G: 84,09 ± 43,85 ng/ml, p=0,001). Análises de múltiplas comparações demonstraram diferenças significativas nos níveis de P1NP entre P vs. E, p=0,031; P vs. G, p < 0,001 e E vs. G, p=0,039. Não houve diferença entre os grupos com relação aos níveis de CTX, OPG/RANKL, fatores de risco para osteoporose ou parâmetros relacionados à doença. Após análise multivariada, apenas níveis baixos de P1NP permaneceram como fator de risco independente para perda de massa óssea (p < 0,013)...

Objective: To determine the one-year incidence of bone loss in premenopausal lupus patients and the value of bone markers as predictors of this complication. Methods: Sixty-three premenopausal SLE patients were evaluated at baseline and after one-year of follow-up. Bone mineral density changes (DXA) above the least significant change (LSC) were considered significant, as recommended by International Society for Clinical Densitometry. Serum levels of bone markers were determined at baseline: N-terminal propeptide of type 1 collagen (P1NP) and C-terminal telopeptide of type 1 collagen (CTX) by electrochemiluminescence; osteoprotegerin (OPG) and receptor activator of nuclear factor kB ligand (RANKL) by ELISA. Results: 36.5% of patients presented bone loss and 17.5% bone gain at lumbar spine and/or femur. Patients were divided in three groups: bone mass loss (BL), no bone mass change (NC) and bone mass gain (BG). Patients with BL e NC took similar cumulative, mean and maximum GC doses during the study, but patients with BG took lower doses (BG vs. BL and BG vs. NC, p < 0.05). Baseline P1NP levels were different in the three groups (BL: 36.95 ± 23.37 vs. NC: 54.63 ± 30.82 vs. BG: 84.09 ± 43.85 ng/ml, p=0.001). Further multiple comparison analysis demonstrated significant differences in P1NP between BL vs. NC, p=0.031; BL vs. BG, p < 0.001 and NC vs. BG, p=0.039. No difference was observed concerning the levels of CTX, OPG/RANKL, risk factors for osteoporosis or disease related parameters. After multivariate analysis only lower P1NP levels remained as an independent risk factor for bone loss (p < 0.013). Conclusion: This study provides original evidence that lower levels of P1NP, the most specific bone formation marker, are predictive of bone loss in the next year in premenopausal SLE patients...