Effect of biological disease-modifying antirheumatic drugs on body composition in patients with rheumatoid arthritis: a systematic review and meta-analysis

Abstract Background: Rheumatoid arthritis (RA) generates an inflammatory profile that predisposes to total and visceral fatty accumulation and reduced fat free mass (FFM). This metabolic disorder contributes to poor functionality, increased cardiovascular risk and higher mortality. This study aimed to address a systematic review with meta-analysis to determine the effect of biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) on body composition (BC) of patients with RA. Methods: The search was conducted at the electronic databases PubMed, Cochrane Library, Embase, Lilacs and grey literature. This investigation was carried until July 2021. Outcomes of interest were total weight, body mass index (BMI), fat mass (FM) and FFM. A meta-analysis comparing these outcomes in RA patients under bDMARD treatment versus controls was performed. Results: Out of 137 studies reviewed, 18 were selected: fifteen prospective cohorts, two retrospective cohorts, and one cross-sectional study. The studies comprised 1221 patients, 778 on bDMARD treatment and 443 controls, which included RA patients under conventional synthetic DMARD (csDMARD). No study addressing BC analysis in patients using tsDMARD was found. The mean age and duration of the disease was 56.7 years and 6.77 years, respectively. Ten studies demonstrated a significant increase of total weight in 88.2% of patients and 42.3% for BMI. In studies that analyzed BC by double X-ray absorptiometry (DXA), the increase in total weight and BMI correlated positively to the increase in FFM. The meta-analysis carried out in five studies showed no significant difference of the mean difference for total weight 0.12 kg (95% CI − 5.58, 5.82), BMI 0.08 kg/m2 (95% CI − 1.76, 1.92), FM − 0.08 kg (95% IC − 5.31, 5.14), and FFM − 2.08 kg (95% CI − 7.37, 3.21). Conclusion: This systematic review suggests a possible impact of bDMARDs on BC of RA patients, even though, the meta-analysis carried out in a small part of these studies was not able to confirm significant variation in BC components. Trial registration: PROSPERO code: CRD42020206949.

Guidelines on COVID-19 vaccination in patients with immune-mediated rheumatic diseases: a Brazilian Society of Rheumatology task force

Abstract Objective: To provide guidelines on the coronavirus disease 2019 (COVID-19) vaccination in patients with immune-mediated rheumatic diseases (IMRD) to rheumatologists considering specific scenarios of the daily practice based on the shared-making decision (SMD) process. Methods: A task force was constituted by 24 rheumatologists (panel members), with clinical and research expertise in immunizations and infectious diseases in immunocompromised patients, endorsed by the Brazilian Society of Rheumatology (BSR), to develop guidelines for COVID-19 vaccination in patients with IMRD. A consensus was built through the Delphi method and involved four rounds of anonymous voting, where five options were used to determine the level of agreement (LOA), based on the Likert Scale: (1) strongly disagree; (2) disagree, (3) neither agree nor disagree (neutral); (4) agree; and (5) strongly agree. Nineteen questions were addressed and discussed via teleconference to formulate the answers. In order to identify the relevant data on COVID-19 vaccines, a search with standardized descriptors and synonyms was performed on September 10th, 2021, of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and LILACS to identify studies of interest. We used the Newcastle-Ottawa Scale to assess the quality of nonrandomized studies. Results: All the nineteen questions-answers (Q&A) were approved by the BSR Task Force with more than 80% of panelists voting options 4—agree—and 5—strongly agree—, and a consensus was reached. These Guidelines were focused in SMD on the most appropriate timing for IMRD patients to get vaccinated to reach the adequate covid-19 vaccination response. Conclusion: These guidelines were developed by a BSR Task Force with a high LOA among panelists, based on the literature review of published studies and expert opinion for COVID-19 vaccination in IMRD patients. Noteworthy, in the pandemic period, up to the time of the review and the consensus process for this document, high-quality evidence was scarce. Thus, it is not a substitute for clinical judgment.

Chronic use of hydroxychloroquine did not protect against COVID-19 in a large cohort of patients with rheumatic diseases in Brazil

Abstract Background: There is a lack of information on the role of chronic use of hydroxychloroquine during the SARS-CoV-2 outbreak. Our aim was to compare the occurrence of COVID-19 between rheumatic disease patients on hydroxychloroquine with individuals from the same household not taking the drug during the first 8 weeks of community viral transmission in Brazil. Methods: This baseline cross-sectional analysis is part of a 24-week observational multi-center study involving 22 Brazilian academic outpatient centers. All information regarding COVID-19 symptoms, epidemiological, clinical, and demographic data were recorded on a specific web-based platform using telephone calls from physicians and medical students. COVID-19 was defined according to the Brazilian Ministry of Health (BMH) criteria. Mann-Whitney, Chi-square and Exact Fisher tests were used for statistical analysis and two binary Final Logistic Regression Model by Wald test were developed using a backward-stepwise method for the presence of COVID-19. Results: From March 29th to May 17st, 2020, a total of 10,443 participants were enrolled, including 5166 (53.9%) rheumatic disease patients, of whom 82.5% had systemic erythematosus lupus, 7.8% rheumatoid arthritis, 3.7% Sjögren's syndrome and 0.8% systemic sclerosis. In total, 1822 (19.1%) participants reported flu symptoms within the 30 days prior to enrollment, of which 3.1% fulfilled the BMH criteria, but with no significant difference between rheumatic disease patients (4.03%) and controls (3.25%). After adjustments for multiple confounders, the main risk factor significantly associated with a COVID-19 diagnosis was lung disease (OR 1.63; 95% CI 1.03-2.58); and for rheumatic disease patients were diagnosis of systemic sclerosis (OR 2.8; 95% CI 1.19-6.63) and glucocorticoids above 10 mg/ day (OR 2.05; 95% CI 1.31-3.19). In addition, a recent influenza vaccination had a protective effect (OR 0.674; 95% CI 0.46-0.98). Conclusion: Patients with rheumatic disease on hydroxychloroquine presented a similar occurrence of COVID-19 to household cohabitants, suggesting a lack of any protective role against SARS-CoV-2 infection. Trial registration Brazilian Registry of Clinical Trials (ReBEC; RBR - 9KTWX6).

Rectus femoris muscle mass evaluation by ultrasound: facilitating sarcopenia diagnosis in pre-dialysis chronic kidney disease stages

OBJECTIVES: We evaluated the validity and reliability of ultrasonography measurement of rectus femoris cross-sectional area compared to computed tomography in patients in pre-dialysis chronic kidney disease and analyzed the association between these measurements and the diagnosis of sarcopenia. METHODS: One hundred patients with nondialysis chronic kidney disease were evaluated. Sarcopenia was defined using the criteria of the Foundation for the National Institutes of Health Sarcopenia Project (FNIH). The rectus femoris cross-sectional area was evaluated using ultrasonography and computed tomography. RESULTS: The prevalence of sarcopenia was 29% according to the FNIH criteria. The difference in mean rectus femoris cross-sectional area by ultrasonography and computed tomography was 3.97 mm, with a strong correlation between the two methods (p<0.001). Bland-Altman plot analysis showed good agreement between computed tomography and ultrasonography. Rectus femoris cross-sectional area was significantly correlated with muscle strength (r=0.300, p=0.002), lean body mass in the upper limbs (r=0.286, p=0.004), and lean body mass in the lower limbs (r=0.271, p=0.006). The prevalence of sarcopenia was 12% (n=12) based on the definition of low muscle mass according to ultrasonography of the rectus femoris cross-sectional area. CONCLUSION: Ultrasonography was demonstrated to be a valid and reliable method for evaluating the rectus femoris cross-sectional area in patients in pre-dialysis chronic kidney disease.

Sarcopenia na doença renal crônica / Sarcopenia in chronic kidney disease

A sarcopenia é uma condição crônica associada ao processo fisiológico de envelhecimento e é definida pela redução da massa, força e função musculares. Na Doença Renal Crônica (DRC), a sarcopenia é prevalente, e associa-se ao aumento da morbimortalidade e à ocorrência de complicações cardiovasculares. Ao analisarmos a sarcopenia em pacientes com insuficiência renal, destacam-se mecanismos complexos que contribuem para a perda de massa muscular, como ativação de mediadores que estimulam o sistema da ubiquitina-proteossoma (SUP) dependente de ATP, inflamação, acidose metabólica, angiotensina II e alguns fatores hormonais. A abordagem terapêutica da sarcopenia na DRC inclui a realização de exercícios, correção da acidose metabólica, reposição hormonal e tratamento da resistência insulínica. Desta forma, é de suma importância o reconhecimento precoce da sarcopenia nesta população, com o intuito de estabelecer intervenções terapêuticas eficazes, evitando-se, assim, toda a gama de complicações associadas à perda de massa muscular na DRC.

Sarcopenia is a chronic condition associated with physiological aging process and is defined by the reduction of the mass, muscle strength and function. In Chronic Kidney Disease (CKD), sarcopenia is prevalent and is associated with increased morbidity and mortality and the occurrence of cardiovascular complications. By analyzing sarcopenia in patients with renal insufficiency, complex mechanisms that contribute to loss of muscle mass are highlighted, such as activation of mediators that stimulate the ubiquitin-proteasome system (SUP) ATP-dependent, inflammation, metabolic acidosis, angiotensin II and some hormonal factors. The therapeutic approach to sarcopenia in CKD includes exercises, correction of metabolic acidosis, hormone replacement therapy and insulin resistance. Thus, it is of paramount importance early recognition of sarcopenia in this population, in order to establish effective therapeutic interventions, thus avoiding the full range of complications associated with muscle wasting in CKD.

Associação de hipovitaminose D com Lúpus Eritematoso Sistêmico e inflamação / Association of hypovitaminosis D with Systemic Lupus Erythematosus and inflammation

Introdução: Atualmente, é descrita elevada prevalência de hipovitaminose D no Lúpus Eritematoso Sistêmico (LES), a qual se associa a algumas manifestações clínicas e maior atividade inflamatória. Objetivo: Avaliar a associação entre insuficiência de vitamina D com LES e marcadores inflamatórios. Métodos: Estudo transversal, tendo sido avaliados 45 pacientes com LES e 24 controles sem a doença. Níveis de 25-hidroxivitamina D [25(OH)D] menores que 30 ng/mL foram considerados insuficientes. A atividade da doença foi avaliada pelo Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Foram avaliados, ainda, proteína C reativa ultrassensível (PCRus) e interleucina-6 (IL-6) para verificação do status inflamatório. Para avaliação do envolvimento renal, foram realizados análise de elementos anormais e sedimentoscopia urinárias (EAS), hematúria e piúria quantitativas, proteinúria e depuração de creatinina em urina de 24 horas e anti-DNA de dupla hélice sérico. Resultados: A prevalência de insuficiência de 25(OH)D foi de 55% nos pacientes lúpicos e 8% nos participantes controles (p = 0,001). A mediana da 25(OH)D foi menor nos pacientes do que no grupo controle. Os pacientes com insuficiência de 25(OH)D apresentaram níveis mais elevados de IL-6 e maior prevalência de hematúria ao EAS. Não houve correlação entre vitamina D, nefrite lúpica e SLEDAI. Conclusão: Em nosso estudo, a insuficiência de vitamina D foi mais prevalente em pacientes com LES e se associou com níveis mais elevados de IL-6 e presença de hematúria. .

Introduction: Nowadays it is described a high prevalence of hypovitaminosis D in Systemic Lupus Erythematosus (SLE), which is associated with some clinical manifestations and increased inflammatory activity. Objective: To evaluate the association between vitamin D insufficiency with SLE and inflammatory markers. Methods: Cross-sectional study, in which have been evaluated 45 SLE patients and 24 controls without the disease. Levels of 25-hydroxyvitamin D [25(OH) D] less than 30 ng/mL were considered inadequate. Disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). High sensitivity C reactive protein (hsCRP) and interleukin-6 (IL-6) were evaluated for verification of the inflammatory status. For assessment of renal involvement, analysis of abnormal elements and urinay sediment (AES), quantitative hematuria and pyuria, proteinuria and creatinine clearance in 24-hour urine and serum anti-double stranded DNA were performed. Results: The prevalence of 25(OH)D insufficiency was 55% in SLE patients and 8% in the controls participants (p = 0.001). The median of 25(OH)D was lower in patients than in controls. Patients with insufficient 25(OH)D had higher levels of IL-6 and higher prevalence of hematuria in the AES. There was no correlation between vitamin D and SLEDAI or lupus nephritis. Conclusion: In our study, vitamin D deficiency was more prevalent in patients with SLE and was associated with higher levels of IL-6 and hematuria. .

Eritema elevatum diutinum como diagnóstico diferencial das doenças reumatológicas: relato de caso / Eritema elevatum diutinum como diagnóstico diferencial das doenças reumatológicas: case report

O eritema elevatum diutinum é uma vasculite leucocitoclástica cutânea crônica e rara, caracterizada por pápulas, placas e nódulos vermelhos, purpúreos e amarelados, distribuídos simetricamente sobre as superfícies extensoras das extremidades. Está associado a vários processos autoimunes, neoplásicos e infecciosos, principalmente malignidades hematológicas (cerca de 30 por cento dos casos). Artralgia e artrite são sintomas frequentes, que afetam por volta de 40 por cento dos pacientes, o que indica a necessidade de sua inclusão no diagnóstico diferencial das doenças reumatológicas, principalmente se em conjunto com outras apresentações da vasculite leucocitoclástica, caracterizadas pela combinação de manifestações reumáticas com alterações cutâneas características. Descrevemos o caso de uma paciente de 18 anos que desenvolveu eritema elevatum diutinum, cujo diagnóstico baseou-se nas características morfológicas, no padrão de distribuição das lesões cutâneas e nos achados histopatológicos de vasculite leucocitoclástica. O principal sintoma sistêmico era uma artrite severa.

Erythema elevatum diutinum is a chronic and rare cutaneous leukocytoclastic vasculitis, characterized by red, purple and yellow papules, plaques and nodules, distributed symmetrically on the extensor surfaces of the limbs. It is associated with several autoimmune, neoplastic and infectious processes, mainly hematological malignancies in about 30 percent of the cases. Joint pain and arthritis are frequent symptoms, affecting approximately 40 percent of the patients, indicating the need for its inclusion in the differential diagnosis of rheumatic diseases, chiefl y the other presentations of leukocytoclastic vasculitis, which are characterized by the combination of rheumatic manifestations and peculiar cutaneous lesions. We report the case of an 18-year-old female patient who developed erythema elevatum diutinum and whose diagnosis was based on the morphologic characteristics, the distribution pattern of the cutaneous lesions and the histopathological fi ndings of leukocytoclastic vasculitis. The major systemic symptom was severe arthritis.

Fibromialgia / Fibromyalgia

A fibromialgia é uma síndrome caracterizada por dor difusa e pontos dolorosos sem a evidência de sinovite, miosite ou outros sinais inflamatórios clínicos e laboratoriais. Acomete preferencialmente o sexo feminino entre 30 e 50 anos, podendo atingir qualquer faixa etária. A sua etiologia ainda não foi definida, apesar da extensa investigação, sendo relacionada a alterações de humor, infecção, distúrbios do sono e disfunções de neurotransmissores. O quadro clínico se caracteriza por dor difusa, alteração da qualidade do sono e do humor, fadiga, parestesia, cefaleia, edema subjetivo, rigidez articular, tonteira, zumbidos, precordialgia atípica e alterações digestivas, o que confunde o diagnóstico e atrasa o início do tratamento. Mudança no estilo de vida, atividade física regular, suporte psicológico e utilização de drogas específicas podem alterar o curso da história natural da doença e aliviar o sofrimento do paciente.