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1.
RMD Open ; 7(1)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33574116

RESUMO

BACKGROUND: The SARS-CoV-2 pandemic is a global health problem. Beside the specific pathogenic effect of SARS-CoV-2, incompletely understood deleterious and aberrant host immune responses play critical roles in severe disease. Our objective was to summarise the available information on the pathophysiology of COVID-19. METHODS: Two reviewers independently identified eligible studies according to the following PICO framework: P (population): patients with SARS-CoV-2 infection; I (intervention): any intervention/no intervention; C (comparator): any comparator; O (outcome) any clinical or serological outcome including but not limited to immune cell phenotype and function and serum cytokine concentration. RESULTS: Of the 55 496 records yielded, 84 articles were eligible for inclusion according to question-specific research criteria. Proinflammatory cytokine expression, including interleukin-6 (IL-6), was increased, especially in severe COVID-19, although not as high as other states with severe systemic inflammation. The myeloid and lymphoid compartments were differentially affected by SARS-CoV-2 infection depending on disease phenotype. Failure to maintain high interferon (IFN) levels was characteristic of severe forms of COVID-19 and could be related to loss-of-function mutations in the IFN pathway and/or the presence of anti-IFN antibodies. Antibody response to SARS-CoV-2 infection showed a high variability across individuals and disease spectrum. Multiparametric algorithms showed variable diagnostic performances in predicting survival, hospitalisation, disease progression or severity, and mortality. CONCLUSIONS: SARS-CoV-2 infection affects both humoral and cellular immunity depending on both disease severity and individual parameters. This systematic literature review informed the EULAR 'points to consider' on COVID-19 pathophysiology and immunomodulatory therapies.


Assuntos
/epidemiologia , Imunidade Celular , Imunidade Humoral , Pandemias , /genética , Adulto , /virologia , Criança , Citocinas/metabolismo , Armadilhas Extracelulares/imunologia , Feminino , Humanos , Linfócitos/imunologia , Masculino , Fenótipo , Índice de Gravidade de Doença
2.
Ann Rheum Dis ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33589438

RESUMO

OBJECTIVE: To summarise the available information on efficacy and safety of immunomodulatory agents in SARS-CoV-2 infection. METHODS: As part of a European League Against Rheumatism (EULAR) taskforce, a systematic literature search was conducted from January 2019 to 11 December 2020. Two reviewers independently identified eligible studies according to the Population, Intervention, Comparator and Outcome framework and extracted data on efficacy and safety of immunomodulatory agents used therapeutically in SARS-CoV-2 infection at any stage. The risk of bias was assessed with validated tools. RESULTS: Of the 60 372 records, 401 articles were eligible for inclusion. Studies were at variable risk of bias. Randomised controlled trials (RCTs) were available for the following drugs: hydroxychloroquine (n=12), glucocorticoids (n=6), tocilizumab (n=4), convalescent plasma (n=4), interferon beta (n=2), intravenous immunoglobulins (IVIg) (n=2) and n=1 each for anakinra, baricitinib, colchicine, leflunomide, ruxolitinib, interferon kappa and vilobelimab. Glucocorticoids were able to reduce mortality in specific subsets of patients, while conflicting data were available about tocilizumab. Hydroxychloroquine was not beneficial at any disease stage, one RCT with anakinra was negative, one RCT with baricitinib+remdesivir was positive, and individual trials on some other compounds provided interesting, although preliminary, results. CONCLUSION: Although there is emerging evidence about immunomodulatory therapies for the management of COVID-19, conclusive data are scarce with some conflicting data. Since glucocorticoids seem to improve survival in some subsets of patients, RCTs comparing glucocorticoids alone versus glucocorticoids plus anticytokine/immunomodulatory treatment are warranted. This systematic literature review informed the initiative to formulate EULAR 'points to consider' on COVID-19 pathophysiology and immunomodulatory treatment from the rheumatology perspective.

3.
Ann Rheum Dis ; 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33547062

RESUMO

OBJECTIVES: Severe systemic inflammation associated with some stages of COVID-19 and in fatal cases led therapeutic agents developed or used frequently in Rheumatology being at the vanguard of experimental therapeutics strategies. The aim of this project was to elaborate EULAR Points to consider (PtCs) on COVID-19 pathophysiology and immunomodulatory therapies. METHODS: PtCs were developed in accordance with EULAR standard operating procedures for endorsed recommendations, led by an international multidisciplinary Task Force, including rheumatologists, translational immunologists, haematologists, paediatricians, patients and health professionals, based on a systemic literature review up to 15 December 2020. Overarching principles (OPs) and PtCs were formulated and consolidated by formal voting. RESULTS: Two OPs and fourteen PtCs were developed. OPs highlight the heterogeneous clinical spectrum of SARS-CoV-2 infection and the need of a multifaceted approach to target the different pathophysiological mechanisms. PtCs 1-6 encompass the pathophysiology of SARS-CoV-2 including immune response, endothelial dysfunction and biomarkers. PtCs 7-14 focus on the management of SARS-CoV-2 infection with immunomodulators. There was evidence supporting the use of glucocorticoids, especially dexamethasone, in COVID-19 cases requiring oxygen therapy. No other immunomodulator demonstrated efficacy on mortality to date, with however inconsistent results for tocilizumab. Immunomodulatory therapy was not associated with higher infection rates. CONCLUSIONS: Multifactorial pathophysiological mechanisms, including immune abnormalities, play a key role in COVID-19. The efficacy of glucocorticoids in cases requiring oxygen therapy suggests that immunomodulatory treatment might be effective in COVID-19 subsets. Involvement of rheumatologists, as systemic inflammatory diseases experts, should continue in ongoing clinical trials delineating optimal immunomodulatory therapy utilisation in COVID-19.

5.
RMD Open ; 6(2)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32665433

RESUMO

OBJECTIVE: To evaluate the effect of guselkumab on enthesitis and dactylitis in a phase II trial of patients with active psoriatic arthritis (PsA). METHODS: This was a phase II, randomised, placebo-controlled, double-blind trial of adults with active PsA (≥3 swollen and ≥3 tender joints and C reactive protein ≥0.3 mg/dL) despite conventional synthetic disease-modifying anti-rheumatic drug, non-steroidal anti-inflammatory drug, and/or oral corticosteroid therapy. Patients were randomised to subcutaneous injections of guselkumab 100 mg or placebo at weeks 0, 4 and every 8 weeks, with placebo crossover to guselkumab at week 24. Dactylitis was scored on a scale of 0-3 on each digit; enthesitis was assessed using the Leeds Enthesitis Index (0-6). Other assessments included American College of Rheumatology (ACR) and Psoriasis Area and Severity Index responses. RESULTS: Of 149 randomised patients, 107 patients had enthesitis (mean score=2.7) and 81 patients had dactylitis (mean dactylitis score=5.7) at baseline. Mean improvements in enthesitis and dactylitis at week 24 were greater in the guselkumab group versus placebo and sustained through week 56. Similar results were observed for the proportions of patients with resolution of enthesitis and dactylitis. At week 56, mean improvements in enthesitis and dactylitis among patients who switched from placebo to guselkumab treatment were similar to those in the guselkumab group. In the guselkumab group, ACR20 responders had greater improvements in enthesitis and dactylitis versus non-responders (week 24). CONCLUSIONS: At week 24, the guselkumab group had greater mean improvements in enthesitis and dactylitis and greater proportions of patients with resolution of enthesitis and dactylitis versus placebo. ACR20 response was associated with improvements in enthesitis and dactylitis. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT02319759.URL: https://clinicaltrials.gov/ct2/show/NCT02319759; Registered 18 December 2014.

6.
RMD Open ; 6(2)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32669454

RESUMO

This clinical case series describes our experience with the use of Janus kinase 1/2 inhibitor baricitinib in two patients suffering from refractory adult-onset Still's disease (AOSD) as well as in one case suffering from AOSD-like autoinflammatory disease in the context of myelodysplastic syndrome. All patients suffered from disease non-responsive to conventional Disease-modifying antirheumatic drugs (DMARDs) as well as biological therapies including interleukin (IL)-1 and IL-6 blockade, relying instead on high daily doses of prednisolone. We also report the first case of Pneumocystis jirovecii infection following baricitinib use.

8.
Ann Rheum Dis ; 79(6): 700-712, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32434812

RESUMO

OBJECTIVE: To update the European League Against Rheumatism (EULAR) recommendations for the pharmacological treatment of psoriatic arthritis (PsA). METHODS: According to the EULAR standardised operating procedures, a systematic literature review was followed by a consensus meeting to develop this update involving 28 international taskforce members in May 2019. Levels of evidence and strengths of recommendations were determined. RESULTS: The updated recommendations comprise 6 overarching principles and 12 recommendations. The overarching principles address the nature of PsA and diversity of both musculoskeletal and non-musculoskeletal manifestations; the need for collaborative management and shared decision-making is highlighted. The recommendations provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs and local glucocorticoid injections are proposed as initial therapy; for patients with arthritis and poor prognostic factors, such as polyarthritis or monoarthritis/oligoarthritis accompanied by factors such as dactylitis or joint damage, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drugs (bDMARDs) targeting tumour necrosis factor (TNF), interleukin (IL)-17A or IL-12/23 should be initiated, taking into account skin involvement if relevant. If axial disease predominates, a TNF inhibitor or IL-17A inhibitor should be started as first-line disease-modifying antirheumatic drug. Use of Janus kinase inhibitors is addressed primarily after bDMARD failure. Phosphodiesterase-4 inhibition is proposed for patients in whom these other drugs are inappropriate, generally in the context of mild disease. Drug switches and tapering in sustained remission are addressed. CONCLUSION: These recommendations provide stakeholders with an updated consensus on the pharmacological management of PsA, based on a combination of evidence and expert opinion.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Glucocorticoides/uso terapêutico , Sociedades Médicas , Consenso , Conferências de Consenso como Assunto , Tomada de Decisão Compartilhada , Europa (Continente) , Humanos , Interleucina-12/antagonistas & inibidores , Interleucina-17/antagonistas & inibidores , Interleucina-23/antagonistas & inibidores , Inibidores de Janus Quinases/uso terapêutico , Inibidores da Fosfodiesterase 4/uso terapêutico , Medicamentos Sintéticos/uso terapêutico , Revisões Sistemáticas como Assunto , Fator de Necrose Tumoral alfa/antagonistas & inibidores
9.
Ann Rheum Dis ; 79(8): 1044-1054, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32404344

RESUMO

BACKGROUND: The human enthesis conventional T cells are poorly characterised. OBJECTIVES: To study the biology of the conventional T cells in human enthesis. METHODS: CD4+ and CD8+ T cells were investigated in 25 enthesis samples using immunofluorescence, cytometrically, bulk RNAseq and quantitative real-time PCR following anti-CD3/CD28 bead stimulation to determine interleukin (IL)-17A and tumour necrosis factor (TNF) levels. T-cell receptor (TCR) repertoires were characterised and a search for putative T-cell reactivity was carried out using TCR3 database. The impact of pharmacological antagonism with retinoic acid receptor-related orphan nuclear receptor gamma t inhibitor (RORγti), methotrexate and phosphodiesterase type 4 inhibitor (PDE4i) was investigated. RESULTS: Immunofluorescence and cytometry suggested entheseal resident CD4+ and CD8+ T cells with a resident memory phenotype (CD69+/CD45RA-) and tissue residency gene transcripts (higher NR4A1/AhR and lower KLF2/T-bet transcripts). Both CD4+ and CD8+ T cells showed increased expression of immunomodulatory genes including IL-10 and TGF-ß compared with peripheral blood T cells with entheseal CD8+ T cells having higher CD103, CD49a and lower SIPR1 transcript that matched CD4+ T cells. Following stimulation, CD4+ T cells produced more TNF than CD8+ T cells and IL-17A was produced exclusively by CD4+ T cells. RNAseq suggested both Cytomegalovirus and influenza A virus entheseal resident T-cell clonotype reactivity. TNF and IL-17A production from CD4+ T cells was effectively inhibited by PDE4i, while RORγti only reduced IL-17A secretion. CONCLUSIONS: Healthy human entheseal CD4+ and CD8+ T cells exhibit regulatory characteristics and are predicted to exhibit antiviral reactivity with CD8+ T cells expressing higher levels of transcripts suggestive of tissue residency. Inducible IL-17A and TNF production can be robustly inhibited in vitro.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Ligamentos Articulares/imunologia , Linfócitos T Reguladores/imunologia , Tendões/imunologia , Adulto , Linfócitos T CD4-Positivos/imunologia , Feminino , Humanos , Interleucina-17/imunologia , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/imunologia
11.
RMD Open ; 5(2): e001067, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31749987

RESUMO

Objective: Non-specific musculoskeletal pain is common in subjects destined to develop psoriatic arthritis (PsA). We evaluated psoriatic patients with arthralgia (PsOAr) compared with psoriasis alone (PsO) and healthy controls (HCs) using ultrasonography (US) to investigate the anatomical basis for joint symptoms in PsOAr and the link between these imaging findings and subsequent PsA transition. Methods: A cross-sectional prevalence analysis of clinical and US abnormalities (including inflammatory and structural lesions) in PsOAr (n=61), PsO (n=57) and HCs (n=57) was performed, with subsequent prospective follow-up for PsA development. Results: Tenosynovitis was the only significant sonographic feature that differed between PsOAr and PsO (29.5% vs 5.3%, p<0.001), although synovitis and enthesitis were numerically more frequent in PsOAr. Five patients in PsOAr and one in PsO group developed PsA, with an incidence rate of 109.2/1000 person-years in PsOAr vs 13.4/1000 person-years in PsO (p=0.03). Visual Analogue Scale pain, Health Assessment Questionnaire, joint tenderness and US active enthesitis were baseline variables associated with PsA development. Conclusion: Tenosynovitis was associated with arthralgia in subjects with psoriasis. Baseline US evidence of enthesitis was associated with clinical PsA development in the longitudinal analysis. These findings are relevant for enriching for subjects at risk of imminent PsA development.


Assuntos
Artralgia/diagnóstico , Artralgia/etiologia , Artrite Psoriásica/complicações , Artrite Psoriásica/patologia , Ultrassonografia , Idoso , Artralgia/epidemiologia , Artrite Psoriásica/epidemiologia , Estudos de Casos e Controles , Comorbidade , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Índice de Gravidade de Doença , Avaliação de Sintomas , Ultrassonografia/métodos , Estados Unidos/epidemiologia
12.
Ann Rheum Dis ; 78(11): 1559-1565, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31530557

RESUMO

OBJECTIVES: Murine models of interleukin (IL)-23-driven spondyloarthritis (SpA) have demonstrated entheseal accumulation of γδT-cells which were responsible for the majority of local IL-17A production. However, IL-23 blockers are ineffective in axial inflammation in man. This study investigated γδT-cell subsets in the normal human enthesis to explore the biology of the IL-23/17 axis. METHODS: Human spinous processes entheseal soft tissue (EST) and peri-entheseal bone (PEB) were harvested during elective orthopaedic procedures. Entheseal γδT-cells were evaluated using immunohistochemistry and isolated and characterised using flow cytometry. RNA was isolated from γδT-cell subsets and analysed by qPCR. Entheseal γδT-cells were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, anti-CD3/28 or IL-23 and IL-17A production was measured by high-sensitivity ELISA and qPCR. RESULTS: Entheseal γδT-cells were confirmed immunohistochemically with Vδ1 and Vδ2 subsets that are cytometrically defined. Transcript profiles of both cell populations suggested tissue residency and immunomodulatory status. Entheseal Vδ2 cells expressed high relative abundance of IL-23/17-associated transcripts including IL-23R, RORC and CCR6, whereas the Vδ1 subset almost completely lacked detectable IL-23R transcript. Following PMA stimulation IL-17A was detectable in both Vδ1 and Vδ2 subsets, and following CD3/CD28 stimulation both subsets showed IL-17A and IL-17F transcripts with neither transcript being detectable in the Vδ1 subset following IL-23 stimulation. CONCLUSION: Spinal entheseal Vδ1 and Vδ2 subsets are tissue resident cells with inducible IL-17A production with evidence that the Vδ1 subset does so independently of IL-23R expression.


Assuntos
Entesopatia/imunologia , Interleucina-17/biossíntese , Linfócitos Intraepiteliais/metabolismo , Receptores de Interleucina/metabolismo , Subpopulações de Linfócitos T/metabolismo , Humanos
13.
Ann Rheum Dis ; 78(9): 1167-1178, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31278139

RESUMO

Although the pathogenic mechanisms underlying axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) are not fully elucidated, several lines of evidence suggest that immune responses mediated by interleukin 17A (IL-17A) play a pivotal role in both diseases. This is best highlighted by the significant clinical efficacy shown with inhibitors of IL-17A in treating axSpA and PsA. Nevertheless, a number of knowledge gaps exist regarding the role of IL-17A in the pathophysiology of spondyloarthritis in man, including its cellular origin, its precise role in discrete disease processes such enthesitis, bone erosion, and bone formation, and the reasons for the discrepant responses to IL-17A inhibition observed in certain other spondyloarthritis manifestations. In this review, we focus on the latest data from studies investigating the role of IL-17A in ankylosing spondylitis (AS) and PsA that build on existing and emerging scientific knowledge in the field. Key remaining research questions are also highlighted to guide future research.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Psoriásica/metabolismo , Interleucina-17/fisiologia , Espondilartrite/metabolismo , Artrite Psoriásica/tratamento farmacológico , Biomarcadores/metabolismo , Humanos , Interleucina-17/antagonistas & inibidores , Espondilartrite/tratamento farmacológico
14.
Ann Rheum Dis ; 78(7): 929-933, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31018959

RESUMO

OBJECTIVE: We investigated whether the normal human spinal enthesis contained resident myeloid cell populations, capable of producing pivotal proinflammatory cytokines including tumour necrosis factor (TNF) and interleukin (IL)-23 and determined whether these could be modified by PDE4 inhibition. METHODS: Normal human enthesis soft tissue (ST) and adjacent perientheseal bone (PEB) (n=15) were evaluated using immunohistochemistry (IHC), digested for myeloid cell phenotyping, sorted and stimulated with different adjuvants (lipopolysaccharide and mannan). Stimulated enthesis fractions were analysed for inducible production of spondyloarthropathy disease-relevant mediators (IL-23 full protein, TNF, IL-1ß and CCL20). Myeloid populations were also compared with matched blood populations for further mRNA analysis and the effect of PDE4 inhibition was assessed. RESULTS: A myeloid cell population (CD45+ HLADR+ CD14+ CD11c+) phenotype was isolated from both the ST and adjacent PEB and termed 'CD14+ myeloid cells' with tissue localisation confirmed by CD14+ IHC. The CD14- fraction contained a CD123+ HLADR+ CD11c- cell population (plasmacytoid dendritic cells). The CD14+ population was the dominant entheseal producer of IL-23, IL-1ß, TNF and CCL20. IL-23 and TNF from the CD14+ population could be downregulated by a PDE4I and other agents (histamine and 8-Bromo-cAMP) which elevate cAMP. Entheseal CD14+ cells had a broadly similar gene expression profile to the corresponding CD14+ population from matched blood but showed significantly lower CCR2 gene expression. CONCLUSIONS: The human enthesis contains a CD14+ myeloid population that produces most of the inducible IL-23, IL-1ß, TNF and CCL20. This population has similar gene expression profile to the matched blood CD14+ population.


Assuntos
Células do Tecido Conjuntivo/metabolismo , Interleucina-23/biossíntese , Células Mieloides/metabolismo , Quimiocina CCL20/biossíntese , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Células Dendríticas/metabolismo , Humanos , Imuno-Histoquímica , Interleucina-1beta/biossíntese , Receptores de Lipopolissacarídeos/metabolismo , Fator de Necrose Tumoral alfa/biossíntese
16.
Rheumatology (Oxford) ; 57(1): 32-40, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28387854

RESUMO

The recognition of the primacy of enthesitis in animal models of spondyloarthritis and the prevalence of clinically occult enthesopathy in psoriatic subjects and of persistent joint pain in PsA subjects who have ostensibly good reduction of joint swelling under biological therapy has highlighted the potential impact of polyenthesitis in psoriatic disease. In daily practice, the formal demonstration of enthesitis is challenging for the following reasons: the relatively avascular nature of enthesis, often leading to the absence of overt clinical inflammatory signs; the frequent lack of elevation of inflammatory markers; and finally, the limitations of current imaging techniques to provide supportive evidence for inflammation in these areas. Consequently, enthesitis may present as widespread pain indistinguishable from FM or may emerge as the dominant feature after successful biological therapy for suppression of synovitis. The unmet needs in the differentiation between FM and enthesitis in psoriatic disease patients are highlighted and critically evaluated in this article.


Assuntos
Artrite Psoriásica/diagnóstico , Entesopatia/diagnóstico , Fibromialgia/diagnóstico , Antirreumáticos/uso terapêutico , Artrite Psoriásica/diagnóstico por imagem , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/fisiopatologia , Produtos Biológicos/uso terapêutico , Diagnóstico Diferencial , Entesopatia/diagnóstico por imagem , Entesopatia/fisiopatologia , Fibromialgia/diagnóstico por imagem , Fibromialgia/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Cintilografia , Espondiloartropatias/diagnóstico , Espondiloartropatias/diagnóstico por imagem , Espondiloartropatias/tratamento farmacológico , Espondiloartropatias/fisiopatologia , Ultrassonografia
17.
Clin Rheumatol ; 36(3): 719-723, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27981462

RESUMO

This study hypothesises that an educational leaflet about psoriatic arthritis (PsA) will improve psoriasis patients' attendance for screening for PsA. A random sample of patients ≥18 years old with a coded diagnosis of psoriasis and no diagnosis of PsA, rheumatoid arthritis or ankylosing spondylitis were identified from five GP surgeries in Yorkshire, UK. Patients were randomised 1:1 to receive study information alone or with the educational leaflet, with an invitation to attend for a screening examination by a dermatologist and rheumatologist. Nine hundred thirty-two invitation packs were sent to recruit 191 (20.5%) participants. One hundred sixty-nine (88.5%) had current or previous psoriasis and 17 (10.1%) had previously undiagnosed PsA. The estimated prevalence of PsA was 18.1% (95% CI: 16.2, 20.1%).The response rate was lower than expected and was not significantly higher when patients received the educational leaflet (22.8 vs 18.3%, p = 0.08). Response rates varied by practice (14.7 to 30.6%). However, deprivation scores for each practice revealed a significant increase in response with the leaflet for deprivation decile of 3 (p < 0.001) but no significant differences in the other practices. An educational leaflet about PsA improves attendance for screening in primary care, but only in those practices with higher levels of socioeconomic deprivation.


Assuntos
Artrite Psoriásica/diagnóstico , Artrite Psoriásica/etiologia , Folhetos , Educação de Pacientes como Assunto , Atenção Primária à Saúde , Psoríase/complicações , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Classe Social , Fatores Socioeconômicos
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