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Systemic sclerosis (SSc) rarely overlaps with noninfective granulomatous conditions, such as sarcoidosis or pneumoconiosis.1A 73-year-old White man with anti-Scl70 positive SSc was evaluated for arthralgia, fever, and weight loss.
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Inflammatory rheumatic diseases are different pathologic conditions associated with a deregulated immune response, codified along a spectrum of disorders, with autoinflammatory and autoimmune diseases as two-end phenotypes of this continuum. Despite pathogenic differences, inflammatory rheumatic diseases are commonly managed with a limited number of immunosuppressive drugs, sometimes with partial evidence or transferring physicians' knowledge in different patients. In addition, several randomized clinical trials, enrolling these patients, did not meet the primary pre-established outcomes and these findings could be linked to the underlying molecular diversities along the spectrum of inflammatory rheumatic disorders. In fact, the resulting patient heterogeneity may be driven by differences in underlying molecular pathology also resulting in variable responses to immunosuppressive drugs. Thus, the identification of different clinical subsets may possibly overcome the major obstacles that limit the development more effective therapeutic strategies for these patients with inflammatory rheumatic diseases. This clinical heterogeneity could require a diverse therapeutic management to improve patient outcomes and increase the frequency of clinical remission. Therefore, the importance of better patient stratification and characterization is increasingly pointed out according to the precision medicine principles, also suggesting a new approach for disease treatment. In fact, based on a better proposed patient profiling, clinicians could more appropriately balance the therapeutic management. On these bases, we synthetized and discussed the available literature about the patient profiling in regard to therapy in the context of inflammatory rheumatic diseases, mainly focusing on randomized clinical trials. We provided an overview of the importance of a better stratification and characterization of the clinical heterogeneity of patients with inflammatory rheumatic diseases identifying this point as crucial in improving the management of these patients.
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In the past 20 years, earlier diagnosis and more intensive management have considerably improved the prognosis of rheumatoid arthritis (RA), with milder disease course achieved in particular in seropositive patients. In contrast, seronegative RA has remained largely neglected, and continues to be surrounded by uncertainties regarding its correct diagnosis, clinical phenotype, optimal treatment strategies and relevant outcomes.The purpose of this review is to summarise new insights about the pathogenic, clinical and prognostic peculiarities of seronegative RA that emerged during 2022, and that make this disease subset at least partially different from its seropositive counterpart.
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Artrite Reumatoide , Fator Reumatoide , Humanos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Prognóstico , Progressão da DoençaRESUMO
OBJECTIVES: The safety of COVID-19 vaccination in rheumatic patients treated with biological (b) and targeted synthetic (ts) disease-modifying anti-rheumatic drugs (DMARDs) remains poorly explored. METHODS: Reactogenicity, safety and disease flares following each of the two doses of the BNT162b2 mRNA vaccine was evaluated in 186 patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis treated with b/tsDMARDs, who discontinued anti-rheumatic treatments around vaccination. A group of 53 healthy controls was used for comparison. RESULTS: The frequency and severity of systemic events was similar to that reported in the general population, and no particular safety concerns emerged. The use of methotrexate reduced systemic reactogenicity (adjORs [95% CI] 0.49 [0.25-0.94] and 0.63 [0.32-0.99] after each vaccine dose), whilst no specific effects of different b/tsDMARDs were seen. Flares around vaccination were reported by 24.5% of the patients. Factors associated with flares were active disease (adjORs [95% CI] 2.8 [1.01-8.09] and 1.86 [0.99-6.03] after each vaccine dose) and use of JAKi (adjORs [95% CI] 3.96 [1.39-11.27] and 3.10 [0.99-7.85]). The percentage of cases requiring change or increase in DMARD therapy due to persistent worsening of disease activity at follow-up visits was low (3.2%). CONCLUSIONS: The safety of mRNA COVID-19 vaccination in arthritis patients on treatment with b/tsDMARDs is reassuring. In a regimen of peri-vaccine drug interruption, transient flares of the disease more commonly occur in association with active arthritis and use of shorter half-life drugs. Most flares do not require treatment escalation or change.
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Antirreumáticos , Artrite Reumatoide , Vacinas contra COVID-19 , COVID-19 , Humanos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Exacerbação dos SintomasRESUMO
OBJECTIVES: RA is a chronic inflammatory disease in which possible interstitial lung disease (ILD) is an extra-articular manifestation that carries significant morbidity and mortality. RF and ACPA are included in the RA classification criteria but prognostic and diagnostic biomarkers for disease endotyping and RA-ILD are lacking. Anti-protein arginine deiminase antibodies (anti-PAD) are a novel class of autoantibodies identified in RA. This study aimed to assess clinical features, ACPA and anti-PAD antibodies in RA patients with articular involvement and ILD. METHODS: We retrospectively collected joint erosions, space narrowing, clinical features and lung involvement of a cohort of 71 patients fulfilling the 2010 ACR/EULAR RA classification criteria. Serum samples from these patients were tested for ACPA IgG (QUANTA Flash CCP3), and anti-PAD3 and anti-PAD4 IgG, measured with novel assays based on a particle-based multi-analyte technology (PMAT). RESULTS: Anti-PAD4 antibodies were significantly associated with radiographic injury (P = 0.027) and erosions (P = 0.02). Similarly, ACPA levels were associated with erosive disease (P = 0.014). Anti-PAD3/4 double-positive patients displayed more joint erosions than patients with anti-PAD4 antibodies only or negative for both (P = 0.014 and P = 0.037, respectively). RA-ILD (15.5%, 11/71 patients) was associated with older age (P < 0.001), shorter disease duration (P = 0.045) and less erosive disease (P = 0.0063). ACPA were elevated in RA-ILD, while anti-PAD4 were negatively associated (P = 0.043). CONCLUSION: Anti-PAD4 and anti-PAD3 antibodies identify RA patients with higher radiographic injury and bone erosions. In our cohort, ILD is associated with lower radiographic and erosive damage, as well as low levels of anti-PAD4 antibodies.
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Artrite Reumatoide , Doenças Pulmonares Intersticiais , Humanos , Desiminases de Arginina em Proteínas , Estudos Retrospectivos , Proteína-Arginina Desiminase do Tipo 4 , Artrite Reumatoide/complicações , Autoanticorpos , Pulmão , Imunoglobulina GRESUMO
INTRODUCTION: Drug-free remission (DFR) and its maintenance have been defined as the most desirable outcome for rheumatoid arthritis (RA) patients. DFR is linked to resolution of arthritis-related symptoms and restoration of normal functioning. However, there is currently no consensus if an optimal strategy, upon the initiation of treatment to the proper drugs withdrawal, is enough to induce it, or whether it is a predetermined condition related to patients' intrinsic characteristics. AREAS COVERED: This review focuses on two key concepts around DFR. First, we analyze patients' intrinsic factors that may increase the chance of DFR, regardless of therapeutic choices. Second, we discuss on the evidence that it can be induced thanks to adequate, extrinsic disease management. Finally, we provide a glimpse into consequences of drugs discontinuation. EXPERT OPINION: The early initiation of DMARD and the subsequent strict monitoring and drug adjustments are of primary importance to allow patients to achieve DFR, irrespective of initial treatment strategy. Once remission is obtained and maintained, it is possible to gradually taper and discontinue drugs with no dramatic consequences on the disease course. Among those who stop medication, ACPA-negative patients more often maintain the remission. Thus, DFR might depend on a combination of intrinsic and extrinsic factors.
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Antirreumáticos , Artrite Reumatoide , Humanos , Indução de Remissão , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/diagnóstico , Antirreumáticos/uso terapêutico , Progressão da Doença , Quimioterapia Combinada , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the associations between the Patient Global Assessment (PGA) and measures of disease activity in patients with rheumatoid arthritis (RA) in relation to disease duration and autoantibody status. METHODS: 1412 patients from three independent cohorts were studied: a prospective cohort of 810 patients with early RA followed up for 24 months; a cross-sectional cohort of 210 patients with established RA in low disease activity; a cross-sectional cohort of 401 patients with established RA in moderate-to-high disease activity. Correlations of the PGA were analysed by Pearson's coefficients and multivariable linear regression at baseline and at months 6, 12 and 24 in the overall populations and after stratification for autoantibody subgroup and remission status (Boolean remission, PGA near remission and non-remission). RESULTS: In patients with early RA in non-remission, swollen joints correlated independently with the PGA; the correlation became progressively weaker but persisted at all time points in autoantibody-positive patients (adjusted r=0.30-0.12) but lost significance after month 12 in autoantibody-negative patients. Swollen joints independently correlated with the PGA also in near remission until month 12 (adjusted r=0.18-0.16) in autoantibody-positive patients. No independent correlations of inflammatory variables were instead found in patients with established RA irrespective of disease activity and autoantibody status. CONCLUSIONS: In the early phases of RA, particularly in autoantibody-positive patients, inflammatory variables directly correlate with the PGA across different disease activity states. The optimal cut-off values of the PGA capable of identifying absence of disease should be better explored in relation to disease duration and autoantibody status.
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Antirreumáticos , Artrite Reumatoide , Humanos , Autoanticorpos , Estudos Prospectivos , Estudos Transversais , Artrite Reumatoide/tratamento farmacológico , Índice de Gravidade de Doença , Indução de Remissão , Antirreumáticos/uso terapêuticoRESUMO
Bone mineral density (BMD) reduction and fragility fractures still represent a major source of morbidity in rheumatoid arthritis (RA) patients, despite adequate control of the disease. An increasing number of clinical and experimental evidence supports the role of autoantibodies, especially anti-citrullinated protein antibodies (ACPAs), in causing localized and generalised bone loss in ways that are both dependent on and independent of inflammation and disease activity. The human receptor activator of nuclear factor kappa B and its ligand-the so-called RANK-RANKL pathway-is known to play a key role in promoting osteoclasts' activation and bone depletion, and RANKL levels were shown to be higher in ACPA-positive early untreated RA patients. Thus, ACPA-positivity can be considered a specific risk factor for systemic and periarticular bone loss. Through the inhibition of the RANK-RANKL system, denosumab is the only antiresorptive drug currently available that exhibits both a systemic anti-osteoporotic activity and a disease-modifying effect when combined with conventional synthetic or biologic disease-modifying anti-rheumatic drugs (DMARDs). Thus, the combination of DMARD and anti-RANKL therapy could be beneficial in the prevention of fragility fractures and structural damage in the subset of RA patients at risk of radiographic progression, as in the presence of ACPAs.
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Differences in clinical presentation, response to treatment, and long-term outcomes between autoantibody-positive and -negative rheumatoid arthritis (RA) highlight the need for a better comprehension of the immunopathogenic events underlying the two disease subtypes. Whilst the drivers and perpetuators of autoimmunity in autoantibody-positive RA have started to be disclosed, autoantibody-negative RA remains puzzling, also due its wide phenotypic heterogeneity and its possible misdiagnosis. Genetic susceptibility appears to mostly rely on class I HLA genes and a number of yet unidentified non-HLA loci. On the background of such variable genetic predisposition, multiple exogeneous, endogenous, and stochastic factors, some of which are not shared with autoantibody-positive RA, contribute to the onset of the inflammatory cascade. In a proportion of the patients, the immunopathology of synovitis, at least in the initial stages, appears largely myeloid driven, with abundant production of proinflammatory cytokines and only minor involvement of cells of the adaptive immune system. Better understanding of the complexity of autoantibody-negative RA is still needed in order to open new avenues for targeted intervention and improve clinical outcomes.
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Anticorpos Antiproteína Citrulinada/imunologia , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Autoimunidade , Meio Ambiente , Predisposição Genética para Doença/genética , Fator Reumatoide/imunologia , Animais , Feminino , Antígenos HLA-B/imunologia , Cadeias HLA-DRB1/imunologia , Humanos , Estilo de Vida , Masculino , Sinovite/imunologiaAssuntos
Antirreumáticos/imunologia , Artrite Reumatoide/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Imunogenicidade da Vacina/efeitos dos fármacos , Artrite Reumatoide/tratamento farmacológico , Vacina BNT162 , COVID-19/imunologia , Feminino , Glucocorticoides/imunologia , Humanos , Masculino , Metotrexato/imunologia , Pessoa de Meia-Idade , SARS-CoV-2/imunologiaRESUMO
Se presenta el caso de un paciente con un pólipo pediculado único ubicado en la tercera porción del duodeno cuyo diagnóstico histopatológico correspondió a una lesión inflamatoria y fibrosa, es decir, benigna. Se describieron detalladamente la etiología, patología, clínica, diagnóstico y tratamiento de los pólipos y otros tumores benignos del intestino delgado
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Pessoa de Meia-Idade , Humanos , Masculino , Pólipos Intestinais/cirurgia , Duodeno/patologia , Duodeno/cirurgiaRESUMO
Se presenta el caso de una paciente con un pseudoquiste esplénico sintomático, que con toda seguridad se originó como consecuencia de un traumatismo torácico antiguo (20 años antes), el cual fue diagnosticado con el empleo del ultrasonido y la tomografía axial computarizada y tratado exitosamente con la esplenectomía. Se describen detalladamente la historia, incidencia, etiopatogenia, clínica, diagnóstico y tratamiento de los quistes esplénicos. Se revisaron los índices bibliográficos nacional y latinoamericanos hasta diciembre de 1986 y no se encontró ningún reporte sobre los seudoquistes del bazo