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OBJECTIVES: To assess, in spondyloarthritis (SpA), the discriminative value of the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and their associations with clinical features in this population. METHODS: In this multicentre study involving 20 rheumatology centres, clinical and ultrasound examinations of the lower limb large entheses were performed in 413 patients with SpA (axial SpA and psoriatic arthritis) and 282 disease controls (osteoarthritis and fibromyalgia). 'Active enthesitis' was defined as (1) power Doppler (PD) at the enthesis grade ≥1 plus entheseal thickening and/or hypoechoic areas, or (2) PD grade >1 (independent of the presence of entheseal thickening and/or hypoechoic areas). RESULTS: In the univariate analysis, all OMERACT lesions except enthesophytes/calcifications showed a significant association with SpA. PD (OR=8.77, 95% CI 4.40 to 19.20, p<0.001) and bone erosions (OR=4.75, 95% CI 2.43 to 10.10, p<0.001) retained this association in the multivariate analysis. Among the lower limb entheses, only the Achilles tendon was significantly associated with SpA (OR=1.93, 95% CI 1.30 to 2.88, p<0.001) in the multivariate analyses. Active enthesitis showed a significant association with SpA (OR=9.20, 95% CI 4.21 to 23.20, p<0.001), and unlike the individual OMERACT ultrasound lesions it was consistently associated with most clinical measures of SpA disease activity and severity in the regression analyses. CONCLUSIONS: This large multicentre study assessed the value of different ultrasound findings of enthesitis in SpA, identifying the most discriminative ultrasound lesions and entheseal sites for SpA. Ultrasound could differentiate between SpA-related enthesitis and other forms of entheseal pathology (ie, mechanical enthesitis), thus improving the assessment of entheseal involvement in SpA.
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Entesopatia , Espondilartrite , Ultrassonografia Doppler , Humanos , Feminino , Masculino , Entesopatia/diagnóstico por imagem , Adulto , Pessoa de Meia-Idade , Ultrassonografia Doppler/métodos , Espondilartrite/diagnóstico por imagem , Espondilartrite/complicações , Artrite Psoriásica/diagnóstico por imagem , Artrite Psoriásica/complicações , Índice de Gravidade de Doença , Tendão do Calcâneo/diagnóstico por imagem , Tendão do Calcâneo/patologia , Estudos de Casos e ControlesRESUMO
OBJECTIVE: This study aims to evaluate the active and chronic lesions in sacroiliac joints and lumbar spine over a decade of TNFi therapy in patients with AS. METHODS: The study enrolled patients with AS under treatment with a TNFi for over a decade. The patients underwent a new MRI scan of their lumbar spine and sacroiliac joint (SIJ). Two readers evaluated all images. Inflammation of SIJ (SIS), SIJ structural damage (SSS) including Fat Metaplasia, Erosions, Backfill and Ankylosis, and Spondyloarthritis Research Consortium of Canada Bone marrow edema (SPARCC) spine score were recorded. RESULTS: In the study, 15 patients were included, with 80% being male. The mean age during their first MRI was 38.1 (± 11.9) years old, and the majority (86.7%) tested positive for HLA-B27. While TNFi improved both BASDAI and BASFI scores, there was a noticeable increase in MRI acute lesions in the SIJ over time, where the median score increased from 0 (0-4) to 3 (0-10) after ten years (p = 0.028). After a decade of treatment, the median SPARCC spine score also increased from 0 (0-9) to 5 (0-16), p = 0.093. Finally, it was observed that there was a significant positive correlation between ESR and SIS erosions in cases of chronic lesions (r = 0.819, p < 0.001). CONCLUSIONS: While TNFi have significantly improved the treatment of AS, this study shows that acute lesions can still develop despite treatment. A personalized approach that adapts MRI assessment to each patient's specific requirements may help detect changes early and enable doctors to intervene promptly to prevent further damage.
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Relapsing polychondritis (RP) is a rare autoimmune disease characterized by inflammation of the cartilage structures of the body with typical features of auricular chondritis, nasal and ocular inflammation, audio-vestibular damage, as well as respiratory tract manifestations. It is associated with several autoimmune diseases and many other disorders. Tumor necrosis factor alpha (TNFα) inhibitors treat many chronic inflammatory disorders. They have proven effective and relatively safe in many clinical trials and observational studies. However, several autoimmune phenomena and paradoxical inflammation have been described with TNFα inhibitors, among them RP. This report presents a 43-year-old man with psoriatic arthritis treated with ABP-501 (Amgevita), an adalimumab (ADA) biosimilar and who developed RP, 8 months after the initiation of the treatment. This, is the first report of RP development during TNFα inhibitors biosimilar. We concluded that rheumatologists dealing with patients treated with TNFα inhibitors (originators or biosimilars), should be aware of several paradoxical reactions which may emerge and RP, is one of them.
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Doenças Autoimunes , Medicamentos Biossimilares , Policondrite Recidivante , Masculino , Humanos , Adulto , Medicamentos Biossimilares/efeitos adversos , Fator de Necrose Tumoral alfa/uso terapêutico , Doenças Autoimunes/complicações , Policondrite Recidivante/complicações , Policondrite Recidivante/diagnóstico , Policondrite Recidivante/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Inflamação/complicaçõesRESUMO
Rheumatoid arthritis (RA) is considered the most common form of autoimmune arthritis. The disease's prevalence is around 0.5-1% worldwide, but it seems to vary among different populations. The aim of this study was to estimate the prevalence of self-reported diagnosed RA in the general adult population in Greece. The data were derived from the Greek Health Examination Survey EMENO, a population-based survey performed between 2013 and 2016. Of the 6006 participants (response rate 72%), 5884 were eligible for this study. Prevalence estimates were calculated according to the study design. Prevalence of self-reported RA was estimated to be overall 0.5% (95% CI 0.4-0.7) being approximately three times higher in women than in men (0.7% vs 0.2%, p value = 0.004). A decrease in the prevalence of RA was observed in urban areas of the country. In contrast, higher disease rates were reported in individuals with lower socioeconomic status. Multivariable regression analysis showed that gender, age, and income were related to the occurrence of the disease. Osteoporosis and thyroid disease were the two comorbidities observed at statistically significant higher rates in individuals with self-reported RA. The prevalence of self-reported RA in Greece is similar to that reported in other European countries. Gender, age, and income are the main factors related to the disease's prevalence in Greece.
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Artrite Reumatoide , Masculino , Adulto , Humanos , Feminino , Grécia/epidemiologia , Prevalência , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Comorbidade , Inquéritos EpidemiológicosRESUMO
OBJECTIVES: Retroperitoneal fibrosis (RPF) is mostly idiopathic (iRPF); however, it can be secondary to drugs, malignancies, infections, or, as recently recognised, can be part of the IgG4-related diseases. The aim of our study was i) to describe the presenting clinical/laboratory/imaging features and treatment modalities used in patients with iRPF and ii) to evaluate factors potentially associated with disease relapse. METHODS: The medical records of patients diagnosed with iRPF and followed in four tertiary medical units in Athens, Greece from 2000 to 2018 were retrospectively evaluated. RESULTS: Sixty-seven patients with iRPF were included in the study. Seventy-three per cent were males, with a mean age at diagnosis 56.0±9.2 years. Low-back pain (63%) and constitutional symptoms (57%) were the commonest presenting symptoms. Elevated acute-phase reactants (78%), anaemia (43%) and impaired renal function (41%) were the most common laboratory findings. Serum IgG4 at diagnosis was evaluated in 36/67 patients and 36% of them had elevated levels (mean 297.7±166.3mg/dL). Diagnosis was mainly based on abdominal CT and/or MRI. Clinical/laboratory/radiological presentation did not differ between patients with elevated and normal serum IgG4 levels. Steroids were used as first-line treatment in 98%. Relapse occurred in 28.6% after a mean of 43.1±31.8 months. Relapse did not associate to initial clinical/imaging findings or to any treatment used, however patients with increased serum IgG4 had a significantly higher relapse rate (75% vs. 25%, p=0.005). CONCLUSIONS: Relapse occurred in one-fifth of patients independently of the initial clinical/radiographic presentation or treatment used. iRPF patients with baseline elevated serum IgG4 levels have a higher relapse rate.
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Fibrose Retroperitoneal , Proteínas de Fase Aguda , Doença Crônica , Feminino , Grécia , Humanos , Imunoglobulina G , Masculino , Recidiva , Fibrose Retroperitoneal/diagnóstico por imagem , Fibrose Retroperitoneal/tratamento farmacológico , Estudos RetrospectivosRESUMO
OBJECTIVES: To investigate humoral responses and safety of mRNA SARS-CoV-2 vaccines in systemic autoimmune and autoinflammatory rheumatic disease (SAARD) patients subjected or not to treatment modifications during vaccination. METHODS: A nationwide, multicenter study, including 605 SAARD patients and 116 controls, prospectively evaluated serum anti-SARS-CoV-2 S1-protein IgG antibody titers, side-effects, and disease activity, one month after complete vaccination, in terms of distinct treatment modification strategies (none, partial and extended modifications). Independent risk factors associated with hampered humoral responses were identified by data-driven multivariable logistic regression analysis. RESULTS: Patients with extended treatment modifications responded to vaccines similarly to controls as well as SAARD patients without immunosuppressive therapy (97.56% vs 100%, p = 0.2468 and 97.56% vs 97.46%, p > 0.9999, respectively). In contrast, patients with partial or without therapeutic modifications responded in 87.50% and 84.50%, respectively. Furthermore, SAARD patients with extended treatment modifications developed higher anti-SARS-CoV-2 antibody levels compared to those without or with partial modifications (median:7.90 vs 7.06 vs 7.1, p = 0.0003 and p = 0.0195, respectively). Mycophenolate mofetil (MMF), rituximab (RTX) and methotrexate (MTX) negatively affected anti-SARS-CoV-2 humoral responses. In 10.5% of vaccinated patients, mild clinical deterioration was noted; however, no differences in the incidence of deterioration were observed among the distinct treatment modification SAARD subgroups. Side-effects were generally comparable between SAARD patients and controls. CONCLUSIONS: In SAARD patients, mRNA SARS-CoV-2 vaccines are effective and safe, both in terms of side-effects and disease flares. Treatment with MMF, RTX and/or MTX compromises anti-SARS-CoV-2 antibody responses, which are restored upon extended treatment modifications without affecting disease activity.
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Vacina de mRNA-1273 contra 2019-nCoV/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Doenças Autoimunes/imunologia , Vacina BNT162/imunologia , Doenças Hereditárias Autoinflamatórias/imunologia , Doenças Reumáticas/imunologia , Vacina de mRNA-1273 contra 2019-nCoV/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/tratamento farmacológico , Vacina BNT162/efeitos adversos , COVID-19/prevenção & controle , Feminino , Grécia , Doenças Hereditárias Autoinflamatórias/tratamento farmacológico , Humanos , Imunoglobulina G/sangue , Masculino , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Estudos Prospectivos , Doenças Reumáticas/tratamento farmacológico , Rituximab/efeitos adversos , Rituximab/uso terapêutico , SARS-CoV-2/imunologia , Adulto JovemRESUMO
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation that, if left untreated, can cause joint destruction and physical impairments. The inflammatory process is systematic, and it is associated with increased morbidity and mortality. Over the last years, mortality presents a decreasing trend; still, there is a high burden of cardiovascular disease (CVD) in RA that seems to be related to coronary atherosclerosis. Chronic inflammation, physical inactivity, and drugs used to treat RA are some of the reasons. Thus, the management of CVD risk is essential and involves the patient's stratification using distinct parameters that include assessment of the blood lipid profile. However, 'dyslipidemia' in RA patients follows a different pattern under the impact of inflammatory processes, while therapies that target the underlying disease change the levels of specific lipid components. In this review, we explore the relationship between blood lipids and inflammation in the so-called Îlipid paradoxÎ in RA, and we present the existing knowledge over the influence of antirheumatic drugs on the lipid profile of RA patients.
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Artrite Reumatoide/complicações , Doenças Cardiovasculares/etiologia , Dislipidemias/etiologia , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Progressão da Doença , Dislipidemias/sangue , Dislipidemias/metabolismo , Fatores de Risco de Doenças Cardíacas , Humanos , Metabolismo dos Lipídeos , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Inibidores do Fator de Necrose Tumoral/efeitos adversosRESUMO
Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease with diverse clinical picture and outcome. The disease affects primarily middle-aged females and involves the exocrine glands leading to dry mouth and eyes. When the disease extends beyond the exocrine glands (systemic form), certain extraglandular manifestations involving liver, kidney, lungs, peripheral nervous system and the skin may occur. Primary SS is considered the crossroad between autoimmunity and lymphoproliferation, since approximately 5% of patients develop NHL associated lymphomas. As with every chronic disease with complex aetiopathogenesis and clinical heterogeneity, pSS has certain unmet needs that have to be addressed: a) classification and stratification of patients; b) understanding the distinct pathogenetic mechanisms and clinical phenotypes; c) defining and interpreting the real needs of patients regarding the contemporary diagnostic and therapeutic approaches; d) physician and patients' training regarding the wide spectrum of the disease; e) creating common policies across European countries to evaluate and manage SS patients. To achieve these goals, an intense effort is being currently undertaken by the HarmonicSS consortium in order to harmonise and integrate the largest European cohorts of pSS patients. In this review, we present an overview of our perception and vision, as well as new issues arising from this project such as harmonisation protocols and procedures, data sharing principles and various ethical and legal issues originating from these approaches.
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Medicina de Precisão/métodos , Síndrome de Sjogren , Xerostomia , Autoimunidade , Europa (Continente) , Feminino , Humanos , Pessoa de Meia-Idade , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/genéticaRESUMO
OBJECTIVES: To address the need for automatically assessing the quality of clinical data in terms of accuracy, relevance, conformity, and completeness, through the concise development and application of an automated method which is able to automatically detect problematic fields and match clinical terms under a specific domain. METHODS: The proposed methodology involves the automated construction of three diagnostic reports that summarise valuable information regarding the types and ranges of each term in the dataset, along with the detected outliers, inconsistencies, and missing values, followed by a set of clinically relevant terms based on a reference model which serves as a set of terms which describes the domain knowledge of a disease of interest. RESULTS: A case study was conducted using anonymised data from 250 patients who were diagnosed with primary Sjögren's syndrome (pSS), yielding reliable outcomes that were highlighted for clinical evaluation. Our method was able to successfully identify 28 features with detected outliers, and unknown data types, as well as, identify outliers, missing values, similar terms, and inconsistencies within the dataset. The data standardisation method was able to match 76 out of 85 (89.41%) pSS-related terms according to a standard pSS reference model which has been introduced by the clinicians. CONCLUSIONS: Our results confirm the clinical value of the data curation method towards the improvement of the dataset quality through the precise identification of outliers, missing values, inconsistencies, and similar terms, as well as, through the automated detection of pSS-related relevant terms towards data standardisation.
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Curadoria de Dados , Síndrome de Sjogren , Confiabilidade dos Dados , HumanosRESUMO
OBJECTIVES: To evaluate the long-term outcomes of patients with multi-relapsing antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), who received sequentially therapy with cyclophosphamide and rituximab, upon new onset of aggressive vasculitis. METHODS: We retrospectively studied patients with multiple-relapsing AAV, who were treated with the standard regimen plus rituximab, given in sequence, upon a major relapse, compared to historical patients, who had been treated with the standard regimen alone in the same setting. The main outcomes of interest were relapse rates and frequency of adverse events. RESULTS: Of 147 patients with biopsy proven AAV, 35 (23.8%) experienced at least one major relapse, of whom, 14 (9.5%) received the sequential regimen and were compared to 21 (14.3%) historic patients, who had received the standard regimen alone for the same reason. Patients in both groups achieved remission in similar rates, but those treated with the sequential regimen experienced a significant decline in the relapse rate afterwards, compared to their corresponding rate prior to study entry [0.07 episodes of relapse per patient-year (95%CI: 0.03-0.2) vs. 0.38 (95%CI: 0.35-0.60) respectively, (p=0.004)]. The need for cyclophosphamide was significantly decreased in patients in whom cyclophosphamide was followed by rituximab [3.3(0-10.5) grams vs. 14.5 (4-177) grams, (p<0.0001)] but not in controls [17.2(0-108) grams vs. 14.5(0-63) grams, p=0.61]. CONCLUSIONS: Our data show that sequential therapy with cyclophosphamide and rituximab, upon a major relapse, in patients with frequently relapsing AAV, is associated with prolonged remission, allowing minimization of the ultimate exposure to cyclophosphamide.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Anticorpos Anticitoplasma de Neutrófilos/sangue , Ciclofosfamida/administração & dosagem , Imunossupressores/administração & dosagem , Rituximab/administração & dosagem , Adolescente , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Biomarcadores/sangue , Ciclofosfamida/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recidiva , Sistema de Registros , Indução de Remissão , Estudos Retrospectivos , Rituximab/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Rheumatoid arthritis (RA) is a complex autoimmune disease that affects millions of people worldwide, with a systemic impact. This review explores the role of non-biological conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in its management. AREAS COVERED: We discuss the effectiveness and safety of key csDMARDs such as Nonsteroidal anti-inflammatory drugs, corticosteroids, Hydroxychloroquine, Sulfasalazine, Methotrexate, and Leflunomide in relieving symptoms and slowing the progression of the disease. We also highlight the importance of combination therapy using csDMARDs, supported by clinical studies demonstrating the benefits of various csDMARD combinations. Early intervention with these drugs is emphasized to prevent joint damage, improve clinical symptoms, and enhance patient outcomes. EXPERT OPINION: Overall, csDMARDs have proven pivotal in managing RA, providing cost-effective and versatile treatment options. We acknowledge the advantages of biologics but highlight the associated challenges, making the choice between non-biological and biological drugs a personalized decision. This comprehensive overview aims to provide a deeper understanding of RA treatment strategies, contributing to improving the quality of life for patients with this chronic condition.
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Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Humanos , Produtos Biológicos/uso terapêutico , Qualidade de Vida , Artrite Reumatoide/tratamento farmacológico , Antirreumáticos/efeitos adversos , Metotrexato/uso terapêutico , Quimioterapia Combinada , Resultado do TratamentoRESUMO
Calcium pyrophosphate deposition (CPPD) disease is a form of crystal-induced arthropathy that arises from the accumulation of calcium pyrophosphate crystals within joints and soft tissues. This process leads to inflammation and damage to the affected joints. It can present asymptomatically or as acute or chronic inflammatory arthritis. Risk factors and comorbidities, including prior joint injury, osteoarthritis, hereditary or familial predisposition, and metabolic diseases, should be evaluated in CPPD cases. The management of CPPD remains a challenge in the sparsity of randomized controlled trials. The lack of such trials makes it difficult to establish evidence-based treatment protocols for CPPD. This review provides an overview of the current pharmacological management of CPPD, focusing on reducing inflammation, alleviating symptoms, and preventing acute flares. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and colchicine are effective in managing acute CPP arthritis. Colchicine may also be used prophylactically to prevent recurrent flares. In cases where other treatments have failed, anakinra, an interleukin-1 receptor antagonist, can be administered to alleviate acute flares. The management of chronic CPP inflammatory arthritis includes NSAIDs and/or colchicine, followed by hydroxychloroquine, low-dose glucocorticoids, and methotrexate, with limited data on efficacy. Tocilizumab can be used in refractory cases. In small studies, synovial destruction using intra-articular injection of yttrium 90 can decrease pain. To date, no disease-modifying therapies exist that reduce articular calcification in CPPD.
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INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease that significantly impacts patients' quality of life. While treatment options have expanded over the years, including the introduction of tumor necrosis factor-alpha (TNFα) inhibitors (TNFi), optimizing withdrawal strategies for these agents remains a challenge. AREAS COVERED: This review examines the current evidence on TNFi withdrawal strategies in RA, focusing on factors influencing withdrawal decisions such as disease activity monitoring, treatment response, patient characteristics, and biomarkers. A comprehensive literature search was conducted, including randomized controlled trials, observational studies, and expert guidelines. The pathophysiology of RA, current pharmacological agents, and the treat-to-target strategy are discussed to provide a holistic understanding of RA management. EXPERT OPINION: Withdrawal strategies could be suitable for certain patients, keeping in mind that several factors influence withdrawal decisions, including treatment response, disease activity and monitoring, and patient characteristics. The decision to withdraw TNFi must balance the benefits against the potential risks of disease flare and long-term treatment-related adverse effects. Combining DMARDs and TNFi early improves outcomes, supporting tapering strategies for cost-effectiveness and flare prevention. Future directions, including precision medicine approaches, patient-centered care models, and health economics analyses, are proposed to further optimize RA management and improve patient outcomes.
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Antirreumáticos , Artrite Reumatoide , Fator de Necrose Tumoral alfa , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Antirreumáticos/uso terapêutico , Antirreumáticos/efeitos adversos , Antirreumáticos/administração & dosagem , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologia , Qualidade de VidaRESUMO
INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune disorder with a characteristic chronic inflammation of the synovium that may lead to the destruction of the joints in untreated patients. Interestingly, despite the availability of several effective treatments, many patients do not achieve remission or low disease activity or may experience disease relapse.Following the above unmet needs, bispecific antibodies (BsAbs) have emerged as a new approach to improve the disease's treatment. BsAbs are designed to simultaneously target two different proteins involved in RA pathogenesis, leading to enhanced efficacy and reduced side effects compared to traditional monoclonal antibodies (mAbs). AREAS COVERED: In this review, we discuss the development of BsAbs for RA treatment, including their mechanism of action, efficacy, and safety profile. We also deal with the challenges and future directions in this field. EXPERT OPINION: BsAbs show promise in preclinical and clinical evaluations for treating RA. Further research is needed to optimize design and dosage and identify ideal patient groups. BsAbs can benefit disease management and improve outcomes of RA patients.
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Anticorpos Biespecíficos , Antirreumáticos , Artrite Reumatoide , Desenvolvimento de Medicamentos , Humanos , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/administração & dosagem , Anticorpos Biespecíficos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Animais , Antirreumáticos/farmacologia , Antirreumáticos/efeitos adversos , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Drogas em Investigação/farmacologia , Drogas em Investigação/administração & dosagem , Drogas em Investigação/efeitos adversosRESUMO
Cases of systemic lupus erythematosus (SLE) following psoriatic arthritis (PsA) or vice versa are uncommon. Due to the complexity of autoimmune diseases and the rarity of such cases, comprehensive global data on the co-occurrence of these conditions are limited. Moreover, the pathophysiology concerning the coexistence of SLE and PsA has yet to be fully understood. Interestingly, the progression of both diseases appears to be significantly influenced by the key interleukin (IL) 17, particularly IL-17A. Here, we report 7 cases of SLE and PsA coexistence. In 5 of these cases, PsA occurred before the development of SLE, while in the remaining 2 cases, SLE was diagnosed before PsA. The PsA was characterized mainly by peripheral arthritis without any axial involvement, while the manifestations of SLE varied, with 3 developing systematic severe manifestations. Therapeutic challenges were posed in all cases, as treating one condition could worsen the other. Finally, we review the literature providing the current knowledge on the coexistence of these conditions. Overall, all reported cases emphasize the importance of personalized treatment and careful monitoring for patients with both SLE and PsA.
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Rheumatoid arthritis (RA) is a chronic inflammatory disease mainly affecting the peripheral diarthrodial joints symmetrically and also presenting many extra-articular manifestations. Morbidity and mortality in RA patients are higher compared to the general population. Cardiovascular (CV) disease is one of the most common causes of death in these patients. Classical or traditional risk factors for atherosclerosis development occur more frequently in RA patients compared to those without this condition. Studies have showed that RA patients often present comorbidities such as hypertension, dyslipidemia, diabetes mellitus and obesity. However, the high incidence of CV events occurring in RA patients is not explained by the presence of traditional risk factors. Systemic inflammation, as it is expressed with the presence of proinflammatory cytokines and increased acute phase reactants, may contribute to the development of premature atherosclerosis in these patients. In this review, we explore the risk factors for CV disease, the generation of dyslipidemia, the lipid paradox and the role of systemic inflammation in the atherosclerotic process in RA. We discuss also the role of early therapeutic intervention that suppresses inflammation which may have beneficial effects on CV disease in RA patients.
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BACKGROUND: Tumor necrosis factor alpha (TNFα) is a pivotal cytokine involved in the pathogenesis of certain inflammatory diseases, such as rheumatoid arthritis (RA), spondyloarthropathies, and inflammatory bowel diseases. In the last two decades, TNFα inhibitors (TNFi) have revolutionized the treatment and outcome of the above disorders. However, the use of TNFi has been associated with the development of many autoimmune phenomena and paradoxical skin manifestations that may present as the same type of clinical indications for which the TNFi effectively used. Thus, they may display as arthritis, uveitis, colitis, psoriasis, and several other cutaneous clinical manifestations, among them the development of morphea, a localized scleroderma skin lesion. CASE PRESENTATION: We describe a 58-year-old woman with seronegative RA, refractory to methotrexate, who was treated with ABP-501 (Hefiya), an adalimumab (ADA) biosimilar and developed an oval-shaped, deep skin lesion of approximately 3.5cm in size, affecting the left part of her back compatible with morphea 3 months after the initiation of therapy. ADA biosimilar was discontinued and two months later, she had substantial skin improvement. CONCLUSION: This is the first report of morphea manifestation during TNFi biosimilar since the patient had no other trigger factors for morphea development like trauma and infections. Physicians dealing with patients treated with TNFi biosimilars should be aware of paradoxical skin reactions, among them morphea; thus, close monitoring, a minute and careful clinical examination, and a follow- up check are required.
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Adalimumab , Antirreumáticos , Medicamentos Biossimilares , Esclerodermia Localizada , Humanos , Feminino , Esclerodermia Localizada/induzido quimicamente , Esclerodermia Localizada/tratamento farmacológico , Pessoa de Meia-Idade , Adalimumab/efeitos adversos , Adalimumab/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Medicamentos Biossimilares/efeitos adversos , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/complicaçõesRESUMO
Objective: To assess the impact conferred by NOD2 variants on the clinical spectrum of patients with systemic autoinflammatory diseases (SAIDs) in Greece. Methods: Consecutive patients (n=167) with confirmed SAIDs who underwent screening by next generation sequencing (NGS) targeting 26 SAID-associated genes, and carried at least one NOD2 gene variant, were retrospectively studied. The demographic, clinical and laboratory parameters were recorded. Results: In total, 24 rare NOD2 variants in 23/167 patients (14%) were detected. Notably, 18 patients had at least one co-existing variant in 13 genes other than NOD2. Nine patients had juvenile- and 14 adult-onset disease. All patients presented with symptoms potentially induced by the NOD2 variants. In particular, the candidate clinical diagnosis was Yao syndrome (YAOS) in 12 patients (7% of the whole SAID cohort). The clinical spectrum of patients with YAOS (mean episode duration 8 days) was fever (n=12/12), articular symptoms (n=8), gastrointestinal symptoms (n=7; abdominal pain/bloating in 7; diarrhea in 4; oral ulcers in 3), serositis (n=7), and rash (n=5), while the inflammatory markers were elevated in all but one patient. Most of these patients showed a poor response to nonsteroidal anti-inflammatory drugs (n=7/9), colchicine (n=6/8) and/or anti-TNF treatment (n=3/4), while a complete response was observed in 6/10 patients receiving steroids and 3/5 on anti-IL1 treatment. Another 8 patients were diagnosed with either FMF (n=6) or PFAPA syndrome (n=2) presenting with prominent diarrhea (n=7), oral ulcers (n=2), periorbital swelling and sicca-like symptoms (n=1), or maculopapular rash (n=1). One patient had a clinically undefined SAID, albeit characterized by oral ulcers and diarrhea. Finally, one patient presented with chronic relapsing urticaria with periorbital edema and inflammatory markers, and another one had a Crohn-like syndrome with good response to anti-IL-1 but refractory to anti-TNF treatment. Conclusion: NOD2 variants were detected in 1 out of 7 SAID patients and seem to have an impact on disease phenotype and treatment response. Further studies should validate combined molecular and clinical data to better understand these distinct nosological entities.