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1.
Medicine (Baltimore) ; 99(10): e19439, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32150095

RESUMEN

INTRODUCTION: Immune checkpoint inhibitors (ICIs) represent an important advance in the treatment of melanoma. ICIs may induce autoimmune phenomena caused by concurrent activation of the immune system against normal cells. During the last years, cases of musculoskeletal side effects, especially immune-mediated arthritis (IA), have been increasingly reported. PATIENT CONCERNS: We present a 59-year-old woman, who was treated with pembrolizumab for a relapsed BRAF V600E mutated cutaneous malignant melanoma. The patient presented with right knee arthritis on week 30. DIAGNOSIS: The erythrocyte sedimentation rate and serum C-reactive protein levels were elevated, while rheumatoid factor and anti-cyclic citrullinated peptide antibodies were negative. Imaging confirmed the presence of fluid mainly in the suprapatellar bursa. Synovial fluid analysis revealed an inflammatory effusion, while other etiologies of inflammatory arthritis were excluded. INTERVENTIONS: Arthritis improved with an intra-articular injection of 8 mg dexamethasone. Twelve days later the arthritis relapsed in both knees, and although it was resistant to nonsteroidal anti-inflammatory treatment, it improved with systemic steroids. Tapering of methylprednisolone dose was feasible with the coadministration of leflunomide and subsequently hydroxychloroquine. OUTCOMES: Arthritis resolved and the patient is free of complications and disease activity 20 months after the initiation of the second line systemic treatment. CONCLUSIONS: We present an unusual case of IA associated with pembrolizumab treatment. The originality of the current report is based on the late occurrence, the monoarticular initial distribution, and uncommon location of IA at the knee.


Asunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Artritis Reumatoide/diagnóstico , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Artritis Reumatoide/inducido químicamente , Diagnóstico Diferencial , Femenino , Humanos , Articulación de la Rodilla , Persona de Mediana Edad , Líquido Sinovial
2.
Medicine (Baltimore) ; 99(12): e19568, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32195966

RESUMEN

This study aimed to evaluate the relationship between Bell's palsy and rheumatoid arthritis in a national sample cohort from Korea.Data were collected for individuals ≥20 years old from 2002 to 2013 in the Korean National Health Insurance Service-National Sample Cohort. We extracted data for patients with rheumatoid arthritis (n = 7628) and 1:4-matched controls (n = 30,512) and analyzed the occurrence of Bell's palsy in both groups. Matching was performed based on age, sex, income, and region of residence. Rheumatoid arthritis was diagnosed according to International Classification of Disease-10 (ICD-10) codes (M05-M06) and the prescription of biological agents and/or disease-modifying antirheumatic drugs. Bell's palsy patients were diagnosed according to ICD-10 code H912 and treatment ≥2 times with steroids. Adjusted hazard ratios (HRs) were calculated using stratified Cox proportional hazard models for the Charlson comorbidity index and 95% confidence intervals (CIs). Subgroup analyses based on age and sex were also performed.The rates of Bell's palsy were similar between the rheumatoid arthritis group (0.5% [38/7628]) and the control group, with no significant difference (0.4% [124/30,512], P = .270). The adjusted HR for Bell's palsy was 1.12 (95% CI, 0.78-1.62) in the rheumatoid arthritis group (P = .540). In the subgroup analyses according to age and sex, the relationship between Bell's palsy and rheumatoid arthritis did not reach statistical significance.The risk of Bell's palsy was not increased in patients with rheumatoid arthritis.


Asunto(s)
Artritis Reumatoide/diagnóstico , Artritis Reumatoide/epidemiología , Parálisis de Bell/diagnóstico , Parálisis de Bell/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Parálisis de Bell/tratamiento farmacológico , Comorbilidad , Femenino , Humanos , Incidencia , Clasificación Internacional de Enfermedades/normas , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Prevalencia , República de Corea/epidemiología , Factores de Riesgo , Adulto Joven
5.
Gene ; 722: 144098, 2020 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-31494241

RESUMEN

This study evaluated the possible association between SNPs in cytokines coding genes, namely IL10, IL6 and IFNG, cytokines serum levels and clinical assessment' scores in patients with Rheumatoid Arthritis(RA). SNPs genotyping was performed in 126 RA patients and 177 healthy individuals with Taqman probes specific for IL10 -1082 (T>C, rs1800896);INFG -1616 (A>G, rs2069705) and IL6 -174 (G>C, rs1800795) variants,positioned in regulatory regions. Cytokine Bead Array (CBA) was used to measure cytokine levels. We found association between INFG -1616 G allele(p = 0.0210; OR = 1.605) and INFG -1616 GG genotype (p = 0.0268; OR =2.609) and RA susceptibility. We also observed association between IL10 -1082 TT genotype and high clinical disease activity index (CDAI) values (p = 0.026; OR = 1.906; 95% CI = 1.082 - 3.359), IL10 -1082 CC genotype and low CDAI values (p = 0.016; OR = 0.256) and INFG -1616 AA and high CDAI values (p = 0.025; OR = 2.919). IL10 -1082 CC also exhibited the lowest IL-10 levels than IL10 -1082 TT (p = 0.020) and IL10 -1082 TC (p = 0.032). Finally, we verified higher IL-6 value in the RA patients than healthy control group (p = 0.007) and an association between high IL-6 levels and increased CDAI (r = 0.4648, p = 0.0015); DAS 28 (r = 0.3933, p= 0.0091), presence of bone erosions (r = 0.3170, p = 0.0361), ESR levels(r = 0.3041, p = 0.0448) and IFN-γ levels (r = 0.3049, p = 0.0468).Altogether, we suggest that IL10 -1082 (T>C, rs1800896) and INFG -1616(A>G, rs2069705) polymorphisms as well as IL-6 levels alterations may play a role for prognostic and disease follow-up.


Asunto(s)
Artritis Reumatoide/genética , Interferón gamma/genética , Interleucina-10/genética , Interleucina-6/genética , Polimorfismo de Nucleótido Simple , Adulto , Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Interferón gamma/sangre , Interleucina-10/sangre , Interleucina-6/sangre , Masculino , Persona de Mediana Edad
6.
PLoS One ; 14(12): e0226255, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31851711

RESUMEN

BACKGROUND: Confounding by disease severity is an issue in pharmacoepidemiology studies of rheumatoid arthritis (RA), due to channeling of sicker patients to certain therapies. To address the issue of limited clinical data for confounder adjustment, a patient-level prediction model to differentiate between patients prescribed and not prescribed advanced therapies was developed as a surrogate for disease severity, using all available data from a US claims database. METHODS: Data from adult RA patients were used to build regularized logistic regression models to predict current and future disease severity using a biologic or tofacitinib prescription claim as a surrogate for moderate-to-severe disease. Model discrimination was assessed using the area under the receiver (AUC) operating characteristic curve, tested and trained in Optum Clinformatics® Extended DataMart (Optum) and additionally validated in three external IBM MarketScan® databases. The model was further validated in the Optum database across a range of patient cohorts. RESULTS: In the Optum database (n = 68,608), the AUC for discriminating RA patients with a prescription claim for a biologic or tofacitinib versus those without in the 90 days following index diagnosis was 0.80. Model AUCs were 0.77 in IBM CCAE (n = 75,579) and IBM MDCD (n = 7,537) and 0.75 in IBM MDCR (n = 36,090). There was little change in the prediction model assessing discrimination 730 days following index diagnosis (prediction model AUC in Optum was 0.79). CONCLUSIONS: A prediction model demonstrated good discrimination across multiple claims databases to identify RA patients with a prescription claim for advanced therapies during different time-at-risk periods as proxy for current and future moderate-to-severe disease. This work provides a robust model-derived risk score that can be used as a potential covariate and proxy measure to adjust for confounding by severity in multivariable models in the RA population. An R package to develop the prediction model and risk score are available in an open source platform for researchers.


Asunto(s)
Artritis Reumatoide/fisiopatología , Bases de Datos Factuales , Revisión de Utilización de Seguros , Antirreumáticos/administración & dosificación , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Piperidinas/administración & dosificación , Pirimidinas/administración & dosificación , Pirroles/administración & dosificación , Índice de Severidad de la Enfermedad
7.
Medicine (Baltimore) ; 98(50): e18415, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31852165

RESUMEN

RATIONALE: Urinary obstruction are relatively rare complications of autoimmune diseases including systemic lupus erythematosus and systemic vasculitis. It has never been reported in rheumatoid arthritis (RA). PATIENT CONCERNS: We report a case of a female patient with seropositive RA who presented with gross hematuria associated with worsening joint symptoms, found to have acute kidney injury (AKI), bilateral hydronephrosis with bilateral renal pelvis, and ureteral wall thickening. Uroscopy with biopsy demonstrated inflammation without evidence of malignancy. DIAGNOSES: Rheumatoid arthritis related inflammation and obstruction of the urinary tract. INTERVENTIONS: Prednisone 50 mg daily (tapering began 1 month later), iguratimod 50 mg daily, and leflunomide 20 mg daily were prescribed. OUTCOMES: The patient responded well to steroids and immunosuppressive therapy with complete resolution of hematuria, renal injury, and hydronephrosis. LESSONS: Our case showed that RA might cause local inflammation involving the urinary tract which leads to obstruction and AKI.


Asunto(s)
Artritis Reumatoide/complicaciones , Obstrucción Ureteral/etiología , Antiinflamatorios/uso terapéutico , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Progresión de la Enfermedad , Femenino , Hematuria/etiología , Humanos , Hidronefrosis/etiología , Inmunosupresores/uso terapéutico , Persona de Mediana Edad , Prednisona/uso terapéutico , Obstrucción Ureteral/tratamiento farmacológico
8.
J Hand Surg Asian Pac Vol ; 24(4): 447-451, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31690205

RESUMEN

Background: The objective of this retrospective study was to evaluate the outcomes of ulnar stump stabilization after ulna head resection using the FCU tendon by investigating the rate of postoperative extensor tendon rupture and click on forearm rotation. Methods: Wrist synovectomy (distal radioulnar joint (DRUJ), radiocarpal and midcarpal joints) and ulnar head resection combined with ulnar stump stabilizing procedure were performed in 58 wrists of 53 patients with RA in our hospital. Before operation, the dorsal subluxation ratio (DSR) of the ulnar head was measured with a multi-slice computed tomography (CT) images. The stabilization of ulnar stump after head resection was performed by the value of the DSR or the instability before the operation. Results: There was neither extensor tendon rupture nor click on forearm rotation in all the patients. Smooth forearm rotation was achieved by ulnar head resection and stabilizing procedure for the ulnar stump. The active range of forearm supination and pronation increased significantly from 68° ± 23° (mean ± SD) to 80° ± 10°, and from 69° ± 17° to 74° ± 13°. The grip power increased from 117 ± 62 mmHg to 185 ± 55 mmHg. In the assessment using 3DCT, the preoperative DSR of 54% improved to 8% on the whole (n = 58). In the wrists with extensor tendon rupture (n = 36), the preoperative DSR of 58% improved to 12%. In the wrists without tendon rupture (n = 22), the preoperative DSR of 46% improved to 2%. Conclusions: The operative technique of ulnar stump stabilization using the FCU tendon was one of the suitable procedure to prevent complications after ulnar head resection.


Asunto(s)
Artritis Reumatoide/cirugía , Osteotomía/métodos , Tendones/cirugía , Cúbito/cirugía , Articulación de la Muñeca/cirugía , Adulto , Anciano de 80 o más Años , Artritis Reumatoide/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rango del Movimiento Articular/fisiología , Estudios Retrospectivos , Rotura , Traumatismos de los Tendones/prevención & control , Tomografía Computarizada por Rayos X , Cúbito/diagnóstico por imagen , Articulación de la Muñeca/diagnóstico por imagen , Articulación de la Muñeca/fisiopatología
9.
Medicine (Baltimore) ; 98(48): e18218, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31770283

RESUMEN

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by joint destructions and human leukocyte antigen (HLA)-DRB1 is an important genetic risk factor for RA and influences the phenotype of RA. The clinical features of elder age onset RA (EORA) were known to be different from those of younger age onset RA (YORA). Previous studies reported the different association pattern of DRB1 alleles with YORA or EORA. The associations of DRB1 genotype with these RA subsets remained almost unknown. We investigated the genotype association of DRB1 with YORA or EORA in Japanese populations.HLA genotyping was performed in Japanese RA patients and the association of allele or genotype carrier frequencies were analyzed.The genotype frequency of DRB104:05/DRB104:06 (P = .0204, OR 7.69, 95%CI 1.39-42.72), DRB104:05/DRB112:01 (P = .0050, OR 5.53, 95%CI 1.71-17.88), and DRB104:05/DRB115:01 (P = .0124, OR 3.34, 95%CI 1.39-8.02) in YORA was higher than EORA. However, the frequencies of DRB101:01/DRB104:05 in YORA was tended to be lower than EORA (P = .0784, OR 0.14, 95%CI 0.01-2.42). The gene dosage effect of the shared epitope alleles was detected in EORA, but not in YORA. Trans-complementing DQ heterodimer molecules, formed by DQA1 and DQB1 of the haplotypes with and without shared epitope alleles, might explain the higher genotype frequencies of "shared epitope /not shared epitope". Linear regression analyses showed the primary role of DQB104:01 allele for the age at onset of RA.This is the first report for the associations of DRB1 genotype with YORA or EORA in the Japanese population and the differential distribution of the genotypes was noted between these RA subsets. The involvement of DQ molecules for the age at onset of RA was suggested.


Asunto(s)
Edad de Inicio , Artritis Reumatoide , Cadenas HLA-DRB1/genética , Adulto , Anciano , Alelos , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/epidemiología , Artritis Reumatoide/genética , Correlación de Datos , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Pruebas Inmunológicas/métodos , Japón/epidemiología , Masculino , Persona de Mediana Edad
10.
Mayo Clin Proc ; 94(12): 2488-2498, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31759675

RESUMEN

OBJECTIVE: To determine the prevalence of comorbidities in rheumatoid arthritis (RA), discover which comorbidities might predispose to developing RA, and identify which comorbidities are more likely to develop after RA. PATIENTS AND METHODS: We performed a case-control study using a single-center biobank, identifying 821 cases of RA (143 incident RA) between January 1, 2009, and February 28, 2018, defined as 2 diagnosis codes plus a disease-modifying antirheumatic drug. We matched each case to 3 controls based on age and sex. Participants self-reported the presence and onset of 74 comorbidities. Logistic regression models adjusted for race, body mass index, education, smoking, and Charlson comorbidity index. RESULTS: After adjustment for confounders and multiple comparisons, 11 comorbidities were associated with RA, including epilepsy (odds ratio [OR], 2.13; P=.009), obstructive sleep apnea (OR, 1.49; P=.001), and pulmonary fibrosis (OR, 4.63; P<.001), but cancer was not. Inflammatory bowel disease (OR, 3.82; P<.001), type 1 diabetes (OR, 3.07; P=.01), and venous thromboembolism (VTE; OR, 1.80; P<.001) occurred more often before RA diagnosis compared with controls. In contrast, myocardial infarction (OR, 3.09; P<.001) and VTE (OR, 1.84; P<.001) occurred more often after RA diagnosis compared with controls. Analyses restricted to incident RA cases and their matched controls mirrored these results. CONCLUSION: Inflammatory bowel disease, type 1 diabetes, and VTE might predispose to RA development, whereas cardiovascular disease, VTE, and obstructive sleep apnea can result from RA. These findings have important implications for RA pathogenesis, early detection, and recommended screening.


Asunto(s)
Artritis Reumatoide/complicaciones , Artritis Reumatoide/epidemiología , Adulto , Anciano , Artritis Reumatoide/diagnóstico , Estudios de Casos y Controles , Comorbilidad , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo
11.
South Med J ; 112(10): 535-538, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31583414

RESUMEN

OBJECTIVES: Anti-cyclic citrullinated peptide antibody (ACPA) has excellent specificity and prognostic value in patients with early rheumatoid arthritis (RA). The American College of Rheumatology included ACPA in their 2010 classification criteria for RA, but we hypothesize that primary care physicians (PCPs) underuse ACPA, even when clinical suspicion for RA is high. We aimed to describe their use of diagnostic testing in patients who were referred to a rheumatologist and eventually diagnosed as having RA. METHODS: In this retrospective cohort study, a systematic abstraction tool was used to review the medical records of patients seen between January 1, 2010 and June 15, 2014 in two rheumatology clinics: one private practice and one community health center associated with an academic medical center. For purposes of hypothesis generation, we compared the characteristics of patients with and without testing using unpaired t tests or Fisher exact tests. RESULTS: We identified 173 patients with RA referred from 141 different PCPs: 82.7% were women with a mean ± standard deviation age of 55.5 ± 18.6 years. ACPA and rheumatoid factor were ordered in 28.9% (95% confidence interval 22.6-36.2) and 41.0% (95% confidence interval 33.9-48.6) of patients, respectively. Imaging was underused. Almost half (45.7%, or 37/81) of the patients with documented symptom duration had a delay of at least 1 year before referral; however, ACPA utilization was not associated with the delay to treatment initiation. CONCLUSIONS: Most PCPs failed to order diagnostic tests for RA before referring a patient with polyarthritis who eventually received a diagnosis of RA. We also observed delays in diagnosis, with half of the patients waiting >1 year from symptom onset to diagnosis. These findings suggest educational efforts for PCPs should focus on emphasizing earlier diagnostic workups, especially ACPA, in patients suspected to have RA.


Asunto(s)
Artritis Reumatoide/diagnóstico , Autoanticuerpos/inmunología , Factor Reumatoide/inmunología , Artritis Reumatoide/inmunología , Artritis Reumatoide/metabolismo , Autoanticuerpos/metabolismo , Biomarcadores/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factor Reumatoide/metabolismo
12.
Best Pract Res Clin Rheumatol ; 33(4): 101440, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31585842

RESUMEN

Skin lesions occur, often at very early stages, in many of the most frequent inflammatory rheumatic diseases such as in systemic lupus erythematosus (SLE), dermatomyositis (DM), systemic sclerosis (SSc), Sjögren's syndrome, rheumatoid arthritis (RA), and psoriatic arthritis. It is important to recognize the different specific cutaneous lesions in SLE (e.g., "butterfly" rash in acute, annular or psoriasiform photosensitive lesions in the subacute form, and discoid lesions in the chronic form) for an early diagnosis and to estimate the associated risks of internal disease, whereas nonspecific lesions (exanthema, vasculitis, and alopecia) can be part of SLE flares. Cutaneous lesions in DM (Gottron's papules and sign, heliotrope rash, dystrophic cuticles, and nailfold capillary abnormalities) may occur before any clinically evident muscular or systemic organ involvement and are of utmost importance for early diagnosis. The pattern of cutaneous lesions and associated autoantibodies also allow the distinction of different phenotypes, either more prone to life-threatening interstitial lung disease (MDA-5) or with higher risk for neoplasia (TIF1-γ). Many other skin lesions, although not specific, require further investigation to look for a possible underlying inflammatory rheumatic disease: non-pruritic urticarial lesions in anti-C1q-associated urticarial vasculitis, Still's disease or hereditary auto-inflammatory syndromes, transient macular purpura of vasculitis in Sjögren's syndrome, Behçet's disease, or RA, Raynaud's phenomenon in SSc and mixed connective tissue disease, erythema nodosum or other panniculitis in RA, Behçet's disease and SLE, pustular eruptions in Behçet's disease, psoriasis, and hereditary auto-inflammatory syndromes. After reviewing in detail the cutaneous manifestations of the most frequent inflammatory rheumatic diseases, we describe a topographic and morphological approach to skin rashes, calling attention to facial rashes, hand involvement, scalp, nail, or leg lesions or to some morphological aspects of skin lesions (annular, pustular, urticarial, or exanthematous) that may be the initial manifestations of inflammatory rheumatic diseases. The importance of skin lesions is confirmed by their presence as part of the classification criteria of many inflammatory rheumatic diseases. They also contribute to early diagnosis, to characterize disease phenotypes, to aid in effective patient management, and, ultimately, to impact on disease prognosis.


Asunto(s)
Artritis Reumatoide , Dermatomiositis , Exantema , Lupus Eritematoso Sistémico , Enfermedades Reumáticas , Síndrome de Sjögren , Artritis Reumatoide/complicaciones , Artritis Reumatoide/diagnóstico , Dermatomiositis/complicaciones , Dermatomiositis/diagnóstico , Exantema/etiología , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/diagnóstico , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico , Enfermedades de la Piel
13.
Wiad Lek ; 72(9 cz 1): 1676-1682, 2019.
Artículo en Polaco | MEDLINE | ID: mdl-31586982

RESUMEN

Rheumatoid arthritis (RA) is a chronic, systemic connective tissue disease, characterized by progressive, destructive polyarthritis with internal organs involvement due to active, systemic inflammation. The onset of disease occurs usually in 4th or 5th decade of life. Since the general population is ageing, beginning of RA in older age is more and more common. The term elderly onset of rheumatoid arthritis (EORA) describes the disease with onset at age over 60. Several observational studies indicated, that proportion of women and men is comparable in EORA. Clinical course of the disease is characterized by sudden onset with general constitutional symptoms, high disease activity and inflammatory parameters. Involvement of large joints is more common, specially shoulder joints. Antibodies typical for RA (rheumatoid factor, anti-citrullinated peptide) are usually negative. More advanced destructive changes of joints and functional impairment are also characteristic for EORA patients in comparison with younger onset of RA (YORA). In clinical practice the use of methotrexate and biological drugs is less common, and glucocorticosteroids more common in EORA. Due to high RA activity, patients with EORA should be treated in the same way as YORA, with careful monitoring due to higher risk of adverse events associated with treatment.


Asunto(s)
Artritis Reumatoide/diagnóstico , Edad de Inicio , Anciano , Artritis Reumatoide/terapia , Femenino , Glucocorticoides/uso terapéutico , Humanos , Inflamación , Masculino , Metotrexato/uso terapéutico
14.
Best Pract Res Clin Rheumatol ; 33(4): 101438, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31627994

RESUMEN

Multiple studies have shown that there is a pre-clinical period preceding the development of rheumatoid arthritis (RA). During this period, complex interactions between the environmental and genetic causes occur, and the expression "preclinical RA" has been proposed to define it. Early treatment intervention is associated with less joint damage and has an increased possibility of achieving remission. In this review, we provide an overview of the preclinical phases of RA, new immunological and imaging biomarkers, and the clinical features, and the management of individuals at-risk of developing RA.


Asunto(s)
Artritis Reumatoide , Autoanticuerpos , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/inmunología , Biomarcadores , Humanos
15.
Artículo en Inglés | MEDLINE | ID: mdl-31627124

RESUMEN

Here we show the determination of different polyamines (putrescine, cadaverine, spermidine) and related compounds (gamma-aminobutyric acid and l-ornithine) in saliva samples. These compounds are known to be biomarkers for several diseases. We have optimised an in situ derivatization process using ethyl chloroformate, an automated microextraction by packed sorbent and the determination of the corresponding products using a programmed temperature vaporizer coupled to a gas chromatograph - mass spectrometer. After finding that saliva matrix has an effect on the analysis, quantitation was performed using the one-point standard additions method and normalization to IS. This allows the detection of the analytes in the range of µg/L within a matrix obtained by a non-invasive procedure. The method has been successfully validated and it has been used in the determination of these compounds in six saliva samples finding that putrescine and cadaverine present the highest concentrations in the subject diagnosed with rheumatoid arthritis. For ornithine and spermidine, the highest concentrations were found for male subjects, especially heavy smokers. All concentrations found for the compounds were in good agreement with data found in bibliography.


Asunto(s)
Cromatografía de Gases y Espectrometría de Masas/métodos , Poliaminas/análisis , Saliva/química , Artritis Reumatoide/diagnóstico , Técnicas Biosensibles/métodos , Femenino , Humanos , Límite de Detección , Masculino , Ornitina/análisis , Reproducibilidad de los Resultados , Microextracción en Fase Sólida/métodos , Temperatura Ambiental , Ácido gamma-Aminobutírico/análisis
16.
BMC Musculoskelet Disord ; 20(1): 420, 2019 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-31506089

RESUMEN

BACKGROUND: We aimed to evaluate the prevalence of foot and/or ankle arthritis (FAA) and its impact on clinical indices in patients with rheumatoid arthritis (RA). METHODS: This cross-sectional study used data from the Korean College of Rheumatology Biologics & Targeted therapy registry to observe clinical outcomes of patients undergoing biologics therapy and conventional therapy. FAA was defined as ≥1 tender or swollen joint in the ankle and/or 1st-5th metatarsophalangeal (MTP) joints. Disease Activity Score 28 (DAS28), Routine Assessment of Patient Index Data 3 (RAPID3), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) were assessed. RESULTS: Among 2046 patients, 598 had FAA. The ankle joint was the most commonly involved joint in FAA (tender joint, 71.4%; swollen joint, 59.5%), followed by the third and second MTP joints. Patients with FAA showed higher DAS28, RAPID3, SDAI, and CDAI scores. FAA presence was significantly associated with non-remission as per DAS28-ESR (odds ratio, 3.4; 95% confidence interval, 2.0-5.8), DAS28-CRP (3.6, 2.4-5.3), SDAI (6.3, 2.8-14.6), CDAI (7.6, 2.4-24.3), and RAPID3 (5.6, 2.7-11.5) indices on adjusting for age, sex, disease duration, presence of rheumatoid factor, presence of anti-cyclic citrullinated peptide antibody, lung disease, use of methotrexate, and previous use of biological disease-modifying anti-rheumatic drugs. Patients with FAA were less likely to achieve remission of SDAI (n = 6, 1.0%) and CDAI (n = 3, 0.5%) than that of DAS28-ESR (n = 21, 3.5%), DAS28-CRP (n = 38, 6.4%), and RAPID3 (n = 12, 2.0%). CONCLUSIONS: FAA represents a severe disease activity and is an independent risk factor for non-remission in patients with RA.


Asunto(s)
Articulación del Tobillo/patología , Artritis Reumatoide/epidemiología , Articulación Metatarsofalángica/patología , Índice de Severidad de la Enfermedad , Adulto , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Inducción de Remisión/métodos , Factores de Riesgo , Encuestas y Cuestionarios , Insuficiencia del Tratamiento
17.
J Immunol Res ; 2019: 6728694, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31534975

RESUMEN

Autoimmune diseases (AIDs) are complex diseases characterized by persistent or recurrent inflammation, alteration of immune response, and production of specific autoantibodies. It is known that different AIDs share several susceptibility genetic loci. Tumor necrosis factor alpha inducible protein 3 (TNFAIP3) encodes the ubiquitin-modifying enzyme A20, which downregulates inflammation by restricting NF-κB, a transcription factor that regulates expression of various proinflammatory genes. Variants in TNFAIP3 gene have been described as associated with susceptibility to several AIDs. Here, we analyzed two TNFAIP3 polymorphisms in Italian patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjogren's syndrome (pSS), to verify if the genetic variability of TNFAIP3 gene is involved in genetic predisposition to AIDs also in the Italian population. We recruited 313 SLE patients, 256 RA patients, 195 pSS patients, and 236 healthy controls. Genotyping of rs2230926 and rs6920220 in TNFAIP3 gene was performed by an allelic discrimination assay. We carried out a case/control association study and a genotype/phenotype correlation analysis. A higher risk to develop SLE was observed for rs2230926 (P = 0.02, OR = 1.92). No association was observed between this SNP and the susceptibility to pSS or RA. However, the rs2230926 variant allele seems to confer a higher risk to develop lymphoma in pSS patients, while in RA patients, the presence of RF resulted significantly associated with the variant allele. Regarding the rs6920220 SNP, we observed a significant association of the variant allele with SLE (P = 0.03, OR = 1.53), pSS (P = 0.016, OR = 1.69), and RA (P = 0.0001, OR = 2.35) susceptibility. Furthermore, SLE patients carrying the variant allele showed a higher risk to develop pericarditis, pleurisy, and kidney complications. Our results support the importance of the TNFAIP3 gene variant role in the development of different autoimmune diseases in the Italian population and furtherly confirm a sharing of genetic predisposing factors among these three pathologies.


Asunto(s)
Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/genética , Alelos , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/genética , Estudios de Casos y Controles , Frecuencia de los Genes , Genotipo , Humanos , Italia , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/genética , Fenotipo , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/genética
18.
PLoS Med ; 16(9): e1002901, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31513665

RESUMEN

BACKGROUND: The inflammatory contribution to type 2 diabetes (T2D) has suggested new therapeutic targets using biologic drugs designed for rheumatoid arthritis (RA). On this basis, we aimed at investigating whether interleukin-1 (IL-1) inhibition with anakinra, a recombinant human IL-1 receptor antagonist, could improve both glycaemic and inflammatory parameters in participants with RA and T2D compared with tumour necrosis factor (TNF) inhibitors (TNFis). METHODS AND FINDINGS: This study, designed as a multicentre, open-label, randomised controlled trial, enrolled participants, followed up for 6 months, with RA and T2D in 12 Italian rheumatologic units between 2013 and 2016. Participants were randomised to anakinra or to a TNFi (i.e., adalimumab, certolizumab pegol, etanercept, infliximab, or golimumab), and the primary end point was the change in percentage of glycated haemoglobin (HbA1c%) (EudraCT: 2012-005370-62 ClinicalTrial.gov: NCT02236481). In total, 41 participants with RA and T2D were randomised, and 39 eligible participants were treated (age 62.72 ± 9.97 years, 74.4% female sex). The majority of participants had seropositive RA disease (rheumatoid factor and/or anticyclic citrullinated peptide antibody [ACPA] 70.2%) with active disease (Disease Activity Score-28 [DAS28]: 5.54 ± 1.03; C-reactive protein 11.84 ± 9.67 mg/L, respectively). All participants had T2D (HbA1c%: 7.77 ± 0.70, fasting plasma glucose: 139.13 ± 42.17 mg). When all the enrolled participants reached 6 months of follow-up, the important crude difference in the main end point, confirmed by an unplanned ad interim analysis showing the significant effects of anakinra, which were not observed in the other group, led to the study being stopped for early benefit. Participants in the anakinra group had a significant reduction of HbA1c%, in an unadjusted linear mixed model, after 3 months (ß: -0.85, p < 0.001, 95% CI -1.28 to -0.42) and 6 months (ß: -1.05, p < 0.001, 95% CI -1.50 to -0.59). Similar results were observed adjusting the model for relevant RA and T2D clinical confounders (male sex, age, ACPA positivity, use of corticosteroids, RA duration, T2D duration, use of oral antidiabetic drug, body mass index [BMI]) after 3 months (ß: -1.04, p < 0.001, 95% CI -1.52 to -0.55) and 6 months (ß: -1.24, p < 0.001, 95% CI -1.75 to -0.72). Participants in the TNFi group had a nonsignificant slight decrease of HbA1c%. Assuming the success threshold to be HbA1c% ≤ 7, we considered an absolute risk reduction (ARR) = 0.42 (experimental event rate = 0.54, control event rate = 0.12); thus, we estimated, rounding up, a number needed to treat (NNT) = 3. Concerning RA, a progressive reduction of disease activity was observed in both groups. No severe adverse events, hypoglycaemic episodes, or deaths were observed. Urticarial lesions at the injection site led to discontinuation in 4 (18%) anakinra-treated participants. Additionally, we observed nonsevere infections, including influenza, nasopharyngitis, upper respiratory tract infection, urinary tract infection, and diarrhoea in both groups. Our study has some limitations, including open-label design and previously unplanned ad interim analysis, small size, lack of some laboratory evaluations, and ongoing use of other drugs. CONCLUSIONS: In this study, we observed an apparent benefit of IL-1 inhibition in participants with RA and T2D, reaching the therapeutic targets of both diseases. Our results suggest the concept that IL-1 inhibition may be considered a targeted treatment for RA and T2D. TRIAL REGISTRATION: The trial is registered with EU Clinical Trials Register, EudraCT Number: 2012-005370-62 and with ClinicalTrial.gov, number NCT02236481.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Receptores de Interleucina-1/antagonistas & inhibidores , /uso terapéutico , Anciano , Antirreumáticos/efectos adversos , Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/inmunología , Biomarcadores/sangre , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/inmunología , Femenino , Hemoglobina A Glucada/metabolismo , Humanos , Proteína Antagonista del Receptor de Interleucina 1/efectos adversos , Italia , Masculino , Persona de Mediana Edad , Receptores de Interleucina-1/inmunología , Factores de Tiempo , Resultado del Tratamiento , /efectos adversos
19.
Autoimmun Rev ; 18(11): 102391, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31520804

RESUMEN

Over the last decade, many epigenetic mechanisms that contribute in the pathogenesis of autoimmune disorders have been revealed. MicroRNAs (miRNAs) are small, non-coding, RNA molecules that bind to messenger RNAs and disrupt the transcription of target genes. Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease in which a plethora of epigenetic changes take place. Current research on RA epigenetics has focused mainly on miRNAs. Genetic variance of some miRNA genes, especially miR-499, might predispose an individual to RA development. Additionally, altered expression of many miRNAs has been discovered in several cells, tissues and body fluids in patients with RA. MiRNAs expression also differs depending on disease's stage and activity. Serum miR-22 and miR-103a might predict RA development in susceptible individuals (pre-RA), while serum miR-16, miR-24, miR-125a and miR-223 levels are altered in early RA (disease duration <12 months) patients compared to established RA or healthy individuals. Moreover, serum miR-223 levels have been associated with RA activity and disease relapse. What is more, serum levels of several miRNAs, including miR-125b and miR-223, could be used to predict response to RA treatment. Finally, miRNA analogs or antagonists have been used as therapeutic regimens in experimental arthritis models and have demonstrated promising results. In conclusion, the research on the miRNA alterations in RA sheds light to several aspects of RA pathogenesis, introduces new biomarkers for RA diagnosis and treatment response prediction and offers the opportunity to discover new, targeted drugs for patients with RA.


Asunto(s)
Artritis Reumatoide/genética , MicroARNs , Animales , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Humanos
20.
Int J Mol Sci ; 20(18)2019 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-31491989

RESUMEN

Rheumatoid arthritis is an autoimmune disease that causes serious functional loss in patients. Early and accurate diagnosis of rheumatoid arthritis may attenuate its severity. Despite a diagnosis guideline in the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis, the practical difficulties in its diagnosis highlight the need of developing new methods for diagnosing rheumatoid arthritis. The current study aimed to identify rheumatoid arthritis diagnostic biomarkers by using a proteomics approach. Serum protein profiling was conducted using mass spectrometry, and five distinguishable biomarkers were identified therefrom. In the validation study, the five biomarkers were quantitatively verified by multiple reaction monitoring (MRM) analysis. Two proteins, namely serum amyloid A4 and vitamin D binding protein, showed high performance in distinguishing patients with rheumatoid arthritis from healthy controls. Logistic analysis was conducted to evaluate how accurately the two biomarkers distinguish patients with rheumatoid arthritis from healthy controls. The classification accuracy was 86.0% and 81.4% in patients with rheumatoid arthritis and in healthy controls, respectively. Serum amyloid A4 and vitamin D binding protein could be potential biomarkers related to the inflammatory response and joint destruction that accompany rheumatoid arthritis.


Asunto(s)
Artritis Reumatoide/metabolismo , Biomarcadores , Espectrometría de Masas , Proteoma , Proteómica , Anciano , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/genética , Biología Computacional/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Componente Principal , Proteómica/métodos
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