Genetic Variants Influencing Joint Damage in Mexican Americans and European Americans With Rheumatoid Arthritis.

Joint destruction in rheumatoid arthritis (RA) is heritable, but knowledge on specific genetic determinants of joint damage in RA is limited. We have used the Immunochip array to examine whether genetic variants influence variation in joint damage in a cohort of Mexican Americans (MA) and European Americans (EA) with RA. We studied 720 MA and 424 EA patients with RA. Joint damage was quantified using a radiograph of both hands and wrists, scored using Sharp's technique. We conducted association analyses with the transformed Sharp score and the Immunochip single nucleotide polymorphism (SNP) data using PLINK. In MAs, 15 SNPs from chromosomes 1, 5, 9, 17 and 22 associated with joint damage yielded strong p-values (p < 1 × 10(-4) ). The strongest association with joint damage was observed with rs7216796, an intronic SNP located in the MAP3K14 gene, on chromosome 17 (ß ± SE = -0.25 ± 0.05, p = 6.23 × 10(-6) ). In EAs, 28 SNPs from chromosomes 1, 4, 6, 9, and 21 showed associations with joint damage (p-value < 1 × 10(-4) ). The best association was observed on chromosome 9 with rs59902911 (ß ± SE = 0.86 ± 0.17, p = 1.01 × 10(-6) ), a synonymous SNP within the CARD9 gene. We also observed suggestive evidence for some loci influencing joint damage in MAs and EAs. We identified two novel independent loci (MAP3K14 and CARD9) strongly associated with joint damage in MAs and EAs and a few shared loci showing suggestive evidence for association.

Systemic inflammation and cardiovascular risk factors predict rapid progression of atherosclerosis in rheumatoid arthritis.

OBJECTIVE: To estimate atherosclerosis progression and identify influencing factors in rheumatoid arthritis (RA). METHODS: We used carotid ultrasound to measure intima-media thickness (IMT) in RA patients, and ascertained cardiovascular (CV) risk factors, inflammation markers and medications. A second ultrasound was performed approximately 3 years later. We calculated the progression rate by subtracting the baseline from the follow-up IMT, divided by the time between the two scans. We used logistic regression to identify baseline factors predictive of rapid progression. We tested for interactions of erythrocyte sedimentation rate (ESR) with CV risk factors and medication use. RESULTS: Results were available for 487 RA patients. The mean (SD) common carotid IMT at baseline was 0.571 mm (0.151). After a mean of 2.8 years, the IMT increased by 0.050 mm (0.055), p≤0.001, a progression rate of 0.018 mm/year (95% CI 0.016 to 0.020). Baseline factors associated with rapid progression included the number of CV risk factors (OR 1.27 per risk factor, 95% CI 1.01 to 1.61), and the ESR (OR 1.12 per 10 mm/h, 95% CI 1.02 to 1.23). The ESR×CV risk factor and ESR×medication product terms were significant, suggesting these variables modify the association between the ESR and IMT progression. CONCLUSIONS: Systemic inflammation and CV risk factors were associated with rapid IMT progression. CV risk factors may modify the role of systemic inflammation in determining IMT progression over time. Methotrexate and antitumour necrosis factor agents may influence IMT progression by reducing the effect of the systemic inflammation on the IMT.

The number of flares patients experience impacts on damage accrual in systemic lupus erythematosus: data from a multiethnic Latin American cohort.

PURPOSE: To determine the association between the number of flares systemic lupus erythematosus (SLE) patients experience and damage accrual, independently of other known risk factors. METHODS: SLE patients (34 centres, nine Latin American countries) with a recent diagnosis (≤2 years) and ≥3 evaluations were studied. Disease activity was ascertained with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and damage with the SLICC/ACR Damage Index (SDI). Flare was defined as an increase ≥4 points in the SLEDAI between two study visits. An ambidirectional case- crossover design was used to determine the association between the number of flares and damage accrual. RESULTS: 901 patients were eligible for the study; 500 of them (55.5%) experienced at least one flare, being the mean number of flares 0.9 (SD: 1.0). 574 intervals from 251 patients were included in the case-crossover design since they have case and control intervals, whereas, the remaining patients did not. Their mean age at diagnosis was 27.9 years (SD: 11.1), 213 (84.9%) were women. The mean baseline SDI and SLEDAI were 1.3 (1.3) and 13.6 (8.1), respectively. Other features were comparable to those of the entire sample. After adjusting for possible confounding variables, the number of flares, regardless of their severity, was associated with damage accrual (SDI) OR 2.05, 95% CI 1.43 to 2.94, p<0.001 (OR 2.62, 95% CI 1.31 to 5.24, p=0.006 for severe and OR 1.91, 95% CI 1.28 to 2.83, p=0.001 for mild-moderate). CONCLUSIONS: The number of flares patients experience, regardless of their severity, increases the risk of damage accrual, independently of other known risk factors.

The PTPN22 C1858T variant as a risk factor for rheumatoid arthritis and systemic lupus erythematosus but not for systemic sclerosis in the Colombian population.

OBJECTIVES: C1858T single nucleotide polymorphism in PTPN22 encoding the R620W allele variant of Lyp-PTPN22 (a protein phosphatase negatively regulating T-cell activation) has been associated with autoimmunity. This work has investigated the possible association between PTPN22 C1858T (rs2476601) polymorphism and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) in a Colombian population. METHODS: A case-control study included 1,042 samples from 413 RA, 94 SLE and 101 SSc patients and 434 healthy controls. The TaqMan allele discrimination assay was used for genotyping. RESULTS: The case-control study provided robust evidence of association between allele 1858T and RA (p=5E-05), as well as between 1858T and SLE (p=0.004). These observations were confirmed for both diseases by meta-analysis (p=2E-04, pooled OR 1.9; 1.3-2.7 95% CI for RA; p<0.0001, pooled OR 2.8, 1.8-4.5 95% CI for SLE). No significant association was observed between 1858T and SSc (p=0.98, OR 1.11, 0.46-2.65 95% CI). CONCLUSIONS: The study suggested that the PTPN22 1858T variant influences RA and SLE genetic background but not that of SSc in the Colombian population.

Panniculitis: another clinical expression of gout.

Gouty panniculitis is an unusual clinical manifestation of gout, characterized by the deposition of monosodium urate crystals in the lobular hypodermis. Its pathogenesis is poorly understood but is associated with hyperuricemia, and the clinical presence of indurate subcutaneous plaques, which may precede or appear subsequently to the articular clinical expression of tophaceous gout. The aim of this report is to describe the clinical characteristics and potential risk factors for the development of lobular panniculitis secondary to chronic tophaceous gout. This is a retrospective clinical review of 6 patients with gouty panniculitis seen at the rheumatology service at the National University of Colombia. All cases fulfill diagnostic criteria for gout. The presenting clinical characteristics of each case were analyzed. All 6 patients were men, with an average age of 26 years. Two patients initially presented with cutaneous manifestations, and in the remainder 4 joint involvements preceded the cutaneous manifestations. Articular involvement first developed in lower extremities, of intermittent nature, and subsequent occurrence of polyarthritis of upper and lower extremities. A positive family history of gout was observed in half of the patients. Smoking and high alcohol intake were relevant risk factors. On physical examination, all exhibited the presence of erythematous, irregular surface, deep indurate subcutaneous plaques. Biopsy of skin and deep dermis including panniculus revealed the presence of granulomatous inflammatory changes with deposition of amorphous eosinophilic material surrounded by palisading histocytes and lymphocytes. Characteristic negative birefringent monosodium urate crystals were observed in the synovial fluid of patients with arthritis. All patients exhibited high levels of serum uric acid and were non-complaint to treatment with allopurinol, NSAIDs, and colchicine. Gouty panniculitis should be considered in the differential diagnosis of panniculitis, especially in the presence of high levels of uric acid. It is usually observed in the third decade of life and may appear prior to the inflammatory articular manifestations of tophaceous gout.

A genetic association study of carotid intima-media thickness (CIMT) and plaque in Mexican Americans and European Americans with rheumatoid arthritis.

BACKGROUND AND AIMS: Little is known about specific genetic determinants of carotid-intima-media thickness (CIMT) and carotid plaque in subjects with rheumatoid arthritis (RA). We have used the Metabochip array to fine map and replicate loci that influence variation in these phenotypes in Mexican Americans (MAs) and European Americans (EAs). METHODS: CIMT and plaque were measured using ultrasound from 700 MA and 415 EA patients with RA and we conducted association analyses with the Metabochip single nucleotide polymorphism (SNP) data using PLINK. RESULTS: In MAs, 12 SNPs from 11 chromosomes and 6 SNPs from 6 chromosomes showed suggestive associations (p < 1 × 10-4) with CIMT and plaque, respectively. The strongest association was observed between CIMT and rs17526722 (SLC17A2 gene) (ß ± SE = -0.84 ± 0.18, p = 3.80 × 10-6). In EAs, 9 SNPs from 7 chromosomes and 7 SNPs from 7 chromosomes showed suggestive associations with CIMT and plaque, respectively. The top association for CIMT was observed with rs1867148 (PPCDC gene, ß ± SE = -0.28 ± 0.06, p = 5.11 × 10-6). We also observed strong association between plaque and two novel loci: rs496916 from COL4A1 gene (OR = 0.51, p = 3.15 × 10-6) in MAs and rs515291 from SLCA13 gene (OR = 0.50, p = 3.09 × 10-5) in EAs. CONCLUSIONS: We identified novel associations between CIMT and variants in SLC17A2 and PPCDC genes, and between plaque and variants from COL4A1 and SLCA13 that may pinpoint new candidate risk loci for subclinical atherosclerosis associated with RA.

Data on genetic associations of carotid atherosclerosis markers in Mexican American and European American rheumatoid arthritis subjects.

Carotid Intima-media thickness (CIMT) and plaque are well established markers of subclinical atherosclerosis and are widely used for identifying subclinical atherosclerotic disease. We performed association analyses using Metabochip array to identify genetic variants that influence variation in CIMT and plaque, measured using B-mode ultrasonography, in rheumatoid arthritis (RA) patients. Data on genetic associations of common variants associated with both CIMT and plaque in RA subjects involving Mexican Americans (MA) and European Americans (EA) populations are presented in this article. Strong associations were observed after adjusting for covariate effects including baseline clinical characteristics and statin use. Susceptibility loci and genes and/or nearest genes associated with CIMT in MAs and EAs with RA are presented. In addition, common susceptibility loci influencing CIMT and plaque in both MAs and EAs have been presented. Polygenic Risk Score (PRS) plots showing complementary evidence for the observed CIMT and plaque association signals are also shown in this article. For further interpretation and details, please see the research article titled "A Genetic Association Study of Carotid Intima-Media Thickness (CIMT) and Plaque in Mexican Americans and European Americans with Rheumatoid Arthritis" which is being published in Atherosclerosis (Arya et al., 2018) [1].(Arya et al., in press) Thus, common variants in several genes exhibited significant associations with CIMT and plaque in both MAs and EAs as presented in this article. These findings may help understand the genetic architecture of subclinical atherosclerosis in RA populations.

Glucocorticoid dose thresholds associated with all-cause and cardiovascular mortality in rheumatoid arthritis.

OBJECTIVE: To delineate daily and cumulative glucocorticoid dose thresholds associated with increased mortality rates in rheumatoid arthritis (RA). METHODS: We studied RA patients recruited from rheumatology clinics. Annually, we assessed the glucocorticoid dose, demographic, socioeconomic, clinical, and laboratory features of RA, cardiovascular (CV) risk factors, and vital status. We used Cox proportional hazards regression to assess associations between the daily or cumulative glucocorticoid dose and death, adjusting for potential confounders and for the propensity to receive glucocorticoids. We tested strata of the glucocorticoid dose to delineate the threshold associated with death. RESULTS: We studied 779 RA patients with a total of 7,203 person-years of observation, during which 237 of them died, yielding a mortality rate of 3.2 per 100 person-years (95% confidence interval [95% CI] 2.8-3.7). One hundred twenty of the deaths were due to CV causes, yielding a CV mortality rate of 1.8 (95% CI 1.5-2.1). Exposure to glucocorticoids was associated with a dose-dependent increase in death from all causes, with a ratio (HR) of 1.07 per mg of prednisone per day (95% CI 1.05-1.08). Compared to patients who were not receiving corticosteroids, the minimum daily prednisone dose threshold associated with an increase in all-cause mortality was 8-15 mg, with an adjusted HR of 1.78 (95% CI 1.22-2.60). For the cumulative dose of glucocorticoids, the minimum dosage associated with all-cause mortality was 40 gm (HR 1.74 [95% CI 1.25-2.44]). CONCLUSION: Glucocorticoid use in RA is associated with a dose-dependent increase in mortality rates, with a daily threshold dose of 8 mg, at which the number of deaths increased in a dose-dependent manner. These findings may assist clinicians in selecting the appropriate glucocorticoid dosage for RA patients who require these agents.

Does the "Hispanic paradox" occur in rheumatoid arthritis? Survival data from a multiethnic cohort.

OBJECTIVE: Despite lower socioeconomic status (SES) and higher disease burden, Hispanics in the US paradoxically display equal or lower mortality on average than non-Hispanic whites. Our objective was to determine if the "Hispanic paradox" occurs among patients with rheumatoid arthritis (RA). METHODS: In a cohort of 706 RA patients, we compared differences in RA severity and comorbidity between Hispanic and non-Hispanic white ethnic groups at baseline. Cox proportional hazards models were used to estimate and compare mortality risk between Hispanics and non-Hispanic whites. RESULTS: We studied 706 patients with RA, of whom 434 were Hispanic and 272 were non-Hispanic white. Hispanics had significantly lower SES, greater inflammation, as well as higher tender and swollen joint counts. Patients were observed for 6,639 patient-years, during which time 229 deaths occurred by the censoring date (rate 3.4 per 100 person-years; 95% confidence interval 3.0, 3.9). Age- and sex-adjusted mortality was not significantly different between the 2 ethnic groups (hazard ratio [HR] 0.96). After adjustment for comorbidities, RA severity, and level of acculturation, mortality among Hispanics was lower (HR 0.56, P = 0.004). CONCLUSION: Despite greater severity in most clinical manifestations and lower SES among Hispanics, paradoxically, their mortality was not increased. Further research is needed to understand the mechanisms underlying this survival paradox.

Risk factors associated with pulmonary arterial hypertension in Colombian patients with systemic sclerosis: review of the literature.

OBJECTIVE: Considering the significant morbidity and mortality of pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc) and the lack of precise information on disease in Latin America, we investigated the clinical and laboratory characteristics associated with PAH in Colombian patients with SSc and review the literature. METHODS: This multicenter study included patients followed at 5 rheumatology units that were systematically assessed using a pretested questionnaire on clinical and immunological variables, focusing on PAH. Conditional logistic regression was employed to assess association between PAH and specific clinical characteristics. A systematic review of the literature was performed through electronic databases. RESULTS: Of a total of 349 patients with SSc, 61 (17%) met the criteria for PAH. Pulmonary fibrosis [adjusted odds ratio (AOR) 7.37, 95% CI 3.67-14.81, p < 0.0001], microstomia (AOR 3.3, 95% CI 1.70-6.28, p < 0.0001), gastroesophageal reflux (AOR 2.41, 95% CI 1.31-4.43, p = 0.005), dysphagia (AOR 2.7, 95% CI 1.49-4.77, p = 0.001), hyperpigmentation (AOR 2.15, 95% CI 1.11-4.16, p = 0.02), and hypopigmentation (AOR 2.4, 95% CI 1.26-4.64, p = 0.008) were the most prevalent clinical characteristics associated with PAH, while anemia (AOR 5.4, 95% CI 1.98-14.93, p = 0.001) was observed as the unique laboratory risk factor. Association between subtypes of SSc and PAH was not observed. Significant differences in both clinical and laboratory data were observed among different series. CONCLUSION: PAH may be a frequent complication of SSc in the Colombian population regardless of disease subtype. The identified clinical and laboratory risk factors might assist earlier diagnosis and guide decisions on therapeutic interventions on this critical complication of SSc. The reasons underlying the reported divergences among patients from different ethnicities are not fully understood, but it is most likely that both genetic and environmental factors are responsible for them.

Artritis reumatoide temprana / Early rheumatoid arthritis

La artritis reumatoide es una enfermedad crónica e incapacitante que afecta grandes y pequeñas articulaciones. La característica más importante de la enfermedad es la poliartritis o sinovitis simétrica que típicamente afecta las manos, muñecas y pies inicialmente y posteriormente puede afectar cualquier articulación sinovial como rodillas, tobillos, codos y hombros. La prevalencia en la mayoría de cohortes es de aproximadamente 1 por ciento. En este artículo resaltamos la importancia de reconocer tempranamente la enfermedad con el fin de lograr una mejor respuesta terapéutica, menos invalidez, menos pérdida de días de trabajo y disminución de los costos directos e indirectos del tratamiento

Sindrome Sapho: presentacion del primer caso en Colombia / Sapho syndrome

El síndrome SAPHO (sinovitis, acné, pustulosis, hiperostosis y osteítis) se caracteriza por compromiso simultáneo de piel, articulaciones y hueso. En este artículo presentamos el primer caso de SAPHO en Colombia y revisamos los aspectos más relevantes de la literatura con respecto a este síndrome

Artropatias que producen puentes oseos / Arthropaties and osseous bridging

En este artículo se revisan las artropatías más frecuentes que producen puentes óseos, con énfasis en los hallazgos radiológicos de la columna vertebral. Se muestran también otros hallazgos radiológicos que pueden ayudar en el diagnóstico diferencial de estas entidades, como la sacroilitis de la espondilitis anquilosante o la osteolisis de la artritis psoriátíca

Sindrome de tunel del carpo y neuropatia cubital con acroosteolisis simulando esclerodermia / Acroosteolisis of interfalangeal joint associated with multiple trauma secondary to ulnar and carpal tunnel neuropathy simulating systemic sclerosis disease

Informamos un caso de acrosteolisis de interfalángicas dístales (IFD) asociado a múltiples traumas secundarios a neuropatía cubital y del túnel del carpo, que simulaba una esclerodermia

Calcinosis distrofica pulmonar asociada a esclerosis sistemica: Informe del primer caso en Colombia / Dystrophic calcinosis associated with systemic sclerosis: first case in Colombia

La asociación de calcinosis pulmonar con esclerosis sistémica no ha sido descrita en la literatura médica. Las clases de calcificación pulmonar se restringen a los tipos metastásico y distrófico; en las enfermedades de tejido conectivo el tipo de calcinosis predominante es el distrófico, asociándose principalmente a dermatopolimiositis y esclerosis sistémica. Describimos el primer caso de calcinosis pulmonar asociada a esclerosis sistémica

Reacciones adversas cutaneas durante la terapia con medicamentos antirreumaticos / Cutaneus adverse effect to antirheumatic drugs

Presentamos en este artículo las reacciones adversas cutáneas que se presentan con más frecuencia durante el tratamiento antirreumático que usamos a diario quienes trabajamos con pacientes reumáticos y que debemos conocer para diagnosticarlas y tratarlas tempranamente

Sindrome Sapho / Sapho syndrome

En este documento se revisa extensamente la literatura con respecto al síndrome SAPHO, con énfasis en los aspectos históricos, criterios de clasificación, las manifestaciones clínicas, hallazgos de laboratorio y tratamiento. Para lograr este objetivo se buscaron las referencias bibliográficas mas significativas del tema en las bases de datos disponibles

Antimalaricos como drogas inductoras de remision en la artritis reumatoidea / Antimalarial drugs for treatmet of rheumatoid arthritis

En este artículo hacemos una revisión extensa y actualizada sobre los aspectos mas importantes de la cloroquina y de la hidroxicloroquina como medicamentos inductores de remisión en la artritis reumatoide. Se analizan los efectos secundarios de estos medicamentos y se comentan sus beneficios como monoterapia así como su utilización en terapia combinada

Lupus en Latinoamericana y el papel de los latinoamericanos / Lupus in Latinoamerica

En este artículo queremos resaltar el papel y la contribución de los investigadores latinoamericanos en el estudio del lupus eritematoso sistémico (LES). Probablemente el primer caso de lupus en el mundo se dio en Latinoamérica y lo constituye una momia Peruana, de la cultura Huari, cuya muerte ocurrió aproximadamente hacia 890 años AD, que fue estudiada exhaustivamente en forma macro y con microscopía de luz y electrónica, al igual que con radiología. Desde finales del siglo XIX hasta nuestros días, han sido innumerables los aportes de los latinoamericanos en el desarrollo del conocimiento del LES. En esta revisión se muestran de manera general, los primeros estudios realizados acerca de esta enfermedad en Latinoamérica, y de manera particular, los aportes más significativos en el conocimiento del LES realizados por países como Chile, Perú, Guatemala, Colombia, Argentina, Ecuador, México, Venezuela, Brasil y el grupo Gladel (Grupo latinoamericano de estudio del LES). La información generada en este artículo provino del aporte bibliográfico de cada uno de los países mencionados