Lucía Silva

The C677T polymorphism in the MTHFR gene is associated with the toxicity of methotrexate in a Spanish rheumatoid arthritis population.

Objective: Methotrexate (MTX) is the first-choice drug for the treatment of rheumatoid arthritis (RA) patients. However, 30% of RA patients discontinue therapy within 1 year, usually because of adverse effects. Previous studies have reported conflicting results on the association of polymorphisms in the MTHFR gene with the toxicity of MTX in RA. The aim of this study was to assess the involvement of the C677T and A1298C polymorphisms in the MTHFR gene in the toxicity of MTX in a Spanish RA population. Methods: The study included retrospectively 468 Spanish RA patients treated with MTX. Single nucleotide polymorphism (SNP) genotyping was performed using the oligonucleotide microarray technique. Allele and genotype association analyses with regard to MTX toxicity and a haplotype association test were also performed. Results: Eighty-four out of the 468 patients (18%) had to discontinue therapy due to adverse effects or MTX toxicity. The C677T polymorphism (rs1801133) was associated with increased MTX toxicity [odds ratio (OR) 1.42, 95% confidence interval (CI) 1.01–1.98, p = 0.0428], and the strongest association was shown in the recessive model (OR 1.95, 95% CI 1.08–3.53, p = 0.0246). The A1298C polymorphism (rs1801131) was not associated with increased MTX toxicity (OR 0.94, 95% CI 0.65–1.38, p = 0.761). A borderline significant risk haplotype was found: 677T-1298A (OR 1.40, 95% CI 1.00–1.96, p = 0.0518). Conclusion: These results demonstrate that the C677T polymorphism in the MTHFR gene is associated with MTX toxicity in a Spanish RA population.

Accuracy of physical examination in subacromial impingement syndrome

OBJECTIVE Shoulder pain is a common complaint, frequently caused by subacromial impingement syndrome (SIS). There are a number of physical examination (PE) manoeuvres that explore the subacromial space. MRI provides an accurate anatomic image of the subacromial space, being the current gold standard in the diagnosis of SIS. The aim of this study is to evaluate the accuracy of the PE in the diagnosis of SIS and/or subacromial-subdeltoid bursitis (SSB) confirmed by MRI. METHODS Consecutive outpatients with an episode of shoulder pain were prospectively included in the study. They were examined by a rheumatologist and, within 3 days, an MRI was done. Sensitivity, specificity, positive and negative predictive values, and accuracy of PE manoeuvres were calculated using a 2 x 2 table. RESULTS Fourteen males and 16 females were included. All the tests exhibited acceptable sensitivity. As a result Yocum manoeuvre was considered the most sensitive and most accurate for SIS. With regard to SSB, the Gerber test was the most sensitive. The majority of the PE manoeuvres showed low specificity. CONCLUSIONS Most PE manoeuvres identify reasonably well subacromial impingement of the shoulder, although, in general, they have low specificity. The Yocum test has the best sensitivity and precision. Our data suggest that imaging techniques should be recommended to better define shoulder lesions.

Prediction of functional impairment and remission in rheumatoid arthritis patients by biochemical variables and genetic polymorphisms

OBJECTIVE To develop a model to predict RA outcome based on biochemical variables and single nucleotide polymorphisms (SNPs). METHODS We collected baseline data from RA patients. SNP genotyping was performed using an oligonucleotide microarray. Remission and severe disability were investigated as outcomes of the study. Logistic regression models and receiver operating characteristic (ROC) curves were used to determine sensitivity (S), specificity (Sp) and likelihood ratio (LR). RESULTS Six hundred and thirty-two patients (375 in the study and 257 in the validation) were included. Twenty-two out of 152, and 19 out of 208 patients had an HAQ > 2. The model obtained to predict disability included levels of the anti-cyclic citrullinated peptide (anti-CCP) antibodies, ESR and SNP rs2070874 in the IL-4 gene. Homozygous and heterozygous carriers of the IL-4 33T allele had a decreased risk of severe disability. The discriminative power had an area under the curve (AUC) of 0.792 (95% CI 0.694, 0.889), with S 41%, Sp 95% and LR +7.6. Twenty-one out of 268 and 17 out of 211 patients were in remission in the study and validation cohorts, respectively. The model included absence of anti-CCP antibodies and the SNP rs2476601 on the PTPN22 gene. Homozygous and heterozygous carriers of the PTPN22 1858T allele had a decreased probability of remission. The discriminative power had an AUC of 0.842 (95% CI 0.756, 0.928), with S 76%, Sp 86% and LR + 5.4. Predictive ability was confirmed on the validation cohort. CONCLUSIONS We have developed two models based on laboratory variables that are associated with relevant outcomes for RA patients at disease onset.

Comprehensive Description of Clinical Characteristics of a Large Systemic Lupus Erythematosus Cohort from the Spanish Rheumatology Society Lupus Registry (RELESSER) With Emphasis on Complete Versus Incomplete Lupus Differences

AbstractSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement and pronounced racial and ethnic heterogeneity. The aims of the present work were (1) to describe the cumulative clinical characteristics of those patients included in the Spanish Rheumatology Society SLE Registry (RELESSER), focusing on the differences between patients who fulfilled the 1997 ACR-SLE criteria versus those with less than 4 criteria (hereafter designated as incomplete SLE (iSLE)) and (2) to compare SLE patient characteristics with those documented in other multicentric SLE registries.RELESSER is a multicenter hospital-based registry, with a collection of data from a large, representative sample of adult patients with SLE (1997 ACR criteria) seen at Spanish rheumatology departments. The registry includes demographic data, comprehensive descriptions of clinical manifestations, as well as information about disease activity and severity, cumulative damage, comorbidities, treatments and mortality, using variables with highly standardized definitions.A total of 4.024 SLE patients (91% with ≥4 ACR criteria) were included. Ninety percent were women with a mean age at diagnosis of 35.4 years and a median duration of disease of 11.0 years. As expected, most SLE manifestations were more frequent in SLE patients than in iSLE ones and every one of the ACR criteria was also associated with SLE condition; this was particularly true of malar rash, oral ulcers and renal disorder. The analysis—adjusted by gender, age at diagnosis, and disease duration—revealed that higher disease activity, damage and SLE severity index are associated with SLE [OR: 1.14; 95% CI: 1.08–1.20 (P < 0.001); 1.29; 95% CI: 1.15–1.44 (P < 0.001); and 2.10; 95% CI: 1.83–2.42 (P < 0.001), respectively]. These results support the hypothesis that iSLE behaves as a relative stable and mild disease. SLE patients from the RELESSER register do not appear to differ substantially from other Caucasian populations and although activity [median SELENA-SLEDA: 2 (IQ: 0–4)], damage [median SLICC/ACR/DI: 1 (IQ: 0–2)], and severity [median KATZ index: 2 (IQ: 1–3)] scores were low, 1 of every 4 deaths was due to SLE activity.RELESSER represents the largest European SLE registry established to date, providing comprehensive, reliable and updated information on SLE in the southern European population.

Optimización del tratamiento clásico de la artritis reumatoide

vadas, la presencia de factor reumatoide y de anticuerpos antipéptidos citrulinados, la existencia de erosiones radiológicas y la presencia del epítopo compartido. También se ha demostrado que la actividad inflamatoria clínica y analítica mantenidas tienen relación con el desarrollo de enfermedad erosiva durante la evolución de la AR, por lo que, en general, se acepta que la actividad inflamatoria mantenida en el tiempo se traduce en erosiones radiológicas y en deterioro funcional futuro. Con estos datos, es verosímil que una actuación rápida y enérgica para controlar la actividad inflamatoria de la enfermedad en las primeras fases de su evolución podría alterar favorablemente el curso de la enfermedad. Los datos que ponen de manifiesto que una intervención terapéutica precoz puede modificar el curso de la AR proceden de ensayos clínicos controlados, metaanálisis y estudios de casos y controles. Tres ensayos clínicos aleatorizados, controlados con placebo y con doble enmascaramiento han puesto de manifiesto que el tratamiento con un fármaco antirreumático modificador de enfermedad (FAME), añadido a los antiinflamatorios no esteroideos, es beneficioso en los pacientes con AR de inicio, incluso usando FAME que no se caracterizan por un efecto terapéutico especialmente poderoso en la AR, como la hidroxicloroquina o el auranofin. Un metaanálisis realizado por Anderson et al sobre 14 ensayos clínicos aleatorizados, controlados y con doble enmascaramiento, que incluían en conjunto a 1.435 pacientes, concluyó que existía una relación significativa entre la duración de la AR y la probabilidad de respuesta a un FAME. Más recientemente, Nell et al, mediante un estudio observacional de casos y controles, han puesto de manifiesto que iniciar el FAME durante los primeros 3 meses de la enfermedad reduce el daño radiológico tras 36 meses de seguimiento, comparado con una instauración del FAME entre los 3 y 12 meses de evolución de la AR. Por tanto, la optimización del tratamiento clásico de la AR exige un diagnóstico rápido de la enfermedad de inicio y la inmediata instauración de terapia con un FAME adecuado, habitualmente metotrexato (MTX), con incremento progresivo de la dosis en caso de no obtener una respuesta satisfactoria. Correspondencia: Dr. J.L. Andréu. Servicio de Reumatología. Hospital Universitario Puerta de Hierro. San Martín de Porres, 4. 28035 Madrid. España. Correo electrónico: jlandreu@arrakis.es Durante las últimas 2 décadas del pasado siglo se ha afianzado la idea de que la artritis reumatoide (AR) no es una enfermedad con un pronóstico favorable, ya que la mayoría de los pacientes presenta un deterioro estructural, funcional y social muy relevante durante el curso de la enfermedad y que incluso la supervivencia global se encuentra reducida en los pacientes con AR. Además, también se pone de manifiesto que el manejo convencional de la AR, basado en el uso de agentes químicos, siguiendo el paradigma de la pirámide terapéutica, no es capaz de brindar un control de la enfermedad adecuado, suficiente y duradero.

Tratamiento de fondo del síndrome seco. ¿Qué puede aportar el reumatólogo?

No effective treatment has been documented for the glandular primary Sjögren syndrome (PSS) despite the development of oral and biologic agents that have significant activity against other autoimmune disorders. Some disease-modifying agents have been empirically evaluated for the treatment of PSS. Targeting B cells also seems very promising in SSP because of the B-cell hyperactivity recognized in this desease. This article reviews existing data on the use of disease-modifying therapy for glandular of SSP. To date, published studies and trials of oral DMARDs for the treatment of SSP have shown disappointing results. B-cell modulation is clearly a promising therapy for PSS. Many challenges in trial design and execution are evident from the studies reviewed.