Efecto de los antimaláricos sobre los diferentes dominios del índice de daño SLICC en pacientes de la cohorte GLADEL / Effect of antimalarials on the different domains of the SLICC damage index in patients of the GLADEL cohort

Objetivos: Estimar el efecto de los antimaláricos (AM) sobre los diferentes dominios del índice de daño SLICC (SDI). Métodos: Se estudiaron pacientes con diagnóstico clínico reciente (≤2 años) de lupus eritematoso sistémico (LES) de la cohorte GLADEL. Variable de estudio: aumento en los dominios del SDI desde el ingreso a la cohorte. Variables independientes: características sociodemográficas, clínicas, laboratorio y tratamientos. El efecto de los AM, como variable dependiente del tiempo, sobre los dominios más frecuentes del SDI (ajustado por factores de confusión) fue examinado con un modelo de regresión de Cox multivariado. Resultados: De 1466 pacientes estudiados, 1049 (72%) recibieron AM con un tiempo medio de exposición de 30 meses (Q1-Q3: 11-57) y 665 pacientes (45%) presentaron daño durante un seguimiento medio de 24 meses (Q1-Q3: 8-55); 301 eventos fueron cutáneos, 208 renales, 149 neuropsiquiátricos, 98 musculoesqueléticos, 88 cardiovasculares y 230 otros. Después de ajustar por factores de confusión, el uso de AM se asoció a un menor riesgo de daño renal (HR 0,652; IC 95%: 0,472-0,901) y en el límite de la significancia estadística (HR 0,701, IC 95%: 0,481-1,024) para el dominio neuropsiquiátrico. Conclusión: En GLADEL, el uso de AM se asoció independientemente a un menor riesgo de daño acumulado renal.

Objective: To assess the effects of antimalarials (AM) over the items of the SLICC Damage Index (SDI). Methods: Patients with recent (≤2 years) diagnosis of systemic lupus erythematosus (SLE) from the GLADEL cohort were studied. End-point: increase in items SDI since cohort entry. Independent variables (socio-demographic, clinical, laboratory and treatment) were included. The effect of AM as a time dependent variable on most frequent SDI items (adjusting for potential confounders) was examined with a multivariable Cox regression model. Results: Of the 1466 patients included in this analysis, 1049 (72%) received AM with a median exposure time of 30 months (Q1-Q3: 11-57). Damage occurred in 665 (45%) patients during a median follow-up time of 24 months (Q1-Q3: 8-55). There were 301 integument, 208 renal, 149 neuropsychiatric, 98 musculoskeletal, 88 cardiovascular and 230 others less frequently represented damages. After adjusting for potential confounders at any time during follow-up, a lower risk of renal damage (HR 0.652; 95% CI: 0.472-0.901) and borderline for neuropsychiatric damage (HR 0.701, 95% CI: 0.481-1.024) was found. Conclusion: In the GLADEL cohort, after adjustment for possible confounding factors, AM were independently associated with a reduced risk of renal damage accrual.

Effects of Amerindian Genetic Ancestry on Clinical Variables and Therapy in Patients with Rheumatoid Arthritis.

OBJECTIVE: To define whether Amerindian genetic ancestry correlates with clinical and therapeutic variables in admixed individuals with rheumatoid arthritis (RA) from Latin America. METHODS: Patients with RA (n = 1347) and healthy controls (n = 1012) from Argentina, Mexico, Chile, and Peru were included. Samples were genotyped for the Immunochip v1 using the Illumina platform. Clinical data were obtained through interviews or the clinical history. RESULTS: Percentage of Amerindian ancestry was comparable between cases and controls. Morning stiffness (p < 0.0001, OR 0.05), rheumatoid factor (RF; p < 0.0001, OR 0.22), radiographic changes (p < 0.0001, OR 0.05), and higher number of criteria were associated with lower Amerindian ancestry after Bonferroni correction. Higher Amerindian ancestry correlated only with weight loss (pBonferroni < 0.0001, OR 2.85). Increased Amerindian ancestry correlated with higher doses of azathioprine (p < 0.0001, OR 163.6) and sulfasalazine (p < 0.0001, OR 48.6), and inversely with methotrexate (p = 0.001, OR 0.35), leflunomide (p = 0.001, OR 0.16), and nonsteroidal antiinflammatory drugs (pBonferroni = 0.001, OR 0.37). Only the presence of RF and weight loss were modified after confounders adjustment. CONCLUSION: Amerindian ancestry protects against most major clinical criteria of RA, but regarding the association of RF with increased European ancestry, age, sex, and smoking are modifiers. Ancestry also correlates with the therapeutic profiles.

ANCA-associated pauci-immune glomerulonephritis: always pauci-immune?

OBJECTIVES: Anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is considered "pauci-immune" with absent or mild glomerular tuft staining for immunoglobulin (Ig) and/or complement. However, it is not unusual to see some immune deposits (ID) within glomeruli on immunofluorescence (IF). We determined to evaluate the prevalence and clinical significance of immune deposits in ANCA-associated GN. METHODS: We included all patients with ANCA associated vasculitis with renal biopsies between January 2002 and May 2014: granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis and renal limited vasculitis. Patients were divided into Group A: biopsy without ID (≤2+ intensity of immunostaining) and Group B: biopsy with ID (>2+ intensity of immunostaining). Serum creatinine, estimated glomerular filtration rate (eGFR) at time of the biopsy, amount of proteinuria and hematuria, requirement of dialysis and extra renal involvement were recorded. RESULTS: Fifty-three patients (75.4% females) were included. Mean age at biopsy was 66.3 years. Typical pauci-immune GN was found in 39 patients (73.5%, group A). In 14 patients (26.4%, group B) examination revealed substantial deposition of Ig or complement in the mesangium and/or along the glomerular capillary wall. The only difference comparing both groups was significantly higher proteinuria in group B (mean 1.6/24 h (SD: 10.7) vs. 0.8/24 h (SD: 7.6), p=0.0036). CONCLUSIONS: In ANCA GN at least a quarter of patients were not "pauci-immune" (26.4%). In this subgroup, immune deposits were only associated with a significantly higher proteinuria. Further basic and clinical research is needed to elucidate the significance of immune deposition in ANCA GN.

Validation in Spanish of a screening questionnaire for the detection of psoriatic arthritis in patients with psoriasis.

OBJECTIVE: A patient self-administered questionnaire [PsA Screening and Evaluation (PASE)] has been developed and validated in English, but has not been tried in Spanish speaking populations. This study aimed to adapt and validate PASE in Spanish to screen Spanish speaking psoriasis patients for signs and symptoms of inflammatory arthritis. METHODS: Initial translation from English to Spanish (forward translation) was performed by two independent translators and the resulting versions were synthesized during a consensus meeting. The questionnaire was tried in a pilot study and resulted in a change in the agreement scale for a frequency scale with wording adaptation [Spanish PASE (PASE-S)]. RESULTS: One hundred and eleven patients were screened with PASE-S; 25 with PsA (without previous treatments), 23 with psoriasis, 22 with psoriasis and OA and 41 with OA without psoriasis. The diagnosis of psoriasis was performed by a dermatologist, and a rheumatologist determined the diagnosis of PsA or OA. Patients with PsA had statistically significant higher symptoms, function and total PASE-S scores compared with those without PsA. Receiver operator curves showed an area under the curve of 0.79 (95% CI 0.69, 0.89) for the total score. A cut-off value ≥34 showed sensitivity of 76%, and specificity of 74.4% for the diagnosis of PsA. CONCLUSION: The validated PASE questionnaire is a self-administered tool that can be used to screen for PsA among patients with psoriasis in a Spanish speaking population. PASE was able to distinguish between symptoms of PsA and OA.

Incidence and prevalence of psoriatic arthritis in Buenos Aires, Argentina: a 6-year health management organization-based study.

OBJECTIVES: Studies regarding epidemiology of PsA are lacking in Latin America. We estimated the incidence and prevalence of PsA in a University Hospital-based Health Management Organization in Buenos Aires [Hospital Italiano Medical Care Program (HIMCP)]. POPULATION: for incidence calculation, the population at risk was all adult members of the HIMCP, with continuous affiliation for at least 1 year from January 2000 to January 2006. Each person was followed until he/she voluntarily left the HIMCP, death or finalization of the study (final dates) contributing time at risk since January 2000 or enrolment date (whichever occurred later) to that final date. Case ascertainment: medical records of all patients with the problem psoriasis and/or PsA in the HIMCP problem-oriented computer-based patient record system, or registered in rheumatologists and/or dermatologists databases, were revised. Patients fulfilling CASPAR criteria were included. STATISTICAL ANALYSIS: incidence rate (IR) was calculated with 95% CIs. Cumulative prevalence was estimated on 1 January 2006 (denominator population ==88,112). RESULTS: In the study period, 138,288 persons contributed a total of 558,878 person-years, of whom 35 developed PsA (IR 6.26; 95% CI 4.2, 8.3 cases per 100,000 person-years). There were 12 females: IR 3.64 (95% CI 1.6, 5.7) cases per 100,000 person-years; and 23 males: IR 10.02 (95% CI 5.9, 14.1) cases per 100,000 person-years. On 1 January 2006, 65 prevalent cases were identified: prevalence 74 (95% CI 57, 94) cases per 100,000 members. CONCLUSIONS: The incidence and prevalence of PsA in this Latin American country was similar to that reported in other studies from Europe and the USA.

[Insipid diabetes as initial presentation of Wegener's granulomatosis]. / Diabetes Insípida como forma de presentación de Granulomatosis de Wegener.

Wegener's granulomatosis is a granulomatous necrotizing vasculitis which predominantly affects the respiratory tract, kidney, and less frequently other organs such as the nervous system. The latter may occur in up to 54% of cases and when it does it is more frequently of the peripheral nerves. We present a 19 year old woman who commenced her disease with involvement of respiratory sinuses, lungs and kidney and who developed central insipid diabetes (CID) at onset. The CID persisted in spite of adequate response of the other organs and systems with immunosuppresor treatment. The development of CID in the context of vasculitis should suggest this as a possible mechanism.

[Treatment and prognosis]. / Tratamiento y pronóstico.

Diagnosis should include mandatory muscle biopsy to identify inclusion body myositis. Most forms of inflammatory myopathies are still treated similarly, although treatment strategies remain empirical and controlled trials are few. Muscle strength and CPK levels remain the most frequently used measures to monitor disease activity and response to therapy. Corticosteroids are the main pillar of drug therapy but simultaneous use of corticosteroid-sparing drugs may be considered from the start. The most frequently used drugs for combined therapy are methotrexate, azathioprine and antimalarials in cases of dermatomyositis. In refractory cases, especially if life threatening, rituximab has appeared to be effective although there are no controlled trials, and there is some consensus that this should be used prior to Immunoglobulin. Anti TNF antibodies have not been useful in these diseases. Cyclosporin (especially with lung involvement) and Mofetil mycophenolate may also have a role in non responding cases. Treatment of inclusion body myositis remains unsatisfactory.

Anti-inflamatorios no esteroideos: Situación 2005: [revisión] / Non-Steroidal Anti-Inflammatory Drugs: Update 2005: [revision]

Los anti-inflamatorios no esteroideos (AINEs) constituyen una de las drogas más usadas en el mundo, ya sean prescriptas como de venta libre. Son efectivas para controlar la inflamación, pero frecuentemente son utilizadas solamente para controlar el dolor o la fiebre. La prescripción en gerontes es casi cuatro veces mayor que en la población joven, siendo la primera una población de mayor riesgo. De acuerdo a datos de EE.UU., se estima que alrededor del 5% de todas las internaciones se debe a efectos adversosproducidos por drogas, de las cuales un 30% se deberían a AINEs, cuyos efectos adversos son bien conocidos. El descubrimiento de las isoenzimas 1 y 2 de la ciclooxigenasa (COX-1 y 2) y la aparición de AINEs COX-2 selectivosha resultado en una mayor seguridad sobre el tracto gastrointestinal. La percepción inicial de que también podría haber menos efectos sobre el filtrado glomerular desapareció rápidamente, confirmándose que los COX-2 selectivos tenían efectos similares a los AINEs clásicos. Progresivamente apareció evidencia de que la inhibición selectiva de la COX-2 podría generar una situación pro-trombótica con mayor riesgo de accidentes cardiovasculares y cerebrales en pacientes predispuestos. Esto ha llevado al retiro del mercado de por lo menos dos de estas drogas. En otras áreas, el rol de la COX-2 ha abierto puertas interesantes en enfermedad de Alzheimer y cáncer de colon, por mencionar sólo dos. El rol de la COX-2 en otros tejidos es sumamente interesante, probablemente muy relevante, pero no está aún completamente comprendido.El aumento del riesgo cardiovascular obliga a ser muy selectivos en la indicación de estas drogas. Esta situación genera problemas en los pacientes con enfermedad reumática que deben tomarlos durante períodos prolongados.

Non-steroidal anti-inflammatory drugs (NSAID) are one of the most commonly used medications throughout the world,both prescribed and over the counter. Although effective in controlling inflammation, they are frequently used just to treat fever or pain. Prescription in elder patients, a higher risk group, is almost four times that in younger people. Side effects are well known and it is estimated that in the USA around 5% of hospital admissions are related to drugs. Of these, NSAID side effects would account for 30%. The discovery of COX-2 iso-enzymes and of COX-2 selective NSAID has provided for a better gastrointestinal safety profile when compared with traditional NSAID. The initial perception that they may have less effect on renal blood flowwas quickly proved incorrect confirming that COX-2 selective NSAID and non-selective NSAID have similar renal sideeffects. Selective COX-2 inhibition appears to generate a pro-thrombotic state which has been shown to increase cardiovascular side effects in predisposed patients. This has resulted in the discontinuation of two drugs from the market. In other areas, such as Alzheimer´s disease and colon cancer, to name but two, the role of COX-2 has opened interesting pathways. The role of COX-2 in other tissues is interesting and may be very relevant, but it is yet not completely understood. Increased cardiovascular risk determines that we should be very careful when prescribing these drugs. This situation is problematic in patients with rheumatic diseases who need to take these medications over prolonged periods of time.

Anti-inflamatorios no esteroideos: situación 2005 / Non-steroidal anti-inflammatory drugs: update 2005

Los anti-inflamatorios no esteroideos (AINEs) constituyen una de las drogas más usadas en el mundo, ya sean prescriptascomo de venta libre. Son efectivas para controlar la inflamación, pero frecuentemente son utilizadas solamente paracontrolar el dolor o la fiebre. La prescripción en gerontes es casi cuatro veces mayor que en la población joven, siendo laprimera una población de mayor riesgo.De acuerdo a datos de EE.UU., se estima que alrededor del 5% de todas lasinternaciones se debe a efectos adversosproducidos por drogas, de las cuales un 30% se deberían a AINEs, cuyos efectos adversos son bien conocidos.El descubrimiento de las isoenzimas 1 y 2 de la ciclooxigenasa (COX-1 y 2) y la aparición de AINEs COX-2 selectivosha resultado en una mayor seguridad sobre el tracto gastrointestinal. La percepción inicial de que también podría habermenos efectos sobre el filtrado glomerular desapareció rápidamente, confirmándose que los COX-2 selectivos teníanefectos similares a los AINEs clásicos. Progresivamente apareció evidencia de que la inhibición selectiva de la COX-2podría generar una situación pro trombótica con mayor riesgo de accidentes cardiovasculares y cerebrales en pacientespredispuestos. Esto ha llevado al retiro del mercado de por lo menos dos de estas drogas.En otras áreas, el rol de la COX-2 ha abierto puertas interesantes en enfermedad de Alzheimer y cáncer de colon, pormencionar sólo dos. El rol de la COX-2 en otros tejidos es sumamente interesante, probablemente muy relevante, pero noestá aún completamente comprendido.El aumento del riesgo cardiovascular obliga a ser muy selectivos en la indicación de estas drogas. Esta situación generaproblemas en los pacientes con enfermedad reumática que deben tomarlos durante períodos prolongados.

[Polymyalgia rheumatica revisited]. / Actualización en polimialgia reumática.

Polymyalgia rheumatica is an inflammatory disorder that usually affects persons over the age of 50 causing proximal muscle pain and stiffness, and an elevated erythrocyte sedimentation rate. Although increasingly recognized in this age group, it remains a diagnosis of exclusion and although several diagnostic criteria have been proposed, none has been clearly accepted. While polymyalgia rheumatica is associated with giant cell arteritis, obtaining a temporal artery biopsy is not recommended in patients with polymyalgia rheumatica without symptoms of giant cell arteritis. Early diagnosis and low dose corticosteroid therapy improve patients' clinical features and functional status. Treatment usually lasts between 12 and 24 months and the majority of patients manage to discontinue treatment completely.

Consultations for work related low back pain in Argentina.

OBJECTIVE: Low back pain (LBP) is a common cause of disability among people of working age. We investigated the incidence of consultation for work related LBP and of work absence, and determined the prevalence of continued work disability due to LBP in Argentina. METHODS: Our study population comprised 139,740 fulltime workers (mean age 34.4 yrs, range 17-79). An episode of work related LBP was defined as patient consulting because of acute LBP while at work or while traveling to/from work. RESULTS: In a 6 month period 360 episodes of acute LBP were reported in 69,329 worker-years of exposure to risk; thus the episode incidence rate was 5.2/1000 worker-years. This was the third most frequent work related injury. Twenty-one patients (5.8% of episodes) were lost to followup. Those with LBP were significantly older than the population at risk (p < 0.001) and were predominantly men (p < 0.001). In 244 episodes (72%) pain onset was related to heavy physical work and in 46 (13.6%) it followed trauma to the back. Surgery was performed in 9 (2.7%) cases. In total, 322 (98%) patients were absent beyond the day of the injury (median number of days of work absence, 7 days; range 0-422 days). Surgical patients lost significantly more days of work (p < 0.01). Seven patients (2%) remained off work more than 180 days: 2 were declared disabled, 3 moved to lighter jobs, and only 2 (28.5%) returned to their previous job. CONCLUSION: The incidence of consultation for work related LBP was 5.2/1000 worker-years. This was the third most frequent work related injury. Most patients had some work absenteeism. Surgery did not shorten recovery times. Only a minority of patients off work for 6 months or more were able to return to their previous job.

Actualizacion en polimialgia reumática / Polymyalgia rheumatica revisited

Polymyalgia rheumatica is an inflammatory disorder that usually affects persons over the age of 50 causing proximal muscle pain and stiffness, and an elevated erythrocyte sedimentation rate. Although increasingly recognized in this age group, it remains a diagnosis of exclusion and although several diagnostic criteria have been proposed, none has been clearly accepted. While polymyalgia rheumatica is associated with giant cell arteritis, obtaining a temporal artery biopsy is not recommended in patients with polymyalgia rheumatica without symptoms of giant cell arteritis. Early diagnosis and low dose corticosteroid therapy improve patients' clinical features and functional status. Treatment usually lasts between 12 and 24 months and the majority of patients manage to discontinue treatment completely