Rheumatoid Arthritis: Spain

Zarranz Ventura J, De Nova E, Moreno-Montañés J. · Departamento de oftalmología, Clínica Universitaria de Navarra, Pamplona 31008, Spain. · An Sist Sanit Navar. · Pubmed #19169303 links to  free full text

Abstract: Systemic diseases affecting the cornea have a wide range of manifestations. The detailed study of all pathologies that cause corneal alteration is unapproachable, so we have centered our interest in the most prevalent or characteristic of them. In this paper we have divided these pathologies in sections to facilitate their study. Pulmonar and conective tissue (like colagen, rheumatologic and idiopathic inflamatory diseases), dermatologic, cardiovascular, hematologic, digestive and hepatopancreatic diseases with corneal alteration are described. Endocrine and metabolic diseases, malnutrition and carential states are also studied, as well as some otorhinolaryngologic and genetic diseases that affect the cornea. Finally, a brief report of ocular toxicity induced by drugs is referred.

Benítez Del Castillo JM, Díaz-Valle D, Pato E, López-Abad C, Alejandre N. · Unidad de superficie e inflamación ocular, Hospital Clínico San Carlos, Madrid 28040, Spain. · An Sist Sanit Navar. · Pubmed #19169297 links to  free full text

Abstract: Ocular inflammation is a common clinical manifestation related to several autoimmune systemic disorders, specially spondyloarthropaties. In this group, there are different clinical diseases that are related to special uveitic patterns. Several discriminative patterns have been defined that closely link uveitis with certain systemic or ophthalmic diseases. Unilateral recurrent anterior acute uveitis is the most frequent form of uveitis related to spondyloarthropaties, and is sometimes the initial manifestation of an undiagnosed spondyloarthropaty. The collaboration of ophthalmologists, rheumatologists and internal medicine specialists is very important for the correct management and treatment of these patients.

Fernández-Cruz E, Alecsandru D, Rodríguez-Sainz C. · Servicio de Inmunología Clínica, Hospital General Universitario Gregorio Marañón, Madrid, España. · Actas Dermosifiliogr. · Pubmed #19080985 links to  free full text

Abstract: Biological therapies have revolutionized the treatment of chronic systemic diseases in which the immune system disorders form a part of the disease mechanism. In these diseases, the patients follow different drug treatments for long periods of time that causes serious adverse reactions and often obtain unsatisfactory efficacy results. Due to the research conducted in the last 10 years, biological drugs have been introduced into the treatment that are aimed against specific targets, such as inflammatory and immunopathological responses that give rise to tissue injury. The new biological therapies have improved the currently available treatments due to greater efficacy, fast action and greater tolerability. The present work aims to provide a global and up-dated view on the biological agents used most in the usual clinical practice and their importance in the management of the chronic immunologically based inflammatory diseases.

Ramos-Casals M, Brito-Zerón P, Soto MJ, Cuadrado MJ, Khamashta MA. · Laboratory of Autoimmune Diseases Josep Font, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Autoimmune Diseases, Hospital Clínic, Barcelona, Spain. · Best Pract Res Clin Rheumatol. · Pubmed #19028367 No free full text.

Abstract: Anti-TNF agents are increasingly being used for a rapidly expanding number of rheumatic and systemic autoimmune diseases. As a result of this use, and of the longer follow-up periods of treatment, there are a growing number of reports of the development of autoimmune processes related to anti-TNF agents. The clinical characteristics, outcomes, and patterns of association with the different anti-TNF agents used in all reports of autoimmune diseases developing after TNF-targeted therapy, were analyzed through a baseline Medline search of articles published between January 1990 and May 2008 (www.biogeas.org). A total of 379 cases of autoimmune diseases secondary to TNF-targeted therapies were identified. The anti-TNF agents were administered for rheumatoid arthritis in more than 80% of cases. The use of anti-TNF agents has been associated with an increasing number of cases of autoimmune diseases, principally cutaneous vasculitis, lupus-like syndrome, systemic lupus erythematosus and interstitial lung disease. Other autoimmune diseases associated with TNF-targeted therapies have been recently described, e.g. sarcoidosis, antiphospholipid syndrome-related features, and autoimmune hepatitis or uveitis. Large, prospective, postmarketing studies are required to evaluate the risk of developing autoimmune diseases in patients receiving TNF-targeted therapies.

Ramos-Casals M, Muñoz S, Zerón PB. · Laboratory of Autoimmune Diseases "Josep Font," IDIBAPS, Department of Autoimmune Diseases, C/Villaroel 170, Hospital Clinic, Barcelona 08036, Spain. · Rheum Dis Clin North Am. · Pubmed #18984409 No free full text.

Abstract: Patients who have chronic hepatitis C virus infection present some extrahepatic manifestations that may mimic the clinical, immunologic, and histologic manifestations of primary Sjögren's syndrome (SS). Various demographic, clinical, and immunologic features may aid differentiation between the two processes. Chronic hepatitis C virus infection should be considered an exclusion criterion for the classification of primary SS, not because it mimics primary SS, but because the virus may be implicated in the development of SS in a specific subset of patients.

Sánchez Cano D, Callejas Rubio JL, Ortego Centeno N. · Unidad de Enfermedades Autoinmunes Sistémicas, Hospital Universitario San Cecilio, Granada, Spain. · Med Clin (Barc). · Pubmed #18928740 No free full text.

Abstract: Tumor necrosis factor (TNF) alpha plays a central role in both the inflammatory response and that of the immune system. Thus, its blockade with the so-called anti-TNF agents (infliximab, etanercept and adalimumab) represents an important tool for the management of a variety of disorders, such as rheumatoid arthritis, the spondyloarthropathies, inflammatory bowel disease and psoriasis. Nonetheless, theoretically, some other autoimmune and inflammatory disorders may benefit from these agents. We intend to update on these off-label uses of anti-TNF blockers in this review.

López-Pedrera C, Barbarroja N, Aguirre MA, Torres LA, Velasco F, Cuadrado MJ. · Unidad de Investigación, Hospital Universitario Reina Sofía, Cordoba, Spain. · Lupus. · Pubmed #18827055 No free full text.

Abstract: Several systemic autoimmune conditions, including rheumatoid arthritis, systemic lupus erythematosus and antiphospholipid syndrome, are characterised by enhanced atherosclerosis and, consequently, higher cardiovascular morbidity and mortality rates. The association of these diseases with atherosclerosis suggests a common pathogenic mechanism. Genomic and proteomic studies performed on atherosclerotic plaques have further confirmed the presence of a gene and protein profile similar to that observed in autoimmune diseases with cardiovascular risks. Human sera and body fluids have been analysed and have resulted in the identification of auto-antibodies that can be used as diagnostic markers in specific autoimmune diseases, and proteomic fingerprints of blood cells, tissues and body fluids have resulted in the identification of individual proteins or patterns of protein expression that are deregulated. The information provided by these proteomic studies is of diagnostic and therapeutic potential. In this review, we discuss new approaches available for assessing thrombotic risk in autoimmune diseases, focusing in the genomic and proteomic methods now available to deep into the origin of the mechanisms associated with vascular involvement in systemic autoimmune diseases. The increasing data available suggests that when treating patients with these autoimmune disorders, paying attention to the increased risk of cardiovascular disease is essential.

Guhl G, García-Díez A. · Department of Dermatology, Hospital Universitario de la Princesa, Madrid, Spain. · Dermatol Clin. · Pubmed #18793988 No free full text.

Abstract: Neutrophilic panniculitis encompasses a heterogeneous group of diseases histopathologically characterized by an inflammatory infiltrate in the subcutaneous fat mainly composed of mature neutrophils. This group of panniculitides includes alpha(1)-antitrypsin deficiency, infectious panniculitis, factitious panniculitis, subcutaneous Sweet syndrome, neutrophilic/pustular panniculitis associated with rheumatoid arthritis, erythema nodosum-like lesions of Behçet disease, bowel bypass panniculitis, and iatrogenic panniculitis. This article reviews subcutaneous Sweet syndrome, which is a rare idiopathic panniculitis characterized by a dense neutrophilic infiltrate in the subcutis and is often related to hematologic malignancies. The relationship of subcutaneous Sweet syndrome and erythema nodosum is discussed as well as the differential diagnosis with other neutrophilic panniculitis.

Ladero JM. · Gastroenterology Service (Liver Unit), Hospital Clínico San Carlos. Complutense University, Madrid. Spain. · Curr Drug Metab. · Pubmed #18680473 No free full text.

Abstract: Polymorphic N-acetyl transferases (NAT) 1 and 2 are involved in detoxification of xenobiotic arylamines and hydralazines. These common environmental chemicals may be related to the pathogenesis of many spontaneous disorders, mainly malignancies, but also disimmune or degenerative diseases, for which a polygenic predisposition has been suggested. Hence, polymorphic NAT genes (NAT2 has been the most studied one) may be low-penetrance risk genes for some of these disorders. Although a relation of risk may be definitely discarded for systemic lupus erythematosus (SLE), inflammatory bowel disease and endometriosis, more research is needed for rheumatoid arthritis, Parkinson's, Alzheimer's, Behçet's and periodontal diseases , as current results are inconclusive but suggest a possible relation with NAT2 polymorphism. In diabetes mellitus the possible relation with the rapid phenotype may be due to acquired metabolic changes and more genotyping studies are needed. NAT2 slow metabolizers are more prone to the side effects of polymorphically acetylated drugs, as is the SLE-like syndrome induced by hydralazine and procainamide, the side effects due to sulphasalazine and the skin rash secondary to many sulphonamides. Future research should be based on well-designed studies, with adequate sample sizes and homogeneous recruitment criteria, to obviate the proliferation of small studies that are time- and resource-consuming without offering definite answers.

Penela P, Murga C, Ribas C, Salcedo A, Jurado-Pueyo M, Rivas V, Aymerich I, Mayor F. · Departamento de Biologia Molecular and Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Universidad Autonoma de Madrid, Madrid, Spain. · Arch Physiol Biochem. · Pubmed #18618354 No free full text.

Abstract: G protein-coupled receptor kinase 2 (GRK2) is a key modulator of G protein-coupled receptors and other plasma membrane receptors stimulated by chemotactic messengers. On top of that, GRK2 has been reported to interact with a variety of signal transduction proteins related to cell migration such as MEK, Akt, PI3Kgamma or GIT. Interestingly, the levels of expression and activity of this kinase are altered in a number of inflammatory disorders (as rheumatoid arthritis or multiple sclerosis), thus suggesting that it may play an important role in the onset or development of these pathologies. This review summarizes the mechanisms involved in the control of GRK2 expression and function and highlights novel functional interactions of this protein that might help to explain how altered GRK2 levels affects cell migration in different cell types and pathological settings.

Alonso-Ruiz A, Pijoan JI, Ansuategui E, Urkaregi A, Calabozo M, Quintana A. · Rheumatology service (Cruces Hospital), Barakaldo, Spain. · BMC Musculoskelet Disord. · Pubmed #18419803 links to  free full text

Abstract: BACKGROUND: To analyse available evidence on the efficacy and safety of anti-TNFalpha drugs (infliximab, etanercept and adalimumab) for treating rheumatoid arthritis (RA). METHODS: We searched systematically for randomised controlled clinical trials on treatment of RA with anti-TNFalpha drugs, followed by a systematic review with metaanalysis. Trials were searched from MEDLINE, EMBASE and Cochrane Library databases. The American College of Rheumatology (ACR) efficacy response criteria were used. Safety parameters provided by the trials were also assessed. Positive and undesired effects were estimated using combined relative risks (RR), number needed to treat (NNT) and number needed to harm (NNH). Heterogeneity was evaluated by Cochrane's Q and I2 statistics. RESULTS: Thirteen trials (7087 patients) met the inclusion criteria. The combined RR to achieve a therapeutic response to treatment with recommended doses of any anti-TNFalpha drug was 1.81 (95% CI 1.43-2.29) with a NNT of 5 (5-6) for ACR20. NNT for ACR50 [5 (5-6)] and ACR70 [7 (7-9)] were similar. Overall therapeutic effects were also similar regardless of the specific anti-TNFalpha drug used and when higher than recommended doses were administered. However, lower than recommended doses elicited low ACR70 responses (NNT 15). Comparison of anti-TNFalpha drugs plus methotrexate (MTX) with MTX alone in patients with insufficient prior responses to MTX showed NNT values of 3 for ACR20, 4 for ACR50 and 8 for ACR70. Comparison of anti-TNFalpha drugs with placebo showed a similar pattern. Comparisons of anti-TNFalpha drugs plus MTX with MTX alone in patients with no previous resistance to MTX showed somewhat lower effects. Etanercept and adalimumab administered as monotherapy showed effects similar to those of MTX. Side effects were more common among patients receiving anti-TNFalpha drugs than controls (overall combined NNH 27). Patients receiving infliximab were more likely to drop out because of side effects (NNH 24) and to suffer severe side effects (NNH 31), infections (NNH 10) and infusion reactions (NNH 9). Patients receiving adalimumab were also more likely to drop out because of side effects (NNH 47) and to suffer injection site reactions (NNH 22). Patients receiving etanercept were less likely to drop out because of side effects (NNH for control versus etanercept 26) but more likely to experience injection site reactions (NNH 5). CONCLUSION: Anti-TNFalpha drugs are effective in RA patients, with apparently similar results irrespective of the drug administered. Doses other than those recommended are also beneficial. The main factor influencing therapeutic efficacy is the prior response to DMARD treatment. The effect of treatment with etanercept or adalimumab does not differ from that obtained with MTX. The published safety profile for etanercept is superior but the fact that no patients are treated with higher than recommended doses requires explanation.

Pérez Pampín E, Gómez-Reino Carnota JJ. · Servicio de Reumatología, Hospital Clínico Universitario, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, La Coruña, España. · Med Clin (Barc). · Pubmed #18341834 No free full text.

Abstract: In the last decade, tumor necrosis factor (TNF) antagonists had supposed an important therapeutic advance in the treatment of patients with rheumatoid arthritis (RA) in both early and established RA. Three agents currently available--infliximab, etanercept, and adalimumab--have been designed to modify the biologic effects of TNF. Infliximab and adalimumab are monoclonal antibodies, whereas etanercept is a soluble protein, with different pharmacokinetic and pharmacodynamic properties, conditioning some possible adverse effects. Although comparative studies are not available, the 3 drugs have demonstrated efficacy and security, with a better quality of life of patients with RA. Infliximab, etanercept and adalimumab have been proved alone and in combination with methotrexate, with a better therapeutic, clinical, radiological and functional response in the group under combined therapy. Both clinical trials and post-market experience have demonstrated the security of these drugs, minimizing the risks with an adequate selection of patients.

Lago R, Gómez R, Lago F, Gómez-Reino J, Gualillo O. · Santiago University Clinical Hospital, Research Laboratory 4 (NEIRID LAB, Laboratory of Neuro Endocrine Interactions in Rheumatology and Inflammatory Diseases), Calle Choupana s/n, 15706 Santiago de Compostela, Spain. · Cell Immunol. · Pubmed #18289518 No free full text.

Abstract: Leptin, a 16 kDa non-glycosylated polypeptide produced primarily by adipocytes and released into the systemic circulation, exerts a multitude of regulatory functions including energy utilization and storage, regulation of various endocrine axes, bone metabolism, and thermoregulation. In addition to leptin's best known role as regulator of energy homeostasis, several studies indicate that leptin plays a pivotal role in immune and inflammatory response. Because of its dual nature as a hormone and cytokine, leptin can be nowadays considered the link between neuroendocrine and immune system. The increase in leptin production that occurs during infections and inflammatory processes strongly suggests that this adipokine is a part of the cytokines network which governs inflammatory/immune response and host defence mechanisms. Indeed, leptin plays a relevant role in inflammatory processes involving either innate or adaptive immune responses. Several studies have implicated leptin in the pathogenesis of autoimmune inflammatory conditions such as encephalomyelitis, type I diabetes, bowel inflammation and also articular degenerative diseases such as rheumatoid arthritis and osteoarthritis. Although the mechanisms by which leptin exerts its action as modulator of inflammatory/immune response are likely to be more complex than predicted and far to be completely depicted, there is a general consensus about its pivotal role as pro-inflammatory and immune-modulating agent. Here, we review the most recent advances on leptin biology with a particular attention to its adipokine facet, even though its role as metabolic hormone will be also addressed.

Brito-Zerón P, Ramos-Casals M. · Laboratorio de Enfermedades Autoinmunes Josep Font, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Barcelona, España. · Med Clin (Barc). · Pubmed #18261383 No free full text.

Abstract: The natural history of primary Sjögren's syndrome has been little studied. Some studies agree that, although it is not a benign disease, it is characterized by a steady evolution of the predominant symptoms (sicca and general manifestations). However, there are 2 main exceptions to this chronic course: the development of vasculitic manifestations, and the high incidence of lymphomas, both processes being related to the excess of mortality in patients with primary Sjögren's syndrome. Recent studies have prospectively analyzed the outcome of this disease in a large series of patients and identified those factors present at diagnosis prospectively associated with an adverse outcome. The main prognostic factors identified are severe involvement of the exocrine glands, vasculitis, hypocomplementemia and cryoglobulins at diagnosis. These features identify a specific subset of patients diagnosed with primary Sjögren's syndrome in whom a closer follow-up, and probably an earlier and more robust therapeutic management, should be mandatory.

Sánchez-Pernaute O, Ospelt C, Neidhart M, Gay S. · Fundación Jiménez Díaz, Madrid, Spain. · J Autoimmun. · Pubmed #18155418 No free full text.

Abstract: The innate immune response needs to be tightly regulated to balance elimination of microorganisms with the magnitude of inflammation. The rupture of this balance is crucial for the outcome of diseases such as rheumatoid arthritis (RA) in which an overflowed proinflammatory response is associated with self-damage. Epigenetics alludes to systems controlling gene expression and silencing independent of the germline, but stable enough to be inherited by daughter cells upon mitosis. We will show in this review how pathological processes in RA can be shaped by epigenetics, which may in turn explain differences in phenotypes between subgroups of patients and also between subsets of fibroblasts within the joint. On the whole, the concourse of epigenetic mechanisms can precipitate the aggressive behaviour of cells and the rupture of peripheral tolerance. Targeting these emerging regulatory pathways is a promising approach for RA therapeutics.

Ramos-Casals M, Brito-Zerón P, Font J. · Servei de Malalties Autoimmunes, Hospital Clínic, C/Villarroel, 170, 08036 Barcelona, Spain. · Clin Rev Allergy Immunol. · Pubmed #17992594 No free full text.

Abstract: Sjögren's syndrome (SS) is a systemic autoimmune disease that mainly affects the exocrine glands and usually presents as persistent dryness of the mouth and eyes because of functional impairment of the salivary and lacrimal glands. The histological hallmark is a focal lymphocytic infiltration of the exocrine glands, and the spectrum of the disease extends from an organ-specific autoimmune disease (autoimmune exocrinopathy) to a systemic process with diverse extraglandular manifestations. In the absence of an associated systemic autoimmune disease, patients with this condition are classified as having primary SS. The differential diagnosis includes processes that specifically involve the exocrine glands. On the one hand, some chronic viral infections may induce lymphocytic infiltration of the exocrine glands, in some cases indistinguishable from that observed in primary SS. On the other hand, some processes may mimic the clinical picture of SS through nonlymphocytic infiltration of the exocrine glands. This review focuses on these two groups of diseases that mimic SS (infections and infiltrating processes).

Bridges SL. · Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham 35294, USA. · Bull NYU Hosp Jt Dis. · Pubmed #17922665 links to  free full text

Abstract: Clinicians have an increasing number of therapeutic agents available for the treatment of rheumatoid arthritis (RA). Pharmacogenetics, the study of genetic variation underlying differential response to drugs, seeks to improve treatment of individual patients. Multiple markers of treatment response have been analyzed in RA, but many of the studies are small and retrospective in nature. There are many obstacles to personalized medicine for RA patients, including incomplete understanding of disease pathogenesis, effecting changes in physician behavior, and acceptance of costs by health insurers. Despite these many obstacles, there are many reasons for optimism for future personalized medicine in RA. There have been remarkable advances in genomics, proteomics, and statistical analyses of large amounts of data. The goal of identifying genetic, serum, and clinical factors that allow profiling of individual patients to predict optimal treatment regimens is a worthy pursuit which will hopefully improve clinical care of RA patients.

Ramos-Casals M, Khamashta MA. · Department ofAutoimmune Diseases, IDIBAPS Hospital Clinic, Barcelona, Spain. · Ann N Y Acad Sci. · Pubmed #17893970 No free full text.

Abstract: Dr. Josep Font (Barcelona, 1953-2006) devoted his professional career to the care of patients with systemic autoimmune diseases (SAD). In 1995, he created the Department of Autoimmune Diseases at the Hospital Clinic in Barcelona, a pioneering unit in Europe specifically dedicated to the clinical management of these patients. The research output of Dr. Font has been prodigious, with a total of over 500 scientific articles published in 25 years, and was especially focused on the clinical and immunological characterization of systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (SS). This review briefly analyzes some of the main contributions of Josep Font to our current knowledge about these diseases. In SLE, the research was centered on the epidemiological and clinical characterization, the study of cardiovascular and vasculitic involvements, and the investigation of the etiopathogenic role of the innate immunity. In primary SS, basic research conducted by Dr. Font contributed to a better understanding of the autoimmune etiopathogenesis of the disease, while the clinical research expanded our knowledge about the systemic and immunological expression of the disease and its frequent association with lymphoma, other SAD, and chronic viral infections.

Puig-Sanz L. · Servicio de Dermatología, Hospital de la Santa Creu i Sant Pau, Barcelona, España. · Actas Dermosifiliogr. · Pubmed #17663929 links to  free full text

Abstract: It has long been recognized the epidemiological association of psoriasis, especially the most severe forms, with several diseases that share a common pathogenic substrate involving TNF-alpha and different target organs (arthritis and Crohn's disease, for example), as well as an increased risk of coronary heart disease and occlusive cardiovascular disease. In the patient with severe psoriasis there is also an increased prevalence of obesity, dyslipemia, adult diabetes mellitus, alcohol abuse and tobacco habit which contribute to the increased risk of mortality associated with atherosclerosis. Recently it has been identified the so-called metabolic syndrome, characterized by the association of abdominal obesity, atherogenic dyslipemia, hypertension, insulin resistance with or without glucose intolerance and a proinflammatory and prothrombotic state as a risk factor for cardiovascular disease. There is evidence that in rheumatoid arthritis as well as in psoriasis, chronic inflammation has a pathogenic role in the metabolic syndrome and associated comorbidities, and its adequate treatment may contribute to revert it. The dermatologist should recognize the elements of the metabolic syndrome and propose the patient with psoriasis, in addition to the optimal dermatologic treatment, changes in life habits and appropriate drug therapy to reduce the risk of cardiovascular morbi-mortality.

Ramos-Casals M, Brito-Zerón P. · Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic, Barcelona, Spain. · Rheumatology (Oxford). · Pubmed #17586555 No free full text.

Abstract: Sjögren's syndrome (SS) is a systemic autoimmune disease that mainly affects the exocrine glands and usually presents as persistent dryness of the mouth and eyes. SS primarily affects white perimenopausal women, with an incidence of 4-5 cases per 100 000. Recent studies have analysed new therapeutic approaches, focusing mainly on the use of biological agents. B-cell targeted therapies seem to be the most promising agents in primary SS, especially rituximab, which has been used in more than 50 reported cases. Other promising B-cell targeted therapies include epratuzumab and belimumab, while T-cell targeted agents (efalizumab, abatacept, alefacept) should currently be considered as possible future options. In the near future, biological agents will play key roles in the treatment of severe involvement, broadening the therapeutic options in primary SS and offering a more optimistic point of view of the treatment of this disease, which, at present, is often considered to lack adequate specific therapy. However, the possible risks and benefits of using these agents should be carefully balanced, and a reasonable assessment of the risk of serious adverse events versus the benefits of treatment should be made. The use of biological agents targeting molecules and receptors involved in the aetiopathogenesis of primary SS opens a new era in the therapeutic management of patients with primary SS.

Carmona L, Ortiz A, Abad MA. · Unidad de Investigación, Fundación Espanola de Reumatología, Madrid, Spain. · Acta Reumatol Port. · Pubmed #17572650 No free full text.

Abstract: Despite the biological rationale for switching between TNF-antagonists, there is not a definitive answer from a clinical point of view. METHODS: We performed a systematic review. The strategy for the literature search included synonyms for the active drugs, trade names, and different synonyms for biologic therapies, plus the words "switch" or "switching", limited to studies in humans. The time limit was March 1st 2007. From 256 initial hits in Medline and Embase, plus 13 abstracts from rheumatology meetings, we finally included 33 studies. RESULTS AND DISCUSSION: The most frequently died switches are those between etanercept and infliximab. The mean number of patients studied per type of switch was 126. There are, apart from retrospective observational studies and cases series, 5 prospective cohorts from biologic registries, 1 randomised open-label clinical trial and 1 phase IV clinical trial, all seven of which are of moderate to good quality. There results are promising but not excellent. Any switch, especially those between monoclonal antibodies, have an effect size that is usually lower than that of a first biologic. When the switch is due to an adverse event with the first TNF-antagonist, however, the response rate of the second one is high. Perhaps the best alternative when a first TNF-antagonist fails is to start a different type of biologic, and leave the switch to another TNF-antagonist in the case of adverse event to the previous one.

Páramo JA, Rodríguez JA, Orbe J. · Servicio de Hematología y Hemoterapia, Clínica Universitaria, Pamplona, Navarra, España. · Med Clin (Barc). · Pubmed #17565884 No free full text.

Abstract: The recognition that inflammation is a hallmark of atherosclerotic disease and its complications has led to a series of studies reporting high prevalence of atherosclerosis in chronic inflammatory diseases. Indeed, chronic immune diseases, such as systemic lupus erythematosus and rheumatoid arthritis, are associated with proinflammation, accelerated atherosclerosis and increased incidence of cardiovascular disease. Since the susceptibility towards cardiovascular events cannot be explained by classical risk factors, disease-specific pathways have been put forward as additional risk factors, potentially important for future prevention and treatment of atherosclerosis associated with chronic inflammatory diseases.

Cobo-Ibáñez T, Martín-Mola E. · Hospital Universitario La Paz, Servicio de Reumatología, Paseo de la Castellana 261, 28046 Madrid, Spain. · Expert Opin Pharmacother. · Pubmed #17563271 No free full text.

Abstract: Etanercept is a dimeric fusion protein based on the p75 TNF-alpha receptor. It binds to TNF-alpha and blocks its biologic activity. In randomized, double-blind, placebo-controlled trials, etanercept has therapeutic activity in rheumatoid arthritis, psoriatic arthritis, polyarticular-course juvenile idiopathic arthritis and ankylosing spondylitis. Etanercept improves joint inflammation, physical function and slows/halts structural damage, especially when combined with methotrexate. A sustained response is observed in a substantial percentage of patients. Although some safety issues should be considered before starting etanercept treatment, in general terms, etanercept is a well tolerated drug with an acceptable safety profile. The use of any TNF-alpha antagonist must be in agreement with the National Recommendations for Biologic Therapy, and in difficult clinical situations, a balance between risk/benefit needs to be obtained.

García-Patos V. · Department of Dermatology, Hospital Universitario Vall d'Hebron, Professor of Dermatology, Universidad Autónoma de Barcelona, Barcelona, Spain. · Semin Cutan Med Surg. · Pubmed #17544962 No free full text.

Abstract: Rheumatoid nodules are the most common extra-articular manifestation of rheumatoid arthritis. Dermatologist may be concerned with the diagnosis and management of rheumatoid nodules, although most patients will probably be under the care of a rheumatologist. This article focuses in clinical, pathogenic, diagnostic, and therapeutic aspects of rheumatoid nodules. Classic rheumatoid nodules commonly occur in genetically predisposed patients with severe, seropositive arthritis. However, they may appear in other clinical settings. Accelerated rheumatoid nodulosis, especially involving the hands, has been reported in patients receiving methotrexate, antitumor necrosis factor alpha biologic drugs or leflunomide therapy for rheumatoid arthritis. Rheumatoid nodulosis is characterized by multiple rheumatoid nodules, recurrent joint symptoms with minimal clinical or radiologic involvement, and a benign clinical course. Pseudorheumatoid nodules have been reported in healthy children. Although histologically almost indistinguishable from true rheumatoid nodules, some consider these lesions to be a form of deep granuloma annulare.

Balsa A, Pascual-Salcedo D, Martín J. · Servicio de Reumatología, Hospital Universitario La Paz, Madrid, España. · Med Clin (Barc). · Pubmed #17537367 No free full text.

Abstract: Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic inflammation of the synovial joints leading to progressive joint destruction. The serum of these patients contains a large repertoire of autoantibodies, mainly rheumatoid factor, which is part of the ACR classification criteria in spite of having only moderate specificity. Antibodies directed to citrullinated proteins provide clinicians with a valuable tool for early diagnosis. It has been shown that these antibodies can be detected years before presentation of the first symptom and are very useful for diagnosis and prognosis, due to good sensitivity and specificity and prediction of development of erosive disease. The immune response against citrullinated antigens is characteristic of an immuno-genetic subtype of disease, in which the combined role of genes, environmental factors and autoimmunity has become the prime suspected for disease pathogenesis. A model is proposed of how these antibodies are produced and lead to chronic synovial inflammation.