Rheumatoid Arthritis: USA

Abraham AK, Ramanathan M, Weinstock-Guttman B, Mager DE. · Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Amherst, NY 14260, USA. · Biochem Pharmacol. · Pubmed #19428330 No free full text.

Abstract: Restoration of dysregulated bone homeostasis is a therapeutic goal in many diseases including osteoporosis, rheumatoid arthritis and metastatic cancer. The molecular pathways regulating bone remodeling are major therapeutic targets, and studies continue to reveal endogenous factors that may be pathologically up- or down-regulated and lead to an uncoupling of bone formation and resorption. The purpose of this commentary is to highlight new mechanisms of bone homeostatic regulation mediated through the induction of endogenous interferon-beta (IFN-beta). The receptor activator of nuclear factor-kappaB (RANK) ligand (RANKL) is an important factor in the bone resorption cascade, and the RANK-RANKL interaction has been shown to induce IFN-beta and osteoclastogenesis via induction of the c-fos gene. Subsequent binding of IFN-beta to its biological receptor initiates a signal transduction cascade through the classic JAK/STAT pathway, causing an inhibition of c-fos protein production and osteoclast proliferation and differentiation (negative feedback). Another mechanism pertinent to the anti-resorptive effect of IFN-beta is the induction of nitric oxide which has been shown to inhibit osteoclast formation. The role of IFN-beta in bone metabolism could warrant its systematic evaluation as a potential adjunct to therapeutic regimens of osteolytic diseases. Here we also provide discussion of the potential challenges to optimizing IFN-beta pharmacotherapy for such purposes.

Lin E, Freedman JE, Beaulieu LM. · Whitaker Cardiovascular Institute, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. · Cardiovasc Ther. · Pubmed #19426249 No free full text.

Abstract: Toll-like receptors (TLRs) are germline-encoded receptors that recognize various pathogen-associated molecular patterns (PAMPs). They are key components of the innate immunity which are activated in response to pathogens as well as non-pathogenic components of damaged tissues. TLR agonists have been developed to treat allergies, cancers, and chronic infections by upregulating the innate immune system. TLR antagonists may be used to treat a number of inflammatory conditions, such as rheumatoid arthritis and systemic lupus erythematosus. Recent research also has shown that TLRs are involved in the pathogenesis of atherosclerosis, thrombosis, myocardial remodeling, ischemic/reperfusion injury, and valvular disease. This article reviews the current experimental and clinical evidence for the role of TLRs in the cardiovascular system, and examines the mechanisms by which TLR antagonists could potentially be used in targeted therapy.

Linsley PS, Nadler SG. · Regulus Therapeutics, Carlsbad, CA, USA. · Immunol Rev. · Pubmed #19426230 No free full text.

Abstract: SUMMARY: This volume covers many topics in the field of T-cell costimulation. The need for such a volume is testament to the growth of the field. From its beginning as a concept in the 1980s, we have now progressed to the point where many molecules now have functionally defined roles in T-cell costimulation. In addition, the field has progressed 'from bench to bedside'. Abatacept [cytotoxic T-lymphocyte antigen-4 (CTLA-4)-immunoglobulin (Ig) (CTLA-4-Ig)], an inhibitor of CD28-mediated T-cell costimulation, was approved for the treatment of moderate-to-severe rheumatoid arthritis in 2006 by the Food and Drug Administration and in 2007 by the European Medicines Agency. This chapter first presents a personal historical perspective on the early basic studies on the elucidation of the CD28/B7 T-cell costimulatory pathway and the discovery of CTLA-4-Ig. We next present an overview of studies of CTLA-4-Ig in preclinical animal studies. The material discussed in these first two sections is selective rather than exhaustive; their purpose is to provide context for the final section, a summary of human clinical studies performed with abatacept.

Culpepper L. · Boston Medical Center, 1 Boston Medical Center Place, Dowling 5, Boston, MA 02118, USA. · J Clin Psychiatry. · Pubmed #19371503 No free full text.

Abstract: Patients with generalized anxiety disorder (GAD) often have multiple medical comorbidities. The adrenal system and genetic and environmental factors are intermediaries between anxiety and medical illnesses such as chronic pain conditions and gastrointestinal, cardiovascular, endocrine, and respiratory disorders. Medical disorders associated with anxiety include migraine, rheumatoid arthritis, peptic ulcer disease, irritable bowel syndrome, coronary heart disease, hyperthyroidism, diabetes, asthma, and chronic obstructive pulmonary disorder. Compared to people with pain conditions without GAD, individuals with pain conditions and GAD experience and register pain differently; they also have increased awareness of symptoms. Comorbid medical illnesses may influence treatment choice for GAD. Treatment of anxiety in young patients with GAD needs to be long-term to decrease vulnerability to medical conditions.

Plenge RM. · Division of Rheumatology, Immunology and Allergy, Brigham and Women's, Hospital, Harvard Medical School, Boston, USA. · Curr Opin Rheumatol. · Pubmed #19365266 No free full text.

Abstract: PURPOSE OF REVIEW: Recent human genetic discoveries have increased our understanding of rheumatoid arthritis (RA) susceptibility. These discoveries are reviewed and placed in the context of potential important clinical applications. RECENT FINDINGS: Genome-wide association studies and related methodologies have expanded the number of validated RA risk loci beyond HLA-DRB1 'shared epitope' alleles to include additional major histocompatibility complex risk alleles and more than 10 regions outside the major histocompatibility complex locus. The newly discovered risk alleles are common in the general population, and most have a modest effect on risk of RA (odds ratio approximately 1.15 per copy of each risk allele). Although the actual causal mutation and causal gene for most loci remain to be determined, these studies are beginning to reveal general themes: many risk loci are associated with other autoimmune diseases, many genes fall within discrete biological pathways (e.g., the NF-kappaB signaling pathway), and human genetics can subset disease into clinically meaningful categories (e.g., presence or absence of autoantibodies). SUMMARY: Approximately one-third of the genetic basis of RA can be explained by known risk loci. Future studies need to pinpoint the actual causal mutations, expand the number of risk loci, and translate these discoveries to improve care of patients with RA.

Kokkalis ZT, Schmidt CC, Sotereanos DG. · Department of Orthopaedic Surgery, Allegheny General Hospital, Pittsburgh, PA 15212, USA. · J Hand Surg Am. · Pubmed #19345885 No free full text.

Abstract: The purpose of this article is to provide an update and analyze current management, treatment options, and outcomes of elbow arthritis. This article focuses on studies that have been published in the past 5 years. Nonoperative management may provide symptomatic relief in the early stages of the disease process for most patients. Surgical treatment is guided by disease etiology and severity, patient age, and functional demands. Arthroscopic or open synovectomy, debridement arthroplasty, and interposition arthroplasty are generally recommended for the young and active patient population, whereas for low-demand and elderly patients with end-stage painful arthritis, total elbow arthroplasty is considered a more suitable surgical option. Advances in arthroscopic techniques and implant design have led to substantial improvements in treatment of elbow arthritis.

Bajaj S, Pattamapaspong N, Middleton W, Teefey S. · Mallinckrodt Institute of Radiology, Washington University in St Louis, St Louis, MO, USA. · J Hand Surg Am. · Pubmed #19345884 No free full text.

This publication has no abstract.

Patel RV, Clark LN, Lebwohl M, Weinberg JM. · University of Miami Miller School of Medicine, Miami, Florida, USA. · J Am Acad Dermatol. · Pubmed #19344980 No free full text.

Abstract: BACKGROUND: There are multiple therapeutic options for the treatment of moderate to severe psoriasis. The process of choosing among potential treatment options requires both the physician and the patient to weigh the benefits of individual modalities against their potential risks. Traditional systemic therapies for psoriasis, including methotrexate (MTX) and cyclosporine (CsA), have a well-documented array of toxicities, particularly end-organ toxicities. Over the past several years, the use of biologic therapies for the treatment of moderate to severe psoriasis has been a major clinical and research focus. With the advent of these novel immunosuppressive therapies, one of the central safety issues surrounding these agents is their potential to increase the risk of malignancy. OBJECTIVE: Our objective was to review the risk of malignancy associated with therapies for moderate to severe psoriasis, including phototherapy, traditional systemic therapies, and biologic therapies. We reviewed the existing body of literature in order to define the known incidence of malignancy associated with psoralen and ultraviolet A (PUVA), narrowband and broadband ultraviolet B (UVB), MTX, CsA, mycophenolate mofetil (MMF), and biologic therapies, including alefacept, efalizumab, infliximab, etanercept, adalimumab, and ustekinumab. RESULTS: PUVA, when given long term, is associated with increased risks of cutaneous squamous cell carcinoma and malignant melanoma. Reviews of studies on UVB, both narrowband and broadband, do not indicate any increased risk of nonmelanoma skin cancer or melanoma. The traditional systemic psoriasis therapies-MTX, CsA, and MMF-may be associated with an increased risk of lymphoproliferative disorders during treatment, demonstrated in clinical trials in patients with rheumatoid arthritis and documented in case reports concerning psoriasis patients. The risk of malignancy with biologic therapy is still unclear. However, the majority of studies examining this carcinogenic risk suggest that tumor necrosis factor-alpha inhibitors may cause a slightly increased risk of cancer, including nonmelanoma skin cancer and hematologic malignancies. LIMITATIONS: The majority of studies cited in this review lack the power and randomization of large clinical trials, as well as the long-term follow-up periods which would further substantiate the hypothetical link between these antipsoriatic treatment regimens and the potential for malignancy. Because of the substantial lack of clinical data, the majority of studies evaluated focus on the treatment of patients with rheumatoid arthritis, which is a systemic inflammatory disorder comparable to psoriasis. Additionally, the increased risk of malignancy associated with psoriasis itself is a confounding factor. CONCLUSION: Many of the therapies for moderate to severe psoriasis, including PUVA, traditional systemic therapies, and some biologic therapies, may increase the risk of malignancy. Appropriate patient counseling and selection, as well as clinical follow-up, are necessary to maximize safety with these agents. Further long-term study is necessary to more precisely quantify the risks associated with biologic therapies.

Villa-Forte A. · Center for Vasculitis Care and Research, Orthopedic and Rheumatologic Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA. · Curr Opin Rheumatol. · Pubmed #19342955 No free full text.

Abstract: PURPOSE OF REVIEW: To review the current uses of antitumor necrosis factor alpha (TNFalpha) therapies for non-rheumatoid arthritis inflammatory joint diseases. Emphasis is given to important questions regarding long-term use of anti-TNFalpha therapies. RECENT FINDINGS: TNFalpha blockade is one of the anticytokine therapies with major impact in the treatment of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and juvenile idiopathic arthritis among the inflammatory joint diseases. As a result of the impressive response to TNFalpha inhibitors, new agents continue to be developed and a few are currently being tested in phase III trials. The evaluation of a potential relationship between inflammation and structural damage in ankylosing spondylitis has been an important focus of recent studies and will likely result in a better understanding and use of anti-TNFalpha therapy. Other aspects of treatment such as long-term safety and selection of patients who will likely have a major response have been evaluated in recent studies and will continue to be important topics in future research. SUMMARY: As TNFalpha inhibitors have been a major advance in the treatment of a number of inflammatory joint diseases and have been widely available in clinical practice, future research will need to continuously assess longitudinal efficacy and safety.

Kaplan MJ. · Division of Rheumatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. · Nat Rev Rheumatol. · Pubmed #19337285 No free full text.

Abstract: Patients with chronic inflammatory disorders are at increased risk of developing premature cardiovascular disease. Despite significant advances in our understanding of the effects of inflammatory pathways on the vasculature, clear guidelines on the management of traditional and nontraditional cardiovascular risk factors in patients with systemic autoimmunity are lacking. Thus, rigorous studies assessing the individual contributions of the various treatments used in autoimmune disorders, as well as their effects on atherosclerosis development in these conditions, are needed. Furthermore, effective screening methods are needed to identify those patients with inflammatory disease who are at the highest risk for atherosclerotic complications, and who would benefit from early intervention. There is a clear need for a unifying explanation of the factors that promote premature cardiovascular disease in patients with chronic inflammatory disorders. Nevertheless, ongoing advances in the understanding of immune-mediated vascular damage mean that we are edging closer to the development of disease-specific preventive strategies to ameliorate or abrogate premature cardiovascular disease in these patients.

Brent LH. · Albert Einstein Medical Center, Einstein Arthritis Center, Philadelphia, PA 19141, USA. · Postgrad Med. · Pubmed #19332973 links to  free full text

Abstract: Continuing advances in the treatment of inflammatory arthritides such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) have made remission a realistic goal for patients. Despite these advances, early diagnosis of inflammatory arthritis by primary care physicians (PCPs) and subsequent referral to a rheumatologist remain a challenge. Delayed diagnosis and referral, which may extend to several years in some cases, may lead to irreversible joint destruction and compromised function. The aim of this review is to aid PCPs in preventing the potential delay in disease recognition and patient referral by highlighting the currently accepted criteria for disease activity, clinical response, and remission of RA, AS, and PsA. In addition, a discussion of the benefits and risks of the currently approved traditional disease-modifying antirheumatic drugs and biologic treatments, and the importance of comanagement of these conditions across specialties, will be addressed. Because PCPs are often the first point of contact for disease recognition, they can play a critical role in the management of these patients.

Liao KP, Alfredsson L, Karlson EW. · Brigham and Women's Hospital, Boston, Massachusetts 02141, USA. · Curr Opin Rheumatol. · Pubmed #19318947 No free full text.

Abstract: PURPOSE OF REVIEW: To examine new environmental factors and provide updates on known risk factors for rheumatoid arthritis (RA) in the past 2 years (2006-2008). This review is timely given the expanding information on treatment, pathogenesis and genetic risk factors for RA. RECENT FINDINGS: High consumption of red meat does not increase risk of RA, whereas alcohol intake may be protective. The role of vitamin D and oral contraceptives as modifiers of disease risk remains equivocal. Other factors associated with increased risk of RA include higher birthweight, living in the northeastern United States compared with other regions of the country, and lower socioeconomic status. Duration of breastfeeding is inversely associated with RA risk. Several studies have now demonstrated that anti-citrullinated protein antibody positive RA has a specific association with environmental risk factors such as smoking. SUMMARY: Recent studies have increased our understanding of environmental exposures that modify risk for RA such as smoking and alcohol intake. Other factors such as birthweight, breastfeeding, socioeconomic status and region of birth have also been demonstrated to contribute to risk. ACPA status is associated with specific environmental factors and is therefore important to incorporate into present and future studies.

Pauley KM, Cha S, Chan EK. · Department of Oral Surgery & Diagnostic Sciences, University of Florida, Gainesville, FL 32610-0424, USA. · J Autoimmun. · Pubmed #19303254 No free full text.

Abstract: MicroRNAs (miRNAs) are small conserved non-coding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3' untranslated region (UTR) of specific messenger RNAs (mRNAs) for degradation or translational repression. miRNA-mediated gene regulation is critical for normal cellular functions such as the cell cycle, differentiation, and apoptosis, and as much as one-third of human mRNAs may be miRNA targets. Emerging evidence has demonstrated that miRNAs play a vital role in the regulation of immunological functions and the prevention of autoimmunity. Here we review the many newly discovered roles of miRNA regulation in immune functions and in the development of autoimmunity and autoimmune disease. Specifically, we discuss the involvement of miRNA regulation in innate and adaptive immune responses, immune cell development, T regulatory cell stability and function, and differential miRNA expression in rheumatoid arthritis and systemic lupus erythematosus.

Wood KL, Twigg HL, Doseff AI. · Department of Medicine, The Ohio State University Medical Center, Columbus, OH, USA. · Front Biosci. · Pubmed #19273309 No free full text.

Abstract: Expansion of CD8+ lymphocyte subsets are found in many states with chronic antigenic exposure including HIV, multiple myeloma, rheumatoid arthritis, CMV infection, transplantation and even normal aging. These expansions are characterized by the expression of CD57 antigen and the loss of CD28-. These lymphocytes are thought to represent clonally expanded cytotoxic T lymphocytes (CTL) that have become senescent and lack proliferative ability. These cells also demonstrate suppressive properties and have been linked with immunodeficiency raising the question of the function of these cells in relationship to immunoregulation. Alterations in the CD95/Fas apoptotic pathway and changes in pro-survival factors such as Hsp27 likely contribute to this lymphocyte subset expansion. Further understanding of the normal CD8+ lymphocyte response to antigen and the factors that lead to abnormal continued expansion in certain disease states will be crucial to understanding the pathogenesis of chronic antigenic stimulation.

Fox BA, Stephens MM. · East Tennessee State University, Family Physicians of Kingsport, Tennessee 37660, USA. · Drugs Today (Barc). · Pubmed #19271029 No free full text.

Abstract: Osteoarthritis (OA) is the most common arthritis affecting the aging population. This degenerative disease can cause significant pain and functional disability in affected individuals. Despite advances in the retardation of rheumatoid arthritis with disease-modifying agents, comparable oral agents have been relatively unavailable for OA. The mainstays of therapy continue to be acetaminophen and nonsteroidal antiinflammatory medications to manage symptoms. Unfortunately, these medications can precipitate severe adverse events in some patients or may be contraindicated, leaving few choices remaining to control pain and suffering. Glucosamine sulfate and chondroitin sulfate have been evaluated in many studies as agents to relieve pain, improve functional activity, and slow disease progression in OA especially of the hip and knee. Studies have reported conflicting results regarding improvement in the pain and disability associated with OA with the use of glucosamine and chondroitin as single agents; however, when improvement has been demonstrated, the formulation has primarily been glucosamine sulfate combined with chondroitin sulfate. Recently, as a result of information implicating the role of reactive oxygen species and oxidative cellular stress reactions on the onset of neurodegenerative and inflammatory disorders, it has been theorized that medications that could control or alter these reactions might improve or prevent the onset of these conditions. Primorine is a combination of products thought to alter these biochemical oxidative byproducts. Based on current evidence, the use of a combination product of glucosamine sulfate and chondroitin sulfate seems to have the greatest potential as a therapeutic intervention for patients at increased risk from the adverse events of accepted current oral therapies. The use of primorine and its combination of products as an intervention in OA has theoretical advantages but its benefits are unproven. A new product, relamine, is a combination of these three formulations. While no studies have evaluated glucosamine sulfate, chondroitin sulfate and primorine in a single product, it may be an option for those who wish to try an alternate therapy for OA, as there appears to be a low risk for serious adverse events.

Pan Z. · Alpharetta, Georgia, USA. · Drug News Perspect. · Pubmed #19259548 No free full text.

Abstract: Bruton's tyrosine kinase (Btk) is an important mediator in multiple signal transduction pathways. Fifteen years of research have revealed a complex role for Btk in hematopoietic cells. These studies suggest that Btk may be a promising target for therapeutic intervention for several complicated diseases. Inhibitors targeting the Btk kinase domain have been developed and show clear beneficial effects in animal models of rheumatoid arthritis, lymphoma and other diseases. Here, an overview of these studies is presented with an emphasis on results stemming from medicinal chemistry research.

Felton DA. · Department of Prosthodontics, University of North Carolina School of Dentistry, Chapel Hill, NC 27599, USA. · J Prosthodont. · Pubmed #19254297 No free full text.

Abstract: INTRODUCTION: Complete edentulism is the terminal outcome of a multifactorial process involving biological factors and patient-related factors. It continues to represent a tremendous global health care burden, and will for the foreseeable future. The purpose of this review is to determine what comorbid factors exist for the completely edentulous patient. METHODS: This literature review evaluated articles obtained via the National Library of Medicine's PubMed Website, using keywords of edentulism with various combinations of the terms comorbidity, incidence, health, nutrition, cancer, cardiovascular health, diabetes, osteoporosis, smoking, asthma, dementia, and rheumatoid arthritis. Abstracts were selected and screened, and selected full-text articles were reviewed. Articles were limited to those with adequate patient cohorts and a minimum of 2-year follow-up data. RESULTS: Edentulism was found to be a global issue, with estimates for an increasing demand for complete denture prostheses in the future. Completely edentulous patients were found to be at higher risk for poor nutrition, coronary artery plaque formation (odds ratio 2.32), to be smokers (odds ratio 2.42), to be asthmatic and edentulous in the maxillary arch (odds ratio 10.52), to being diabetic (odds ratio 1.82), to having rheumatoid arthritis (odds ratio 2.27), and to having certain cancers (odds ratios varying from 1.54 to 2.85, depending on the type of cancer). Chronic residual ridge resorption continues to be the primary intraoral complication of edentulation, and there appear to be few opportunities to reduce bone loss in the edentulous patient. CONCLUSIONS: While the completely edentulous patient seems to be at risk for multiple systemic disorders, whether development of these disorders is causal or casual has not been determined. To minimize the loss of residual alveolar ridges, exemplary complete denture therapy, along with the establishment of routine recall systems, should be the ultimate goal of treatment of this patient cohort.

Momeni M, Brindle K. · Rheumatology Division and Department of Radiology, The George Washington University, 2150 Pennsylvania Ave NW, Washington, DC 20037, USA. · Ann N Y Acad Sci. · Pubmed #19250230 No free full text.

Abstract: The superior soft tissue contrast and multiplanar capability of magnetic resonance imaging has contributed to earlier diagnosis and implementation of effective treatment for a variety of arthropathies. Owing to overlapping clinical signs and symptoms, MRI plays a role in delineating the features and stages of these conditions. With the advent of disease-modifying therapies, it is important to diagnose inflammatory arthropathy as early as possible. In this chapter, we discuss the pathophysiology of bone erosion and joint space narrowing, as well as the role of MRI in the imaging of the seropositive and seronegative inflammatory arthropathies.

Katz JD, Nayyar G. · Rheumatology Division, The George Washington University, Washington, DC, USA. · Ann N Y Acad Sci. · Pubmed #19250226 No free full text.

Abstract: In this chapter background medical information pertinent to the use of MRI and/or ultrasound in various musculoskeletal conditions is presented. Appreciation of the genetic, biochemical, histological, and immunological features of rheumatic diseases will be of benefit to the technician responsible for performing and interpreting these types of interrogations. For example, recognizing that cartilage disorder predates bone findings in osteoarthritis will help identify early versus late degenerative findings. Similarly, understanding the fibrovascular nature of rheumatoid pannus will help guide the use of more sophisticated ultrasound techniques such as power Doppler.

Birnbaum H, Shi L, Pike C, Kaufman R, Sun P, Cifaldi M. · Analysis Group, 111 Huntington Avenue, 10th Floor, MA 02199, Boston, USA. · Expert Opin Pharmacother. · Pubmed #19236197 No free full text.

Abstract: BACKGROUND: Rheumatoid arthritis (RA) causes pain and serious functional impacts and substantially affects patients' daily lives, including their ability to work. OBJECTIVE: This review examines recent studies of patients with RA treated with TNF antagonists and the impacts these therapies have on the workplace. METHODS: A total of 133 articles and 14 poster abstracts were reviewed that matched specific criteria. RESULTS/CONCLUSION: The results of early studies of TNF antagonists varied regarding their effects on patients with RA in the workplace. However, recent studies of adalimumab showed positive impacts across a range of workplace burdens. Treatments such as adalimumab may help employees with RA to remain in the workforce and lead to reduced workplace costs to the employers and employees.

Channual J, Wu JJ, Dann FJ. · School of Medicine, University of California-Irvine, Irvine, CA, USA. · Dermatol Ther. · Pubmed #19222518 No free full text.

Abstract: Psoriasis (PsO) and psoriatic arthritis (PsA) are chronic T cell-mediated inflammatory diseases that manifest not only in the skin and joints but also in the form of cardiometabolic disturbances, which include insulin resistance, dyslipidemia, and obesity. Thus, PsO and PsA patients are predisposed to metabolic syndrome (MetS), diabetes, and cardiovascular disease. In recent years, the introduction of targeted therapy in the form of tumor necrosis factor-alpha (TNF-alpha) antagonists, such as infliximab, etanercept, and adalimumab has been an important and effective addition to the treatment armamentarium for PsO and PsA. Although TNF-alpha antagonists have produced promising results clinically in reducing cutaneous and joint manifestations of PsO and PsA, their effects on MetS components in these patients are presently unclear. This review summarizes the current limited evidence on the effects of TNF-alpha antagonists on MetS components in PsO and PsA patients and extrapolates from related literature in rheumatoid arthritis, which is also a T cell-mediated inflammatory disease, for additional information.

Rozenblit M, Lebwohl M. · Mount Sinai School of Medicine, 5 E. 98th Street, New York, NY 10029-6501, USA. · Dermatol Ther. · Pubmed #19222517 No free full text.

Abstract: The prevalence of psoriasis is estimated to be 2.2% in the United States, and 6-39% of patients with psoriasis also develop psoriatic arthritis. New advances have been made in developing treatment options. A new human tumor necrosis factor (TNF)-alpha antibody, golimumab, has been shown to significantly improve symptoms of psoriatic arthritis. In addition, clinical trials of certolizumab pegol, a PEGylated Fab' fragment of an anti-TNF-alpha monoclonal antibody, show promising results for treating rheumatoid arthritis and suggest that it may be applicable for treating psoriasis and psoriatic arthritis in the future. New biologic therapies also include antibodies to interleukin-12 and interleukin-23. Phase II studies suggest that ustekinumab is effective in alleviating symptoms of psoriasis and psoriatic arthritis. However, longer studies with radiographic evaluation will be required before their impact on joint destruction can be assessed.

Vassallo R, Ryu JH. · Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. · Semin Respir Crit Care Med. · Pubmed #19221962 No free full text.

Abstract: Cigarette smoking has been associated with several diffuse lung diseases in which both bronchiolar and interstitial lung inflammation appear to result from chronic tobacco smoke inhalation. These diseases occur primarily in relatively young adult smokers and include desquamative interstitial pneumonia, respiratory bronchiolitis-associated interstitial lung disease, and pulmonary Langerhans cell histiocytosis. Although these diseases are associated with characteristic histopathologic and radiological features, there is significant overlap among these diseases, and some smokers may exhibit features indicative of the broad spectrum of smoking-related interstitial and bronchiolar lung injury patterns. Cigarette smoking has also been associated with acute eosinophilic pneumonia, and it increases the risk of developing other fibrotic interstitial lung diseases such as idiopathic pulmonary fibrosis and rheumatoid arthritis-associated interstitial lung disease. Although relatively uncommon, these smoking-related diffuse lung diseases should be recognized by clinicians as an important subset in the spectrum of interstitial lung diseases in which smoking cessation forms a central part of disease management. With the exception of acute eosinophilic pneumonia, which responds well to corticosteroid therapy, the role of corticosteroid and other immune-suppressive treatments in the management of smoking-related interstitial lung diseases is not entirely clear and is probably of limited utility, particularly in the absence of smoking cessation.

Lee BH, Tudares MA, Nguyen CQ. · Department of Oral Biology, College of Dentistry, University of Florida, PO Box 100424, Gainesville, FL 32610, USA. · Arch Immunol Ther Exp (Warsz). · Pubmed #19219532 No free full text.

Abstract: Sjögren's syndrome (SjS) is chronic autoimmune disease manifested by the loss of saliva and/or tear secretion by salivary and/or lacrimal glands, respectively. The pathogenesis of the disease remains elusive, perhaps due to the multiple triggers of the disease. However, substantial advances have been made in attempting to resolve the complexity of SjS using both animal models and human subjects. The primary objectives of this review are to provide a better understanding of the disease processes with major emphasis on the use of mouse models, how genetic predisposition plays a role in the natural history of the disease, as well as a presentation of new findings pertaining to the role of T(H)1, T(H)2, and T(H)17 cells in the pathogenesis of SjS.

Nguyen CQ, Peck AB. · Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, Florida 32610, USA. · Ocul Surf. · Pubmed #19214349 No free full text.

Abstract: Sjogren syndrome (SS) is one of the most common autoimmune diseases. Early clinical manifestations of SS are primarily decreased tear and saliva secretion, leading to dry eye and dry mouth syndromes, but in its later stages, it can become systemic, even resulting in B cell lymphomas. The use of new animal models, coupled with new technologies, is providing exciting insights into the pathogenesis, genetic predisposition, and, possibly, early diagnosis of SS. This article reviews newly described features of SS identified in experimental animal models and their relationship to human disease. New technologies, such as genomics and proteomics, may permit identification of potential candidate genes and biomarkers for disease diagnosis. Current studies using appropriate animal models in parallel with studies of human subjects are rapidly establishing a foundation for new intervention strategies that go beyond merely treating symptoms.