Showing papers in "Rheumatic Diseases Clinics of North America in 2015"
TL;DR: In this review, current knowledge is discussed regarding the epidemiology of PsA, including disease manifestations, classification criteria for adult and juvenilePsA, methods for recognizing early PsA; use of screening tools and knowledge of risk factors for PsA%; and medical comorbidities associated with PsA.
Abstract: Psoriatic arthritis (PsA) is a chronic systemic inflammatory disorder characterized by joint and entheseal inflammation with a prevalence of 0.05% to 0.25% of the population and 6% to 41% of patients with psoriasis. PsA is a highly heterogeneous inflammatory arthritis. In this review, current knowledge is discussed regarding the epidemiology of PsA, including disease manifestations, classification criteria for adult and juvenile PsA, methods for recognizing early PsA, including use of screening tools and knowledge of risk factors for PsA, and medical comorbidities associated with PsA.
310 citations
TL;DR: This model is supported by results of genetic studies, pointing toward the signaling pathways of nuclear factor-κB, interferon-γ, and interleukin (IL)-23 as well as antigen presentation as central axes of the psoriatic inflammation.
Abstract: Psoriasis is a common, chronic inflammatory skin disease most often appearing in the form of well-demarcated, scaly plaques. These lesions highlight the fundamental processes underlying its pathogenesis, namely, inflammation and epidermal hyperproliferation. Both phenomena are considered consequences of an intimate interplay between the innate and the adaptive immune system. This concept is supported by results of genetic studies, pointing toward the signaling pathways of nuclear factor-κB, interferon-γ, and interleukin (IL)-23 as well as antigen presentation as central axes of the psoriatic inflammation. Efficacy of biologics targeting tumor necrosis factor-α, IL-23, or IL-17 provides further evidence in favor of this model.
137 citations
TL;DR: All health care providers caring for patients with PsA should be aware of the relevant comorbidities and should have an understanding of how these comorbbidities affect management.
Abstract: Epidemiologic studies have shown that, in patients with psoriatic arthritis (PsA), associated comorbidities may occur more frequently than expected. This article discusses related comorbidities in patients with PsA. Identifying these comorbidities may affect the management and treatment decisions for these patients to ensure an optimal clinical outcome. All health care providers caring for patients with PsA should be aware of the relevant comorbidities and should have an understanding of how these comorbidities affect management. The common comorbidities include cardiovascular disease, metabolic syndrome, obesity, diabetes, fatty liver disease, inflammatory bowel disease, ophthalmic disease, kidney disease, osteoporosis, depression, and anxiety.
103 citations
TL;DR: Systemic sclerosis occurs in susceptible individuals and is stimulated by initiating events that are poorly understood at present, and better understanding of the interplay of these factors is likely to contribute to improved treatment options.
Abstract: Systemic sclerosis is a multisystem disorder with a high associated mortality. The hallmark abnormalities of the disease are in the immune system, vasculature, and connective tissue. Systemic sclerosis occurs in susceptible individuals and is stimulated by initiating events that are poorly understood at present. In order for the disease phenotype to appear there is dysfunction in the homoeostatic mechanisms of immune tolerance, endothelial physiology, and extracellular matrix turnover. The progression of disease is not sequential but requires simultaneous dysfunction in these normal regulatory mechanisms. Better understanding of the interplay of these factors is likely to contribute to improved treatment options.
94 citations
TL;DR: There have been no large, well-controlled prospective studies investigating therapies for RA-ILD and further studies are needed to better understand pathogenic mechanisms of disease that lead to lung involvement in these patients.
Abstract: Rheumatoid arthritis (RA) affects approximately 1% of the US population frequently has extra-articular manifestations. Most compartments of the lung are susceptible to disease. Interstitial lung disease (ILD) and airways disease are the most common forms of RA-related lung disease. RA-ILD carries the worst prognosis and most often manifests in a histologic pattern of usual interstitial pneumonia or nonspecific interstitial pneumonia. There have been no large, well-controlled prospective studies investigating therapies for RA-ILD. Treatment usually entails immunomodulatory agents. Further studies are needed to better understand pathogenic mechanisms of disease that lead to lung involvement in these patients.
85 citations
TL;DR: Specific clinical and imaging features distinguish psoriatic arthritis from other forms of arthritis such as rheumatoid arthritis, gout, osteoarthritis, and other form of spondyloarth arthritis.
Abstract: Psoriatic arthritis is an inflammatory musculoskeletal disease affecting almost a third of patients with psoriasis. Clinical presentations are complex and varied and include peripheral arthritis, axial disease, dactylitis, and enthesitis, as well as skin and nail manifestations. We lack diagnostic biomarkers, but specific clinical and imaging features distinguish psoriatic arthritis from other forms of arthritis such as rheumatoid arthritis, gout, osteoarthritis, and other forms of spondyloarthritis.
81 citations
TL;DR: The diagnosis of interstitial lung disease hinges on careful clinical evaluation and pulmonary function tests and high-resolution computed tomography, and effective therapeutic options are still limited.
Abstract: Systemic sclerosis is a heterogeneous disease of unknown etiology with limited effective therapies. It is characterized by autoimmunity, vasculopathy, and fibrosis and is clinically manifested by multiorgan involvement. Interstitial lung disease is a common complication of systemic sclerosis and is associated with significant morbidity and mortality. The diagnosis of interstitial lung disease hinges on careful clinical evaluation and pulmonary function tests and high-resolution computed tomography. Effective therapeutic options are still limited. Several experimental therapies are currently in early-phase clinical trials and show promise.
75 citations
TL;DR: The pathophysiology of the gastrointestinal tract is reviewed and new mechanisms to explain gastrointestinal dysmotility are highlighted, but treatment remains symptomatic.
Abstract: The gastrointestinal tract, affecting more than 90% of patients, is the internal organ most frequently involved in systemic sclerosis. Any part of the gastrointestinal tract can be affected, from the mouth to the anus. Patients often experience reduced quality of life and impaired social life. Although only 8% have severe gastrointestinal involvement, mortality is high in those patients. Recent studies on the pathophysiology of the disease highlight new mechanisms to explain gastrointestinal dysmotility, but treatment remains symptomatic. This article reviews the pathophysiology of the gastrointestinal tract and discusses the investigation and management of the disease.
69 citations
TL;DR: The current model of psoriatic arthritis implicates both the IL-23/IL-17 axis and the tumor necrosis factor (TNF) pathways in disease pathogenesis, and an array of genes may code for an autoinflammatory loop, potentially activated by mechanical stress and dysbiosis in the skin or gut.
Abstract: The current model of psoriatic arthritis implicates both the IL-23/IL-17 axis and the tumor necrosis factor (TNF) pathways in disease pathogenesis. Although specific major histocompatibility complex class I molecules are associated with the psoriatic disease phenotype, no specific antigen or autoantibody has been identified. Instead, an array of genes may code for an autoinflammatory loop, potentially activated by mechanical stress and dysbiosis in the skin or gut. Danger signals released by innate immune cells activate a Th1 and Th17 response that leads to synovitis, enthesitis, axial inflammation, and altered bone homeostasis characterized by pathologic bone resorption and new bone formation.
63 citations
TL;DR: Small vessel vasculitis in the skin manifests with palpable purpura on the lower extremities and prompts a complete physical examination, history, and review of systems, as well as biopsies for routine processing and direct immunofluorescence to confirm the diagnosis.
Abstract: Small vessel vasculitis of the skin typically manifests with palpable purpura on the lower extremities. This clinical presentation should prompt confirmatory biopsies for standard processing, as well as direct immunofluorescence. A thorough history, review of systems, and physical examination, as well as targeted laboratory workup, are essential to identifying patients with potentially severe systemic vasculitis or underlying medical conditions. For those patients with small vessel vasculitis confined to the skin, the prognosis is excellent. Most cases resolve in about 1 month. However, an important subset of patients can develop chronic, recurrent disease, for which effective management is often difficult.
60 citations
TL;DR: Significant problems faced by patients with systemic sclerosis are summarized, including depression, anxiety, fatigue, sleep disruption, pain, pruritus, body image dissatisfaction, and sexual dysfunction.
Abstract: Patients with systemic sclerosis (SSc; also called scleroderma) have to cope with not only the physical impacts of the disease but also the emotional and social consequences of living with the condition. Because there is no cure for SSc, improving quality of life is a primary focus of treatment and an important clinical challenge. This article summarizes significant problems faced by patients with SSc, including depression, anxiety, fatigue, sleep disruption, pain, pruritus, body image dissatisfaction, and sexual dysfunction, and describes options to help patients cope with the consequences of the disease.
TL;DR: Although immunosuppression remains the mainstay of treatment, antifibrotic agents may offer new avenues of treatment for patients with SSc-ILD in the future.
Abstract: Although scleroderma-associated interstitial lung disease (SSc-ILD) is a significant contributor to both morbidity and mortality, its pathogenesis is largely unclear. Pulmonary function tests and high-resolution computed tomographic scanning continue to be the most effective tools to screen for lung involvement and to monitor for disease progression. More research and better biomarkers are needed to identify patients most at risk for developing SSc-ILD as well as to recognize which of these patients will progress to more severe disease. Although immunosuppression remains the mainstay of treatment, antifibrotic agents may offer new avenues of treatment for patients with SSc-ILD in the future.
TL;DR: Treatment strategies such as treating PsA early in the disease course, treating to target and tight control, use of background methotrexate to reduce immunogenicity, and various cost-saving strategies are all being tested with biologic medicines for PsA.
Abstract: Biologic medications, therapeutic proteins that inhibit or modulate proinflammatory immune cells and cytokines, have significantly altered clinicians' ability to effectively treat psoriatic arthritis (PsA). The first widely used biologics have been those targeting tumor necrosis factor alpha. Five agents (etanercept, infliximab, adalimumab, golimumab, and certolizumab) have shown significant benefit in all clinical domains of PsA as well as inhibiting progressive joint destruction. Treatment strategies such as treating PsA early in the disease course, treating to target and tight control, use of background methotrexate to reduce immunogenicity, and various cost-saving strategies are all being tested with biologic medicines for PsA.
TL;DR: To better understand disease susceptibility and progression requires replication in larger cohorts, fine-mapping efforts, new technologies, and functional studies of genetic variants, gene-gene interactions and gene-environmental interactions.
Abstract: There is a strong familial component to psoriatic disease as well as a complex array of genetic, immunologic, and environmental factors. The dominant genetic effect is located on chromosome 6p21.3 within the major histocompatibility complex region, accounting for one-third of genetic contribution. Genome-wide association studies (GWAS) identified additional genes, including skin barrier function, innate immune response, and adaptive immune response genes. To better understand disease susceptibility and progression requires replication in larger cohorts, fine-mapping efforts, new technologies, and functional studies of genetic variants, gene-gene interactions and gene-environmental interactions. New technologies available include next-generation sequencing, copy number variation analysis, and epigenetics.
TL;DR: Musculoskeletal (MSK) involvement in SSc occurs more frequently than expected and some of the existing composite and organ-specific indices of disease activity and/or disease severity in S Sc include MSK manifestations.
Abstract: Systemic sclerosis (SSc; scleroderma) is a chronic autoimmune connective tissue disease characterized by microvascular obliteration and sclerosis of the skin and internal organs. Although the clinical hallmark of the disease is the appearance of taut tethering of the skin, one of the earliest manifestations of SSc is a painful symmetrical arthropathy ranging from minimal arthralgia to overt polyarthritis. Musculoskeletal (MSK) involvement in SSc occurs more frequently than expected. Arthralgia is the most commonly reported manifestation. Some of the existing composite and organ-specific indices of disease activity and/or disease severity in SSc include MSK manifestations.
TL;DR: The relationship between thrombosis and inflammation as it relates to APS and systemic vasculitis is explored and the different therapeutic implications for immunosuppression or anticoagulation are explored.
Abstract: The major manifestations of antiphospholipid syndrome (APS) are caused by thrombosis within the venous or arterial vasculature, whereas the vascular lesions in systemic vasculitis result from an inflammatory infiltrate in the vessel wall. There is an association between vascular thrombosis and inflammation, however, as vasculitis can occur in APS and thromboembolic complications are seen in systemic vasculitis. Although differentiating between vasculitis and antiphospholipid-associated thrombosis can be difficult, it may be crucial to do so given the different therapeutic implications for immunosuppression or anticoagulation. This article explores the relationship between thrombosis and inflammation as it relates to APS and systemic vasculitis.
TL;DR: Pulmonary pathologies seen in rheumatoid arthritis, systemic sclerosis, myositis, systemic lupus erythematosus, Sjögren syndrome, and mixed CTD are covered.
Abstract: The pathologic correlates of interstitial lung disease (ILD) secondary to connective tissue disease (CTD) comprise a diverse group of histologic patterns. Lung biopsies in patients with CTD-associated ILD tend to demonstrate simultaneous involvement of multiple anatomic compartments of the lung. Certain histologic patterns tend to predominate in each defined CTD, and it is possible in many cases to confirm connective tissue-associated lung disease and guide patient management using surgical lung biopsy. This article will cover the pulmonary pathologies seen in rheumatoid arthritis, systemic sclerosis, myositis, systemic lupus erythematosus, Sjogren syndrome, and mixed CTD.
TL;DR: The magnitude of the problem and pathophysiology of RP are first discussed, with an emphasis on recent advances in understanding of the disease process.
Abstract: Raynaud phenomenon (RP) and associated digital ischemia can be among the most vexing clinical problems for patients with systemic sclerosis (scleroderma). Understanding the treatment approach to RP and associated ischemia and how to prevent digital ulcers is important for clinicians caring for these patients. This article reviews the management of RP and digital ischemic ulcers. The magnitude of the problem and pathophysiology of RP are first discussed, with an emphasis on recent advances in understanding of the disease process. Options for the practical pharmacologic and nonpharmacologic interventions for RP and digital ischemic ulcers are detailed.
TL;DR: The ACR/EULAR classification criteria for SSc have good sensitivity and specificity but do not substitute for diagnostic criteria.
Abstract: The American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria for the classification of systemic sclerosis (SSc) were developed to classify more patients with SSc for studies and improve on previous criteria. The new classification criteria have the following criteria: skin thickening of the fingers extending proximal to the metacarpophalangeal joints. Seven additive items are each given a numerical weight: skin thickening, fingertip lesions, telangiectasia, abnormal nail fold capillaries, lung involvement, Raynaud's phenomenon, and SSc-related autoantibodies. The ACR/EULAR classification criteria for SSc have good sensitivity and specificity but do not substitute for diagnostic criteria.
TL;DR: Hepatitis C virus is the most common cause of CryoVas and treatment with antivirals can be curative in mild cases, whereas rituximab is highly effective in treating active vasculitis in more severe cases.
Abstract: Cryoglobulins are immunoglobulins that precipitate at temperatures less than 37°C They occur secondary to infectious, autoimmune, and malignant processes In the Brouet classification, type I cryoglobulinemia is caused by hyperviscosity, whereas type II and III manifestations are caused by vasculitis in target organs (primarily skin, peripheral nerves, and kidney) New classification criteria were recently proposed that may help with study and treatment of cryoglobulinemic vasculitis (CryoVas) Hepatitis C virus is the most common cause of CryoVas and treatment with antivirals can be curative in mild cases, whereas rituximab is highly effective in treating active vasculitis in more severe cases
TL;DR: More information is needed on the impact of early diagnosis and treatment on outcome, according to phenotype, to guide policy on psoriatic arthritis.
Abstract: Although early reports suggested psoriatic arthritis was, with the exception of arthritis mutilans, a relatively mild arthritis, later studies have challenged this view. The burden of skin disease adds to disability and impaired quality of life. Patients in secondary care manifest increased morbidity and mortality, mainly owing to cardiovascular disease. A subset of patients, primarily men with oligoarticular disease, demonstrates low levels of joint involvement without disability. The socioeconomic impact of the disease is significant. We require more information on the impact of early diagnosis and treatment on outcome, according to phenotype, to guide policy.
TL;DR: An overview of the status, virtues, and limitations of imaging modalities in PsA is provided, focusing on radiography, US, and MRI.
Abstract: Psoriatic arthritis (PsA) is an inflammatory joint disease characterized by arthritis and often enthesitis in patients with psoriasis, presenting a wide range of manifestations in various patterns. Imaging procedures are primarily conventional radiography, ultrasonography (US), and magnetic resonance imaging (MRI); other modalities such as computed tomography are not used routinely. Imaging is an integral part of management of PsA. In this article, we provide an overview of the status, virtues, and limitations of imaging modalities in PsA, focusing on radiography, US, and MRI.
TL;DR: In this paper, different pulmonary manifestations seen in these three systemic rheumatologic conditions are reviewed, i.e., systemic lupus erythematosus, Sjogren syndrome, and mixed connective tissue disease.
Abstract: Interstitial lung disease is a common and often life-threatening manifestation of different connective tissue disorders, often affecting its overall prognosis. Systemic lupus erythematosus, Sjogren syndrome, and mixed connective tissue disease, although all unique diseases, can have lung manifestations as an important part of these conditions. This article reviews the different pulmonary manifestations seen in these 3 systemic rheumatologic conditions.
TL;DR: The current knowledge of genetics in SSc is discussed by exploring the observational evidence, the different genetic studies, and their modalities as well as the most relevant genes discovered by these, with an emphasis on microRNA.
Abstract: Systemic Sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and internal organs, as well as vasculopathy and immune dysregulation. SSc is a clinically heterogeneous disease and presents with 3 distinct subphenotypes, limited, diffuse and “sine” based on the severity of skin involvement. This classification also reflects internal organ involvement which can range from minimal to rapidly progressive disease resulting in premature death. Finally, SSc is characterized by the production of mutually exclusive antinuclear antibodies (ANA) subtypes that are associated with different clinical manifestations, disease phenotypes and prognosis.
SSc is a complex disease that entails abnormalities in several different pathways. Its pathogenesis is not well understood but several studies have established that SSc occurs in a genetically susceptible host presumably after encountering environmental exposures or other external triggers.1-3 Genetic studies performed so far reveal that multiple genetic loci contribute to disease susceptibility in SSc.4 The purpose of this review is to discuss the current knowledge of SSc genetics by exploring the observational evidence, the different genetic studies performed to date as well as the most relevant genes discovered by these. We will also explore the concept of gene expression variation and the recently discovered field of epigenetics.
TL;DR: The epidemiology, proposed pathogenesis, manifestations, and the most current treatment paradigms for these syndromes are reviewed.
Abstract: Cogan and Behcet syndromes are considered large vessel vasculitides. Both are rare diseases, with varied clinical manifestations affecting multiple organ systems. Although both have hallmark symptoms (ocular and vestibuloauditory inflammation in Cogan syndrome and aphthous ulcers in Behcet syndrome), neither has confirmatory diagnostic testing. Delayed diagnosis can result in poor outcomes. In both syndromes, large vessel arterial inflammation may result in severe morbidity and mortality. Treatment strategies in both syndromes vary based on organ system involvement and severity of manifestations. In this article, the epidemiology, proposed pathogenesis, manifestations, and the most current treatment paradigms for these syndromes are reviewed.
TL;DR: Scleroderma renal crisis is a rare complication of systemic sclerosis (SSc) that remains severe Prompt recognition and initiation of therapy with an angiotensin-converting-enzyme inhibitor offer the best chance to achieve a good outcome as mentioned in this paper.
Abstract: Scleroderma renal crisis is a rare complication of systemic sclerosis (SSc) that remains severe Prompt recognition and initiation of therapy with an angiotensin-converting-enzyme inhibitor offer the best chance to achieve a good outcome SSc prevalence is poorly known, with disparities among countries
TL;DR: Current therapeutic strategies consisting of glucocorticoids in conjunction with conventional or biologic agents for both induction of remission and remission maintenance are outlined and future research directions include investigation of the optimal duration and frequency of maintenance therapy and development of targeted therapeutic agents.
Abstract: This article provides an update on the diagnosis and management of the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides, granulomatosis with polyangiitis (formerly Wegener), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss). Focus is on new schemes of classification and the importance of ANCAs in the diagnosis and prognosis of these systemic vasculitides. Current therapeutic strategies consisting of glucocorticoids in conjunction with conventional or biologic agents for both induction of remission and remission maintenance are outlined. Future research directions include investigation of the optimal duration and frequency of maintenance therapy and development of targeted therapeutic agents.
TL;DR: 9 challenging vasculitis mimickers are reviewed: fibromuscular dysplasia, calciphylaxis, segmental arterial mediolysis, antiphospholipid syndrome, hypereosinophilic syndrome, lymphomatoid granulomatosis, malignant atrophic papulosis, livedoid vasculopathy, and immunoglobulin G4-related disease.
Abstract: The need to distinguish true primary systemic vasculitis from its multiple potential mimickers is one of the most challenging diagnostic conundrums in clinical medicine. This article reviews 9 challenging vasculitis mimickers: fibromuscular dysplasia, calciphylaxis, segmental arterial mediolysis, antiphospholipid syndrome, hypereosinophilic syndrome, lymphomatoid granulomatosis, malignant atrophic papulosis, livedoid vasculopathy, and immunoglobulin G4-related disease.
TL;DR: The prevention of osteoporotic hip fractures through the use of a metabolic bone evaluation in order to reduce costs, morbidity, and mortality and different types of fragility fractures are reviewed.
Abstract: Hip fractures due to osteoporosis have become a major public health concern impacting both healthcare expenditure and patient outcomes. Despite established interventions, 1 year patient mortality is approximately 25 %. A majority of patients who experience a hip fracture suffer residual functional impairments and are at greater risk of subsequent fracture. This chapter will discuss the prevention of osteoporotic hip fractures through the use of a metabolic bone evaluation in order to reduce costs, morbidity, and mortality. In addition, this chapter will also review different types of fragility fractures, which are a major consequence of osteoporosis. Both surgical and pharmacological strategies for the treatment of osteoporotic fragility fractures of both the hip and pelvis are also reviewed in this chapter. A brief introduction of the dynamics of a fracture liaison service will be provided in order to establish a logarithm for anti-osteoporotic care. Overall, this chapter will discuss osteoporosis management, fragility fracture risk factors, and interventions to treat and prevent osteoporosis-related fragility fractures.
TL;DR: The prognosis for improvement, or at least stabilization, of neurologic function is good with prompt and aggressive treatment, but the diagnosis continues to be challenging.
Abstract: Primary angiitis of the central nervous system (PACNS) is a rare disease, although it is increasingly recognized both in adults and children. Little is known about pathogenesis, but efforts at classification into subtypes are being made, and the distinction of PACNS from reversible cerebral vasoconstriction syndrome has been a major advance. The prognosis for improvement, or at least stabilization, of neurologic function is good with prompt and aggressive treatment, but the diagnosis continues to be challenging. Refinement of treatment strategies is needed. Multicenter collaboration may be crucial to make additional progress via randomized trials.