Cardiovascular Manifestations in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic inflammatory disorder that characteristically affects the joints. RA has extra-articular manifestations that can impact multiple organ systems including the heart, lungs, eyes, skin, and brain. Cardiovascular involvement is a leading cause of mortality in RA. Cardiovascular manifestations of RA include accelerated atherosclerosis, heart failure, pericarditis, myocarditis, endocarditis, rheumatoid nodules, and amyloidosis. Inflammation is an important mediator of endothelial dysfunction and is a key driver of cardiovascular risk and complications in patients with RA. Prompt identification of cardiac pathologies in patients with RA is essential for appropriate management and treatment. Choosing the most appropriate treatment regimen is based on individual patient factors. In this article, we provide a comprehensive review of the epidemiology, pathophysiology, clinical manifestations, diagnosis, and medical management of cardiovascular manifestations of RA. We also discuss the relationship between anti-rheumatic medications, specifically non-steroidal anti-inflammatory drugs, corticosteroids, methotrexate, statins, tumor necrosis factor inhibitors, interleukin-6 inhibitors, Janus kinase inhibitors, and cardiovascular disease.

Antiphospholipid Syndrome: Thrombotic and Vascular Complications.

Antiphospholipid syndrome is a rare, autoimmune thrombophilia defined by vascular thrombosis and pregnancy morbidity, in the setting of documented persistent antiphospholipid antibodies including the lupus anticoagulant, anticardiolipin antibodies, or anti-ß2 glycoprotein I antibodies. The presence of antiphospholipid antibodies can be completely asymptomatic, or they can lead to clinical manifestations as severe as catastrophic antiphospholipid syndrome, which involves widespread coagulopathy over a very short period of time. The degree of risk associated with antiphospholipid syndrome depends on the characteristics of the antiphospholipid antibody profile and on the presence of additional thrombotic risk factors. The current standard treatment for unprovoked thrombosis is long-term warfarin. Treatment to prevent recurrent obstetric complications is low-dose aspirin and prophylactic heparin in pregnant patients. The use of direct oral anticoagulants in patients with antiphospholipid syndrome is still being debated. Their use is generally contraindicated, especially in high-risk patients, such as those with all 3 antiphospholipid antibodies present, but they may potentially be of some use in some low-risk patients.

Dual-Energy Computed Tomography (DECT) Resolves the Diagnostic Dilemma in an Atypically Presenting Case of Gout.

Gout is a common inflammatory arthropathy that presents as acute monoarthritis, most commonly of the first metatarsophalangeal (MTP) joint. Chronic polyarticular involvement may lead to confusion with other inflammatory arthropathies, including rheumatoid arthritis (RA). A thorough history, physical examination, synovial fluid analysis, and imaging are keys to establishing a correct diagnosis. Although a synovial fluid analysis remains the gold standard, the affected joints may be difficult to access by arthrocentesis. In cases where a large monosodium urate (MSU) crystal deposition is in the soft tissues - the ligaments, bursae, and tendons, it becomes a clinical impossibility. In such cases, dual-energy computed tomography (DECT) can assist in differentiating gout from other inflammatory arthropathies, including RA. Additionally, DECT can perform quantitative analysis of tophaceous deposits and, therefore, assess response to treatment.

Hydroxychloroquine and Cardiotoxicity.

Hydroxychloroquine (HCQ) has been used for rheumatological diseases such as systemic lupus erythematous and rheumatoid arthritis and demonstrated to improve clinical symptoms and reduce long-term sequelae. The drug is metabolized in the liver, is primarily excreted through the kidney, and works by modulating major histocompatibility complex (MHC) and various cytokines, suppressing the immune system in the process. Prolonged administration and high dosages of HCQ have been associate with cardiotoxic effects such as bradycardia, tachycardia, QT prolongation, atrioventricular block, and cardiomyopathy. Common cardiac biopsy findings of HCQ-induced toxicity are enlarged and vacuolated cells on light microscopy along with the presence of myelinoid and curvilinear bodies on transmission electron microscopy. HCQ cardiotoxicity is not very well recognized, and there are no current guidelines for routine cardiac function monitoring from either rheumatology or cardiology societies.

Cardiovascular Manifestations of Systemic Sclerosis: An Overview of Pathophysiology, Screening Modalities, and Treatment Options.

Systemic sclerosis, previously known as scleroderma, is a heterogeneous, systemic disease that is defined by its 3 pathological hallmarks: the production of autoantibodies, small vessel vasculopathy, and fibroblast dysfunction, leading to an increased deposition of extracellular matrix. We conducted a review of the available literature that covers the cardiovascular manifestations of SSc: electrical conduction abnormalities, pulmonary hypertension, pericardial disease, and atherosclerosis. Within each major category, we will discuss the definition, diagnostics, and available treatment options. Increased mortality from cardiovascular complications necessitates early screening and management. Annual screening with noninvasive modalities is encouraged. The current management of each complication generally follows the management algorithms of patients regardless of SSc status and is dependent on the severity of the patient's clinical presentation.

Sarcoid Heart Disease: Review of Current Knowledge.

Sarcoidosis is a granulomatous disease with the potential of multiple organ system involvement and its etiology remains unknown. Cardiac involvement is associated with worse clinical outcome, and has been reported to be 20-30% in white and as high as 58% in Japanese populations with sarcoidosis. Clinical manifestations of cardiac sarcoidosis highly depend on the extent and location of granulomatous inflammation. The most frequent presentations include heart block, tachyarrhythmia, or heart failure. Endomyocardial biopsy is the most specific diagnostic test, but has poor sensitivity due to often patchy involvement. The diagnosis of cardiac sarcoidosis remains challenging due to nonspecific imaging findings. Both 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and cardiac magnetic resonance imaging can be used to evaluate cardiac sarcoidosis, but evaluate different stages of the disease process. FDG-PET detects metabolically active inflammatory cells while cardiac magnetic resonance imaging with late gadolinium enhancement reveals areas of myocardial necrosis and fibrosis. Aggressive therapy of symptomatic cardiac sarcoidosis is often sought due to the high risk of sudden death and/or progression to heart failure. Prednisone 20-40 mg a day is the recommended initial treatment. In refractory or severe cases, higher doses of prednisone, 1-1.5 mg/kg/d (or its equivalent) and addition of a steroid-sparing agent have been utilized. Methotrexate is added most commonly. Long-term improvement has been reported with the use of a combination of weekly methotrexate and prednisone versus prednisone alone. After initiation of treatment, a cardiac FDG-PET scan may be performed 2-3 months later to assess treatment response.

Cardiac Manifestations of Systemic Lupus Erythematous: An Overview of the Incidence, Risk Factors, Diagnostic Criteria, Pathophysiology and Treatment Options.

Systemic lupus erythematosus (SLE) is a complex connective tissue disease that can potentially affect every organ of the human body. In some cases, SLE may present with diverse cardiac manifestations including pericarditis, myocarditis, valvular disease, atherosclerosis, thrombosis, and arrhythmias. Heart disease in SLE is associated with increased morbidity and mortality. It is unclear whether traditional treatments for coronary artery disease significantly impact mortality in this population. Current therapeutic agents for SLE include glucocorticoids, hydroxychloroquine, mycophenolate mofetil, azathioprine, methotrexate, cyclophosphamide, and B cell-directed therapies. This article will provide a comprehensive review and update on this important disease state.

Cardiac Manifestations in Idiopathic Inflammatory Myopathies: An Overview.

Idiopathic inflammatory myopathies are a group of autoimmune diseases that are characterized by muscle inflammation resulting in elevated muscle enzyme release and distinctive biopsy findings. This group of conditions includes polymyositis, dermatomyositis, inclusion body myositis, and necrotizing autoimmune myopathy. Although they have many similarities, the inflammatory myopathies differ in their clinical, pathological, and treatment realms. Extramuscular manifestations may involve many organs that include the skin, joints, heart, lungs, and gastrointestinal tract. Cardiovascular involvement is one of the leading causes of mortality in polymyositis and dermatomyositis. Surveillance and prevention of cardiovascular risk factors are therefore essential. In this article, we review the epidemiology, pathophysiology, clinical manifestations, diagnosis, and management of cardiovascular complications of idiopathic inflammatory myopathies with the main focus on polymyositis and dermatomyositis.

Localized Scleroderma: A Clinical Review.

Localized scleroderma (LS) is characterized by excessive collagen deposition leading to thickening of the dermis, subcutaneous tissue or both. The outcome for most patients with localized scleroderma is directly related to the type and stage of the affected tissue. The major challenge for untreated patients is not increased mortality risk, rather deformity and growth defects from skin, muscle and bone abnormalities. Treatment is individualized to type and stage of the lesion and may include pharmacologic and non-pharmacologic therapies. Among the pharmacologic modalities, methotrexate with systemic glucocorticoids is currently the mainstay of treatment. More controlled trials are needed to determine the length of treatment and the maintenance dose of this combination therapy.

Long-Term Assessment of Fibromyalgia in Patients with Culture-Confirmed Lyme Disease.

Background: Fibromyalgia occurs in 2% to 8% of the general population. One of the triggers may be Lyme disease. Methods: Patients with culture-confirmed Lyme disease who originally presented with erythema migrans have been evaluated annually in a prospective study to determine their long-term outcome. In 2011-2013, subjects were evaluated for fibromyalgia by interview and tender point examination. Results: 100 subjects were assessed, 52% of whom were male; the mean age was 64.9 years (median 64 years, range 42-86 years). The mean duration of follow-up was 15.4 years (median 16 years, range 11-20 years). At least twenty-four (24%) subjects had experienced a second episode of erythema migrans before the evaluation for fibromyalgia. One patient (1%, 95% C.I.: 0.025 to 5.4%) met criteria for fibromyalgia. The symptoms consistent with fibromyalgia began more than 19 years after Lyme disease was diagnosed. Conclusions: Fibromyalgia was observed in only 1% of 100 patients with culture-confirmed early Lyme disease, a frequency consistent with that found for the general population. This article is protected by copyright. All rights reserved.

Hydroxychloroquine in systemic lupus erythematosus and rheumatoid arthritis and its safety in pregnancy.

INTRODUCTION: The antimalarial drug hydroxychloroquine (HCQ) is widely used to treat various rheumatic diseases. Many autoimmune diseases occur in women of child-bearing age who may become pregnant while on therapy, which raises concerns regarding the teratogenicity of HCQ and its effect on the outcome of the pregnancy. There is a lack of data regarding the safety of HCQ during pregnancy. AREAS COVERED: In this review, the authors attempt to identify relevant publications by searching MEDLINE, Cochrane database, Ovid-Currents Clinical Medicine, Ovid-Embase:Drugs and Pharmacology, EBSCO, Web of Science and SCOPUS using the search terms HCQ and/or pregnancy. A basis for the mechanism of action of HCQ is provided. EXPERT OPINION: HCQ has been shown by numerous studies over the past 15 years to be efficacious in the treatment of autoimmune diseases, including systemic lupus erythematosus, discoid lupus erythematosus and rheumatoid arthritis. HCQ does not appear to be associated with any increased risk of congenital defects, spontaneous abortions, fetal death, prematurity or decreased numbers of live births in patients with autoimmune diseases. Therefore, in the author's opinion, HCQ is safe for the treatment of autoimmune diseases during pregnancy.

Gout and hyperuricemia.

Hyperuricemia is an elevated uric acid level in blood. Gout is a common systemic metabolic disease characterized by deposition of monosodium urate monohydrate crystals with resultant acute intense inflammation of the involved joint. The clinical spectrum ranges from asymptomatic hyperuricemia to intermittent acute episodes of gouty arthritis to chronic tophaceous gout and chronic gouty arthropathy.

Systematic review of hydroxychloroquine use in pregnant patients with autoimmune diseases.

OBJECTIVE: The purpose of this study is to compare the incidence of congenital defects, spontaneous abortions, number of live births, fetal death and pre-maturity in women with autoimmune diseases taking HCQ during pregnancy. METHODS: The authors searched MEDLINE, Cochrane data base, Ovid-Currents Clinical Medicine, Ovid-Embase:Drugs and Pharmacology, EBSCO, Web of Science, and SCOPUS using the search terms HCQ and/or pregnancy. We attempted to identify all clinical trials from 1980 to 2007 regardless of language or publication status. We also searched Cochrane Central Library and http://www.Clinical trials.gov for clinical trials of HCQ and pregnancy. Data were extracted onto standardized forms and were confirmed. RESULTS: The odds ratio (OR) of congenital defects in live births of women taking HCQ during pregnancy was 0.66, 95% confidence intervals (CI) 0.25, 1.75. The OR of a live birth for women taking HCQ during pregnancy was 1.05 (95% CI 0.58, 1.93). The OR of spontaneous abortion in women taking HCQ during pregnancy was 0.92 (95% CI 0.49, 1.72). The OR of fetal deaths in women taking HCQ during pregnancy was 0.97 (95% CI 0.14, 6.54). The OR of pre-mature birth defined as birth before 37 weeks in women taking HCQ during pregnancy was 1.10 (95% CI 0.75, 1.61). CONCLUSION: HCQ is not associated with any increased risk of congenital defects, spontaneous abortions, fetal death, pre-maturity and decreased numbers of live births in patients with auto-immune diseases.

Atherosclerosis and systemic lupus erythematosus.

Large increases in mortality related to premature atherosclerosis with coronary artery disease have been reported in patients with systemic lupus erythematosus (SLE). The current pathogenic hypothesis for atherosclerosis involves not only the classic factors identified in the Framingham study, but also includes chronic inflammation, corticosteroid therapy, excess of traditional risk factors, autoantibodies, immune complexes (containing antibodies to phospholipids, to oxidized low-density lipoproteins, and to endothelial cells), and cytokine-producing activated T cells. Early risk factor intervention and effective control of inflammation should be incorporated into the management of SLE to protect against atherosclerosis.