Venous thromboembolism in systemic autoimmune diseases: A narrative review with emphasis on primary systemic vasculitides.

Venous thromboembolism (VTE) is a prevalent multifactorial health condition associated with significant morbidity and mortality. Population-based epidemiological studies have revealed an association between systemic autoimmune diseases and deep venous thrombosis (DVT)/VTE. The etiopathogenesis of increased risk of VTE in systemic autoimmune diseases is not entirely clear but multiple contributors have been explored, especially in the context of systemic inflammation and disordered thrombogenesis. Epidemiologic data on increased risk of VTE in patients with primary systemic vasculitides (PSV) have accumulated in recent years and some of these studies suggest the increased risk while patients have active diseases. This could lead us to hypothesize that venous vascular inflammation has a role to play in this phenomenon, but this is unproven. The role of immunosuppressive agents in modulating the risk of VTE in patients with PSV is not yet clear except for Behçet's disease, where most of the studies are retrospective. Sensitizing physicians to this complication has implications for prevention and optimal management of patients with these complex diseases. This review will focus on the epidemiology and available evidence regarding pathogenesis, and will attempt to summarize the best available data regarding evaluation and treatment of these patients.

Antiphospholipid antibody-associated non-infective mitral valve endocarditis successfully treated with medical therapy.

Non-bacterial endocarditis lesions associated with antiphospholipid antibodies (aPLs) in the absence of other criteria for antiphospholipid syndrome or systemic lupus erythematosus is termed an aPL-associated cardiac valve disease. Evidence regarding the management of this condition is sparse. A rare case is described of a 20-year-old female who presented with an incidental finding of 'vegetations on a heart valve'. Echocardiography revealed mitral valve leaflet thickening and echodensities with moderate mitral regurgitation. She had an elevated partial thromboplastin time that did not correct with a mixing study, and elevated levels of antiocardiolipin antibodies. Hence, a diagnosis of aPL-associated cardiac valve disease was made, and the patient commenced on warfarin, hydroxychloroquine, and a short course of oral prednisone. At one year after diagnosis the patient remained symptom-free, and follow up echocardiography revealed resolution of the vegetations with minimal mitral regurgitation. Further evidence is needed to guide the therapy of this rare condition.

Paraneoplastic rheumatologic syndromes.

PURPOSE OF REVIEW: To describe rheumatic syndromes that can be a paraneoplastic manifestation of an underlying malignancy. The pathogenesis of paraneoplastic rheumatologic diseases is complex and not fully understood in the majority of instances. In the absence of a defined pathogenic link between the malignancy and the rheumatic syndrome, the association between these diseases has been based on concurrence and a parallel clinical course. RECENT FINDINGS: This is an updated review of paraneoplastic presentations of synovitis, bone disease, myositis, and vasculitis. SUMMARY: Although paraneoplastic rheumatic syndromes are rare, clinicians should be aware that they can be the first sign of an occult malignancy and that early recognition is vital for early cancer diagnosis and treatment.

Testicular vasculitis: findings differentiating isolated disease from systemic disease in 72 patients.

Testicular vasculitis (TV) may be part of systemic (testicular) vasculitis (STV) or may exist as single-organ/isolated (testicular) vasculitis (ITV). In the current study we sought to identify clinical and histologic features that distinguish STV from ITV. The distinction was deemed important because it is already well established that in other forms of single organ vasculitis, surgical therapy alone may be curative. We identified patients with biopsy-proven TV from pathology databases from our institution and from an English-language PubMed search. Patients were included if data were available to determine TV extent confidently. Data recorded included clinical, laboratory, and histologic features; treatment; and clinical follow-up. The study included 72 patients with TV (mean age, 42 yr; range, 4-78 yr) (7 from our institution). About 74% of patients presented with painful testicular swelling/mass, 10% with a painless testicular swelling/mass, and 4% with epididymal swelling/mass. Eleven percent had no testicular complaints and vasculitis was discovered at autopsy or in other surgical interventions. Vasculitis involved the testicle in 80.3% of cases, the epididymis in 44.6%, and the spermatic cord in 30.6%. Thirty-seven (51%) patients had ITV and 35 (49%) had STV. No differences between ITV and STV patients were found in regards to age, presenting testicular features, duration of testicular symptoms, and time of follow-up. Compared to ITV patients, STV patients presented more often with constitutional/musculoskeletal symptoms (74.3% vs. 8.3%, respectively; p = 0.0001), elevated erythrocyte sedimentation rate (94.7% vs. 16%; p = 0.0001), and anemia (50% vs. 0%; p = 0.0001). Neoplasm was more frequently suspected in ITV than in STV (74.2% vs. 31.6%; p = 0.001), but only occurred in 2 ITV patients. Long-term glucocorticoid therapy was given only to STV patients, and 59.1% of them also received cytotoxic agents. ITV was diagnosed more often by orchiectomy (81.1% vs. 42.9%; p = 0.001) and less frequently by testicular biopsy (2.7% vs. 28.6%; p = 0.003) than STV. Nongranulomatous inflammation affecting medium-sized vessels occurred in most patients with both ITV and STV. Among STV, polyarteritis nodosa was the most frequently diagnosed (63%), followed by Wegener granulomatosis (17%).In summary, TV occurs as ITV in men usually presenting with a testicular mass in the absence of systemic symptoms and normal laboratory results. In most ITV patients, a testicular neoplasm is initially suspected, and TV is an unexpected finding. After surgical removal, ITV does not require systemic therapy. Polyarteritis nodosa is the systemic vasculitis most frequently associated with testicular involvement.

Three unusual mimics of primary angiitis of the central nervous system.

To present three rare mimics of primary angiitis of the central nervous system (PACNS). We describe 3 patients with rare diseases that can mimic PACNS at clinical presentation and neuroimaging. We describe the clinical course of these patients and also present a review of the literature regarding these three diagnoses. All 3 patients presented with neurological symptoms and had abnormal findings on neuroimaging suggestive of PACNS. After detailed history, careful review of systems, thorough laboratory workup and consideration of lack of a response to immunosuppressive therapy, PACNS was ruled out with identification of an alternative diagnosis. PACNS is a rare disease and a diagnostic challenge with many differentials. A thorough investigation and awareness of unusual disorders is critical in avoiding misdiagnosis.

Left Atrial Appendage Closure in Atrial Fibrillation: A World without Anticoagulation?

Atrial Fibrillation (AF) is a common arrhythmia with an incidence that is as high as 10% in the elderly population. Given the large proportion of strokes caused by AF as well as the associated morbidity and mortality, reducing stroke burden is the most important part of AF management. While warfarin significantly reduces the risk of AF-related stroke, perceived bleeding risks and compliance limit its widespread use in the high-risk AF population. The left atrial appendage is believed to be the "culprit" for thrombogenesis in nonvalvular AF and is a new therapeutic target for stroke prevention. The purpose of this review is to explore the evolving field of percutaneous LAA occlusion. After briefly highlighting the risk of stroke with AF, problems with warfarin, and the role of the LAA in clot formation, this article discusses the feasibility and efficacy of various devices which have been developed for percutaneous LAA occlusion.

Emerging viral infections in rheumatic diseases.

OBJECTIVES: To review the current literature regarding emerging viral pathogens in the context of rheumatic diseases with the intent of increasing awareness among rheumatologists and treating physicians, aiming at early recognition and treatment of these patients. METHODS: We reviewed case reports, case series, review articles, and original reports from PubMed (www.pubmed.gov) regarding various aspects influencing spread of infectious diseases including epidemiology and viral and human factors that are potentially responsible for the emergence of new viral pathogens. By consensus, we generated a list of emerging viral pathogens pertinent regarding presentation with rheumatologic manifestations and then short-listed several with particular clinical relevance including hepatitis B, human immunodeficiency virus, and Chikungunya viruses for discussion in greater detail. RESULTS: There has been a change in the epidemiology and clinical rheumatic manifestations of previously known viral pathogens as well as the emergence of new viral pathogens as a consequence of factors such as changes in environmental temperature and its consequences, changes in vector and parasite biology, and human influences such as treatment and immunization. CONCLUSIONS: Rheumatologists need to be cognizant of the changing landscape of emerging viral pathogens as they may present with myriad clinical features. Recognition of these pathogens is important to guide correct treatment and prognosis. Given the current scenario of global epidemiologic factors that influence viral emergence, we should expect a growing number of future emerging pathogens. Ongoing research directed at understanding pathogenesis and transmission as well as developing better preventive strategies may help counter the threat posed by emerging pathogens.

Statins and the reduction of sudden cardiac death: antiarrhythmic or anti-ischemic effect?

Sudden cardiac death is an important cause of cardiovascular mortality with the majority of cases occurring in low-risk groups. HMG-CoA reductase inhibitors (statins) have recently been shown to reduce the incidence of ventricular tachycardia (VT)/fibrillation (VF) and sudden cardiac death, and this has been attributed to their pleiotropic effects. However, it is unclear whether this occurs through an 'indirect' anti-ischemic or 'direct' antiarrhythmic effect. We systematically reviewed articles published on MEDLINE between January 1996 and December 2009 focusing on the reduction of VT/VF and sudden cardiac death by statins and the potential mechanisms. Studies reporting sudden cardiac death or VT/VF outcomes with statin use (n = 23) or the pathophysiology of sudden cardiac death reduction by statins (n = 19) were included. We found that statins have been shown to reduce VT/VF and sudden cardiac death only in subjects with underlying coronary artery disease or ischemic cardiomyopathy. No definite benefits were seen with statins in sudden cardiac death and VT/VF in patients with non-ischemic cardiomyopathy. There is insufficient evidence to point toward a benefit in populations at low risk for VT/VF. In conclusion, an anti-ischemic rather than a primary antiarrhythmic effect emerges as the likely mechanism of sudden cardiac death reduction with statins.

Tumor necrosis factor inhibitors and lung disease: a paradox of efficacy and risk.

OBJECTIVE: Tumor necrosis factor inhibitors (TNFi) are being increasingly used for a wide range of indications. There are increasing reports of pulmonary toxicity related to the use of TNFi. In this review, we have attempted to synthesize the available literature regarding noninfectious complications related to TNFi use. METHODS: We reviewed case reports, case series, and clinical trials accessed from the PubMed database (www.pubmed.gov), European League Against Rheumatism web archive (http://www.abstracts2view.com/eular/index.php), and the British Society of Rheumatology Biologics Register Newsletter website (http://www.rheumatology.org.uk/publications) using 23 search terms. RESULTS: There are increasing data available about use of TNFi in treatment of systemic inflammatory rheumatologic disorders and their attempted use for various pulmonary indications. Currently reported noninfectious pulmonary complications related to TNFi use include most commonly granulomatous disease and pulmonary fibrosis/interstitial lung disease and rarely alveolar hemorrhage and antisynthetase syndrome. De novo granulomatous disease seems to be mostly reversible, whereas pulmonary fibrosis carries the worst prognosis especially in the setting of prior lung fibrosis. CONCLUSIONS: Serious and potentially fatal pulmonary toxicity has been reported during the use of TNFi, specifically from pulmonary fibrosis. Increased awareness during trial design and increased postmarketing surveillance is needed to provide more information about the epidemiology of these complications. Early recognition of these complications may help avert therapeutic misadventures.

Update on vasculitis.

The primary systemic vasculitides comprise a broad group of diseases identified by their clinical, histopathologic, and therapeutic characteristics. These unique entities have a broad spectrum of organ involvement and severity, which influences the approach to diagnosis and treatment. Immunosuppressive and cytotoxic agents are used to manage most vasculitic diseases. Long-term outcome is influenced by chronic sequelae from organ damage, disease relapses, and medication side effects. Further research is needed to understand these diseases and discover more efficacious yet less toxic therapeutic options. This review will focus on vasculitic syndromes more likely to be presented to an allergist/immunologist in an outpatient setting.

Cardiac amyloidosis treated with an implantable cardioverter defibrillator and subcutaneous array lead system: report of a case and literature review.

BACKGROUND: Preventing ventricular arrhythmias in patients with cardiac amyloidosis is challenging since the amyloid protein deposition in the myocardium may interfere with the normal cardiac electric excitation. Most of these patients succumb to either progressive congestive heart failure, or sudden cardiac death (SCD). Implantable cardioverter defibrillator (ICD) offers a near sure means of preventing SCD. HYPOTHESIS: Myocardial infiltration with amyloid results in elevated defibrillation threshold (DFT). Intra-operative strategies may fail to lower DFT during implantation. METHODS: We present a case of a 64-year-old female who had cardiac amyloidosis, and was successfully treated with an ICD and a subcutaneous array lead system. CONCLUSION: A subcutaneous array lead system is useful in reducing the DFT, and can terminate ventricular tachycardia or fibrillation by allowing more energy delivery and efficient defibrillation.

Levetiracetam for managing neurologic and psychiatric disorders.

PURPOSE: The role of levetiracetam in different epileptic, nonepileptic, neurologic, and psychiatric disorders is discussed. SUMMARY: Levetiracetam, an antiepileptic drug (AED), was first approved as an adjunctive therapy for the treatment of partial epilepsy in adults. It is currently being used in the treatment of multiple seizure disorders, including generalized tonic-clonic; absence; myoclonic, especially juvenile myoclonic; Lennox-Gastaut syndrome; and refractory epilepsy in children and adults. Data are emerging on possible uses of levetiracetam outside the realm of epilepsy because of its unique mechanisms of action. There is preliminary evidence about the efficacy of levetiracetam in the treatment of different psychiatric disorders, including anxiety, panic, stress, mood and bipolar, autism, and Tourette's syndrome. The most serious adverse effects associated with levetiracetam use are behavioral in nature and might be more common in patients with a history of psychiatric and neurobehavioral problems. CONCLUSION: Levetiracetam is an effective AED with potential benefits in other neurologic and psychiatric disorders. The benefit-risk ratio in an individual patient with a specific condition should be used to determine its optimal use. Levetiracetam's use in nonepileptic conditions is not recommended until more data become available from larger trials.

Asymptomatic wide complex tachycardia: a case report.

Wide complex tachycardias are a commonly encountered entity in coronary care units, intensive care units and emergency departments. Though, these arrhythmias are potentially fatal, they need to recognized first and treated appropriately. Associated physical signs are helpful in this. We present a case of a 54-year-old-female who recently underwent placement of an implantable cardioverter-defibrillator for cardiomyopathy and developed tachycardia.

The role of optical coherence tomography in vascular medicine.

Optical coherence tomography (OCT) is an emerging imaging modality that provides high-resolution, microstructural information on atherosclerotic plaques in biological systems. Intracoronary OCT can identify thin-cap fibroatheroma and other vulnerable plaques that may be responsible for acute coronary events. These characteristics make OCT helpful in guiding coronary management and interventions, including stent apposition and early identification of procedure-related complications. OCT is being assessed for its potential role in carotid plaque characterization and in the diagnosis of peripheral arterial atherosclerosis. Its current use in studying carotid and cerebral vasculature and in the diagnosis of peripheral arterial diseases is limited and ill defined, but it is finding increasing application in these areas. Its performance can be further improved by increasing the signal to noise ratio and by using dynamic focus tracking techniques. It can potentially be used to monitor the progression and regression of atherosclerosis in the coronary, cerebral and peripheral vasculature. New indications for its use in vascular medicine are emerging as its technology continues to improve over time.

Atrial fibrillation: a historical perspective.

Atrial fibrillation (AF) has undoubtedly become one of the most well-studied arrhythmias today in terms of pathophysiology and diagnostic and therapeutic (interventional) electrophysiology. Although it lends itself to an apparently easy diagnosis on the surface electrocardiography, myriad electromechanical mechanisms underlie its origin. We have now reached an era of technology that makes AF not only "treatable" but potentially "curable." This article aims at walking through the historical "corridors" and "mazes" that led to the present day understanding of this common yet complex arrhythmia.

Non-occlusive mesenteric ischemia leading to 'pneumatosis intestinalis': a series of unfortunate hemodynamic events.

BACKGROUND: Non-occlusive mesenteric ischemia (NOMI) is not uncommon in intensive care units. NOMI indicate ischemia of bowel wall without any significant obstruction in the mesenteric arteries. Common causes of NOMI include sepsis, severe cardiac failure, and any critical illness. Mesenteric circulation can suffer due to low cardiac output leading to very unfortunate outcomes. Pneumatosis Intestinalis is a radiologic sign which represent gas in the bowel wall, and could indicate mesenteric ischemia. CASE PRESENTATION: We present a fatal case of a patient who developed NOMI secondary to multiple factors. Patient died after a long protracted course in the hospital secondary to severe septic shock. CONCLUSION: This case emphasizes the importance of early detection and management of NOMI in a patient with low cardiac output and abdominal pain. In majority of the studies, NOMI is associated with high morbidity and mortality.

Vasculitis involving the breast: a clinical and histopathologic analysis of 34 patients.

Vasculitis of the breast (VB) may be an isolated finding or a manifestation of systemic vasculitis. In the current study we sought to characterize isolated VB (IVB) and compare it to VB in the setting of systemic vasculitis. We studied VB cases in the literature and patients cared for at our institution. We analyzed clinical, laboratory, and histologic features (including vessel size and type of inflammatory infiltrates); course of illness; biopsy procedure; and treatment. Based on the presence of localized or systemic disease at the time of disease presentation and during the follow-up, we divided patients into 3 groups: IVB (Group 1), VB with proven or indirect evidence of systemic vasculitis (Group 2), and VB with possible systemic involvement (Group 3). We identified a total of 34 cases of VB (30 from PubMed [National Library of Medicine, Bethesda, MD] and 4 from our pathology database). All patients presented with breast lesions, which were the only expression of disease in 16 (47%). Eighteen, 6, and 10 patients belonged to Group 1, 2, and 3, respectively. Constitutional symptoms were present less often in Group 1. Musculoskeletal symptoms occurred only in Groups 2 and 3. Patients in Groups 2 and 3 had higher erythrocyte sedimentation rates and lower hemoglobin levels, and also received corticosteroids more frequently than those in Group 1. No differences were found in the other analyzed parameters between groups. In summary, VB is uncommon, and in about half of the cases, occurs in the form of IVB. Histologic characteristics do not correlate with disease extent. In IVB patients, constitutional and musculoskeletal manifestations are usually absent. Such patients generally do not require systemic therapy and may be cured by resection alone.