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.

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.

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.

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.

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.

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.

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.

Atrial fibrillation: a historical perspective.

Atrial fibrillation (AF) undoubtedly has 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 a surface ECG, myriad electromechanical mechanisms underlie its origin. An era of technology has been reached that makes AF not only "treatable" but also potentially "curable." This article aims at walking through the historical corridors and maze that have led to the present-day understanding of this most common yet complex arrhythmia.

Recurrent syncope following radiation therapy.

This case report describes a 51-year-old man who presented with syncope. His electrocardiogram showed an abnormally long pause and the electrophysiology study revealed a prolonged H-V interval. This was attributed to the radiation therapy he received to the chest. He was successfully treated with implantation of a permanent pacemaker. This case highlights this rare complication of radiation-induced conduction system disease and management of this potentially life-threatening condition.

Global warming and infectious disease.

Global warming has serious implications for all aspects of human life, including infectious diseases. The effect of global warming depends on the complex interaction between the human host population and the causative infectious agent. From the human standpoint, changes in the environment may trigger human migration, causing disease patterns to shift. Crop failures and famine may reduce host resistance to infections. Disease transmission may be enhanced through the scarcity and contamination of potable water sources. Importantly, significant economic and political stresses may damage the existing public health infrastructure, leaving mankind poorly prepared for unexpected epidemics. Global warming will certainly affect the abundance and distribution of disease vectors. Altitudes that are currently too cool to sustain vectors will become more conducive to them. Some vector populations may expand into new geographic areas, whereas others may disappear. Malaria, dengue, plague, and viruses causing encephalitic syndromes are among the many vector-borne diseases likely to be affected. Some models suggest that vector-borne diseases will become more common as the earth warms, although caution is needed in interpreting these predictions. Clearly, global warming will cause changes in the epidemiology of infectious diseases. The ability of mankind to react or adapt is dependent upon the magnitude and speed of the change. The outcome will also depend on our ability to recognize epidemics early, to contain them effectively, to provide appropriate treatment, and to commit resources to prevention and research.

3-dimensional mapping and radiofrequency ablation of atrial flutter in a patient with interrupted inferior vena cava.

The presence of isolated interrupted inferior vena cava (IVC) is very rare. Though the occurrence of typical atrial flutter in this setting has recently been described, the use of 3-dimensional activation mapping to aid the management of such patients has not yet been described. We report the successful ablation of this arrhythmia in a 63-year-old woman using the superior route through the internal jugular vein with the help of a mapping system.

Implantable cardioverter defibrillator therapy in patients with ischemic or non-ischemic cardiomyopathy and nonsustained ventricular tachycardia.

BACKGROUND: Mortality benefit from implantable cardioverter defibrillator (ICD) therapy in ischemic cardiomyopathy (ICM) with non-sustained ventricular tachycardia (NS-VT) and inducible VT is well defined. Although NS-VT may suggest an increased risk of sudden cardiac death (SCD) in non-ischemic cardiomyopathy (NICM), the role of ICD therapy is unclear. This retrospective study compares follow-up data in these two groups after ICD implantation. METHODS: 153 consecutive patients with ICD implantation for NS-VT were analyzed. ICM patients received an ICD if they had inducible VT at electrophysiology study (EPS). NICM patients did not routinely undergo EPS before ICD implantation. RESULTS: There were 48 patients (33 males) in NICM group and 105 patients (89 males) in the ICM group. Baseline characteristics including mean ejection fraction (EF), distribution in various New York Heart Association (NYHA) classes, and the mean duration of follow up in the two groups were similar. 50% of the patients in the NICM group and 36% in the ICM group received appropriate therapies (p = 0.106). The mean number of appropriate therapies in the two groups were similar (23.3 +/- 56.7 and 22.5 +/- 59.5 respectively, p = NS). The percentage of patients with inappropriate therapies in the two groups were 27% and 23% respectively (p = NS). Patients in the NICM group received appropriate ICD discharges at a greater rate (p = 0.02). CONCLUSION: Patients undergoing ICD implantation for NICM and NS-VT receive appropriate ICD therapy at a greater rate than those implanted for ICM, NS-VT, and a positive EPS. Although these data do not prove survival benefit in NICM, they suggest a beneficial effect.

Does device-based testing save time during automatic implantable cardioverter-defibrillator implantation?

BACKGROUND: Defibrillation testing can be done either via an external cardiac defibrillator or directly via the implanted defibrillator during implantation (device-based testing). The advantage of one testing methodology over the other has not been adequately studied. METHODS AND RESULTS: Seventy-four patients (72% men) were randomized into two groups depending on the defibrillation testing methodology used--external cardiac defibrillation and device-based testing groups. R-wave, pacing threshold, pacing impedance, defibrillation threshold, defibrillation pathway impedance and total procedure time were not significantly different between the two groups. CONCLUSIONS: Device-based testing did not significantly reduce the procedure time. Lead and defibrillation parameters were similar in both the groups; lead repositioning and replacement were required in three patients in the external cardiac defibrillation group.

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.

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.