Ankoor Shah

Gout, Hyperuricemia, and the Risk of Cardiovascular Disease: Cause and Effect?

Gout and hyperuricemia have long been suspected to be risk factors for cardiovascular disease. However, studies have frequently failed to distinguish whether these entities have an independent effect on cardiovascular risk or serve as markers for other risk factors. In vitro and animal studies suggest that uric acid is a biologically active compound that can increase inflammatory mediators known to lead to vascular damage. In contrast, uric acid also has potentially protective effects as a strong antioxidant, approaching the potency of vitamin C. Large clinical trials demonstrate a consistent relationship between elevated serum uric acid and a variety of cardiovascular diseases, although the strength of association varies greatly. We review the evidence for and against an independent role for hyperuricemia and/or gout in cardiovascular pathology.

The Pathologic and Clinical Intersection of Atopic and Autoimmune Disease

Hypersensitivity reactions of the immune system have been broadly categorized into the atopic and autoimmune depending on whether the antigen triggering the reaction is endogenous (or self) or exogenous, the types of cellular and humoral components involved, and the clinical symptoms. Research into the pathophysiology of the resultant disease states has focused on a dichotomy between Th1 and Th2 T helper lymphocytes thought to govern autoimmune and atopic disease, respectively. Recent discoveries, however, have served to dispute this paradigm and have provided additional insight into the roles of Th17 cells, B-lymphocytes and T regulatory cells as well as the considerable communication and commonalities between the complex signaling pathways. Furthermore, clinical studies have served to challenge the idea that the presence of atopy and autoimmunity are mutually exclusive states. Finally, application of recent approaches to treatment—biologic targeted therapy in autoimmunity and induction of immune tolerance in atopic disease—to both disease states have shown mixed but promising results.

T cell large granular lymphocyte leukemia associated with rheumatoid arthritis and neutropenia

T cell large granular lymphocyte leukemia (T-LGL) is a disease characterized by clonal expansion of cytotoxic T cells (CTLs). It generally follows an indolent course and is notable for an association with chronic inflammation, neutropenia and rheumatoid arthritis (RA). We present herein a case of a patient with rheumatoid arthritis (RA), neutropenia, large granular lymphocytosis, and an expanded clonal population of peripheral blood CD3(+)CD8(+)TCRalphabeta CTLs, consistent with the diagnosis of T-LGL. T-LGL is part of a spectrum of large granular lymphocytic (LGL) disorders, which includes the more common indolent variety of this disease (as illustrated by the case herein), an aggressive but rare form of this leukemia, natural killer (NK) cell LGL leukemia, Feltys syndrome (FS), and chronic large granular lymphocytosis. T-LGL appears to be a relatively rare disease, but the true prevalence is not known. FS occurs in less than 1% of patients with RA and is typically defined by the triad of destructive arthritis, neutropenia, and variable splenomegaly. A subset of patients with FS will demonstrate polyclonal expansion of LGLs, implying a relationship between proliferation of LGLs and the mechanisms of neutropenia. Thus, T-LGL leukemia and FS with LGL expansion in the setting of RA is classically distinguished by the clonality of the CTL population, with monoclonality in T-LGL and polyclonality in FS. Despite this difference, T-LGL and FS are often similar in their clinical and biological behavior. Both may respond to immunosuppressive therapy, and pursue a smoldering course typical of a chronic inflammatory disease.

Better Medicine by Default

Background. American health care is transitioning to electronic physician ordering. These computerized systems are unique because they allow custom order interfaces. Although these systems provide great benefits, there are also potential pitfalls, as the behavioral sciences have shown that the very format of electronic interfaces can influence decision making. The current research specifically examines how defaults in electronic order templates affect physicians’ treatment decisions and medical errors. Methods. Forty-five medical residents completed order sets for 3 medical case studies. Participants were randomly assigned to receive order sets with either “opt-in” defaults (options visible but unselected) or “opt-out” defaults (options visible and preselected). Results compare error rates between conditions and examine the type and severity of errors most often made with opt-in versus opt-out defaults. Results. Opt-out defaults resulted in a greater number of items ordered and specifically increased commission errors (overordering) compared with opt-in defaults. However, while opt-in defaults resulted in fewer orders, they also increased omission errors. When the severity of the errors is taken into account, the default effects seem limited to less severe errors. Conclusion. The defaults used in electronic order sets influence medical treatment decisions when the consequences to a patient’s health are low. This pattern suggests that physicians cognitively override incorrect default choices but only to a point, and it implies tradeoffs that maximize accuracy and minimize cognitive effort. Results indicate that defaults for low-impact items on electronic templates warrant careful attention because physicians are unlikely to override them.

Size Matters - Nanotechnology and Therapeutics in Rheumatology and Immunology

Nanotechnology, or the use of technology at the submicron scale, and its application to medicine (nanomedicine) draws from many ideas and technological advancements across myriad fields of materials technology and has improved biomedical understanding. Nanotechnology puts current materials science on the same physical scale as classic immune mediating substances, including viruses, moieties found on prokaryotic bacteria, and antigen presenting cells. Functionalized nanoparticles, fullerenes, liposomes, nanogels, and virus-like particles, are several examples of nanotechnology that are currently being applied to the treatment of oncologic and infectious diseases. However, the majority of the current commercial utilization of nanomedicine has been directed towards creating improved vaccines in order to prevent infectious diseases. These processes may have direct applications toward the creation of vaccines used to treat autoimmune disease as well. Current therapeutics utilizing nanotechnology, are gaining traction in treatments for gout and rheumatoid arthritis, and experimental animal models have demonstrated success in using the above technologies to improve the effectiveness and safety of current standard treatment of rheumatologic illnesses. Here we review many of the common forms of nanoparticles used in medical applications as well as where they have found a role in rheumatology. Continued technical feasibility, ongoing safety studies, and lingering questions on cost are all issues that have not yet been resolved in regards to widespread application in rheumatology and immunology.

Review: Hematopoietic Stem Cell Transplantation for Scleroderma: Effective Immunomodulatory Therapy for Patients With Pulmonary Involvement.

As seen from both patients’ and physicians’ points of view, there is wide agreement that systemic sclerosis (SSc) is one of the autoimmune disorders with the highest morbidity and mortality rates. In this review, we will follow the evolution of a new approach to its treatment. Support for using hematopoietic stem cell transplantation (HSCT) for SSc arose from seminal studies of genetic and antigen‐induced experimental models of autoimmune disease that demonstrated that high‐dose immunosuppression followed by either allogeneic (same species) or autologous (self) bone marrow transplantation (BMT) could prevent and even reverse damage from autoimmune diseases. Three decades after these initial preclinical observations, our understanding of the therapeutic potential of immune restoration following autologous HSCT has deepened, and the clinical evidence for its application in scleroderma has broadened. In this review we will examine the outcome of conventional therapy for scleroderma lung disease; detail the techniques, toxicities, and results of HSCT for SSc; and explore the biology of immune restoration following autologous transplantation. We will compare the design and outcomes of randomized trials comparing HSCT with cyclophosphamide (CYC) treatment and formulate criteria for the timely referral of patients with scleroderma lung disease for HSCT.

Thoracic endografting in a patient with hereditary hemorrhagic telangiectasia presenting with a descending thoracic aneurysm

A 53-year-old woman with no classic risk factors for aneurysm disease presented with the sudden onset of chest pain and dyspnea. A large descending thoracic aortic aneurysm with focal type B dissection was identified and excluded by emergency thoracic endografting. Further postoperative evaluation revealed a history of epistaxis, perioral telangiectasias, hepatic hypervascularity, and a mutation in the gene expressing activin receptor-like kinase 1 (ALK1), leading to a diagnosis of hereditary hemorrhagic telangiectasia. Aortic aneurysms associated with hereditary hemorrhagic telangiectasia are extremely rare, and to our knowledge, this is the first report of thoracic endografting in this patient population.

Patient-reported outcome instruments for assessing Raynaud’s phenomenon in systemic sclerosis: A SCTC Vascular Working Group Report

The episodic nature of Raynaud’s phenomenon in systemic sclerosis has led to a reliance on patient-reported outcome instruments such as the Raynaud’s Condition Score diary. Little is known about the utilization in routine clinical practice and health professional attitudes toward existing patient-reported outcome instruments for assessing systemic sclerosis-Raynaud’s phenomenon. Members of the Scleroderma Clinical Trials Consortium Vascular Working Group (n = 28) were invited to participate in a survey gauging attitudes toward the Raynaud’s Condition Score diary and the perceived need for novel patient-reported outcome instruments for assessing patient-reported outcome. Nineteen Scleroderma Clinical Trials Consortium Vascular Working Group members (68% response rate) from academic units based in North America (n = 9), Europe (n = 8), South America (n = 1) and Australasia (n = 1) took part in the survey. There was broad consensus that Raynaud’s Condition Score diary returns could be influenced by factors including seasonal variation in weather, efforts made by patients to avoid or ameliorate attacks of Raynaud’s phenomenon, habituation to Raynaud’s phenomenon symptoms, evolution of Raynaud’s phenomenon symptom characteristics with progressive obliterative microangiopathy, patient-coping strategies, respondent burden and placebo effect. There was consensus that limitations of the Raynaud’s Condition Score diary might be a barrier to drug development (79% of respondents agree/strongly agree) and that a novel patient-reported outcome instrument for assessing systemic sclerosis-Raynaud’s phenomenon should be developed with the input of both clinicians and patients (84% agree/strongly agree). Perceived potential limitations of the Raynaud’s Condition Score diary have been identified along with concerns that such factors might impede drug development programs for systemic sclerosis-Raynaud’s phenomenon. There is support within the systemic sclerosis community for the development of a novel patient-reported outcome instrument for assessing systemic sclerosis-Raynaud’s phenomenon.

Class I and II HLA antibodies in pediatric patients with thalassemia major

HLA alloimmunization is a potential complication of red blood cell (RBC) transfusion with detrimental consequences for future organ or hematopoietic stem cell transplantation.

Atypical Cutaneous Presentations of Sarcoidosis: Two Case Reports and Review of the Literature

Purpose of ReviewThe goal of this review is to provide the reader with an updated summary of the cutaneous manifestations of systemic sarcoidosis, with a particular emphasis on the predilection of sarcoidosis for scars, tattoos, and other areas of traumatized skin.Recent FindingsWhile the mechanism underlying the propensity for traumatized skin to develop sarcoidosis lesions remains unclear, several theories have been proposed including the idea that cutaneous sarcoidosis represents an exuberant, antigen-driven foreign-body response, as well as the theory that traumatized skin represents an immunocompromised district with altered local immune trafficking and neural signaling.SummaryIn this review, we present two cases in which the development of cutaneous lesions in scars and tattoos was integral to the diagnosis of systemic sarcoidosis. We then review the various cutaneous manifestations of systemic sarcoidosis, the clinical characteristics and differential diagnosis of scar and tattoo sarcoidosis, the proposed mechanism by which traumatized skin is prone to developing sarcoidosis lesions, and current treatments for cutaneous sarcoidosis.