Sabeeda Kadavath

Life-threatening complications of adult-onset Still's disease.

Adult-onset Still’s Disease (AOSD) since its description in 1971 has proven to be a very complex and challenging disease entity. This rare auto-inflammatory disease is classically described by the “Still’s triad” of fever, rash, and arthritis, although the atypical cases frequently outnumber the typical ones. The exact pathogenesis and etiologic factors responsible for the clinical features remain largely obscure, despite recent suggestive cytokine biology findings. Diagnosis is made on clinical grounds, following the exclusion of mimickers of infectious, autoimmune or neoplastic etiology, with the additional consideration of non-specific laboratory abnormalities such as peripheral leukocytosis and elevation of serum ferritin and other acute phase reactants. The disease manifestations are protean and can include diverse complications, affecting multiple organ systems. Moreover, the severity of the organ involvement can vary considerably, representing a wide spectrum from the self-limited to severe. The mainstay of therapy has evolved from the traditional use of corticosteroids and oral immunosupressants to the newer targeted treatments with biologic agents. The scope of this review is to alert the clinician to the existence of life-threatening AOSD complications, namely the macrophage activation syndrome, disseminated intravascular coagulopathy, thrombotic thrombocytopenic purpura, diffuse alveolar hemorrhage, and pulmonary arterial hypertension. Such knowledge may lead in earlier recognition, prompt treatment, and, ideally, improved patient outcomes.

Adult-onset Still's disease—pathogenesis, clinical manifestations, and new treatment options

Abstract Adult-onset Stills disease (AOSD), a systemic inflammatory disorder, is often considered a part of the spectrum of the better-known systemic-onset juvenile idiopathic arthritis, with later age onset. The diagnosis is primarily clinical and necessitates the exclusion of a wide range of mimicking disorders. AOSD is a heterogeneous entity, usually presenting with high fever, arthralgia, skin rash, lymphadenopathy, and hepatosplenomegaly accompanied by systemic manifestations. The diagnosis is clinical and empirical, where patients are required to meet inclusion and exclusion criteria with negative immunoserological results. There are no clear-cut diagnostic radiological or laboratory signs. Complications of AOSD include transient pulmonary hypertension, macrophage activation syndrome, diffuse alveolar hemorrhage, thrombotic thrombocytopenic purpura and amyloidosis. Common laboratory abnormalities include neutrophilic leukocytosis, abnormal liver function tests, and elevated acute-phase reactants (ESR, CRP, ferritin). Treatment consists of anti-inflammatory medications. Non-steroidal anti-inflammatory drugs have limited efficacy, and corticosteroid therapy and disease-modifying anti-rheumatic drugs are usually required. Recent advances have revealed a pivotal role of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-6, IL-8, and IL-18 in disease pathogenesis, giving rise to the development of novel targeted therapies aiming at optimal disease control. The review aims to summarize recent advances in pathophysiology and potential therapeutic strategies in AOSD.

A novel therapeutic approach in pulmonary arterial hypertension as a complication of adult-onset Still's disease: targeting IL-6

Adult‐onset Stills Disease (AOSD), often though as the adult variant of systemic juvenile idiopathic arthritis (JIA), has an incidence of 1–3 cases per 1 million. Cardinal manifestations include fever, arthritis, skin rash, sore throat, hepatosplenomegaly and lymphadenopathy. Prolongation in diagnosing this disease results from its similarity to infectious, malignant and rheumatic diseases and lack of biomarkers. Pulmonary arterial hypertension (PAH) is a rare pulmonary complication of AOSD, and we are aware of only six cases reported in literature to date. Here we present a patient with AOSD who has developed pulmonary hypertension as a complication. We report a case of AOSD complicated by PAH treated successfully with tocilizumab, a humanized monoclonal antibody to human interleukin (IL)‐6 receptor. A Pubmed and Medline search for evidence of pulmonary hypertension in AOSD and use of IL‐6 inhibition in management was performed. Data for this study was collected from the patients chart records. No infectious or neoplastic cause of her disease was identified and after extensive diagnostic workup, the patient was diagnosed with AOSD fulfilling Yamaguchi criteria. After initiation of IL‐6 therapy the patient was followed over time to monitor the hemodynamic changes in pulmonary vasculature. Following treatment with Tocilizumab, the patient showed dramatic improvement in her clinical symptoms and remains in remission, through combination of tocilizumab (8 mg/kg), methotrexate and prednisone. Improvement of systemic symptoms, right heart catheterization (RHC) findings and the VECTRA‐DA score served as a measure of treatment response. Tocilizumab has been effective in demonstrating marked improvement in both the clinical and laboratory parameters. Tocilizumab is an effective novel treatment for AOSD with PAH. This is the first documented report of successful use of tocilizumab in AOSD patients presenting with PAH. Prospective comparative studies could help validate its efficacy and safety.

Can traumatic injury trigger psoriatic arthritis? A review of the literature

Traumatic injury as a trigger for the subsequent development of psoriatic arthritis (PsA) has been implicated by several case reports and case series. However, it is still unclear whether trauma is the inciting event or just an incidental finding. It is thought that the interplay of genetic, immunologic, and environmental factors, such as trauma, may trigger the development of PsA. At least two hypotheses of how trauma may be linked to the development of PsA have surfaced and involve a “deep Koebner effect,” the concept of a synovio-entheseal complex and activation of the innate immune system by biomechanical factors. The role of neuropeptides such as substance P and vasoactive intestinal peptide has been highlighted in the synovium after trauma. Better understanding of this phenomenon would shed light into the pathophysiology of Psa and help the development of preventive and therapeutic strategies.

Prognostic impact of atrial fibrillation on clinical outcomes of acute coronary syndromes, heart failure and chronic kidney disease

Atrial fibrillation (AF) is the most common type of sustained arrhythmia, which is now on course to reach epidemic proportions in the elderly population. AF is a commonly encountered comorbidity in patients with cardiac and major non-cardiac diseases. Morbidity and mortality associated with AF makes it a major healthcare burden. The objective of our article is to determine the prognostic impact of AF on acute coronary syndromes, heart failure and chronic kidney disease. Multiple studies have been conducted to determine if AF has an independent role in the overall mortality of such patients. Our review suggests that AF has an independent adverse prognostic impact on the clinical outcomes of acute coronary syndromes, heart failure and chronic kidney disease.

Impact of atrial fibrillation on outcomes with motor vehicle accidents

BACKGROUND We examined the effect of AF a commonly encountered arrhythmia with significant morbidity on mortality following a motor vehicle accident (MVA) related hospitalization. METHODS The Nationwide Inpatient Sample (NIS) was queried to identify patients with AF (ICD-9 CM 427.31) and MVA (ICD-9 CM E810.0-E819.9), considered separately and together, from 2003 through 2012. Baseline characteristics were identified and multilevel mixed model multivariate analysis was employed to verify the impact of AF on in-patient mortality in survivors. RESULTS Of an estimated 2,978,630 MVA admissions reported, 79,687 (2.6%) hospitalizations also had a diagnosis of AF. The in-hospital mortality was 2.6% in MVA alone and 7.6% in MVA and AF. In multivariate analysis, after adjustment for age, gender, Charlson Comorbidity Index (CCI), the Trauma Mortality Prediction Model (TMPM), and hospital characteristics, AF was independently associated with in-hospital mortality [Odds ratio (OR) 1.52, confidence interval (CI) 1.41-1.69, P value<0.0001]. In patients with MVA and AF, increasing age, CCI, and TMPM were associated with higher mortality. Female gender is associated with lower mortality (OR 0.84, CI 0.81-0.88, P -0.0016). Most patients with MVA and AF had a CHADS2 score of 2 (34.6%). Mortality and transfusion rates were higher in MVA and AF patients compared to patients with MVA alone across all CHADS2 scores. CONCLUSION In patients with a MVA, the presence of AF is an independent risk factor for in-hospital mortality.

Clinical Application of Fractional Flow Reserve-Guided Percutaneous Coronary Intervention for Stable Coronary Artery Disease.

Revascularization in stable ischemic heart disease (SIHD) is indicated in patients on optimal medical therapy with angina and/or demonstrable ischemia and a significant stenosis in one or more epicardial coronary arteries. Angiography alone, however, cannot accurately determine the hemodynamic significance of coronary lesions, particularly those of intermediate stenosis severity. A lesion may appear significant on coronary angiogram but may not have functional significance. Percutaneous coronary intervention (PCI) of functionally insignificant coronary artery lesions may have serious consequences; therefore, judicious decision-making in the cardiac catheterization laboratory is indicated. For this reason, it is becoming increasingly important to show that a stenosis is capable to induce myocardial ischemia prior to intervention. Fractional flow reserve (FFR) has emerged as a useful tool for this purpose. In this review, we will briefly discuss the principle of FFR, current evidence and rationale supporting its use, and comparison with other modalities.

Use of B lymphocyte stimulator inhibitor belimumab may be associated with a decrease in the serum concentration of epidermal growth factor in patients with primary Sjögren’s syndrome

B cell activating factor (BAFF), also called the B lymphocyte stimulator, has been known to show increased expression in primary Sjögren’s syndrome (pSS) which could explain increased B cell activation characteristic of this disease. Belimumab, a fully human IgG1λ recombinant monoclonal antibody directed against B lymphocyte stimulator (Blys), has been reported to be efficacious in systemic lupus erythematosus (SLE) through its B cell-mediated action. Randomized controlled trials of belimumab in a selected target population of pSS patients are further warranted.

Canakinumab in autoimmune and autoinflammatory rheumatic diseases

Introduction: Novel biologic agents targeting interleukin-1 (IL-1) have been recently utilized in rheumatic diseases where only limited therapeutic options exist, particularly the autoinflammatory syndromes. Canakinumab, a recombinant fully humanized IL-1β long-acting monoclonal antibody has been recently approved for clinical use in several indications and is being studied in others. Areas covered: Various studies have evaluated the efficacy and safety of this drug in cryopyrin-associated periodic syndrome (CAPS), systemic juvenile idiopathic arthritis (sJIA) and gout. Moreover, several case series of promising efficacy in orphan autoinflammatory diseases have recently emerged in the literature. Expert opinion: The pathophysiological role of IL-1β inhibition in rheumatic diseases and the role of this novel pharmacological agent in therapeutic intervention need to be studied further. The pivotal role of IL-1 in the pathogenesis of auto-inflammatory diseases and the emerging importance of IL-1b inhibition for the treatment of a wide-spectrum of diseases has the potential to reshape the therapeutic landscape.