Immune reconstitution inflammatory syndrome associated with biologic therapy.

The use of biologics in the treatment of autoimmune disease, cancer, and other immune conditions has revolutionized medical care in these areas. However, there are drawbacks to the use of these medications including increased susceptibility to opportunistic infections. One unforeseen risk once opportunistic infection has occurred with biologic use is the onset of immune reconstitution inflammatory syndrome (IRIS) upon drug withdrawal. Although originally described in human immunodeficiency virus (HIV) patients receiving highly active antiretroviral therapy, it has become clear that IRIS may occur when recovery of immune function follows opportunistic infection in the setting of previous immune compromise/suppression. In this review, we draw attention to this potential pitfall on the use of biologic drugs.

Pleural effusion, pneumothorax, and lung entrapment in rheumatoid arthritis.

Rheumatoid arthritis (RA)-associated pleural effusions are usually small and asymptomatic with no need for intervention, but complex and symptomatic rheumatoid pleural effusions may be seen and are associated with significant morbidity and mortality. Pleural effusions may develop before, concurrently with, or after the joint manifestations of RA. The classic features of RA-associated pleural effusions include high cell counts and protein, lipid, and lactate dehydrogenase levels and very low glucose levels, along with distinctive cytopathologic findings: slender spindle-shaped cells, multinucleated giant cells, eosinophilic granular debris, and the absence of mesothelial cells. Rarely, rheumatoid pleural involvement can include pneumothorax or can be severe enough to progress to lung entrapment, which may cause significant restrictive lung disease and require surgical therapy. Rheumatoid pleural involvement may not always correlate with joint activity but can be a significant cause of shortness of breath for patients with RA.

Utility of immunologic testing in suspected rheumatologic disease.

The use of diagnostic testing in the clinical practice of medicine has been a shifting landscape from the time that the first blood test was utilized. This is no different in the field of immunology and in particular rheumatology. As the field of immunology is relatively young, the clinical tests are not well established and therefore guidelines for use are still under debate. In this review, we seek to look at some of the key autoantibodies, as well as other tests that are available to diagnose suspected rheumatologic disease, and examine how to best use these tests in the clinic. In particular, we will focus on the anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies, complement, cryoglobulins, rheumatoid factor, and anti-citrullinated protein antibodies.

Immune Checkpoint Inhibitor-induced Inflammatory Arthritis: Current Approaches to Management.

The introduction of immune checkpoint inhibitors (ICIs) has changed the landscape of the treatment of cancer. Several immune-related adverse events (irAEs) have now been described such as ICI-inflammatory arthritis (IA), sicca syndrome, polymyalgia rheumatica, myositis, and vasculitis as a consequence of immune activation. The onset of the ICI-IA can vary from after the first infusion of ICIs to a delayed presentation a year or more after ICI initiation. Ultimately, baseline patient and tumor characteristics, the types of immunotherapies used, pre-existing autoimmune diseases, and/or other irAEs, as well as patient preferences will all shape the discussions around ICI-IA management.

Pulmonary hypertension in rheumatic diseases: epidemiology and pathogenesis.

The focus of this review is to increase awareness of pulmonary arterial hypertension (PAH) in patients with rheumatic diseases. Epidemiology and pathogenesis of PAH in rheumatic diseases is reviewed, with recommendations for early screening and diagnosis and suggestion of possible role of immunosuppressive therapy in treatment for PAH in rheumatic diseases. A MEDLINE search for articles published between January 1970 and June 2012 was conducted using the following keywords: pulmonary hypertension, scleroderma, systemic sclerosis, pulmonary arterial hypertension, connective tissues disease, systemic lupus erythematosus, mixed connective tissue disease, rheumatoid arthritis, Sjogren's syndrome, vasculitis, sarcoidosis, inflammatory myopathies, dermatomyositis, ankylosing spondylitis, spondyloarthropathies, diagnosis and treatment. Pathogenesis and disease burden of PAH in rheumatic diseases was highlighted, with emphasis on early consideration and workup of PAH. Screening recommendations and treatment were touched upon. PAH is most commonly seen in systemic sclerosis and may be seen in isolation or in association with interstitial lung disease. Several pathophysiologic processes have been identified including an obliterative vasculopathy, veno-occlusive disease, formation of microthrombi and pulmonary fibrosis. PAH in systemic lupus erythematosus is associated with higher prevalence of antiphospholipid and anticardiolipin antibodies and the presence of Raynaud's phenomenon. Endothelial proliferation with vascular remodeling, abnormal coagulation with thrombus formation and immune-mediated vasculopathy are the postulated mechanisms. Improvement with immunosuppressive medications has been reported. Pulmonary fibrosis, extrinsic compression of pulmonary arteries and granulomatous vasculitis have been reported in patients with sarcoidosis. Intimal and medial hyperplasia with luminal narrowing has been observed in Sjogren's syndrome, mixed connective tissue disease and inflammatory myopathies. Pulmonary arterial hypertension (PAH) associated with rheumatic diseases carries a particularly grim prognosis with faster progression of disease and poor response to therapy. Though largely associated with systemic sclerosis, it is being increasingly recognized in other rheumatic diseases. An underlying inflammatory component may explain the poor response to therapy in patients with rheumatic diseases and is a rationale for consideration of immunosuppressive therapy in conjunction with vasodilator therapy in treatment for PAH. Further studies identifying pathogenetic pathways and possible targets of therapy, especially the role of immunomodulatory medications, are warranted.

Diffuse alveolar hemorrhage and Libman-Sacks endocarditis as a manifestation of possible primary antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of circulating autoantibodies against phospholipid-binding plasma proteins, leading to an increased risk of thrombosis and pregnancy loss. The most common manifestation of lung disease in APS is pulmonary embolism, which may often be the presenting symptom. We present a 30-year-old man with probable primary APS (with no history of thromboses) presenting with diffuse alveolar hemorrhage, an uncommon presentation. He was also found to have severe mitral valve regurgitation and during valve replacement surgery had cardiac vegetations compatible with a presentation of Libman-Sacks endocarditis. There are only 21 other reported cases of diffuse alveolar hemorrhage occurring as a result of APS. This is the first case of Libman-Sacks endocarditis in the setting of probable APS and alveolar hemorrhage.Diffuse alveolar hemorrhage should be considered as a nonthrombotic manifestation of APS, even in the absence of known thromboses, and may be the presenting symptom.

Do bugs control our fate? The influence of the microbiome on autoimmunity.

Autoimmune disease has traditionally been thought to be due to the impact of environmental factors on genetically susceptible individuals causing immune dysregulation and loss of tolerance. However, recent literature has highlighted the importance of the microbiome, (a collective genome of microorganisms in a given niche) in immune homeostasis. Increasingly, it has been recognized that disruptions in the commensal microflora may lead to immune dysfunction and autoimmunity. This review summarizes recent studies investigating the interplay between the microbiome and immune-mediated organ-specific diseases. In particular, we review new findings on the role of the microbiome in inflammatory bowel disease, celiac disease, psoriasis, rheumatoid arthritis, type I diabetes, and multiple sclerosis.

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.

The epidemiology of Sjögren's syndrome.

Sjögren's syndrome is a chronic systemic autoimmune disease characterized by lymphocytic infiltration of exocrine glands. It can present as an entity by itself, primary Sjögren's syndrome (pSS), or in addition to another autoimmune disease, secondary Sjögren's syndrome (sSS). pSS has a strong female propensity and is more prevalent in Caucasian women, with the mean age of onset usually in the 4th to 5th decade. Clinical presentation varies from mild symptoms, such as classic sicca symptoms of dry eyes and dry mouth, keratoconjunctivitis sicca, and xerostomia, to severe systemic symptoms, involving multiple organ systems. Furthermore, a range of autoantibodies can be present in Sjögren's syndrome (anti-SSA/Ro and anti-SSB/La antibodies, rheumatoid factor, cryoglobulins, antinuclear antibodies), complicating the presentation. The heterogeneity of signs and symptoms has led to the development of multiple classification criteria. However, there is no accepted universal classification criterion for the diagnosis of Sjögren's syndrome. There are a limited number of studies that have been published on the epidemiology of Sjögren's syndrome, and the incidence and prevalence of the disease varies according to the classification criteria used. The data is further confounded by selection bias and misclassification bias, making it difficult for interpretation. The aim of this review is to understand the reported incidence and prevalence on pSS and sSS, the frequency of autoantibodies, and the risk of malignancy, which has been associated with pSS, taking into account the different classification criteria used.

Interstitial lung disease in systemic sclerosis: pathophysiology, current and new advances in therapy.

Systemic sclerosis is an autoimmune connective tissue disorder characterized by fibrosis of the skin and visceral organs. Interstitial lung disease (ILD) is a major complication of this disease and along with pulmonary arterial hypertension is the leading cause of mortality in scleroderma patients. The pathogenesis of pulmonary fibrosis is characterized by epithelial cell injury, activation of the coagulation pathway and inflammation, which create a profibrogenic environment in the lung in the setting of autoimmunity. The current standard of treatment for ILD in systemic sclerosis is cyclophosphamide. In view of the modest benefits in pulmonary function seen with cyclophosphamide in two recent trials and its significant toxicity, the search for alternative treatments is ongoing. With the advances in our understanding of the pathogenic mechanisms of pulmonary fibrosis, many promising therapeutic agents have come into view, but their efficacy needs to be evaluated before they can be recommended clinically. This review discusses the pathogenesis of pulmonary fibrosis with a focus on the potential target pathways, the current treatment options and recent advances in the treatment of ILD in systemic sclerosis.

Compliance and fixed-dose combination therapy.

Despite data on the importance of blood pressure control in preventing cardiovascular and cerebrovascular events, only 34% of hypertensive patients have their blood pressure under control. The National Council on Patient Information and Education has estimated that the compliance rate is just over 30% for chronic conditions like hypertension. Polypharmacy and complex treatment regimens have been identified as important, modifiable risk factors for medication noncompliance. Fixed-dose combination regimens are attractive options because of the improved antihypertensive efficacy resulting from the dual mechanistic action of components targeting different effector mechanisms. One drug in the fixed-dose combination may negate an adverse effect of the other medication. Above all, fixed-dose combination therapy reduces pill burden and improves medication compliance, which can translate into better cardiovascular outcomes. Fixed-dose combinations should be used routinely for the management of hypertension and should also be considered when initiating therapy for patients with newly diagnosed hypertension.