-
Annals of the Rheumatic Diseases Jan 2021Clinical heterogeneity, unpredictable course and flares are characteristics of systemic lupus erythematosus (SLE). Although SLE is-by and large-a systemic disease,... (Review)
Review
Clinical heterogeneity, unpredictable course and flares are characteristics of systemic lupus erythematosus (SLE). Although SLE is-by and large-a systemic disease, occasionally it can be organ-dominant, posing diagnostic challenges. To date, diagnosis of SLE remains clinical with a few cases being negative for serologic tests. Diagnostic criteria are not available and classification criteria are often used for diagnosis, yet with significant caveats. Newer sets of criteria (European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019) enable earlier and more accurate classification of SLE. Several disease endotypes have been recognised over the years. There is increased recognition of milder cases at presentation, but almost half of them progress overtime to more severe disease. Approximately 70% of patients follow a relapsing-remitting course, the remaining divided equally between a prolonged remission and a persistently active disease. Treatment goals include long-term patient survival, prevention of flares and organ damage, and optimisation of health-related quality of life. For organ-threatening or life-threatening SLE, treatment usually includes an initial period of high-intensity immunosuppressive therapy to control disease activity, followed by a longer period of less intensive therapy to consolidate response and prevent relapses. Management of disease-related and treatment-related comorbidities, especially infections and atherosclerosis, is of paramount importance. New disease-modifying conventional and biologic agents-used alone, in combination or sequentially-have improved rates of achieving both short-term and long-term treatment goals, including minimisation of glucocorticoid use.
Topics: Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal, Humanized; Autoantibodies; Azathioprine; Calcineurin Inhibitors; Cardiovascular Diseases; Cyclophosphamide; Disease Management; Female; Glucocorticoids; Heart Valve Diseases; Humans; Hydroxychloroquine; Hypertension, Pulmonary; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis; Lupus Vasculitis, Central Nervous System; Macrophage Activation Syndrome; Methotrexate; Mycophenolic Acid; Myocarditis; Outcome Assessment, Health Care; Pericarditis; Phenotype; Pregnancy; Pregnancy Complications; Prognosis; Purpura, Thrombocytopenic, Idiopathic; Quality of Life; Recurrence; Rituximab; Severity of Illness Index; Survival Rate; Uterine Cervical Neoplasms
PubMed: 33051219
DOI: 10.1136/annrheumdis-2020-218272 -
Blood Sep 2020The mature red blood cell (RBC) lacks a nucleus and organelles characteristic of most cells, but it is elegantly structured to perform the essential function of... (Review)
Review
The mature red blood cell (RBC) lacks a nucleus and organelles characteristic of most cells, but it is elegantly structured to perform the essential function of delivering oxygen and removing carbon dioxide from all other cells while enduring the shear stress imposed by navigating small vessels and sinusoids. Over the past several decades, the efforts of biochemists, cell and molecular biologists, and hematologists have provided an appreciation of the complexity of RBC membrane structure, while studies of the RBC membrane disorders have offered valuable insights into structure-function relationships. Within the last decade, advances in genetic testing and its increased availability have made it possible to substantially build upon this foundational knowledge. Although disorders of the RBC membrane due to altered structural organization or altered transport function are heterogeneous, they often present with common clinical findings of hemolytic anemia. However, they may require substantially different management depending on the underlying pathophysiology. Accurate diagnosis is essential to avoid emergence of complications or inappropriate interventions. We propose an algorithm for laboratory evaluation of patients presenting with symptoms and signs of hemolytic anemia with a focus on RBC membrane disorders. Here, we review the genotypic and phenotypic variability of the RBC membrane disorders in order to raise the index of suspicion and highlight the need for correct and timely diagnosis.
Topics: Anemia, Hemolytic; Blood Proteins; Body Water; Cytoskeleton; Desiccation; Erythrocyte Membrane; Erythrocytes, Abnormal; Genetic Association Studies; Humans; Ion Channels; Models, Molecular; Mutation; Protein Conformation; Structure-Activity Relationship
PubMed: 32702754
DOI: 10.1182/blood.2019000946 -
Nature Reviews. Rheumatology Sep 2017First described in the early 1980s, antiphospholipid syndrome (APS) is a unique form of acquired autoimmune thrombophilia in which patients present with clinical... (Review)
Review
First described in the early 1980s, antiphospholipid syndrome (APS) is a unique form of acquired autoimmune thrombophilia in which patients present with clinical features of recurrent thrombosis and pregnancy morbidity and persistently test positive for the presence of antiphospholipid antibodies (aPL). At least one clinical (vascular thrombosis or pregnancy morbidity) and one lab-based (positive test result for lupus anticoagulant, anticardiolipin antibodies and/or anti-β2-glycoprotein 1 antibodies) criterion have to be met for a patient to be classified as having APS. However, the clinical spectrum of APS encompasses additional manifestations that can affect many organs and cannot be explained exclusively by patients being in a prothrombotic state; clinical manifestations not listed in the classification criteria (known as extra-criteria manifestations) include neurologic manifestations (chorea, myelitis and migraine), haematologic manifestations (thrombocytopenia and haemolytic anaemia), livedo reticularis, nephropathy and valvular heart disease. Increasingly, research interest has focused on the development of novel assays that might be more specific for APS than the current aPL tests. This Review focuses on the current classification criteria for APS, presenting the role of extra-criteria manifestations and lab-based tests. Diagnostic approaches to difficult cases, including so-called seronegative APS, are also discussed.
Topics: Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Diagnostic Tests, Routine; Female; Humans; Male; Needs Assessment; Sensitivity and Specificity; Severity of Illness Index
PubMed: 28769114
DOI: 10.1038/nrrheum.2017.124 -
Virology Journal Mar 2008The morbidity and mortality associated with cytomegalovirus (CMV) infection in immunocompromised patients (especially in HIV-infected patients and transplant... (Review)
Review
BACKGROUND
The morbidity and mortality associated with cytomegalovirus (CMV) infection in immunocompromised patients (especially in HIV-infected patients and transplant recipients), as well as with congenital CMV infection are well known. In contrast, relatively little attention has been paid to the morbidity and mortality that CMV infection may cause in immunocompetent patients.
METHODS
We reviewed the evidence associated with severe manifestations of CMV infection in apparently immunocompetent patients and the potential role of antiviral treatment for these infections. We searched in PubMed, Scopus, and the Cochrane Library for the period of 1950-2007 to identify relevant articles.
RESULTS
We retrieved 89 articles reporting on severe CMV infection in 290 immunocompetent adults. Among these reports, the gastrointestinal tract (colitis) and the central nervous system (meningitis, encephalitis, transverse myelitis) were the most frequent sites of severe CMV infection. Manifestations from other organ-systems included haematological disorders (haemolytic anaemia, thrombocytopenia), thrombosis of the venous or arterial vascular system, ocular involvement (uveitis), and lung disease (pneumonitis). The clinical practice reported in the literature has been to prescribe antiviral treatment for the most severe manifestations of monophasic meningoencephalitis (seizures and coma), ocular involvement, and lung involvement due to CMV.
CONCLUSION
Severe life-threatening complications of CMV infection in immunocompetent patients may not be as rare as previously thought.
Topics: Adolescent; Adult; Aged; Central Nervous System Viral Diseases; Cytomegalovirus; Cytomegalovirus Infections; Female; Gastrointestinal Diseases; Humans; Immunocompetence; Infant; Male; Middle Aged; Pregnancy; Pregnancy Complications, Infectious; Severity of Illness Index
PubMed: 18371229
DOI: 10.1186/1743-422X-5-47 -
Blood Advances Jun 2019The terminology applied to autoimmune hemolytic anemia (AIHA) seems inconsistent. We aimed to evaluate the consistency of definitions used for diagnosis and treatment.... (Comparative Study)
Comparative Study
The terminology applied to autoimmune hemolytic anemia (AIHA) seems inconsistent. We aimed to evaluate the consistency of definitions used for diagnosis and treatment. In this systematic review of literature from January 2006 to December 2015, we assessed heterogeneity in the definition of AIHA and its subtypes, refractory disease, disease phase, severity, criteria for treatment response, and response durability. A Medline search for anemia, hemolytic, autoimmune was supplemented with keyword searches. Main exclusions were conference abstracts, animal and non-English studies, and studies with <10 cases. Of 1371 articles retrieved, 1209 were excluded based on titles and abstracts. Two authors independently reviewed 10% and 16% of abstracts and full papers, respectively. After full-paper review, 84 studies were included. AIHA was most frequently (32 [52%] of 61) defined as hemolytic anemia with positive direct antiglobulin test (DAT) and exclusion of alternatives, but 10 of 32 also recognized DAT-negative AIHA. A lower threshold for diagnosis of DAT-negative AIHA was observed in literature on chronic lymphocytic leukemia. Definitions of anemia, hemolysis, and exclusion criteria showed substantial variation. Definitions of primary/secondary cold agglutinin disease/syndrome were not consistent. Forty-three studies provided criteria for treatment response, and other than studies from 1 center, these were almost entirely unique. Other criteria were rarely defined. Only 7, 0, 3, 2, 2, and 3 studies offered definitions of warm AIHA, paroxysmal cold hemoglobinuria, mixed AIHA, AIHA severity, disease phase, and refractory AIHA, respectively. Marked heterogeneity in the time period sampled indicates the need to standardize AIHA terminology.
Topics: Anemia, Hemolytic, Autoimmune; Coombs Test; Erythrocytes; Hemoglobinuria, Paroxysmal; Hemolysis; Humans; Immunoglobulin G; Publications; Severity of Illness Index; Terminology as Topic
PubMed: 31235526
DOI: 10.1182/bloodadvances.2019000036 -
Cureus Jun 2022Eculizumab, first-line therapy for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), has infectious side effects in addition to... (Review)
Review
Eculizumab, first-line therapy for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), has infectious side effects in addition to its therapeutic benefits. This study aims to discuss the mechanism of development of infections, prevention, and timely treatment to prevent complications such as septic shock and mortality. The study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist and reporting guidelines for systematic review. Inclusion and exclusion criteria were determined. A total of 10 research papers were extracted after exploring Pubmed and Google Scholar from 2001 to 2021. The New Castle Ottawa Questionnaire for non-randomized clinical trials and the National Institutes of Health (NIH) quality assessment tool for case reports and case series were used to assess the risk of bias. The studies included in this systematic review describe infections with , , unusual species, , and . The main goal of this review is to impress upon the seriousness of the infectious complications associated with eculizumab. Health care providers should maintain a high index of suspicion for early identification and treatment.
PubMed: 35784997
DOI: 10.7759/cureus.25640 -
Cureus May 2023Drug-induced hemolytic anemia is rare and can occur either by an immune-mediated mechanism or a non-immune-mediated mechanism. The drugs most frequently associated...
Drug-induced hemolytic anemia is rare and can occur either by an immune-mediated mechanism or a non-immune-mediated mechanism. The drugs most frequently associated with immune-mediated hemolysis are penicillins and cephalosporins. It is usually difficult to distinguish drug-induced hemolysis from other more common causes of hemolysis; therefore, a high index of clinical suspicion is required to make the diagnosis. In this case report, we present a case of vancomycin-induced immune hemolytic anemia in a 75-year-old patient who developed hemolytic anemia after starting vancomycin for joint infection. Hematological parameters improved after the discontinuation of vancomycin. Mechanism and management of drug-induced immune hemolytic anemia are also reviewed in this report.
PubMed: 37216133
DOI: 10.7759/cureus.39191 -
American Family Physician Nov 2000Anemia is a common problem that is often discovered on routine laboratory tests. Its prevalence increases with age, reaching 44 percent in men older than 85 years.... (Review)
Review
Anemia is a common problem that is often discovered on routine laboratory tests. Its prevalence increases with age, reaching 44 percent in men older than 85 years. Normocytic anemia is the most frequently encountered type of anemia. Anemia of chronic disease, the most common normocytic anemia, is found in 6 percent of adult patients hospitalized by family physicians. The goals of evaluation and management are to make an accurate and efficient diagnosis, avoid unnecessary testing, correct underlying treatable causes and ameliorate symptoms when necessary. The evaluation begins with a thorough history and a careful physical examination. Basic diagnostic studies include the red blood cell distribution width, corrected reticulocyte index and peripheral blood smear; further testing is guided by the results of these studies. Treatment should be directed at correcting the underlying cause of the anemia. A recent advance in treatment is the use of recombinant human erythropoietin.
Topics: Adult; Anemia, Aplastic; Anemia, Hemolytic; Child; Chronic Disease; Erythrocytes; Female; Humans; Middle Aged; Patient Education as Topic; Teaching Materials
PubMed: 11126852
DOI: No ID Found -
Frontiers in Physiology 2015The goal here is to describe our current understanding of heme metabolism and the deleterious effects of "free" heme on immunological processes, endothelial function,... (Review)
Review
The goal here is to describe our current understanding of heme metabolism and the deleterious effects of "free" heme on immunological processes, endothelial function, systemic inflammation, and various end-organ tissues (e.g., kidney, lung, liver, etc.), with particular attention paid to the role of hemopexin (HPX). Because heme toxicity is the impetus for much of the pathology in sepsis, sickle cell disease (SCD), and other hemolytic conditions, the biological importance and clinical relevance of HPX, the predominant heme binding protein, is reinforced. A perspective on the function of HPX and haptoglobin (Hp) is presented, updating how these two proteins and their respective receptors act simultaneously to protect the body in clinical conditions that entail hemolysis and/or systemic intravascular (IVH) inflammation. Evidence from longitudinal studies in patients supports that HPX plays a Hp-independent role in genetic and non-genetic hemolytic diseases without the need for global Hp depletion. Evidence also supports that HPX has an important role in the prognosis of complex illnesses characterized predominantly by the presence of hemolysis, such as SCD, sepsis, hemolytic-uremic syndrome, and conditions involving IVH and extravascular hemolysis (EVH), such as that generated by extracorporeal circulation during cardiopulmonary bypass (CPB) and from blood transfusions. We propose that quantitating the amounts of plasma heme, HPX, Hb-Hp, heme-HPX, and heme-albumin levels in various disease states may aid in the diagnosis and treatment of the above-mentioned conditions, which is crucial to developing targeted plasma protein supplementation (i.e., "replenishment") therapies for patients with heme toxicity due to HPX depletion.
PubMed: 26175690
DOI: 10.3389/fphys.2015.00187