- StatPearls [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- Hypersensitivity reactions (HR) are immune responses that are exaggerated or inappropriate against an antigen or allergen. Coombs and Gell classified hypersensitivity reactions into four forms. Type ...
Hypersensitivity reactions (HR) are immune responses that are exaggerated or inappropriate against an antigen or allergen. Coombs and Gell classified hypersensitivity reactions into four forms. Type I, type II, and type III hypersensitivity reactions are known as immediate hypersensitivity reactions (IHR) because occur within 24 hours. Antibodies including IgE, IgM, and IgG mediate them. Type I or Anaphylactic Response Anaphylactic Responseis mediated by IgE antibodies that are produced by the immune system in response to environmental proteins (allergens) such as pollens, animal danders or dust mites. These antibodies (IgE) bind to mast cells and basophils, which contain histamine granules that are released in the reaction and cause inflammation. Type I hypersensitivity reactions can be seen in bronchial asthma, allergic rhinitis, allergic dermatitis, food allergy, allergic conjunctivitis, and anaphylactic shock. Anaphylaxis Anaphylaxis is a medical emergency because can lead to an acute, life-threatening respiratory failure. It is an IgE-mediated process. It is the most severe form of an allergic reaction, where mast cells suddenly release a large amount of histamine and later on leukotrienes. In severe cases intense bronchospasm, laryngeal edema, cyanosis, hypotension, and shock are present. Allergic bronchial asthma Allergic bronchial asthma is an atopic disease, characterized by bronchospasm. It may also be a chronic inflammatory disease. In its etiology, and environmental factors along with a genetic background play an important role. The diagnosis is dependent on history and examination. In allergic bronchial asthma, IgE is elevated, and sputum eosinophilia is common. Epidemiologically, a positive skin prick test or specific IgE are risk factors for asthma. Allergic rhinitis Allergic rhinitis is another atopic disease where histamine and leukotrienes are responsible for rhinorrhea, sneezing and nasal obstruction. Allergens are similar to those found in bronchial asthma. Nasal polyps may be seen in chronic rhinitis. Allergic conjunctivitis Allergic conjunctivitis presents with rhinitis and is IgE-mediated. Itching and eye problems including watering, redness, and swelling always occur. Food allergy One must differentiate food allergy (IgE-mediated) from food intolerance that can be cause for a variety of etiology including malabsorption and celiac disease. It is more frequent in children as seen in cow's milk allergy. Food allergy symptoms mostly affect the respiratory tract, the skin, and the gut. Skin prick tests are helpful to test for food allergens that can trigger severe reactions, e.g., peanuts, eggs, fish, and milk. Atopic eczema Atopic eczema is an IgE-mediated disease that affects the skin and has an immunopathogenesis very similar to that of allergic asthma and allergic rhinitis, which are present in more than half of the diseased. Radioallergosorbent (RAST) may reveal the specificity of the IgE antibody involved but has little help in management. Drug allergy Drugs may cause allergic reactions by any mechanism of hypersensitivity. For example, penicillin may cause anaphylaxis, which is IgE-mediated but must responses be trivial. Penicillin cross-reacts with other semisynthetic penicillins including monobactams and carbapenems and may also cross-react with other antibiotics such as cephalosporins. Type II or Cytotoxic-Mediated Response IgG and IgM mediate cytotoxic-mediated response against cell surface and extracellular matrix proteins. The immunoglobulins involved in this type of reaction damages cells by activating the complement system or by phagocytosis. Type II hypersensitivity reactions can be seen in immune thrombocytopenia, autoimmune hemolytic anemia, and autoimmune neutropenia. Immune thrombocytopenia (ITP) ITP is an autoimmune disorder that occurs at any age. Phagocytes destroy sensitized platelets in the peripheral blood. Clinically, it manifests by thrombocytopenia with shortened platelet survival and increased marrow megakaryocytes. Sudden onset of petechiae and bleeding from the gums, nose, bowel, and urinary tract occurs. Bleeding can accompany infections, drug reactions, malignancy and other autoimmune disorders such as thyroid disease and SLE. Autoimmune hemolytic anemia (AIHA) There are two types of immune hemolytic anemia: IgG-mediated (warm AIHA) and IgM-mediated (cold AIHA). The warm type may be idiopathic autoimmune or secondary to other diseases such as malignancy affecting the lymphoid tissues. The cold type may be idiopathic or secondary to infections such as Epstein-Barr virus. The primary clinical sign of the two is jaundice. The laboratory diagnosis is made by a positive Coombs test, which identifies immunoglobulins and C3 on red blood cells. Autoimmune neutropenia Autoimmune neutropenia may be present with bacterial and fungal infections, or it may occur alone or with autoimmune diseases (SLE, RA, autoimmune hepatitis), infections and lymphoma. Bone marrow examination is needed if neutropenia is severe. For associated autoimmune disorders, an autoimmune antibody panel is necessary (ANA, ENA, and dsDNA). Hemolytic disease of the fetus and the newborn (erythroblastosis fetalis) The maternal immune system suffers an initial sensitization to the fetal Rh+ red blood cells during birth, when the placenta tears away. The first child escapes disease but the mother, now sensitized, will be capable of causing a hemolytic reaction against a second Rh+ fetus, which develops anemia and jaundice once the maternal IgG crosses the placenta. Myasthenia gravis Myasthenia gravis is an autoimmune disorder caused by antibodies to post-synaptic acetylcholine receptors that interfere with the neuromuscular transmission. It is characterized by extreme muscular fatigue, double vision, bilateral ptosis, deconjugate eye movements, difficulty swallowing, and weakness in upper arms. Babies born to myasthenic mothers can have transient muscle weakness due to pathogenic IgG antibodies that cross the placenta. Goodpasture syndrome Goodpasture syndrome is a type II hypersensitivity reaction characterized by the presence of nephritis in association with lung hemorrhage. In most patients, it is caused by cross-reactive autoantigens that are present in the basement membranes of the lung and kidney. A number of patients with this problem exhibit antibodies to collagen type IV, which is an important component of basement membranes. Pemphigus Pemphigus causes a severe blistering disease that affects the skin and mucous membranes. The sera of patients with pemphigus have antibodies against desmoglein-1 and desmoglein-3, which are components of desmosomes, which form junctions between epidermal cells. Pemphigus is strongly linked to HLA-DR4 (DRB1*0402), which is a molecule that presents one of the autoantigens involved in the immunopathogenesis of this disease (desmoglein-3). Type III or Immunocomplex Reactions These are also mediated by IgM and IgG antibodies that react with soluble antigens forming antigen-antibody complexes. The complement system becomes activated and releases chemotactic agents that attract neutrophils and cause inflammation and tissue damage as seen in vasculitis and glomerulonephritis. Type III hypersensitivity reactions can classically be seen in serum sickness and Arthus reaction. Serum sickness Serum sickness can be induced with massive injections of foreign antigen. Circulating immune complexes infiltrate the blood vessel walls and tissues, causing an increased vascular permeability and leading to inflammatory processes such as vasculitis and arthritis. It was a complication of anti-serum prepared in animals to which some individuals produced antibodies to the foreign protein. It was also experienced in the treatment with antibiotics such as penicillin. Arthus reaction Arthus reaction is a local reaction seen when a small quantity of antigens is injected into the skin repeatedly until detectable levels of antibodies (IgG) are present. If the same antigen is inoculated, immune complexes develop at the mentioned local site and in the endothelium of small vessels. This reaction is characterized by the presence of marked edema and hemorrhage, depending on the administered dose of the foreign antigen.
- Clinical approach to the management of Intestinal Failure Associated Liver Disease (IFALD) in adults: A position paper from the Home Artificial Nutrition and Chronic Intestinal Failure Special Interest Group of ESPEN. [Journal Article]
- CNClin Nutr 2018 Jul 09
- We recommend that intestinal failure associated liver disease (IFALD) should be diagnosed by the presence of abnormal liver function tests and/or evidence of radiological and/or histological liver ab...
We recommend that intestinal failure associated liver disease (IFALD) should be diagnosed by the presence of abnormal liver function tests and/or evidence of radiological and/or histological liver abnormalities occurring in an individual with IF, in the absence of another primary parenchymal liver pathology (e.g. viral or autoimmune hepatitis), other hepatotoxic factors (e.g. alcohol/medication) or biliary obstruction. The presence or absence of sepsis should be noted, along with the duration of PN administration. Abnormal liver histology is not mandatory for a diagnosis of IFALD and the decision to perform a liver biopsy should be made on a case-by-case basis, but should be particularly considered in those with a persistent abnormal conjugated bilirubin in the absence of intra or extra-hepatic cholestasis on radiological imaging and/or persistent or worsening hyperbilirubinaemia despite resolution of any underlying sepsis and/or any clinical or radiological features of chronic liver disease. Nutritional approaches aimed at minimising PN overfeeding and optimising oral/enteral nutrition should be instituted to prevent and/or manage IFALD. We further recommend that the lipid administered is limited to less than 1 g/kg/day, and the prescribed omega-6/omega-3 PUFA ratio is reduced wherever possible. For patients with any evidence of progressive hepatic fibrosis or overt liver failure, combined intestinal and liver transplantation should be considered.
- Autoimmune hepatitis - primary biliary cholangitis overlap syndrome. Long-term outcomes of a retrospective cohort in a university hospital. [Journal Article]
- GHGastroenterol Hepatol 2018 Jul 12
- CONCLUSIONS: AIH-PBC overlap syndrome accounts for a significant proportion of patients with AIH, with greater progression to cirrhosis, indication of liver transplantation and possibly retransplantation. This higher risk of adverse outcomes suggests closer monitoring, probably with follow-up until confirmed histopathological remission.
- Increased Expression of Aryl Hydrocarbon Receptor in Peripheral Blood Mononuclear Cells of Patients with Autoimmune Hepatitis. [Journal Article]
- MEMiddle East J Dig Dis 2018; 10(2):105-108
- CONCLUSIONS: Th22 cells may play an important role in the pathogenesis of AIH.
- The course and delivery of a pregnancy in a patient with autoimmune hepatitis complicated by cirrhosis of the liver. [Journal Article]
- GPGinekol Pol 2018; 89(6):339-340
- Piecemeal necrosis is due to the immunologic synapse formation and internalization of intact TCR-MHC II complexes by CD4 T cells. [Journal Article]
- EMExp Mol Pathol 2018 Jul 16; 105(1):150-152
- The nature of the immunologic synapse in autoimmune hepatitis is defined. This process involves the T cell receptor (TCR) which binds to the hepatocyte antigen presenting major histocompatibility com...
The nature of the immunologic synapse in autoimmune hepatitis is defined. This process involves the T cell receptor (TCR) which binds to the hepatocyte antigen presenting major histocompatibility complex (MHC) on the plasma membrane. This complex is quickly removed from the liver cell and taken into the T cell cytoplasm to be digested by the lysosome. The liver cell is gradually diminished to the point of its total removal by the lymphocytes binding to it.
- Pathogenic role of tissue-resident memory T cells in autoimmune diseases. [Review]
- ARAutoimmun Rev 2018 Jul 10
- The tissue-resident memory T (TRM) cells constitute a newly identified subset of memory T cells which are non-circulating and they persist for long-term in epithelial barrier tissues, including skin,...
The tissue-resident memory T (TRM) cells constitute a newly identified subset of memory T cells which are non-circulating and they persist for long-term in epithelial barrier tissues, including skin, lung, gastrointestinal tract and reproductive tract, and in non-barrier tissues, including brain, kidney, pancreas and joint. These cells provide rapid on-site immune protection against previous exposed pathogens in peripheral tissues. There cells are transcriptionally, functionally and phenotypically distinguished from circulating effector memory T cells. In addition to their protective functions, increasing evidence reveals that autoreactive and/or aberrantly activated TRM cells may be involved in the pathogenesis of autoimmune disorders such as psoriasis and, as recently reported, may contribute to vitiligo, autoimmune hepatitis and rheumatoid arthritis. Therefore, this review aims to summarize the current progress in the biology of TRM cells, such as the newly identified TRM markers, upstream regulators, and the functions of TRM cells. We also discuss the contributions of TRM cells to the development of autoimmunity to broaden our understanding of autoimmune diseases and to provide novel potential therapeutic strategies for these diseases.
- Support of precision medicine through risk-stratification in autoimmune liver diseases - histology, scoring systems, and non-invasive markers. [Review]
- ARAutoimmun Rev 2018 Jul 10
- Autoimmune liver diseases (AILDs) are complex conditions, which arise from the interaction between a genetic susceptibility and unknown environmental triggers. They represent a relevant cause of live...
Autoimmune liver diseases (AILDs) are complex conditions, which arise from the interaction between a genetic susceptibility and unknown environmental triggers. They represent a relevant cause of liver failure and liver transplantation worldwide. As a testimony of our progress in understanding the biology of AILDs and the disease progression is the overall median survival which has increased over the last decade. However, there are still major challenges such as the lack of therapies and surveillance strategies in primary sclerosing cholangitis (PSC), the management and treatment of non-responders to first-line therapies in primary biliary cholangitis (PBC) and the need for tailoring immunosuppressive drugs in autoimmune hepatitis (AIH). The different disease course and treatment response in patients with AILDs might be related to a heterogeneous genetic background between individuals which translates in a heterogeneous clinical phenotype. Thus, it becomes essential to personalise management and treatment based on specific risk profiles, e.g. low-risk and high-risk, based on genetic and molecular signatures. It is now possible, thanks to the development of large-scale AILDs patient cohorts, that such diseases can be analysed using various high-throughput methods like gene expression profiling, next generation sequencing and other omics technologies to identify unique fingerprints based on which a personalised or tailor-made management and therapy can be developed. The final aim being to facilitate treatment decision-making that balances patient-specific risks and preferences. This is critical especially now with the current and forthcoming availability of more efficacious medications. To reach this point we need specific interventions such as creating bigger biobanks, sequencing more genomes and linking biological information to health-related data. We have already identified subsets of patients with different risk profiles among patients with PBC, PSC and AIH by using clinical tools such as liver histology, laboratory investigation and non-invasive methods. In this manuscript, we review the clinical features and investigations that already enable us to individualize the care of PBC patients and that might support the development of precision medicine (PM) in AILDs.
- Patients with urticaria are at a higher risk of anaphylaxis: A nationwide population-based retrospective cohort study in Taiwan. [Journal Article]
- JDJ Dermatol 2018 Jul 13
- The clinical features of urticaria and anaphylaxis are similar, and they share common causal immune-mediated pathways. We aimed to investigate the risk of anaphylaxis among patients with urticaria. A...
The clinical features of urticaria and anaphylaxis are similar, and they share common causal immune-mediated pathways. We aimed to investigate the risk of anaphylaxis among patients with urticaria. A 12-year population-based retrospective cohort study was conducted. Investigated subjects were identified from the Taiwan National Health Insurance Research Database by the International Classification of Disease, Ninth Revision, Clinical Modification. We included 126 031 subjects with newly diagnosed urticaria and 252 062 matched controls between 2000 and 2013. Risk of anaphylaxis among patients with urticaria was calculated by calculating adjusted hazards ratios (HR) after matching for confounding comorbidities. Urticaria was more common in women than it was in men (58% vs 42%), with a peak onset age of 20-40 years. The number of comorbidities including asthma, allergic rhinitis, herpes zoster, hepatitis B and C, rheumatoid arthritis and gout were higher in patients with urticaria than that in age- and sex-matched controls. The crude HR for anaphylaxis among urticaria subjects was 2.883 (95% confidence interval [CI], 2.787-2.982; P < 0.001). After adjustment for potential confounders which have been proposed to increase the risk of anaphylaxis, patients with urticaria were found to be at a significantly high risk of anaphylaxis with an adjusted HR of 2.529 (95% CI, 2.442-2.619; P < 0.001). We conclude that the incidence rate of anaphylaxis is significantly high in patients with urticaria in Taiwan.
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- Recent advances in understanding liver fibrosis: bridging basic science and individualized treatment concepts. [Review]
- FF1000Res 2018; 7
- Hepatic fibrosis is characterized by the formation and deposition of excess fibrous connective tissue, leading to progressive architectural tissue remodeling. Irrespective of the underlying noxious t...
Hepatic fibrosis is characterized by the formation and deposition of excess fibrous connective tissue, leading to progressive architectural tissue remodeling. Irrespective of the underlying noxious trigger, tissue damage induces an inflammatory response involving the local vascular system and the immune system and a systemic mobilization of endocrine and neurological mediators, ultimately leading to the activation of matrix-producing cell populations. Genetic disorders, chronic viral infection, alcohol abuse, autoimmune attacks, metabolic disorders, cholestasis, alterations in bile acid composition or concentration, venous obstruction, and parasite infections are well-established factors that predispose one to hepatic fibrosis. In addition, excess fat and other lipotoxic mediators provoking endoplasmic reticulum stress, alteration of mitochondrial function, oxidative stress, and modifications in the microbiota are associated with non-alcoholic fatty liver disease and, subsequently, the initiation and progression of hepatic fibrosis. Multidisciplinary panels of experts have developed practice guidelines, including recommendations of preferred therapeutic approaches to a specific cause of hepatic disease, stage of fibrosis, or occurring co-morbidities associated with ongoing loss of hepatic function. Here, we summarize the factors leading to liver fibrosis and the current concepts in anti-fibrotic therapies.