NSAID Hypersensitivity Reactions
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NSAID Hypersensitivity Reactions
NSAID or nonsteroidal anti-inflammatory drug hypersensitivity reactions encompasses a broad range of allergic or allergic-like symptoms that occur within minutes to hours after ingesting aspirin or other NSAID nonsteroidal anti-inflammatory drugs. Hypersensitivity drug reactions differ from drug toxicity reactions in that drug toxicity reactions result from the pharmacological action of a drug, are dose-related, and can occur in any treated individual (see nonsteroidal anti-inflammatory drugs section on adverse reactions for NSAID-induced toxic reactions); hypersensitivity reactions are idiosyncratic reactions to a drug. Although the term NSAID was introduced to signal a comparatively low risk of adverse effects, NSAIDs do evoke a broad range of hypersensitivity syndromes. These syndromes have recently been classified by the European Academy of Allergy and Clinical Immunology Task Force on NSAIDs Hypersensitivity. __TOC__ Classification The classification organizes the hypersensi ...
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Nonsteroidal Anti-inflammatory Drugs
Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of use, but largely include an increased risk of gastrointestinal ulcers and bleeds, heart attack, and kidney disease. The term ''non-steroidal'', common from around 1960, distinguishes these drugs from corticosteroids, which during the 1950s had acquired a bad reputation due to overuse and side-effect problems after their initial introduction in 1948. NSAIDs work by inhibiting the activity of cyclooxygenase enzymes (the COX-1 and COX-2 isoenzymes). In cells, these enzymes are involved in the synthesis of key biological mediators, namely prostaglandins, which are involved in inflammation, and thromboxanes, which are involved in blood clotting. There are two general types of NSAIDs available: non-selective, and COX-2 selective. Most NSAI ...
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Lipoxin A4
A lipoxin (LX or Lx), an acronym for lipoxygenase interaction product, is a bioactive autacoid metabolite of arachidonic acid made by various cell types. They are categorized as nonclassic eicosanoids and members of the specialized pro-resolving mediators (SPMs) family of polyunsaturated fatty acid (PUFA) metabolites. Like other SPMs, LXs form during, and then act to resolve, inflammatory responses. Initially, two lipoxins were identified, lipoxin A4 (LXA4) and LXB4, but more recent studies have identified epimers of these two LXs: the epi-lipoxins, 15-epi-LXA4 and 15-epi-LXB4 respectively. History LXA4 and LXB4 were first described by Serhan, Hamberg, and the Nobel laurate Samuelsson in 1984. They reported that human blood neutrophils, when stimulated, make these two lipoxins and that neutrophils, when stimulated by either of the LXs, mounted superoxide anion (O2−) generation and degranulation responses. Both responses are considered to be pro-inflammatory in that, while ...
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Maculopapular Rash
A maculopapular rash is a type of rash characterized by a flat, red area on the skin that is covered with small confluent bumps. It may only appear red in lighter-skinned people. The term "maculopapular" is a compound: ''macules'' are small, flat discolored spots on the surface of the skin; and ''papules'' are small, raised bumps. It is also described as erythematous, or red. This type of rash is common in several diseases and medical conditions, including scarlet fever, measles, Ebola virus disease, rubella, secondary syphilis (Congenital syphilis, which is asymptomatic, the newborn may present this type of rash), erythrovirus ( parvovirus B19), chikungunya (alphavirus), zika, smallpox (which has been eradicated), varicella (when vaccinated persons exhibit symptoms from the modified form), heat rash, and sometimes in Dengue fever. It is also a common manifestation of a skin reaction to the antibiotic amoxicillin or chemotherapy drugs. Cutaneous infiltration of leukemic cells may ...
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Allergy
Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermatitis, allergic asthma, and anaphylaxis. Symptoms may include red eyes, an itchy rash, sneezing, coughing, a runny nose, shortness of breath, or swelling. Note: food intolerances and food poisoning are separate conditions. Common allergens include pollen and certain foods. Metals and other substances may also cause such problems. Food, insect stings, and medications are common causes of severe reactions. Their development is due to both genetic and environmental factors. The underlying mechanism involves immunoglobulin E antibodies (IgE), part of the body's immune system, binding to an allergen and then to a receptor on mast cells or basophils where it triggers the release of inflammatory chemicals such as histamine. Diagnosis is ty ...
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Anaphylaxis
Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the following: an itchy rash, throat closing due to swelling which can obstruct or stop breathing; severe tongue swelling which can also interfere with or stop breathing; shortness of breath, vomiting, lightheadedness, loss of consciousness, low blood pressure, and medical shock. These symptoms typically start in minutes to hours and then increase very rapidly to life-threatening levels. Urgent medical treatment is required to prevent serious harm or death, even if the patient has used an epipen or has taken other medications in response, and even if symptoms appear to be improving. Common causes include allergies to insect bites and stings, allergies to foods – including nuts, milk, fish, shellfish, eggs and some fresh fruits or dried fruits; a ...
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Urticarial
Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasting skin change. Fewer than 5% of cases last for more than six weeks. The condition frequently recurs. Hives frequently occur following an infection or as a result of an allergic reaction such as to medication, insect bites, or food. Psychological stress, cold temperature, or vibration may also be a trigger. In half of cases the cause remains unknown. Risk factors include having conditions such as hay fever or asthma. Diagnosis is typically based on the appearance. Patch testing may be useful to determine the allergy. Prevention is by avoiding whatever it is that causes the condition. Treatment is typically with antihistamines such as diphenhydramine and cetirizine. In severe cases, corticosteroids or leukotriene inhibitors may also b ...
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Interleukin-5
Interleukin 5 (IL5) is an interleukin produced by type-2 T helper cells and mast cells. Function Through binding to the interleukin-5 receptor, interleukin 5 stimulates B cell growth and increases immunoglobulin secretion - primarily IgA. It is also a key mediator in eosinophil activation. Structure IL-5 is a 115-amino acid (in human, 133 in the mouse) -long TH2 cytokine that is part of the hematopoietic family. Unlike other members of this cytokine family (namely interleukin 3 and GM-CSF), this glycoprotein in its active form is a homodimer. Tissue expression The IL-5 gene is located on chromosome 11 in the mouse, and chromosome 5 in humans, in close proximity to the genes encoding IL-3, IL-4, and granulocyte-macrophage colony-stimulating factor (GM-CSF), which are often co-expressed in TH2 cells. Interleukin-5 is also expressed by eosinophils and has been observed in the mast cells of asthmatic airways by immunohistochemistry. IL-5 expression is regulated by seve ...
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RANTES
Chemokine (C-C motif) ligand 5 (also CCL5) is a protein which in humans is encoded by the ''CCL5'' gene. The gene has been discovered in 1990 by ''in situ'' hybridisation and it is localised on 17q11.2-q12 chromosome. It is also known as RANTES (regulated on activation, normal T cell expressed and secreted). RANTES was first described by Dr. Tom Schall who named the protein, the original source of the name Rantes was from the Argentine movie ''Man Facing Southeast'' about an alien who shows up in a mental ward who was named Rantés, the rather clunky acronym was only made to fit the name. Function CCL5 belongs to the CC subfamily of chemokines, due to its adjacent cysteines near N terminus. It is an 8kDa protein acting as a classical chemotactic cytokine or chemokine. It consists of 68 amino acids. CCL5 is proinflammatory chemokine, recruiting leukocytes to the site of inflammation. It is chemotactic for T cells, eosinophils, and basophils, but also for monocytes, natural-ki ...
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Eotaxin-1
C-C motif chemokine 11 also known as eosinophil chemotactic protein and eotaxin-1 is a protein that in humans is encoded by the CCL11 gene. This gene is encoded on three exons and is located on chromosome 17. Function CCL11 is a small cytokine belonging to the CC chemokine family. CCL11 selectively recruits eosinophils by inducing their chemotaxis, and therefore, is implicated in allergic responses. The effects of CCL11 are mediated by its binding to a G-protein-linked receptor known as a chemokine receptor. Chemokine receptors for which CCL11 is a ligand include CCR2, CCR3 and CCR5. However, it has been found that eotaxin-1 (CCL11) has high degree selectivity for its receptor, such that they are inactive on neutrophils and monocytes, which do not express CCR3. Clinical significance Increased CCL11 levels in blood plasma are associated with aging in mice and humans. Additionally, it has been demonstrated that exposing young mice to CCL11 or the blood plasma of older mice ...
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Chemokines
Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addition to playing a major role in the activation of host immune responses, chemokines are important for biological processes, including morphogenesis and wound healing, as well as in the pathogenesis of diseases like cancers. Cytokine proteins are classified as chemokines according to behavior and structural characteristics. In addition to being known for mediating chemotaxis, chemokines are all approximately 8-10 kilodaltons in mass and have four cysteine residues in conserved locations that are key to forming their 3-dimensional shape. These proteins have historically been known under several other names including the ''SIS family of cytokines'', ''SIG family of cytokines'', ''SCY family of cytokines'', ''Platelet factor-4 superfamily'' or '' ...
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Urticaria
Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasting skin change. Fewer than 5% of cases last for more than six weeks. The condition frequently recurs. Hives frequently occur following an infection or as a result of an allergic reaction such as to medication, insect bites, or food. Psychological stress, cold temperature, or vibration may also be a trigger. In half of cases the cause remains unknown. Risk factors include having conditions such as hay fever or asthma. Diagnosis is typically based on the appearance. Patch testing may be useful to determine the allergy. Prevention is by avoiding whatever it is that causes the condition. Treatment is typically with antihistamines such as diphenhydramine and cetirizine. In severe cases, corticosteroids or leukotriene inhibitors may also be ...
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Angioedema
Angioedema is an area of swelling ( edema) of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs. Often it is associated with hives, which are swelling within the upper skin. Onset is typically over minutes to hours. The underlying mechanism typically involves histamine or bradykinin. The version related to histamine is due to an allergic reaction to agents such as insect bites, foods, or medications. The version related to bradykinin may occur due to an inherited problem known as C1 esterase inhibitor deficiency, medications known as angiotensin-converting enzyme inhibitors, or a lymphoproliferative disorder. Treatment to protect the airway may include intubation or cricothyroidotomy. Histamine-related angioedema can be treated with antihistamines, corticosteroids, and epinephrine. In those with bradykinin-related disease a C1 esterase inhibitor, ecallantide, or icati ...
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