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The Journal of Investigative Dermatology Jul 1978Basophilic leukocytes constitute a significant proportion of the cellular infiltrates in many forms of delayed-in-onset hypersensitivity reactions in human beings,... (Review)
Review
Basophilic leukocytes constitute a significant proportion of the cellular infiltrates in many forms of delayed-in-onset hypersensitivity reactions in human beings, guinea pigs, and other animals. In this paper, I review current information on the role of basophils in the reactions, and present similarities and differences between Jones-Mote and classic delayed hypersensitivities.
Topics: Animals; Antigen-Antibody Reactions; Basophils; Guinea Pigs; Humans; Hypersensitivity, Delayed; Skin; Skin Tests
PubMed: 355569
DOI: 10.1111/1523-1747.ep12544415 -
British Journal of Clinical Pharmacology May 2011Drug-induced hypersensitivity reactions can cause a variety of serious diseases by involving drug-specific T-cells. Many of these reactions have been explained by the... (Review)
Review
Drug-induced hypersensitivity reactions can cause a variety of serious diseases by involving drug-specific T-cells. Many of these reactions have been explained by the hapten concept, which postulates that small chemical compounds need to bind covalently to proteins to be recognized by the immune system. Due to their chemical reactivity, haptens stimulate the innate immunity by binding covalently to endogenous proteins and form so called hapten-carrier complexes, which are antigenic and induce T-cell responses. In recent years, a new concept has been developed since drug-induced hypersensitivity reactions were also observed with chemically unreactive drugs. This concept implies direct and reversible interactions of the drug between T-cell receptors (TCR) and major histocompatability complex (MHC) molecules. Therefore it was termed pharmacological interactions with immune receptors (p-i concept). Early observations on drug reacting T-cell clones (TCC) let believe that drugs bind first to the T-cell receptor since HLA molecules could be exchanged without affecting the drug reactivity. However, MHC molecules were always required for full activation of TCC. According to its strong HLA-B*5701 association, recent data on abacavir suggest that a drug could first bind to the peptide binding groove of the MHC molecule. The thereby modified HLA molecule can then be recognized by specific T-cells. Consequently, two types of reactions based on the p-i mechanism may occur: on the one hand, drugs might preferentially bind directly to the TCR, whereas in defined cases with strong HLA association, drugs might bind directly to the MHC molecule.
Topics: Drug Hypersensitivity; Genetic Predisposition to Disease; Haptens; Humans; Hypersensitivity, Delayed; Lymphocyte Activation; Major Histocompatibility Complex; T-Lymphocytes
PubMed: 21480949
DOI: 10.1111/j.1365-2125.2010.03764.x -
Journal of Investigative Medicine High... 2022Many pediatric rheumatic diseases can be safely managed with biologic therapy. Severe allergic reactions to these medications are uncommon. We report the case of a...
Many pediatric rheumatic diseases can be safely managed with biologic therapy. Severe allergic reactions to these medications are uncommon. We report the case of a 2-year-old male with systemic-onset juvenile idiopathic arthritis and secondary macrophage activation syndrome (MAS), whose treatment was complicated by severe allergic reactions to biologics, including drug reaction with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity reaction (DIHR) likely due to anakinra, and anaphylactoid reaction to intravenous tocilizumab. These required transition to canakinumab, cyclosporine, and corticosteroids, with later development of interstitial lung disease and MAS flare needing transition from canakinumab to tofacitinib, which led to disease control. Whether lung disease is a manifestation of DRESS/DIHR to canakinumab remains unclear. High index of suspicion of hypersensitivity reactions for timely diagnosis and drug discontinuation is critical, especially in patients with active disease who might be at increased risk of these adverse events.
Topics: Antirheumatic Agents; Arthritis, Juvenile; Biological Products; Child, Preschool; Humans; Hypersensitivity; Hypersensitivity, Delayed; Macrophage Activation Syndrome; Male
PubMed: 35225032
DOI: 10.1177/23247096221077836 -
Military Medical Research Mar 2023
Topics: Humans; Tuberculin Test; Tuberculin; Hypersensitivity; Gene Expression; Hypersensitivity, Delayed
PubMed: 36922897
DOI: 10.1186/s40779-023-00450-2 -
Theranostics 2021Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are important regulators of inflammation. The exact impact of ROS/RNS on cutaneous delayed-type...
Immunomodulatory role of reactive oxygen species and nitrogen species during T cell-driven neutrophil-enriched acute and chronic cutaneous delayed-type hypersensitivity reactions.
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are important regulators of inflammation. The exact impact of ROS/RNS on cutaneous delayed-type hypersensitivity reaction (DTHR) is controversial. The aim of our study was to identify the dominant sources of ROS/RNS during acute and chronic trinitrochlorobenzene (TNCB)-induced cutaneous DTHR in mice with differently impaired ROS/RNS production. TNCB-sensitized wild-type, NADPH oxidase 2 (NOX2)- deficient (gp91), myeloperoxidase-deficient (MPO), and inducible nitric oxide synthase-deficient (iNOS) mice were challenged with TNCB on the right ear once to elicit acute DTHR and repetitively up to five times to induce chronic DTHR. We measured ear swelling responses and noninvasively assessed ROS/RNS production by employing the chemiluminescence optical imaging (OI) probe L-012. Additionally, we conducted extensive analyses of inflamed ears focusing on ROS/RNS production and the biochemical and morphological consequences. The L-012 OI of acute and chronic DTHR revealed completely abrogated ROS/RNS production in the ears of gp91 mice, up to 90 % decreased ROS/RNS production in the ears of MPO mice and unaffected ROS/RNS production in the ears of iNOS mice. The DHR flow cytometry analysis of leukocytes derived from the ears with acute DTHR confirmed our L-012 OI results. Nevertheless, we observed no significant differences in the ear swelling responses among all the experimental groups. The histopathological analysis of the ears of gp91 mice with acute DTHRs revealed slightly enhanced inflammation. In contrast, we observed a moderately reduced inflammatory immune response in the ears of gp91 mice with chronic DTHR, while the inflamed ears of MPO mice exhibited the strongest inflammation. Analyses of lipid peroxidation, 8-hydroxy-2'deoxyguanosine levels, redox related metabolites and genomic expression of antioxidant proteins revealed similar oxidative stress in all experimental groups. Furthermore, inflamed ears of wild-type and gp91 mice displayed neutrophil extracellular trap (NET) formation exclusively in acute but not chronic DTHR. MPO and NOX2 are the dominant sources of ROS/RNS in acute and chronic DTHR. Nevertheless, depletion of one primary source of ROS/RNS exhibited only marginal but conflicting impact on acute and chronic cutaneous DTHR. Thus, ROS/RNS are not a single entity, and each species has different properties at certain stages of the disease, resulting in different outcomes.
Topics: Acute Disease; Animals; Chronic Disease; Dermatitis, Allergic Contact; Female; Hypersensitivity, Delayed; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils; Nitric Oxide Synthase Type II; Peroxidase; Reactive Nitrogen Species; Reactive Oxygen Species; T-Lymphocytes
PubMed: 33391487
DOI: 10.7150/thno.51462 -
European Annals of Allergy and Clinical... Nov 2015Recent studies have demonstrated a low cross-reactivity between β-lactam antibiotics and carbapenems in IgE-mediated reactions. There are no studies on cross-reactivity...
Recent studies have demonstrated a low cross-reactivity between β-lactam antibiotics and carbapenems in IgE-mediated reactions. There are no studies on cross-reactivity of meropenem in patients with non-immediate hypersensitivity to cephalosporins. We describe a case of a 13-year-old male, admitted in Neurosurgery with a severe extradural empyema complicating frontal sinusitis, submitted to an emergent bifrontal craniotomy. A generalized maculopapular exanthema, fever and malaise, appeared by the 7th day of meningeal doses of ceftriaxone, clindamycin and vancomycin. Those were replaced by meropenem, with posterior worsening of the reaction and mucosal involvement. A new scheme with amikacin, metronidazole and linezolid was done with improvement. Skin prick, intradermal and patch tests to penicillins, ceftriaxone and meropenem were negative. Lymphocyte transformation test was positive to ceftriaxone and negative to meropenem.Non-immediate T cell mechanism seems to be involved. Diagnosis work-up couldn't exclude cross-reactivity between ceftriaxone and meropenem.
Topics: Adolescent; Anti-Bacterial Agents; Antibody Specificity; Ceftriaxone; Cross Reactions; Drug Hypersensitivity; Drug Substitution; Humans; Hypersensitivity, Delayed; Immunoglobulin E; Intradermal Tests; Lymphocyte Activation; Male; Meropenem; Predictive Value of Tests; Risk Factors; Thienamycins
PubMed: 26549341
DOI: No ID Found -
Ugeskrift For Laeger Sep 2018Local anaesthetics (LA) are frequently used, but allergy to LA is very rare. It can only be verified in about 1% of the patients referred with suspected allergy.... (Review)
Review
Local anaesthetics (LA) are frequently used, but allergy to LA is very rare. It can only be verified in about 1% of the patients referred with suspected allergy. Reactions may be due to vasovagal or toxic reactions, allergies to additives or other products used during administration. Suspicion of allergy should be investigated to rule out or confirm allergy. In case of allergy to LA, search of a safe alternative ensures the patients future ability to receive LA treatment. The investigation method depends on, whether a type I- or type IV reaction is suspected.
Topics: Algorithms; Anesthetics, Local; Drug Hypersensitivity; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate
PubMed: 30274575
DOI: No ID Found -
European Annals of Allergy and Clinical... Jan 2019The current therapy with direct trombin inhibitors (DTI) is indicated for the prevention of stroke in non-valvular atrial fibrillation. Side effects are reported,...
Delayed hypersensitivity to new oral anticoagulants. Demonstration of cross reactivity for the drug category and definition of non-irritant concentrations for patch tests.
The current therapy with direct trombin inhibitors (DTI) is indicated for the prevention of stroke in non-valvular atrial fibrillation. Side effects are reported, particularly skin hypersensitivity, for this whole category of drugs as well as for other modern antiplatelet and anticoagulant drugs. For their clinical features, these reactions appear as delayed T-cell mediated drug hypersensitivity, but at present there are no diagnostic methods of investigation. We reported a case of delayed skin reaction to edoxaban and we found the non-irritant concentration for patch test in the whole category of drugs. The patch test resulted positive for edoxaban. A successive challenge with alternative DTIs and/or a switch to warfarin is proposed as alternative therapy.
Topics: Aged; Anticoagulants; Cross Reactions; Drug Hypersensitivity; Factor Xa Inhibitors; Female; Humans; Hypersensitivity, Delayed; Patch Tests; Pyridines; Thiazoles
PubMed: 30066999
DOI: 10.23822/EurAnnACI.1764-1489.71 -
The Journal of Allergy and Clinical... Oct 2020Delayed immune-mediated adverse drug reactions (IM-ADRs) are defined as reactions occurring more than 6 hours after dosing. They include heterogeneous clinical...
Delayed immune-mediated adverse drug reactions (IM-ADRs) are defined as reactions occurring more than 6 hours after dosing. They include heterogeneous clinical phenotypes that are typically T-cell-mediated reactions with distinct mechanisms across a wide spectrum of severity from benign exanthems through to life-threatening cutaneous or organ-specific diseases. For mild reactions such as benign exanthem, considerations for delabeling are similar to immediate reactions and may include a graded or single-dose drug challenge with or without preceding skin or patch testing. Evaluation of challenging cases such as the patient who is on multiple drugs at the time a severe delayed IM-ADR occurs should prioritize clinical ascertainment of the most likely phenotype and implicated drug(s). Although not widely available and validated, procedures such as patch testing, delayed intradermal skin testing, and laboratory-based functional drug assays or genetic (human leukocyte antigen) testing may provide valuable information to further help risk stratify patients and identify the likely implicated and/or cross-reactive drug(s). The decision to use a drug challenge as a diagnostic or delabeling tool in a patient with a severe delayed IM-ADR should weigh the risk-benefit ratio, balancing the severity and priority for the treatment of the underlying, and the availability of alternative efficacious and safe treatments.
Topics: Drug Hypersensitivity; Humans; Hypersensitivity, Delayed; Intradermal Tests; Skin; Skin Tests; T-Lymphocytes
PubMed: 33039012
DOI: 10.1016/j.jaip.2020.07.005 -
Skin Resident Memory T Cells May Play Critical Role in Delayed-Type Drug Hypersensitivity Reactions.Frontiers in Immunology 2021Delayed-type drug hypersensitivity reactions (dtDHR) are immune-mediated reactions with skin and visceral manifestations ranging from mild to severe. Clinical care is... (Review)
Review
Delayed-type drug hypersensitivity reactions (dtDHR) are immune-mediated reactions with skin and visceral manifestations ranging from mild to severe. Clinical care is negatively impacted by a limited understanding of disease pathogenesis. Though T cells are believed to orchestrate disease, the type of T cell and the location and mechanism of T cell activation remain unknown. Resident memory T cells (T) are a unique T cell population potentially well situated to act as key mediators in disease pathogenesis, but significant obstacles to defining, identifying, and testing T in dtDHR preclude definitive conclusions at this time. Deeper mechanistic interrogation to address these unanswered questions is necessary, as involvement of T in disease has significant implications for prediction, diagnosis, and treatment of disease.
Topics: Animals; Disease Susceptibility; Drug Hypersensitivity; Humans; Hypersensitivity, Delayed; Immunologic Memory; Lymphocyte Activation; Skin; T-Lymphocyte Subsets; T-Lymphocytes
PubMed: 34497600
DOI: 10.3389/fimmu.2021.654190