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American Journal of Physiology. Cell... Nov 2023Sarcoidosis is a complex inflammatory fibrotic disease that affects multiple organ systems. It is characterized by the infiltration of lymphocytes and mononuclear... (Review)
Review
Sarcoidosis is a complex inflammatory fibrotic disease that affects multiple organ systems. It is characterized by the infiltration of lymphocytes and mononuclear phagocytes, which form non-caseating granulomas in affected organs. The lungs and intrathoracic lymph nodes are the most commonly affected organs. The underlying cause of sarcoidosis is unknown, but it is believed to occur in genetically predisposed individuals who are exposed to pathogenic organisms, environmental contaminants, or self and non-self-antigens. Recent research has suggested that the microbiome may play a role in the development of respiratory conditions, including sarcoidosis. Additionally, metabolomic studies have identified potential biomarkers for monitoring sarcoidosis progression. This review will focus on recent microbiome and metabolomic findings in sarcoidosis, with the goal of shedding light on the pathogenesis and possible diagnostic and therapeutic approaches.
Topics: Humans; Sarcoidosis; Lung
PubMed: 37746695
DOI: 10.1152/ajpcell.00316.2023 -
Journal of Investigational Allergology... 2020The European Medicines Agency (EMA) defines excipients as the constituents of a pharmaceutical form apart from the active substance. Delayed hypersensitivity reactions... (Review)
Review
The European Medicines Agency (EMA) defines excipients as the constituents of a pharmaceutical form apart from the active substance. Delayed hypersensitivity reactions (DHRs) caused by excipients contained in the formulation of medications have been described. However, there are no data on the prevalence of DHRs due to drug excipients. Clinical manifestations of allergy to excipients can range from skin disorders to life-threatening systemic reactions. The aim of this study was to perform a literature review on allergy to pharmaceutical excipients and to record the DHRs described with various types of medications, specifically due to the excipients contained in their formulations. The cases reported were sorted alphabetically by type of medication and excipient, in order to obtain a list of the excipients most frequently involved for each type of medication.
Topics: Disease Management; Disease Susceptibility; Drug Compounding; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Excipients; Humans; Hypersensitivity, Delayed; Pharmaceutical Preparations
PubMed: 32376520
DOI: 10.18176/jiaci.0562 -
International Journal of Molecular... Jul 2021In accordance with the development of human technology, various medications have been speedily developed in the current decade. While they have beneficial impact on... (Review)
Review
In accordance with the development of human technology, various medications have been speedily developed in the current decade. While they have beneficial impact on various diseases, these medications accidentally cause adverse reactions, especially drug eruption. This delayed hypersensitivity reaction in the skin sometimes causes a life-threatening adverse reaction, namely Stevens-Johnson syndrome and toxic epidermal necrolysis. Therefore, how to identify these clinical courses in early time points is a critical issue. To improve this problem, various biomarkers have been found for these severe cutaneous adverse reactions through recent research. Granulysin, Fas ligands, perforin, and granzyme B are recognized as useful biomarkers to evaluate the early onset of Stevens-Johnson syndrome and toxic epidermal necrolysis, and other biomarkers, such as miRNAs, high mobility group box 1 protein (HMGB1), and S100A2, which are also helpful to identify the severe cutaneous adverse reactions. Because these tools have been currently well developed, updates of the knowledge in this field are necessary for clinicians. In this review, we focused on the detailed biomarkers and diagnostic tools for drug eruption and we also discussed the actual usefulness of these biomarkers in the clinical aspects based on the pathogenesis of drug eruption.
Topics: Animals; Biomarkers; Diagnosis, Differential; Drug Eruptions; Humans; Stevens-Johnson Syndrome
PubMed: 34299145
DOI: 10.3390/ijms22147527 -
Journal of Immunological Methods Sep 2021Drug hypersensitivity reactions (DHRs) occur in certain people and are often not predictable. DHRs can be classified as immediate and delayed reactions regarding to... (Review)
Review
Drug hypersensitivity reactions (DHRs) occur in certain people and are often not predictable. DHRs can be classified as immediate and delayed reactions regarding to onset of clinical manifestations. Both reactions are considered to be an important public health problem because they can lead to life-threatening conditions; however, this review article will focus on delayed DHRs. The most important points for diagnosis of delayed DHRs are the recognition of drug hypersensitivity characteristics and culprit drug identification. While it is usually difficult to identify a culprit drug; clinical evaluation using the causality assessment method, a non-invasive process, can identify the culprit drug without the need for intensive investigation. Delayed DHRs can cause life-threatening conditions; therefore, in vivo skin tests, as well as drug provocation tests, have to be cautiously performed by a drug allergist and have not been recommended in uncontrolled conditions. ENDA/EAACI has recommended that in vitro tests (if available) be performed prior to any in vivo tests. Therefore, in vitro diagnostic tests can be alternative methods to identify a culprit drug for delayed DHR diagnosis as there is no or very low risk for patients under investigation. There are many testing approaches to identify causative agents for delayed DHRs such as: the lymphocyte transformation test (LTT), cytokine/mediator detection assays (i.e. ELISA and flow cytometry-based bead assays), multiplex bead-based immunoassay and ELISpot. The LTT is the most standardized method whereas it has been available in medical schools affiliated with university hospitals. Other in vitro tests, like cytokine detection assays, have also been used, even though they are still being evaluated. They could supplement LTT results that would provide drug allergist's with documentary evidence and prevent risk to patients by avoiding in vivo or drug provocation testing. Hence, the in vitro tests have been promising tests contributing to the management of the delayed DHR work-up process in clinical practice.
Topics: Cytokines; Drug Hypersensitivity; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Humans; Hypersensitivity, Delayed; Immunologic Tests; Lymphocyte Activation; Lymphocytes; Predictive Value of Tests; Reproducibility of Results; Risk Factors
PubMed: 34216607
DOI: 10.1016/j.jim.2021.113098 -
American Family Physician Jan 2024Sarcoidosis is a multisystem granulomatous inflammatory disease of unknown etiology that can involve any organ. Ongoing dyspnea and dry cough in a young to middle-aged...
Sarcoidosis is a multisystem granulomatous inflammatory disease of unknown etiology that can involve any organ. Ongoing dyspnea and dry cough in a young to middle-aged adult should increase the suspicion for sarcoidosis. Symptoms can present at any age and affect any organ system; however, pulmonary sarcoidosis is the most common. Extrapulmonary manifestations often involve cardiac, neurologic, ocular, and cutaneous systems. Patients with sarcoidosis can exhibit constitutional symptoms such as fever, unintentional weight loss, and fatigue. The early recognition and diagnosis of sarcoidosis are challenging because there is no diagnostic standard for testing, initial symptoms vary, and patients may be asymptomatic. Consensus guidelines recommend a holistic approach when diagnosing sarcoidosis that focuses on clinical presentation and radiographic findings, biopsy with evidence of noncaseating granulomas, involvement of more than one organ system, and elimination of other etiologies of granulomatous disease. Corticosteroids are the initial treatment for active disease, with refractory cases often requiring immunosuppressive or biologic therapies. Transplantation can be considered for advanced and end-stage disease depending on organ involvement.
Topics: Adult; Middle Aged; Humans; Sarcoidosis; Sarcoidosis, Pulmonary; Adrenal Cortex Hormones; Dyspnea; Diagnosis, Differential
PubMed: 38227868
DOI: No ID Found -
European Annals of Allergy and Clinical... Dec 2023Metamizole, a non-steroidal anti-inflammatory drug from the pyrazolone group, is a frequent cause of immediate hypersensitivity reactions and, more rarely, of delayed...
Metamizole, a non-steroidal anti-inflammatory drug from the pyrazolone group, is a frequent cause of immediate hypersensitivity reactions and, more rarely, of delayed drug hypersensitivity reactions. Due to its favorable pharmacokinetic characteristics, metamizole is widely used in the postoperative period for pain control. Retrospective study of patients referred for allergological study between January 2012 and June2022 for postoperative hypersensitivity reactions. Clinical and diagnostic data were collected through review of patients' medical records. Twenty patients with postoperative hypersensitivity reactions were referred, of which 10 presented delayed reactions. We analyzed the results of skin prick, intradermal and patch tests performed with an intravenous metamizole solution as well as provocation tests performed with metamizole and acetylsalicylic acid. Cross-reactivity to non-steroidal anti-inflammatory drugs was excluded by confirmation of clinical tolerance to non-steroidal anti-inflammatory drugs or by acetylsalicylic acid provocation test. In 7 of the 10 patients a delayed reaction to metamizole was diagnosed. These reactions were characterized as maculopapular exanthema, occurring in multiple postoperative settings. Skin tests were negative, except in one patient with late mild erythema in the ipsilateral upper limb and no reaction at the site of intradermal injection. Delayed hypersensitivity was demonstrated by late positive metamizole provocation tests. This study demonstrated that for a correct diagnosis a high degree of suspicion about possible delayed hypersensitivity drug reactions to metamizole in the postoperative setting is needed. In the investigation, provocation test with metamizole was decisive for diagnostic confirmation.
PubMed: 38054601
DOI: 10.23822/EurAnnACI.1764-1489.317 -
Vaccine Jul 2023Basophil activation test (BAT) can tackle multiple mechanisms underlying acute and delayed hypersensitivity to drugs and vaccines and might complement conventional...
Basophil activation test (BAT) can tackle multiple mechanisms underlying acute and delayed hypersensitivity to drugs and vaccines and might complement conventional allergy diagnostics but its role in anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-related hypersensitivity is ill-defined. Therefore, 89 patients with possible hypersensitivity (56 % with delayed mucocutaneous manifestations) to anti-SARS-CoV-2 vaccines were tested with BAT for Macrogol 3350, DMG-PEG 2000, PEG 20000, polysorbate-80 and trometamol and compared to 156 subjects undergoing pre-vaccine BAT. A positive BAT was associated with delayed reaction onset (p = 0.010) and resolution (p = 0.011). BAT was more frequently positive to DMG-PEG 2000 than to other excipients in both groups (p < 0.001). DMG-PEG 2000 reactivity was less frequent in vaccine-naïve (6 %) than vaccinated subjects (35 %, p < 0.001) and associated with mRNA-1273 vaccination. DMG-PEG 2000 BAT might therefore have a diagnostic role in subjects with delayed hypersensitivity reactions. Natural immunity might be a key player in basophil activation.
Topics: Humans; Basophils; Excipients; COVID-19 Vaccines; COVID-19; SARS-CoV-2; Hypersensitivity; Hypersensitivity, Delayed
PubMed: 37349223
DOI: 10.1016/j.vaccine.2023.06.039 -
Frontiers in Pharmacology 2024Cystic fibrosis transmembrane conductance regulator modulators are the only available treatment for cystic fibrosis. Although elexacaftor/tezacaftor/ivacaftor...
Cystic fibrosis transmembrane conductance regulator modulators are the only available treatment for cystic fibrosis. Although elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is well-tolerated, rash has been reported as very frequent. In severe rashes, ELX/TEZ/IVA withdrawal is necessary, leading to clinical deterioration. The objective of the study is to increment the experience of ELX/TEZ/IVA desensitization. Adult patients who developed a delayed hypersensitivity rash to ELX/TEZ/IVA between December 2021 and February 2023 and required withdrawal due to ineffective rescue medication were included. Skins test for ELX/TEZ/IVA and IVA were conducted to establish hypersensitivity mechanism. Balijepally ELX/TEZ/IVA desensitization protocol was selected. In cases where desensitization had to be discontinued due to rash, an extended desensitization was proposed. Clinical and health-related quality of life parameters were collected before ELX/TEZ/IVA and after desensitization. 162 patients (81 women, 31.2 [23.8-42.5] years) started ELX/TEZ/IVA, developing rash 12 of them (7.4%, six women). Six patients (five women) required stopping ELX/TEZ/IVA and were selected for desensitization. Skin tests indicated delayed type-IV hypersensitivity in one patient. Two patients presented adequate tolerance to desensitization; while, four patients developed rash. Three of these patients, successfully concluded extended desensitization (one patient declined participation). No significant clinical deterioration or quality of life worsening was observed during desensitization; in fact, there was an improvement in practically all mesured parameters. All five patients who resumed ELX/TEZ/IVA are currently receiving therapy with good tolerance. Desensitization to ELX/TEZ/IVA could be a successful and safe strategy for reintroducing this essential treatment in cases of a delayed hypersensitivity rash.
PubMed: 38933680
DOI: 10.3389/fphar.2024.1392986 -
Clinical Reviews in Allergy & Immunology Jun 2022Confirming drug imputability is an important step in the management of cutaneous adverse drug reactions (CADR). Re-challenge is inconvenient and in many cases life... (Review)
Review
Confirming drug imputability is an important step in the management of cutaneous adverse drug reactions (CADR). Re-challenge is inconvenient and in many cases life threatening. We review the literature on ideal patch testing technique for specific CADRs. Testing should be performed approximately 3 months after the resolution of the eruption using standard patch testing techniques. Commercially available patch test preparations are available for a minority of drugs, so in most cases, testing should be performed with the drug at various recommended concentrations and in different vehicles. Testing to all known excipients, such as dyes, vehicles and preservatives is also important. Immunosuppressive medications should be discontinued or down titrated to the lowest tolerable dose to decrease the risk of false negative reactions. We provide an overview of expert recommendations and extant evidence on the utility of patch testing for identifying the culprit drug in common CADRs and for specific drug or drug classes. Overall, there appears to be significant variability in the patch test positivity of different drugs, which is likely the result of factors intrinsic to the drug such as dermal absorption (as a function of lipophilicity and molecular size) and whether the drug itself or a downstream metabolite is implicated in the immune reaction. Drugs with high patch test positivity rates include beta-lactam antibiotics, aromatic anticonvulsants, phenytoin, and corticosteroids, among others. Patch testing positivity varies both as a function of the drug and type of CADR. The sum of the evidence suggests that patch testing in the setting of morbilliform eruptions, fixed drug eruption, acute generalized exanthematous pustulosis, and possibly also drug-induced hypersensitivity syndrome, photoallergic and eczematous reactions may be worthwhile, although utility of testing may vary on the specific drug in question for the eruption. It appears to be of limited utility and is not recommended in the setting of other complex CADR, such as SJS/TEN and leukocytoclastic vasculitis.
Topics: Anticonvulsants; Drug Eruptions; Drug Hypersensitivity; Exanthema; Humans; Hypersensitivity, Delayed; Patch Tests
PubMed: 35113364
DOI: 10.1007/s12016-022-08924-2 -
Contact Dermatitis Jul 2022The skin is frequently exposed to chemical stress by organic chemicals or metal ions that can directly or indirectly challenge its immune components and may lead to... (Review)
Review
The skin is frequently exposed to chemical stress by organic chemicals or metal ions that can directly or indirectly challenge its immune components and may lead to T-cell-mediated delayed-type hypersensitivity reactions. The disruption of the skin's homeostasis by exposure to contact sensitizers (CSs) can trigger an inflammatory immune response that results in eczema and allergic contact dermatitis. The recognition of these chemicals depends on the expression of pattern recognition receptors on sentinel skin cells, mainly the innate resident immune cells orchestrating the skin's immune response and involving both oxidative and inflammatory pathways. The main driver of these both pathways is the Nrf2/Keap1 pathway, a major ubiquitous regulator of cellular oxidative and electrophilic stress, activated in various innate immune cells of the skin, including keratinocytes and epidermal Langerhans cells in the epidermis and dermal dendritic cells in the dermis. Nrf2 also shows a strong protective capacity by downregulating inflammatory pathways. In this review, the important role of Nrf2 in the regulation of the immune response to CSs will be discussed and highlighted.
Topics: Dermatitis, Allergic Contact; Humans; Immunity, Innate; Kelch-Like ECH-Associated Protein 1; NF-E2-Related Factor 2; Skin
PubMed: 35165896
DOI: 10.1111/cod.14073