Subject(s)
Anaphylaxis , COVID-19 Vaccines , COVID-19 , Polyethylene Glycols , Humans , Anaphylaxis/etiology , Anaphylaxis/chemically induced , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Polyethylene Glycols/adverse effects , Polysorbates/adverse effects , SARS-CoV-2Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Dipyrone , Drug Hypersensitivity , Hypersensitivity, Delayed , Ibuprofen , Humans , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Dipyrone/adverse effects , Drug Hypersensitivity/diagnosis , Hypersensitivity, Delayed/diagnosis , Ibuprofen/adverse effects , Lymphocyte ActivationSubject(s)
Angioedemas, Hereditary/complications , Factor XII Deficiency/complications , Hemorrhage/etiology , Hemorrhage/prevention & control , Heparin, Low-Molecular-Weight/therapeutic use , Pregnancy Complications , Tranexamic Acid/therapeutic use , Angioedemas, Hereditary/etiology , Drug Therapy, Combination , Female , Heparin, Low-Molecular-Weight/administration & dosage , Humans , Pregnancy , Tranexamic Acid/administration & dosageSubject(s)
Allergens/immunology , Desensitization, Immunologic/methods , Drug Hypersensitivity/therapy , Hypersensitivity, Delayed/therapy , Lenalidomide/immunology , T-Lymphocytes/immunology , Aged , Drug Hypersensitivity/diagnosis , Humans , Hypersensitivity, Delayed/diagnosis , Immunologic Tests , Lymphocyte Activation , Male , Treatment OutcomeABSTRACT
BACKGROUND AND OBJECTIVE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a complex multisystemic severe drug hypersensitivity reaction whose diagnosis and management are troublesome. DRESS syndrome requires management by various specialists. The correct identification of the culprit drug is essential to ensure safe future therapeutic options for the patient. There are no previous Spanish guidelines or consensus statements on DRESS syndrome. Objective: To draft a review and guidelines on the clinical diagnosis, allergy work-up, management, treatment, and prevention of DRESS syndrome in light of currently available scientific evidence and the experience of experts from multiple disciplines. METHODS: These guidelines were drafted by a panel of allergy specialists from the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC), together with other medical specialists involved in the management of DRESS syndrome and researchers from the PIELenRed consortium. A review was conducted of scientific papers on DRESS syndrome, and the expert panel evaluated the quality of the evidence of the literature and provided grades of recommendation. Whenever evidence was lacking, a consensus was reached among the experts. RESULTS: The first Spanish guidelines on DRESS syndrome are now being published. Important aspects have been addressed, including practical recommendations about clinical diagnosis, identification of the culprit drug through the Spanish pharmacovigilance system algorithm, and the allergy work-up. Recommendations are provided on management, treatment, and prevention. Algorithms for the management of DRESS in the acute and recovery phases have been drawn up. Expert consensus-based stepwise guidelines for the management and treatment of DRESS syndrome are provided.
Subject(s)
Drug Hypersensitivity Syndrome/diagnosis , Liver/metabolism , Skin/pathology , Algorithms , Allopurinol/adverse effects , Anti-Bacterial Agents/adverse effects , Anticonvulsants/adverse effects , Comorbidity , Consensus , Drug Hypersensitivity Syndrome/drug therapy , Drug Hypersensitivity Syndrome/epidemiology , Eosinophilia , Expert Testimony , Humans , Leukocytosis , Liver/pathology , Risk Factors , Spain/epidemiologySubject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Drug Eruptions/diagnosis , Drug Eruptions/etiology , Etoricoxib/adverse effects , Lymphocyte Activation/immunology , Lymphocytes/immunology , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Etoricoxib/administration & dosage , Female , Humans , Lymphocytes/metabolism , Middle AgedSubject(s)
Drug Hypersensitivity Syndrome/etiology , Drug Hypersensitivity Syndrome/immunology , Exanthema/chemically induced , Exanthema/immunology , Lymphocyte Activation/immunology , Sulfadiazine/immunology , Sulfamethoxazole/immunology , Female , Humans , Lymphocyte Activation/drug effects , Middle Aged , Sulfadiazine/adverse effects , Sulfamethoxazole/adverse effectsABSTRACT
BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe delayed hypersensitivity reaction. The determination of drug causality is complex. The lymphocyte transformation test (LTT) has been reported positive in more than 50% of DRESS cases. Nevertheless, the sensitivity and specificity of LTT specifically in DRESS have not yet been established. Rechallenge with the culprit drug is contraindicated and cannot be used as gold standard for sensitivity and specificity determination. OBJECTIVE: To estimate the sensitivity and specificity of LTT in a clinically defined series of patients with DRESS. METHODS: Some 41 patients diagnosed with DRESS were included in the study. The results of the algorithm of the Spanish Pharmacovigilance System were used as the standard for a correct diagnosis of drug causality. A standard LTT was performed with involved drugs in acute or recovery samples. A stimulation index (SI) ≥2 in at least one concentration except for beta-lactams (SI ≥3) and contrast media (SI ≥4) was considered positive. Contingency tables and ROC curves were used for analysis. RESULTS: Sensitivity and specificity of LTT in the recovery phase of DRESS were 73% and 82%, respectively, whereas in the acute phase, they were only 40% and 30%, respectively. Comparison of skin tests and LTT confirmed a higher sensitivity and specificity of LTT in DRESS. LTT showed high sensitivity (S) and specificity (Sp) for anticonvulsants (S 100%, Sp 100%; P = .008), anti-TB drugs (S 87.5%, Sp 100%; P = .004), and beta-lactams (S 73%, Sp 100%; P = .001). ROC curves revealed that the best criteria for LTT positivity for all drugs are SI ≥2 in at least one concentration, increasing overall sensitivity to 80%, and for beta-lactams from 73% to 92%. CONCLUSIONS AND CLINICAL RELEVANCE: LTT is a good diagnostic tool for drug causality in DRESS, mainly when performed in the recovery phase.
Subject(s)
Algorithms , Drug Hypersensitivity Syndrome/diagnosis , Drug Hypersensitivity Syndrome/etiology , Lymphocyte Activation/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Drug Hypersensitivity Syndrome/immunology , Female , Humans , Lymphocyte Activation/drug effects , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity , Young AdultSubject(s)
Allergens/immunology , Anaphylaxis/etiology , Food Hypersensitivity/etiology , Female , Humans , Meat Products , Middle AgedABSTRACT
Chagas disease is a parasitosis endemic to South America. It is normally treated with benznidazole as first choice, which has been associated with numerous cutaneous reactions. However, very few benznidazole-associated severe cutaneous adverse reactions have been reported to date. The rise of Chagas disease in nonendemic countries represents a growing public health challenge. We report two patients who met the criteria for drug reaction with eosinophilia and systemic symptoms syndrome and Stevens-Johnson syndrome/toxic epidermal necrolysis according to the RegiSCAR scoring systems. They were thus deemed overlapping cases, with a lymphocyte transformation test positive for benznidazole. Both required intensive care unit admission and both survived. Considering the rising application of this drug for trypanosomiasis in immigrant populations, clinicians should be aware of this newly reported, potentially life-threatening risk.
Subject(s)
Chagas Disease/drug therapy , Drug Eruptions/etiology , Nitroimidazoles/adverse effects , Stevens-Johnson Syndrome/etiology , Trypanocidal Agents/adverse effects , Adult , Dermatitis, Exfoliative/chemically induced , Edema/chemically induced , Female , Humans , Male , Stevens-Johnson Syndrome/diagnosisSubject(s)
Angioedema/prevention & control , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Aspirin/administration & dosage , Aspirin/adverse effects , Coronary Artery Disease/drug therapy , Desensitization, Immunologic/methods , Drug Hypersensitivity/prevention & control , Angioedema/chemically induced , Angioedema/diagnosis , Angioedema/immunology , Anti-Inflammatory Agents, Non-Steroidal/immunology , Aspirin/immunology , Drug Administration Schedule , Drug Hypersensitivity/diagnosis , Drug Hypersensitivity/etiology , Drug Hypersensitivity/immunology , Humans , Immune Tolerance , Immunologic Tests , Male , Middle Aged , Treatment OutcomeABSTRACT
We have functionalized the sides of fd bacteriophage virions with oligonucleotides to induce DNA hybridization driven self-assembly of high aspect ratio filamentous particles. Potential impacts of this new structure range from an entirely new building block in DNA origami structures, inclusion of virions in DNA nanostructures and nanomachines, to a new means of adding thermotropic control to lyotropic liquid crystal systems. A protocol for producing the virions in bulk is reviewed. Thiolated oligonucleotides are attached to the viral capsid using a heterobifunctional chemical linker. A commonly used system is utilized, where a sticky, single-stranded DNA strand is connected to an inert double-stranded spacer to increase inter-particle connectivity. Solutions of fd virions carrying complementary strands are mixed, annealed, and their aggregation is studied using dynamic light scattering (DLS), fluorescence microscopy, and atomic force microscopy (AFM). Aggregation is clearly observed on cooling, with some degree of local order, and is reversible when temperature is cycled through the DNA hybridization transition.
Subject(s)
Bacteriophage M13/metabolism , DNA/chemistry , Virion/metabolism , Bacteriophage M13/isolation & purification , Capsid Proteins/chemistry , Capsid Proteins/metabolism , DNA/metabolism , Light , Microscopy, Atomic Force , Microscopy, Fluorescence , Nanostructures/chemistry , Nucleic Acid Conformation , Nucleic Acid Hybridization , Oligonucleotides/chemistry , Oligonucleotides/metabolism , Scattering, RadiationABSTRACT
BACKGROUND: DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome is characterized by fever, rash, eosinophilia, and multiorgan failure. Previous reports have described differences in clinical and laboratory findings of DRESS syndrome depending on the inducing drug. Piperacillin has been reported as the drug responsible for this syndrome in 3 patients. OBJECTIVE: To analyze and describe the clinical, laboratory, and allergy study findings of piperacillin-induced DRESS. PATIENTS AND METHODS: Retrospective case series of patients diagnosed with DRESS associated with piperacillin-tazobactam (Pip/Taz) according to the Kardaun diagnostic score criteria. Assessment of causality was established using the Spanish Pharmacovigilance System and the lymphocyte transformation test (LTT). The allergy study included skin and epicutaneous tests. RESULTS: Eight patients were diagnosed with DRESS due to Pip/Taz (3 probable and 5 definite cases). Skin rash was observed in all cases and facial edema in 50%; the mean latency period was 18 days. Fever was present in 7 patients. Liver and kidney injuries were detected in 6 and 3 patients, respectively. All patients had eosinophilia and a full recovery. The LTT to Pip/Taz was strongly positive in all patients, with a stimulation index of over 6. Three of 3 patients had a positive intradermal test to Pip/Taz, and 1 of 4 had a positive patch test. All patients had a negative LTT to carbapenems. CONCLUSIONS: We have reported on the first case series of piperacillin-induced DRESS. A latency period of 18 days, skin rash, eosinophilia, fever, liver injury, and good prognosis were the most common features. The allergy study, and the LTT in particular, was highly useful for identifying Pip/Taz as the culprit drug and piperacillin as the responsible active ingredient.