Drug allergy to antibiotics may occur in the form of immediate or non-immediate (delayed) hypersensitivity reactions. Immediate reactions are usually IgE-mediated whereas non-immediate hypersensitivity reactions are usually non-IgE or T-cell mediated. The clinical manifestations of antibiotic allergy may be cutaneous, organ-specific (e.g., blood dyscracias, hepatitis, interstitial nephritis), systemic (e.g., anaphylaxis, drug induced hypersensitivity syndrome) or various combinations of these. Severe cutaneous adverse reactions manifesting as Stevens Johnson syndrome or toxic epidermal necrolysis (TEN) may be potentially life-threatening. The management of antibiotic allergy begins with the identification of the putative antibiotic from a detailed and accurate drug history, complemented by validated in-vivo and in-vitro allergological tests. This will facilitate avoidance of the putative antibiotic through patient education, use of drug alert cards, and electronic medical records with in-built drug allergy/adverse drug reaction prescription and dispensing checks. Knowledge of the evidence for specific antibiotic cross-reactivities is also important in patient education. Apart from withdrawal of the putative antibiotic, immunomodulatory agents like high-dose intravenous immunoglobulins may have a role in TEN. Drug desensitization where the benefits outweigh the risks, and where no alternative antibiotics can be used for various reasons, may be considered in certain situations. Allergological issues pertaining to electronic drug allergy alerts, computerized physician prescriptions and decision support systems, and antibiotic de-escalation in antimicrobial stewardship programmes are also discussed.
Anaphylaxis ; Anti-Bacterial Agents ; Complement System Proteins ; Drug Hypersensitivity ; Electronic Health Records ; Electronics ; Electrons ; Epidermal Necrolysis, Toxic ; Hepatitis ; Hypersensitivity ; Immunoglobulins, Intravenous ; Patient Education as Topic ; Prescriptions ; Stevens-Johnson Syndrome ; T-Lymphocytes

Drug allergy to antibiotics may occur in the form of immediate or non-immediate (delayed) hypersensitivity reactions. Immediate reactions are usually IgE-mediated whereas non-immediate hypersensitivity reactions are usually non-IgE or T-cell mediated. The clinical manifestations of antibiotic allergy may be cutaneous, organ-specific (e.g., blood dyscracias, hepatitis, interstitial nephritis), systemic (e.g., anaphylaxis, drug induced hypersensitivity syndrome) or various combinations of these. Severe cutaneous adverse reactions manifesting as Stevens Johnson syndrome or toxic epidermal necrolysis (TEN) may be potentially life-threatening. The management of antibiotic allergy begins with the identification of the putative antibiotic from a detailed and accurate drug history, complemented by validated in-vivo and in-vitro allergological tests. This will facilitate avoidance of the putative antibiotic through patient education, use of drug alert cards, and electronic medical records with in-built drug allergy/adverse drug reaction prescription and dispensing checks. Knowledge of the evidence for specific antibiotic cross-reactivities is also important in patient education. Apart from withdrawal of the putative antibiotic, immunomodulatory agents like high-dose intravenous immunoglobulins may have a role in TEN. Drug desensitization where the benefits outweigh the risks, and where no alternative antibiotics can be used for various reasons, may be considered in certain situations. Allergological issues pertaining to electronic drug allergy alerts, computerized physician prescriptions and decision support systems, and antibiotic de-escalation in antimicrobial stewardship programmes are also discussed.
Anaphylaxis ; Anti-Bacterial Agents ; Complement System Proteins ; Drug Hypersensitivity ; Electronic Health Records ; Electronics ; Electrons ; Epidermal Necrolysis, Toxic ; Hepatitis ; Hypersensitivity ; Immunoglobulins, Intravenous ; Patient Education as Topic ; Prescriptions ; Stevens-Johnson Syndrome ; T-Lymphocytes

Nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity reactions (HSRs) are often nonimmunologically mediated reactions which present with immediate HSR type manifestations. These are mediated by cyclooxygenase inhibition resulting in shunting towards the excessive production of leukotrienes. Important disease associations include asthma, nasal polyposis, and chronic spontaneous urticaria, especially among adults. The European Network on Drug Allergy/Global Allergy and Asthma European Network 2013 classification of NSAID HSR comprises nonselective HSR i.e., NSAID exacerbated respiratory disease (NERD), NSAIDs exacerbated cutaneous disease (NECD), NSAIDs induced urticarial-angioedema (NIUA); and selective (allergic) HSR i.e., single NSAID induced urticaria/angioedema or anaphylaxis, NSAIDs-induced delayed HSR. Much of the literature on genetic associations with NSAID HSR originate from Korea and Japan; where genetic polymorphisms have been described in genes involved in arachidonic acid metabolism, basophil/mast cell/eosinophil activation, various inflammatory mediators/cytokines, and different HLA genotypes. The Asian phenotype for NSAID HSR appears to be predominantly NIUA with overlapping features in some adults and children. NECD also appears to be more common than NERD, although both are not common in the Asian paediatric population. Between adults and children, children seem to be more atopic, although over time when these children grow up, it is likely that the prevalence of atopic adults with NSAID HSR will increase. Low-dose aspirin desensitization has been shown to be effective in the treatment of coronary artery disease, especially following percutaneous coronary intervention.
Adult ; Anaphylaxis ; Anti-Inflammatory Agents, Non-Steroidal ; Arachidonic Acid ; Asian Continental Ancestry Group ; Aspirin ; Asthma ; Child ; Classification ; Coronary Artery Disease ; Drug Hypersensitivity ; Genotype ; Humans ; Hypersensitivity ; Japan ; Korea ; Leukotrienes ; Metabolism ; Percutaneous Coronary Intervention ; Phenotype ; Polymorphism, Genetic ; Prevalence ; Prostaglandin-Endoperoxide Synthases ; Urticaria

Drug desensitization is the induction, within hours to days, of a temporary state of tolerance to a drug which the patient has developed a hypersensitivity reaction to. It may be used for IgE and non-IgE mediated allergic reactions, and certain non-allergic reactions. The indication for desensitization is where no alternative medications are available for the treatment of that condition, and where the benefits of desensitization outweigh the risks. Desensitization is a therapeutic modality for drug allergy (similar to allergen specific immunotherapy for allergic rhinitis and insect venom anaphylaxis). In contrast, the drug provocation test is a diagnostic modality used to confirm or refute the diagnosis of drug allergy. This review discusses the clinical applications of desensitization for the treatment of common infectious, metabolic and cardiovascular diseases, and oncological conditions in the Asia-Pacific region.
Anaphylaxis ; Cardiovascular Diseases ; Diagnosis ; Drug Hypersensitivity ; Humans ; Hypersensitivity ; Immunoglobulin E ; Immunotherapy ; Insects ; Rhinitis, Allergic ; Stevens-Johnson Syndrome ; Venoms

No abstract available.
Climate Change ; Climate ; Environmental Pollution

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions (SCAR) to drugs which are associated with significant morbidity and mortality. High risk drugs in Asia are similar to those reported worldwide. Human leukocyte antigen (HLA)-related risk alleles for carbamazepine and allopurinol SCAR are unique to Asians. Although prognostic scoring systems like the SCORTEN have been used for more than a decade, pitfalls and caveats need to be recognized, in particular in patients with multiple medical co-morbidities and systemic features in SJS/TEN. In centres without a tertiary Burns Centre, SJS/TEN patients can still be managed successfully in general and dermatology wards with well-executed supportive/nursing care. Controversy remains regarding the effectiveness of immunomodulation in reducing SJS/TEN morbidity, mortality and hastening re-epithelialization. Despite paucity of robust evidence, intravenous immunoglobulins and ciclosporin remain the most commonly used modalities worldwide. Acute and long-term ocular effects are an important source of morbidity for which emerging ophthalmic therapies appear promising. Quality of life issues have now become an important outcome in patients with SJS/TEN as they often impact survivors' future attitudes towards pharmacotherapy. Even though pharmacogenetic testing for high-risk drugs appears to be the panacea for preventing carbamazepine- and allopurinol-induced SJS/TEN in ethnic Asians, many issues remain before health regulators in our region can conclusively determine whether testing should be made mandatory or highly recommended as standard of care.
Alleles ; Allopurinol ; Asia ; Asian Continental Ancestry Group ; Burns ; Carbamazepine ; Cicatrix ; Cyclosporine ; Dermatology ; Drug Therapy ; HLA Antigens ; Humans ; Immunoglobulins, Intravenous ; Immunomodulation ; Leukocytes ; Mortality ; Pharmacogenetics ; Quality of Life ; Re-Epithelialization ; Standard of Care ; Stevens-Johnson Syndrome

Allergic conjunctivitis (AC), which may be acute or chronic, is associated with rhinitis in 30%–70% of affected individuals, hence the term allergic rhinoconjunctivitis (AR/C). Seasonal and perennial AC is generally milder than the more chronic and persistent atopic and vernal keratoconjunctivitis. Natural allergens like house dust mites (HDM), temperate and subtropical grass and tree pollen are important triggers that drive allergic inflammation in AC in the Asia-Pacific region. Climate change, environmental tobacco smoke, pollutants derived from fuel combustion, Asian dust storms originating from central/north Asia and phthalates may also exacerbate AR/C. The Allergies in Asia Pacific study and International Study of Asthma and Allergies in Childhood provide epidemiological data on regional differences in AR/C within the region. AC significantly impacts the quality of life of both children and adults, and these can be measured by validated quality of life questionnaires on AR/C. Management guidelines for AC involve a stepped approach depending on the severity of disease, similar to that for allergic rhinitis and asthma. Topical calcineurin inhibitors are effective in certain types of persistent AC, and sublingual immunotherapy is emerging as an effective treatment option in AR/C to grass pollen and HDM. Translational research predominantly from Japan and Korea involving animal models are important for the potential development of targeted pharmacotherapies for AC.
Adult ; Allergens ; Asia ; Asian Continental Ancestry Group ; Asthma ; Calcineurin Inhibitors ; Child ; Climate Change ; Conjunctivitis, Allergic ; Desensitization, Immunologic ; Drug Therapy ; Dust ; Epidemiology ; Humans ; Hypersensitivity ; Inflammation ; Japan ; Korea ; Models, Animal ; Poaceae ; Pollen ; Pyroglyphidae ; Quality of Life ; Rhinitis ; Rhinitis, Allergic ; Seasons ; Smoke ; Sublingual Immunotherapy ; Tobacco ; Translational Medical Research ; Trees

No abstract available.
Asian Continental Ancestry Group ; Humans

Biomarkers/blood* ; COVID-19/diagnosis* ; Chemokine CXCL10/blood* ; Humans ; Lung Diseases/virology* ; Severity of Illness Index

BACKGROUND: Antituberculosis (anti-TB) drug allergy often involves multiple concurrently administered drugs which subsequently need to be reinitiated as no better alternatives exist. OBJECTIVE: To describe the results of tailored sequential desensitization-rechallenge (D-R) for anti-TB drug allergy. METHODS: Consecutive patients who had undergone D-R to anti-TB drugs between 1 September 1997 and 31 January 2012 were recruited. Following resolution of the acute reaction, anti-TB drug was restarted at 1:6,000 to 1:3 of the final daily dose (FDD), with gradual single or multiple step daily dose escalation to the FDD. Subsequent drugs were sequentially added ≥3 days later when the preceding drug was tolerated. Full blood count and liver function tests were monitored prior to addition of each new drug. RESULTS: There were 11 patients of whom 10 were male, predominantly Chinese (8 patients). Regimens comprised at least 3 drugs: isoniazid (INH), rifampicin (RIF), ethambutol (EMB), pyrazinamide (PZA), or streptomycin. All patients had nonimmediate reactions, with cutaneous eruptions, where maculopapular exanthema (MPE) was the most common (8 patients). Drug-induced hypersensitivity syndrome (DIHS) occurred in 6 patients, and Stevens Johnson syndrome (SJS) in 2 patients. D-R to INH was successful in 7/9 patients (77.8%) and to RIF/EMB/PZA/streptomycin in all. Of the 2 patients who failed INH D-R, 1 developed fever and MPE on day 3, the other MPE on day 8. D-R with INH and RIF respectively was successful in 2 patients with SJS. Among DIHS patients, 1 failed D-R with INH (fever and MPE on day 3). There were 23/25 (92%) successful D-R among the 11 patients. All patients completed TB treatment of ≥5 months' duration with no cases of drug-resistant TB. CONCLUSION: Tailored sequential TB drug D-R is successful where no better alternative therapies are available, with careful dose escalation and close monitoring, and after a careful risk-benefit assessment.
Asian Continental Ancestry Group ; Complementary Therapies ; Drug Eruptions ; Drug Hypersensitivity Syndrome ; Drug Hypersensitivity ; Ethambutol ; Exanthema ; Fever ; Humans ; Hypersensitivity ; Isoniazid ; Liver Function Tests ; Male ; Pyrazinamide ; Retrospective Studies ; Rifampin ; Risk Assessment ; Stevens-Johnson Syndrome ; Streptomycin