Drug hypersensitivity reactions in Asia: regional issues and challenges

There are geographical, regional, and ethnic differences in the phenotypes and endotypes of patients with drug hypersensitivity reactions (DHRs) in different parts of the world. In Asia, aspects of drug hypersensitivity of regional importance include IgE-mediated allergies and T-cell-mediated reactions, including severe cutaneous adverse reactions (SCARs), to beta-lactam antibiotics, antituberculous drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) and radiocontrast agents. Delabeling of low-risk penicillin allergy using direct oral provocation tests without skin tests have been found to be useful where the drug plausibility of the index reaction is low. Genetic risk associations of relevance to Asia include human leucocyte antigen (HLA)-B*1502 with carbamazepine SCAR, and HLA-B*5801 with allopurinol SCAR in some Asian ethnic groups. There remains a lack of safe and accurate diagnostic tests for antituberculous drug allergy, other than relatively high-risk desensitization regimes to first-line antituberculous therapy. NSAID hypersensitivity is common among both adults and children in Asia, with regional differences in phenotype especially among adults. Low dose aspirin desensitization is an important therapeutic modality in individuals with cross-reactive NSAID hypersensitivity and coronary artery disease following percutaneous coronary intervention. Skin testing allows patients with radiocontrast media hypersensitivity to confirm the suspected agent and test for alternatives, especially when contrasted scans are needed for future monitoring of disease relapse or progression, especially cancers.

Asia Pacific Association of Allergy Asthma and Clinical Immunology White Paper 2020 on climate change, air pollution, and biodiversity in Asia-Pacific and impact on allergic diseases

Air pollution, climate change, and reduced biodiversity are major threats to human health with detrimental effects on a variety of chronic noncommunicable diseases in particular respiratory and cardiovascular diseases. The extent of air pollution both outdoor and indoor air pollution and climate change including global warming is increasing-to alarming proportions particularly in the developing world especially rapidly industrializing countries worldwide. In recent years, Asia has experienced rapid economic growth and a deteriorating environment and increase in allergic diseases to epidemic proportions. Air pollutant levels in many Asian countries especially in China and India are substantially higher than are those in developed countries. Moreover, industrial, traffic-related, and household biomass combustion, indoor pollutants from chemicals and tobacco are major sources of air pollutants, with increasing burden on respiratory allergies. Here we highlight the major components of outdoor and indoor air pollutants and their impacts on respiratory allergies associated with asthma and allergic rhinitis in the Asia-Pacific region. With Asia-Pacific comprising more than half of the world's population there is an urgent need to increase public awareness, highlight targets for interventions, public advocacy and a call to action to policy makers to implement policy changes towards reducing air pollution with interventions at a population-based level.

Nonsteroidal anti-inflammatory drug hypersensitivity in the Asia-Pacific

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.

Shellfish/crustacean oral allergy syndrome among national service pre-enlistees in Singapore

BACKGROUND: All Singaporean males undergo medical screening prior to compulsory military service. A history of possible food allergy may require referral to a specialist Allergy clinic to ensure that special dietary needs can be taken into account during field training and deployment. OBJECTIVE: To study the pattern of food allergy among pre-enlistees who were referred to a specialist allergy clinic to work up suspected food allergy. METHODS: Retrospective study of all pre-enlistees registered in the Clinical Immunology/Allergy New Case Registry referred to the Allergy Clinic from 1 August 2015 to 31 May 2016 for suspected food allergy. RESULTS: One hundred twenty pre-enlistees reporting food allergy symptoms other than rash alone were referred to the Allergy Clinic during the study period. Of these, 77 (64.2%) had food allergy. Among those with food allergy, mean age was 19.1 ± 1.5 years. They comprised predominantly Chinese (66.2%) and Malays (20.8%). The most commonly reported foods were shellfish/crustaceans (78%), peanut (15.6%), and egg (6.5%). Self-limiting oral allergy syndrome, OAS (itchy lips and throat with/without lip angioedema) was the most common manifestation (n = 33, 42.9%) followed by anaphylaxis (n = 23, 29.9%). Majority of OAS was from shellfish/crustacean (90.6%); of which shrimp (30.3%), crab (15.2%), and lobster (3.0%) were the most common. Mild childhood asthma (69.7%), allergic rhinitis (6.3%), and eczema (6.1%) were the most common atopic conditions among individuals with shellfish/crustacean OAS. This pattern was similar for shellfish/crustacean anaphylaxis. Skin prick tests were most commonly positive for shrimp (OAS 87.1% vs. anaphylaxis 100%), crab (OAS 95.8% vs. 90.9%), and lobster (OAS 91.7% vs. 63.6%). CONCLUSION: OAS to shellfish/crustaceans was more common than anaphylaxis among this study population of young males referred for food allergy symptoms other than rash alone.

Aerobiology in Asian airway allergic diseases

No abstract available.

Allergic conjunctivitis in Asia

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.

A retrospective study on sequential desensitization-rechallenge for antituberculosis drug allergy

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.

Stevens-Johnson syndrome / toxic epidermal necrolysis: an Asia-Pacific perspective

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.

The effects of environmental pollution and climate change on allergic diseases

No abstract available.

Clinical applications of drug desensitization in the Asia-Pacific region

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.

Update on the Management of Antibiotic Allergy

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.

Update on the Management of Antibiotic Allergy

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.