Background: Allergy to penicillin is commonly reported in many countries and is an overwhelming global public health concern. Penicillin allergy labels can lead to the use of less effective antibiotics and can be associated with antimicrobial resistance. Appropriate assessment of suspected penicillin allergy (often including skin testing, followed by drug provocation testing [DPT] performed by allergists) can prevent the unnecessary restriction of penicillin or delabelling. Many countries in the Asia Pacific (AP) have very limited access to allergy services, and there are significant disparities in the methods of evaluating penicillin allergy. Therefore, a clinical pathway for the management of penicillin allergy is essential. Objectives: To develop a risk-stratified clinical pathway for delabeling penicillin allergy, taking into account the distinct epidemiology, patient/sensitization profiles, and disparities of allergy services or facilities within the AP. Methods: A risk-stratified penicillin allergy delabeling clinical pathway was formulated by the Drug Allergy Committee of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology. and members of the Penicillin Allergy Disparities survey in AP each representing one country/region of the AP. The clinical pathway was tested based on a database of anonymized patients who were sequentially referred for and completed penicillin allergy evaluation in Hong Kong. Results: The clinical pathway was piloted employing a “hub-and-spoke” approach to foster multidisciplinary collaboration between allergists and nonallergists. A simulation run of the algorithm on a retrospective Hong Kong cohort of 439 patients was performed. Overall, 367 (84%) of patients were suitable for direct DPT and reduced the need for skin testing or specialist’s care for 357 (97%) skin test-negative individuals. Out of the skin test-negative patients, 345 (94%) patients had a negative DPT. Conclusions: This risk-stratification strategy for direct oral DPT can reduce the need for unnecessary skin testing in patients with low-risk penicillin allergy histories. The hub and spoke model of care may be considered for further piloting and validation in other AP populations that lack adequately trained allergists.

Oral immunotherapy (OIT) can help children with persistent food allergies achieve sustained unresponsiveness (SU). However, the optimal therapeutic period for obtaining SU remains unclear. We aimed to retrospectively investigate the association between the OIT treatment period and achievement of SU. We enrolled patients who received OIT for peanut allergy between January 1, 2018 and December 31, 2022. OIT comprised the build-up phase, maintenance phase, complete avoidance, and an oral food challenge (OFC) for confirming SU. The peanut dose in the OFC was gradually increased to 3,000 mg (peanut protein: 795 mg), which was subsequently maintained for ≥5 months. SU was defined as a negative response to 795 mg of peanut protein after ≥2 weeks of complete avoidance. We evaluated the therapeutic OIT period for achieving SU using Kaplan-Meier analysis. Forty-eight patients underwent peanut OIT. The starting age at OIT initiation was 8 (interquartile range [IQR], 7-10) years. Forty-one (85%) patients had a history of anaphylaxis. The median specific immunoglobulin E concentration to peanut and Ara h 2 at OIT initiation was 85.3 (IQR, 33.7-100) and 57.6 (IQR, 21.9-100) UA/mL, respectively. The median observational period was 2.1 (IQR, 1.6-3.0) person-years (PY). Thirty-four (71%) patients achieved SU, with the rate of SU achievement gradually increasing with the therapeutic period. The median period until SU achievement was 2.1 (95% confidence interval, 1.6-2.5) PY. The rate of SU achievement slowed down after 2.7 PY. OIT for at least 2.7 PY can increase the rate of SU achievement. The protocol No. 3107.

Streptococcus pneumoniae (pneumococcus) is a significant cause of bacterial infections ranging from mild infections affecting the respiratory tract such as otitis media and sinusitis to severe diseases including bacteremia, pneumonia, and invasive pneumococcal disease (IPD) (eg, meningitis, septic arthritis, and endocarditis). Pneumococcal vaccines were first developed in the 1970s as capsular pneumococcal polysaccharide vaccines, which were T-cell independent and hence lacked immunologic memory. Subsequently in the year 2000, pneumococcal conjugate vaccines (PCV) conjugated to a protein to increase immunogenicity were developed and made commercially available. The increasing number of pneumococcal serotypes identified and the expanding pipeline of PCV vaccines with improved immunogenicity have significantly reduced the morbidity and mortality associated with IPD in high-risk patients. Pneumococcal vaccines also play an important role in the diagnosis and immunophenotyping of children and adults with inborn errors of immunity (IEI) given the increasing diversity/heterogeneity of IEI presenting with primary and/or specific antibody deficiency. Other than the quantitation of serotype levels in routine clinical care, other measurements of immune response including the functional activity of antibodies, antibody avidity, cell-mediated immunity, and immunological memory remain limited to clinical trials during vaccine development.

The most common cause of erythema multiforme (EM) in children is infectious diseases which account for approximately 90% of cases. Drug eruptions are another common cause. Here we are reporting about a male patient aged 14 years with lymphadenitis who developed severe diffuse erythema during the course of treatment with medications including several antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs). Based on the pathological findings of the skin biopsy, the skin rash was due to EM. Upon investigating the underlying cause of EM, viral antibody was positive for Coxsackie A6, lymphocyte transformation testing (LTT) was positive for one of the NSAIDs, and the patch test (PT) was positive for amoxicillin. Based on the pattern of distribution of the skin rash, the cause of EM was considered to be drug-induced eruption due to amoxicillin. In this case, we did not derive a diagnosis of drug eruption without investigating the possibility of drug induction, because most cases of EM in children are induced by infection and the antibody against Coxsackie A6 was elevated. To diagnose the possibility of amoxicillin-induced EM, it was important to distinguish between the distribution patterns of infectious versus drug-induced EM and to evaluate the possibility of drug induction by both LTT and PT. If the diagnosis of amoxicillin-induced EM, had not been made, the potential recurrence of EM with amoxicillin could have occurred.

Drug-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are non-immunoglobulin E-mediated severe cutaneous adverse reactions with a high risk of morbidity, mortality, and physical and mental health impact. These are associated with certain high-risk drugs, human leukocyte antigen (HLA)-specific genotypes and ethnicities. HLA class I-restricted oligoclonal CD8 cytotoxic T-cell responses occur at the tissue level in SJS/TEN. Cytotoxic T cells are the T effector cells that result in keratinocyte apoptosis (cell death) mediated by T effector molecules granzyme B, perforin, granulysin, gamma interferon, tumor necrosis factor-alpha, and lipocalin-2. The clinical hallmarks of SJS/TEN include fever, ≥2 mucosal involvements (ocular, oral, and genital), and positive Nikolsky sign with epidermal detachment. Systematic reviews on immunomodulatory treatments remain limited by the paucity of randomized controlled trials, heterogeneity of studies, and non-standardization of outcome measures. Preventive HLA genotype screening before the prescription of carbamazepine and allopurinol may further reduce the incidence of SJS/TEN. The role of immunomodulatory treatments in SJS/TEN is at present not supported by robust evidence from systematic reviews given the lack of randomized controlled trials. The evidence for improved survival with off-label use of corticosteroids plus intravenous immunoglobulins, ciclosporin plus intravenous immunoglobulins, and ciclosporin alone has not been demonstrated by network meta-analyses and meta-regression. In the real-world clinical setting, systemic corticosteroids (in SJS and overlap SJS/TEN), ciclosporin, and etanercept (in TEN) appear to be the off-label treatments currently most widely used.

BackgroundEosinophils are major effector cells of allergic disease and excellent markers of eosinophilic inflammation. Accurate and reliable biomarkers are helpful in the diagnosis, treatment, and control of allergic disease.ObjectiveThis study aimed to investigate an alternate marker of eosinophilic inflammation, eosinophil-derived neurotoxin (EDN), in a number of allergic diseases.MethodsThree hundred ninety-six elementary school-age children with various allergic conditions were recruited for this study. Subgroups included food allergies (FAs), atopic dermatitis (AD), bronchial asthma (BA), and allergic rhinitis (AR). EDN levels in these groups were compared to those in 93 healthy controls (HC).ResultsAll subjects with allergic disease had elevated levels of serum EDN (median [interquartile range]: FA, 124.2 ng/mL [59.13–160.5 ng/mL]; AD, 110.8 ng/mL [57.52–167.9 ng/mL]; BA, 131.5 ng/mL [60.60–171.0 ng/mL]; AR, 91.32 ng/mL [46.16–145.0 ng/mL]) compared to HC (38.38 ng/mL [32.40–55.62 ng/mL]) (p < 0.0001). These elevated levels were consistent throughout the age range (6–12 years) of the healthy study subjects (p = 0.0679). EDN levels also correlated well with total immunoglobulin E (Rs = 0.5599, p < 0.0001). Looking at all individuals with an allergic disease, the area under the curve was 0.790.ConclusionsDirect measures of eosinophilic inflammation are needed for accurate diagnosis, treatment, and monitoring of allergic diseases. EDN may be a worthy biomarker of eosinophil activity and a useful screening tool for allergic diseases including FA, AD, BA, and AR.

1Philippine Society of Allergy Asthma & Immunology, Pasig City, the Philippines. Correspondence to Maria Carmela Kasala. Philippine Society of Allergy Asthma & Immunology, Unit 2504 Medical Plaza Ortigas, 25 San Miguel Avenue, Pasig City, the Philippines. e-mail; [email protected] Received April 21, 2022; Accepted April 22, 2022; previously published online April 22, 2022

Cytokine release syndrome (CRS) is a type of hypersensitivity reaction which has been previously described with chemotherapy and monoclonal antibodies, but not with antibiotics. We present 2 pediatric cases of Amoxicillin/Clavulanic acid (Augmentin) anaphylaxis resembling CRS. Both our patients presented during the index reaction with symptoms suggestive of an acute systemic inflammatory response mimicking sepsis. Their symptomology was reproducible at drug provocation test as anaphylaxis, but with suboptimal response to intramuscular adrenaline. Their infective workups were unremarkable and illnesses followed a self-limiting course. All these point towards a severe hypersensitivity reaction resembling CRS.