OBJECTIVE: Here, we sought to investigate whether genetic polymorphisms at IL13 are associated with the development of challenge-proven IgE-mediated food allergy.
METHOD: We genotyped nine IL13 "tag" single nucleotide polymorphisms (tag SNPs) in 367 challenge-proven food allergic cases, 199 food-sensitized tolerant cases and 156 non-food allergic controls from the HealthNuts study. 12-month-old infants were phenotyped using open oral food challenges. SNPs were tested using Cochran-Mantel-Haenszel test adjusted for ancestry strata. A replication study was conducted in an independent, co-located sample of four paediatric cohorts consisting of 203 food allergic cases and 330 non-food allergic controls. Replication sample phenotypes were defined by clinical history of reactivity, 95% PPV or challenge, and IL13 genotyping was performed.
RESULTS: IL13 rs1295686 was associated with challenge-proven food allergy in the discovery sample (P=.003; OR=1.75; CI=1.20-2.53). This association was also detected in the replication sample (P=.03, OR=1.37, CI=1.03-1.82) and further supported by a meta-analysis (P=.0006, OR=1.50). However, we cannot rule out an association with food sensitization. Carriage of the rs1295686 variant A allele was also associated with elevated total plasma IgE.
CONCLUSIONS AND CLINICAL RELAVANCE: We show for the first time, in two independent cohorts, that IL13 polymorphism rs1295686 (in complete linkage disequilibrium with functional variant rs20541) is associated with challenge-proven food allergy.
OBJECTIVE: To determine whether genetic variants in and around SPINK5 are associated with IgE-mediated food allergy.
METHOD: We genotyped 71 "tag" single nucleotide polymorphisms (tag-SNPs) within a region spanning ~263 kb including SPINK5 (~61 kb) in n=722 (n=367 food-allergic, n=199 food-sensitized-tolerant and n=156 non-food-allergic controls) 12-month-old infants (discovery sample) phenotyped for food allergy with the gold standard oral food challenge. Transepidermal water loss (TEWL) measures were collected at 12 months from a subset (n=150) of these individuals. SNPs were tested for association with food allergy using the Cochran-Mantel-Haenszel test adjusting for ancestry strata. Association analyses were replicated in an independent sample group derived from four paediatric cohorts, total n=533 (n=203 food-allergic, n=330 non-food-allergic), mean age 2.5 years, with food allergy defined by either clinical history of reactivity, 95% positive predictive value (PPV) or challenge, corrected for ancestry by principal components.
RESULTS: SPINK5 variant rs9325071 (A⟶G) was associated with challenge-proven food allergy in the discovery sample (P=.001, OR=2.95, CI=1.49-5.83). This association was further supported by replication (P=.007, OR=1.58, CI=1.13-2.20) and by meta-analysis (P=.0004, OR=1.65). Variant rs9325071 is associated with decreased SPINK5 gene expression in the skin in publicly available genotype-tissue expression data, and we generated preliminary evidence for association of this SNP with elevated TEWL also.
CONCLUSIONS: We report, for the first time, association between SPINK5 variant rs9325071 and challenge-proven IgE-mediated food allergy.
Methods: A survey instrument was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to collect both structured and semi-structured data on X-linked agammaglobulinemia. The survey was sent to 54 centers around the world chosen on the basis of World Allergy Organization participation and/or registration in the European Society for Immunodeficiencies. There were 40 centers that responded, comprising 32 countries.
Results: This study reports on 783 patients from 40 centers around the world. Problems with diagnosis are highlighted by the reported delays in diagnosis>24 months in 34% of patients and the lack of genetic studies in 39% of centers Two infections exhibited regional variation. Vaccine-associated paralytic poliomyelitis was seen only in countries with live polio vaccination and two centers reported mycobacteria. High rates of morbidity were reported. Acute and chronic lung diseases accounted for 41% of the deaths. Unusual complications such as inflammatory bowel disease and large granular lymphocyte disease, among others were specifically enumerated, and while individually uncommon, they were collectively seen in 20.3% of patients. These data suggest that a broad range of both inflammatory, infectious, and autoimmune conditions can occur in patients. The breadth of complications and lack of data on management subsequently appeared as a significant challenge reported by centers. Survival above 20 years of age was lowest in Africa (22%) and reached above 70% in Australia, Europe and the Americas. Centers were asked to report their challenges and responses (n = 116) emphasized the difficulties in access to immunoglobulin products (16%) and reflected the ongoing need for education of both patients and referring physicians.
Conclusions: This is the largest study of patients with X-linked agammaglobulinemia and emphasizes the continued morbidity and mortality of XLA despite progress in diagnosis and treatment. It presents a world view of the successes and challenges for patients and physicians alike. A pivotal finding is the need for education of physicians regarding typical symptoms suggesting a possible diagnosis of X-linked agammaglobulinemia and sharing of best practices for the less common complications.
METHODS: This is a five-year retrospective review on contact sensitisation in adults patch-tested with the European Standard and extended series between 2011 and 2015 in the Department of Dermatology, Hospital Kuala Lumpur.
RESULTS: There were 689 adults (M:F= 1:2.04; mean age 40.5 years) who were patch-tested. The majority (175, 25.4%) were white collar workers and 118 (17.1%) were healthcare workers. The provisional diagnoses of patients included contact dermatitis (80.8%); endogenous eczema (7.9%); hand eczema (3.2%); hand and foot eczema (3.5%); foot eczema (1.4%) and photodermatitis (1.2%). The allergens selected for testing were based on past and present history of exposure. Almost all (688, 99.8%) were patch-tested with the European standard allergens and 466 (67.6%) were tested with the extended series. About three quarter (528, 76.6%) developed at least one positive reaction. The top five most frequent reactions were to nickel sulphate (35.3%); potassium dichromate (16.5%); methylchloroisothiazolinone (12.9%), fragrance mix I (12.6%), and cobalt chloride (10.2%). The commonest sensitisations identified in the extended series were palladium chloride (23/105, 21.9%), stannous chloride (18/85, 21.2%), miconazole (7/44, 15.9%), gold(I)sodium thiosulfate (16/105, 15.2%) and thimerosal (29/202, 14.4%).
CONCLUSION: Contact sensitisation was detected in 76.6% of adults patch-tested. Nickel sulphate was found to be the most frequently sensitising allergen. The rising prevalence of methylchloroisothiazolinone/methylisothiazolinone sensitization poses significant concern.
CONCLUSIONS: Use of evolocumab robustly lowers LDL-C and is equally efficacious in lowering the risk of cardiovascular events and safe in Asians as it is in others.
OBJECTIVE: The present study aimed to measure the agreement between BAT and immunoassay in diagnosis of penicillin allergy.
METHOD: BAT was performed using penicillin G (Pen G), penicillin V (Pen V), penicilloyl-polylysine (PPL), minor determinant mix (MDM), amoxicillin (Amx) and ampicillin (Amp) in 25 patients. Immunoassay of total IgE (tIgE) and specific IgE (sIgE) antibodies to Pen G, Pen V, Amx and Amp were quantified. Skin prick test (SPT) using PPL-MDM, Amx, Amp and Clavulanic acid were also performed.
RESULTS: Minimal agreement was observed between BAT and immunoassay (k=0.25). Of two BAT-positive patients, one patient is positive to Amx (59.27%, SI=59) and Amp (82.32%, SI=82) but sIgE-negative to all drug tested. This patient is also SPT-positive to both drugs. Another patient is BAT-positive to Pen G (10.18%, SI=40), Pen V (25.07%, SI=100) and Amp (19.52%, SI=79). In sIgE immunoassay, four patients were sIgE-positive to at least one of the drugs tested. The sIgE level of three patients was between low and moderate and they were BAT-negative. One BAT-positive patient had a high level of sIgE antibodies (3.50-17.5kU/L) along with relatively high specific to total IgE ratio ≥0.002 (0.004-0.007).
CONCLUSIONS: The agreement between BAT and immunoassay is minimal. Performing both tests provides little increase in the sensitivity of allergy diagnosis work-up for immediate reactions to penicillin.
OBJECTIVE: The main objective of this survey was to evaluate the epidemiology of FA, as well as the availability of resources and practices for management of FA and anaphylaxis by health care providers across Asia.
METHODS: From June 2022 to September 2022, a questionnaire-based survey comprising 66 questions was electronically sent to member societies of the Asia Pacific Association of Allergy Asthma and Clinical Immunology by using Survey Monkey.
RESULTS: A total of 20 responses were received from 15 member countries and territories. Compared with the pediatric data, there was a lack of prevalence data for FA in adults. Except for Australia and Japan, most regions had between 0.1 and 0.5 allergists per 100,000 population and some had fewer than 0.1 allergists per 100,000 population. The perceived rate of FA in regions with a short supply of allergists was high. Although specific IgE tests and oral food challenges were available in all regions, the median wait time for oral food challenges at government facilities was 37 days (interquartile range = 10.5-60 days). Seven regions still relied on prescriptions of ampules and syringes of injectable adrenaline, and adrenaline autoinjectors were not accessible in 4 regions. Oral immunotherapy as FA treatment was available in half of the surveyed countries and territories.
CONCLUSIONS: Our study offers a cross-sectional evaluation of the management practices for FA in each Asia Pacific Association of Allergy Asthma and Clinical Immunology member country or territory. Urgent actions are required to enhance allergy services, improve the accessibility and affordability of adrenaline autoinjectors, and conduct robust epidemiologic studies.
OBJECTIVE: We aim to report the frequency of liver disease among psoriasis patients, describe the clinical features, treatment modalities and quality of life.
METHODS: This was a multi-center cross-sectional study of psoriasis patients notified to the Malaysian Psoriasis Registry (MPR) from January 2007 to December 2018.
RESULTS: Of 21,735 psoriasis patients, 174 (0.8%) had liver disease. The three most common liver diseases were viral hepatitis (62.1%), fatty liver (14.4%) and liver cirrhosis (10.9%). The male-to-female ratio was 3.8:1. Mean age of onset of psoriasis was higher in those with liver disease compared to those without (37.25 ± 13.47 years vs 33.26 ± 16.96 years, p 10% and/or DLQI > 10) (59.3%vs49.9%, p = 0.027), psoriatic arthropathy (21.1%vs13.0%, p = 0.002), and nail involvement (78.2%vs56.1%, p
METHODS: This was a prospective study conducted from 15th January 2022 till 15th October 2022 at Dermatology Clinic, Hospital Melaka. Subjects with clinical dermatomycoses were included in this study. The samples were collected from skin, nails and hairs clinically affected by tinea corporis/cruris/pedis, onychomycosis and tinea capitis respectively. A potassium hydroxide (KOH) study was performed on the sample in which the fungal hyphae/yeast positive subjects were sent for fungal culture and fungal PCR test.
RESULT: A total of 222 clinical samples from skin, nails and hairs with a clinical suspicion of dermatomycoses yielded fungal hyphae/yeast in KOH. Majority of the samples were collected from skin (138, 62.2%), followed by nails (65, 29.3%) and hairs (19, 8.6%). Male to female ratio was 1.18: 1. The age ranged from 2 to 87 with the median of 55.5-yearsold. Out of 222 samples, 150 (67.6%) were fungal culture positive. From fungal culture positive samples, 87 samples were from tinea corporis, 50 samples were from onychomycoses and 13 samples were from tinea capitis. Trichophyton rubrum (39, 44.8%) was the commonest dermatophyte isolated in tinea corporis/cruris/pedis. Nondermatophyte moulds (NDM, 35, 70%) were the main fungi isolated in onychomycosis. Microsporum canis (7/53.8%) was the principal causative fungus among patients with tinea capitis. Among 150 fungal culture positive samples, 76 were fungal PCR positive. Only 38 samples consistently isolated same fungal species in both fungal culture and PCR test.
CONCLUSION: Majority of tinea corporis and tinea capitis fungal culture isolated dermatophytes, especially Trichophyton rubrum and Microsporum canis, respectively. Non-dermatophyte moulds were mainly isolated in onychomycosis.
METHODS: This is a retrospective study on all HIV-infected MSM with syphilis between 2011 and 2015. Data was collected from case notes in five centres namely Hospital Kuala Lumpur, Hospital Sultanah Bahiyah, Hospital Umum Sarawak, University of Malaya Medical Centre and Hospital Sungai Buloh.
RESULTS: A total of 294 HIV seropositive MSM with the median age of 29 years (range 16-66) were confirmed to have syphilis. Nearly half (47.6%) were in the age group of 20-29 years. About a quarter (24.1%) was previously infected with syphilis. Eighty-three patients (28.2%) had other concomitant sexually transmitted infection with genital warts being the most frequently reported (17%). The number of patients with early and late syphilis in our cohort were almost equal. The median pre-treatment non-treponemal antibody titre (VDRL or RPR) for early syphilis (1:64) was significantly higher than for late syphilis (1:8) (p<0.0001). The median CD4 count and the number of patients with CD4 <200/μl in early syphilis were comparable to late syphilis. Nearly four-fifth (78.9%) received benzathine-penicillin only, 5.8% doxycycline, 1.4% Cpenicillin, 1% procaine penicillin, and 12.4% a combination of the above medications. About 44% received treatment and were lost to follow-up. Among those who completed 1 -year follow-up after treatment, 72.3% responded to treatment (serological non-reactive - 18.2%, four-fold drop in titre - 10.9%; serofast - 43.6%), 8.5% failed treatment and 17% had re-infection. Excluding those who were re-infected, lost to follow-up and died, the rates of treatment failure were 12.1% and 8.8% for early and late syphilis respectively (p=0.582).
CONCLUSION: The most common stage of syphilis among MSM with HIV was latent syphilis. Overall, about 8.5% failed treatment at 1-year follow-up.
METHODS AND RESULTS: The discussion ranged from examining scientific literature supporting the efficacy of established prebiotics, to the prospects for establishing health benefits associated with novel compounds, isolated from different sources.
CONCLUSIONS: While many promising candidate prebiotics from across the globe have been highlighted in preliminary research, there are a limited number with both demonstrated mechanism of action and defined health benefits as required to meet the prebiotic definition. Prebiotics are part of a food industry with increasing market sales, yet there are great disparities in regulations in different countries. Identification and commercialization of new prebiotics with unique health benefits means that regulation must improve and remain up-to-date so as not to risk stifling research with potential health benefits for humans and other animals.
SIGNIFICANCE AND IMPACT OF STUDY: This summary of the workshop discussions indicates potential avenues for expanding the range of prebiotic substrates, delivery methods to enhance health benefits for the end consumer and guidance to better elucidate their activities in human studies.
MATERIALS AND METHODS: This is a 5-year retrospective study of patients who developed positive reactions to fragrance allergens at the Department of Dermatology, Hospital Kuala Lumpur, Malaysia between January 2017 and December 2021. Patch tests were performed with European Baseline Series and relevant extended series. Patch test readings were recorded according to the International Contact Dermatitis Research Group recommendation.
RESULTS: A total of 854 patients underwent patch test during the study period with 133 (15.6%) patients developing at least one positive reaction to fragrance allergens. The median age of patients at presentation was 40 years (range 16-79) old with 78.2% females. The most common initial presentation was hand eczema (55.6%). Other commonly involved sites include face (38.3%), leg (35.3%) and trunk (22.6%). The most frequent sensitising fragrance allergens were Fragrance Mix I (10.5%), Balsam of Peru (7.1%) and Fragrance Mix II (4.9%). Sixty patients (45%) developed positive reaction to more than one fragrance allergens. Twelve patients (9%) developed positive patch test reactions to their own products such as skincare, hair dye and hand wash. Current relevance was recorded in 96 patients (72.2 %).
CONCLUSION: Contact sensitisation to fragrance allergens was detected in about 15% of our patients who underwent patch test. The most common sensitising allergens were Fragrance Mix I and II and Balsam of Peru.