OBJECTIVE: To determine the clinical characteristics, culprit drugs and outcome of patients with AGEP.
METHODS: A retrospective note review of all AGEP patients seen from 2001-2015.
RESULTS: Among 21 AGEP patients, 76% were Malays, 9.5% Chinese, 9.5% Indians, and 5% Iban. Sixteen were females and 5 were males. Median age of patients was 40 years (IQR: 26). The main culprit drug was amoxicillin (10 cases), followed by cloxacillin (three cases), phenytoin (two cases) and one case each of carbamazepine, sulphasalazine, allopurinol, cephalexin, ceftriaxone, celecoxib and herbal product. The median time from drug initiation to onset of AGEP was 3 days (IQR: 5.5). Fever was documented in 52.4 %, mucosal involvement 9.5%, purpura 4.7% and blisters 4.7%. Neutrophilia was observed in 63.6% of patients and eosinophilia in 28.5%. While most patients required admission (67%), all achieved complete recovery within 15 days without any sequela.
CONCLUSIONS: AGEP predominantly affects Malay females in this study. The most common culprit drug was amoxicillin. Our patients exhibited the classic clinical manifestations of AGEP and confirmed the generally benign nature of this reaction upon drug withdrawal. Although the overall prognosis is good, prompt diagnosis of AGEP is important because drug withdrawal is the mainstay therapy.
OBJECTIVES: To consider which items from a long list of candidate items to exclude and which to cluster into outcome domains.
METHODS: The study used an international and multistakeholder approach, involving patients, dermatologists, surgeons, the pharmaceutical industry and medical regulators. The study format was a combination of formal presentations, small group work based on nominal group theory and a subsequent online confirmation survey.
RESULTS: Forty-one individuals from 13 countries and four continents participated. Nine items were excluded and there was consensus to propose seven domains: disease course, physical signs, HS-specific quality of life, satisfaction, symptoms, pain and global assessments.
CONCLUSIONS: The HISTORIC consensus meetings I and II will be followed by further e-Delphi rounds to finalize the core domain set, building on the work of the in-person consensus meetings.
METHODS: This cross-sectional study employed a validated, self-administered questionnaire which was administered to 543 first-year pharmacy students from nine different private universities. Factor analysis was utilised to extract key factors from the responses. Descriptive and inferential statistics were used to analyse the data.
KEY FINDINGS: Eight factors motivating students' decision to study pharmacy emerged from the responses, accounting for 63.8% of the variance observed. Students were primarily motivated by intrinsic interests, with work conditions and profession attributes also exerting significant influence. In terms of choice of private university, nine factors were identified, accounting for 73.8% of the variance observed. The image of the school and university were most influential factors in this context, followed by university safety, programme attributes and financial factors.
CONCLUSIONS: First-year pharmacy students in the private higher education sector are motivated by intrinsic interest when choosing to study pharmacy over other courses, while their choice of private university is influenced primarily by the image of the school and university.
OBJECTIVE: To describe the clinical spectrum and identify risk factors for chronicity of cutaneous vasculitis.
METHODS: Retrospective data analysis of 275 patients diagnosed with cutaneous vasculitis from January 2008 to December 2013.
RESULTS: The mean age was 33.7 (±17.89) years, with female predominance. The majority of patients were Malays (67.3%). Skin biopsy was performed in 110 (40%) patients. The commonest sign was palpable purpura (30.6%). The aetiology remained elusive in 51.3% of patients. Common identifiable causes include infection (19.7%) and connective tissue disease (10.2%). Extracutaneous features were noted in 46.5% of patients. Erythrocyte sedimentation rate and antinuclear antibody were raised in 124 of 170 and 27 of 175 patients with documented results respectively. Cutaneous vasculitis was the presenting symptom in seven patients with newly diagnosed systemic lupus erythematosus. Anti Streptolysin O Titre was positive in 82 of 156 patients with documented results. Despite antibiotics, 31.7% of them had chronic lesions. Prednisolone alone was used in 20% of patients while 16.4% needed steroid-sparing agents. Most patients who needed systemic therapy (62%) had unidentifiable aetiology. Among the 155 patients who remained under follow up, 36.4% had chronic disease, one patient succumbed due to septicaemia, and the rest fully recovered within three months. The presence of ulcerative lesion was significantly associated with developing chronic vasculitis (p=0.003).
CONCLUSION: The clinical spectrum of cutaneous vasculitis in our population was similar to other studies. Ulcerative lesion predicts a chronic outcome.
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.
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 the incidence, clinical features and risk factors of cADRs among hospitalized patients.
METHODS: A prospective study was conducted among medical inpatients from July to December 2014.
RESULTS: A total of 43 cADRs were seen among 11 017 inpatients, yielding an incidence rate of 0.4%. cADR accounted for hospitalization in 26 patients. Previous history of cADR was present in 14 patients, with 50% exposed to the same drug taken previously. Potentially lifethreatening severe cutaneous adverse reactions (SCAR), namely drug reaction with eosinophilia and systemic symptoms (DRESS: 14 cases) and Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN: 6 cases) comprise almost 50% of cADRs. The commonest culprit drug group was antibiotics (37.2%), followed by anticonvulsants (18.6%). Cotrimoxazole, phenytoin and rifampicin were the main causative drugs for DRESS. Anticonvulsants were most frequently implicated in SJS/TEN (66.7%). Most cases had "probable" causality relationship with suspected drug (69.8%). The majority of cases were of moderate severity (65.1%), while 18.6% had severe reaction with 1 death recorded. Most cases were not preventable (76.7%). Older age (> 60 years) and mucosal involvement were significantly associated with a more severe reaction.
CONCLUSION: The incidence of cADRs was 0.4%, with most cases classified as moderate severity and not preventable. The commonest reaction pattern was DRESS, while the main culprit drug group was antibiotics. Older age and mucosal membrane involvement predicts a severe drug reaction.