Epidemiology and risk factors for drug allergy.

The aim of this review was to describe the current evidence-based knowledge of the epidemiology, prevalence, incidence, risk factors and genetic associations of drug allergy. Articles published between 1966 and 2010 were identified in MEDLINE using the key words adult, adverse drug reaction reporting systems, age factors, anaphylactoid, anaphylaxis, anaesthetics, antibiotics, child, drug allergy, drug eruptions, ethnic groups, hypersensitivity, neuromuscular depolarizing agents, neuromuscular nondepolarizing agents, sex factors, Stevens Johnson syndrome and toxic epidermal necrolysis. Additional studies were identified from article reference lists. Relevant, peer-reviewed original research articles, case series and reviews were considered for review. Current epidemiological studies on adverse drug reactions (ADRs) have used different definitions for ADR-related terminology, often do not differentiate immunologically and non-immunologically mediated drug hypersensitivity, study different study populations (different ethnicities, inpatients or outpatients, adults or children), utilize different methodologies (spontaneous vs. non-spontaneous reporting, cohort vs. case-control studies), different methods of assessing drug imputability and different methods of data analyses. Potentially life-threatening severe cutaneous adverse reactions (SCAR) are associated with a high risk of morbidity and mortality. HLA associations for SCAR associated with allopurinol, carbamazepine and abacavir have been reported with the potential for clinical use in screening prior to prescription. Identification of risk factors for drug allergy and appropriate genetic screening of at-risk ethnic groups may improve the outcomes of drug-specific SCAR. Research and collaboration are necessary for the generation of clinically-relevant, translational pharmacoepidemiological and pharmacogenomic knowledge, and success of health outcomes research and policies on drug allergies.

Controversies in Drug Allergy: Drug Allergy Pathways.

Drug allergy pathways are standardized approaches for patients reporting prior drug allergies with the aim of quality improvement and promotion of antibiotic stewardship. At the International Drug Allergy Symposium during the 2018 American Academy of Allergy, Asthma, and Immunology/World Allergy Organization Joint Congress in Orlando, Florida, drug allergy pathways were discussed from international perspectives with a focus on beta-lactam allergy pathways and pragmatic approaches for acute care hospitals. In this expert consensus document, we review current pathways, and detail important considerations in devising, implementing, and evaluating beta-lactam allergy pathways for hospitalized patients. We describe the key patient and institutional factors that must be considered in risk stratification, the central feature of pathway design. We detail shared obstacles to widespread beta-lactam allergy pathway implementation and identify potential solutions to address these challenges.

Outcomes of chronic hepatitis B infection in Oriental patients with rheumatic diseases.

INTRODUCTION: The aim of this study was to ascertain the outcomes of chronic hepatitis B (CHB) infection following immunosuppressive therapy in 38 consecutive oriental patients with systemic rheumatic diseases. MATERIALS AND METHODS: This is a retrospective consecutive, non-comparative study. RESULTS: The majority of patients were female (26, 68.4%), predominantly Chinese (92.1%), with a mean age 54 +/- 14 years (range, 16 to 87). The mean duration of rheumatic disease was 9 +/- 11 years (range, 0.1 to 48), with rheumatoid arthritis (52.6%) and systemic lupus erythematosus (23.7%) being the most common. The mean duration of CHB infection was 6 +/- 5 years (range, 0.1 to 17), with the majority diagnosed during pre-methotrexate screening (50.0%) and asymptomatic transaminitis following initiation of immunosuppressive therapy (23.7%). Upon diagnosis of rheumatic disease, all patients had normal alanine aminotransferase (ALT). Of these, 18.2% were positive for hepatitis B e antigen (HBeAg) and 78.1% were positive for anti- HBe antibody. Twenty (52.6%) developed ALT elevation, which was more than twice the upper limit of normal in 12 patients. ALT normalised spontaneously in 12 patients without hepatic decompensation or change in therapy. Seven (18.4%) patients received lamivudine for 18 +/- 22 months (range, 2 to 61). Two patients developed YMDD mutation subsequently treated with adefovir (1) and adefovir/lamivudine (1). There were 3 (7.9%) hepatitis B virus (HBV)-unrelated deaths [infection (2), genitourinary malignancy (1)], and 1 from HBV-reactivation complicated by septicaemia. None have developed hepatocellular carcinoma. CONCLUSION: Elevated ALT occurred in 52.6% of patients, with only 18.4% requiring anti-viral therapy for HBV reactivation. HBV-related mortality was low. With the appropriate precautionary measures, prednisolone and immunosuppressants (except methotrexate and leflunomide) may be used safely in patients where clinically indicated.

Comparison of elderly- and young-onset rheumatoid arthritis in an Asian cohort.

OBJECTIVE: To describe the demographic characteristics, clinical features, functional status and quality of life of elderly-onset (EORA) and young-onset (YORA) rheumatoid arthritis (RA) patients in an Asian cohort. METHODS: We studied all RA patients in our prospective disease registry, utilizing baseline data. EORA was defined as disease onset at 60 years or older. We collected data from January 2001 to December 2012. RESULTS: There were 1206 patients in our cohort, of which 178 (14.8%) had EORA, with a mean age of onset of 66.7 ± 5.6 years. There were more males in the EORA than YORA group (23.0% vs. 14.7%, P = 0.005). EORA patients were diagnosed sooner after symptom onset and had a higher number of comorbidities (median 2 [inter-quartile range 1-3] vs. 1 (0-2), P < 0.001). They were less likely to be rheumatoid factor positive, had higher erythrocyte sedimentation rate values and lower hemoglobin concentrations. There was no significant difference in joint counts, Disease Activity Score of 28 joints activity score and prevalence of radiographic erosions. Though EORA patients had worse Health Assessment Questionnaire scores and poorer functional status than YORA ones, they had lower pain scores and higher scores in the general health and mental component summary of the Short Form-36. EORA patients received significantly lower numbers of disease-modifying anti-rheumatic drugs. CONCLUSIONS: EORA and YORA patients had different demographic characteristics. Although they had similar disease activities, EORA patients received less intensive treatment. EORA patients had a higher number of RA-related co-morbidities and poorer physical functioning but they coped better emotionally and mentally.

Urine sVCAM-1 and sICAM-1 levels are elevated in lupus nephritis.

AIM: We sought to evaluate the relationship of urine levels of soluble cellular adhesion molecules sVCAM-1 (vascular) and sICAM-1 (intercellular) in systemic lupus erythematosus (SLE) patients with or without lupus nephritis, and to explore their correlation with renal disease activity. METHODS: Paired serum and urine samples of 121 Asian SLE patients, and urine samples of 19 normal healthy controls were collected. Demographic data, disease activity and damage scores, and selected laboratory parameters, including levels of anti-double stranded DNA antibody, complements C3, C4, and creatinine were captured. Renal disease activity was scored with renal SLE Activity Measure revised (rSLAM-R). Serum and urine sVCAM-1 and sICAM-1 levels were assayed by enzyme-linked immunosorbent assay. RESULTS: Urinary sVCAM-1 and sICAM-1 were elevated in SLE patients compared to controls. Significantly higher levels of urine sVCAM-1 found in patients with active lupus nephritis correlated with rSLAM-R. In addtion, significantly more patients with active lupus nephritis had detectable levels of urine sICAM-1, but no correlation with renal activity was observed. CONCLUSION: Urinary sVCAM-1 may serve as a potential biomarker for early diagnosis of lupus nephritis as levels correlated with even mild abnormalities of urine sediment. In addition, both urine sVCAM-1 and sICAM-1 levels may be useful in identifying patients at risk of lupus nephritis.

Association of a common complement receptor 2 haplotype with increased risk of systemic lupus erythematosus.

A genomic region on distal mouse chromosome 1 and its syntenic human counterpart 1q23-42 show strong evidence of harboring lupus susceptibility genes. We found evidence of linkage at 1q32.2 in a targeted genome scan of 1q21-43 in 126 lupus multiplex families containing 151 affected sibpairs (nonparametric linkage score 2.52, P = 0.006). A positional candidate gene at 1q32.2, complement receptor 2 (CR2), is also a candidate in the murine Sle1c lupus susceptibility locus. To explore its role in human disease, we analyzed 1,416 individuals from 258 Caucasian and 142 Chinese lupus simplex families and demonstrated that a common three-single-nucleotide polymorphism CR2 haplotype (rs3813946, rs1048971, rs17615) was associated with lupus susceptibility (P = 0.00001) with a 1.54-fold increased risk for the development of disease. Single-nucleotide polymorphism 1 (rs3813946), located in the 5' untranslated region of the CR2 gene, altered transcriptional activity, suggesting a potential mechanism by which CR2 could contribute to the development of lupus. Our findings reveal that CR2 is a likely susceptibility gene for human lupus at 1q32.2, extending previous studies suggesting that CR2 participates in the pathogenesis of systemic lupus erythematosus.