Follow-up of penicillin allergy labels 1 year after successful penicillin delabeling.

BACKGROUND: Penicillin allergy delabeling confers many benefits, including reduced patient morbidity and mortality and improved health economics. Reports suggest that both patients and clinicians often remain hesitant to take and prescribe penicillins, respectively, after penicillin delabeling. However, follow-up of an individual's penicillin allergy label and incorporation of this into relevant health care records after delabeling have not been well studied in the Australian population. OBJECTIVE: To evaluate the status of penicillin allergy labels in the community 1 year after penicillin delabeling at a tertiary hospital in Australia. METHODS: A cross-sectional study was performed using follow-up interviews with patients and community primary care providers after 1 year from the date of patients' penicillin delabeling at a tertiary hospital in New South Wales, Australia. The main outcome measures that were evaluated included patient willingness to accept penicillin for future infections, patient self-reported receipt of penicillin-based antibiotics after delabeling, accuracy of penicillin allergy labels in the records of the primary care provider, and prescription of penicillin-based antibiotics by the general practitioner. RESULTS: A total of 86 patients were included in this study. The percentage of patients with a correct penicillin allergy status at 1-year follow-up was 94% in the hospital electronic medical record but only 37% in primary care records. At 1-year follow-up, 14% of delabeled patients continued to reject penicillin prescriptions. CONCLUSION: Better strategies are required to increase patient confidence in receiving penicillins after penicillin delabeling and to ensure that penicillin allergy labels are translated into the medical records at the primary care level.

A retrospective review of immunology patients with primary and/or secondary immunodeficiency, demonstrating the benefits of the rapid transitioning from intravenous immunoglobulin to subcutaneous immunoglobulin at the onset of the COVID-19 pandemic.

Forty-four of 50 immunology patients with primary or secondary immunodeficiency receiving intravenous immunoglobulin at a hospital in New South Wales, Australia, were rapidly enrolled in the subcutaneous immunoglobulin (SCIg) programme at the onset of the 2020 COVID-19 pandemic. Health and economic outcomes demonstrated that SCIg provides clinical efficacy as evidenced by the number of infections and maintenance of IgG levels, and also facilitates cost reduction in immunoglobulin maintenance programmes.

Oral food challenge outcomes in children and adolescents in a tertiary centre: A 5-year experience.

AIM: Oral food challenges (OFC) are an important tool in the assessment of food allergy. We sought to identify factors available at initial assessment visit which were associated with successful outcome or challenge failure in Australian children. METHODS: We conducted a retrospective review of all paediatric patients who underwent OFC in our allergy service over a 5-year period. Clinical data comprising patient demographics, co-morbidities, skin prick test (SPT) results, nature of previous reactions, elapsed time since previous reactions and outcome at OFC were recorded. RESULTS: Four hundred and fifty-six OFCs were conducted, with 56 cases (12.3%) resulting in a reaction. Likelihood of reaction at OFC was significantly increased for patients with atopic dermatitis (odds ratio 1.99). When stratified by food substance, atopic dermatitis had the strongest association with reaction within the peanut group (odds ratio 3.2), and no association was demonstrated for soy or prawn. Increasing SPT wheal size (P < 0.001) and previous history of anaphylaxis to the challenge food (P < 0.001) correlated with failure at OFC. A low-risk group was identified, of patients with no clear history of prior reaction to the challenge food, and SPT result <3 mm. CONCLUSIONS: Factors identified at assessment visit which correlated with reaction at OFC are atopic dermatitis, prior history of anaphylaxis, and increasing SPT wheal size. Domiciliary OFC could be considered in a select low-risk group of patients undergoing food challenge. This study was performed at a single centre with limited sample size, further large-scale and multicentre study verification of our data will provide more accurate representation of the Australian demographic.

The utility of surrogate markers in predicting HLA alleles associated with adverse drug reactions in Vietnamese.

BACKGROUND: Screening for HLA-A*31:01/HLA-B*15:02, HLA-B*57:01 and HLA-B*58:01 is recommended in selected populations for prevention of carbamazepine, abacavir, and allopurinol-induced severe cutaneous adverse reactions (SCARs). Compared to conventional methods for detection of HLA alleles, PCR using a tag single nucleotide polymorphism (SNP) can be cost-effective, particularly where the surrogate marker SNP is in absolute linkage disequilibrium with the relevant HLA allele. OBJECTIVE: To determine guidelines for prevention of SCARs though predictive screening for the Australian Vietnamese population, the prevalence of four HLA alleles (HLA-A*31:01, HLA-B*15:02, HLA-B*57:01 and HLA-B*58:01) was examined. The utility of surrogate markers, rs2395029 and rs9263726, was investigated to predict for the presence of HLA-B*57:01 and HLA-B*58:01, respectively. METHODS: Genotyping for specific HLA alleles was performed in 152 healthy Vietnamese living in Sydney using validated and established PCR-based methods. SNP genotyping was conducted using restriction-fragment-length-polymorphism analysis. RESULTS: rs2395029 and rs9263726 strongly correlated with HLA-B*57:01 (κ = 1, p < 0.001) and HLA-B*58:01 (Κ = 0.9, p < 0.001) with 100% sensitivity and 100% negative predictive value for predicting the HLA-B*57:01 and HLA-B*58:01 carriers, respectively. A high prevalence of carriers of HLA-A*31:01 (3.29%), HLA-B*15:02 (14.47%), HLA-B*57:01 (6.58%) and HLA-B*58:01 (9.21%) was revealed. Conclusions: Screening is recommended for these alleles in Australian Vietnamese prior to introducing relevant therapies. SNPs, rs2395029 and rs9263726, can be successfully used as surrogate markers for HLA-B*57:01 and HLA-B*58:01 in this population.

IgE-mediated chlorhexidine allergy-Cross-reactivity with other biguanide disinfectants.

BACKGROUND: Chlorhexidine (CHX) is a widely utilized disinfectant that can cause IgE-mediated urticaria/anaphylaxis. The cross-reactivity of patients with IgE-mediated CHX allergy with other disinfectants, which share structural similarities with CHX like polyhexanide (polyhexamethylene biguanide; PHMB), alexidine (ALX), or octenidine (OCT), is unknown. METHODS: Forty-four patients with anaphylaxis or urticaria upon CHX exposure and positive skin prick test (SPT) and/or positive CHX ImmunoCAP test (Phadia TFS, Uppsala, Sweden) were recruited. IgE to the biguanide and/or hexamethylene structure was investigated with PHMB ImmunoCAP (n = 32) and by basophil activation tests (BAT) with CHX and ALX (n = 37). Inhibition tests of CHX and PHMB ImmunoCAPs by CHX, ALX, PHMB, and OCT were performed. RESULTS: IgE reactivity to PHMB as surrogate marker for biguanide/hexamethylene reactivity was detected in 5/32 sera. Seven of 37 patients showed a positive BAT with ALX, but only under optimized conditions. Binding to CHX ImmunoCAP was inhibited by ALX in 1/32 sera, and binding to PHMB was blocked by ALX (1/5) and by OCT in another (1/5). In SPT, 9/10 patients were positive for CHX and 3 of them with ALX (only at highest concentration at 5 mg/mL). A further patient reacted primarily with OCT and showed IgE cross-reactivity with CHX, ALX, and PHMB. CONCLUSION: The IgE response to CHX seems polyclonal. The chloroguanide ending of CHX is the main epitope for the IgE and is suitable as screening assay to detect CHX reactivity. IgE-reactivities with the biguanide or hexamethylene components of other disinfectants (ALX, PHMB) can be detected by SPT, PHMB ImmunoCAP, and ALX-BAT in 15%-33% of CHX-allergic patients.

Histological diagnosis of immune checkpoint inhibitor induced acute renal injury in patients with metastatic melanoma: a retrospective case series report.

BACKGROUND: Immune checkpoint inhibitors (ICI) have become the standard of care in many oncological conditions but are associated with a spectrum of renal immune-related adverse events (IrAEs). We aimed to describe the spectrum, histology, management and outcomes of renal IrAE in patients with metastatic melanoma undergoing ICI therapy. METHODS: We conducted a retrospective review of 23 patients with a diagnosis of metastatic melanoma treated with ICI between January 2017 and April 2019 who developed a renal IrAE. Baseline demographic data, biochemical and histopathological results, management and outcomes were analyzed. RESULTS: The majority of patients who developed renal irAE were male and received combination immunotherapy. The median time of onset from initiation of ICI therapy to renal IrAE was 4 months. 52% of the treated renal IrAE had histopathologically confirmed renal IrAE. The most common histological pattern of injury was acute tubulo-interstitial nephritis (92%). One patient developed anti-GBM disease with non-dialysis dependent stage 5 CKD. In tubulointerstitial injury, there was no association between peak creatinine, renal recovery and histologically reported inflammation or fibrosis. Patients with renal IrAE demonstrated persisting renal dysfunction at 3, 6 and 12 months with a mean baseline, 3 and 12 month creatinine of 90.0 µmol/L, 127.0 µmol/L and 107.5 µmol/L respectively. CONCLUSION: Renal IrAE is most commonly attributable to steroid responsive acute tubulointerstitial nephritis. The outcome of rarer pathologies such as anti-GBM disease may be adversely affected by a delayed diagnosis. There is persisting renal dysfunction following an episode of renal IrAE that may have impact on future renal and overall survival outcomes.

Safety of direct drug provocation testing in adults with penicillin allergy and association with health and economic benefits.

BACKGROUND: Nonprescription of penicillin-containing antibiotics in patients diagnosed with penicillin allergy is associated with morbidity and mortality. Adverse reactions to penicillins comprise type A and B reactions. OBJECTIVE: To assess the feasibility of penicillin allergy evaluation without penicillin skin testing (PST) for adult patients with type B reactions and the health and economic benefits of this process. METHODS: Inpatients at an Australian tertiary hospital between April 1, 2017, and April 30, 2018, with a diagnosis of type B penicillin allergy, requiring a penicillin-containing antibiotic for treatment, were included. All patients underwent clinical history review, PST, and drug provocation testing (DPT). RESULTS: Seventy-one patients were enrolled. Sixty-three reported a history of type B or unknown adverse reactions. No patients had a history of anaphylaxis requiring intubation or epinephrine within the last 10 years or a history suggesting Gell and Coombs type 2, 3, or 4 (severe) hypersensitivity reaction. Seven did not complete DPT because the treating team used a ß-lactam antibiotic other than amoxicillin. Fifty-four of 56 remaining patients (96%) completed 3-day DPT to amoxicillin with no adverse reaction. Two experienced mild cutaneous reactions. Penicillin allergy evaluation was significantly associated with reduced length of stay, reduced hospital expenditure on bed and second-line antibiotics, and reduced readmission rates. CONCLUSION: Penicillin allergy evaluation with DPT without PST may be feasible for all adult patients with a reported history of type B reactions to penicillins who do not have a history of anaphylaxis within the last 10 years or a type 2, 3, or 4 (severe) hypersensitivity reaction.

Integrating basophil activation tests into evaluation of perioperative anaphylaxis to neuromuscular blocking agents.

BACKGROUND: Neuromuscular blocking agents (NMBAs) remain the leading cause of perioperative anaphylaxis in Australia. Standard evaluation comprises history, skin tests, and in vitro specific immunoglobulin E tests. Drug provocation tests to suspected NMBA culprits are associated with a significant risk. Basophil activation testing (BAT) is a potentially useful in vitro test that is not commercially available in Australia or as part of standard evaluation. METHODS: All patients attending the Anaesthetic Allergy Clinic in Sydney, Australia between May 2017 and July 2018 exposed to an NMBA before the onset of anaphylaxis during their anaesthetic qualified for the study. We recruited 120 patients sequentially who received standard evaluation plus BAT using CD63, CD203c, and CD300a as surface activation markers. RESULTS: BAT results were expressed as % upregulation above the negative control and stimulation index (mean fluorescence index of stimulated sample divided by the negative control). We calculated cut-offs of 4.45% and 1.44 for CD63, and 8.80% and 1.49 for CD203c, respectively. Sensitivity was 77% with specificity of 76%. A subgroup of 10 patients with NMBA anaphylaxis had no sensitisation on skin tests. BAT using CD63 and CD203c showed sensitisation in six of these 10, and adding CD300a identified sensitisation in nine patients. BAT was positive in seven of nine patients with anaphylaxis of unknown aetiology. CONCLUSIONS: BAT may be a useful supplement to the standard evaluation in diagnosing NMBA anaphylaxis in patients with suggestive histories, but no sensitisation on skin tests. Ongoing study of this specific group of patients is required to clarify its utility in clinical practice.

Assessing cross-reactivity to neuromuscular blocking agents by skin and basophil activation tests in patients with neuromuscular blocking agent anaphylaxis.

BACKGROUND: Following diagnosis of neuromuscular blocking agent (NMBA) anaphylaxis, identifying safe alternatives for subsequent anaesthesia is critical. A patient with anaphylaxis to one NMBA can also have an allergic reaction to other NMBAs (cross-reactivity). Whilst drug provocation testing is standard for identifying or excluding allergy, there is significant risk. In vitro, after an allergen activates basophils, basophils express surface activation markers that can be measured by basophil activation testing (BAT). We compared cross-reactivity between NMBAs assessed by BAT against that by skin testing. METHODS: All patients attending an anaesthetic allergy clinic in Sydney, Australia between May 2017 and July 2018 diagnosed with NMBA anaphylaxis qualified for this study comparing intradermal skin tests and BAT with a panel of NMBAs (rocuronium, vecuronium, pancuronium, suxamethonium, cisatracurium). RESULTS: Of the 61 patients participating, sensitisation on skin testing and on BAT completely matched in only nine patients (15%). Sensitisation was not in agreement for pancuronium, cisatracurium and rocuronium, but was in agreement for vecuronium and suxamethonium. Nine patients with negative skin tests subsequently tolerated cisatracurium, and one false positive on BAT to cisatracurium was detected. CONCLUSIONS: The utility of BAT in identifying safe NMBAs for subsequent anaesthesia needs further evaluation. BAT detects a different cross-reactivity profile to skin tests. Negative skin testing and BAT might increase confidence in performing drug provocation testing, but this and follow-up of subsequent anaesthesia in our cohort is necessary to determine the clinical significance of BAT sensitisation.