Background: Cross-reactivity between cephalosporins, and penicillins, is mainly explained by R1 side-chain similarity. However, data on cross-reactivity patterns in cephalosporin-allergic patients, with and without preexisting penicillin allergy labels, are lacking. Objective: We sought to determine whether R1 side-chain groups account for cross-reactivity between cephalosporins, and penicillins with similar R groups, in a cohort of patients with cephalosporin allergy labels, with and without a penicillin allergy history. Methods: A retrospective audit (February 2016 to November 2021) of adult outpatients with cephalosporin allergy labels, who underwent skin prick / intradermal testing and/or oral provocation challenges, was performed at 2 Australian tertiary hospitals. Results: We identified 212 patients with a single cephalosporin allergy label; 97 had coexisting penicillin allergy labels. Fifty-eight (27.4%) patients were confirmed as allergic to the index cephalosporin (47 to cefazolin). The cephalosporin skin testing and oral provocation challenge results were adequately explained by R1 side-chain patterns. Most (87.5%) of the cephalosporin-allergic patients with penicillin allergy labels tolerated a penicillin challenge and were delabelled. However, positive penicillin skin test results were found in 5 (10.2%) cefazolin-allergic patients without preexisting penicillin allergy labels. Conclusions: R1 side-chain groups explained most test outcomes in this study. However, some positive penicillin skin testing results were identified without a history of penicillin allergy. Future research investigating the safety of supervised graded penicillin challenges in cephalosporin-allergic patients is needed.

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe mucocutaneous adverse drug reactions associated with high morbidity and mortality. Current treatment regimens are largely supportive, and evidence for adjunctive systemic therapies remains limited. Recent research has implicated the Janus Kinase (JAK) signal transducer and activator of transcription (STAT) pathway in SJS/TEN pathogenesis, raising interest in JAK inhibitors as potential targeted therapies. This scoping review aimed to evaluate the existing literature on the use of JAK inhibitors in the management of SJS/TEN, summarise clinical outcomes and identify key research gaps. This scoping review was conducted in accordance with PRISMA-ScR guidelines. A systematic search of Medline, Web of Science, Embase and Scopus was conducted from inception up to 12 June 2025. Nine studies were included, comprising eight case reports and one translational research study, reporting on 15 patients (median age 45 years) treated with ruxolitinib (n = 7), tofacitinib (n = 5) or abrocitinib (n = 3). Most cases involved severe or treatment-refractory disease. Among the eight cases where time to re-epithelialisation was reported, six described 20%-30% re-epithelialisation by day 7 and one described 95% re-epithelialisation by day 16. No JAK inhibitor-related adverse events were reported. Preclinical studies supported a mechanistic role for the JAK/STAT pathway in keratinocyte apoptosis and inflammation. JAK inhibitors show promise as a novel therapeutic approach in SJS/TEN; however, current evidence is limited by small sample sizes, disease severity, concomitant therapies and potential publication bias. Well-designed prospective trials are needed to determine efficacy, safety and optimal use in this life-threatening condition.

preponderance (71%). Allergy testing was performed for a range of clinical reactions including skin reactions ( n = 15), unknown reaction ( n = 3), and 42% of cases with anaphylaxis ( n = 13). Cephalosporin testing was performed in 12 cases due to a prior reaction to Cephalosporins, 13 cases due to a history of reaction to Penicillins, and six cases due to a reaction to both antibiotics. Twenty-fi ve patients had a history of reactions to one drug and six patients had a history of reactions to multiple drugs of both Penicillin and Cephalosporin. Cephalexin ( n = 6) and Amoxicillin ( n = 8) were the most common culprit drugs in these cohorts. Skin and intradermal testing was positive in fi ve cases. Penicillin ( n = 2), Cephalosporins ( n = 1), and both of Penicillins and Cephalosporins ( n = 2). These fi ve patients did not proceed to an antibiotic oral challenge. Twenty-six patients proceeded to an oral antibiotic challenge. There were two positive challenges to amoxicillin and these patients subsequently tolerated Ceclor. We de-labelled eight cases of those with a history of anaphylaxis (62%), 13 cases of those with skin reactions (87%), and three cases of those with unknown reaction (100%).

preponderance (71%). Allergy testing was performed for a range of clinical reactions including skin reactions ( n = 15), unknown reaction ( n = 3), and 42% of cases with anaphylaxis ( n = 13). Cephalosporin testing was performed in 12 cases due to a prior reaction to Cephalosporins, 13 cases due to a history of reaction to Penicillins, and six cases due to a reaction to both antibiotics. Twenty-fi ve patients had a history of reactions to one drug and six patients had a history of reactions to multiple drugs of both Penicillin and Cephalosporin. Cephalexin ( n = 6) and Amoxicillin ( n = 8) were the most common culprit drugs in these cohorts. Skin and intradermal testing was positive in fi ve cases. Penicillin ( n = 2), Cephalosporins ( n = 1), and both of Penicillins and Cephalosporins ( n = 2). These fi ve patients did not proceed to an antibiotic oral challenge. Twenty-six patients proceeded to an oral antibiotic challenge. There were two positive challenges to amoxicillin and these patients subsequently tolerated Ceclor. We de-labelled eight cases of those with a history of anaphylaxis (62%), 13 cases of those with skin reactions (87%), and three cases of those with unknown reaction (100%).

Cryoglobulinaemic vasculitis is an immune-complex-mediated, systemic inflammatory syndrome usually involving small-to-medium vessels due to precipitation of cryoglobulins at <37°C. It can involve any organ but most commonly affects the skin. Associated conditions include infections (hepatitis C and HIV), haematological disorders (chronic lymphocytic lymphoma, monoclonal gammopathy of uncertain significance and multiple myeloma), autoimmune conditions (systemic lupus erythematosus and Sjogren syndrome) or as a complication following vaccination (influenza, pneumococcal and hepatitis B vaccines). Biochemical hallmarks include detection of serum cryoglobulin with low C4 levels. We describe a case of previous healthy patient with transient cryoglobulinaemic vasculitis after first dose of ChAdOx1 nCoV-19 vaccine (AstraZeneca/Oxford).

Introduction Severe cutaneous adverse reactions (SCAR) are a group of T cell-mediated hypersensitivities associated with significant morbidity, mortality and hospital costs. Clinical phenotypes include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP). In this Australasian, multicentre, prospective registry, we plan to examine the clinical presentation, drug causality, genomic predictors, potential diagnostic approaches, treatments and long-term outcomes of SCAR in Australia and New Zealand.Methods and analysis Adult and adolescent patients with SCAR including SJS, TEN, DRESS, AGEP and another T cell-mediated hypersensitivity, generalised bullous fixed drug eruption, will be prospectively recruited. A waiver of consent has been granted for some sites to retrospectively include cases which result in early mortality. DNA will be collected for all prospective cases. Blood, blister fluid and skin biopsy sampling is optional and subject to patient consent and site capacity. To develop culprit drug identification and prevention, genomic testing will be performed to confirm human leukocyte antigen (HLA) type and ex vivo testing will be performed via interferon-γ release enzyme linked immunospot assay using collected peripheral blood mononuclear cells. The long-term outcomes of SCAR will be investigated with a 12-month quality of life survey and examination of prescribing and mortality data.Ethics and dissemination This study was reviewed and approved by the Austin Health Human Research Ethics Committee (HREC/50791/Austin-19). Results will be published in peer-reviewed journals and presented at relevant conferences.Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN12619000241134).

Toxic epidermal necrolysis (TEN) is a rare and life-threatening mucocutaneous disease triggered by a reaction to a drug. Despite reported mortality of 30%, management differs between healthcare settings. Our hospital was established in February 2015 becoming the new state burns centre in Western Australia (WA). Following this, we collaborated on comprehensive multidisciplinary guidelines for the management of TEN. These guidelines are updated annually to reflect the weight of emerging evidence in managing TEN. Our aim was to review the management and outcomes of TEN patients presenting to our hospital between February 2015 and May 2021 (inclusive). We collected data for 10 patients on year, age, ethnicity, gender, medical history, culprit drug and exposure, SCORTEN, length of stay, maximum percentage of skin detachment, mucosal surface involvement, ophthalmic amniotic membrane transplant, burns unit input/admission, intensive care unit admission, weight, systemic treatment(s), complications and outcome. We excluded 7 out of 17 flagged patients who did not strictly meet the definition of TEN as greater than 30% epidermal detachment, with epidermal detachment defined as bullae, erosions, and/or positive Nikolsky. We found that the mortality rate in WA from TEN is improving compared with two previous WA studies, with a mortality rate in our study of 20% (2 deaths). Though limited by small sample size and retrospective design, our study suggests a shift towards at least one systemic therapy per patient (most commonly cyclosporine), the growing use of etanercept and the ophthalmic use of amniotic membrane transplants. It demonstrates the importance of burns unit input and the utility of comprehensive multidisciplinary guidelines. While the management and outcomes of TEN patients in WA are continuing to improve, we support calls for large registry data to facilitate evidence growth and collaboration for this rare life-threatening condition.

score under 7 and 86% a CDLQI score of 4 or less.Two patients have discontinued use, due to insufficient engagement with follow up requirements.There have been no significant side effects noted.7 of 24 patients have had 2 follow up assessments and further data continues to be collected ongoing, which will be updated prior to poster presentation. Conclusion:Our findings support recent evidence that Dupilumab is an effective treatment for children with severe atopic dermatitis, including in patients under 12 years old.

The use of information communication technology to enable specialist allergy and immunology (AI) consultation via telemedicine with the patient has expanded significantly during the coronavirus disease 2019 pandemic,1 with patient outcomes and perceptions positive for most information communication technology–enabled consultations.2

Importance:Penicillin allergy is a significant public health issue for patients, antimicrobial stewardship programs, and health services. Validated clinical decision rules are urgently needed to identify low-risk penicillin allergies that potentially do not require penicillin skin testing by a specialist.Objective:To develop and validate a penicillin allergy clinical decision rule that enables point-of-care risk assessment of patient-reported penicillin allergies.Design, Setting, and Participants:In this diagnostic study, a multicenter prospective antibiotic allergy-tested cohort of 622 patients from 2 tertiary care sites in Melbourne, Australia (Austin Health and Peter MacCallum Cancer Centre) was used for derivation and internal validation of a penicillin allergy decision rule. Backward stepwise logistic regression was used to derive the model, including clinical variables predictive of a positive penicillin allergy test result. Internal validation of the final model used bootstrapped samples and the model scoring derived from the coefficients. External validation was performed in retrospective penicillin allergy-tested cohorts consisting of 945 patients from Sydney and Perth, Australia, and Nashville, Tennessee. Patients who reported a penicillin allergy underwent penicillin allergy testing using skin prick, intradermal, or patch testing and/or oral challenge (direct or after skin testing). Data were collected from June 26, 2008, to June 3, 2019, and analyzed from January 9 to 12, 2019.Main Outcomes and Measures:The primary outcome for the model was any positive result of penicillin allergy testing performed during outpatient or inpatient assessment.Results:From an internal derivation and validation cohort of 622 patients (367 female [59.0%]; median age, 60 [interquartile range{IQR}, 48-71] years) and an external validation cohort of 945 patients (662 female [70.1%]; median age, 55 [IQR, 38-68] years), the 4 features associated with a positive penicillin allergy test result on multivariable analysis were summarized in the mnemonic PEN-FAST: penicillin allergy, five or fewer years ago, anaphylaxis/angioedema, severe cutaneous adverse reaction (SCAR), and treatment required for allergy episode. The major criteria included an allergy event occurring 5 or fewer years ago (2 points) and anaphylaxis/angioedema or SCAR (2 points); the minor criterion (1 point), treatment required for an allergy episode. Internal validation showed minimal mean optimism of 0.003 with internally validated area under the curve of 0.805. A cutoff of less than 3 points for PEN-FAST was chosen to classify a low risk of penicillin allergy, for which only 17 of 460 patients (3.7%) had positive results of allergy testing, with a negative predictive value of 96.3% (95% CI, 94.1%-97.8%). External validation resulted in similar findings.Conclusions and Relevance:In this study, PEN-FAST was found to be a simple rule that accurately identified low-risk penicillin allergies that do not require formal allergy testing. The results suggest that a PEN-FAST score of less than 3, associated with a high negative predictive value, could be used by clinicians and antimicrobial stewardship programs to identify low-risk penicillin allergies at the point of care.

BACKGROUND:Vancomycin is a prevalent cause of the severe hypersensitivity syndrome drug reaction with eosinophilia and systemic symptoms (DRESS), which leads to significant morbidity and mortality and commonly occurs in the setting of combination antibiotic therapy, affecting future treatment choices. Variations in HLA class I in particular have been associated with serious T cell-mediated adverse drug reactions, which has led to preventive screening strategies for some drugs. OBJECTIVE:We sought to determine whether variation in the HLA region is associated with vancomycin-induced DRESS. METHODS:Probable vancomycin-induced DRESS cases were matched 1:2 with tolerant control subjects based on sex, race, and age by using BioVU, Vanderbilt's deidentified electronic health record database. Associations between DRESS and carriage of HLA class I and II alleles were assessed by means of conditional logistic regression. An extended sample set from BioVU was used to conduct a time-to-event analysis of those exposed to vancomycin with and without the identified HLA risk allele. RESULTS:Twenty-three subjects met the inclusion criteria for vancomycin-associated DRESS. Nineteen (82.6%) of 23 cases carried HLA-A*32:01 compared with 0 (0%) of 46 of the matched vancomycin-tolerant control subjects (P = 1 × 10-8) and 6.3% of the BioVU population (n = 54,249, P = 2 × 10-16). Time-to-event analysis of DRESS development during vancomycin treatment among the HLA-A*32:01-positive group indicated that 19.2% had DRESS and did so within 4 weeks. CONCLUSIONS:HLA-A*32:01 is strongly associated with vancomycin-induced DRESS in a population of predominantly European ancestry. HLA-A*32:01 testing could improve antibiotic safety, help implicate vancomycin as the causal drug, and preserve future treatment options with coadministered antibiotics.

Background: Vancomycin is a prevalent cause of the severe hypersensitivity syndrome drug reaction with eosinophilia and systemic symptoms (DRESS), which leads to significant morbidity and mortality and commonly occurs in the setting of combination antibiotic therapy, affecting future treatment choices. Variations in HLA class I in particular have been associated with serious T cell-mediated adverse drug reactions, which has led to preventive screening strategies for some drugs. Objective: We sought to determine whether variation in the HLA region is associated with vancomycin-induced DRESS. Methods: Probable vancomycin-induced DRESS cases were matched 1:2 with tolerant control subjects based on sex, race, and age by using BioVU, Vanderbilt's deidentified electronic health record database. Associations between DRESS and carriage of HLA class I and II alleles were assessed by means of conditional logistic regression. An extended sample set from BioVU was used to conduct a time-to-event analysis of those exposed to vancomycin with and without the identified HLA risk allele. Results: Twenty-three subjects met the inclusion criteria for vancomycin-associated DRESS. Nineteen (82.6%) of 23 cases carried HLA-A*32:01 compared with 0 (0%) of 46 of the matched vancomycin-tolerant control subjects (P = 1 x 10(-8)) and 6.3% of the BioVU population (n = 54,249, P = 2 x 10(-16)). Time-to-event analysis of DRESS development during vancomycin treatment among the HLA-A*32:01-positive group indicated that 19.2% had DRESS and did so within 4 weeks. Conclusions: HLA-A*32:01 is strongly associated with vancomycin-induced DRESS in a population of predominantly European ancestry. HLA-A*32:01 testing could improve antibiotic safety, help implicate vancomycin as the causal drug, and preserve future treatment options with coadministered antibiotics.

Vancomycin is a prevalent cause of the severe hypersensitivity syndrome drug reaction with eosinophilia and systemic symptoms (DRESS), which leads to significant morbidity and mortality and commonly occurs in the setting of combination antibiotic therapy, affecting future treatment choices. Variations in HLA class I in particular have been associated with serious T cell-mediated adverse drug reactions, which has led to preventive screening strategies for some drugs.We sought to determine whether variation in the HLA region is associated with vancomycin-induced DRESS.Probable vancomycin-induced DRESS cases were matched 1:2 with tolerant control subjects based on sex, race, and age by using BioVU, Vanderbilt's deidentified electronic health record database. Associations between DRESS and carriage of HLA class I and II alleles were assessed by means of conditional logistic regression. An extended sample set from BioVU was used to conduct a time-to-event analysis of those exposed to vancomycin with and without the identified HLA risk allele.Twenty-three subjects met the inclusion criteria for vancomycin-associated DRESS. Nineteen (82.6%) of 23 cases carried HLA-A*32:01 compared with 0 (0%) of 46 of the matched vancomycin-tolerant control subjects (P = 1 × 10-8) and 6.3% of the BioVU population (n = 54,249, P = 2 × 10-16). Time-to-event analysis of DRESS development during vancomycin treatment among the HLA-A*32:01-positive group indicated that 19.2% had DRESS and did so within 4 weeks.HLA-A*32:01 is strongly associated with vancomycin-induced DRESS in a population of predominantly European ancestry. HLA-A*32:01 testing could improve antibiotic safety, help implicate vancomycin as the causal drug, and preserve future treatment options with coadministered antibiotics.

New cancer immunotherapies have dramatically improved survival in several types of advanced malignancies in recent years, in particular metastatic melanoma and non-small cell lung cancer. Immune checkpoint inhibitors (ICIs) have been the most effective of these new immunotherapies. ICIs are monoclonal antibodies which target regulatory molecules involved in T-cell activation, including cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1) and its ligand (PD-L1). However, ICIs can cause a wide spectrum of immune-related adverse events (irAEs), which differ significantly from the side-effects of cytotoxic chemotherapy. These irAEs develop as a direct consequence of the immune dysregulation induced by ICIs. Toxicity is common and most frequently involves the skin, gastrointestinal tract, liver and endocrine system. Most irAEs are mild and easily managed, however life-threatening complications can arise. ICI therapy may need to be interrupted or ceased when toxicity occurs. Treatment with systemic corticosteroids is generally effective, although additional immunosuppressive therapy may be required in severe or refractory cases. At present there are no biomarkers able to reliably predict those patients at greatest risk of developing toxicity.

BACKGROUND: Approximately 10-20% of hospitalized patients are labeled as penicillin allergic, and this is associated with significant health and economic costs.OBJECTIVES: We looked at the effectiveness of penicillin allergy de-labeling in clinical practice with the aim of deriving risk stratification models to guide testing strategies.METHODS: Consecutive patients aged 15 years or more, referred to a Western Australian public hospital drug allergy service between 2008 and 2013 for beta-lactam allergy, were included. Follow-up surveys were conducted. Results of skin prick testing and intradermal testing (SPT/IDT) and oral challenge (OC), and follow-up of post testing antibiotic usage were the main outcomes.RESULTS: SPT/IDT was performed in 401 consecutive patients with immediate (IMM) (<= 1 hour) (n = 151) and nonimmediate (NIM) (> 1 hour) (n = 250) reactions. Of 341 patients, 42 (12.3%) were SPT/IDTD to >= 1 penicillin reagents, including 35/114 (30.4%) in the IMM group and 7/227 (3.1%) in the NIM group (P <.0001). Of 355 SPT/IDT patients, 3 (0.8%), all in the IMM group, had nonserious positive OC reactions to single dose penicillin VK (SPT/IDT negative predictive value [NPV] 99.2%). Selective or unrestricted beta-lactam was recommended in almost 90% overall, including 238/250 (95.2%) in the NIM group and 126/151 (83.4%) in the IMM group (P = .0001). Of 182 patients, 137 (75.3%) were following the allergy label modifications (ALM) at the time of follow-up.CONCLUSIONS: Penicillin SPT/IDT/OC safely de-labels penicillin-allergic patients and identifies selective beta-lactam allergies; however, incomplete adherence to ALM recommendations impairs effectiveness. Infrequent SPT/IDTD and absent OC reactions in patients with NIM reactions suggest OC alone to be a safe and cost-effective de-labeling strategy that could improve the coverage of penicillin allergy de-labeling in lower risk populations. (C) 2015 American Academy of Allergy, Asthma & Immunology

Post-infectious glomerulonephritis (PIGN) is predominantly a childhood illness which is becoming less common in developed countries. Streptococcal infections precede the majority of cases, in which immunofluorescence typically demonstrates mesangial and capillary loop IgG and C3. IgA-dominant PIGN is more recently described and most commonly follows Staphylococcal infections. Histopathology and electron microscopy findings are often similar to Streptococcal-associated PIGN, however IgA is by definition the dominant (or co-dominant) immunoglobulin present. Two cases of IgA-dominant PIGN are reported here. In both cases methicillin-susceptible Staphylococcus aureus (MSSA) infection preceded the development of haematuria/proteinuria. The first case is a 60-year-old woman, with reduced C3/C4 and mildly elevated creatinine. Renal biopsy immunofluorescence, histopathology and electron microscopy findings were consistent with IgA-dominant PIGN. The second case is a 68-year-old woman with elevated creatinine, with normal C3/C4. On histopathology, some glomeruli showed mild mesangial hypercellularity and endocapillary proliferation with focal segmental necrosis and small/early crescents. Electron microscopy showed mostly mesangial changes, with some capillary damage but no hump-like subepithelial or subendothelial deposits. Immunofluorescence showed mesangial IgA and C3 deposits, with IgA in some capillary loops. Features were not entirely typical of PIGN, however in the clinical context were consistent with IgA-dominant PIGN. These cases display the pathological variation that may occur in IgA-dominant PIGN. Post-infectious glomerulonephritis (PIGN) is predominantly a childhood illness which is becoming less common in developed countries. Streptococcal infections precede the majority of cases, in which immunofluorescence typically demonstrates mesangial and capillary loop IgG and C3. IgA-dominant PIGN is more recently described and most commonly follows Staphylococcal infections. Histopathology and electron microscopy findings are often similar to Streptococcal-associated PIGN, however IgA is by definition the dominant (or co-dominant) immunoglobulin present. Two cases of IgA-dominant PIGN are reported here. In both cases methicillin-susceptible Staphylococcus aureus (MSSA) infection preceded the development of haematuria/proteinuria. The first case is a 60-year-old woman, with reduced C3/C4 and mildly elevated creatinine. Renal biopsy immunofluorescence, histopathology and electron microscopy findings were consistent with IgA-dominant PIGN. The second case is a 68-year-old woman with elevated creatinine, with normal C3/C4. On histopathology, some glomeruli showed mild mesangial hypercellularity and endocapillary proliferation with focal segmental necrosis and small/early crescents. Electron microscopy showed mostly mesangial changes, with some capillary damage but no hump-like subepithelial or subendothelial deposits. Immunofluorescence showed mesangial IgA and C3 deposits, with IgA in some capillary loops. Features were not entirely typical of PIGN, however in the clinical context were consistent with IgA-dominant PIGN. These cases display the pathological variation that may occur in IgA-dominant PIGN.