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Background: Severe cutaneous adverse reactions (SCAR) are a group of delayed presumed T-cell mediated hypersensitivities associated with significant morbidity and mortality. Despite their shared global healthcare burden and impact, the clinical phenotypes, genomic predisposition, drug causality, and treatment outcomes may vary. We describe the establishment and results from the first Australasian registry for SCAR (AUS-SCAR), that via a collaborative network advances strategies for the prevention, diagnosis and treatment of SCAR. Methods: Prospective multi-center registry of SCAR in Australian adult and adolescents, with planned regional expansion. The registry collects externally verified phenotypic data drug causality, therapeutics and long-term patient outcomes. In addition, biorepository specimens and DNA are collected at participating sites. Results: we report on the first 100 patients enrolled in the AUS-SCAR database. DRESS (50%) is the most predominant phenotype followed by SJS/TEN (39%) and AGEP (10%), with median age of 52 years old (IQR 37.5, 66) with 1:1 male-to-female ratio. The median latency for all implicated drugs is highly variable but similar for DRESS (median 15 days IQR 5,25) and SJS/TEN (median 21 days, IQR 7,27), while lowest for AGEP (median 2.5 days, IQR 1,8). Antibiotics (54.5%) are more commonly listed as primary implicated drug compare with non-antibiotics agent (45.5%). Mortality rate at 90 days was highest in SJS/TEN at 23.1%, followed by DRESS (4%) and AGEP (0%). Conclusion: In the first prospective national phenotypic and biorepository of SCAR in the southern hemisphere we demonstrate notable differences to other reported registries; including DRESS-predominant phenotype, varied antibiotic causality and low overall mortality rate. This study also highlights the lack of standardised preventative pharmacogenomic measures and in vitro/in vivo diagnostic strategies to ascertain drug causality. Trial registration: ANZCTR ACTRN12619000241134. Registered 19 February 2019.

Abstract Background The lymphocyte transformation test (LTT) is an in vitro assay used to diagnose drug induced hypersensitivity reactions by detecting the activation and expansion of drug-specific memory T cells to the suspected implicated drug. Traditionally radiolabelled thymidine (3H-thymidine) has been used but requires the handling and disposal of radioactive materials. Objective To examine safe alternatives to 3H-thymidine, test assay modifications for improved assay sensitivity and evaluate the modified LTT in patients with DRESS and AGEP. Methods Four proliferation detection assays (BRDU, CyQUANT™, MTT and XTT) were screened for LTT sensitivity. XTT the most sensitive and practical was selected for further evaluation Modifications like autologous serum (AS) and regulatory T cell depletion (T-REG) were tested for improved assay sensitivity. Finally, an initial evaluation of the XTT–LTT was performed in 8 patients with DRESS and 2 with AGEP including cytokine testing. Results Of the non-radioactive alternatives we tested, XTT a colorimetric assay was the most sensitive and practical to move to evaluation. The addition of AS increased background signal. Depletion of T-REGs improved sensitivity but cell sorting time and risk of contamination limited benefit. Of eight patients diagnosed with DRESS and 2 with AGEP tested with XTT–LTT assay results showed our assay matched clinical findings of implicated drugs in 8/10 patients when using a stimulation index (SI) ≥ 2 and 8/10 with analysis by ANOVA. All ten patients were correctly diagnosed by either analysis. Conclusion XTT appears to be a safe, viable alternative to 3H-thymidine, with high sensitivity and allowing direct cytokine quantification on specific patient cells.

Background: The mechanism of immediate reactions to drugs or vaccines containing polyethylene glycol (PEG) and PEG derivatives is not fully elucidated. It is considered in many instances to be IgE-mediated. Diagnosis and management of PEG allergy is topical, as BNT162b and mRNA-1273 contain PEG (2[PEG-2000]-N), and ChAdOx1-S and NVX-CoV2373 contain polysorbate 80. mRNA vaccines contain PEG 2000, which encapsulates the mRNA to impair its degradation. This PEG MW is specific to mRNA vaccines and is not used in other drugs and vaccines. PEG 2000 allergy is not well studied, as higher PEG molecular weights are implicated in most of the PEG allergy published in the literature. Methods: We performed a literature review on PEG allergy and sought to evaluate the safety and effectiveness of our protocol for assessment of PEG 2000 and polysorbate 80 reactions in an outpatient clinic setting. All patients referred to our drug allergy service between 1 July 2021 and 31 December 2021 with suspected immediate allergy to PEG or its derivatives were eligible for the study. Skin testing (ST) and basophil activation testing (BAT) were performed for all patients to multiple PEG molecular weights (MWs). Results: We reviewed twenty patients during the study period. Five patients were allergic. Fifteen patients had a masquerade of allergy and were enrolled as control patients. PEG 2000, polysorbate 80, BNT162b, and ChAdOx1-S had excellent performance characteristics on skin testing. BAT showed high specificity for all vaccines and PEG MWs. Discussion: In our small study, we found ST and BAT to add useful information, particularly for PEG 2000 allergy. Further study of our protocol in larger patient cohorts will provide more information on its performance characteristics and usefulness.

Background. Microscopic polyangiitis (MPA) can manifest with atypical features such as pulmonary fibrosis and chronic obstructive pulmonary disease (COPD), which are atypical and unusual features of small vessel vasculitis. Case Presentation. This paper presents two patients with microscopic polyangiitis and respiratory symptoms attributable to atypical pulmonary manifestations. Pulmonary fibrosis was present in both cases, with COPD also present in one patient. Management involved methylprednisone, prednisone, and cyclophosphamide. The second patient also received azathioprine. Both patients responded well to immunosuppressive treatment; however, pulmonary fibrosis and COPD were refractory to immunosuppression. Conclusion. Pulmonary manifestations including pulmonary fibrosis, emphysema, and bronchiectasis are observed in MPA. Evaluation of MPA in unexplained cases should be performed to avoid delays in diagnosis and management. Patients who present with MPA with pulmonary manifestations may respond to treatment, but their pulmonary features demonstrate a refractory nature to such management.

Background Endovascular procedures are standard of care for an increasing range of cerebrovascular diseases. Many endovascular devices contain plastic and are coated with a hydrophilic polymer which has been rarely described to embolize, resulting in distal granulomatous inflammatory lesions within the vascular territory. Methods We reviewed three cases of cerebral granulomatous reactions that occurred after endovascular intervention for internal carotid aneurysms. The patient procedure details, presentation, relevant investigations, and treatment course are described. We also provide a literature review on endovascular granulomatous reactions. Results These three cases represent the largest biopsy proven series of cerebral granulomatosis following endovascular intervention. We highlight the variable clinical presentation, with two of the three cases having an unusually delayed onset of up to 4 years following the intervention. We show the characteristic histological findings of granulomatous lesions with foreign body material consistent with a type IV reaction, radiological abnormalities of enhancing lesions within the vascular territory of the intervention, and the requirement of prolonged immunosuppression for maintenance of clinical remission, with two of the three patients requiring a corticosteroid sparing agent. In comparison with the available literature, in addition to hydrophilic gel polymer, we discuss that plastic from the lining of the envoy catheter may be a source of embolic material. We also discuss the recommendations of the Food and Drug Administration and the implementation of novel biomaterials for the prevention of these reactions in the future. Conclusions There is a need for increased awareness of this severe complication of cerebral endovascular procedures and further longitudinal studies of its prevalence, optimal management and preventative measures. [ABSTRACT FROM AUTHOR]

The article discusses a 36-year-old woman presented with severe abdominal pain, and a computed tomography scan revealed mural inflammation of the ascending colon coherent with angio-oedema.