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Background Penicillin allergy labels are prevalent, and removal of incorrect labels improves patient outcomes and health economics. Labels may be classified as “low-risk” or “non–low-risk,” of which the symptoms of the latter chiefly suggest immunoglobulin E–mediated etiology. Traditionally, “non–low-risk” allergy labels are evaluated by penicillin skin testing followed by graded multistep penicillin drug provocation testing (DPT). Objective To evaluate the safety of assessing “non–low-risk” labels with single-step direct DPT. Methods We consecutively enrolled inpatients and outpatients of a teaching hospital in Sydney, Australia, with penicillin allergy labels requiring penicillin for first-line treatment. Patients were classified as “low-risk” or “non–low-risk” based on the allergy labels. All patients proceeded directly to amoxicillin DPT, unless there was a history of anaphylaxis within 10 years of assessment to a beta-lactam (except for cefazolin) or Gell and Coombs type 2, type 3, or severe type 4 reaction. This was followed by a course of amoxicillin. Results A total of 149 patients (41 inpatients, 108 outpatients) were enrolled. No patient was excluded from the study. No patient experienced life-threatening reactions to the protocol. There were 85 patients who reported “non–low-risk” allergy labels. One patient developed generalized pruritus and rash that resolved with standard-dose antihistamines, 2 developed delayed benign maculopapular exanthem, and 3 experienced diarrhea during the course of amoxicillin. Conclusion In our cohort, direct single-step DPT was safe, with only 6 patients with “non–low-risk” allergy experiencing benign reactions. We hope that further studies can be performed into single-step direct DPT to evaluate “non–low-risk” penicillin allergy labels. Trial Registration ClinicalTrials.gov Identifier: LNR/16/HAWKE/452.

Common variable immunodeficiency (CVID) is established as a heterogeneous collection of disorders of immune dysregulation rather than an infectious complication of antibody deficiency. Approximately 70% of patients have one or more of the non-infectious complications of autoimmunity, enteropathy, polyclonal lymphocytic and malignancy. The CVID-disorders represent a particular challenge as they fall under an umbrella diagnosis governed currently by non-universal diagnostic criteria. The rubric of CVID is shrinking as next generation sequencing is progressively and rapidly identifying the genetic basis for many of its disorders. Although identification of monogenic cause of CVID allows for naming of separate or specific entities, it still provides valuable insight into the immune dysregulation of these disorders along with recognition of a polygenic basis of disease and cellular changes observed in innate and adaptive immune pathways. Cellular abnormalities in the T-cell (reduced regulatory T cells (Tregs) and increased T follicular helper cells), and B-cell compartments (reduced switched memory B-cells and increased peripheral CD21low cells) along with an increase in innate lymphoid cells type 3 promote a milieu for inflammation. Immune dysregulation also results from increased microbial translocation from impaired gastrointestinal barrier function in CVID-patients with loss of Tregs. An understanding of the manifestations and mechanisms of immune dysregulation allows for improved vigilance in screening for the diagnosis, monitoring for complications of disease and the continued development and introduction of targeted therapies for non-infectious phenotypes.

Aim: To examine gene expression in different clinical phenotypes of allopurinol-induced severe cutaneous adverse reactions (SCARs). Materials & methods: Gene expression profiling was performed using microarray on 11 RNA samples (four controls, three hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms, four Stevens–Johnson syndrome/toxic epidermal necrolysis) followed by quantitative real-time PCR in a total of 11 SCARs patients and 11 controls. Results: The biological pathways which were significantly enriched in differentially expressed genes in Stevens–Johnson syndrome/toxic epidermal necrolysis compared with hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms patients included; cell surface interactions at the vascular wall, immunoregulatory interactions at the immunological synapse and MyD88 signaling pathways. Overexpression of miR146a occurred in allopurinol-tolerant HLA-B*58:01 carriers. Conclusion: Biological pathways are identified which appear to be implicated in determining clinical phenotypes in allopurinol-induced SCARs. Overexpression of miR146a is potentially important for allopurinol tolerance in HLA-B*58:01 carriers.

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 (? = 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.

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.To evaluate the status of penicillin allergy labels in the community 1 year after penicillin delabeling at a tertiary hospital in Australia.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.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.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.

Objectives Progressive supranuclear palsy (PSP) is a neurodegenerative condition characterised by Parkinsonian features, cervical dystonia and ophthalmoparesis. Paraneoplastic PSP has previously been reported in the literature in association with several different cancer types but is very rare.1–3 Methods Case review. Results A 74 year old Chinese man was diagnosed with Stage 1b EGFR positive lung adenocarcinoma and underwent a left upper lobectomy. Twelve months later he presented with rapidly progressive neck stiffness, reduction in motor function and gait (over 8 weeks) and recalcitrant disequilibrium. He had hypomimia, frontalis over-activation, blepharospasm, blepharotremor and a supranuclear gaze palsy. There was marked axial rigidity, bradykinesia and cervical dystonia. An MRI brain and spine were unremarkable. Vestibular function tests were normal. Serum antineuronal antibodies were negative. The CSF analysis was unremarkable. The patient responded to plasma exchange on a two to three-weekly basis with significant improvement in saccadic eye movements and Parkinsonism. However, disequilibrium remained a persistent problem despite the discovery and excision of a second EGFR wild type non-small cell lung cancer, and Rituximab was recently started. Cervical dystonia was treated partially with Botulinum toxin injections, but the patient responded poorly to L-dopa. Conclusions This suspected paraneoplastic disease exhibits several features of PSP. In particular, the supranuclear palsy, Parkinsonism and dystonia are similar to the typical syndrome. However, the rapidly progressive presentation and disequilibrium are unusual and a response to plasma exchange, suggests humorally mediated neuronal pathology. In rapidly evolving PSP-like cases with cancer, investigation for immunopathology is warranted. References Dash D, Choudhary R, Ramanujam B, Vasantha PM, Tripathi M. Paraneoplastic syndrome mimicking progressive supranuclear palsy. J Clin Neurosci 2016 Oct;32:162–3. doi:10.1016/j.jocn.2016.02.032. Epub 2016 Jun 16. PMID: 27318371. Takkar A, Mehta S, Gupta N, Bansal S, Lal V. Anti- RI antibody associated progressive supranuclear palsy like presentation in a patient with breast carcinoma. J Neuroimmunol 2020 Oct 15;347:577345. doi:10.1016/j.jneuroim.2020.577345. Epub 2020 Jul 26. PMID: 32763584. Tan JH, Goh BC, Tambyah PA, Wilder-Smith E. Paraneoplastic progressive supranuclear palsy syndrome in a patient with B-cell lymphoma. Parkinsonism Relat Disord 2005 May;11(3):187–91. doi:10.1016/j.parkreldis.2004.09.003. PMID: 15823484.

Objectives Neurosarcoidosis may present with longitudinally extensive transverse myelitis (LETM) posing a diagnostic challenge. We describe the clinical features, radiology and management of five patients with spinal neurosarcoidosis (SNS). Methods We retrospectively identified five patients with a diagnosis of SNS and the clinical, radiological and pathological data were reviewed. Results There were three females and two males who were, on average, 49 years at onset. A histopathological diagnosis of sarcoid was confirmed in two cases (lymph node and cerebral lesion) and the diagnosis was radiological in the others (LETM with persistent enhancement in 3 patients and the trident sign in 2 patients). The average span of the spinal cord lesions was 4 vertebral bodies. Three patients had FDG-avid mediastinal lymph nodes. Cerebral disease was identified in two cases, and cardiac involvement in one. Two patients required spinal decompression surgery. All patients received intravenous and oral steroids and some had rituximab (n=2), tocilizumab (n=1), cyclophosphamide(n=1), adalimumab (n=2), and infliximab (n=4). Disease control was achieved with TNF-alpha (tumour necrosis factor-alpha) blocking in 4 cases and another responded to cyclophosphamide. The mean follow-up was 55 months. Conclusions SNS is a cause of LETM and can be suspected by the trident sign on MRI. Persistent enhancement may be another differentiating feature. Spinal cord oedema requiring surgery may occur and patients typically respond to treatment with TNF-alpha inhibitors. References Flanagan EP, Kaufmann TJ, Krecke KN, Aksamit AJ, Pittock SJ, Keegan BM, Giannini C, Weinshenker BM. Discriminating long myelitis of neuromyelitis optica from sarcoidosis. Ann Neurol 2016 Mar;79(3):437–47. Zalewski NL, MD, Krecke KN, Weinshenker BG, MD, Aksamit AJ, Conway BL, McKeon A, Flanagan EP. Central canal enhancement and the trident sign in spinal cord sarcoidosis. Neurology 2016 Aug 16;87(7):743–4.

Background Primary central nervous system vasculitis (PCNSV) is a rare disorder that normally develops with bilateral brain lesions. We report a case of pathologically confirmed hemispheric PCNSV with associated brain atrophy and symptoms of focal dystonia. Method Case report. Result A 45-year-old female presented with fluctuating apraxia, dystonia, cognitive dysfunction and numbness of the face. She had embouchure dystonia. She was taking lamotrigine for a longstanding history of well controlled partial seizures. A cerebral MRI revealed multiple left hemispheric cortical and subcortical white matter lesions. Many of the lesions enhanced. The lesions came and went over a period of three years but cortical atrophy of the fronto-parietal gyri developed. The CSF demonstrated matched oligoclonal bands. The autoimmune serology was negative. A cerebral PET demonstrated hypo-metabolism in the affected areas.A cortical lesion that was enhancing was biopsied and the histology showed several small foci of punctuate necrosis (infarcts) with lymphohistiocytic infiltration of blood vessels consistent with small vessel vasculitis. The patient was treated with prednisone and mycophenolate and improved clinically, albeit her clarinet playing did not return to pre-morbid levels. The MRI lesions resolved and did not recur. Conclusion Focal vasculitis is rare but may result in neuronal loss and specific cortical damage and atrophy, in this case leading to embouchure dystonia. References Salvarani C, Brown RD Jr, Hunder GG. Adult primary central nervous system vasculitis. Lancet 2012 Aug 25;380(9843):767–77. Ho MG, Chai W, Vinters HV, Hathout G, Mishra S, Yim C, Valdes-Sueiras M, Nishimura R. Unilateral hemispheric primary angiitis of the central nervous system. J Neurol 2011 Sep;258(9):1714–6. Unihemispheric central nervous syste.

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.

The management of malignancy with immunotherapy is a rapidly evolving field and immune checkpoint inhibitors (ICI) are being used and trialed in an increasing number of malignancies. Monoclonal antibodies that target programmed death-1 (PD-1) and cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) enable the patient to generate an immune response to tumor cells, but have also generated T cell–mediated autoimmune responses described in several organs. To date, the most common autoimmune side effects have been colitis, hepatitis, and pneumonitis. Myocarditis is a rare complication of immune checkpoint inhibitor therapy and is more commonly described in the context of combination therapy with ipilimumab (anti-CTLA-4 antibody) and nivolumab (anti-PD-1 antibody).1, 2, 3 In most cases the myocarditis is fatal3 and although some isolated cases report some positive treatment outcomes,4, 5 the best management of cardiac complications is not well established. A recent case series comprising 35 patients with ICI-induced myocarditis reported 7 cases of nivolumab-induced myocarditis, of which 100% experienced a major cardiovascular event.6 We report the first successful management of ventricular storm precipitated by checkpoint inhibitor–mediated fulminant myocarditis, using a combination of antiarrhythmics, antitachycardia and overdrive pacing, direct current cardioversion, and sedation with concurrent immunosuppression, including rabbit-anti-thymocyte globulin (r-ATG).

Two cases in which a neurological disorder was identified pathologically to be due to a granulomatous infiltration were found after diagnosis to have an associated testicular seminoma with pathologically proven lymphatic metastasis. We present the clinical and imaging features, and pathological appearances of the lymphatic tissue and the brain. We summarise the literature to date and discuss the pathogenesis of the disorder and its treatment.

Aims: To determine genetic susceptibility markers for carbamazepine (CBZ) and allopurinol-induced severe cutaneous adverse reactions (SCARs) in Vietnamese. Methods: A case–control study was performed involving 122 patients with CBZ or allopurinol-induced SCARs and 120 drug tolerant controls. Results: HLA-B*58:01 was strongly associated with allopurinol-induced SCARs and strongly correlated with SNP rs9263726. HLA-B*15:02 was associated with CBZ-induced Stevens–Johnson syndrome/toxic epidermal necrolysis but not with drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms. No association was found between HLA-A*31:01 and CBZ-induced SCARs. HLA-B*58:01 and rs3909184 allele A with renal insufficiency were shown to increase the risk of allopurinol-induced SCARs. Conclusion: HLA-B*58:01 and HLA-B*15:02 confer susceptibility to allopurinol-induced SCARs and CBZ-induced SJS/TEN in Vietnamese. SNP rs9263726 can be used as a surrogate marker in identifying HLA-B*58:01.

BackgroundEndovascular 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.MethodsWe 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.ResultsThese 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.ConclusionsThere 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.

Susac’s syndrome is a rare and debilitating disease characterized by the triad of encephalopathy, branch retinal artery occlusions, and sensorineural hearing loss. All manifestations may not be clinically apparent at presentation resulting in delayed diagnosis. Early recognition of the syndrome may prevent disease sequelae such as permanent cognitive, visual, and hearing loss. We present such a case of Susac’s syndrome that was also refractory to conventionally prescribed combination of immunosuppressive treatments including high-dose potent corticosteroids, intravenous cyclophosphamide, methotrexate, plasma exchange, rituximab, and mycophenolate. His disease was stabilized with infliximab in combination with a tapering course of low-dose prednisone. After 2 years of remission with TNF treatment, consideration is being given to ceasing therapy. He has the sequelae of bilateral sensorineural hearing loss but no visual impairment or cognitive deficits on follow-up with neuropsychometric testing. This is the first case report to our knowledge of the successful use of infliximab for a patient with Susac’s syndrome that was necessary following treatment with cyclophosphamide and then rituximab.

The advent of immune checkpoint inhibitors (ICIs) for cancer therapy has heralded increasing frequency of immune-related adverse events including endocrinopathies, hepatitis, colitis and rarely myocarditis and myasthenia gravis (MG). The heterogeneity in clinical presentations regardless of organ-specific involvement can lead to delayed recognition and management of these events and adverse health outcomes. We describe a case of ICI-induced subclinical focal myocarditis that was recognised and treated in the broader context of MG. It is essential that patients with ICI-induced MG should be screened and monitored for myocarditis, a potentially fatal complication.

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.

In a population-based analysis including a large database restricted to patients over age 70, the authors demonstrate that the A91V polymorphism in the familial hemophagocytic lymphohistiocytosis–related gene is a nonpathological polymorphism that confers no increase in cancer, death, or immunopathology.

HLA-A*31:01 and HLA-B*15:02 have been widely reported to confer genetic susceptibility to carbamazepine (CBZ)-induced severe cutaneous adverse reactions (SCARs). Accordingly, the screening for these alleles has been highly recommended to prevent SCAR prior to introducing CBZ therapy. Although a number of methods are available for screening of HLA-A*31:01 or HLA-B*15:02 alleles separately, developing an assay that can detect both these alleles would be more clinically practical, cost-effective and less time-consuming. Therefore, in this study, a multiplex polymerase chain reaction (PCR) using TaqMan Probe was designed and validated to be able to detect HLA-A*31:01 and HLA-B*15:02. In comparison with Luminex-SSO/SBT/SSB, the multiplex PCR assay for detection of HLA-A*31:01 and HLA-B*15:02 had a perfect agreement in the validation group of 125 samples. The method was able to detect the target genes at the DNA concentration of 0.037 ng/μL. The unit cost of this assay is less than $5 USD with total time of 110 minutes.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease associated with anti-nuclear antibodies (ANA), extractable nuclear antigens (ENA), and anti-double stranded DNA antibodies. Glomerulonephritis (GN) with immune complex deposition is found in 50% of cases.1 Twenty per cent of patients with SLE have antineutrophil cytoplasmic antibodies (ANCA), which in certain patients is associated with ANCA-associated vasculitis (AAV).2 The ANCA detected in such cases is reported in the literature as antimyeloperoxidase antibodies (MPO) rather than antiproteinase 3 (PR3) antibodies.3 The prevalence of dual-positive AAV is up to 9% but these cases are not associated with SLE.4 This is the first report of a case of SLE/AAV involving AAV (necrotising pauci-immune GN) with both anti-MPO and anti-PR3 antibodies. A 70-year-old woman presented with thrombocytopenia (platelets 17×109/L), renal failure (creatinine 260 µmol/L) and deep vein thrombosis. She has a 10-year history of SLE characterised by panniculitis, photosensitivity, polyarthritis, oral ulceration, sicca symptoms, relapsing polychondritis, pulmonary hypertension, interstitial lung disease and pulmonary thromboembolism due to secondary antiphospholipid syndrome. Her laboratory investigations revealed a high titre (>2560) homogeneous ANA, anti-double-stranded-DNA antibodies and persistently elevated anticardiolipin and anti-beta-2 glycoprotein 1 antibodies. Her symptoms were non-responsive to methotrexate and leflunomide. A renal biopsy performed 1 year prior to presentation for a creatinine 110 µmol/L demonstrated hypertensive changes with no features of lupus nephritis. Following the …

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 β-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.

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.