Search

Within the first 4 months of the Western Australian COVID-19 immunisation program, 49 suspected anaphylaxis cases were reported to the vaccine safety surveillance system. Twelve reports met Brighton Collaboration case definition, corresponding to rates of 15.9 and 17.7 per million doses of Vaxzevria and Comirnaty administered, respectively. This article is protected by copyright. All rights reserved.

Background Calculated globulin fraction is derived from the liver function tests by subtracting albumin from the total protein. Since immunoglobulins comprise the largest component of the serum globulin concentration, increased or decreased calculated globulins and may identify patients with hypogammaglobulinaemia or hypergammaglobulinaemia, respectively. Methods A retrospective study of laboratory data over 2.5 years from inpatients at three tertiary hospitals was performed. Patients with paired calculated globulins and immunoglobulin results were identified and clinical details reviewed. The results of serum electrophoresis testing were also assessed where available. Results A total of 4035 patients had paired laboratory data available. A calculated globulin ≤20 g/L (4th percentile) were seen in patients with either liver disease (37%), haematological malignancy (36%), autoimmune disease (13%) or infections (9%). Conclusions Calculated globulin is an inexpensive and easily available test that assists in the identification of hypogammaglobulinaemia or hypergammaglobulinaemia which may prompt further investigation and reduce diagnostic delays.

Pemphigus encompasses of a group of rare, and often severe, intraepidermal bullous dermatoses that are mediated by autoantibodies that act against adhesion proteins of the desmosome. The current international consensus is that the use of intravenous CD20 inhibitors should be first-line in the management of moderate-to-severe cases of pemphigus, however Australia is yet to adopt this. Systemic corticosteroids, combined with conventional corticosteroid-sparing immunosuppressive agents such as azathioprine, mycophenolate mofetil, cyclosporin and methotrexate is still recommended as first-line therapy in Australia despite overwhelming evidence that combining rituximab with a rapid corticosteroid tapering regime is more effective in the treatment of moderate-to-severe pemphigus, and leads to fewer severe adverse effects. We propose a therapeutic approach that echoes the international consensus and recommend that rituximab, an anti-CD20 monoclonal antibody, be listed in the formularies of Australian Public Hospitals and on the Pharmaceutical Benefits Scheme for use in moderate to severe pemphigus.

Background Granulomatous polyangiitis (GPA) is a rare multisystem autoimmune disease of unknown aetiology that is pathologically characterised by necrotising vasculitis, tissue necrosis and granulomatous inflammation, typically in the presence of anti-neutrophil cytoplasmic antibodies (ANCA). However infectious diseases may induce high titre ANCA and mimic vasculitis. Tuberculosis may share many clinical features with GPA including fever, arthralgia, granulomatous inflammation and pulmonary lesions and patients. Case presentation A 39 year old patient was admitted with ocular irritation and redness, arthralgia and multiple new pulmonary lesions. The past medical history was significant for two episodes of tuberculosis previously requiring prolonged treatment. ANCA antibodies were positive and CT showed multiple pulmonary lesions including cavitatory lesions. After extensive investigation, the patient was treated for GPA with high dose immune suppression with good clinical response. Conclusions Here we review the diagnostic considerations between differentiating GPA and tuberculosis in patients from endemic regions. It is recommended that biopsies of lung lesions, sputum microscopy and multidisciplinary team input are sought as part of the workup when these two differentials are being considered.

Coeliac disease (CD) diagnosis is based on clinical assessment, detection of specific autoantibodies and histological examination of small intestinal biopsies. The European Society of Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines have recently been updated and recommend CD may be diagnosed without a biopsy or HLA typing in symptomatic patients with high titre IgA tissue transglutaminase antibodies (aTTG) and positive endomysial antibodies (EMA). However, the need for EMA in patients with high level aTTG has been questioned. We aimed to determine the diagnostic benefit of HLA typing, EMA and IgG antibodies to deamidated gliadin (DGP) in children with high level aTTG. We prospectively evaluated children presenting for assessment of possible CD. All patients underwent small bowel biopsy, serological testing and HLA typing. Results were analysed and correlated with histopathological diagnosis. A total of 209 children were assessed; 61.5% were found to have CD and 29% could have avoided biopsy as per 2020 ESPGHAN guidelines. Titres of aTTG ≥60 U/mL or DGP ≥28 U/mL gave 100% specificity and 100% positive predictive value (PPV) for CD. HLA typing and EMA did not improve the PPV of patients with aTTG ≥60 U/mL, but addition of DGP ≥28 U/mL improved diagnostic sensitivity whilst retaining 100% specificity. Addition of HLA and EMA testing in patients with high titre aTTG antibodies does not improve diagnostic performance and may possibly be omitted from the serological workup in these patients. Our data support combining aTTG and DGP testing and optimising cut-offs to maximise specificity as an alternative biopsy-free diagnostic approach.

Muscular polyarteritis nodosa where disease is isolated to skeletal muscle is a rare and often poorly recognised clinical entity. Patients typically present with fever and severe muscle pain limiting ability to ambulate without rise in creatine kinase. Often there is a significant delay between presentation and diagnosis, which requires histological confirmation. Musculoskeletal MRI is a sensitive investigation that can lead to timely biopsy and improve diagnostic yield. Early diagnosis of this condition is essential as patients typically respond favourably to corticosteroid treatment. Here we report 4 cases of muscular polyarteritis nodosa and review the reported literature.

Variants in MAGT1 have been identified as the cause of an immune deficiency termed X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection and neoplasia (XMEN) disease. Here, we describe 2 cases of XMEN disease due to novel mutations in MAGT1, one of whom presented with classical features of XMEN disease and another who presented with a novel phenotype including probable CNS vasculitis, HHV-8 negative multicentric Castelman disease and severe molluscum contagiosum, thus highlighting the clinical diversity that may be seen in this condition. Peripheral blood immunophenotyping of these 2 patients, together with an additional 4 XMEN patients, revealed reduced NKG2D expression, impaired CD28 expression on CD8+ T cells, CD4+ T cell lymphopenia, an inverted CD4:CD8 ratio and decreased memory B cells. In addition, we showed for the first time alterations to the CD8+ T cell memory compartment, reduced CD56hi NK cells, MAIT and iNKT cells, as well as compromised differentiation of naive CD4+ T cells into IL-21-producing Tfh-type cells in vitro. Both patients were treated with supplemental magnesium with limited benefit. However, one patient has undergone allogeneic haematopoietic stem cell transplant, with full donor chimerism and immune reconstitution. These results expand our understanding of the clinical and immunological phenotype in XMEN disease, adding to the current literature, which we further discuss here.

Background The extra-intestinal manifestation of tracheobronchitis is a rare complication of ulcerative colitis (UC). Here, we present a case of UC-related tracheobronchitis wherein the positive clinical effects of infliximab are demonstrated. Case presentation We report the case of a 39-year old woman who presented with a chronic productive cough on a distant background of surgically managed ulcerative colitis (UC). Our patient failed to achieve a satisfactory clinical improvement despite treatment with high dose inhaled corticosteroids, oral corticosteroids and azathioprine. Infliximab therapy was commenced and was demonstrated to achieve macroscopic and symptomatic remission of disease. Conclusions We present the first case report documenting the benefits of infliximab in UC-related tracheobronchitis.

The role of autoantibody testing for patients with interstitial lung disease is an evolving area. Recent guidelines recommend routine anti-nuclear antibodies, rheumatoid factor, and anti-citrullinated cyclic peptide antibody testing for patients undergoing diagnostic evaluation for interstitial lung disease, with further autoantibody testing reserved for selected cases guided by rheumatological features. Even this approach may miss patients with clinically significant autoantibodies when interstitial lung disease is the dominant or first manifestation of autoimmune disease. We retrospectively performed autoimmune serology in a clinically well characterised cohort of interstitial lung disease patients. Using stored serum, additional testing was performed to ensure all patients had complete autoantibody profiles including anti-nuclear antibodies, extractable nuclear antigen antibodies, double-stranded DNA antibodies, rheumatoid factor, anti-citrullinated cyclic peptide antibodies, anti-neutrophil cytoplasmic antibodies, and myositis antibodies. Eighty patients with interstitial lung disease, and available stored serum, were assessed. Mean age at interstitial lung disease diagnosis was 65.2 years and 42 patients were male. Positive autoimmune serology was found in 56 of 80 (70.0%) patients; the most common positive result was anti-nuclear antibodies (n=34; 42.5%). Myositis antibodies were detected in 13 of 80 (16.2%) patients. Four (5%) patients had elevated anti-citrullinated cyclic peptide antibodies, and two (2.5%) patients had detectable myeloperoxidase antibodies. Eleven (13.7%) patients with negative anti-nuclear antibodies had other significant disease associated autoantibodies. An extended panel of autoantibody testing may detect cases of connective tissue disease associated interstitial lung disease, regardless of clinical or radiological subtype, and prior to extra-pulmonary manifestations of systemic autoimmunity.

Current understanding of cross-reactivity in severe cutaneous adverse reactions to beta-lactam antibiotics is limited, thereby making recommendations for future prescribing difficult. The underlying immunopathogenesis of these reactions is not completely understood but involves interactions between small molecule drugs, T cells and HLA molecules. Historically, these reactions were considered to be specific to the inciting antibiotic and therefore likely to have minimal cross-reactivity. We assessed patients presenting with non-SJS/TEN severe cutaneous adverse reactions to a tertiary hospital drug allergy clinic. In our case series cross-reactivity or co-reactivity commonly occurred among the beta-lactam antibiotic class, however further research is required to investigate and understand patterns of cross-reactivity. Based on our experience we provide clinicians with a practical algorithm for testing for cross-reactivity in non-SJS/TEN severe cutaneous adverse reactions.