Post-Orgasmic Illness Syndrome Successfully Treated with Omalizumab: A Case Report.

Post-orgasmic illness syndrome (POIS) is a rare disorder associated with a debilitating symptoms post-ejaculation associated with significant impairment in quality of life. The mechanism of the disease is unclear, but hypersensitivity to semen and/or seminal fluid has been postulated. We present a case of POIS successfully treated with omalizumab suggesting a possible role for this therapy in POIS treatment and management.

Adverse event reports of anaphylaxis after Comirnaty and Vaxzevria COVID-19 vaccinations, Western Australia, 22 February to 30 June 2021.

Within the first 4 months of the Western Australian COVID-19 immunisation programme, 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.

Treatment of pemphigus in Australia: Aligning current practises with global recommendations.

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.

Diversity of XMEN Disease: Description of 2 Novel Variants and Analysis of the Lymphocyte Phenotype.

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 naïve 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.

Diagnosis and management of severe combined immunodeficiency in Australia and New Zealand.

This consensus document outlines the recommendations from the Australasian Society of Clinical Immunology and Allergy Transplantation and Primary Immunodeficiency group for the diagnosis and management of patients with severe combined immunodeficiency. It also provides a proposed framework for the early investigation, management and supportive care prior to haematopoietic stem cell transplantation.

Role of HLA-DQ typing and anti-tissue transglutaminase antibody titers in diagnosing celiac disease without duodenal biopsy in type 1 diabetes: A study of the population-based pediatric type 1 diabetes cohort of Western Australia.

AIM: The primary aim of the present study was to determine if it is cost effective to use human leukocyte antigen (HLA) typing as a first-line screening test for celiac disease (CD) in children with type 1 diabetes (T1D), as recommended by the European Society of Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN). The second aim was to investigate whether anti-tissue transglutaminase IgA (anti-tTGA) antibodies can be used to diagnose CD without the need for a confirmatory duodenal biopsy in T1D. METHODS: Data for all T1D patients aged <18 years, who attended the diabetes clinics in Western Australia up to June 2017, were extracted from the Western Australian Children's Diabetes Database (WACDD) and analyzed for their demographic data and CD permissive HLA alleles (DQ2, DQ8, and DQ7). For T1D patients already diagnosed with CD, the mode of diagnosis of CD, anti-tTGA titers, and CD permissive HLA alleles were analyzed. RESULTS: Of the 936 eligible T1D patients identified, HLA-DQ typing was available for 551 (59%). Of these 551 patients, 504 (91.2%) were positive for celiac permissive HLA alleles. Eight percent (n = 75) of the T1D patients had a co-diagnosis of CD. High anti-tTGA titers were observed in those who were diagnosed with a positive duodenal biopsy. CONCLUSION: HLA-DQ typing is not cost effective as a first-line screening test for CD in T1D patients because of over-representation of CD permissive HLA alleles in this group. Anti-tTGA titers may be useful in diagnosing CD in T1D without duodenal biopsy, as high levels were found to be strongly predictive of CD.

Tracheobronchitis in ulcerative colitis: a case report of therapeutic response with infliximab and review of the literature.

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.

Pre-exposure prophylaxis for HIV prevention during pregnancy and lactation: forget not the women and children.

Pregnancy is known to be a time of increased susceptibility to acquiring to human immunodeficiency virus (HIV) infection and this increased maternal risk places the unborn child at risk of vertical transmission. Pre-exposure prophylaxis (PrEP) involves the provision of antiretroviral therapy to an HIV-negative individual with ongoing risk of HIV exposure to limit the likelihood of HIV transmission. The inclusion of PrEP as part of a comprehensive strategy is recognised as an effective and safe means of reducing HIV infection in serodiscordant couples, thereby reducing the risk of vertical transmission of HIV. Current data suggest that PrEP is safe to continue during pregnancy and breastfeeding in HIV-negative women who remain vulnerable to acquiring HIV. The recent Pharmaceutical Benefits Scheme subsidisation of PrEP has reduced the financial and practical obstacles of PrEP provision, and a subsequent increase in patient awareness and acceptance of PrEP is expected. The framework for appropriately identifying and managing at-risk pregnant and lactating women requiring PrEP is poorly defined and warrants further clarification to better support clinicians and this patient group. This review discusses the current recommendations highlighting the gaps in the guidelines and makes some recommendations for future guideline development.

The significance of anti-granulocyte-macrophage colony-stimulating factor antibodies in cryptococcal infection: case series and review of antibody testing.

We report two cases of cryptococcosis, associated with anti-granulocyte-macrophage colony-stimulating factor antibodies. We review this recently identified acquired form of autoimmune immune deficiency and discuss the potential applications of granulocyte-macrophage colony-stimulating factor antibody testing by enzyme-linked immunosorbent assay.

An immunodiagnostic assay for quantitation of specific IgE to the major pollen allergen component, Pas n 1, of the subtropical Bahia grass.

BACKGROUND: Pollens of the Panicoideae subfamily of grasses including Bahia (Paspalum notatum) are important allergen sources in subtropical regions of the world. An assay for specific IgE to the major molecular allergenic component, Pas n 1, of Bahia grass pollen (BaGP) would have immunodiagnostic utility for patients with pollen allergy in these regions. METHODS: Biotinylated Pas n 1 purified from BaGP was coated onto streptavidin ImmunoCAPs. Subjects were assessed by clinical history of allergic rhinitis and skin prick test (SPT) to aeroallergens. Serum total, BaGP-specific and Pas n 1-specific IgE were measured. RESULTS: Pas n 1 IgE concentrations were highly correlated with BaGP SPT (r = 0.795, p < 0.0001) and BaGP IgE (r = 0.915, p < 0.0001). At 0.23 kU/l Pas n 1 IgE, the diagnostic sensitivity (92.4%) and specificity (93.1%) for the detection of BaGP allergy was high (area under receiver operator curve 0.960, p < 0.0001). The median concentrations of Pas n 1 IgE in non-atopic subjects (0.01 kU/l, n = 67) and those with other allergies (0.02 kU/l, n = 59) showed no inter-group difference, whilst grass pollen-allergic patients with allergic rhinitis showed elevated Pas n 1 IgE (6.71 kU/l, n = 182, p < 0.0001). The inter-assay coefficient of variation for the BaGP-allergic serum pool was 6.92%. CONCLUSIONS: Pas n 1 IgE appears to account for most of the BaGP-specific IgE. This molecular component immunoassay for Pas n 1 IgE has potential utility to improve the sensitivity and accuracy of diagnosis of BaGP allergy for patients in subtropical regions.

Increasing recognition of dermatomyositis with subcutaneous edema - is this a poorer prognostic marker?

Subcutaneous edema as a presenting feature of dermatomyositis has infrequently been described and is thought to signify a more aggressive disease course. We report a case involving a 38-year-old man who presented with significant subcutaneous edema involving his neck and upper body; he later developed clinical features and biopsy results consistent with dermatomyositis. Only sixteen previous cases of dermatomyositis with subcutaneous edema involving adults have been published in the literature and we aim to review disease progression, prognosis, and optimal treatment of the condition.

Quantitative serum immunoglobulin tests.

What is the test? Immunoglobulins are protein molecules. They contain antibody activity and are produced by the terminal cells of B-cell differentiation known as 'plasma cells'. There are five classes of immunoglobulin (Ig): IgG, IgM, IgA, IgD and IgE. In normal serum, about 80% is IgG, 15% is IgA, 5% is IgM, 0.2% is IgD and a trace is IgE. Quantitative serum immunoglobulin tests are used to detect abnormal levels of the three major classes (IgG, IgA and IgM). Testing is used to help diagnose various conditions and diseases that affect the levels of one or more of these immunoglobulin classes. Some conditions cause excess levels, some cause deficiencies, and others cause a combination of increased and decreased levels. IgD and IgE will not be discussed in this article.

Antinuclear antibody test.

The antinuclear antibody (ANA) test is widely used as a serological marker of autoimmune disease. Antinuclear antibodies are immunoglobulins or antibodies that bind to one or more antigens expressed within the nucleus of human cells. Used selectively, the ANA test can be a useful laboratory tool to help confirm or exclude the diagnosis of systemic rheumatic disease. However, the relatively high prevalence of ANAs in other inflammatory conditions, as well as healthy individuals, can make a positive result difficult to interpret.

Intrapleural therapy for pleural infection from bronchopleural fistula in an adult with hyper-IgE syndrome.

We presented the case of an adult patient with hyper-IgE syndrome (HIES) who was admitted acutely with a large hydropneumothorax from lung consolidation, a bronchopleural fistula and pleural infection. He has had recurrent pulmonary and skin infections since childhood and longstanding pneumatoceles. He was treated with systemic antibiotics and chest tube drainage. Administration of two doses of low-dose intrapleural therapy (1 mg tissue plasminogen activator and 5 mg deoxyribonuclease) allowed complete evacuation of his residual loculated pleural fluid, aided resolution of his infection without provoking a significant air leak and avoided the need for surgery.

A Novel Targeted Amplicon Next-Generation Sequencing Gene Panel for the Diagnosis of Common Variable Immunodeficiency Has a High Diagnostic Yield: Results from the Perth CVID Cohort Study.

With the advent of next-generation sequencing (NGS), monogenic forms of common variable immunodeficiency (CVID) have been increasingly described. Our study aimed to identify disease-causing variants in a Western Australian CVID cohort using a novel targeted NGS panel. Targeted amplicon NGS was performed on 22 unrelated subjects who met the formal European Society for Immunodeficiencies-Pan-American Group for Immunodeficiency diagnostic criteria for CVID and had at least one of the following additional criteria: disease onset at age <18 years, autoimmunity, low memory B lymphocytes, family history, and/or history of lymphoproliferation. Candidate variants were assessed by in silico predictions of deleteriousness, comparison to the literature, and classified according to the American College of Medical Genetics and Genomics-Association for Molecular Pathology criteria. All detected genetic variants were verified independently by an external laboratory, and additional functional studies were performed if required. Pathogenic or likely pathogenic variants were detected in 6 of 22 (27%) patients. Monoallelic variants of uncertain significance were also identified in a further 4 of 22 patients (18%). Pathogenic variants, likely pathogenic variants, or variants of uncertain significance were found in TNFRSF13B, TNFRSF13C, ICOS, AICDA, IL21R, NFKB2, and CD40LG, including novel variants and variants with unexpected inheritance pattern. Targeted amplicon NGS is an effective tool to identify monogenic disease-causing variants in CVID, and is comparable or superior to other NGS methods. Moreover, targeted amplicon NGS identified patients who may benefit from targeted therapeutic strategies and had important implications for family members.

Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes.

TNFRSF13B encodes transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), a B cell- specific tumor necrosis factor (TNF) receptor superfamily member. Both biallelic and monoallelic TNFRSF13B mutations were identified in patients with common variable immunodeficiency disorders. The genetic complexity and variable clinical presentation of TACI deficiency prompted us to evaluate the genetic, immunologic, and clinical condition in 50 individuals with TNFRSF13B alterations, following screening of 564 unrelated patients with hypogammaglobulinemia. We identified 13 new sequence variants. The most frequent TNFRSF13B variants (C104R and A181E; n=39; 6.9%) were also present in a heterozygous state in 2% of 675 controls. All patients with biallelic mutations had hypogammaglobulinemia and nearly all showed impaired binding to a proliferation-inducing ligand (APRIL). However, the majority (n=41; 82%) of the pa-tients carried monoallelic changes in TNFRSF13B. Presence of a heterozygous mutation was associated with antibody deficiency (P< .001, relative risk 3.6). Heterozygosity for the most common mutation, C104R, was associated with disease (P< .001, relative risk 4.2). Furthermore, heterozygosity for C104R was associated with low numbers of IgD(-)CD27(+) B cells (P= .019), benign lymphoproliferation (P< .001), and autoimmune complications (P= .001). These associations indicate that C104R heterozygosity increases the risk for common variable immunodeficiency disorders and influences clinical presentation.

Cross With Caution: Antibiotic Cross-Reactivity and Co-Reactivity Patterns in Severe Cutaneous Adverse Reactions.

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.