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Biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) have been an important advance in the management of inflammatory arthritis, but are expensive medications, carry a risk of infection and other adverse effects, and are often perceived as a burden by patients. We used GRADE methodology to develop recommendations for dose reduction and discontinuation of b/tsDMARD in people with rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA) and psoriatic arthritis (PsA) who have achieved a low disease activity state or remission. The recommendations form part of the Australian Living Guideline for the Pharmacological Management of Inflammatory Arthritis, an NHMRC-endorsed 'living' guideline, in which recommendations are updated in near real-time as new evidence emerges. Conditional recommendations were made in favour of dose reduction in RA and AxSpA but not in PsA. Abrupt discontinuation of b/tsDMARD is not recommended in any of the three diseases.

The development of vaccines against SARS-CoV2 has been a key public health response to the COVID-19 pandemic. However, since their introduction, there have been reports of anaphylactic reactions to vaccines in individuals with history of allergic reactions to other vaccines, excipients or to COVID vaccines.A dedicated adult COVID vaccine allergy clinic with a standardised allergy testing protocol was set up to investigate safety and suitability of available COVID vaccines in Australia.Patients referred to a state-wide COVID-19 vaccine allergy clinic between March and August 2021 with a history of allergy underwent skin-prick testing and intradermal testing to both available vaccine formulations (BNT162b2 and ChAdOx1-S), excipients (polyethylene glycol and polysorbate 80), excipient-containing medications and controls. Basophil activation testing was conducted in few subjects with convincing history of immediate type reactions.Fifty-three patients underwent testing for possible excipient allergy (n = 19), previous non-COVID vaccine reaction (n = 13) or previous reaction to dose 1 of COVID-19 vaccine (n = 21). Patients were predominantly female (n = 43, 81%), aged 18-83 (median 54) years. Forty-four patients tested negative and 42 of these received at least their first dose of a COVID-19 vaccine. Nine patients tested positive to excipients or excipient-containing medication only (n = 3), or vaccines (n = 6). Five patients were positive to just BNT162b2, 3/5 have been vaccinated with ChAdOx1-S. One who was skin test positive to both vaccines, but negative BAT to ChAdOx1-S was successfully vaccinated with ChAdOx1-S.Even in a high-risk population, most patients can be vaccinated with available COVID-19 vaccines. This paper reports local experiences using a combined allergy testing protocol with skin testing and BAT during the pandemic.

Background IgG4 related disease (IgG4RD) is a newly described multisystem fibro-inflammatory disorder. There is a paucity of literature describing the Australian experience of this rare condition. Aims To characterise the Royal Adelaide Hospital IgG4RD cohort with biopsy-proven disease. Methods A search of the Frome Road SA Pathology database was performed for all tissue biopsies containing the phrase 'IgG4 positive'. Case notes were reviewed for clinical details, laboratory and radiology results. Histological features according to the Boston Criteria were used. Patients with available case notes, highly suggestive or probable histology and clinical features to suggest IgG4RD were included. Results Twenty patients had definite or probable IgG4RD and suggestive clinical features; median age 59 (20-76), male : female 1.5:1. There was considerable delay in diagnosis (median diagnosis at 64 months). Organ involvement included: 11 exocrine gland, seven pancreatobiliary, seven nodal, seven soft tissue, five retro-orbital, three retroperitoneal fibrosis and two renal. Systemic symptoms at diagnosis were seen in eight patients. Seven (35%) had an elevated serum IgG4 (>1.35 g/L) at diagnosis. Only 12 (60%) required immunosuppressive treatment (corticosteroids); of these, four (20%) required a steroid-sparing agent and four (20%) required B-cell depleting therapy (rituximab). The median duration of follow up was 18 months. Conclusions This is the first characterised Australian cohort with generalised IgG4RD, a rare, relatively indolent and under-recognised multisystem disorder. Diagnosis is difficult given lack of awareness of this rare condition among physicians, its presentation as a great disease mimic, challenges with histopathological assessment and the absence of a suitable serum biomarker.

We describe the use of radiotherapy for parotid IgG4‐related disease (IgG4‐RD), initially misdiagnosed as Kimura's disease, with sustained good partial response in a 37‐year‐old male. To the best of our knowledge, this is the first reported case of radiation for extra‐orbital IgG4‐RD, albeit inadvertently.

Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. Although TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4-8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 (a disintegrin and metalloprotease thrombospondin, number 13) activity. A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. Although early confirmation of aHUS is often not possible, except in the minority of patients in whom auto-antibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA.

Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. While TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4-8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 activity (a disintegrin and metalloprotease thrombospondin, number 13). A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. While early confirmation of aHUS is often not possible, except in the minority of patients in whom autoantibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA.

Background: The EVOLVE (evaluating evidence, enhancing efficiencies) initiative aims to drive safer, higher-quality patient care through identifying and reducing low-value practices. Aims: To determine the Australian Rheumatology Association's (ARA) top five' list of low-value practices. Methods: A working group comprising 19 rheumatologists and three trainees compiled a preliminary list. Items were retained if there was strong evidence of low value and there was high or increasing clinical use and/or increasing cost. All ARA members (356 rheumatologists and 72 trainees) were invited to indicate their top five' list from a list of 12-items through SurveyMonkey in December 2015 (reminder February 2016). Results: A total of 179 rheumatologists (50.3%) and 19 trainees (26.4%) responded. The top five list (percentage of rheumatologists, including item in their top five list) was: Do not perform arthroscopy with lavage and/or debridement for symptomatic osteoarthritis of the knee nor partial meniscectomy for a degenerate meniscal tear (73.2%); Do not order anti-nuclear antibody (ANA) testing without symptoms and/or signs suggestive of a systemic rheumatic disease (56.4%); Do not undertake imaging for low back pain for patients without indications of an underlying serious condition (50.8%); Do not use ultrasound guidance to perform injections into the subacromial space as it provides no additional benefit in comparison to landmark-guided injection (50.3%) and Do not order anti-double-stranded DNA antibodies in ANA negative patients unless the clinical suspicion of systemic lupus erythematosus remains high (45.3%). Conclusions: This list is intended to increase awareness among rheumatologists, other clinicians and patients about commonly used low-value practices that should be questioned.

In South Australia, between 2000 and 2014, 57 patients with idiopathic inflammatory myositis (IIM) were treated with intravenous immunoglobulin (IVIg). We reviewed disease characteristics to determine predictors of response to therapy and IVIg dosing and duration to identify opportunities to rationalise IVIg use. Patients with dermatomyositis/polymyositis had a response rate of 77% and were more likely than inclusion body myositis to respond to therapy. Consideration should be given to the use of the lowest possible dose of IVIg and to the undertaking of trials of cessation of IVIg in patients with stable IIM.

Background IgE-mediated allergy to the wheat protein omega-5-gliadin (O5G) is associated with wheat-dependent exercise-induced anaphylaxis (WDEIA), where exercise acts as a cofactor, triggering anaphylaxis after wheat ingestion. The wider application of O5G-specific IgE (sIgE) testing has revealed that the manifestations of O5G allergy extend beyond WDEIA. Aims This study documents clinical manifestations in a large series of patients with sIgE to O5G. Methods A retrospective clinical audit was performed on adult patients with a positive O5G sIgE (>0.35kU/L) between 2007 and 2013 compared with a group who had negative O5G sIgE. Clinical characteristics and skin prick test (SPT) results were examined. Results Sixty-seven patients were characterised, 26 of whom presented with food-dependent exercise-induced allergy, whilst others presented with exercise-induced symptoms without apparent food association (16/67), idiopathic anaphylaxis (10/67), food-induced allergic symptoms without exercise (10/67) or recurrent acute urticaria (5/67). Specific IgE to O5G had 91% sensitivity and 92% specificity for wheat-related allergic symptoms. SPT had sensitivity of 92% and specificity of 84%. Conclusion WDEIA is the most common manifestation of O5G allergy, but patients may present with a variety of allergic manifestations, and wheat allergy is not always obvious on history. Non-exercise cofactors or a lack of cofactors were identified in many patients. A distinctive feature of this allergy is that despite regular wheat ingestion, allergic reactions to wheat occur infrequently. Testing for sIgE to O5G should be considered in patients presenting with exercise-induced urticaria/anaphylaxis, idiopathic anaphylaxis and recurrent acute (but not chronic) urticaria.

Background Churg–Strauss syndrome (CSS) is a rare, idiopathic systemic vasculitis. There is emerging evidence of an association between the presence or absence of antineutrophil cytoplasmic antibodies (ANCA) and clinical phenotype. Thromboembolism is an increasingly recognised complication of the disease. Aims Given the paucity of Australian data, the aim of this study was to examine the clinical and laboratory features of CSS in a single Australian centre. Methods We performed a retrospective review of all patients who fulfilled the American College of Rheumatology classification criteria for CSS managed at the Department of Immunology, Royal Adelaide Hospital between 2002 and 2008. Results Nineteen patients were included. All patients had asthma and most had upper airway involvement. Peripheral nerve, musculoskeletal, gastrointestinal and cutaneous involvement was common. Renal and cardiac involvement was uncommon in this series. Histological confirmation was obtained in 15 patients (78.9%). Ten patients (52.6%) were ANCA+, and these were more likely to have musculoskeletal involvement, such as arthralgia or myalgia (odds ratio 57, P = 0.005). Thrombosis was a feature at diagnosis in six patients (31.6%); two of these recurred with relapse. Sixteen patients (84.2%) were followed up; five died, and mean survival was 8.9 years. Conclusions This is the first Australian study to focus on CSS. Our results demonstrate similar presentation and prognosis of CSS to previous descriptions; however, we noted that musculoskeletal involvement was more common in ANCA+ patients. In our series, thrombosis was a significant complication and we suggest that thromboprophylaxis may be warranted.

Background: Urticaria, angioedema and anaphylaxis are common adverse reactions to non-steroidal anti-inflammatory drugs (NSAIDs). Aim: To investigate the clinical characteristics of NSAID-induced acute hypersensitivity reactions with structured oral drug challenges. Methods: Patients with NSAID-induced urticaria, angioedema or anaphylaxis were challenged with either the homologous NSAID to confirm diagnosis or a heterologous NSAID to investigate cross-reactivity. Data were analysed retrospectively and supplemented by a telephone questionnaire. Results: Sixty-eight patients (mean age 48.3, 53 females) reported a total of 75 instances of NSAID-induced reactions of which 64% were purely cutaneous and 36% were systemic anaphylaxis. Ibuprofen was the most frequent cause of reactions (35%), however, diclofenac was the most frequent cause of anaphylaxis (48%). Seventeen out of 40 (43%) homologous NSAID challenges were positive; presentation with anaphylaxis or reaction to diclofenac predicted a positive challenge. Only 7 of 28 (25%) of heterologous NSAID challenges were positive. Structured challenges enabled us to identify 23 (34%) patients with selective reactivity to a single NSAID, 19 (28%) patients with cross-reactivity to multiple NSAIDs and 23 (34%) patients in whom NSAID hypersensitivity was not reproduced. Selective reactors presented most often with anaphylaxis and some had a background of beta-lactam antibiotic allergy. Cross-reactive patients often had a background of chronic urticaria and presented with milder reactions. Conclusion: In the absence of a reliable in vitro test, structured drug challenges allow identification of selective and cross-reactive NSAID hypersensitivity syndromes. NSAID-induced anaphylaxis is often associated with selective hypersensitivity and patients may not need to avoid other NSAIDs.

Background and aims: Intragam® 10 NF is the next generation 10% intravenous immunoglobulin with three pathogen reduction steps and a noncarbohydrate stabiliser. This open label, cross-over study in patients with primary immunodeficiency was designed to evaluate whether Intragam 10 NF differed in its pharmacokinetics (PK) compared with Intragam P and to assess Intragam 10 NF safety and tolerability. Methods: Nineteen primary immunodeficiency patients were administered one cycle of their existing Intragam P dose (0.2–0.8 g/kg 3–4 weekly), followed by seven cycles of Intragam 10 NF administered at the same dosing schedule as Intragam P. The primary objective was to compare serum immunoglobulin G (IgG) trough levels. Secondary endpoints were PK variables, safety and tolerability. Results: There was no significant within-patient difference in the average trough immunoglobulin G concentration between Intragam P and Intragam 10 NF (8.76 g/L, 8.55 g/L respectively) (geometrical mean ratio 1.034; 95% confidence interval 0.996–1.073; P = 0.079). Mean PK parameters for both products were similar, with all 95% confidence interval encompassing 1.0 except for time to maximum concentration. Time to maximum concentration occurred earlier with Intragam 10 NF compared with Intragam P, with a shorter infusion time (mean 1.75 h vs 2.52 h respectively; P

Aim: To ascertain the mortality risk and investigate clinical and serological factors influencing survival of patients listed on the South Australian Scleroderma Register (SASR). Methods: The SASR is a population-based register, which was commenced in 1993 and has actively sought to recruit all scleroderma patients diagnosed in SA over a 15-year period. Clinical and serological details have been accessed from questionnaires or from clinical and laboratory files. Standardized mortality ratio (SMR) was calculated and survival analyses performed on all living and deceased patients listed on this SASR (n= 786). Results: Patients with scleroderma had increased mortality compared with the general SA population (SMR 1.46 (95% confidence interval (CI) 1.28–1.69)). Factors that adversely altered survival included older age at onset, male gender, diffuse skin involvement, presence of scleroderma renal crisis, pulmonary fibrosis, pulmonary arterial hypertension, cancer and anti-topoisomerase (Scl-70) and anti-U1 RNP antibodies, while a trend was observed with increased nailfold capillary dropout. Mean age of death for patients with limited scleroderma was 74.1 years (95% CI 72.5–75.7), diffuse scleroderma 62.9 years (95% CI 59.4–66.4) and overlap disease 57.8 years (95% CI 48.7–66.9). Survival improved over the 15-year study period. Conclusions: Scleroderma substantially reduces life expectancy. Survival is influenced by age at onset, gender, diffuse involvement of skin fibrosis, visceral involvement, development of cancer, extent of microvascular capillary damage and by the presence of scleroderma-associated antibodies, Scl-70 and RNP. Scleroderma renal crisis continues to carry high mortality. Survival improved over the 15-year study period.

We report a case of type I cryoglobulinaemia in a 52-year-old man who presented with widespread cutaneous necrosis. The diagnosis could not be established early on, as repeated testing for cryoglobulin was negative despite a careful collection method. The diagnosis was made 1 year later, on an incidental full blood smear that revealed crystals, which is an uncommon way to diagnose this condition. We discuss the difficulties we faced in establishing the diagnosis and emphasise the need for repeat cryoglobulin testing in this clinical setting. In such cases, examination of a blood smear should be considered.

Summary Immunophenotyping of acute myeloid leukaemia (AML) has controversial implications with regards to prognosis. The aims of the present study were to determine the frequency of leukaemia-associated phenotypes (LAP) in AML and to correlate their presence with response to induction chemotherapy. We analysed bone marrow samples at diagnosis from 84 AML patients using triple staining flow cytometry with routine standard panel of monoclonal antibodies. The association of LAP and response to induction chemotherapy was evaluated retrospectively. LAP were observed in 54 (64%) patients: lineage infidelity in 19 (35%), asynchronous antigen expression in 28 (52%), and lack of expected lineage specific antigens in 19 (35%). Significant correlation was found between LAP and responses to induction chemotherapy. Response to induction chemotherapy was more frequent in the absence of LAP (P

Chronic urticaria is a disease consisting of spontaneous pruritic welts, present on all or most days for more than 6 weeks. It is commonly supposed to be allergic in origin, although allergy is not the cause in the majority of cases, and it has therefore been termed 'chronic idiopathic urticaria'. Recent evidence indicates that at least a subset of patients in whom no extrinsic or internal cause can be identified are in fact autoimmune in origin. This is based mainly on the detection of pathogenic autoantibodies to the high-affinity immunoglobulin E receptor FcepsilonR1, which are thought to activate cutaneous mast cells. In this article, we review the evidence that has given rise to this autoimmune 'paradigm' and its impact on diagnosis and management.

Although common variable immunodeficiency (CVID) is sometimes associated with sarcoidosis/granulomatous disease, there have only been isolated reports of selective immunoglobulin A (IgA) deficiency and granulomatous disease. We present a patient with IgA deficiency who developed Heerfordt syndrome, a variant of neurosarcoidosis. This specific entity has not been previously reported to occur in IgA deficiency. Our case expands the reported associations of IgA deficiency and provides another example to the paucity of reported cases of sarcoidosis occurring in patients with IgA deficiency. As CVID and IgA deficiency have common underlying genetic factors, such an association is biologically plausible.

A 72-year-old man presented with erythema and induration of his calves and forearms. He had a past history of stage 1 colorectal carcinoma, treated with resection and primary anastamosis 4 years earlier. A diagnosis of eosinophilic fasciitis was made based on the characteristic clinical appearance, peripheral blood eosinophilia and a skin biopsy. There was no improvement in the condition following treatment with prednisolone or methotrexate. One year later, abnormal liver function studies were noted, and an abdominal computed tomography scan and subsequent needle biopsy of the liver confirmed a neoplastic lesion in the liver consistent with a metastatic colorectal carcinoma. Systemic chemotherapy with oxaliplatin, 5-fluorouracil and capecitabine was commenced, and resulted in partial remission of the colorectal carcinoma. Simultaneously, the indurations of the forearms and calves also improved, suggesting that the eosinophilic fasciitis was a paraneoplastic phenomenon.

Rituximab is a chimeric monoclonal antibody specific for human CD20 that causes selective transient depletion of the CD20+ B-cell subpopulation. We report the first case of systemic lupus erythematosus (SLE) pneumonitis resistant to conventional treatments that responded well to rituximab and review current reports on the use of rituximab in SLE.