Clinical associations of patients with anti-3-hydroxy-3-methylglutaryl CoA reductase antibody-associated immune-mediated necrotising myopathy.

BACKGROUND: Anti-3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) antibodies are associated with a subtype of immune-mediated necrotising myopathy (IMNM). AIMS: To determine clinical associations of anti-HMGCR antibodies for anti-HMGCR-associated IMNM (HMGCR-IMNM) among a cohort of patients in Western Australia and to determine whether serial HMGCR antibody levels parallel disease activity. METHODS: Adult patients with positive anti-HMGCR antibodies detected by enzyme-linked immunosorbent assay between January 2015 and November 2019 were included. Symptoms, examination findings, imaging findings and blood test results were reviewed retrospectively using patient records and laboratory database results. RESULTS: Among 26 patients with positive anti-HMGCR antibodies, 23 were diagnosed with HMGCR-IMNM representing a positive predictive value (PPV) of 88%. Myopathy was frequently severe at diagnosis with limb weakness graded as Medical Research Council score 3 or below in 78% of patients, bulbar muscle weakness in 39% and an average creatine kinase (CK) at diagnosis of 7986 U/L. The majority (83%) required at least two therapies to maintain remission, 48% had at least one flare of disease and 57% did not achieve CK normalisation. Correlation between CK and anti-HMGCR antibody level at diagnosis was low (r = 0.04). Anti-HMGCR antibodies fell with treatment in 10 of 12 patients, but remained persistently positive in 83% of patients. CONCLUSIONS: The PPV of anti-HMGCR antibodies for HMGCR-IMNM in this Western Australian cohort is 88%. Patients typically present with proximal limb weakness, dysphagia and markedly elevated CK, and, despite multiagent immunosuppression, a significant number of patients have evidence of persistent biochemical myositis. Anti-HMGCR antibodies did not correlate with CK levels at diagnosis.

Remission and low disease activity in psoriatic arthritis publications: a systematic literature review with meta-analysis.

OBJECTIVES: Remission (REM) or low disease activity (LDA) is the treatment target in psoriatic arthritis (PsA). The objective of this study was to assess the reporting and prevalence of REM/LDA in published studies of PsA. METHODS: This was a systematic literature review of all clinical papers published in PubMed, EMBASE or Cochrane database in English between 2012 and 2019 in the field of PsA. Data were collected regarding reporting of REM/LDA by very low disease activity/minimal disease activity (VLDA/MDA), Disease Activity index for Psoriatic Arthritis (DAPSA), or Disease Activity Score 28 joints (DAS28). The pooled rates of REM and LDA by each definition were calculated by random effect meta-analysis. RESULTS: In all, 258 publications (corresponding to 114 651 patients), of which 81 (31%) were randomized controlled trials, were analysed: patients' mean age was 49.4 ( 4.4) years; with a mean disease duration of 8.5 ( 3.8) years. REM/LDA was reported in 91/258 (35.3%) publications. VLDA/MDA was used in 61/91 (67.0%) studies, DAPSA in 27/91 (29.6%) and DAS28 in 28/91 (30.7%), with 40/91 (43.9%) papers reporting several of these definitions. The pooled prevalence (lower-upper limits) of REM was 13.1% (10.9-15.4), 23.1% (16.8-30.1) and 42.1% (33.9-50.4) using VLDA, DAPSA-REM and DAS28, respectively. For LDA the pooled prevalence was 36.3% (32.3-40.5), 52.8% (41.8-63.6) and 60.4% (52.5-68.0) using MDA, DAPSA-LDA and DAS28, respectively. CONCLUSION: REM/LDA status was reported in only1/3 of recent studies on PsA, with important variations in the frequency of these outcomes according to the definition used: 13.1-42.1% for REM, and 36.3-60.4% for LDA. This highlights the need for consensus.

Non-immediate heparin and heparinoid cutaneous allergic reactions: a role for fondaparinux.

Non-immediate allergic cutaneous reactions to heparins have been increasingly reported, typically manifesting as large, eczematous plaques at sites of subcutaneous injection. Patients may demonstrate cross-reactivity between unfractionated heparin, low molecular weight heparin and semi-synthetic heparinoids, making finding an alternative difficult. Fondaparinux has been identified as a useful alternative in such patients; here we present the first two documented cases in Australia and a literature review.

Trabecular bone score (TBS) in Cushing's disease: TBS gain after hypercortisolism normalization.

CONTEXT: Hypercortisolism frequently induces trabecular bone loss, more pronounced at the lumbar spine, resulting in osteoporosis, and thus an increase in fracture risk. Several studies have shown bone mass recovery in patients with Cushing's disease (CD) after treatment. OBJECTIVE: To examine treatment effects on TBS (trabecular bone score) in addition to aBMD (areal bone mineral density) in a cohort of patients with CD. DESIGN AND SETTING: Single-center retrospective longitudinal study in patients diagnosed with CD and successfully treated following surgery and/or medical treatment. PATIENTS: We included 31 patients with median age and BMI (body mass index) of 37.7 [28.4;43.3] years old and 27.7 [25.8;30.4] kg/m2, respectively. Median 24 h urinary cortisol before treatment was 213.4 [168.5;478.5] µg/24 h. All subjects were completely biochemically controlled or cured after treatment. MAIN OUTCOME MEASURES: aBMD and TBS were evaluated at AP Spine (L1-L4) with DXA prodigy (GE-Lunar), QDR 4500 (Hologic), and TBS iNsight® (Med-Imaps) before and after treatment. RESULTS: Absolute TBS and aBMD gains following cure of CD were significant (p < 0.0001, and p < 0.001, respectively). aBMD and TBS increased by +3.9 and 8.2 % respectively after cure of CD. aBMD and TBS were not correlated before (p = 0.43) and after treatment (p = 0.53). Linear regression analyses showed that TBS gain was independent of baseline BMI and that low TBS at baseline was predictive of TBS gain after treatment. CONCLUSION: The more significant improvement of microarchitecture assessed by TBS than aBMD and the absence of correlation between TBS and aBMD suggest that TBS may be an adequate marker of bone restoration after cure of CD. To support this conclusion, future studies with larger sample sizes and longer follow-up periods should be carried out.

Unusual Case of Painful Glossitis and Xerostomia Following Vaccination with Pfizer-BioNTech SARS-CoV-2 (BNT162b2).

BACKGROUND Adverse events following immunization (AEFIs) remain under recognized, particularly when the symptoms experienced are uncommon and mimic natural disease. In the context of the worldwide effort to provide protection against SARS-CoV-2 using multiple doses of vaccination and with the availability of multiple vaccines, the early recognition and prompt treatment of AEFIs has increased importance, as does the ability to carefully select an alternative after an AEFI occurs. CASE REPORT A 60-year-old woman presented for clinical immunology review with a 9-month history of glossitis and xerostomia. Onset of symptoms occurred following her first vaccination with a COVID-19 vaccine (BNT162b2). After partial interval improvement, her symptoms progressively worsened after a second vaccination and third booster vaccination with BNT162b2. While undergoing reviews from multiple specialists for possible underlying connective tissue disease, and with other causes of her symptoms being excluded, the patient's symptoms progressed, with worsening tongue swelling with new fissuring and xerostomia. The patient experienced an unintentional weight loss of 8 kg due to oral discomfort. It was only after this time that an AEFI was considered the cause of her presentation, after all other diagnostic considerations were considered unlikely. Targeted, symptomatic, localized treatment with topical oral corticosteroids was initiated, followed by a gradual tapering regimen, with excellent response. CONCLUSIONS This case highlights the need to consider AEFIs early in the differential diagnosis of unusual presentations and the importance of considering a trial of targeted symptomatic treatment for patients, even if diagnostic uncertainty remains.

Acute management of anaphylaxis in pregnancy.

BACKGROUND: Anaphylaxis in pregnancy is rare but can potentially be associated with significant morbidity and mortality for the mother, fetus and neonate. With appropriate and timely management, even severe anaphylaxis can be managed with excellent maternal and fetal outcomes. OBJECTIVE: The aim of this article is to provide an illustrative case and highlight current recommendations for diagnosis and management of acute maternal anaphylaxis, which have recently been reviewed and developed into a guideline by the Australasian Society of Clinical Immunology and Allergy. DISCUSSION: An understanding of management of anaphylaxis in pregnancy is essential knowledge in the general practice setting. The recommended dosage and administration of adrenaline (epinephrine) for anaphylaxis is the same in pregnant and non-pregnant patients: 0.5 mg adrenaline intramuscularly in the mid-outer thigh (or dose of 0.01 mg/kg if <50 kg). The use of adrenaline in maternal anaphylaxis is supported by various international guidelines.

Dry-reagent gold nanoparticle-based lateral flow biosensor for the simultaneous detection of Vibrio cholerae serogroups O1 and O139.

Cholera is a communicable disease caused by consumption of contaminated food and water. This potentially fatal intestinal infection is characterised by profuse secretion of rice watery stool that can rapidly lead to severe dehydration and shock, thus requiring treatment to be given immediately. Epidemic and pandemic cholera are exclusively associated with Vibrio cholerae serogroups O1 and O139. In light of the need for rapid diagnosis of cholera and to prevent spread of outbreaks, we have developed and evaluated a direct one-step lateral flow biosensor for the simultaneous detection of both V. cholerae O1 and O139 serogroups using alkaline peptone water culture. Serogroup specific monoclonal antibodies raised against lipopolysaccharides (LPS) were used to functionalize the colloidal gold nanoparticles for dual detection in the biosensor. The assay is based on immunochromatographic principle where antigen-antibody reaction would result in the accumulation of gold nanoparticles and thus, the appearance of a red line on the strip. The dry-reagent dipstick format of the biosensor ensure user-friendly application, rapid result that can be read with the naked eyes and cold-chain free storage that is well-suited to be performed at resource-limited settings.