Background: Mutations in the TMEM 173 gene underlie a type I interferon associated disease, STING associated vasculopathy with onset in infancy (SAVI).Patients suffer cutaneous vasculopathy and interstitial lung disease, but are not known to suffer life-threatening infection.Case: We describe a child who presented with Pneumocystis jirovecii pneumonia in early life, from which he recovered.He went on to suffer failure to thrive, developmental delay, livido reticularis and vesicular rash, but without cutaneous vasculitis, and with normal C-reactive protein and erythrocyte sedimentation rates.At three years of age he developed lifethreatening pulmonary hypertension Methods: Whole genome sequencing was performed using the Illumina HiSeqX10 platform and the Seave platform was used for bioinformatic analysis.mRNA expression of interferon-stimulated genes and inflammatory cytokines from peripheral blood mononuclear cells (PBMCs) was determined by qPCR.Luciferase assay was used to model IFNb and NFkB activity in vitro.Results: WGS revealed a novel de novo mutation p.Arg284Ser in STING.mRNA analysis revealed constitutive IFN-gene activation, which correlated to STING activation in vitro.The patient was treated with corticosteroids and the JAK inhibitor Ruxolitinib, resulting in a rapid improvement of pulmonary hypertension, general wellbeing and resolution of the IFN gene signature.However, he did go on to evolve a nasal septal erosion suggesting incomplete control of disease.Conclusions: The p.Arg284Ser variant in STING is pathogenic through a gain-of function mechanism.Absence of cutaneous vasculitis, systemic inflammation and the presentation with an opportunistic infection are atypical raising the possibility that different variants may potentially manifest with an atypical SAVI phenotype.
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.
Patients frequently report antibiotic allergies; however, only 10% of labelled patients have a true allergy.We investigated the documentation of antibiotic 'allergy' labels (AAL) and the effect of labelling on clinical outcomes, in a West Australian adult tertiary hospital.Retrospective cross-sectional analysis of patients captured in the 2013 and 2014 National Antimicrobial Prescribing Surveys was carried out. Data were collected on documented antibiotic adverse drug reactions, antibiotic cost, prescribing appropriateness, prevalence of multi-drug resistant organisms, length of stay, intensive care admission and readmissions.Of the 687 patients surveyed, 278 (40%) were aged 70 or above, 365 (53%) were male and 279 (41%) were prescribed antibiotics. AAL were recorded in 122 (18%) patients and the majority were penicillin labels (n = 87; 71%). Details of AAL were documented for 80 of 141 (57%) individual allergy labels, with 61 describing allergic symptoms. Patients with beta-lactam allergy labels received fewer penicillins (P = 0.0002) and more aminoglycosides (P = 0.043) and metronidazole (P = 0.021) than patients without beta-lactam labels. Five patients received an antibiotic that was contraindicated according to their allergy status. Patients with AAL had significantly more hospital readmissions within 4 weeks (P = 0.001) and 6 months (P = 0.025) of discharge, compared with unlabelled patients. The majority (81%) of readmitted labelled patients had major infections.AAL are common, but poorly documented in hospital records. Patients with AAL are significantly more likely to require alternative antibiotics and hospital readmissions. There may be a role for antibiotic allergy delabelling to mitigate the clinical and economic burdens for patients with invalid allergy labels.
Plasma cell mucositis (PCM) is a rare non-neoplastic plasma cell proliferative disorder of the mucous membranes, which typically presents as soft tissue lesions involving oral, upper airway or genital mucosa. Laryngeal involvement resulting in stridor has been reported in four other cases previously, with three requiring tracheostomy. We present a case of supraglottic stenosis in a 53-year-old woman presenting with dysphonia and stridor, requiring surgical resection on three occasions accompanied by tracheostomy on two occasions; biopsy was consistent with PCM. Due to relapsing disease activity, high-dose prednisolone and mycophenolate mofetil were commenced with prednisolone eventually being ceased. After 2 years of mycophenolate mofetil therapy, the patient’s disease has been controlled without need for further surgical intervention. This is the first reported case of prolonged symptomatic improvement with the use of systemic immunosuppressive therapy with mycophenolate mofetil in PCM.
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.
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