Objective:We examined a cohort of Australian patients with statin exposure who developed a necrotizing autoimmune myopathy (NAM) associated with a novel autoantibody against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and describe the clinical and therapeutic challenges of managing these patients and an optimal therapeutic strategy.Methods:Clinical, laboratory, EMG, and histopathologic results and response to immunomodulation are reported in 6 Australian patients with previous statin exposure and antibodies targeting HMGCR.Results:All patients presented with painless proximal weakness following statin therapy, which persisted after statin cessation. Serum creatine kinase (CK) levels ranged from 2,700 to 16,200 IU/L. EMG was consistent with a myopathic picture. Muscle biopsies revealed a pauci-immune necrotizing myopathy. Detailed graphical representation of the clinical course of these patients showed a close association with rising CK and an increase in clinical weakness signifying relapses, particularly upon weaning or ceasing steroids. All 6 patients were responsive to initial steroid therapy, with 5 relapsing upon attempts to wean steroids. Both CK and clinical strength improved with the reinstitution of immunotherapy, in particular steroids and IV immunoglobulin (IVIg). All patients required treatment with varying multiagent immunosuppressive regimens to achieve clinical remission, including prednisone (n = 6), IVIg (n = 5), plasmapheresis (n = 2), and additional therapy including methotrexate (n = 6), cyclophosphamide (n = 2), rituximab (n = 2), azathioprine (n = 1), and cyclosporine (n = 1).Conclusions:Recognition of HMGCR antibody–associated NAM is important because these patients are responsive to immunosuppression, and early multiagent therapy and a slow and cautious approach to withdrawing steroids may improve outcomes.
Anti-HMGCR antibodies are seen in all subtypes of IIM and IMNM and are associated strongly with statin use and HLA-DR11. Muscle Nerve 52: 196-203, 2015.
The induction of fibroblast apoptosis and their clearance by phagocytes is essential for normal wound healing and prevention of scarring. However, little is known about the clearance of apoptotic fibroblasts and whether apoptotic cells are active participants in the recruitment and activation of phagocytes. In this study, we provide the first evidence that apoptotic fibroblasts actively release increased amounts of thrombospondin (TSP1) to actively recruit macrophages. Expression of TSP1 and its receptor CD36 was increased on the surface of apoptotic fibroblasts. By chemical cross-linking and immunoprecipitation we show that TSP1 and CD36 were directly associated. This was confirmed by confocal microscopy. Blockade of either CD36 or TSP1 on apoptotic fibroblasts inhibited phagocytosis. Blockade of ␣v3 integrins as well as CD36 and TSP1 on macrophages inhibited phagocytosis. In contrast, phosphatidylserine or lectins were not involved. These findings suggest that apoptotic fibroblasts release TSP1 as a signal to recruit macrophages while the up-regulated expression of the CD36/TSP1 complex on their cell surface may form a ligand bridging the fibroblast to a complex consisting of ␣v3/CD36/TSP1 on macrophages.
A subcommittee of the Drug and Therapeutics committee has been established to review drug allergies and adverse drug reactions (ADRs) encountered in the hospital. The multidisciplinary team consists of a consultant immunologist, general medical practitioner, allergy team pharmacist(s), director of pharmacy (organisational Governance representative), allergy nurse, and external expert (senior university staff ).The ADR review group was established 5 years ago and meets bimonthly. Staffs are encouraged to report hospital encountered allergies/ADRs to the group who takes varied and appropriate actions and interventions. Various tools have been developed via this group to better manage drug allergies, and projects and publications have ensued.A form has been developed and widely made available to the organisation, to be completed by any healthcare professional, who encounters a patient with ADR/drug allergy. The completed forms are submitted to the allergy pharmacist who collates them and presents them to the group at the bimonthly ADR group meetings. Each reported ADR is discussed in detail and appropriate action implemented. This includes updating patient hospital records, reporting to the national Pharmacovigilance database and providing feedback to General Practitioners, patients and carers.This group also monitors new research, trends in ADR reports, provide feedback to clinical teams, and undertakes research and service improvement projects. The group also undertakes and organises education of the hospital staff regarding allergies and ADR management.The ADR review group works as an advocate for improved patient safety and the prevention of drug errors. The group works closely with ASCIA representatives to share learnings and initiatives. We feel other institutions would benefit from a similar structure. TEN is an extremely rare complication of drug treatment (estimated at 1-2 cases per million each year). 1 Chronic non-granulomatous supraglottitis is an unusual disease rarely reported in paediatric medical literature.
P18 A RARE CASE OF CHRONIC NON GRANULOMATOUS SUPRAGLOTTITIS AND TOXIC EPIDERMAL NECROLYSIS (TEN) SECONDARY TO ITS TREATMENT IN A TEENAGE GIRL
2Case history: A 13-year-old girl presented to our regional hospital on 6 February 2017 with gradually worsening history of dysphonia, lethargy, and weight loss (7.3%) since October 2016. She had two courses of oral Augmentin-duo for ongoing symptoms of fever, dyspnoea and cough by November 2016. A chest X-ray was suggestive of left sided consolidation at the time. Paired sera 4 weeks apart in January and February showed positive IgA, IgG and negative IgM antibody titres to Chlamydiae Pneumoniae and she was given a 5-week course of doxycycline for a presumptive diagnosis of atypical pneumonia. Cough, dyspnoea and chest X-ray abnormalities resolved by January 2011. Her only significant past medical history was eczema.Systemic examination was normal except mild inspiratory stridor. Direct flexible laryngoscopy (DFL) revealed appearance of supraglottitis. She...
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