Necrotizing Myopathy Research Articles

Benefits of Early Versus Late Initiation of Intravenous Immunoglobulin in the Treatment of Patients With Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Immune-Mediated Necrotizing Myopathy.

No clinical trials have been conducted to establish optimal and effective treatment in patients with immune-mediated necrotizing myopathy (IMNM), which can have a refractory course with increased morbidity from permanent muscle damage, especially in patients who experience delay in diagnosis and treatment. A subset of autoimmune necrotizing myopathy is associated with antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Treatment involves withdrawing statins and using a combination of immunosuppressant and immunomodulatory treatment. Our study aims to provide longitudinally collected data on outcomes of early versus late initiation of intravenous Ig (IVIG) using our myositis center cohort of patients with anti-HMGCR IMNM. We conducted a retrospective chart review of 31 adult patients of the Oregon Health and Science University Myositis Center who were diagnosed with anti-HMGCR IMNM from September 2016 through October 2022 and reviewed physical examination, serologic laboratory data, and their treatment including prednisone reception as well as treatment response at 0 (the evaluation immediately before IVIG initiation), 3, 6, and 12 months on treatment. We divided this cohort into those who received IVIG at or before six months after receiving the diagnosis of anti-HMGCR IMNM and refer this as the cohort with nondelayed treatment, and those who received IVIG after six months following their diagnosis, which we referred to as the cohort with delayed treatment. Diagnosis of anti-HMGCR IMNM was defined as per the 2016 European Neuromuscular Centre criteria as having all three of elevated serum creatine kinase (CK), proximal muscle weakness, and anti-HMGCR antibodies. We evaluated the response to treatment by using a limited total improvement score (TIS) as per 2016 American College of Rheumatology/EULAR myositis response criteria. Among the 31 total patients, 19 were included within the cohort with nondelayed treatment, and 12 within the cohort with delayed treatment. The two cohorts had a comparable amount of time between the onset of symptoms and diagnosis; however, the cohort with delayed treatment had a significantly longer time between diagnosis and IVIG treatment (P < 0.001). At disease onset, cohorts had a comparable serum CK (P > 0.999), but patients with delayed treatment had an expected lower serum CK (P = 0.016) at the 0-month time point. At the 0-month time point, nine of the patients with nondelayed treatment (47%) required the use of a walker or wheelchair, whereas eight of the cohort with delayed treatment (66%) did. Patients who received nondelayed treatment demonstrated significant improvement in manual muscle testing 8 at the 12-month intervals (P < 0.001). Average serum CK values of all patients measured at the 3, 6, and 12 months did not significantly differ between the groups with nondelayed and delayed treatment. TIS improved more in the group with nondelayed treatment than in the group with delayed treatment (P = 0.002 at 3 months, P = 0.019 at 6 months, and P = 0.001 at 12 months). Seven patients in the group with delayed treatment had permanent residual muscle weakness requiring walker or wheelchair use at 12 months, whereas none of the patients in the group with nondelayed treatment did. Though our results have limitations, they contribute to a growing body of evidence that suggests that IVIG may prove to be a valuable addition to an early and aggressive induction regimen in patients afflicted by anti-HMGCRIMNM, particularly those with moderate to severe weakness requiring the use of a wheelchair or walking aids. Delay in IVIG treatment may lead to the development of permanent residual weakness and long-term disability.

Muscle involvement in systemic sclerosis: high mortality not associated with nature of histological lesions.

The aim of this study was to determine the association between different histological patterns and prognosis in patients with SSc and histologically proven muscle involvement. A multicentre retrospective study was conducted of a cohort of scleroderma patients who had undergone muscle biopsy. The biopsies were reviewed in a coordinated manner to classify patients based on histological findings. Three different patterns were observed: fibrosing myopathy (FM), inflammatory myopathy (IM) and necrotizing myopathy (NM). Rates of survival, muscle relapse, and cardiac and pulmonary events were compared between these three groups. Among 71 scleroderma patients with muscle biopsy specimens available for review, 33 (46.5%) were classified in the FM group, 18 (25.5%) in the IM group, and 20 (28%) in the NM group. The median follow-up time was 6.4 years (interquartile range, 2.2-10.9 years) and 21 patients died during follow-up, primarily from heart disease and infections. The 10-year survival rate after the first non-Raynaud's disease symptom was 80% and the cumulative incidence of muscle relapse was 25%. Neither factor differed significantly between the three groups. The risk of pulmonary events was lowest in the OM group, significantly lower than in the FM group (hazard ratio, 0.17; 95% CI, 0.04-0.67) and non-significantly lower than in the IMNM group (hazard ratio, 0.28; 95% CI, 0.06-1.24). The risk of cardiac events did not differ significantly between the three groups. The mortality rate of scleroderma patients with muscle involvement was not associated with their histological patterns.

P13 Calciphylaxis as a rare skin manifestation in a patient with an inflammatory myositis

Abstract Introduction Calciphylaxis is a rare but severe vascular complication that can occur in patients with inflammatory myositis. It is characterised by an abnormal deposition of calcium in small and medium sized vessels which can then lead to occlusion and tissue ischemia. It is also known as calcific uremic arteriolopathy, primarily associated with end-stage renal disease, but can also manifest in other clinical settings, including myositis. Myositis encompasses various autoimmune disorders such as polymyositis and dermatomyositis. The exact mechanisms underlying the development of calciphylaxis in myositis are not entirely understood. However, chronic inflammation associated with myositis can trigger this condition. Case description A 70-year-old woman presented to the emergency department in April 2021 with one month history of persistent shortness of breath on exertion and fatigue. A thorough investigation was carried out with auto-immune profile being negative and the radiological appearances were consistent with cryptogenic organizing pneumonia (COP). Treatment was initiated promptly with corticosteroids. Further HRCTs were done to assess the patient’s progress, and revealed a general improvement of the peri bronchial distribution of lung infiltrates. In June 2021, she was diagnosed with acute diverticulitis with localized perforation and was managed conservatively. In October 2021, she contracted COVID-19. She recovered well but presented in December 2021 with a 3-week history of increasing breathlessness, symmetrical arm weakness and rash over her lower limbs. A creatine kinase (CK) was sent which came back with a high value of 3907 IU/L. She was then referred to the rheumatology team. Further investigations revealed a cytoplasmic ANA stain but negative myositis antibody profile, an increase in Troponin T, and pericardial effusion. MRI of the upper limbs showed acute proximal upper limb myositis, worse on the left. Subsequent muscle biopsy showed a necrotizing myopathy. The rash on her calves was initially described as a livedo-like rash, though with skin breakdown, necrotic and ulcerated areas. A skin biopsy was reported as non-uremic calciphylaxis. She was treated for myositis with corticosteroids and intravenous immunoglobulins (chosen due to concerns regarding infection given the diverticular perforation). Her leg ulcers were regularly dressed with light compression and treated with antibiotics. These measures improved her muscle strength, CK and troponin. Leg ulcers were slow to heal but did improve over a period of ten months. Regarding her abdominal perforation, she had two surgeries but developed small bowel obstruction in December 2022. Despite surgical intervention, her condition deteriorated and, unfortunately, she passed away. Discussion The co-occurrence of calciphylaxis and myositis poses several interesting questions for medical professionals. The pathogenesis of calciphylaxis in end-stage renal disease is thought to be related to abnormalities in calcium and phosphate metabolism. However, in myositis it is unclear. Chronic inflammation and tissue damage associated with myositis likely play a role in the initiation of the calcification process. Patients with myositis-associated calciphylaxis typically present with painful skin lesions which often start as small, purplish, or mottled patches that progress to necrotic ulcers. These lesions most commonly occur in the lower extremities but can also involve the abdomen, buttocks, or upper extremities. The ulcers are often non-healing and prone to secondary infection leading to a considerable risk of complications. The condition is associated with significant morbidity and mortality. Calciphylaxis in the context of myositis poses diagnostic and treatment challenges given the rarity of the condition. Differentiating it from other causes of tissue necrosis and skin ulcerations requires careful evaluation of clinical history, laboratory tests, imaging, and skin biopsies. This case involved a multidisciplinary approach including dermatologists, rheumatologists, vascular, pain management and wound care specialists. Treatment strategies aim to address wound care, pain management, secondary infection control, controlling inflammation in myositis, optimising renal function and potentially interventions targeting calcium and phosphate metabolism. Overall, calciphylaxis in myositis presents a significant clinical challenge that requires early recognition, prompt diagnosis, and a multidisciplinary treatment approach for managing this complex condition and improving patient outcomes. This condition requires further research to better understand the pathogenesis and outcomes with different treatments. Key learning points The most important learning point in this case for us was the multidisciplinary team required approach to manage this rare condition. Collaboration among rheumatology, dermatology, vascular and wound care specialties helped us to optimise treatment strategies for this condition. Identifying and addressing the underlying causes of calciphylaxis is essential. In myositis, autoimmune processes should be managed appropriately. Proper wound care is crucial to prevent infection and promote wound healing. Wound care specialists can provide guidance on appropriate dressings and techniques to optimise wound healing. Calciphylaxis-associated pain can be severe and may need involvement of pain management team for monitoring and adjustment of medications. Calciphylaxis can be a rare skin manifestation of inflammatory myositis.

STATIN ASSOCIATED IMMUNE MEDIATED NECROTIZING MYOPATHY (SA-IMNM) AND SUBSEQUENT USE OF NON-STATIN LDL-C LOWERING DRUGS

STATIN ASSOCIATED IMMUNE MEDIATED NECROTIZING MYOPATHY (SA-IMNM) AND SUBSEQUENT USE OF NON-STATIN LDL-C LOWERING DRUGS

Purtscher-like retinopathy in a patient with systemic tacrolimus vasculopathy.

Purtscher-like retinopathy is a rare occlusive retinal microangiopathy, whose pathogenesis has not been totally defined yet. Most frequent cause of Purtscher-like retinopathy is acute pancreatitis, but it may be triggered by other systemic or toxic conditions. We report herein a case of Purtscher-like retinopathy in the context of systemic tacrolimus vasculopathy. A 56-years old male with history of kidney transplant was referred to local emergency room because of a global worsening of health conditions, with fatigue, muscular pain and diuresis contraction. During hospitalization the patient came to our attention for sudden and severe visual acuity impairment in both eyes. Extensive ophthalmological assessment, optical coherence tomography (OCT) and fluorescein angiography (FA) were performed disclosing a marked drop in best corrected visual acuity (BCVA) (20/200 in the right eye and 10/400 in the left eye) caused by a bilateral severe occlusive retinal microangiopathy complicated by diffuse retinal ischaemia and neovascular glaucoma. Muscular biopsy showed a necrotizing myopathy with autoimmune features, as indicated by conspicuous upregulation of MHC-I complex and microangiopathic changes, consistent with tacrolimus toxicity. Tacrolimus administration was interrupted, and intravenous glucocorticoids were administered. The large areas of retinal ischemia and neovascular glaucoma were treated with pan-retinal photocoagulation and intravitreal injections of bevacizumab with complete regression of iris neovascolarization. BCVA measured 20/200 in both eyes at last follow-up visit, 20 months after symptoms onset. Purtscher-like retinopathy should be suspected in patients under treatment with calcineurin inhibitors especially in case of sudden and severe bilateral visual impairment.

ODP136 A Rare Case of Necrotizing Myopathy after Statin Use

Abstract Introduction Statin associated necrotizing autoimmune myopathy is an extremely rare side effects of stain use. The incidence is approximately 2-3/100,000 Patients treated with statins. It usually associated with significant proximal muscle weakness, strikingly elevated creatine kinase (CK) levels and persistent symptoms despitestatin discontinuation. Here, we present a case with necrotizing myopathy after statin use as a reminder to clinicians for appropriately suspicious of this phenomenon while on treatment of statins. Clinical case: A 35 year old male with a past medical history of Autism, Type 2 Diabetes Mellitus, Hyperlipidemia, and Hypertension was brought to emergency room for right leg pain. Family states he had difficulty walking for a few weeks and had a fall from couch a week ago. Initial Vitals showed HR at 134 bpm, temp 35.9, BP 157/85 mmHg, RR 19 breaths/min. Labs showed Creatinine. 3.29 mg/dL, CO2 24 mmol/L, Na 141 mmol/L, K 4.2 mmol/L, Ca 9.5 mg/dL, glucose 265 mg/dL, AST/ALT 914/919 units/L, CK&amp;gt;14,000 units/L, WBC 9.2 thou/mcL, Hb 12.6 g/dL, TSH 9.42 mcIU/mL, Free T3 1.41 pg/mL, Free T4 0.95 mcg/dL. Urinalysis showed large blood with RBC of 1. Myoglobin&amp;gt;8750 mcg/L. Neuro motor exam showed strength 4/5 in bilateral lower extremities. His home medications including atorvastatin 20 mg nightly for 2 years, metformin and olmesartan, which all had been held. He was treated for rhabdomyolysis with aggressive hydration and Creatinine was improving. However, CK continued trending up to 42,915 units/L on day 5 with unreleased symptoms of lower extremity weakness. Neurology was consulted. Differential diagnosis of myopathy were suspected. His CK was continue to trend up to 45,585 units/L on day 10. Decision was made to have muscle biopsy with pathology showed: necrotizing myopathy without any clear evidence of inflammation. Although some autoimmune necrotizing myopathy may not show inflammation like those seen with HMG-CR antibodies or signal recognition antigen antibodies. Autoantibodies against 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGCR Ab) was above 550. Following the biopsy, he received IV Solu-medrol 1g daily×4 doses, and then PO Prednisone 80 mg daily and then tapered down to 40 mg daily. He was also promptly started on IVIG 400 mg/kg/day for 5 days and methotrexate 7.5 mg weekly. His CK started to improve, down to 5815 units/L three weeks later. No significant improvement of strength. Conclusion Our case demonstrates that the appropriate diagnosis of statin induced necrotizing autoimmune myopathy with muscle biopsy and HMGCR Ab. We also wanted to alert future clinicians to have an early suspicious of such rare side effect and initiate treatment as early as possible which may bring the maximum benefit for patients. Presentation: No date and time listed

Impairment of muscular endothelial cell regeneration in dermatomyositis.

Inflammatory myopathies are heterogeneous in terms of etiology, (immuno)pathology, and clinical findings. Endothelial cell injury, as it occurs in DM, is a common feature of numerous inflammatory and non-inflammatory vascular diseases. Vascular regeneration is mediated by both local and blood-derived mechanisms, such as the mobilization and activation of so-called proangiogenic cells (PACs) or early endothelial progenitor cells (eEPCs). The current study aimed to evaluate parameters of eEPC integrity in dermatomyositis (DM), compared to necrotizing myopathy (NM) and to non-myopathic controls. Blood samples from DM and NM patients were compared to non-myositis controls and analyzed for the following parameters: circulating CD133+/VEGFR-2+ cells, number of colony-forming unit endothelial cells (CFU-ECs), concentrations of angiopoietin 1, vascular endothelial growth factor (VEGF), and CXCL-16. Muscle biopsies from DM and NM subjects underwent immunofluorescence analysis for CXCR6, nestin, and CD31 (PECAM-1). Finally, myotubes, derived from healthy donors, were stimulated with serum samples from DM and NM patients, subsequently followed by RT-PCR for the following candidates: IL-1β, IL-6, nestin, and CD31. Seventeen (17) DM patients, 7 NM patients, and 40 non-myositis controls were included. CD133+/VEGFR-2+ cells did not differ between the groups. Both DM and NM patients showed lower CFU-ECs than controls. In DM, intramuscular CD31 abundances were significantly reduced, which indicated vascular rarefaction. Muscular CXCR6 was elevated in both diseases. Circulating CXCL-16 was higher in DM and NM in contrast, compared to controls. Serum from patients with DM but not NM induced a profound upregulation of mRNS expression of CD31 and IL-6 in cultured myotubes. Our study demonstrates the loss of intramuscular microvessels in DM, accompanied by endothelial activation in DM and NM. Vascular regeneration was impaired in DM and NM. The findings suggest a role for inflammation-associated vascular damage in the pathogenesis of DM.

S2293 Dysphagia in Statin-Induced Necrotizing Myopathy: An Uncommon Cause of Dysphagia in Adults

Introduction: Dysphagia due to statin induced myopathy is a rare condition. Statin generally is well tolerated and commonly used to reduce cardiovascular risk. However, myositis, a common complication of statin therapy, can cause disruption in the mechanism of muscles participating in swallowing. Here, we present a rare case of statin induced rhabdomyolysis and myositis causing dysphagia. Case Description/Methods: A 58-year-old male with metabolic syndrome on statin therapy, was admitted for progressive solid food dysphagia, weakness, and myalgia. Initial vital signs were within normal limits. Physical exam was significant for profound weakness in all extremities. Initial labs were significant for an elevated creatine kinase (CK) of 19,387 U/L suggestive of rhabdomyolysis. CK continued to remain elevated despite aggressive fluid resuscitation. Statin therapy was subsequently held. Additional work up included a muscle biopsy which demonstrated severe necrotizing myopathy. Given the muscle biopsy findings in setting of statin use, 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase (HMGCR) IgG antibodies were checked and found to be significantly elevated at above 550 CU (normal less than 20 CU). Patient was then diagnosed with Anti-HMG-CoA Reductase Positive Immune Mediated Necrotizing Myopathy (anti-HMGCR positive IMNM). Patient was then started on immunosuppressive therapy. However, patient’s dysphagia continued to worsen. Given ongoing dysphagia and inability to fulfill all nutritional needs, patient underwent percutaneous endoscopic gastrostomy tube placement. Patient’s condition stabilized after treatment with immunosuppressive therapy. Discussion: IMNM is a type of auto-immune myopathy that is debilitating due to characteristics of severe muscle weakness and possible muscle necrosis. Biopsy of patients with necrotizing myositis will show myofiber necrosis. The distinguishing feature of HMG-CoA reductase IMNM is the presence of statin therapy. The duration of statin therapy does not appear to affect the development of IMNM. Prior studies have shown that about 6 percent of patients with biopsy proven IMNM also found to have positive anti-HMGCR antibodies. Of those patients with positive antibodies on muscle biopsy, 80 percent had history of statin therapy. Physicians should recognize signs of anti-HMGCR IMNM, such as progressive dysphagia early on in disease process, so the appropriate treatment can be initiated to prevent significant morbidity.Figure 1.: Muscle biopsy showing numerous pale necrotic myofibers (stars) and basophilic regenerating myofibers (asterisks) in varying stages of necrosis and regeneration. Image courtesy of Dr. Mari Perez-Rosendahl MD, University of Califorina, Irvine.

S3283 A Tough Pill to Swallow: A Case Series of Statin-Induced Necrotizing Autoimmune Myopathy Manifesting as Dysphagia and Transaminitis

Introduction: Statins are commonly used to prevent cardiovascular disease. However, a small subset of patients may develop autoimmune myopathy, a form of inflammatory myositis characterized by proximal muscle weakness and in some cases, dysphagia. We present two cases highlighting statin-induced necrotizing autoimmune myopathy (SINAM), a rare entity affecting roughly 2 cases per 1 million people. Case Description/Methods: Two Hispanic men, aged 60 and 71, presented with dysphagia and transaminitis. They reported gradual onset of proximal muscle weakness and weight loss and were taking atorvastatin 20mg and 80mg, respectively. Case 1: Labs revealed ALP 58 IU/L, AST 238 U/L, ALT 407 U/L, CK 7228 U/L, normal CRP, ESR, and HMG CoA reductase (HMGCR) antibodies 257 U/mL. EGD was unrevealing. MRI of the pelvis/femur showed patchy, symmetric intramuscular edema in leg muscles (Figure 1). Muscle biopsy revealed myonecrosis consistent with immune-mediated necrotizing myopathy. Case 2: Labs revealed ALP 79 IU/L, AST 571 U/L, ALT 373 U/L, CK 8392 U/L, CRP 19.2 mg/L, ESR 67 mm/hr, and HMGCR antibodies 367 U/mL. Muscle biopsy was not pursued. Both cases revealed negative viral hepatitis, ANA, myositis panel, smooth muscle Ab, LKM-1 Ab, total IgG, ferritin, anti-mitochondrial Ab, and alpha-1 antitrypsin. Both patients were started on high-dose steroids. Case 1 patient had minimal improvement and was subsequently started on mycophenolate and rituximab. He remains under close monitoring. Case 2 patient had persistent severe weakness and dysphagia, therefore intravenous immunoglobulin (IVIG) and mycophenolate were added. However, dysphagia persists despite a consistent decrease in muscle enzymes. He remains hospitalized and is pending PEG tube placement. (Figure) Discussion: SINAM is a rare variant of idiopathic inflammatory myopathy characterized by proximal muscle weakness and myofiber necrosis after statin exposure. Diagnosis is made with positive antibodies to HMGCR and may avoid the need for muscle biopsy in the appropriate clinical context. Cessation of statin and initiation of glucocorticoids are first-line treatments. However, many cases are refractory to steroid monotherapy. Other therapies such as IVIG and immunosuppressants serve a role in refractory disease. Alternative lipid-lowering agents should be used, and statins must not be rechallenged. These cases emphasize that muscle weakness, dysphagia and transaminitis should be evaluated diligently as early recognition can lead to initiation of life-saving treatment.Figure 1.: A-D. MRI pelvis/femur showing bilateral patchy and symmetric intramuscular edema in leg muscles.

Dengue infection triggered immune mediated necrotizing myopathy in children: a case report and literature review

BackgroundImmune-mediated necrotizing myopathy (IMNM) is a subgroup of idiopathic inflammatory myopathies manifesting with progressive weakness, elevated serum creatine kinase (CK) levels, and necrotizing myopathic features on muscle biopsy. There is a paucity of data on the clinical presentation of IMNM in children. We report a paediatric patient who developed anti-3-hydroxy-3-methylglutaryl-CoA reductase (anti-HMGCR)-positive necrotizing myopathy after recent dengue infection.Case presentationA previously healthy 9-year-old boy presented with acute proximal muscle weakness after recovery from dengue infection. Five days after the fever subsided, he could not stand from a squatting position. He denied having skin rash, arthritis, or other systemic features. He had marked elevation of CK level of 30,833 mg/dL and was put on steroid therapy. The patient initially responded to oral prednisolone, however the weakness persisted and muscle enzymes increased as steroids were decreased. He was then referred to our hospital for further assessment. Subsequent investigation revealed anti-HMGCR positivity along with specific histopathological findings consistent with IMNM. The patient was treated with six cycles of intravenous immunoglobulin (IVIG) monthly, then followed by a gradual taper of prednisolone and oral methotrexate weekly with complete recovery in motor power.ConclusionsOur report presents a child with clinical manifestations of IMNM which can be categorized as acute onset of muscle weakness following dengue infection. Two key points supporting a diagnosis in this case are clinical response after immunosuppressive therapy and absence of rashes found in juvenile dermatomyositis.

Statin-induced autoimmune necrotizing myopathy: A case report

The AMJ is a peer-reviewed, triannual health journal published by Anuradhapura Clinical Society (ACS).The Journal strives to be a forum for all health professionals to publish original research and review articles in their area of expertise. The AMJ publishes articles in clinical medicine, public health and health promotion. Our priority is given to manuscripts on health related issues which affects the communities living in rural tropical communities. Established as a journal in 2006 as a publication parallel to ACS annual scientific sessions, the journal was relaunched as a proper journal in 2013. Anuradhapura Medical Journal is a member of COPE and is included on DOAJ.

Statin Induced Autoimmune Necrotizing Myopathy (SIANM): An Alarming Adverse Event of a Familiar Medication

Statins are a widely prescribed medication that lowers serum cholesterol by inhibiting the HMG-CoA reductase enzyme, a rate-limiting step in cholesterol synthesis. Myopathy is one of the well-known adverse effects of statins, mainly when prescribed with the fibrates. However, statin-induced autoimmune necrotizing myopathy (SIANM) is an infrequent and severe complication. Hence, all clinicians should be more vigilant regarding this complication and treat it early to prevent acute kidney injury (AKI).

Statin-induced necrotizing autoimmune myopathy: a systematic review.

Statins are a class of lipid-lowering medications used worldwide by millions of people and are safe for frequent use in most patients. However, they cause necrotizing autoimmune myopathy in some patients. We reviewed case reports of 80 patients from 2010 to present diagnosed with statin-induced necrotizing autoimmune myopathy (SINAM), aiming to analyze the clinical, physiological, serologic characteristics and outcomes of SINAM. The mean age of these patients was 66 ±9.4, the majority being male (61.3%). All patients reported proximal muscle weakness, and a few had myalgias, extra muscular symptoms such as dysphagia, and pulmonary complications. Most of the patients were on atorvastatin, simvastatin, or rosuvastatin. The mean creatine kinase was 10,094.2 ±7,351.7 U/l, and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase enzyme was positive for 93.8% of patients. The majority of patients were started on steroids; other treatments were also used. Prompt cessation of statins and initiation of immunosuppressants reduced morbidity and mortality.

Therapeutic plasma exchange for the treatment of refractory necrotizing autoimmune myopathy.

IntroductionNecrotizing autoimmune myopathy (NAM) is strongly associated with pathognomonic autoantibodies targeting 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR) or signal recognition particle (SRP), whose levels in turn are correlated with serum creatine kinase (CK) and necrosis. Thus, NAM may be amenable to therapeutic plasma exchange (TPE) to remove pathogenic antibodies and improve patient symptoms.MethodsA retrospective case series and literature review of patients presenting with NAM and undergoing treatment with TPE was performed. Clinical data including patient demographics, symptoms, physical exam findings, muscle biopsy, lower extremity imaging, prior therapy, and duration from diagnosis to TPE initiation were collected retrospectively for adult patients with NAM treated with TPE after failing to respond to immunomodulatory therapy. Laboratory data including change in CK levels and myositis‐specific antibody titers from baseline were measured in some patients.ResultsSix patients (median age at diagnosis 52.5 years, interquartile range [IQR] 35.8‐64.5 years, four male/two female) underwent a median of 7.5 (IQR: 5‐10) TPE procedures with 5% albumin as replacement. All patients exhibited a statistically significant reduction in CK level from pre‐TPE baseline (range: 43.0%‐58.7% reduction). Responses in this cohort were best in patients with antibodies targeting HMGCR and SRP, which are most strongly associated with NAM. These results compare favorably to a literature review of NAM patients (n = 19) treated with TPE, who also exhibited positive clinical and laboratory responses across varying treatment lengths.ConclusionTPE can play a role in the management of NAM, particularly in patients with HMGCR or SRP antibodies who are refractory to pharmacologic immunosuppression.

High prevalence of necrotising myopathy pattern in muscle biopsies of patients with anti-Jo-1 antisynthetase syndrome.

Until now, researchers have not provided a well-defined muscle histological pattern for antisynthetase syndrome (ASSD). Therefore, we aimed to analyse the muscle biopsies of patients with anti-Jo-1 ASSD. This study included 26 patients with anti-Jo-1 ASSD admitted for investigation of the disease and obligatorily with muscle impairment, from 2010 to 2021, whose serial frozen muscle sections were analysed. Patients' mean age at disease diagnosis was 42.8±11.6 years, and the female gender was most predominant. Concerning muscle biopsies, cell infiltrates were present in 76.9% of the samples, and they were mainly located at the endomysium area (70%), with a predominance of macrophages (92.9%). Fiber muscle necrosis was present in 92.3% and was diffused in 54.2%. Expression of MHC-I was seen in all samples. Samples were mostly marked by the presence of CD68+ and discreet/low CD4+ and CD8+ staining, which is consistent with a higher predominance of observed necrosis and macrophage cell infiltrates. In general, 38.5% of patients had a necrotising myopathy pattern in muscle biopsies, whereas 34.6% and 26.9% had a general inflammatory myopathy pattern and nonspecific myopathy, respectively. This necrotising myopathy pattern was not associated with the demographic, clinical, or laboratory data. Our data show that almost 40% of patients with well-defined anti-Jo-1 ASSD with objective muscle impairment have a necrotising myopathy pattern in their muscle biopsies. Although this pattern is more classically related to immune-mediated necrotising myopathies, in association with clinical manifestations and the presence of anti-Jo-1 autoantibodies, this characteristic may lead to ASSD diagnosis.

SERONEGATIVE AUTOIMMUNE NECROTIZING MYOPATHY: ITS COURSE ACCELERATED BY COXSACKIE B INFECTION

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: We present a patient with necrotizing myopathy and rapid progression of muscle weakness, including respiratory muscles, leading to hypercapnic respiratory failure requiring mechanical ventilation following a myopericardial infection thought to be secondary to coxsackie B virus (CVB). This suggests that CVB accelerated the progression of the antibody-negative Immune mediated necrotizing myopathy (IMNM). CASE PRESENTATION: A 43 year old woman was hospitalized with proximal muscle weakness for 4 months with 2 weeks of substernal chest pain, which worsens when lying down and relieved when leaning forward. Progressive dyspnea on exertion and led to hypercapnic respiratory failure requiring mechanical ventilation. Laboratory and imaging findings were significant for creatinine kinase of 4,796, a troponin of 6.22, elevated antibody titers for CVB 1-6, and a pericardial effusion on echocardiogram. Pertinent negatives include acetylcholine receptor antibody (ab), antinuclear ab, skeletal muscle ab, Anti-signal recognition particle (SRP) and anti-hydroxy-3-methylglutarylCoA reductase (HMGCR) auto-ab. Due to a suspicion for inflammatory myopathy on MRI, a biopsy of quadriceps muscle showed predominant necrosis with minimal inflammation (monocytes, lymphocytes), myophagocytosis, and patchy MHC upregulation. Electromyogram (EMG) was negative for neuropathy or myasthenia gravis [4]. The constellation of findings was consistent with autoimmune necrotizing myopathy, its course complicated by myopericarditis thought to be secondary to CVB. The patient received IVIG, rituximab and high dose steroids, and was discharged to a long term acute care facility, where the patient's strength gradually improved. She was eventually weaned off of ventilator support. DISCUSSION: Necrotizing myopathy is a relatively recently defined form of autoimmune myopathy characterized by less inflammation and more necrosis in muscle tissue than seen in polymyositis [1]. Autoimmune myopathies are rare, with a prevalence of 9–14 cases per 100,000 people [5, 6]. Seronegative IMNM has not been characterized as well as seropositive IMNM [4]. While European Neuromuscular Centre criteria do not require muscle biopsy to diagnose seropositive IMNM, a muscle biopsy is essential/required for diagnosis of seronegative IMNM [3, 4]. CONCLUSIONS: In the setting of myocarditis likely secondary to CVB, the patient's myopathy rapidly worsened to include respiratory muscles and led to mechanical ventilation. This course of events strongly raises the possibility that coxsackie B infection led to acceleration of myopathy. REFERENCE #1: Adler BL, Christopher-Stine L. Triggers of inflammatory myopathy: insights into pathogenesis. Discov Med 2018;25:75–83. REFERENCE #2: Dalakas MC. Myositis: are autoantibodies pathogenic in necrotizing myopathy? Nat Rev Rheumatol 2018;14:251–2. REFERENCE #3: Khan NAJ, Khalid S, Ullah S, et al. Necrotizing autoimmune myopathy: a rare variant of idiopathic inflammatory myopathies. J Investig Med High Impact Case Rep 2017;5:232470961770903. DISCLOSURES: No relevant relationships by Erik Anderson, source=Web Response No relevant relationships by Amanda Eng, source=Web Response No relevant relationships by Padmanabhan Krishnan, source=Web Response

A CASE OF ANTI-SRP IMMUNE-MEDIATED NECROTIZING MYOPATHY WITH COEXISTING PULMONARY SARCOIDOSIS

A CASE OF ANTI-SRP IMMUNE-MEDIATED NECROTIZING MYOPATHY WITH COEXISTING PULMONARY SARCOIDOSIS

Consumer-based activity trackers in evaluation of physical activity in myositis patients.

Inflammatory myopathies are characterized by muscle weakness that limits the activities of daily living. Daily step count is an accepted metric of physical activity. Wearable technologies such as Fitbit® enable tracking of daily step counts. We assessed the psychometric properties of Fitbit® and compared the accuracy of Fitbit® step counts to ActiGraph®. This was a pilot, proof of concept, prospective observational study with four visits at 0, 1, 3 and 6months in PM, DM, necrotizing myopathy (NM) or anti-synthetase syndrome (AS) subjects. Six core set measures (manual muscle testing, physician global disease activity, patient global disease activity, and extra-muscular disease activity, HAQ-Disability Index and creatine kinase), three functional tests (six-min walk, timed up-and-go, sit-to-stand tests) and SF-36 physical function-10 (PF10) were collected at each visit. Patients wore waist-worn Fitbit® One and ActiGraph® T3X-BT concurrently for 7 days/month for 6months. Twenty-four (10 DM, 8 PM/NM, 6 AS) patients (17 females/7 males; 91% Caucasian) were enrolled. Test-retest reliability of daily steps was strong in 1-month follow-up (ICC 0.89). Daily steps and peak 1-min cadence showed moderate-strong correlations with physician global disease activity, patient global disease activity, HAQ-Disability Index, SF-36 PF10 and all three functional tests. Fitbit® and ActiGraph® step counts demonstrated good agreement and strong correlation (ICC 0.96). Fitbit® daily steps and peak 1-min cadence are reliable and valid measures of physical activity in a cohort of myositis patients. This pilot data suggests that Fitbit® has a potential for use in clinical practice and trials to monitor physical activity in myositis patients, but larger studies are needed for further validation.

Cutaneous involvement in anti-HMGCR positive necrotizing myopathy

ObjectiveAnti-3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) positive immune-mediated necrotizing myopathy (IMNM) is a rare disease. It is induced by exogenous substances, most often by statins. Little is known about cutaneous manifestations of HMGCR positive IMNM and about HMGCR antibody positivity in other diseases. MethodsThe characteristics of patients with anti-HMGCR autoantibodies measured at our laboratory between January 2012 and September 2020 were studied. Characteristics of patients with IMNM were compared to those patients with positive antibodies but without muscle involvement. Associations of IMNM with other organ involvements were searched for. ResultsOf the 32 patients studied, 23 showed characteristics of IMNM, 9 did not fulfill current classification criteria but most showed signs of connective tissue diseases. Patients with IMNM were older (66 and 35 years, respectively; 0.92 (0.73–0.98); p < 0.001), had more frequent statin exposure (87% and 33%, respectively; 0.84 (0.61–0.94); p = 0.005) and higher mean peak CK (8717U/l and 329U/l, respectively; 1.0 (0.85–1.0); p < 0.001). 13/23 (56%) of IMNM patients showed cutaneous lesions; none of the patients suffered from cancer; only three IMNM patients showed drug-free complete remission. Incidence of IMNM in the catchment area of our center is at least 2.7/Mio/year. ConclusionCutaneous lesions were found to be more frequent in anti-HMRCR positive IMNM than previously reported. Titer of anti-HMGCR antibodies and CK levels were significantly higher in IMNM than in other autoimmune connective tissue diseases. The data support the hypothesis of an antigen-driven response in IMNM, and suggests an activation of autoreactive B-lymphocytes in non-IMNM patients.

P152 The incidence of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies may be higher than we think

Abstract Background/Aims Statins are associated with muscle symptoms, from myalgia with normal CK, to rhabdomyolysis. A sub-group have an autoimmune necrotising myopathy with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies. This can present variably, from mild self-limiting illness to severe myopathy unresponsive to statin withdrawal, requiring long-term immunosuppression. A study from New Zealand estimated the incidence of anti-HMGCR-associated myositis to be 1 in 90,000 statin users, and an incidence of 1 in 500,000 has been estimated in a US population. Anti-HMGCR antibodies were first reported in 2010. As they are new, and testing is not widely available, they may be under-recognised in the routine assessment of patients with myopathies. However, detection is important as prompt immunosuppression may be needed. Methods We compared the 2019 incidence of anti-HMGCR antibodies in Southern England from two different laboratory groups, utilising different testing criteria. The St George’s and Berkshire Surrey Pathology Services (StG/BSPS) laboratories serve a population of 3.25 million and test anti-HMGCR antibodies solely on clinician request. The Southampton laboratory serves a population of 2.33 million and tests anti-HMGCR as part of the immunoblot for all myositis-associated antibodies and where clinical details suggest myositis or ILD. Results In 2019, 14 tests were performed by StG/BSPS and 662 by Southampton, with anti-HMGCR positives of 5 (36%) and 28 (4.2%) respectively. Adjusted to include only the adult population, the incidence of anti-HMGCR antibodies is 1 in 514,000 in the StG/BSPS area versus 1 in 66,000 in the Southampton area. We estimate statins to be used in 308,000 adults in the StG/BSPS and in 220,000 in the Southampton areas, assuming treatment in 12% of adults and age demographics representative of the national population. This suggests an incidence of anti-HMGCR antibodies of approximately 1 in 62,000 statin users in the StG/BSPS area and 1 in 8,000 statin users in the Southampton area, though statin exposure was not confirmed in all positive cases. Preliminary data from 17 anti-HMGCR positive cases shows that 76% had taken statins, for an average duration of 5.84 years (range 0.75-16 years). Median peak CK was 6489 (range 241-27555). 76% required immunosuppression, of which 70% required two or more different treatments. Conclusion The 7.7-fold higher incidence from the Southampton laboratory reflects a proactive approach, selecting far more samples for anti-HMGCR assessment than specifically requested by clinicians. This demonstrates under-awareness of this antibody in routine care. We propose adoption of an algorithm to trigger more widespread testing for anti-HMGCR antibodies, to identify cases amongst those with statin-associated myalgia or myositis, and in others without statin exposure. This will lead to better understanding of the spectrum of clinical disease associated with anti-HMGCR antibodies, as well as early detection and treatment of those who develop a necrotising myopathy. Disclosure V.M.K. Joseph: None. E.C. Rose: None. M. Lloyd: None. C.J. Edwards: None. S.K. Amar: None. T. Forster: None. K.A. Smith: None. R.D. Wheeler: None. P.D.W. Kiely: None.