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BackgroundThe main systemic sclerosis (SSc) manifestations are skin thickening, microangiopathy and ischemic changes in tissues, fibrotic damage to the lungs, heart, kidneys, and digestive system, arthritis, and myopathy. Acute phase reactants (APR) like erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) reflect inflammation activity in various inflammatory conditions. Ferritin is a protein bound to iron;low serum ferritin indicates iron deficiency and/or anemia. Instead, high ferritin levels are associated with inflammatory and non-inflammatory conditions such as dermatomyositis, pulmonary fibrosis, lupus, systemic COVID-19, vasculitis, tissue damage, thromboembolic complications, and metastatic cancer. The possible role of ferritin in SSc as APR is unclear.ObjectivesWe aimed to assess whether ferritin levels can reflect the severity of SSc and predict the outcome.Methods241 files of SSc patients with information on serum ferritin level (ferritin over 300 mg/dL is considered elevated) who visited the Rambam Rheumatology Institute in the years 2004-2021were used for retrospective analysis. Patients' demographic, clinical, laboratory, imaging, and respiratory function data were collected from electronic hospital files. Statistics included Student's T-test, Pearson's chi-squared test, and Kaplan-Meier curve;statistical significance was determined as p<0.05.Results36 patients (FerEl-SSc) had elevated ferritin values;the rest (n=205) represented the second group (FerNor-SSc). Significant differences were seen in gender (male 44.4% - 15.6%), disease duration (4.56 - 7.7 years), modified Rodnan skin score (12.3 - 6.9), as well as in incidence of lung (65.7% - 38.7%), heart (51.4% - 21.1%), and renal (28.6% - 5.9%) involvement. Increased ferritin correlated with elevated ESR, CRP, creatinine, creatine kinase, troponin, and reduced hemoglobin, impaired pulmonary function tests and reduced left ventricular ejection fraction on echocardiography. Patients with elevated ferritin had a significant increase in mortality rates (52.8% and 35.1%) and non-significant reduction in survival.ConclusionOur study demonstrated that ferritin has a potential as a sensitive marker for SSc severity in term of skin thickening, vital organ complications, and mortality. The ferritin test is simple and inexpensive, it can add to the complex SSc assessment and contribute to treatment decision-making in complicated SSc.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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BackgroundAnti-MDA5 antibody-positive dermatomyositis (anti-MDA5+DM) is a rare autoimmune disease associated with a high mortality rate due to rapid-progressive interstitial lung disease (RP-ILD), particularly in East Asia[1]. MDA5, acts as a cytoplasmic sensor of viral RNA, thus activating antiviral responses including the type I interferon (IFN) signaling pathway[2]. The involvement of type 1 IFN in the pathogenesis of MDA5+DM has been proposed based on the significantly elevated expression of its downstream stimulated genes(ISG) in muscle, skin, lung, and peripheral blood[3;4]. Janus kinase inhibitor, which targets the IFN pathway, combined with glucocorticoid could improve the survival of early-stage MDA5+DM-ILD patients[5]. In clinical practice, there is still an urgent demand for sensitive biomarkers to facilitate clinical risk assessment and precise treatment.ObjectivesThis study aimed to investigate the clinical significance of interferon score, especially IFN-I score, in patients with anti-MDA5+DM.MethodsDifferent subtypes of idiopathic inflammatory myopathy, including anti-MDA5+DM(n=61), anti-MDA5-DM(n=20), antisynthetase syndrome(ASS,n=22),polymyositis(PM,n=6) and immune-mediated necrotizing myopathy(IMNM,n=9), and 58 healthy controls were enrolled.. A multiplex quantitative real-time PCR(RT-qPCR) assay using four TaqMan probes was utilized to evaluate two type I ISGs (IFI44, MX1, which are used for IFN-I score), one type II ISG (IRF1), and one housekeeping gene (HRPT1). Clinical features and disease activity index were compared between high and low IFN-I score groups in 61 anti-MDA5+DM patients. The association between laboratory findings and the predictive value of baseline IFN-I score level for mortality was analyzed.ResultsThe IFN scores were significantly higher in patients with anti-MDA5+DM than in HC (Figure 1A). The IFN-I score correlated positively with serum IFN α(r = 0.335, P =0.008), ferritin (r = 0.302, P = 0.018), and Myositis Disease Activity Assessment Visual Analogue Scale (MYOACT) score(r=0.426, P=0.001). Compared with patients with low IFN-I scores, patients with high IFN-I scores showed increased MYOACT score, CRP, AST, ferritin, and the percentages of plasma cells (PC%) but decreased lymphocyte count, natural killer cell count, and monocyte count. The 3-month survival rate was significantly lower in patients with IFN-I score > 4.9 than in those with IFN-I score ≤ 4.9(72.9% vs. 100%, P=0.044)(Figure 1B).ConclusionIFN score, especially IFN-I score, detected by multiplex RT-qPCR, can be a valuable biomarker for monitoring disease activity and predicting mortality in anti-MDA5+DM patients.References[1]I.E. Lundberg, M. Fujimoto, J. Vencovsky, R. Aggarwal, M. Holmqvist, L. Christopher-Stine, A.L. Mammen, and F.W. Miller, Idiopathic inflammatory myopathies. Nat Rev Dis Primers 7 (2021) 86.[2]G. Liu, J.H. Lee, Z.M. Parker, D. Acharya, J.J. Chiang, M. van Gent, W. Riedl, M.E. Davis-Gardner, E. Wies, C. Chiang, and M.U. Gack, ISG15-dependent activation of the sensor MDA5 is antagonized by the SARS-CoV-2 papain-like protease to evade host innate immunity. Nat Microbiol 6 (2021) 467-478.[3]G.M. Moneta, D. Pires Marafon, E. Marasco, S. Rosina, M. Verardo, C. Fiorillo, C. Minetti, L. Bracci-Laudiero, A. Ravelli, F. De Benedetti, and R. Nicolai, Muscle Expression of Type I and Type II Interferons Is Increased in Juvenile Dermatomyositis and Related to Clinical and Histologic Features. Arthritis Rheumatol 71 (2019) 1011-1021.[4]Y. Ye, Z. Chen, S. Jiang, F. Jia, T. Li, X. Lu, J. Xue, X. Lian, J. Ma, P. Hao, L. Lu, S. Ye, N. Shen, C. Bao, Q. Fu, and X. Zhang, Single-cell profiling reveals distinct adaptive immune hallmarks in MDA5+ dermatomyositis with therapeutic implications. Nat Commun 13 (2022) 6458.[5]Z. Chen, X. Wang, and S. Ye, Tofacitinib in Amyopathic Dermatomyositis–Associated Interstitial Lung Disease. New England Journal of Medicine 381 (2019) 291-293.AcknowledgementsThis work was supported by the National Natural Science Foundation of China [81974251], and Shanghai Hospital Develop ent Center, Joint Research of New Advanced Technology Project [SHDC12018106]Disclosure of InterestsNone Declared.
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About 80% of the patients recovering from COVID-19 have inflammation symptoms, like brain fog, myopathy, myalgia, muscle weariness, headache, mental tiredness, asthenia, adynamia, dizziness, tinnitus, hearing loss, telogenic effluvium and mood disturbances. Here, we demonstrate how transcranial and systemic photobiomodulation using near-infrared LEDs emitting 850 nm wavelength light enhanced cognition and reduced pain. Participants were separated into transcranial photobiomodulation with near-infrared LEDs (850 nm, 10W, 10 minutes), photobiomodulation with a punctual cutaneous application (850nm, 10W, 10-40 minutes), and both treatments. All patients underwent 10-day treatments at least. © 2023 SPIE.
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Purpose: The nutritional and anthropometric status can be essential in determining their immune response to vaccines. The purpose of this paper was to investigate the association between diet quality and anthropometric indices with the side effects of the Pfizer-BioNTech COVID-19 vaccine and the SARS-CoV-2 immunoglobulin G titer among Kurdish adults. Design/methodology/approach: This cross-sectional survey-based study was conducted between December 2021 and February 2022. This paper included data on 115 adults, 20-89 years old, from the Kurdistan region. Dietary information was collected using a short food frequency questionnaire, and diet quality was assessed using a plant-based healthy diet score. A blood test was performed to measure the SARS-CoV-2 immunoglobin G (IgG) titer after the vaccination's first and second doses. Findings: Overweight and obese subjects reported more local pain, myalgia, headache, local bruising and local reactions after receiving the first dose of the vaccine (p = 0.04). People on a less healthy diet reported more local pain, myalgia and headache (p = 0.04) and more local bruising and reactions (p = 0.01) after receiving the second dose of the vaccine. On the other hand, the authors observed that those with healthy dietary habits had more IgG titer after the first and second doses of vaccination than those with less healthy dietary habits (p = 0.001). Originality/valueThe results showed that participants with a healthy diet and normal weight status had fewer side effects of the Pfizer-BioNTech COVID-19 vaccine than obese people and those with a less healthy diet.
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Coronavirus disease 2019 (COVID-19) is a respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that can induce myopathy, which can evolve into potentially life-threatening muscle weakness, including diaphragmatic paralysis. We present a case report of a 57-year-old female treated in the medical ICU for acute respiratory distress syndrome (ARDS) triggered by active COVID-19 infection, who subsequently developed worsening respiratory weakness from underlying COVID-19 myopathy manifesting as respiratory muscle weakness. Our patient's muscle biopsy highlights the development of muscle atrophy without evidence of inflammatory myopathy, making the presence of pre-existing autoimmune myopathy unlikely. While literature cites different biochemical etiologies for the development of myopathy, the exact mechanism behind this phenomenon is not yet defined.
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SARS-CoV-2 has been associated with multiple disease processes and chronic sequela. Much less understood are the neurological effects, ranging from headaches, pro-thrombotic state, encephalitis, and myopathic processes. Many case reports have documented post-SARS-CoV-2 virus effects; however, this case highlights the possibility of a less commonly described neurological manifestation possibly related to the BNT162b2 mRNA Pfizer vaccine. There is scant literature on immune-mediated necrotizing myopathy (IMNM) triggered after COVID-19 vaccination. The BNT162b2 mRNA COVID-19 vaccine (Pfizer, BioNTech) has proven to be safe and effective in reducing transmission of COVID-19, but post-vaccination neurological events, including venous sinus thrombosis, transverse myelitis, and immune-mediated diseases, such as Guillain-Barré syndrome, have been reported. We report a case of IMNM with HMG-CoA reductase antibody positivity in the setting of BNT162b2 vaccination. The patient presented with progressive muscle weakness with rhabdomyolysis and necrotizing autoimmune myopathy proven on muscle biopsy after the second dose of the BNT162b2 vaccine. Ultimately, this case report highlights the importance of clinical suspicion for early diagnosis and initiation of treatment after symptoms concerning necrotizing myopathy.
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This review highlights ten important advances in the neuromuscular disease field that were reported in 2021. As with prior updates in this article series, the overarching topics include (i) advances in understanding of fundamental neuromuscular biology; (ii) new / emerging diseases; (iii) advances in understanding of disease etiology and pathogenesis; (iii) diagnostic advances; and (iv) therapeutic advances. Within this general framework, the individual disease entities that are discussed in more detail include neuromuscular complications of COVID-19 (another look at the topic first covered in the 2021 review), autosomal recessive myopathy caused by MLIP mutations, autosomal recessive neuromuscular disease caused by VWA1 mutations, Leber's hereditary optic neuropathy, myopathies with autophagic defects, tRNA synthetase-associated Charcot-Marie-Tooth disease, systemic sclerosis-associated myopathy, humoral immune endoneurial microvasculopathy, and late-onset Pompe disease. In addition, the review highlights a few other advances (including new insights into mechanisms of muscle and nerve regeneration and the use of gene expression profiling to better characterize different subtypes of immune-mediated myopathies) that will be of significant interest for clinicians and researchers who specialize in neuromuscular disease.
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This review highlights ten important advances in the neuromuscular disease field that were first reported in 2020. The overarching topics include (i) advances in understanding of fundamental neuromuscular biology; (ii) new / emerging diseases; (iii) advances in understanding of disease etiology and pathogenesis; (iv) diagnostic advances; and (v) therapeutic advances. Within this broad framework, the individual disease entities that are discussed in more detail include neuromuscular complications of COVID-19, supervillin-deficient myopathy, 19p13.3-linked distal myopathy, vasculitic neuropathy due to eosinophilic granulomatosis with polyangiitis, spinal muscular atrophy, idiopathic inflammatory myopathies, and transthyretin neuropathy/myopathy. In addition, the review highlights several other advances (such as the revised view of the myofibrillar architecture, new insights into molecular and cellular mechanisms of muscle regeneration, and development of new electron microscopy tools) that will likely have a significant impact on the overall neuromuscular disease field going forward.
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Immune-mediated necrotizing myopathy (IMNM) is a rare, progressive disease that accounts for about 19% of all inflammatory myopathies. Dysphagia occurs in about 20%-30% of IMNM patients. This case results in the third presumptive instance of IMNMwith dysphagia as the initial symptom. Given that isolated dysphagia in IMNM is atypical to the conventional symptoms in the late stage of the disease, it is critical for clinicians to have a high degree of suspicion for IMNM due to the aggressive nature of the disease and its refractoriness to treatment. Additionally, this case also highlights an atypical autoantibody, PL-7, being positive in an IMNM patient who presents with dysphagia as an initial symptom.
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Following infection with SARS-CoV-2, a substantial minority of people develop lingering after-effects known as 'long COVID'. Fatigue is a common complaint with a substantial impact on daily life, but the neural mechanisms behind post-COVID fatigue remain unclear. We recruited 37 volunteers with self-reported fatigue after a mild COVID infection and carried out a battery of behavioural and neurophysiological tests assessing the central, peripheral and autonomic nervous systems. In comparison with age- and sex-matched volunteers without fatigue (n = 52), we show underactivity in specific cortical circuits, dysregulation of autonomic function and myopathic change in skeletal muscle. Cluster analysis revealed no subgroupings, suggesting post-COVID fatigue is a single entity with individual variation, rather than a small number of distinct syndromes. Based on our analysis, we were also able to exclude dysregulation in sensory feedback circuits and descending neuromodulatory control. These abnormalities on objective tests may aid in the development of novel approaches for disease monitoring.
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a considerable global effect, posing notable challenges for clinicians, the pandemic becoming one of the most imperative international health emergencies lately. Among other more frequent manifestations, SARS-CoV-2 disease may also give rise to skeletal muscle involvement. Viral-induced skeletal muscle involvement is a potentially severe manifestation of COVID-19 (Coronavirus Disease 2019) and may be either acute, or in the context of "long-COVID”. The present review aimed to illustrate few aspects about pathomechanisms, clinical and paraclinical frames, and treatment options for SARS-CoV-2-induced muscle involvement. Notably, it has been stated that SARS-CoV-2 may have the ability to invade muscle myocytes directly, the disease having a variety of clinical manifestations, from myalgia and muscle weakness to rhabdomyolysis. Nevertheless, it is also important to take into account that most of patients with severe forms receiving mechanical ventilation for more than one week may have complications such as CIM (critical illness myopathy) and/or CIP (critical illness polyneuropathy) that may be clinically similar to SARS-CoV-2-induced myositis, yet may be differentiated paraclinically from it. Additionally, it was hypothesized that SARS-CoV-2 infection may constitute a trigger for autoimmune diseases such as polymyositis/ dermatomyositis. Presently, there are no diagnosis criteria and no specific therapeutic strategy for SARS-CoV-2-induced myositis. © 2022, Amaltea Medical Publishing House. All rights reserved.
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Introduction: Immune mediated necrotizing myopathy (IMNM) is a rare, but progressive disease that accounts for about 19% of all inflammatory myopathies. Dysphagia occurs in 20-30% of IMNM patients. It often follows proximal muscle weakness and ensues in the later stages of the disease. We report a rare case of IMNM, presenting with dysphagia as the initial symptom, followed by proximal muscle weakness. Case Description/Methods: A 74-year-old male with a past medical history of coronary artery disease, hypertension, and hyperlipidemia presented to the ED with 2-3 weeks of intractable nausea, vomiting, and dysphagia for solids and liquids. Vital signs were stable, and initial labs displayed an AST of 188 U/L and ALT of 64 U/L with a normal bilirubin. Computed tomogram of the chest, abdomen, and pelvis were negative. An esophagram showed moderate to severe tertiary contraction, no mass or stricture, and a 13 mm barium tablet passed without difficulty. Esophagogastroduodenoscopy exhibited a spastic lower esophageal sphincter. Botox injections provided no significant relief. He then developed symmetrical proximal motor weakness and repeat labs demonstrated an elevated creatine kinase (CK) level of 6,357 U/L and aldolase of 43.4 U/L. Serology revealed positive PL-7 autoxantibodies, but negative JO-1, PL-12, KU, MI-2, EJ, SRP, anti-smooth muscle, and anti-mitochondrial antibodies. Muscle biopsy did not unveil endomysial inflammation or MHC-1 sarcolemmal upregulation. The diagnosis of IMNM was suspected. A percutaneous endoscopic gastrostomy feeding tube was placed as a mean of an alternative route of nutrition. He was started on steroids and recommended to follow up with outpatient rheumatology. He expired a month later after complications from an unrelated COVID-19 infection. Discussion(s): The typical presentation of IMNM includes painful proximal muscle weakness, elevated CK, presence of myositis-associated autoantibodies, and necrotic muscle fibers without mononuclear cell infiltrates on histology. Dysphagia occurs due to immune-mediated inflammation occurring in the skeletal muscle of the esophagus, resulting in incoordination of swallowing. Immunotherapy and intravenous immunoglobulin are often the mainstay of treatment. Our patient was unique in presentation with dysphagia as an initial presenting symptom of IMNM, as well as elevated enzymes from muscle breakdown. It is critical as clinicians to have a high degree of suspicion for IMNM due to the aggressive nature of the disease and refractoriness to treatment.
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Background/Aims Through the COVID pandemic there have emerged reports of autoimmunity or new rheumatic diseases presenting in patients after they had COVID-19. This is thought to be caused by cross-reactivity of the COVID-19 spike protein to human antigens. Given the use of mRNA COVID-19 vaccinations which express the spike protein we might expect to see presentation of new rheumatic diseases following their use. We discuss a case where this appears to have occurred. Methods Our patient is a 24-year-old male with mixed phenotype acute leukaemia who had been treated with allogenic stem cell transplant and was currently in remission. He presented with fevers, palpitations, myalgia and bilateral arm and leg swelling. Symptoms began the day after receiving the first dose of an mRNA COVID-19 vaccination (Pfizer/BioNTech.) There were no other symptoms or recent change in medications. Physical examination revealed tender oedema in his forearms, biceps and thighs bilaterally with sparring of the hands. He had reduced power with shoulder (MRC 3/5), elbow (4), wrist (4+) and hip (4) movements. Observations revealed tachycardia and fevers up to 40C. Results Laboratory studies showed markedly elevated C-reactive protein (202), creatinine kinase (6697) and troponin (593) whilst investigations for infection were negative. An autoimmune panel was positive for anti- PM-SCL-75-Ab. An electrocardiogram showed sinus tachycardia. Echocardiogram was normal. Bilateral upper limb dopplers revealed no deep vein thrombus. An MRI of his thighs showed diffuse symmetrical oedema within the muscles, in keeping with an inflammatory myositis. A quadricep muscle biopsy showed evidence of MHC class 1 up-regulation, suggesting an inflammatory process. In addition, there were numerous macrophages evident in the endomysium. While this can be seen in graft-versus-host disease (GVHD), they would usually be found in the perimysium. After discussion between haematology, rheumatology and neurology, this was felt to be a case of vaccine induced myositis and myocarditis. Autoimmune myositis was thought to be less likely due to the relative sparing of the hands and the absence of Raynaud's phenomenon. 1 gram of intravenous methylprednisolone was then given for 3 days. The patient had a marked response with defervescence, improving laboratory markers, improved myalgia and decreased limb swelling. The patient was stepped down to a reducing regime of prednisolone and discharged. Due to relapse whilst weaning he has started on mycophenalate mofetil and rituximab and now continues to improve. Conclusion There are case reports of myositis following COVID-19 vaccination but our patient's case is complicated by the differential diagnosis of GVHD and concurrent myocarditis. Ongoing work is needed to clarify the exact link between vaccination and the presentation of a new inflammatory myositis, but it is important to recognise and start treatment early in order to preserve muscle bulk and ensure recovery.
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BACKGROUND: According to previous reports, most cases of inflammatory myopathy following mRNA vaccination can be classified as idiopathic inflammatory myopathy (IIM), particularly dermatomyositis (DM), owing to their similar clinical features and courses. However, some patients have different clinical features and courses. We report a rare case of transient inflammatory myopathy involving the masseter muscle following the third dose of COVID-19 mRNA vaccination. CASE PRESENTATION: An 80-year-old woman presented with a history of fever and fatigue for 3 months soon after receiving the third COVID-19 mRNA vaccination. Her symptoms progressed to jaw pain and inability to open her mouth. She also experienced mild proximal muscle weakness in the lower limbs but no skin manifestations or daily difficulties. Fat-saturated T2-weighted magnetic resonance imaging showed bilateral high-intensity signals for the masseter and quadriceps muscles. The patient experienced spontaneous resolution of fever and improvement of symptoms 5 months after onset. The timing of the onset of symptoms, the lack of detectable autoantibodies, and the atypical presentation of myopathy in the masseter muscles, in addition to the spontaneous mild course of the disease, all indicate the substantial role of mRNA vaccination in this myopathy. Since then, the patient has been followed up for 4 months without any recurrence of symptoms or any additional treatment. CONCLUSION: It is important to recognize that the course of myopathy after COVID-19 mRNA vaccination could be different from that of typical IIMs.
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Coronavirus disease 2019 (COVID-19) is the most dramatic pandemic of the new millennium and patients with serious infection can stay in intensive care unit (ICU) for weeks in a clinical scenario of systemic inflammatory response syndrome, likely related to the subsequent development of critical illness polyneuropathy (CIP). It is in fact now accepted that COVID-19 ICU surviving patients can develop CIP;moreover, prone positioning-related stretch may favor the onset of positioning-related peripheral nerve injuries (PNI). Therefore, the urgent need to test drug candidates for the treatment of these debilitating sequelae is emerged even more. For the first time in medical literature, we have successfully treated after informed consent a 71-year-old Italian man suffering from post-COVID-19 CIP burdened with positioning-related PNI of the left upper extremity by means of ultramicronized palmitoylethanolamide 400 mg plus ultramicronized luteolin 40 mg (Gl & igrave;alia), two tablets a day 12 hours apart for 6 months. In the wake of our pilot study, a larger clinical trial to definitively ascertain the advantages of this neuroprotective, neurotrophic, and anti-inflammatory therapy is advocated.
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Post-Coronavirus disease 2019 (COVID-19) development of polymyositis is rare, with very few cases documented in the literature. In patients developing vague symptoms after recovery from COVID-19, it is important to investigate all avenues, including the possibility of polymyositis. Polymyositis is typically characterized as symmetrical muscle weakness and histological, electrical, and chemical evidence of muscle injury. Patients identified can be treated with immunosuppressants to return some quality of life and prevent disease progression. In this report, we describe a 58-year-old Caucasian male who presented with symptoms of weakness, myalgias, and arthralgias, six months after recovering from flu-like symptoms of COVID-19. The patient was tested for other autoimmune etiologies and myopathies without positive results. He was treated with prednisone and reported moderate improvement in symptoms. Unfortunately, the patient declined a muscle biopsy or electromyographic testing. According to the criteria for polymyositis set by the Myositis Association and the response to therapy, the patient's symptoms pointed to a likely diagnosis of post-COVID-19 polymyositis.
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The proceedings contain 255 papers. The topics discussed include: molecular pathology of mitochondrial disorders;defining causal genes at MHC in SLE - implications for myositis and other diseases that share MHC risk;role of mitochondria in skeletal muscle dysfunction in myositis;selective T cell depletion for inclusion body myositis: why and how;inclusion body myositis in 2022: from physiopathogenesis to clinical trials;autoantibodies and complement in experimental IMNM: from pathogenesis to therapy?;reliability of immunoassays for myositis autoantibodies;when JM patients lose their 'J': transition challenges in myositis car;fatigue and well-being of children with chronic inflammatory disease;physical fitness in long-term JDM;Eular Covid and COVAX registries' update: focus on myositis;and outcomes, biomarkers, and novel treatments for the skin in dermatomyositis.
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Background. Evaluation of physical function is fundamental in the management of idiopathic inflammatory myopathies (IIMs). Patient-Reported Outcome Measurement Information System (PROMIS) is a National Institute of Health initiative established in 2004 to develop patient-reported outcome measures with improved validity and efficacy. The present study aims to investigate the physical function status of IIM patients compared to those with non-IIM autoimmune diseases (AIDs) and healthy controls (HCs) utilizing PROMIS Physical Function (PF) data obtained in the coronavirus disease-2019 (COVID-19) Vaccination in Autoimmune Diseases (COVAD) study, a large-scale, international self-reported e-survey assessing the safety of COVID-19 vaccines in AID patients. Methods. The survey data regarding demographics, IIM and AID diagnosis, disease activity, fatigue and pain VAS, and PROMIS PF short form-10a were extracted from the COVAD study database. The disease activity (active vs inactive) of each patient was assessed in 3 different ways: (1) physician's assessment (active if there was increased immunosuppression), (2) patient's assessment (active vs inactive as per patient), and (3) current steroid use. These 3 definitions of disease activity were applied independently to each patient. PROMIS PF-10a scores were compared between each disease category (IIMs vs non-IIM AIDs vs HCs), stratified by disease activity based on the 3 definitions stated above, employing negative binomial regression model, and the predicted PROMIS PF-10a score adjusted for age, gender, and ethnicity was calculated. Factors affecting PROMIS PF-10a scores other than disease activity were identified by multivariable regression analysis in the patients with inactive disease (IIMs or non-IIM AIDs). The association between fatigue or pain VAS and PROMIS PF-10a scores was also assessed. Results. 1057 IIM patients, 3635 non-IIM AID patients, and 3981 HCs responded to the COVAD survey until August 2021. The median age of the respondents was 43 [IQR 30-56] years old, and 74.8% were female. Among IIM patients, dermatomyositis was the most prevalent diagnosis (34.8%), followed by inclusion body myositis (IBM) (23.6%), polymyositis (PM) (16.2%), anti-synthetase syndrome (11.8%), overlap myositis (7.9%), and immune-mediated necrotizing myopathy (IMNM) (4.6%). The predicted mean of PROMIS PF-10a scores was significantly lower in IIMs compared to non-IIM AIDs or HCs (36.3 [95% (CI) 35.5-37.1] vs 41.3 [95% CI 40.2-42.5] vs 46.2 [95% CI 45.8-46.6], p<0.001), irrespective of disease activity (Figure 1). The results were consistent across analyses using different disease activity definitions (physician's assessment, patient's assessment, and steroid use), while the largest difference between active IIMs and non-IIM AIDs was observed when the disease activity was defined by patient's assessment (35.0 [95% CI 34.1-35.9] vs 40.1 [95% CI 38.7-41.5]). Considering the subgroups of IIMs, the scores were significantly lower in IBM in comparison with non-IBM IIMs (p<0.001). The independent factors associated with low PROMIS PF-10a scores in the patients with inactive disease were older age, female gender, and the disease category being IBM, PM, or IMNM. Higher fatigue or pain VAS was associated with lower PROMIS PF-10a scores in each disease category (p<0.001), while the scores were still lower in IIMs compared to non-IIM AIDs even after being adjusted for fatigue and pain. Conclusion. Physical function is significantly impaired in IIMs compared to non-IIM AIDs or HCs, even in patients with inactive disease. The elderly, women, and IBM groups are the worst affected, suggesting that developing targeted strategies to minimize functional disability in certain groups may improve patient-reported physical function and disease outcomes.
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Background. SARS-CoV-2 infection can be accompanied by neuromuscular disorders. Rhabdomyolysis and Guillain-Barre syndrome have been described repeatedly. There are case reports of inflammatory myopathies manifesting during COVID-19, presenting as dermatomyositis, polymyositis or immune-mediated necrotizing myopathy, with dermatomyositis-like presentations most commonly reported. Larger cases series are from postmortem examinations of COVID-19 patients, where variable inflammatory pathology of the skeletal muscle has been found frequently but without local detection of the actual virus. Thus, autoimmune mechanisms or the systemic interferon response are discussed as causes. We report a case of focal inflammatory myopathy with perimysial pathology of the temporalis muscle occurring with acute, but mild COVID-19. Methods. Case report of clinical observations, cranial MRI, histopathological, and laboratory findings. 3T cranial MRI was performed with gadolinium contrast. Open temporalis muscle biopsy was performed. The sample underwent standard cryohistological studies as well as immunohistochemistry with antibodies against MHC-I and II, CD3, CD4, CD19, CD68, anti-MAC, p62 and MxA. Testing for auto-antibodies was based on immunoblots or ELISA. RT-PCR for SARS-CoV-2 was run with RNA extracted from cryopreserved muscle. Results. A Caucasian woman in her 60s with no history of autoimmune or muscle complaints developed swelling and pain of the right jaw musculature five days after testing positive for SARS-CoV-2 due to respiratory tract symptoms. In addition, she experienced trismus, but no further neuromuscular complaints. The course of respiratory tract symptoms stayed mild. She had been vaccinated previously with single shot SARS-CoV-2 vector vaccine. Due to persistent swelling and complaints, giant cells arteritis was excluded by unresponsiveness to five days oral steroids and sonography of the temporal artery. Cranial MRI was performed nearly four weeks after the SARS-CoV-2 infection and showed marked swelling and oedema of the temporalis muscle. Its biopsy showed numerous CD68 and acid phosphatase positive cells infiltrating from perimysial perivascular foci towards the endomysium with perimysial damage but little damage of adjacent, perifascicular muscle fibres. Muscle fibres did not react with anti-MHC-II, anti-MAC or -MxA. Capillaries did not react with anti-MAC or -MxA. SARS-CoV-2 RNA was not detected in muscle tissue. Serum creatine kinase was not elevated in the subacute phase. Slightly elevated ANA titre led to detection of autoantibodies against proliferating cell nuclear antigen (PCNA). No pathological results for other autoantibodies, including myositis-specific antibodies and anti-ds-DNA, were found in blood. Neither were antibodies against hepatitis C and B viruses. Retesting 15 weeks after infection, anti-PCNA immunoblot was still positive, but ELISA did not indicate a pathologic titre. The swelling, myalgia and trismus regressed spontaneously a month after onset, yet the latter still persists at the time of reporting. Conclusion. Our case diverges from the majority of COVID-19 associated my-ositis reports in the unusual location of the focal myositis and the histopathological pattern of predominantly perimysial damage and histiocytic infiltration. It concurs with the literature as no SARS-CoV2 RNA could be detected in the muscle. Anti-PCNA is associated very rarely with myositis. Other associated disorder (systemic lupus erythematosus, chronic viral hepatitis B or C) were not found. Increased levels of autoantibodies are reported in COVID-19 and mostly attributed to loss of self-tolerance during the acute disease phase. Interestingly, the structural protein M of SARS-CoV-2 appears to interact notably with PCNA in infected cells. Still, the causal connection between the myositis and COVID-19 in this case is based on the close temporal association in the absence of alternative, competing explanations from the medical history and findings.
ABSTRACT
Introduction. The poster of the Dutch Myositis Working Group (DMWG) aims to inform people about her goals, activities and ambitions. The group is run by seven patients, representing all types of myositis, supported by Spierziekten Nederland, the umbrella patient organization for neuromuscular disorders in The Netherlands and 4 myositis specialists as medical advisors. Chair: Ingrid de Groot. Contact email: myositis@spierziekten.nl Goals and ambitions of the Dutch myositis working group: * I n collaboration with medical advisors to provide information about IIM (idiopathic inflammatory myopathies) or myositis to newly diagnosed patients and their families: IIM types, symptoms, diagnosis, (new) treatment options, prognosis, inform them about the myositis expertise centres etc. * To connect and support people with all types of IIM: dermatomyositis (DM), polymyositis (PM), Anti Synthetase Syndrome (ASyS), immune mediated necrotizing myopathy (IMNM), juvenile dermatomyositis (JDM), overlap myositis. * To raise awareness of myositis among the public, health care professionals and researchers, pharmaceutical companies? * To collaborate with clinicians, researchers and funds on a national and international level with the aim to improve (clinical) care and research. * To stimulate and participate in the development and conducting of clinical trials. * To collaborate with myositis working groups and patient organisations abroad. * To represent the patient perspective within in the Myositis Network Netherlands and (inter)national myositis study groups. * Patient advocacy. Activities and services: * In person or online meetings aiming to offer moral support and an opportunity to share experiences, concerns etc. or just to socialize. Three times a year we organize separate meetings for people with IBM, for people with other IIM and for caregivers. * Website updates on treatment, guidelines, (inter)national research, activities and actualities (e.g. Covid situation). * Supply patients with brochures for GP/ family doctor, physiotherapist etc. * Online (secured) platform for members. * Annual patient conference with diagnosis specific scientific programs. * Monthly newsletters: these are personalized which means they contain mainly news on the receivers type of IIM (e.g. IBM or ASyS) and information on general topics concerning all people with IIM or neuromuscular disorder. * In person meetings and / or online webinars on general topics e.g. living with a chronic condition, work, pain, fatigue. * Annual meetings with medical advisors: the working group pays a visit to all medical advisors in their respective hospitals. * Representation at (inter)national conferences. * Representation in projects such as guidelines development. * Collaboration in (inter)national studies leading to enrolling Dutch patients, researchers and clinicians in multi-centre studies, (co-) authorships in publications and to presentations during conferences (Treat NMD, IMACS, MNN). * To advise and recommend on research proposals from patient perspective. * To advise decision makers on continuation of expert centres from patient perspective. Collaborations: * Myositis Network Netherlands: patient representation on the board. * OMERACT (Outcome Measures in Rheumatology): Patient Research Partner of the Myositis Working Group. * IMACS (International Myositis Assessment and Clinical Studies Group): steering committee member of Exercise & Rehabilitation Group, led by Helene Alexanderson, ass.prof PhD, RPT). * ENMC (European Neuromuscular Centre): patient representation in myositis workshops. * EULAR (European League against Rheumatism): member of PARE and Patient Research Partner. * GCOM. * ERN - NMD (European Reference Network for Neuromuscular Diseases): member of NMD working group led by em. prof. dr. Marianne de Visser. * Patient organizations for people living with myositis . We are in this together Since myositis is a (very) rare disease, the 'myositis community' is a small one although we're happy to say that it is expanding quite rapidly. Through our inte sive involvement in several national and international studies and research projects we now have close contacts with many myositis experts across the globe, which makes it easier to keep up with actualities and developments concerning research, treatment etc. and to disseminate this knowledge to our members. This helps us to inform, support and advocate for the Dutch people living with myositis and their families and at the same time it offers opportunities to give something back: by sharing with the research community and clinicians our experiential knowledge of the consequences of myositis on everyday life. That way we can contribute to more meaningful research. We can only go forward if we do this together! That is why we are very ambitious in our efforts to contribute to myositis research. Here we list our collaborative efforts: * In 2019 the Myositis Network Netherlands of clinicians and researchers with expertise in IIM was established in which the DMWG is representing the patient perspective by a member on the board. * In OMERACT Myositis Working Group a member of the DMWG is one of the two Patient Research Partners and as such an equal partner of this study aiming to define a set of core patient reported domains with regard to the quality of life and respective instruments for use in IIM. The involvement of the DMWG has led to the opportunity for Dutch patients to participate in Delphi surveys and to an opportunity for Dutch myositis clinics to collaborate in the longitudinal study that emerged from this. * The IMACS network is an important part of our international network. One of our DMWG members is member of the Executive Committee of the Exercise & Rehabilitation Group and as such can facilitate for Dutch patients to become involved in the current study with the ultimate objective to develop recommendations for exercise in all types of IIM. * Members of the DMWG participated in several ENMC workshops on IIM as patient representatives and will continue to do so in the future. * Through a PARE membership in EULAR and membership of the study group of 'collaborative research' the DMWG hopes to raise awareness of myositis within the influential EULAR community and to speak up on behalf of the patients in Europe living with IIM. * One of our members is member of the GCOM committee responsible for the patient program of GCOM and shares the ambitions of this GCOM committee to increase the involvement of patients in this very important IIM conference. * One DMWG member joined the ERN- Neuromuscular Disease group and as such represents the people with IIM living throughout Europe. * DMWG has ambitions to empower people living with IIM and to connect with them, crossing borders by doing so. We have close and amicable relationships with patient organisations in Australia, Czech Republic, Germany, Sweden, UK and USA. * Empowering patients is one of our goals and we accomplished this for instance in Sweden. On invitation by prof. dr. Ingrid Lundberg our chair visited the Karolinska Institute, spent a week with their myositis team and in return was one of the speakers on the annual patient meeting and helped the Swedish patients establish their own myositis working group.