Immune-mediated necrotizing myopathy: A comprehensive review of the pathogenesis, clinical features, and treatments.

Immune-mediated necrotizing myopathy (IMNM) is a rare and newly recognized autoimmune disease within the spectrum of idiopathic inflammatory myopathies. It is characterized by myositis-specific autoantibodies, elevated serum creatine kinase levels, inflammatory infiltrate, and weakness. IMNM can be classified into three subtypes based on the presence or absence of specific autoantibodies: anti-signal recognition particle myositis, anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase myositis, and seronegative IMNM. In recent years, IMNM has gained increasing attention and emerged as a research hotspot. Recent studies have suggested that the pathogenesis of IMNM is linked to aberrant activation of immune system, including immune responses mediated by antibodies, complement, and immune cells, particularly macrophages, as well as abnormal release of inflammatory factors. Non-immune mechanisms such as autophagy and endoplasmic reticulum stress also participate in this process. Additionally, genetic variations associated with IMNM have been identified, providing new insights into the genetic mechanisms of the disease. Progress has also been made in IMNM treatment research, including the use of immunosuppressants and the development of biologics. Despite the challenges in understanding the etiology and treatment of IMNM, the latest research findings offer important guidance and insights for delving deeper into the disease's pathogenic mechanisms and identifying new therapeutic strategies.

Myositis developing after Covid-19 mRNA vaccine: Case Report.

Vaccine-related side effects are common. Usually, pain, edema, redness and tenderness may be seen at the injection site. Symptoms such as fever, fatigue, myalgia may occur. The coronavirus 2019 disease (Covid-19) has affected many people around the world. Although the vaccines that have been used play an active role in the fight against the pandemic, adverse events still continue to be reported. We present a 21-year-old patient who was diagnosed as having myositis after receiving covid vaccine with complaints of pain in her left arm two days after the 2nd dose of BNT162b2 mRNA Covid-19 vaccine, followed by inability to stand up from sitting and squatting and difficulty in going up and down stairs. Keywords: vaccine, myositis, creatine kinase, IVIG.

Polymyositis following varicella and mumps infection in adults: report of two cases.

Idiopathic immune myopathies (IIMs) are autoimmune diseases caused by immune-mediated muscle damage. The etiology remains unclear. Epidemiological and experimental studies, both in animals and humans, hint at viruses as major environmental factors able to trigger aberrant immune responses through many different mechanisms. However, only a few cases of either dermatomyositis or polymyositis following a specific viral infection have been reported in the literature. The objective of this study is to describe the clinical features and the treatment strategy of 2 cases of polymyositis developing shortly after chickenpox and mumps, respectively, and to review the existing literature on the topic. The clinical records of the 2 patients suspected to have developed inflammatory myositis following a viral infection were reviewed. Their clinical history, main laboratory findings, and treatment outcome are presented here. Moreover, a literature search was performed in the PubMed and MEDLINE databases to identify reports describing the association between viral infections and IIMs in patients aged ≥18. The 2 patients reported here developed polymyositis shortly after chickenpox and mumps, respectively, suggesting a causal role for viruses in triggering autoimmunity. Only a few reports published between 1990 and 2020 were found in the literature, possibly linking infections to myositis development. Intravenous immunoglobulin and rituximab were effective for the treatment of viral-triggered polymyositis.

Response to: myositis after SARS-CoV-2 vaccination occurs more frequently than assumed and is probably causally related.

We thank Finsterer et al. for the attention paid to our publication; we recognize the validity of the points mentioned in their letter to the editor and will try to answer the observations made.

Myositis after SARS-CoV-2 vaccination occurs more frequently than assumed and is probably causally related.

We read with interest the article by Camargo-Coronel et al. reporting on a systematic review of patients with idiopathic, inflammatory myopathy developing after anti-SARS-CoV-2 vaccinations.

Benign Acute Childhood Myositis: Our Experience on Clinical Evaluation.

BACKGROUND: Benign acute childhood myositis (BACM) is a transient condition mainly affecting children of school age characterized by muscle pain, typically localized to the calf muscle with symmetrical lower extremity pain and difficulty in walking. Usually, the symptomatology is preceded by a viral infection including influenza, parainfluenza, rotavirus, and mycoplasma. METHODS: The case series was conducted in four pediatric hospitals in Catania, Italy, over a 12-year observational period. Clinical examination, laboratory data, course, treatment, and complications of the affected children were extracted from electronic medical records of each hospital. RESULTS: For the case series, 50 children diagnosed with BACM were enrolled: the mean age of affected children was 5.35 years, 86% of were males, and in 56% the affections occurred during the winter. In the affected children, the clinical picture was characterized by previous fever and/or symptoms of inflammation of the upper airways, and followed by pain in the lower extremities up to uncoordinated gait. In 17 cases the etiological agent was isolated, including the influenza virus type B as the most frequent and influenza virus type A, Mycoplasma pneumoniae, beta-hemolytic streptococcus, and herpes simplex virus. Children were treated with supportive therapy. In all the children the muscular symptomatology had a good evolution with progressive marked reduction of pain and of the high level of CKemia. Neither clinical recurrences nor sequelae were reported. CONCLUSION: BACM shows to have in most of the cases a favorable evolution, a spontaneous remission of symptoms, and a good prognosis. However, the disorder generates parental distress for the acute presentation and the striking muscle dysfunction. It is worthy a rapid and early diagnosis to avoid unnecessary diagnostic investigations and a careful follow-up necessary to exclude persistence of symptoms or creatine kinase elevation.

Necrotizing enterovirus myositis in a pediatric renal transplant recipient.

BACKGROUND: Enteroviruses can cause severe infections, including viral myocarditis, meningitis, acute flaccid myelitis, and viral myositis. METHODS/RESULTS: We report a 3-year-old female renal transplant recipient who presented to a tertiary care hospital with elevated serum liver aminotransferases and subsequently developed proximal muscle pain, weakness, and respiratory distress during the first week of hospitalization. Imaging of the lower extremities revealed diffuse myositis of the proximal thigh and pelvic muscles. A muscle biopsy was obtained and revealed necrotizing myositis with immunostaining positive for enterovirus, consistent with a diagnosis of enterovirus necrotizing myositis. She had complete resolution of symptoms with steroids, intravenous immune globulin, reduced tacrolimus dose, and physical therapy. CONCLUSIONS: Enterovirus myositis should be included in the differential diagnosis for necrotizing myositis following renal transplantation in children.

Characterization and management of neurological adverse events during immune-checkpoint inhibitors treatment: an Italian multicentric experience.

BACKGROUND: Neurological immune-related adverse events (nirAEs) are rare toxicities of immune-checkpoint inhibitors (ICI). With the increase of ICI oncological indications, their incidence is growing. Their recognition and management remain nevertheless challenging. METHODS: A national, web-based database was built to collect cases of neurological symptoms in patients receiving ICI and not attributable to other causes after an adequate workup. RESULTS: We identified 27 patients who developed nirAEs (20 males, median age 69 years). Patients received anti-PD1/PDL1 (78%), anti-CTLA4 (4%), or both (19%). Most common cancers were melanoma (30%) and non-small cell lung cancer (26%). Peripheral nervous system was mostly affected (78%). Median time to onset was 43.5 days and was shorter for peripheral versus central nervous system toxicities (36 versus 144.5 days, p = 0.045). Common manifestations were myositis (33%), inflammatory polyradiculoneuropathies (33%), and myasthenia gravis (19%), alone or in combination, but the spectrum of diagnoses was broad. Most patients received first-line glucocorticoids (85%) or IVIg (15%). Seven patients (26%) needed second-line treatments. At last follow-up, four (15%) patients were deceased (encephalitis, 1; myositis/myasthenia with concomitant myocarditis, 2; acute polyradiculoneuropathy, 1), while seven (26%) had a complete remission, eight (30%) partial improvement, and six (22%) stable/progressing symptoms. ICI treatment was discontinued in most patients (78%). CONCLUSIONS: Neurological irAEs are rare but potentially fatal. They primarily affect neuromuscular structures but encompass a broad range of presentations. A prompt recognition is mandatory to timely withheld immunotherapy and administrate glucocorticoids. In corticoresistant or severely affected patients, second-line treatments with IVIg or plasmapheresis may result in additional benefit.

Orbital myositis in systemic lupus erythematosus: a case-based review.

Ocular complications occur in up to one-third of patients with systemic lupus erythematosus (SLE). Among them, orbital myositis (OM) is considered a rare manifestation that affects the extraocular muscles and causes pain and restriction with eye movement. We report a case of OM in a 48-year-old female with SLE and secondary Sjogren's Syndrome, who presented headache, periorbital edema, and painful ocular movements in both eyes, with no other systemic manifestations. An orbital magnetic resonance image revealed thickening of the right medial rectus and left lateral rectus muscles. Laboratory tests were normal and there was no further disease activity. The patient was treated with prednisone 1 mg/Kg/day with a resolution of symptoms. We found 13 additional cases of OM from our literature review (11 SLE patients and 2 with discoid lupus erythematosus). There was a female predominance in these cases with a mean age of 43.6 years (SD ± 16.9). Their main clinical features included eye pain, swelling, proptosis, diplopia, and limitations in extraocular muscles, while in most of them, there was no other active systemic manifestation. Treatment with steroids led to the complete resolution of symptoms in most of these patients. The available evidence suggests that it is essential to have a high index of suspicion for OM in SLE patients even when there is no systemic disease activity so that proper treatment is initiated early.

Kawasaki disease malingering as juvenile dermatomyositis: case-based review : Myositis in Kawasaki disease.

Kawasaki disease (KD) is a medium vessel vasculitis that predominantly affects children below 5. Diagnosis of KD is based on the presence of characteristic clinical manifestations as there are no definite diagnostic laboratory investigations for the diagnosis of this disease. Presence of atypical clinical features such as myositis often pose diagnostic challenge for the treating physicians. Presence of myositis and severe muscular weakness in KD is distinctly unusual and may lead to delays in diagnosis and administration of definite therapy. We report a 10-year-old boy who presented with fever, rash and proximal muscle and pharyngeal weakness. A clinical possibility of toxic shock syndrome or juvenile dermatomyositis was initially considered. However, he continued to have fever and developed periungual peeling of skin in fingers. Hence, a possibility of KD with myositis was considered. He showed prompt response to intravenous immunoglobulin and methylprednisolone. We also provide a review of similarly reported cases of KD myositis. It is important for clinicians to be aware of this atypical clinical presentation to avoid delays in diagnosis and treatment of KD.

Bilateral Paraneoplastic Orbital Myositis Associated With Malignant Melanoma and Multiple Myeloma.

Paraneoplastic extraocular muscle enlargement has been reported in a small number of patients with cancers including breast or lymphoma, usually presenting with bilateral multiple muscle involvement. Such myositis may be autoimmune. Furthermore, orbital inflammation is a recognized complication of immune-modulation therapy used to treat melanoma, such as ipilimumab. Extraorbital myositis has been described in myeloma, and polymyositis in melanoma. We present a case of bilateral, asymmetrical extraocular muscle enlargement with spontaneous resolution in a patient with simultaneous new diagnoses of metastatic malignant melanoma and multiple myeloma. A similar episode 7 months before diagnosis also resolved spontaneously. The authors believe this to be the first reported case of paraneoplastic orbital myositis associated with multiple myeloma or untreated malignant melanoma.

An anti-RANKL treatment reduces muscle inflammation and dysfunction and strengthens bone in dystrophic mice.

Duchenne muscular dystrophy (DMD) is the most severe form of muscular dystrophy which leads to progressive muscle degeneration and inflammation. The receptor activator of nuclear factor NF-κB ligand (RANKL) and its receptor (RANK), which are expressed in bone and skeletal and cardiac muscles, form a signaling network upstream from nuclear factor-kappa B (NF-κB). We thus hypothesized that prolonged silencing RANKL/RANK signaling would significantly improve DMD. We showed that RANK and RANKL protein levels were increased in the microenvironment of myofibers of 5-month-old utrophin haploinsufficient mdx (mdx/utrn+/-) mice and that a 4 mg/kg dose of anti-RANKL antibody every 3 d for 28 days is optimal and more effective than 1 mg/kg every 3 d for improving the ex vivo maximum specific force (sP0) of dystrophic EDL muscles from mdx/utrn+/- mice. This functional improvement was associated with a reduction in muscle edema, damage, and fibrosis and a marked reduction in serum CK levels. The anti-RANKL treatment inhibited the NF-κB pathway, increased the proportion of anti-inflammatory and non-cytotoxic M2 macrophages, and reduced the number of centrally-nucleated myofibers and the frequency of small myofibers, suggesting that anti-RANKL inhibits the cycle of degeneration/regeneration in dystrophic mice. A three-point bending test showed that a 28-d anti-RANKL treatment increases the mechanical properties of bone in mdx/utrn+/- dystrophic mice. In conclusion, the anti-RANKL treatment protected against skeletal muscle dysfunctions while enhancing bone mechanical properties, filling two needs with one deed in the context of muscular dystrophy.

Refining myositis associated with primary Sjögren's syndrome: data from the prospective cohort ASSESS.

OBJECTIVES: To refine the prevalence, characteristics and response to treatment of myositis in primary SS (pSS). METHODS: The multicentre prospective Assessment of Systemic Signs and Evolution in Sjögren's Syndrome (ASSESS) cohort of 395 pSS patients with ≥60 months' follow-up was screened by the 2017 EULAR/ACR criteria for myositis. Extra-muscular complications, disease activity and patient-reported scores were analysed. RESULTS: Before enrolment and during the 5-year follow-up, myositis was suspected in 38 pSS patients and confirmed in 4 [1.0% (95% CI: 0.40, 2.6)]. Patients with suspected but not confirmed myositis had higher patient-reported scores and more frequent articular and peripheral nervous involvement than others. By contrast, disease duration in patients with confirmed myositis was 3-fold longer than without myositis. Two of the four myositis patients fulfilled criteria for sporadic IBM. Despite receiving three or more lines of treatment, they showed no muscle improvement, which further supported the sporadic IBM diagnosis. The two other patients did not feature characteristics of a myositis subtype, which suggested 'pure' pSS myositis. Steroids plus MTX was then efficient in achieving remission. CONCLUSIONS: Myositis, frequently suspected, occurs in 1% of pSS patients. Especially when there is resistance to treatment, sporadic IBM should be considered and might be regarded as a late complication of this disease.

Focal vasculitic myositis as a primary manifestation of Behçet's disease: a case series of 10 Korean patients in a locomotive medicine clinic.

OBJECTIVES: Muscle involvement in Behçet's disease (BD) is rare, and several cases have been reported in the literature. Therefore, this study aimed to describe the clinical, laboratory and imaging findings in adult patients presenting with BD-associated myositis before the diagnosis of BD. METHODS: We retrospectively screened patients who visited a locomotive medicine clinic presenting with myalgia, local swelling, or tenderness of extremities without an established diagnosis of BD. We enrolled patients whose pain in the extremities was proven to be suggestive of focal vasculitic myositis and who were eventually diagnosed as having BD at the initial visit or during follow-up. We thoroughly reviewed the clinical, histological and imaging findings and treatment outcomes in patients who presented with focal vasculitic myositis as the primary manifestation of BD. RESULTS: Ten adult patients with focal vasculitic myositis as the primary manifestation of BD were enrolled. The lower and upper extremities were affected in eight and two patients, respectively. The affected lower extremities were the calf (n = 6) and thigh muscles (n = 2). The common findings of MRI included high signal intensity of the affected muscles and intermuscular fascia on fat-suppressed images, suggestive of myofascitis and oedematous changes in the subcutaneous layer. The results of skin or muscle biopsy were suggestive of vasculitis. All the patients were pain-free at the short-term follow-up (1-3 weeks) after oral steroid therapy. CONCLUSION: Focal vasculitic myositis can be a primary manifestation of BD warranting medical attention. BD-associated myositis responds well to oral steroid therapy.

Immune-mediated neuromuscular complications of graft-versus-host disease.

INTRODUCTION/AIMS: We aimed to describe the clinical phenotype, histopathological findings and overall survival (OS) of the immune-mediated neuromuscular complications of graft-versus-host disease (GVHD). METHODS: We conducted a retrospective chart review of adult patients presenting with immune-mediated neuromuscular complications of GVHD to Mayo Clinic, between April 2013 and July 2018.We collected clinical and laboratory characteristics, histopathological findings, response to treatment and survival data. RESULTS: We identified 20 patients with a mean age at presentation of 55 y. Mean time from transplant to neurological presentation was 14 mo. Myositis was the most common complication seen in 17 patients, manifesting with predominantly axial and/or proximal weakness. Eleven patients had a muscle biopsy showing diffuse perimysial, predominantly macrophagic infiltration in 10, 3 of them with perimysial perivascular lymphocytic collections, and endomysial and perimysial lymphocytic infiltration in 1. Only two patients had a neuropathic complication: one each with acute inflammatory demyelinating polyradiculoneuropathy and neuralgic amyotrophy. A single patient had a myasthenic syndrome presenting with fluctuating foot drop. Nineteen patients were treated and all responded to immunosuppressive agents; however, 11 had further GVHD flares requiring escalation of therapy. After a median follow-up of 83 mo, seven (35%) patients died: five from progressive GVHD and two from infections. The 5-y OS from time of transplant was 68%. DISCUSSION: Myositis is the most common immune-mediated neuromuscular complication of GVHD while peripheral neuropathy and myasthenic syndromes appear less common. The macrophage-predominant infiltration on muscle biopsy deserves further study to better clarify the role of macrophages in GVHD pathogenesis.

Myositis in systemic lupus erythematosus.

OBJECTIVES: Myositis is an infrequent feature of SLE and may often be overlooked. We aimed to estimate the incidence of myositis in SLE, and to determine demographic and clinical factors associated with it. METHODS: Within our lupus cohort, we identified potential myositis cases using the SLICC Damage Index for muscle atrophy or weakness, the SLEDAI-2K item for myositis, and annually measured serum creatinine kinase. Cases were confirmed through chart review. We performed descriptive analyses of prevalent myositis cases as of January 2000. From that point onward, we studies patients without myositis to determine risk of incident myositis, using cohort analyses adjusted for demographic variables (age, sex, race/ethnicity). RESULTS: As of January 2000, there were 5 prevalent myositis cases in our SLE cohort. Among 560 SLE patients with a study visit from January 2000 onward, with no history of myositis at baseline, 5 new cases (4 females, 1 male) were identified over an average follow-up of 8.5 years (incidence 1.05 cases per 1000 person-years). There was a higher proportion of Caucasians in the non-myositis group versus myositis group, with a trend for fewer females in the myositis cases. Arthritis, Raynaud's phenomenon, and anti-Smith antibodies were common pre-existing features, occurring in all incident myositis cases. In Cox regression analyses adjusting for age, race/ethnicity and sex, non-Caucasian patients had a markedly increased risk of developing myositis. CONCLUSION: We found a low incidence of myositis in our SLE cohort. A cluster of variables, particularly non-Caucasian race/ethnicity, arthritis, Raynaud's phenomenon, and anti-Smith antibodies were associated with risk of developing myositis in SLE. These variables may aid clinicians in identifying SLE patients at highest risk for this important complication.

Clinical Characteristics of Myositis Associated with Graft-Versus-Host Disease.

PURPOSE OF REVIEW: Recipients of allogeneic hematopoietic stem cell transplantation (HSCT) are at increased risk for inflammatory myositis; histological subsets reported include dermatomyositis, necrotising myopathy and chronic graft-versus-host disease (cGVHD)-related myositis. Though corticosteroids and various immunosuppressive therapies have been used, there is a lack of consensus guidelines dictating therapy. RECENT FINDINGS: Recent evidence suggests the fascia as a preferential target in cGVHD myositis, with conditioning regimens promoting fascial microtrauma. Positron emission tomography (PET) can be a useful diagnostic tool, and case reports suggest that the Bruton's tyrosine kinase inhibitor ibrutinib may have therapeutic potential. Emerging therapies include targeted B cell depletion with rituximab, and extracorporeal photophoresis. Clinicians need to be vigilant for the development of inflammatory myositis post-allogeneic HSCT as most patients respond to treatment. Advances in immunohistochemistry to determine the dominant cell type and cytokine profile may enable targeted and individualised therapies.

COVID-19 and Myositis: What We Know So Far.

PURPOSE: Myositis as a rare manifestation of COVID-19 is only recently being reported. This review examines the current literature on COVID-19-induced myositis focusing on etiopathogenesis, clinical presentations, diagnostic practices, and therapeutic challenges with immunosuppression, and the difficulties experienced by rheumatologists in established myositis in the COVID-19 era. RECENT FINDINGS: COVID-19 is associated with a viral myositis attributable to direct myocyte invasion or induction of autoimmunity. COVID-19-induced myositis may be varied in presentation, from typical dermatomyositis to rhabdomyolysis, and a paraspinal affliction with back pain. It may or may not present with acute exponential elevations of enzyme markers such as creatine kinase (CK). Virus-mediated muscle inflammation is attributed to ACE2 (angiotensin-converting enzyme) receptor-mediated direct entry and affliction of muscle fibers, leading on to innate and adaptive immune activation. A greater recognition of the stark similarity between anti-MDA5-positive myositis with COVID-19 has thrown researchers into the alley of exploration - finding common etiopathogenic basis as well as therapeutic strategies. For patients with established myositis, chronic care was disrupted during the pandemic with several logistic challenges and treatment dilemmas leading to high flare rates. Teleconsultation bridged the gap while ushering in an era of patient-led care with the digital transition to tools of remote disease assessment. COVID-19 has brought along greater insight into unique manifestations of COVID-19-related myositis, ranging from direct virus-induced muscle disease to triggered autoimmunity and other etiopathogenic links to explore. A remarkable shift in the means of delivering chronic care has led patients and caregivers worldwide to embrace a virtual shift with teleconsultation and opened doorways to a new era of patient-led care.

Influenza-associated myositis: a single-centre, 5-year retrospective study.

We aimed to describe the clinical epidemiology of influenza-associated myositis (IAM) over a 5-year period. We identified ICD-10-coded myositis cases retrospectively 2011-2015 and performed limited chart reviews. We excluded myositis with non-viral causes and cross-referenced with laboratory records of influenza tests to identify confirmed IAM. We defined probable IAM as viral myositis occurring during the influenza season without alternative cause. We described epidemiological and clinical features of IAM and compared IAM with all hospitalised influenza. We identified 283 cases of viral myositis with seasonal peaks (May to October, 85% of cases); 69 were tested for influenza, 52 (78%) were positive. Given the strong seasonality concurrent with the influenza season, we estimated that 80% (95% CI 76-85) of viral myositis is attributable to IAM annually. Of 226 cases of IAM, 21% (n = 49) were confirmed and the remaining probable. IAM was associated with being male (82%), aged 5-9 (73%), and influenza B (86%). The majority had bilateral calf pain; mean creatinine kinase (CK) value was 3579 U/L, and no cases had renal impairment.Conclusion: Childhood viral myositis shows strong association with the influenza season. IAM is clinically stereotyped, age restricted, and benign in most and strongly associated with influenza B. What is Known: • Childhood viral myositis has been reported in association with influenza for decades, more frequently with influenza B and in school-aged children. What is New: • Here, we show over a 5-year period that viral myositis is strongly seasonal with up to 80% of cases attributable to influenza. • Influenza-associated myositis (IAM) typically occurs in boys, aged 5-9 years, with influenza B and is most often benign. Early clinical recognition may avoid unnecessary treatment and testing.

Unilateral Ptosis, Proptosis, and Orbital Myositis After Shingles Vaccination.

Vaccinations for shingles are recommended for most adults over 60 years of age and are typically well tolerated. The present case describes acute onset of unilateral ptosis, proptosis, and orbital myositis developing within days after administration of shingles vaccination. The episode resolved to baseline after 1 week of treatment with steroids. To the authors' knowledge, this is first reported case of orbital inflammation following shingles vaccination. Given the temporal relationship and rapid response to treatment, this may represent an autoimmune reaction to the shingles vaccine.