Current approach to muscle imaging in myositis.

PURPOSE OF REVIEW: Muscle imaging is commonly utilized in idiopathic inflammatory myopathies (IIM) for diagnostic evaluation, selection of muscle biopsy site, and differentiating between disease activity versus damage. In this review, we discuss the current state and recent developments in the use of muscle imaging modalities including muscle magnetic resonance imaging (MRI), ultrasound (US), and positron emission tomography (PET) scan. RECENT FINDINGS: Muscle MRI is a clinically useful tool in evaluation of IIM with studies showing good correlations between pattern of morphological changes on MRI and histopathological findings on muscle biopsy. The use of computer aided diagnostics to enable quantification of muscle pathology will be a welcome development for future studies and trials. New studies highlight that muscle US could be a particularly useful point of care tool in longitudinal monitoring of patients with active myositis. Muscle FDG-PET scan shows inflammatory activity in IIM muscle and can also provide additional information on extra-muscular manifestations and cancer screening. Utilization of novel tracers is an exciting development for IIM evaluation. SUMMARY: Muscle MRI remains the gold standard for muscle imaging in IIM. Growing literature on muscle US and PET scan highlight their promising applications in IIM.

Precise identification and tracking of HMGCR-reactive CD4+ T cells in the target tissue of patients with anti-HMGCR immune-mediated necrotising myopathy.

BACKGROUND: Anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR)-positive immune-mediated necrotising myopathy (IMNM) is characterised by the presence of IgG autoantibodies against HMGCR and a strong association with specific HLA-DR alleles. Although these findings implicate HMGCR-specific CD4+T-cells in the disease's pathogenesis, no such cells have been described. In this study, we aimed to identify and characterise HMGCR-reactive CD4+T-cells and assess their presence in affected muscle tissue from patients with anti-HMGCR+IMNM. METHODS: Peripheral blood mononuclear cells from patients with anti-HMGCR+IMNM (n=10) and dermatomyositis (DM; n=10) were stimulated with HMGCR protein and peptides identified using a natural antigen processing assay (NAPA; n=6). CD4+T-cell activation was assessed by CD154 upregulation via flow cytometry. T-cell receptor ß(TCR) sequencing was performed on paired HMGCR-reactive T-cells and muscle biopsy tissue (n=5). RESULTS: CD4+T-cell responses to HMGCR protein were higher in patients with anti-HMGCR+IMNM compared with DM (median 0.06 vs 0.00, p=0.0059). These responses were enriched in Th1-Th17 cells, and when present, they positively correlated with anti-HMGCR antibody levels (r2=0.89, p=0.0012). NAPA revealed convergent presentation of seven HMGCR core peptides, with substantial overlap in the peptide repertoires between patients. These HMGCR peptides elicited robust CD4+T-cell responses, with 9/10 anti-HMGCR+IMNM patients responding to at least one peptide, compared with 1/10 DM (p=0.0003). Analysis of HMGCR-reactive TCRs ß yielded antigen-reactive motifs that were enriched in muscle biopsies (projection score 0.03 vs 0.63, p=0.007). CONCLUSION: HMGCR-antigen-reactive CD4+T-cells are present in the circulation and target tissue of patients with anti-HMGCR+IMNM, suggesting an active role for these cells in the pathogenesis of anti-HMGCR+IMNM.

Evaluating CA-125 and PET/CT for cancer detection in idiopathic inflammatory myopathies.

OBJECTIVE: This study aims to evaluate the diagnostic accuracy of CA-125 and PET/CT in detecting cancer among adult patients with idiopathic inflammatory myopathy (IIM). METHODS: We conducted a retrospective study of a single-centre cohort of adult IIM patients enrolled from 2003 to 2020. Data on CA-125 and PET/CT tests conducted within five years of IIM symptom onset were extracted from electronic medical records. The outcomes assessed included true positive, false-positive, true negative, and false-negative results. RESULTS: Among 1432 patients with IIM, 250 CA-125 tests were conducted on 205 patients within the first five years of symptom onset, yielding a false-positive rate of 3.1% and a false-negative rate of 14.3%. Most false positives were associated with endometriosis or uterine fibroids, but additional medical procedures were often carried out to investigate the false-positive results. For PET/CT, 149 tests were performed on 139 patients, resulting in a false-positive rate of 5.5% and a false-negative rate of 28.6%. Lymphadenopathy and lung nodules were the predominant causes of false positives, while melanoma, low-stage breast cancer, and prostate cancer were the most frequent cancers missed (false negatives). CONCLUSION: False positive and false-negative results are prevalent in CA-125 and PET/CT testing for adult patients with newly diagnosed idiopathic inflammatory myopathy. Understanding the causes of these inaccuracies can aid clinicians in making informed decisions during patient care.

Collaborative research in myositis-related disorders: MIHRA, a global shared community model.

Myositis International Health and Research Collaborative Alliance (MIHRA) is a newly formed purpose-built non-profit charitable research organization dedicated to accelerating international clinical trial readiness, global professional and lay education, career development and rare disease advocacy in IIM-related disorders. In its long form, the name expresses the community's scope of engagement and intent. In its abbreviation, MIHRA, conveys linguistic roots across many languages, that reflects the IIM community's spirit with meanings such as kindness, community, goodness, and peace. MIHRA unites the global multi-disciplinary community of adult and pediatric healthcare professionals, researchers, patient advisors and networks focused on conducting research in and providing care for pediatric and adult IIM-related disorders to ultimately find a cure. MIHRA serves as a resourced platform for collaborative efforts in investigator-initiated projects, consensus guidelines for IIM assessment and treatment, and IIM-specific career development through connecting research networks.MIHRA's infrastructure, mission, programming and operations are designed to address challenges unique to rare disease communities and aspires to contribute toward transformative models of rare disease research such as global expansion and inclusivity, utilization of community resources, streamlining ethics and data-sharing policies to facilitate collaborative research. Herein, summarises MIHRA operational cores, missions, vision, programming and provision of community resources to sustain, accelerate and grow global collaborative research in myositis-related disorders.

Transcriptional derepression of CHD4/NuRD-regulated genes in the muscle of patients with dermatomyositis and anti-Mi2 autoantibodies.

OBJECTIVES: Myositis is a heterogeneous family of diseases including dermatomyositis (DM), immune-mediated necrotising myopathy (IMNM), antisynthetase syndrome (AS) and inclusion body myositis (IBM). Myositis-specific autoantibodies define different subtypes of myositis. For example, patients with anti-Mi2 autoantibodies targeting the chromodomain helicase DNA-binding protein 4 (CHD4)/NuRD complex (a transcriptional repressor) have more severe muscle disease than other DM patients. This study aimed to define the transcriptional profile of muscle biopsies from anti-Mi2-positive DM patients. METHODS: RNA sequencing was performed on muscle biopsies (n=171) from patients with anti-Mi2-positive DM (n=18), DM without anti-Mi2 autoantibodies (n=32), AS (n=18), IMNM (n=54) and IBM (n=16) as well as 33 normal muscle biopsies. Genes specifically upregulated in anti-Mi2-positive DM were identified. Muscle biopsies were stained for human immunoglobulin and protein products corresponding to genes specifically upregulated in anti-Mi2-positive muscle biopsies. RESULTS: A set of 135 genes, including SCRT1 and MADCAM1, was specifically overexpressed in anti-Mi2-positive DM muscle. This set was enriched for CHD4/NuRD-regulated genes and included genes that are not otherwise expressed in skeletal muscle. The expression levels of these genes correlated with anti-Mi2 autoantibody titres, markers of disease activity and with the other members of the gene set. In anti-Mi2-positive muscle biopsies, immunoglobulin was localised to the myonuclei, MAdCAM-1 protein was present in the cytoplasm of perifascicular fibres, and SCRT1 protein was localised to myofibre nuclei. CONCLUSIONS: Based on these findings, we hypothesise that anti-Mi2 autoantibodies could exert a pathogenic effect by entering damaged myofibres, inhibiting the CHD4/NuRD complex, and subsequently derepressing the unique set of genes defined in this study.

Coexisting autoantibodies against transcription factor Sp4 are associated with decreased cancer risk in patients with dermatomyositis with anti-TIF1γ autoantibodies.

OBJECTIVES: In dermatomyositis (DM), autoantibodies are associated with unique clinical phenotypes. For example, anti-TIF1γ autoantibodies are associated with an increased risk of cancer. The purpose of this study was to discover novel DM autoantibodies. METHODS: Phage ImmunoPrecipitation Sequencing using sera from 43 patients with DM suggested that transcription factor Sp4 is a novel autoantigen; this was confirmed by showing that patient sera immunoprecipitated full-length Sp4 protein. Sera from 371 Johns Hopkins patients with myositis (255 with DM, 28 with antisynthetase syndrome, 40 with immune-mediated necrotising myopathy, 29 with inclusion body myositis and 19 with polymyositis), 80 rheumatological disease controls (25 with Sjogren's syndrome, 25 with systemic lupus erythematosus and 30 with rheumatoid arthritis (RA)) and 200 healthy comparators were screened for anti-SP4 autoantibodies by ELISA. A validation cohort of 46 anti-TIF1γ-positive patient sera from the University of Pittsburgh was also screened for anti-Sp4 autoantibodies. RESULTS: Anti-Sp4 autoantibodies were present in 27 (10.5%) patients with DM and 1 (3.3%) patient with RA but not in other clinical groups. In patients with DM, 96.3% of anti-Sp4 autoantibodies were detected in those with anti-TIF1γ autoantibodies. Among 26 TIF1γ-positive patients with anti-Sp4 autoantibodies, none (0%) had cancer. In contrast, among 35 TIF1γ-positive patients without anti-Sp4 autoantibodies, 5 (14%, p=0.04) had cancer. In the validation cohort, among 15 TIF1γ-positive patients with anti-Sp4 autoantibodies, 2 (13.3%) had cancer. By comparison, among 31 TIF1γ-positive patients without anti-Sp4 autoantibodies, 21 (67.7%, p<0.001) had cancer. CONCLUSIONS: Anti-Sp4 autoantibodies appear to identify a subgroup of anti-TIF1γ-positive DM patients with lower cancer risk.

Correlation of muscle ultrasound with clinical and pathological findings in idiopathic inflammatory myopathies.

INTRODUCTION/AIMS: In idiopathic inflammatory myopathies (IIMs), the change in muscle echogenicity and its histopathological basis are not well understood. We quantitatively measured muscle echogenicity in patients with IIMs and evaluated its correlation with disease activity and histopathological findings. METHODS: This study involved patients with IIMs who underwent both ultrasonography (US) and muscle biopsy, as well as age- and sex-matched rheumatoid arthritis patients as inflammatory disease controls. On US, axial images of the right biceps brachii and vastus medialis were obtained. Standardized histopathological scoring was used to quantitatively measure each pathological domain. RESULTS: Forty-two patients (17 with inclusion body myositis [IBM] and 25 with IIMs other than IBM) and 25 controls were included. The muscle echo intensity (EI) of patients with IIMs was significantly higher than that of controls. Muscle EI showed significant correlations with creatine kinase (r = 0.66, p < .001) and muscle strength (r = -0.73, p < .0001) in patients with non-IBM IIMs. In patients with IBM, moderate correlation was found between muscle EI and quadriceps muscle strength (r = -0.53, p = .028). Histopathologically, the number of infiltrating CD3+ inflammatory cells correlated with muscle EI in the non-IBM group (r = 0.56, p = .017), but not in the IBM group. DISCUSSION: Muscle EI may be useful as a surrogate marker of muscle inflammation in non-IBM IIM. Increased muscle EI may be difficult to interpret in patients with long-standing IBM, which has advanced and complex histopathology.

Anti-MDA5-positive dermatomyositis and remission in a single referral centre population.

OBJECTIVES: To describe a single-centre North American adult cohort of anti-MDA5-positive dermatomyositis patients, with emphasis on drug-free long-term remission. METHODS: We conducted an observational retrospective cohort study of anti-MDA5-positive DM patients. All consented patients seen in the Johns Hopkins Myositis Centre from 2003-2020 with suspected muscle disease were routinely screened for myositis-specific autoantibodies. All sera were screened for anti-MDA5 autoantibodies by line blot; positives were verified by enzyme-linked immunoassay. Patients whose sera were anti-MDA5 positive by both assays (n=52) were followed longitudinally. If clinical status was unavailable, structured telephone interviews were conducted. Clinical remission was defined as being off all immunosuppression >1 year while remaining asymptomatic. RESULTS: 38/52 (73%) of the patients were women with a median age at disease-onset of 47 (IQR 40-54). Twenty-five of the patients (48%) were White, 16 (30%) were Black and 3 (6%) were Asian. Most patients (42/52, 80%) had interstitial lung disease, defined by inflammatory or fibrotic changes on high resolution computed tomography (HRCT). 18/52 (35%) of patients required pulse-dose methylprednisolone, 4/52 (8%) experienced spontaneous pneumothorax/pneumomediastinum, 6/52 (12%) required intubation, and 5/52 (10%) died. Over longitudinal follow-up (median 3.5 years), 9 (18%) patients achieved clinical remission. The median time from symptom onset to clinical remission was 4 years, and the median duration of sustained remission was 3.5 years (range 1.4-7.8). No demographic or disease characteristics were significantly associated with remission. CONCLUSIONS: In this single centre, tertiary referral population of anti-MDA5-positive dermatomyositis, ~20% of patients experienced long-term drug-free remission after a median disease duration of 4 years. No clinical or biologic factors were associated with clinical remission.

Risk Factors for Infection and Health Impacts of the Coronavirus Disease 2019 (COVID-19) Pandemic in People With Autoimmune Diseases.

BACKGROUND: People with autoimmune or inflammatory conditions taking immunomodulatory/suppressive medications may have higher risk of novel coronavirus disease 2019 (COVID-19). Chronic disease care has also changed for many patients, with uncertain downstream consequences. METHODS: We included participants with autoimmune or inflammatory conditions followed by specialists at Johns Hopkins. Participants completed periodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcare. We assessed whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterized pandemic-associated changes to care and mental health. RESULTS: In total, 265 (5.6%) developed COVID-19 over 9 months of follow-up (April-December 2020). Patient characteristics (age, race, comorbidity, medications) were associated with differences in social distancing behaviors during the pandemic. Glucocorticoid exposure was associated with higher odds of COVID-19 in models incorporating behavior and other potential confounders (odds ratio [OR]: 1.43; 95% confidence interval [CI]: 1.08, 1.89). Other medication classes were not associated with COVID-19 risk. Diabetes (OR: 1.72; 95% CI: 1.08, 2.73), cardiovascular disease (OR: 1.68; 95% CI: 1.24, 2.28), and kidney disease (OR: 1.76; 95% CI: 1.04, 2.97) were associated with higher odds of COVID-19. Of the 2156 reporting pre-pandemic utilization of infusion, mental health or rehabilitative services, 975 (45.2%) reported disruptions therein, which disproportionately affected individuals experiencing changes to employment or income. CONCLUSIONS: Glucocorticoid exposure may increase risk of COVID-19 in people with autoimmune or inflammatory conditions. Disruption to healthcare and related services was common. Those with pandemic-related reduced income may be most vulnerable to care disruptions.

Prevalence of avascular necrosis in idiopathic inflammatory myopathies: a single-centre experience.

OBJECTIVES: To assess the prevalence of avascular necrosis (AVN) in a large cohort of patients with idiopathic inflammatory myopathies (IIM) and define the major associated risk factors. METHODS: We retrospectively reviewed the electronic medical records of all patients with a definitive diagnosis of IIM enrolled in our registry between 2003 and 2017, and followed until 2020. Pertinent demographic, clinical, serologic and imaging data were collected. A matched group of patients without AVN was then selected for comparison. RESULTS: A total of 1680 patients were diagnosed with IIM. Fifty-one patients developed AVN, with an overall prevalence of 3%. Musculoskeletal MRI was available for 1085 patients and AVN was present in 46 patients (43 lower extremities and 3 upper extremities MRI studies), with a relative prevalence of 4.2%. Most patients with AVN were Caucasian females (57%) with a mean (s.d.) age at diagnosis of 44.5 (12.4) years. Sixty-one percent had DM and 29% had PM. The median time from onset of IIM to diagnosis of AVN was 46 months. The hip joint was most commonly involved in 76% of cases, followed by the knee joint in 15% and shoulder joint in 9%. Some 81% of patients were asymptomatic. Established risk factors for AVN were not found to be associated with the development of AVN in IIM patients. CONCLUSION: Although mostly asymptomatic and incidental, the overall prevalence of AVN in IIM was 3% and the prevalence by MRI was 4.2%. None of the established risk factors was found to be associated with AVN development.

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

INTRODUCTION: Necrotizing 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. METHODS: A 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. RESULTS: Six 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. CONCLUSION: TPE can play a role in the management of NAM, particularly in patients with HMGCR or SRP antibodies who are refractory to pharmacologic immunosuppression.

Rapidly progressive interstitial lung disease in patients with anti-melanoma differentiation-associated gene 5-positive dermatomyositis: serial changes on HRCT.

BACKGROUND: Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibodies in patients with dermatomyositis are associated with rapidly progressive interstitial lung disease (RP-ILD). Computed tomography (CT) plays a central role in the diagnosis of RP-ILD and may help characterize the temporal changes. METHODS: We report five anti-MDA5-positive dermatomyositis patients with serial CT scans spanning their acute RP-ILD disease course. RESULTS: Our case series highlights the variable imaging pattern that can manifest in this setting, including diffuse alveolar damage and nonspecific interstitial pneumonia patterns. Three patients in our series died within 4 months of their disease onset, whereas the other two patients survived. CONCLUSION: The serial CT changes in anti-MDA5 disease are dynamic and variable; therefore, it is imperative to maintain a broad differential when faced with these HRCT patterns to improve the diagnosis and management of this underrecognized entity.

The Value of Musculoskeletal Ultrasound for Evaluation of Postinfectious Lyme Arthritis.

BACKGROUND: Inflammatory arthritis is the most common late manifestation of untreated Lyme disease in the United States. While antimicrobial therapy is effective in resolving swelling and pain for 90% of patients, many patients have persistent inflammation, termed postinfectious Lyme arthritis (PILA). Current outcome measures for Lyme arthritis have several limitations, as improvement is considered a dichotomous outcome based solely on physical examination. There is growing interest in the use of ultrasonography to better define outcomes in inflammatory arthritis, and this is particularly relevant for conditions such as late Lyme arthritis and PILA, which are monoarticular or oligoarticular. We describe results from a series of 5 patients who underwent ultrasound evaluations leading to a diagnosis of PILA. METHODS: This is a case series describing 5 patients with PILA who were referred for evaluation and treatment of symptomatic joints. RESULTS: Musculoskeletal ultrasound showed significant joint pathology, even in cases with minimal clinical findings. Synovitis, effusions, enthesitis/tendinopathy, and bone erosions were seen and helped confirm the presence of ongoing inflammatory arthritis. CONCLUSIONS: Marked inflammatory change-with synovitis, enthesitis and erosions-can be seen in selected patients with PILA. Systematic sonographic evaluation of patients with PILA is needed to further evaluate pathology and treatment response.

Ultrasound assessment of sarcopenia in patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the efficacy of ultrasound (US) as a diagnostic tool for sarcopenia in patients with rheumatoid arthritis (RA). METHODS: Female RA patients aged >50 years and matched controls were cross-sectionally assessed. Sarcopenia was diagnosed based on the 2019-updated Asian Working Group for Sarcopenia definition. The cross-sectional area (CSA) and echo intensity (EI) of the biceps brachii, rectus femoris, and EI of the vastus lateralis were examined bilaterally. Correction for subcutaneous fat and calculation of the recorrected EI (rcEI) were performed. We performed logistic regression using both muscle rcEI and CSA with receiver operating curve analysis to evaluate the discriminative performance per muscle group. RESULTS: Seventy-eight consecutive RA patients and 15 age-and sex-matched controls were assessed. Sarcopenia was diagnosed in 34 RA patients (43.6%). The rcEI of examined muscles were significantly higher, whereas CSA were significantly lower in sarcopenic RA patients than in non-sarcopenic patients and matched controls. The combined discriminative performance of rcEI and CSA was superior to those of rcEI or CSA alone. CONCLUSIONS: This study suggests the use of US for the diagnosis of sarcopenia in RA patients. The diagnostic performance increases when both echogenicity and CSA are considered together rather than individually.

Ultrasound Doppler and tenosynovial fluid analysis in tenosynovitis.

OBJECTIVE: To assess Doppler ultrasound (US) and tenosynovial fluid (TSF) characteristics in tenosynovitis within common rheumatic conditions, as well as their diagnostic utility. METHODS: Subjects with tenosynovitis underwent Doppler US and US-guided TSF aspiration for white cell count (WCC) and crystal analysis. Tenosynovial Doppler scores (DS) were semiquantitatively graded. TSF WCC and DS were compared using Kruskal-Wallis tests and logistic regression between non-inflammatory conditions (NIC), inflammatory conditions (IC) and crystal-related conditions (CRC). Receiver operating curves, sensitivity and specificity assessed the ability of WCC and DS to discriminate IC from NIC. RESULTS: We analysed 100 subjects from 14 sites. The mean age was 62 years, 65% were female, and the mean TSF volume was 1.2 mL. Doppler signal was present in 93.7% of the IC group and was more frequent in IC than in NIC group (OR 6.82, 95% CI 1.41 to 32.97). The TSF median WCC per 109/L was significantly higher in the IC (2.58, p<0.001) and CRC (1.07, p<0.01) groups versus the NIC group (0.38). A TSF cut-off of ≥0.67 WCC per 109/L optimally discriminated IC versus NIC with a sensitivity and specificity each of 81.3%. In the IC group, 20 of 48 (41.7%) subjects had a TSF WCC <2.00 per 109/L. CONCLUSIONS: A negative DS helps rule out IC in tenosynovitis, but a positive DS is non-specific and merits TSF testing. Unlike synovial fluid, a lower TSF WCC better discriminates IC from NIC. US guidance facilitates aspiration of minute TSF volume, which is critical for diagnosing tenosynovial CRC.

Machine learning algorithms reveal unique gene expression profiles in muscle biopsies from patients with different types of myositis.

OBJECTIVES: Myositis is a heterogeneous family of diseases that includes dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotising myopathy (IMNM), inclusion body myositis (IBM), polymyositis and overlap myositis. Additional subtypes of myositis can be defined by the presence of myositis-specific autoantibodies (MSAs). The purpose of this study was to define unique gene expression profiles in muscle biopsies from patients with MSA-positive DM, AS and IMNM as well as IBM. METHODS: RNA-seq was performed on muscle biopsies from 119 myositis patients with IBM or defined MSAs and 20 controls. Machine learning algorithms were trained on transcriptomic data and recursive feature elimination was used to determine which genes were most useful for classifying muscle biopsies into each type and MSA-defined subtype of myositis. RESULTS: The support vector machine learning algorithm classified the muscle biopsies with >90% accuracy. Recursive feature elimination identified genes that are most useful to the machine learning algorithm and that are only overexpressed in one type of myositis. For example, CAMK1G (calcium/calmodulin-dependent protein kinase IG), EGR4 (early growth response protein 4) and CXCL8 (interleukin 8) are highly expressed in AS but not in DM or other types of myositis. Using the same computational approach, we also identified genes that are uniquely overexpressed in different MSA-defined subtypes. These included apolipoprotein A4 (APOA4), which is only expressed in anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) myopathy, and MADCAM1 (mucosal vascular addressin cell adhesion molecule 1), which is only expressed in anti-Mi2-positive DM. CONCLUSIONS: Unique gene expression profiles in muscle biopsies from patients with MSA-defined subtypes of myositis and IBM suggest that different pathological mechanisms underly muscle damage in each of these diseases.

Ultrasound can differentiate inclusion body myositis from disease mimics.

INTRODUCTION: The diagnosis of inclusion body myositis (IBM) can be challenging, and its presentation can be confused with other forms of myositis or neuromuscular disorders. In this study we evaluate the ability of quantitative muscle ultrasound to differentiate between IBM and mimicking diseases. METHODS: Patients 50 years of age and older were included from two specialty centers. Muscle echogenicity and muscle thickness of four characteristically involved muscles in IBM were measured and compared with polymyositis (PM)/dermatomyositis (DM), other neuromuscular disorders, and healthy controls. RESULTS: Echogenicity was higher and muscle thickness generally lower in all four muscles in IBM compared with PM/DM and normal controls. When comparing IBM with the comparator groups, the flexor digitorum profundus was the most discriminative muscle. DISCUSSION: Ultrasound appears to be a good test to differentiate established IBM from PM/DM and neuromuscular controls, with value as a diagnostic tool for IBM.

Diagnostic Value of Muscle Ultrasound for Myopathies and Myositis.

PURPOSE OF REVIEW: The purpose of this review is to critically discuss the use of ultrasound in the evaluation of muscle disorders with a particular focus on the emerging use in inflammatory myopathies. RECENT FINDINGS: In myopathies, pathologic muscle shows an increase in echogenicity. Muscle echogenicity can be assessed visually, semi-quantitatively, or quantitatively using grayscale analysis. The involvement of specific muscle groups and the pattern of increase in echogenicity can further point to specific diseases. In pediatric neuromuscular disorders, the value of muscle ultrasound for screening and diagnosis is well-established. It has also been found to be a responsive measure of disease change in muscular dystrophies. In chronic forms of myositis like inclusion body myositis, ultrasound is very suitable for detecting markedly increased echogenicity and atrophy in affected muscles. Acute cases of muscle edema show only a mild increase in echogenicity, which can also reverse with successful treatment. Muscle ultrasound is an important imaging modality that is highly adaptable to study various muscle conditions. Although its diagnostic value for neuromuscular disorders is high, the evidence in myositis has only begun to accrue in earnest. Further systematic studies are needed, especially in its role for detecting muscle edema.

Muscle endurance deficits in myositis patients despite normal manual muscle testing scores.

INTRODUCTION: It is unclear whether quantitating muscle endurance adds nonredundant information useful for the care of patients with muscular disease. METHODS: Records were retrospectively reviewed for all Johns Hopkins Myositis Center patients with a muscle endurance assessment (n = 128, 226 patient-visits). Muscle endurance and strength were quantitated with the Myositis Functional Index-2 (FI2) and manual muscle testing (MMT), respectively. RESULTS: Composite FI2 muscle endurance scores were comparable in inclusion body myositis (n = 58), dermatomyositis (n = 31), and polymyositis (n = 39). Overall, muscle endurance correlated with and evolved similarly to strength, inversely to serum creatine kinase. However, in patients with normal or near-normal strength (mean MMT > 9.75/10), muscle endurance was typically abnormal and highly variable (mean FI2, 5.6/10; interquartile range, 3.3-7.8/10). DISCUSSION: Muscle endurance testing may identify muscle impairment inadequately described by MMT, particularly in patients with high MMT scores. Muscle Nerve 59:70-75, 2019.