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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.
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Saúde Global , Miosite , Adulto , Humanos , Criança , Doenças Raras/diagnóstico , Doenças Raras/terapia , Coesão Social , Miosite/diagnóstico , Miosite/terapiaRESUMO
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.
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Artrite Reumatoide , Dermatomiosite , Miosite , Neoplasias , Humanos , Autoanticorpos , Fator de Transcrição Sp4RESUMO
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.
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Dermatomiosite , Miosite , Adulto , Feminino , Humanos , Masculino , Autoanticorpos , Dermatomiosite/complicações , Helicase IFIH1 Induzida por Interferon , Miosite/complicações , Estudos Retrospectivos , Pessoa de Meia-IdadeRESUMO
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.
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Doenças Autoimunes , COVID-19 , Doenças Autoimunes/epidemiologia , Teste para COVID-19 , Humanos , Pandemias , Fatores de Risco , SARS-CoV-2RESUMO
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.
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Miosite/complicações , Osteonecrose/complicações , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Osteonecrose/diagnóstico por imagem , Prevalência , Sistema de Registros , Estudos RetrospectivosRESUMO
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.
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Dermatomiosite , Doenças Pulmonares Intersticiais , Humanos , Helicase IFIH1 Induzida por Interferon , Dermatomiosite/diagnóstico por imagem , Dermatomiosite/complicações , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/complicações , Autoanticorpos , Progressão da DoençaRESUMO
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.
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Miosite de Corpos de Inclusão/diagnóstico por imagem , Miosite de Corpos de Inclusão/fisiopatologia , Ultrassonografia de Intervenção/métodos , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Neuromusculares/diagnóstico por imagem , Doenças Neuromusculares/fisiopatologia , Estudos Retrospectivos , Ultrassonografia de Intervenção/normasRESUMO
PURPOSE OF REVIEW: The management of patients with idiopathic inflammatory myositis (IIM) can be complex and challenging due to the myriad of complications they can experience. The continued use of corticosteroids, in addition to the rise of combination immunosuppressive therapy, has contributed to the ongoing concern for infection. Perhaps the most feared infection in IIM patients is Pneumocystis jirovecii pneumonia (PJP) given its infrequent occurrence yet high mortality. The field has been, and continues to be, without evidence-based guidelines to help clinicians determine which patients with IIM to prescribe prophylaxis. Herein, we review this literature to provide the clinician with an up-to-date view of infections in IIM. RECENT FINDINGS: In the past 5 years, a number of studies have been reported highlighting various infectious complications, which help us better understand their frequency and associated risk factors. In addition, data has been published on the potential harms of PJP prophylaxis, to better inform the risk/benefit of our decision-making. Infection remains a major contributor to morbidity and mortality in IIM. A better understanding of which patient subgroups are at risk for particular infections will inform optimal management strategies.
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Imunossupressores/efeitos adversos , Miosite/complicações , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/etiologia , Antibioticoprofilaxia/efeitos adversos , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Incidência , Controle de Infecções , Infecções/epidemiologia , Infecções/etiologia , Miosite/tratamento farmacológico , Pneumonia por Pneumocystis/induzido quimicamente , Pneumonia por Pneumocystis/epidemiologia , Pneumonia por Pneumocystis/microbiologia , Vacinas/uso terapêuticoRESUMO
PURPOSE OF REVIEW: Idiopathic inflammatory myopathies (IIM) have considerable impact on patient symptoms and quality of life. We have reviewed the evolution of patient-centered care and use of patient-reported outcome measures (PROMs) for adults with IIM. RECENT FINDINGS: Use of PROMs in myositis care and research is limited, although the importance of incorporation into routine practice and trials has become increasingly recognized. Several key domains/measures have been identified including the patient global assessment of disease activity, physical function as measured by the health assessment questionnaire-disability index (HAQ-DI), Short Form Health Survey-36 (SF-36), or the Patient-Reported Outcome Measurement Information System ® (PROMIS®) in adult IIM. Data are limited for these instruments concerning their reliability, content and construct validity, and responsiveness. Incorporation of the patient perspective into clinical care and research may be used to address the unmet/unaddressed needs of the patient living with myositis. Several ongoing projects aim to bring validated PROMs to the IIM community.
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Miosite/terapia , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Avaliação da Deficiência , Humanos , Miosite/diagnóstico , Índice de Gravidade de DoençaRESUMO
PURPOSE OF REVIEW: New research continues to provide important insights into the utility of antibody specificities. This review provides an update of recent findings, and the important insights they provide into disease mechanism. RECENT FINDINGS: A growing number of autoantibodies have been discovered in scleroderma patients with unique clinical associations. A subgroup of these antibodies may have functional consequences and contribute to disease pathogenesis, driving the vascular and fibrotic phenotype. Recent research into the relationship between malignancy and scleroderma onset provides important new insights into disease mechanism, and highlights the utility of autoantibodies as unique research probes. SUMMARY: Continued advances in the study of scleroderma antibody specificities has led to important insights into disease pathogenesis and clinical subgrouping. These advances include newly described specificities, functional antibodies and an emerging understanding of the cancer-scleroderma relationship.
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Autoanticorpos/imunologia , Imunidade Inata , Escleroderma Sistêmico/imunologia , Humanos , FenótipoRESUMO
PURPOSE OF REVIEW: To review advances in the management of idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-associated ILD) in the past 5 years, with highlights in myositis-specific antibody (MSA) groups. RECENT FINDINGS: With the recent advent of widespread MSA testing, the study of specific homogeneous autoantibody-based subgroups of IIM-associated ILD is now possible. The prevalence, severity, prognosis, and response to treatment are under study for these individual MSAs. Early evidence suggests that PL-7- and PL-12-positive patients are more likely to have ILD and worse severity, compared to Jo-1 patients. Many medications have been efficacious for the treatment of IIM-associated ILD, including calcineurin inhibitors, rituximab, and cyclophosphamide. We suggest vigilant screening and monitoring of ILD in IIM patients with focus on the potential side effects associated with therapy and thus advocate appropriate vaccination, PCP prophylaxis, and bone health protection. Many different agents are used to manage patients with ILD with no comparative effectiveness studies to guide the clinician. The possibility of using MSAs to help guide treatment decisions is an appealing, although unproven, focus of research. Unfortunately, the rarity of non-Jo-1 myositis-specific antibodies has precluded robust study of response to treatment and overall management. Ongoing clinical trials and working groups are coordinating efforts to provide evidence-based management.
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Autoanticorpos/análise , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Miosite/complicações , Doenças Autoimunes/imunologia , Azatioprina/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/imunologia , Ácido Micofenólico/uso terapêutico , Miosite/imunologia , Rituximab/uso terapêuticoRESUMO
OBJECTIVES: Pneumocystis jiroveci pneumonia (PJP) is an opportunistic infection with high mortality among patients with underlying rheumatologic conditions. Given the paucity of prospective data to guide treatment, clinical guidelines to initiate PJP prophylaxis are based on expert opinion and identify patients on ≥20 mg daily prednisone for ≥4 weeks duration for treatment. Herein we describe the PJP experience in rheumatic disease over a 20-year period at a single academic medical centre to investigate this 20 mg threshold and risk associated with lymphocyte counts, co-existing lung disease and immunosuppressive medications. METHODS: We conducted a retrospective review of all admitted patients who received a PJP or PCP ICD-9 code (136.3) from January 1996 through October 2015. RESULTS: Twenty-one cases of confirmed PJP (by immunofluorescence or polymerase chain reaction) were reviewed, averaging to one case/year. The most common underlying rheumatologic conditions were inflammatory myopathy, lupus, and granulomatosis with polyangiitis. None of these 21 patients was receiving PJP prophylaxis upon admission. Eighteen (86%) were receiving ≥20 mg prednisone daily at the time of PJP diagnosis. Of the 3 treated with <20 mg prednisone, all received concomitant immunosuppressive medications, 2 with cyclophosphamide. Overall, there was a 43% (9/21) mortality rate. Immunosuppressant medication use, interstitial lung disease, or lymphocyte count did not impact mortality risk. CONCLUSIONS: PJP portends high mortality yet is a largely preventable complication of rheumatic disease treatment. Consideration to initiate prophylaxis should be made for patients exceeding the daily 20 mg prednisone threshold, and those receiving cyclophosphamide.
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Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Infecções Oportunistas/etiologia , Pneumonia por Pneumocystis/etiologia , Doenças Reumáticas/tratamento farmacológico , Adulto , Idoso , Quimioprevenção , Ciclofosfamida/efeitos adversos , Feminino , Glucocorticoides/efeitos adversos , Granulomatose com Poliangiite/tratamento farmacológico , Granulomatose com Poliangiite/imunologia , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Miosite/tratamento farmacológico , Miosite/imunologia , Infecções Oportunistas/imunologia , Infecções Oportunistas/mortalidade , Infecções Oportunistas/prevenção & controle , Pneumocystis carinii , Pneumonia por Pneumocystis/imunologia , Pneumonia por Pneumocystis/mortalidade , Pneumonia por Pneumocystis/prevenção & controle , Prednisona/efeitos adversos , Estudos Retrospectivos , Doenças Reumáticas/imunologia , Rituximab/efeitos adversos , Adulto JovemRESUMO
OBJECTIVE: Immune checkpoint inhibitor (ICI) therapies have dramatically improved outcomes in multiple cancers. ICI's mechanism of action involves immune system activation to augment anti-tumor immunity. Patients with pre-existing autoimmune diseases, such as systemic sclerosis (SSc), were excluded from initial ICI clinical trials due to concern that such immune system activation could precipitate an autoimmune disease flare or new, severe immune related adverse events (irAE). In the present study, we report our experience with ICIs in patients with pre-existing SSc. METHODS: Patients with SSc who received ICI therapy for cancer were identified from the Johns Hopkins Scleroderma Center Research Registry. Through chart review and prespecified definitions, we identified whether patients experienced worsening SSc activity or new irAEs. SSc disease activity worsening was pre-defined as an increase in modified Rodnan skin score (mRSS), new scleroderma renal crisis, progression of interstitial lung disease (ILD) on CT scan, increased Raynaud's phenomenon frequency or severity, new pulmonary hypertension, or myositis flare. IrAEs also included active inflammatory arthritis and dermatitis. RESULTS: Eight patients with SSc who received ICI therapy for cancer were included. Overall, SSc symptoms remained stable during and after ICI therapy. None of the patients with long-standing sine or limited cutaneous SSc (lcSSc) had progressive skin thickening after ICI therapy. One patient, who was early in his diffuse cutaneous SSc (dcSSc) disease course, experienced worsening skin thickening and renal crisis. Three patients (38 %) experienced a total of five irAEs (grade 2: diarrhea, mucositis and dermatitis; grade 3: pneumonitis, and grade 4: nephritis). The patient with grade 4 nephritis developed scleroderma renal crisis and immune checkpoint related nephritis simultaneously. There were no deaths due to irAEs. CONCLUSION: In this study, ICI therapy was well tolerated in patients with longstanding, sine or lcSSc. IrAE were common but generally manageable. Patients with early, active SSc may be at greater risk from ICI therapy, but more research is needed.
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Inibidores de Checkpoint Imunológico , Neoplasias , Escleroderma Sistêmico , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/imunologia , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Idoso , Adulto , Resultado do Tratamento , Progressão da DoençaRESUMO
BACKGROUND: International focus groups with patients with idiopathic inflammatory myopathies (IIM) conducted by the OMERACT Myositis Working Group over the years demonstrated the pain as an important symptom experienced by these patients. In this study, we aimed to examine the frequency and degree of pain interference, the aspects of daily life impacted by pain, and the factors associated with pain interference in adults with IIM. METHODS: This was a prospective observational study with two visits. The patients who fulfilled the probable/definite IIM (ACR/EULAR Myositis Classification Criteria) were enrolled. Pain interference was assessed with PROMIS pain interference form (6a). Myositis core set measures and PROMIS fatigue (7a) and physical function (8b) were obtained at both visits. Logistic regression and linear mixed models were performed to assess the association between pain interference and other parameters. RESULTS: A total of 129 patients with IIM (60 % females) were recruited from U.S., South Korea, Netherlands, Sweden, and Australia. Approximately 71 % reported pain interference. The patients in the greater pain interference group were more likely to be female, had significantly worse patient/physician global disease activity, fatigue, and physical function than those in the lower pain interference group. The most commonly impacted life aspect was household chores. Manual muscle testing, patient/physician global disease activity, fatigue, and physical function were all significantly associated with pain interference score >60. CONCLUSION: The majority of the patients with IIM experience the impact of pain on their daily activities, particularly household chores. Myositis disease activity, duration, and subtype could be associated with greater pain interference.
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Atividades Cotidianas , Miosite , Humanos , Miosite/fisiopatologia , Miosite/complicações , Miosite/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Dor/etiologia , Dor/fisiopatologia , Idoso , Medição da DorRESUMO
BACKGROUND: Validated patient-reported outcome measures to assess disease impact in patients with adult idiopathic inflammatory myopathies (IIMs) are needed. The objective of this study was to assess the construct validity of PROMIS Pain Interference, Fatigue, and Physical Function measures in comparison with core disease activity measures. METHODS: Adults with IIM, excluding inclusion body myositis, from OMERACT Myositis Working Group (MWG) clinic sites completed PROMIS Short Form v1.0-Pain Interference 6a, PROMIS Short Form v1.0-Fatigue 7a, and PROMIS Short Form v2.0-Physical Function 8b measures. Core disease activity measures including patient and physician global disease activity assessments, manual muscle testing, serum creatine kinase activity, and Health Assessment Questionnaire Disability Index (HAQ-DI) were simultaneously assessed. To evaluate construct validity, a priori hypotheses for the expected correlations between PROMIS measures, age, and core disease measures were determined by >70 % agreement among MWG members and were compared against observed Pearson's correlations. Internal consistency of items and floor or ceiling effects for the PROMIS measures were also assessed. Subgroup analysis according to IIM subtype (dermatomyositis vs. non-dermatomyositis IIM) was performed. RESULTS: 135 adults with IIM from 5 countries across North America, Europe, Asia, and Australia were included. For construct validity, a priori hypotheses were confirmed for 5 of 6 (83 %) PROMIS Pain Interference, 4 of 5 (80 %) PROMIS Fatigue, and 3 of 4 (75 %) PROMIS Physical Function correlations. Internal consistency was high for each PROMIS measure (Cronbach's alpha >0.9). Ceiling effects were observed only for PROMIS Pain Interference, with low/no pain in 29 % of patients. Subgroup analysis between dermatomyositis (n = 65) and non-dermatomyositis (n = 70) subtypes demonstrated similar correlations between PROMIS measures and disease activity measures. CONCLUSIONS: PROMIS Short Form v1.0-Pain Interference 6a, PROMIS Short Form v1.0-Fatigue 7a, and PROMIS Short Form v2.0-Physical Function 8b measures demonstrate strong construct validity when compared to core disease activity measures in IIM, with consistent results across IIM subtypes. These findings support the use of these selected PROMIS measures to assess core domains of interest for measuring life impact in IIMs.
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OBJECTIVE: To determine the clinical phenotype and outcomes of patients with idiopathic inflammatory myopathies (IIMs) and myocarditis. METHODS: Using the Johns Hopkins Myositis Center Research Registry, we identified 31 adult patients with IIM-out of a total of 3082 with confirmed or suspected muscle disease-with an encounter code of myocarditis from 2004 to 2021. Of these, 14 adult patients with IIM were adjudicated to have clinical myocarditis. Information about demographics, autoantibodies, and clinical outcomes was retrospectively collected and analyzed. RESULTS: Of 14 patients with IIM with clinical myocarditis, the median age at IIM diagnosis was 49 (IQR 35-56) years, and the median age at myocarditis diagnosis was 54 (IQR 36-61) years. The median duration between IIM diagnosis and myocarditis was 3 (IQR 2-9) years. The majority of patients were female (8/14, 57%) and Black (10/14, 71%). Antisynthetase syndrome was the most common IIM subtype (9/14, 64%). Anti-Jo1 (n = 4) and anti-PL12 (n = 3) were the most frequent autoantibodies. At myocarditis diagnosis, most patients (11/14, 79%) had active myositis, defined as elevated creatine kinase and/or muscle weakness; required hospitalization (13/14, 93%); and had reduced left ventricular ejection fraction (LVEF < 50%; 10/14, 71%). Despite intensification of immunosuppression, the 5-year overall survival rate from IIM diagnosis was 84%, and the 5-year overall survival rate from myocarditis diagnosis was 53%. Systolic dysfunction (LVEF < 40%) at final evaluation was observed in all expired patients (n = 6). CONCLUSION: Clinical presentations of myocarditis in this select cohort of patients with IIM were severe and heterogeneous with poor outcomes despite intensification of immunosuppression, potentially reflecting late detection of myocarditis.
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Miocardite , Miosite , Humanos , Masculino , Feminino , Estudos Retrospectivos , Miocardite/diagnóstico , Volume Sistólico , Função Ventricular Esquerda , Miosite/complicações , Miosite/diagnóstico , AutoanticorposRESUMO
BACKGROUND AND OBJECTIVES: Sporadic inclusion body myositis (IBM) is the most common acquired myopathy in individuals older than 50 years. The disorder is slowly progressive, and although many therapies have been investigated, response has generally been poor. Clinical heterogeneity may influence treatment responsiveness; however, data regarding heterogeneity in IBM are limited and often conflicting. We aim to identify clinically distinct subgroups within a large IBM cohort and prognostic factors for disease progression. METHODS: Clinical, histologic, radiologic, and electrophysiologic data were analyzed for all patients with IBM and other forms of myositis enrolled in a longitudinal cohort from The Johns Hopkins Myositis Center from 2003 to 2018. Patients with IBM were included if they met at least one of the following criteria: Griggs possible, European Neuromuscular Centre 2011 probable, or Lloyd-Greenberg data-derived criteria for IBM. Univariate, multivariate, and graphical analyses were used to identify prognostic factors in patients with IBM. Thus, linear and logistic regressions were used to adjust for potential confounding variables. The evolution of creatine kinase and muscle strength was studied using multilevel linear regression models. Nonmodifiable risk factors (sex, race, disease duration, and age at the onset of first symptoms) were used as adjusting covariates for the regression analyses. RESULTS: Among the 335 patients meeting the inclusion criteria for IBM, 64% were male with an average age of disease onset of 58.7 years and delay to diagnosis of 5.2 years. Initial misdiagnosis (52%) and immunosuppressant treatment (42%) were common. Less than half (43%) of muscle biopsies demonstrated all 3 pathologic hallmarks: endomysial inflammation, mononuclear cell invasion, and rimmed vacuoles. Black patients had significantly weaker arm abductors, hip flexors, and knee flexors compared with non-Black patients. Female patients had stronger finger flexors and knee extensors compared with their male counterparts. Younger age (<50 years) at onset was not associated with increased weakness. DISCUSSION: Our study demonstrates that female and Black patients have distinct clinical phenotypes and trajectories within the overarching IBM clinical phenotype. These subgroups may have different responses to therapies, which may influence the design of future clinical trials in IBM.
Assuntos
Miosite de Corpos de Inclusão , Miosite , Masculino , Feminino , Humanos , Miosite de Corpos de Inclusão/patologia , Imunossupressores , Força Muscular , InflamaçãoRESUMO
OBJECTIVE: To inform guidance for cancer detection in patients with idiopathic inflammatory myopathy (IIM), we evaluated the diagnostic yield of computed tomography (CT) imaging for cancer screening/surveillance within distinct IIM subtypes and myositis-specific autoantibody strata. METHODS: We conducted a single-center, retrospective cohort study in IIM patients. Overall diagnostic yield (number of cancers diagnosed/number of tests performed), percentage of false positives (number of biopsies performed not leading to cancer diagnosis/number of tests performed), and test characteristics were determined on CT of the chest and abdomen/pelvis. RESULTS: Within the first 3 years since IIM symptom onset, a total of 9 of 1,011 (0.9%) chest CT scans and 12 of 657 (1.8%) abdomen/pelvis CT scans detected cancer. Diagnostic yields for both CT of the chest and CT of the abdomen/pelvis were highest in dermatomyositis, specifically anti-transcription intermediary factor 1γ (2.9% and 2.4% for CT of the chest and abdomen/pelvis, respectively). The highest percentage of false positives was in patients with antisynthetase syndrome (ASyS) (4.4%) and immune-mediated necrotizing myopathy (4.4%) on CT of the chest, and ASyS (3.8%) on CT of the abdomen/pelvis. Patients ages <40 years old at IIM onset had both low diagnostic yields (0% and 0.5%) and high false-positive rates (1.9% and 4.4%) for CT of the chest and abdomen/pelvis, respectively. CONCLUSION: In a tertiary referral cohort of IIM patients, CT imaging has a wide range of diagnostic yield and frequency of false positives for contemporaneous cancer. These findings suggest that cancer detection strategies targeted according to IIM subtype, autoantibody positivity, and age may maximize cancer detection while minimizing the harms and costs of over-screening.