Diagnosis Of Idiopathic Inflammatory Myopathies Research Articles

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

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. 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. 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. 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.

MRI and muscle imaging for idiopathic inflammatory myopathies.

Although idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases nearly all patients display muscle inflammation. Originally, muscle biopsy was considered as the gold standard for IIM diagnosis. The development of muscle imaging led to revisiting not only the IIM diagnosis strategy but also the patients’ follow‐up. Different techniques have been tested or are in development for IIM including positron emission tomography, ultrasound imaging, ultrasound shear wave elastography, though magnetic resonance imaging (MRI) remains the most widely used technique in routine. Whereas guidelines on muscle imaging in myositis are lacking here we reviewed the relevance of muscle imaging for both diagnosis and myositis patients’ follow‐up. We propose recommendations about when and how to perform MRI on myositis patients, and we describe new techniques that are under development.

P029 Idiopathic inflammatory myopathy and axonal peripheral polyneuropathy in a poorly controlled coeliac disease patient

Background/Aims The current mainstay treatment of idiopathic inflammatory myopathies (IIM) includes steroid therapy with treatment escalation to steroids -sparing immunosuppressants to maintain remission. Nevertheless, some patients may not fully recover to their normal muscle strength, while exposing to potential side effects of these drugs. We report the first case of IIM and axonal peripheral polyneuropathy in a poorly controlled coeliac patient, who made complete recovery with adherence to gluten-free diet. Methods A 76-year-old white Caucasian lady, who was previously independent, presented with 6-weeks history of pain and weakness in both legs. She required the use of a wheelchair to get around as she was unable to weight bear as the result of the pain. She denied any change to regular medications, history of trauma, new rash, joint swelling, or B-symptoms. There was no history of smoking, alcohol, statins, or steroid use. She was previously diagnosed with coeliac disease 10 years ago but had opted not to adhere to a gluten-free diet due to personal preference. Results On examination, there was significant muscle tenderness on palpation of bilateral lower limbs. The rest of systemic examination was unremarkable. Duodenal biopsy revealed severe villous atrophy and chronic lymphocytic and plasma cell inflammation, which reinforced the diagnosis of coeliac disease. All immunology screen including ANA, ENA, ds-DNA, myositis and vasculitis screen were negative except anti-RO-52. This patient did not have any clinical feature of Sjogren’s or systemic lupus erythematosus. EMG revealed fibrillation potentials, positive sharp waves, and myotonic discharges in the paraspinal, upper and lower limbs muscles. It also demonstrated underlying axonal peripheral polyneuropathy. Muscle biopsy showed features consistent with the diagnosis of idiopathic inflammatory myopathy. This patient was started on a gluten-free diet during admission. Interestingly, we discovered that her creatinine kinase level had improved spontaneously along with the clinical improvement of her presenting symptoms. As her symptoms have completely resolved, she was discharged home. She was never started on steroid or immunosuppressant due to her significant clinical improvement. At three-month follow up, her creatinine kinase level had normalised, and she remained in remission while adhering to a gluten-free diet. Conclusion To the best of our knowledge, there is no reported case of complete clinical resolution of IIM with gluten withdrawal in coeliac disease patients, without the need of steroid or immunosuppressants. In addition, the concomitant of myopathy and polyneuropathy, as some described as neuromyositis, is extremely rare. The pathophysiology remains unclear; however, it is proposed that neuropathy could be an extra-muscular manifestation of IIM.The clinical remission of IIM in our patient with adherence to a gluten-free diet provide an alternative treatment option to the current recommended regimes of steroid and immunosuppressants. Such non-pharmacological approach is favourable, especially in the current SARS-CoV-2 pandemic. Disclosure Y. Tan: None. A. Mohamedalhadi: None. F. Wood: None.

P090 Validation of hospital episode statistics data to enable national registration of idiopathic inflammatory myopathies

Abstract Background/Aims The National Congenital Anomaly and Rare Disease Registration Service (NCARDRS) aims to register all patients in England with congenital or rare diseases. Maintaining ongoing contemporaneous registers requires substantial time and resource, so novel methodologies for identification and registration of rare disorders such as the idiopathic inflammatory myopathies (IIMs) need development. Hospital Episode Statistics (HES) are routinely recorded data from every hospital admission within the National Health Service (NHS) England. This study aims to validate diagnostic ICD-10 codes within HES as a method of identifying and recording cases of IIM. Methods In collaboration with the Registration of Complex Rare Diseases - Exemplars in Rheumatology (RECORDER) project we extracted all Finished Consultant Episodes (FCE) at one hospital trust between 2010-2019 with diagnostic ICD-10 codes indicating either dermatomyositis or polymyositis under NCARDRS section 251 legal permissions (CAG 10-02(d)/2015). Co-occurring interstitial lung disease (ILD) was also considered due to ILDs association with IIMs. Hospital rheumatology and immunology databases were interrogated to identify all outpatients with IIM. Hospital electronic care records were reviewed to confirm coding accuracy. The total number of FCEs at the trust was calculated from NHS Digital reports. Sensitivity and specificity of each code and various code combination algorithms were calculated. Results HES ICD-10 codes identified 530 individuals, of whom 388 had records confirming IIM diagnosis. 146 additional patients were found through hospital records. This gives these codes a positive predictive value (PPV) of 73.1% and sensitivity of 72.7%. Due to the rarity of IIM coded FCEs compared to all FCEs, the specificity is 100.0% for every code. Dermatomyositis codes M331 and M339 had PPV 94.8% and 93.4% respectively. Juvenile DM (M330) and paraneoplastic myositis (M360) whilst rarely used had a high PPV of 91.6% and 100% respectively. Myositis unspecified (M609), was the worst performing code with PPV 61.4%. Excluding M609 from the analysis, PPV improved to 85.9%. Adding an ILD code made specificity 94.2% and sensitivity 15.5%, however it did find 51.5% of the known IIM-ILD patients. Strategies to improve PPV without impacting sensitivity were attempted. The highest PPV of 95.3% was found by selecting patients who had at least 2 different codes recorded, however sensitivity was only 30.7%. By then adding patients who also had one of the high performing codes the PPV dropped to 91.73% but sensitivity improved to 60.7%. Conclusion This is the first validation cohort to show that IIM ICD code combinations in HES have high positive predictive values, and sensitivities of up to 72.7%. The relative importance of sensitivity, specificity and PPV vary according to the research question being asked, but algorithms tested in this study could be applied across all NHS trusts to enable robust and cost-effective whole-population research into the epidemiology of IIM. Disclosure J.R. Hannah: None. P. Gordon: None. J. Galloway: None. E.J. Peach: Grants/research support; Vifor Pharma. P.C. Lanyon: Grants/research support; Vifor Pharma. M. Bythell: None. F.A. Pearce: Grants/research support; Vifor Pharma.

A novel grey scale and Power Doppler ultrasonographic score for idiopathic inflammatory myopathies: Siena Myositis Ultrasound Grading Scale.

No clear-cut guidelines exist on the use of diagnostic procedures for idiopathic inflammatory myopathies (IIM) and only minimal and conflicting data report the use of ultrasound (US). In this regard, we aimed to assess if grey-scale (GS) and Power Doppler (PD) US, graded with a 0-3-point scale, may be a reliable tool in a cohort of patients affected by IIM. All patients underwent US examination of both thighs in axial and longitudinal scans. Oedema and atrophy, both assessed in GS and PD, were graded with a 0-3-point scale. Spearman's test was used to identify the correlations between US and clinical and serological variables. A total of 20 patients were included. Six and two patients were evaluated twice and three times, respectively. Muscle oedema was found to be directly correlated with physician global assessment (PhGA), serum myoglobin and PD and negatively with disease duration. PD score was positively correlated to PhGA and negatively to disease duration. Muscle atrophy directly correlated with Myositis Damage Index, disease duration and patient's age. The single-thigh sub-analysis evidenced a direct correlation between PD score and Manual Muscle Test. In our cohort, we found that oedema and PD are strictly related to early, active myositis, suggesting that an inflamed muscle should appear swollen, thickened and with Doppler signal. Conversely, muscle atrophy reflects the age of the patient and the overall severity of the disease. Such findings shed a new, promising, light on the role of US in diagnosis and monitoring of IIMs.

Evaluation of risk factors and biomarkers related to arterial and venous thrombotic events in idiopathic inflammatory myopathies

Objectives: This study aimed to assess the contribution of traditional/disease-related risk factors and biomarkers linked to arterial and venous thrombotic events (TEs) in patients with idiopathic inflammatory myopathies (IIMs). Method: The occurrence of arterial and/or venous TEs at the time of or after IIM diagnosis was retrospectively evaluated in a cohort of 253 patients with IIMs, resulting in a final population of 246 IIM patients, 51 with reported TE (cases) and 195 without a history of TE (comparators). Information on disease characteristics and traditional risk factors for arterial and venous TE (essential hypertension, diabetes, dyslipidaemia, smoking, malignancy) was retrieved. Serum levels of anti-phospholipid antibodies (aPLs) and adhesion molecules were analysed at the time of IIM diagnosis and at the time of the TE in cases. Results: One in five IIM patients (21%) had experienced a TE, arterial TE in 22 and venous TE in 29 patients, with a peak prevalence within 5 years after diagnosis. Among traditional/disease-related risk factors, only older age was associated with both arterial and venous TEs, after adjusting for other covariates. Low serum levels of e-selectin were associated with higher odds of developing a TE, without specific association with either arterial or venous TEs. Only 6% of IIM patients had aPLs, with no significant difference between cases and comparators. Conclusions: An increased risk of both venous and arterial TEs should be considered in IIM patients, particularly close to diagnosis and in elderly people. Low serum levels of e-selectin may predict TE in IIM patients, but the underlying biological mechanism is not known.

The aetiopathogenic significance, clinical relevance and therapeutic implications of vasculopathy in idiopathic inflammatory myopathy.

It is 120 years since 'angiomyositis' was included alongside 'polymyositis' and 'dermatomyositis' in an attempt to propose a taxonomy that reflected the major clinical characteristics of idiopathic inflammatory myopathy (IIM). Endothelial injury, perivascular inflammation and capillary loss are important histological findings in affected tissues in IIM. Overt vascular clinical features including RP and abnormal nailfold capillaroscopy (NC) are also common in IIM. Despite the presence of endothelial injury, perivascular inflammation and capillary loss in affected tissues in IIM, and the presence of clinical features such as RP and NC abnormalities, the pathogenic and therapeutic implications of vasculopathy in IIM have been somewhat overlooked. RP and NC abnormalities are not always present, providing a valuable opportunity to explore aetiopathogenic factors driving vasculopathy within autoimmune rheumatic disease. The present review examines the aetiopathogenic, prognostic and therapeutic significance of vasculopathy in IIM. We describe the prevalence and clinical relevance of vasculopathy in IIM, and consider how vasculopathy may be better utilized to support improved IIM diagnosis and disease classification. Areas of unmet research need are highlighted where relevant.

Overall and site-specific cancer before and after diagnosis of idiopathic inflammatory myopathies: A nationwide study 2002–2016

ObjectiveTo examine the association between idiopathic inflammatory myopathy (IIM) and cancer before and after IIM diagnosis. MethodsWe used prospectively collected nationwide register data to design a case-control study to investigate the occurrence of cancer before IIM, and a cohort study to investigate the occurrence of cancer after IIM. Patients diagnosed with IIM between 2002 and 2016 in Sweden, were compared to the general population. The association between cancer and IIM was estimated before and after IIM diagnosis via logistic regression and Cox regression models, respectively. ResultsWe included 1419 patients with IIM and 7045 individuals from the general population. The overall odds of cancer before IIM diagnosis were increased in IIM compared to the general population, adjusted odds ratio (AOR) 1.5, 95% confidence interval (CI) 1.3–1.8. This association was also noted after IIM diagnosis, adjusted hazard ratio (AHR) 1.7 (95% CI 1.4–2.0), or one additional cancer in every 125 IIM patients per year. Colorectal (AOR 2.1), lung (AOR 5.4) and ovarian (AOR 7.0) cancers were associated with IIM before diagnosis. Oropharyngeal (AHR 9.1) and cervical (AHR 3.8) cancers, malignant melanoma (AHR 3.2) and non-melanoma skin cancer (AHR 3.1) were associated with IIM after diagnosis. Adenocarcinomas were associated with dermatomyositis before diagnosis and squamous cell cancers after IIM diagnosis. Lymphatic hematopoietic cancers were associated with IIM both before and after diagnosis. ConclusionsThe cancer types that occur before IIM diagnosis differ from the ones that occur after diagnosis. This may have an impact on screening decisions for IIM.

Review of Cancer Screening Investigations in New Diagnoses of Idiopathic Inflammatory Myopathies at a Single Tertiary Hospital.

Review of Cancer Screening Investigations in New Diagnoses of Idiopathic Inflammatory Myopathies at a Single Tertiary Hospital.

The significance of myositis autoantibodies in idiopathic inflammatory myopathy concomitant with interstitial lung disease.

This study identified factors associated with interstitial lung disease (ILD) in patients with idiopathic inflammatory myopathy (IIM) based on the latest classification and recent advances in autoantibody serology. We retrospectively analyzed data of 173 patients who underwent complete myositis autoantibody serology examination in a medical center in Taiwan from July 2018 to February 2020. After exclusion of patients who did not receive a final diagnosis of IIM, clinical features, serology data, concomitant diseases, treatment, presence of respiratory failure, and mortality rate of the remaining 97 patients were analyzed. Of IIM patients in our cohort, 47.4% had ILD. ILD was significantly associated with subtypes of IIM, older age of onset, presence of mechanic's hand, and presence of anti-Jo-1 and anti-Ro52 antibodies. Among five IIM subtypes, overlap myositis (OM) and dermatomyositis (DM) were significantly associated with a higher prevalence rate of ILD (67.5% in OM and 53.3% in DM). Among patients with OM, the presence of anti-Jo-1 (100%), anti-PL-7 (100%), and anti-EJ antibodies (77.8%) was most significantly associated with ILD. The latest classification of IIM, older age of onset, presence of mechanic's hand, and presence of anti-Jo-1 and anti-Ro52 antibodies were significantly associated with ILD. Among five IIM subtypes, OM and DM had higher prevalence rate of ILD. Among OM patients, the presence of anti-Jo-1, anti-EJ, and anti-PL-7 antibodies was significantly associated with ILD. The study results may help physicians to timely screen and monitor pulmonary function in high-risk groups.

AUTOIMMUNE MYOPATHIES: P.308 Characteristics of chest CT-scan patterns of idiopathic inflammatory myopathies: association with myositis-specific autoantibodies

Interstitial lung disease (ILD), one of the most common extramuscular manifestations of idiopathic inflammatory myopathies (IIMs), is associated with poor prognosis. Myositis-specific autoantibody (MSA)-positivity is a key finding for IIM diagnosis. To date, no large-scale study on a European IIM population has assessed CT ILD features and MSAs. To identify different lung patterns associated with IIMs and evaluate potential relationships between the CT ILD findings and MSA. All consecutive IIM patients referred to an internal medicine department between 2003 and 2019 were included.

The Low Prevalence of Inclusion Body Myositis in an Outpatient Rheumatology Myositis Cohort.

IntroductionSporadic inclusion body myositis (IBM) is a rare type of myopathy of unknown etiology typified by the presence of distinctive muscle fiber inclusions. IBM belongs to a larger family of conditions called the idiopathic inflammatory myopathies (IIM). This study seeks to compare the prevalence, clinical manifestations, and disease course of IBM patients to a cohort of polymyositis (PM) and dermatomyositis (DM) patients in an outpatient rheumatology myositis cohort.MethodsWe conducted a retrospective chart review of all adult patients attending rheumatology clinics at the Cook County Hospital from 2006 to 2011 with the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) diagnoses of idiopathic inflammatory myopathies (IIM). Data collected included patient demographics, serial muscle strength testing, serial creatine kinase (CK), muscle biopsies, and immunosuppressive therapies received. ResultsWe identified 112 patients with IIM with the following breakdown: 66 - dermatomyositis, 42 - polymyositis, and four - IBM. These four patients represent the primary cohort. They had a mean age of 67 years (range 62-74), the mean follow-up period of 15 months (range 3-47), mean initial muscle strength in the weakest group of 3.75 (range 2-5, standard deviation [SD]=1.3), mean initial CK of 1,968 U/L (range 313-4,795, SD=1,970), mean final muscle strength in the weakest group of 3.75 (range 3-4, SD=0.5), mean final CK of 1,326 U/L (range 213-2,943, SD=1,200).ConclusionsOur IBM patients had many features similar to other described IBM cohorts, including older age, male predominance, slow progression (stable CK and muscle strength), and lack of response to immunosuppressive therapy. Interestingly, we found a low prevalence of IBM in our outpatient rheumatology IIM cohort.

Myositis-specific autoantibodies in adults with idiopathic inflammatory myopathy: correlations with diagnosis and disease activity.

To determine the relationship of myositis autoantibodies with the diagnosis and severity of idiopathic inflammatory myopathy (IIM) using the 2017 EULAR/ACR idiopathic inflammatory myopathy classification criteria and the myositis disease activity assessment tool (MDAAT). Patients who met the new diagnostic criteria were tested for serum myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs), and then classified into different subgroups based on autoantibody positivity. Patients were also diagnosed with possible IIM, probable IIM, and definite IIM. The MDAAT was used to evaluate muscular and extramuscular disease activity. The relationships of diagnostic classification with positivity for different myositis autoantibodies were determined. There were 118 patients, and 81% of them had one or more myositis autoantibody. Anti-Jo-1 was the most common MSA, and anti-Ro-52 was the most common MAA. Sixteen patients (14%) had possible IIM, 36 (31%) had probable IIM, and 66 (56%) had definite IIM. MSA-positive patients were significantly more common in the definite IIM group, but MAA positivity was unrelated to diagnostic classification. Positivity for MSAs or MAAs had no correlations with muscle disease activity. Extramuscular disease activity was greater in MSA-positive than MSA-negative patients, but MAA positivity had no significant association with extramuscular disease activity. MSA positivity aids in the diagnosis of IIM. MSA positivity was associated with greater extramuscular disease activity. Improving the clinical application of MSAs may enhance the individualized treatment of patients with IMM. Key Points • In this paper, we explore the relationships between the myositis autoantibodies and the diagnosis and the disease activity of inflammatory myopathy. • Positive myositis-specific autoantibodies is associated with the establishment of diagnosis and higher extramuscular disease activity. • Thus, more extensive application of myositis autoantibodies maybe the key for further disease assessment and research.

AB0610 SEASONAL VARIATION IN IDIOPATHIC INFLAMMATORY MYOPATHIES INCIDENCE AND PRESENTATION: A RETROSPECTIVE STUDY IN BEIJING AND HONG KONG

Background:Seasonal patterns of disease onset and severity in idiopathic inflammatory myopathies (IIMs) as a whole are conflicting [1-3]. In recent years, over 10 myositis-specific antibodies (MSAs) have been identified. They are able to divide patients into homogenous subgroups and inform on prognosis [4].Objectives:The objective of the study was to investigate the seasonal variation of onset of IIMs characterised serologically.Methods:This was a multi-centred retrospective observational study. Consecutive Chinese patients with IIMs admitted to the rheumatology wards of the participating major regional hospitals in Beijing and Hong Kong from July 2013 to June 2018 were recruited. The diagnosis of IIMs was based on the Bohan and Peter’s criteria with definite or probable cases being included [5]. Patients with clinically amyopathic disease must have the typical Gottron’s papules or heliotrope rash as determined by rheumatologists or dermatologists, and with no symptoms or signs of muscle involvement according to Sontheimer [6]. Patients with juvenile myositis, inclusion body myositis, cancer-associated myositis and myositis associated with other connective tissue disease were excluded. A commercial line blot immunoassay kit (EUROLINE) was used to detect the MSAs.Results:All together 495 patients were studied. The mean age of the patients at disease onset was 48.1 years (S.D. 13.3). There was a female predominance (68.3%). The subgroups of IIMs were: dermatomyositis (61.0%), polymyositis (21.8%), clinically amyopathic dermatomyositis (12.9%), immune mediated necrotising myopathy (3.8%) and nonspecific myositis (0.4%). No particular seasonal pattern in disease onset was observed in IIM patients as a whole (Figure 1) or in any classical subgroups. However, significantly more patients with any one MSA had their disease started in the first half of the year (p=0.007) as shown in Figure 2. Patients with either anti-synthetase or anti-MDA5 antibodies, which are associated with interstitial lung disease, had more frequent disease onset from November to February, which might coincide with the local flu season. It was also found that MSA positivity was associated with infection of the patient (p=0.005). Further analyses showed that patients with MSAs which are typically associated with severe skin disease (MDA5, TIF1g, NXP2, SAE) had more hospitalisation from April to September where excessive sun exposure is expected. There were no major differences between the Beijing and Hong Kong subgroups.Conclusion:Apparent seasonal patterns were noticed in our ethno-serologically defined IIM patients. Certain environmental factors, particularly infection or UV exposure, could be potential triggers. Our findings could shed light on the identification of etiologic factors and enhance our understanding of disease pathogenesis.

Temporal relationship between idiopathic inflammatory myopathies and malignancies and its mortality: a nationwide population-based study.

To examine the temporal relationship between malignancies and idiopathic inflammatory myopathies (IIMs) and its impact on mortality. A retrospective cohort for IIM patients was conducted using the Korean National Health Insurance Service databases. We observed more than 5years before and after the diagnosis of IIM (2002~2016) to identify IIM patients who developed any malignancy and classified these patients into two groups: the cancer-associated myositis (CAM) group, who developed malignancy within 3years before or after the diagnosis of IIM and the cancer-not-associated myositis (CNAM) group, who developed malignancy beyond 3years of IIM onset. The survival rates of the two groups were compared. We identified 1072 incident cases of IIM between 2007 and 2011. A total 225 patients of these patients were diagnosed with malignancy. The development of malignancy was frequent within 1year before and after the time of IIM diagnosis. The common sites of malignancies in the CAM group differed from those in the CNAM group: the lung, hematologic malignancy, and the liver were common in both groups, but thyroid and oropharynx followed them in CAM while prostate, stomach, breast, and thyroid followed them in CNAM. CAM patient mortality was worse compared with CNAM patients (log-rank test, p < 0.01). Among IIM patients with malignancy, common sites of malignancy were different between the CAM and CNAM groups, and patients with CAM had poor prognosis compared with CNAM patients. Key Points • The malignancies commonly occurred in incident idiopathic inflammatory myopathy (IIM) patients, especially within 1year before and after the initial IIM diagnosis. • Patients with malignancy had poor survival compared with patients without malignancy. • Among the IIM patients with malignancy, patients who developed malignancy within 3years of IIM diagnosis (cancer-associated myositis, or CAM, group) showed higher mortality than cancer-not-associated myositis, CNAM group. • We also found that the common types of malignancy were different between the CAM and CNAM groups.

TLR expression in peripheral monocyte subsets of patients with idiopathic inflammatory myopathies: association with clinical and immunological features

BackgroundMonocytes and toll-like receptors (TLR) have been found in the inflammatory infiltrate of muscle biopsies in patients with idiopathic inflammatory myopathies (IIM), suggesting an important role of these cells in the pathogenesis of myositis. The monocyte subsets, their TLR expression in peripheral blood and their relationship with the clinical characteristics of patients with IIM has not been addressed.MethodsWe recruited 45 patients with IIM diagnosis and 15 age and sex-adjusted healthy controls. We assessed the disease activity and damage, performed a nailfold capillaroscopy and registered the cardio-pulmonary parameters from the medical charts. Monocyte subsets, their expression of TLR2 and TLR4 and the serum Th1/Th2/Th17 cytokines levels were evaluated by flow cytometry. We expressed quantitative variables as medians and interquartile ranges (IQR) or minimum and maximum (min–max). Differences between groups were assessed with Mann–Whitney U and the Kruskal–Wallis tests. Correlation between quantitative variables was assessed with Spearman Rho.ResultsTwenty-nine patients were women (64.4%) and 32 (71.1%) had dermatomyositis. In comparison to healthy controls, patients with active IIM had a higher percentage of intermediate monocytes and lower amounts of classical monocytes. Patients with IIM had a higher expression of TLR4 in all their monocyte subsets, regardless of disease activity and prednisone treatment. Serum IL-6 correlated with the TLR2 expression in every monocyte subset and the expression of TLR2 in intermediate monocytes was higher among patients with dysphagia. Subjects with nailfold capillaroscopy abnormalities had a higher amount of TLR2+ classical and non-classical monocytes and those with interstitial lung disease (ILD) had a higher percentage of TLR4+ non-classical monocytes. The classical and intermediate monocytes from patients with anti Mi2 antibodies had a higher expression of TLR4. The percentage of intermediate monocytes and the expression of TLR4 in all monocyte subsets showed a good diagnostic capacity in patients with IIM.ConclusionPatients with IIM have a differential pool of monocyte subsets with an enhanced expression of TLR2 and TLR4, which correlates with disease activity and distinctive clinical features including dysphagia, ILD, vasculopathy, and pro-inflammatory cytokines. These immunological features might be useful as a potential diagnostic tool as well as novel disease activity biomarkers in IIM.

Pregnancy outcomes in women with idiopathic inflammatory myopathy, before and after diagnosis-a population-based study.

ObjectivesTo examine pregnancy outcomes among births to women with idiopathic inflammatory myopathy (IIM) in relation to time of IIM diagnosis using population-based data.MethodsThis study used Swedish nationwide registers to identify all singleton births that occurred between 1973 and 2016 among women diagnosed with IIM between 1998 and 2016 and among women unexposed to IIM. We classified births according to the IIM status of the mother at time of delivery: post-IIM (n = 68), 1–3 years pre-IIM (n = 23), >3 years pre-IIM (n = 710) and unexposed to IIM (n = 4101). Multivariate regression models were used to estimate relative risks of adverse pregnancy outcomes in post-IIM births and pre-IIM births separately, in comparison with their non-IIM comparators.ResultsWe found that post-IIM births had increased risks of caesarean section [adjusted relative risk (aRR) = 1.98; 95% CI: 1.08, 3.64], preterm birth (aRR = 3.35; 95% CI: 1.28, 8.73) and low birth weight (aRR = 5.69; 95% CI: 1.84, 17.55) compared with non-IIM comparators. We also noticed higher frequencies of caesarean section and instrumental delivery in 1–3 years pre-IIM births than in the non-IIM comparators.ConclusionWomen who gave birth after IIM diagnosis had higher risks of caesarean section, preterm birth and low birth weight. These results further underline the importance of special care and close monitoring of women with IIM. Higher frequencies of caesarean section and instrumental delivery in pre-IIM births highlight the need for future research on the influence of subclinical features of IIM on pregnancy outcomes.

Prevalence of polymyalgia rheumatica in a cohort of patients with idiopathic inflammatory myopathy.

Polymyalgia rheumatica (PMR) is a common rheumatological condition occurring in adults aged over 50years. The association of PMR with other autoimmune diseases such as rheumatoid arthritis is complex. There is a clear relationship with giant cell arteritis. We sought to determine whether there is any association between PMR and idiopathic inflammatory myopathy (IIM). We undertook a database study of adult patients with a diagnosis of IIM under the care of the Rheumatology Department of the Royal Adelaide Hospital, and retrospectively determined the frequency of PMR in this patient cohort. Patients were considered to have PMR if this had been diagnosed by a physician or if they satisfied all five of the following clinical criteria: (1) bilateral shoulder and/or pelvic girdle aching, (2) morning stiffness exceeding 45min, (3) age greater than 50years, (4) duration more than 2weeks, and (5) evidence of an elevated erythrocyte sedimentation rate or C-reactive protein. Amongst 82 patients with IIM, seven (8.5%) were found to have PMR. There was a disproportionate representation of necrotizing autoimmune myopathy (NAM) in patients with IIM/PMR (5/7) compared with patients with IIM alone (19/75), p = 0.02. There was a high prevalence of antibodies to 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in patients with IIM/PMR (4/7, 57%) compared with those with IIM alone (9/32, 28%), p = 0.19. The prevalence of PMR in our IIM cohort was much higher than the population prevalence 0.91-1.53% and it appears there is a specific association with NAM and anti-HMGCR antibodies. Further studies are required to confirm these findings and explore mechanisms of shared disease susceptibility.Key Points• Idiopathic inflammatory myositis, in particular, statin-associated necrotizing myositis and anti-HMG co-A reductase antibodies, may have a previously unrecognized association with polymyalgia rheumatica.

The use and diagnostic value of testing myositis-specific and myositis-associated autoantibodies by line immuno-assay: a retrospective study.

Aims:Line immune-assays (LIA) for the detection of myositis-specific antibodies (MSA) are used widely for characterization of idiopathic inflammatory myopathies (IIM). Their current use and significance for the diagnosis of IIM remains unclear.Methods:In this retrospective analysis, we retrieved clinical diagnoses of patients tested for MSA and myositis-associated antibodies (MAA) Jo-1, Mi-2α, Mi-2β, TIF1γ, SRP, MDA-5, NXP-2, SAE, PL-7, PL-12, EJ, OJ, PM-Scl100, PM-Scl75 and Ku. We calculated clinical specificity, clinical sensitivity, negative- and positive predictive values (PPV) as well as positive and negative likelihood ratios.Results:In total, we analyzed 3167 samples. After exclusion of repeated measurements and patients with insufficient clinical information, data of 1118 patients were available for analysis. A total of 242 patients tested positive for at least one antibody, of which 45 patients had a diagnosis of IIM; 25 IIM patients were negative for all MSA/MAA. Clinical specificity of MSA/MAA for the diagnosis of IIM ranged between 94.2% and 99.9%. Clinical sensitivity and PPV across all antibodies tested ranged from 0.0% to 12.9% and 0.0% to 72.7%, respectively.Conclusion:In clinical practice MSA/MAA are used widely for diagnostic work-up of IIM, resulting in a low pre-test probability. Clinicians should be aware that PPVs for most MSA/MAA are low.

Serum fatty acid-binding protein 3 levels differentiate active from inactive myositis and correlate with response to therapy

Background: Delay in the diagnosis of idiopathic inflammatory myopathies (IIMs) and resultant muscle wasting leads to a setting, wherein conventional biomarkers fail to identify inflammation amid damage. Fatty acid-binding protein 3 (FABP3) has a selective location and function lending unique potential as a specific biomarker in IIM. Methods: Patients with IIM (ACR/EULAR criteria) prospectively evaluated for clinical features and laboratory data were screened to identify cases without ongoing infection, pregnancy, and renal disease. Clinical data and sera of patients and healthy controls were retrieved, and case details supplanted with standard outcome measures. For the inception cohort, 6-month follow-up sera were used for comparison of FABP3 using ELISA. Nonparametric tests were used for analysis and results expressed as median and interquartile range. Results: One hundred and thirty two IIM patients (M:F 1:3.1) of age 38 (24.5–46.0) years and 0.9 (2.3–5.1) year long disease were compared with ten healthy controls. FABP3 levels were higher in active (5.73 vs. 2.91 ng/ml, P = 0.0351) disease, more so in early IIM (n = 16, 21, 3.84 vs. 0.00 ng/ml, P = 0.002). Levels fell with treatment in responders (n = 7, 14.5–7.5 ng/dl, P = 0.03) but not in nonresponders. A serum FABP3 ≥ 4.066 had a high specificity (80.6%) to distinguish active from inactive myositis, albeit lower than conventional biomarkers. Conclusion: Serum FABP3 is elevated in active IIM, especially early disease, and decreases with treatment among responders. FABP3 has a favorable specificity but insufficient sensitivity, limiting role as a stand-alone biomarker. It might be useful in early IIM, without renal or cardiac involvement, pending further validation.