anti-Jo-1 Research Articles

Clinical analysis for 108 cases of dermatomyositis

To investigate the clinical characteristics of dermatomyositis, to investigate the types and clinical features of dermatomyositis complicated with malignant tumor, and to provide evidence for clinical diagnosis, treatment and prognostic evaluation. Methods: The clinical manifestations and laboratory test results for 108 cases of dermatomyositis with complications in the Second Xiangya Hospital of Central South University were analyzed. Results: Patients aged from 14 to 60 years accounted for 62.96%. The first symptom was single skin rash (54.63%), and the most characteristic cutaneous features were asymmetrical proximal myositis with various degrees (97.22%). The visceral involvement was as follows: the digestive tract (31.48%), the heart (19.44%), the lung (26.85%), and the thyroid damage (12.96%). Twelve (11.11%) patients were combined with malignant tumor. The positive rates for albumin (ALB), glutamic oxalacetic transaminase (AST), glutamic-pyruvic transaminase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme (CK-MB), erythrocyte sedimentation rate (ESR), anti Jo-1 antibody, anti ribonucleoprotein (RNP) antibody, and anti-topoisomerasel (Scl) antibody were 25.93%, 46.30%, 28.70%, 87.04%%, 51.85%, 26.85%, 55.56%, 2.27%, 8.99%, and 2.27%, respectively. The patients were divided into a tumor group and a non-tumor group. The chi-square test results from clinical symptoms and laboratory tests suggested that increase of ESR was a risk factor for dermatomyositis combining tumor. The main strategy of therapy was corticosteroids. Conclusion: Dermatomyositis possesses typical skin lesions and dermatitis is the most common initial symptom of dermatomyositis. In clinic, diagnosis of dermatomyositis should be timely combined with muscle enzymes test, electromyography and muscle biopsy. Dermatomyositis can easily involve many organs. Thus relevant examinations (such as chest X-ray and CT) should be done preventively. Rapid ESR is a risk factor for dermatomyositis complicated with malignant tumor and it can be used as an index to guide clinical diagnosis.

Lung Diseases in Inflammatory Myopathies.

Lung involvement is the leading cause of mortality in inflammatory myopathy. A careful assessment of clinical and serologic manifestations especially myositis-associated autoantibodies allows precise classification of the different phenotypes of inflammatory myopathy and stratification of the risk of lung involvement. About three out of four patients with inflammatory myopathy develop interstitial lung disease (ILD), which represents the main cause of morbidity and mortality. In patients with a confirmed diagnosis of inflammatory myopathy, the approach to the diagnosis of ILD includes assessment of clinical and functional severity, evaluation of the high-resolution computed tomography pattern of disease, which often suggests nonspecific interstitial pneumonia or organizing pneumonia. Bronchoalveolar lavage to rule out infection is often performed; however, video-assisted thoracoscopic lung biopsy is now generally discouraged, unless malignancy is suspected. The so-called antisynthetase syndrome characterized by the combination of mechanics' hands, Raynaud' phenomenon, myositis often mild or absent, and presence of one of the anti-tRNA synthetase antibodies is associated with a 70% risk of ILD, especially in subjects with antibodies other than anti-Jo1 antibodies (i.e., anti-PL7 or -PL12 antibodies). Treatment depends on both severity and progression of ILD, often including a combination of corticosteroids and immunosuppressive therapy. Rituximab-based regimen has showed promising results in retrospective studies for the management of refractory or rapidly progressive forms of ILD. Clinical trials are ongoing to evaluate the actual efficacy of this strategy on mortality related to lung disease. Secondary pulmonary complications of inflammatory myopathy include opportunistic infections, aspiration pneumonia, pneumomediastinum, ventilatory failure due to diaphragmatic muscular weakness, drug-induced pneumonitis, and rarely pulmonary hypertension.

New Case of Anti-Synthetase Syndrome Associated with Cirrhosis Post HVB

The anti-synthetase syndrome is represented by the association of in-flammatory myopathy (polymyositis/dermatomyositis), interstitial pneu-monitis, Raynaud’s syndrome, inflammatory polyarthritis, and characteristic skin abnormalities. We found also a clinical aspects of Mechanic’s hand with high level of anti-synthetases. We report the case of a 66-year-old patient with polyar- thralgias of large and small inflammatory joints, myositis, Raynaud’s phenomenon, and cutaneous involvement of the hands and feet, with fissure hyperkeratosis feet and an appearance of mechanic’s hands. The patient had an inflammatory syndrome, elevated muscle enzymes, positivity of anti-Jo1 antibodies, PID at chest CT and the presence of inflammatory mononuclear cell infiltrates at muscle biopsy. The evolution under immunosuppressive treatment combining corticosteroids and methotrexate was marked by an oedemato-ascitic decompensation of a post-HVB cirrhosis unknown.

Increased Serum Matrix Metalloproteinase-9 Levels are Associated with Anti-Jo1 but not Anti-MDA5 in Myositis Patients.

Matrix metalloproteinases 9 (MMP9) is a member of the zinc-ion-dependent proteinases family and plays a pathogenic role in chronic inflammatory autoimmune diseases. However, its roles in the pathogenesis of myositis have not been elucidated. In this study, we aimed to determine the gene expression and serum level of MMP9 and their relationship with clinical features and serological parameters in myositis. Our results showed that MMP9 mRNA in peripheral blood mononuclear cells (PBMC) was upregulated in myositis patients compared to that in healthy controls. Myositis patients positive for anti-Jo1 antibodies exhibited significantly higher serum MMP9 than anti-MDA5 positive or antibody-negative patients and healthy controls. However, the presence of interstitial lung disease (ILD) did not affect MMP9 levels. We further identified that anti-Jo1-positive myositis patients showed higher numbers of white blood cells (WBC), lymphocytes and neutrophils; increased levels of creatine kinase (CK), lactate dehydrogenase (LDH), and C-reactive protein (CRP); and higher erythrocyte sedimentation rate (ESR) than anti-MDA5 positive patients. In addition, serum MMP-9 levels were positively correlated with WBCs, neutrophils, CK, CRP, ESR, and LDH in myositis patients. In vitro experiments showed that purified serum IgG from Jo-1-positive patients could stimulate PBMCs to release more MMP9 than the IgG from MDA-5-positive sera. These results indicated that increased MMP9 in anti-Jo1-positive myositis patients was associated with the extent of muscle involvement, but not pulmonary damage. The distinct pattern of serum MMP9 perhaps clarifies the differences in pathophysiology between anti-Jo1 and anti-MDA5 in patients with myositis.

Patients with anti-Jo1 antibodies display a characteristic IgG Fc-glycan profile which is further enhanced in anti-Jo1 autoantibodies

IgG Fc-glycans affect IgG function and are altered in autoimmune diseases and autoantibodies. Anti-histidyl tRNA synthetase autoantibodies (anti-Jo1) are frequent in patients with idiopathic inflammatory myopathies (IIM) and anti-synthetase syndrome (ASS) with associated interstitial lung disease (ILD). Thus, we hypothesized that the total-IgG Fc-glycans from Jo1+ versus Jo1− patients and anti-Jo1-IgG would show characteristic differences, and that particular Fc-glycan features would be associated with specific clinical manifestations. By proteomics based mass spectrometry we observed a high abundance of agalactosylated IgG1 Fc-glycans in ASS/IIM patients (n = 44) compared to healthy age matched controls (n = 24). Using intra-individual normalization of the main agalactosylated glycan (FA2) of IgG1 vs FA2-IgG2, ASS/IIM and controls were distinguished with an area under the curve (AUC) of 79 ± 6%. For Jo1+ patients (n = 19) the AUCs went up to 88 ± 6%. Bisected and afucosylated Fc-glycans were significantly lower in Jo1+ compared to Jo1− patients. Anti-Jo1-IgG enriched from eleven patients contained even significantly lower abundances of bisected, afucosylated and galactosylated forms compared to matched total-IgG. ASS and ILD diagnosis, as well as lysozyme and thrombospondin correlated with Jo1+ characteristic Fc-glycan features. These results suggest that the anti-Jo1+ patient Fc-glycan profile contains phenotype specific features which may underlie the pathogenic role of Jo1 autoantibodies.

Nailfold Capillaroscopy Characteristics of Antisynthetase Syndrome and Possible Clinical Associations: Results of a Multicenter International Study.

To describe nailfold videocapillaroscopy (NVC) features of patients with antisynthetase syndrome (AS) and to investigate possible correlations with clinical and serological features of the disease. We retrospectively analyzed NVC images of 190 patients with AS [females/males 3.63, mean age 49.7 ± 12.8 yrs, median disease duration 53.7 mos (interquartile range 82), 133 anti-Jo1 and 57 non-anti-Jo1-positive patients]. For each patient, we examined number of capillaries, giant capillaries, microhemorrhages, avascular areas, ramified capillaries, and the presence of systemic sclerosis (SSc)-like pattern. Finally, we correlated NVC features with clinical and serological findings of patients with AS. Concomitantly, a historical cohort of 75 patients with antinuclear antibody-negative primary Raynaud phenomenon (RP) and longterm followup was used as a control group (female/male ratio 4.13/1, mean age 53.9 ± 17.6 yrs) for NVC measures. NVC abnormalities were observed in 62.1% of AS patients compared with 29.3% of primary RP group (p < 0.001). An SSc-like pattern was detected in 67 patients (35.3%) and it was associated with anti-Jo1 antibodies (p = 0.002) and also with a longer disease duration (p = 0.004). Interestingly, there was no significant correlation between the presence of SSc-like pattern and RP, and only 47% of patients with SSc-like pattern had RP. NVC abnormalities are commonly observed in AS, independently from the occurrence of RP. The presence of an SSc-like pattern could allow identification of a more defined AS subtype, and prospective studies could confirm the association with clinical and serological features of AS.

Development of a New Classification System for Idiopathic Inflammatory Myopathies Based on Clinical Manifestations and Myositis-Specific Autoantibodies

Idiopathic inflammatory myopathies are heterogeneous in their pathophysiologic features and prognosis. The emergence of myositis-specific autoantibodies suggests that subgroups of patients exist. To develop a new classification scheme for idiopathic inflammatory myopathies based on phenotypic, biological, and immunologic criteria. An observational, retrospective cohort study was performed using a database of the French myositis network. Patients identified from referral centers for neuromuscular diseases were included from January 1, 2003, to February 1, 2016. Of 445 initial patients, 185 patients were excluded and 260 adult patients with myositis who had complete data and defined historical classifications for polymyositis, dermatomyositis, and inclusion body myositis were enrolled. All patients were tested for anti-histidyl-ARN-t- synthetase (Jo1), anti-threonine-ARN-t-synthetase (PL7), anti-alanine-ARN-t-synthetase (PL12), anti-complex nucleosome remodeling histone deacetylase (Mi2), anti-Ku, anti-polymyositis/systemic scleroderma (PMScl), anti-topoisomerase 1 (Scl70), and anti-signal recognition particle (SRP) antibodies. A total of 708 variables were collected per patient (eg, cancer, lung involvement, and myositis-specific antibodies). Unsupervised multiple correspondence analysis and hierarchical clustering analysis to aggregate patients in subgroups. Among 260 participants (163 [62.7%] women; mean age, 59.7 years; median age [range], 61.5 years [48-71 years]), 4 clusters of patients emerged. Cluster 1 (n = 77) included patients who were male, white, and older than 60 years and had finger flexor and quadriceps weakness and findings of vacuolated fibers and mitochondrial abnormalities. Cluster 1 regrouped patients who had inclusion body myositis (72 of 77 patients [93.5%]; 95% CI, 85.5%-97.8%; P < .001). Cluster 2 (n = 91) regrouped patients who were women and had high creatine phosphokinase levels, necrosis without inflammation, and anti-SRP or anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies corresponding to immune-mediated necrotizing myopathy (53 of 91 [58.2%]; 95% CI, 47.4%-68.5%; P < .001). Cluster 3 (n = 52) regrouped patients who had dermatomyositis rash and anti-Mi2, anti-melanoma differentiation-associated protein 5 (MDA5), or anti-transcription intermediary factor-1γ (TIF1γ) antibodies, mainly corresponding with patients who had dermatomyositis (43 of 52 [82.7%]; 95% CI, 69.7%-91.8%; P < .001). Cluster 4 (n = 40) was defined by the presence of anti-Jo1 or anti-PL7 antibodies corresponding to antisynthetase syndrome (36 of 40 [90.0%]; 95% CI, 76.3%-97.2%; P < .001). The classification of an independent cohort (n = 50) confirmed the 4 clusters (Cohen κ light, 0.8; 95% CI, 0.6-0.9). These findings suggest a classification of idiopathic inflammatory myopathies with 4 subgroups: dermatomyositis, inclusion body myositis, immune-mediated necrotizing myopathy, and antisynthetase syndrome. This classification system suggests that a targeted clinical-serologic approach for identifying idiopathic inflammatory myopathies may be warranted.

Detection of autoantibodies in dermatomyositis

Some autoantibodies have been identified to be closely associated with the clinical phenotypes and prognosis of dermatomyositis, such as anti-melanoma differentiation-associated gene 5 (MDA5) antibody, anti-transcriptional intermediary factor 1-γ (TIF-1γ) antibody, anti-nuclear matrix protein-2 (NXP-2) antibody, anti-glycyl-tRNA synthetase (anti-EJ) antibody, anti-nucleosome remodelling and histone deacetylase complex (anti-Mi-2) antibody, anti-histidyl-tRNA synthetase (anti-Jo-1) antibody, and so on. Anti-MDA5, anti-EJ and anti-Jo-1 antibodies are all related to dermatomyositis complicated by interstitial lung disease, especially anti-MDA5 antibody, which is significantly associated with the occurrence, disease activity and high mortality of dermatomyositis complicated by interstitial lung disease. Usually, anti-MDA5 antibody-positive patients have poor response to conventional immunosuppressive treatments. Anti-TIF-1γ and anti-NXP-2 antibodies are related to cancer-associated dermatomyositis. Moreover, anti-TIF-1γ and anti-NXP-2 antibodies are linked to some other distinctive clinical phenotypes of dermatomyositis. For example, obviously increased occurrence of psoriasis-like lesions and hyperkeratotic papules of palms is observed in anti-TIF-1γ antibody-positive patients, while muscle weakness in the forearms, lower legs and neck occurs more commonly in anti-NXP-2 antibody-positive patients. However, anti-Mi-2 antibody-positive patients have significantly decreased risk of interstitial lung disease and prolonged duration of treatment. Thus, wide application of the detection of these autoantibodies will be helpful to guide the diagnosis and treatment of dermatomyositis. Key words: Dermatomyositis; Autoantibodies; Antibodies, anti-MDA5; Antibodies, anti-TIF-lγ; Antibodies, anti- NXP-2; Antibodies, anti-EJ; Antibodies, anti- Mi-2; Antibodies, anti- Jo-1

Clinical features and imaging findings of interstitial lung disease in antisynthetase syndrome

Objective To investigate the clinical features and imaging findings of interstitial lung disease in antisynthetase syndrome(AS-ILD)and to compare the characteristics among AS specificities. Methods A total of 59 cases with AS-ILD at our hospital during the last 5 years were retrospectively reviewed, including anti-Jo1 positive in 37 cases and anti-PL7 positive in 6 cases and anti-PL12 positive in 6 cases and anti EJ positive in 10 cases. There were 14 males and 45 females aged (51±12) years. The clinical features including myositis, arthritis, fever, mechanic's hands , rash, proximal dysphagia, raynaud phenomenon were identified. Two radiologists evaluated the pattern, distribution and the ILD pattern of the lung abnormalities on HRCT findings. Based on the anti synthetase antibody positive subtype, 59 patients could be divided into four groups;then the differences of clinical features and HRCT findings between different subtypes were analyzed. χ2 test was performed for the comparison of the differences between anti-Jo1 antibody positive and the other 3 group. Results (1)Myositis and arthritis were the most common AS manifestations, which were 61.02% (36/59) and 50.85%(30/59) respectively. (2)The lung abnormalities were predominantly basal(91.53%, 54/59) and peripheral(59.32%, 35/59). Ground-grass opacities(79.66%, 47/59)and reticulations(76.27%, 45/59) were found most frequently. Non-specific interstitial pneumonia(NSIP) was the most common HRCT pattern(64.41%, 38/59). (3) As compared with anti-Jo1 positive AS patients, anti-PL12 positive AS patients showed a high rate of traction bronchiectasis at diagnosis(83.33%, 5/6), while the difference was statistically significant(χ2=7.206, P=0.015). The prevalence of pericardial effusion(40.00%, 4/10) was significantly higher in the group of the anti-EJ positive AS patients than that with anti-Jo1 antibody AS(χ2=6.317, P=0.044). Conclusions Myositis and arthritis are the predominant clinical features. NSIP is the most common HRCT pattern in AS-ILD patients. There are some differences of signs among various subtypes, indicating that the difference of fibrosis in the lung and inflammatory reaction in the body being correlated with the AS specificities. Key words: Antisynthetase syndrome; Interstitial lung disease; anti-Jo1 antibody

An effective algorithm for the serological diagnosis of idiopathic inflammatory myopathies: The key role of anti-Ro52 antibodies

BackgroundPatients with suspected idiopathic inflammatory myopathies (IIM) are commonly tested for the presence of anti-nuclear antibodies (ANA) by indirect immunofluorescence (IIF) on HEp-2 cell substrates. However, ANA-IIF false negative tests may occur in IIM because some antigens, such as Jo1 and Ro52, may be scarcely expressed on HEp-2 cells. In addition, cytoplasmic staining is often not appropriately investigated by a specific antibody assay, leading to decreased clinical sensitivity of the ANA test. We evaluated the diagnostic impact of different strategies using different combination of myositis-related autoantibody tests. MethodsSera from 51 patients with an established diagnosis of IIM were tested for ANA by IIF on HEp-2 cells and for myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA) by lineblot methods. ResultsForty-four/51 (86.3%) samples tested positive with at least one of the three methods and seven were negative with all methods. Of the 44 positive samples, 9 (20.5%) tested negative for the ANA-IIF test and positive for MAA/MSA. Anti-Ro52 were the most prevalent autoantibodies in IIM patients (21/51; 41%), frequently associated with anti-Jo1 antibodies (13/21; 62%). 13 (16%) anti-Ro52 and anti-Jo1 negative samples were reactive to MSA. ConclusionsOur findings suggest that when IIM is clinically suspected, the optimal diagnostic algorithm is to associate the ANA-IIF screening test with a specific test for anti-Ro52 and anti-Jo1 antibodies. Should all these tests be negative, serological tests for MSA are recommended.

COULD ANTI-SYNTHETASE SYNDROME BE A GOOD PREDICTOR FACTOR FOR INTERSTITIAL LUNG DISEASE?

Anti-synthetase syndrome (SAS) is an autoimmune inflammatory myopathy, whose immune profile is dominated by anti-RNA synthetase antibodies (ARS), with a specific clinical phenotype. The major diagnostic criteria of SAS include the triad of myositis, arthritis and interstitial lung disease (ILD), on the background of positive anti-ARS antibodies. ILD in SAS, has a good evolution compared to the one in PM/DM, due to protective presence of anti Jo-1 antibodies.

Autoantibodies in children with juvenile dermatomyositis: A single centre experience from North-West India.

The objective of this study is to determine autoantibody profile in children with juvenile dermatomyositis (JDM). Children who were diagnosed with JDM (either recently diagnosed during the study period or follow-up patients) were included in the study. Autoantibodies were detected with commercially available Immunodot kit. Thirty patients were included in the study. Nine out of thirty patients (30%) were positive for one of the 12 autoantibodies tested. Anti-SRP antibody was most common antibody detected in 3 patients followed by anti-MDA-5 antibody in 2 patients; while anti-Jo1 antibody, anti-TIF1-γ antibody, anti-Mi-2 antibody, and anti-PM-Scl antibody were positive in 1 patient each. A different disease phenotype was observed with each autoantibody. The patient with anti-Jo1 antibody had a severe systemic disease in the form of interstitial lung disease; patients with anti-MDA-5 antibody and anti-Mi2 antibody had more severe skin disease with mild muscle disease and patients with anti-SRP antibody had significant skin and muscle disease. Anti-TIF1-γ and anti-PM-Scl antibodies were seen in patients with features of overlap syndrome (myositis-scleroderma). Estimation of autoantibodies may serve as an adjunct tool in delineating and defining distinct clinical phenotypes in children diagnosed with juvenile dermatomyositis. They may also help in prognostication.

Myalgia in Patients with Dermatomyositis and Polymyositis Is Attributable to Fasciitis Rather Than Myositis: A Retrospective Study of 32 Patients who Underwent Histopathological Examinations.

To determine the association between fasciitis and the clinical variables in patients with dermatomyositis (DM) and polymyositis (PM). We retrospectively reviewed the medical records of 32 patients (24 DM, 8 PM) with newly diagnosed DM and PM and in whom fascia and muscle specimens were histopathologically examined. The relationship between fasciitis and the clinical variables was statistically analyzed. These included age, sex, myalgia, muscle weakness, creatine kinase (CK) and aldolase activities, anti-Jo1 antibody, interstitial lung disease, and malignancy. Twenty (62.5%) of the 32 patients who underwent the histopathological examination of a fascia specimen had fasciitis, including 18 (75%) of 24 patients with DM and 2 (25%) of 8 patients with PM. The frequency of fasciitis was significantly higher among the patients with DM than among the patients with PM (p < 0.05). Histopathologically, fasciitis in PM was very mild in comparison to that in DM. The frequency of myalgia in patients with fasciitis was significantly higher than that in patients without fasciitis (p < 0.05). However, myalgia was not associated with myositis. There were no significant differences in the patients with and without fasciitis in age, sex, manual muscle test 8 scores, CK or aldolase activities, or the presence of anti-Jo1 antibodies and malignancy. The frequency of fasciitis was significantly higher among patients with DM than among those with PM. Fasciitis, rather than myositis, was associated with myalgia.

Interstitial lung disease and myositis-specific and associated autoantibodies: Clinical manifestations, survival and the performance of the new ATS/ERS criteria for interstitial pneumonia with autoimmune features (IPAF)

Objectiveto describe the clinical manifestations and survival of patients with ILD and myositis-specific and associated autoantibodies, and to evaluate the performance of the new ATS/ERS classification criteria for IPAF. Patients and methodsPatients with ILD and positive in at least one of the following autoantibodies: anti-Jo-1, anti-Ej, anti-PL7, anti-PL 12, anti-PM/SCL 75 and anti-PM/SCL100 were included. Patients were separated into three groups according to their autoantibody profile: 1. Jo-1 positive patients, 2. Non-Jo-1 antisynthetase autoantibody positive patients, and 3. PM/SCL positive patients. Relevant clinical characteristics were registered. Patients were evaluated had they fulfilled Bohan and Peter's criteria (BPC) for inflammatory myopathies. We evaluated the performance of the IPAF ATS/ERS proposal to classify as such the patients that did not fulfilled BPC, and evaluated whether IPAF patients had a worse survival that BPC patients. ResultsSixty-eight patients were included. Jo-1 was the most frequent autoantibody (65%), followed by non Jo1 anti-synthetase autoantibodies (31%). Non-Jo1 patients had lower Creatin Kinase serum levels at the baseline and less frequency of arthritis. Only 50% of patients fulfilled BPC. All patients not complying with BPC did comply with IPAF criteria. There was no difference in survival between IPAF and BPC patients. Anti Jo-1 positive was associated to survival and the extent of lung inflammation was associated to mortality. ConclusionsPatients differ in clinical manifestations according to the autoantibody profile. All patients not complying with BPC did comply with the new IPAF criteria. There was no difference in survival between BPC and IPAF patients. Jo-1 patients had a better survival. Extent of lung inflammation was associate to mortality.

Antisynthetase syndrome: Pulmonary computed tomography findings of adult patients with antibodies to aminoacyl-tRNA synthetases

ObjectivesTo describe the pulmonary CT findings in patients with anti-ARS-antibody-positive interstitial lung disease (anti-ARS-ILD) MethodsThe CT findings of 64 patients with anti-ARS-ILD were retrospectively reviewed. The images were retrospectively reviewed independently by 2 chest radiologists, and the final decision on the CT findings was made by a third chest radiologist. ResultsThere were 16 male and 48 female patients, aged 54.2±13.4 years. Sixteen patients had anti Jo-1, 24 had anti-EJ, 9 had anti-PL-7, 7 had anti-PL-12, 5 had anti-KS, and 3 had anti-OJ antibodies. Overall, 63 patients (98.4%) had CT findings predominantly in the lower lobe; 61 patients (95.3%) showed peripheral opacities, and 47 patients (73.4%) showed peribronchovascular opacities. Ground-glass attenuation, consolidation, and reticulation showed similar distribution patterns. Regarding detailed CT findings, 89.1% of patients had lower volume loss, 76.6% had interlobular septal thickening, and 67.2% had thickening of bronchovascular bundles. The final radiologic diagnoses were as follows: inconsistent with usual interstitial pneumonia (UIP) in 63 patients (98.4%), which included nonspecific interstitial pneumonia (NSIP) in 35 patients (55.6%), organizing pneumonia (OP) in 4 patients (6.3%), and OP with fibrosis in 22 patients (34.9%). ConclusionsThe characteristic CT findings of patients with anti-ARS-ILD were areas of ground-glass attenuation and reticulation, predominantly distributed as lower and peribronchovascular lesions, which is compatible with NSIP. One-third of patients showed OP with fibrosis.

Testing for myositis specific autoantibodies: Comparison between line blot and immunoprecipitation assays in 57 myositis sera

ObjectiveTo analyze the performance of a line blot assay for the identification of autoantibodies in sera of patients affected by myositis, compared with immunoprecipitation (IP) as gold standard. Methods66 sera of patients with myositis (23 polymyositis, 8 anti-synthetase syndromes, 29 dermatomyositis and 6 overlap syndromes) were tested by commercial LB (Euroimmun, Lubeck, Germany); 57 sera were analyzed also by IP of K562 cell extract radiolabeled with 35S-methionine. Inter-rater agreement was calculated with Cohen's k coefficient. ResultsMyositis-specific antibodies (MSA) were detected in 36/57 sera (63%) by IP and in 39/66 sera (59%) by LB. The most frequent MSA found by LB were anti-Jo1 and anti-Mi2 found in 15% (10/66) of sera, followed by anti-NXP2 and anti-SRP detected in 106% (7/66) of sera. Anti-TIF1gamma and anti-MDA5 were found in 6 (9%) and 5 sera (7.6%), respectively.A good agreement between methods was found only for anti-TIF1γ, anti-MDA5 and anti-NXP-2 antibodies, while a moderate agreement was estimated for anti-Mi2 and anti-EJ. By contrast, a high discordance rate for the detection of anti-Jo1 antibodies was evident (k: 0.3).Multiple positivity for MSA were found in 11/66 (17%) by LB and 0/57 by IP (p: 0001). Comparing the clinical features of these 11 sera, we found total discrepancies between assays in 3 sera (27.3%), a relative discrepancy due to the occurrence of one discordant autoantibody (not confirmed by IP) in 5 cases (45.5%) and a total discrepancy between LB and IP results, but with a relative concordance with clinical features were found in other 3 sera (27.3%). The semiquantitative results do not support the interpretation of the data. ConclusionsThe use of LB assay allowed the detection of new MSA, such as anti-MDA5, anti-MJ and anti-TIF1gamma antibodies, previously not found with routine methods. However, the high prevalence of multiple positivities and the high discondant rate of anti-Jo1 antibodies could create some misinterpretation of the results from the clinical point of view. These data should be confirmed by enlarging the number of myositis cases.

A Case Of Autoimmune Hepatitis With Microadenoma Of Pituitary

Here, a case of autoimmune hepatitis in 34 yrs old lady has been described. She presented with prolonged jaundice, amenorrhea, arthritis and lactation. In laboratory examination, her aminotransferases, alkaline phosphatase and all immunoglobulins were raised. Her serum was positive for antinuclear antibody, anti SLA antibody and antibody to F-actin. Other autoantibodies like anti ds DNA, anti SSA, anti SSB, anti Scl 70, anti Jo-1, anti-centromere and anti-cardiolipinAb were negative. There were no clinical features of any other autoimmune disease. On MRI examination, microadenoma of pituitary gland was detected and her serum prolactin & T4 level were also high. She was finally diagnosed as a case of AIH with pituitary microadenomaand anti SLA Ab, which is an uncommon entity.She was kept on steroid and Bromocriptine, but follow up could not be done. This case suggests that AutoImmune Hepatitis (AIH) with ANA, F-actin and anti SLAAb may present with Prolactinoma.

Pulse Steroids for Refractory Antisynthetase Syndrome: A Booster Therapy?

SESSION TITLE: Diffuse Lung Disease Student/Resident Case Report Posters SESSION TYPE: Student/Resident Case Report Poster PRESENTED ON: Tuesday, October 27, 2015 at 01:30 PM - 02:30 PM INTRODUCTION: Anti-synthetase syndrome (ASS) is an autoimmune condition characterized by inflammatory myositis and interstitial lung disease. Our case of refractory ASS suggests that administering pulse steroids may enhance standard treatment. CASE PRESENTATION: A 43 year-old woman presented with cough, arthralgias and dyspnea progressive over six months. No fever, rash or muscle weakness. Physical exam revealed hypoxia, bibasilar crackles, and mechanic's hands. Autoimmune serologies including ANA, anti-dsDNA, anti-smith, rheumatoid factor, anti-SSA, anti-SSB, anti-SCl-70, and anti-centromere were negative. Anti-Jo1 antibody was positive (6.7 index). Creatinine kinase (200 U/L) and aldolase (11.9 U/L) were elevated. Chest CT revealed fibrotic changes, consolidation without honeycombing in lower lobes and ground glass opacities (GGO) in upper lobes. Pulmonary function testing demonstrated moderate restriction and severely impaired diffusion (DLCO) at 39% predicted. The diagnosis was antisynthetase syndrome. The patient received 60 mg of prednisone daily with rapid improvement in symptoms and radiographic findings. However, tapering steroids failed and 3 grams of daily mycophenolate was added to her regimen. Six weeks later, she deteriorated further with worsening hypoxia, arthralgias, mechanic's hands, DLCO (32% predicted) and progressive GGO and lower lobe infiltration. We administered solumedrol 1 gram daily for three days with rapid clinical improvement and resumed her regimen of daily prednisone and mycophenolate. Within three weeks, the CT chest showed marked clearing and DLCO improved to 39% predicted. At four months post-pulse steroids, she remains on mycophenolate and prednisone (tapered to 20 mg/day) with resolved hypoxia, minimal CT findings and DLCO improved to 46% predicted. DISCUSSION: Prednisone 1mg/kg/day is first line monotherapy for ASS but is often combined with other immunosuppressants. Up to 25% of cases may be refractory, with reported 45% mortality at 20 months. Rituximab is the common therapy for refractory ASS but may present a high infection-related mortality risk. We suggest that in patients with rapidly deteriorating or refractory ASS, pulse steroids may enhance response to standard therapy as a ‘booster' treatment. The rapid response is advantageous since uncontrolled inflammation may lead to irreversible fibrotic changes. CONCLUSIONS: Refractory ASS often has a poor outcome. Current treatments are based on expert recommendations or case series without strong level of evidence. Pulse steroids may offer an effective adjunct to therapy with acute deterioration of ASS. Reference #1: Marie I et al. Interstitial lung disease in patients with antisynthetase syndrome. Arthritis Care & Research. 2013 May; 65 (5): 800-808 Reference #2: Anderson H et al. Long-term experience with rituximab in ASS-related ILD. Rheumatology (2015) doi; 10.1093/rheumatology/kev004; March 2015 DISCLOSURE: The following authors have nothing to disclose: Marie Rosalette Mortel, Pius Ochieng, Mary Salvatore, Mary O Sullivan No Product/Research Disclosure Information

Recurrent Cardiac Tamponade: An Unusual Presentation of Intrahepatic Cholangiocarcinoma

A 48-year-old woman presented with 8 months of sharp mid chest pain, weight loss and new-onset shortness of breath. Vital signs and physical exam were unremarkable. Initial echocardiogram revealed a normal left ventricle with diastolic right ventricular compression, and a large pericardial effusion with diastolic right atrial collapse. (Figure 1) CT imaging of the abdomen showed a new 7.1cm hypodense mass in the right hepatic lobe.Figure 1A pericardial window was performed with pericardium, xifoid cartilage and mediastinum lymph node biopsies. Bacterial, fungal, and mycobacterial smears and cultures were negative. The lymph node biopsy showed non-caseating granulomatous inflammation. b ACE levels were normal and there was no hiliar adenopathy. Anti-nuclear antibody was positive (speckled pattern 1:40). Rheumatoid factor, dsDNA, Anti Scl-70, Anti RPR, Anti Smith, Anti Jo1 and Anti centromere antibodies were negative. Hepatitis, Coxsackie, Echovirus and Brucella serologic tests were also negative. Patient was readmitted 1 month later with similar symptoms and was found to have recurrent cardiac tamponade. A second pericardial window was performed with drainage of 600mL of fluid. Epithelial membrane antigen (EMA) positive neoplastic cells were identified in the pericardial fluid. A triple phase CT scan showed persistence of the hepatic mass in segment IV A/B suggestive of cholangiocarcinoma (CCA) or a single metastatic lesion. (Figure 2,3) Workup for adenocarcinoma of unknown primary was performed including bone scan, breast US, mammogram, upper endoscopy and colonoscopy. No primary source was identified. Finally a CT guided biopsy of the liver mass confirmed moderately differentiated adenocarcinoma. Immunohistochemistry was positive for Keratin and DPC-4 suggesting intrahepatic CCA.Figure 2Figure 3Intrahepatic CCA is a locally aggressive disease that rapidly metastasizes to other liver segments and to the peritoneum. Patients generally succumb before developing pulmonary or brain metastases. This is the first report of CCA presenting with cardiac tamponade, surprisingly without pulmonary or mediastinal involvement. The first pericardial was non-diagnostic. This illustrates the value of repeat biopsy and immunohistochemistry when clinically indicated.

Clinical Spectrum Time Course in Anti Jo-1 Positive Antisynthetase Syndrome: Results From an International Retrospective Multicenter Study.

Anti Jo-1 antibodies are the main markers of the antisynthetase syndrome (ASSD), an autoimmune disease clinically characterized by the occurrence of arthritis, myositis, and interstitial lung disease (ILD). These manifestations usually co-occur (for practical purpose complete forms) in the same patient, but cases with only 1 or 2 of these findings (for practical purpose incomplete forms) have been described. In incomplete forms, the ex novo occurrence of further manifestations is possible, although with frequencies and timing not still defined. The aim of this international, multicenter, retrospective study was to characterize the clinical time course of anti Jo-1 positive ASSD in a large cohort of patients. Included patients should be anti Jo-1 positive and with at least 1 feature between arthritis, myositis, and ILD. We evaluated the differences between complete and incomplete forms, timing of clinical picture appearance and analyzed factors predicting the appearance of further manifestations in incomplete ASSD. Finally, we collected 225 patients (58 males and 167 females) with a median follow-up of 80 months. At the onset, complete ASSD were 44 and incomplete 181. Patients with incomplete ASSD had frequently only 1 of the classic triad findings (110 cases), in particular, isolated arthritis in 54 cases, isolated myositis in 28 cases, and isolated ILD in 28 cases. At the end of follow-up, complete ASSD were 113, incomplete 112. Only 5 patients had an isolated arthritis, only 5 an isolated myositis, and 15 an isolated ILD. During the follow-up, 108 patients with incomplete forms developed further manifestations. Single main feature onset was the main risk factor for the ex novo appearance of further manifestation. ILD was the prevalent ex novo manifestation (74 cases). In conclusion, ASSD is a condition that should be carefully considered in all patients presenting with arthritis, myositis, and ILD, even when isolated. The ex novo appearance of further manifestations in patients with incomplete forms is common, thus indicating the need for an adequate clinical and instrumental follow-up. Furthermore, the study clearly suggested that in ASSD multidisciplinary approach involving Rheumatology, Neurology, Pneumology, and Internal Medicine specialists is mandatory.