Jo-1 Antibody Research Articles

The Jo-1 mystery

A 51-year-old male patient presented with fever, myalgia, and bilateral thigh pain, followed by proximal weakness of limbs. Laboratory features were suggestive of inflammatory polymyositis (PM). He initially responded to steroids, but subsequently, the patient’s clinical condition deteriorated. In the initial investigations, there was no evidence of any malignancy. Over the next 2 months, he had a catastrophic downhill course—progressive pancytopenia, acute abdominal pain, and features of mesenteric panniculitis and he eventually was diagnosed with acute myeloid leukemia (AML).This case underscores the high index of suspicion for underlying malignancy while managing cases of refractory PM and emphasizes the importance of comprehensive diagnostic evaluation and interdisciplinary collaboration in managing patients with complex autoimmune and hematological conditions. Jo-1 antibody, also known as anti-histidyl-tRNA synthetase antibody, is a specific type of autoantibody associated with a group of autoimmune diseases collectively known as idiopathic inflammatory myopathies (IIMs), particularly polymyositis (PM) and dermatomyositis (DM). Here, we present a case report highlighting the rare clinical association between Jo-1-positive PM and hematological malignancy. The presence of Jo-1 antibodies in this context may suggest potential immune dysregulation or paraneoplastic phenomena linking PM and AML. Accurate diagnosis and timely intervention are crucial for managing patients with complex autoimmune and hematological conditions, especially when they present with atypical clinical features and show poor response to treatment.

Relationship between Jo-1 B Cell Epitope Profile and Clinical Features of Anti-Synthetase Syndrome.

Anti-histidyl-transfer RNA synthetase (Jo-1) antibodies are associated with myositis as well as different extramuscular organ complications comprising the anti-synthetase syndrome. This study aimed to clarify the relationship between anti-Jo-1 epitope recognition patterns and specific clinical features of this syndrome. B cell epitope mapping was performed via enzyme-linked immunosorbent assay in 180 patients who were anti-Jo-1 antibody-positive using overlapping peptides/protein fragments spanning the amino-terminal 151 amino acids of Jo-1 as substrate antigens. Statistical associations with clinical features were assessed through rank-sum, correlation, and cluster analyses. The level of reactivity against subfragments spanning amino acids 1-151 of Jo-1 paralleled that of full-length Jo-1, confirming the immunodominance of this amino-terminal region. The corresponding frequencies of reactivity to peptides 1 (amino acids [aa] 1-21), 3 (aa 27-47), 4 (aa 40-60), 10 (aa 118-138), and 11 (aa 131-151) were 6.1%, 42.5%, 6.8%, 6.7%, and 20.3%. While anti-full-length Jo-1 antibodies were significantly associated with Raynaud phenomenon, anti-fragment A2 (aa 1-60) and A3 (aa 1-90) antibodies were associated with proximal muscle weakness, Raynaud phenomenon, arthritis, and sicca syndrome. Anti-fragment A4 (aa 1-120) and A5 (aa 1-151) antibodies were also associated with sicca syndrome. Peptide 1 (aa 1-21) antibodies were associated with Raynaud phenomenon and dysphagia. Whereas anti-peptide 3 (aa 27-47) antibodies were also linked to Raynaud phenomenon, anti-peptide 9 (aa 105-125) antibodies were associated with mechanic's hands. Autoantibodies targeting different amino-terminal subfragments and/or peptides of Jo-1 were associated with specific clinical features of the anti-synthetase syndrome, demonstrating the biomarker potential of B cell epitope profiling in this disorder.

Clinical features associated with the presence of anti-Ro52 and anti-Ro60 antibodies in Jo-1 antibody-positive anti-synthetase syndrome.

Anti-SSA antibodies target two unrelated proteins, Ro52 (E3 ligase) and Ro60 (RNA binding protein). Previous studies indicate that anti-Ro52 antibodies are frequently associated with various myositis-specific autoantibodies (MSAs)-including anti-tRNA synthetase antibodies-and that the coexistence of MSAs and anti-Ro52 antibodies may portend worse clinical outcomes. Although not well-described in the setting of myositis, work from our animal model of HRS (histidyl-tRNA synthetase)-induced myositis suggests that anti-Ro60 antibodies may also be linked to specific MSAs such as anti-HRS/Jo-1. We therefore aimed to demonstrate the prevalence and clinical characteristics of Ro52 and Ro60 antibody positivity in patients possessing Jo-1 antibodies. To establish the immunological link between anti-synthetase, anti-Ro52, and anti-Ro60 antibodies, we evaluated the relative titers of these antibodies in blood and bronchoalveolar lavage fluid (BALF) of mice following immunization with HRS/Jo-1. In parallel, we used ELISA-based approaches to assess sera from 177 anti-Jo1 antibody-positive patients for the presence of anti-Ro52 and/or anti-Ro60 antibodies. We then determined statistical associations between co-existing anti-Jo-1, anti-Ro52, and/or anti-Ro60 antibodies and clinical manifestations associated with the anti-synthetase syndrome. Mice immunized with HRS had higher levels of anti-Ro52 and anti-Ro60 antibodies in serum and BALF than PBS-immunized mice. In 177 anti-Jo-1 antibody-positive patients, the prevalence of anti-Ro52 and anti-Ro60 antibodies was 36% and 15%, respectively. The frequency of dry eye/dry mouth, interstitial pneumonia, and pulmonary events over time differed between patients with various combinations of anti-Ro52 and anti-Ro60 antibodies. While anti-Ro52 antibodies generally correlated with statistically significant increases in each of these clinical manifestations, the presence of Ro60 antibodies alone was associated with decreased frequency of ILD. Anti-Ro52 and/or anti-Ro60 antibodies are often co-expressed with anti-Jo1 antibodies, defining clinical subsets with different disease course/outcomes.

Anti-synthetase syndrome in a child with pneumomediastinum: a case report and literature review

BackgroundAnti-synthetase syndrome (ASS) is a group of rare clinical subtypes within inflammatory myopathies, predominantly affecting adult females. Instances of critical illness associated with ASS in children are even rarer.Case presentationWe report the case of a 7-year-old boy finally diagnosed with ASS, combined with pneumomediastinum. He presented with intermittent fever persisting for 12 days, paroxysmal cough for 11 days, chest pain, and shortness of breath for 4 days, prompting admission to our hospital. Pre-admission chest CT revealed diffuse pneumomediastinum, subcutaneous pneumatosis in the neck and bilateral chest wall, consolidation, atelectasis, and reticular nodular shadowing in both lungs, as well as pericardial effusion and bilateral pleural effusions. Laboratory tests revealed a positive result for serum MP immunoglobulin M (MP-IgM) and MP immunoglobulin G (MP-IgG). The patient was initially diagnosed with mycoplasma pneumoniae (MP) infection, and following 3 days of antibiotic treatment, the patient's tachypnea worsened. Positive results in muscle enzyme antibody tests included anti–PL-12 antibody IgG, anti–Jo-1 antibody IgG, and anti–RO-52 antibody IgG. Ultrasonography detected moderate effusions in the right shoulder, bilateral elbow, and knee joints. Corticosteroids pulse therapy was initiated on the 27th day following disease onset, and continued for 3 days, followed by sequential therapy for an additional 12 days. The child was discharged on the 43rd day, and subsequent follow-up revealed a significant improvement in consolidation and interstitial lesions in both lungs.ConclusionsASS in children may combine with rapidly progressive interstitial lung disease (RPILD) and pneumomediastinum. It is crucial to promptly identify concurrent immunologic abnormalities during the outbreak of MP, particularly when the disease exhibits rapid progression with ineffective conventional antibiotic therapy.

5 cases of silicosis complicated with connective tissue diseases

Long-term inhalation of silica dust can cause silicosis, but also may induce autoimmune diseases, such as systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, anti-histidyl tRNA synthetase antibody (JO-1 antibody) syndrome. These two diseases can be isolated or combined. In this paper, the clinical characteristics of 5 cases of silicosis complicated with connective tissue diseases were analyzed and summarized to strengthen the clinical understanding of silicosis complicated with connective tissue diseases, so as to reduce its misdiagnosis and missed diagnosis, and provide reference for clinicians in diagnosis and treatment.

Contribution of Complement, Microangiopathy and Inflammation in Idiopathic Inflammatory Myopathies.

Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group characterized by muscle weakness and skin symptoms and are categorized into six subtypes: dermatomyositis (DM), polymyositis (PM), anti-synthetase syndrome (ASS), immune-mediated myopathy (IMNM), inclusion body myopathy (IBM), and overlap myositis. Myositis-specific autoantibodies were detected for the diagnosis and classification of IIM. This review highlights the pathogenic contributions of the complement system, microangiopathy, and inflammation in IIM. Deposition of complement around capillaries and/or the sarcolemma was observed in muscle biopsy specimens from patients with DM, ASS, and IMNM, suggesting the pathomechanism of complement-dependent muscle and endothelial cell injury. A recent study using human muscle microvascular endothelial cells showed that Jo-1 antibodies from ASS induce complement-dependent cellular cytotoxicity in vitro. Based on both clinical and pathological observations, antibody- and complement-mediated microangiopathy may contribute to the development of DM and anti-Jo-1 ASS. Juvenile DM is characterized by the loss of capillaries, perivascular inflammation, and small-vessel angiopathies, which may be related to microinfarction and perifascicular atrophy. Several serum biomarkers that reflect the IFN1 signature and microangiopathy are elevated in patients with DM. The pathological observation of myxovirus resistance protein A (MxA), which suggests a type 1 interferon (IFN1) signature in DM, supports the diagnosis and further understanding of the pathomechanism of IIM. A recent report showed that an increase in triggering receptor expressed on myeloid cells (TREM-1) around perimysial blood vessels and muscles in patients with IIM plays a role in triggering inflammation and promoting the migration of inflammatory cells by secreting proinflammatory cytokines, such as tumor necrosis factor α. The deposition of complement in muscles and capillaries is a characteristic feature of DM, ASS, and IMNM. Microangiopathy plays a pathogenic role in DM, possibly resulting in perifascicular atrophy. Further understanding of the detailed pathomechanism regarding complement, microangiopathy, and inflammation may lead to novel therapeutic approaches for IIM.

Clinical value of chemiluminescence method for detection of antinuclear antibody profiles.

Antinuclear antibodies (ANAs) are crucial in diagnosing autoimmune diseases, mainly systemic lupus erythematosus (SLE). This study aimed to compare the performance of chemiluminescence assay (CLIA) and line immunoassay (LIA) in detecting ANAs in patients with autoimmune diseases, evaluate their diagnostic accuracy for SLE, and develop a novel diagnostic model using CLIA-detected antibodies for SLE. Specimens from patients with autoimmune diseases and physical examination specimens were collected to parallel detect specific antibodies. Individual antibodies' diagnostic performance and a model combining multiple antibodies were assessed. The findings provide valuable insights into improving the diagnosis of SLE through innovative approaches. To compare the performance of CLIA and LIA in detecting ANAs in patients with autoimmune diseases, assess their accuracy for SLE, and develop a novel diagnostic model using CLIA-detected antibodies for SLE. Specimens have been obtained from 270 patients with clinically diagnosed autoimmune disorders, as well as 130 physical examination specimens. After that, parallel detection of anti-double-stranded DNA (dsDNA) antibody, anti-histone (Histone) antibody, anti-nucleosome (Nuc) antibody, anti-Smith (Sm) antibody, anti-ribosomal P protein (Rib-P) antibody, anti-sicca syndrome A (Ro60) antibody, anti-sicca syndrome A (Ro52) antibody, anti-sicca syndrome (SSB) antibody, anti-centromere protein B (Cenp-B) antibody, anti-DNA topoisomerase 1 (Scl-70) antibody, anti-histidyl tRNA synthetase (Jo-1) antibody, and anti-mitochondrial M2 (AMA-M2) antibody was performed using CLIA and LIA. The detection rates, compliance rates, and diagnostic performance for SLE were compared between the two methodologies, followed by developing a novel diagnostic model for SLE. CLIA and LIA exhibited essentially comparable detection rates for anti-dsDNA antibody, anti-Histone antibody, anti-Nuc antibody, anti-Sm antibody, anti-Rib-P antibody, anti-Ro60 antibody, anti-Ro52 antibody, anti-SSB antibody, anti-Cenp-B antibody, anti-DNAScl-70 antibody, anti-Jo-1 antibody and anti-AMA-M2 antibody (P > 0.05). The two methods displayed identical results for the detection of anti-dsDNA antibody, anti-Histone antibody, anti-Nuc antibody, anti-Sm antibody, anti-Ro60 antibody, anti-Ro52 antibody, anti-SSB antibody, anti-Cenp-B antibody, anti-Scl-70 antibody, and anti-AMA-M2 antibody (Kappa > 0.7, P < 0.05), but showed a moderate agreement for the detection of anti-Rib-P antibody and anti-Jo-1 antibody (Kappa = 0.671 and 0.665; P < 0.05). In addition, the diagnostic performance of these antibodies detected by both methods was similar for SLE. The diagnostic model's area under the curve values, sensitivity, and specificity, including an anti-dsDNA antibody and an anti-Ro60 antibody detected by CLIA, were 0.997, 0.962, and 0.978, respectively. These values were higher than the diagnostic performance of individual antibodies. CLIA and LIA demonstrated excellent overall consistency in detecting ANA profiles. A diagnostic model based on CLIA-detected antibodies can successfully contribute to developing a novel technique for detecting SLE.

Clinical implications and mechanism of complement C1q in polymyositis.

Polymyositis (PM) is the most common autoimmune disease in neurology and among muscle disorders; it is of great significance to thoroughly understand the mechanism of PM to find new diagnosis and treatment methods. This research intends to elucidate the clinical implications and mechanisms of complement C1q in polymyositis (PM). One hundred fifteen PM patients (research group, RG) and 120 healthy subjects (control group, CG) who visited our hospital between March 2017 and March 2020 were selected. Peripheral blood C1q and creatine kinase (CK) levels of both groups were measured, and their correlations with clinical symptoms and prognostic recurrence of PM. Additionally, to further understand the mechanism of action of C1q in PM, we purchased BALB/c mice and grouped them as follows: control group with normal feeding, PM group with PM modeling, intervention group with PM modeling, and intraperitoneal injection of gC1qR monoclonal antibody 60.11, a C1q protein receptor. Inflammatory factors and muscle histopathology were detected in all groups of mice. Finally, rat macrophages (mø) were isolated, and changes in the biological behavior of mø were observed after silencing the expression of gC1qR. Serum C1q and CK were both higher in RG than in CG, with favorable diagnostic effects on PM (P < 0.05). C1q and CK increased in symptomatic anti-ribonuclear protein antibody (RNP)-positive patients but decreased in anti Jo-1 antibody (Jo-1)- and anti-neutrophil cytoplasmic antibody (ANCA)-positive patients (P < 0.05). PM mice were observed with elevated gC1qR, while model mice exhibited severe infiltration of inflammatory cells in muscle tissue, increased pro-IFs, and reduced anti-IFs, and the animals in the intervention group showed improved conditions (P < 0.05). Finally, it was found that CD68, CD86 protein, and invasion capacity of gC1qR-sh-transfected cells decreased, while CD206 and CD163 increased (P < 0.05). C1q is elevated in PM and is strongly linked to the pathological process of PM. Inhibition of gC1qR expression reduced inflammatory infiltration in PM mice.

P07 Not just simple hand eczema: a case of Jo-1-positive antisynthetase syndrome (‘mechanic’s hands’)

Abstract Antisynthetase syndrome is a rare inflammatory muscle disease related to dermatomyositis and polymyositis. Anti-Jo-1 antibodies are the most detected antibodies in antisynthetase syndrome. The main clinical features of antisynthetase syndrome are myositis, polyarthritis, interstitial lung disease, mechanic’s hands and Raynaud phenomenon. A 50-year-old man with a background of inflammatory muscle disease and interstitial lung disease, for which he is under the care of respiratory and rheumatology teams, was referred to the dermatology department by his general practitioner with refractory xerotic dry fissured skin on his fingers and feet. He reported itchy, sore and painful dry, cracked skin on both his hands, mainly on the fingertips. It did not affect the rest of his body. He trialled potent topical steroids and emollients, but his condition did not improve. He was on a reducing course of prednisolone 15 mg daily and on long-term oxygen therapy at home for interstitial lung disease. On clinical examination, he had an eczematous-looking eruption. The appearance of his hands was in keeping with ‘mechanic’s hands’. Together with the underlying diagnosis of interstitial lung disease, a diagnosis of antisynthetase syndrome was suspected. Blood tests revealed a fibrinogen of 5.39 g L−1 [reference interval (RI) 1.50–4.50], lupus creatine kinase of 1591 IU L−1 (RI 40–320), positive antibodies to Ro (SS-A) and positive antibodies to Jo-1. Jo-1 antibodies are found in dermatomyositis or polymyositis. Ro antibodies are associated with Sjogren syndrome (primary or secondary) or systemic lupus erythematosus, and serum may be antinuclear antibody negative. Therefore, we suspected a diagnosis of antisynthetase syndrome. A patch test showed a positive reaction to nickel, which was deemed to be in keeping with antisynthetase syndrome hand eruption, or ‘mechanic’s hands’. The patient was commenced on mycophenolate, a low dose of acitretin 10 mg and emollients and reported a significant improvement in symptoms. Repeat blood tests were scheduled for 3 months, including lipid profile and liver function test, for monitoring purposes. A follow-up was arranged for 12 weeks. He had a background of recurrent hospital attendance with pericardial effusions and chest symptoms and was tested for COVID-19 multiple times. This case demonstrates the importance of multidisciplinary coordination with rheumatology and respiratory colleagues in antisynthetase syndrome.

Jo-1 Antibodies From Myositis Induce Complement-Dependent Cytotoxicity and TREM-1 Upregulation in Muscle Endothelial Cells.

Muscle microangiopathy due to dysfunction of endothelial cells because of inflammation is a critical hallmark of dermatomyositis (DM); however, its pathomechanism remains unclear. The aim of this study was to evaluate the effect of immunogloblin G (IgG) from patients with idiopathic inflammatory myopathies (IIM) on muscle endothelial cells in vitro. Using a high-content imaging system, we analyzed whether IgG purified from sera from patients with IIM (n = 15), disease controls (DCs: n = 7), and healthy controls (HCs: n = 7) can bind to muscle endothelial cells and induce complement-dependent cellular cytotoxicity. IgGs from Jo-1 antibody myositis could bind to muscle endothelial cells and caused complement-dependent cell cytotoxicity. RNA-seq demonstrated the upregulation of genes associated with tumor necrosis factor (TNF)-α, triggering receptor expressed on myeloid cells-1 (TREM-1), CD25, and mitochondria pathways after exposure to IgG from the Jo-1, signal recognition particle (SRP), and polymyositis (PM) groups. The high-content imaging system showed that TREM-1 expression in the Jo-1, SRP, and PM groups was increased in comparison with DCs and HCs and that the TNF-α expression in the Jo-1 group was higher in comparison with the SRP, PM, DC, and HC groups. The expression of TREM-1 was observed in biopsied capillaries and the muscle membrane from patients with Jo-1 and in biopsied muscle fiber and capillaries from patients with DM and SRP. The depletion of Jo-1 antibodies by IgG of patients with Jo-1 antibody myositis reduced the Jo-1 antibody-induced complement-dependent cellular cytotoxicity in muscle endothelial cells. Jo-1 antibodies from Jo-1 antibody myositis show complement-dependent cellular cytotoxicity in muscle endothelial cells. IgGs from patients with Jo-1, SRP, and DM increase the TREM-1 expression in endothelial cells and muscles.

E079 Preliminary analysis of autoantibody profiles of autoimmune inflammatory myopathies: study from a single North Indian tertiary care centre

Abstract Background/Aims Studies in autoimmune inflammatory myositis (AIM) have shown a strong role of autoantibodies in the diagnosis and prognosis of patients with myositis. This ongoing study shares the preliminary data of 139 patients with AIM from a North Indian tertiary care centre. This prospective, observational study was conducted at a 1250-bedded hospital to assess the prevalence of myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA) in patients from the Indian subcontinent with AIM and the correlation of these antibodies with clinical features. Methods From November 2016 to September 2022, patients with AIM (satisfying the Bohan and Peter criteria of 1975) attending the Rheumatology and Clinical Immunology Department of Medanta Hospital were included after taking their informed consent, and divided into subgroups as dermatomyositis (DM), polymyositis (PM), CTD-associated myositis (CTD-M), cancer-associated myositis (CAM), and juvenile myositis (JM). The Institutional Ethics Committee approved the study. Clinical data and sera from patients were collected and analysed. Results The study included 139 individuals with a mean age of 45.4 years. Fifty-two had DM, 49 had PM, 25 had CTD-M, 6 had CAM, and 7 had JM. ANA positivity was found in 67.70%, MSA in 22.3%, MAA in 25.4%, and both in 12.3%. Antibodies against Mi-2 were identified in 13 (28.9%) patients, Jo-1 in 14 (32.50%), PL-7 in 3 (6.7%), PL-12 in 4 (8.9%), SRP in 9 (20%), and MDA-5 and NXP2 in 1 (2.2%) patient each. Antibodies against Ro were found in 28 (57.1%) of the patients, RNP in 8 (16.3%), and PM-Scl in 9 (18.4%). Mi-2 antibodies were mostly identified in DM patients and were significantly associated with skin rash. SRP positivity was mostly found mainly in PM. Raynaud's and ILD were linked to the presence of Jo-1 and Ro antibodies. Malignancy screening was negative in NXP2 and TIF1γ antibody-positive patients. Conclusion MSA was found in 22.3% of cases and MAA in 25.4%. Mi-2 antibodies were linked to rash, but none had ILD, whereas Jo-1 antibodies were linked to mechanic hands, arthritis, and ILD. We aim to gather more strong results in the future as additional patients are recruited in this continuing trial. Disclosure S. Dhuria: None. P. Khatri: None. N. Negalur: None. K. Telang: None. S. Ghosh: None. D. Yadavalli: None. V. Singal: None. R. Gupta: None.

S2045 Idiopathic AA Amyloidosis Presenting With Rectal Involvement and Intractable Hematochezia

Introduction: Amyloidosis is a group of complex diseases caused by the misfolding, aggregation, and deposition of proteins as insoluble fibrils within tissues leading to progressive organ damage. Secondary amyloidosis is often associated with chronic inflammatory diseases and affects the GI tract in an estimated 60% of cases. The vast majority involve the upper GI tract, especially the duodenum, with only a small subset affecting the colon or rectum. Case Description/Methods: A 47-year-old man with PMH of ESRD on HD and HTN presented with several episodes of hematochezia for the past 1 day. His abdomen was diffusely tender. Laboratory findings revealed a hemoglobin of 7.6 g/dL and a leukocyte count of 14.9 k/uL. Patient had several previous admissions over the past 2 years for hematochezia with no clear etiologies found with multiple unremarkable EGD and colonoscopies. Rheumatology was consulted given concern for an underlying autoimmune process. Serology was negative for RF, ANA, dsDNA, RNP, SSA/SSB, SCL-70, JO-1, Smith, TPO, CCP, and Centromere antibody. Colonoscopy revealed erythematous mucosa throughout the length of the colon. Biopsies taken from the duodenum, ileum, right and left colon, and the rectum revealed deposition of amorphous eosinophilic consistent with amyloid. Specimens analyzed LM-MS detected peptide fragments consistent with AA amyloidosis. The ileum, jejunum, transverse and descending colon had preserved architecture without signs of amyloid deposition. Of note, upper GI endoscopy from the year prior showed no signs of disease, suggesting a rapid progression of amyloidosis throughout the GI tract (Figure). Discussion: The clinical manifestations of secondary amyloidosis vary depending on the organs affected. Involvement of the GI tract is more common in AL amyloidosis than in AA amyloidosis, and both diseases preferentially affect the upper GI tract, most commonly the duodenum. GI amyloidosis often presents with non-specific clinical findings such as diarrhea, obstruction, malabsorption, bleeding, erosion, or ischemia, and may represent a significant clinical challenge in its differentiation from other intestinal diseases such as IBD or malignancy. Although uncommon, GI manifestations of amyloidosis should be considered as a differential for patients in which standard therapies for intestinal disorders have not yielded clinical improvement.Figure 1.: Rectum (left) and rectosigmoid junction (right) with friable mucosa.

A CASE OF ANTISYNTHETASE SYNDROME: THE IMPORTANCE OF HISTORY IN DISTINGUISHING ETIOLOGY OF INTERSTITIAL LUNG DISEASE IN A COVID-19 WORLD

A CASE OF ANTISYNTHETASE SYNDROME: THE IMPORTANCE OF HISTORY IN DISTINGUISHING ETIOLOGY OF INTERSTITIAL LUNG DISEASE IN A COVID-19 WORLD

Dermatomyositis following COVID-19 infection

IntroductionViruses have been shown to reveal autoimmune diseases like type1 diabetes and systemic connectivities like dermatomyositis (DM). Coronavirus disease 2019 (COVID-19) is best known for its respiratory symptoms but multiple systems could be affected in acute or post COVID-19 infection period. Clinical dermatomyositis following COVID-19 infection was exceptionally reported.ObservationWe report a case of a 61-year- woman with no medical history observed in March 2021 with bilateral edema. Doppler ultrasound demonstrated a superficial venous thrombosis of saphenous veins. The patient had a suspicious epidemiological history, and her chest CT scans showed lung damage similar to that caused by COVID-19. PCR test for Coronavirus confirmed the infection. She was treated by curative anticoagulation, steroids and oxygen therapy. Two months after her leaving, she was presented in internal medicine's department with pulmonary embolism despite good anti coagulation. Her PCR test for Coronavirus was negative. At her admission, she was complained of asthenia weight loss and pain in scapular and pelvic muscles. Physical examination revealed erythematous patches with edema in periorbital areas. Chest auscultation found bilateral basal lung crepitation. Bilateral proximal muscle weakness in upper and lower extremities was objectified. Oral examination found ulcerations in the lower gingiva. We found signs of arthritis in wrists and proximal interphalangeal joints. Biological tests showed anemia (hemoglobin =8.6 g/dl), accelerated erythrocyte sedimentation rate (65 mm H1) ; high C-reactive protein(119 mg/l)d biological myolysis and cytolydid (Creatinin kinase = 1052 U/l, LDH = 478 AST/ALT 238 U/l/119 U/l). Infectious investigations including HCV, HBV and HIV serology were negative. Thyroid function test was in normal range. Neoplastic research was negative. Immunologic analysis revealed positive antinuclear antibodies (ANA) with anti JO1 antibodies. Anti cardiolipin antibodies and kit-myositis were negatives. Electromyographic findings revealed inflammatory myositis. The patient was treated by high doses of steroids then progressively decreased. Good progress was noticed.ConclusionDermatomyositis is an inflammatory myopathy relatively rare. An elevation of its incidence was noticed during the pandemic period coinciding of corona virus [1]. Viral infections could induce autoimmunity and may be the eliciting event in the pathogenesis of myositis [2]. In our case, dermatomyositis is hypothetically linked to viral trigger on the background of genetic predisposition. The spectrum of complications following COVID-19 is broad but incidence is too rare including Idiopathic thrombocytopenic purpura, Guillain-Barré syndrome and autoimmune haemolytic anaemia recorded in 1, 5 and 7 patients respectively, 4–13 days following onset of COVID-19 symptoms. We assume that true dermatomyositis, triggered by COVID-19 may occur and the immunopathogenicity is via type 1 IFN pathway. Tanboon et al. commented that 58-year-old COVID-19 patient reported to have myositis may actually have dermatomyositis.

PNEUMONIA MASQUERADING AS ANTI-SYNTHETASE SYNDROME

TOPIC: Lung Pathology TYPE: Fellow Case Reports INTRODUCTION: Anti-synthetase syndrome (ASS) is a rare autoimmune disorder, characterized by anti-aminoacyl transfer RNA synthetase antibodies along with clinical features that can include interstitial lung disease, myositis, Raynaud's phenomenon, non-erosive arthritis, unexplained fever, and/or mechanic's hands. [1] Most patients with ASS with lung involvement present with chronic lung changes, we are describing a case of atypical presentation of ASS lung disease with organizing pneumonia. CASE PRESENTATION: A 60-year-old woman with a history of obstructive sleep apnea, asthma/COPD, and hypothyroidism presented with progressive shortness of breath. The patient had two recent hospitalizations for asthma exacerbation and pneumonia. Chest CT showed patchy scattered ground-glass opacities and consolidative changes with mild traction bronchiectasis changes. Autoimmune workup was positive for anti-SSA (mildly) and ANA but negative for RF, anti-smith, RNP, SSB, SCL70, centromere, PR3, MPO, RNA-Pol 3, and CCP antibodies. Myositis panel was positive for PL-12 Ab. Lung biopsy was consistent with a predominant pattern of organizing pneumonia. In the absence of myositis, the patient was diagnosed with ASS. The patient was initiated on mycophenolic acid and prednisone therapy. Initial pulmonary function tests showed FEV1/FVC is 74, FEV1 is 1.33L (61% of predicted) and FVC is 1.79L (66% of predicted), following treatment repeat PFTs in 3 months showed FEV1/FVC is 68, FEV1 is 1.45L (65% of predicted) and FVC is 2.13L (76% of predicted). Her exercise capacity improved with a six-minute walk test showing a walk distance of 177m with 3 L oxygen before treatment which improved to 435 m with 1 L oxygen post-treatment after 3 months. DISCUSSION: ASS is a group of inflammatory myopathies that requires evidence of anti-aminoacyl transfer RNA synthetase autoantibody and one or more of the following: mechanic's hands, Raynaud's phenomenon, myositis, ILD, arthritis, and/or unexplained fever. [2] Most cases are either misdiagnosed as idiopathic ILD or inflammatory myopathy. CONCLUSIONS: We presented a case of ASS with biopsy-proven organizing pneumonia. Organizing pneumonia is a very rare presentation of ASS and should be kept in mind while evaluating patients with ASS. REFERENCE #1: 1. Stone KB, Oddis CV, Fertig N, Katsumata Y, Lucas M, Vogt M, Domsic R, Ascherman DP. Anti–Jo-1 antibody levels correlate with disease activity in idiopathic inflammatory myopathy. Arthritis & Rheumatism. 2007; 56:3125–3131. [PubMed: 17763431] REFERENCE #2: 2. References Connors GR, Christopher-Stine L, Oddis CV, Danoff SK. Interstitial lung disease associated with the idiopathic inflammatory myopathies: What progress has been made in the past 35 years? Chest. 2010; 138:1464–1474. [PubMed: 21138882] DISCLOSURES: No relevant relationships by Bharat Bhandari, source=Web Response No relevant relationships by Rahat Hussain, source=Web Response No relevant relationships by Soma Sundara Shravan Jyothula, source=Web Response

Successful Heart Transplantation in a Pan-Inflammatory Patient with Interstitial Lung Disease

Introduction We present a case with multiple comorbidities posing a dilemma regarding the need for multi-organ transplant or not being a candidate for any transplant. Case Report 58 year old Hispanic female was referred with decompensated heart failure (CHF), in cardiogenic shock. She had a history of nonischemic cardiomyopathy on home milrinone therapy. She had interstitial lung disease (ILD) on chronic therapy with high-dose hydroxychloroquine (HCQ), mycophenolate (MMF) and prednisone. She had an overlap syndrome consisting of inflammatory arthritis, ILD and myositis for four years, with a history of recurrent myositis flares treated with intravenous immunoglobulin. Presenting creatinine was impaired at 1.9mg/dL. Catheterization on milrinone 0.375mcg/kg/min showed RA 27, PA 60/41 (44), PCWP 33 with a Fick cardiac index 1.7, PAPi of 0.7 and SVR 23WU. Her initial response to diuresis was poor with worsening creatinine so she received an axillary intra-aortic balloon pump (IABP). Positive serologies included highly elevated Jo-1 antibody (185 AU/mL, reference 1000 U/L but repeat levels were normal. Endomyocardial biopsy showed inflammatory lymphocyte and macrophage infiltration. Following aggressive diuresis, HRCT chest showed persistent bilateral ground-glass opacities with interlobular thickening and lower lobe bronchiectasis consistent with ILD without honeycombing. Repeat PFT showed stable FVC of 41% predicted. After multidisciplinary discussion, she was listed status 2 for heart transplant only. Given the relative stability of her restrictive lung disease, concomitant lung transplant was not pursued. HCQ was stopped. She received a heart transplant the next day with basiliximab induction. She was extubated post-operative day 1 and on day 10 she is off inotropes and on tacrolimus, MMF and steroid taper, with no ongoing acute issues. Summary The patient's presentation was dramatic with cardiogenic shock and the decision was time-sensitive given the dependence on IABP. She was not an LVAD candidate given the RV failure (low PAPi). The transplant workup was done methodically yet urgently, with excellent multidisciplinary response, resulting in a successful heart transplant.

Mycophenolate in idiopathic inflammatory myositis: outcome data of a large South Asian cohort.

Consensus on treatment of idiopathic inflammatory myositis (IIM), particularly with regard to flares and interstitial lung disease (ILD), does not exist. We studied the long-term outcome and treatment response in our large, retrospective cohort of adult South-Asian patients exclusively with IIM. Electronic records of IIM patients satisfying inclusion and exclusion criteria were studied longitudinally at presentation, at 3, 6, 12, 18 and 24 months and thereafter yearly till their last follow up (F/u) visit. Depending on clinical, imaging, and muscle enzyme profile during the F/u period, patients were categorised as complete (CR) and partial responders (PRs). Parameters favouring CR were assessed using multivariate logistic regression analysis. Outcome parameters and flares on immunosuppressants (IS) were then assessed in patients with/without ILD. Two hundred thirty-two patients with median F/u duration of 44.5 months (25-80.25) were included. ILD was seen in 40.1%. Patients with non-Jo1 anti-synthetase antibodies (n=26) were numerically more than those with Jo-1 antibody (n=24). CR status was attained by 50.9% patients. Absence of pericardial effusion (p=0.042, OR 4.223, 95% CI: 1.05-16.9) and presence of Gottron's rash (p=0.044, OR 1.78, 95% CI 1.017-3.121) at baseline predicted CR by multivariate regression. Majority received mycophenolate during the entire F/u period. Discontinuation of steroids was feasible in 51.7% after a median duration of 24 months (18-42). After excluding patients with ILD, flares were numericallylesser in patients only on mycophenolate compared with those only on methotrexate (p=0.06). Further flares were curtailed when switchedfrom other agentsto mycophenolate. Mycophenolate is an effective treatmentoption in IIM patients with and without co-existing ILD. Presence of Gottron's rash and absence of pericardial effusion were found to be predictors of favourable clinical outcome in this largest single-centre study.

The Association of Myositis Specific Antibodies in Patients with Inflammatory Myositis: Preliminary Data in Indian Patients.

Context:Autoantibodies have a role in the diagnosis and prognosis in Autoimmune Inflammatory Myositis (AIM).Aims:The aim of this work was to study the prevalence and clinical correlation of myositis specific and associated antibodies (MSA and MAA) in AIM.Setting and Design:This was a cross-sectional observational study.Methods and Materials:Consecutive AIM patents were divided into groups as dermatomyositis (DM), polymyositis (PM), CTD-associated myositis (CTD-M), cancer-associated myositis (CAM) and juvenile myositis (JM). Their data along with serum samples were collected after obtaining informed consent. Sera was analyzed for IgG antibodies against Jo-1, PL-7, PL-12, EJ, SRP, Mi-2, MDA-5, TIF1γ, SAE1, SAE2, NXP2 and SSA/R052kD using the microELISA technique. The institutional ethics committee approved the study.Statistical Analysis:SPSS software (version 24.0) was used. P value < 0.05 was considered statistically significant.Results:There were 48 patients (DM = 19, PM = 19, CTD-M = 5, CAM = 2, JM = 3) included. MSA were positive in 37.5% patients. Antibodies against Mi-2 were present in 6 (12.5%), Jo-1 in 5 (10.4%), 2 (4.1%) each had PL-7 and SRP antibodies. One patient (2%) each had MDA-5, NXP2 and TIf1g antibodies. Jo-1 antibody was associated with mechanic's hands and ILD. There was a significant association of rash in the Mi-2 group with none of the patients having ILD. Malignancy screening was negative in NXP2 and TIF1g antibody-positive patients. Ro52 was the most common MAA (33.3%) and was associated with mechanic's hand.Conclusion:MSA was present in almost 40% of the cohort. Anti Jo-1 antibody was associated with mechanic's hands and ILD. None of the Mi-2 patients had ILD, which may point to a protective role of this antibody for ILD. The association of newer antibodies in Indian patients needs to be further studied in larger cohorts.

The prevalence, clinical features, predictive factors and investigations to screen for cancer in patients with inflammatory myositis

Objectives:To describes the epidemiology of cancer in patients with idiopathic inflammatory myopathies (IIM) treated at 2 tertiary centers in Riyadh, Saudi Arabia.Methods:This was a retrospective multi-center study evaluating the prevalence and the type of malignancy in an IIM population in King Saud University Medical City and King Abdulaziz Medical City between August 2017 to August 2018.Results:In total, 60 patients were included. Four had neoplasms (6.7%), 2 men had lymphoma, a woman had breast cancer and a second, ovarian cancer. Two patients died due to cancer or its complications. Older age (age >40 years), dysphagia, necrotic rash, absence of interstitial lung disease, high erythrocyte sedimentation rate and a negative anti Jo-1 antibody were potentially predictive risk factors for neoplasm. All patients diagnosed with cancer-associated myositis were investigated with routine and invasive modalities. Three of the 4 patients had abnormal findings in both modalities. One patient, the routine investigations were unremarkable, but a computed tomography of the pelvis revealed an ovarian mass that was subsequently diagnosed as malignant.Conclusion:An individualized approach might be more appropriate for high risk patients. Larger prospective studies are required to confirm the findings of the current study.

A Challenging Case of Atypical Adult Onset Still's Disease Clinically Mimicking Dermatomyositis with Distinctive Histopathologic Findings

A 23-year-old woman from Bangladesh presented with a 6-week history of spiking fevers, myalgias, arthralgias, pruritic rash, marked granulocytosis and lymphadenopathy. On presentation to the emergency department she had brown lichenified plaques on the upper chest and neck; her back had flagellate-like erythema. Hand exam revealed hyperpigmented papules over the metacarpophalangeal joints without periungual capillary loop dilatation. Labs were notable for: minimally positive ANA (1:40), mild transaminitis (AST 56, ALT 73), as well as elevated aldolase (13.8), LDH (1,368), sedimentation rate (>140), C reactive protein (7.5) and ferritin (10,248). She also had a negative Anti Jo1 antibody, rheumatoid factor, and CK (<20). An extensive infectious workup was negative. CT of the chest/ abdomen showed generalized lymphadenopathy with mild splenomegaly. Punch biopsies from the hands and back revealed multiple necrotic keratinocytes mainly in the upper epidermis and within parakeratotic stratum corneum, infiltration of lymphocytes and neutrophils in the papillary and mid dermis and numerous intradermal eosinophils without evidence of vasculitis. In the setting of meeting original Yamaguchi criteria for Adult Onset Still’s Disease (AOSD), negative infectious workup, constellation of lab and imaging findings and characteristic histopathologic findings, the patient was diagnosed with atypical AOSD. She was treated with systemic steroids and had resolution of her symptoms. Atypical presentations of AOSD clinically mimicking dermatomyositis show a distinguishing pattern on histology: dyskeratotic and necrotic keratinocytes in the upper layers of the epidermis, inflammatory infiltrate in the upper and mid dermis, and no evidence of vasculitis, as seen in this patient.