Rituximab-induced neutropenia in a patient with inflammatory myopathy and systemic sclerosis overlap disease

Background:Peripheral myositis in systemic sclerosis (SSc) is associated with poor prognosis and myocarditis1but non-inflammatory myopathy, which also represents a significant cause of disability in SSc remains poorly understood. Cardiovascular magnetic resonance (CMR) T1 mapping studies in asymptomatic SSc patients show increased extracellular volume (ECV), suggestive of diffuse fibrosis in both the myocardium and thoracic muscle2.Objectives:To evaluate the feasibility of T1 mapping MRI and determine ECV in peripheral muscle of SSc patients with and without myopathy and explore the association between cardiac and peripheral muscle T1 mapping in SSc.Methods:This was a hypothesis-generating pilot and feasibility study. SSc patients, fulfilling the 2013 ACR/EULAR criteria, with no cardiovascular disease or myositis but either minimal muscle symptoms (non-inflammatory myopathy) or no muscle involvement and healthy volunteers (HV) underwent peripheral muscle T1 mapping-MRI for native T1 and extracellular volume (ECV) quantification of the dominant thigh. Patients also had T1 mapping CMR, and creatine-kinase (CK) measured. Non-inflammatory myopathy was defined as current/history of minimally raised CK (<600 IU/l) +/- presence of clinical signs-symptoms (including proximal myasthenia and/or myalgia) +/- a Manual Muscle Testing (MMT) score <5 in the thighs.Results:12 SSc patients and 10 HV were recruited. SSc patients had a median (IQR) age of 52 (41,65) years, 9/12 had limited cutaneous SSc, 4/12 interstitial lung disease, 7/12 non-inflammatory myopathy. Higher skeletal muscle ECV was recorded in SSc patients compared to HV [mean (SD) 23(11)%, vs 11(4)% p=0.04]. Skeletal muscle native T1 values were comparable between the 2 groups although modestly higher in SSc patients [mean (SD) 1396ms (56) vs 1387ms (42)] (Figure 1A).Peripheral muscle ECV associated with CK (R2=0.307, rho=0.554, p=0.061) and was higher in SSc patients with evidence of myopathy compared to those with no myopathy [28 (10)% vs 15 (5)%, p=0.023] (Figure 1B). An ECV of 22% was determined to best identify myopathy with a sensitivity of 71% and a specificity of 80%.SSc patients had raised myocardial ECV and native T1 with means (SD) of 31 (3) % and 1287 (54) ms respectively (normal reference range ECV ≤29%, native T1 ≤1240ms). No clear association between myocardial and peripheral muscle ECV (rho=-0.485) or between myocardial ECV and peripheral muscle native T1 (rho=0.470) of SSc patients was observed.Conclusion:This pilot study to determine ECV-MRI of the peripheral muscle showed higher ECV in SSc patients compared to HV, suggesting the presence of diffuse fibrosis in the peripheral muscle of SSc patients. These data support further investigation to understand the pathophysiological involvement and relationship of peripheral and cardiac muscle in SSc.References:[1]Follansbee WP et al, Am Heart J. 1993[2]Barison A et al, Eur Heart J Cardiovasc Imaging. 2015Disclosure of Interests:Raluca-Bianca Dumitru: None declared, Alex Goodall: None declared, David Broadbent: None declared, Ananth Kidambi: None declared, Sven Plein: None declared, Francesco Del Galdo: None declared, Ai Lyn Tan: None declared, John Biglands: None declared, Maya H Buch Grant/research support from: Pfizer, Roche, and UCB, Consultant of: Pfizer; AbbVie; Eli Lilly; Gilead Sciences, Inc.; Merck-Serono; Sandoz; and Sanofi

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Systemic Sclerosis in Zimbabwe: Autoantibody Biomarkers, Clinical, and Laboratory Correlates

Frontiers in Immunology ◽

10.3389/fimmu.2021.679531 ◽

2021 ◽

Vol 12 ◽

Author(s):

Elopy N. Sibanda ◽

Yvonne Dube ◽

Mazvita Chakawa ◽

Takafira Mduluza ◽

Francisca Mutapi

Keyword(s):

Systemic Sclerosis ◽

Clinical Chemistry ◽

Pulmonary Function Tests ◽

Rna Polymerase Iii ◽

Inflammatory Myopathy ◽

Reference Ranges ◽

Thyroid Function Tests ◽

Asian Patients ◽

Function Tests ◽

Gi Symptoms

IntroductionSystemic sclerosis (SScl) is an autoimmune disease whose prevalence is rarely reported in Africa. Autoantibodies are the biomarkers of the condition, precede overt disease and determine disease phenotypes. SSc specific autoantibodies also vary between racial groupings. Objective: To investigate the clinical and laboratory characteristics of Zimbabwean patients who were reactive SSc specific autoantibodies.Materials and Method240 patients, 173 of them female with SSc specific autoantibodies were included. Autoantibodies were detected by indirect immunofluorescence microscopy and immunoblotting using a panel of 13 SScl (Euroimmun Ag., Germany). Demographic, clinical and laboratory parameters relevant to the monitoring of SScl were captured. These included pulmonary function tests, hematology, clinical chemistry, serology and thyroid function tests. Allergy skin prick tests (SPT) to inhalant and food allergen sources were conducted when indicated.ResultsAll the 240 patients (median age was 36 years) expressed SSc specific autoantibodies. 86% were Black, 11% White and 3% Asian and a fifth (20%) were younger than 16 years. Eleven (4.6%) fulfilled the ACR/EULAR classification of SSc. Clinically they had limited cutaneous (n=6), diffuse cutaneous (n=3) and SScl/inflammatory myopathy overlap (n=2). The most frequently detected antibodies anti-RNA polymerase III (RNAP) 55%, anti-Th/To (28%) anti-RNAP 11 (22%), anti-CENPB (18%) and anti-Scl-70/ATA (13%). Racial variations in the expression of these antibodies were apparent between Black, White and Asian patients. The majority (95%), who did not fulfil the ARA/EULAR criteria were symptomatic. Raynaud’s Phenomenon was documented in 24%. Respiratory symptoms included coughing, dyspnea and wheezing. There was a restrictive ventilatory defect with increased FEV1/FVC ratio. Pruritus, urticaria and skin depigmentation were the main cutaneous features while constipation, bloating, Gastroesophageal reflux disease (GERD) and abdominal pain dominated GI symptoms. Mean blood pressure readings while normal varied with biomarkers. Haematology and biochemistry parameters were within normal reference ranges.ConclusionThe expression of SSc specific autoantibodies is common and associated with known SSc symptoms. The types and frequency of autoantibodies varied with racial groupings. A fifth of the patients were children below the age of 16 years.

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Ultrastructural Aspects of Apoptosis in Systemic Sclerosis Inflammatory Myopathy

Microscopy Research ◽

10.4236/mr.2018.61001 ◽

2018 ◽

Vol 06 (01) ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Héctor J. Finol ◽

Héctor Luis Osorio-Vega ◽

Radharani Dorta-Ledezma ◽

Antonio Roschman-González ◽

Blanca Muller ◽

...

Keyword(s):

Systemic Sclerosis ◽

Inflammatory Myopathy

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The clinicoserological spectrum of inflammatory myopathy in the context of systemic sclerosis and systemic lupus erythematosus

Indian Journal of Rheumatology ◽

10.4103/injr.injr_136_20 ◽

2020 ◽

Vol 0 (0) ◽

pp. 0

Author(s):

JohnD Pauling ◽

Sarah Skeoch ◽

JulieJ Paik

Keyword(s):

Systemic Lupus Erythematosus ◽

Systemic Sclerosis ◽

Lupus Erythematosus ◽

Inflammatory Myopathy ◽

Systemic Lupus

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Thrombospondin-1 mediates muscle damage in brachio-cervical inflammatory myopathy and systemic sclerosis

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000694 ◽

2020 ◽

Vol 7 (3) ◽

pp. e694 ◽

Cited By ~ 4

Author(s):

Xavier Suárez-Calvet ◽

Jorge Alonso-Pérez ◽

Ivan Castellví ◽

Ana Carrasco-Rozas ◽

Esther Fernández-Simón ◽

...

Keyword(s):

Systemic Sclerosis ◽

Muscle Biopsy ◽

Transforming Growth Factor ◽

Immunosuppressive Treatment ◽

Inflammatory Myopathy ◽

Response To Treatment ◽

Muscle Involvement ◽

Thrombospondin 1

ObjectiveTo describe the clinical, serologic and histologic features of a cohort of patients with brachio-cervical inflammatory myopathy (BCIM) associated with systemic sclerosis (SSc) and unravel disease-specific pathophysiologic mechanisms occurring in these patients.MethodsWe reviewed clinical, immunologic, muscle MRI, nailfold videocapillaroscopy, muscle biopsy, and response to treatment data from 8 patients with BCIM-SSc. We compared cytokine profiles between patients with BCIM-SSc and SSc without muscle involvement and controls. We analyzed the effect of the deregulated cytokines in vitro (fibroblasts, endothelial cells, and muscle cells) and in vivo.ResultsAll patients with BCIM-SSc presented with muscle weakness involving cervical and proximal muscles of the upper limbs plus Raynaud syndrome, telangiectasia and/or sclerodactilia, hypotonia of the esophagus, and interstitial lung disease. Immunosuppressive treatment stopped the progression of the disease. Muscle biopsy showed pathologic changes including the presence of necrotic fibers, fibrosis, and reduced capillary number and size. Cytokines involved in inflammation, angiogenesis, and fibrosis were deregulated. Thrombospondin-1 (TSP-1), which participates in all these 3 processes, was upregulated in patients with BCIM-SSc. In vitro, TSP-1 and serum of patients with BCIM-SSc promoted proliferation and upregulation of collagen, fibronectin, and transforming growth factor beta in fibroblasts. TSP-1 disrupted vascular network, decreased muscle differentiation, and promoted hypotrophic myotubes. In vivo, TSP-1 increased fibrotic tissue and profibrotic macrophage infiltration in the muscle.ConclusionsPatients with SSc may present with a clinically and pathologically distinct myopathy. A prompt and correct diagnosis has important implications for treatment. Finally, TSP-1 may participate in the pathologic changes observed in muscle.

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Brachio-cervical inflammatory myopathy associated with systemic sclerosis. Case series and review of literature

Reumatismo ◽

10.4081/reumatismo.2021.1397 ◽

2021 ◽

Vol 73 (2) ◽

pp. 122-130

Author(s):

C.S.R. Araujo ◽

R. Miossi ◽

F.H.C. De Souza ◽

M.D. Costa ◽

A.M.S. Da Silva ◽

...

Keyword(s):

Systemic Sclerosis ◽

Inflammatory Myopathy ◽

Elevated Serum ◽

Case Series ◽

Response To Treatment ◽

Published Data ◽

Muscle Involvement ◽

Mhc I ◽

Scapular Winging ◽

Tertiary Center

This study was aimed at describing a case series of brachio-cervical inflammatory myopathy (BCIM) associated with systemic sclerosis (SSc), due to its rarity and limited coverage in published data. Another aim was to provide a literature review. We reported four cases of BCIM-SSc from our tertiary center. In addition, we researched the literature and found six articles featuring 17 patients who fit this phenotype. We pooled all cases and reported their features. Most patients were female and had limited SSc, and the median time of BCIM presentation was three years after SSc diagnosis. Asymmetric muscle involvement, scapular winging, dropped head, axial weakness, camptocormia, dysphagia, and dermatomyositis stigmas were common features. All patients had esophageal involvement. Most had positive antinuclear antibody results, a scleroderma pattern in their capillaroscopy images, elevated serum creatine phosphokinase, myopathic electrophysiology, and muscle involvement in magnetic resonance imaging. Muscle histopathological findings varied widely, but in general all showed the presence of lymphoid infiltrates, muscle atrophy, increased MHC-I expression, MAC deposits, vasculopathy, and muscle fiber necrosis. The response to immunosuppressive therapy was highly irregular. BCIM-SSc is a rare disorder that shares many similar phenotypes among the described cases, but has a highly heterogeneous response to treatment. At present, more data on the physiopathology, clinical features, and treatment is still needed.

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Anti-RuvBL1/2 autoantibodies in patients with systemic sclerosis or idiopathic inflammatory myopathy and a nuclear speckled pattern

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-220004 ◽

2022 ◽

pp. annrheumdis-2021-220004

Author(s):

Jean-Baptiste Vulsteke ◽

Yves Piette ◽

Carolien Bonroy ◽

Patrick Verschueren ◽

Daniel Blockmans ◽

...

Keyword(s):

Systemic Sclerosis ◽

Inflammatory Myopathy ◽

Idiopathic Inflammatory Myopathy ◽

Speckled Pattern

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Z-line degradation and phagocytosis of sarcomeric fragments in myonecrosis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100077529 ◽

1983 ◽

Vol 41 ◽

pp. 790-791

Author(s):

Melinda L. Estes ◽

Samuel M. Chou

Keyword(s):

Vastus Lateralis ◽

Inflammatory Myopathy ◽

Muscle Disease ◽

White Female ◽

Inflammatory Cell Infiltrate ◽

Limb Weakness ◽

Muscle Diseases ◽

History Of ◽

The Right ◽

Mononuclear Inflammatory Cell

Many muscle diseases show common pathological features although their etiology is different. In primary muscle diseases a characteristic finding is myofiber necrosis. The mechanism of myonecrosis is unknown. Polymyositis is a primary muscle disease characterized by acute and subacute degeneration as well as regeneration of muscle fibers coupled with an inflammatory infiltrate. We present a case of polymyositis with unusual ultrastructural features indicative of the basic pathogenetic process involved in myonecrosis.The patient is a 63-year-old white female with a one history of proximal limb weakness, weight loss and fatigue. Examination revealed mild proximal weakness and diminished deep tendon reflexes. Her creatine kinase was 1800 mU/ml (normal < 140 mU/ml) and electromyography was consistent with an inflammatory myopathy which was verified by light microscopy on biopsy muscle. Ultrastructural study of necrotizing myofiber, from the right vastus lateralis, showed: (1) degradation of the Z-lines with preservation of the adjacent Abands including M-lines and H-bands, (Fig. 1), (2) fracture of the sarcomeres at the I-bands with disappearance of the Z-lines, (Fig. 2), (3) fragmented sarcomeres without I-bands, engulfed by invading phagocytes, (Fig. 3, a & b ), and (4) mononuclear inflammatory cell infiltrate in the endomysium.

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