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Frontiers in Medicine 2024Idiopathic inflammatory myopathies (IIMs) encompass a diverse group of diseases characterized by considerable variability in clinical manifestations, antibody profiles,...
Myositis-associated antibodies predict the severity of lung involvement in adult patients with inflammatory myositis - a cohort study of 70 adult patients with myositis in a single center.
INTRODUCTION
Idiopathic inflammatory myopathies (IIMs) encompass a diverse group of diseases characterized by considerable variability in clinical manifestations, antibody profiles, and responsiveness to immunosuppressive therapies. This study aimed to investigate the association between organ involvement and distinct myositis autoantibodies in individuals with IIM in a single-center cohort.
METHODS
Patients with ICD diagnoses M33.1, M33.2, M33.9, or M609 who (1) had been tested with Euroline blot assay for myositis autoantibodies and (2) met the classification criteria of definite/probable polymyositis (PM) or dermatomyositis (DM), anti-synthetase syndrome (ASS), or inclusion body myositis (IBM) were included. Medical journals were retrospectively examined with respect to clinical disease features.
RESULTS
Seventy patients (median age 58 years; 66% females) were included and represented the following diagnosis: PM ( = 23), DM ( = 21), ASS ( = 23), and IBM ( = 3). Most of the patients (87%) presented a muscle biopsy indicative of myositis. The presence of autoantibodies was as follows: myositis-specific antibodies, MSA ( = 53), myositis-associated antibodies, MAA ( = 33), both MSA + MAA ( = 24), MSA only ( = 29), MAA only ( = 9), no MSA, or MAA ( = 8). Anti-Jo-1 was the most common MSA (19%), whereas the most common MAA was anti-Ro/SSA52 (31%). We observed a significant association between antibody patterns and lung disease. In our cohort, 47% of the patients in the whole study group, 86% of patients with anti-SSA52, and 100% with anti-Jo-1 had pulmonary involvement. Patients with both MSA and MAA had a higher incidence of lung disease and decreased CO-diffusion capacity. This was especially prominent in anti-Ro/SSA52-positive patients. Interestingly, none of the patients suffered from lung disease if only antibodies against Mi-2α, Mi-2β, NXP2, HMGCR, and TIF1γ were present or no MSA/MAA were detected.
DISCUSSION
The simultaneous presence of both MAA and MSA indicates an increased risk of lung involvement in patients with inflammatory myopathies. The presence of any MAA, and especially anti-Ro/SSA52, is associated with more severe pulmonary disease. Our data suggest that MAA antibodies might be relevant markers for early detection and treatment of lung involvement in IIM.
PubMed: 38606156
DOI: 10.3389/fmed.2024.1340310 -
Journal of Clinical Medicine Feb 2024Idiopathic inflammatory myopathies (IIMs) are a group of autoimmune disorders often complicated by interstitial lung disease (ILD). The clinical characteristics and...
BACKGROUND
Idiopathic inflammatory myopathies (IIMs) are a group of autoimmune disorders often complicated by interstitial lung disease (ILD). The clinical characteristics and outcomes of IIM-associated ILD have been reported variably, but the literature on rural populations is scarce.
METHODS
A retrospective cross-sectional study was conducted at a rural tertiary academic medical center. Twenty-nine patients met the final inclusion criteria. The primary outcome was to assess the disease state and immunological and radiographic features of IIM-associated ILD. Secondary outcomes included disease progression, ILD exacerbation, mortality rate, and factors associated with poor outcome.
RESULTS
Dermatomyositis (n = 15, 51.72%) followed by polymyositis (n = 8, 27.58%) were predominant myopathies. The most common autoantibodies were anti-Jo1 antibodies (n = 11, 37.93%). Indeterminate usual interstitial pneumonitis (41.30%, n = 12) was the most common radiographic pattern followed by non-specific interstitial pneumonia (n = 5, 17.24%). ILD exacerbation (n = 14, 66.66%) and mortality rate (n = 6, 20.69%) were high. Albumin levels were significantly lower in patients who died.
CONCLUSIONS
The clinical characteristics of patients with IIM-associated ILD in rural Appalachia exhibit notable distinctions, and outcomes are worse compared to other populations. Larger studies are needed to investigate other prognostics factors and longitudinal trends of clinical characteristics and outcomes of IIM-associated ILD in rural populations.
PubMed: 38592101
DOI: 10.3390/jcm13051294 -
BMC Pulmonary Medicine Apr 2024Autoimmune pulmonary alveolar proteinosis (APAP) is a diffuse lung disease that causes abnormal accumulation of lipoproteins in the alveoli; however, its pathogenesis...
A case of autoimmune pulmonary alveolar proteinosis during the course of treatment of rapidly progressive interstitial pneumonia associated with anti-MDA5 antibody-positive dermatomyositis.
BACKGROUND
Autoimmune pulmonary alveolar proteinosis (APAP) is a diffuse lung disease that causes abnormal accumulation of lipoproteins in the alveoli; however, its pathogenesis remains unclear. Recently, APAP cases have been reported during the course of dermatomyositis. The combination of these two diseases may be coincidental; however, it may have been overlooked because differentiating APAP from a flare-up of interstitial pneumonia associated with dermatomyositis is challenging. This didactic case demonstrates the need for early APAP scrutiny.
CASE PRESENTATION
A 50-year-old woman was diagnosed with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatitis and interstitial pneumonia in April 2021. The patient was treated with corticosteroids, tacrolimus, and cyclophosphamide pulse therapy for interstitial pneumonia complicated by MDA5 antibody-positive dermatitis, which improved the symptoms and interstitial pneumonia. Eight months after the start of treatment, a new interstitial shadow appeared that worsened. Therefore, three additional courses of cyclophosphamide pulse therapy were administered; however, the respiratory symptoms and interstitial shadows did not improve. Respiratory failure progressed, and 14 months after treatment initiation, bronchoscopy revealed turbid alveolar lavage fluid, numerous foamy macrophages, and numerous periodic acid-Schiff-positive unstructured materials. Blood test results revealed high anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody levels, leading to a diagnosis of APAP. The patient underwent whole-lung lavage, and the respiratory disturbance promptly improved. Anti-GM-CSF antibodies were measured from the cryopreserved serum samples collected at the time of diagnosis of anti-MDA5 antibody-positive dermatitis, and 10 months later, both values were significantly higher than normal.
CONCLUSIONS
This is the first report of anti-MDA5 antibody-positive dermatomyositis complicated by interstitial pneumonia with APAP, which may develop during immunosuppressive therapy and be misdiagnosed as a re-exacerbation of interstitial pneumonia. In anti-MDA5 antibody-positive dermatomyositis, APAP comorbidity may have been overlooked, and early evaluation with bronchoalveolar lavage fluid and anti-GM-CSF antibody measurements should be considered, keeping the development of APAP in mind.
Topics: Female; Humans; Middle Aged; Pulmonary Alveolar Proteinosis; Dermatomyositis; Autoantibodies; Lung Diseases, Interstitial; Cyclophosphamide; Dermatitis; Interferon-Induced Helicase, IFIH1; Autoimmune Diseases
PubMed: 38589870
DOI: 10.1186/s12890-024-02989-9 -
RMD Open Apr 2024We aimed to explore a new and readily available practical marker for rapidly progressive interstitial lung disease (RP-ILD) and poor short-term outcomes in patients with...
AIM
We aimed to explore a new and readily available practical marker for rapidly progressive interstitial lung disease (RP-ILD) and poor short-term outcomes in patients with idiopathic inflammatory myopathies (IIM).
METHODS
A total of 1822 consecutive patients with IIM between 2009 and 2021 were evaluated retrospectively. All proven cases of naïve ILD with complete medical records were included. Red cell distribution width (RDW) values at the initial stage, 3 months and last follow-up were collected. The clinical characteristics and outcomes of the patients were recorded.
RESULTS
We identified 532 patients with IIM with an average follow-up of 4 years. ILD prevalence was higher in patients of elevated RDW (p<0.001). The patients with ILD and elevated RDW had lower levels of PaO/FiO, FVC% and DLco% and a higher prevalence of RP-ILD than those with normal RDW (p<0.001). Prognostic analysis revealed that RDW was an independent risk factor for prognosis in patients with IIM-ILD (HR=2.9, p=0.03). Patients with dermatomyositis (DM) with RP-ILD with a change in RDW within 3 months (∆RDW-3) greater than 0 were more likely to die within 3 months. Moreover, the prevalence of ∆RDW-3>0 was higher in patients with RP-ILD and positive for anti-melanoma differentiation-associated gene 5 antibody who died within 3 months (87.5%) compared with those alive at 3 months (24.6%) (p<0.001).
CONCLUSION
These findings suggest that repeated RDW assays could assist physicians in identifying patients with DM-ILD who were at a high risk of RP-ILD and death.
Topics: Humans; Dermatomyositis; Retrospective Studies; Erythrocyte Indices; Lung Diseases, Interstitial; Myositis
PubMed: 38580342
DOI: 10.1136/rmdopen-2023-003931 -
Swiss Medical Weekly Mar 2024We report the first case of anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis as a systemic immune-related adverse event in a 64-year-old...
We report the first case of anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis as a systemic immune-related adverse event in a 64-year-old man receiving pembrolizumab to treat advanced lung cancer. The patient experienced hypothyroidism, myalgia, skin involvement, dyspnoea and diarrhoea. Laboratory tests revealed raised inflammatory markers, hypercreatinekinasemia and anti-MDA5 autoantibodies. Electroneuromyography and pathognomonic signs on physical examination confirmed the diagnosis of pauci-myopathic dermatomyositis. Pembrolizumab was discontinued and immunosuppressive therapy led to rapid and progressive improvement, with complete remission of dermatomyositis. This case report widens the spectrum of systemic immune-related adverse events associated with pembrolizumab.
Topics: Humans; Male; Middle Aged; Antibodies, Monoclonal, Humanized; Autoantibodies; Dermatomyositis; Interferon-Induced Helicase, IFIH1; Lung Diseases, Interstitial; Lung Neoplasms
PubMed: 38579289
DOI: 10.57187/s.3513 -
Annals of Medicine and Surgery (2012) Apr 2024Dermatomyositis (DM), sometimes referred to as inflammatory and degenerative changes in the skin and muscles, is a rare autoimmune disorder. DM is distinguished by...
INTRODUCTION AND IMPORTANCE
Dermatomyositis (DM), sometimes referred to as inflammatory and degenerative changes in the skin and muscles, is a rare autoimmune disorder. DM is distinguished by myopathic disease, symmetrical proximal muscle weakness, and increased creatine kinase (CK).
CASE PRESENTATION
A 30-year-old-female presented to the department of dermatology with a history of chronic right hand pain spreading to the shoulder, severe tachycardia, and dyspenia that increased during routine tasks like using the bathroom. What makes this case unique is that the CPK developed without doubling, and the final concentration was 207 ng/ml. Other common clinical symptoms include amyopathic/hypomyopathic muscle involvement and DM-specific rash (Gottron's papules, heliotrope rash), and these manifestations were in our patients. Sun protection, topical treatment with corticosteroids and/or calcineurin inhibitors, and systemic medication should be utilized for all individuals with nonvasculopathic disease. In our case, the patient stopped using azathioprine and began taking methotrexate.
CLINICAL DISCUSSION
Sun protection, topical therapy with corticosteroids and/or calcineurin inhibitors, and systemic medication should be utilized in layers for all individuals with nonvasculopathic illnesses. Mycophenolat Mofetil is beneficial in treating refractory illnesses as well as individuals with interstitial lung disease or substantial skin disease.
CONCLUSION
Even if test findings are not conclusive, dermatomyositis should always be considered when muscular weakness manifests. It's important to distinguish the disorder from connective tissue diseases like lupus erythematosus. In fact, to correctly diagnose DM, if there are any doubts, a muscle biopsy is required.
PubMed: 38576947
DOI: 10.1097/MS9.0000000000001682 -
Frontiers in Immunology 2024We performed a single-arm meta-analysis to evaluate the efficacy and safety of JAK inhibitors in the treatment of dermatomyositis (DM)/ polymyositis (PM). (Meta-Analysis)
Meta-Analysis
INTRODUCTION
We performed a single-arm meta-analysis to evaluate the efficacy and safety of JAK inhibitors in the treatment of dermatomyositis (DM)/ polymyositis (PM).
METHODS
Relevant studies from four databases were systematically searched until April 25, 2023. The primary endpoint was Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) and other outcomes were Manual Muscle Testing (MMT) and Creatine Kinase (CK). According to the type of JAK and medication regimen, we conducted subgroup analyses. The registration number in PROSPERO was CRD42023416493.
RESULTS
According to the selection criteria, we identified 7 publications with a total of 91 patients. Regarding skin lesions, the CDASI decreased by 17.67 (95% CI: -20.94 ~ -14.41). The CK increased by 8.64 U (95% CI: -28.25 ~ 45.53). About muscle lesions, MMT increased by 10.31 (95% CI: -2.83 ~ 23.46). Subgroup analysis revealed that different types of JAK inhibitors had various degrees of reduction. CDASI in patients treated with RUX had the lowest one [-20.00 (95% CI: -34.9 ~ -5.1)], followed by TOF [-18.29 (95% CI: -21.8 ~ -14.78)] and BAR [-11.2 (95% CI: -21.51 ~ -0.89)]. Additionally, the mean reduction in CDASI in patients treated with TOF alone was 16.16 (95% CI: -21.21 ~ -11.11), in combination with other immunosuppressants was 18.59 (95% CI: -22.74 ~ -14.45). For safety evaluation, one patient developed Orolabial HSV, and two patients developed thromboembolism events.
DISCUSSION
In summary, this meta-analysis demonstrated that JAK inhibitors can potentially treat DM/PM without severe adverse reactions.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42023416493, identifier CRD42023416493.
Topics: Humans; Dermatomyositis; Immunosuppressive Agents; Janus Kinase Inhibitors; Polymyositis; Skin
PubMed: 38576610
DOI: 10.3389/fimmu.2024.1382728 -
Sarcoidosis, Vasculitis, and Diffuse... Mar 2024Anti-aminoacyl-tRNA synthetase (ARS) antibodies form a condition called Antisynthetase syndrome (ASSD). While interstitial lung disease (ILD) is a particularly frequent...
BACKGROUND AND AIM
Anti-aminoacyl-tRNA synthetase (ARS) antibodies form a condition called Antisynthetase syndrome (ASSD). While interstitial lung disease (ILD) is a particularly frequent manifestation of ASSD and is closely associated with morbidity and mortality, few studies have been conducted on its characteristics on high-resolution computed tomography (HRCT). In this study, we clarified the HRCT findings in patients with anti-ARS antibody-positive ILD (ARS-ILD). Methods: The HRCT findings at the time of the ILD diagnosis in 24 ARS-ILD patients were retrospectively evaluated by 2 pulmonologists and one radiologist. We also assessed the clinical symptoms, physical examination findings, and laboratory data including the type of anti-ARS antibodies. For a further analysis, the data of patients were divided into two groups: the polymyositis (PM)/dermatomyositis (DM) group and the non-PM/DM group.
RESULTS
The ratio of men to women was almost 1:1. The median age at the time of the diagnosis was 53 years old. Anti-glycyl (anti-EJ) and anti-histidyl (anti-Jo-1) antibodies were more common than others. An analysis of the HRCT patterns of 23 ARS-ILD patients showed that the most common pattern was the nonspecific interstitial pneumonia (NSIP) pattern. The second most common pattern was the usual interstitial pneumonia (UIP) pattern. Between the PM/DM and non-PM/DM groups, no clear trends were noted in the age, sex ratio, proportion of HRCT patterns, or type of anti-ARS antibodies.
CONCLUSIONS
This retrospective study demonstrated that ARS-ILD patients, regardless of myositis symptoms, most often showed the NSIP pattern on HRCT, as previously reported. However, unlike previous reports, the UIP pattern on HRCT was not rare.
PubMed: 38567566
DOI: 10.36141/svdld.v41i1.14144 -
Frontiers in Immunology 2024Lupus pathogenesis is mainly ascribed to increased production and/or impaired clearance of dead cell debris. Although self-reactive T and B lymphocytes are critically...
Reduced expressions of apoptosis-related proteins TRAIL, Bcl-2, and TNFR1 in NK cells of juvenile-onset systemic lupus erythematosus patients: relations with disease activity, nephritis, and neuropsychiatric involvement.
BACKGROUND
Lupus pathogenesis is mainly ascribed to increased production and/or impaired clearance of dead cell debris. Although self-reactive T and B lymphocytes are critically linked to lupus development, neutrophils, monocytes, and natural killer (NK) cells have also been implicated. This study assessed apoptosis-related protein expressions in NK cells of patients with juvenile-onset systemic lupus erythematosus (jSLE) and relations to disease activity parameters, nephritis, and neuropsychiatric involvement.
METHODS
Thirty-six patients with jSLE, 13 juvenile dermatomyositis (JDM) inflammatory controls, and nine healthy controls had Fas, FasL, TRAIL, TNFR1, Bcl-2, Bax, Bim, and caspase-3 expressions in NK cells (CD3-CD16+CD56+) simultaneously determined by flow cytometry. Disease activity parameters included Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, erythrocyte sedimentation rate, C-reactive protein level, anti-double strain DNA antibody level, complement fractions C3 and C4 levels.
RESULTS
Patients with jSLE had a profile of significantly reduced expression of TRAIL, Bcl-2, and TNFR1 proteins in NK cells when compared to healthy controls. Similar profile was observed in patients with jSLE with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. Patients with jSLE with positive anti-dsDNA also had reduced expression of Bax in NK cells when compared healthy controls and to those with negative anti-dsDNA. Yet, patients with jSLE with negative anti-dsDNA had reduced mean fluorescence intensity (MFI) of Bim in NK cells compared to healthy controls. Patients with jSLE with nephritis also had reduced MFI of Fas in NK cells when compared to those without nephritis. In addition, in patients with jSLE, the proportion of FasL-expressing NK cells directly correlated with the SLEDAI-2K score (rs = 0.6, p = 0.002) and inversely correlated with the C3 levels (rs = -0.5, p = 0.007). Moreover, patients with jSLE had increased NK cell percentage and caspase-3 protein expression in NK cells when compared to JDM controls.
CONCLUSION
This study extends to NK cells an altered profile of TRAIL, Bcl-2, TNFR1, Fas, FasL, Bax, Bim, and caspase-3 proteins in patients with jSLE, particularly in those with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. This change in apoptosis-related protein expressions may contribute to the defective functions of NK cells and, consequently, to lupus development. The full clarification of the role of NK cells in jSLE pathogenesis may pave the way for new therapies like those of NK cell-based.
Topics: Humans; Antibodies, Antinuclear; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Dermatomyositis; Killer Cells, Natural; Lupus Erythematosus, Systemic; Lupus Nephritis; Receptors, Tumor Necrosis Factor, Type I
PubMed: 38562920
DOI: 10.3389/fimmu.2024.1327255 -
Journal of Medical Case Reports Apr 2024To our knowledge, there is no previous report in the literature of non-traumatic neglected complete cervical spine dislocation characterized by anterior spondyloptosis...
BACKGROUND
To our knowledge, there is no previous report in the literature of non-traumatic neglected complete cervical spine dislocation characterized by anterior spondyloptosis of C4, extreme head drop, and irreducible cervicothoracic kyphosis.
CASE PRESENTATION
We report the case of a 33-year-old Caucasian man with a 17-year history of severe immune polymyositis and regular physiotherapy who presented with severe non-reducible kyphosis of the cervicothoracic junction and progressive tetraparesia for several weeks after a physiotherapy session. Radiographs, computed tomography, and magnetic resonance imaging revealed a complete dislocation at the C4-C5 level, with C4 spondyloptosis, kyphotic angulation, spinal cord compression, and severe myelopathy. Due to recent worsening of neurological symptoms, an invasive treatment strategy was indicated. The patient's neurological status and spinal deformity greatly complicated the anesthetic and surgical management, which was planned after extensive multidisciplinary discussion and relied on close collaboration between the orthopedic surgeon and the anesthetist. Regarding anesthesia, difficult airway access was expected due to severe cervical angulation, limited mouth opening, and thyromental distance, with high risk of difficult ventilation and intubation. Patient management was further complicated by a theoretical risk of neurogenic shock, motor and sensory deterioration, instability due to position changes during surgery, and postoperative respiratory failure. Regarding surgery, a multistage approach was carefully planned. After a failed attempt at closed reduction, a three-stage surgical procedure was performed to reduce displacement and stabilize the spine, resulting in correct spinal realignment and fixation. Progressive complete neurological recovery was observed.
CONCLUSION
This case illustrates the successful management of a critical situation based on a multidisciplinary collaboration involving radiologists, anesthesiologists, and spine surgeons.
Topics: Male; Humans; Adult; Cervical Vertebrae; Spinal Cord Compression; Spinal Injuries; Radiography; Kyphosis
PubMed: 38556889
DOI: 10.1186/s13256-024-04446-x