Objective. To investigate whether fasciitis is histopathologically demonstrable in patients with dermatomyositis (DM), and to analyze the process of inflammatory progression in myopathy accompanying DM.Methods. STIR or fat-suppressed T2-weighted magnetic resonance imaging (MRI) and en bloc biopsy were performed in 14 patients with newly diagnosed adult-onset DM. The severity of inflammatory cell infiltration around the fascial and intramuscular small blood vessels was evaluated using the total vascular inflammation score (TVIS).Results. In all patients, MRI revealed abnormal hyperintensity in the fascia and in marginal sites of the muscle, predominantly over central sites. En bloc biopsy revealed the presence of fasciitis in most of the patients, as shown by inflammatory infiltrates around the fascial small blood vessels. In those patients who underwent en bloc biopsy earlier than 2 months after the appearance of muscle symptoms, the TVIS of the fascia was significantly higher than the TVIS of the muscle. In contrast, in those patients who underwent en bloc biopsy >2 months after muscle symptom onset, the TVIS of the fascia did not differ significantly from the TVIS of the muscle. Conclusion.Fasciitis was histopathologically demonstrated in patients with newly diagnosed adultonset DM as early as 2 months after the onset of muscle symptoms. These results indicate that fasciitis is a common lesion of DM and suggest that the fascial microvasculature is the primary site of inflammatory cell infiltration in DM. Fasciitis may contribute to muscle symptoms in patients with DM without myositis.
ObjectiveTo define the characteristic findings on MRI of skeletal muscles in patients with dermatomyositis (DM) relative to those in patients with other idiopathic inflammatory myopathies (IIMs) and to assess their diagnostic performance in DM.MethodsThirty-six patients with DM, 17 patients with amyopathic DM, 19 patients with polymyositis and 16 patients with non-IIM classified by the 2017 European League Against Rheumatism/American College of Rheumatology criteria were included in this study. The following MRI findings (short-tau inversion recovery [STIR] and gadolinium-enhanced fat-suppressed T1-weighted imaging [Gd-T1WI]) for proximal limb muscles were compared between the disease groups and between myositis-specific autoantibodies/myositis-associated autoantibodies (MSAs/MAAs)-positive and MSAs/MAAs-negative groups: structures with high signal intensity (HSI) (subcutaneous, fascia, muscle); distributions of HSI areas in muscle (diffuse, patchy, peripheral) and patterns of HSI in muscle (honeycomb, foggy, strong HSI). Univariate, multivariate and receiver-operating characteristic [ROC] analyses were performed to assess the diagnostic performance of MRI in DM.ResultsThe characteristic MRI findings in patients with DM were subcutaneous HSI, fascial HSI, peripheral distribution and honeycomb pattern. The MRI findings in the MSAs/MAAs-positive group included more frequent fascial HSI but less frequent foggy pattern compared with the MSAs/MAAs-negative group. Likelihood of DM score ≥ 3 (obtained by counting the number of characteristic MRI findings in patients with DM) showed good diagnostic performance in DM (STIR: sensitivity 72.2%, specificity 88.5%, area under ROC curve [AUC] 84.9%; Gd-T1WI: sensitivity 81.2%, specificity 91.5%, AUC 89.9%).ConclusionThe characteristic MRI findings of skeletal muscles can predict patients with DM as well as patients with MSAs/MAAs.
Objective.To evaluate the clinical significance of serum levels of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), and angiopoietin-2 (Ang-2) in patients with rheumatoid arthritis (RA).Methods.The subjects were 70 patients with RA. Serum VEGF, Ang-1, and Ang-2 levels were determined by ELISA. As indices of disease activity, serum levels of C-reactive protein (CRP) and matrix metalloprotease (MMP)-3 were examined, and the 28-joint count Disease Activity Score (DAS28)-CRP was calculated. Power Doppler ultrasonography was performed in the bilateral wrists, elbows, shoulders, knees and ankles. The synovial blood flow signals were scored using a 3-grade scale (0–2), and the total of the scores in the 10 joints was regarded as the total signal score (TSS).Results.Serum VEGF level showed significant correlations with serum CRP and MMP-3 levels, DAS28-CRP, and TSS. Serum Ang-1 level showed significant correlations with serum MMP-3 level and DAS28-CRP. Serum Ang-2 level showed significant correlations with serum CRP level and TSS.Conclusion.The serum VEGF level is important as an index of the activity of RA based on angiogenesis and a prognostic factor regarding joint destruction. Serum Ang-1 level may be useful as an index of sustained arthritis based on the maintenance of newly formed vessels. Serum Ang-2 level may reflect a state of marked angiogenesis.
BackgroundProkineticin 2 (PK2) expression is upregulated in mice with collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis. The purpose of our study was to investigate the effects of PK2 inhibition on CIA.MethodsPK2, prokineticin receptor (PKR) 1, and PKR2 mRNA transcripts in the joints of CIA mice were measured by real-time PCR on Days 21, 28, and 35 (n = 15/day). Localization of PKR1 and PKR2 proteins was examined immunohistochemically. PKRA7, a PK2 antagonist, was administered intraperitoneally for 2 weeks to CIA mice, and the severity of arthritis was compared between treated (n = 12) and untreated (n = 12) mice. The gene expression levels of inflammatory cytokines IL-1β, IL-6, TNF-α, and VEGF were also measured by real-time PCR and compared between treated (n = 6) and untreated (n = 6) CIA mice. The data was statistically analyzed, and P values of less than 0.05 were considered significant.ResultsIn the thickened synovial membrane, PKR1 protein was expressed in infiltrating neutrophils, while PKR2 expression was found in macrophage-like mononuclear cells. PK2 gene expression was significantly more pronounced on Days 28 and 35 than on Day 21 (2.15 and 2.03 versus 1.00, P = 0.0311 and 0.0247; Dunn’s multiple comparison). PKR2 gene expression levels were significantly higher on Days 28 and 35 compared to Day 21 (25.4 and 39.3 versus 1.0, P = 0.002 and < 0.0001; Dunn’s multiple comparison). Administration of PKRA7 suppressed the severity of arthritis (P < 0.001; two-way analysis of variance). A gene expression analysis of inflammatory cytokines revealed significantly reduced IL-1β and lL-6 expression in the joints of PKRA7-treated mice compared to untreated mice (0.1 versus 1.0, P = 0.0043 and 0.04 versus 1.0, P = 0.0022, respectively; Mann-Whitney test).ConclusionsPK2 inhibition suppressed arthritis in mice with CIA.
In our limited population, PDUS was useful for the detection of fasciitis associated with DM, especially in the early stage of disease. The increased blood flow signal as detected by PDUS is involved in angiogenesis accompanying fasciitis in patients with DM.
A 15-year-old young woman received the Human papillomavirus (HPV) vaccines. Following the second HPV vaccination, intermittent fever, myalgia, arthritis and malar rash developed, and she was admitted to our hospital. Laboratory studies showed positive results for antinuclear antibody, anti-dsDNA antibody and anti-Sm antibody. Systemic lupus erythematosus (SLE) was diagnosed according to the Systemic Lupus International Collaborative Clinics 2012. Magnetic resonance imaging showed abnormal hyperintense areas in the fascia, and en bloc biopsy showed fasciitis. Treatment with prednisolone resulted in an amelioration of the symptoms. Reportedly, SLE developed after HPV vaccinations in some patients. Most such patients have a past or family history of autoimmune disease and presented SLE symptoms after the second vaccination. We describe herein a patient in whom SLE developed in association with HPV vaccination.
Both prophylactic and therapeutic administration of endostatin inhibited type II CIA in mice. The administration method using an osmotic pump is useful.
We appreciate the comments provided by Dr. Bhansing and colleagues 1 in response to our article 2. Recently, Bhansing, et al showed a significant 2-fold increase in the fascia thickness of the deltoid muscles on ultrasonography (US) in patients with dermatomyositis (DM) and polymyositis (PM) relative to healthy controls 3. Additionally, they showed that the deltoid fascial thickness on US in patients with DM and PM was not associated with various clinical variables, including the disease duration, serum creatine kinase, the Health Assessment Questionnaire-Disability Index score, sex, antinuclear antibody, anti-Jo1, the subtype of idiopathic inflammatory myopathy, the clinical disease state, and the presence of interstitial lung disease. In our study, the histopathological examination of fascia specimens from patients with DM and PM demonstrated that the frequency and severity of fasciitis in patients with DM was significantly higher than in patients with PM. We agree that the deltoid fascial thickness on US was increased in DM. Among the patients in our analysis, all of those who were positive for anti-Jo1 antibodies had fasciitis, irrespective of whether they had skin symptoms. The individual antiaminoacyl-tRNA synthetase antibodies, including the anti-Jo1 antibody, may be associated with fasciitis in DM and PM. In both our study and the study by Bhansing, et al, PM was diagnosed according to the Bohan and Peter criteria 4. PM, as defined by the Bohan and Peter criteria, includes antisynthetase syndrome, immune-mediated necrotizing myopathy, overlap myositis, and other similar diseases. Their study population could also have included different phenotypes in the PM group. Further studies are required to confirm the association between these different phenotypes and fasciitis. We analyzed the relationship between histopathologically proven fasciitis and the clinical variables in patients with DM and PM, and found that among the clinical variables, only myalgia (and not myositis) was associated with fasciitis. However, it may be difficult to prove whether fascial thickness on US is associated with clinical symptoms, including myalgia in patients with DM and PM. The fascia consists of 3 layers: an outer layer (collagen fibers adjacent to the subcutaneous tissue), a middle layer (massive collagen fiber bundles), and an inner layer (loose connective tissue adjacent to muscle tissue) 5. The innervation was abundantly distributed, especially in the outer and inner layers in the fascia (but not in the middle layer) 6. In our previous study, fascial inflammation in DM was observed in not only the middle layer (fascia), but also the outer (epifascial tissue) and inner (subfascial tissue) layers 7. The fascia on US is mainly derived from the middle layer. Moreover, the fascial thickening on US may have many causes other than fasciitis, including-but not limited tofibrosis and edema. Conversely, the increased blood flow that was detected by power Doppler ultrasonography (PDUS) is involved in the inflammation of all layers of...
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