Abstract
Objective
Cutaneous polyarteritis nodosa (CPAN) is a necrotizing vasculitis of the middle-size vessels, confined to the skin. We conducted a systematic review in order to identify studies ...evaluating the different treatment modalities used in CPAN.
Methods
This systematic review was conducted according to PRISMA guidelines, registered in PROSPERO: CRD42020222195. PubMed/Medline databases were searched from inception to December of 2020 using the terms: (Polyarteritis nodosaTitle/Abstract) AND ((therapyTitle/Abstract) OR (managementTitle/Abstract) OR (treatmentTitle/Abstract))’ and ‘Cutaneous arteritis Title/Abstract’. Articles evaluating pertaining to the management of CPAN in adults were eligible for inclusion.
Results
A total of seven eligible case series with 325 unique patients were included. No study included a control population. In general, systemic corticosteroids were widely used as induction treatment. Immunosuppressive agents combined with corticosteroids were AZA, hydroxychloroquine, sulfasalazine, sulphapyridine, CYC, MTX, mycophenolate, tacrolimus, rituxima and thalidomide. Other agents utilized in the studies were dapsone, colchicine, non-steroid anti-inflammatory drugs, salicylates, warfarin and clopidogrel. In some studies, the presence of ulcerations was associated with an increased risk of relapse.
Conclusion
The evidence available regarding the management of patients with CPAN is limited at best. Further studies are needed in order to evaluate the effect of treatment on disease remission, relapses and mortality.
The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune diseases (collectively known as myositis) affecting the skeletal muscles as well as other organ systems such as ...skin, lungs, and joints. The primary forms of myositis include polymyositis (PM), dermatomyositis (PM), and immune-mediated necrotizing myopathy (IMNM). Patients with these diseases experience progressive proximal muscle weakness, have characteristic muscle biopsy findings, and produce autoantibodies that are associated with unique clinical features. One distinguishing feature of these patients is that they are also known to have an increased risk of cancer. Since the first description of the association in 1916, it has been extensively reported in the medical literature. However, there have been significant variations between the different studies with regard to the degree of cancer risk in patients with IIM. These discrepancies can, in part, be attributed to differences in the definition of malignancy-associated myositis used in different studies. In recent years, significant advances have been made in defining specific features of IIM that are associated with the development of malignancy. One of these has been myositis-specific antibodies (MSAs), which are linked to distinct clinical phenotypes and categorize patients into groups with more homogeneous features. Indeed, patients with certain MSAs seem to be at particularly increased risk of malignancy. This review attempts a systematic evaluation of research regarding the association between malignancy and myositis.
Objective
This open‐label 12‐week study was conducted to evaluate the efficacy and safety of tofacitinib, a JAK inhibitor, in treatment‐refractory active dermatomyositis (DM).
Methods
Tofacitinib in ...extended‐release doses of 11 mg was administered daily to 10 subjects with DM. Prior to treatment, a complete washout of all steroid‐sparing agents was performed. The primary outcome measure was assessment of disease activity improvement based on the International Myositis Assessment and Clinical Studies group definition of improvement. Response rate was measured as the total improvement score according to the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) myositis response criteria. Secondary outcome measures included Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) scores, chemokine levels, immunohistochemical analysis of STAT1 expression in the skin, RNA sequencing analysis, and safety.
Results
At 12 weeks, the primary outcome was met in all 10 subjects. Five (50%) of 10 subjects experienced moderate improvement in disease activity, and the other 50% experienced minimal improvement according to the 2016 ACR/EULAR myositis response criteria. The secondary outcome of the mean change in the CDASI activity score over 12 weeks was statistically significant (mean ± SD 28 ± 15.4 at baseline versus 9.5 ± 8.5 at 12 weeks) (P = 0.0005). Serum chemokine levels of CXCL9/CXCL10 showed a statistically significant change from baseline. A marked decrease in STAT1 signaling in association with suppression of interferon target gene expression was demonstrated in 3 of 9 skin biopsy samples from subjects with dermatomyositis. The mean ± SD level of creatine kinase in the 10 subjects at baseline was 82 ± 34.8 IU/liter, highlighting that disease activity was predominantly located in the skin.
Conclusion
This is the first prospective, open‐label clinical trial of tofacitinib in DM that demonstrates strong clinical efficacy of a pan‐JAK inhibitor, as measured by validated myositis response criteria. Future randomized controlled trials using JAK inhibitors should be considered for treating DM.
Objective
Prior investigations demonstrated that autoantibodies recognizing cytosolic 5′‐nucleotidase 1A (NT5C1A) are found in 33–76% of patients with inclusion body myositis (IBM) but are observed ...only rarely in patients with polymyositis (PM). Thus, anti‐NT5C1A may help distinguish IBM from PM. Although 4–21% of patients with dermatomyositis (DM) were shown to be anti‐NT5C1A antibody positive, the clinical features of anti‐NT5C1A–positive patients with DM have not been described. Furthermore, the prevalence of anti‐NT5C1A antibodies in other rheumatic conditions has not been reported. This study was undertaken to define the prevalence and clinical features of anti‐NT5C1A–positive patients with DM, PM, IBM, or other systemic autoimmune diseases.
Methods
We screened for anti‐NT5C1A autoantibodies in patients with IBM, DM, PM, Sjögren's syndrome (SS), or systemic lupus erythematosus (SLE) and in healthy volunteers. Clinical characteristics were compared between patients who were anti‐NT5C1A positive and those who were anti‐NT5C1A negative.
Results
Anti‐NT5C1A autoantibodies were detected in 71 (61%) of 117 patients with IBM, 2 (5%) of 42 patients with PM, 2 (5%) of 42 healthy volunteers, 24 (15%) of 159 patients with DM, 10 (23%) of 44 patients with SS, and 13 (14%) of 96 patients with SLE. No anti‐NT5C1A antibody–positive patients with SS or SLE had muscle involvement. Anti‐NT5C1A–positive patients with IBM had a lower prevalence of rimmed vacuoles (62% versus 83% of antibody‐negative patients; P = 0.02). No differences in the clinical characteristics of antibody‐positive and antibody‐negative patients with DM, SS, or SLE were observed.
Conclusion
Anti‐NT5C1A is a common target of circulating autoantibodies, especially in IBM but also in several different autoimmune diseases. In SLE and SS, anti‐NT5C1A autoreactivity is not associated with muscle disease.
Introduction
The diagnosis of inclusion body myositis (IBM) can be challenging, and its presentation can be confused with other forms of myositis or neuromuscular disorders. In this study we evaluate ...the ability of quantitative muscle ultrasound to differentiate between IBM and mimicking diseases.
Methods
Patients 50 years of age and older were included from two specialty centers. Muscle echogenicity and muscle thickness of four characteristically involved muscles in IBM were measured and compared with polymyositis (PM)/dermatomyositis (DM), other neuromuscular disorders, and healthy controls.
Results
Echogenicity was higher and muscle thickness generally lower in all four muscles in IBM compared with PM/DM and normal controls. When comparing IBM with the comparator groups, the flexor digitorum profundus was the most discriminative muscle.
Discussion
Ultrasound appears to be a good test to differentiate established IBM from PM/DM and neuromuscular controls, with value as a diagnostic tool for IBM.
We analyzed the prevalence of anti-mitochondrial autoantibodies (AMA) in adult- and juvenile-onset myositis longitudinal cohorts and investigated phenotypic differences in myositis patients with AMA. ...We screened sera from myositis patients including 619 adult- and 371 juvenile-onset dermatomyositis (DM, JDM), polymyositis (PM, JPM), inclusion body myositis (IBM), or amyopathic DM patients and from healthy controls, including 164 adults and 92 children, for AMA by ELISA. Clinical characteristics were compared between myositis patients with and without AMA. AMA were present in 5% of adult myositis patients (16 of 216 DM, 10 of 222 PM, 4 of 140 IBM, 1 of 19 amyopathic DM), 1% of juvenile myositis patients (3 of 302 JDM, 1 of 25 JPM), and 1% of both adult and juvenile healthy controls. In patients with adult-onset myositis, AMA were associated with persistent muscle weakness, Raynaud’s phenomenon, dysphagia, and cardiomyopathy. Adult myositis patients with AMA may have more severe or treatment refractory disease, as they more frequently received glucocorticoids and intravenous immunoglobulin. In juvenile myositis, children with AMA often had falling episodes and dysphagia, but no other clinical features or medications were significantly associated with AMA. AMA are present in 5% of adult myositis patients and associated with cardiomyopathy, dysphagia, and other signs of severe disease. The prevalence of AMA is not increased in patients with juvenile myositis compared to age-matched healthy controls. Our data suggest that the presence of AMA in adult myositis patients should prompt screening for cardiac and swallowing involvement.
Key Points
• Approximately 5% of a large North American cohort of adult myositis patients have anti-mitochondrial autoantibodies.
• Adults with anti-mitochondrial autoantibodies often have chronic weakness, Raynaud’s, dysphagia, cardiomyopathy, and more severe disease.
• Anti-mitochondrial autoantibodies are rare in juvenile myositis and not associated with a specific clinical phenotype.
ABSTRACT
Introduction: Patients with self‐limited statin‐related myopathy improve spontaneously when statins are stopped. In contrast, patients with statin‐associated autoimmune myopathy have ...autoantibodies recognizing 3‐hydroxy‐3‐methyl‐glutaryl‐coenzyme A reductase (HMGCR) and usually require immunosuppressive therapy to control their disease. On initial presentation, it can sometimes be difficult to distinguish between these 2 diseases, as both present with muscle pain, weakness, and elevated serum creatine kinase (CK) levels. The goal of this study was to determine whether patients with severe self‐limited statin‐related myopathy also make anti‐HMGCR autoantibodies. Methods: We screened 101 subjects with severe self‐limited cerivastatin‐related myopathy for anti‐HMGCR autoantibodies. Results: No patient with severe self‐limited cerivastatin‐related myopathy had anti‐HMGCR autoantibodies. Conclusion: Anti‐HMGCR autoantibody testing can be used to help differentiate whether a patient has self‐limited myopathy due to cerivastatin or autoimmune statin‐associated myopathy; these findings may apply to other statins as well. Muscle Nerve 54: 142–144, 2016
The objectives of this study were to compare the clinical features of patients with SLE with and without myopathy and to describe the muscle biopsy features of patients with SLE myopathy.
This nested ...case-control study included all subjects enrolled in the Hopkins Lupus Cohort database from May 1987 to June 2016. Subjects with elevated creatine kinase along with evidence of muscle oedema on MRI, myopathic electromyography and/or myopathic muscle biopsy features were defined as having SLE myopathy. Demographic, serological and clinical features were compared between patients with SLE with and without myopathy. Muscle biopsies were histologically classified as polymyositis, dermatomyositis, necrotising myopathy or non-specific myositis.
From among 2437 patients with SLE, 179 (7.3%) had myopathy. African American patients were more likely to develop myositis than Caucasian patients (p<0.0001). Compared with those without myopathy, patients with SLE myopathy were more likely to have malar rash (OR 1.67, 1.22-2.29), photosensitivity (OR 1.43, 1.04-1.96), arthritis (OR 1.81, 1.21-2.69), pleurisy (OR 1.77, 1.3-2.42), pericarditis (OR 1.49, 1.06-2.08), acute confusional state (OR 2.07, 1.09-3.94), lymphopaenia (OR 1.64, 1.2-2.24), anti-double-stranded DNA antibodies (OR 1.52, 1.09-2.13), lupus anticoagulant (OR 1.42, 1-2), cognitive impairment (OR 1.87, 1.12-3.13), cataract (OR 1.5, 1.04-2.18), pulmonary hypertension (OR 1.98, 1.13-3.47), pleural fibrosis (OR 2.01, 1.27-3.18), premature gonadal failure (OR 1.9, 1.05-3.43), diabetes (OR 1.92, 1.22-3.02) or hypertension (OR 1.45, 1.06-2). Among 16 muscle biopsies available for review, the most common histological classifications were necrotising myositis (50%) and dermatomyositis (38%).
Patients with SLE myopathy have a higher prevalence of numerous SLE disease manifestations. Necrotising myopathy and dermatomyositis are the most prevalent histopathological features in SLE myopathy.
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