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Modern Rheumatology Jan 2019Although rheumatologists, neurologists and dermatologists see patients with polymyositis (PM) and dermatomyositis (DM), their management appears to vary depending on the...
Although rheumatologists, neurologists and dermatologists see patients with polymyositis (PM) and dermatomyositis (DM), their management appears to vary depending on the physician's specialty. The aim of the present study was to establish the treatment consensus among specialists of the three fields to standardize the patient care. We formed a research team supported by a grant from the Ministry of Health, Labor and Welfare, Japan. Clinical questions (CQ) on the management of PM and DM were raised. A published work search on CQ was performed primarily using PubMed. Using the nominal group technique, qualified studies and results in the published work were evaluated and discussed to reach consensus recommendations. They were sent out to the Japan College of Rheumatology, Japanese Society of Neurology and Japanese Dermatological Association for their approval. We reached a consensus in 23 CQ and made recommendations and a decision tree for management was proposed. They were officially approved by the three scientific societies. In conclusion, a multidisciplinary treatment consensus for the management of PM and DM was established for the first time.
Topics: Consensus; Dermatology; Dermatomyositis; Disease Management; Humans; Japan; Neurology; Polymyositis; Practice Guidelines as Topic; Rheumatology; Societies, Medical
PubMed: 30565491
DOI: 10.1080/14397595.2018.1521185 -
Acta Dermato-venereologica Mar 2019Anti-transcriptional intermediary factor-1γ (TIF-1γ) autoantibody may be associated with cancer in adult patients with dermatomyositis. The aim of this study was to... (Meta-Analysis)
Meta-Analysis
Anti-transcriptional intermediary factor-1γ (TIF-1γ) autoantibody may be associated with cancer in adult patients with dermatomyositis. The aim of this study was to evaluate the risk of cancer in the presence of anti-TIF-1γ autoantibody in adult dermatomyositis. A comprehensive database search of EMBASE, MEDLINE and the Cochrane Library up to May 2018 was performed using the main key words "dermatomyositis", ""myositis", "inflammatory myopathies" and "anti-TIF-1". Eighteen studies, with a total of 1,962 dermatomyositis, were included in the meta-analysis. The pooled prevalence of cancer-associated dermatomyositis in patients with anti-TIF-1γ autoantibody was 0.41 (95% confidence interval (CI) 0.36-0.45). In the presence of anti-TIF-1γ autoantibody, the overall diagnostic odds ratio of cancer was 9.37 (95% CI 5.37-16.34) with low heterogeneity (Cochran's Q: 14.88 (df = 17, p = 0.604); I2 = 0%). The results of this systematic review confirm that detection of anti-TIF-1γ autoantibody is a valuable tool to identify a subset of adult dermatomyositis patients with higher risk of cancer.
Topics: Autoantibodies; Dermatomyositis; Humans; Neoplasms; Predictive Value of Tests; Prevalence; Prognosis; Risk Assessment; Risk Factors; Transcription Factors
PubMed: 30460368
DOI: 10.2340/00015555-3091 -
The Cochrane Database of Systematic... Jan 2018Approximately one-third of individuals with interstitial lung disease (ILD) have associated connective tissue disease (CTD). The connective tissue disorders most... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Approximately one-third of individuals with interstitial lung disease (ILD) have associated connective tissue disease (CTD). The connective tissue disorders most commonly associated with ILD include scleroderma/systemic sclerosis (SSc), rheumatoid arthritis, polymyositis/dermatomyositis, and Sjögren's syndrome. Although many people with CTD-ILD do not develop progressive lung disease, a significant proportion do progress, leading to reduced physical function, decreased quality of life, and death. ILD is now the major cause of death amongst individuals with systemic sclerosis.Cyclophosphamide is a highly potent immunosuppressant that has demonstrated efficacy in inducing and maintaining remission in autoimmune and inflammatory illnesses. However this comes with potential toxicities, including nausea, haemorrhagic cystitis, bladder cancer, bone marrow suppression, increased risk of opportunistic infections, and haematological and solid organ malignancies.Decision-making in the treatment of individuals with CTD-ILD is difficult; the clinician needs to identify those who will develop progressive disease, and to weigh up the balance between a high level of need for therapy in a severely unwell patient population against the potential for adverse effects from highly toxic therapy, for which only relatively limited data on efficacy can be found. Similarly, it is not clear whether histological subtype, disease duration, or disease extent can be used to predict treatment responsiveness.
OBJECTIVES
To assess the efficacy and adverse effects of cyclophosphamide in the treatment of individuals with CTD-ILD.
SEARCH METHODS
We performed searches on CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science up to May 2017. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles.
SELECTION CRITERIA
We included randomised controlled parallel-group trials that compared cyclophosphamide in any form, used individually or concomitantly with other immunomodulating therapies, versus non-cyclophosphamide-containing therapies for at least six months, with follow-up of at least 12 months from the start of treatment.
DATA COLLECTION AND ANALYSIS
We imported studies identified by the search into a reference manager database. We retrieved the full-text versions of relevant studies, and two review authors independently extracted data. Primary outcomes were change in lung function (change in forced vital capacity (FVC) % predicted and diffusing capacity of the lung for carbon monoxide (DLCO) % predicted), adverse events, and health-related quality of life measures. Secondary outcomes included all-cause mortality, dyspnoea, cough, and functional exercise testing. When appropriate, we performed meta-analyses and subgroup analyses by severity of lung function, connective tissue disease diagnosis, and radiological pattern of fibrosis. We assessed the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and created 'Summary of findings' tables.
MAIN RESULTS
We included in the analysis four trials with 495 participants (most with systemic sclerosis). We formed two separate comparisons: cyclophosphamide versus placebo (two trials, 195 participants) and cyclophosphamide versus mycophenolate (two trials, 300 participants). We found evidence to be of low quality, as dropout rates were high in the intervention groups, and as we noted a wide confidence interval around the effect with small differences, which affected the precision of results.The data demonstrates significant improvement in lung function with cyclophosphamide compared with placebo (post-treatment FVC % mean difference (MD) 2.83, 95% confidence interval (CI) 0.80 to 4.87; P = 0.006) but no significant difference in post-treatment DLCO (% MD -1.68, 95% CI -4.37 to 1.02; P = 0.22; two trials, 182 participants).Risk of adverse effects was increased in the cyclophosphamide treatment groups compared with the placebo groups, in particular, haematuria, leukopenia, and nausea, leading to a higher rate of withdrawal from cyclophosphamide treatment. The data demonstrates statistically significant improvement in one-measure of quality of life in one trial favouring cyclophosphamide over placebo and clinically and statistically significant improvement in breathlessness in one trial favouring cyclophosphamide compared with placebo, with no significant impact on mortality.Trialists reported no significant impact on lung function when cyclophosphamide was used compared with mycophenolate at 12 months (FVC % MD -0.82, 95% CI -3.95 to 2.31; P = 0.61; two trials, 149 participants; DLCO % MD -1.41, 95% CI -10.40 to 7.58; P = 0.76; two trials, 149 participants).Risk of side effects was increased with cyclophosphamide versus mycophenolate, in particular, leukopenia and thrombocytopenia.The data demonstrates no significant impact on health-related quality of life, all-cause mortality, dyspnoea, or cough severity in the cyclophosphamide group compared with the mycophenolate group. No trials reported outcomes associated with functional exercise tests.We performed subgroup analysis to determine whether severity of lung function, connective tissue disease diagnosis, or radiological pattern had any impact on outcomes. One trial reported that cyclophosphamide protected against decreased FVC in individuals with worse fibrosis scores, and also showed that cyclophosphamide may be more effective in those with worse lung function. No association could be made between connective tissue disease diagnosis and outcomes.
AUTHORS' CONCLUSIONS
This review, which is based on studies of varying methodological quality, demonstrates that overall, in this population, small benefit may be derived from the use of cyclophosphamide in terms of mean difference in % FVC when compared with placebo, but not of the difference in % DLCO, or when compared with mycophenolate. Modest clinical improvement in dyspnoea may be noted with the use of cyclophosphamide. Clinical practice guidelines should advise clinicians to consider individual patient characteristics and to expect only modest benefit at best in preserving FVC. Clinicians should carefully monitor for adverse effects during treatment and in the years thereafter.Further studies are required to examine the use of cyclophosphamide; they should be adequately powered to compare outcomes within different subgroups, specifically, stratified for extent of pulmonary infiltrates on high-resolution computed tomography (HRCT) and skin involvement in SSc. Studies on other forms of connective tissue disease are needed. Researchers may consider comparing cyclophosphamide (a potent immunosuppressant) versus antifibrotic agents, or comparing both versus placebo, in particular, for those with evidence of rapidly progressive fibrotic disease, who may benefit the most.
Topics: Connective Tissue Diseases; Cyclophosphamide; Humans; Immunosuppressive Agents; Lung; Lung Diseases, Interstitial; Quality of Life; Randomized Controlled Trials as Topic; Scleroderma, Systemic; Vital Capacity
PubMed: 29297205
DOI: 10.1002/14651858.CD010908.pub2 -
Irish Journal of Medical Science Aug 2018Dermatomyositis (DM) is an idiopathic inflammatory myositis. The principal characteristics are cutaneous rash, muscle ache, and muscle weakness. In the past,... (Review)
Review
BACKGROUND
Dermatomyositis (DM) is an idiopathic inflammatory myositis. The principal characteristics are cutaneous rash, muscle ache, and muscle weakness. In the past, associations have been established between DM and malignancy, including colorectal cancer.
METHODS
A systematic PubMed and Scopus search was conducted.
RESULTS
The median age of the patients was 65 years (range 40-82). The majority were female (17 out of 27, 63%). Adenocarcinoma was the most frequent histological type of colorectal neoplasm. DM manifested before the diagnosis of colorectal cancer in 21 out of 27 patients (77.8%). At the time of the first presentation, creatine kinase was at a median level of 514.5 U/L (range 50-11,744), and serum antibodies were present in 11 out of 27 patients (40.7%). Immediate improvement of DM symptoms after surgery occurred in 14 out of 26 patients (53.8%). Recurrence of cancer in the form of distal metastasis was present in 5 out of 26 patients (19.2%). Cancer recurrence occurred within a median of 7.9 months (range 2-21) after surgery. In 7 out of 26 patients (26.9%), DM symptoms recurred during the post-operative period. Death was reported in 23 out of 27 patients (85.2%).
CONCLUSION
It is of paramount importance to perform a systematic diagnostic workup for malignancy, always including colonoscopy, in DM patients, since there is a high incidence of cancer in DM patients. Surgical treatment of colorectal tumors should precede the treatment of DM, as DM will frequently regress after a successful resection of malignancy.
Topics: Adult; Aged; Aged, 80 and over; Colorectal Neoplasms; Dermatomyositis; Female; Humans; Male; Middle Aged
PubMed: 29168152
DOI: 10.1007/s11845-017-1716-7 -
Clinical Rheumatology Apr 2018The objective of this study is to report a Brazilian patient and his family with inclusion body myopathy associated with Paget's disease of bone and frontotemporal... (Review)
Review
The objective of this study is to report a Brazilian patient and his family with inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD). A systematic review of the literature on the valosin-containing protein (VCP) mutation was also performed. The proband (patient) was initially treated as a case of possible refractory polymyositis with Paget's disease and later as an inclusion body myopathy. However, after admission to our service, and considering his personal and familial antecedents, whole exome sequencing was performed revealing valosin-containing protein (VCP) c.290G>A (p.Gly97Glu) mutation in the patient and his nine family members. The clinical presentation of the patient and his family was characterized by different degrees and evaluations of IBMPFD. According to the literature, only one family (Chinese) has this same VCP mutation concomitantly with different IBMPFD phenotype manifestations. The present study shows that IBMPFD should be considered as a differential diagnosis in patients with inflammatory myopathies associated to bone disease and/or cognitive impairment. Moreover, the study expands the genotypic spectrum of missense mutations of VCP gene in a Brazilian family with variable phenotypes.
Topics: Brazil; Female; Frontotemporal Dementia; Genotype; Humans; Male; Middle Aged; Muscular Dystrophies, Limb-Girdle; Myositis, Inclusion Body; Osteitis Deformans; Pedigree; Phenotype; Valosin Containing Protein
PubMed: 29127544
DOI: 10.1007/s10067-017-3913-1 -
Journal of B.U.ON. : Official Journal... 2017Dermatomyositis (DM) represents an auto-immune inflammatory myopathy. In this review, we analyzed the incidence of DM as a clinical manifestation highlighting the... (Meta-Analysis)
Meta-Analysis
PURPOSE
Dermatomyositis (DM) represents an auto-immune inflammatory myopathy. In this review, we analyzed the incidence of DM as a clinical manifestation highlighting the peculiar clinical and treatment characteristics of this disease when occurring in the context of different malignancies.
METHODS
A systematic literature review was performed based on database search in PubMed/Medline and included English articles until December 2016.
RESULTS
In up to 20% of cases DM appears as a paraneoplastic syndrome associated with multiple malignancies such as ovarian, breast, prostate, lung, nasopharyngeal and colorectal cancer, and non-Hodgkin lymphomas. It can be presented either before, in the time, or after cancer diagnosis. Systemic sclerosis and mixed connective-tissue disease represent common coinciding disorders. Particular caution should be given in the radiotherapy because the microvascular endothelial radiation damage and autoimmune inflammatory collagen vascular disease caused by DM may be additive. There is a higher risk of late toxicity in the presence of other concurrent vascular diseases, including diabetes, hypertension or administration of chemotherapy. Prednisone represents the first-line treatment option but immunosuppressive drugs such as azathioprine and methotrexate may also be incorporated in the therapeutic armamentarium especially when DM is associated with malignancy. Intravenous immunoglobulin could be a promising alternative in prednisone-resistant cases. The effectiveness of therapies with antigen-specific agents such as monoclonal antibodies is currently under investigation.
CONCLUSIONS
Timely diagnosis coupled with a treatment plan focused on muscular endurance and improvement of skin lesions and other symptoms offer a favorable response to therapy along with the achievement of a higher quality of life for these patients.
Topics: Anti-Inflammatory Agents; Clinical Trials as Topic; Dermatomyositis; Humans; Neoplasms; Paraneoplastic Syndromes; Prednisone; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 28952230
DOI: No ID Found -
PloS One 2016Interstitial lung disease (ILD) is an extramuscular manifestation that results in increased morbidity and mortality from polymyositis (PM) and dermatomyositis (DM). The... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Interstitial lung disease (ILD) is an extramuscular manifestation that results in increased morbidity and mortality from polymyositis (PM) and dermatomyositis (DM). The aim of this study was to systematically evaluate risk factors associated with the development of ILD in PM/DM.
METHODS
Observational studies were identified from searching PubMed, Medline, Embase, and the Cochrane Library. Pooled odds ratios (ORs) or standardized mean differences (SMDs) and corresponding 95% confidence intervals (CIs) were obtained for the relationships between risk factors and ILD in PM/DM using either fixed- or random-effects models, whichever were appropriate. Heterogeneity tests, sensitivity analyses, and publication bias assessments were also performed.
RESULTS
Twenty-three studies were selected for a meta-analysis that included 834 patients and 1245 control subjects. Risk factors that may have increased the risk of developing ILD in PM/DM patients included older age at diagnosis (SMD, 0.35; 95% CI, 0.18-0.52; P < 0.0001), arthritis/arthralgia (OR, 3.17; 95% CI, 1.99-5.04; P < 0.00001), fever (OR, 2.31; 95% CI, 1.42-3.76; P = 0.0007), presence of anti-Jo-1 antibodies (OR, 3.34; 95% CI, 2.16-5.16; P < 0.00001), elevated erythrocyte sedimentation rate (ESR; SMD, 0.48; 95% CI, 0.32-0.64; P < 0.00001), presence of anti-MDA5 antibodies (OR, 18.26; 95% CI, 9.66-34.51; P < 0.00001), and elevated C-reactive protein level (CRP; OR, 3.50; 95% CI, 1.48-8.28; P = 0.004). Meanwhile, malignancy (OR, 0.36; 95% CI, 0.18-0.72; P = 0.004) reduced the risk of developing ILD in PM/DM patients.
CONCLUSION
Our meta-analysis results suggest that the association between PM/DM and ILD may be due to such risk factors as older age at diagnosis, arthritis/arthralgia, fever, presence of anti-Jo-1 antibodies, elevated ESR, presence of anti-MDA5 antibodies, and elevated CRP level, while malignancy was associated with a reduced risk of developing ILD. Thus, these variables may be used to guide screening processes for ILD in patients with PM/DM.
Topics: Demography; Dermatomyositis; Female; Humans; Lung Diseases, Interstitial; Male; Polymyositis; Publication Bias; Risk Factors
PubMed: 27171228
DOI: 10.1371/journal.pone.0155381 -
The British Journal of Dermatology Dec 2018Clinically amyopathic dermatomyositis (CADM) affects a subset of 5-20% of patients with dermatomyositis and is defined as the presence of cutaneous features of...
Clinically amyopathic dermatomyositis (CADM) affects a subset of 5-20% of patients with dermatomyositis and is defined as the presence of cutaneous features of dermatomyositis without clinical muscle weakness for ≥ 6 months. There is no consensus on first-line treatment for CADM and whether treatment should differ from treatment of classic dermatomyositis with muscle weakness. We carried out a systematic review of published literature about treatment of adult patients with CADM, via the Embase, Medline, CINAHL and ClinicalTrials.gov databases on 17 February 2015. The aim was to establish which treatments have been used for adult-onset CADM and what evidence is available regarding the efficacy of these treatments including topical treatments, dapsone, antimalarials, intravenous immunoglobulin (IVIG), nonsteroidal oral immunosuppressants and biological therapies. Eighteen cases series and 42 case reports were found. These provided data on 153 adult patients who met the inclusion criteria. No randomized controlled trials or robust observational studies were found. The majority of patients (60%) had tried more than one treatment due to side-effects or lack of efficacy. Antimalarial agents were the most commonly used treatment type. In the majority of patients (55%), antimalarial treatments were discontinued due to lack of improvement or inability to wean concomitant steroids. IVIG was the treatment that led to improvement or remission in the greatest proportion of patients. Further robust, high-quality studies are needed to assess treatment efficacy in CADM without bias.
Topics: Adult; Antimalarials; Dermatomyositis; Humans; Immunoglobulins, Intravenous; Treatment Outcome
PubMed: 27167896
DOI: 10.1111/bjd.14726 -
International Braz J Urol : Official... 2016Improved targeted therapies for rheumatic diseases were developed recently resulting in a better prognosis for affected patients. Nowadays, patients are living longer... (Review)
Review
BACKGROUND
Improved targeted therapies for rheumatic diseases were developed recently resulting in a better prognosis for affected patients. Nowadays, patients are living longer and with improved quality of life, including fertility potential. These patients are affected by impaired reproductive function and the causes are often multifactorial related to particularities of each disease. This review highlights how rheumatic diseases and their management affect testicular function and male fertility.
MATERIALS AND METHODS
A systematic review of literature of all published data after 1970 was conducted. Data was collected about fertility abnormalities in male patients with systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, ankylosing spondylitis, Behçet disease and gout. Two independent researchers carried out the search in online databases.
RESULTS
A total of 19 articles were included addressing the following diseases: 7 systemic lupus erythematosus, 6 Behçet disease, 4 ankylosing spondylitis, 2 rheumatoid arthritis, 2 dermatomyositis and one gout. Systemic lupus erythematosus clearly affects gonadal function impairing spermatogenesis mainly due to antisperm antibodies and cyclophosphamide therapy. Behçet disease, gout and ankylosing spondylitis patients, including those under anti-TNF therapy in the latter disease, do not seem to have reduced fertility whereas in dermatomyositis, the fertility potential is hampered by disease activity and by alkylating agents. Data regarding rheumatoid arthritis is scarce, gonadal dysfunction observed as consequence of disease activity and antisperm antibodies.
CONCLUSIONS
Reduced fertility potential is not uncommon. Its frequency and severity vary among the different rheumatic diseases. Permanent infertility is rare and often associated with alkylating agent therapy.
Topics: Alkylating Agents; Behcet Syndrome; Dermatomyositis; Gout; Humans; Infertility, Male; Lupus Erythematosus, Systemic; Male; Rheumatic Diseases; Spondylitis, Ankylosing
PubMed: 27120778
DOI: 10.1590/S1677-5538.IBJU.2014.0595 -
Clinical Rheumatology Dec 2015The purpose of this study is to examine the efficacy and safety of tacrolimus (FK506) in the management of polymyositis (PM)/dermatomyositis (DM). The Cochrane Central... (Review)
Review
The purpose of this study is to examine the efficacy and safety of tacrolimus (FK506) in the management of polymyositis (PM)/dermatomyositis (DM). The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, and China National Knowledge Infrastructure (CNKI) were searched to find articles published between May 1980 and April 2015 concerning tacrolimus therapy in PM/DM. The initial search yielded 107 articles. In the end, eight studies met our inclusion criteria and involved a total of 134 patients who received tacrolimus therapy for DM/PM. All studies were non-randomized. Oral tacrolimus of 0.075 mg/kg/day or 1.0-3.5 mg/d was administered twice daily or once daily together with glucocorticoids (GCs). According to comprehensive analysis of the studies, 93.3 % (42/45) and 64.7 % (11/17) of patients showed improvement in muscle strength and physical function status. The creatine kinase (CK) levels of 100 % (68/68) of patients decreased. The average dosage of GCs was reduced from 33.8 to 11.5 mg/day in PM/DM patients after the addition of tacrolimus. In the subject population, 65 patients had interstitial lung disease (ILD). After treatment, the forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) improved or stabilized in 89.3 % (25/28) and 81.3 % (13/16) of patients, respectively. The commonly adverse events were nephrotoxicity, hypomagnesemia, tremors, and hypertension, but they were slight among these patients. Current evidence appears to support the use of tacrolimus in refractory PM/DM and PM/DM-ILD patients. Tacrolimus seems to be a safe drug that improves both muscle strength and lung function, and it is well tolerated by patients. However, this conclusion should be confirmed by large-sample, randomized controlled studies.
Topics: Dermatomyositis; Drug Therapy, Combination; Glucocorticoids; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Polymyositis; Tacrolimus; Treatment Outcome
PubMed: 26328518
DOI: 10.1007/s10067-015-3065-0