Myositis and Cancer

The idiopathic inflammatory myopathies (IIM), classically dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM), are acquired systemic autoimmune disorders defined by chronic muscle weakness and inflammation of unknown aetiology. The combination of clinical, laboratory, electromyographic, and histological features is the basis of diagnosis, as well as exclusion of several mimicking conditions (Bohan & Peter, 1975; Dalakas & Hohlfeld, 2003; Mann et al, 2010; Mastaglia & Phillips, 2002). IIM are the most common causes of acquired muscle disease in adults, but are still rare conditions with an estimated overall prevalence of 50 to 100 cases per million (Oddis et al., 1990; Prieto & Grau 2010; Wilson et al., 2008). In recent years, taking into account additional clinical, immunological and histological features, new phenotypes among IIM, such as antisynthetase syndrome, autoimmune necrotizing myopathy, connective tissue disorder-associated myositis, or cancer-associated myositis (CAM), have been described (Cox et al., 2010; Dalakas, 2010; Dimachkie, 2011; Rider & Miller, 2011; Targoff, 2008). The association between cancer and IIM has been widely reported in the medical literature, particularly in DM patients (Buchbinder et al., 2001; Sigurgeirsson et al., 1992). Cancer screening is a common practice in patients recently diagnosed with IIM, but there is not consensus about how, and how often screening should be performed. The aim of this chapter is to describe the epidemiological, clinical, laboratory, and histological reported features about CAM, to analyze the current potentially approach to preclude malignancy in IIM, and to provide an advisable algorithm in the diagnosis of occult cancer in myositis

Role of MUC1 rs4072037 polymorphism and serum KL-6 levels in patients with antisynthetase syndrome

Mucin 1/Krebs von den Lungen-6 (KL-6) is proposed as a serum biomarker of several interstitial lung diseases (ILDs), including connective tissue disorders associated with ILD. However, it has not been studied in a large cohort of Caucasian antisynthetase syndrome (ASSD) patients. Consequently, we assessed the role of MUC1 rs4072037 and serum KL-6 levels as a potential biomarker of ASSD susceptibility and for the differential diagnosis between patients with ILD associated with ASSD (ASSD-ILD?+) and idiopathic pulmonary fibrosis (IPF). 168 ASSD patients (149 ASSD-ILD?+), 174 IPF patients and 523 healthy controls were genotyped for MUC1 rs4072037 T?>?C. Serum KL-6 levels were determined in a subgroup of individuals. A significant increase of MUC1 rs4072037 CC genotype and C allele frequencies was observed in ASSD patients compared to healthy controls. Likewise, MUC1 rs4072037 TC and CC genotypes and C allele frequencies were significantly different between ASSD-ILD+ and IPF patients. Additionally, serum KL-6 levels were significantly higher in ASSD patients compared to healthy controls. Nevertheless, no differences in serum KL-6 levels were found between ASSD-ILD+ and IPF patients. Our results suggest that the presence of MUC1 rs4072037 C allele increases the risk of ASSD and it could be a useful genetic biomarker for the differential diagnosis between ASSD-ILD+ and IPF patients

HLA association with the susceptibility to anti-synthetase syndrome

Objective: To investigate the human leukocyte antigen (HLA) association with anti-synthetase syndrome (ASSD). Methods: We conducted the largest immunogenetic HLA-DRB1 and HLA-B study to date in a homogeneous cohort of 168 Caucasian patients with ASSD and 486 ethnically matched healthy controls by sequencing-based-typing. Results: A statistically significant increase of HLA-DRB1*03:01 and HLA-B*08:01 alleles in patients with ASSD compared to healthy controls was disclosed (26.2% versus 12.2%, P=1.56E-09, odds ratio-OR [95% confidence interval-CI]=2.54 [1.84-3.50] and 21.4% versus 5.5%, P=18.95E-18, OR [95% CI]=4.73 [3.18-7.05]; respectively). Additionally, HLA-DRB1*07:01 allele was significantly decreased in patients with ASSD compared to controls (9.2% versus 17.5%, P=0.0003, OR [95% CI]=0.48 [0.31-0.72]). Moreover, a statistically significant increase of HLA-DRB1*03:01 allele in anti-Jo-1 positive compared to anti-Jo-1 negative patients with ASSD was observed (31.8% versus 15.5%, P=0.001, OR [95% CI]=2.54 [1.39-4.81]). Similar findings were observed when HLA carrier frequencies were assessed. The HLA-DRB1*03:01 association with anti-Jo-1 was unrelated to smoking history. No HLA differences in patients with ASSD stratified according to the presence/absence of the most representative non-anti-Jo-1 anti-synthetase autoantibodies (anti-PL-12 and anti-PL-7), arthritis, myositis or interstitial lung disease were observed. Conclusions: Our results support the association of the HLA complex with the susceptibility to ASSD

Role of MUC1 rs4072037 polymorphism and serum KL-6 levels in patients with antisynthetase syndrome

Mucin 1/Krebs von den Lungen-6 (KL-6) is proposed as a serum biomarker of several interstitial lung diseases (ILDs), including connective tissue disorders associated with ILD. However, it has not been studied in a large cohort of Caucasian antisynthetase syndrome (ASSD) patients. Consequently, we assessed the role of MUC1 rs4072037 and serum KL-6 levels as a potential biomarker of ASSD susceptibility and for the differential diagnosis between patients with ILD associated with ASSD (ASSD-ILD +) and idiopathic pulmonary fibrosis (IPF). 168 ASSD patients (149 ASSD-ILD +), 174 IPF patients and 523 healthy controls were genotyped for MUC1 rs4072037 T > C. Serum KL-6 levels were determined in a subgroup of individuals. A significant increase of MUC1 rs4072037 CC genotype and C allele frequencies was observed in ASSD patients compared to healthy controls. Likewise, MUC1 rs4072037 TC and CC genotypes and C allele frequencies were significantly different between ASSD-ILD+ and IPF patients. Additionally, serum KL-6 levels were significantly higher in ASSD patients compared to healthy controls. Nevertheless, no differences in serum KL-6 levels were found between ASSD-ILD+ and IPF patients. Our results suggest that the presence of MUC1 rs4072037 C allele increases the risk of ASSD and it could be a useful genetic biomarker for the differential diagnosis between ASSD-ILD+ and IPF patients

Inflammatory myopathy in adults, health-related quality of life, and wellbeing: a round trip between immune disease and wellness

Health-related quality of life (HRQoL) and wellbeing are poorer in patients with chronic conditions than in the general population, and this is the case of individuals with myositis. Research has shown a negative relationship between this disease and wellbeing, but there is little data on the effect that enhanced wellbeing has on the disease course. HRQoL, wellbeing, and other related concepts are examined here with special emphasis on the benefits of positive status in the physical, environmental, psychological, and social function areas for reducing the severity of the clinical course and organ damage in a chronic condition such as myositis. The factors affecting HRQoL, and wellbeing are analyzed to delineate specific strategies that will lead to improvements in the life of adult patients with myositis. The mechanisms implicated in these changes are also discussed. Myositis refers to a heterogeneous group of chronic systemic autoimmune diseases. HRQoL and wellbeing are poor in these patients, and evidence suggests that improvements in this line can have positive repercussions on the course and outcome of the disease. Strategies to improve HRQoL and wellbeing should be designed for adults with myositis.</p