Management of Cancer-Associated Myositis.

Purpose of the Review: Cancer-associated myositis (CAM) is defined as when cancer appears within 3 years of myositis onset. Dermatomyositis and seronegative immune-mediated necrotizing myopathy are the phenotypes mostly related to cancer. In general, treatment principles in myositis patients with and without CAM are similar. However, some aspects of myositis management are particular to CAM, including (a) the need for a multidisciplinary approach and a close relationship with the oncologist, (b) the presence of immunosuppressive and antineoplastic drug interactions, and (c) the role of the long-term immunosuppressive therapy as a risk factor for cancer relapse or development of a second neoplasm. In this review, we will also discuss immunotherapy in patients treated with checkpoint inhibitors as a treatment for their cancer. Recent Findings: Studies on cancer risk in patients treated with long-term immunosuppressive drugs, in autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis, and in solid organ transplant recipients have shed some light on this topic. Immunotherapy, which has been a great advance for the treatment of some types of malignancy, may be also of interest in CAM, given the special relationship between both disorders. Summary: Management of CAM is a challenge. In this complex scenario, therapeutic decisions must consider both diseases simultaneously. Supplementary Information: The online version contains supplementary material available at 10.1007/s40674-022-00197-2.

Anti-HMGCR Specificity of HALIP: A Confirmatory Study.

A distinctive new indirect immunofluorescence pattern in liver tissue has been associated with anti-HMGCR autoantibodies. It is known as HALIP (HMGCR Associated Liver Immunofluorescence Pattern). In this study, we furthered the original studies to demonstrate the association of anti-HMGCR antibodies with the HALIP. Human anti-HMGCR antibodies from patients' sera were purified and incubated with rat triple tissue (kidney/stomach/liver). A characteristic HALIP was observed. Additionally, a colocalization assay of human anti-HMGCR antibodies with rabbit polyclonal anti-HMGCR antibodies showed colocalization of both immunofluorescence patterns. This study confirms that the HALIP is due to human anti-HMGCR antibodies.

Anti-TIF-1γ Antibody Detection Using a Commercial Kit vs In-House Immunoblot: Usefulness in Clinical Practice.

Objectives: Anti-TIF-1γ autoantibody detection is important for cancer screening in patients with dermatomyositis. The gold standard for anti-TIF-1γ detection, immunoprecipitation, is only available from a few specialized laboratories worldwide, so commercial ELISA/immunoblot tests have emerged in recent years. To analyze their usefulness in diagnosing cancer-associated dermatomyositis, we compared Euroimmun Euroline profile with our previously validated in-house immunoblot assay with human recombinant TIF-1γ. Methods: We included 308 adult patients from Hospital de la Santa Creu I Sant Pau and Vall Hebrón Hospital (Barcelona, Spain) tested for anti-TIF-1γ autoantibodies using the Euroline profile and an in-house immunoblot assay. Results: A total of 27 anti-TIF-1γ were detected by the Euroline and 12 by the in-house assay. Fair agreement was observed between Euroline and the in-house immunoblot Cohen's kappa 0.3163. Expected prevalence of anti-TIF-1γ autoantibodies was observed for the two methods for dermatomyositis and undifferentiated connective tissue diseases, but unexpectedly high prevalence of anti-TIF-1γ autoantibodies was detected by Euroline compared to the in-house immunoblot for other diseases (16.5% Euroline vs 0.8% in-house immunoblot, p<0.01). The in-house IB compared to Euroline more reliably detected cancer in patients with DM with anti-TIF-1γ antibodies (p=0.0014 vs p=0.0502 for in-house immunoblot vs Euroline). Conclusion: We recommend using a second validated method to confirm Euroline-detected anti-TIF-1γ antibodies when the dermatomyositis diagnosis is not definitive. Furthermore, in the context of definite DM diagnosis with negative anti-TIF-1γ antibodies by Euroline and no other myositis specific antibody, is also recommendable to confirm by a second validated method.

PET Scan: Nuclear Medicine Imaging in Myositis.

PURPOSE OF REVIEW: Positron emission tomography (PET) combined with computed tomography (CT) has proven useful as a cancer screening technique in patients with inflammatory myopathy, mainly dermatomyositis. In this review, we focus on advances in this direction and other potential applications of PET/CT in patients with inflammatory myopathy. RECENT FINDINGS: Cancer screening by PET/CT seems suitable and cost-effective in patients with myositis. It has also shown value as a hybrid technique for diagnosing myositis versus controls and could be of interest for differentiating between polymyositis and sporadic inclusion body myositis. Quantification of muscle activity by PET/CT seems reliable. Preliminary data suggest that it could also be used to diagnose and measure the activity of the disease in the lung. PET/CT should be in the toolbox of physicians managing patients with myositis. The multiple applications of PET/CT include its value for cancer screening, measuring the activity of the disease in muscle, and helping to differentiate between myositis phenotypes. The possibility to diagnose and monitor inflammatory lung activity remains to be demonstrated in well-designed studies.

Statin-induced myalgia and myositis: an update on pathogenesis and clinical recommendations.

INTRODUCTION: Musculoskeletal manifestations are well-recognized side effects of treatment with statins. New advances in this field have appeared in recent years. This review focuses on the diagnosis of these conditions and their underlying pathogenesis, in particular immune-mediated necrotizing myopathy. Areas covered: Clinical phenotypes including rhabdomyolysis, myalgia and/or mild hyperCKemia, self-limited toxin statin myopathy, and immune-mediated necrotizing myopathy are herein described. Therapeutic recommendations and a diagnostic algorithm in statin-associated myopathy are also proposed. The etiology and pathogenesis of statin-induced myopathy has mainly focused on the anti-HMGCR antibodies and the responsibility of the immune-mediated necrotizing myopathy is discussed. The fact that patients who have not been exposed to statins may develop statin-associated autoimmune myopathy with anti-HMGCR antibodies is also addressed. The literature search strategy included terms identified by searches of PubMed between 1969 and December 2017. The search terms 'myositis', 'statin-induced autoimmune myopathy', 'immune-mediate necrotizing myopathy', 'statins', 'muscular manifestations', and 'anti-HMGCR antibodies' were used. Expert commentary: Full characterization of the known phenotypes of statin toxicity and the specific role of the anti-HMGCR in those exposed and not exposed (i.e. juvenile forms) to statins and in some types of neoplasms is of paramount relevance.

Statins and myositis: the role of anti-HMGCR antibodies.

Muscle toxicity is a recognized adverse effect of statin use. Recently, a new myositis syndrome was described in association with antibodies directed against the pharmacologic target of statins, anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR antibody). The patient's genetic background, characteristic histologic patterns (immune-mediated necrotizing myopathy), and presence of anti-HMGCR antibodies define the syndrome. In most patients, statin discontinuation is insufficient to reverse the myositis symptoms, and immunosuppressive therapy is needed. The mechanisms by which these antibodies may lead to disease are not fully elucidated. Several important questions remain unsolved and warrant further research.

[Statins and autoimmunity]. / Estatinas y autoinmunidad.

Statins are the most widely used drugs for both primary and secondary prevention of cardiovascular diseases and those associated with atherosclerosis. About 25 million people are on statin therapy in the world. Although they are well tolerated by most patients and have a safety profile, some patients have muscle level alterations. The biological effects associated with these drugs are known as pleiotropic; they are of such interest and diversity that explains, in part, some of the actions of statins, especially in relation to inflammation and the immune system. Some patients have certain immune disorders that can turn into an undesirable clinical expression. Recent studies have shown that they can trigger autoimmune phenomena. Pathologies have been described in which these agents act as triggers such as immune-mediated necrotizing myopathy or indirectly in dermatomyositis or autoimmune hepatitis, among others. Given the high number of people being treated with statins, we believe that this is a clinically relevant problem and therefore worthy of study.