1960: From Clinical Amyopathy to Severe Oropharyngeal Dysphagia in Pure Dermatomyositis: A Greater Extent of Muscle Weakness Is Associated with a Higher Cancer Prevalence

Hao Cheng Shen¹, Victoria Ivensky², Yves Troyanov³, Josiane Bourre-Tessier¹, Farah Zarka², Sabrina Hoa⁴, Jessica Nehme², Jean-Paul Makhzoum⁵, Anne-Marie Mansour², Rosalie-Selene Meunier², Alexandra Mereniuk², Darosa Lim⁶, Jean-Pierre Raynauld¹, Eric Rich¹, Jean-Richard Goulet¹, Marianne Landry⁷, Maude Bouchard-Marmen⁸, Valerie Leclair⁹, Hugues Allard-Chamard¹⁰, Marie Hudson¹¹, Erin O'Ferrall¹², Rami Massie¹², Jason Karamchandani¹³, Benjamin Ellezam¹⁴, Ira N. Targoff¹⁵, Minoru Satoh¹⁶, Marvin Fritzler¹⁷, Jean-Luc Senecal¹, Alain Meyer¹⁸ and Oceane Landon-Cardinal¹, ¹Centre hospitalier de l'Université de Montréal (CHUM), Université de Montréal, Montréal, QC, Canada, ²Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montreal, QC, Canada, ³Hôpital du Sacré-Coeur de Montréal, Centre hospitalier de l'Université de Montreal (CHUM), Université de Montréal, Montreal, QC, Canada, ⁴University of Montreal, Brossard, QC, Canada, ⁵Vasculitis Clinic, Canadian Network for Research on Vasculitides, Hopital du Sacre-Coeur de Montreal, Montreal, QC, Canada, ⁶University of Pennsylvania, Philadelphia, PA, ⁷Hôpital de LaSalle, Montreal, QC, Canada, ⁸CHU de Québec, Université Laval, Quebec City, QC, Canada, ⁹Jewish General Hospital, McGill University, Montreal, QC, Canada, ¹⁰Université de Sherbrooke, Sherbrooke, QC, Canada, ¹¹McGill University, Montréal, QC, Canada, ¹²Montreal Neurological Institute, McGill University, Montreal, QC, Canada, ¹³McGill University Health Center (MUHC), McGill University, Montreal, QC, Canada, ¹⁴CHU Sainte-Justine, Université de Montréal, Montreal, QC, Canada, ¹⁵Veteran's Affairs Medical Center, University of Oklahoma Health Sciences Center, Oklahoma Medical Research Foundation, Oklahoma City, OK, ¹⁶University of Occupational and Environmental Health, Kitakyushu, Japan, ¹⁷University of Calgary, Calgary, AB, Canada, ¹⁸Hôpitaux Universitaires de Strasbourg, Strasbourg, France

Background/Purpose: The risk of cancer is increased in patients with pure dermatomyositis (DM), i.e. patients with a DM rash and without an anti-MDA-5 syndrome, a suspected or confirmed anti-synthetase syndrome or scleromyositis. The aim of this study was to describe the relationship between the extent of muscle involvement and the prevalence of cancer in serologically-defined subsets of pure DM.

Methods: Patients with pure DM were selected from a retrospective cohort of incident autoimmune myositis (AIM) seen in two rheumatology academic centers between 2000 and 2021. All patients were classified by expert opinion into one of three serologically distinct groups: group 1 (anti-TIF1γ autoantibodies), group 2 (non-anti-TIF1γ autoantibodies) and group 3 (seronegative/not tested). The degree of muscle involvement was stratified in four mutually exclusive categories: clinically amyopathic (CADM), proximal muscle weakness alone, proximal muscle weakness with moderate dysphagia (no aspiration) on video fluoroscopy swallow study (VFSS) and proximal muscle weakness with severe dysphagia (by VFSS or clinical aspiration). A diagnosis of cancer within (±) three years of AIM was recorded.

Results: Of 250 patients with AIM, 64 had pure DM. Anti-TIF1γ autoantibodies were positive in 24 (37.5%) patients, anti-Mi-2 in 9 (14.1%), anti-NXP2 in 7 (10.9%) and anti-SAE in 5 (7.8%), while 9 (14.1%) patients were seronegative and 10 (15.6%) untested. Cancer occurred in 29 of 64 (45.3%) patients: 11 of 24 (45.8%) in group 1, 6 of 21 (28.6%) in group 2, and 12 of 19 (63.2%) in group 3 (Figure 1). When stratified by extent of muscle weakness, cancer was seen in 18.8% (n=3/16) of CADM, 41.4% (n=12/29) of patients with proximal muscle weakness alone, 44.4% (n=4/9) of those with moderate dysphagia and 100% (n=10/10) of patients with severe dysphagia (p=0.0003 by Fisher's Exact Test) (Figure 1, panel A). A statistically significant gradual increase in cancer frequency with incremental extent of muscle weakness was also seen in group 1 (p=0.017) (Figure 1, panel B). All 3 patients with CADM and cancer survived, whereas all 10 patients with severe dysphagia and cancer died from their cancer.

Conclusion: In pure DM, cancer prevalence within 3 years of AIM diagnosis significantly increases with increasing extent of muscle weakness. Severe oropharyngeal dysphagia combined with proximal weakness is associated with the highest prevalence of cancer and poorest prognosis. Assessing the extent of muscle involvement in pure DM may improve cancer risk stratification.




H. Shen: None; V. Ivensky: None; Y. Troyanov: None; J. Bourre-Tessier: Abbvie, 2, AstraZeneca, 2, Gsk, 2, 6, Teva, 2; F. Zarka: None; S. Hoa: Boehringer-Ingelheim, 5; J. Nehme: None; J. Makhzoum: None; A. Mansour: None; R. Meunier: None; A. Mereniuk: None; D. Lim: None; J. Raynauld: None; E. Rich: None; J. Goulet: None; M. Landry: None; M. Bouchard-Marmen: None; V. Leclair: None; H. Allard-Chamard: AbbVie/Abbott, 1, 5, 6, Amgen, 1, 6, AstraZeneca, 1, 6, Bristol-Myers Squibb(BMS), 1, 5, 6, Celltrion, 1, 6, Eli Lilly, 1, 5, 6, Fresenius Kabi, 5, 6, GlaxoSmithKlein(GSK), 1, Hoffmann-La Roche, 1, 6, Janssen, 1, 6, Mantra Pharma, 6, Novartis, 1, 5, 6, Pfizer, 1, 5, 6, Sanofi, 5, Sobi, 6, Viela Bio, 5, Xencor, 5; M. Hudson: AstraZeneca, 6, Boehringer-Ingelheim, 1, 5, 6, Bristol-Myers Squibb(BMS), 5, Merck, 6, UCB, 5; E. O'Ferrall: None; R. Massie: None; J. Karamchandani: None; B. Ellezam: None; I. Targoff: OMRF Clinical Immunology Laboratory, 2; M. Satoh: None; M. Fritzler: None; J. Senecal: None; A. Meyer: None; O. Landon-Cardinal: None.