|
1
|
Tonutti A, Ceribelli A, Gremese E, Colafrancesco S, De Santis M, Selmi C. Cancer in connective tissue disease. Front Immunol 2025; 16:1571700. [PMID: 40416966 PMCID: PMC12098390 DOI: 10.3389/fimmu.2025.1571700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Accepted: 04/15/2025] [Indexed: 05/27/2025] Open
Abstract
The association between cancer and autoimmunity is well-recognized, as represented by the increased incidence of cancer among patients with systemic autoimmune diseases; however, the underlying mechanisms remain only partially understood. On the one hand, malignancy may trigger a breakdown of immune tolerance in predisposed individuals, as autoimmune syndromes often emerge shortly after cancer diagnosis, suggesting that tumor antigens might initiate an autoimmune response. However, by involving persistent responses and the creation of a pro-inflammatory environment, the chronic immune activation characteristic of autoimmunity may promote oncogenesis. This scenario is further complicated by the use of immunosuppressive therapies for autoimmune conditions, which, as seen in transplant immunology, are associated with a higher risk of cancer, although data in rheumatology have not yielded definitive conclusions. Connective tissue diseases include systemic lupus erythematosus, primary Sjögren syndrome, idiopathic inflammatory myopathies, systemic sclerosis, mixed connective tissue disease, and undifferentiated forms. These conditions have been variably associated with an increased risk of cancer, both at the time of disease onset and in patients with long-standing autoimmune conditions, providing a paradigm for investigating this complex interplay. Despite recent progress, many unmet needs remain that warrant further research.
Collapse
Affiliation(s)
- Antonio Tonutti
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Angela Ceribelli
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Elisa Gremese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Serena Colafrancesco
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Maria De Santis
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Carlo Selmi
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Milan, Italy
| |
Collapse
|
|
2
|
Teboul A, Allenbach Y, Tubach F, Belin L, Cassius C, Demortier J, Dossier A, Faucon C, Kasser C, Mekinian A, Monseau G, Fouchard M, Chambrelan E, Viguier M, Kluger N, Mahévas T, Bergeret B, Bachmeyer C, Lenormand C, Hotz C, Diaz E, Cordel N, Benveniste O, Bessis D, Bouaziz JD, Chasset F. Prognostic factors for patients with cancer-associated dermatomyositis: a retrospective, multicentre cohort study of 73 patients. Rheumatology (Oxford) 2025; 64:2970-2978. [PMID: 39589730 DOI: 10.1093/rheumatology/keae629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 10/18/2024] [Accepted: 10/21/2024] [Indexed: 11/27/2024] Open
Abstract
OBJECTIVES To investigate factors associated with DM complete clinical response and overall survival with a focus on the use of immunosuppressive therapies in patients with cancer-associated DM. METHODS We performed a multicentre, retrospective cohort study. Multivariable survival analyses used a Cox model with time-dependent covariates and adjustments with inverse probability censoring weighting. RESULTS We included 73 patients with cancer-associated DM. Median follow-up was 3.92 years. Overall, 40 (54.8%) patients achieved cancer remission, with DM complete clinical response in 28/40 (70.0%). DM complete clinical response was associated with cancer remission (hazard ratio [HR] 2.46, 95% CI [1.13-5.32]) and younger age (HR 0.68, 95% CI [0.49-0.95]). Risk of mortality was associated with sustained cancer activity (HR 12.93, 95% CI [2.42-69.25]), male sex (HR 2.82, 95% CI [1.19-6.70]), and older age (HR 1.86, 95% CI [1.26-2.79]) but not sustained DM activity (HR 0.40, 95% CI [0.13-1.26]). Oral corticosteroid use was a protective factor only on univariate analysis (HR 0.18, 95% CI [0.08-0.42]). CONCLUSION This study provides strong evidence of a significant association between the evolutions of DM and cancer, both in terms of overall survival and DM complete clinical response. Immunosuppressive treatments for DM were not significantly associated with mortality. TRIAL REGISTRATION ClinicalTrials.gov, NCT04637672.
Collapse
Affiliation(s)
- Alexandre Teboul
- Service de Dermatologie et Allergologie, Hôpital Tenon, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Paris, France
- Département de Santé Publique, Hôpital Pitié Salpêtrière, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Paris, France
| | - Yves Allenbach
- Département de Médecine Interne et Immunologie Clinique, Centre de Référence Myopathies Inflammatoires, Centre de Recherche en Myologie U974, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Sorbonne Université, Paris, France
| | - Florence Tubach
- Département de Santé Publique, Hôpital Pitié Salpêtrière, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Paris, France
| | - Lisa Belin
- Département de Santé Publique, Hôpital Pitié Salpêtrière, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Paris, France
| | - Charles Cassius
- Service de Dermatologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris Université Paris Cité, Faculté de Médecine, Paris, France
| | - Juliette Demortier
- Département de Médecine Interne et Immunologie Clinique, Centre de Référence Myopathies Inflammatoires, Centre de Recherche en Myologie U974, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Sorbonne Université, Paris, France
| | - Antoine Dossier
- Service de Médecine Interne, Hôpital Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Caroline Faucon
- Service de Dermatologie, Hôpital Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Camille Kasser
- Department of Internal Medicine, Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Arsène Mekinian
- Department of Internal Medicine, Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Grégoire Monseau
- Service de Réanimation, Centre Hospitalier de Périgueux, Périgueux, France
| | | | | | - Manuelle Viguier
- Department of Dermatology-Venereology, Hôpital Robert Debré, EA7509, IRMAIC, Université Reims Champagne Ardenne, Reims, France
| | - Nicolas Kluger
- Department of Dermatology, Allergology and Venereology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - Thibault Mahévas
- Service de Dermatologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris Université Paris Cité, Faculté de Médecine, Paris, France
| | | | - Claude Bachmeyer
- Service de médecine interne, Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses d'origine Inflammatoire (CEREMAIA), Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Paris, France
| | - Cédric Lenormand
- Service de Dermatologie, Hôpital Civil, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
| | - Claire Hotz
- Service de Dermatologie, Hôpital Jacques Puel, Centre Hospitalier de Rodez, Rodez, France
| | - Emmanuelle Diaz
- Service de Dermatologie, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil, France
| | - Nadège Cordel
- Department of Dermatology and Clinical Immunology, Guadeloupe University Hospital, Pointe-à-Pitre, Guadeloupe, France
| | - Olivier Benveniste
- Département de Médecine Interne et Immunologie Clinique, Centre de Référence Myopathies Inflammatoires, Centre de Recherche en Myologie U974, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Sorbonne Université, Paris, France
| | - Didier Bessis
- Service de Dermatologie, Centre Hospitalier Universitaire de Montpellier, Université de Montpellier, Montpellier, France
| | - Jean-David Bouaziz
- Service de Dermatologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris Université Paris Cité, Faculté de Médecine, Paris, France
| | - François Chasset
- Service de Dermatologie et Allergologie, Hôpital Tenon, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Paris, France
| |
Collapse
|
|
3
|
Martins EF, Cappello CH, Shinjo SK, Appenzeller S, de Souza JM. Idiopathic Inflammatory Myopathies: Recent Evidence Linking Pathogenesis and Clinical Features. Int J Mol Sci 2025; 26:3302. [PMID: 40244108 PMCID: PMC11989767 DOI: 10.3390/ijms26073302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 03/25/2025] [Accepted: 03/28/2025] [Indexed: 04/18/2025] Open
Abstract
Idiopathic inflammatory myopathies are rare and complex representatives of systemic connective tissue diseases. Described initially as only two entities, recent advances in molecular and imaging techniques now divide them into many subtypes, each with unique pathogenesis and clinical phenotypes. Dermatomyositis and its juvenile form are the most prevalent subtypes and are characterized by systemic vasculopathy and humoral autoimmunity. Genetic predisposition and environmental triggers initiate immune tolerance breakdown, leading to autoantibody production, complement activation, and tissue damage. Anti-synthetase syndrome primarily affects the lungs, where immune responses to aminoacyl-RNA synthetases drive vasculopathy, lung inflammation, and fibrosis. Immune-mediated necrotizing myopathies are muscle-specific, with autoantibodies inducing fiber necrosis and atrophy. Lastly, sporadic inclusion body myositis is a slowly progressive myopathy in which dysfunctional protein handling and autophagy are more important pathogenic elements than muscle inflammation itself. The expanding body of basic science evidence can be overwhelming, making it challenging to connect pathogenic mechanisms to clinical manifestations. This review aims to address this challenge by presenting recent insights into myositis pathogenesis from a practical perspective, reinforcing the links between basic science and clinical semiology.
Collapse
Affiliation(s)
- Eunice Fragoso Martins
- Department of Internal Medicine, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas 13083-881, Brazil
- Post-Graduate Program in Medical Sciences, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas 13083-887, Brazil
| | - Carla Helena Cappello
- Department of Orthopedics, Rheumatology and Traumatology, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas 13083-887, Brazil
- Post-Graduate Program in Child and Adolescent Health, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas 13083-888, Brazil
| | - Samuel Katsuyuki Shinjo
- Division of Rheumatology, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 01246-903, Brazil
| | - Simone Appenzeller
- Department of Orthopedics, Rheumatology and Traumatology, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas 13083-887, Brazil
| | - Jean Marcos de Souza
- Department of Internal Medicine, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas 13083-881, Brazil
| |
Collapse
|
|
4
|
Luo M, Lu XX, Meng DY, Hu J. Small cell lung cancer with peripheral neuropathy as the first symptom: Two case reports. World J Clin Cases 2025; 13:99421. [PMID: 40144482 PMCID: PMC11670026 DOI: 10.12998/wjcc.v13.i9.99421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 10/15/2024] [Accepted: 11/26/2024] [Indexed: 12/12/2024] Open
Abstract
BACKGROUND Small cell lung cancer (SCLC) is the most malignant type of lung cancer. Even in the latent period and early stage of the tumor, SCLC is prone to produce distant metastases with complex and diverse clinical manifestations. SCLC is most closely related to paraneoplastic syndrome, and some cases present as paraneoplastic peripheral neuropathy (PPN). PPN in SCLC appears early, lacks specificity, and often occurs before diagnosis of the primary tumor. It is easy to be misdiagnosed as a primary disease of the nervous system, leading to missed diagnosis and delayed diagnosis and treatment. CASE SUMMARY This paper reports two cases of SCLC with limb weakness as the first symptom. The first symptoms of one patient were rash, limb weakness, and abnormal electromyography. The patient was repeatedly referred to the hospital for limb weakness and rash for > 1 year, during which time, treatment with hormones and immunosuppressants did not lead to significant improvement, and the condition gradually aggravated. The patient was later diagnosed with SCLC, and the dyskinesia did not worsen as the dermatomyositis improved after antineoplastic and hormone therapy. The second case presented with limb numbness and weakness as the first symptom, but the patient did not pay attention to it. Later, the patient was diagnosed with SCLC after facial edema caused by tumor thrombus invading the vein. However, he was diagnosed with extensive SCLC and died 1 year after diagnosis. CONCLUSION The two cases had PPN and abnormal electromyography, highlighting its correlation with early clinical indicators of SCLC.
Collapse
Affiliation(s)
- Man Luo
- Department of Neurology, Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
| | - Xiao-Xi Lu
- Department of Information Technology, Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
| | - Dan-Yang Meng
- Department of Neurology, Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
| | - Jin Hu
- Department of Neurology, Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
| |
Collapse
|
|
5
|
Metko D, Bednar DE, Alkhayal F, Pavlova V, Legault K, Abu-Hilal M. Characteristics of Patients With Adult-Onset Dermatomyositis at 2 Tertiary Care Centres in Ontario, Canada. J Cutan Med Surg 2025; 29:124-130. [PMID: 39588556 PMCID: PMC11979310 DOI: 10.1177/12034754241301409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2024]
Abstract
Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by progressive muscle weakness and distinctive cutaneous findings. The exact incidence and prevalence of DM in the general population is largely unknown, and data on demographic and clinical features in patients in Canada are lacking. This study aimed to comprehensively evaluate the patients with DM in Southwestern Ontario, Canada. A retrospective chart review was conducted for patients with adult-onset DM at 2 tertiary care centres in Ontario, Canada, over a 13 year period. One hundred fourteen patients were included. The mean age was 59, and 80% of patients were female. Skin and muscle involvement coincided in 63% of patients, while skin predated muscle involvement in 11%. Most common characteristic skin manifestations included Gottron's papules (69%), Heliotrope sign (66%), V sign (61%), and Shawl sign (56%). Among the 114 patients, 88 (77%) were myopathic while 26/114 (23%) were clinically amyopathic dermatomyositis. In the myopathic type, upper extremity weakness, lower extremity weakness, and dysphagia were present in 87%, 81%, and 29% of patients, respectively. Elevated creatine kinase, C-reactive protein, lactate dehydrogenase, and erythrocyte sedimentation rate were found in 66%, 35%, 33%, and 32%, respectively. Lung disease was reported in 39%, particularly interstitial lung disease. Other associated features included malignancy, cardiovascular disease, and less commonly gastrointestinal disease. DM is a multifaceted autoimmune disease with distinct cutaneous and muscular findings. Our study results align with the growing body of evidence supporting DM as a complex systemic disease with the potential involvement of other organs such as the pulmonary, cardiovascular, and gastrointestinal systems.
Collapse
Affiliation(s)
- Dea Metko
- Michael G. DeGroote School of Medicine, Hamilton, ON, Canada
| | | | - Fares Alkhayal
- Division of Dermatology, McMaster University, Hamilton, ON, Canada
| | - Viktoria Pavlova
- Michael G. DeGroote School of Medicine, Hamilton, ON, Canada
- Division of Rheumatology, McMaster University, Hamilton, ON, Canada
| | - Kimberly Legault
- Michael G. DeGroote School of Medicine, Hamilton, ON, Canada
- Division of Rheumatology, McMaster University, Hamilton, ON, Canada
| | - Mohannad Abu-Hilal
- Michael G. DeGroote School of Medicine, Hamilton, ON, Canada
- Division of Dermatology, McMaster University, Hamilton, ON, Canada
| |
Collapse
|
|
6
|
Kawamura Y, Shimomura A, Taniyama T, Hirai H, Hashimoto K, Honda Y, Kitagawa D, Kaneko H, Shimizu C. Preoperative Systemic Chemotherapy Including Immune Checkpoint Inhibitors for Patients with Tumor-Associated Dermatomyositis. Case Rep Oncol 2025; 18:231-238. [PMID: 39980498 PMCID: PMC11825135 DOI: 10.1159/000543579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 01/09/2025] [Indexed: 02/22/2025] Open
Abstract
Introduction Immune checkpoint inhibitors (ICIs), used in cancer immunotherapy, enhance the immune system's ability to attack cancer cells. However, this activation can lead to severe immune-associated adverse events due to overactivation. In autoimmune diseases, the immune system mistakenly targets the body's tissues, producing autoantibodies that cause inflammation and tissue damage. Despite the increasing use of ICIs, limited information exists on their effects and potential harms in patients with active autoimmune diseases, making it challenging to predict outcomes and manage risks for these patients. Case Presentation We report a case of a patient with breast cancer presenting with a rash and muscle weakness. The simultaneous onset of these symptoms, along with the rapid growth of the breast tumor, led to a diagnosis of tumor-associated dermatomyositis (DM). The patient presented with locally advanced triple-negative breast cancer and received preoperative chemotherapy, including ICIs. Conclusion The administration of preoperative chemotherapy, including ICIs, to a patient with breast cancer and tumor-associated DM was found to be a safe and effective treatment approach. There is a need to better understand the interplay between ICIs and autoimmune diseases and to develop safe and effective treatment strategies for this unique patient population.
Collapse
Affiliation(s)
- Yukino Kawamura
- Department of Breast and Medical Oncology, National Center for Global Health and Medicine, Tokyo, Japan
- Course of Advanced and Specialized Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Akihiko Shimomura
- Department of Breast and Medical Oncology, National Center for Global Health and Medicine, Tokyo, Japan
- Course of Advanced and Specialized Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Tomoko Taniyama
- Department of Breast and Medical Oncology, National Center for Global Health and Medicine, Tokyo, Japan
| | - Hoshie Hirai
- Department of Breast Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Kazuki Hashimoto
- Department of Breast Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Yayoi Honda
- Department of Breast Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Dai Kitagawa
- Department of Breast Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Hiroshi Kaneko
- Division of Rheumatic Disease, National Center for Global Health and Medicine, Tokyo, Japan
| | - Chikako Shimizu
- Department of Breast and Medical Oncology, National Center for Global Health and Medicine, Tokyo, Japan
| |
Collapse
|
|
7
|
Luo R, Xia D, Yu S. A meta-analysis of melanoma risk in idiopathic inflammatory myopathy patients. Z Rheumatol 2024; 83:299-304. [PMID: 38285215 PMCID: PMC11655601 DOI: 10.1007/s00393-024-01473-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/27/2023] [Indexed: 01/30/2024]
Abstract
BACKGROUND Idiopathic inflammatory myopathy (IIM) is a group of chronic acquired autoimmune diseases. The association between IIM and malignancies has been observed for decades. No meta-analysis has been conducted to summarize the relationship between IIM and melanoma. Herein, we specifically wanted to investigate whether IIM is associated with a higher incidence of melanoma. METHODS We searched both Chinese and English databases (CNKI, VIP, Wanfang, PubMed, Embase, Web of Science) for studies on IIM related to melanoma published up to October 2023. Two independent authors reviewed all literature to identify studies according to predefined selection criteria. Fixed effects models were applied to pool the risk. Publication bias was also evaluated and sensitivity analysis performed. RESULTS A total of 1660 articles were initially identified but only four cohort studies met the criteria. Thus, 4239 IIM patients were followed up. The pooled overall risk ratio/hazard ratio was 3.08 (95% confidence interval [CI] 0.79-5.37) and the standardized incidence ratio was 6.30 (95% CI 1.59-11.02). CONCLUSION The present meta-analysis suggests that IIM patients are at a significantly higher risk of developing melanoma.
Collapse
Affiliation(s)
- Rui Luo
- General medicine department, The first People's hospital of Longquanyi District Chengdu, Sichuan, China.
| | - Dan Xia
- General medicine department, The first People's hospital of Longquanyi District Chengdu, Sichuan, China
| | - Siyang Yu
- General medicine department, The first People's hospital of Longquanyi District Chengdu, Sichuan, China
| |
Collapse
|
|
8
|
Maier JA, Castiglioni S, Petrelli A, Cannatelli R, Ferretti F, Pellegrino G, Sarzi Puttini P, Fiorina P, Ardizzone S. Immune-Mediated Inflammatory Diseases and Cancer - a dangerous liaison. Front Immunol 2024; 15:1436581. [PMID: 39359726 PMCID: PMC11445042 DOI: 10.3389/fimmu.2024.1436581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 08/29/2024] [Indexed: 10/04/2024] Open
Abstract
Patients with Immune-Mediated Inflammatory Diseases (IMIDs) are known to have an elevated risk of developing cancer, but the exact causative factors remain subject to ongoing debate. This narrative review aims to present the available evidence concerning the intricate relationship between these two conditions. Environmental influences and genetic predisposition lead to a dysregulated immune response resulting in chronic inflammation, which is crucial in the pathogenesis of IMIDs and oncogenic processes. Mechanisms such as the inflammatory microenvironment, aberrant intercellular communication due to abnormal cytokine levels, excessive reparative responses, and pathological angiogenesis are involved. The chronic immunosuppression resulting from IMIDs treatments further adds to the complexity of the pathogenic scenario. In conclusion, this review highlights critical gaps in the current literature, suggesting potential avenues for future research. The intricate interplay between IMIDs and cancer necessitates more investigation to deepen our understanding and improve patient management.
Collapse
Affiliation(s)
- Jeanette A Maier
- Department of Biomedical and Clinical Sciences, Università di Milano, Milano, Italy
| | - Sara Castiglioni
- Department of Biomedical and Clinical Sciences, Università di Milano, Milano, Italy
| | - Alessandra Petrelli
- Department of Clinical Sciences and Community Health, University of Milan, Milano, Italy
| | | | | | | | - Piercarlo Sarzi Puttini
- Department of Biomedical and Clinical Sciences, Università di Milano, Milano, Italy
- IRCCS Ospedale Galeazzi-Sant'Ambrogio, Milano, Italy
| | - Paolo Fiorina
- Department of Biomedical and Clinical Sciences, Università di Milano, Milano, Italy
| | - Sandro Ardizzone
- Gastroenterology Unit, ASST Fatebenefratelli-Sacco, Milano, Italy
| |
Collapse
|
|
9
|
Li H, Xu Y, Guo Q, Zhang T, Zhou S, Wang Q, Tian Y, Cheng Y, Guo C. Causality Assessment Between Idiopathic Inflammatory Myopathies and Lung Cancer: A Bidirectional 2-Sample Mendelian Randomization. J Clin Rheumatol 2024; 30:138-144. [PMID: 38351510 PMCID: PMC11913233 DOI: 10.1097/rhu.0000000000002075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/21/2024]
Abstract
BACKGROUND Although observational studies have revealed associations between idiopathic inflammatory myopathies (IIMs) and lung cancer (LC), they have not established a causal relationship between these 2 conditions. METHODS We used a 2-sample Mendelian randomization approach to examine the bidirectional causal associations between IIMs and LC, using single-nucleotide polymorphisms selected from high-quality genome-wide association studies in the FinnGen database. Sensitivity analyses were conducted to assess potential heterogeneity and pleiotropy impacts on the Mendelian randomization results. RESULTS Our analysis demonstrated a positive causal effect of genetically increased IIM risk on LC (odds ratio, 1.114; 95% confidence interval, 1.057-1.173; p = 5.63 × 10 -5 ), particularly on the lung squamous cell carcinoma subtype (odds ratio, 1.168, 95% confidence interval, 1.049-1.300, p = 0.00451), but not on lung adenocarcinoma or small cell lung cancer. No causal effect of LC on IIMs was identified. Sensitivity analyses indicated that horizontal pleiotropy was unlikely to influence causality, and leave-one-out analysis confirmed that the observed associations were not driven by a single-nucleotide polymorphism. CONCLUSION Our findings offer compelling evidence of a positive causal relationship between IIMs and LC, particularly with regard to lung squamous cell carcinoma, in the European population. Conversely, there is no evidence of LC causing IIMs. We recommend that LC diagnosis consider the specific characteristics of IIMs.
Collapse
Affiliation(s)
| | | | - Qin Guo
- Department of Rheumatology and Immunology, The People's Hospital of Baoan Shenzhen, The Second Affiliated Hospital of Shenzhen University, Shenzhen
| | - Tiantian Zhang
- Department of Rheumatology and Immunology, The People's Hospital of Baoan Shenzhen, The Second Affiliated Hospital of Shenzhen University, Shenzhen
| | - Shufen Zhou
- Department of Rheumatology and Immunology, The People's Hospital of Baoan Shenzhen, The Second Affiliated Hospital of Shenzhen University, Shenzhen
| | - Qianqian Wang
- Department of Rheumatology and Immunology, The People's Hospital of Baoan Shenzhen, The Second Affiliated Hospital of Shenzhen University, Shenzhen
| | - Ye Tian
- Department of Rheumatology and Immunology, The People's Hospital of Baoan Shenzhen, The Second Affiliated Hospital of Shenzhen University, Shenzhen
| | - Yuanxiong Cheng
- Department of Respiratory and Critical Care Medicine, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China
| | - Chengshan Guo
- Department of Rheumatology and Immunology, The People's Hospital of Baoan Shenzhen, The Second Affiliated Hospital of Shenzhen University, Shenzhen
| |
Collapse
|
|
10
|
Norrito RL, Puleo MG, Pintus C, Basso MG, Rizzo G, Di Chiara T, Di Raimondo D, Parrinello G, Tuttolomondo A. Paraneoplastic Cerebellar Degeneration Associated with Breast Cancer: A Case Report and a Narrative Review. Brain Sci 2024; 14:176. [PMID: 38391750 PMCID: PMC10887192 DOI: 10.3390/brainsci14020176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 01/23/2024] [Accepted: 02/07/2024] [Indexed: 02/24/2024] Open
Abstract
Paraneoplastic neurological syndromes (PNSs) are an uncommon complication of cancer, affecting nearby 1/10,000 subjects with a tumour. PNSs can involve all the central and peripheral nervous systems, the muscular system, and the neuromuscular junction, causing extremely variable symptomatology. The diagnosis of the paraneoplastic disease usually precedes the clinical manifestations of cancer, making an immediate recognition of the pathology crucial to obtain a better prognosis. PNSs are autoimmune diseases caused by the expression of common antigens by the tumour and the nervous system. Specific antibodies can help clinicians diagnose them, but unfortunately, they are not always detectable. Immunosuppressive therapy and the treatment of cancer are the cornerstones of therapy for PNSs. This paper reports a case of PNSs associated with breast tumours and focuses on the most common paraneoplastic neurological syndromes. We report a case of a young female with a clinical syndrome of the occurrence of rigidity in the right lower limb with postural instability with walking supported and diplopia, with a final diagnosis of paraneoplastic cerebellar degeneration and seronegative rigid human syndrome associated with infiltrating ductal carcinoma of the breast.
Collapse
Affiliation(s)
- Rosario Luca Norrito
- U.O.C di Medicina Interna con Stroke Care, Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", University of Palermo, 90127 Palermo, Italy
| | - Maria Grazia Puleo
- U.O.C di Medicina Interna con Stroke Care, Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", University of Palermo, 90127 Palermo, Italy
| | - Chiara Pintus
- U.O.C di Medicina Interna con Stroke Care, Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", University of Palermo, 90127 Palermo, Italy
| | - Maria Grazia Basso
- U.O.C di Medicina Interna con Stroke Care, Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", University of Palermo, 90127 Palermo, Italy
| | - Giuliana Rizzo
- U.O.C di Medicina Interna con Stroke Care, Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", University of Palermo, 90127 Palermo, Italy
| | - Tiziana Di Chiara
- U.O.C di Medicina Interna con Stroke Care, Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", University of Palermo, 90127 Palermo, Italy
| | - Domenico Di Raimondo
- U.O.C di Medicina Interna con Stroke Care, Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", University of Palermo, 90127 Palermo, Italy
| | - Gaspare Parrinello
- U.O.C di Medicina Interna con Stroke Care, Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", University of Palermo, 90127 Palermo, Italy
| | - Antonino Tuttolomondo
- U.O.C di Medicina Interna con Stroke Care, Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", University of Palermo, 90127 Palermo, Italy
| |
Collapse
|
|
11
|
De Jesus AV, De Souza JM. Clinically amyopathic dermatomyositis associated with cutaneous ulcerations: a case-based review. Ann Med Surg (Lond) 2024; 86:1210-1214. [PMID: 38333314 PMCID: PMC10849458 DOI: 10.1097/ms9.0000000000001669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 12/20/2023] [Indexed: 02/10/2024] Open
Abstract
Introduction and importance Dermatomyositis (DM) is an autoimmune myopathy primarily affecting both muscles and skin. When muscle weakness is not clinically apparent, but characteristic skin lesions are present, the condition is referred to as clinically amyopathic dermatomyositis (CADM). Case presentation The authors present the case of a 52-year-old female with a typical DM rash, interstitial pneumonia, and multiple skin ulcers. The skin biopsy was consistent with DM, and there were no signs of muscle involvement. Myositis-related and myositis-specific autoantibodies were also negative. Significant improvement was not observed until the patient received successive monthly pulses of methylprednisolone and the introduction of methotrexate. This treatment regimen allowed for the complete tapering of prednisone and resulted in sustained disease control. Clinical discussion In addition to the case presentation, a narrative literature review was conducted using the MEDLINE database, and an evidence-based treatment flowchart is proposed. CADM is a subtype of DM, related to higher incidences of interstitial lung disease, skin vasculopathy and malignancy. When ulcers or interstitial pneumonia are present, treatment should be early and aggressive. Active screening for neoplasms is recommended, particularly within the first 5 years. Conclusion The authors presented a case of seronegative CADM featuring skin vasculopathy, successfully treated with consecutive methylprednisolone pulses. Our literature review emphasized the importance of focused CADM management trials, highlighting the need for further research.
Collapse
Affiliation(s)
| | - Jean Marcos De Souza
- Faculdade de Ciencias Medicas, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil
| |
Collapse
|
|
12
|
Nakano Y, Nishida K, Okamoto N, Gohma I, Yasuhara Y. Anti-MDA5 Antibody-Positive Clinically Amyopathic Dermatomyositis Associated With Multiple Heterologous Carcinomas: A Case Report. Cureus 2024; 16:e54660. [PMID: 38523968 PMCID: PMC10960095 DOI: 10.7759/cureus.54660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/21/2024] [Indexed: 03/26/2024] Open
Abstract
Dermatomyositis (DM), an autoimmune disorder, is linked to increased malignancy risk. A 53-year-old man with anti-melanoma differentiation-associated gene 5 (MDA5)-positive clinically amyopathic dermatomyositis (CADM) and rapidly progressing interstitial lung disease (RP-ILD) developed heterochronous gastric and colorectal cancers. Early endoscopic screenings led to successful curative resections, preventing recurrence. Despite low cancer incidence assumptions in patients with anti-MDA5-positive RP-ILD, this case advocates for reevaluation and periodic cancer screenings to enhance management, considering the improved survival with intensive therapy. Vigilance for multiple carcinomas at various time points is vital in CADM management.
Collapse
Affiliation(s)
- Yoshio Nakano
- Respiratory Medicine, Sakai City Medical Center, Osaka, JPN
| | - Koji Nishida
- Respiratory Medicine, Sakai City Medical Center, Osaka, JPN
| | - Norio Okamoto
- Respiratory Medicine, Sakai City Medical Center, Osaka, JPN
| | - Iwao Gohma
- Respiratory Medicine, Sakai City Medical Center, Osaka, JPN
| | | |
Collapse
|
|
13
|
Allenzara A, Sadeghi N, Alvarez C, Maczuga S, Helm M, Olsen N, Nelson A, Foulke G. Obesity is an independent risk factor for cancer development following diagnosis of dermatomyositis. Semin Arthritis Rheum 2024; 64:152283. [PMID: 37984228 PMCID: PMC10842776 DOI: 10.1016/j.semarthrit.2023.152283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 09/23/2023] [Accepted: 10/17/2023] [Indexed: 11/22/2023]
Abstract
Patients with dermatomyositis (DM) are at an increased risk of cancer development, especially around the time of diagnosis of DM. Obesity is also a risk factor in the general population for cancer development. This study aimed to assess the association between cancer in DM patients with and without obesity as defined by ICD code and BMI data. In this analysis of patients with DM, logistic regression modeling of the odds of cancer outcome was performed for patients with DM and obesity compared to those without obesity, adjusted for age and sex. A total of 12,722 patients with DM were identified, of whom 6,055 had available BMI data. DM patients who were coded obese at any point had significantly higher odds 1.98 (95 % Confidence interval (CI) 1.70, 2.30) of a subsequent cancer diagnosis. This association was also found in the subgroup analysis with available BMI where patients with obesity (BMI ≥30 kg/m2) had an increased odds of cancer 1.23 (1.02, 1.49) when compared to patients with BMI <30 kg/m2 with DM. In time to event analysis any obesity code was associated with a 16 % increased hazard of cancer (adjusted hazard ratio 1.16 [95 % CI 1.02, 1.31]). Overall, the most frequent type of cancer was breast cancer, however patients with DM and obesity had higher frequencies of lymphoma, colorectal, melanoma, uterine, renal cancers compared to patients with DM without obesity.
Collapse
Affiliation(s)
- Astia Allenzara
- University of North Carolina at Chapel Hill, Division of Rheumatology, Allergy and Immunology and Thurston Arthritis Research Center, Chapel Hill, NC, USA.
| | - Nakisa Sadeghi
- University of North Carolina, School of Medicine, Chapel Hill, NC, USA
| | - Carolina Alvarez
- University of North Carolina at Chapel Hill, Division of Rheumatology, Allergy and Immunology and Thurston Arthritis Research Center, Chapel Hill, NC, USA
| | - Steve Maczuga
- Penn State Health Milton S Hershey Medical Center, Department of Dermatology, Hershey, PA, USA
| | - Matthew Helm
- Penn State Health Milton S Hershey Medical Center, Department of Dermatology, Hershey, PA, USA
| | - Nancy Olsen
- Penn State Health Milton S Hershey Medical Center, Division of Rheumatology, Hershey, PA, USA
| | - Amanda Nelson
- University of North Carolina at Chapel Hill, Division of Rheumatology, Allergy and Immunology and Thurston Arthritis Research Center, Chapel Hill, NC, USA; University of North Carolina, School of Medicine, Chapel Hill, NC, USA
| | - Galen Foulke
- Penn State Health Milton S Hershey Medical Center, Department of Dermatology, Hershey, PA, USA; Penn State Health Milton S Hershey Medical Center, Department of Public Health Sciences, Hershey, PA, USA
| |
Collapse
|
|
14
|
Bednar ED, Legault K, Pavlova V, Abu-Hilal M. Risk factors for malignancy in adult-onset dermatomyositis. J Eur Acad Dermatol Venereol 2024; 38:e122-e124. [PMID: 37641818 DOI: 10.1111/jdv.19478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 08/22/2023] [Indexed: 08/31/2023]
Affiliation(s)
- E D Bednar
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
- Division of Dermatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - K Legault
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
- Division of Rheumatology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - V Pavlova
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
- Division of Rheumatology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - M Abu-Hilal
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
- Division of Dermatology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| |
Collapse
|
|
15
|
Sabaté-Ortega J, Bujons-Buscarons E, Fina-Planas C, Vilanova-Anducas N, Vidal-Sarró N, Sala-González N. Paraneoplastic dermatomyositis associated with urothelial cancer: report of a case and systematic review of the literature. Front Oncol 2023; 13:1223627. [PMID: 38023222 PMCID: PMC10644711 DOI: 10.3389/fonc.2023.1223627] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Accepted: 10/10/2023] [Indexed: 12/01/2023] Open
Abstract
Background The idiopathic inflammatory myopathies (IIM) are a collection of autoimmune diseases that have a substantial impact on the entire body and include conditions such as dermatomyositis (DM), polymyositis (PM), sporadic inclusion body myositis, and immune-mediated necrotizing myopathy. These disorders are characterized by symptoms such as muscular weakness, pain, and dermal rash. This systematic review is intended to explore the potential link between bladder cancer and DM/PM. Methods We performed a comprehensive systematic search on PubMed and Scopus until August 2022 to identify relevant research studies. The studies that met our inclusion criteria focused on patients with urinary bladder cancer and dermatomyositis, and/or polymyositis. Results The patients' median age was 65.5 years (47-79), with the majority being male (15, 39.47%). Bladder cancer manifested before PM/DM in 5 (13.15%) patients, while in the majority of cases occurred after the cancer diagnosis. The stage of cancer at the time of the initial PM/DM diagnosis were mostly locally (11/20, 50%).During the first presentation, the patients had a median creatine kinase level of 2227 U/L, ranging between 44 and 10471. In one case, anti-TIF-1γ antibodies were found to be present. Among the cases with reported medical history (20/38), treatment immediately improved DM symptoms in 16 patients(53.8%) and in 3 patients(15%), symptoms of DM resurfaced during the period after the operation. Death was reported in 14 (36.8%) patients. Conclusion In conclusion, our study provides knowledge and understanding for identifying specific risk factors in patients with the coexistence of bladder cancer and DM/PM and their management. During the initial and follow-up screening, age, gender, and the clinicopathological subgroup of myositis should be considered to ensure proper management of the condition.
Collapse
Affiliation(s)
- Josep Sabaté-Ortega
- Oncology Department, Catalan Institute of Oncology, Hospital Universitari Dr. Josep Trueta, Girona, Spain
| | - Elisabet Bujons-Buscarons
- Oncology Department, Catalan Institute of Oncology, Hospital Universitari Dr. Josep Trueta, Girona, Spain
| | - Clàudia Fina-Planas
- Oncology Department, Catalan Institute of Oncology, Hospital Universitari Dr. Josep Trueta, Girona, Spain
| | | | - Noemí Vidal-Sarró
- Department of Pathology, Hospital Universitari de Bellvitge.L’Hospitalet, Barcelona, Spain
| | - Núria Sala-González
- Oncology Department, Catalan Institute of Oncology, Hospital Universitari Dr. Josep Trueta, Girona, Spain
| |
Collapse
|
|
16
|
Pace M, Cannella R, Di Stefano V, Lupica A, Alonge P, Morici G, Brighina F, Brancato F, Midiri F, Galia M. Usefulness and Clinical Impact of Whole-Body MRI in Detecting Autoimmune Neuromuscular Disorders. Brain Sci 2023; 13:1500. [PMID: 37891867 PMCID: PMC10605918 DOI: 10.3390/brainsci13101500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 09/28/2023] [Accepted: 10/04/2023] [Indexed: 10/29/2023] Open
Abstract
Autoimmune neuromuscular diseases are a group of heterogenous pathologies secondary to the activation of the immune system that damage the structures of the peripheric nerve, the neuromuscular junction, or the skeleton muscle. The diagnosis of autoimmune neuromuscular disorders comprises a combination of data from clinical, laboratory, electromyography, imaging exam, and biopsy. Particularly, the whole-body MRI examination in the last two decades has been of great use in the assessment of neuromuscular disorders. MRI provides information about the structures involved and the status of activity of the disease. It can also be used as a biomarker, detect the pattern of specific muscle involvement, and is a useful tool for targeting the optimal muscle site for biopsy. In this work, we summarized the most used technical protocol of whole-body MRI and the role of this imaging technique in autoimmune neuromuscular disorders.
Collapse
Affiliation(s)
- Mario Pace
- Section of Radiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University Hospital “Paolo Giaccone”, Via del Vespro 129, 90127 Palermo, Italy; (M.P.); (R.C.); (G.M.)
| | - Roberto Cannella
- Section of Radiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University Hospital “Paolo Giaccone”, Via del Vespro 129, 90127 Palermo, Italy; (M.P.); (R.C.); (G.M.)
| | - Vincenzo Di Stefano
- Section of Neurology, Department of Biomedicine, Neuroscience and Advanced Diagnostic (BIND), University of Palermo, 90127 Palermo, Italy; (V.D.S.); (A.L.); (P.A.); (F.B.)
| | - Antonino Lupica
- Section of Neurology, Department of Biomedicine, Neuroscience and Advanced Diagnostic (BIND), University of Palermo, 90127 Palermo, Italy; (V.D.S.); (A.L.); (P.A.); (F.B.)
| | - Paolo Alonge
- Section of Neurology, Department of Biomedicine, Neuroscience and Advanced Diagnostic (BIND), University of Palermo, 90127 Palermo, Italy; (V.D.S.); (A.L.); (P.A.); (F.B.)
| | - Giulio Morici
- Section of Radiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University Hospital “Paolo Giaccone”, Via del Vespro 129, 90127 Palermo, Italy; (M.P.); (R.C.); (G.M.)
| | - Filippo Brighina
- Section of Neurology, Department of Biomedicine, Neuroscience and Advanced Diagnostic (BIND), University of Palermo, 90127 Palermo, Italy; (V.D.S.); (A.L.); (P.A.); (F.B.)
| | - Federica Brancato
- Department of Surgical, Oncological and Oral Science (Di.Chir.On.S.), University of Palermo, 90133 Palermo, Italy;
| | - Federico Midiri
- IRCCS Ospedale Galeazzi-Sant’Ambrogio, Via Cristina Belgioioso 173, 20161 Milano, Italy;
| | - Massimo Galia
- Section of Radiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University Hospital “Paolo Giaccone”, Via del Vespro 129, 90127 Palermo, Italy; (M.P.); (R.C.); (G.M.)
| |
Collapse
|
|
17
|
Akagi H, Wada T. A Case in Which Breast Cancer Developed at the Same Time As Dermatomyositis, and the Onset of New Cancer Was Able to Be Predicted by the Exacerbating Skin Symptoms and Parallel Increase in the Anti-TIF1-γ Antibody Levels. Intern Med 2023; 62:3057-3062. [PMID: 37839875 PMCID: PMC10641192 DOI: 10.2169/internalmedicine.0569-22] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 01/10/2023] [Indexed: 10/17/2023] Open
Abstract
Dermatomyositis (DM) is an idiopathic inflammatory myopathy. The incidence of malignancy in DM patients is quite high. Anti-transcription intermediary factor 1-γ (anti-TIF1-γ) antibody is more prevalent in DM patients with malignancy than in those without malignancy. A 70-year-old woman developed hoarseness and difficulty swallowing. A physical examination revealed skin abnormalities. Breast cancer was found in her right breast. She was positive for anti-TIF1-γ antibody. Chemotherapy reduced the tumor size, decreased the anti-TIF1-γ antibody level, and improved her symptoms. About 2.5 years later, however, her skin symptoms worsened, and anti-TIF1-γ antibody levels increased again, and colorectal cancer was found. Treatment with endoscopic mucosal resection (EMR) improved her symptoms again. Our case suggests that the exacerbating skin symptoms and parallel increase in the anti-TIF1-γ antibody level led to the detection of a second cancer after treatment of the first cancer in this case of DM.
Collapse
Affiliation(s)
| | - Tatsuhiko Wada
- Department of Rheumatology and Infectious Diseases, Kitasato University School of Medicine, Japan
| |
Collapse
|
|
18
|
Floyd-Ellis V, Taylor A. Dermatomyositis: a debilitating paraneoplastic phenomenon following a diagnosis of localised squamous cell carcinoma of the cervix. BMJ Case Rep 2023; 16:e253640. [PMID: 37591620 PMCID: PMC10441080 DOI: 10.1136/bcr-2022-253640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/21/2023] [Indexed: 08/19/2023] Open
Abstract
This case report describes the management of a patient, recently diagnosed with Stage IIIC cervical cancer, presenting with significant proximal muscle weakness, dysphagia and cutaneous changes over the hands, knees and outer thighs bilaterally. Following multiple investigations, this clinical presentation was proven to be dermatomyositis as a paraneoplastic phenomenon, a rare diagnosis with cervical cancer.Improvement of the presenting symptoms followed commencement of radical chemoradiation to the primary tumour plus administration of high dose steroids and intravenous immunoglobulins.As demonstrated in this case, and accompanying literature review, dermatomyositis is a rare complication of cervical cancer but should be considered as urgent treatment of the underlying malignancy is imperative. Involving members of the multidisciplinary team, including dieticians and physiotherapists, is of utmost importance to optimise the patient's recovery from such a debilitating diagnosis.
Collapse
Affiliation(s)
- Victoria Floyd-Ellis
- School of Medicine, Cardiff University, Cardiff, UK
- Clinical Oncology, Royal Marsden Hospital NHS Trust, London, UK
| | | |
Collapse
|
|
19
|
Connolly CM, Paik JJ. Clinical pearls and promising therapies in myositis. Expert Rev Clin Immunol 2023; 19:797-811. [PMID: 37158055 PMCID: PMC10330909 DOI: 10.1080/1744666x.2023.2212162] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 05/05/2023] [Indexed: 05/10/2023]
Abstract
INTRODUCTION Idiopathic inflammatory myopathies (IIMs) represent a diverse group of systemic autoimmune disorders with variable clinical manifestations and disease course. Currently, the challenges of IIMs are multifold, including difficulties in timely diagnosis owing to clinical heterogeneity, limited insights into disease pathogenesis, as well as a restricted number of available therapies. However, advances utilizing myositis-specific autoantibodies have facilitated the definition of subgroups as well as the prediction of clinical phenotypes, disease course, and response to treatment. AREAS COVERED Herein we provide an overview of the clinical presentations of dermatomyositis, anti-synthetase syndrome, immune-mediated necrotizing myopathy, and inclusion body myositis. We then provide an updated review of available and promising therapies for each of these disease groups. We synthesize current treatment recommendations in the context of case-based construct to facilitate application to patient care. Finally, we provide high-yield, clinical pearls relevant to each of the subgroups that can be incorporated into clinical reasoning. EXPERT OPINION There are many exciting developments on the horizon for IIM. As insights into pathogenesis evolve, the therapeutic armamentarium is expanding with many novel therapies in development, holding promise for more targeted treatment approaches.
Collapse
Affiliation(s)
- Caoilfhionn M. Connolly
- Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Julie J. Paik
- Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| |
Collapse
|
|
20
|
Moutinho-Pereira S, Navarro M, Capela C, Brito C. Paraneoplastic dermatomyositis associated with vocal cord carcinoma. BMJ Case Rep 2023; 16:e255606. [PMID: 37316283 PMCID: PMC10277030 DOI: 10.1136/bcr-2023-255606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/03/2023] [Indexed: 06/16/2023] Open
Affiliation(s)
- Sara Moutinho-Pereira
- Departamento de Medicina, Serviço de Medicina Interna, Unidade Local de Saúde de Matosinhos EPE, Senhora da Hora, Portugal
| | | | - Carlos Capela
- Serviço de Medicina Interna, Hospital de Braga, Braga, Portugal
| | - Celeste Brito
- Department of Dermatology, Hospital de Braga, Braga, Portugal
| |
Collapse
|
|
21
|
Alenzi F, Alotaibi J, Alnasser M, Alokaily F. Clinical and laboratory characteristics of idiopathic inflammatory myositis in Saudi patients: A retrospective study in a single tertiary centre. Saudi Med J 2023; 44:492-497. [PMID: 37182927 PMCID: PMC10187745 DOI: 10.15537/smj.2023.44.5.20220213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 04/19/2023] [Indexed: 05/16/2023] Open
Abstract
OBJECTIVES Idiopathic inflammatory myositis (IIM) in Saudi patients has been poorly studied owing to the lack of available data. This study aimed to identify the clinical and laboratory features of patients at a single tertiary care center. METHODS This retrospective study reviewed the medical records of Prince Sultan Military Medical City, Riyadh, Saudi Arabia to collect clinical and laboratory data between December 2022 and February 2017 as follows: age at disease onset, gender, follow-up duration and disease duration; clinical symptoms; laboratory result; presence and type of myositis-specific autoantibody or myositis-associated autoantibody; and type of immunosuppression, presence of malignancy, disease course, and outcome. RESULTS There were 26 patients with a mean age of 36.16±13.48, and 84.6% were women. The most prevalent form of IIM was dermatomyositis (n=16, 61.5%), and the most affected organ was the skin. weakness was observed in 25 patients (96.2%), and dysphagia was the most common alarm sign (n=10, 38.5%). During follow-up, the creatine kinase level was elevated at the beginning of the disease and then decreased following treatment, with a mean of 277.73 IU/L. Of the total patients, 17 (68%) were positive for anti-nuclear antibody and 5 (19.2%) were positive for anti-Jo-1. CONCLUSION In our patients, dermatomyositis was the most common form of myositis, and skin manifestations were the most prevalent clinical characteristics. None of the patients developed a malignancy or died.
Collapse
Affiliation(s)
- Fahidah Alenzi
- From the Department of Clinical Science (Alenzi), College of Medicine, Princess Nourah bint Abdulrahman University; and from the Division of Rheumatology, Department of Medicine (Alotaibi, Alnasser, Alokaily), Prince Sultan Military Medical City, Riyadh, Kingdom of Saudi Arabia
| | - Jawaher Alotaibi
- From the Department of Clinical Science (Alenzi), College of Medicine, Princess Nourah bint Abdulrahman University; and from the Division of Rheumatology, Department of Medicine (Alotaibi, Alnasser, Alokaily), Prince Sultan Military Medical City, Riyadh, Kingdom of Saudi Arabia
| | - Manal Alnasser
- From the Department of Clinical Science (Alenzi), College of Medicine, Princess Nourah bint Abdulrahman University; and from the Division of Rheumatology, Department of Medicine (Alotaibi, Alnasser, Alokaily), Prince Sultan Military Medical City, Riyadh, Kingdom of Saudi Arabia
| | - Fahdah Alokaily
- From the Department of Clinical Science (Alenzi), College of Medicine, Princess Nourah bint Abdulrahman University; and from the Division of Rheumatology, Department of Medicine (Alotaibi, Alnasser, Alokaily), Prince Sultan Military Medical City, Riyadh, Kingdom of Saudi Arabia
| |
Collapse
|
|
22
|
Didona D, Solimani F, Caposiena Caro RD, Sequeira Santos AM, Hinterseher J, Kussini J, Cunha T, Hertl M, Didona B. Dermatomyositis: a comprehensive review of clinical manifestations, serological features, and therapeutic approaches. Ital J Dermatol Venerol 2023; 158:84-98. [PMID: 37153943 DOI: 10.23736/s2784-8671.23.07458-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/10/2023]
Abstract
Dermatomyositis (DM) is an autoimmune disorder, which belongs to a group of rare autoimmune dermatoses characterized by different skin features and variable muscle involvement. We recognize four main variants of DM: classic DM, clinically amyopathic DM, paraneoplastic DM, and juvenile DM. Clinically, patients show several skin features, but heliotrope rash, and violaceous papules located at the interphalangeal or metacarpophalangeal joints (Gottron's papules) are the most frequently observed. Together with skin features, patients show muscle involvement, most commonly with symmetrical weakness of the proximal muscles. DM belongs to the facultative paraneoplastic dermatoses and a wide range of solid or hematologic malignancies can be detected in DM patients. Serologically, a wide range of autoantibodies can be detected in patients with DM. Indeed, distinct serotypes can be related to specific phenotypes with specific clinical features, carrying a different risk for systemic involvement and for malignancies. Systemic corticosteroids are still considered the first-line approach, but several steroid-sparing agents, such as methotrexate, azathioprine or mycophenolate mofetil, have been reported as effective in treating DM. Furthermore, new class of drugs, such as monoclonal antibodies, purified immunoglobulins or Janus kinase inhibitors are becoming more relevant in the clinical practice or are currently under investigation. In this work, we aim to offer a clinical overview of the diagnostic workout, the characteristics of DM variants, the role of autoantibodies in DM, and the management of this life-threatening systemic disorder.
Collapse
Affiliation(s)
- Dario Didona
- Department of Dermatology and Allergology, Philipps University of Marburg, Marburg, Germany -
| | - Farzan Solimani
- Berlin Institute of Health at Charité-Universitätsmedizin Berlin BIH, Biomedical Innovation Academy, BIH Charité Clinician Scientist Program, Berlin, Germany
- Department of Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | | | | | - Julia Hinterseher
- Department of Dermatology and Allergology, Philipps University of Marburg, Marburg, Germany
| | - Jacqueline Kussini
- Department of Dermatology and Allergology, Philipps University of Marburg, Marburg, Germany
| | - Tomas Cunha
- Department of Dermatology and Allergology, Philipps University of Marburg, Marburg, Germany
| | - Michael Hertl
- Department of Dermatology and Allergology, Philipps University of Marburg, Marburg, Germany
| | - Biagio Didona
- Department of Dermatology, Istituto Dermopatico dell'Immacolata (IDI)-IRCCS, Rome, Italy
| |
Collapse
|
|
23
|
Patasova K, Lundberg IE, Holmqvist M. Genetic Influences in Cancer-Associated Myositis. Arthritis Rheumatol 2023; 75:153-163. [PMID: 36053262 PMCID: PMC10107284 DOI: 10.1002/art.42345] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 07/28/2022] [Accepted: 08/31/2022] [Indexed: 02/02/2023]
Abstract
Idiopathic inflammatory myopathies (IIMs) comprise a heterogeneous group of rare immune-mediated disorders that primarily affect muscles but also lead to dysfunction in other organs. Five different clinical subphenotypes of IIM have been distinguished: dermatomyositis, polymyositis, inclusion body myositis, antisynthetase syndrome, and immune-mediated necrotizing myopathy. Excess mortality and morbidity associated with IIM are largely attributed to comorbidities, particularly cancer. The risk of malignancy is not equally distributed among IIM groups and is particularly high among patients with dermatomyositis. The cancer risk peaks around 3 years on either side of the IIM diagnosis and remains elevated even 10 years after the onset of the disease. Lung, colorectal, and ovarian neoplasms typically arise before the onset of IIM, whereas melanoma, cervical, oropharyngeal, and nonmelanoma skin cancers usually develop after IIM diagnosis. Given the close temporal proximity between IIM diagnosis and the emergence of malignancy, it has been proposed that IIM could be a consequence rather than a cause of cancer, a process known as a paramalignant phenomenon. Thus, a separate group of IIMs related to paramalignant phenomenon has been distinguished, known as cancer-associated myositis (CAM). Although the relationship between IIM and cancer is widely recognized, the pathophysiology of CAM remains elusive. Given that genetic factors play a role in the development of IIM, dissection of the molecular mechanisms shared between IIM and cancer presents an opportunity to examine the role of autoimmunity in cancer development and progression. In this review, the evidence supporting the contribution of genetics to CAM will be discussed.
Collapse
Affiliation(s)
- Karina Patasova
- Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
| | - Ingrid E Lundberg
- Rheumatology Division, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Marie Holmqvist
- Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
| |
Collapse
|
|
24
|
Chua CG, Low JZ, Lim WY, Manghani M. Characteristics of anti-transcriptional intermediary factor 1 gamma autoantibody-positive dermatomyositis patients in Singapore. ANNALS OF THE ACADEMY OF MEDICINE, SINGAPORE 2022. [DOI: 10.47102/annals-acadmedsg.2022278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Introduction: This study aimed to determine the clinical profile and outcome of anti-transcriptional intermediary factor 1 gamma autoantibody (anti-TIF1-γ Ab)-positive dermatomyositis patients and propose cancer screening programmes based on regional cancer trends.
Method: Data on history, physical findings and investigations were collected using chart review on dermatomyositis patients seen at a tertiary hospital in Singapore from 1 January 2015 to 30 June 2021. Comparisons were made between anti-TIF1-γ Ab-positive and anti-TIF1-γ Ab-negative dermatomyositis.
Results: Ninety-six dermatomyositis patients were analysed and 36 patients were positive for anti-TIF1-γ Ab. Anti-TIF1-γ Ab-positive patients had more frequent heliotrope rashes, shawl sign, periungual erythema, holster sign, Gottron’s papules, dysphagia and truncal weakness (P<0.05). They had less frequent interstitial lung disease, polyarthritis, cutaneous ulcers, palmar papules and mechanic’s hands (P<0.05). After 48 months of follow-up, a higher proportion of anti-TIF1-γ Ab-positive patients developed cancer compared with Ab-negative patients (63.9% versus 8.5%; odds ratio 19.1, 95% confidence interval 6.1–59.8; P<0.001). Nasopharyngeal carcinoma (NPC) and breast cancer were the most common malignancies, followed by bowel, lung and non-Hodgkin lymphoma. Most malignancies (78.3%) occurred within 13 months prior to, or 4 months after the onset of dermatomyositis. The mortality rate for anti-TIF1-γ Ab-positive patients was significantly higher than Ab-negative patients (36.1% vs 16.7%, P=0.031), and Kaplan-Meier survival estimates at 24 months were 66% and 89%, respectively (P=0.0153).
Conclusion: These observational data support periodic screening of NPC and other malignancies in patients with anti-TIF1-γ Ab-positive dermatomyositis in Singapore.
Keywords: Autoantibody, cancer, dermatomyositis, nasopharyngeal carcinoma, transcriptional intermediary factor 1 gamma
Collapse
|
|
25
|
Batista NVR, Valdez RMA, Silva EMVDM, Melo TS, Pereira JRD, Warnakulasuriya S, Santos-Silva AR, Duarte ALBP, Mariz HDA, Gueiros LA. Association between autoimmune rheumatic diseases and head and neck cancer: Systematic review and meta-analysis. J Oral Pathol Med 2022; 52:357-364. [PMID: 36504468 DOI: 10.1111/jop.13396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 08/25/2022] [Accepted: 09/29/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Personal history of autoimmune rheumatic diseases has been implicated in the development of malignant neoplasms. Our aim was to assess the risk of head and neck (H&N) cancers in patients with autoimmune rheumatic diseases. METHODS The articles search included PubMed, EMBASE, LILACS, The Cochrane Library, CINAHL, Scopus, Web of Science, and Google Scholar with no language restrictions for studies published from inception of the databases to August 20, 2022, assessing the risk of H&N cancer in patients with autoimmune rheumatic diseases. Studies were included if they reported the standardized incidence ratio (SIR) with corresponding 95% confidence intervals (CIs). The primary outcome was risk of H&N cancers in patients with autoimmune rheumatic diseases compared with the general population. Pooled summary estimates were calculated using a random-effects model, and subgroup analyses were done to establish whether risk of H&N cancers varied according to study site. RESULTS Our search identified 5378 records, of which 32 cohort studies were eligible for systematic review and 24 for meta-analysis (including 273 613 patients). A significant association was found between H&N cancer and autoimmune rheumatic diseases (SIR = 2.35; 95% CI: 1.57-3.50; p < 0.01, I2 = 94%). CONCLUSION Our study suggests that patients with autoimmune rheumatic diseases had a significantly increased risk of H&N cancer compared with the general population, including thyroid, oral, and nasopharyngeal cancers. These findings have implications for the individualized screening of these patients and the planning of oncology units. The protocol is registered with PROSPERO, number CRD42020197827.
Collapse
Affiliation(s)
| | | | | | - Thayanara Silva Melo
- Oral Medicine Unit, Department of Clinic and Preventive Dentistry, Universidade Federal de Pernambuco, Recife, Brazil
| | - José Ricardo Dias Pereira
- Oral Medicine Unit, Department of Clinic and Preventive Dentistry, Universidade Federal de Pernambuco, Recife, Brazil
| | - Saman Warnakulasuriya
- Department of Oral Medicine, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, UK
| | - Alan Roger Santos-Silva
- Department of Oral Diagnosis, Piracicaba Dental School, Universidade Estadual de Campinas, Piracicaba, Brazil
| | | | | | - Luiz Alcino Gueiros
- Oral Medicine Unit, Department of Clinic and Preventive Dentistry, Universidade Federal de Pernambuco, Recife, Brazil
| |
Collapse
|
|
26
|
Goldman N, Han J, LaChance A. Diagnosis and Management of Cutaneous Manifestations of Autoimmune Connective Tissue Diseases. Clin Cosmet Investig Dermatol 2022; 15:2285-2312. [PMID: 36320926 PMCID: PMC9618245 DOI: 10.2147/ccid.s360801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 10/19/2022] [Indexed: 11/20/2022]
Abstract
The cutaneous features of autoimmune connective tissue disease pose a unique challenge to patients and clinicians managing these conditions. In this review, we outline the key elements of diagnosis and treatment of cutaneous lupus erythematosus, dermatomyositis, systemic sclerosis, and morphea. This article also aims to present an update on gold standard as well as new and emerging therapies for these conditions. Overall, dermatologists can play a key role in diagnosing and treating autoimmune connective tissue diseases and this review intends to provide an up-to-date toolkit to guide clinical dermatologists in this endeavor.
Collapse
Affiliation(s)
- Nathaniel Goldman
- Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
- New York Medical College, School of Medicine, Valhalla, NY, USA
| | - Joseph Han
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Avery LaChance
- Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| |
Collapse
|
|
27
|
Kardes S, Gupta L, Aggarwal R. Cancer and myositis: Who, when, and how to screen. Best Pract Res Clin Rheumatol 2022; 36:101771. [PMID: 35970749 DOI: 10.1016/j.berh.2022.101771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Cancer screening in idiopathic inflammatory myopathies (IIMs) is essential because an increased risk of cancer in IIMs has been well demonstrated. However, a consensus regarding cancer screening approaches is lacking. Therefore, the approach presented in this review reflects available evidence and our clinical experiences. Patients with IIMs should be evaluated for 3 distinct types of risk categories: (a) clinical with their history, physical examination, and laboratory parameters; (b) based on IIMs subtypes; and (c) based on serology - myositis specific and associated autoantibodies. Further, according to these characteristics, patients should be classified as low risk, moderate risk, and high risk for cancer. In our approach, all patients with IIM within 3 years of disease onset should undertake cancer screening according to their risk stratification. First, irrespective of risk, all patients should undergo age and gender-appropriate screening as per local guidelines. Patients at low-risk stratification should undertake basic cancer screening with routine blood counts, labs, and imaging; at moderate-risk stratification, patients should undertake enhanced cancer screening including CT chest; and at high-risk stratification, patients should undertake comprehensive cancer screening including PET/CT at baseline. Consensus guidelines among all major stakeholders, including rheumatologists, neurologists, dermatologists, and oncologists representing different parts of the world, establishing uniform cancer screening approaches in patients with IIM, are the need of the hour.
Collapse
Affiliation(s)
- Sinan Kardes
- Department of Medical Ecology and Hydroclimatology, Istanbul Faculty of Medicine, Istanbul University, Turkey.
| | - Latika Gupta
- Department of Rheumatology, Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, UK; City Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK; Division of Musculoskeletal and Dermatological Sciences, Centre for Musculoskeletal Research, School of Biological Sciences, The University of Manchester, Manchester, UK.
| | - Rohit Aggarwal
- Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
| |
Collapse
|
|
28
|
Ji-Xu A, Le ST, Maverakis E. Janus kinase inhibitors and risk of internal malignancy in dermatomyositis. J DERMATOL TREAT 2022; 33:2881-2882. [PMID: 35694732 DOI: 10.1080/09546634.2022.2089323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Antonio Ji-Xu
- Department of Dermatology, University of California, Davis, Sacramento, CA, USA
| | - Stephanie T Le
- Department of Dermatology, University of California, Davis, Sacramento, CA, USA
| | - Emanual Maverakis
- Department of Dermatology, University of California, Davis, Sacramento, CA, USA
| |
Collapse
|
|
29
|
Silva AMS, Campos ED, Zanoteli E. Inflammatory myopathies: an update for neurologists. ARQUIVOS DE NEURO-PSIQUIATRIA 2022; 80:238-248. [PMID: 35976321 PMCID: PMC9491410 DOI: 10.1590/0004-282x-anp-2022-s131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 04/29/2022] [Indexed: 06/15/2023]
Abstract
Idiopathic inflammatory myopathies (IIM) are a heterogenous group of treatable myopathies. Patients present mainly to the rheumatologist and neurologists, complaining of acute or subacute onset of proximal weakness. Extramuscular manifestations may occur, including involvement of the lungs, skin, and joints. Classically, the diagnosis used to be made based on the creatine kinase level increase, abnormalities in electroneuromyography and presence of inflammatory infiltrates in the muscle biopsy. Recently, the importance of autoantibodies has increased, and now they may be identified in more than half of IIM patients. The continuous clinicoseropathological improvement in IIM knowledge has changed the way we see these patients and how we classify them. In the past, only polymyositis, dermatomyositis and inclusion body myopathy were described. Currently, immune-mediated necrotizing myopathy, overlap myositis and antisynthetase syndrome have been considered the most common forms of IIM in clinical practice, increasing the spectrum of classification. Patients previously considered to have polymyositis, in fact have these other forms of seropositive IIM. In this article, we reviewed the new concepts of classification, a practical way to make the diagnosis and how to plan the treatment of patients suffering from IIM.
Collapse
Affiliation(s)
| | - Eliene Dutra Campos
- Universidade de São Paulo, Faculdade de Medicina, Departamento de Neurologia, São Paulo SP, Brazil
| | - Edmar Zanoteli
- Universidade de São Paulo, Faculdade de Medicina, Departamento de Neurologia, São Paulo SP, Brazil
| |
Collapse
|
|
30
|
Pathophysiological Mechanisms and Treatment of Dermatomyositis and Immune Mediated Necrotizing Myopathies: A Focused Review. Int J Mol Sci 2022; 23:ijms23084301. [PMID: 35457124 PMCID: PMC9030619 DOI: 10.3390/ijms23084301] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 03/31/2022] [Accepted: 04/05/2022] [Indexed: 12/15/2022] Open
Abstract
Idiopathic inflammatory myopathies (IIM), collectively known as myositis, are a composite group of rare autoimmune diseases affecting mostly skeletal muscle, although other organs or tissues may also be involved. The main clinical feature of myositis is subacute, progressive, symmetrical muscle weakness in the proximal arms and legs, whereas subtypes of myositis may also present with extramuscular features, such as skin involvement, arthritis or interstitial lung disease (ILD). Established subgroups of IIM include dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), anti-synthetase syndrome (ASyS), overlap myositis (OM) and inclusion body myositis (IBM). Although these subgroups have overlapping clinical features, the widespread variation in the clinical manifestations of IIM suggests different pathophysiological mechanisms. Various components of the immune system are known to be important immunopathogenic pathways in IIM, although the exact pathophysiological mechanisms causing the muscle damage remain unknown. Current treatment, which consists of glucocorticoids and other immunosuppressive or immunomodulating agents, often fails to achieve a sustained beneficial response and is associated with various adverse effects. New therapeutic targets have been identified that may improve outcomes in patients with IIM. A better understanding of the overlapping and diverging pathophysiological mechanisms of the major subgroups of myositis is needed to optimize treatment. The aim of this review is to report on recent advancements regarding DM and IMNM.
Collapse
|
|
31
|
Trallero-Araguás E, Gil-Vila A, Martínez-Gómez X, Pinal-Fernández I, Alvarado-Cardenas M, Simó-Perdigó M, Selva-O'Callaghan A. Cancer screening in idiopathic inflammatory myopathies: Ten years experience from a single center. Semin Arthritis Rheum 2022; 53:151940. [PMID: 35051890 PMCID: PMC11678788 DOI: 10.1016/j.semarthrit.2021.12.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 11/12/2021] [Accepted: 12/06/2021] [Indexed: 12/20/2022]
Abstract
OBJECTIVE There is a well-recognized association between cancer and myositis, so cancer screening at diagnosis is recommended. We aim to report the results of our cancer screening strategy and to ascertain the reliability of using PET/CT to identify cancer-associated myositis (CAM) in a large cohort of patients with myositis from a single center over 10 years. METHODS This retrospective observational study included all patients diagnosed with any type of myositis except for inclusion body myositis. Cancer screening strategy was individualized according to clinical and serological data, including PET/CT as the main test to detect occult cancer (OC). Procedures derived from a positive PET/CT were registered. Qualitative data expressed as percentages, and quantitative data as the median with the interquartile range were analyzed. A ROC curve was used to estimate the reliability of PET/CT for CAM diagnosis. RESULTS Seventy-seven out of 131 patients underwent a PET/CT for OC screening. The performance of the PET/CT in patients with myositis at disease onset yielded an area under the curve ROC of 0.87 (0.73-0.97) for CAM diagnosis. Invasive procedures in 7 (9%) patients without a final diagnosis of cancer did not cause derived complications. Patients not evaluated for OC did not develop cancer after a median follow-up of 3.3 years (1.7-6.7). CONCLUSION Cancer screening strategy should be individualized. PET/CT at myositis onset seems to be an efficient approach to rule out CAM. This practice does not seem to significantly increase harm to patients related to the additional tests needed to clarify inconclusive results.
Collapse
Affiliation(s)
- Ernesto Trallero-Araguás
- Rheumatology Department, Vall d'Hebron General Hospital, Calle Benet Cortada 38, Piso3, Puerta 1, Sant Cugat del Vallés, Barcelona 08174, Spain.
| | - Albert Gil-Vila
- Internal Medicine Department, Vall d'Hebron General Hospital, Barcelona, Spain; Departament de Medicina, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - X Martínez-Gómez
- Preventive Medicine and Epidemiology, Vall d'Hebron General Hospital, Universitat Autonoma de Barcelona, Spain
| | - Iago Pinal-Fernández
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Johns Hopkins University School of Medicine, Baltimore, United States; Faculty of Health Sciences, Universitat Oberta de Catalunya, Barcelona, Spain
| | - M Alvarado-Cardenas
- Internal Medicine Department, Vall d'Hebron General Hospital, Barcelona, Spain
| | - M Simó-Perdigó
- Nuclear Medicine Department, Vall d'Hebron General Hospital, Barcelona, Spain
| | | |
Collapse
|
|
32
|
Jauniaux B, Alexander M, Ismail A. Incidence of systemic autoimmune myopathies and their risk of cancer in Leeds, UK: an 11-year epidemiological study. Rheumatol Adv Pract 2022; 6:rkac023. [PMID: 35474883 PMCID: PMC9024320 DOI: 10.1093/rap/rkac023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 03/10/2022] [Indexed: 12/02/2022] Open
Abstract
Objectives The aims were to identify all incident adult cases of systemic autoimmune myopathies (SAMs) in the city of Leeds, UK, and to estimate the risk of cancer in SAMs as compared with the general population. Methods Cases of SAMs were ascertained by review of all muscle biopsy reports from the Neuropathology Laboratory. A review of medical records was undertaken for each case to review the clinical diagnosis and collect epidemiological data such as age, ethnicity, sex and comorbidities, including cancer. Leeds denominator population numbers were publicly obtainable. Results A total of 206 biopsy reports were identified and, after review, 50 incident cases were included in the study between June 2010 and January 2021. Of the 50 cases, 27 were male and 23 were female. The mean incidence rate of SAMs in Leeds throughout the study period was 7.42/1 000 000 person-years. The proportion of SAMs cases with a confirmed malignancy was 22%. Compared with the general population, the relative risk of cancer was significantly greater in the SAMs population (31.56; P < 0.01). Conclusions The incidence rate of SAMs in Leeds was consistent with data from previous literature; however, disagreement exists between different methods of SAMs case inclusion due to varying clinical criteria and definitions. SAMs are associated with an increased risk of cancer, but the pathogenesis of this relationship still requires investigating. This study supports the practice of malignancy screening and long-term surveillance in patients with SAMs.
Collapse
Affiliation(s)
| | | | - Azzam Ismail
- Department of Histopathology, St James’s University Hospital, Leeds, UK
| |
Collapse
|
|
33
|
Zhao L, Xie S, Zhou B, Shen C, Li L, Pi W, Gong Z, Zhao J, Peng Q, Zhou J, Peng J, Zhou Y, Zou L, Song L, Zhu H, Luo H. Machine Learning Algorithms Identify Clinical Subtypes and Cancer in Anti-TIF1γ+ Myositis: A Longitudinal Study of 87 Patients. Front Immunol 2022; 13:802499. [PMID: 35237262 PMCID: PMC8883045 DOI: 10.3389/fimmu.2022.802499] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 01/20/2022] [Indexed: 01/09/2023] Open
Abstract
BackgroundAnti-TIF1γ antibodies are a class of myositis-specific antibodies (MSAs) and are closely associated with adult cancer-associated myositis (CAM). The heterogeneity in anti-TIF1γ+ myositis is poorly explored, and whether anti-TIF1γ+ patients will develop cancer or not is unknown at their first diagnosis. Here, we aimed to explore the subtypes of anti-TIF1γ+ myositis and construct machine learning classifiers to predict cancer in anti-TIF1γ+ patients based on clinical features.MethodsA cohort of 87 anti-TIF1γ+ patients were enrolled and followed up in Xiangya Hospital from June 2017 to June 2021. Sankey diagrams indicating temporal relationships between anti-TIF1γ+ myositis and cancer were plotted. Elastic net and random forest were used to select and rank the most important variables. Multidimensional scaling (MDS) plot and hierarchical cluster analysis were performed to identify subtypes of anti-TIF1γ+ myositis. The clinical characteristics were compared among subtypes of anti-TIF1γ+ patients. Machine learning classifiers were constructed to predict cancer in anti-TIF1γ+ myositis, the accuracy of which was evaluated by receiver operating characteristic (ROC) curves.ResultsForty-seven (54.0%) anti-TIF1γ+ patients had cancer, 78.7% of which were diagnosed within 0.5 years of the myositis diagnosis. Fourteen variables contributing most to distinguishing cancer and non-cancer were selected and used for the calculation of the similarities (proximities) of samples and the construction of machine learning classifiers. The top 10 were disease duration, percentage of lymphocytes (L%), percentage of neutrophils (N%), neutrophil-to-lymphocyte ratio (NLR), sex, C-reactive protein (CRP), shawl sign, arthritis/arthralgia, V-neck sign, and anti-PM-Scl75 antibodies. Anti-TIF1γ+ myositis patients can be clearly separated into three clinical subtypes, which correspond to patients with low, intermediate, and high cancer risk, respectively. Machine learning classifiers [random forest, support vector machines (SVM), extreme gradient boosting (XGBoost), elastic net, and decision tree] had good predictions for cancer in anti-TIF1γ+ myositis patients. In particular, the prediction accuracy of random forest was >90%, and decision tree highlighted disease duration, NLR, and CRP as critical clinical parameters for recognizing cancer patients.ConclusionAnti-TIF1γ+ myositis can be separated into three distinct subtypes with low, intermediate, and high risk of cancer. Machine learning classifiers constructed with clinical characteristics have favorable performance in predicting cancer in anti-TIF1γ+ myositis, which can help physicians in choosing appropriate cancer screening programs.
Collapse
Affiliation(s)
- Lijuan Zhao
- Department of Rheumatology, Xiangya Hospital of Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, China
- Provincial Clinical Research Center for Rheumatic and Immunologic Diseases, Xiangya Hospital of Central South University, Changsha, China
| | - Shuoshan Xie
- Department of Nephrology, Hunan Provincial People’s Hospital and The First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Bin Zhou
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Chuyu Shen
- Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Liya Li
- Department of Rheumatology, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Weiwei Pi
- Department of Oncology, The First People’s Hospital of Changde City, Changde, China
| | - Zhen Gong
- Department of Rheumatology, Yiyang Central Hospital, Yiyang, China
| | - Jing Zhao
- Department of Rheumatology, The First Affiliated Hospital of Jishou University, Jishou, China
| | - Qi Peng
- Department of Rheumatology, Yueyang People’s Hospital, Yueyang, China
| | - Junyu Zhou
- Department of Rheumatology, Xiangya Hospital of Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, China
- Provincial Clinical Research Center for Rheumatic and Immunologic Diseases, Xiangya Hospital of Central South University, Changsha, China
| | - Jiaqi Peng
- Huaihua No.1 People’s Hospital Affiliated to Nanhua University, Huaihua, China
| | - Yan Zhou
- Department of Obstetrics and Gynecology, Zhuzhou Central Hospital, Zhuzhou, China
| | - Lingxiao Zou
- Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Liang Song
- Huaihua No.1 People’s Hospital Affiliated to Nanhua University, Huaihua, China
| | - Honglin Zhu
- Department of Rheumatology, Xiangya Hospital of Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, China
- Provincial Clinical Research Center for Rheumatic and Immunologic Diseases, Xiangya Hospital of Central South University, Changsha, China
- *Correspondence: Honglin Zhu, ; Hui Luo,
| | - Hui Luo
- Department of Rheumatology, Xiangya Hospital of Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, China
- Provincial Clinical Research Center for Rheumatic and Immunologic Diseases, Xiangya Hospital of Central South University, Changsha, China
- *Correspondence: Honglin Zhu, ; Hui Luo,
| |
Collapse
|
|
34
|
Pacheco M, Ferreira H, Silva C, Silva J, Matias E, Antunes T, Almeida JS. Antinuclear Antibody (ANA) and Anti-Mi-2-Alpha Positive Dermatomyositis Hinting a Cancer Diagnosis. Cureus 2022; 14:e21844. [PMID: 35291538 PMCID: PMC8896541 DOI: 10.7759/cureus.21844] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/02/2022] [Indexed: 11/17/2022] Open
Abstract
Dermatomyositis (DM) is a relatively uncommon inflammatory myopathy that has been linked to cancer. We report the case of an 81-year-old woman with cecum adenocarcinoma presenting with antinuclear antibody (ANA) and anti-Mi-2-alpha antibody-positive DM. The patient complained of anorexia, symmetric proximal muscle weakness and skin rash and presented with elevated muscle enzymes. A skin and muscle biopsy supported the diagnosis of DM as did the limbs magnetic resonance imaging (MRI) and electromyography. A diagnosis of localized adenocarcinoma of the cecum was made through colonoscopy and the patient was successfully surgically managed, with decreasing muscle enzymes at discharge and gradual recovery of muscle strength. The presence of both ANA and anti-Mi-2 autoantibodies has classically been described as comprising a better prognosis with a lower risk of underlying malignancy. This case highlights the importance of pursuing a cancer diagnosis in elderly patients presenting with DM even in presence of less predisposing immunological profiles.
Collapse
|
|
35
|
Update on Malignancy in Myositis—Well-Established Association with Unmet Needs. Biomolecules 2022; 12:biom12010111. [PMID: 35053259 PMCID: PMC8773676 DOI: 10.3390/biom12010111] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Revised: 01/06/2022] [Accepted: 01/09/2022] [Indexed: 12/31/2022] Open
Abstract
Idiopathic inflammatory myopathies are a group of rare connective tissue diseases with a well-documented association with malignancy. The mechanisms underlying the increased risk of neoplasms in the course of myositis are not fully understood. The Pubmed database has been thoroughly screened for articles concerning cancer-associated myositis (CAM). The article summarizes the current state of knowledge on the epidemiology and pathogenesis of CAM. Furthermore, it analyses potential risk and protective factors for developing CAM, with particular emphasis on the association with distinct serological profiles. The review summarizes recommendations proposed so far for the management of CAM and presents a novel scheme for cancer screening proposed by the authors. Moreover, promising areas requiring further research were indicated.
Collapse
|
|
36
|
Padniewski JJ, Nelson E, Mian I, Laczniak A, Ives S, Nasr R. Paraneoplastic myopathy in pancreatic cancer: a case report and literature review. J Community Hosp Intern Med Perspect 2021; 11:847-851. [PMID: 34804404 PMCID: PMC8604545 DOI: 10.1080/20009666.2021.1982487] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Dermatomyositis (DM) and polymyositis (PM) are both immune-mediated inflammatory myopathies known to occur in paraneoplastic syndromes associated with a new diagnosis of malignancy, most commonly breast, ovarian, lung, pancreatic, stomach, colorectal, and Non-Hodgkin’s lymphoma1 in DM and breast, lung, bladder cancer, and Non-Hodgkin’s lymphoma in PM. 2,3,4 While inflammatory markers such as creatine kinase (CK) may be elevated with either DM or PM, marked elevation is rare. Herein, we report a case of newly diagnosed pancreatic cancer presenting with inflammatory myopathy and marked CK elevation. We review the frequency of PM as a paraneoplastic syndrome, the association with marked CK elevation, and the association with pancreatic cancer.
Collapse
Affiliation(s)
| | - Elizabeth Nelson
- Department of Medicine , Hennepin Healthcare Internal Medicine Residency, Minneapolis, MN, USA
| | - Istiaq Mian
- Department of Medicine, SSM Health, Madison, WI, USA
| | | | - Samuel Ives
- Division of General Internal Medicine, Hennepin Healthcare, Minneapolis, MN, USA
| | - Rawad Nasr
- Division of General Internal Medicine, Hennepin Healthcare, Minneapolis, MN, USA.,Division of Rheumatology, Hennepin Healthcare, Minneapolis, MN, USA
| |
Collapse
|
|
37
|
Oldroyd AGS, Allard AB, Callen JP, Chinoy H, Chung L, Fiorentino D, George MD, Gordon P, Kolstad K, Kurtzman DJB, Machado PM, McHugh NJ, Postolova A, Selva-O'Callaghan A, Schmidt J, Tansley S, Vleugels RA, Werth VP, Aggarwal R. A systematic review and meta-analysis to inform cancer screening guidelines in idiopathic inflammatory myopathies. Rheumatology (Oxford) 2021; 60:2615-2628. [PMID: 33599244 PMCID: PMC8213426 DOI: 10.1093/rheumatology/keab166] [Citation(s) in RCA: 88] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 01/26/2021] [Accepted: 02/11/2021] [Indexed: 02/04/2023] Open
Abstract
Objectives To identify clinical factors associated with cancer risk in the idiopathic inflammatory myopathies (IIMs) and to systematically review the existing evidence related to cancer screening. Methods A systematic literature search was carried out on Medline, Embase and Scopus. Cancer risk within the IIM population (i.e. not compared with the general population) was expressed as risk ratios (RR) for binary variables and weighted mean differences (WMD) for continuous variables. Evidence relating to cancer screening practices in the IIMs were synthesized via narrative review. Results Sixty-nine studies were included in the meta-analysis. DM subtype (RR 2.21), older age (WMD 11.19), male sex (RR 1.53), dysphagia (RR 2.09), cutaneous ulceration (RR 2.73) and anti-transcriptional intermediary factor-1 gamma positivity (RR 4.66) were identified as being associated with significantly increased risk of cancer. PM (RR 0.49) and clinically amyopathic DM (RR 0.44) subtypes, Raynaud’s phenomenon (RR 0.61), interstitial lung disease (RR 0.49), very high serum creatine kinase (WMD −1189.96) or lactate dehydrogenase (WMD −336.52) levels, and anti-Jo1 (RR 0.45) or anti-EJ (RR 0.17) positivity were identified as being associated with significantly reduced risk of cancer. Nine studies relating to IIM-specific cancer screening were included. CT scanning of the thorax, abdomen and pelvis appeared to be effective in identifying underlying asymptomatic cancers. Conclusion Cancer risk factors should be evaluated in patients with IIM for risk stratification. Screening evidence is limited but CT scanning could be useful. Prospective studies and consensus guidelines are needed to establish cancer screening strategies in IIM patients.
Collapse
Affiliation(s)
- Alexander G S Oldroyd
- National Institute for Health Research Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester, UK.,Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.,Centre for Epidemiology Versus Arthritis, University of Manchester, Manchester, UK.,Department of Rheumatology, Salford Royal NHS Foundation Trust, Salford, UK
| | - Andrew B Allard
- Royal National Hospital for Rheumatic Diseases, Royal United Hospitals Bath NHS Foundation Trust, Bath, UK
| | - Jeffrey P Callen
- Division of Medicine, Department of Medicine, University of Louisville, Louisville, KY, USA
| | - Hector Chinoy
- National Institute for Health Research Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester, UK.,Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.,Department of Rheumatology, Salford Royal NHS Foundation Trust, Salford, UK
| | - Lorinda Chung
- Division of Immunology and Rheumatology, Department of Medicine and Dermatology, Stanford University, Stanford, USA.,Palo Alto Health Care System, Palo Alto, USA
| | - David Fiorentino
- Department of Dermatology, School of Medicine, Stanford University, Stanford, CA, USA
| | - Michael D George
- Division of Rheumatology, Philadelphia, PA, USA.,Division of Epidemiology, University of Pennsylvania, Philadelphia, PA, USA
| | - Patrick Gordon
- Department of Rheumatology, King's College Hospital NHS Foundation Trust, London, UK
| | - Kate Kolstad
- Department of Dermatology, School of Medicine, Stanford University, Stanford, CA, USA
| | | | - Pedro M Machado
- Centre for Rheumatology and Department of Neuromuscular Diseases, University College London, London, UK.,National Institute for Health Research University College London Hospitals Biomedical Research Centre, University College London Hospitals NHS Trust, London, UK.,Department of Rheumatology, Northwick Park Hospital, London North West University Healthcare NHS Trust, London, UK
| | - Neil J McHugh
- Department of Pharmacy and Pharmacology, University of Bath, Bath, UK
| | - Anna Postolova
- Department of Immunology and Rheumatology, Stanford Health Care, Stanford, CA, USA
| | - Albert Selva-O'Callaghan
- Systemic Autoimmune Unity, Vall D'Hebron General Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain
| | - Jens Schmidt
- Department of Neurology, Neuromuscular Centre, Göttingen, Germany
| | - Sarah Tansley
- Royal National Hospital for Rheumatic Diseases, Royal United Hospitals Bath NHS Foundation Trust, Bath, UK.,Department of Neurology, Neuromuscular Centre, Göttingen, Germany
| | - Ruth Ann Vleugels
- Harvard Medical School, Boston, MA, USA.,Department of Dermatology, Brigham and Women's Hospital, Boston, MA, USA
| | - Victoria P Werth
- Department of Dermatology, University of Pennsylvania, Philadelphia, USA.,Division of Dermatology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, USA
| | - Rohit Aggarwal
- Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| |
Collapse
|
|
38
|
Masetti R, Tiri A, Tignanelli A, Turrini E, Argentiero A, Pession A, Esposito S. Autoimmunity and cancer. Autoimmun Rev 2021; 20:102882. [PMID: 34229048 DOI: 10.1016/j.autrev.2021.102882] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Accepted: 04/28/2021] [Indexed: 12/20/2022]
Abstract
In many autoimmune rheumatic diseases, there is an increased risk of cancer compared to the general population. The link between autoimmunity and cancer is dynamic and bidirectional. Recent advances in terms of knowledge of biology, epidemiology, and long-term outcomes for the autoimmune rheumatic diseases have revealed several new connections between these two entities. Data suggest that chronic inflammation from the rheumatic diseases or their therapies may contribute to the onset and promotion of cancer. Conversely, antitumor immune responses may become cross-reactive with self-tissues resulting in the development of autoimmunity. In this review, we discuss about the potential mechanisms that link autoimmune rheumatic diseases and cancer and the association of malignancies with common autoimmune disorders. The increased incidence of malignancy in autoimmune rheumatic diseases has been largely described, although the biology underpinning this relationship should be further investigated. The development of evidence-based cancer screening recommendations in patients with autoimmune rheumatic diseases is complex due to the heterogeneity of clinical rheumatic phenotypes, cancer sites at risk and exposure to anti-neoplastic and anti-rheumatic treatment. In order to lay the foundation of risk stratification and targeted cancer screening, larger longitudinal cohort studies that provide a more detailed framework of the links between cancer and autoimmunity are urgently needed.
Collapse
Affiliation(s)
- Riccardo Masetti
- Pediatric Clinic, IRCCS Ospedale Maggiore Policlinico Sant'Orsola, Department of Medicine and Surgery, University of Bologna, Bologna, Italy
| | - Alessandra Tiri
- Pediatric Clinic, Department of Medicine and Surgery, Azienda Ospedaliera-Universitaria, University of Parma, Parma, Italy
| | - Anna Tignanelli
- Pediatric Clinic, Department of Medicine and Surgery, Azienda Ospedaliera-Universitaria, University of Parma, Parma, Italy
| | - Elena Turrini
- Pediatric Clinic, Department of Medicine and Surgery, Azienda Ospedaliera-Universitaria, University of Parma, Parma, Italy
| | - Alberto Argentiero
- Pediatric Clinic, Department of Medicine and Surgery, Azienda Ospedaliera-Universitaria, University of Parma, Parma, Italy
| | - Andrea Pession
- Pediatric Clinic, IRCCS Ospedale Maggiore Policlinico Sant'Orsola, Department of Medicine and Surgery, University of Bologna, Bologna, Italy
| | - Susanna Esposito
- Pediatric Clinic, Department of Medicine and Surgery, Azienda Ospedaliera-Universitaria, University of Parma, Parma, Italy.
| |
Collapse
|
|
39
|
Aljohani G, Bin Awad EA, Alshahrani K, Alsaqar MM, Albogami B, Almotywee SH, Almaimouni H, Dirar AS, Alrashid A, Rajendram R, Masuadi E, Omair MA. The prevalence, clinical features, predictive factors and investigations to screen for cancer in patients with inflammatory myositis. A case series from two tertiary care centers in Riyadh, Saudi Arabia. Saudi Med J 2021; 42:100-104. [PMID: 33399178 PMCID: PMC7989309 DOI: 10.15537/smj.2021.1.25590] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Objectives: To describes the epidemiology of cancer in patients with idiopathic inflammatory myopathies (IIM) treated at 2 tertiary centers in Riyadh, Saudi Arabia. Methods: This was a retrospective multi-center study evaluating the prevalence and the type of malignancy in an IIM population in King Saud University Medical City and King Abdulaziz Medical City between August 2017 to August 2018. Results: In total, 60 patients were included. Four had neoplasms (6.7%), 2 men had lymphoma, a woman had breast cancer and a second, ovarian cancer. Two patients died due to cancer or its complications. Older age (age >40 years), dysphagia, necrotic rash, absence of interstitial lung disease, high erythrocyte sedimentation rate and a negative anti Jo-1 antibody were potentially predictive risk factors for neoplasm. All patients diagnosed with cancer-associated myositis were investigated with routine and invasive modalities. Three of the 4 patients had abnormal findings in both modalities. One patient, the routine investigations were unremarkable, but a computed tomography of the pelvis revealed an ovarian mass that was subsequently diagnosed as malignant. Conclusion: An individualized approach might be more appropriate for high risk patients. Larger prospective studies are required to confirm the findings of the current study.
Collapse
Affiliation(s)
- Ghassan Aljohani
- Department of Medicine, King Abdulaziz Medical City, Ministry of National Guard - Health Affairs, King Saud University, Riyadh, Kingdom of Saudi Arabia. E-mail.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
40
|
Lin TL, Wu CY, Juan CK, Chang YT, Chen YJ. Long-Term Risk of Autoimmune Diseases other than Systemic Lupus Erythematosus in Cutaneous Lupus Erythematosus-Alone Patients: A 10-Year Nationwide Cohort Study. Dermatology 2021; 238:92-100. [PMID: 34062538 DOI: 10.1159/000515524] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Accepted: 02/27/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Up to 25% of patients with cutaneous lupus erythematosus (CLE) can develop systemic lupus erythematosus (SLE). However, the risk of autoimmune diseases other than SLE in CLE patients who have only skin manifestations (CLE-alone) has rarely been explored. OBJECTIVE To investigate the long-term risk and independent factors of non-SLE autoimmune diseases among CLE-alone patients. METHOD A nationwide cohort study using the Taiwanese National Health Insurance Research Database 1997-2013. CLE patients and matched subjects were included. Cumulative incidences of autoimmune diseases after 1 year of CLE-alone diagnosis were compared. Cox proportional hazard model was also performed. RESULTS A total of 971 CLE-alone patients and 5,175 reference subjects were identified. The 10-year cumulative incidence of autoimmune diseases other than SLE was significantly elevated in the CLE-alone cohort (9.00%, 95% confidence interval [CI] 6.72-11.29) than in the reference cohort (4.20%, 95% CI 3.53-4.87%) (p < 0.001). CLE-alone was independently associated with non-SLE autoimmune diseases (adjusted hazard ratio 1.55, 95% CI 1.10-2.18). Among CLE-alone patients, females and those taking long-term systemic corticosteroids (a proxy for extensive disease) were associated with non-SLE autoimmune diseases after adjusting for the number of repeated autoimmune laboratory tests. CONCLUSION CLE-alone is independently associated with future non-SLE autoimmune diseases.
Collapse
Affiliation(s)
- Teng-Li Lin
- Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chun-Ying Wu
- Faculty of Medicine and Graduate Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Translational Medicine, Department of Medicinal Research, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan.,Department of Public Health and Graduate Institute of Clinical Medical Sciences, China Medical University, Taichung, Taiwan.,Department of Life Sciences and Rong Hsing Research Center for Translational Medicine, National Chung-Hsing University, Taichung, Taiwan.,Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan
| | - Chao-Kuei Juan
- Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan.,Faculty of Medicine and Graduate Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Yun-Ting Chang
- Faculty of Medicine and Graduate Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Ju Chen
- Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan.,Faculty of Medicine and Graduate Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.,Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan
| |
Collapse
|
|
41
|
Klukas J, Pudszuhn A, Kusch K, Obermueller T, Hofmann VM. [Dermatomyositis as a paraneoplastic syndrome of head-neck-cancer: Case series & literature review]. Laryngorhinootologie 2021; 100:542-549. [PMID: 33906244 DOI: 10.1055/a-1408-6551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
INTRODUCTION Dermatomyositis (DM) is a rare disease with the clinical manifestation of weakness and pain of proximal muscles as well as lilac-coloured skin lesions. One fifth of the cases is associated with the occurrence of a malignant tumor disease. The aim of this study is to evaluate the relevance of DM as a paraneoplastic syndrome in head and neck cancer taken into account the current literature. MATERIAL/METHODS After retrospective analysis of medical records of head-neck-cancer patients treated between 2008 and 2018, 8 patients with DM were detected: 4 patients with tonsil carcinoma, 1 patient with nasopharyngeal carcinoma, 1 patient carcinoma of the parotid gland and two patients with lymphoma. The diagnosis, therapy and treatment results of these cases are described. Furthermore, a selective analysis of the literature (pubmed) about DM with head-neck cancer was conducted. A total of 290 cases were identified: In 283 cases, the tumors were located in the nasopharynx, in five cases in the tonsil and in two cases in the hypopharynx. CONCLUSION DM as a paraneoplastic syndrome of head and neck tumors is rare and more often associated with nasopharyngeal cancer and rarely with tonsil cancer. The clustering of DM with head and neck tumors regarding ethnicity (nasopharyngeal carcinoma - Asian origin, tonsillar carcinoma- Caucasian origin) might be due to the regional different incidences of these tumor entities.In patients with DM, especially in presence of cervical lymphadenopathy a tumor in the head and neck area should be evaluated. The course of tumor-associated DM is positively influenced by tumor therapy. The consistent therapy and monitoring of DM is fundamental for a successful tumor treatment as well.
Collapse
Affiliation(s)
- Jana Klukas
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Klinik für Hals-Nasen-Ohrenheilkunde, Campus Benjamin Franklin
| | - Annett Pudszuhn
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Klinik für Hals-Nasen-Ohrenheilkunde, Campus Benjamin Franklin
| | - Kerstin Kusch
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Klinik für Dermatologie, Venerologie und Allergologie, Campus Benjamin Franklin
| | - Theresa Obermueller
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Klinik für Hals-Nasen-Ohrenheilkunde, Campus Benjamin Franklin
| | - Veit M Hofmann
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Klinik für Hals-Nasen-Ohrenheilkunde, Campus Benjamin Franklin
| |
Collapse
|
|
42
|
Irekeola AA, Shueb RH, E. A. R. ENS, Wada Y, Abdul Rahman Z, Ahmad S, Mohamud R, Mat Lazim N, Yean CY. Prevalence of Nasopharyngeal Carcinoma in Patients with Dermatomyositis: A Systematic Review and Meta-Analysis. Cancers (Basel) 2021; 13:cancers13081886. [PMID: 33919987 PMCID: PMC8071042 DOI: 10.3390/cancers13081886] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 03/25/2021] [Accepted: 04/03/2021] [Indexed: 01/02/2023] Open
Abstract
Simple Summary This first systematic review and meta-analysis on the prevalence of nasopharyngeal carcinoma in patients suffering dermatomyositis was necessitated by the absence of a true and reliable prevalence estimate necessary to adequately inform medical preparedness and decisions. Following a careful review of literature and data analyses, a prevalence of 3.3% was found. It is hoped that a clear knowledge of the actual prevalence of nasopharyngeal carcinoma in dermatomyositis patients would not only help sensitize clinicians and patients about the frequency of these disease conditions but would also enhance the adoption of precautions essential to mitigate their co-occurrence in patients. Abstract For more than 50 years, nasopharyngeal carcinoma (NPC) has been associated with dermatomyositis (DM), a rare idiopathic inflammatory disorder that mainly affects the skin and muscles. Although the association between these rare diseases is well-documented, the actual prevalence of NPC in DM patients remains unknown. Here, a systematic review and meta-analysis of published data was conducted in accordance with the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Electronic databases including PubMed, Scopus, ScienceDirect, and Google Scholar were searched without year or language restrictions for studies reporting the occurrence of NPC in DM patients. The study protocol was lodged with PROSPERO (CRD42021225335). A total of 95 studies covering 303 cases of NPC among 16,010 DM patients was included. Summary estimates were calculated using the random-effects model. The pooled prevalence of NPC in DM was 3.3% (95% CI, 2.5–4.3). When stratified according to study location, higher prevalence estimates were obtained for Hong Kong (36.5%), Malaysia (27.7%), and Singapore (11.9%). There was a predominance of cases among male DM patients compared with females, and most patients were aged 40 and above. Many of the NPC cases were found to be diagnosed after the diagnosis of DM. It is therefore pertinent to screen for NPC in DM patients, especially among older DM patients in the Asian region.
Collapse
Affiliation(s)
- Ahmad Adebayo Irekeola
- Department of Medical Microbiology and Parasitology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia; (A.A.I.); (E.N.S.E.A.R.); (Y.W.); (Z.A.R.); (C.Y.Y.)
- Microbiology Unit, Department of Biological Sciences, College of Natural and Applied Sciences, Summit University Offa, Offa PMB 4412, Nigeria
| | - Rafidah Hanim Shueb
- Department of Medical Microbiology and Parasitology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia; (A.A.I.); (E.N.S.E.A.R.); (Y.W.); (Z.A.R.); (C.Y.Y.)
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
- Correspondence:
| | - Engku Nur Syafirah E. A. R.
- Department of Medical Microbiology and Parasitology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia; (A.A.I.); (E.N.S.E.A.R.); (Y.W.); (Z.A.R.); (C.Y.Y.)
| | - Yusuf Wada
- Department of Medical Microbiology and Parasitology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia; (A.A.I.); (E.N.S.E.A.R.); (Y.W.); (Z.A.R.); (C.Y.Y.)
- Department of Zoology, Faculty of Life Sciences, Ahmadu Bello University, Zaria 810211, Nigeria
| | - Zaidah Abdul Rahman
- Department of Medical Microbiology and Parasitology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia; (A.A.I.); (E.N.S.E.A.R.); (Y.W.); (Z.A.R.); (C.Y.Y.)
- Hospital Universiti Sains Malaysia, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
| | - Suhana Ahmad
- Department of Immunology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia; (S.A.); (R.M.)
| | - Rohimah Mohamud
- Department of Immunology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia; (S.A.); (R.M.)
| | - Norhafiza Mat Lazim
- Department of Otorhinolaryngology-Head and Neck Surgery, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia;
| | - Chan Yean Yean
- Department of Medical Microbiology and Parasitology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia; (A.A.I.); (E.N.S.E.A.R.); (Y.W.); (Z.A.R.); (C.Y.Y.)
| |
Collapse
|
|
43
|
Dermatomyositis associated with gastrointestinal malignancies - report of two cases and a literature review. Postepy Dermatol Alergol 2021; 38:343-345. [PMID: 36751537 PMCID: PMC9880788 DOI: 10.5114/ada.2021.106217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Accepted: 09/30/2019] [Indexed: 11/17/2022] Open
|
|
44
|
Abstract
Paraneoplastic skin manifestations associated with malignancies are extremely polymorphous. Clinicians should be familiar with paraneoplastic dermatoses to establish an early diagnosis of the underlying neoplasm. Lack of familiarity with cutaneous clues for internal malignancies may delay diagnosis and treatment of cancer. In this review, we describe several paraneoplastic autoimmune dermatoses, including paraneoplastic autoimmune multiorgan syndrome, paraneoplastic bullous pemphigoid, and paraneoplastic dermatomyositis.
Collapse
Affiliation(s)
- D Didona
- Klinik für Dermatologie und Allergologie, Philipps-Universität Marburg, Baldingerstr., 35043, Marburg, Deutschland.
| | - M Hertl
- Klinik für Dermatologie und Allergologie, Philipps-Universität Marburg, Baldingerstr., 35043, Marburg, Deutschland
| |
Collapse
|
|
45
|
Hsu JL, Liao MF, Chu CC, Kuo HC, Lyu RK, Chang HS, Chen CM, Wu YR, Chang KH, Weng YC, Chang CW, Chiang HI, Cheng CK, Lee PW, Huang CC, Ro LS. Reappraisal of the incidence, various types and risk factors of malignancies in patients with dermatomyositis and polymyositis in Taiwan. Sci Rep 2021; 11:4545. [PMID: 33633147 PMCID: PMC7907377 DOI: 10.1038/s41598-021-83729-5] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Accepted: 01/14/2021] [Indexed: 12/13/2022] Open
Abstract
Our study aimed to investigate the incidence, risk factors and time to occurrence of malignancy in patients with dermatomyositis (DM) and polymyositis (PM). The electronic medical records of 1100 patients with DM and 1164 patients with PM were studied between January 2001 and May 2019. Malignancies after myositis were diagnosed in 61 (5.55%) patients with DM and 38 (3.26%) patients with PM. The cumulative incidence of malignancies in patients with DM were significantly higher than patients with PM (hazard ratio = 1.78, log-rank p = 0.004). Patients with DM had a greater risk of developing malignancy than those with PM at 40–59 years old (p = 0.01). Most malignancies occurred within 1 year after the initial diagnosis of DM (n = 35; 57.38%). Nasopharyngeal cancer (NPC) was the most common type of malignancy in patients with DM (22.95%), followed by lung, and breast cancers. In patients with PM, colorectal, lung and hepatic malignancies were the top three types of malignancy. The risk factors for malignancy included old age (≥ 45 years old) and low serum levels of creatine phosphokinase (CPK) for patients with DM and male sex and low serum levels of CPK for patients with PM. Low serum levels of CPK in patients with myositis with malignancy represented a low degree of muscle destruction/inflammation, which might be attributed to activation of the PD-L1 pathway by tumor cells, thus inducing T-cell dysfunction mediating immune responses in myofibers. A treatment and follow-up algorithm should explore the occurrence of malignancy in different tissues and organs and suggested annual follow-ups for at least 5.5 years to cover the 80% cumulative incidence of malignancy in patients with DM and PM.
Collapse
Affiliation(s)
- Jung-Lung Hsu
- Department of Neurology, New Taipei Municipal TuCheng Hospital, Chang Gung Memorial Hospital and Chang Gung University, New Taipei City, Taiwan.,Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang-Gung University, Linkou, Taoyuan, Taiwan.,Graduate Institute of Mind Brain and Consciousness, Taipei Medical University, Taipei, Taiwan.,Brain and Consciousness Research Center, Shuang Ho Hospital, New Taipei City, Taiwan
| | - Ming-Feng Liao
- Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang-Gung University, Linkou, Taoyuan, Taiwan
| | - Chun-Che Chu
- Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang-Gung University, Linkou, Taoyuan, Taiwan
| | - Hung-Chou Kuo
- Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang-Gung University, Linkou, Taoyuan, Taiwan
| | - Rong-Kuo Lyu
- Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang-Gung University, Linkou, Taoyuan, Taiwan
| | - Hong-Shiu Chang
- Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang-Gung University, Linkou, Taoyuan, Taiwan
| | - Chiung-Mei Chen
- Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang-Gung University, Linkou, Taoyuan, Taiwan
| | - Yih-Ru Wu
- Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang-Gung University, Linkou, Taoyuan, Taiwan
| | - Kuo-Hsuan Chang
- Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang-Gung University, Linkou, Taoyuan, Taiwan
| | - Yi-Ching Weng
- Department of Neurology, New Taipei Municipal TuCheng Hospital, Chang Gung Memorial Hospital and Chang Gung University, New Taipei City, Taiwan.,Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang-Gung University, Linkou, Taoyuan, Taiwan
| | - Chun-Wei Chang
- Department of Neurology, New Taipei Municipal TuCheng Hospital, Chang Gung Memorial Hospital and Chang Gung University, New Taipei City, Taiwan.,Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang-Gung University, Linkou, Taoyuan, Taiwan
| | - Hsing-I Chiang
- Department of Neurology, New Taipei Municipal TuCheng Hospital, Chang Gung Memorial Hospital and Chang Gung University, New Taipei City, Taiwan.,Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang-Gung University, Linkou, Taoyuan, Taiwan
| | - Chih-Kuang Cheng
- Department of Neurology, New Taipei Municipal TuCheng Hospital, Chang Gung Memorial Hospital and Chang Gung University, New Taipei City, Taiwan.,Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang-Gung University, Linkou, Taoyuan, Taiwan
| | - Pai-Wei Lee
- Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | - Chin-Chang Huang
- Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang-Gung University, Linkou, Taoyuan, Taiwan
| | - Long-Sun Ro
- Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang-Gung University, Linkou, Taoyuan, Taiwan.
| |
Collapse
|
|
46
|
A Study on Dermatomyositis and the Relation to Malignancy. CURRENT HEALTH SCIENCES JOURNAL 2021; 47:377-382. [PMID: 35003769 PMCID: PMC8679146 DOI: 10.12865/chsj.47.03.07] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Accepted: 09/27/2021] [Indexed: 11/16/2022]
Abstract
The idiopathic inflammatory myopathies (IIM) are a group of heterogeneous systemic diseases which include as main subtypes: polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM). The key feature of IIMs is the muscle weakness, accompanied by a characteristic skin rash in DM patients. The overall risk for malignancy in IIM is higher compared to the age-and sex-matched general population. Most epidemiologic studies have included only PM and DM patients and reported consistently higher rates of malignancy in DM. Most common types of cancer in DM are adenocarcinoma of the lung, ovary or gastrointestinal tract, melanoma and non-Hodgkins lymphoma. The highest risk for malignancy is seen in the first year after DM diagnosis. Multiple disease features have been linked to the development of cancer in DM. These include: older age, male sex, skin necrosis, Gottron sign, heliotrope rash, dysphagia, low complement C4, lymphocytosis, poor response to corticosteroids and rapid disease progression. Our study included 23 patients with DM, divided into two groups based on the association of malignancy, in order to compare clinical and demographic features, laboratory markers and analyze characteristic of cancer development.
Collapse
|
|
47
|
Terakawa K, Sawa N, Mizuno H, Sekine A, Hayami N, Ikuma D, Kawada M, Hiramatsu R, Sumida K, Yamanouchi M, Hasegawa E, Suwabe T, Hoshino J, Kinowaki K, Ohashi K, Fujii T, Ubara Y. Renal Squamous Cell Carcinoma-related Polymyositis in a Patient with Autosomal Dominant Polycystic Kidney Disease. Intern Med 2021; 60:1237-1242. [PMID: 33853995 PMCID: PMC8112967 DOI: 10.2169/internalmedicine.5375-20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
A 74-year-old Japanese woman diagnosed with autosomal dominant polycystic kidney disease (ADPKD) was admitted to our institute for the further examination of right-side groin pain developing in the past week. The patient was diagnosed with polymyositis (PM). Diagnostic imaging showed a mass lesion measuring 8 cm and a renal stone in the right kidney. Immediately following surgical resection of the right kidney, the patient's serum CK decreased to the normal range. A histopathological analysis showed well-differentiated squamous cell carcinoma. In conclusion, this case showed a close relationship between the occurrence of squamous cell carcinoma and the development of PM in an ADPKD patient.
Collapse
Affiliation(s)
- Kanako Terakawa
- Nephrology Center and Department of Rheumatology, Toranomon Hospital, Japan
| | - Naoki Sawa
- Nephrology Center and Department of Rheumatology, Toranomon Hospital, Japan
- Okinaka Memorial Institute for Medical Research, Japan
| | - Hiroki Mizuno
- Nephrology Center and Department of Rheumatology, Toranomon Hospital, Japan
| | - Akinari Sekine
- Nephrology Center and Department of Rheumatology, Toranomon Hospital, Japan
| | - Noriko Hayami
- Nephrology Center and Department of Rheumatology, Toranomon Hospital, Japan
| | - Daisuke Ikuma
- Nephrology Center and Department of Rheumatology, Toranomon Hospital, Japan
| | - Masahiro Kawada
- Nephrology Center and Department of Rheumatology, Toranomon Hospital, Japan
| | - Rikako Hiramatsu
- Nephrology Center and Department of Rheumatology, Toranomon Hospital, Japan
| | - Keiichi Sumida
- Nephrology Center and Department of Rheumatology, Toranomon Hospital, Japan
| | | | - Eiko Hasegawa
- Nephrology Center and Department of Rheumatology, Toranomon Hospital, Japan
| | - Tatsuya Suwabe
- Nephrology Center and Department of Rheumatology, Toranomon Hospital, Japan
| | - Junichi Hoshino
- Nephrology Center and Department of Rheumatology, Toranomon Hospital, Japan
- Okinaka Memorial Institute for Medical Research, Japan
| | | | - Kenichi Ohashi
- Department of Pathology, Toranomon Hospital, Japan
- Department of Pathology, Yokohama City University Hospital Graduate School of Medicine, Japan
| | | | - Yoshifumi Ubara
- Nephrology Center and Department of Rheumatology, Toranomon Hospital, Japan
- Okinaka Memorial Institute for Medical Research, Japan
| |
Collapse
|
|
48
|
Dani L, Ian Che W, Lundberg IE, Hellgren K, Holmqvist M. Overall and site-specific cancer before and after diagnosis of idiopathic inflammatory myopathies: A nationwide study 2002-2016. Semin Arthritis Rheum 2020; 51:331-337. [PMID: 33508731 DOI: 10.1016/j.semarthrit.2020.12.009] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 12/14/2020] [Accepted: 12/21/2020] [Indexed: 01/01/2023]
Abstract
OBJECTIVE To examine the association between idiopathic inflammatory myopathy (IIM) and cancer before and after IIM diagnosis. METHODS We used prospectively collected nationwide register data to design a case-control study to investigate the occurrence of cancer before IIM, and a cohort study to investigate the occurrence of cancer after IIM. Patients diagnosed with IIM between 2002 and 2016 in Sweden, were compared to the general population. The association between cancer and IIM was estimated before and after IIM diagnosis via logistic regression and Cox regression models, respectively. RESULTS We included 1419 patients with IIM and 7045 individuals from the general population. The overall odds of cancer before IIM diagnosis were increased in IIM compared to the general population, adjusted odds ratio (AOR) 1.5, 95% confidence interval (CI) 1.3-1.8. This association was also noted after IIM diagnosis, adjusted hazard ratio (AHR) 1.7 (95% CI 1.4-2.0), or one additional cancer in every 125 IIM patients per year. Colorectal (AOR 2.1), lung (AOR 5.4) and ovarian (AOR 7.0) cancers were associated with IIM before diagnosis. Oropharyngeal (AHR 9.1) and cervical (AHR 3.8) cancers, malignant melanoma (AHR 3.2) and non-melanoma skin cancer (AHR 3.1) were associated with IIM after diagnosis. Adenocarcinomas were associated with dermatomyositis before diagnosis and squamous cell cancers after IIM diagnosis. Lymphatic hematopoietic cancers were associated with IIM both before and after diagnosis. CONCLUSIONS The cancer types that occur before IIM diagnosis differ from the ones that occur after diagnosis. This may have an impact on screening decisions for IIM.
Collapse
Affiliation(s)
- Lara Dani
- Rheumatology Division, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
| | - Weng Ian Che
- Clinical Epidemiology Division, Departement of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
| | - Ingrid E Lundberg
- Rheumatology Division, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Karin Hellgren
- Rheumatology Division, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Clinical Epidemiology Division, Departement of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
| | - Marie Holmqvist
- Rheumatology Division, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Clinical Epidemiology Division, Departement of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
| |
Collapse
|
|
49
|
Sung YK, Jung SY, Kim H, Choi S, Im SG, Cha EJ, Jang EJ, Yoo DH, Cho SK. Temporal relationship between idiopathic inflammatory myopathies and malignancies and its mortality: a nationwide population-based study. Clin Rheumatol 2020; 39:3409-3416. [DOI: 10.1007/s10067-019-04782-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 08/24/2019] [Accepted: 09/11/2019] [Indexed: 10/24/2022]
|
|
50
|
Nakanishi Y, Yamaguchi K, Yoshida Y, Sakamoto S, Horimasu Y, Masuda T, Nakashima T, Miyamoto S, Iwamoto H, Hirata S, Fujitaka K, Hamada H, Sugiyama E, Hattori N. Coexisting TIF1γ-positive Primary Pulmonary Lymphoepithelioma-like Carcinoma and Anti-TIF1γ Antibody-positive Dermatomyositis. Intern Med 2020; 59:2553-2558. [PMID: 32581161 PMCID: PMC7662058 DOI: 10.2169/internalmedicine.4702-20] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Anti-transcriptional intermediary factor 1γ (anti-TIF1γ) antibody-positive dermatomyositis (DM) is strongly associated with cancer, although the mechanism of action is still unclear. We herein describe the first known case of an 80-year-old woman diagnosed with TIF1γ-positive primary pulmonary lymphoepithelioma-like carcinoma (LELC) coexisting with anti-TIF1γ antibody-positive DM. The diagnosis of LELC can only be made by a surgical lung biopsy, and not by a computed tomography-guided biopsy, because of heavy lymphocytic infiltration. This instructive case reaffirmed the importance of active screening for malignancy in patients with anti-TIF1γ antibody-positive DM. Interestingly, the results also suggested that the strong relationship which exists between anti-TIF1γ antibody-positive DM and cancer is potentially caused by tumor-derived TIF1γ.
Collapse
Affiliation(s)
- Yu Nakanishi
- Department of Respiratory Internal Medicine, Hiroshima University Hospital, Japan
| | - Kakuhiro Yamaguchi
- Department of Respiratory Internal Medicine, Hiroshima University Hospital, Japan
| | - Yusuke Yoshida
- Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Japan
| | - Shinjiro Sakamoto
- Department of Respiratory Internal Medicine, Hiroshima University Hospital, Japan
| | - Yasushi Horimasu
- Department of Respiratory Internal Medicine, Hiroshima University Hospital, Japan
| | - Takeshi Masuda
- Department of Respiratory Internal Medicine, Hiroshima University Hospital, Japan
| | - Taku Nakashima
- Department of Respiratory Internal Medicine, Hiroshima University Hospital, Japan
| | - Shintarou Miyamoto
- Department of Respiratory Internal Medicine, Hiroshima University Hospital, Japan
| | - Hiroshi Iwamoto
- Department of Respiratory Internal Medicine, Hiroshima University Hospital, Japan
| | - Shintaro Hirata
- Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Japan
| | - Kazunori Fujitaka
- Department of Respiratory Internal Medicine, Hiroshima University Hospital, Japan
| | - Hironobu Hamada
- Department of Respiratory Internal Medicine, Hiroshima University Hospital, Japan
| | - Eiji Sugiyama
- Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Japan
| | - Noboru Hattori
- Department of Respiratory Internal Medicine, Hiroshima University Hospital, Japan
| |
Collapse
|