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Erschienen in: Rheumatology International 5/2019

21.02.2019 | Genes and Disease

Liver dysfunction in anti-melanoma differentiation-associated gene 5 antibody-positive patients with dermatomyositis

verfasst von: Takao Nagashima, Yasuyuki Kamata, Masahiro Iwamoto, Hitoaki Okazaki, Noriyoshi Fukushima, Seiji Minota

Erschienen in: Rheumatology International | Ausgabe 5/2019

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Abstract

The objective was to investigate the clinical and histological features of liver dysfunction in patients with polymyositis (PM) or dermatomyositis (DM).A total of 115 patients (38 with PM and 77 with DM), who were admitted to our hospital between 2001 and 2012, were retrospectively reviewed. Liver dysfunction was defined as an alanine transaminase (ALT) level ≥ 60 U/l and a disproportionate ALT elevation relative to the creatine kinase level. The histological findings from liver biopsies were also assessed.The frequencies of liver dysfunction were 3% and 17% in the patients with PM and DM, respectively. Liver dysfunction was not observed in the patients who had malignancies. Among the patients with DM with no malignancies (n = 50), 20% had liver dysfunction, and all of the patients with liver dysfunction were positive for the anti-melanoma differentiation-associated gene 5 (MDA5) antibody. Compared with those in the patients who did not have liver dysfunction, the ALT, alkaline phosphatase, γ-glutamyl transferase, and KL-6 levels were significantly elevated in the patients who had liver dysfunction. Six patients, comprising four with DM and two with PM, underwent liver biopsies, and the common histological findings associated with DM were steatosis, hepatocyte ballooning, increases in the pigmented macrophage numbers, and glycogenated nuclei. Hemophagocytosis was detected in two of three patients with DM who underwent liver biopsies and bone marrow aspirations. In conclusion, Liver dysfunction might be an extramuscular manifestation in patients with DM who are anti-MDA5 antibody-positive. Steatosis and hepatocyte ballooning could be common histological features.
Literatur
1.
Zurück zum Zitat Volochayev R, Csako G, Wesley R, Rider LG, Miller FW (2012) Laboratory test abnormalities are common in polymyositis and dermatomyositis and differ among clinical and demographic groups. Open Rheumatol J 6:54–63CrossRefPubMedPubMedCentral Volochayev R, Csako G, Wesley R, Rider LG, Miller FW (2012) Laboratory test abnormalities are common in polymyositis and dermatomyositis and differ among clinical and demographic groups. Open Rheumatol J 6:54–63CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Bohan A, Peter JB, Bowman RL, Pearson CM (1977) Computer-assisted analysis of 153 patients with polymyositis and dermatomyositis. Medicine (Baltimore) 56:255–286CrossRef Bohan A, Peter JB, Bowman RL, Pearson CM (1977) Computer-assisted analysis of 153 patients with polymyositis and dermatomyositis. Medicine (Baltimore) 56:255–286CrossRef
3.
Zurück zum Zitat Mathur T, Manadan AM, Thiagarajan S, Hota B, Block JA (2014) Serum transaminases are frequently elevated at time of diagnosis of idiopathic inflammatory myopathy and normalize with creatine kinase. J Clin Rheumatol 20:130–132CrossRefPubMed Mathur T, Manadan AM, Thiagarajan S, Hota B, Block JA (2014) Serum transaminases are frequently elevated at time of diagnosis of idiopathic inflammatory myopathy and normalize with creatine kinase. J Clin Rheumatol 20:130–132CrossRefPubMed
4.
Zurück zum Zitat Edge K, Chinoy H, Cooper RG (2006) Serum alanine aminotransferase elevations correlate with serum creatine phosphokinase levels in myositis. Rheumatology 45:487–488CrossRefPubMed Edge K, Chinoy H, Cooper RG (2006) Serum alanine aminotransferase elevations correlate with serum creatine phosphokinase levels in myositis. Rheumatology 45:487–488CrossRefPubMed
5.
Zurück zum Zitat Kojima H, Uemura M, Sakurai S, Ann T, Ishii Y, Imazu H, Yoshikawa M, Ichijima K, Fukui H (2002) Clinical features of liver disturbance in rheumatoid diseases: clinicopathological study with special reference to the cause of liver disturbance. J Gastroenterol 37:617–625CrossRefPubMed Kojima H, Uemura M, Sakurai S, Ann T, Ishii Y, Imazu H, Yoshikawa M, Ichijima K, Fukui H (2002) Clinical features of liver disturbance in rheumatoid diseases: clinicopathological study with special reference to the cause of liver disturbance. J Gastroenterol 37:617–625CrossRefPubMed
6.
Zurück zum Zitat Wada T, Abe G, Kudou T, Ogawa E, Nagai T, Tanaka S, Hirohata S (2016) Liver damage in patients with polymyositis and dermatomyositis. Kitasato Med J 46:40–46 Wada T, Abe G, Kudou T, Ogawa E, Nagai T, Tanaka S, Hirohata S (2016) Liver damage in patients with polymyositis and dermatomyositis. Kitasato Med J 46:40–46
7.
Zurück zum Zitat Takahashi A, Abe K, Yokokawa J, Iwadate H, Kobayashi H, Watanabe H, Irisawa A, Ohira H (2010) Clinical features of liver dysfunction in collagen diseases. Hepatol Res 40:1092–1097CrossRefPubMed Takahashi A, Abe K, Yokokawa J, Iwadate H, Kobayashi H, Watanabe H, Irisawa A, Ohira H (2010) Clinical features of liver dysfunction in collagen diseases. Hepatol Res 40:1092–1097CrossRefPubMed
10.
Zurück zum Zitat Noda S, Asano Y, Tamaki Z, Takekoshi T, Sugaya M, Sato S (2010) A case of dermatomyositis with “liver disease associated with rheumatoid diseases” positive for anti-liver-kidney microsome-1 antibody. Clin Rheumatol 29:941–943CrossRefPubMed Noda S, Asano Y, Tamaki Z, Takekoshi T, Sugaya M, Sato S (2010) A case of dermatomyositis with “liver disease associated with rheumatoid diseases” positive for anti-liver-kidney microsome-1 antibody. Clin Rheumatol 29:941–943CrossRefPubMed
11.
Zurück zum Zitat Matsumoto T, Kobayashi S, Shimizu H, Nakajima M, Watanabe S, Kitami N, Sato N, Abe H, Aoki Y, Hoshi T, Hashimoto H (2000) The liver in collagen diseases: pathologic study of 160 cases with particular reference to hepatic arteritis, primary biliary cirrhosis, autoimmune hepatitis and nodular regenerative hyperplasia of the liver. Liver 20:366–373CrossRefPubMed Matsumoto T, Kobayashi S, Shimizu H, Nakajima M, Watanabe S, Kitami N, Sato N, Abe H, Aoki Y, Hoshi T, Hashimoto H (2000) The liver in collagen diseases: pathologic study of 160 cases with particular reference to hepatic arteritis, primary biliary cirrhosis, autoimmune hepatitis and nodular regenerative hyperplasia of the liver. Liver 20:366–373CrossRefPubMed
12.
Zurück zum Zitat Gono T, Kawaguchi Y, Satoh T, Kuwana M, Katsumata Y, Takagi K, Masuda I, Tochimoto A, Baba S, Okamoto Y, Ota Y, Yamanaka H (2010) Clinical manifestation and prognostic factor in anti-melanoma differentiation-associated gene 5 antibody-associated interstitial lung disease as a complication of dermatomyositis. Rheumatology 49:1713–1719CrossRefPubMed Gono T, Kawaguchi Y, Satoh T, Kuwana M, Katsumata Y, Takagi K, Masuda I, Tochimoto A, Baba S, Okamoto Y, Ota Y, Yamanaka H (2010) Clinical manifestation and prognostic factor in anti-melanoma differentiation-associated gene 5 antibody-associated interstitial lung disease as a complication of dermatomyositis. Rheumatology 49:1713–1719CrossRefPubMed
13.
Zurück zum Zitat Nakashima R, Imura Y, Kobayashi S, Yukawa N, Yoshifuji H, Nojima T, Kawabata D, Ohmura K, Usui T, Fujii T, Okawa K, Mimori T (2010) The RIG-I-like receptor IFIH1/MDA5 is a dermatomyositis-specific autoantigen identified by the anti-CADM-140 antibody. Rheumatology 49:433–440CrossRefPubMed Nakashima R, Imura Y, Kobayashi S, Yukawa N, Yoshifuji H, Nojima T, Kawabata D, Ohmura K, Usui T, Fujii T, Okawa K, Mimori T (2010) The RIG-I-like receptor IFIH1/MDA5 is a dermatomyositis-specific autoantigen identified by the anti-CADM-140 antibody. Rheumatology 49:433–440CrossRefPubMed
14.
Zurück zum Zitat Bohan A, Peter JB (1975) Polymyositis and dermatomyositis (first of two parts). N Engl J Med 292:344–347CrossRefPubMed Bohan A, Peter JB (1975) Polymyositis and dermatomyositis (first of two parts). N Engl J Med 292:344–347CrossRefPubMed
15.
Zurück zum Zitat Sontheimer RD (2002) Would a new name hasten the acceptance of amyopathic dermatomyositis (dermatomyositis sine myositis) as a distinctive subset within the idiopathic inflammatory dermatomyopathies spectrum of clinical illness? J Am Acad Dermatol 46:626–636CrossRefPubMed Sontheimer RD (2002) Would a new name hasten the acceptance of amyopathic dermatomyositis (dermatomyositis sine myositis) as a distinctive subset within the idiopathic inflammatory dermatomyopathies spectrum of clinical illness? J Am Acad Dermatol 46:626–636CrossRefPubMed
16.
Zurück zum Zitat Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41:1313–1321CrossRef Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41:1313–1321CrossRef
17.
Zurück zum Zitat Gono T, Kawaguchi Y, Hara M, Masuda I, Katsumata Y, Shinozaki M, Ota Y, Ozeki E, Yamanaka H (2010) Increased ferritin predicts development and severity of acute interstitial lung disease as a complication of dermatomyositis. Rheumatology 49:1354–1360CrossRefPubMed Gono T, Kawaguchi Y, Hara M, Masuda I, Katsumata Y, Shinozaki M, Ota Y, Ozeki E, Yamanaka H (2010) Increased ferritin predicts development and severity of acute interstitial lung disease as a complication of dermatomyositis. Rheumatology 49:1354–1360CrossRefPubMed
18.
Zurück zum Zitat Isoda K, Takeuchi T, Kotani T, Hata K, Shoda T, Ishida T, Yoshida S, Kimura Y, Makino S, Hanafusa T (2014) Pre-treatment ferritin level and alveolar-arterial oxygen gradient can predict mortality rate due to acute/subacute interstitial pneumonia in dermatomyositis treated by cyclosporine a/glucocorticosteroid combination therapy: a case control study [corrected]. PLoS One 9:e89610CrossRefPubMedPubMedCentral Isoda K, Takeuchi T, Kotani T, Hata K, Shoda T, Ishida T, Yoshida S, Kimura Y, Makino S, Hanafusa T (2014) Pre-treatment ferritin level and alveolar-arterial oxygen gradient can predict mortality rate due to acute/subacute interstitial pneumonia in dermatomyositis treated by cyclosporine a/glucocorticosteroid combination therapy: a case control study [corrected]. PLoS One 9:e89610CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Gono T, Sato S, Kawaguchi Y, Kuwana M, Hanaoka M, Katsumata Y, Takagi K, Baba S, Okamoto Y, Ota Y, Yamanaka H (2012) Anti-MDA5 antibody, ferritin and IL-18 are useful for the evaluation of response to treatment in interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis. Rheumatology 51:1563–1570CrossRefPubMed Gono T, Sato S, Kawaguchi Y, Kuwana M, Hanaoka M, Katsumata Y, Takagi K, Baba S, Okamoto Y, Ota Y, Yamanaka H (2012) Anti-MDA5 antibody, ferritin and IL-18 are useful for the evaluation of response to treatment in interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis. Rheumatology 51:1563–1570CrossRefPubMed
20.
Zurück zum Zitat Banderas DZ, Escobedo J, Gonzalez E, Liceaga MG, Ramirez JC, Castro MG (2012) gamma-Glutamyl transferase: a marker of nonalcoholic fatty liver disease in patients with the metabolic syndrome. Eur J Gastroenterol Hepatol 24:805–810CrossRefPubMed Banderas DZ, Escobedo J, Gonzalez E, Liceaga MG, Ramirez JC, Castro MG (2012) gamma-Glutamyl transferase: a marker of nonalcoholic fatty liver disease in patients with the metabolic syndrome. Eur J Gastroenterol Hepatol 24:805–810CrossRefPubMed
21.
Zurück zum Zitat Takahashi Y, Fukusato T (2014) Histopathology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol 20:15539–15548CrossRefPubMedPubMedCentral Takahashi Y, Fukusato T (2014) Histopathology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol 20:15539–15548CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Lackner C, Gogg-Kamerer M, Zatloukal K, Stumptner C, Brunt EM, Denk H (2008) Ballooned hepatocytes in steatohepatitis: the value of keratin immunohistochemistry for diagnosis. J Hepatol 48:821–828CrossRefPubMed Lackner C, Gogg-Kamerer M, Zatloukal K, Stumptner C, Brunt EM, Denk H (2008) Ballooned hepatocytes in steatohepatitis: the value of keratin immunohistochemistry for diagnosis. J Hepatol 48:821–828CrossRefPubMed
23.
Zurück zum Zitat Satapathy SK, Kuwajima V, Nadelson J, Atiq O, Sanyal AJ (2015) Drug-induced fatty liver disease: An overview of pathogenesis and management. Ann Hepatol 14:789–806CrossRefPubMed Satapathy SK, Kuwajima V, Nadelson J, Atiq O, Sanyal AJ (2015) Drug-induced fatty liver disease: An overview of pathogenesis and management. Ann Hepatol 14:789–806CrossRefPubMed
24.
Zurück zum Zitat Kanel GC, Korula J (1992) General aspects of the liver and liver diseases. In: Altas of Liver Pathology. W.B. Saunders, Philadelphia Kanel GC, Korula J (1992) General aspects of the liver and liver diseases. In: Altas of Liver Pathology. W.B. Saunders, Philadelphia
25.
Zurück zum Zitat Nati M, Haddad D, Birkenfeld AL, Koch CA, Chavakis T, Chatzigeorgiou A (2016) The role of immune cells in metabolism-related liver inflammation and development of non-alcoholic steatohepatitis (NASH). Rev Endocr Metab Disord 17:29–39CrossRefPubMed Nati M, Haddad D, Birkenfeld AL, Koch CA, Chavakis T, Chatzigeorgiou A (2016) The role of immune cells in metabolism-related liver inflammation and development of non-alcoholic steatohepatitis (NASH). Rev Endocr Metab Disord 17:29–39CrossRefPubMed
26.
Zurück zum Zitat Huang W, Metlakunta A, Dedousis N, Zhang P, Sipula I, Dube JJ, Scott DK, O’Doherty RM (2010) Depletion of liver Kupffer cells prevents the development of diet-induced hepatic steatosis and insulin resistance. Diabetes 59:347–357CrossRefPubMed Huang W, Metlakunta A, Dedousis N, Zhang P, Sipula I, Dube JJ, Scott DK, O’Doherty RM (2010) Depletion of liver Kupffer cells prevents the development of diet-induced hepatic steatosis and insulin resistance. Diabetes 59:347–357CrossRefPubMed
27.
Zurück zum Zitat Barbuio R, Milanski M, Bertolo MB, Saad MJ, Velloso LA (2007) Infliximab reverses steatosis and improves insulin signal transduction in liver of rats fed a high-fat diet. J Endocrinol 194:539–550CrossRefPubMed Barbuio R, Milanski M, Bertolo MB, Saad MJ, Velloso LA (2007) Infliximab reverses steatosis and improves insulin signal transduction in liver of rats fed a high-fat diet. J Endocrinol 194:539–550CrossRefPubMed
28.
Zurück zum Zitat Tilg H, Moschen AR (2010) Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology 52:1836–1846CrossRef Tilg H, Moschen AR (2010) Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology 52:1836–1846CrossRef
29.
Zurück zum Zitat Gono T, Miyake K, Kawaguchi Y, Kaneko H, Shinozaki M, Yamanaka H (2012) Hyperferritinaemia and macrophage activation in a patient with interstitial lung disease with clinically amyopathic DM. Rheumatology 51:1336–1338CrossRefPubMed Gono T, Miyake K, Kawaguchi Y, Kaneko H, Shinozaki M, Yamanaka H (2012) Hyperferritinaemia and macrophage activation in a patient with interstitial lung disease with clinically amyopathic DM. Rheumatology 51:1336–1338CrossRefPubMed
Metadaten
Titel
Liver dysfunction in anti-melanoma differentiation-associated gene 5 antibody-positive patients with dermatomyositis
verfasst von
Takao Nagashima
Yasuyuki Kamata
Masahiro Iwamoto
Hitoaki Okazaki
Noriyoshi Fukushima
Seiji Minota
Publikationsdatum
21.02.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Rheumatology International / Ausgabe 5/2019
Print ISSN: 0172-8172
Elektronische ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-019-04255-2

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