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Muscle Biopsy Findings in Combination With Myositis‐Specific Autoantibodies Aid Prediction of Outcomes in Juvenile Dermatomyositis

OBJECTIVE: Juvenile dermatomyositis (DM) is a rare and severe autoimmune condition characterized by rash and proximal muscle weakness. While some patients respond to standard treatment, others do not. This study was carried out to investigate whether histopathologic findings and myositis‐specific au...

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Autores principales: Deakin, Claire T., Yasin, Shireena A., Simou, Stefania, Arnold, Katie A., Tansley, Sarah L., Betteridge, Zoe E., McHugh, Neil J., Varsani, Hemlata, Holton, Janice L., Jacques, Thomas S., Pilkington, Clarissa A., Nistala, Kiran, Wedderburn, Lucy R., Armon, Kate, Ellis‐Gage, Joe, Roper, Holly, Briggs, Vanja, Watts, Joanna, McCann, Liza, Roberts, Ian, Baildam, Eileen, Hanna, Louise, Lloyd, Olivia, Wadeson, Susan, Riley, Phil, McGovern, Ann, Ryder, Clive, Scott, Janis, Thomas, Beverley, Southwood, Taunton, Al‐Abadi, Eslam, Wyatt, Sue, Jackson, Gillian, Amin, Tania, Wood, Mark, VanRooyen, Vanessa, Burton, Deborah, Davidson, Joyce, Gardner‐Medwin, Janet, Martin, Neil, Ferguson, Sue, Waxman, Liz, Browne, Michael, Friswell, Mark, Swift, Alison, Jandial, Sharmila, Stevenson, Vicky, Wade, Debbie, Sen, Ethan, Smith, Eve, Qiao, Lisa, Watson, Stuart, Duong, Claire, Venning, Helen, Satyapal, Rangaraj, Stretton, Elizabeth, Jordan, Mary, Mosley, Ellen, Frost, Anna, Crate, Lindsay, Warrier, Kishore, Stafford, Stefanie, Hasson, Nathan, Maillard, Sue, Halkon, Elizabeth, Brown, Virginia, Juggins, Audrey, Smith, Sally, Lunt, Sian, Enayat, Elli, Kassoumeri, Laura, Beard, Laura, Glackin, Yvonne, Almeida, Beverley, Marques, Raquel, Dowle, Stefanie, Papadopoulou, Charis, Murray, Kevin, Ioannou, John, Suffield, Linda, Al‐Obaidi, Muthana, Lee, Helen, Leach, Sam, Smith, Helen, McMahon, Anne‐Marie, Chisem, Heather, Kingshott, Ruth, Wilkinson, Nick, Inness, Emma, Kendall, Eunice, Mayers, David, Etherton, Ruth, Bailey, Kathryn, Clinch, Jacqui, Fineman, Natalie, Pluess‐Hall, Helen, Vallance, Lindsay, Akeroyd, Louise, Leahy, Alice, Collier, Amy, Cutts, Rebecca, De Graaf, Hans, Davidson, Brian, Hartfree, Sarah, Pratt, Danny
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5091622/
https://www.ncbi.nlm.nih.gov/pubmed/27214289
http://dx.doi.org/10.1002/art.39753
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author Deakin, Claire T.
Yasin, Shireena A.
Simou, Stefania
Arnold, Katie A.
Tansley, Sarah L.
Betteridge, Zoe E.
McHugh, Neil J.
Varsani, Hemlata
Holton, Janice L.
Jacques, Thomas S.
Pilkington, Clarissa A.
Nistala, Kiran
Wedderburn, Lucy R.
Armon, Kate
Ellis‐Gage, Joe
Roper, Holly
Briggs, Vanja
Watts, Joanna
McCann, Liza
Roberts, Ian
Baildam, Eileen
Hanna, Louise
Lloyd, Olivia
Wadeson, Susan
Riley, Phil
McGovern, Ann
Ryder, Clive
Scott, Janis
Thomas, Beverley
Southwood, Taunton
Al‐Abadi, Eslam
Wyatt, Sue
Jackson, Gillian
Amin, Tania
Wood, Mark
VanRooyen, Vanessa
Burton, Deborah
Davidson, Joyce
Gardner‐Medwin, Janet
Martin, Neil
Ferguson, Sue
Waxman, Liz
Browne, Michael
Friswell, Mark
Swift, Alison
Jandial, Sharmila
Stevenson, Vicky
Wade, Debbie
Sen, Ethan
Smith, Eve
Qiao, Lisa
Watson, Stuart
Duong, Claire
Venning, Helen
Satyapal, Rangaraj
Stretton, Elizabeth
Jordan, Mary
Mosley, Ellen
Frost, Anna
Crate, Lindsay
Warrier, Kishore
Stafford, Stefanie
Hasson, Nathan
Maillard, Sue
Halkon, Elizabeth
Brown, Virginia
Juggins, Audrey
Smith, Sally
Lunt, Sian
Enayat, Elli
Kassoumeri, Laura
Beard, Laura
Glackin, Yvonne
Almeida, Beverley
Marques, Raquel
Dowle, Stefanie
Papadopoulou, Charis
Murray, Kevin
Ioannou, John
Suffield, Linda
Al‐Obaidi, Muthana
Lee, Helen
Leach, Sam
Smith, Helen
McMahon, Anne‐Marie
Chisem, Heather
Kingshott, Ruth
Wilkinson, Nick
Inness, Emma
Kendall, Eunice
Mayers, David
Etherton, Ruth
Bailey, Kathryn
Clinch, Jacqui
Fineman, Natalie
Pluess‐Hall, Helen
Vallance, Lindsay
Akeroyd, Louise
Leahy, Alice
Collier, Amy
Cutts, Rebecca
De Graaf, Hans
Davidson, Brian
Hartfree, Sarah
Pratt, Danny
author_facet Deakin, Claire T.
Yasin, Shireena A.
Simou, Stefania
Arnold, Katie A.
Tansley, Sarah L.
Betteridge, Zoe E.
McHugh, Neil J.
Varsani, Hemlata
Holton, Janice L.
Jacques, Thomas S.
Pilkington, Clarissa A.
Nistala, Kiran
Wedderburn, Lucy R.
Armon, Kate
Ellis‐Gage, Joe
Roper, Holly
Briggs, Vanja
Watts, Joanna
McCann, Liza
Roberts, Ian
Baildam, Eileen
Hanna, Louise
Lloyd, Olivia
Wadeson, Susan
Riley, Phil
McGovern, Ann
Ryder, Clive
Scott, Janis
Thomas, Beverley
Southwood, Taunton
Al‐Abadi, Eslam
Wyatt, Sue
Jackson, Gillian
Amin, Tania
Wood, Mark
VanRooyen, Vanessa
Burton, Deborah
Davidson, Joyce
Gardner‐Medwin, Janet
Martin, Neil
Ferguson, Sue
Waxman, Liz
Browne, Michael
Friswell, Mark
Swift, Alison
Jandial, Sharmila
Stevenson, Vicky
Wade, Debbie
Sen, Ethan
Smith, Eve
Qiao, Lisa
Watson, Stuart
Duong, Claire
Venning, Helen
Satyapal, Rangaraj
Stretton, Elizabeth
Jordan, Mary
Mosley, Ellen
Frost, Anna
Crate, Lindsay
Warrier, Kishore
Stafford, Stefanie
Hasson, Nathan
Maillard, Sue
Halkon, Elizabeth
Brown, Virginia
Juggins, Audrey
Smith, Sally
Lunt, Sian
Enayat, Elli
Kassoumeri, Laura
Beard, Laura
Glackin, Yvonne
Almeida, Beverley
Marques, Raquel
Dowle, Stefanie
Papadopoulou, Charis
Murray, Kevin
Ioannou, John
Suffield, Linda
Al‐Obaidi, Muthana
Lee, Helen
Leach, Sam
Smith, Helen
McMahon, Anne‐Marie
Chisem, Heather
Kingshott, Ruth
Wilkinson, Nick
Inness, Emma
Kendall, Eunice
Mayers, David
Etherton, Ruth
Bailey, Kathryn
Clinch, Jacqui
Fineman, Natalie
Pluess‐Hall, Helen
Vallance, Lindsay
Akeroyd, Louise
Leahy, Alice
Collier, Amy
Cutts, Rebecca
De Graaf, Hans
Davidson, Brian
Hartfree, Sarah
Pratt, Danny
author_sort Deakin, Claire T.
collection PubMed
description OBJECTIVE: Juvenile dermatomyositis (DM) is a rare and severe autoimmune condition characterized by rash and proximal muscle weakness. While some patients respond to standard treatment, others do not. This study was carried out to investigate whether histopathologic findings and myositis‐specific autoantibodies (MSAs) have prognostic significance in juvenile DM. METHODS: Muscle biopsy samples (n = 101) from patients in the UK Juvenile Dermatomyositis Cohort and Biomarker Study were stained, analyzed, and scored for severity of histopathologic features. In addition, autoantibodies were measured in the serum or plasma of patients (n = 90) and longitudinal clinical data were collected (median duration of follow‐up 4.9 years). Long‐term treatment status (on or off medication over time) was modeled using generalized estimating equations. RESULTS: Muscle biopsy scores differed according to MSA subgroup. When the effects of MSA subgroup were accounted for, increased severity of muscle histopathologic features was predictive of an increased risk of remaining on treatment over time: for the global pathology score (histopathologist's visual analog scale [hVAS] score), 1.48‐fold higher odds (95% confidence interval [95% CI] 1.12–1.96; P = 0.0058), and for the total biopsy score (determined with the standardized score tool), 1.10‐fold higher odds (95% CI 1.01–1.21; P = 0.038). A protective effect was identified in patients with anti–Mi‐2 autoantibodies, in whom the odds of remaining on treatment were 7.06‐fold lower (95% CI 1.41–35.36; P = 0.018) despite muscle biopsy scores indicating more severe disease. In patients with anti–nuclear matrix protein 2 autoantibodies, anti–transcription intermediary factor 1γ autoantibodies, or no detectable autoantibody, increased histopathologic severity alone, without adjustment for the effect of MSA subtype, was predictive of the risk of remaining on treatment: for the hVAS global pathology score, 1.61‐fold higher odds (95% CI 1.16–2.22; P = 0.004), and for the total biopsy score, 1.13‐fold higher odds (95% CI 1.03–1.24; P = 0.013). CONCLUSION: Histopathologic severity, in combination with MSA subtype, is predictive of the risk of remaining on treatment in patients with juvenile DM and may be useful for discussing probable treatment length with parents and patients. Understanding these associations may identify patients at greater risk of severe disease.
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spelling pubmed-50916222016-11-09 Muscle Biopsy Findings in Combination With Myositis‐Specific Autoantibodies Aid Prediction of Outcomes in Juvenile Dermatomyositis Deakin, Claire T. Yasin, Shireena A. Simou, Stefania Arnold, Katie A. Tansley, Sarah L. Betteridge, Zoe E. McHugh, Neil J. Varsani, Hemlata Holton, Janice L. Jacques, Thomas S. Pilkington, Clarissa A. Nistala, Kiran Wedderburn, Lucy R. Armon, Kate Ellis‐Gage, Joe Roper, Holly Briggs, Vanja Watts, Joanna McCann, Liza Roberts, Ian Baildam, Eileen Hanna, Louise Lloyd, Olivia Wadeson, Susan Riley, Phil McGovern, Ann Ryder, Clive Scott, Janis Thomas, Beverley Southwood, Taunton Al‐Abadi, Eslam Wyatt, Sue Jackson, Gillian Amin, Tania Wood, Mark VanRooyen, Vanessa Burton, Deborah Davidson, Joyce Gardner‐Medwin, Janet Martin, Neil Ferguson, Sue Waxman, Liz Browne, Michael Friswell, Mark Swift, Alison Jandial, Sharmila Stevenson, Vicky Wade, Debbie Sen, Ethan Smith, Eve Qiao, Lisa Watson, Stuart Duong, Claire Venning, Helen Satyapal, Rangaraj Stretton, Elizabeth Jordan, Mary Mosley, Ellen Frost, Anna Crate, Lindsay Warrier, Kishore Stafford, Stefanie Hasson, Nathan Maillard, Sue Halkon, Elizabeth Brown, Virginia Juggins, Audrey Smith, Sally Lunt, Sian Enayat, Elli Kassoumeri, Laura Beard, Laura Glackin, Yvonne Almeida, Beverley Marques, Raquel Dowle, Stefanie Papadopoulou, Charis Murray, Kevin Ioannou, John Suffield, Linda Al‐Obaidi, Muthana Lee, Helen Leach, Sam Smith, Helen McMahon, Anne‐Marie Chisem, Heather Kingshott, Ruth Wilkinson, Nick Inness, Emma Kendall, Eunice Mayers, David Etherton, Ruth Bailey, Kathryn Clinch, Jacqui Fineman, Natalie Pluess‐Hall, Helen Vallance, Lindsay Akeroyd, Louise Leahy, Alice Collier, Amy Cutts, Rebecca De Graaf, Hans Davidson, Brian Hartfree, Sarah Pratt, Danny Arthritis Rheumatol Pediatric Rheumatology OBJECTIVE: Juvenile dermatomyositis (DM) is a rare and severe autoimmune condition characterized by rash and proximal muscle weakness. While some patients respond to standard treatment, others do not. This study was carried out to investigate whether histopathologic findings and myositis‐specific autoantibodies (MSAs) have prognostic significance in juvenile DM. METHODS: Muscle biopsy samples (n = 101) from patients in the UK Juvenile Dermatomyositis Cohort and Biomarker Study were stained, analyzed, and scored for severity of histopathologic features. In addition, autoantibodies were measured in the serum or plasma of patients (n = 90) and longitudinal clinical data were collected (median duration of follow‐up 4.9 years). Long‐term treatment status (on or off medication over time) was modeled using generalized estimating equations. RESULTS: Muscle biopsy scores differed according to MSA subgroup. When the effects of MSA subgroup were accounted for, increased severity of muscle histopathologic features was predictive of an increased risk of remaining on treatment over time: for the global pathology score (histopathologist's visual analog scale [hVAS] score), 1.48‐fold higher odds (95% confidence interval [95% CI] 1.12–1.96; P = 0.0058), and for the total biopsy score (determined with the standardized score tool), 1.10‐fold higher odds (95% CI 1.01–1.21; P = 0.038). A protective effect was identified in patients with anti–Mi‐2 autoantibodies, in whom the odds of remaining on treatment were 7.06‐fold lower (95% CI 1.41–35.36; P = 0.018) despite muscle biopsy scores indicating more severe disease. In patients with anti–nuclear matrix protein 2 autoantibodies, anti–transcription intermediary factor 1γ autoantibodies, or no detectable autoantibody, increased histopathologic severity alone, without adjustment for the effect of MSA subtype, was predictive of the risk of remaining on treatment: for the hVAS global pathology score, 1.61‐fold higher odds (95% CI 1.16–2.22; P = 0.004), and for the total biopsy score, 1.13‐fold higher odds (95% CI 1.03–1.24; P = 0.013). CONCLUSION: Histopathologic severity, in combination with MSA subtype, is predictive of the risk of remaining on treatment in patients with juvenile DM and may be useful for discussing probable treatment length with parents and patients. Understanding these associations may identify patients at greater risk of severe disease. John Wiley and Sons Inc. 2016-10-09 2016-11 /pmc/articles/PMC5091622/ /pubmed/27214289 http://dx.doi.org/10.1002/art.39753 Text en © 2016 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Pediatric Rheumatology
Deakin, Claire T.
Yasin, Shireena A.
Simou, Stefania
Arnold, Katie A.
Tansley, Sarah L.
Betteridge, Zoe E.
McHugh, Neil J.
Varsani, Hemlata
Holton, Janice L.
Jacques, Thomas S.
Pilkington, Clarissa A.
Nistala, Kiran
Wedderburn, Lucy R.
Armon, Kate
Ellis‐Gage, Joe
Roper, Holly
Briggs, Vanja
Watts, Joanna
McCann, Liza
Roberts, Ian
Baildam, Eileen
Hanna, Louise
Lloyd, Olivia
Wadeson, Susan
Riley, Phil
McGovern, Ann
Ryder, Clive
Scott, Janis
Thomas, Beverley
Southwood, Taunton
Al‐Abadi, Eslam
Wyatt, Sue
Jackson, Gillian
Amin, Tania
Wood, Mark
VanRooyen, Vanessa
Burton, Deborah
Davidson, Joyce
Gardner‐Medwin, Janet
Martin, Neil
Ferguson, Sue
Waxman, Liz
Browne, Michael
Friswell, Mark
Swift, Alison
Jandial, Sharmila
Stevenson, Vicky
Wade, Debbie
Sen, Ethan
Smith, Eve
Qiao, Lisa
Watson, Stuart
Duong, Claire
Venning, Helen
Satyapal, Rangaraj
Stretton, Elizabeth
Jordan, Mary
Mosley, Ellen
Frost, Anna
Crate, Lindsay
Warrier, Kishore
Stafford, Stefanie
Hasson, Nathan
Maillard, Sue
Halkon, Elizabeth
Brown, Virginia
Juggins, Audrey
Smith, Sally
Lunt, Sian
Enayat, Elli
Kassoumeri, Laura
Beard, Laura
Glackin, Yvonne
Almeida, Beverley
Marques, Raquel
Dowle, Stefanie
Papadopoulou, Charis
Murray, Kevin
Ioannou, John
Suffield, Linda
Al‐Obaidi, Muthana
Lee, Helen
Leach, Sam
Smith, Helen
McMahon, Anne‐Marie
Chisem, Heather
Kingshott, Ruth
Wilkinson, Nick
Inness, Emma
Kendall, Eunice
Mayers, David
Etherton, Ruth
Bailey, Kathryn
Clinch, Jacqui
Fineman, Natalie
Pluess‐Hall, Helen
Vallance, Lindsay
Akeroyd, Louise
Leahy, Alice
Collier, Amy
Cutts, Rebecca
De Graaf, Hans
Davidson, Brian
Hartfree, Sarah
Pratt, Danny
Muscle Biopsy Findings in Combination With Myositis‐Specific Autoantibodies Aid Prediction of Outcomes in Juvenile Dermatomyositis
title Muscle Biopsy Findings in Combination With Myositis‐Specific Autoantibodies Aid Prediction of Outcomes in Juvenile Dermatomyositis
title_full Muscle Biopsy Findings in Combination With Myositis‐Specific Autoantibodies Aid Prediction of Outcomes in Juvenile Dermatomyositis
title_fullStr Muscle Biopsy Findings in Combination With Myositis‐Specific Autoantibodies Aid Prediction of Outcomes in Juvenile Dermatomyositis
title_full_unstemmed Muscle Biopsy Findings in Combination With Myositis‐Specific Autoantibodies Aid Prediction of Outcomes in Juvenile Dermatomyositis
title_short Muscle Biopsy Findings in Combination With Myositis‐Specific Autoantibodies Aid Prediction of Outcomes in Juvenile Dermatomyositis
title_sort muscle biopsy findings in combination with myositis‐specific autoantibodies aid prediction of outcomes in juvenile dermatomyositis
topic Pediatric Rheumatology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5091622/
https://www.ncbi.nlm.nih.gov/pubmed/27214289
http://dx.doi.org/10.1002/art.39753
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AT murraykevin musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT ioannoujohn musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT suffieldlinda musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT alobaidimuthana musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT leehelen musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT leachsam musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT smithhelen musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT mcmahonannemarie musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT chisemheather musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT kingshottruth musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT wilkinsonnick musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT innessemma musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT kendalleunice musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT mayersdavid musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT ethertonruth musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT baileykathryn musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT clinchjacqui musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT finemannatalie musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT pluesshallhelen musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT vallancelindsay musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT akeroydlouise musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT leahyalice musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT collieramy musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT cuttsrebecca musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT degraafhans musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT davidsonbrian musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT hartfreesarah musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis
AT prattdanny musclebiopsyfindingsincombinationwithmyositisspecificautoantibodiesaidpredictionofoutcomesinjuveniledermatomyositis