title: Predictors of acquired lipodystrophy in juvenile-onset dermatomyositis and a gradient of severity.
abstract: We describe the clinical features of 28 patients with juvenile dermatomyositis (JDM) and 1 patient with adult-onset dermatomyositis (DM), all of whom developed lipodystrophy (LD) that could be categorized into 1 of 3 phenotypes, generalized, partial, or focal, based on the pattern of fat loss distribution. LD onset was often delayed, beginning a median of 4.6 years after diagnosis of DM. Calcinosis, muscle atrophy, joint contractures, and facial rash were DM disease features found to be associated with LD. Panniculitis was associated with focal lipoatrophy while the anti-p155 autoantibody, a newly described myositis-associated autoantibody, was more associated with generalized LD. Specific LD features such as acanthosis nigricans, hirsutism, fat redistribution, and steatosis/nonalcoholic steatohepatitis were frequent in patients with LD, in a gradient of frequency and severity among the 3 sub-phenotypes. Metabolic studies frequently revealed insulin resistance and hypertriglyceridemia in patients with generalized and partial LD. Regional fat loss from the thighs, with relative sparing of fat loss from the medial thighs, was more frequent in generalized than in partial LD and absent from DM patients without LD. Cytokine polymorphisms, the C3 nephritic factor, insulin receptor antibodies, and lamin mutations did not appear to play a pathogenic role in the development of LD in our patients. LD is an under-recognized sequela of JDM, and certain DM patients with a severe, prolonged clinical course and a high frequency of calcinosis appear to be at greater risk for the development of this complication. High-risk JDM patients should be screened for metabolic abnormalities, which are common in generalized and partial LD and result in much of the LD-associated morbidity. Further study is warranted to investigate the pathogenesis of acquired LD in patients with DM.
authors.affiliation: From Office of Clinical Research (AB, GM, LJN, DMC, TPO, PJB, FWM, LGR), National Institute of Environmental Health Sciences; National Institute of Diabetes Digestive and Kidney Diseases (KIR, EO, EC); Department of Radiology (AP) and Nutrition Department (NS), Clinical Center; National Cancer Institute (DK, MT); National Institutes of Health (NIH), Bethesda, Maryland; Penn State Milton S. Hershey Medical Center (AB), Hershey, Pennsylvania; University of Michigan (EO), Ann Arbor, Michigan; Veterans Affairs Medical Center, University of Oklahoma Health Sciences Center, and Oklahoma Medical Research Foundation (INT), Oklahoma City, Oklahoma; Medical University of South Carolina (JPP), Charleston, South Carolina; Center for Biologics Evaluation and Research (MRH, JL, SRB), Food and Drug Administration, Bethesda, Maryland; Warren Alpert Medical School of Brown University (LBG), Providence, Rhode Island; Columbia University (LI), New York, New York, United States; and Facultad de Medicina/CRIB (MRH, JL), Universidad de Castilla-La Mancha, Albacete, Spain.
authors.forename: April
authors.initials: A
authors.lastname: Bingham
authors.forename: Gulnara
authors.initials: G
authors.lastname: Mamyrova
authors.forename: Kristina I
authors.initials: KI
authors.lastname: Rother
authors.forename: Elif
authors.initials: E
authors.lastname: Oral
authors.forename: Elaine
authors.initials: E
authors.lastname: Cochran
authors.forename: Ahalya
authors.initials: A
authors.lastname: Premkumar
authors.forename: David
authors.initials: D
authors.lastname: Kleiner
authors.forename: Laura
authors.initials: L
authors.lastname: James-Newton
authors.forename: Ira N
authors.initials: IN
authors.lastname: Targoff
authors.forename: Janardan P
authors.initials: JP
authors.lastname: Pandey
authors.forename: Danielle Mercatante
authors.initials: DM
authors.lastname: Carrick
authors.forename: Nancy
authors.initials: N
authors.lastname: Sebring
authors.forename: Terrance P
authors.initials: TP
authors.lastname: O'Hanlon
authors.forename: Maria
authors.initials: M
authors.lastname: Ruiz-Hidalgo
authors.forename: Maria
authors.initials: M
authors.lastname: Turner
authors.forename: Leslie B
authors.initials: LB
authors.lastname: Gordon
authors.forename: Jorge
authors.initials: J
authors.lastname: Laborda
authors.forename: Steven R
authors.initials: SR
authors.lastname: Bauer
authors.forename: Perry J
authors.initials: PJ
authors.lastname: Blackshear
authors.forename: Lisa
authors.initials: L
authors.lastname: Imundo
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Miller
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Rider
mesh_terms: D000052:Acanthosis Nigricans / Q000209:etiology; D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D050218:Body Fat Distribution; D002114:Calcinosis / Q000209:etiology; D016022:Case-Control Studies; D002648:Child; D003286:Contracture / Q000209:etiology; D003882:Dermatomyositis / Q000150:complications*; D005076:Exanthema / Q000209:etiology; D005148:Facial Dermatoses / Q000209:etiology; D005234:Fatty Liver / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D005544:Forecasting; D006628:Hirsutism / Q000209:etiology; D006801:Humans; D015228:Hypertriglyceridemia / Q000209:etiology; D007333:Insulin Resistance; D008060:Lipodystrophy / Q000145:classification / Q000209:etiology*; D008297:Male; D009133:Muscular Atrophy / Q000209:etiology; D015434:Panniculitis / Q000209:etiology; D010641:Phenotype; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D015415:Biomarkers