Scientific Publications by FDA Staff

Medicine 2008 Mar;87(2):70-86

Predictors of Acquired Lipodystrophy in Juvenile-Onset Dermatomyositis and a Gradient of Severity.

Bingham A, Mamyrova G, Rother KI, Oral E, Cochran E, Premkumar A, Kleiner D, James-Newton L, Targoff IN, Pandey JP, Carrick DM, Sebring N, O'Hanlon TP, Ruiz-Hidalgo M, Turner M, Gordon LB, Laborda J, Bauer SR, Blackshear PJ, Imundo L, Miller FW, Rider LG, Childhood Myositis Heterogeneity Study Group

Rider, LG (reprint author), Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, Off Clin Res, CRC 4-2352,MSC 1301,10 Ctr Dr, Bethesda, MD 20892 USA Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, Off Clin Res, Bethesda, MD 20892 USA NIDDK, Bethesda, MD 20892 USA NCI, Bethesda, MD 20892 USA NIH, Bethesda, MD 20892 USA Penn State Milton S Hershey Med Ctr, Hershey, PA USA Univ Michigan, Ann Arbor, MI 48109 USA Univ Oklahoma, Hlth Sci Ctr, Vet Affairs Med Ctr, Oklahoma City, OK USA Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA Med Univ S Carolina, Charleston, SC 29425 USA US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA Columbia Univ, New York, NY USA Univ Castilla La Mancha, Fac Med, CRIB, Albacete, Spain

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.