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 Address reprint requests to: Lisa G. Rider, MD, Environmental Autoimmunity Group, National Institute of Environmental Health Sciences, National Institutes of Health, CRC 4-2352, MSC 1301, 10, Center Drive, Bethesda, MD 20892-1301. Fax: 301-451-5588; email: E-mail: riderl@mail.nih.gov. * These authors contributed equally to this work. † Contributors to this study are listed in the appendix. NIH Public AccessAuthor Manuscript Medicine (Baltimore) NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 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.

Cutaneous Manifestations in Dermatomyositis: Key Clinical and Serological Features—a Comprehensive Review

“…In a US cohort, generalized lipodystrophy was reported to be associated with these antibodies [33]. In a subsequent report of US cohort, anti-TIF1γ/α antibody-positive patients showed classic JDM features, including Gottron papules, heliotrope and malar rashes, periungual abnormalities, photosensitivity, linear extensor erythema, cuticular overgrowth, V-neck sign, shawl sign, lipodystrophy, and erythroderma [26].…”

Metreleptin for metabolic disorders associated with generalized or partial lipodystrophy

“…Patients with acquired generalized lipodystrophy (AGL) may show severe metabolic complications similar to patients with CGL, while patients with acquired partial lipodystrophy (Barraquer-Simmons syndrome), who invariably have well preserved lower body fat, have lesser incidence of metabolic complications compared with other lipodystrophy syndromes. Rare forms of acquired partial lipodystrophy associated with auto-inflammatory syndromes may, however, be associated with significant metabolic abnormalities [12][13][14]. The most prevalent form of lipodystrophy is seen in association with HIV infection (LD-HIV), with 40-50% of patients on long-term antiretroviral therapy being affected by either generalized lipoatrophy or partial fat loss involving the face and extremities [15].…”

Idiopathic Inflammatory Myopathies: an Update on Classification and Treatment with Special Focus on Juvenile Forms

“…Lipodystrophy, occurring in 10 % of cases, is another JDM complication characterised by progressive loss of subcutaneous fat in a widespread manner [10]. Figures 2 and 3 show Gottron sign, lipodystrophy and calcinosis in 52-year-old female patients with a 48-year history of DM. Overlap myositis is the second most common clinical JIIM phenotype, occurring in 6-11 % of subjects [11].…”