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.

FIGURE 1

A., B., C. Features of the generalized lipodystrophy (LD) phenotype in a patient with juvenile dermatomyositis. Loss of subcutaneous fat from the entire lower and upper extremity, buccal fat loss, and acanthosis nigricans are typical features of generalized LD. Figure A demonstrates dystrophic calcification in the thighs in the region of the LD, as well as possible muscle hypertrophy. Generalized hyperpigmentation is evident, as well as parotid enlargement in Figure C.

FIGURE 2

A. and B. Features of the partial LD phenotype in a patient with juvenile onset-dermatomyositis. Increased fat deposition in the thighs and abdomen of a partial LD patient, accompanied by a loss of fat from the calves and feet.

FIGURE 3

Features of focal LA in 2 patients with juvenile-onset dermatomyositis. Localized skin LA and subcutaneous dimpling is seen in the right buttock (A) and left mid-thigh (B), in regions of calcinosis.

FIGURE 4

A. Thigh MRI from a DM patient with generalized LD showing loss of anterior, lateral, and posterior subcutaneous fat. There is increased medial relative to lateral subcutaneous fat. B. Abdominal MRI from the same patient showing loss of subcutaneous abdominal fat and increase in intraabdominal fat.

FIGURE 5

A. A biopsy from the thigh at a site of LD showing atrophic changes in the subcutaneous fat from an adult DM patient with partial LD. There is shrinkage of individual adipocytes associated with increased capillary vascularity. There was no significant inflammation at this site. This biopsy was taken 2.3 years after onset of DM and 4 months after onset of LD (hematoxylin-eosin, original magnification × 200). B. A biopsy from the left upper arm at a site of subcutaneous fat loss from the same patient. There are deep dermal changes associated with calcinosis of the subcutaneous adipose tissue. The upper dermis and the epidermis were normal. This biopsy was obtained 2 years after onset of DM and 1 month after onset of LD (hematoxylin-eosin, original magnification × 100).