Article

Skin involvement in juvenile dermatomyositis is associated with loss of end row nailfold capillary loops.

Department of Pediatrics, Division of Immunology/ Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
The Journal of Rheumatology (Impact Factor: 3.17). 09/2004; 31(8):1644-9.
Source: PubMed

ABSTRACT To determine associations of dermatological findings in children with juvenile dermatomyositis (JDM) with specific nailfold capillary (NFC) structural abnormalities.
Sixty newly diagnosed, previously untreated children who met the Bohan-Peter criteria for definite JDM were seen between 1993 and 2002. They were classified by duration of untreated disease and by a disease activity score (DAS) composed of separate subscores for dermatological (DAS skin) and musculoskeletal (DAS muscle) findings. Routine NFC measurements yielded the number of end row loops, arboreal (bushy), and dilated capillary loops. Laboratory testing included muscle enzymes, von Willebrand Factor Antigen, and neopterin.
DAS skin, but not DAS muscle, was associated with NFC end row capillary loss (rs = -0.394, p = 0.008). End row capillary loss (reflecting avascularity), arboreal (bushy), and dilated capillary loops (reflecting change in vascular morphology) were each associated with longer untreated symptom duration (rs = -0.401, rs = 0.534, rs = 0.371).
End row capillary loss measured by NFC was associated with the dermatological, but not musculoskeletal manifestations of JDM, suggesting that damage to skin and muscle may each have distinct disease pathophysiology. In JDM, skin involvement indicates a vasculopathy that progresses with increasing duration of untreated disease and is not revealed by standard serological laboratory tests. We propose that the cutaneous manifestations of JDM are associated with vascular disease and warrant aggressive therapy.

0 Bookmarks
 · 
90 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective To evaluate the effect of duration of untreated disease on vascular cell adhesion molecule 1 (VCAM-1) and microRNA (miRNA) expression in muscle biopsy samples from children with juvenile dermatomyositis (DM) as well as its effect on soluble VCAM-1 (sVCAM-1) and tumor necrosis factor α (TNFα) concentrations in sera from these children. Methods We enrolled 28 untreated children with juvenile DM and 8 pediatric controls. Eleven children with juvenile DM had short duration of untreated disease (symptoms for ≤2 months before muscle biopsy), and 17 had long duration of untreated disease (symptoms for >2 months before muscle biopsy). Vascular structures, characterized by immunofluorescence using antibodies against von Willebrand factor, VCAM-1, and α-smooth muscle actin, were measured for total area and intensity. Circulating sVCAM-1 and TNFα levels were determined in patients with short duration of untreated disease, patients with long duration of untreated disease, and controls. Differential expression of microRNA-126 (miR-126) in muscle biopsy samples from the 2 patient groups and the control group was detected by miRNA expression profiling and confirmed by quantitative reverse transcription–polymerase chain reaction in muscle biopsy samples from the 3 groups. ResultsJuvenile DM patients with short duration of untreated disease had significantly higher total positive area and intensity/high power field of VCAM-1 expression than did juvenile DM patients with long duration of untreated disease (P = 0.043 and P = 0.015, respectively) or controls (P = 0.004 and P = 0.001, respectively). Von Willebrand factor antigen–positive vasculature displayed greater VCAM-1 intensity in patients with short duration of untreated disease than in patients with long duration of untreated disease (P = 0.001). Circulating levels of sVCAM-1 and TNFα were significantly higher in patients with short duration of untreated disease than in controls (P = 0.013 and P = 0.048, respectively). The miRNA miR-126, a negative regulator of VCAM-1 expression, was significantly decreased (3.39-fold; P < 0.006) in patients with short duration of untreated disease compared to controls, while miR-126 expression in patients with long duration of untreated disease did not differ significantly compared to controls. Conclusion In patients with short duration of untreated disease, miR-126 down-regulation is associated with increased VCAM-1 in both muscle and blood, suggesting that VCAM-1 plays a critical role early in juvenile DM disease pathophysiology, augmented by TNFα.
    Arthritis & Rheumatology 11/2012; 64(11). · 7.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To compare systolic cardiac function in patients with juvenile dermatomyositis (JDM) with matched controls and examine associations between systolic and diastolic cardiac function and disease variables. Fifty-nine patients, examined at follow-up, median 16.8 years (2-38 years) after disease onset, were compared with 59 age-matched and sex-matched controls. Echocardiography was performed and analysed blinded to patient information. We used mitral annulus displacement to assess the relative long-axis shortening of the left ventricle (long-axis strain) and early diastolic tissue velocity (e'), as markers for systolic and diastolic function, respectively. Disease activity and organ damage were assessed at follow-up by clinical examination and retrospectively by chart review. Long-axis strain was reduced in patients compared with controls (16.6% (2.5) vs 17.7% (2.0), mean (SD), p=0.001), whereas no difference was seen between patients with active and inactive disease. Disease duration correlated with systolic and diastolic function (rsp=-0.50 and rsp=-0.73, both p<0.001) and so did Myositis Damage Index (MDI) 1 year (rsp=-0.36 and rsp=-0.46) and MDI at follow-up (rsp=-0.33 and rsp=-0.60), all p<0.01. High early disease activity score (DAS) in skin (DAS skin 1 year), but not in muscle, predicted systolic (standardised β=-0.28, p=0.011, R(2)=48%) and diastolic dysfunction (β=-0.36, p<0.001, R(2)=72%) at follow-up. Long-axis strain was reduced in JDM patients compared with controls, suggesting systolic dysfunction. Impaired systolic and diastolic function was predicted by DAS skin 1 year. This indicates a common pathway to two different cardiac manifestations in JDM, perhaps with similar pathogenesis as skin affection.
    Annals of the rheumatic diseases 07/2013; · 9.27 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective To test 4-year-olds, using 14 maneuvers of the Childhood Myositis Assessment Scale (CMAS), comparing healthy children with those with juvenile dermatomyositis (DM). Methods Healthy 4-year-olds (n = 28) completed the CMAS. Their scores were compared with children with juvenile DM (n = 18) who had a muscle Disease Activity Score (DAS-M) of 0. ResultsThe healthy children achieved a mean ± SD CMAS score of 46.6 ± 2.3 (interquartile range 46–47). There were no significant differences between boys and girls, and the scores were not significantly associated with height or weight. The greatest variation involved items that assessed endurance. Item 1, neck raise, yielded a mean ± SD score of 28.2 ± 19.3 seconds, with a mean ± SD CMAS score of 2.5 ± 0.9 (maximum score 5). Item 3, leg lift, yielded a mean ± SD score of 55.5 ± 37.3 seconds, with a mean ± SD CMAS score of 3.1 ± 1.1 (maximum score 5). Item 5, sit-ups maneuver, yielded a mean ± SD score of 5.3 ± 1.1 sit-ups. Almost identical data were obtained for the 18 treated children with juvenile DM who had normal strength on the DAS-M. Conclusion Healthy children ages 4 years do not achieve the total CMAS score of 52 attained by older children. Both boys and girls were remarkably consistent, with a mean CMAS score of 46.6. Children ages 4 years with juvenile DM with a DAS-M of 0 also achieved a CMAS score of 46.6. We conclude that half of 4-year-old children achieve a mean CMAS score of 46 or 47, not a total CMAS score of 52, suggesting that weakness may be overdiagnosed in 4-year-olds with an inflammatory myopathy.
    Arthritis Care & Research. 10/2013; 65(10).

Preview

Download
1 Download
Available from