Original article
Skin disease is more recalcitrant than muscle disease: A long-term prospective study of 184 children with juvenile dermatomyositis

https://doi.org/10.1016/j.jaad.2020.12.032Get rights and content

Background

Persistent skin manifestations, especially calcinoses, contribute to morbidity in children with juvenile dermatomyositis.

Objective

To compare the course of skin and muscle involvement and document frequency of calcinosis in juvenile dermatomyositis.

Methods

Prospective cohort study of 184 untreated children with juvenile dermatomyositis (July 1971 to May 2019) at a single children's hospital.

Results

Disease Activity Scores (DASs) were persistently higher for skin versus muscle at all points; clinical inactivity (DAS ≤2) occurred earlier for muscle than skin. Among vascular features for DAS for skin, eyelid margin capillary dilatation was most frequent (54.3%) and persisted longest. Intravenous methylprednisolone reduced DAS for skin more than oral prednisone at 12 months (P = .04). Overall, 16.8% of patients (n = 31) had calcifications, with 4.9% at enrollment. Despite therapy, 25.0% of calcifications recurred and 22.6% failed to resolve; of the latter, 71.4% (n = 5) were present at enrollment. Children with persistent calcifications had longer duration of untreated disease than those whose calcifications resolved (mean 12.5 months) (P < .001). Hydroxychloroquine did not improve DAS for skin (P = .89).

Limitations

DAS does not quantify nailfold capillary dropout.

Conclusions

In juvenile dermatomyositis, skin disease presents with greater activity and is more recalcitrant to therapies than muscle disease. Early and aggressive treatment can limit the severity and persistence of calcifications identified later in the disease course.

Introduction

Juvenile dermatomyositis, a rare autoimmune disease, affects 2.3 to 4.1 US children per million per year.1, 2, 3 Defining features are symmetric proximal muscle weakness and a characteristic skin eruption, most often localized to the face and overlying joints.4 Juvenile dermatomyositis may lead to severe sequelae, including dystrophic calcifications, persistent cutaneous inflammation, and organ involvement with functional limitations.5, 6, 7

Validated in 2003,8 the Disease Activity Score (DAS) continues to be a widely used measure for quantifying skin and muscle activity in juvenile dermatomyositis.9, 10, 11, 12, 13 The 20-point scale uses 11 possible points for muscle and 9 points for skin manifestations. Scored skin features include severity of skin erythema and Gottron papules, distribution, and the presence of erythema and telangiectasia at specific locations (eyelid, periungual region, and palate). The DAS monitors disease severity and response to treatment, and has been shown to predict juvenile dermatomyositis functional outcomes, such as cardiac dysfunction with high early Disease Activity Score–Skin (DAS-S) scores.14 The DAS-S has the strongest correlation with the physician's visual analog scale.15

Prompt initiation of appropriate therapy is linked to optimal outcomes and reduction of long-term disability.16, 17, 18 Although skin features often precede muscle complaints, calcinoses are a later complication. Calcinosis is a poorly understood and feared complication of juvenile dermatomyositis, contributing to significant morbidity. Reported to be present in 30% to 50% of juvenile dermatomyositis patients,19, 20, 21 calcinoses often involve the extremities22 and soft tissues, may be related to repeated local trauma, and are associated with longer disease duration before therapy.23,24 Risk of calcification has been linked to delayed or suboptimal treatment5,25 and the TNFA-308 GA or AA genotype.26

Using long-term tracking of DAS-S and Disease Activity Score–Muscle (DAS-M) scores,8,9 this study compared skin and muscle activity, as well as patterns of calcifications, during the juvenile dermatomyositis disease course in 485 children at a single center.

Section snippets

Patient selection and study design

Data from this single-center cohort study were extracted from the Juvenile Myositis Registry, currently a Research Electronic Data Capture database (hosted by Northwestern University Feinberg School of Medicine),27 begun in July 1971 that includes all juvenile dermatomyositis patients treated at The Ann and Robert H. Lurie Children's Hospital of Chicago through May 2019. Clinical and laboratory data were captured for 184 children and adolescents who met inclusion criteria of diagnosis of

Results

The 184 untreated juvenile dermatomyositis patients (Table I) were predominantly female individuals (75%), non-Hispanic White (72.2%), and of the TNFA-308 GG genotype (69%). The mean duration of untreated disease at enrollment was 10.4 months (standard deviation [SD] 17.5 months). At entry, skin involvement was classified as minimal (Gottron papules only, 0.6%), mild (45.2%), moderate (45.2%), or severe (9.0%). Skin distribution was described as focal (59.1%; limited to joint regions), diffuse

Discussion

Given the collection of data for 48 years, this study provides a historical and comprehensive look at the management of juvenile dermatomyositis. The data confirm that juvenile dermatomyositis patients present with greater skin than muscle involvement, and that skin features require more time for resolution.36 This is an important consideration because persistent skin disease not only significantly affects quality of life but also can foster calcification and ulceration that can be life

Strengths and limitations

With data captured during almost 5 decades, this study is the largest cohort study of untreated juvenile dermatomyositis patients from a single center, to our knowledge. Most patients were treated and evaluated by a single physician (L.M.P.), ensuring uniform scoring. However, the DAS has certain limitations. For example, nailfold capillary dropout is associated with more chronic disease and greater disease severity,17,48 but it is not quantified in the DAS. Our group's ongoing investigation of

Conclusions

This cohort study confirms that both skin and muscle involvement should guide diagnosis and treatment of juvenile dermatomyositis. Clinicians should be aware of eyelid margin capillary dilatation, which tends to persist, in addition to other characteristic skin features that are better recognized. Early and aggressive treatment with therapies such as intravenous methylprednisolone can help limit the severity of skin disease.

Conflicts of interest

None disclosed.

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  • Funding sources: Supported by the Vivian Allison and Daniel J. Pachman Fund (Pachman), the Cure JM Foundation (Morgan, Pachman), and R-21 AR077565 from the National Institute of Arthritis, Metabolic and Skin Diseases (Pachman). Research Electronic Data Capture is supported at Feinberg School of Medicine by the Northwestern University Clinical and Translational Science (NUCATS) Institute. NUCATS is funded in part by a Clinical and Translational Science Award grant from the National Institutes of Health UL1TR001422.

    The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

    IRB approval status: Reviewed and approved by the Lurie Children's Institutional Review Board (IRB 2019-2734).

    Reprints not available from the authors.

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