Sunlight, the first noninfectious environmental factor identified in juvenile myositis, alters autoantibody expression and may shift the disease phenotype from muscle only (myositis) to involvement of skin as well as muscle (dermatomyositis), Mona Shah, PhD, from the National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, Maryland, and George Washington University School of Medicine, Washington, DC, and colleagues from the Childhood Myositis Heterogeneity Collaborative Study Group report in an article published online July 2 in Arthritis & Rheumatism.
"There are clinical implications regarding the role of ultraviolet radiation (UVR), especially sun exposure, in altering and maybe even in propagating the disease, so patients may want to use careful photoprotective measures," senior author Lisa G. Rider, MD, told Medscape Medical News.
"More attention to treating the skin disease also might be an implication. Some people have put more emphasis on treating the muscle disease and seen it as unrelated to the skin, but the UV data show that the muscle and skin manifestations may be more connected than had been recognized," said Dr. Rider, who is deputy chief of the Environmental Autoimmunity Group, National Institute of Environmental Sciences.
Juvenile dermatomyositis (JDM), which includes skin rashes and photosensitivity, is the most common idiopathic inflammatory myopathy in children, the authors report. JDM is associated with the anti-p155/140 autoantibody, which recognizes proteins with molecular weights of 155 and 140 kDa, presumptively identified as transcriptional intermediary factor 1 γ. Juvenile polymyositis (JPM) is less common and is associated with autoantibody anti-MJ, which recognizes nuclear matrix protein 2.
The researchers used registry data accumulated over the course of 15 years to investigate the relationship between UVR exposure in the month before symptom onset, the prevalence of JDM vs JPM, and autoantibody expression in 271 patients with JDM and 27 patients with JPM. All participants were enrolled in the nationwide registry and had undergone myositis autoantibody testing.
As a proxy for sunlight exposure, the researchers used US National Weather Service calculations of the UV index, which integrates UVA and UVB. "We looked at short-term UV exposure 1 month before first symptom. Other studies had looked at a median time for the whole population," Dr. Rider said.
The investigators studied the association between UVR exposure and clinical and autoantibody subgroups, using regression models stratified by sex and race. They reported that as the patients' highest UV index in the month before symptom onset rose, odds of JDM (vs JPM) increased for girls. The odds of having anti-p155/140 autoantibodies were associated with average and highest UV indices, and this association was strongest in white males, accounting for a 30% increased odds ratio. UV index was not associated with anti-MJ autoantibodies.
The researchers conclude, "Across US geoclimatic regions, the average UV index was associated with increasing odds of JDM and anti-p155/140 autoantibodies but decreasing odds of anti-MJ autoantibodies."
"The implication of our study is that sunlight exposure might shift disease expression. We had hypothesized previously that there were both genetic and environmental factors for the disease. There had been hints from uncontrolled studies of infectious disease, but this is the first noninfectious environmental factor to be associated with juvenile myositis," Dr. Rider said.
She added that anti-p155/140 autoantibodies are often associated with photosensitive skin rashes, whereas anti-MJ autoantibodies are not. "It is interesting that these 2 antibodies also have the same relationship with UVR exposure. It may be that the autoantigens associated with anti-p155/140 are upregulated by UVR exposure, but those associated with anti-MJ are not," she said.
"In the study by Shah et al, they did not specify first myositis-related symptoms of the patients examined. Although skin symptoms generally precede muscle symptoms in JDM, I would like to know the ratio of skin symptom–preceding cases and muscle symptom–preceding cases in JDM and the association of UV index and the ratio in their study," Yoshinao Muro, MD, PhD, told Medscape Medical News. Dr. Muro, who was not involved in the study, is a specialist in autoantibody analysis in connective tissue diseases. He is associate professor, Division of Connective Tissue Disease and Autoimmunity, Department of Dermatology, Nagoya University Graduate School of Medicine, Japan.
Dr. Muro's concern was whether autoantibodies such as anti-p155/140 could be induced by only 1 month of UV exposure, as disease-associated autoantibodies appear years before disease onset in other autoimmune diseases.
"It is still unclear whether the autoantibodies are pathogenic or they are just an epiphenomenon. However, if a certain genetic background is found to be associated with the production of anti-p155/140 in future studies, juveniles having such a genetic background might better avoid UV exposure," Dr. Muro said.
Dr. Muro would also like to see individual data on UVR exposure and outdoor activities. "Kids who have many outdoor activities as well as trips are also more likely to be exposed to infections, so we should be always aware of other environmental factors in this kind of study," Dr. Muro said.
The study was supported in part by the Intramural Research Programs of the National Institute of Environmental Health Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, and the Center for Biologics Evaluation and Research of the US Food and Drug Administration. One coauthor is a consultant to the Oklahoma Medical Research Foundation Clinical Immunology Laboratory. The other authors and Dr. Muro have disclosed no relevant financial relationships.
Arthritis Rheum. Published online July 2, 2013. Abstract
Medscape Medical News © 2013 WebMD, LLC
Send comments and news tips to email@example.com.
Cite this: Juvenile Dermatomyositis May Be Triggered by UV Exposure - Medscape - Jul 05, 2013.