Juvenile dermatomyositis (JDM) is a multisystem disease of uncertain origin that is defined by chronic inflammation of striated muscle and the skin (1). Similarities and differences between JDM and adult dermatomyositis (ADM) have been reported (1). We know that persistent muscle impairment, despite immunosuppressive therapy, is a common symptom for both patients with JDM and ADM. However, there is less information regarding the pathophysiology of JDM compared with ADM.
In patients with ADM, immunosuppressive therapy, including glucocorticoids, has suppressive effects on the gene expression of the inflammatory pathways in skeletal muscle, but it also changes the expression of genes involved in skeletal muscle tissue remodeling, which may negatively affect muscle regeneration and growth (2). The altered gene expression has been associated with lipid uptake and lipolysis in response to immunosuppressive therapy, which may also have a negative effect on muscle performance (2). It has been suggested that for patients with ADM, muscle impairment may persist, while the inflammation associated with the myositis improves after glucocorticoid therapy. The same pathophysiology may apply for JDM. Furthermore, in JDM, this mechanism may present not only as persistent muscle impairment, but also as persistent skin ulcers, despite immunosuppressive therapy (3,4). This is because a relationship between dermatitis and lipid metabolism has been reported (5). For both ADM and JDM, muscle biopsies reveal signs of inflammation, including infiltrating macrophages in the muscle fibers (6,7), whereas activated macrophages are present in skin ulcers with calcinosis in JDM (8).
Liposteroid [dexamethasone palmitate (DP)] is a lipid emulsion containing dexamethasone, which was developed in Japan (9). This agent provides greater efficacy, and much less risk for systemic adverse effects, than dexamethasone, because the lipid emulsion is easily taken up by phagocytes (10). When the same dose of DP or dexamethasone sodium phosphate (DSP) is administrated, the uptake of DP is 8-time higher, it is hydrolyzed slowly, and the anti-inflammatory effect on macrophages is 5- to 6-time higher than DSP (9,10). In addition, DP has fewer side effects, for example, it has little inhibitory effect on the hypothalamus-pituitary-adrenal axis compared with DSP (9).
Japanese physicians have used liposteroid therapy to treat rheumatoid arthritis (11). Recently, Japanese researchers reported the clinical efficacy and utility of liposteroid in the treatment of diseases associated with macrophage activation, including hemophagocytic lymphohistiocytosis (12), pulmonary hemosiderosis (13), and graft-versus-host disease (14). There are no reports regarding the clinical utility of liposteroid for the treatment of JDM and ADM. However, we reported successful liposteroid therapy of JDM-associated macrophage activation syndrome (15). This was the first case to show the efficacy, with no adverse events, in high-dose liposteroid therapy for JDM-associated macrophage activation syndrome. Although investigation of the effects of the lipid emulsion in liposteroid on lipid metabolism needs to be performed, and case reports regarding the use of liposteroid therapy for treatment of JDM and ADM need to be accumulated in order to confirm the clinical utility of liposteroid therapy for these conditions, there is some evidence that this agent may be effective for reducing side effects in patients with JDM and ADM, especially the muscle impairment and skin ulcers that persist despite immunosuppressive therapy.
Conflicts of Interest: The author has no conflicts of interest to declare.
- Rider LG, Lindsley CB, Miller FW. Juvenile dermatomyositis. In: Petty RE, Laxer RM, Lindsley CB, et al. editors. Textbook of pediatric rheumatology. 7th ed. Philadelphia: Saunders Elsevier, 2016:351-83.
- Loell I, Raouf J, Chen YW, et al. Effects on muscle tissue remodeling and lipid metabolism in muscle tissue from adult patients with polymyositis or dermatomyositis treated with immunosuppressive agents. Arthritis Res Ther 2016;18:136. [Crossref] [PubMed]
- Wakiguchi H, Takei S, Imanaka H, et al. Severe gluteal skin ulcers in an infant with juvenile dermatomyositis. Eur J Dermatol 2016;26:192-3. [PubMed]
- Wakiguchi H, Takei S, Kawano Y. Axillary Skin Ulcers in Infants with Juvenile Dermatomyositis. Pediatr Neonatol 2016. [Epub ahead of print]. [Crossref] [PubMed]
- Kendall AC, Nicolaou A. Bioactive lipid mediators in skin inflammation and immunity. Prog Lipid Res 2013;52:141-64. [Crossref] [PubMed]
- Nagaraju K, Casciola-Rosen L, Lundberg I, et al. Activation of the endoplasmic reticulum stress response in autoimmune myositis: potential role in muscle fiber damage and dysfunction. Arthritis Rheum 2005;52:1824-35. [Crossref] [PubMed]
- Li CK, Varsani H, Holton JL, et al. MHC Class I overexpression on muscles in early juvenile dermatomyositis. J Rheumatol 2004;31:605-9. [PubMed]
- Shimizu M, Ueno K, Ishikawa S, et al. Role of activated macrophage and inflammatory cytokines in the development of calcinosis in juvenile dermatomyositis. Rheumatology (Oxford) 2014;53:766-7. [Crossref] [PubMed]
- Wakiguchi H, Ohga S. Clinical utility of the liposteroid therapy: Potential effects on the macrophage activation. Nihon Rinsho Meneki Gakkai Kaishi 2016;39:190-6. [Crossref] [PubMed]
- Mizushima Y, Hamano T, Yokoyama K. Tissue distribution and anti-inflammatory activity of corticosteroids incorporated in lipid emulsion. Ann Rheum Dis 1982;41:263-7. [Crossref] [PubMed]
- Hoshi K, Mizushima Y, Shiokawa Y, et al. Double-blind study with liposteroid in rheumatoid arthritis. Drugs Exp Clin Res 1985;11:621-6. [PubMed]
- Nishiwaki S, Nakayama T, Murata M, et al. Dexamethasone palmitate successfully attenuates hemophagocytic syndrome after allogeneic stem cell transplantation: macrophage-targeted steroid therapy. Int J Hematol 2012;95:428-33. [Crossref] [PubMed]
- Doi T, Ohga S, Ishimura M, et al. Long-term liposteroid therapy for idiopathic pulmonary hemosiderosis. Eur J Pediatr 2013;172:1475-81. [Crossref] [PubMed]
- Nishiwaki S, Nakayama T, Murata M, et al. Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions. PLoS One 2014;9:e96252. [Crossref] [PubMed]
- Wakiguchi H, Hasegawa S, Hirano R, et al. Successful control of juvenile dermatomyositis-associated macrophage activation syndrome and interstitial pneumonia: distinct kinetics of interleukin-6 and -18 levels. Pediatr Rheumatol Online J 2015;13:49. [Crossref] [PubMed]