Chapter 149: Juvenile Dermatomyositis

BACKGROUND

Juvenile dermatomyositis (JDM) is the most common pediatric acquired inflammatory myopathy. This diffuse vasculopathy primarily involves inflammation in skin and striated muscle, which often leads to significant weakness and physical limitations. However, despite its nomenclature JDM is a multisystem disease. Characteristic cutaneous features, which classically include heliotrope rash and Gottron papules, aid in the diagnosis. The etiology of this condition is unknown, and has an estimated incidence of 1 to 3 in 1 million children,^1,2 with approximately a 2:1 female predominance. Affected children are typically between 4 and 10 years of age with an average age of onset of 7 years. Outcomes in JDM may vary, but historically there was significant morbidity; without adequate treatment, one-third of affected persons will have moderate to severe disability. Mortality attributable to the disease occurs in one-third of children.^3,4

PATHOGENESIS

Despite extensive research, the pathogenesis of JDM remains unknown. There is often seasonal clustering of new cases of JDM, suggesting an environmental or infectious trigger. Association with specific infectious processes raises the possibility of molecular mimicry as a mechanism in JDM,^5-7 but no single agent has been identified. There appears to be genetic susceptibility, with HLA associations HLA-DQA1*0501, HLA-DQA*0301, HLA-DRB1*0301, and HLA-B8 described in patients with JDM,^8-10 and TNF-α-308A allele has been associated with a prolonged disease course.¹¹

Abnormalities in humoral-mediated immunity, cell-mediated immunity, and immune complex disease have also been implicated in the pathogenesis, but these results have been varied.^12-17 Some research suggests a role of major histocompatibility complex (MHC)-I, where there is overexpression in JDM and myositis-associated antibodies. Elevated immunoglobulin levels and myositis-specific autoantibodies, which have been identified most patients with JDM,¹⁸ suggest a humoral component to the pathogenesis of JDM. Type 1 interferons have also been implicated and are thought to contribute to enhanced MHC-I expression, cell cytotoxicity, and activation of T cells. Additional research suggests a possible role of maternal microchimerism, where maternal cells trigger an immune response akin to graft-versus-host disease in the child.^19,20

Despite this broad range of possibilities in the pathogenesis of this condition, it is generally accepted that JDM occurs in a genetically susceptible patient in response to an environmental or infectious trigger, with a disruption in normal immune functioning.

CLINICAL PRESENTATION

Children with JDM are diagnosed at less than 18 years of age, and typically present with proximal muscle weakness and a pathognomonic rash. There is a heterogeneous presentation to JDM, which can vary from mild to severe skin involvement and mild to severe weakness, and the presentation may be acute or insidious. The formal diagnosis of JDM is based on the Bohan and Peter criteria²¹ (Table 149-1; www.imm.ki.se/biostatistics/calculators/iim). Weakness may have broad clinical presentations including nonspecific malaise, myalgia, decreased general stamina and endurance with activities, difficulty in ...