Etiology

Evidence suggests that the etiology of JDM is multifactorial, based on genetic predisposition and an unknown environmental trigger. HLA alleles such as B8, DRB1*0301, DQA1*0501, and DQA1*0301 have been associated with increased susceptibility to JDM in selected populations. Maternal microchimerism may play a part in the etiology of JDM by causing graft versus host disease or autoimmune phenomena. Persistent maternal cells have been found in blood and tissue samples of children with JDM. An increased number of these maternal cells are positive for HLA-DQA1*0501, which may assist with transfer or persistence of chimeric cells. Specific cytokine polymorphisms in tumor necrosis factor-α (TNF-α) promoter and variable number tandem repeats of the interleukin-1 receptor antagonist (IL-1Ra) also may increase genetic susceptibility. These polymorphisms are common in the general population. A history of infection in the 3 mo prior to disease onset is commonly reported; multiple studies have failed to produce a causative organism. Constitutional signs and upper respiratory symptoms predominate, but one third of patients report preceding gastrointestinal (GI) symptoms. Group A streptococcus, upper respiratory infections, GI infections, coxsackievirus B, toxoplasma, enteroviruses, parvovirus B19, and multiple other organisms have been postulated as possible pathogens in the etiology of JDM. Despite these concerns, results of serum antibody testing and polymerase chain reaction amplification of the blood and muscle tissue for multiple infectious diseases have not been revealing. Environmental factors may also play a contributing role, with geographic and seasonal clustering reported; however, no clear theory of etiology has emerged.

Epidemiology

The incidence of JDM is approximately 3 cases/1 million children/yr without racial predilection. Peak age of onset is between 4 and 10 yr. There is a second peak of dermatomyositis onset in late adulthood (45-64 yr), but adult-onset dermatomyositis appears to be a distinctly separate entity in prognosis and etiology. In the USA, the ratio of girls to boys with JDM is 2 : 1. Multiple cases of myositis in a single family are rare, but familial autoimmune disease may be increased in families with children who have JDM than in families of healthy children. Reports of seasonal association have not been confirmed, although clusters of cases may occur.

Pathogenesis

Type I interferons may be important in the pathogenesis of juvenile dermatomyositis. Interferon upregulates genes critical in immunoregulation and major histocompatibility class (MHC) class I expression, activates natural killer (NK) cells, and supports dendritic cell maturation. Upregulation of gene products controlled by type I interferons occurs in patients with dermatomyositis, potentially correlating with disease activity and holding promise as clinical biomarkers.

It appears that children with genetic susceptibility to JDM (HLA-DQA1*0501, HLA-DRB*0301) may have prolonged exposure to maternal chimeric cells and/or an unknown environmental trigger. Once triggered, an inflammatory cascade with type I interferon response leads to upregulation of MHC class I expression and maturation of dendritic cells. Overexpression of MHC class I upregulates adhesion molecules, which influence migration of lymphocytes, leading to inflammatory infiltration of muscle. In an autoregulatory feedback loop, muscle inflammation increases the type I interferon response, regenerating the cycle of inflammation. Cells involved in the inflammatory cascade include NK cells (CD56), T-cell subsets (CD4, CD8, Th17), monocytes/macrophages (CD14), and plasmacytoid dendritic cells. Neopterin, interferon-inducible protein 10 (IP-10), monocyte chemoattractant protein (MCP), myxovirus resistance protein (MxA), and von Willebrand factor products as well as other markers of vascular inflammation may be elevated in patients with JDM who have active inflammation.

Clinical Manifestations

Children with JDM present with either rash, insidious onset of weakness, or both. Fevers, dysphagia or dysphonia, arthritis, muscle tenderness, and fatigue are also commonly reported at diagnosis.

Rash develops as the first symptom in 50% of cases and appears concomitant with weakness only 25% of the time. Children often exhibit extreme photosensitivity to ultraviolet light exposure with generalized erythema in sun-exposed areas. If seen over the chest and neck, this erythema is known as the “shawl sign.” Erythema is also commonly seen over the knees and elbows. The characteristic heliotrope rash (Fig. 153-1) is a blue-violet discoloration of the eyelids that may be associated with periorbital edema. Facial erythema crossing the nasolabial folds is also common, in contrast to the malar rash without nasolabial involvement typical of systemic lupus erythematosus. Classic Gottron papules (Fig. 153-2) are bright pink or pale, shiny, thickened or atrophic plaques over the proximal interphalangeal joints and distal interphalangeal joints and occasionally on the knees, elbows, small joints of the toes, and ankle malleoli. The rash of JDM is sometimes mistaken for eczema or psoriasis. Rarely, a thickened erythematous and scaly rash develops in children over the palms (known as mechanic’s hands) and soles along the flexor tendons, which is associated with anti-Jo-1 antibodies.

Figure 153-1 The facial rash of juvenile dermatomyositis. There is erythema over the bridge of the nose and malar areas with violaceous (heliotropic) discolorations of the upper eyelids.

Figure 153-2 The rash of juvenile dermatomyositis. The skin over the metacarpal and proximal interphalangeal joints may be hypertrophic and pale red (Gottron papules).

Evidence of small vessel inflammation is often visible in the nail folds and gums as individual capillary loops that are thickened, tortuous, or absent (Fig. 153-3). Telangiectasias may be visible to the naked eye but are more easily visualized under capillaroscopy or with use a magnifier such as an ophthalmoscope. Severe vascular inflammation causes cutaneous ulcers on toes, fingers, axillae, or epicanthal folds.

Figure 153-3 Nail-fold capillary pattern in rheumatic disease. A, Normal nail-fold capillary pattern in a healthy child with a homogeneous distribution and uniform appearance of capillary loops. B, The nail-fold capillary pattern in a child with juvenile dermatomyositis shows dropout of capillary end loops, resulting in a wide band of avascularity. Dilated, tortuous capillaries can also be seen. C, Severe periungual telangiectasias may be seen without microscopy.

Weakness associated with JDM is often insidious and difficult to differentiate from fatigue at onset. It is typically symmetric, affecting proximal muscles such as the neck flexors, shoulder girdle, and hip flexors. Parents may report difficulty climbing stairs, combing hair, and getting out of bed. Examination reveals inability to perform a sit-up, head lag in a child after infancy, and Gower sign (use of hands on thighs to stand from a sitting position). Patients with JDM may roll to the side rather than sit straight up from lying to compensate for truncal weakness. Approximately half of children exhibit muscle tenderness as a result of muscle inflammation.

Esophageal and respiratory muscles are also affected, resulting in aspiration or respiratory failure. It is essential to assess for dysphonia or nasal speech, palatal elevation with gag, dysphagia, and gastroesophageal reflux by means of history, physical exam, and swallow study, if symptoms are present. Respiratory muscle weakness can be a medical emergency and lead to respiratory failure. Children with respiratory muscle weakness do not manifest typical symptoms of impending respiratory failure with increased work of breathing, instead demonstrating hypercarbia rather than hypoxemia.

Lipodystrophy and calcinosis (Fig. 153-4