Most JDM patients have MSAs alone or those associated with specific clinical phenotypes (1, 2). Although several phenotypic features are similar in both adult and juvenile MSA patients, some important differences exist (15). For example, the association of an increased risk of malignancy with anti-p155/140 (TIF1) autoantibody is significant in the adults, whereas the association is unclear in juvenile patients (1, 16). The frequency of each MSA differs between adult DM and JDM patients. Anti-synthetase autoantibodies are positive in 20%-30% of adults and are less than 5% in juveniles (2, 15). On the other hand, anti-NXP2 (MJ) autoantibody is rare in adult patients, while it is positive in 20%-25% of juveniles (2), which is the second most frequent MSA in JDM. There are also differences in the rate of MSAs positivity between races. Anti-MDA5 autoantibodies are more common in the Asian population, and anti-SRP autoantibodies are seen primarily in the African American teenage girls (17, 18). Although the same MSAs are present, the prevalence can vary by age and race, and identifying the clinical characteristics of children with MSAs is crucial to estimate prognosis and other aspects of the disease.
Anti-SAE autoantibody is the recently identified MSA first reported in 2007 by Betteridge et al. (19). The target autoantigens are the SUMO-1 activating enzyme heterodimer consisting of 40 kDa SAE1 and 90 kDa SAE2 (3, 19). The frequency of anti-SAE autoantibodies positivity in adult DM patients has been reported to be 5.5%-8% in the European cohorts and 1.5%-3.0% in the Asians (3–8). The clinical presentation at the onset of the illness was characterized by severe cutaneous symptoms and mild myopathic symptoms. During follow-up, patients showed the progression of myositis, dysphagia, and systemic symptoms, such as fever, weight loss, and increased inflammatory markers (3, 4, 7, 13). In addition, a study on Japanese adults showed complications of interstitial pneumonia (4, 13, 20).
Few pediatric cases with anti-SAE antibody have been reported to date, with less than 1% of the juvenile myositis cohort. Only 3 patients (0.7%) had anti-SAE autoantibodies among 379 juvenile myositis patients in the United Kingdom (UK) cohort (11). Of the three patients, two presented with typical rash and limited or no muscle involvement but subsequently developed weakness and raised muscle enzymes. Skin diseases were persistent in both patients. In contrast, the third patient presented with seven-month history of myalgia and weakness with no rash. Myositis was diagnosed based on elevated muscle enzymes with consistent MRI and muscle biopsy findings. This patient developed typical cutaneous features of JDM two years later (11).
Our patient showed typical cutaneous findings of JDM, almost no muscle weakness, and ILD. Although typical cutaneous symptoms have been previously reported in juvenile patients with anti-SAE autoantibodies, no juvenile patients with ILD have been reported. Our patient had ILD from disease onset and was not a rapidly progressive (RP) type, similar to the adult Japanese patients with this autoantibody (4, 13, 20). We have shown that the Asian patients with anti-SAE autoantibodies could have ILD, even in juvenile patients. There have been few reports of pediatric patients from Asia. An association between anti-SAE autoantibody and HLA-DRB1*04-DQA1*03-DQB1*03 haplotype in adult patients with DM has been reported (3), possibly as one of the reasons for the racial differences in phenotype and frequency of these MSA-positive patients. Although the patient had no dysphagia during the 18-month follow-up, other symptoms were similar to those reported in adults, and therefore, we must be cautious about whether muscle weakness or dysphagia will occur in this patient in the near future.
In the Japanese patients, the frequency of anti-MDA5 autoantibody-positive patients is even higher in JDM patients (21). Adult DM or JDM with anti-MDA5 autoantibody-positive patients are often complicated with ILD, which usually shows an RP type with poor prognosis (18, 21). Therefore, combination therapy using three immunosuppressive agents, including corticosteroids, calcineurin inhibitors, and cyclophosphamide, is recommended from the early stage of illness for adult DM patients with ILD (22). When a patient is complicated with ILD, we tend to opt for potent immunosuppressive therapy to improve the prognosis. However, depending on the differences in MSAs, the ILD may not show the RP type, as observed in this patient with anti-SAE autoantibody. Prognostic factors for RP-ILD include positive anti-MDA5 autoantibody, the deterioration of CT findings on a weekly basis, and elevated serum ferritin, KL-6, and IL-18 levels (18, 23). For patients complicated with ILD without these prognostic factors, the possibility of non-RP-ILD should be considered along with the possibility that combination therapy of immunosuppressive agents may be over-treating these patients. As in our patient, JDM patients with ILD should be carefully evaluated before making appropriate treatment choices.
We report a patient with anti-SAE autoantibody-positive JDM complicated by ILD. The patient had no progression of muscle symptoms and dysphagia during an 18-month follow-up period, which differs from the previous reports in adult patients with MSA. There have been no previous reports of pediatric patients complicated with ILD. However, ILD identified in our patient was not an RP type and did not require a cytotoxic agent. Further studies are needed to determine the characteristics of the clinical course in pediatric patients with anti-SAE autoantibodies.