Anti-Ku antibody-positive systemic sclerosis and idiopathic inflammatory myopathies overlap syndrome in children: a report of two cases and a review of the literature.

The occurrence of anti-Ku antibody-positive idiopathic inflammatory myopathy (IIM) in pediatric patients is rare, and therefore, the clinical phenotypes of this disease in such patients remain obscure. We herein report two cases of Japanese female pediatric patients with anti-Ku antibody-positive IIM. One case was unique in that it was complicated by pericardial effusion. Another patient had severe and refractory myositis with immune-mediated necrotizing myopathy. In addition, we reviewed literatures involving a total of 11 pediatric patients with anti-Ku antibody-positive IIM. The median age of the patients was 11 years, and most of them were girls. Skin rash, including erythematous nodules, malar rash, multiple brownish plaques, butterfly rash, heliotrope rash, periorbital edema, and Gottron's papules, was observed in 54.5% of the patients, scleroderma in 81.8%, and skin ulcer in 18.2%. Their serum creatine kinase level ranged from 504 to 10,840 IU/L. Furthermore, joint involvement was observed in 91% of the patients, interstitial lung disease in 18.2%, and esophageal involvement in 9.1%. All patients were treated with corticosteroids in combination with immunosuppressants. Pediatric patients with anti-Ku antibody-positive IIM had unique characteristics compared to adult patients. Skin manifestations, joint involvement and elevation of serum CK levels were more common in children than in adults. In contrast, ILD and esophageal involvement were less common in children than in adults. Although pediatric cases of anti-Ku antibody-positive IIM are rare, patients with IIM need to be tested for the presence of anti-Ku antibodies.

Combined Single Nucleotide Variants of ORAI1 and BLK in a Child with Refractory Kawasaki Disease.

Kawasaki disease (KD) is a systemic vasculitis with an unknown etiology affecting young children. Although intravenous immunoglobulin (IVIG) plus acetylsalicylic acid is effective in most cases, approximately 10-20% of patients do not respond to this therapy. An 8-month-old boy was admitted to a local hospital with the presumptive diagnosis of KD. He received IVIG twice and four series of methylprednisolone pulse therapy from the third to the tenth day of illness. Despite these treatments, his fever persisted with the development of moderate dilatations of the coronary arteries. A diagnosis of refractory KD was made, and infliximab with oral prednisolone was administered without success. Defervescence was finally achieved by cyclosporine A, an inhibitor of the signaling pathway of the calcineurin/nuclear factor of activated T cells (NFAT). Whole-genome sequencing of his deoxyribonucleic acid samples disclosed two single nucleotide variants (SNVs) in disease-susceptibility genes in Japanese KD patients, ORAI1 (rs3741596) and BLK (rs2254546). In summary, the refractory nature of the present case could be explained by the presence of combined SNVs in susceptibility genes associated with upregulation of the calcineurin/NFAT signaling pathway. It may provide insights for stratifying KD patients based on the SNVs in their susceptibility genes.