Systemic lupus erythematosus complicated by anti‐MDA5 antibody‐positive juvenile dermatomyositis: A rare overlap syndrome in childhood

We present the clinical data of a child with systemic lupus erythematosus (SLE) complicated by juvenile dermatomyositis (JDM, positive for anti-melanoma differentiation-associated protein 5 [MDA5] antibodies). The patient was a 10-year-old girl with a chronic course of disease, which mainly presented as red rashes on the face and trunk, accompanied by fever, multiple joint pain, alopecia, and oral ulcers. She was treated in several hospitals successively, and antinuclear antibodies fluctuated between 1:320 and 1:640 positive, along with positive anti-Sm antibodies, anti-nuclear ribonucleoprotein antibodies, anti-double-stranded deoxyribonucleic acid antibodies. Complement levels were normal, leading to a diagnosis of SLE, and the SLE disease activity index was 13 points. Treatment included methylprednisolone (20 mg/day), hydroxychloroquine sulfate (100 mg, twice a day), and mycophenolate mofetil (0.5 g, twice a day), along with symptomatic therapy. In the process of hormone reduction, the rashes were repeatedly aggravated, suggestive of vasculitis-like rashes. The glucocorticoid dose was repeatedly increased, and methotrexate 10 mg/week and belimumab 360 mg were added to control the condition, yet the rashes did not improve significantly. Bilateral subcutaneous panniculitis of the posterior thigh was observed, accompanied by local tissue calcification. Further examination of the myositis antibody spectrum showed that the anti-MDA5 antibody was 1:300 positive. Krebs Von den Lungen-6, complement levels, immunoglobulins, serum ferritin, anti-ds-DNA antibodies, Epstein-Barr virus DNA quantification, cytomegalovirus DNA quantification, and parvovirus B19 (immune globulin G + immune globulin M) antibodies were normal. Chest computed tomography indicated possible bilateral lung infections and minimal pleural effusions bilaterally. Lung lavage nucleic acid testing, bacterial smear, culture, and 1,3-β-D glucan/glactomannanassays were negative. Magnetic resonance imaging revealed diffuse swelling of the buttocks, bilateral thigh muscles and intermuscular spaces, and subcutaneous fascia. Limb electromyography was normal. Skin biopsy of the posterior thigh showed hyperplasia of the squamous epithelium with excessive keratinization and incomplete keratinization, focal basal membrane thickening, an unclear boundary between the basal and dermal layers with scattered lymphocytic infiltration, occasional lymphocytic infiltration around adnexal structures, local interstitial collagen mucoid degeneration, and calcification within the subcutaneous fat layer (Supporting Information: Figure S1). Overlapping syndrome (SLE overlapping JDM, positive anti-MDA5 antibody) was diagnosed and the primary disease was controlled by methylprednisolone 40 mg/day, hydroxychloroquine sulfate 100 mg twice a day, thalidomide 50 mg/day, and tofacitinib 5 mg twice a day. The patient's rashes gradually improved, although the skin biopsy site on the right thigh exhibited slow healing. Inflammatory markers normalized 2 weeks later, and there were no significant changes in the chest computed tomography compared to previous scans. Currently, the patient is undergoing regular follow-up with a gradual tapering of corticosteroids. According to the 2012 Systemic Lupus International Collaborating Clinics criteria, the patient was definitively diagnosed with SLE. After treatment with corticosteroids and immunosuppressants, the rashes were poorly controlled, and bilateral posterior thigh subcutaneous panniculitis, subcutaneous calcification, and interstitial pneumonia appeared. According to the 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for idiopathic inflammatory myopathies and the Chinese diagnosis and treatment guidelines for JDM, the diagnosis of JDM was definite in conjunction with the myositis-related/specific antibody spectrum. Overlapping syndrome is a syndrome that meets the criteria for at least two connective tissue diseases. When SLE overlaps with systemic sclerosis, dermatomyositis (DM)/polymyositis (PM), Sjogren's syndrome, rheumatoid arthritis, and other diseases, the lack of specific serological indicators and clinical manifestations can lead to a missed diagnosis and/or misdiagnosis, which may result in life-threatening complications in severe cases.1 Overlapping syndromes of SLE and myositis include PM/DM, and although myalgia can affect nearly half of SLE patients, SLE-PM/DM is relatively rare. The majority of SLE-PM/DM patients are young women, with a prevalence rate ranging from 4% to 16%, and SLE-DM is the main type.2 Compared with SLE patients, SLE-PM/DM patients were found to be more likely to have alopecia, facial erythema, photosensitivity, arthritis, serositis, cognitive impairment, pulmonary hypertension, as well as an increased risk of stroke, but the incidence of lupus nephritis was not significantly increased.3 Corticosteroids are typically used as first-line treatment, while other immunosuppressants, such as cyclophosphamide, methotrexate, mycophenolate mofetil, and rituximab, have varying degrees of clinical response and remission rates.4 JDM patients are more prone to skin calcification than adult DM patients.5 Due to early mortality and increased standardized mortality rates caused by pulmonary involvement, the prognosis of SLE-myositis overlap syndrome is unfavorable. Based on the clinical characteristics of the present case, refractory rashes with subcutaneous calcification may be a key clinical feature in the overlap of the two conditions. Xianan Jian wrote and edited the manuscript. Xianan Jian, Jiasheng Ma, Nannan Pan, Yan Jiang, and Dandan Li collected the data and reviewed this article. Fengju Li edited the manuscript. All the authors are responsible for the final version of the article. The authors have nothing to report. The authors declare no conflict of interest. A written consent of the patient was obtained for publication of the case, imaging, and all data. The data used in this article are available from the corresponding author upon reasonable request. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.