Because the rash did not improve, he was referred to a dermatologist. A skin biopsy, according to his mother, was unremarkable. The swelling gradually worsened over the next two months, and his mother noticed a new development—ulcers on his fingers (see Figure 1).
He was then referred to a rheumatologist. On examination, he had swelling of the metacarpophalangeal and proximal interphalangeal joints, ulcers at the tips of his fingers and swelling of both ankle joints. Nailfold capillaroscopy was unremarkable. His strength was 4/5 in both upper arms. The laboratory results are in Table 1. He tested negative for anti-nuclear antibodies, anti-Scl 70 antibodies and anti-topoisomerase antibodies.
Figure 1: A 12-year-old Black male presented with digital ulcers and swelling.
Figure 2: High-resolution computed tomography showed evidence of interstitial lung disease.
We initially thought he had systemic sclerosis. However, the lack of antibodies made diagnosis challenging. Due to lack of autoantibodies, but with muscle enzyme elevation and coexisting clinical weakness, myositis was the main diagnostic consideration.
We started treatment with 40 mg of prednisone and 10 mg of oral methotrexate (later increased to 20 mg) for myositis. Due to minimal improvement in his skin ulcers, we changed the methotrexate to a subcutaneous form at the increased dosage. However, the patient developed worsening dyspnea on exertion within a few months.
High-resolution computed tomography showed evidence of interstitial lung disease (see Figure 2). A test for anti-melanoma differentiation-associated protein 5 (MDA-5) antibody was ordered due to a high clinical suspicion of ILD. The results were positive. He was initiated on 250 mg of mycophenolate mofetil twice daily (note: 300 mg/m2, lower than the ideal 600 mg/m2 dose due to leukopenia) and 1 g/kg of intravenous immunoglobulin monthly for four doses, with significant improvement in weakness, ulcers and shortness of breath.
Table 1: Laboratory Results
| TEST | RESULT |
|---|---|
| ANA | Negative |
| Anti-Scl 70 antibody and anti-centromere antibody | Negative |
| Anti-Jo1 antibody | Negative |
| Anti-SSA 52 antibody | Negative |
| AST (aspartate aminotransferase) | 136 U/L (reference range [RR]: 15–37 U/L) |
| ALT (alanine aminotransferase) | 150 U/L (RR: 12–78 U/L) |
| Aldolase | 8.8 U/L (RR: 3.1–8.6 U/L) |
| Erythrocyte sedimentation rate (ESR) | 21 mm/hour (RR: 5–15 mm/hour) |
| Creatinine kinase | 79 mg/dL (RR: 26–308 mg/dL) |
| LD (lactate dehydrogenase) | 351 U/L (RR: 87–241 U/L) |
Discussion
Juvenile dermatomyositis is a rare autoimmune disease characterized by vasculopathy, proximal muscle weakness and pathognomonic rash. Anti-MDA-5 antibody was originally described in a subset of patients with dermatomyositis whose disease was manifested only on skin for prolonged periods of time without muscle weakness.3 The role of anti-MDA-5 antibody in dermatomyositis is not clearly known. It is thought that antibody production occurs during viral infection of skin and lung epithelium.4 Its formation is triggered by release of MDA-5 from infected cells and is believed to injure endothelial cells and other tissues.
The incidence of myositis-specific antibodies in JDM is 10%, with a prevalence of anti-MDA-5 antibody of 7.4%.5 Anti-MDA-5 antibody is associated with clinically amyopathic or hypomyopathic dermatomyositis, ischemic cutaneous ulcerations, rapidly progressive ILD and a poor prognosis. The presentation is well described in the adult population, whereas it is very rare in the pediatric population.
Rheumatologists need to be aware of anti-MDA-5 antibody-associated RP-ILD in patients with juvenile dermatomyositis, the aggressive nature of the disease and the early, intense immunosuppression needed for a favorable prognosis.
Anusha Vuppala, MD, is a first-year rheumatology fellow at Louisiana State University Health Sciences Center in Shreveport.
Sarwat Umer, MD, is an associate professor of medicine–pediatrics at the Center of Excellence for Arthritis and Rheumatology in Shreveport. Dr. Umer completed her fellowship at Louisiana State University Health Sciences Center, Shreveport, and at UT Southwestern, Dallas. She practices in adult and pediatric rheumatology in Shreveport.
Acknowledgment
The authors thank Samina Qureshi Hayat, MD, for her mentoring, advice and continued support of pediatric rheumatology.
Dr. Hayat is chief and director of the Center of Excellence for Arthritis and Rheumatology, Shreveport, La.
References
- 1. Papadopoulou C, McCann LJ. The vasculopathy of juvenile dermatomyositis. Front Pediatr. 2018 Oct 9;6:284.
- 2. Hamaguchi Y, Kuwana M, Hoshino K, et al. Clinical correlations with dermatomyositis-specific autoantibodies in adult Japanese patients with dermatomyositis: A multicenter cross-sectional study. Arch Dermatol. 2011 Apr;147(4):391–398.
- 3. Sato S, Hoshino K, Satoh T, et al. RNA helicase encoded by melanoma differentiation–associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial disease. Arthritis Rheum. 2009 Jul;60(7):2193–2200.
- 4. Fiorentino D, Chung L, Zwerner J, et al. The mucocutaneous and systemic phenotype of dermatomyositis patients with antibodies to MDA5 (CADM-140): A retrospective study. J Am Acad Dermatol. 2011 Jul;65(1):25–34.
- 5. Tansley SL, Betteridge ZE, Gunawardena H, et al. Anti-MDA5 autoantibodies in juvenile dermatomyositis identify a distinct clinical phenotype: A prospective cohort study. Arthritis Res Ther. 2014 July2;16(4);R138.
