Abstract
INTRODUCTION: Juvenile dermatomyositis (JDM) is a rare but serious autoimmune vasculopathy affecting children. It is the commonest childhood idiopathic inflammatory myositis, afflicting roughly 3 per million children per year. It classically presents with proximal, symmetrical myositis and pathognomic cutaneous features such as a heliotrope rash and Gottron’s papules. JDM can be challenging to treat and may require several immunosuppressive therapies. Here, we report the case of an adolescent with complex, treatment-resistant JDM, and the therapeutic challenges encountered throughout her disease course. CASE DESCRIPTION: We present a 15-year-old Pakistani British girl who was diagnosed with JDM based on classical symptoms of proximal muscle weakness (arms, legs, neck), photosensitive rash (face, neck, arms, elbows, hands), Gottron’s papules, and arthritis. She did not have swallowing issues or calcinosis. Her childhood myositis assessment scale (CMAS) score was 17/53, and manual muscle testing 8 (MMT8) score was 35/80. Investigations showed CK 29,691 (0-159 IU/L), AST 1052 (4-50 IU/L), LDH 1873 (140-280 U/L), ESR 47 (0-12 mm/hr). Immunology revealed ANA 1:1280 (negative ENA, dsDNA, normal complements C3/C4), strongly positive Mi2b, positive Ku and weakly positive Mi2a. MRI lower limbs showed extensive myositis of thigh, pelvis and abdominal wall muscles, and muscle biopsy was consistent with inflammatory myositis. Cardiac MRI and CT chest ruled out myocarditis and interstitial lung disease. She was treated with intravenous (IV) and oral steroids, subcutaneous methotrexate, hydroxychloroquine, intravenous immunoglobulin (IVIG), and intensive physiotherapy with excellent response, and she was in remission at six months. Unfortunately, on tapering steroids, she had recurrent flares of her skin disease and myositis (lowest CMAS score 5/53, peak CK 52,848 IU/L), requiring multiple courses of IV, oral, and topical steroids. She was trialled on several disease modifying antirheumatic drugs including mycophenolate mofetil, tacrolimus, IVIG, adalimumab, baricitinib, rituximab, and IV cyclophosphamide (EuroLupus regimen) with variable response; however, none were effective in maintaining remission. At the point of transitioning into adult services, she was on monthly IVIG (2g/kg), methotrexate 20 mg oral weekly, prednisolone 20 mg daily, and hydroxychloroquine 200 mg daily. She unfortunately had further admissions with severe flares of her dermatomyositis (worsening rash, MMT8 48/80, CK > 10,000 IU/L, biopsy and MRI confirmed myositis). Also, for the first time, she developed widespread panniculitis (biopsy proven) affecting her arms, legs, chest. She was retreated with EuroLupus IV cyclophosphamide, IV rituximab 1g x 2, and IV abatacept, with a plan for six-monthly IV rituximab maintenance. She responded well, her JDM went into remission, and she managed to taper and stop her steroids. Subsequently, her immunosuppression was tapered, and she remains in remission on 6-monthly IV rituximab maintenance. DISCUSSION: This case highlights the complexities of managing juvenile dermatomyositis in an adolescent patient with treatment-resistant disease. As expected with anti-Mi2 positive patients, she presented with features of ‘classical JDM’. This phenotype tends to be more responsive to conventional treatment; however, this was not the case for this young patient. She was initially treated with standard first-line treatment (in accordance with EULAR guidelines) and, although she initially responded, she had several relapses of both cutaneous symptoms and myositis, requiring various combinations of immunosuppressants and immunomodulators throughout her disease course. As a result, she required treatment with combination biologic agents which eventually helped to control her disease. Rituximab, a CD20+ B cell depleting agent, has been trialled in refractory dermatomyositis, with a randomised controlled trial showing that 83% of patients with refractory disease given rituximab met the study’s definition of improvement. This young girl eventually managed to stop her steroids, taper her immunosuppression, and she remains in remission on 6-monthly IV rituximab maintenance. In addition to this patient’s typical cutaneous features, she also developed panniculitis, an uncommon manifestation of JDM. The differential diagnosis of her rash was initially broad, with tuberculosis, atypical infection, and drug reactions suspected; however, histology confirmed panniculitis secondary to her dermatomyositis. Though calcinosis can affect up to 40% of patients with JDM, panniculitis is much rarer and infrequently documented in the literature. Her panniculitis resolved with steroids; however, she continues to have calcinosis which is always difficult to treat. Unsurprisingly, her disease course was complicated by several infections (due to her immunosuppression burden), including PVL-positive Staphylococcus aureus skin lesions, buttock abscess (requiring incision and drainage), COVID-19 infection, and community acquired pneumonia, which required critical care admission. KEY LEARNING POINTS: This case highlights the therapeutic challenges in managing refractory juvenile dermatomyositis. Despite presenting with a serological profile typically associated with treatment responsive disease, patients may require multiple lines of immunosuppression, and combination biologics may sometimes be required. Additionally, this case emphasises the need for adaptive treatment approaches guided by response to therapy, and the need for ongoing research into treatments for refractory cases of JDM. Panniculitis, although a rare manifestation of an uncommon disease, may represent the only symptom of active disease/flare, and should be treated with escalation of immunosuppression. In patients who do not respond as expected to standard immunosuppression, the diagnosis should be re-challenged. In our patient, we reconfirmed her diagnosis (via muscle biopsy, skin biopsy, and MRI) when she transitioned into adult services. Finally, this case serves as a reminder of the balance between disease control and treatment-related morbidity, and the need for close monitoring.