INTRODUCTION
Clinically amyopathic dermatomyositis (CADM) is a rare subtype of idiopathic inflammatory myositis, frequently associated with autoantibodies targeting melanoma differentiation-associated protein 5 (MDA5). Anti-MDA5 dermatomyositis accounts for less than 2% of all idiopathic inflammatory myopathies in Europe[1]. The disease was initially described in Japan, where it was discovered that the antigen targeted by the antibodies, MDA5, is a protein involved in the innate immune response to viral infections and is encoded by the melanoma differentiation-associated gene 5. Anti-MDA5 dermatomyositis is commonly characterized by distinctive mucocutaneous and systemic features, including skin ulcerations, palmar papules, arthritis, and interstitial lung disease. Rapidly progressing interstitial lung disease (RP-ILD) is a particularly severe complication of this condition, often associated with rapid progression and poor prognosis. In rarer cases, RP-ILD associated with anti-MDA5 may occur in the absence of both muscle and skin involvement. Currently, there are no epidemiological data on MDA5-associated RP-ILD in patients without either skin or muscle involvement.
The diagnosis of myositis-related acute interstitial pneumonia can be particularly challenging, and this challenge is especially pronounced when the hallmark skin or muscle manifestations are absent, or when there is no prior history of idiopathic inflammatory myopathies. Consequently, despite the high mortality rate, diagnosis is often delayed, highlighting the need for increased awareness of this condition.
Although the disease course is typically severe and carries a high mortality risk, there is no established standard of care. Recent studies and case reports suggest that early intervention with combined immunosuppressive therapy and corticosteroids may improve outcomes if initiated promptly after symptom onset.
This case report describes a 63-year-old previously healthy male diagnosed with anti-MDA5 amyopathic dermatomyositis and RP-ILD, in the absence of both muscle and skin involvement. It highlights the importance of early diagnosis and underscores the aggressive nature of the disease.
CASE DESCRIPTION
A 63-year-old previously healthy male was admitted to hospital on January 21, 2024, complaining of progressive shortness of breath, weakness and a fever reaching 39°C over the past 4 weeks. His symptoms began in late December initially presenting as general malaise, which progressively worsened. During this period the patient had an unintentional weight loss of approximately 6 kg. He had no known comorbidities and was not on any medications. He was an ex-smoker (5-6 pack-years) who had quit smoking some years ago.
On January 9 an outpatient chest X-ray (CXR) revealed bilateral basal bronchopneumonia, and he was started on antibacterial therapy without improvement. Upon admission the patient reported continued weakness and shortness of breath. On physical examination bilateral basal dry crackles were heard on chest auscultation. His oxygen saturation was 95% on a high-concentration oxygen mask. He denied any history of animal exposure, medication use or a family history of a chronic lung disease. The patient had no signs of skin rashes or any musculoskeletal symptoms. A computed tomography (CT) scan was performed, showing signs of interstitial lung disease (Fig. 1). Laboratory tests revealed elevated C-reactive protein levels (93 mg/l), though leucocytosis was absent. The patient was started on therapy with intravenous methylprednisolone 250 mg daily, piperacillin/tazobactam 4.5 g every 6 hours, and oral clarithromycin 500 mg twice daily. Polymerase chain reaction (PCR) for pneumonia pathogens and routine autoimmune antibody screening were negative. Blood tests showed no significant changes, but respiratory failure worsened, prompting the initiation of high-flow nasal cannula therapy. A multidisciplinary team convened, and an extended autoantibody screening (Table 1), including a myositis antibody panel (Table 2), was ordered.
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Figure 1. Computed tomography scan of the patient’s lungs showing ground-glass opacities predominantly in the peripheral lung regions, with associated thickening of the pulmonary interstitium. Gas trapping is observed in the basal lung areas.
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Table 1. Extended autoantibody screening.
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Table 2. Extended myositis antibody panel.
On January 24 the patient’s condition deteriorated rapidly with increasing respiratory failure requiring invasive mechanical ventilation. CT scan revealed acute respiratory distress and pulmonary artery thromboembolism (Fig. 2). The extended myositis antibody panel returned strongly positive for antibodies against melanoma differentiation-associated protein 5 (MDA5) (Table 2) leading to diagnosis of anti-MDA5-associated amyopathic dermatomyositis with RP-ILD (the diagnosis was established within 48 hours of the patient’s admission). Treatment with cyclophosphamide and intravenous immunoglobulin was started.
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Figure 2. Repeat computed tomography scan of the patient’s lungs shows progressive worsening of pulmonary changes, both in intensity and extent, now diffuse in nature. Evidence of pulmonary artery thromboembolism is seen in multiple branches of the pulmonary arteries.
Despite the therapy, the patient’s condition continued to deteriorate with worsening of respiratory failure. On January 30th a multidisciplinary team was convened again and based on available studies, literature reviews and recommendations from other major centres, it was decided to add the calcineurin inhibitor tacrolimus to the treatment regimen. Despite all therapeutic interventions, the patient’s condition continued to deteriorate with progressive respiratory failure. On February 4th the patient ultimately succumbed to his illness.
DISCUSSION
The diagnosis of CADM-associated acute interstitial pneumonia is extremely challenging, especially in cases when a patient does not have characteristic skin or muscle manifestations or a history of idiopathic inflammatory myopathy. Interstitial lung disease is the most important systemic complication in anti-MDA5 dermatomyositis because it may have a rapidly progressive and fatal course[2]. This case highlights the rapid and aggressive progression of the disease despite intensive immunosuppressive therapy and highlights the importance of early recognition. Standardized treatments for patients with RP-ILD have yet to be fully established and are mainly based on case reports and retrospective studies. A combination of high-dose glucocorticoids and calcineurin inhibitors with or without cyclophosphamide is typically the first-line treatment[3]. Even with early disease detection and high levels of immunosuppression the risk of mortality is up to 80%[4]. A multidisciplinary approach, with collaboration between specialized centres, is crucial for early diagnosis and timely initiation of treatment.