Anti-melanoma Differentiation-Associated Gene 5 Dermatomyositis with Rapidly Progressive Interstitial Lung Disease: A Case of Rapidly Developing Shortness of Breath

INTRODUCTION

A newly identified type of idiopathic inflammatory myopathies (IIMs) and the anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis (DM) with rapidly progressive (RP) interstitial lung disease (ILD) has been reported in 7–10% of European cohorts, 25% of Japanese patients with DM,^1,2 and 10–40% of juvenile DM cases.^2,3 Anti-MDA5 DM is usually accompanied by RP-ILD and distinct and variable cutaneous symptoms (such as oral and cutaneous ulcerations, painful palmar papules, and macules), frequently on a backdrop of mild or no muscle involvement with a high early death rate and aggressive course. Most recently, some intriguing new information about this mysterious illness has emerged from a comparison with coronavirus disease 2019 (COVID-19).⁴

We describe a case of anti-MDA5 antibody-associated amyopathic DM presenting with RP ILD to raise awareness of the disease, highlight the significance of myositis-specific antibodies in the diagnosis and treatment of IIMs, and reiterate the importance of getting a complete history of current illness and conducting a comprehensive physical examination.

CASE REPORT

A 48-year-old non-diabetic, non-hypertensive, non-smoker, software engineer from Kolkata, West Bengal, presented to our outpatient department with shortness of breath (Modified Medical Research Council III [MMRC III]) and dry cough for 2 months and progressive swelling of the face, neck, and upper limbs for the past 2 weeks. He had a skin rash over the knuckles, elbow, and chest for the past 6 months [Figure 1a-c]. He had a history of joint pain for the past 4 years, initially oligoarticular, presently polyarticular. There was no history of chest pain, expectoration, wheeze, hemoptysis, fever, Raynaud’s phenomenon, hematuria, or oliguria.

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Figure 1:

(a) Skin rash over chest wall (Shawl sign), (b) Skin rash over knuckles (Gottron’s papules), (c) Cutaneous ulcer over the elbow.

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On the general survey, the patient had cyanosis. He also had subcutaneous emphysema over the chest wall bilaterally. Oxygen saturation was 85% on room air. Their blood pressure (BP) was BP-140/90 mmHg and the respiratory rate was 24/min. Examination of the respiratory system showed that the trachea was central. The percussion note was hyper-resonant over the right side. Decreased vesicular breath sounds on the right side, and bilateral end-inspiratory crepitations were found on auscultation. Examination of the musculoskeletal system revealed bilateral symmetrical polyarthritis with small joint involvement. Muscle strength assessment using the MMRC III 5-point scale showed muscle strength of 5/5. Hepatomegaly was noted during the examination of the gastrointestinal system.

Chest radiographs at admission showed right-sided pneumothorax and pneumomediastinum [Figure 2]. Contrast-enhanced computed tomography thorax revealed a non-specific interstitial pneumonia pattern of interstitial lung involvement with pneumomediastinum and bilateral surgical emphysema [Figure 3a and b]. Laboratory tests showed a hemoglobin of 11% g and a total leukocyte count of 10000/cc with 87% neutrophils. A throat swab was negative for COVID-19 by reverse transcription-polymerase chain reaction. Routine urine examination did not show protein, red cells, or casts. Serum urea was 22 mg/dL, creatinine 0.9 mg/dL, alanine aminotransferase – 386, aspartate aminotransferase – 212, and total bilirubin 1.1. Serum ferritin levels were ferritin – 412 and C-reactive protein – 140. The sputum for acid–fast bacilli smear and cartridge-based nucleic acid amplification test were negative. The autoimmune profile of the patient was serum ANA–3+; homogenous, titer 1:160; serum antineutrophil cytoplasmic antibodies (ANCA) – negative; serum C3, C4 – normal; rheumatoid arthritis factor (RA) factor – positive; anti-double-stranded deoxyribonucleic acid – positive; and anti-anti–Sjögren’s-syndrome-related antigen A (SSA) – positive. Diagnostic workup for myositis showed a normal electromyogram, serum creatine phosphokinase (CPK) – 135 (normal range – 20–200 IU/L), and serum aldolase – 4 (normal – 1–7.5I U/L). Myositis profile was within normal limits. Extended myositis profile revealed MDA5 antibody ++.

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Figure 2:

Chest X-ray showing right-sided pneumothorax (blue arrows), pneumomediastinum with bilateral surgical emphysema.

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Figure 3:

(a) Computed tomography (CT) thorax showing non-specific interstitial pneumonia (NSIP) pattern of interstitial lung disease (ILD) with pneumomediastinum (b) CT thorax showing NSIP pattern of ILD with pneumomediastinum.

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Based on the history and investigations, the final diagnosis was amyopathic (MDA 5 associated) DM with RP ILD and pneumomediastinum. The patient was given an intercostal tube drain at admission and was put on pulse glucocorticoid, pulse cyclophosphamide, and oral prednisolone. Following treatment, dyspnea decreased to MMRC grade II, and the pneumothorax and pneumomediastinum were resolved [Figure 4]. Figure 5 shows the diagnostic flow chart of the patient.

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Figure 4:

Chest X-ray showing resolution of pneumothorax and pneumomediastinum.

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Figure 5:

Diagnostic follow up. CXR: Chest X ray, HRCT-NSIP: High Resolution CT -Non-specific interstitial pneumonia, RA: Rheumatoid arthritis, ESR: Erythrocyte sedimentation rate, CRP: C-reactive protein, dsDNA: anti-double stranded DNA

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DISCUSSION

Amyopathic DM associated with MDA5 is a rare subtype of idiopathic inflammatory myositis.⁵ This subtype is more frequently observed in Asian populations, particularly in women.⁵ It is an autoimmune condition characterized by skin manifestations and RP ILD.⁶ This condition can lead to severe complications, including pneumomediastinum, which is the presence of air in the mediastinum.

Patients with amyopathic DM often present with skin symptoms, which may include heliotrope rash, Gottron’s papules, skin ulcer, and other dermatoses without significant muscle weakness, which is atypical for classic DM.⁶ The major concern in these patients is the RP ILD manifesting as shortness of breath, cough, and hypoxemia.

The lung involvement is often severe and can lead to respiratory failure. In addition, pneumomediastinum is seen due to air leaks from the lungs or airways into the mediastinum, which are often exacerbated by coughing. Symptoms may include chest pain, labored breathing, and subcutaneous emphysema.

The underlying mechanism involves an autoimmune process. The presence of MDA5 antibodies suggests a specific immune response that targets the lungs and skin. Inflammation and fibrosis in the lung interstitium lead to structural changes that predispose patients to pneumothorax or pneumomediastinum.

Diagnosis of pneumothorax or pneumomediastinum is by chest radiography. Screening for ILD should be done using high-resolution computed tomography of the chest, which shows lower zone ground-glass opacities in over 80% of cases. Other findings include non-septal linear or plate-like opacities and interlobular septal thickening with the absence of intralobular reticular opacities, bronchiectasis, and honeycombing.⁴ A computed tomography (CT) scan is also useful to diagnose the presence and extent of ILD and also to rule out trauma, esophageal rupture, or other significant pathologies that could explain the pneumomediastinum. Blood tests are conducted to detect specific autoantibodies, including anti-MDA5 antibodies.⁷ Elevated levels of muscle enzymes such as creatine kinase and aldolase may also be checked, although they are often normal in amyopathic dermatomyositis (ADM).⁸

Most cases are self-limiting and require supportive care such as bed rest, oxygen therapy to enhance the absorption of air and analgesics for pain relief. Patients are often hospitalized for observation due to the risk of complications such as tension pneumomediastinum or respiratory failure. There is no specific treatment for MDA5-positive ADM, but early and aggressive immunosuppressive therapy is often recommended for patient management and prevention of relapse.⁹ Treatment of ILD involves immunosuppressive therapies tailored to the severity of lung involvement. In a small cohort of eight such patients, Hirsch et al.,⁹ showed improvement in forced vital capacity (FVC) in all patients and improvement in diffusing capacity of the lungs for carbon monoxide (DLCO) in five of the eight patients. An improvement in the CT imaging morphological findings was observed in 4 patients.

The prognosis for patients with amyopathic DM and associated ILD can vary significantly. While pneumomediastinum itself is often benign and resolves spontaneously, the underlying ILD poses a significant risk for morbidity. Close monitoring and appropriate treatment are essential to manage both respiratory symptoms and prevent complications associated with pneumomediastinum.

CONCLUSION

Amyopathic DM with MDA5 antibodies presents unique challenges due to its association with RP ILD and potential complications like pneumomediastinum. A multidisciplinary approach is often required for optimal management of these complex cases.