Inflammatory Myopathy-Associated Interstitial Lung Disease

Inflammatory myopathy associated interstitial lung disease is lung involvement in dermatomyositis, polymyositis and the antisynthetase syndrome. It occurs in about 20 to 80% depending on the antibody, and it often precedes or follows muscle disease, or occurs without muscle weakness.

Antisynthetase antibodies (anti-Jo-1, PL-7, PL-12 and others) are linked to a subacute or chronic course. Anti-MDA5 antibody dermatomyositis, particularly the clinically amyopathic form, is linked to rapidly progressive disease with high mortality of up to 50 to 70% in some series.

Pathophysiology. Autoantibodies and T cells target the lung, causing organising pneumonia, nonspecific interstitial pneumonia or diffuse alveolar damage. Anti-MDA5 produces a severe innate immune response with high ferritin, interferon signalling and a risk of cytokine storm.

Dyspnoea and cough, with fever, arthritis, Raynaud phenomenon, mechanic's hands, and a heliotrope rash or Gottron papules. Proximal muscle weakness may be absent. Anti-MDA5 disease shows skin ulceration, palmar papules, oral ulcers and rapid hypoxaemia within weeks.

Rapid worsening of dyspnoea, fever and falling oxygen saturation need urgent assessment, especially with high ferritin.

• High resolution CT: nonspecific interstitial pneumonia or organising pneumonia pattern with basal ground glass and consolidation (antisynthetase), or diffuse ground glass and consolidation with peripheral and lower zone distribution (anti-MDA5), with pneumomediastinum in anti-MDA5.
• Serology: myositis specific antibodies (anti-Jo-1, PL-7, PL-12, MDA5, Mi-2, TIF1-gamma, NXP2), antinuclear antibody and Ro52, creatine kinase, aldolase, ferritin (very high in anti-MDA5), and inflammatory markers.
• Lung function: restrictive pattern with reduced DLCO, and respiratory muscle strength when weakness is suspected.
• Muscle assessment: electromyography, muscle MRI, and biopsy when needed. Skin biopsy.
• Malignancy screening in adults with dermatomyositis (CT chest, abdomen and pelvis, mammography, and endoscopy as indicated).
• Bronchoalveolar lavage to exclude infection, especially Pneumocystis, before intensified immunosuppression.

Differential diagnosis.

• Opportunistic infection (Pneumocystis, cytomegalovirus, tuberculosis)
• Drug induced pneumonitis or statin myopathy
• Idiopathic interstitial pneumonia
• Systemic sclerosis or mixed connective tissue disease overlap
• Sarcoidosis
• Respiratory failure from respiratory muscle weakness

• Antisynthetase and chronic disease: prednisolone 1 mg/kg daily (maximum 60 mg) for 4 to 6 weeks, then tapered, with an early steroid sparing agent: tacrolimus 0.075 mg/kg twice daily (trough 5 to 10 ng/mL), or mycophenolate mofetil 500 mg twice daily increased to 1 to 1.5 g twice daily, or azathioprine 1 to 2 mg/kg daily (maximum 150 mg) after thiopurine methyltransferase testing.
• Refractory disease: rituximab 1 g intravenously on days 1 and 15, or cyclophosphamide 500 to 750 mg/m2 intravenously monthly for 6 months, and intravenous immunoglobulin 2 g/kg divided over 2 to 5 days every 4 weeks.
• Anti-MDA5 or rapidly progressive disease: early triple therapy with methylprednisolone 500 to 1000 mg intravenously daily for 3 days then prednisolone 1 mg/kg, tacrolimus (or ciclosporin 3 to 5 mg/kg/day in two doses, trough 100 to 200 ng/mL), and cyclophosphamide 500 to 750 mg/m2 intravenously every 2 to 4 weeks, adding tofacitinib 5 mg twice daily or plasma exchange in refractory cases. Early treatment lowers mortality, and patients are managed in a specialist unit.
• Prophylaxis against Pneumocystis: co-trimoxazole 960 mg three times weekly (or 480 mg daily) for the whole period of high dose immunosuppression, with monitoring for cytomegalovirus.
• Bone protection, proton pump inhibitor, vaccination against influenza, pneumococcus and COVID-19, and physiotherapy for myositis.
• Respiratory support: oxygen, high flow or ventilation as needed.

Complications and prognosis. Chronic fibrosis, respiratory failure, pneumomediastinum and malignancy in adult dermatomyositis. Antisynthetase disease has a good response with 5-year survival of 80 to 90%, while anti-MDA5 disease has a high early mortality.

Monitoring. Creatine kinase, ferritin, spirometry and DLCO every 1 to 3 months initially, CT at 3 to 6 months, and a drug toxicity review (tacrolimus levels, blood count, renal function).

Referral and escalation. Refer to a rheumatology and interstitial lung disease service. Refer to critical care for rapidly progressive disease.