What is the diagnosis for a patient with Interstitial Lung Disease (ILD) showing an Organizing Pneumonia (OP)/Nonspecific Interstitial Pneumonia (NSIP) pattern, strongly positive Antinuclear Antibody (ANA) and anti-Jo1 antibodies, along with elevated Creatine Kinase (CK) levels?

Diagnosis: Antisynthetase Syndrome (Anti-Jo-1 Positive)

This patient has antisynthetase syndrome, specifically anti-Jo-1 positive disease, which explains the constellation of ILD with OP/NSIP pattern, positive ANA, anti-Jo-1 antibodies, and elevated CK levels. 1, 2

Clinical Reasoning

The diagnostic picture is highly characteristic of antisynthetase syndrome rather than isolated polymyositis or dermatomyositis:

• Anti-Jo-1 antibodies are the most common myositis-specific antibody in antisynthetase syndrome, occurring in approximately 16% of inflammatory myopathy patients 3
• ILD with NSIP/OP pattern is the hallmark pulmonary manifestation, present in the majority of anti-Jo-1 positive patients (52% show NSIP pattern, 22% show NSIP overlapping with OP) 4
• Elevated CK levels indicate muscle involvement, though overt myositis may be absent or subtle at presentation 1, 2
• Positive ANA is commonly seen, though less than one-third of antisynthetase syndrome patients have strongly positive ANA; two-thirds are positive for anti-Ro52/SSA 2

Key Diagnostic Features of Antisynthetase Syndrome

Look specifically for these clinical manifestations that complete the antisynthetase syndrome picture 1, 4:

• Mechanic's hands (roughened, cracked skin on lateral fingers and palms) - strongly associated with anti-Jo-1 4
• Arthritis - frequently present, particularly in anti-Jo-1 positive patients 4, 3
• Raynaud phenomenon - part of the classic pentad
• Fever - may be present at disease onset
• Skin manifestations - though less prominent than in classical dermatomyositis 1

Critical Diagnostic Pitfall

Many patients with antisynthetase syndrome are initially misdiagnosed as idiopathic interstitial pneumonia (IIP) because 2:

• ILD may be the presenting and dominant manifestation, preceding or occurring without overt myositis
• Less than one-third meet traditional Bohan and Peter criteria for polymyositis/dermatomyositis 2
• Muscle symptoms may be subtle or absent despite elevated CK 1, 2
• In approximately 50% of cases, antisynthetase syndrome and ILD are diagnosed within 6 months of each other 4

Prognosis and Risk Stratification

Male gender and lower DLCO at presentation are the strongest predictors of mortality in anti-Jo-1 positive ILD 4:

• Overall 10-year survival is 68% 4
• Male gender increases mortality risk (HR = 2.60) 4
• Lower DLCO at presentation predicts worse outcomes (HR = 0.94 per percentage point) 4
• Chronic disease course is more common with anti-Jo-1 positivity 4

Recommended Treatment Approach

Initiate high-dose corticosteroids concurrent with a steroid-sparing agent immediately 1:

• First-line regimen: High-dose methylprednisolone plus methotrexate, azathioprine, or mycophenolate mofetil 1
• For severe disease with extensive ILD: Add intravenous immunoglobulin, cyclophosphamide, rituximab, or cyclosporine to high-dose corticosteroids 1
• Steroid-sparing agents are essential from treatment onset to allow corticosteroid tapering after 2-4 weeks based on response 1
• Cyclosporine with azathioprine may be particularly effective in anti-Jo-1 positive ILD with poor response to steroids and cytotoxic drugs alone 5

Monitoring Strategy

Baseline and serial pulmonary function testing with HRCT surveillance are mandatory 1:

• Perform PFTs (spirometry and DLCO) at baseline and yearly 1
• Obtain baseline HRCT; repeat annually for first 3-5 years in high-risk patients (Jo-1 positive) 1
• Consider PFTs every 3-6 months if high-risk features present 1
• Monitor for disease progression: >10% decline in FVC or >15% decline in DLCO 1