What is the appropriate diagnostic work‑up and management for a 73‑year‑old woman with usual interstitial pneumonia (UIP) pattern pulmonary fibrosis and seropositive rheumatoid arthritis, who stopped adalimumab two months ago, is on prednisone 10 mg daily and sulfasalazine 2 g daily, had herpes zoster one month ago treated with acyclovir, now presents with two weeks of worsening dyspnea after exposure to sick contacts, leukocytosis, hypoxemia, and increased reticulations on chest X‑ray, and should sulfasalazine be continued?

Approach to Acute Deterioration in RA-UIP Patient

This patient requires urgent evaluation for infection-triggered acute deterioration, not true acute exacerbation of IPF, and should receive broad-spectrum antibiotics with supportive care while avoiding high-dose corticosteroids until infection is definitively excluded. 1

Immediate Diagnostic Work-Up

Critical First Steps

• Obtain chest CT (high-resolution if possible) to distinguish new ground-glass opacities (suggesting infection, organizing pneumonia, or acute exacerbation) from progression of baseline reticulations 2, 1
• Collect sputum cultures, blood cultures, and respiratory viral panel (including influenza, RSV, COVID-19) given sick contact exposure and leukocytosis 1
• Perform bronchoscopy with bronchoalveolar lavage (BAL) if diagnosis remains unclear after initial testing, specifically to exclude infection (bacterial, viral, fungal, Pneumocystis jirovecii) and assess for diffuse alveolar damage 2, 1
• Measure procalcitonin and inflammatory markers (CRP, ESR) to help differentiate infectious from non-infectious causes 2

Key Distinction: Infection vs. True Acute Exacerbation

• True acute exacerbation of IPF requires: (1) acute worsening <30 days, (2) new bilateral ground-glass opacities on CT, and (3) exclusion of infection and other identifiable causes 1
• Your patient has clear infection risk factors: recent sick contact exposure, leukocytosis (14,000), and immunosuppression (prednisone 10mg, recent adalimumab, recent herpes zoster) 1, 3
• Infection-triggered deterioration is a distinct entity from true acute exacerbation and requires fundamentally different management 1

Immediate Management Strategy

If Infection Suspected or Not Yet Excluded (Most Likely Scenario)

Initiate broad-spectrum antimicrobials immediately:

• Start empiric coverage for community-acquired pneumonia with respiratory fluoroquinolone (levofloxacin 750mg daily) OR beta-lactam plus macrolide 1
• Add Pneumocystis jirovecii pneumonia (PCP) coverage with trimethoprim-sulfamethoxazole (15-20 mg/kg/day of TMP component divided q6-8h) given chronic steroid use (10mg prednisone) and recent higher-dose immunosuppression 4, 3
• Consider antiviral therapy if influenza or other viral pathogen suspected based on sick contact history 1

Provide supportive care:

• Supplemental oxygen to maintain SpO2 ≥88-90% 1
• Consider non-invasive ventilation (BiPAP) if respiratory failure develops, but avoid intubation unless absolutely necessary (high mortality in IPF patients) 1

DO NOT give high-dose corticosteroids until infection is definitively ruled out, as steroids may worsen outcomes in infected patients 1, 5

If Infection Definitively Excluded (Less Likely)

Only after negative cultures, negative BAL, and negative comprehensive infectious work-up:

• Methylprednisolone pulse therapy 250-1000mg IV daily for 3 days, then taper 1, 4
• Alternative: Prednisone 0.5mg/kg/day with gradual reduction over weeks 1

Sulfasalazine Management Decision

Hold Sulfasalazine Immediately

Sulfasalazine must be discontinued during this acute illness for the following critical reasons:

• Pulmonary toxicity risk: Sulfasalazine can cause fibrosing alveolitis, pneumonitis with eosinophilic infiltration, and interstitial lung disease that is indistinguishable from disease progression 3
• Increased infection risk: The FDA warns that sulfasalazine causes serious infections including fatal sepsis and pneumonia, particularly when associated with agranulocytosis or neutropenia 3
• Myelosuppression: Sulfasalazine causes blood dyscrasias (agranulocytosis, aplastic anemia) that could explain or worsen her leukocytosis and increase infection susceptibility 3
• Diagnostic confusion: Continuing sulfasalazine makes it impossible to determine if worsening is from drug toxicity, infection, or disease progression 3

Monitoring after discontinuation:

• Perform complete blood count with differential immediately and every 2-3 days initially to assess for drug-induced cytopenias 3
• Monitor for signs of serious infection (fever, worsening hypoxemia, hemodynamic instability) given FDA warnings about fatal sepsis with sulfasalazine 3
• Reassess need for sulfasalazine only after acute illness resolves; consider alternative DMARD if pulmonary toxicity suspected 3, 6

Special Considerations for RA-UIP Pattern

This is NOT Idiopathic Pulmonary Fibrosis

• RA-associated UIP behaves differently from IPF: May respond to immunosuppression even with UIP pattern on imaging 7, 6
• Autoimmune features present: Seropositive RA with UIP pattern suggests CTD-ILD, not IPF 2, 7
• Corticosteroids are NOT contraindicated in RA-UIP as they are in true IPF, but timing and indication matter 5, 7, 6

Long-Term Management After Acute Episode Resolves

• Consider steroid-sparing immunosuppression: Mycophenolate mofetil, azathioprine, or rituximab are effective for RA-ILD and allow prednisone reduction 4, 6
• Abatacept emerging as first-line option for RA-ILD patients 6
• Antifibrotic therapy (nintedanib or pirfenidone) should be considered if progressive despite immunosuppression, particularly with UIP pattern 6
• Avoid restarting adalimumab given recent herpes zoster and current acute deterioration; consider alternative biologic with better safety profile for ILD 6

Monitoring During Treatment

• Serial chest imaging every 2-3 days initially to assess response to antimicrobials 1
• Daily assessment of oxygenation (pulse oximetry, ABG if worsening) and respiratory status 1
• Repeat complete blood count every 2-3 days to monitor for sulfasalazine-induced cytopenias and track leukocytosis response 3
• Procalcitonin trends to guide antibiotic duration if initially elevated 2

Critical Pitfalls to Avoid

• Do not assume this is "just IPF progression": RA-UIP with acute deterioration after sick contact is infection until proven otherwise 1, 7
• Do not give high-dose steroids empirically: This could be fatal if infection present, and guidelines recommend steroids only for true acute exacerbation with infection excluded 1, 5
• Do not continue sulfasalazine: Risk of pulmonary toxicity and fatal infection outweighs any benefit during acute illness 3
• Do not delay bronchoscopy if diagnosis unclear: BAL is essential to exclude infection before considering immunosuppressive therapy 2, 1
• Do not forget PCP prophylaxis assessment: Patient on chronic prednisone 10mg should have been on PCP prophylaxis; consider this diagnosis 4