What is the likely cause of NSIP (Nonspecific Interstitial Pneumonia) and cystic lesions in a middle-aged woman with ulcerative colitis on PENTAZA (Pentasa, mesalamine)?

NSIP and Cystic Lesions in Ulcerative Colitis Patient on Pentasa

The most likely diagnosis is mesalamine (Pentasa)-induced interstitial lung disease, specifically NSIP, which is the most commonly reported pulmonary drug toxicity from 5-ASA compounds in IBD patients. 1

Primary Differential Diagnosis

1. Drug-Induced Lung Disease (Most Likely)

Mesalamine/5-ASA compounds are the most common cause of pulmonary manifestations in IBD patients, frequently presenting as interstitial lung disease including NSIP. 1 The typical presentation includes:

• Dyspnea, fever, chest pain, and cough 1
• Peripheral eosinophilia in almost 50% of cases 1
• NSIP pattern on CT with bilateral ground-glass opacities, often with subpleural sparing 1, 2
• Cystic lesions may represent traction bronchiectasis or bronchiolectasis associated with the fibrotic component 1

The radiologic features you describe (NSIP with cystic lesions) align with drug-induced NSIP, which commonly manifests as diffuse ground-glass opacity on CT scans, with progression to fibrosis showing basal distribution and traction bronchiectasis. 2

2. IBD-Related Pulmonary Disease (Less Likely but Possible)

Ulcerative colitis itself can cause pulmonary manifestations independent of medications, though this is less common than drug-induced disease. 1 IBD-specific pulmonary involvement includes:

• Organizing pneumonia (most common IBD-related interstitial pattern) 1
• Various interstitial pneumonias including NSIP, though less common than organizing pneumonia 1
• Bronchiectasis and small airway disease (more common than interstitial disease) 1

Importantly, pulmonary disease in IBD typically parallels intestinal disease activity and/or other extra-intestinal manifestations. 1 If her UC is well-controlled on Pentasa, this makes primary IBD-related lung disease less likely.

3. Other Considerations

The cystic lesions warrant additional consideration:

• Langerhans cell histiocytosis (if she smokes) 1
• Lymphocytic interstitial pneumonia (rare IBD association) 1
• Hypersensitivity pneumonitis (requires exposure history) 1

Diagnostic Approach

Immediate Steps

1. Obtain detailed medication history: Duration of Pentasa use, dose (standard vs. high-dose >3g/day), and temporal relationship between drug initiation and respiratory symptoms 1

2. Check for peripheral eosinophilia: Present in approximately 50% of 5-ASA-induced lung disease 1

3. Assess UC disease activity: Active intestinal disease suggests IBD-related pulmonary involvement; well-controlled disease favors drug toxicity 1

4. Detailed exposure history: Bird exposure, mold, occupational exposures to exclude hypersensitivity pneumonitis 1

5. Smoking history: Essential for evaluating smoking-related ILD patterns 1

Advanced Evaluation

If drug-induced lung disease is suspected, consider therapeutic trial of Pentasa discontinuation before invasive testing. 1 Drug-induced NSIP typically improves with cessation of the offending agent. 1, 2

If diagnosis remains uncertain after drug withdrawal or if she cannot stop Pentasa, proceed with:

• Surgical lung biopsy for definitive histologic diagnosis 1
• Multidisciplinary discussion (pulmonology, radiology, pathology) is essential for accurate diagnosis of interstitial pneumonias 1

Management Recommendations

If Drug-Induced (Most Likely Scenario)

1. Discontinue Pentasa immediately 1
2. Consider systemic corticosteroids for symptomatic relief - drug-induced NSIP typically responds well to steroids 1, 2
3. Switch UC therapy to alternative agent (thiopurines, biologics, or other non-5-ASA options) 1
4. Monitor for improvement: Drug-induced lung disease should improve within weeks to months of drug cessation 1, 2

If IBD-Related Pulmonary Disease

Systemic corticosteroids are first-line therapy for IBD-related interstitial lung disease, particularly organizing pneumonia. 1 However, steroids are less effective for chronic bronchiolitis or severe airway inflammation. 1

Critical Pitfalls to Avoid

1. Do not rechallenge with mesalamine or any 5-ASA compound - paradoxical worsening of colitis can occur with mesalamine sensitivity, making diagnosis elusive, especially if concurrent steroids suppress systemic symptoms 3

2. Do not assume all pulmonary disease in IBD is drug-related - true IBD-associated lung disease exists and requires different management 1

3. Do not delay evaluation of cystic lesions - while likely representing traction bronchiectasis from NSIP, alternative diagnoses (Langerhans cell histiocytosis, lymphocytic interstitial pneumonia) require exclusion 1

4. Recognize that pulmonary symptoms may develop years after colectomy - 8 of 28 patients in one series developed respiratory problems post-colectomy, emphasizing the importance of considering IBD-related pulmonary disease even after "treated" intestinal disease 1

5. NSIP pattern on imaging requires exclusion of connective tissue disease - obtain autoimmune serologies as NSIP is commonly associated with collagen vascular diseases 1