What are the recommended management and treatment options for a patient with interstitial lung disease (ILD) and scarring, as indicated by CT scan findings, and sensitization to specific fungi (including Cladosporium herbarum, Penicillium notatum, and Phoma sp.) as shown by blood work?

Management of ILD with Fungal Sensitization

Your patient likely has chronic hypersensitivity pneumonitis (HP) triggered by household mold exposure, and the priority is immediate environmental remediation combined with immunosuppressive therapy if symptoms are progressive. 1, 2

Diagnostic Clarification

The combination of CT findings showing scarring/fibrosis with elevated IgG antibodies to Cladosporium herbarum, Penicillium notatum, and Phoma species strongly suggests chronic hypersensitivity pneumonitis rather than idiopathic ILD. 3, 2

• Elevated anti-Cladosporium antibodies occur in 35% (12/34) of ILD patients, but when combined with compatible CT findings and exposure history, this points toward fungal HP. 3
• Cladosporium species are ubiquitous in household environments and are recognized as key antigens inducing chronic HP, often misdiagnosed as idiopathic pulmonary fibrosis for years. 2
• The presence of multiple fungal sensitizations (Cladosporium, Penicillium, Phoma) increases the likelihood of environmental mold exposure as the causative factor. 4

Immediate Management Steps

1. Environmental Assessment and Remediation (CRITICAL FIRST STEP)

Conduct a thorough home and workplace environmental inspection for mold, water damage, poor ventilation, and humidity issues. 1, 2

• Look specifically for: visible mold growth, water leaks, damp basements, poor ventilation systems, humidifiers, air conditioning units, and areas with high humidity. 4
• Permanent relocation from the contaminated environment may be necessary - one case series showed complete normalization of clinical, radiological, and functional parameters only after permanent move to new residence. 4
• Temporary avoidance (leaving home for days/weeks) can help confirm diagnosis if symptoms improve away from the environment. 2

2. Baseline Assessment

Obtain the following within 2 weeks: 1, 5

• Pulmonary function tests (PFTs): FVC, TLC, and DLCO to establish baseline and assess severity. 5, 6
• 6-minute walk test with pulse oximetry to detect exercise-induced desaturation indicating gas exchange impairment. 1, 5
• Echocardiogram to evaluate for pulmonary hypertension if there are signs of right heart strain (elevated JVP, peripheral edema, loud P2). 7
• Repeat high-resolution CT reviewed by thoracic radiologist to characterize the pattern (fibrotic vs inflammatory, UIP vs NSIP pattern). 1, 5

3. Multidisciplinary Discussion

Arrange multidisciplinary team (MDT) review with pulmonologist, radiologist, and if available, an ILD specialist to confirm diagnosis and guide treatment strategy. 1, 5

Treatment Algorithm

For Mild Disease (FVC ≥70%, minimal symptoms, <20% fibrosis on CT):

Environmental remediation alone with close monitoring: 6

• Serial PFTs every 3-6 months for first 1-2 years. 1
• Repeat HRCT at 12 months to assess for progression. 6
• Smoking cessation is mandatory if applicable. 6

For Moderate-Severe or Symptomatic Disease:

Initiate immunosuppressive therapy while pursuing environmental remediation: 1, 7

• First-line: Mycophenolate mofetil (MMF) 500-1000mg twice daily, titrated to 1500mg twice daily as tolerated. 1, 7, 5
• Alternative options: Azathioprine 1-2mg/kg/day or rituximab (1000mg IV on days 1 and 15, repeated every 6 months). 1, 7
• Moderate-dose oral corticosteroids (prednisone 20-40mg daily, not exceeding 60mg) for 4-8 weeks, then taper to lowest effective dose or discontinuation. 1

For Progressive Fibrotic Disease:

If there is evidence of progressive pulmonary fibrosis (PPF) - defined as worsening symptoms, physiologic decline (≥5% FVC decline over 12 months), or radiologic progression within past year: 1

• Add antifibrotic therapy: Nintedanib 150mg twice daily OR pirfenidone (titrated to 801mg three times daily). 1, 5, 8
• Continue immunosuppression (MMF or rituximab) alongside antifibrotic therapy to address both inflammatory and fibrotic components. 1
• Monitor for nintedanib side effects: diarrhea (most common), nausea, elevated liver enzymes. 8

For Acute/Rapidly Progressive Disease:

If presenting with acute respiratory failure or rapid deterioration: 1

• High-dose IV methylprednisolone 500-1000mg daily for 3 days, followed by oral prednisone 1mg/kg/day. 1
• Add cyclophosphamide (500-750mg/m² IV monthly for 6 months) OR rituximab if inadequate response to steroids alone. 1
• Provide Pneumocystis jirovecii prophylaxis (trimethoprim-sulfamethoxazole DS three times weekly) when using cyclophosphamide. 1
• Rule out infection with bronchoscopy and BAL before escalating immunosuppression. 1

Monitoring Strategy

Establish rigorous follow-up schedule: 1, 7

• PFTs every 3 months for first year, then every 6 months if stable. A ≥5% decline in FVC over 12 months indicates progression and warrants treatment escalation. 7, 5, 8
• Ambulatory oxygen saturation monitoring every 3-12 months; initiate supplemental oxygen if SpO2 <88% on 6-minute walk test. 7, 8
• Repeat HRCT at 6-12 months to assess treatment response and identify progression. 1
• Clinical assessment for worsening dyspnea, cough, signs of cor pulmonale (RV heave, peripheral edema, elevated JVP). 7

Critical Pitfalls to Avoid

Do not delay treatment while pursuing complete diagnostic workup - early immunosuppression prevents irreversible fibrosis. 7

Do not use high-dose corticosteroids as monotherapy long-term - this increases mortality without addressing underlying pathophysiology and carries significant toxicity. 7

Do not assume all dyspnea is from ILD - exclude cardiac disease, pulmonary hypertension, anemia, deconditioning, and other causes. 7

Do not ignore the possibility of drug-induced lung disease if patient is on DMARDs (methotrexate, leflunomide, TNF-inhibitors, rituximab) - these can cause ILD and may require medication withdrawal. 1

Do not overlook infection - fungal sensitization does not equal active infection, but immunosuppressed patients are at risk for invasive fungal disease requiring antifungal therapy. 1

Supportive Care

Implement comprehensive supportive measures: 8

• Structured pulmonary rehabilitation improves 6-minute walk distance and quality of life. 8
• Supplemental oxygen if resting SpO2 <88% or exercise desaturation below 88%. 7, 8
• Vaccinations: pneumococcal, influenza, COVID-19 to reduce infection risk. 6
• Consider lung transplant evaluation if FVC <50% predicted or progressive decline despite maximal therapy. 8