Differential Diagnosis

The patient's presentation of progressive shortness of breath, persistent dry cough, wheezing, increased fatigue, and reduced exercise tolerance, along with the findings of decreased breath sounds, inspiratory crackles, obstructive airway changes on pulmonary function tests, and mosaic attenuation with bronchial wall thickening on high-resolution CT scan, suggests a pulmonary complication. Given her history of rheumatoid arthritis and long-term methotrexate use, the following differential diagnoses are considered:

• Single Most Likely Diagnosis

  • Methotrexate-induced pulmonary toxicity: This is a well-known complication of methotrexate therapy, especially in patients with rheumatoid arthritis. The symptoms and radiographic findings presented are consistent with this condition, which can range from mild to severe and includes pneumonitis and fibrosis.

• Other Likely Diagnoses

  • Chronic Obstructive Pulmonary Disease (COPD): Although the patient's symptoms and pulmonary function tests suggest obstructive lung disease, COPD would not fully explain the mosaic attenuation and bronchial wall thickening seen on the CT scan without other risk factors such as smoking.
  • Rheumatoid Arthritis-associated Interstitial Lung Disease (RA-ILD): Patients with rheumatoid arthritis are at increased risk of developing interstitial lung disease, which could present with similar symptoms and radiographic findings. However, the obstructive pattern on pulmonary function tests is less typical for ILD.

• Do Not Miss Diagnoses

  • Lymphoma: Given the patient's long-standing rheumatoid arthritis and immunosuppressive therapy, there is an increased risk of lymphoma, which can present with pulmonary involvement. Although less likely, missing this diagnosis could have significant consequences.
  • Infection (e.g., Pneumocystis jirovecii pneumonia): Immunocompromised patients, including those on methotrexate, are at risk for opportunistic infections. Presentations can be atypical, and missing such an infection could be fatal.

• Rare Diagnoses

  • Bronchiolitis Obliterans: A rare condition characterized by fixed airway obstruction, which could be considered in the differential given the obstructive pattern on pulmonary function tests, but it is less likely without a clear exposure history (e.g., to toxic fumes) or other suggestive findings.
  • Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome): A rare autoimmune condition that can involve the lungs and present with asthma-like symptoms, eosinophilia, and vasculitis. It is less likely without other systemic symptoms or eosinophilia.