Can MMF Cause Waxing and Waning Ground-Glass Opacities?
Yes, mycophenolate mofetil (MMF) can cause pulmonary toxicity presenting as ground-glass opacities, but the characteristic "waxing and waning" pattern is not a typical feature of MMF-induced lung injury—this migratory pattern is instead classically associated with simple pulmonary eosinophilia from other drug reactions.
MMF-Associated Pulmonary Toxicity Pattern
MMF causes interstitial lung disorders including pulmonary fibrosis, not the transient migratory pattern seen with eosinophilic drug reactions. 1
The FDA label explicitly warns that "interstitial lung disorders, including fatal pulmonary fibrosis, have been reported rarely" with MMF and should be considered in the differential diagnosis of pulmonary symptoms ranging from dyspnea to respiratory failure 1
Case reports document MMF causing acute respiratory failure with progressive pulmonary fibrosis beginning as early as 10 days post-initiation, which can rapidly progress if not recognized 2
In IPF patients treated with MMF, HRCT evaluation showed deterioration of ground-glass opacity extent (P = 0.02) over 12 months, indicating progression rather than waxing/waning 3
The Waxing and Waning Pattern: Not MMF
The migratory, transient pattern of GGOs that wax and wane is characteristic of simple pulmonary eosinophilia, not MMF toxicity. 4
Simple pulmonary eosinophilia demonstrates nonsegmental consolidation or GGO that is "transient and migratory" with spontaneous resolution within 4 weeks being common 4
This pattern shows "migration and waxing and waning in extent" over months, as documented with drugs like gefitinib 4
The Fleischner Society position paper specifically categorizes this waxing/waning behavior as the "simple pulmonary eosinophilia pattern" of drug-related pneumonitis, distinct from other patterns 4
Clinical Algorithm for Distinguishing MMF Toxicity
When evaluating GGOs in a patient on MMF, look for these distinguishing features:
Timing: MMF toxicity typically begins within days to weeks of initiation, not months 2
Progression: MMF-induced lung disease shows steady progression or persistence, not spontaneous improvement 3, 2
Pattern on HRCT: MMF causes interstitial patterns (reticular opacities, fibrosis) rather than purely migratory consolidations 3
Clinical course: MMF toxicity requires drug discontinuation for improvement; it does not spontaneously resolve while continuing the medication 2
Associated findings: Look for progressive dyspnea and declining pulmonary function tests rather than self-limited symptoms 1, 2
Critical Pitfall to Avoid
Do not continue MMF if pulmonary toxicity is suspected—documented cases show rapid progression to irreversible pulmonary fibrosis when the drug is not promptly discontinued. 2 The patient in the sentinel case report experienced recurrent respiratory failure and progressive fibrosis that only improved after MMF cessation, with some fibrotic changes remaining irreversible 2.
If you observe true waxing and waning GGOs in a patient on MMF, consider alternative diagnoses including infection (particularly opportunistic infections given MMF's immunosuppressive effects), organizing pneumonia from other causes, or concurrent drug reactions from other medications 1, 5.