Several hundred cases of methotrexate pulmonary toxicity have been reported
50% of cases are diagnosed within 4 months of starting methrotrexate
Prevalence: 0.3-7.5%
Pulmonary toxicity occurs in 3-18% of RA patients treated with methotrexate
Toxicity is not related to age, underlying disease, underlying lung disease, or methotrexate dose
Synergism
Few reported cases with Nitrofurantoin use
Methorexate pneumonitis can be precipitated by addition of infliximab
Physiology
Probable hypersensitivity-type reaction (due to presence of peripheral eosinophilia in 50% of cases)
Diagnosis
ABG: hypoxemia
CBC: eosinophilia is present in at least 50% of cases
CXR/Chest CT Patterns
Homogeneous Infiltrate: multi-lobar involvement
Interstitial Infiltrates: lower-lobe predominance
Hilar Adenopathy/Pleural Effusion (seen in 10-15% of cases)
PFT’s: distinct from many other chemo-related pulmonary toxicities, the DLCO does not decline prior to onset of symptoms
FOB: important to rule out PCP, as PCP incidence is increased in setting of methotrexate use (with or without concomitant steroid use)
Hypercellularity with lymphocytosis
OLB: weakly-formed, non-caseating granulomas (seen in 33% of cases on biopsy)
These are unusual in other forms of chemo-associated lung disease
No cellular atypia (as is seen in other cytotoxic drug toxicities)
Lymphocytic infiltration: increases the probability of methrotrexate toxicity being etiologic
Clinical
Dyspnea/dry cough/fever starting anywhere from a few days-several weeks after start of methotrexate
Treatment
Withdraw Drug + Corticosteroids: almost always reversible with or without steroids
Reinstitution of Methotrexate: interestingly, in cases with previously demonstrated methotrexate toxicity, drug may be restarted after resolution of pulmonary symptoms, without recurrent signs of further toxicity
Few case reports of fatal reactions in patients receiving intrathecal methotrexate or from PO methotrexate administration after prior intrathecal methotrexate dosing
Pleural Effusion (see Pleural Effusion-Exudate, [[Pleural Effusion-Exudate]]): occurs in 10-15% of cases
