Hyper-Acute Methotrexate Pneumonitis in a Patient With Crohnʼs Disease

Abstract

Case: A 64 year-old female with Crohn's colitis presented with 2 weeks of fevers, drenching night sweats, malaise, dry cough and dyspnea. She had developed a severe flare of Crohn's colitis 4 months earlier that was refractory to infliximab, necessitating surgical management with colectomy and diverting ileostomy. Post-operatively, she developed peristomal pyoderma gangrenosum for which she was to receive adalimumab and methotrexate(MTX) 10 mg oral every week. Two days after her first dose of MTX, she developed the presenting symptoms that worsened after her second dose. This occurred prior to initiation of adalimumab. On presentation, patient was tachycardic to 120s, hypoxic and febrile to 101°F. Rales were audible over both lung fields. Laboratory values were within ranges of normal except mild renal insufficiency. Chest CT (figure 1) showed diffuse ground glass opacities with centrilobular prominence. Non-invasive workup for infectious etiologies was negative. On bronchoscopy and bronchoalveolar lavage (BAL), antigen testing and cultures did not reveal evidence of bacterial, viral, mycobacterial or fungal infection. Elevated lymphocyte (54%) and eosinophil (11%) counts were noted on the BAL fluid cell differential. A diagnosis of MTX-induced pneumonitis (MIP) was made. She was started on 40 mg/day prednisone with tapering over 5 weeks. After 4 weeks on corticosteroids, the patient's symptoms resolved. A follow-up chest CT (figure 2) showed resolution of radiographic abnormalities.Figure 1Figure 2Discussion: MTX is an immunosuppressive with efficacy as monotherapy in induction and remission of Crohn's disease. Concurrent use of MTX with anti-TNFα agents can prevent anti-drug antibody formation and foster higher drug levels. MTX is associated with serious lung toxicity with MIP as the most common manifestation. MIP presents with non-specific acute or gradually progressive symptoms of cough, dyspnea, fevers and can progress to respiratory failure. MIP generally occurs after months of low-dose oral MTX therapy. Of the only two previous case reports of MTX-related pulmonary disease reported in Crohn's disease(CD) symptom onset was at 2-18 months after initiation of MTX. This is the first case of hyper-acute MIP in CD with symptom onset within a few days of MTX initiation. MIP diagnosis is made based on a composite of clinical history, radiological findings and BAL results. CT chest imaging can demonstrate diffuse groundglass opacities with or without consolidation, centrilobular nodules or traction bronchiectasis. BAL findings have lymphocytic and eosinophilic predominance with increase in the CD4/CD8 ratio. The treatment of MIP is MTX withdrawal. Corticosteroid therapy can be considered based on severity, duration and progression of symptoms.