Methotrexate-induced pulmonary toxicity in psoriatic arthritis (PsA): case presentation and literature review

Abstract

A 45-year-old female with a 4-week history of psoriatic arthritis developed cough, fever, and progressive shortness of breath 2 weeks following initiation of methotrexate therapy. High resolution CT of chest revealed bilateral basal interstitial involvement and diffuse ground glass opacities. Patient, though, died despite immediate discontinuation of methotrexate and initiation of treatment with IV methylprednisolone and cyclophosphamide. Post-mortem examination showed diffuse interstitial pulmonary fibrosis. Methotrexate-induced pulmonary toxicity is a serious event, unpredictable, and unusual, especially in patients with psoriatic arthritis, and although reversible, it may be fatal.

Use of Methotrexate in the Treatment of Inflammatory Bowel Diseases

“…87, 88 Meta-analyses in patients with RA suggest a decreasing incidence of pulmonary toxicity; most likely due to improved selection criteria of patients for MTX therapy. 89 This is also supported by the fact that no increased incidence of pulmonary complications is reported in more strictly controlled randomized trials in IBD, psoriatic arthritis and psoriasis.…”

Fatal methotrexate toxicity: could it have been avoided?

“…It was not anticipated that this patient will have a fatal outcome as we frequently treat patients of PTD with methotrexate at our facility and had never encountered any such major problem. However, fatal methotrexate toxicity has been recorded in patients of autoimmune disorders4 where it may be attributed to altered cellular response, in parallel to altered immune response, despite the lower drug doses used.…”

Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: An Australian and New Zealand perspective Part 1 Historical and established therapies

“…Commonly reported side effects included upper respiratory tract infection, urinary tract infection, nausea, headache and myalgia. In other settings methotrexate use has been associated with hepatic fibrosis [133] and pulmonary toxicity [134]. Table 1 Summary of therapies investigated without evidence of efficacy or not being further investigated for multiple sclerosis Open label study Adverse effects 15-deoxyspergualin (gusperimus) [46] Phase II RCT Terminated due to lack of efficacy Oral tolerance (myelin) [47,48] Phase III RCT No evidence of clinical benefit Acyclovir/valacyclovir [49][50][51] Phase II RCT Primary outcome measures not met TNFa mAb (infliximab) [52] Case reports Increased MRI activity T cell receptor peptide vaccination [53] Phase I No evidence of benefit Anti-CD4 mAb [54] Phase II RCT (RMS) No evidence of benefit Anti-LFA-1 [55] Phase I No evidence of benefit TGF-b2 [56] Phase I No evidence of benefit, concerns regarding nephrotoxicity Sulfasalazine [57] Phase III RCT Primary end-point not met Extracorporeal photophoresis [58] Phase II RCT (PMS) No evidence of benefit TNFR-Ig fusion protein (lenercept) [59] Phase II RCT Increased frequency of new lesions in treated arm Altered peptide ligand (MBP) [60,61] Phase II RCT No evidence of clinical benefit Linomide (roquinimex) [62] Phase III RCT Terminated due to serious cardiovascular adverse events Interleukin-10 [63] Phase II RCT No evidence of benefit IGF-1 [64] Pilot study No evidence of benefit Estriol [65] Cross-over trial (RMS) No evidence of clinical benefit Lofepramine, vitamin B 12 & phenylalanine [66] Phase II RCT Primary end-point not met Cannabinoids [67,68] Small RCT No evidence of benefit Hyperbaric oxygen [69] Cochrane meta-analysis No evidence of benefit PDE4 inhibitor (ibudilast) [70] Open label study Terminated due to lack of efficacy Thiazolidinediones [71] Pilot study MRI outcome positive, but clinically negative Hydrolytic enzymes …”