Background: Eosinophilic Fasciitis (EF) is a disease of unknown origin initially characterized by limb or trunk edema, and collagenous thickening of the subcutaneous fascia in later stages. Eosinophilia in peripheral blood is commonly observed. Being a rare disease, evidence regarding treatment is mainly based on case series and anecdotal evidence. The mainstay systemic treatment is prednisone, and Methotrexate (MTX) up to doses of 25 mg/week is the leading prednisone-sparing agent. Mycophenolate can be considered in refractory cases. As an alternative we explored the use of intravenous (i.v.) pulse MTX. We already showed this to be a potentially effective and safe treatment option in a prospective single-arm study ¹ , but more data on adverse events (AEs) are needed.

Objectives: To present an overview of AEs of high dose i.v. pulse MTX in refractory EF.

Methods: Adult patients with EF based on clinical appearance combined with histology and/or MRI, who were unresponsive to prednisone combined with low-dose MTX or presenting with severe disease, were selected for this retrospective cohort study. Patients received 6-9 monthly infusions of 4 mg/kg MTX followed by oral folinic acid rescue therapy, which is comparable to treatment schedules for trophoblast disease. An additional number of six pulses could be administered in case of a partial effect or flare. Safety data were monitored during each visit and classified according to the Common Terminology Criteria for Adverse Events (CTCAE) from the National Institute of Health (2009).

Results: Twenty-seven patients (26 with EF, one with deep linear morphea) were included in this study (five males), with a mean age of 59 (sd 11.5) years, based on clinical presentation and histology and/or MRI. Previous treatment data were available for 22 patients of which 21 received oral prednisone (20-60 mg) whether or not combined with low dose MTX and/or UVA1 therapy. All patients reported ≥ 1 AEs at some stage, exactly 100 in total. ‘ Gastro-intestinal disorders ’ (n=36) and ‘ General disorders and administration site conditions ’ (n=15) were most common; especially nausea (n=6) and fatigue (n=11). One patient was hospitalized for blood transfusion. In four cases, treatment was discontinued due to AEs (acute kidney injury (AKI), depression, nausea/vomiting, and leukopenia resp.). Each reported AE appeared reversible. The patient with AKI had an MTX level in the toxic range; methotrexate-induced crystal nephropathy seemed the most likely explanation, probably due to a combination of high body weight (and thus high absolute dosage of MTX) and the concomitant use of omeprazole. Oral folinic acid rescue therapy was prolonged, together with 500 cc i.v. fluid, after which kidney function normalized.

Conclusion: AEs were common among patients receiving high dose i.v. pulse MTX, especially nausea and fatigue, but were generally mild and reversible in all cases. This is in line with studies performed with patients with trophoblast disease. One episode of reversible AKI occurred that seemed to be related to high body weight and the use of concomitant medication. The safety profile of i.v. pulse MTX thus seems auspicious, but the case of AKI illustrates that further data on safety is needed.

REFERENCES:

[1] Mertens JS et al. High-dose intravenous pulse methotrexate in patients with eosinophilic fasciitis. JAMA Dermatol 2016; 1(152):1262-5.

Disclosure of Interests: None declared