Management of granulomatous foreign body reaction to fillers with methotrexate.

Background: Granulomatous foreign body reactions (GFBR) have been reported after injection with almost every soft tissue fillers, more commonly with non-biodegradable ones. Such granulomatosis is rare but can cause significant discomfort owing to their aesthetic and functional repercussions.

Objective: To determine whether immunomodulation with low doses of methotrexate is effective in the treatment of GFBR to filler material.

Methods: Clinical case series of four patients with severe, treatment-resistant GFBR to non-biodegradable fillers in the Department of Dermatology of Bordeaux University Hospital, Bordeaux, France, successfully treated with oral or subcutaneous methotrexate, 10-15 mg weekly during 6 months. Adverse events were monitored throughout the treatment once weekly the first month then once monthly the remaining 5 months.

Results: Four women with a mean age of 73.7 years (66-85 years) and nodularity of the face were included and treated up to 6 months. Histological findings were consistent with GFBR to liquid injectable silicone in 2 cases, polymethylmethacrylate in 1 case and hydroxyethylmethacrylate in the last case. The delay after injection of the filler material was from 17 to 30 years. In one patient, inflammatory lesions followed dental care. After 6 months of treatment with 10-15 mg once weekly, all patients were cleared. Three patients developed a mild hepatic cytolysis (grade 1 or 2). Methotrexate could be maintained in those 3 cases and was discontinuated after 6 months in all cases. Two patients developed recurrence of lesions, 28 and 9 months, respectively, after treatment stops, requiring reintroduction of treatment. The two other patients remained cleared after 6 months of follow-up.

Conclusion: Low doses of methotrexate appear to offer a low-risk therapeutic alternative in resistant and severe GFBR to fillers. A prospective study with long-term follow-up is required to confirm these preliminary observations.