Management of granulomatous foreign body reaction to fillers with methotrexate

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.

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

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.

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.

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.