Pyoderma gangrenosum-like lesion secondary to methylenetetrahydrofolate reductase mutation: an unusual presentation of a rare disease

Abstract

Pyoderma gangrenosum (PG)-like ulcerations are a rare clinical manifestation of methylenetetrahydrofolate reductase (MTHFR) mutation. We describe a patient considered to have PG who was treated with long-term high doses of systemic corticosteroids and multiple immunosuppressive agents for several years. In spite of this continuous aggressive therapy, the lesions did not improve but continued to get worse. She developed many significant and catastrophic side effects to them. When referred to our dermatology centre, on investigation, it was discovered that she has an MTHFR mutation. It seemed reasonable to presume that PG-like lesions were related to it. Treatment with a biologically active form of folate-[6S]-5-MTHF-with vitamins B6 and B12 was initiated. It was considered to be beneficial and capable of reducing hyperhomocysteinaemia and endothelial damage consequent from it. Since the institution of this treatment, the patient has begun to show very gradual but slow and incremental improvement.

Keywords: dermatology; genetics.

Figure 1

Simplified scheme of folate-dependent homocysteine metabolism. Due to deficiency of methylenetetrahydrofolate reductase (MTHFR), 5,10-MTHF is not able to convert into 5-MTHF, which leads to the development of hyperhomocysteinaemia. Supplementation with [6S]-5-MTHF is an adequate alternative to folate for decreasing homocysteine concentration.

Figure 2

(A) Anterior view of the ulceration 15×20 cm with violaceous border and yellow–pink granulation base on the right lower extremity. (B) Posterior view of the right lower extremity demonstrating the circumferential extend of the ulceration.