Efficacy and systemic absorption of topical tacrolimus used in pyoderma gangrenosum

Sir, We report a case of a patient with pyoderma gangrenosum (PG) successfully treated with ciclosporin and topical tacrolimus. An increase in serum creatinine forced us to decrease the doses. The plasma level of tacrolimus was high. The patient was a 77‐year‐old man, with recent surgery for left total hip prosthesis. One week after surgery, an ulceration appeared around the suture area and progressed rapidly, with severe local pain and general malaise. A biopsy at the margin of the lesion showed a sharply demarcated ulceration, in which haemorrhage, necrosis and massive infiltration of polymorphonuclear neutrophils were present. Infection of the prosthesis was excluded. The diagnosis of PG was made, based on clinical and histopathological grounds. Several investigations did not disclose any associated disorder. Systemic treatment with ciclosporin (5 mg kg–1 day–1) was started, without any clinical benefit after 15 days (the lesion continued to increase in size). Tacrolimus (0·1% ointment) was then applied to the margins of the PG ulceration (18 × 12 cm) once daily (± 7·5 g day–1). The result was highly beneficial, with a quick response: no further extension, regression of the inflammatory border and pain relief. Plasma renal parameters 19 days after starting ciclosporin (4 days for tacrolimus) were normal. The day after, serum creatinine was 1·5 (normal 0·6–1·4) mg dL–1 and increased progressively within 3 days, to 2·2 mg dL–1. Creatinine clearance was 30 mL min–1. Serum tacrolimus concentration was 10·2 ng mL–1. Ciclosporin concentration was 307 ng mL–1 (therapeutic values 75–350). Thus, systemic ciclosporin was tapered to 2 mg kg–1 day–1 and tacrolimus 0·03% ointment was used instead of 0·1%. Creatinine levels returned to normal and tacrolimus absorption was not detectable any more. Complete healing of PG was obtained after 6 weeks, with classical cribriform scars.