A 61-year-old man was diagnosed with stage IIIB BRAF V600E mutant
melanoma in October 2012. He was treated with a combination
therapy of
dabrafenib and
trametinib. He remained
in complete remission for 18 months and the treatment was well tolerated after
dose reduction because of
pyrexia. In March 2013, he developed bilateral pitting
edema of the legs with an erythematous, slightly infiltrated
rash on his back and upper arms. His face was edematous, with a heliotrope
rash-like aspect. Eye examination showed bilateral
blepharitis. Additional blood test showed
inflammation and
acute kidney injury Rifle category failure. A skin and kidney biopsy indicated a granulomatous
inflammation. A complete workup for other causes of granulomatous
inflammation was negative. Treatment with
dabrafenib and
trametinib was stopped and
corticosteroids were initiated, with a rapid beneficial effect on both the kidney function and
skin rash. When
corticosteroids were halted after 1 month, a rapid decline in the kidney function was observed. After reintroduction of
corticosteroids, kidney function normalized and
steroids could be tapered gradually over 6 months. To our knowledge,
interstitial nephritis has not been described in patients on BRAF-targeted nor
MEK-targeted
therapy for
melanoma, although it has been described in a
melanoma patient treated with the
immune checkpoint inhibitor,
ipilimumab. Currently, the patient has no sign of local or distal recurrence of
melanoma, notwithstanding that treatment with
dabrafenib and
trametinib has been stopped for 10 months and no other antimelanoma
therapy was initiated.