Scurvy in a patient on vemurafenib.

Introduction

Vitamin C deficiency, or scurvy, is uncommon in the Western world. Here, we present a patient who had scurvy diagnosed while receiving vemurafenib treatment for metastatic melanoma, which improved with vitamin C supplementation.

Case report

A 66-year-old white man with stage IIIC melanoma diagnosed in 2009 was treated with high-dose interferon alfa-2b for 1 year. He subsequently had subcutaneous and brain metastases and underwent 2 cycles of high-dose interleukin-2 and whole-brain irradiation. Given disease progression, vemurafenib was initiated at 960 mg twice daily after testing confirmed the BRAF V600E mutation. After 4 months of treatment, systemic symptoms of severe fatigue, anorexia/dysgeusia, and arthralgias developed as did cutaneous manifestations including xerosis, a keratosis pilaris–like eruption on the trunk and extremities, and corkscrew hairs on the upper back, which were not present before vemurafenib therapy (Fig 1, Fig 2). The clinical symptoms were consistent with several reported side effects of vemurafenib; however, the additional finding of corkscrew hairs prompted the consideration of vitamin C deficiency resulting in scurvy. Other findings of scurvy such as petechiae, gingivitis, and poor wound healing were not present. Further investigation found low plasma vitamin C levels on 2 independent determinations 1 week apart (0.0 mg/dL and 0.1 mg/dL [0.4–2.0 mg/dL]). Upon questioning, the patient reported decreased appetite with specific reduced intake of fruits and vegetables since starting vemurafenib. Therapeutic supplementation of ascorbic acid (125 mg twice daily) and increased dietary consumption of foods rich in vitamin C were recommended; after 6 weeks, a vitamin C level was within normal limits at 0.7 mg/d, and he experienced significant reduction in fatigue and arthralgias. After 12 weeks, the keratosis pilaris–like eruption improved, and the corkscrew hairs resolved (Fig 3). The patient's vemurafenib dose remained stable throughout this time. Within 1 month, the patient had recurrence in the right axilla and brain; he died from his disease 8 months after the diagnosis of scurvy.

Fig 1

Clinical presentation of scurvy. Perifollicular erythema, keratosis pilaris–like eruption, and corkscrew hairs on the upper back of a patient with vitamin C deficiency receiving vemurafenib for metastatic melanoma (inset with higher magnification of corkscrew hair surrounded by ink dots).

Fig 2

Histopathologic presentation of scurvy. Punch biopsy of a corkscrew hair shows a hair shaft cut on multiple cross sections with a rare eosinophil underlying the dermis. (Hematoxylin-eosin stain, original magnifications ×4 and inset, ×20.)

Fig 3

Resolution of corkscrew hairs and improvement in keratosis pilaris–like eruption after treatment with vitamin C.

Discussion

Cutaneous side effects associated with vemurafenib include photosensitivity, alopecia, xerosis, papillomas, squamous cell carcinomas, panniculitis, keratosis pilaris–like eruptions, facial erythema, palmar-plantar hyperkeratosis, and acneiform eruptions.1, 2, 3, 4 Dysgeusia and decreased appetite are common side effects, reported in 13% and 18.8%, respectively, of 468 patients combined from the phase II and phase III trials. It is not known if vemurafenib directly contributes to vitamin C deficiency or if the association is mediated by the symptoms of anorexia and taste disturbance, which may lead to decreased consumption of fruits and vegetables. After this patient had vitamin C deficiency diagnosed, we measured vitamin C levels in 3 other patients taking vemurafenib. We identified 1 patient with vitamin C deficiency who did not have any signs or symptoms of scurvy (particularly no keratosis pilaris–like eruption); 2 others who had the keratosis pilaris–like eruption (no corkscrew hairs) had normal vitamin C levels. Therefore, we cannot conclude whether there is a direct relationship between vemurafenib and vitamin C deficiency or whether the association is mediated simply by decreased appetite or metastatic disease. Currently, we obtain baseline vitamin C levels on patients before treatment with vemurafenib and follow-up levels if symptoms of scurvy or decreased appetite are present. Given that scurvy rarely occurs in the United States, it is important for dermatologists and oncologists to be aware of this potential association so that they can monitor patients for symptoms and test and treat accordingly.