Ibrutinib induced leg ulcer successfully treated with platelet-rich plasma.

Abstract

Dear Editor, Ibrutinib is an oral irreversible inhibitor of Bruton s tyrosine kinase, currently approved for the treatment of chronic lymphocytic leukemia (CLL). We report the first case of chronic ulcer in leg induced by Ibrutinib, successfully treated with platelet-rich plasma (PRP). A 59-year-old man with newly diagnosed CLL treated with Ibrutinib for 4 months, presented with a 4-weeks history of an extremely painful ulcer in his right leg. Visual Analogic Scale (VAS) score of pain was 10/10. Physical examination showed a 6 × 5 cm superficial ulcer, with irregular edges and a purpuric peripheral halo, located in the distal posterior aspect of the right leg. The wound bed was mainly covered with fibrin and slough (Figure 1). Patient did not referred any traumatic or pressure history. He was not taking any other pro-ulcerating medication. He received treatment with oral antibiotics for 2 weeks without improvement. A skin biopsy was performed. Histopathological examination demonstrated a thick epidermis, with partial epidermal loss areas, dehiscence between epidermis and dermis in some areas, associated with mild fibrosis; pyoderma gangrenosum was excluded. These findings were compatible with an unspecific ulcer, probably associated with Ibrutinib treatment due to the absence of other medical history background. Doppler ultrasonography of the lower extremities and anklebrachial pressure index (ABPI) were performed and discarded a vascular etiology of the ulcer. Traditional wound dressings based on moist wound and including multilayer elastic compression bandages were performed during 6 months, but we could not see any changes in wound size. VAS of pain was 8/10. Due to the lack of improvement, from the Hematology Department decided to reduce Ibrutinib dosing. To promote healing, we started treatment with intralesional autologous PRP along wound edges. After injection, wound was covered with calcium-alginate dressings and multilayer compression bandage. PRP was injected for three times, every 7 days. In the first wound dressing after procedure, we could observe a mild hematoma in perilesional skin, that solved spontaneously in 1 week. Patient referred progressive pain reduction after procedure, showing a total pain suppression in 10 days after injections (VAS score 0/10). In the second week after PRP, we could notice a partial healing of the wound and reduction of fibrin and slough component (Figure 2). We could observe total epithelization of the wound in 12 weeks (Figure 3). Finally, due to a tachicardiomiopathy, discontinuation of ibrutinib was decided. After 1 year of follow-up, no recurrence of the ulcer or new wounds have been observed. Ibrutinib is generally well tolerated. Hair and nail changes are the most frequently described long-term adverse effects. Regarding skin toxicity, there are few cases reported about panniculitis, pityriasis rosea-like, skin and soft tissue infections, and neutrophilic dermatosis. Up to date and to the best of our knowledge, this is the first reported case of a spontaneous skin ulcer induced by Ibrutinib. The improvement of the wound observed after ibrutinib dose reduction, supports the causal relationship between the ulcer and the drug. Bleeding events have been reported in ibrutinib-treated patients. This could explain not only the susceptibility to bleed after injection but the retarded wound healing in our patient. Although conventional wound care is the elementary treatment modality for treating chronic wounds, there are some chronic wounds that will need advanced wound therapies to achieve healing, like PRP. PRP is a simple, well tolerated, and inexpensive technique