Remission of Psoriasis in a Patient with Hepatocellular Carcinoma Treated with Sorafenib

Discussion

The overexpression of VEGF on psoriatic keratinocytes and up-regulation of VEGF receptors in microvasculature of psoriatic lesions has now been established as elevated levels of VEGF can be detected in the serum of human psoriasis patients and correlate with disease activity (1). Sorafenib is a multikinase inhibitor, effective in liver and renal cancer, which blocks tumor proliferation and angiogenesis through targeting VEGFR (7). On this basis, drugs against VEGF or its receptor could be considered as future therapies for psoriasis (8). In accordance with our observation, a patient with metastatic hypernephroma treated with sorafenib presented remission of his psoriatic lesions (4). We suggest that inhibition of VEGFR, leading to angiogenesis down-regulation, is the common mechanism in HCC therapy and psoriasis remission induced by sorafenib.

However, cutaneous toxicity is relatively common in patients receiving sorafenib. The most frequent cutaneous side-effect is the hand-foot syndrome, while other described adverse skin reactions include facial and acral erythema, stomatitis, alopecia and pruritus. Less commonly, multiple squamous cell carcinoma, keratoacanthoma and epidermoid cysts have also been described (9). The development of psoriasiform eruptions in patients treated with sorafenib seems paradoxical, although reported (10-13), since this drug blocks the activity of VEGF, a cytokine whose role in psoriasis pathogenesis is well-documented. A case of sorafenib-related presentation of psoriasis in a HCC patient has been reported. Dysfunctional CD4⁺CD25⁺ T cells, which cause an imbalance between regulatory and effector T-cell functions, are found in patients with psoriasis. According to the authors, tyrosine kinase inhibitors, such as sorafenib, may block the signal transduction pathways in both regulatory and effector T cells (10). In another case, sorafenib was implicated in the development of the psoriasiform eruption in a 59-year-old man diagnosed with nodular HCC secondary to alcoholic liver cirrhosis (11), while another HCC patient developed cutaneous psoriatic lesions following sorafenib therapy (12).

Other biological therapies administered in various advanced cancers have also been involved in psoriasis remission or even exacerbation. Erlotinib inhibits the tyrosine kinase of epidermal growth factor receptor (EGFR) and is successfully used in pancreatic and lung cancer treatment. EGFR is essential in skin development and function and may have a role in the pathogenesis of psoriasis. Although cutaneous side-effects are very common in patients treated with erlotinib, two cases of patients with lung cancer and concomitant psoriasis treated with erlotinib with complete resolution of the skin problems have been reported (14). Bevacizumab, another monoclonal antibody against VEGF, is used for treatment of several cancers and retinopathies. In a report, a patient with metastatic renal cell cancer, psoriasis and psoriatic arthritis, experienced a complete remission of psoriasis during bevacizumab therapy without any other management (15). Finally, among others, the anti-VEGF/anti-TNF-α decoy receptor (Valpha) showed beneficial action against psoriasis (16, 17).

In conclusion, herein, we present the case of a patient with HCC, also suffering from psoriasis, who showed complete remission of his psoriatic lesions after sorafenib administration. Several targeted therapies have demonstrated potential to treat psoriasis as clinical observations of psoriasis remission following administration of bevacizumab, erlotinib, sorafenib and others in cancer patients are encouraging. Contradictory results regarding these drugs' association with psoriasis have also been reported in the literature. More research and well-designed studies, both in novel drugs and those already marketed for other indications, are needed in order to determine their value as potential novel therapies for psoriasis.