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Dramatic effect of sunitinib with rapid but transient improvement for psoriasis in a patient with metastatic renal carcinoma

Dear Editor, A 56-year-old Japanese man who had prolonged fever and a feeling of residual urine was diagnosed with renal cancer with possible peritoneal dissemination by computed tomography examination. He received an operation of transperitoneal extirpation of the left kidney, which was however left untreated due to peritoneal dissemination and intestinal metastasis. The patient was admitted for further treatment with molecularly targeted therapy, and was then referred to our dermatology department, because he had had plaque-type psoriasis for 20 years. He had been treated with topical corticosteroids and vitamin D3 ointment which had proved ineffective. Physical examination revealed multiple scaly erythematous plaques that spread over the trunk, upper and lower limbs, and scalp (Fig. 1a,b). The estimated Psoriasis Area and Severity Index (PASI) score was 15.7. Administration of 50 mg/day p.o. sunitinib (Sutent R Z; Pfizer, Groton, CT, USA) was started for renal cancer. Two weeks later, the psoriatic lesions dramatically improved (Fig. 1c,d), with a markedly reduced PASI score of 2.0. However, due to severe cutaneous adverse effects (hand– foot syndrome; grade III), hypertension, edema, elevated serum thyroid stimulating hormone and infection of operation scar, sunitinib was interrupted after 2 months from initiation. Cutaneous psoriasis relapsed with flare-up 1 month after sunitinib was discontinued, and thereafter he has been treated with topical corticosteroids and vitamin D3 ointment without significant effects. Several cases have been reported in which tyrosine kinase inhibitors were effective for psoriasis. Sunitinib is a multikinase inhibitor that targets vascular endothelial growth factor (VEGF) receptors 1–3, platelet-derived growth factor (PDGF) receptors-a and -b, c-Kit, Flt-3, colony-stimulating factor receptor 1, and glial cell line-derived neurotrophic factor receptor, which is used for advanced renal cell carcinoma. There are a few reports demonstrating favorable effects of molecularly targeted therapies for co-existent psoriasis resistant to standard therapies. In our case, it is without doubt that sunitinib exhibited advanced effects for psoriasis, although a challenge test could not be done. VEGF is one of the key molecules which plays important roles in the pathogenesis of psoriasis, namely: (i) increased expression of VEGF, as well as VEGF-A receptors, is detected in the psoriatic epidermis; (ii) serum VEGF levels are elevated in correlation with disease severity; (iii) K14-VEGF transgene develops psoriasis-like skin changes in mice; and (iv) treatment with anti-VEGF antibody reduces skin inflammation in a mouse model of psoriasis. Inhibition of VEGF signaling may result in beneficial effects for psoriasis within a short period, whereas it should be noted that these anti-psoriatic effects are not persistent but transient. On the other hand, complete blockade of VEGF signaling pathways may also induce adverse reactions, and even worsen psoriasis, due to the inflammatory and immune feedback reactions in certain cases. Finally, in renal cell carcinoma, immune dysfunctions shift towards T-helper (Th)2 type, which is reversed to Th1 by sunitinib. Because psoriasis is mediated by Th1/ Th17 type T-cell subsets, the mechanism of favorable effects of sunitinib in our case was considered to be mainly due to blockade of the VEGF pathway, rather than improvement of cytokine balance.