Korean J Dermatol.  2022 Nov;60(9):628-630.

Delayed-Onset Perforating Phenomenon in a Patient with Sorafenib-Induced Psoriasiform Eruption

• Song CH
• Song SY
• Kim JE
• Ro YS
• Ko JY

Abstract

Sorafenib is an inhibitor of receptor tyrosine kinases and the rat sarcoma/mitogen-activated protein kinase (RAS/MAPK) pathway that is approved for the treatment of patients with metastatic hepatocellular carcinoma (HCC) and renal cell carcinoma. Sorafenib is known to have various cutaneous adverse effects, including hand-foot reaction, facial and scalp eruption, xerosis, and alopecia1. A 56-year-old man presented with non-painful, nonpruritic psoriasiform lesions that has been present for approximately 1 month (Fig. 1A∼E). Six months prior to presentation, he had been prescribed sorafenib at a daily dosage of 600∼800 mg after diagnosis of HCC with distant metastasis to the lung. A punch biopsy showed psoriasiform dermatitis (Fig. 1F, G). The skin lesions improved gradually after discontinuing sorafenib. However, at 1 month after discontinuation of sorafenib, considering the dose-dependent adverse effect of the medication, the patient resumed sorafenib at 400 mg daily after an oncology consultation. The lesions recurred beginning at 1 week after restarting sorafenib. A clinical diagnosis of sorafenib-associated psoriasiform drug eruption was made. The sorafenib treatment was maintained at 400 mg daily in conjunction with concurrent phototherapy and topical and intralesional corticosteroids for thick erythematous plaques, and intermittent systemic corticosteroid treatment when the cutaneous eruptions flared up. After approximately 2 years of sorafenib treatment, the patient presented with new crusting lesions without any other systemic adverse reactions. Multiple papules and plaques with central hyperkeratotic and crusted papules were present (Fig. 2A∼D). Punch biopsy showed a ‘perforating phenomenon’ (PP) (Fig. 2E∼G). The brownish hyperkeratotic crusts occurred consistently in prolonged psoriasiform plaques and resolved over time (Fig. 2A∼D). The psoriasiform eruptions and delayed-onset PP persisted with continuing sorafenib use (Fig. 2H). Along with a dose-decrease of sorafenib at 400mg daily, he was treated with systemic and topical corticosteroids, intralesional triamcinolone injection and narrowband ultraviolet B therapy. However, the patient showed recurrent cutaneous lesions aggravation upon tapering the dosage of corticosteroid. The psoriasiform lesions improved and then worsened with sorafenib dose change, and the PP featured hyperkeratotic crusts within multiple, long-lasting psoriasiform plaques. This phenomenon might have occurred to eliminate connective tissue or inflammatory material2 and differs from the appearance of transepidermal elimination in previously reported sorafenib-associated acquired perforating dermatosis cases3,4. Transepidermal elimination is a similar process to wound healing2, and considering that our patient had no history of diabetes, renal insufficiency, and trauma, our case might have exhibited the perforating and resolving phenomenon in response to the abnormal psoriasiform drug eruption. The RAS/MAPK cascade that is inhibited by sorafenib could be activated paradoxically; due to its role in antiangiogenesis, this activation results in epidermal disruption. The reduction and suppression of the hepatocyte growth factor-enhanced expression of matrix metalloproteinase induced by sorefenib could influence homeostasis of dermal elastic fibres, resulting in their disruption5. A few cases of psoriasiform drug eruption and PP after administration of sorafenib and other various tyrosine kinase inhibitors have been reported. The PP could represent a manifestation of the resolution of inflammation whereby the psoriasiform hyperplasia and the proliferated dermal tissue might be eliminated via a trans-epidermal route.

Keyword

Acquired perforating dermatosis; Perforating disease; Sorafenib-induced