A psoriasiform drug eruption induced by polyethylene glycol interferon-alpha-2b, successfully treated by narrow band ultraviolet B therapy

ARTICLE

ejd.2011.1596

Auteur(s) : Shinji Kuwabara kaijiyamato@yahoo.co.jp, Hideki Maejima, Akira Watarai, Yuko Hamada, Kensei Katsuoka

Department of Dermatology, Kitasato University School of Medicine, 1-15-1 Kitasato Sagamihara, Kanagawa 228-8555, Japan

Polyethylene glycol interferon-alpha-2b (PEG-IFN-α-2b), a cytokine with pleiotropic activities, is a useful agent for treating several chronic viral and malignant diseases [1]. Common side-effects include fatigue, fever, nausea, marrow suppression, vomiting, alopecia and triggered or exacerbated psoriasis. A patient who received narrow band ultraviolet B (NBUVB) phototherapy which was useful for controlling a psoriasis-form eruption induced by PEG- IFN-α-2b is presented.

A 65-year-old Japanese man was treated with combined injected 200 μg of PEG-IFN-α-2b and 1,000 mg/day oral ribavirin for type C hepatitis and liver cirrhosis. He and his family had no history of psoriasis. He noticed erythema on the arm at injection sites two weeks after receiving these therapies. The erythema began to enlarge and disseminated to involve his whole body with severe itching within two weeks. Ribavirin was discontinued, the dose of PEG-IFN-α-2b was reduced to 100 μg weekly and corticosteroid ointment treatment was given. Despite these efforts, whitish scales with erythema appeared on his body, mimicking psoriasis vulgaris (figure 1A). A skin biopsy specimen confirmed a psoriasis-like reaction that included numerous neutrophils and some eosinophilic leukocytes, which infiltrated into the subcorneal layer and hypertrophic epidermis (figure 1B). On laboratory examination, peripheral blood cell counts were normal. Aspartate transaminase was 69 IU.L^-1, alanine transaminase was 47 IU.L^-1. HCV RNA was increased 7.3×105 copies.mL^-1. The application of corticosteroid and calcipotriol ointments did not clear the eruption. NBUVB phototherapy was then started. The erythema cleared with 19 phototherapy sessions, involving a total dose of 11.39 J.cm^-2. After phototherapy, the erythema did not recur (Fig.1c). A biopsy of the photo-treated skin showed pigmentation in the basal layer (Fig 1d). Patch tests and drug lymphocyte stimulated tests for PEG- IFN-α-2b and ribavirin were negative. But the patient was diagnosed as having a psoriasis-form drug eruption induced by PEG-IFN-α-2b. No dermatological or other side effects were observed during treatment with lamivudine over the 15-month follow-up period.

IFN-α played a role in the pathogenesis in psoriasis. Environmental factors trigger psoriasis [2]. In the initiation phase, stressed keratinocytes release self DNA to form complexes with CpGDNA and LL-37, which in turn activate plasmacytoid dendritic cells (pDCs) to produce IFN-α. IFN-α, interleukin-12/23 and tumour necrosis factor activate dermal DCs. Dermal DCs migrate to the skin-draining lymphs to naive T cells and promote their differentiation into T helper 1 (TH1) and TH17 cells [2].

A study of IFN-α production in psoriasis-form eruptions showed that the expression of antibodies against MxA in the epidermis was comparable to that in psoriasis and healthy controls. MxA is specifically induced by type I IFNs (IFN-α/β). MxA expression in infiltrated cells is significantly higher in a psoriasis-form eruption than in psoriasis and healthy controls [3]. Cytokine levels in the patient's eruption and psoriasis were analyzed using antibodies against CD3 (Dako, Glostrup, Denmark), CD4 (Nichirei, Tokyo, Japan), CD8 (Dako), CXCR3 (PharMingen, San Diego, CA, USA), CXCL9 (Mab392; R&D system, Minneapolis, MN, USA), and MxA (Santa Cruz Biotechnology, Santa Cruz, CA, USA). MxA, CD3 and CD4 expressions were higher in the epidermis of psoriasis-form eruptions than in treated skin. The expressions of other antibodies were not different between the two areas. Psoriasis-form eruptions induced by PEG-IFN-α-2b usually appear several weeks after the start of PEG-IFN-α-2b and require its discontinuation [4,5]. The continuation of PEG-IFN-α-2b therapy was required for treatment of type C hepatitis and liver cirrhosis, so he was treated with NBUVB phototherapy for the skin eruptions while PEG-IFN-α-2b was continued. NBUVB phototherapy appears to be a potential treatment for psoriasis-form eruptions induced by IFN-α which allows IFN-α therapy to be continued.

Disclosure

Financial support: none. Conflict of interest: none.

References

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