Erythrodermic psoriasis after discontinuation of ixekizumab.

Introduction

Erythroderma is defined as generalized redness and scaling affecting more than 90% of the skin surface and often accompanied by systemic complications such as hypothermia, dehydration, and electrolyte imbalance. Treatment is targeted at the underlying cause, and preexisting dermatoses are identified in 65% of patients. Psoriasis is the most common underlying disease in erythrodermic adults, accounting for almost half of cases, and can be triggered by withdrawal of medications, infection, or irritant contact dermatitis.

Discontinuation of cyclosporine, methotrexate, and oral corticosteroids is well described in instances preceding the development of erythrodermic psoriasis, but there are fewer reports in instances after withdrawal of biological treatments. Discontinuation of efalizumab, an anti-CD11a antibody that inhibits T-cell activity, resulted in rebound psoriasis in approximately 5% of patients and erythroderma in less than 1% of patients. This medication is no longer commercially available, as more effective, targeted biological treatment options are available and continue to increase in number.

Ixekizumab is a humanized anti–interleukin-17A monoclonal antibody that has recently been approved for the treatment of moderate-to-severe plaque psoriasis. To our knowledge, this is the first report of erythrodermic psoriasis after withdrawal of ixekizumab.

Case report

A 59-year-old woman with a long history of severe plaque psoriasis and psoriatic arthritis experienced near clearance after treatment with ixekizumab during a clinical trial. After the trial ended, treatment with ixekizumab was discontinued, with subsequent worsening of the psoriasis over the next 6 weeks, ultimately requiring hospital admission.

Examination found exfoliative erythroderma with thick scaling throughout (Figs 1 and 2). Mucosal involvement and Nikolsky sign were absent. Fingernails and toenails were hyperkeratotic and discolored. Punch biopsy demonstrated classic features of psoriasis (Fig 3, A and B). Therapy with cyclosporine was initiated promptly at presentation and within 2 weeks near resolution was achieved, with the goal to taper cyclosporine while transitioning to a biologic therapy or methotrexate.

Fig 1

Exfoliative erythroderma on bilateral lower extremities.

Fig 2

Exfoliative erythroderma of face.

Fig 3

Classic features of psoriasis are seen, including regular epidermal hyperplasia, hypogranulosis, dilated vessels within the dermal papillae, and numerous neutrophils in the stratum corneum and epidermis. (A and B, Hematoxylin-eosin stain; original magnifications: A, ×100; B, ×200.)

Discussion

Ixekizumab has proven to be highly effective in the treatment of moderate-to-severe plaque psoriasis. After the induction phase of treatment, the medication is injected subcutaneously every 4 weeks for maintenance. Based on data from the UNCOVER trial, the mean half-life of ixekizumab is 13 days, and elimination occurs through intracellular catabolism. In this study, researchers rerandomized a group of responders after 12 weeks of treatment. The median time to relapse in this group was 164 days, but without report of erythroderma. Reinitiation of treatment allowed 71% of patients who experienced relapse to regain adequate disease control within 12 weeks. In clinical practice, most patients can expect longer treatment durations before discontinuation.

Erythrodermic psoriasis is a potentially life-threatening condition that should be recognized early and treated appropriately. Withdrawal from effective treatments, including ixekizumab, may trigger erythrodermic psoriasis. Thus, close clinical follow-up may be prudent after abrupt discontinuation of this and other systemic therapy in patients with psoriasis.