Psoriatic Skin Lesions Induced by Certolizumab Pegol

A 26-year-old woman with Crohn disease was seen with a widespread pustular eruption, most prominent on the hands and feet, after treatment with certolizumab pegol was initiated 4 months earlier. Psoriasiform plaques were widespread over the trunk, extremities (Figure 1), and scalp, and she also had substantial palmoplantar involvement. Over her lateral malleoli were pink-red scaly plaques rimmed with pustules (Figure 2). She denied personal or family history of psoriasis. Two punch biopsy specimens from the left lateral malleolus revealed focal mild spongiosis, parakeratosis, slight acanthosis, a predominantly lymphocytic inflammatory dermal infiltrate, and exocytosis of neutrophils.

Certolizumab treatment was discontinued, and an oral prednisone regimen, 30 mg/d, was begun for her Crohn disease. This treatment suppressed her pustular eruption and resulted in predominantly guttate psoriasiform plaques. Given her active Crohn disease and cutaneous lesions, methotrexate therapy was initiated at 15 mg/wk and then titrated to 25 mg/wk. The patient experienced good initial cutaneous response to methotrexate; however, she developed elevated liver enzymes, fever, and telogen effluvium after 5 doses, and her drug treatment was switched to 6-mercaptopurine. Palmoplantar and extremity psoriatic lesions recurred, and treatment was begun with narrowband UV-B phototherapy, 3 times weekly, and a topical combination of calcipotriene, 0.005%, cream and betamethasone dipropionate, 0.064%, cream twice daily. The patient experienced substantial cutaneous response, and the disease did not rebound after her prednisone regimen was tapered to 0.

Certolizumab pegol (Cimzia; UCB Pharma, Brussels, Belgium) is an anti–tumor necrosis factor (anti-TNF) antibody composed of a pegylated humanized Fab fragment¹ and approved by the US Food and Drug Administration for the treatment of Crohn disease and rheumatoid arthritis. One of us (J.S.) communicated our findings to UCB Pharma, and as a result, the Cimzia product insert was changed to reflect this possible cutaneous adverse reaction. At least 1 published case of a pustular and psoriasiform eruption after certolizumab treatment initiation has recently been reported.²

Since 2003, induction and exacerbation of psoriasis have been reported as rare adverse effects of TNF blockade therapy.³ The largest review to our knowledge⁴ comprises 127 cases of anti-TNF–induced psoriasiform eruptions associated with infliximab (55.1%), etanercept (27.6%), and adalimumab (17.3%) and found a prevalence of psoriasis during TNF blockade ranging from 0.5% to 5.3%, with onset of psoriatic lesions varying from a few days to 4 years after therapy began (average time to lesion onset, 10.5 months).⁴ Proposed causes include an imbalance of TNF and interferon α, misdiagnosis, infection, and autoreactive T-cell activation. A leading mechanism proposed to explain this phenomenon is that TNF blockade results in increased interferon α expression by plasmacytoid dendritic cells, cells found in early psoriatic lesions and normal-appearing psoriatic skin, leading to homing of helper T cells, type 1, to the skin via interferon α induction of interleukin 15.⁵

The most common cutaneous psoriasiform manifestation observed following TNF blockade was palmoplantar pustulosis (PPP), followed by plaque-type psoriasis, then guttate lesions. The increased incidence of PPP may be linked to a preponderance of TNF in eccrine sweat glands of affected individuals.⁴

Discontinuation of treatment or switching to a different anti-TNF agent or even using alternate therapies for psoriasis is often required to induce resolution of the psoriasiform eruption.⁴ New onset or exacerbation of psoriasis by TNF blockade appears to be a class effect and not a drug-specific reaction.

Correspondence: Dr Choate, Department of Dermatology, Yale University School of Medicine, 333 Cedar St, LCI 501, New Haven, CT 06520 (keith.choate@yale.edu).

Financial Disclosure: None reported.