Acute transverse myelitis during treatment with etanercept for severe plaque psoriasis
Authors: Juan Escalas, Nicole Knöpfel, Ana Martin-Santiago, Carmen Calles
Journal: Journal of the American Academy of Dermatology (2013)

To the Editor: Tumor necrosis factor alpha (TNF-α) inhibitors constitute a class of biologic treatments used in the management of psoriasis. Although these biologics have favored significant clinical improvement, there have been concerns for emerging side effects.1Rustin M.H. Long-term safety of biologics in the treatment of moderate-to-severe plaque psoriasis: review of current data.Br J Dermatol. 2012; 167: 3-11Crossref PubMed Scopus (89) Google Scholar We present a case of a patient with no prior history of demyelinating disease, who developed acute transverse myelitis (ATM) while being treated for chronic plaque psoriasis and psoriatic arthritis with etanercept. A 40-year-old woman with a 12-year history of psoriasis, treated with etanercept (50 mg weekly) for 21 months, presented with a 5-day history of paresthesias and muscular weakness that began over the lower extremities and gradually extended to the abdomen. The patient did not complain of any imbalance, gait disturbance, urinary or bowel incontinence, or any change in mental status. Neurologic examination revealed segmental sensory dysfunction with bilateral loss of pain and vibration sensation at levels C8-D1. The rest of the examination was unremarkable. Cerebrospinal fluid examination and laboratory results indicative of infectious or autoimmune cause were negative. Cranial magnetic resonance imaging (MRI) and visual evoked potentials were normal. MRI of the spinal cord revealed a hyperintense lesion at the third cervical (C3) level on T2-weighted images with intense contrast enhancement after gadolinium injection (Fig 1, A). Diagnosis of ATM was rendered. Etanercept was immediately discontinued and the patient was given intravenous methylprednisolone 1000 mg/day for 5 days in hospital. She was discharged with a short taper of prednisone, and clinical and imaging evaluation at 6 months showed complete resolution of ATM (Fig 1, B). The patient was started on ustekinumab, a human interleukin 12/23 monoclonal antibody. Treatment was successful with clearing of erythematous squamous lesions and no recurrence of neurologic symptoms or demyelination. TNF-α drugs have been used for the treatment of rheumatoid arthritis, psoriatic arthritis, psoriasis, ankylosing spondylitis, juvenile chronic arthritis, and Crohn's disease. Several studies have raised the possibility that TNF-α inhibitors may be associated with neurologic adverse events including central and peripheral nervous system demyelination.2Scheinfeld N. A comprehensive review and evaluation of the side effects of the tumor necrosis factor alpha blockers etanercept, infliximab and adalimumab.J Dermatolog Treat. 2004; 15: 280-294Crossref PubMed Scopus (281) Google Scholar In 2006, Sukal et al reported a case of demyelinating disease in a patient with psoriasis treated with etanercept.3Sukal S.A. Nadiminti L. Granstein R.D. Etanercept and demyelinating disease in a patient with psoriasis.J Am Acad Dermatol. 2006; 54: 160-164Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar Recently, Mahil et al published a review summarizing clinical data extracted on 65 reported cases of central nervous system demyelination in patients receiving TNF-α inhibitors.4Mahil S.K. Andrews T.C. Brierley C. Barker J.N. Smith C.H. Demyelination during tumour necrosis factor antagonist therapy for psoriasis: a case report and review of the literature.J Dermatolog Treat. 2013; 24: 38-49Crossref PubMed Scopus (20) Google Scholar Ustekinumab is a fully human monoclonal antibody against IL12/23 p40 approved for the treatment of moderate to severe plaque psoriasis. Targeting IL12/23 pathway has been examined for multiple sclerosis treatment in a phase 2 study.5Segal B.M. Constantinescu C.S. Raychaudhuri A. Kim L. Fidelus-Gort R. Kasper L.H. et al.Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: a phase II, double-blind, placebo-controlled, randomized, dose-ranging study.Lancet Neurol. 2008; 7: 796-804Abstract Full Text Full Text PDF PubMed Scopus (409) Google Scholar In our case, there was no clinical or laboratory finding indicative of any disease as the cause of ATM and given the temporal relationship, we considered the possibility of an adverse effect to etanercept. During follow-up, clinical indicators and MRI findings showed amelioration upon cessation of treatment. At present, the patient remains under treatment with ustekinumab at regular doses and maintains good clinical response without development of severe adverse effects. Given the uncertainty in this area, it seems reasonable to avoid the use of anti-TNF-α agents and offer an alternative regimen in patients with a personal or family history of demyelinating disease.