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Posterior reversible encephalopathy syndrome (PRES) in a patient taking adalimumab for spondyloarthritis
Joint Bone Spine 83 (2016) 243–244
Available online at
ScienceDirect www.sciencedirect.com
Letter to the Editor Posterior reversible encephalopathy syndrome (PRES) in a patient taking adalimumab for spondyloarthritis
a r t i c l e
i n f o
Keywords: Adalimumab Posterior reversible encephalopathy syndrome Spondyloarthropathy TNF␣ antagonist Pharmacovigilance
Posterior reversible encephalopathy syndrome (PRES) is a rare clinicoradiological entity [1,2]. The clinical manifestations consist of headaches, confusion, visual disturbances, convulsions, nausea, vomiting, and focal neurological deficits. Severe acute hypertension is a possible complication. Drug-induced cases of PRES have been reported. Here, we report the third case of PRES during TNF␣ antagonist therapy. This 58-year-old woman diagnosed with spondyloarthritis at 35 years of age was taking a nonsteroidal anti-inflammatory drug and methotrexate (20 mg/week). She had well-controlled hypertension. Persistent activity of her spondyloarthritis prompted the introduction of adalimumab; her Quantiferon-TB test was negative and she had no evidence of demyelinating disease. One month later, she started experiencing headaches, unsteadiness, horizontal diplopia, and vomiting. The physical examination showed a postural tremor of the upper limbs, brisk deep tendon reflexes, and an extensor plantar reflex on the right. She had no focal neurological deficit. Her blood pressure was 140/90 mmHg. Her peripheral blood cell counts were normal and she had no evidence of systemic inflammation. Findings were negative from blood cultures and from serological tests for HIV, HBV, HCV, CMV, EBV, and Lyme disease. Tests for antinuclear antibodies were negative. Cerebrospinal fluid examination showed 49 lymphocytes, 0.86 g/L protein, and a normal glucose level. PCR assays were negative for JC papovavirus, CMV, HSV, EBV, and VZV. No anti-TNF antibodies were detected. Magnetic resonance imaging (MRI) showed supra- and infratentorial white matter disease with involvement of both superior cerebellar peduncles, manifesting as low signal on T1 images and high signal on T2 images (Fig. 1). Diffusion-weighted imaging and spectroscopy were normal. A diagnosis of PRES was given. Both the timing of symptom onset in our patient and previous reports of PRES during TNF␣ antagonist therapy [3,4] strongly suggested a causal relationship with adalimumab, which was stopped. The clinical manifestations were
Fig. 1. Magnetic resonance imaging, FLAIR sequence, before adalimumab discontinuation.
resolved and follow-up MRI performed 2 weeks after treatment discontinuation was normal. At last follow-up 2 years later, she had no evidence of further neurological manifestations. This is the first reported case of PRES during adalimumab therapy. The MRI findings ruled out a cerebrovascular accident, infectious encephalitis, vasculitis, and multiple sclerosis. In PRES, an early MRI finding is non-ischemic edema of the white matter, often in a symmetrical distribution. The sensitivity of MRI can be increased by using FLAIR sequences. Diffusion-weighted imaging differentiates vasogenic edema (normal or elevated apparent diffusion coefficient) from cytotoxic edema (very low apparent diffusion coefficient). The parietal and occipital regions are common sites of involvement, whereas the cerebellum is less often affected [3]. The pathophysiological mechanisms are unclear, particularly in drug-induced cases. Neurotoxic effects and alterations in the blood-brain barrier have been suggested. The drugs incriminated to date include cyclosporin and anti-cancer drugs (cytarabine, cisplatin, gemcitabine). Two cases during TNF␣ antagonist therapy have been reported: one in a male taking etanercept for rheumatoid arthritis [5] and another in an 8-year-old girl taking infliximab for Crohn’s disease. The time from TNF␣ antagonist initiation to symptom onset was 2 weeks and 2 months in these patients, respectively. The MRI returned to normal within 3 months after bolus glucocorticoid therapy in the male with rheumatoid arthritis and within 1 year after infliximab discontinuation in the girl with Crohn’s disease. Both patients recovered fully, in agreement with the course in our case. The girl with Crohn’s disease experienced seizures and neurodevelopmental delay during the first year but was free of neurological abnormalities after 2 years. PRES is a serious potential complication of TNF␣ antagonist therapy that can be life threatening or cause residual impairments.
http://dx.doi.org/10.1016/j.jbspin.2015.08.002 1297-319X/© 2015 Published by Elsevier Masson SAS on behalf of the Société Française de Rhumatologie.
244
Letter to the Editor / Joint Bone Spine 83 (2016) 243–244
The early clinicoradiological diagnosis of PRES is crucial to allow immediate discontinuation of the TNF␣ antagonist. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Monteiro ML, Hoyt WF, Imes RK. Puerperal cerebral blindness. Transient bilateral occipital involvement from presumed cerebral venous thrombosis. Arch Neurol 1984;41:1300–1. [2] Hinchey J, Chaves C, Appignani B, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996;334:494–500. [3] Schwartz RB. Hyperperfusion encephalopathies: hypertensive encephalopathy and related conditions. Neurologist 2002;8:22–34. [4] Haddock R, Garrick V, Horrocks I, et al. A case of posterior reversible encephalopathy syndrome in a child with Crohn’s disease treated with infliximab. J Crohns Colitis 2011;5:623–7. [5] Kastrup O, Diener HC. TNF-antagonist etanercept induced reversible posterior leukoencephalopathy syndrome. J Neurol 2008;255:452–3.
Thibault Mahévas a Olivier Lidove a Salim Ahmed Yahia b Salhi Hayet c Bernadette Xerri-Campano a Jean-Marc Ziza a,∗ a Service de rhumatologie-médecine interne, groupe hospitalier Diaconesses-Croix-Saint-Simon, 125, rue d’Avron, 75020 Paris, France b Service de rhumatologie, hôpital Henri-Mondor, 94000 Créteil, France c Service de neurologie, hôpital Henri-Mondor, 94000 Créteil, France ∗ Corresponding author. E-mail address: [email protected] (J.-M. Ziza)
Accepted 3 March 2015 Available online 21 October 2015
Available online at
ScienceDirect www.sciencedirect.com
Letter to the Editor Posterior reversible encephalopathy syndrome (PRES) in a patient taking adalimumab for spondyloarthritis
a r t i c l e
i n f o
Keywords: Adalimumab Posterior reversible encephalopathy syndrome Spondyloarthropathy TNF␣ antagonist Pharmacovigilance
Posterior reversible encephalopathy syndrome (PRES) is a rare clinicoradiological entity [1,2]. The clinical manifestations consist of headaches, confusion, visual disturbances, convulsions, nausea, vomiting, and focal neurological deficits. Severe acute hypertension is a possible complication. Drug-induced cases of PRES have been reported. Here, we report the third case of PRES during TNF␣ antagonist therapy. This 58-year-old woman diagnosed with spondyloarthritis at 35 years of age was taking a nonsteroidal anti-inflammatory drug and methotrexate (20 mg/week). She had well-controlled hypertension. Persistent activity of her spondyloarthritis prompted the introduction of adalimumab; her Quantiferon-TB test was negative and she had no evidence of demyelinating disease. One month later, she started experiencing headaches, unsteadiness, horizontal diplopia, and vomiting. The physical examination showed a postural tremor of the upper limbs, brisk deep tendon reflexes, and an extensor plantar reflex on the right. She had no focal neurological deficit. Her blood pressure was 140/90 mmHg. Her peripheral blood cell counts were normal and she had no evidence of systemic inflammation. Findings were negative from blood cultures and from serological tests for HIV, HBV, HCV, CMV, EBV, and Lyme disease. Tests for antinuclear antibodies were negative. Cerebrospinal fluid examination showed 49 lymphocytes, 0.86 g/L protein, and a normal glucose level. PCR assays were negative for JC papovavirus, CMV, HSV, EBV, and VZV. No anti-TNF antibodies were detected. Magnetic resonance imaging (MRI) showed supra- and infratentorial white matter disease with involvement of both superior cerebellar peduncles, manifesting as low signal on T1 images and high signal on T2 images (Fig. 1). Diffusion-weighted imaging and spectroscopy were normal. A diagnosis of PRES was given. Both the timing of symptom onset in our patient and previous reports of PRES during TNF␣ antagonist therapy [3,4] strongly suggested a causal relationship with adalimumab, which was stopped. The clinical manifestations were
Fig. 1. Magnetic resonance imaging, FLAIR sequence, before adalimumab discontinuation.
resolved and follow-up MRI performed 2 weeks after treatment discontinuation was normal. At last follow-up 2 years later, she had no evidence of further neurological manifestations. This is the first reported case of PRES during adalimumab therapy. The MRI findings ruled out a cerebrovascular accident, infectious encephalitis, vasculitis, and multiple sclerosis. In PRES, an early MRI finding is non-ischemic edema of the white matter, often in a symmetrical distribution. The sensitivity of MRI can be increased by using FLAIR sequences. Diffusion-weighted imaging differentiates vasogenic edema (normal or elevated apparent diffusion coefficient) from cytotoxic edema (very low apparent diffusion coefficient). The parietal and occipital regions are common sites of involvement, whereas the cerebellum is less often affected [3]. The pathophysiological mechanisms are unclear, particularly in drug-induced cases. Neurotoxic effects and alterations in the blood-brain barrier have been suggested. The drugs incriminated to date include cyclosporin and anti-cancer drugs (cytarabine, cisplatin, gemcitabine). Two cases during TNF␣ antagonist therapy have been reported: one in a male taking etanercept for rheumatoid arthritis [5] and another in an 8-year-old girl taking infliximab for Crohn’s disease. The time from TNF␣ antagonist initiation to symptom onset was 2 weeks and 2 months in these patients, respectively. The MRI returned to normal within 3 months after bolus glucocorticoid therapy in the male with rheumatoid arthritis and within 1 year after infliximab discontinuation in the girl with Crohn’s disease. Both patients recovered fully, in agreement with the course in our case. The girl with Crohn’s disease experienced seizures and neurodevelopmental delay during the first year but was free of neurological abnormalities after 2 years. PRES is a serious potential complication of TNF␣ antagonist therapy that can be life threatening or cause residual impairments.
http://dx.doi.org/10.1016/j.jbspin.2015.08.002 1297-319X/© 2015 Published by Elsevier Masson SAS on behalf of the Société Française de Rhumatologie.
244
Letter to the Editor / Joint Bone Spine 83 (2016) 243–244
The early clinicoradiological diagnosis of PRES is crucial to allow immediate discontinuation of the TNF␣ antagonist. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Monteiro ML, Hoyt WF, Imes RK. Puerperal cerebral blindness. Transient bilateral occipital involvement from presumed cerebral venous thrombosis. Arch Neurol 1984;41:1300–1. [2] Hinchey J, Chaves C, Appignani B, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996;334:494–500. [3] Schwartz RB. Hyperperfusion encephalopathies: hypertensive encephalopathy and related conditions. Neurologist 2002;8:22–34. [4] Haddock R, Garrick V, Horrocks I, et al. A case of posterior reversible encephalopathy syndrome in a child with Crohn’s disease treated with infliximab. J Crohns Colitis 2011;5:623–7. [5] Kastrup O, Diener HC. TNF-antagonist etanercept induced reversible posterior leukoencephalopathy syndrome. J Neurol 2008;255:452–3.
Thibault Mahévas a Olivier Lidove a Salim Ahmed Yahia b Salhi Hayet c Bernadette Xerri-Campano a Jean-Marc Ziza a,∗ a Service de rhumatologie-médecine interne, groupe hospitalier Diaconesses-Croix-Saint-Simon, 125, rue d’Avron, 75020 Paris, France b Service de rhumatologie, hôpital Henri-Mondor, 94000 Créteil, France c Service de neurologie, hôpital Henri-Mondor, 94000 Créteil, France ∗ Corresponding author. E-mail address: [email protected] (J.-M. Ziza)
Accepted 3 March 2015 Available online 21 October 2015