BACKGROUND: Despite recent development of direct acting antivirals for treatment of hepatitis C, the current standard of care may still include pegylated-interferon, which is associated with frequent and, at times, serious adverse events.CASE PRESENTATION: Here we report for the first time on a severe case of classic neuromyelitis optica (i.e., optic-spinal form) in a 32 year-old Egyptian man with chronic hepatitis C treated with pegylated-interferon \u3b12a for 4 months.CONCLUSIONS: Treating physicians must be alerted on rare but important unexpected complications of interferon, in order to consider carefully its use especially when they deal with patients not in dire need of urgent treatment

A. Bandera

A. Gori

A. Soria

C. Ferrarese

D. Mangioni

L. Brighina

AIR Universita degli studi di Milano

Mangioni et al. BMC Pharmacology and Toxicology 2014, 15:56
http://www.biomedcentral.com/2050-6511/15/56CASE REPORT Open AccessA case of classic neuromyelitis optica (Devic’s
syndrome) triggered by pegylated-interferon α
Davide Mangioni1*, Alessandro Soria1, Laura Brighina2, Alessandra Bandera1, Carlo Ferrarese2 and Andrea Gori1Abstract
Background: Despite recent development of direct acting antivirals for treatment of hepatitis C, the current standard
of care may still include pegylated-interferon, which is associated with frequent and, at times, serious adverse events.
Case presentation: Here we report for the first time on a severe case of classic neuromyelitis optica (i.e., optic-spinal
form) in a 32 year-old Egyptian man with chronic hepatitis C treated with pegylated-interferon α2a for 4 months.
Conclusions: Treating physicians must be alerted on rare but important unexpected complications of interferon, in
order to consider carefully its use especially when they deal with patients not in dire need of urgent treatment.
Keywords: Adverse events, HCV, Neuromyelitis optica, Pegylated-interferonαBackground
Hepatitis C virus (HCV) chronically infects approximately
160 million people worldwide and ranks among the lead-
ing causes of liver disease. Even with recent licensing of
first-generation protease inhibitors, pegylated-interferon α
(Peg-IFNα) plus ribavirin remains the cornerstone of HCV
treatment, especially in genotype 1 and 4 HCV infection
[1]. Adverse events, including a number of neurological
and autoimmune conditions, may be treatment-limiting
and, rarely, life-threatening [2,3].
Case presentation
We report on a 32 year-old Egyptian man with chronic
hepatitis C (genotype 4) diagnosed on July 2012. His med-
ical history was otherwise unremarkable, particularly con-
cerning neurologic or autoimmune disease. On October
2012, following liver biopsy (which showed mild liver
disease: Ishak fibrosis 1) we began administering anti-
viral therapy with pegylated-interferon-α2a plus ribavi-
rin, obtaining an early virological response with no
significant side effects.
In early February 2013, after 12 weeks of therapy, the
patient complained about a rapid and progressive wors-
ening of vision in his left eye. An urgent ophthalmologist
examination diagnosed a retrobulbar optic neuritis, the* Correspondence: d.mangioni@campus.unimib.it
1Division of Infectious Diseases, Department of Internal Medicine, San
Gerardo Hospital, University of Milano-Bicocca, 20900 Monza, Italy
Full list of author information is available at the end of the article
© 2014 Mangioni et al.; licensee BioMed Cent
Commons Attribution License (http://creativec
reproduction in any medium, provided the or
Dedication waiver (http://creativecommons.or
unless otherwise stated.symptoms of which spontaneously resolved a few days
later. Two weeks after the onset of ocular symptoms, the
patient returned to the emergency room for acute lower
limb weakness accompanied by constipation and urinary
retention. Neurological examination showed no abnor-
malities, except for a bilateral lower limb hyposthenia.
Lumbar puncture revealed a moderate increase of the
cerebrospinal fluid (CSF) proteins and normal CSF glu-
cose, 15 leukocytes/μL (predominantly mononuclear), and
absence of oligoclonal bands; CSF cultures and virological
analyses were requested. As viral encephalitis was sus-
pected, the patient was admitted to the Infectious Diseases
ward, anti-HCV therapy was discontinued, and acyclovir
was started. A few days later, neurological examination
showed clear clinical deterioration, with flaccid paraplegia,
constipation, hypoesthesia from D10 down (including the
perineal region) and anesthesia below the knee. A spinal
cord magnetic resonance imaging (MRI) demonstrated
signs of longitudinally extensive transverse myelitis, affect-
ing the entire spinal cord and spreading upwards to the
lower regions of the medulla oblongata [Figure 1a].
The patient was then transferred to the Neurology
Department, as central nervous system (CNS) demyelin-
ating disease was now suspected. Based on negative CSF
cultures and virological analyses, acyclovir was stopped
and intravenous corticosteroid boluses were initiated. To
complete the diagnostic process we performed brain
MRI, electromyography and blood screening panel for
autoimmune diseases, all of which were normal. We alsoral Ltd. This is an Open Access article distributed under the terms of the Creative
ommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and
iginal work is properly credited. The Creative Commons Public Domain
g/publicdomain/zero/1.0/) applies to the data made available in this article,
Figure 1 Spinal cord MRI images before (a) and after (b) immunosuppressive treatment. a: Sagittal spinal cord MRI image demonstrating
signs of longitudinally extensive transverse myelitis that affects the entire spinal cord and spreads upwards to the lower regions of the medulla
oblongata. b: Sagittal spinal cord MRI image which shows a clear reduction of the areas with altered signal intensity.
Mangioni et al. BMC Pharmacology and Toxicology 2014, 15:56 Page 2 of 3
http://www.biomedcentral.com/2050-6511/15/56tested the presence of plasma Anti-aquaporin4 anti-
bodies (AQP4-Ab) which turned out to be positive, con-
firming the diagnosis of neuromyelitis optica (NMO). In
early March, due to lack of response to the high-dose ster-
oid therapy, the patient underwent therapeutic plasma-
pheresis, followed by intravenous immunoglobulin. Spinal
cord MRI showed a reduction of the areas with altered sig-
nal intensity [Figure 1b]; nonetheless, there was only a
modest clinical improvement. The patient then continued
steroid therapy with prednisone at immunosuppressive
dosages, and at late March he was transferred to the spinal
unit department to proceed with a rehabilitation program.
On July 2013, after 4 months of physiotherapy and steroid
treatment, the patient showed full recovery of sphincter con-
trol and had recommenced walking with assistance. At that
time he still suffered from a deficit in proprioceptive sensibil-
ity, as well as pronounced fatigability during movement.
Our examinations ruled out viral myelitis, neurological
complications of systemic diseases such as systemic lupus
erythematous (SLE), Sjogren’s syndrome and sarcoidosis
and atypical presentation of multiple sclerosis (MS). The
radiological findings on spinal cord MRI and, later, evi-
dence of AQP4-Ab confirmed the diagnosis of NMO.
Devic’s disease is an idiopathic autoimmune syndrome of
the CNS characterized by severe attacks of optic neuritis
and myelitis. Although the NMO phenotype can occur in
contexts of MS or several systemic autoimmune diseases, it
is considered a distinct syndrome, especially since the iden-
tification of the disease-specific antibody anti-aquaporin 4
(AQP4-Ab, or NMO-Ig) in more than 70% of patients with
Devic’s disease [4]. AQP4-Ab is thought to play a critical
role in producing the lesions by triggering an immune at-
tack against the aquaporine channel type 4, which is the
predominant water channel in the CNS and particularly
expressed in the optic nerves and spinal cord [5]. Thus,to our knowledge this is the first description of a severe
case of classic NMO (i.e., optic-spinal form) triggered
by Peg-IFNα.
We can infer that a prolonged exposure of the patient’s
immune system to the immunomodulatory activity of Peg-
IFNα could have broken the immune tolerance and started
an autoimmune reaction, eventually leading to the clinical
manifestations of the neuromyelitis optica. In support of our
inference, it has been observed that patients with auto-
immune and inflammatory diseases (mainly SLE, but also
reumatoid artrithis and MS) possess endogenous IFNα in-
ducers (immune complexes that activate natural IFNα pro-
ducing cells), which cause continuous IFNα production and
subsequent chronic stimulation of the immune system [6,7].
Conclusions
Worldwide, Peg-IFNα will likely remain a predominant
treatment for chronic hepatitis C over the next few years,
even though its side effects are sometimes unpredictable
and severe. We report this case in order to alert treating
physicians about rare but important unexpected complica-
tions of interferon. Those kind of life-threatening or long
term disabling side effects should be of concern, making it
advisable to achieve balance between benefits and risks of
IFNα-based regimen, especially in patients not in urgent
need of starting therapy, in the hopes that quick develop-
ment of (and broader access to) new tolerable directing-
acting antivirals will make IFNα-free therapy possible in a
near future.
Consent
Written informed consent was obtained from the patient
for publication of this Case report and any accompanying
images. A copy of the written consent is available for re-
view by the Editor of this journal.
Mangioni et al. BMC Pharmacology and Toxicology 2014, 15:56 Page 3 of 3
http://www.biomedcentral.com/2050-6511/15/56Abbreviations
HCV: Hepatitis C virus; Peg-IFNα: Pegylated-interferon α; CSF: Cerebrospinal
fluid; MRI: Magnetic resonance imaging; CNS: Central nervous system;
NMO: Neuromyelitis optica; AQP4-Ab: Antibody anti-aquaporin 4;
SLE: Systemic lupus erythematous; MS: Multiple sclerosis.
Competing interests
Financial competing interests:
This study was supported by Anlaids Sezione Lombarda.
Non-financial competing interests:
The authors declare that they have no competing interest.
Authors’ contribution
DM wrote the first draft. AS contributed to the manuscript preparation.
LB followed the patient in the neurology department and contributed to
the manuscript preparation. AB revised the manuscript. CF followed the
patient in the Neurology Department and revised the manuscript. AG
followed the patient in the Division of Infectious Diseases and revised the
manuscript. All authors read and approved the final manuscript.
Acknowledgments
We are grateful to Anlaids Sezione Lombarda for their continuous support.
Thanks to all the staff of the Division of Infectious Diseases, ward and
outpatient clinic.
Author details
1Division of Infectious Diseases, Department of Internal Medicine, San
Gerardo Hospital, University of Milano-Bicocca, 20900 Monza, Italy.
2Department of Neurology, San Gerardo Hospital, University of
Milano-Bicocca, Monza, Italy.
Received: 14 August 2014 Accepted: 24 September 2014
Published: 30 September 2014
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doi:10.1186/2050-6511-15-56
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A case of classic neuromyelitis optica (Devic's syndrome) triggered by pegylated-interferon α

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A case of classic neuromyelitis optica (Devic&apos;s syndrome) triggered by pegylated-interferon &#945;

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A case of classic neuromyelitis optica (Devic's syndrome) triggered by pegylated-interferon α