chronic inflammatory demyelinating polyneuropathy following treatment with peglated interferon 2a for chronic hepatitis c virus infection

Letters to Editor Access this article online Quick Response Code: Website: www.neurologyindia.com PMID: *** DOI: 10.4103/0028-3886.76883 Received: 17-11-2010 Review completed: 08-12-2010 Accepted: 20-12-2010 Chronic inflammatory demyelinating polyneuropathy following treatment with peglated interferon α-2a for chronic hepatitis C virus infection Sir, The etiopathogenisis of chronic inflammatory demyelinating polyneuropathy (CIDP) is unknown yet Peglated interferon α-2a is an antiviral biological agent, which is widely used to treat chronic viral hepatitis Although neurological complications such as myasthenia gravis, axonal neuropathy, and central nervous system demyelination have been reported[1,2] during interferon-α therapy, CIDP is rarely reported Here, we report a patient with chronic hepatitis C virus (HCV) infection, who developed CIDP during treatment with Peglated interferon α-2a A 47-year-old man, who was a diagnosed case of chronic HCV infection in October 2009, was commenced on Peglated interferon α-2a treatment 180 µg subcutaneously once a week in March 2010 After months of antiviral treatment (in May 2010), he developed numbness and weakness of both lower and upper limbs gradually He received Vitamin B12 treatment, but with no improvement He discontinued Peglated treatment in June 2010, but his neurological symptoms deteriorated gradually He presented to us with motor weakness (4/5 grade) of all the four limbs Deep tendon reflexes were absent Both hands were dry and rough and hand nails were fragile Hypoesthesia was noted in the outer part of the lower legs Cerebrospinal fluid (CSF) was clear, with normal pressure (120 mmH2O), leukocytes/mm3, normal glucose (4.2 mmol/L) and chloride (120 mmol/L), and elevated protein (2.0 g/L) Nerve conduction studies revealed reduced conduction velocity in both the median nerves, conduction block in both median nerves and left Neurology India | Jan-Feb 2011 | Vol 59 | Issue ulnar nerves, prolonged F-wave latency in left ulnar nerve, reduced F-wave frequency in both ulnar nerves, and no H reflex in left tibial nerve [Tables 1-3] Clinical features, electrodiagnostic studies, and CSF findings supported the diagnosis of CIDP [3] He was started on intravenous 10 mg/day Dexamethasone treatment for days, followed by 50 mg/day oral prednisone He did not show any improvement with this treatment for weeks He was started on intravenous immunoglobulin (0.4 g/kg for days), with which he showed marked improvement in his muscle power over the next weeks The patient was discharged with nearly normal muscle power This patient had CIDP and the possible etiology could be the following: HCV infection related, Peglated treatment complication, and Peglated triggered CIDP Interferon α-2a is a broad-spectrum antiviral agent The Table 1: Motor nerve conduction studies Motor nerve Left medianus Wrist-Left APB Elbow-wrist Right medianus Wrist-APB Elbow-wrist Left peroneus Ankle-EDB Fib head-ankle Ab knee-Fib Right peroneus Ankle-EDB Fib head-ankle Ab knee-Fib Left ulnaris Wrist-ADM BL.elbow-wrist Right ulnaris Wrist-ADM BL.elbow-wrist Lat (ms) Amp (mv) CV (m/s) 3.3 8.0 6.4 0.45↓ 3.6 12.5 7.1 2.5↓ 25.5↓ 3.3 9.0 10.6 9.5 8.9 8.7 50.5 56.3 3.8 9.5 11.4 6.4 6.4 6.4 49.6 48.9 2.6 5.8 9.5 2.3 2.5 5.5 8.4 7.1 F (ms) 43.6↓ 23.8, 100% 23.5, 60% 70.9 18.9, 40% 64.3 Table 2: Sensory nerve conduction studies Sensory nerve Left medianus Dig III-wrist Right medianus Dig III-wrist Left peroneus superfic Calf-med Dor Cuton Right peroneus superfic Calf-med Dor Cuton Peak lat (ms) Amp (uv) CV (m/s) 2.8 8.7 65.4 2.4 9.3 66.7 1.96 15.7 51 2.3 13.5 49.6 Table 3: H-reflex Tibialis H reflex Knee-soleus Left Right M-lat (ms) H-lat (ms) 4.0 4.2 34.6 H/M Amp 0.062 141 Letters to Editor common side effects include fever flu-like symptom, myelosuppression and autoimmune diseases such as thyroiditis, thrombocytolytic, rheumatoid symptoms, systemic lupus erythematosus, type I diabetes.[4-8] These symptoms subside following the withdrawal of the medicine Neurological complications such as myasthenia gravis, autonomic neuropathy sensory neuropathy, chronic inflammatory demyelinating neuropathy (CIDP) and acute inflammatory demyelinating neuropathy (AIDP) are rare Two cases of AIDP have been reported in association with peglated interferon α-2a therapy for chronic hepatitis B and C virus infection.[9,10] Makoto Hirotai[11] reported one case of chronic HCV infection, who developed weakness and numbness of all the four limbs during treatment with Peglated The pathogenesis of CIDP is not fully understood; dendritic cells (DCs) probably play an important role in the pathogenesis of CIDP DCs are antigen-presenting cells (APCs) which play a critical role in the regulation of the adaptive immune response DCs are unique APCs and only DCs have the ability to induce a primary immune response in resting naïve T lymphocytes Studies by Salomon et al.[12] suggested that autoimmune diabetes-prone diabetes mouse, deficient in B7-2 costimulation, was protected from developing diabetes but developed spontaneous autoimmune peripheral polyneuropathy The spontaneous autoimmune peripheral polyneuropathy in these mice had many similarities to CIDP in humans Press et al.[13] reported the presence of antigen-loaded DCs in the CSF of patients with CIDP Probably these antigen-loaded DCs then may enter CSF-draining lymphatic vessels and travel to regional lymph nodes, where matured DCs interact with T and B cells to induce and modulate myelin-reactive T and B cell responses, whereas interferon-α could promote maturity of peripheral blood monocyte-derived DCs.[14] These findings suggest that interferon-α probably activates T and B cells via DCs, resulting in CIDP In conclusion, though rare, interferon-α treatment may cause CIDP Since interferon-α is widely used for the treatment of chronic hepatitis C and B virus infections, physicians should be aware of the side effect so that an early diagnosis and treatment can be initiated References 10 11 12 13 14 Konoshi T A case of myasthenia gravis which developed myaesthenic crisis after alpha-interferon therapy for chronic hepatitis C Rinsho Shinkeigaku 1996;36:980-5 Höftberger R, Garzuly F, Dienes HP, Grubits J, Rohonyi B, Fischer G, et al Fulminant central nervous system demyelination associated with interferon-α therapy and hepatitis C virus infection Mult Scler 2007;13:1100-6 Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) Report from an Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force Neurology 1991;41:617-8 Russo MW, Fried MW Side effects of therapy for chronic hepatitis C Gastroenterology 2003;124:1711-9 Tosti A, Misciali C, Bardazzi F, Fanti PA, Varotti C Telogen effluvium due to recombinant interferon alpha-2b Dermatology 1992;184:124-5 Formann E, Stauber R, Denk DM, Jessner W, Zollner G, Munda-Steindl P, et al Sudden hearing loss in patients with chronic hepatitis C treated with peglated interferon/ribavirin Am J Gastroenterol 2004;99:873-7 Kawano T, Shigehira M, Uto H, Nakama T, Kato J, Hayashi K, et al Retinal complications during interferon therapy for chronic hepatitis C Am J Gastroenterol 1996;91:309-13 Meriggioli MN, Rowin J Chronic inflammatory demyelinating polyneuropathy after treatment with interferon-alpha Muscle Nerve 2000;23:433-5 Khiani V, Kelly T, Shibli A, Jensen D, Mohanty SR Acute inflammatory demyelinating polyneuropathy associated with pegylated interferonα-2a therpaty for chronic hepatitis C virus infection World J Gastroenterology 2008;14:318-21 Boz C, Ozmenoglu M, Aktoz G, Velioglu S, Alioglu Z Guillain-Barre syndrome during treatment with interferon α for hepatitis B J Clin Neurosci 2004;11:523-5 Hirotani M, Nakano H, Ura S, Yoshida K, Niino M, Yabe I, et al Chronic inflammatory demyelinating polyneuropathy after treatment with interferon-α Intern Med 2009;48:373-5 Salomon B, Rhee L, Bour-Jordan H, Hsin H, Montag A, Soliven B, et al Development of spontaneous autoimmune peripheral polyneuropathy in B7-2-deficient NOD mice J Exp Med 2001;194:677-84 Press R, Nennesmo I, Kouwenhoven M, Huang YM, Link H, Pashenkov M Dendritic cells in the cerebrospinal fluid and peripheral nerves in Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy J Neuroimmunol 2005;159:165-76 Radvanyi LG, Banerjee A, Weir M, Messner H Low levels of interferonalpha induce CD86 (B7.2) expression and accelerates dendritic cell maturation from human peripheral blood mononuclear cells Scand J Immunol 1999;50:499-509 Access this article online Quick Response Code: PMID: *** DOI: 10.4103/0028-3886.76885 Chang Ying, Han Xue-mei, Gao Yao, Liu Song-yan Department of Neurology, China-Japan Union Hospital, Jinlin University, Changchun,130033, China E-mail: yan1966@163.com 142 Website: www.neurologyindia.com Received: 14-01-2011 Review completed: 14-01-2011 Accepted: 15-01-2011 Neurology India | Jan-Feb 2011 | Vol 59 | Issue Copyright of Neurology India is the property of Medknow Publications & Media Pvt Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use  ... cells via DCs, resulting in CIDP In conclusion, though rare, interferon- α treatment may cause CIDP Since interferon- α is widely used for the treatment of chronic hepatitis C and B virus infections,... demyelination associated with interferon- α therapy and hepatitis C virus infection Mult Scler 2007;13:1100-6 Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) Report... acute inflammatory demyelinating neuropathy (AIDP) are rare Two cases of AIDP have been reported in association with peglated interferon α -2a therapy for chronic hepatitis B and C virus infection. [9,10]