Bell’s palsy during interferon alpha 2a treatment in a case with Behçet uveitis

Introduction

Interferon alpha 2a is a recombinant biological agent that is used for the treatment of several diseases including chronic hepatitis C, hairy cell leukemia, Philadelphia chromosome positive chronic myelogenous leukemia (CML) and AIDS-related Kaposi’s sarcoma. It is also used in Behçet uveitis that is refractory to conventional immunosuppressive agents^1,2. The central (CNS) and peripheral nervous system (PNS) can be affected while using interferon alpha 2a. There are two existing case reports describing Bell’s palsy associated with interferon treatment for chronic hepatitis C infection^3,4. Here we present another case report indicating Bell’s palsy during interferon alpha 2a treatment in Behçet uveitis.

Case report

A 27-year old Turkish, male, taxi driver who has Behçet’s Disease was referred to our clinic for a decrease in visual acuity in his right eye for 2 days. At presentation, the best-corrected visual acuity was 20/320 in his right eye and 20/20 in his left eye. On slit lamp examination, there were keratic precipitates, anterior chamber cells and vitreous cells in his right eye. Fundus examination revealed optic disc edema, macular edema and abundant intraretinal hemorrhages in the inferior temporal part of retina. His left eye seemed to be normal. Optical coherence tomography (Cirrus HD-OCT Model 4000, Carl Zeiss Meditec) (OCT) and fluorescein angiography (FA) was then performed. Central macular thickness (CMT) was 595 µm on OCT. In FA, there was mild hyperfluorescence on both optic discs. In addition, hypofluorescence in the inferior retinal areas due to hemorrhages and staining on the vessel walls in right eye was spotted. Macular edema and peripheral ischemia were also evident. A diagnosis of panuveitis with inferior temporal branch retinal vein occlusion due to Behçet’s Disease was made.

Firstly, high dose steroids (1 gram/day methylprednisolone, intravenously) were prescribed to the patient for 3 days. Dexamethasone eye drops every hour during the day and topical cyclopentolate 1% three times a day were also prescribed. On the third day, the anterior chamber reaction seemed to be decreased but no improvement was observed, either in the vitreous inflammation or the macular edema. As such, the initial high dose steroid treatment was stopped and interferon alpha 2a (Roferon-A, Roche Pharmaceuticals, Hoffmann-La Roche Inc., Switzerland) 4.5 million IU (MIU) subcutaneously on alternate days and 10 mg/day oral prednisolone were prescribed to the patient. At that point, we had decided upon interferon treatment because the patient was young and the first ocular presentation of Behçet’s disease was seriously threatening in terms of visual prognosis. In addition, green argon laser photocoagulation was applied to the ischemic areas of the retina.

The patient was examined weekly for the first month in order to observe the effects of treatment closely. After this, the follow-up was done monthly. In the first month, steroid treatment was tapered slowly and stopped while interferon treatment was continued. In the first 6 months, no adverse effects were observed, best corrected visual acuity improved to 20/32 and the panuveitis and macular edema regressed. CMT was 230 µm after the 6-months of interferon alpha 2a therapy. There were no signs of anterior uveitis or vitreous inflammation. The patient’s oral aphthae, genital ulcers and arthralgia (symptoms of Behçet’s Disease) were also improved. At this stage, the dose of interferon alpha 2a was tapered to 3 MU on alternate days.

One month after tapering the dose, the patient experienced difficulty in closing his right eyelid and stiffness in the right half of his face. His wife also reported that there had been no movement on the right side of his face for about 15 days. There was no history of trauma, infection, cold exposure or any other predisposing factors that might have explained this situation. The patient was tested for several viral infections including herpes viruses, cytomegalovirus (CMV) and Epstein-Barr virus (EBV). All tests were negative. Afterwards, in order to eliminate neurological problems such as brain tumor, stroke or neuro-Behçet disease, the patient was immediately referred to our neurology service. Cranial MRI was normal and the neurological evaluation revealed no pathological findings apart from facial paralysis. As such the patient was diagnosed with Bell’s palsy. Interferon use was considered as a possible reason for this condition and so interferon treatment was tapered and discontinued. Mycophenolate mofetil (720 mg/day, oral) was prescribed for Behçet’s disease because the patient had previously experienced nausea and vomiting with azathioprine, which had been prescribed before as an initial therapy for Behcet’s disease by a rheumatologist. Oral methylprednisolone 48 mg per day was prescribed by the neurologist and gradually tapered (8 mg per week) over 6 weeks. In addition, a program of exercises for the facial muscles was recommended. All symptoms of Bell’s palsy disappeared within 2 months of onset.

Discussion

There is a wide variety of adverse effects due to the use of interferon alpha 2a, including flu-like syndrome (unusual tiredness, fever, chills, muscle aches, and joint pain), injection site reaction (redness, pain at the site of injection), proneness to serious infections, new or worsening autoimmune disease^5–7, myelosuppression^8,9, depression, suicide, suicidal thoughts, and cardiovascular problems^10,11 such as hypotension or hypertension, arrhythmia and myocardial infarction. Patients may also suffer from nausea, vomiting, loss of appetite, diarrhea, cough, dry mouth, dizziness, vertigo, sweating, itching, hair loss, fatigue, abdominal pain, constipation, sore throat, insomnia¹², anxiety and numbness.

Interferon alpha 2a also affects the CNS and PNS. Difficulty of concentration and aggression are the most common CNS problems. Decrease in mental activity, dysphasia, dysarthria, aphasia, aphonia, amnesia, multiple sclerosis-like disease¹³, transient ischemic attacks, encephalopathy, confusion, somnolence and coma may also occur during the use of interferon. It is also known that several symptoms such as ataxia, paresthesia, tremor and peripheral neuropathies^14–18 can be seen if the PNS is affected. In our patient, we encountered Bell’s palsy, a peripheral neuropathy affecting the facial nerve in the 7^th month of interferon therapy. No elucidating factors but interferon were present at the time we diagnosed the patient. Hitherto, there have been two other reports of Bell’s palsy related to the use of interferon^3,4. So it was important for us to call attention to our case as an example of a rare complication of interferon use. In conclusion, physicians should always keep an eye on patients who are being treated with interferon alpha 2a. Physicians should be alert to the rare side effects of interferon treatment as well as the more common and well-known side effects of this agent.

Consent

Written informed consent for publication of his clinical details was obtained from the patient.