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Neuromyelitis Optica; Immunosuppression; Tuberculosis; Hepatitis B

Introduction

Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune demyelinating disorder of the CNS, involving clinical characteristics such as optic neuritis and/or transverse myelitis, and is frequently associated with antibodies to aquaporin 4 (AQP4) channels. The treatment of NMOSD, which includes high dose steroids during flares, and immunomodulatory medications for maintenance, may pose a risk for the reactivation of latent infections like tuberculosis (TB) and hepatitis B (HBV). Herein, we describe a case in which the management of a patient with NMOSD was carefully balanced with the management of latent TB and chronic HBV.

Case

A 54-year-old female with a past medical history of diabetes, heart failure, chronic HBV, latent TB, and AQP4+ NMOSD presented with burning, weakness, numbness, and paresthesia of her left side for three weeks. She was initially diagnosed with NMOSD in 1994 after her initial attack left her with no light perception visual acuity bilaterally. The patient also had a subsequent relapse in 2010 which led to significant weakness which had partially improved. The patient’s NMOSD at the time was managed with azathioprine 100 mg and prednisone 10 mg daily. It is not clear if the patient’s HBV or latent TB were known to her previous treatment team when she was placed on azathioprine and prednisone 10 mg per day. At the time of the subsequent presentation that we present here, the physical exam still demonstrated no light perception, visual acuity and nonreactive pupils. Extraocular movements were intact without ptosis. Facial sensation was diminished V1-V3 on the left to fine touch. Strength was 4/5 diffusely on the left side. Sensation was diminished on the left upper and lower extremity to fine touch and temperature. Reflexes were 3+ on the left.

Treatment with 1000 mg IV methylprednisolone (IVMP) was started empirically due to concern for an NMOSD relapse. Following this, MRI of the brain and spinal cord lacked new or enhancing lesions. Considering that this was most likely a pseudorelapse, IVMP was stopped on the second day. Laboratory studies confirmed latent TB with QuantiFERON Gold and chronic HBV with serology showing HBV core antibody positivity. Chest x-ray showed no signs of active TB. Other studies included a CBC, CMP, and abdominal ultrasound, which was unremarkable for any hepatic pathology other than steatosis.

Following this, the patient was prescribed entecavir 0.5 mg daily for chronic HBV and a 9-month course of isoniazid 300 mg daily and Vitamin B6 50 mg daily for her latent TB. She was discharged a week later, and azathioprine 100 mg daily was continued along with a short course of oral prednisone taper starting at 20 mg every other day.

On follow up one month after her hospitalization, the patient still complained of some weakness and numbness in her left side compared to her baseline. The patient denied any new neurological symptoms. The neurologic examination was unchanged. After this month of consistent treatment for her chronic HBV and latent TB, the patient was started on inebilizumab for maintenance therapy of NMOSD, and the azathioprine was discontinued.

Discussion

This case describes a patient who has received different types of NMOSD treatment in the setting of latent TB and chronic HBV. Careful consideration of the association between immunosuppressive drugs and the reactivation of these latent infections was made, even prior to the patient’s initial presentation. Specifically, there was consideration around the dose and duration of oral prednisone, IVMP, and how long the patient should be managed with entecavir and isoniazid prior to starting inebilizumab.

The 10 mg oral steroid regimen plus azathioprine 100 mg per day prior to hospitalization increased her risk for TB reactivation. In fact, the risk of TB was found to be significant for patients on oral prednisone doses as low as 7.5 mg a day [1]. Further, oral steroids of any dose for a duration longer than 7 days have shown to carry an increased risk of an HBV flare [2]. Despite the risk that her oral steroid regimen carried for an HBV flare, both prior to and after hospitalization, the patient avoided this. While we felt they were warranted while an NMOSD relapse was being ruled out, the short course of high dose IV steroids also carried a risk for reactivating TB. She received 1000 mg IVMP for 2 days prior to the patient’s unremarkable MRI. In a case report of a patient being treated with IVMP for anaphylaxis following a honeybee sting, the patient received a loading dose of 125 mg IVMP and 120 mg daily for three days and developed reactivation of their latent TB [3] . The risk of inebilizumab for reactivation of TB and chronic HBV was also considered. It is recommended that patients starting inebilizumab are screened for both TB and HBV, with active HBV and uncontrolled TB being an absolute contraindication for its use. Likely secondary to hypogammaglobulinemia, CD-19 targeting agents such as inebilizumab are likely to carry an increased risk for HBV reactivation although risk for TB with CD-19 targeting drugs like inebilizumab has not been fully explored [4]. Nevertheless, we considered one month of consistent use of entecavir and isoniazid as enough to consider these infections controlled. Future research should be focused on evaluating the risk of reactivation TB in patients taking inebilizumab while on isoniazid. Research should also be aimed at determining how inebilizumab affects the probability of HBV reactivation while concomitantly being managed with entecavir. Additional studies as such could help support case reports like this in further elucidating the complexities of treating NMOSD with immunosuppressants in the setting of latent TB and HBV.

Conclusion

Reactivation of HBV and latent TB are feared complications of steroid and biologic immunosuppressant use and should be carefully weighed when treating any autoimmune neurologic condition. Overall, this case report highlights a patient who received a variety of immunosuppressive medications for treatment of NMOSD, while also being successfully managed for chronic HBV and latent TB.

Conflict of Interest:

None of the authors have identified a conflict of interest.

Financial Disclosures:

The authors do not declare any financial disclosures.

1. Brassard P, Suissa S, Kezouh A, Ernst P (2011) . Am J Respir Crit Care Med 183:675-678.

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2. Wong GL, Wong VW, Yuen BW, et al. (2020) . J Hepatol 72:57-66.

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3. Patil S, Jadhav A (2019) . J Transl Int Med 7:39-42.

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4. Frampton JE (2020) . Drugs 80 :1259-1264. doi:10.1007/s40265-020-01370-4

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