Herpes Zoster Precipitating First Attack of Neuromyelitis Optica along with Perinuclear Anti-Neutrophilic Cytoplasmic Antibody Positive Vasculitis

Sir

Neuromyelitis Optica spectrum disorder (NMOSD) is a crucial demyelinating astrocytopathy affecting young people with the propensity of devastating relapses.[1] NMOSD may be associated with systemic vasculitis with severe multiorgan failure.[2] Herpes zoster is a double-stranded DNA virus competently known to remain dormant inside the neural ganglia with a high activation potential in later life with varied manifestations.[3] In this case report, we describe a 32-year female presenting with dermatomal painful rash followed by features of asymmetric myelitis who was evaluated to identify longitudinally extensive transverse myelitis (LETM) with positive anti-aquaporin and perinuclear anti-neutrophilic cytoplasmic antibodies (p-ANCA). The association of such presentation is rare, and the exact pathogenesis is unknown.

This 32-year-old female presented with a painful itchy skin rash on the left shoulder and left side of neck for 1 month. It was followed 7 days later by acute-onset gradually progressive tingling and numbness in the left upper limb. After 4 days, she complained of weakness in left side of the body in the form of heaviness, initially in the upper limb and then to involve the lower limb over 48 hours. She complained of urinary incontinence for last 12 days. There is no history of headache, altered sensorium, seizures, fever, blurring of vision, diplopia, redness or eye discharge, abnormal sensations in the face, difficulty in chewing, speaking, hearing, swallowing, or change in voice. The history was negative for weight loss, jaundice, cough, night sweats, joint pain, hair loss, and photosensitivity. She has no history suggestive of diabetes, recent vaccination, contact with tuberculosis, similar illness, or any high-risk behavior.

Her general examination revealed a pulse of 78/min, regular, blood pressure of 116/74 mm Hg, respiratory rate 14/min, temperature of 98.7 F, regular built and nutrition, presence of pallor, without icterus, edema, clubbing, joint tenderness, thyroid swelling, or significant lymphadenopathy. Her skin examination revealed multiple 1 cm circular erythematous crusted lesions that were initially vesicular without umbilication over left cervical four dermatomal segment. Her nervous system examination revealed intact higher mental function, normal cranial nerve examination, including fundus and vision. Her motor system examination revealed spasticity in left limbs with the power of 4+/5 on the left side with hyperreflexia without clonus; the right side of the body was normal in examination. Her sensory analysis showed diminished sensations in the left upper and lower limbs with intact sensations on the right side. The rest of the nervous system examination was unremarkable. Other system examinations, including obstetric examination, were nonsignificant.

Her laboratorical evaluation revealed hemoglobin of 9.2 g/dL, leucocyte count 5800 cells/mm³, normal differential leucocyte count, platelet count 2.07 lac cells/mm³, microcytic-hypochromic picture, random blood glucose 87.3 mg/dL, normal liver and renal functions with normal electrolytes, Vitamin B12 340 pg/mL, folate 25.9 nmol/L, 25-OH vitamin D3 6 ng/mL, normal Angiotensin-converting enzyme levels, negative for HIV, HBsAg, Anti-HCV, and Covid-19 RTPCR tests. Cerebrospinal fluid (CSF) examination showed <5 cells/mm³, protein 23 mg%, and sugar 58.4 mg/dL. CSF was negative for Gram stain, fungal stain, Cartridge-based nucleic acid amplification test (CBNAAT), culture sensitivity, cryptococcal antigen, Japanese encephalitis, Ebstein bar virus, Enterovirus, Herpes Simplex 1 virus, Varicella Zoster virus IgM and IgG, measles virus, and Oligoclonal bands. Her electrophysiological tests revealed visual evoked potential of 111.2 in left eye and 116.6 in right eye, normal nerve conduction study of limbs including F-wave and H reflex. She underwent Magnetic Resonance Imaging study of the cervical spine, which revealed LETM from cervical spinal segment C1–T1 [Figure 1]. She came out to be strongly positive for anti-aquaporin-4 antibodies (titre 1:10 in cell-based assay) and negative for anti-myelin oligodendrocyte glycoprotein, anti-nuclear antibody titre of 1:160 (2+) homogenous pattern, and p-ANCA strongly positive with anti-c-ANCA negative report. Her brain and orbit imaging (MRI) were unremarkable. Her high-resolution computed tomography of chest was completely normal. The other causes of LETM, including toxic, neoplastic, chronic infection such as tuberculosis and sarcoidosis were ruled out.

Figure 1.

(a) Magnetic Resonance Imaging, study of cervical spine demonstrated longitudinally extensive transverse myelitis from cervical spinal segment C1 to T1, (b) On axial section, T2 weighted image hyperintensities in spinal cord, and (c) Post-Contrast sagittal view of cervical spine

She was diagnosed as NMO +ve LETM with p-ANCA +ve state precipitated by herpes zoster infection involving the C4 dermatome of left side. She was treated with pulse methylprednisolone, acyclovir therapy followed by immunomodulators (oral prednisolone and azathioprine) with supportive neuropathic drugs pregabalin, oxcarbazepine, and nutritional Vitamin D3 and iron supplementation. The patient improved drastically and was discharged with the power of 5/5 in all limbs, minimal sensory disturbance, and complete bladder recovery. She was followed 1 month later to find in the normal state of daily living.

DISCUSSION

Our case presented with left-sided C4 dermatomal zoster rash, followed by features of asymmetric myelitis and was evaluated in the line of LETM. The presence of anti-aquaporin-4 antibodies with detection of strongly positive p-ANCA in the background of LETM lead us to the unusual presentation of zoster infection manifesting first attack of NMOSD with systemic vasculitis that is rarely reported in literature. The exact etiopathogenesis of NMOSD is not wholly known.[4] It is postulated that autoimmune or infectious disorders can trigger its onset.[5] Autoimmune diseases, such as Systemic lupus erythematosus, Sjogren's syndrome, myasthenia gravis, etc., are important associations.[6] Some case reports suggest the development of NMOSD after infection with cytomegalovirus, dengue virus, herpes simplex virus, and varicella zoster virus.[7,8,9]

Infections, in general, can trigger autoimmune immunological phenomena by mechanism of epitope molecular mimicry and bystander activation, leading to stimulation of specific T-cells and B-cells to attack aquaporin-4-rich tissues of a mainly neural population. It is not known whether varicella zoster triggered the production of anti-aquaporin-4 antibodies along with p-ANCA antibodies or it precipitated LETM in the background of subclinical anti-aquaporin-positive sera. As per the international consensus diagnostic criteria for NMOSD, the patient fulfilled the initial two criteria (1 core criteria and positive anti-aquaporin antibody).[10]

Infections such as zoster and demyelinating disorders, such as NMOSD, vasculitis, etc. are the important treatable cause of LETM. In this case, herpes zoster infection precipitated the initial presentation of NMOSD in the presence of ANCA +ve vasculitis in the form of asymmetric LETM. The association of herpes zoster with NMOSD is not been well recognized in the past and further studies into such type of immunopathogenesis can explore the concept of para-infectious myelitis and demyelinating disorder of the nervous system. There should be awareness of such co-existent disorders for early diagnosis and better outcomes.

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Conflicts of interest

There are no conflicts of interest.