HSV2 reactivation and myelitis following influenza vaccination

ABSTRACT

We report the case of a 57 year-old woman who developed transverse myelitis and acute HSV-2 reactivation following influenza vaccination. Over the next 5 years, she experienced a fluctuating course of improvement and regression for both myelitis and herpes.

KEYWORDS:

• herpes simplex virus 2 (HSV-2)
• influenza vaccination
• myelitis

Introduction

Herpesvirus 2 (HSV2) is a common chronic viral infection affecting about 16–22% of the adult US population.^1,2 HSV-2 reactivation with adverse symptoms occurs in about 89% of people with primary HSV-2 infection with a median recurrence rate of about 4 per year.² Although many infected individuals are asymptomatic, HSV-2 causes considerable morbidity in many individuals and can cause life threatening infections in neonates and those with compromised immune symptoms.¹ HSV-2 viruses can remain latent in many nerves (especially the sacral nerves), and periodically flare up with viral shedding which may be asymptomatic or associated with symptoms.^3,4

Many factors can increase the risk of HSV-2 reactivation such as stress, fatigue, sun exposure, surgery, infection, fever, and menstrual periods.⁵ A study of 457 consecutive patients with HSV-2 isolated from genital lesions reported that patients who had primary HSV-2 infections lasting 35 or more days had a recurrence rate 1.83 times greater than those who had shorter initial HSV-2 infections (mean 0.66 vs 0.36 recurrences month, p = 0.001).² HSV-2 reactivation rates were also about 20% higher in men than women.²

This case report describes a 62 year-old woman who developed severe HSV-2 reactivation symptoms following influenza vaccination 5 y earlier.

Patient presentation

The patient is a 62 year-old female of English/French/German descent. Her childhood was generally healthy with several childhood infections including varicella at age 8 years, measles at 9, and mumps at 10. Patient had herpes HSV-2 at 24 y of age with blisters on back lasting about 2 months. The patient had back surgery for herniated disk at age 25 y. She married at age 30 and had 2 healthy sons at age 31 and 34 y. At age 43, the patient reinjured her back and had head pressure which was later diagnosed as pseudotumor cerebri. Also at age 43, she had ventriculoperitoneal shunts placed on left side to relieve pressure with some relief. At age 51, the patient went through menopause after losing 80 pounds on a low-carbohydrate diet.

On October 15, 2010 (age 57) she received an influenza vaccination Fluvirin® which contained 15 µg of hemagglutinin from each of 3 viruses A/California/7/2009, NYMC X-181 (H1N1), A/Victoria/210/2009, NYMC X-187 (H3N2), and B/ Brisbane/60/2008 plus thimerosal- 25 µg Hg per dose. Five hours after receiving flu shot she had “hot liquid fluid feeling” all over left side and her left side started vibrating severely. She developed 7 severe HSV-2 blisters on her back and many bouts of migraine headaches. Had swelling of left arm and legs, abnormal vibrations, and “pins and needles” most troubling on left side especially the left head, and fluttering sensations controlled by atenolol. Condition was later diagnosed as transverse myelitis. Had food poisoning on March 2011 with bad herpes blister breakout. A peripheral nerve conduction study on 6/27/11 was essentially normal apart from a slightly reduced right sural sensory amplitude.

Seen by author (AL) first on 7/28/11. Physical exam was generally unremarkable except for wobbly Romberg, pressure and pain on left side- especially left brain region, also pain on medial portion of right leg. On 7/28/11 patient tested positive for neural antibodies to both central nervous system (CNS) (IgA+ IgG) myelin and peripheral nervous system (PNS) myelin (IgA & IgG). She was treated with a variety of drugs over varying periods of time including lorazepam (1 mg QPM PRN), interferon-α (1 ml of 150 U/ml 3 times a week), trazadone 50 mg QD, and low dose naltrexone (2.25 to 4.5 mg).

Her HSV-2 titres (>1.09 considered positive) were as follows: 48.1 on 7/28/11, 5.93 on 1/11/12, 3.7 on 2/21/12, 3.56 on 7/25/12, 3.5 on 8/6/12, and 14.3 on 9/14/15. HSV-1 were negative (<0.91) on 7/28/11.

Over the next 3 y and 10 months, the patients’ medical course fluctuated with the neuropathy and herpes symptoms improving and regressing. Spine MRI in March 2013- noted mild to moderate degenerative disk disease and mild degenerative retrolisthesis of L3 on L4 and L4 on L5. By May 2016, she still had considerable left sided pain and numbness, left extremity edema, and chronic fatigue.

Discussion and conclusion

To the best of our knowledge, this is the first reported case of severe HSV-2 activation with transverse myelitis developing after influenza vaccination. Both the influenza vaccination and HSV-2 reactivation could be potential triggers for the development of myelitis. Myelitis is an uncommon complication in influenza vaccination, with a literature review of cases published between 1979 to 2013 noting 9 cases of myelitis developing after influenza immunization.⁶ A recent case study described a 41 y old man who developed transverse myelitis following influenza immunization.⁷ Acute myelitis can also occur occasionally after polio or HPV vaccination.^6,8 Long term myelitis can also develop following acute HSV-2 infection. One case series reported 7 patients who developed myelitis with paraplegia or tetraplegia following acute HSV-2 infection; all were treated with antiviral therapy but only 2 made a substantial recovery.⁹

Antiviral drugs are the mainstay of treating acute infections HSV-2.¹⁰ Double-blind studies have indicated that use of antiviral drugs such as acyclovir, valacyclovir, and famciclovir moderately reduce risk of HSV-2 recurrences over a 2 to 12 month period by 43 to 59% (results statistically significant).¹¹

Clinicians need to be aware of rare but serious complications developing after influenza vaccination.

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgment

We thank the patient for her cooperation for allowing us to use her case history.