Introduction

Shingles significantly impact older adults^2,3, exacerbating chronic conditions and weakness. It is a painful reactivation of the varicella-zoster virus, increasing in incidence and severity with age, and can lead to complications like post-herpetic neuralgia (PHN).

This results in long-term pain, reduced quality of life, and higher healthcare utilisation. Vaccination, particularly with the enhanced recombinant zoster vaccine (RZV), can effectively reduce both the incidence and severity of shingles, thereby supporting healthy ageing by maintaining function and quality of life, and potentially reducing healthcare costs associated with this debilitating condition.

Guillain-Barré Syndrome (GBS) is a rare, acute inflammatory disease affecting the peripheral nerves, often following an infection. With an incidence of one to two cases per 100,000 individuals annually, it predominantly affects males.⁴ GBS is characterised by progressive muscle weakness, typically starting in the lower extremities and moving upwards, along with diminished reflexes.

It often follows infections such as Campylobacter jejuni, varicella-zoster virus, and cytomegalovirus. Diagnosis is primarily clinical, supported by cerebrospinal fluid analysis and nerve conduction studies. Treatment includes plasma exchange and intravenous immunoglobulin therapy to alleviate symptoms and hasten recovery.

The article explores the connection between shingles, the Shingrix vaccine, and GBS, investigating the potential risk of GBS following the Shingrix vaccination. It aims to raise awareness about the recurrence of GBS post-vaccination, highlighting the importance of monitoring and understanding associated risks.

Understanding shingles

Shingles, caused by reactivation of the varicella-zoster virus, presents as a painful, pruritic, unilateral vesicular rash in a dermatomal distribution. Major complications include PHN, characterised by severe, persistent pain even after the rash heals.⁵ Neurological complications can arise, such as vasculopathy, causing strokes and cognitive issues, segmental weakness, myelopathy, encephalitis, and cranial neuropathies like Ramsay Hunt Syndrome.⁶ Other rare complications include GBS and zoster sine herpete, where pain occurs without a rash. Early antiviral treatment can mitigate symptoms and reduce complications.

Shingles (herpes zoster, HZ) is prevalent in two to three per 1,000 individuals annually, with a lifetime risk of 30%, rising to over 50% by age 85.¹ Key risk factors include:

• old age
• Immunosuppression
• Diabetes
• being of female sex
• white race
• genetic predisposition
• psychological stress
• mechanical trauma.

African Americans have a lower prevalence. Immunocompromised individuals, such as those with human immunodeficiency virus (HIV) or recent transplants, face significantly higher rates. Psychological stress and mechanical trauma notably increase risk, while living with children may reduce risk due to exposure to VZV.

Guillain-barré syndrome (GBS)

The exact cause of GBS is unknown, but it often follows a respiratory or digestive infection. Occasionally, surgery or vaccinations can trigger GBS. The immune system, which normally targets pathogens, mistakenly attacks the body's nerves, particularly the myelin sheath that surrounds them, disrupting nerve signal transmission, leading to symptoms like weakness, numbness, and paralysis.¹⁰

Early symptoms include numbness, pain and muscle weakness, affecting both sides of the body simultaneously. Progression may lead to severe symptoms such as paralysis, difficulty breathing, and problems with eye and facial movements, speech, swallowing and coordination. Symptoms usually worsen rapidly within two weeks, with most people reaching their peak weakness by the third week. Severe cases can impact breathing muscles, requiring hospitalisation and ventilatory support.¹⁰

Infections like Zika virus and COVID-19, as well as the Johnson & Johnson or AstraZeneca COVID-19 vaccines, have been associated with GBS.

The prognosis for GBS is generally positive, with about 80% of patients achieving full recovery. Treatment options include plasma exchange and immunoglobulin therapy, which can help reduce severity and speed up recovery. Recovery typically begins within four weeks of symptom onset, with the recovery phase lasting six to twelve months, although some may take up to three years. Physical therapy aids muscle flexibility and strength, while adaptive devices may assist mobility. Most patients regain motor strength within a year, though some may experience long-term weakness or relapses.

Shingrix vaccine

Shingrix^® is approved for preventing herpes zoster (shingles) and related post-herpetic neuralgia in individuals aged 50 and older, and for adults 18 and older at increased risk. It is a recombinant, adjuvanted varicella zoster vaccine. The recommended dose is two 0.5 mL intramuscular injections, preferably in the deltoid muscle, with the second dose administered 2 months after the first. For immunodeficient or immunosuppressed individuals, the second dose can be given 1-2 months later. Contraindications include hypersensitivity to vaccine components. Common adverse effects include injection site pain, myalgia, fatigue and headache.

Shingrix^® has shown significant effectiveness in preventing shingles in adults aged 50 and over. New data show the vaccine provides at least 10 years of protection. Interim results from the ZOSTER-049 study indicate an efficacy greater than 80% over a follow-up period of 6-10 years. No new safety concerns were identified. Initial trials, ZOE-50 and ZOE-70, showed vaccine efficacy of 97% in adults 50+ and 91% in adults 70+ over four years. These findings confirm the long-term benefits and safety of Shingrix, giving patients and healthcare providers confidence in its durability.

Shingrix, a two-dose non-live supportive vaccine, demonstrated higher efficacy than Zostavax in preventing HZ and PHN across all age groups studied. However, Shingrix was associated with more injection-site and systemic reactions. No significant differences in serious adverse events were noted between the vaccines. Shingrix's enhanced efficacy and comparable safety profile make it a preferable option, despite its higher reactogenicity.

Association between shingrix and GBS

The FDA identified a potential risk of GBS associated with the Shingrix vaccine, placing a black box warning in March 2021.⁷ A study revealed an increased incidence of GBS within 42 days post-vaccination, estimating three cases per million doses in adults 65 and older. GBS is a rare, acute autoimmune disease affecting the peripheral nervous system, often triggered by infections or, occasionally, vaccinations. Despite this association, concrete evidence linking vaccines to GBS remains limited. The FDA continues to monitor and research this potential risk to ensure patient safety.

The FDA's findings show an increased risk of GBS following Shingrix vaccination compared to Zostavax. A self-controlled case series estimated three GBS cases per million Shingrix vaccinations in adults aged 65 and older. Reports noted GBS symptoms typically appearing within 42 days post-vaccination, with some cases recurring. The FDA's black box warning highlights this risk, contrasting with Zostavax, which lacks such a noted association. Further research is needed to solidify these findings and understand the underlying mechanisms.

On March 24, 2021, the FDA announced safety labelling changes for Shingrix to include a new warning about GBS risk following vaccination. This decision was based on a postmarketing observational study that indicated an increased GBS risk within 42 days post-vaccination. Although an association between Shingrix and GBS was observed, the evidence is insufficient to establish a causal relationship. Despite this, the FDA maintains that the benefits of Shingrix, which significantly reduces shingles incidence, outweigh its risks. Healthcare providers and the public are advised to be aware of this updated warning.

Practical considerations for patients 

GBS typically presents with symmetrical limb weakness, starting in the lower limbs, often following a respiratory or gastrointestinal infection. Common symptoms include tingling or pricking sensations in hands and feet, severe pain, facial palsy, and autonomic dysfunction such as pulse and blood pressure changes. Sensory symptoms often precede weakness, and deep-tendon reflexes are usually absent. Cranial nerve involvement can lead to difficulties in eye movement, speech, or swallowing. Onset can be acute or subacute, with symptoms peaking within four weeks and gradual recovery following a plateau phase.

Possible adverse events when taking the Shingrix vaccine include local reactions like pain, redness, and swelling at the injection site, along with systemic reactions such as myalgia, fatigue, headache, shivering, fever, and gastrointestinal symptoms. These symptoms can be severe enough to limit normal activities, affecting approximately 1 out of 10 recipients. Severe allergic reactions are very rare but may include hives, swelling of the face and throat, difficulty breathing, rapid heartbeat, dizziness, and weakness. These reactions typically occur within minutes to hours after vaccination. 

Summary

In conclusion, shingles, caused by varicella-zoster virus reactivation, pose a significant health burden, especially in older adults, with complications like post-herpetic neuralgia. The introduction of the varicella vaccine has indirectly impacted shingles epidemiology. GBS is a rare but serious complication, possibly linked to the Shingrix vaccine, prompting FDA safety labelling changes.

While an association with GBS was observed, causality remains uncertain. Patient awareness of GBS symptoms and adverse event reporting are crucial. Despite potential risks, Shingrix's potency in preventing shingles supports its continued use, emphasising the importance of benefit-risk assessment in vaccination decisions.