A Case of Herpes Zoster Ophthalmicus with Ocular Involvement in an Immunocompromised Patient

Dr Hannah Roomi (BMBS)

Background

Herpes Zoster (HZ) is a viral infection of an individual nerve and its corresponding dermatome following reactivation of latent varicella zoster virus (VZV). Approximately 1 in 4 people will develop herpes zoster in their lifetime, with incidence and severity increasing with age. Other important risk factors for VZV include an immunocompromised state, certain comorbidities, psychological factors and female sex.1 This article presents a case of Herpes Zoster Ophthalmicus with ocular involvement in an immunocompromised 64-year-old male patient.

Case Presentation

A 64-year-old male presented to his GP with a two-day history of acute throbbing pain to the right frontal-temporal region, associated with numbness and watery eyes. The GP treated the patient as probable trigeminal neuralgia and commenced the patient on Amitriptyline 10mg nocte. The patient then presented to the emergency department two days later with increasing pain to the frontal-temporal region and the development of a rash to the right side of his nose as well as pain and cloudy vision in the right eye. A detailed history revealed that the patient had a past medical history of lymphoma that had been treated with chemotherapy and radiotherapy, with the last treatment session being six weeks ago. The patient also had a history of polymyalgia rheumatica (PMR) for which he takes Prednisolone 10mg once a day long-term.

On examination, the patient had a painful erythematous vesicular rash with underlying oedematous skin on the right dorsum nasi and right ala nasi with two additional lesions above his right eyebrow. His right conjunctiva was oedmatous and injected but there was no evidence of any lesions on the cornea. The patient had normal pupillary responses and eye movements bilaterally and, despite the patient reporting clouding of vision, visual field and visual acuity tests were also normal.

The patient had hyper-aesthesia in the ophthalmic branch region of the trigeminal nerve but all other cranial nerves were normal. Full exposure of the patient did not reveal any further skin lesions. There were no signs of meningism and no physical signs of a relapse in his PMR or lymphoma. Slit-lamp examination was performed with dilated pupils, which revealed a hazy right cornea with multiple punctate speckles that stained with fluorescein. The patient’s left eye was normal. The patient had normal intraocular pressure in both eyes.

Routine blood tests were carried out including LDH, CRP and ESR and swabs were taken from the vesicular rash to exclude secondary bacterial infection. The patient was diagnosed with right sided herpes zoster ophthalmicus with ocular involvement and associated superficial punctate keratitis.

The patient was treated with oral Acyclovir 800mg five times a day for seven days as well as lubricating eye drops. Despite the patient being immunocompromised, he did not require inpatient admission or intravenous treatment since he was afebrile and systemically well with only localized lesions. The patient was discharged with safety-net advice and follow-up in the eye clinic was arranged for three days later. 

The patient was followed-up in the eye clinic and was found to have no further ocular complications, with full resolution of symptoms after 2 weeks.

Discussion

Herpes Zoster Ophthalmicus (HZO) represents 10-20% of all Zoster cases2 and occurs due to reactivation of the VZV in the ophthalmic branch of the trigeminal nerve. HZO with ocular involvement accounts for up to 50% of cases without the use of antiviral therapy. Hutchinson’s sign, which is characterized by lesions at the tip, root or side of the nose, signifies involvement of the nasociliary branch of the ophthalmic nerve and warrants urgent referral to Ophthalmology and initiation of treatment to prevent sight-threatening eye complications such as keratitis, uveitis and optic neuritis of the affected eye.

The most common long-term complication of VZV is post-herpetic neuralgia (PHN), which is characterized by varying degrees of constant or intermittent pain along the affected dermatome, hyperalgesia and intense itching and has been shown to be more common in immunocompromised patients. While some cases of PHN may resolve after a few months, up to 50% of those affected will experience symptoms for over a year.3 Furthermore, severe VZV infection can result in cutaneous, pulmonary and neurological complications, which are also most common in immunocompromised individuals. Most varicella-related deaths result from dissemination of the virus with subsequent VZV-induced cell damage and cell lysis that leads to meningoencephalitis, pneumonia and hepatitis.4

Treatment for VSV is centered around early initiation of antiviral medication, such as Aciclovir or Famciclovir, within 72 hours of rash onset to minimize the risk of cutaneous and visceral dissemination that can lead to life-threatening complications and visual morbidity.5 For localized disease, most patients can be treated with oral antiviral medication, however immunocompromised patients with widespread lesions and signs of systemic viraemia will often require IV antiviral treatment. Although the 72-hour window is widely regarded as the mainstay of VSV treatment6, recent studies have shown that treatment is still warranted outside the window if patients are immunocompromised, if new skin lesions are still developing or if ophthalmic or neurologic complications are suspected.7

Considering this, clinicians must maintain a high level of suspicion when assessing immunocompromised patients with neurological pain and/or skin lesions to facilitate timely diagnosis and initiation of treatment. In this case, the patient had several aspects of his medical history that rendered him immunocompromised: history of lymphoma, chemotherapy, radiotherapy, PMR and long-term corticosteroid use8; all of which significantly raise the risk of developing VZV infection and having subsequent systemic complications. Fortunately, the patient had received extensive safety-net advice by his GP regarding any skin changes that may arise, which prompted the patient to seek urgent medical intervention as soon as the lesions arose. In addition to antiviral therapy, the patient only required supportive treatments from an Ophthalmic perspective as topical antivirals have a limited role in HZO treatment9 and topical steroid therapy is only indicated for signs of ocular inflammation. 

Given that immunocompromised individuals have a higher risk of developing Herpes Zoster and Herpes Zoster-related complications, it follows that immunocompromised patients contribute substantially and disproportionately to the public health burden of Herpes Zoster in England.10 The burden of Herpes Zoster is expected to further increase due to the increased lifespan of the general population, including immunocompromised individuals, unless preventative measures such as vaccinations are in place. The only vaccine that is currently licensed for use in the UK is a live-attenuated vaccine, which poses significant risks for immunocompromised patients. However, new recombinant adjuvant subunit vaccines that have been proven to have an immunogenic effect in HIV-infected individuals with a clinically acceptable safety profile,11 may be able to provide suitable protection from Herpes Zoster and the associated complications without the risks posed from a live-attenuated vaccine.

Learning points

  • Herpes Zoster is extremely common in immunocompromised patients and therefore requires a high index of clinical suspicion
  • HZ in immunocompromised individuals is usually associated with more severe infection and more HZ-related complications
  • Hutchinson’s sign is a strong predictor for nasociliary involvement and subsequent ocular complications
  • Prompt administration of antiviral medication reduces the severity of HZ and likelihood of long-term systemic and ocular complications
  • Development of new recombinant adjuvant subunit vaccines may offer suitable vaccination alternatives to live-attenuated varicella vaccine for immunocompromised individuals

References

  1. National Institute for Health and Care Excellence. Shingles [Internet]. [London]: NICE; 1998 [updated 2020 Oct; cited 2020 Dec]. Available from: https://cks.nice.org.uk/topics/shingles/
  2.  Opstelten W, Zaal MJ. Managing ophthalmic herpes zoster in primary care. Bmj. 2005 Jul 14;331(7509):147-51.
  3.  Stankus SJ, Dlugopolski M, Packer D. Management of herpes zoster (shingles) and postherpetic neuralgia. American family physician. 2000 Apr 15;61(8):2437.
  4. Moffat J, Ku CC, Zerboni L, Sommer M, Arvin A. VZV: pathogenesis and the disease consequences of primary infection. InHuman herpesviruses: biology, therapy, and immunoprophylaxis 2007. Cambridge University Press.
  5. Ahmed AM, Brantley JS, Madkan V, Mendoza N, Tyring SK. Managing herpes zoster in immunocompromised patients. Herpes: the journal of the IHMF. 2007 Sep 1;14(2):32-6.
  6.  Balfour Jr HH, Bean B, Laskin OL, Ambinder RF, Meyers JD, Wade JC, Zaia JA, Aeppli D, Kirk LE, Segreti AC, Keeney RE. Acyclovir halts progression of herpes zoster in immunocompromised patients. New England Journal of Medicine. 1983 Jun 16;308(24):1448-53.
  7.  Dowell SF, Bresee JS. Severe varicella associated with steroid use. Pediatrics. 1993 Aug 1;92(2):223-8.
  8.  Neoh C, Harding SP, Saunders D, Wallis S, Tullo AB, Nylander A, Nelson ME. Comparison of topical and oral acyclovir in early herpes zoster ophthalmicus. Eye. 1994 Nov;8(6):688-91
  9.  Yanni EA, Ferreira G, Guennec M, El Hahi Y, El Ghachi A, Haguinet F, Espie E, Bianco V. Burden of herpes zoster in 16 selected immunocompromised populations in England: a cohort study in the Clinical Practice Research Datalink 2000–2012. BMJ open. 2018 Jun 1;8(6).
  10. Lal H, Cunningham AL, Godeaux O, Chlibek R, Diez-Domingo J, Hwang SJ, Levin MJ, McElhaney JE, Poder A, Puig-Barberà J, Vesikari T. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. New England Journal of Medicine. 2015 May 28;372(22):2087-96.

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