Cavernous sinus thrombosis, a rare and potentially lethal complication of herpes zoster ophthalmicus, can easily be missed, with devastating consequences, says a local expert.
Herpes zoster ophthalmicus (HZO) is a well-recognised opportunistic infection representing reactivation of latent varicella-zoster along the ophthalmic division (V1) of the trigeminal nerve – more commonly known as shingles – often affecting both immunocompetent and immunocompromised individuals, although the disease is worse in those cases.
Because of late presentation, often coupled with a delay in appropriate treatment, in South Africa it is frequently a blinding condition, with the disfiguring facial scarring and chronic pain of post-herpetic neuralgia (PHN) that affects many patients compounding the burden of psychosocial morbidity linked to this devastating disease.
In this case study, published in the SA Medical Journal, and authored by ophthalmologist N Narainswami from the Grey’s Hospital Eye Clinic, Pietermaritzburg, a 49-year-old HIV-positive woman, who had been on highly active antiretroviral therapy (HAART) for more than a year, presented with a four-week history of progressive painful visual loss affecting the right eye.
She had attended her local clinic twice during the preceding month with no improvement in symptoms. Of note, she complained of recent-onset double vision, worse on left gaze, and a worsening headache over the past few days.
Clinical examination revealed a vesicular rash along the V1 distribution, with cicatrising lesions in various stages of healing along the lateral aspect of the right nostril.
Her right lid was ptotic, with an injected eye deviated outwards on primary gaze. She had hypoaesthesia of the right cornea and along the V1 dermatomal distribution.
Anterior segment examination was remarkable for an active mild uveitis of the right eye. Ocular motility testing revealed an incomitant squint on versions and markedly severe limited adduction and elevation of the right globe by at least 80% on ductions.
Abduction of the right eye was comparatively less reduced by ~40%. Both pupils were equal and reactive to light, and both optic discs were pink, with no disc swelling seen on direct fundoscopy.
Flourescein dye staining highlighted a dendritic lesion of the inferior left cornea, with tapered ends and absence of terminal bulbs. Otherwise, left ocular examination was unremarkable.
The rest of the neurological assessment was grossly normal, and the patient was haemodynamically stable and afebrile. Her baseline blood panel was normal.
At this point our working diagnosis was HZO with ocular involvement complicated by probable intracranial extension. The pattern of combined oculomotor (CN 3), trigeminal (CN 5) and abducens (CN 6) cranial nerve palsies localised the lesion to the right cavernous sinus. There was no proptosis or chemosis.
The neurology department was consulted, and an emergency contrast computed tomography scan was ordered. The scan revealed an obvious dilation of the superior ophthalmic vein of the right orbit and a filling defect of the right cavernous and transverse sinus in keeping with thrombosis.
The patient was started on intravenous acyclovir, broad-spectrum intravenous antibiotics, low-molecular-weight heparin and warfarin anticoagulation, and co-managed with neurology as an inpatient. She responded well to treatment during her hospital stay. A follow-up magnetic resonance venogram (MRV) revealed patency of all intracranial venous sinuses.
Subsequent follow-ups at three and six months showed progressive improvement in her ptosis and resolution of her ophthalmoplegia, and she no longer complained of horizontal diplopia.
Herpes zoster occurs commonly in SA, and most clinicians will encounter a patient with HZO at some point. Most patients are young immunocompromised adults. The rest are elderly and immunocompetent, with a less severe and somewhat self-limiting disease course.
HZO more commonly affects HIV-positive patients with relatively modest decreases in CD4 counts as opposed to patients with profound immunosuppression. It is therefore thought to be a disease of immune dysregulation rather than severe immunosuppression.
While studies show that PHN and ocular inflammatory disease are the most common complications, there have been a few isolated case reports of cavernous sinus thrombosis as a potentially fatal complication.
Both CT venograms and MRVs were used in these cases to diagnose cavernous sinus venous thrombosis early in management. While an MRV was not readily available after hours for our patient, an emergency contrast CT scan of the brain and orbits by an experienced senior radiologist confirmed the diagnosis.
However, MRV was performed during her hospital stay while she was on antithrombotic therapy to assess whether thrombi detected on the contrast CT scan at diagnosis had resolved. At follow-up after one month her vision had improved in both eyes, and her right ptosis improved further.
She was discharged within a month and given a follow-up appointment at the combined neuro-ophthalmic clinic on discharge.
The important points to highlight in this case are the clues in the history and subsequent clinical examination that suggested a rare life-threatening complication presenting in a relatively common clinical scenario.
Diplopia is usually uncommon in the setting of acute HZO, because inflammatory oedema of the affected eyelid often results in a severe mechanical ptosis that nullifies the visual input for binocular diplopia.
Our patient presented a few weeks after onset of the rash, when some of that eyelid oedema had possibly begun to subside, allowing her eye to partially open. It was at this point that she became aware of the double vision.
The recent worsening headache was also not in keeping with the natural pattern of PHN, which typically announces itself early in the disease process.
The vital clue in the clinical examination was eliciting an ophthalmoplegia, which is not in keeping with a straightforward uncomplicated case of HZO. Lifting a ptotic lid and grossly examining extraocular movements (easily done in less than a minute) can elicit reduced ocular movements.
The cranial nerve palsies identified in this way would alert the clinician to the possibility of a life-threatening complication such as intracranial venous sinus thrombosis.
The consequences of missing such an important clinical sign and delaying urgent neuro-imaging and definitive treatment under multidisciplinary care could potentially be disastrous.
Despite the advent of HAART, HZO remains relatively common in HIV-infected patients. Zostervax and Shingrix are two current herpes zoster vaccines available in SA. While Zostervax is readily available for elderly patients (≥70 years old), because it is a live attenuated vaccine concerns have been raised regarding its use in a younger immunocompromised group.
Shingrix, on the other hand, is considered comparatively safe and effective in the immunocompromised group, but requires Section 21 motivation and is therefore not readily available. GOs, ophthalmologists and internists need to be more pro-active in recommending these vaccines to their patients to decrease the incidence of PHN, blinding ocular sequelae, and by extension rare potentially fatal complications such as cavernous sinus thrombosis.
See more from MedicalBrief archives:
Contracting shingles doubles stroke and heart attack risk
Shingles vaccine may also reduce stroke risk
Women more vulnerable to HIV infection during pregnancy and months after birth
Sight-saving treatment for eye infection or trauma