Vogt-Koyanagi-Harada Disease Mimicking Idiopathic Intracranial Hypertension

ABSTRACT

Vogt-Koyanagi-Harada (VKH) disease is a multisystem autoimmune disorder characterized by an inflammatory response targeting melanocyte-associated antigens in tissues such as the uveal tract, inner ear, meninges, and the skin. The classic presentation is bilateral pan-uveitis (choroiditis and multifocal serous retinal detachment) in association with extra-ocular features such signs of meningeal irritation (headache, neck stiffens), auditory signs (tinnitus, hearing loss), and skin changes (poliosis, vitiligo). This is a case of an incomplete form of VKH presenting predominantly with bilateral disc edema. The patient was erroneously diagnosed as having idiopathic intracranial hypertension at first based on a high CSF opening pressure on lumbar puncture and normal MRI/MRV of the brain. However, atypical features in the case such as mild anterior uveitis and the persistence of headache and auditory signs led to further work up and to the diagnosis of incomplete VKH with bilateral disc edema.

Introduction

Vogt-Koyanagi-Harada (VKH) disease is a multisystem autoimmune disorder characterized by an inflammatory response targeting melanocyte-associated antigens in tissues such as the uveal tract, inner ear, meninges, and the skin.¹ Pigmented racial groups, such as Hispanics, Asians, Native Americans, Middle Easterners, and Asian Indians, are more susceptible to being affected. Classical ocular features of VKH include bilateral granulomatous uveitis, serous retinal detachment, choroidal thickening, and optic disc edema. Common neurological manifestations include meningism (headache, neck stiffness, tinnitus) and cerebrospinal fluid pleocytosis. Systemic cutaneous manifestations typically occur in the late stage of the disease, including vitiligo, poliosis, and alopecia. Other uveomeningeal syndromes that need to be ruled out include infectious causes (Syphilis, Tuberculosis), Behcet’s disease, Sarcoidosis, Lymphoma, and Carcinomatous meningitis.

The diagnosis of VKH is established according to a combination of suggestive clinical and ancillary test findings, while excluding other alternative diagnosis.¹ In its complete form, VKH can be diagnosed according to the revised diagnostic criteria. However, it often presents as incomplete form at early stages mimicking as various neuro-ophthalmological conditions such as papilledema and optic neuritis, thereby imposing diagnostic challenges.² Cases of VKH presenting only with bilateral disc edema with/without headache and signs of meningeal irritation have been reported in the literature.^3–6 Increased intracranial pressure is not a primary feature of the disease. However, inflammatory changes in the central nervous system and the meninges may alter CSF dynamics and cause secondary intracranial pressure elevation. We present a case of incomplete VKH with predominantly bilateral disc edema and mild anterior uveitis that was erroneously diagnosed as idiopathic intracranial hypertension (IIH) at the initial stages.

Case report

A 53-year-old Middle Eastern man presented with progressive headache and blurred vision for a 2-month duration and tinnitus of 8-month duration. He denied any history of cough, shortness of breath, joint swelling, night sweats, or fever. He was assessed by a neurologist upon presentation and was noted to have bilateral papilledema. An MRI/MRV of the brain was ordered which was normal apart from an incidental finding of right parietal calcified cavernoma measuring 13 mm in diameter. His neurologist subsequently performed a lumbar puncture, which showed high opening pressure (40 cm H₂O) with normal CSF constituents and no pleocytosis. He was presumptively diagnosed with IIH. He was started on acetazolamide tablets (500 mg/day), which he used for a few weeks but could not tolerate and was therefore referred for neuro-ophthalmic consultation. Apart from allergic rhinitis, his past medical history was positive for measles and mumps at age 4 and age 10, respectively. He did not report any skin changes such as discoloration or rashes. Past surgical history was positive for hernia repair and tonsillectomy. He was a nonsmoker and a non-alcohol drinker. His visual acuity measured with the Snellen chart was 20/30 for both eyes, and there was no color deficit demonstrated with the Ishihara pseudoisochromatic plates. Intraocular pressure measured by applanation tonometry was 17 mm/Hg in both eyes, and his pupils were equally reactive with no relative afferent pupillary defect. He had conjunctival injection with +2 anterior chamber cells, keratic precipitates, and +1 anterior vitreous cells. Fundus examination showed bilateral disc edema but no serous retinal detachment, retinitis, or choroiditis (Figure 1b,e). Visual field testing showed enlarged blind spots in both eyes and an early superior arcuate defect in the left eye (Figure 1a). Spectral-domain optical coherence tomography (OCT) of the optic nerve head showed thickening of the peripapillary retinal nerve fiber layer, and macular OCT was normal apart from a mild nasal sub-retinal fluid arising from the disc swelling. (Figure 1c,d)

Figure 1.

(a) Humphrey visual field 24–2 showing enlarged blind spots in both eyes and an early superior arcuate defect in the left eye. (right eye on right), (b) fundus photo showing bilateral disc edema and normal maculae, (c) peripapillary retinal nerve fiber layer thickness (PRNFLT) OCT showing increased thickness, (d) B-scan of the macular OCT shows normal maculae and mild sub retinal fluid nasally originating from the disc swelling, (e) optos wide-field fundus photography shows normal retinal periphery with no evidence of retinitis or choroiditis.

OD:right eye, OS: left eye

Laboratory workup was negative for Tuberculosis-Quantiferon assay, HLA-B51 testing, and Syphillis using Venereal disease research laboratory test (VDRL). Angiotensin-converting enzyme levels were normal: 23.7 U/L (normal range: 8.0–52.0), and chest X-ray was normal. Lumbar puncture was repeated and showed an opening pressure of 14 cm H₂O, pleocytosis with WBC of 45 cells/μL (80% polymorphs, 20% lymphocytes), and elevated protein of 521 mg/L. CSF PCR for Cytomegalovirus, Epstein–Barr Virus, Herpes Simplex Virus 1 and 2, and all Enterovirus were all negative.

The patient was diagnosed with incomplete VKH based on bilateral disc edema with concomitant anterior uveitis, positive meningeal, and auditory signs together with CSF pleocytosis. He was started on IV methylprednisolone 1 g/day for 5 days, followed by oral prednisone 60 mg/day (1 mg/kg dose) for 4–6 months and topical prednisone acetate (8 times/day) with cyclopentolate for the treatment of his anterior uveitis. He experienced a marked improvement in headache and tinnitus after the third dose of IV steroids. He was followed up for 6 months with a sustained resolution of symptoms and disc edema upon tapering of his oral steroid. (Figure 2)

Figure 2.

(a) Fundus photo at follow-up two months later showing resolution of the bilateral disc edema and (b) normalization of the OCT PRNFL.

OD: right eye, OS: left eye

Discussion

The diagnosis of VKH is primarily clinical and is based on the revised diagnostic criteria: bilateral intraocular inflammation in the early stages (panuveitis, choroiditis, and focal serous retinal detachment), no history of ocular trauma, presence of neurologic or auditory symptoms (meningism, tinnitus, or hearing loss), and cutaneous findings often in the late stages (poliosis, alopecia, or vitiligo).¹ Incomplete VKH is diagnosed when bilateral intraocular inflammation is present with one additional criterion (neurologic, auditory, or cutaneous), and probable VKH is diagnosed when there is only bilateral ocular inflammation. 1 Isolated optic nerve involvement with or without uveitis has been reported in VKH.^3–6

This case highlights that early VKH can present as an incomplete form with predominantly optic nerve involvement. With the presentation of headache, tinnitus, and mild anterior uveitis, the condition may be misdiagnosed as IIH by non-ophthalmologists. In addition, the classic ocular signs of VKH, such as multifocal serous retinal detachment or choroiditis typically seen in the early phase of the disease, can be absent, as in this case. A Japanese series of 96 patients with VKH has found that around 14% of patients present with a predominantly optic disc swelling subtype with minimal or no sub-retinal fluid, while the rest has the classic serous retinal detachment subtype with sub-retinal fluid. Patients with optic disc swelling-type VKH disease had a longer delay between disease onset and treatment (22.4 days vs. 12.6 days) and a higher likelihood of chronic disease development (64.3% vs. 30.5%). The delay in treatment could be related to the atypical presentation and hence a delay in diagnosis. As a result, these patients may be more likely to develop chronic complications and poorer visual outcome.⁷ In another series, 44% of patients with acute VKH disease with no clinically evident serous retinal detachment were misdiagnosed as having primary optic nerve disorders, with optic disc swelling in 83.3%, while only 50% had serous retinal detachment detectable by OCT.⁸

Finally, some of the diagnostic criteria for VKH such as skin changes may develop during the chronic phase as the disease progresses or may never develop if early treatment is instituted. In one series, up to 9.2% of VKH cases were initially misdiagnosed due to the absence of classic features such as exudative retinal detachment.² In a Japanese series of 49 VKH patients, 39 of 41 with early disease would have been classified as incomplete VKH, 2 as non-VKH, and none as complete VKH even at 2 weeks after symptom onset.⁹

Other uveomeningeal syndromes that can present similarly are infections (tuberculosis, syphilis, viral meningitis), Behcet disease, Sarcoidosis, and lymphoma.

The atypical clinical feature for IIH in this patient (male gender, signs of meningeal irritation, non-pulsatile tinnitus, and bilateral anterior uveitis) raised the suspicion of bilateral disc edema secondary to an inflammatory uveomeningeal syndrome despite a high opening pressure and normal CSF constituents at the first lumbar puncture.

More recently, cases of anti-myelin oligodendrocyte glycoprotein-associated disease (MOGAD) have been associated with IIH-like presentations. However, this has been usually in the form of fulminant-IIH like picture with rapid progression, while the course in our patient was slow and protracted over months.¹⁰ Since IIH is a diagnosis of exclusion, clinicians must maintain a high index of suspicion and rule out inflammatory or infectious causes of bilateral disc swelling when atypical features accompany raised intracranial pressure.

Funding Statement

The author(s) reported there is no funding associated with the work featured in this article.

Disclosure statement

No potential conflict of interest was reported by the author(s).