Abstract
Vogt–Koyanagi–Harada disease is a multisystem inflammatory disorder targeting pigmented tissues. The hallmark is bilateral granulomatous panuveitis with associated serous retinal detachments. It is more prevalent in darkly pigmented races. A genetic predisposition is suspected, but the trigger for onset of this disease is unknown. Diagnosis is based on clinical exam and ancillary testing. Choroidal imaging, including B-scan ultrasonography and optical coherence tomography, can be used to diagnose and monitor this disease. There are four clinical stages of this disease: prodromal, acute uveitic, convalescent, and chronic recurrent. Immunosuppression is the mainstay of treatment. Most patients have good visual prognosis; however, some sequelae of disease can result in permanent vision loss.
Keywords
Vogt–Koyanagi–Harada, Panuveitis, Exudative retinal detachment, Granulomatous uveitis, Inflammatory uveitis
Introduction
Vogt–Koyanagi–Harada (VKH) disease is a multisystem autoimmune disease that targets melanocytes. The hallmark is bilateral granulomatous panuveitis with associated serous retinal detachments. It was first described by Alfred Vogt in Switzerland in 1906. In Japan in 1914, Yoshizo Koyanagi described two patients with uveitis, closely resembling sympathetic ophthalmia, but lacking a history of trauma. Japanese ophthalmologist Einosuke Harada described a case of unusual uveitis in 1923. Later, it was determined that these reports were all part of the same disease, and starting in 1955, the term “Vogt–Koyanagi–Harada” disease was established.
VKH disease is classified into four phases: prodromal, acute uveitic, convalescent, and chronic recurrent. The mainstay of treatment is systemic immunosuppression. At presentation, visual acuity can range from 20/20 to finger counting; however, most patients have good visual outcomes with the majority of patients having final visual acuity of 20/40 or better.
Introduction
Vogt–Koyanagi–Harada (VKH) disease is a multisystem autoimmune disease that targets melanocytes. The hallmark is bilateral granulomatous panuveitis with associated serous retinal detachments. It was first described by Alfred Vogt in Switzerland in 1906. In Japan in 1914, Yoshizo Koyanagi described two patients with uveitis, closely resembling sympathetic ophthalmia, but lacking a history of trauma. Japanese ophthalmologist Einosuke Harada described a case of unusual uveitis in 1923. Later, it was determined that these reports were all part of the same disease, and starting in 1955, the term “Vogt–Koyanagi–Harada” disease was established.
VKH disease is classified into four phases: prodromal, acute uveitic, convalescent, and chronic recurrent. The mainstay of treatment is systemic immunosuppression. At presentation, visual acuity can range from 20/20 to finger counting; however, most patients have good visual outcomes with the majority of patients having final visual acuity of 20/40 or better.
Epidemiology
VKH makes up 3–15% of referrals to uveitis centers. The higher prevalence of VKH in certain races and its association with certain human leukocyte antigen (HLA) haplotypes suggests a genetic predisposition. VKH is more prevalent in more pigmented races including Hispanics, Asians, Native Americans, and Asian Indians. The average age of onset is in the fourth decade of life, though age at time of presentation can vary and has been reported in patients between 3 and 73 years old. Most patients are between 20 and 50 years of age at the time of presentation, and there is a slight female preponderance in most populations, although the Japanese literature suggests a slightly higher prevalence in male population.
Systemic Manifestations
Although the characteristic findings of VKH are related to uveitis, the autoimmune response in VKH is suspected to target both intraocular and extraocular melanocytes. Extraocular manifestations include neurologic, dermatologic, and auditory findings. Neurologic findings include headache, meningismus, and pleocystosis of the cerebrospinal fluid. Poliosis and vitiligo are classic dermatologic findings that occur during the convalescent stage but are not present in the majority of cases. Auditory manifestations include dysacusis, tinnitus, and sensorineural hearing loss.
Clinical Findings
Prodromal Stage
The prodromal stage precedes the onset of ocular findings and typically lasts for 3–5 days. Symptoms include headache, meningismus, tinnitus, dysacusis, flu-like symptoms, and low-grade fevers. Lumbar puncture during this stage shows pleocytosis of the cerebrospinal fluid (CSF) in most patients.
Acute Uveitic Stage
Classic presentation during the acute phase is a bilateral granulomatous panuveitis with serous retinal detachments. This phase lasts several weeks and is typically when patients present to the ophthalmologist with complaints of blurred vision. At the time of presentation, roughly half of the patients have a best corrected visual acuity of 20/200 or worse. Findings include anterior chamber inflammation, keratic precipitates, iris nodules, vitritis, disk edema, hyperemia of the optic nerve head, and exudative retinal detachments. Exudative detachments may be multifocal and can range from small, localized detachments to near-total retinal detachments ( Fig. 12.1A and B ).
Findings are usually bilateral at the time of presentation. In cases of unilateral presentation, the fellow eye typically becomes affected within 2 weeks; however, reports of delayed fellow eye involvement of up to 6 years have been submitted. Unilateral disease has been reported by Forster et al . ; however, this patient had subclinical choroidal thickening on B-scan ultrasonography and a short follow-up of only 3 months, suggesting subclinical disease in the fellow eye that had not yet manifested.
At presentation, most patients have vitritis, bilateral exudative retinal detachments, and anterior uveitis. Fluorescein angiography shows classic multifocal hyperfluorescence with pooling of eye into areas of serous detachment ( Fig. 12.1C and D ). B-scan ultrasonography or enhanced-depth imaging (EDI) optical coherence tomography (OCT) typically shows choroidal thickening ( Figs. 12.2 and 12.3 ). Ancillary testing findings are discussed in more detail below.
Convalescent Stage
The convalescent stage occurs roughly 6 weeks after the acute uveitic stage and lasts for months to years. It is characterized by depigmentation of tissue including a depigmented fundus, known as a “sunset glow” fundus, perilimbal vitiligo (Sugiura’s sign), poliosis, and vitiligo. Circumscribed areas of chorioretinal atrophy can be found in roughly 50% of eyes. Alopecia occurs in 20–30% of patients. Sunset glow fundus can be found in most patients, but mostly common in Asian patients. Sunset glow fundus typically occurs 2–3 months after disease onset. Poliosis and vitiligo, while considered classic findings, are only present in 6–40% and 10–34% of patients, respectively. The recently coined “Ohno’s sign” describes depigmentation of the trabecular meshwork in the convalescent phase.
The frequency of these findings may vary by race or geographic region. For example, Sugiura’s sign is an uncommon finding overall but has a reported prevalence as high as 85% in Japan. Furthermore, the classification and diagnostic criteria of VKH were revised in 2001. This has expanded the number of patients captured under the new definition, which will likely change the frequency of these findings in the literature in the future.
Chronic Recurrent Stage
This final stage may occur in cases not adequately controlled with immunosuppressive agents. Recurrence is typically characterized by anterior uveitis and less commonly present as recurrent serous retinal detachments. Tapering of corticosteroids too rapidly may result in higher rates of recurrence .
Differential Diagnosis
See Box 12.1 .
| Sympathetic ophthalmia |
| Posterior scleritis |
| Primary intraocular lymphoma |
| Central serous chorioretinopathy |
| Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) |
| Sarcoidosis uveitis |
| Uveal effusion syndrome |
| Tubercular uveitis |
| Malignant hypertension |
| Lyme uveitis |
| Syphilitic uveitis |
Diagnostic Criteria
The diagnosis of VKH is a clinical one, based on biomicroscopic examination and ancillary testing. There is no definitive diagnostic test for VKH. The first diagnostic criteria for VKH were established by Sugiura in 1978. These criteria required the presence of CSF pleocystosis, which we now know is not present in all cases of VKH. In 1980, new criteria were published after presentation at the second meeting of the American Uveitis Society. These criteria required clinical findings from three of the following four categories: bilateral iridocyclitis, posterior uveitis, neurologic signs, and integumentary findings. Roughly 20 years later, it was determined that many patients with a clinical diagnosis of VKH did not meet these strict criteria, and therefore, revised diagnostic criteria were set forth in 2001.
The new criteria were constructed in an attempt to more accurately capture patients with a diagnosis of VKH. The committee defining these criteria recognized that VKH disease is a single entity that has variable manifestations in different stages of the disease. They also recognized that not all patients with VKH disease exhibit all manifestations of the disease. Therefore, new criteria were constructed with these points in mind and classify disease into “complete,” “incomplete,” and “probable” VKH ( Table 12.1 ).
| Complete VKH: Criteria 1–5 Needed for Diagnosis |
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| Incomplete VKH |
| Criteria 1 – 3 and 4 or 5 needed for diagnosis (ocular findings+neurologic/auditory or cutaneous findings) |
| Probable VKH |
| Criteria 1 – 3 needed for diagnosis (ocular findings only) |
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