Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Vogt-Koyanagi-Harada Syndrome
Key Concepts
-
Vogt-Koyanagi-Harada (VKH) syndrome is a systemic autoimmune disease, which targets melanin containing cells.
-
Typical manifestations include uveitis with exudative retinal detachments, headache, tinnitus, poliosis, and vitiligo.
-
Posterior pole disease should be treated very aggressively.
Vogt-Koyanagi-Harada (VKH) syndrome is a systemic disorder involving many organ systems with melanin containing cells, including the eyes, ears, skin, and meninges. It includes a constellation of clinical signs and symptoms, and no definitive confirmatory diagnostic tests are available. In the twelfth century, a physician from the Arab world, Mohammad-al-Ghafiqi, described a disease with poliosis, neuralgias, and hearing changes. In more modern times, in 1906, Vogt presented one case in Basel, Switzerland, and in 1929, Koyanagi described in detail six patients with bilateral nontraumatic chronic iridocyclitis associated with poliosis, vitiligo, and dysacousia. In 1926, Harada described essentially posterior uveitis with an exudative retinal detachment associated with a pleocytosis in cerebrospinal fluid (CSF). As more of these cases were recognized, it became clear that many of the features seen in each of these entities overlapped. Babel suggested that these symptoms were manifestations of the same underlying disorder and that only intensity and distribution varied from one patient to the next; it therefore seemed appropriate to call the entity the Vogt-Koyanagi-Harada syndrome, although it sometimes appears in the literature under other names, for example, uveomeningitis.
Clinical Aspects
Although VKH syndrome has been reported throughout the world, its appearance seems to be concentrated in certain racial and ethnic groups. The diagnostic criteria for VKH syndrome have been revised ( Box 25.1 ). It is a common type of endogenous uveitis in Japan, constituting at least 8% of these cases. The same holds true for certain parts of Latin America, particularly Brazil. It is, however, relatively uncommon in the United States and seems to be an exceedingly unusual diagnosis in persons of northern European extraction. Patients diagnosed with VKH syndrome in France have all been of Mediterranean origin. At the National Eye Institute (NEI), examinations of 75 patients with VKH syndrome revealed that most patients (79%) were females. However, Ohno et al., in their series of 186 patients, reported that the disease occurred in more males than females. In the NEI cohort, 44% of the patients were African American, 37% were white, 11% were Hispanic, and 6% were Asian. Interestingly, a high percentage of the patients with VKH syndrome seen at the NEI reported having Native American heritage, albeit a sometimes distant one. This observation is very significant because this certainly may be the unifying genetic bond between patients in the United States and those in Asia. VKH syndrome is commonly seen in the Hispanic population of Southern California, an ethnic group often with Native American ancestry, as well. VKH is generally a disease of persons in the second to fourth decades of life, although the disease has been reported in children. The proportion of pediatric cases among cohorts with VKH syndrome ranges from 3% to 15%. The visual prognosis is generally favorable.
Box 25.1
Revised Criteria for Diagnosis of Vogt-Koyanagi-Harada Syndrome ∗
∗ Modified from Read et al. Revised diagnostic criteria for Vogt-Koyanagi-Harada disease: report of an international committee on nomenclature. Am J Ophthalmol. 2001 May;131(5):647-52.
Complete VKH: Criteria 1–5 must be present
Incomplete VKH: Criteria 1–3 and either 4 or 5 must be present
Probable VKH (isolated ocular disease): Criteria 1–3 must be present
- 1.
No history of penetrating ocular trauma or surgery preceding the initial onset of uveitis
- 2.
No clinical or laboratory evidence suggestive of other ocular disease entities
- 3.
Bilateral ocular involvement (a or b must be met, depending on the stage of disease when the patient is examined)
- a)
Early manifestations of disease
- (1)
Evidence of diffuse choroiditis (with or without anterior uveitis, vitreous inflammatory reaction or optic disc hypermia) which may manifest as (a) focal areas of subretinal fluid or (b) bullous serous retinal detachments
- (1)
- b)
Late manifestations of disease
- (1)
History suggestive of prior presence of early findings noted in 3a and one or more of the late chronic signs below.
- (2)
Ocular depigmentation (Sunset glow fundus or Sugiura sign), nummular chorioretinal depigmented scars or (b) retinal pigment epithelium clumping and/or migration or recurrent or chronic anterior uveitis
- (1)
- a)
- 4.
Neurological/auditory findings (may resolve by time of evaluation)
- (a)
Meningismus (malaise, fever, headache, nausea, abdominal pains, stiffness of the neck and back or a combination of these factors); Note that headache alone is not sufficient to meet the definition of meningismus
- (b)
Tinnitus
- (c)
Cerebrospinal fluid pleocytosis
- (a)
- 5.
Integumentary finding (not preceding onset of central nervous system or ocular disease)
- (a)
Alopecia, or
- (b)
Poliosis, or
- (c)
Vitiligo
- (a)
Systemic Findings
VKH syndrome is a systemic disorder, and the extraocular findings are most important in confirming the diagnosis. Perry and Font stressed that in patients with the Harada form of the disease, some extraocular findings, such as hair and skin alterations, are uncommon.
VKH syndrome is nontraumatic bilateral panuveitis associated with integumentary, neurologic, or auditory signs, according to the revised diagnostic criteria proposed by the American Uveitis Society. On the basis of the revised criteria, typical ocular involvement with only integumentary features or neurologic or auditory manifestations is considered incomplete VKH syndrome, and ocular involvement without extraocular manifestations is categorized as probable VKH syndrome. The incomplete or probable forms of the disease can account for up to 45% to 58% of patients.
VKH syndrome is a multistage disease with prodromal, acute, chronic convalescent, and chronic recurrent stages. Ocular disease can be preceded by the prodromal stage, in which the patient may complain of headache, photophobia, orbital pain, stiff neck, scalp or skin sensitivity, vertigo, and rarely focal neurologic deficits (e.g., cranial nerve palsies). Fever may also be present. In the study by Beniz et al., in a group of mostly Hispanic patients, headache was, by far, the most common neurologic complaint. Others , have reported presentation with mild facial weakness, migraine-like headaches with a sensorimotor hemisyndrome, and cognitive dysfunction.
The patient complaining of central nervous system (CNS) symptoms needs to be evaluated immediately. Lumbar puncture will reveal pleocytosis in 84%, with mostly lymphocytes and monocytes present. The CSF glucose level should show a normal relationship to the serum glucose level. The lumbar puncture result will be abnormal early in the course of the disease because pleocytosis will ultimately disappear, even though the inflammatory disease in the eye may continue. These CSF findings were central to the diagnosis criteria proposed by Sugiura but not to the revised criteria. The CSF pleocytosis and the number of cells noted are significantly higher in those patients who develop a “sunset glow” fundus (see later discussion). Furthermore, this finding is occasionally very helpful in terms of determining the severity of the disease and the aggressiveness of the therapeutic approach. On occasion, it can aid in diagnosis; for example, melanin-laden macrophages in the CSF specimen helped make the diagnosis in a patient with titers positive for syphilis.
The auditory difficulties associated with this disorder are central and will often occur concurrently with the ocular disease. The auditory disorder may, however, be the presenting problem. The hearing loss usually involves the higher frequencies and may affect more than three-quarters of patients with the disorder. Dysacousia, which was observed in 74% of patients in one study, may resolve after several months; however, we and others have noted that it persists for years in some cases. Some patients will have tinnitus without an objective decrease in hearing. When we reviewed 24 patients, we noted that some may, indeed, present with tinnitus and even sudden hearing loss. However, audiologic examinations have revealed many more with hearing alterations. Detailed auditory testing, carried out by competent professionals, is important to rule out a noncentral reason for the reduction in hearing.
Skin lesions may also be a prominent part of the disease complex. Approximately 72% of patients report sensitivity to touch of both hair and skin during the active phase of their disease. Vitiligo and poliosis occur in a large number of patients (63% and 90%, respectively) during the convalescent stage, whereas alopecia was reported in 70% to 73% of one group with VKH syndrome , ( Fig. 25.1 ). It should be noted that different ethnic groups may manifest different systemic symptoms, as suggested by the findings of Beniz et al. These authors found dermatologic involvement only rarely in the group of mostly Hispanic patients with VKH syndrome who were followed up. One area frequently overlooked during an examination for such changes is the axilla.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here