Vogt-Koyanagi-Harada disease (VKH) and sympathetic ophthalmia (SO) are types of T-cell mediated autoimmune granulomatous uveitis. Although the two diseases share common clinical features, they have certain differences in gender predilections. VKH classically has been reported as more prevalent in females than males, yet some studies in Japan and China have not found differences in gender prevalence. Male patients have a higher risk of chorioretinal degeneration, vitiligo, and worse prognosis. Conversely, the changing levels of estrogen/progesterone during pregnancy and the menstrual cycle as well as higher levels of TGF-
Vogt-Koyanagi-Harada disease (VKH) and sympathetic ophthalmia (SO) are both considered ocular T-cell mediated autoimmune diseases. Although the pathogenesis and etiologies are different, the two entities share common clinical manifestations as well as similar pathological and immunohistochemical features [
VKH disease is a multisystemic disorder that involves the eyes, ears, skin, hair, and meninges. Ocular manifestations are characterized by bilateral granulomatous panuveitis with exudative retinal detachments. In the majority of VKH patients, the second eye becomes involved within 2 weeks after initial presentation. Overall, females are more frequently affected with VKH than males [
The typical progression of VKH includes 4 stages: the prodromal, uveitic, chronic, and chronic recurrent stages. The prodromal stage occurs 3–5 days before the ocular disease, mimicking a systemic viral-like presentation. The uveitic stage, which may last for several weeks to months, is characterized by acute anterior uveitis with mutton-fat keratic precipitates, aqueous cells and flare, iris nodules, and synechiae. Severe changes in the posterior segment include vitritis, optic disc swelling, retinal edema, hemorrhages, nonrhegmatogenous exudative retinal detachment, subretinal fibrosis, disciform scars, and RPE abnormality. The focal yellowish-white nodular lesions, known as Dalen-Fuchs nodules, are presented at the subretinal pigment epithelium (RPE) level in the peripheral retina. The Hallmark findings in the uveitic stage are multifocal detachments of the neurosensory retina. Depigmentation of the perilimbus (Sugiura’s sign) and a pale fundus (sunset-glow fundus) are revealed in the chronic stage. The chronic recurrent stage often presents other complications such as cataract, glaucoma, subretinal neovascularization, and subretinal fibrosis [
SO is a rare bilateral granulomatous uveitis that occurs after the uvea of one eye is subjected to a penetrating injury due to trauma or surgery. The injury to one eye (known as the
The clinical presentations are identical in both trauma- and injury-induced SO with an insidious onset. The classic presentation of SO is characterized by an acute granulomatous inflammation in the anterior segment with mutton-fat keratic precipitates, aqueous cells and flare, iridocyclitis, and posterior synechiae. Moderate to severe vitritis with choroidal thickening and infiltration as well as optic disc swelling generally occurs in the posterior segment [
Most studies have reported that females are affected with VKH more frequently than males (Table
Demographic differences of Vogt-Koyanagi-Harada disease (VKH) in the literature.
Author/year | Total: male (%)/female (%); |
Age: mean |
Race or region | Reference |
---|---|---|---|---|
Ohno et al./1977 | 51: 23 (45.1)/28 (54.9) |
NA | African American: 13.7% |
[ |
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Snyder and Tessler/1980 | 20: 8 (40)/12 (60) |
39.7 (10–56) | African American: 11 (55%) |
[ |
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Belfort Jr. et al./1988 | 33: 10 (30)/23 (70) |
NA | White: 60% |
[ |
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Sasamoto et al./1990 | 47: 29 (61.7)/18 (38.3) |
41.1 (14–64) | Japan | [ |
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Beniz et al./1991 | 48: 15 (31.2)/33 (68.8) |
|
Hispanic: 75% |
[ |
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Rubsamen and Gass/1991 | 22: 5 (22.7)/17 (77.3) |
35 (13–73) | Hispanic: 54% |
[ |
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Moorthy et al./1995 | 65: 17 (26.2)/48 (73.8) |
32 (7–71) | Hispanic: 51 (78%) |
[ |
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Lertsumitkul et al./1999 | 75: 16 (21.3)/59 (78.7) |
|
White/native American: 22.7% |
[ |
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Sheu et al./2003 | 39: 21 (53.8)/18 (46.2) |
|
Taiwan | [ |
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Wakabayashi et al./2003 | 19: 5 (26.3)/14 (73.7) |
NA | Japanese | [ |
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Sheu et al./2004 | 31: 19 (61.3)/12 (38.7) |
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Taiwan Chinese | [ |
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Tesavibul and Sansanayuth/2005 | 33: 12 (36.4)/21 (63.6) |
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Thai | [ |
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Sukavatcharin et al./2007 | 48: 18 (37.5)/30 (62.5) |
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Hispanic | [ |
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Chee et al./2007 | 89: 38 (42.1)/51 (57.9) |
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Chinese: 75.28% |
[ |
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Khairallah et al./2007 | 49: 17 (34.7)/32 (65.3) |
35 (16–54) | North Africa | [ |
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Murthy et al./2007 | 45: 7 (15.6)/38 (84.4) |
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South India | [ |
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Tugal-Tutkun et al./2007 | 45: 13 (28.9)/32 (71.1) |
|
Turkish | [ |
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Kiyomoto et al./2007 | 68: 29 (42.6)/39 (57.4) |
|
Japanese | [ |
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Al-Kharashi et al./2007 | 68: 17 (25)/51 (75) |
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Saudi Arabia | [ |
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Hou et al./2008* | 231: 128 (55.4)/103 (44.6) |
|
Chinese | [ |
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Chee et al./2009 | 67: 27 (40.3)/40 (59.7) |
42.3 (5.4–70.9) | Chinese: 79.1% |
[ |
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Lai et al./2009 | 35: 18 (51.4)/17 (48.6) |
|
Hong Kong Chinese | [ |
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Iqniebi et al./2009 | 30: 12 (40)/18 (60) |
NA | Saudi Arabia | [ |
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Meng et al./2009* | 247: 138 (55.9)/109 (44.1) |
33.6 | Chinese | [ |
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Hou et al./2009* | 307: 171 (55.7)/136 (44.3) |
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Chinese | [ |
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Hu et al./2010* | 379: 197 (51.9)/182 (48.1) |
|
Chinese | [ |
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Chee et al./2010 | 28: 13 (46.4)/15 (53.6) |
42.2 (median) (16–77) | Chinese: 64.3% |
[ |
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Jiang et al./2010* | 382: 210 (55)/172 (45) |
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Chinese | [ |
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Shu et al./2010* | 385: 201 (52.2)/184 (47.8) |
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Chinese | [ |
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Al |
76: 16 (21.1)/60 (78.9) |
42.1 (11–76) | Mexican Mestizos | [ |
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Al-Halafi et al./2011 | 256: 95 (37.1)/161 (62.9) |
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Saudi Arabia | [ |
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Chen et al./2012* | 519: 290 (55.9)/229 (44.1) |
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Chinese | [ |
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Yang et al./2012 | 38: 17 (44.7)/21 (55.3) |
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Hong Kong Chinese | [ |
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Chen et al./2012* | 451: 243 (53.9)/208 (46.1) |
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Chinese | [ |
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Morita et al./2013 | 85: 37 (43.5)/48 (56.5) |
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Japanese | [ |
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Alam et al./2013 | 9: 4 (44.4)/5 (55.6) |
28 (16–43) | Pakistanis: | [ |
However, some other studies did not show similar findings. Sasamoto et al. found that only 38% of patients were females in their 47 case series of VKH in a Japanese population [
Interestingly, ocular manifestations of VKH are variable and race dependent, and the “sunset-glow” appearance is more commonly seen in Hispanic and Asian patients [
Several factors have been related to a better prognosis in female patients with VKH. Pregnancy is reported to play a role in VKH prognosis and has a beneficial effect on disease activity [
Sex hormones, including estrogen and progesterone, are believed to mediate the immune response and account for gender differences in the prevalence of autoimmune diseases [
Literature showing VKH amelioration during pregnancy has suggested that sex hormones may influence the course of VKH [
In addition, Sanghvi et al. evaluated 76 regularly menstruating women with acute anterior uveitis and found that the disease commences more frequently in the postovulatory phase of the menstrual cycle [
Based on the association of pregnancy and menstrual cycle with VKH, it is important to assess the menstrual history and to consider adjustments of immunosuppressants, such as corticosteroid treatment, during pregnancy and postpartum [
Although the precise mechanism of VKH is still not clear, genetic factors are thought to play an important role in VKH [
In trauma-induced SO, males are reported to have a higher prevalence than females [
Demographic differences of sympathetic ophthalmia (SO) in the literature.
Author/year | Total: male (%)/female (%) |
Age: mean |
Cause of SO | Race or region | Reference |
---|---|---|---|---|---|
Chan et al./1995 | 32: 16 (50)/16 (50) |
|
Trauma: 23 (71.9%) |
NA | [ |
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Lin and Zhong/1996 | 30: 21 (70)/9 (30) |
32.3 (6–66) | Trauma: 24 (80%) |
Chinese | [ |
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Castiblanco and Adelman/2009 | 86: 62 (72.1)/24 (27.9) |
46 (3–83) | Trauma: 40 (46.5%) |
NA | [ |
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Galor et al./2009 | 85: 50 (60)/35 (40) |
44 (2–91) | Trauma: 53 (62.4%) |
White: 57% |
[ |
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Al-Halafi et al./2011 | 60: 34 (56.7)/26 (43.3) |
|
NA | Saudi Arabia | [ |
There are no clinical differences between males and females in SO due to either trauma or ocular surgery.
Due to the rarity of SO, it is difficult to compare gender differences in the prognosis of SO. However, because SO and VKH share many clinical and pathological similarities, the role of sex hormone and pregnancy could also affect disease severity and presentation, Further clinical and/or experimental studies are required to draw a conclusion.
Both VKH and SO are types of bilateral granulomatous panuveitis that can lead to severe visual loss without effective management. In addition to clinical features, gender predilection in VKH and SO could provide more appropriate therapies for patients. In VKH, with the protective role of estrogen/progesterone, female patients are better protected and have better prognoses. Moreover, the evidence that certain HLA-DR alleles are exclusively associated with VKH in females implies an important genetic background in the pathogenesis of VKH. In SO, although gender differences only exist in the incidence of ocular trauma, we cannot rule out the possible role of gender-based factors in the initiation, progression, and prognosis of SO. Additional gender-based studies may identify other genes or risk factors related to these two autoimmune diseases.
The authors declare that there is no conflict of interests regarding the publication of this paper.