Vogt-Koyanagi-Harada syndrome and ulcerative colitis.

Abstract: The Vogt-Koyanagi-Harada (VKH) syndrome is an uncommon disorder characterized by uveitis and neurologic and cutaneous abnormalities, including tinnitus, vertigo, headache, meningoencephalitis, vitiligo, alopecia, and poliosis. The VKH syndrome has been reported to occur in association with other autoimmune disorders. We report a case of a patient with severe ulcerative colitis who developed VKH syndrome. We postulate that the patient's history of a traumatic brain injury might have been responsible for an abnormal "immunologic milieu" and the occurrence of ulcerative colitis, VKH syndrome, and severe reactive arthritis.

Key Words: brain injury, ulcerative colitis, Vogt-Koyanagi-Harada syndrome

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The Vogt-Koyanagi-Harada (VKH) syndrome is an uncommon disorder characterized by uveitis and neurologic and cutaneous abnormalities, including tinnitus, vertigo, headache, meningoencephalitis, vitiligo, alopecia, and poliosis. Currently, VKH syndrome is thought to be a T-cell-mediated autoimmune disorder in which the process is directed against one or more antigenic components of uveal, dermal, and meningeal melanocytes. VKH syndrome is also associated with other autoimmune disorders, such as autoimmune polyglandular syndrome type 1, (1) hypothyroidism and diabetes mellitus, (2) and Hashimoto's thyroiditis. (3) We report a patient with ulcerative colitis and VKH syndrome.

Discussion

Originally thought of as two separate entities, Vogt-Koyanagi disease (with severe anterior uveitis, frequent vitiligo, and poliosis) and Harada's disease (with bilateral severe posterior uveitis, exudative retinal detachment, and slight anterior uveitis), these disorders are now thought to be a spectrum of one disease because they share clinical characteristics. (4) VKH syndrome is more common in Asians, Native Americans, Hispanics, Asian Indians, and Middle Easterners; (5) it is distinctly uncommon in whites. The peak age incidence is in the thirties, and there is a female preponderance in North American patients. (6)

[FIGURE 1 OMITTED]

Classically, VKH syndrome occurs in three phases. In the first phase, the meningoencephalitic phase, patients may experience headache, meningismus, seizures, muscle weakness, hemi- or paraparesis, and psychosis, which can occur after a prodrome of fever, malaise, headache, nausea, and vomiting. Elevated cerebrospinal fluid protein levels and pleocytosis may be seen.

[FIGURE 2 OMITTED]

In the acute ophthalmic phase, patients can complain of photophobia, eye pain, and decreased visual acuity and may be found to have evidence of anterior or posterior uveitis, iridocyclitis, choroiditis, and exudative retinal detachment. Ultimately, cataracts and glaucoma can occur. This phase typically lasts for a few months but may last up to 10 years. Although permanent loss of visual acuity can occur, prompt treatment with corticosteroids can lead to recovery of vision. (7)

In the convalescent phase, alopecia, vitiligo, and poliosis may occur. The alopecia, which may be limited to small areas or be generalized, occurs in 60% of patients. The incidence of poliosis is similar. (2) Vitiligo may be distributed over the trunk, extremities, or face, especially in the periorbital region, (3) and periumbilical vitiligo may be a striking feature (Sugiura's sign). This phase is usually seen after the neurologic or ocular manifestations but can predate either of these phases.

It is interesting that our patient developed ocular symptoms 2 months after experiencing erythroderma. VKH syndrome can occur both after a prodromal generalized erythema (8) and after cutaneous injury. (9)

Experimental evidence supports an autoimmune cause for VKH syndrome. Melanocytes are found in all areas of involvement (eye, skin, hair, inner ear, and central nervous system (5) ) and antibodies to melanin have been described, (10), (11) as have T lymphocytes with cytotoxic activity against P-36 human melanoma cells. (12) It is therefore not surprising that this entity has been seen with other diseases of immune dysregulation, such as autoimmune polyglandular syndrome type 1, (1) hypothyroidism and diabetes mellitus, (2) Hashimoto's thyroiditis, (3) and Hodgkin's disease. (13), (14)

Our patient was diagnosed with both VKH syndrome and severe ulcerative colitis, which may or may not have been fortuitous. However, a case of concurrent VKH and ulcerative colitis has been reported previously. (15) Unlike our case, in the previously reported case, the ulcerative colitis was quiescent at the time of ocular disease activity.

Interestingly, our patient had also experienced traumatic brain injury several years earlier. Animal models have shown cell-mediated and humoral immune dysfunction after traumatic brain injury. (16), (17) One might speculate that our patient's traumatic brain injury might have been responsible for an abnormal "immunologic milieu" and the occurrence of ulcerative colitis, VKH syndrome, and severe reactive arthritis.

Conclusion

Although the co-occurrence of our patient's VKH syndrome and ulcerative colitis may have been coincidental, mounting evidence suggests an association of VKH syndrome with disorders of immune regulation. Clinicians should maintain a heightened awareness of this association, as prompt treatment of ocular disease with immunosuppression may lead to improved outcomes.

Key Points

* The Vogt-Koyanagi-Harada (VKH) syndrome is characterized by uveitis and neurologic and cutaneous abnormalities.

* VKH syndrome is associated with autoimmune disorders.

* Immunosuppressive therapy is beneficial for patients with VKH syndrome.

No act of kindness, no matter how small, is ever wasted.

--Aesop

Accepted July 10, 2003.

Copyright [c] 2004 by The Southern Medical Association

0038-4348/04/9702-0169

References

(1.) Jovic NS, Nesovic M, Vranjesevic DN, et al. The Vogt-Koyanagi-Harada syndrome: Association with autoimmune polyglandular syndrome type 1. Postgrad Med J 1996;72:495-497.

(2.) Jaggarao N, Voth D, Jacobsen J. The Vogt-Koyanagi-Harada syndrome: Association with hypothyroidism and diabetes mellitus. Postgrad Med J 1989;65:587-588.

(3.) Chi HI, Furue M, Ishibashi Y. Vogt-Koyanagi-Harada's syndrome associated with Hashimoto's thyroiditis. J Dermatol 1994;21:683-686.

(4.) Hettler DL, Levinson JB. A case of Vogt-Koyanagi-Harada syndrome. J Am Optom Assoc 1992;63:90-94.

(5.) Read RW, Rao NA, Cunningham ET. Vogt-Koyanagi-Harada disease. Curr Opin Ophthalmol 2000;11:437-442.

(6.) Moorthy RS, Inomata H, Rao NA. Vogt-Koyanagi-Harada syndrome. Surv Ophthalmol 1995;39:265-292.

(7.) Beniz J, Forster DJ, Lean JS, et al. Variations in clinical features of the Vogt-Koyanagi-Harada syndrome. Retina 1991;11:275-280.

(8.) Wong SS, Ng SK, Lee HM. Vogt-Koyanagi-Harada disease: Extensive vitiligo with prodromal generalized erythroderma. Dermatology 1999;198:65-68.

(9.) Rathinam SR, Namperumalsamy P, Nozik RA, et al. Vogt-Koyanagi-Harada syndrome after cutaneous injury. Ophthalmology 1999;106:635-638.

(10.) Hammer H. Cellular hypersensitivity to uveal pigment confirmed by leucocyte migration tests in sympathetic ophthalmitis and the Vogt-Koyanagi-Harada syndrome. Br J Ophthalmol 1974;58:773-776.

(11.) Matsuda H. Electron microscopic studies on Vogt-Koyanagi-Harada syndrome and sympathetic ophthalmia with special reference to the melanocyte [in Japanese]. Nippon Ganka Gakkai Zasshi 1970;74:1107-1112.

(12.) Maezawa N, Yano A, Taniguchi M, et al. The role of cytotoxic T lymphocytes in the pathogenesis of Vogt-Koyanagi-Harada disease. Ophthalmologica 1982;185:179-186.

(13.) Chuah SY, Lyne AJ, Dronfield MW. Vogt-Koyanagi-Harada syndrome, a rare association of Hodgkin's disease. Postgrad Med J 1991;67:476-478.

(14.) Cipriani D, Landonio G, Canepari C. A case of Vogt-Koyanagi-Harada syndrome in a patient affected by Hodgkin's disease. J Neurol 1989;236:303-304.

(15.) Iversen TH, Sverrisson T. Vogt-Koyanagi-Harada syndrome: A case report. Acta Ophthalmol (Copenh) 1986;64:235-238.

(16.) Ormantaev KS, Nadirov BN, Beliaev NN, et al. The effect of experimental craniocerebral trauma on cell-mediated and humoral immunity reactions [in Russian]. Zh Vopr Neirokhir Im N N Burdenko 1998;4:27-30.

(17.) Lisianyi MI, Rudenko VA, Hniedkova IO, et al. The characteristics of the immune disorders in primary and repeated craniocerebral trauma [in Ukrainian]. Fiziol Zh 1997;43:3-10.

RELATED ARTICLE: Case Report

A 34-year-old white man initially presented to our facility with erythroderma. His medical history was significant for traumatic brain injury sustained during a motor vehicle accident at age 21 (coma for 3 months and residual memory deficit, ataxia, and dysarthria) and severe ulcerative colitis beginning at age 27. Two months after developing erythroderma, he developed the acute onset of bilateral decreased visual acuity and photophobia. He denied meningismus, fever, tinnitus, or hearing loss. He had 20/40 vision in his right eye and 20/60 vision in his left eye with correction. Fundus examination was notable for the finding of faint grayish white areas of discoloration throughout the macula and posterior pole and serous elevation surrounding the optic nerve. Mild macular pucker and macular thickening were also noted, as was sheathing of the retinal veins. Fluorescein angiography revealed tiny areas of hyperfluorescence in the early venous phase with increasing hyperfluorescence as the angiogram proceeded. In the late phases, accumulation of the dye was noted in the subretinal pigment epithelial space resembling cobblestones surrounding the optic nerve. An indocyanine green angiogram showed evidence of hyperpermeability and leakage in the subretinal pigment epithelial space of both eyes consistent with VKH syndrome, and therapy with prednisone 80 mg/d was begun. During the next 6 months, his vision improved and he developed alopecia, poliosis, and vitiligo of his trunk and upper extremities. Furthermore, despite aggressive medical therapy, his ulcerative colitis continued to flare over the next year, ultimately necessitating an abdominal colectomy. He also developed severe reactive arthritis and synovitis of the wrists and hands bilaterally, requiring synovectomy (Figs. 1 and 2).

Daniel G. Federman, MD, Jeffrey D. Kravetz, MD, Christopher B. Ruser, MD, Peter H. Judson, MD, and Robert S. Kirsner, MD

From the Department of Internal Medicine, Yale University School of Medicine, New Haven, CT; Veterans Affairs Connecticut Health Care System, West Haven, CT; Retina Consultants, PC, Hartford, CT; and the Department of Dermatology, University of Miami School of Medicine, Miami, FL.

None of the authors received financial support for this case report or have any financial or other conflict of interests with respect to this case report.

Reprint requests to Daniel G. Federman, MD, VA Connecticut HCS (11ACSL), 950 Campbell Avenue, West Haven, CT 06516. Email: [e-mail]