Uveodermatological Syndrome (UDS) in Dogs

Overview

Pathophysiology

• Target antigens: Tyrosinase-related proteins (enzymes involved in melanin synthesis expressed exclusively by melanocytes). Experimental immunization of Akita dogs with tyrosinase-related protein reproduced the clinical and histological features of UDS (Yamaki et al. 2000).
• Genetic predisposition: The canine leukocyte antigen allele DLA-DQA1*00201 is significantly overrepresented in American Akitas with UDS compared to other DLA Class II alleles (Angles et al. 2005). This mirrors the HLA-DR4 association in human VKH.
• Immune infiltrate: Histopathologically, granulomatous inflammation with lymphocytes, histiocytes, and melanin-laden macrophages is seen in affected uveal tissue and skin.
• Th17 involvement: In human VKH (and by inference in UDS), Th17 CD4+ cells stimulated by IL-23 and secreting IL-17 are present during active uveitis - relevant to treatment with immunosuppressives (Andrews' Diseases of the Skin, p. VKH section).

Signalment / Predisposed Breeds

• Age of onset: 6 months to 6 years
• Sex: No consistent predisposition (contrast to human VKH where females are more affected); one large retrospective found ~2/3 of cases were male (Zarfoss et al. 2018)
• Coat color correlation: Blue-eyed dogs (which have less uveal melanocyte density) may be less susceptible; one unilateral case in a Siberian Husky involved only the brown eye, not the blue eye

Clinical Signs

Ocular Signs (usually the presenting complaint)

• Aqueous flare, keratic precipitates
• Iridal edema, rubeosis iridis (iris neovascularization)
• Posterior synechiae, iris bombe
• Hyphema
• Corneal edema, corneal neovascularization
• Reduced Schirmer tear test / keratoconjunctivitis sicca (KCS) - due to immune-mediated lacrimal adenitis

• Chorioretinitis, vitritis
• Disc edema
• Bullous retinal detachment (can cause sudden blindness)

• Glaucoma - a common sequela of chronic inflammation; frequently the cause of permanent blindness
• Cataracts
• Phthisis bulbi (end-stage shrunken globe)

Dermatologic Signs

• Depigmentation (vitiligo-like): nasal planum, lip margins, eyelids, scrotum, footpads, perianal skin
• Poliosis: patchy leukotrichia (white hair patches), especially on face
• Alopecia: at sites of active depigmentation
• The nasal planum is the most commonly and prominently affected skin site

Histopathology

• Diffuse pyogranulomatous or lymphohistiocytic inflammation of the iris, ciliary body, choroid, and retina
• Macrophages containing melanin granules (melanin phagocytosis)
• Bilateral degeneration and bullous retinal detachment

• Lichenoid interface dermatitis
• Lymphocytic or histiocytic infiltrate at the dermoepidermal junction
• Melanocytopenia (loss of melanocytes from basal epidermis)
• Pigmentary incontinence (melanin dropout into dermis)
• Macrophages loaded with melanin in superficial dermis

Diagnosis

1. Thorough ophthalmic examination - slit-lamp biomicroscopy, indirect ophthalmoscopy, assess for aqueous flare, synechiae, retinal status
2. Intraocular pressure (IOP) measurement - baseline and serial monitoring for glaucoma
3. Schirmer tear test - assess for KCS
4. Skin biopsy - from actively depigmenting margins (not fully depigmented areas); pursue early
5. Ocular ultrasound - evaluate posterior segment when fundus cannot be visualized (e.g., corneal edema, hyphema)
6. Electroretinography - to assess retinal function pre-treatment
7. Aqueocentesis - cytology showing lymphocytes and melanin-laden macrophages supports diagnosis (specialist procedure)

• Infectious uveitis (Brucella, Leishmania, systemic fungal, Ehrlichia, Toxoplasma)
• Systemic hypertension-induced retinal detachment
• Lymphoma (uveal infiltration)
• Lens-induced uveitis
• Vitiligo (skin only, no uveitis)

Treatment

Ocular Treatment

• Topical corticosteroids (prednisolone acetate 1%, dexamethasone) - q2-6h initially
• Topical atropine or tropicamide (mydriasis, prevent synechiae)
• Topical carbonic anhydrase inhibitors or beta-blockers if IOP elevated
• Topical cyclosporine for KCS

• Methylprednisolone acetate - for sustained local anti-inflammatory effect

• When medical management fails: laser cyclophotocoagulation, drainage implants, or enucleation for painful blind eye

Systemic Treatment

• Prednisone / prednisolone: Immunosuppressive doses (2-4 mg/kg/day initially), tapered slowly over months based on response. High-dose early therapy is associated with stronger response.

• Azathioprine: 2 mg/kg/day (q24-48h); monitor CBC for myelosuppression
• Cyclosporine: 5 mg/kg/day; inhibits IFN-gamma and IL-17 production
• Mycophenolate mofetil: used in refractory cases
• Chlorambucil: alternative alkylating agent
• Cyclophosphamide: used in some severe cases

Prognosis

• Clinical remission is achievable but recurrence is common
• Permanent vision loss occurs in many dogs despite aggressive treatment; early diagnosis and early aggressive therapy are the most important prognostic factors
• Remission is defined by: improvement or restoration of vision, prevention of new signs, and arrest of skin depigmentation progression
• Dogs receiving only dermatologic monitoring may still have active subclinical ocular inflammation - ophthalmic follow-up is mandatory even when only skin signs are apparent
• The skin depigmentation (vitiligo component) tends to be permanent even when inflammation is controlled

Comparison with Human VKH

Key References

• Zubricky P, Balicka A, Drahovska Z. Uveodermatological syndrome in dogs: A review of diagnosis, management, and ophthalmic patient needs. Vet Med (Praha). 2025 Jun. PMID: 40778262
• Tham HL, Linder KE, Olivry T. Autoimmune diseases affecting skin melanocytes in dogs, cats and horses: vitiligo and the uveodermatological syndrome. BMC Vet Res. 2019.
• Zarfoss MK et al. Clinical findings and outcomes for dogs with uveodermatologic syndrome. J Am Vet Med Assoc. 2018;252(10):1263-71.
• Angles JM et al. Uveodermatologic (VKH-like) syndrome in American Akita dogs is associated with DQA1*00201. Tissue Antigens. 2005;66:656-665.
• Andrews' Diseases of the Skin (Vogt-Koyanagi-Harada Syndrome section, human VKH)