Polyautoimmunity manifest as inflammatory myopathy, uveitis, and progressive cutaneous depigmentation in a mixed breed dog: a case report.

BACKGROUND: Polyautoimmunity is the expression of more than one autoimmune disease in a single patient. This report documents polyautoimmunity in a mixed breed dog with concurrent uveitis, cutaneous depigmentation, and inflammatory myopathy. CASE PRESENTATION: A 1-year-old male neutered mixed breed dog was presented for progressive generalized leukotrichia and leukoderma, bilateral panuveitis, and masticatory muscle atrophy. The latter progressed to myositis of lingual, pharyngeal, and masticatory muscles confirmed by biopsy. Temporalis muscle was completely replaced by adipose and fibrous tissue, and necrotic myofibers with extensive infiltration of mononuclear cells indicated active myositis of lingual muscle. Skin biopsies showed severe melanin clumping in epidermis, hair follicles, and hair shafts, and perifollicular pigmentary incontinence. Uveitis, depigmentation, and myositis affecting the masticatory, pharyngeal, and tongue muscles were diagnosed based on clinical, histological, and laboratory findings. CONCLUSIONS: To the authors' knowledge, this is the first report of concurrent uveitis, progressive cutaneous depigmentation, and inflammatory myopathy in a dog.

Different MicroRNA profiles in Peripheral Blood mononuclear cells from patients with initial-onset and recurrent vogt-Koyanagi-Harada Disease.

BACKGROUND: Vogt-Koyanagi-Harada (VKH) disease is a common type of uveitis that leads to blindness. The clinical manifestations and treatment solutions are different between initial-onset and recurrent VKH. Therefore, identifying the microRNA (miRNA) profiles from initial-onset and recurrent VKH patients may shed light on the molecular mechanisms underlying the pathogenesis of VKH disease. METHODS AND RESULTS: RNAs isolated from peripheral blood mononuclear cells (PBMCs) from patients with initial-onset VKH, recurrent VKH, and healthy individuals were subjected to high-throughput miRNA sequencing. Pairwise analysis of miRNA sequencing data between groups was conducted to identify differentially expressed miRNAs (DEMs), which were verified using real-time quantitative polymerase chain reaction. After receiver operating characteristic analyses, we found that hsa-miR-4664-3p, hsa-miR-7704, hsa-miR-4504, and hsa-miR-206 may serve as biomarkers of different VKH stages. DEMs were classified into three groups based on their differential expression: DEMs in initial-onset stage, DEMs in recurrent stage, and DEMs common between both VKH stages (shared DEMs). Pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes identified the mitogen-activated protein kinase, tumor necrosis factor, and mechanistic target of rapamycin kinase pathways as significantly enriched among the target genes of recurrent stage and shared DEMs. Furthermore, we mapped a network of competing endogenous RNAs for hsa-miR-206, which we used to identify putative targets for VKH treatment. CONCLUSION: Hsa-miR-4664-3p, hsa-miR-7704, hsa-miR-4504, and hsa-miR-206 may serve as biomarkers for different stages of VKH. Additionally, our competing endogenous RNA network of hsa-miR-206 provides a new direction for VKH treatment.

A case presentation of an IgA nephropathy patient with Vogt-Koyanagi-Harada syndrome.

BACKGROUND: Vogt-Koyanagi-Harada syndrome is a rare disease characterized by skin and eyelash bleaching, chronic granulomatous iridocyclitis and exudative retinal detachment, and aseptic meningitis and encephalopathy. IgA nephropathy complicated by Vogt-Koyanagi-Harada syndrome is very rare, even though they might have similar pathogeneses. Ocular lesions often are not examined when patients are diagnosed with IgA nephropathy, which affects the prognosis. CASE PRESENTATION: We describe a 55-year-old male IgA nephropathy patient who was admitted with high fever and hematuria. Physical examination revealed impaired binocular vision with blurred vision, impaired hearing, and a congestive rash on the chest and back. Renal ultrasound examination showed no abnormalities. Laboratory examination showed that glomerulonephritis was complicated by infection, and anti-infection therapy was ineffective. Bilateral fluorescein angiography showed Vogt-Koyanagi-Harada syndrome. Further renal biopsy confirmed IgA nephropathy. Hormone shock therapy and cyclophosphamide adjuvant therapy were administered, and the patient's symptoms improved. CONCLUSION: For the first time, we reported the case of simultaneous onset of IgA nephropathy and Vogt-Koyanagi-Harada syndrome, which is very rare. The onset of Vogt-Koyanagi-Harada syndrome is rapid and serious, while that of IgA nephropathy is relatively milder, making it easy for specialized doctors to neglect this condition. Doctors should be highly alert to the clinical concomitant occurrence of the two diseases with similar mechanisms, especially in the case of neurological defects and ocular symptoms in IgA nephropathy patients, since timely immunosuppressive treatment may improve the outcome of ocular diseases.

MR findings of the orbit in patients with Vogt-Koyanagi-Harada disease.

PURPOSE: We aimed to evaluate the MR findings of the orbit in patients with Vogt-Koyanagi-Harada disease (VKHD). METHODS: We included 14 patients with clinically diagnosed VKHD, who underwent orbital MR imaging before treatment between May 2011 and August 2017. The mean duration from initial symptom onset to MR imaging was 16 days (range, 2-36 days). Fat-suppressed gadolinium-enhanced T1-weighted images were obtained in six patients. We retrospectively assessed the choroids and Tenon's capsules for the presence of thickening on unenhanced images and abnormal enhancement on contrast-enhanced images. RESULTS: Bilateral choroidal thickening was observed in 14 patients (100%) on T1-weighted images and in 12 patients (85.7%) on T2-weighted images. Choroidal thickening showed posterior pole predominance in 11 patients (78.6%) and diffusely distributed in the remaining three patients (21.4%). Bilateral Tenon's capsule thickening was observed in five patients (35.7%) on T1-weighted images and in 14 patients (100%) on T2-weighted images. On contrast-enhanced images, the choroids and Tenon's capsules were abnormally enhanced in six patients (100%). CONCLUSION: MR imaging sensitively detected abnormalities of the choroids and Tenon's capsules in patients with VKHD. Bilaterality and predominant posterior pole distribution were characteristic of choroidal VKHD.

A challenged case of Vogt-Koyanagi-Harada syndrome: when dermatological manifestations came first.

INTRODUCTION: Vogt-Koyanagi-Harada syndrome (VKHS) is an inflammatory systemic autoimmune disease principally affecting pigmented tissues in the ocular, auditory, integumentary and central nervous systems. Patients are generally women in the fourth decade of life. The prognosis is correlated mainly with the time between diagnosis and the start of treatment and number of recurrent episodes of inflammation. Most complications are mainly ocular. The purpose of this paper is to describe a clinical case of VKHS. MATERIAL AND METHODS: A child with a challenging clinical presentation in which the dermatological symptoms occurred before ocular manifestations. DISCUSSION AND CONCLUSION: VKHS is rare in children and can be a diagnostic challenge. It seemed interesting to share this case as an opportunity to expand our knowledge of the clinical spectrum of diseases and reflect about current diagnostic criteria.

Contribution of dual fluorescein and indocyanine green angiography to the appraisal of posterior involvement in birdshot retinochoroiditis and Vogt-Koyanagi-Harada disease.

PURPOSE: To assess the levels of retinal and choroidal involvement in initial-onset birdshot retinochoroiditis (BRC) and Vogt-Koyanagi-Harada (VKH) disease, two stromal choroiditis entities. METHODS: This retrospective study included patients diagnosed with BRC and VKH, seen during initial-onset disease at the Centre for Ophthalmic Specialized Care, Lausanne, Switzerland. Angiographic signs were quantified, using an established dual fluorescein angiography (FA) and indocyanine green angiography (ICGA) scoring system for uveitis, and the FA/ICGA score ratios were compared between diseases. RESULTS: Among 1793 patients with uveitis seen from 1995 to 2015, 7 newly diagnosed BRC patients and 4 patients with newly diagnosed VKH disease had sufficient data for study inclusion. Patients with BRC and VKH at initial onset had mean FA angiographic scores of 16.91 ± 3.42 and 4.06 ± 1.87; mean ICGA angiographic scores of 21.34 ± 3.49 and 25.75 ± 3.88; and mean FA/ICGA ratios of 0.79 ± 0.21 and 0.16 ± 0.09, respectively. CONCLUSION: This study showed the differential involvements of the retina and choroid in BRC and VKH. The choroid was preponderantly involved in both diseases; thus, ICGA is essential for disease assessment and follow-up. However, these diseases also differed substantially. The origin of inflammation was primarily in the choroid in VKH and in both the choroid and retina in BRC. We recommend dual FA and ICGA for evaluating posterior uveitis, when choroiditis is suspected.

Successful Treatment of Vitiligo Associated with Vogt-Koyanagi-Harada Disease.

Vogt-Koyanagi-Harada disease (VKH) is a rare multisystem disorder with cutaneous, ophthalmic, neurologic, and auditory manifestations. There is a paucity of published literature regarding the management of cutaneous features in VKH. We report a case of VKH-associated vitiligo responsive to topical corticosteroids and topical calcineurin inhibitors.

Vitiligo: Not Simply a Skin Disease.

Melanocytes, the cells responsible for skin pigmentation, are present in other parts of the body, such as the ocular, auditory, nervous, and cardiac systems. Within these systems, their roles serve a different purpose than their classical counterparts in skin as pigment cells. Such roles include cell turnover in retinal pigment epithelium, maintenance of balance and prevention of environmental damage in the auditory neuroepithelium, role-playing as dendritic cells within the leptomeninges, and prevention of oxidative damage in adipose tissue. Vitiligo, commonly known as a skin pigmentation disorder, has also been associated with several systemic disorders, such as Vogt-Koyanagi-Harada disease and Alezzandrini, Kabuki, and MELAS syndromes. Therefore, since these conditions involve compromise of systems in which melanocytes reside, it is not surprising that vitiligo has other systemic associations. The authors present a detailed review of systemic associations of vitiligo and melanocytes' roles in other organ systems with a focus on systemic disease.

FEATURES OF OPTICAL COHERENCE TOMOGRAPHY FOR THE DIAGNOSIS OF VOGT-KOYANAGI-HARADA DISEASE.

BACKGROUND/PURPOSE: To examine the diagnostic value of optical coherence tomography (OCT) for the detection of acute Vogt-Koyanagi-Harada (VKH) disease. METHODS: Clinical charts and OCT images were retrospectively reviewed for patients consecutively diagnosed with acute VKH, subacute VKH, multifocal central serous chorioretinopathy (CSCR), and posterior scleritis. All patients underwent OCT, fundus photography, and fluorescein angiography (FA) before treatment. The characteristics of OCT and FA were analyzed and recorded. RESULTS: The study included 80 eyes with acute VKH, 32 eyes with subacute VKH, 33 eyes with CSCR, and 13 eyes with posterior scleritis. The most common OCT features of VKH disease were hyperreflective dots (70/80; 88%), subretinal membranous structures (64/80; 80%), retinal detachment higher than 450 µm (63/80; 79%), and retinal pigment epithelium (RPE) folds (44/80; 55%). For the detection of VKH disease, sensitivity and specificity were for subretinal membranous structures 80% and 95.6%, respectively, for high retinal detachment 78.8% and 76.1%, respectively, for subretinal hyperreflective dots, 87.5 and 60.9%, respectively, and for RPE folds 55% and 80.4% respectively. Subretinal membranous structures showed the highest positive predictive value (97.3%) and negative predictive value (65.7%) of all OCT assessed features. CONCLUSION: OCT-related morphological signs have a relatively high predictive value for the diagnosis of acute VKH.

Clinical and multimodal imaging characteristics of acute Vogt-Koyanagi-Harada disease unassociated with clinically evident exudative retinal detachment.

The purpose of this study was to describe the clinical and multimodal imaging findings in acute Vogt-Koyanagi-Harada (VKH) disease without clinically evident exudative retinal detachment (ERD). We retrospectively reviewed the charts of 18 patients (36 eyes), diagnosed with acute VKH disease without clinically evident ERD. All patients underwent complete ophthalmic examination, fundus photography, optical coherence tomography (OCT), B-scan ultrasonography, fluorescein angiography (FA), and indocyanine green angiography (ICGA). Of 18 patients, twelve (66.7 %) were female and 6 (33.3 %) were male. Mean age was 39 years (range, 23-60). Ten patients had been referred with an erroneous diagnosis of primary optic nerve disorder (8; 44.4 %) or isolated anterior uveitis (2; 11.1 %). Anterior chamber or vitreous inflammatory reaction was noted in 22 eyes (61.1 %), each. Fundus findings included optic disc swelling in 30 eyes (83.3 %), retinal striae in 20 eyes (55.5 %), and yellowish deep lesions in 3 eyes (8.3 %). OCT showed a shallow, localized subclinical ERD in 18 eyes (50 %), and retinal pigment epithelial folds in 23 eyes (63.9 %). B-scan ultrasonography showed diffuse, low- to medium-reflective choroidal thickening in all eyes. FA disclosed delayed choroidal perfusion in at least one eye of all patients (100 %), mild pinpoint leakage in 21 eyes (58.3 %), optic disc hyperfluorescence in 35 eyes (97.2 %) and choroidal folds in 13 eyes (36.1 %). ICGA findings included delayed choroidal perfusion in 24 eyes (66.7 %), decrease in the number of large choroidal vessels in 36 eyes (100 %), fuzzy choroidal vessels in 35 eyes (97.2 %), and hypofluorescent dark dots in 28 eyes (77.8 %). The association of bilateral optic disc edema with retinal striae and intraocular inflammatory reaction highly suggests acute VKH disease. A multimodal imaging approach including fundus photography, OCT, B-scan ultrasonography, FA, and ICGA provides important clues for the definite diagnosis and help differentiate VKH disease from primary optic nerve disorders.

[Two cases of Vogt-Koyanagi-Harada disease presenting shallow anterior chamber].

PURPOSE: We report two cases of Vogt-Koyanagi-Harada disease (VKH) in which shallow anterior chambers were improved after steroid pulse therapy. CASE: The patients were women aged 65 and 72. They had headaches, decreased visual acuity and shallow anterior chamber in both eyes. There was no inflammation in the anterior chamber. Ultrasound biomicroscopy (UBM) showed ciliary edema, ciliochoroidal detachment, and angle closure. One case showed high intraocular pressure (IOP), and a diagnosis of acute primary angle closure was made. Although cataract surgery was performed in the left eye, postoperative optical coherence tomography (OCT) revealed serous retinal detachment in both eyes. The shallow anterior chamber and UBM findings were improved and serous retinal detachment disappeared after steroid pulse therapy in both cases. CONCLUSION: VKH may cause shallow anterior chamber and angle closure. The inflammatory changes of VKH in the anterior segment, i. e. ciliary edema and ciliochoroidal detachment, may exacerbate the shallow anterior chambers and narrow angles and result in an acute increase in IOP in eyes with short axial length. VKH associated with shallow anterior chamber may be misdiagnosed as acute primary angle closure. For differential diagnosis, examinations of the ocular fundus including OCT are useful.

Absence of recognition of common melanocytic antigens by T cells isolated from the cerebrospinal fluid of a Vogt-Koyanagi-Harada patient.

PURPOSE: Vogt-Koyanagi-Harada (VKH) syndrome is an autoimmune disease characterized by inaugural uveomeningitidis and hearing loss and at late stages a depigmentation in eyes and skin. Melanocytes are the cells common to the four affected tissues, namely eye, brain, inner ear, and skin. Melanocytes are therefore considered as the source of self-antigens. The melanocytic proteins tyrosinase-related protein-1 (TRP1), TRP2, tyrosinase, and gp100 have been proposed as the proteins targeted by autoreactive T cells from VKH patients bearing human leukocyte antigen (HLA)-DRB1*04:05, the HLA allele classically associated with VKH disease. The objective of this work was to determine the antigens recognized by a large number of potentially autoreactive CD4 T lymphocytes obtained from the cerebrospinal fluid of one VKH patient who did not express HLA-DRB1*04:05. METHODS: T cells were isolated from the cerebrospinal fluid of a newly diagnosed HLA-DRB1*14:01,*15:03;-DPB1*01:01,*04:02 patient in the acute phase of the VKH disease and cloned by limiting dilution. Each of the 107 T cell clones, of which 90% were CD4(+), was tested for its ability to secrete cytokines upon contact with autologous antigen-presenting cells loaded with either of the melanocytic proteins TRP1, TRP2, tyrosinase, gp100, Melan-A and KU-MEL-1. The sensitivity of our recombinant bacteria-based approach was validated with a CD4 T cell clone with known antigen specificity. The ability of each of the 107 clones to secrete cytokines upon nonspecific stimulation was verified. RESULTS: None of the 107 T cell clones was able to secrete tumor necrosis factor-α, interferon-γ, interleukin (IL)-5, or IL-17 upon contact with autologous B cells loaded with any of the six common melanocytic proteins. Nine clones secreted high-level IL-17 upon stimulation with beads coated with antibodies. CONCLUSIONS: The self-antigens that triggered the VKH disease in this patient probably derive from proteins other than the six melanocytic proteins mentioned above. Further study of antigens that are recognized by potential autoreactive T cells from VKH patients is likely to benefit from testing a broader set of melanocytic proteins.

Vogt-Koyanagi-Harada disease in an adolescent boy.

Vogt-Koyanagi-Harada (VKH) disease is a rare multiorgan disorder that affects the melanocytes of the eyes, skin, inner ear, and meninges. It is more common in women and in patients 30 to 50 years of age; it is rarely seen in children. We report a 14-year-old boy who meets the criteria for complete VKH disease.

Poliosis circumscripta: overview and underlying causes.

Although traditionally known as "white forelock," poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicles, can involve any hairy area on the body including the scalp, eyebrows, and eyelashes. Microscopically, poliosis demonstrates either decreased or absent melanin and/or melanocytes in the hair bulbs of the affected hair follicles. Classically, poliosis is known to occur in the setting of several genetic syndromes including piebaldism, Waardenburg, and tuberous sclerosis. In addition, poliosis has been described in association with various acquired conditions. These include inflammatory conditions, benign and malignant neoplastic entities that are mainly melanocytic, medications, and others. In this review, we aim to describe the different conditions where poliosis may be encountered, with the aim of helping the clinician to better evaluate any patient presenting with poliosis.

Identification of Hif1α as a Potential Participant in Autoimmune Uveitis Pathogenesis Using Single-Cell Transcriptome Analysis.

Purpose: This study purposed to depict the transcriptional changes associated with autoimmune uveitis (AU) pathogenesis and identify potential therapeutic targets of this disease. Methods: An experimental AU (EAU) model was established with retina antigen and adjuvants. An EAU control group was established with adjuvant only to eliminate nonspecific effects. We conducted single-cell RNA sequencing (scRNA-seq) on cervical draining lymph node cells of EAU, EAU control, and normal mice to identify the EAU-associated transcriptional changes and the potential pathogenic molecules. Subsequent flow cytometry, adoptive transfer experiment, scRNA-seq analysis of human uveitis, and proliferation assessment were conducted to verify the function of the interested molecule in uveitis. Results: The scRNA-seq data suggested that hypoxia-inducible factor 1 alpha (Hif1α) may participate in EAU pathogenesis via regulating T helper (Th)-17, Th1, and regulatory T cells. Hif1α inhibition alleviated EAU symptoms and regulated Th17, Th1, and regulatory T cell proportions. CD4+ T cells with repressed Hif1α expression failed to transfer EAU to naïve mice. In Vogt-Koyanagi-Harada disease, which is a human uveitis, Hif1α was also increased in CD4+ T cells and regulated their proliferation. Conclusions: The results indicate that Hif1α may participate in AU pathogenesis and are, thus, a potential therapeutic target.

Vogt-Koyanagi-Harada syndrome: a rare but important differential diagnosis of viral meningitis.

Vogt-Koyanagi-Harada syndrome (VKHS) is an inflammatory syndrome affecting melanocyte-containing organs. The clinical onset is often acute with neurological and ophthalmological symptoms and there is considerable risk of sequelae if the condition is not promptly diagnosed and treated. We present a case illustrating that VKHS is a rare but important differential diagnosis of viral meningitis.

Spectral domain optical coherence tomography of Vogt-Koyanagi-Harada disease: novel findings and new insights into the pathogenesis.

OBJECTIVE: To provide novel spectral domain optical coherence tomography (SD OCT) findings of Vogt-Koyanagi-Harada (VKH) disease as well as new insights into the pathogenesis of this disease. METHODS: Detailed SD OCT and fluorescein angiography (FA) findings of 18 consecutive VKH patients (11 women and 7 men) from December 2007 to April 2009 who were in acute uveitic stage at presentation were reviewed. All the patients had been followed up for at least 6 months with reevaluation(s) of SD OCT performed in 10 patients. RESULTS: Intraretinal cysts were found to be located in various layers of the outer retina. In addition to the photoreceptor layer, they could also be found between the outer plexiform layer and the outer nuclear layer, or spanning the external limiting membrane. On FA, intraretinal cysts could be hypofluorescent, normofluorescent, or hyperfluorescent. Some intraretinal cysts had a characteristic FA pattern, in which a small round hypofluorescent area was surrounded by a ring of hyperfluorescence (donut-shaped dye pooling). Subretinal fibrinoid deposit appeared in acute uveitic stage in two severe VKH patients and seemed to develop from subretinal exudates and evolved into typical subretinal fibrosis. Gradual transfiguration/migration and progressive proliferation/pigmentation of the subretinal fibrinoid deposit/subretinal fibrosis was observed in one patient. CONCLUSIONS: Intraretinal cysts could form in various layers of the outer retina and may result from extension of choroidal inflammation. Subretinal fibrosis may develop from subretinal exudates in VKH patients and may cause substantial visual impairment.

Iris Manifestations in Inadequately Treated Chronic Recurrent Vogt-Koyanagi-Harada Disease.

PURPOSE: To describe the iris changes in chronic recurrent Vogt-Koyanagi-Harada Disease (VKH). METHODS: Retrospective case series. Clinical features of 3 VKH patients who developed bilateral depigmentation of the iris are described. RESULTS: Patients had delayed diagnosis and inadequately treated chronic recurrent VKH. Patient 1 presented with bilateral multiple contiguous small granulomatous iris stromal lesions, severe diffuse iris swelling more severe near the iris root, producing peripheral iris undulations. Diffuse iris atrophy and peripheral depigmentation subsequently developed. Patient 2 presented with peripheral iris depigmentation, atrophy of the ciliary zone iris stroma and sparing of the sphincter pupillae, giving a 'sunflower appearance.' Patient 3 had extensive iris depigmentation, atrophy, and transillumination defects involving the entire iris. CONCLUSION: Uncontrolled bilateral diffuse granulomatous stromal iris inflammation leads to subsequent depigmentation, transillumination defects and atrophy, beginning in the peripheral iris. Sphincter pupillae is initially spared but complete iris atrophy may develop.

The emerging role of epigenetics and gut microbiota in Vogt-Koyanagi-Harada syndrome.

Vogt-Koyanagi-Harada (VKH) syndrome is an autoimmune disorder characterized often by acute diffuse uveitis, also known as idiopathic uveoencephalitis. The associated complications can potentially affect multiple systems throughout the body, including eyes, ears, skin and nervous system. Although the pathogenesis of VKH syndrome remains unclear, it has been established that the various genetic factors, epigenetic factors and the imbalance in immune regulation can significantly contribute to the development of this disease. In addition, the experimental autoimmune uveitis (EAU) has been commonly used to further explore the pathogenesis of the disease. Herein, in this review article, we discuss about the major research advances made in understanding of the different epigenetic factors and gut microbes involved in the pathogenesis of VKH syndrome as well as EAU. The information discussed can help to better understand the pathogenesis of VKH syndrome, and thereby might provide a basis for finding novel molecular targets and innovative treatment strategies in the future.