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.

Vogt-Koyanagi-Harada disease following ChAdOx1 nCoV-19 and mRNA-1273 vaccination.

Almost all vaccines have been reported to be associated with ocular inflammation, which has caused some concern regarding global mass COVID-19 vaccination efforts. Vogt-Koyanagi-Harada disease (VKHD) is a granulomatous inflammation caused by an autoimmune response against antigens in melanocytes, including those in the eyes. The mechanism by which COVID-19 vaccines are associated with VKHD is still unclear. Here, we report two cases of VKHD following COVID-19 vaccination. The first is a case of probable VKHD that presented with bilateral vision loss after administration of the adenovirus-vectored vaccine ChAdOx1 nCoV-19 (AstraZeneca). The condition improved after intravenous methylprednisolone 1g daily for 3days, followed by oral methotrexate and a slow taper of oral corticosteroids. The second case is a patient with an established diagnosis of well-controlled VKHD who developed a reactivation of the disease after receiving the mRNA-based vaccine (mRNA-1273, Moderna). VKHD is a potential ocular event that could follow COVID-19 vaccination. Awareness of this association is key to early detection and treatment to prevent loss of vision.

Case report: Bilateral panuveitis resembling Vogt-Koyanagi-Harada disease after second dose of BNT162b2 mRNA COVID-19 vaccine.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a serious pandemic. COVID-19 vaccination is urgent needed for limiting SARS-CoV-2 outbreaks by herd immunity. Simultaneously, post-marketing surveillance to assess vaccine safety is important, and collection of vaccine-related adverse events has been in progress. Vision-threatening ophthalmic adverse events of COVID-19 vaccines are rare but are a matter of concern. We report a 45-year-old Japanese male with positive for HLA-DR4/HLA-DRB1*0405, who developed bilateral panuveitis resembling Vogt-Koyanagi-Harada (VKH) disease after the second dose of Pfizer-BioNTech COVID-19 mRNA (BNT162b2) vaccine. Glucocorticosteroid (GC) therapy combined with cyclosporine A (CsA) readily improved the panuveitis. The immune profile at the time of onset was analyzed using CyTOF technology, which revealed activations of innate immunity mainly consisting of natural killer cells, and acquired immunity predominantly composed of B cells and CD8+ T cells. On the other hand, the immune profile in the remission phase was altered by GC therapy with CsA to a profile composed primarily of CD4+ cells, which was considerably similar to that of the healthy control before the vaccination. Our results indicate that BNT162b2 vaccine may trigger an accidental immune cross-reactivity to melanocyte epitopes in the choroid, resulting in the onset of panuveitis resembling VKH disease.

Vogt-Koyanagi-Harada Disease following mRNA-1273 (Moderna) COVID-19 Vaccination.

PURPOSE: To report a case of Vogt-Koyanagi-Harada (VKH) disease following mRNA-1273 (Moderna) COVID-19 vaccination. METHODS: Retrospective case report. RESULTS: A 50-year-old Korean woman developed bilateral serous retinal detachment 35 days after the first dose of COVID-19 mRNA vaccination (mRNA-1273, Moderna). She experienced adverse effects such as erythema and pain at the injection site, headache, myalgia, and allergy symptoms prior to ocular manifestation. She was diagnosed with Vogt-Koyanagi-Harada (VKH) disease. After treatment with oral prednisolone, the serous retinal detachment resolved and vision improved. CONCLUSION: COVID-19 vaccination might be associated with VKH disease development, and the ingredients of the mRNA vaccine or viral peptide encoded by mRNA may have activated the immunological process and induced VKH disease.

Vogt-Koyanagi-Harada Disease Exacerbation Associated with COVID-19 Vaccine.

We describe a case of Vogt-Koyanagi-Harada (VKH) disease exacerbation after COVID-19 vaccination. A 46-year-old woman presented with a bilateral granulomatous uveitis 2 days after the first dose of COVID-19 mRNA vaccine (Comirnaty, Pfizer-BioNTech), and was diagnosed with a complete Vogt-Koyanagi-Harada (VKH) disease 4 days after receiving the second dose of the vaccine. Three weeks before the first dose, she had been consulted for blurred vision and mild headaches. The case resolved with high dose intravenous corticosteroids, followed by oral prednisone. The close temporal relationship between the COVID-19 vaccine doses and the worsening of VKH symptoms strongly suggests COVID-19 vaccination as the trigger of its exacerbation.

De Novo Vogt-Koyanagi-Harada Disease following Covid-19 Vaccine: A Case Report and Literature Overview.

PURPOSE: To describe a case of Vogt-Koyanagi-Harada (VKH) disease after a Covid-19 mRNA vaccine (tozinameran) and to present the results of a pharmacovigilance disproportionality study. METHODS: A retrospective chart review and a pharmacovigilance disproportionality study using the WHO global individual case safety reports database (VigiBase). RESULTS: A 57-year-old female with no medical history developed a VKH disease 3 weeks after Covid-19 mRNA vaccine. Symptoms at onset were headaches and blurred vision associated with aseptic meningitis and bilateral diffuse granulomatous panuveitis with serous retinal detachment. One month from diagnosis and glucocorticoids treatment, the patient recovered. Five similar cases have been reported in VigiBase. VKH disease is disproportionately reported with tozinameran and other vaccines. CONCLUSION: VKH disease is disproportionately reported with tozinameran, suggesting a possible safety signal. Cases after vaccination support the screening for any possible immune triggers such as vaccines when assessing patients with VKH disease.

Vogt-Koyanagi-Harada Disease Associated with COVID-19 mRNA Vaccine.

A 54-year-old Chinese male with no previous ocular history presented to the ophthalmology department for the bilateral acute painless blurring of vision after receiving the 1st dose of COVID-19 mRNA vaccine (PFIZER-BioNTech/COMIRNATY). Clinical examination and imaging tests were consistent with Vogt-Koyanagi-Hara disease. The patient responded well with a high dose of intravenous methylprednisolone followed by a tapering dose of oral prednisolone.

Immune Phenotyping of Patients With Acute Vogt-Koyanagi-Harada Syndrome Before and After Glucocorticoids Therapy.

Previous studies have established that disturbed lymphocytes are involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) syndrome. Accordingly, glucocorticoids (GCs), with their well-recognized immune-suppressive function, have been widely used for treatment of VKH patients with acute relapses. However, the systemic response of diverse immune cells to GC therapy in VKH is poorly characterized. To address this issue, we analyzed immune cell subpopulations and their phenotype, as well as cytokine profiles in peripheral blood from VKH patients (n=25) and health controls (HCs, n=21) by flow cytometry and luminex technique, respectively. For 16 patients underwent GC therapy (methylprednisolone, MP), the aforementioned measurements as well as the transcriptome data from patients before and after one-week's GC therapy were also compared to interrogate the systemic immune response to GC therapy. Lymphocyte composition in the blood was different in VKH patients and HCs. VKH patients had significantly higher numbers of T cells with more activated, polarized and differentiated phenotype, more unswitched memory B cells and monocytes, as compared to HCs. MP treatment resulted in decreased frequencies of T cells and NK cells, inhibited NK cell activation and T cell differentiation, and more profoundly, a marked shift in the distribution of monocyte subsets. Collectively, our findings suggest that advanced activation and differentiation, as well as dysregulated numbers of peripheral lymphocytes are the major immunological features of VKH, and GC therapy with MP not only inhibits T cell activation directly, but also affects monocyte subsets, which might combinatorically result in the inhibition of the pathogenic immune response.

Vogt-Koyanagi-Harada-like Disease following Yellow Fever Vaccination.

Purpose: To report the manifestation of Vogt-Koyanagi-Harada-like disease (VKH) following yellow fever vaccination.Methods: Case report.Results: A 34-year-old immunocompetent male had tinnitus, headache, and decreased vision after a booster dose of yellow fever vaccine. Visual acuity was 20/100 in the right eye and 20/80 in the left, with serous retinal detachment (SRD) and choroidal thickening identified on clinical examination and multimodal imaging. Lumbar puncture revealed pleocytosis and an increased protein content, but extensive investigations ruled out infectious/neurological diseases. Pulse intravenous methylprednisolone was given, followed by a tapering regimen of high-dose oral prednisone. Azathioprine was started early, 3 weeks after initiation of oral steroids. Intraocular inflammation and SRD rapidly resolved, with visual acuity reaching 20/20 in both eyes, after 3 weeks. No recurrence of intraocular inflammation or sign of depigmentation was so far noticed, at 2 years of follow-up.Conclusion: Yellow fever vaccine may be a possible trigger for VKH.

Evolving spectrum of drug-induced uveitis at the era of immune checkpoint inhibitors results from the WHO's pharmacovigilance database.

PURPOSE: Drug-induced uveitis is a rare but sight-threatening condition. We seek to determine the spectrum of drug-induced uveitis at the era of immune checkpoint inhibitors (ICI). METHODS: Retrospective pharmacovigilance study based on adverse drug reactions reported within VigiBase, the WHO international pharmacovigilance database. We included deduplicated individual case safety reports (ICSRs) reported as 'uveitis' at Preferred Term level according to the Medical Dictionary for Drug Regulatory Activities between 1967 and 04/28/2019. We performed a case/non-case analysis to study if suspected drug-induced uveitis were differentially reported for each suspected treatment compared to the full database. We excluded drugs with potential indication bias. RESULTS: 1404 ICSRs corresponding to 37 drugs had a significant over-reporting signal with a median age of 57 [42-68] years and 45.7% of males. We identified five major groups of treatments: bisphosphonates (26.9%), non-antiviral anti-infectious drugs (25.4%), protein kinase inhibitors (15.5%), ICI (15.0%), and antiviral drugs (11.1%). Severe visual loss was reported in 12.1% of cases. ICI and protein kinase inhibitors were the most recently emerging signals. The time to onset between first infusion and uveitis was significantly different between groups ranging from 5 days [2-19] in the bisphosphonate group to 138.5 [47.25-263.75] in protein kinase inhibitors group (p < 0.0001). Anti-Programmed Cell death 1 represented more than 70% of ICI-induced uveitis. We identified Vogt-Koyanagi-Harada (VKH)-like syndrome as being associated with ICI use. CONCLUSIONS: The spectrum of drug-induced uveitis has changed with the evolution of pharmacopeia and the recent emergence of ICIs. VKH-like syndrome has been reported with ICI and protein kinase inhibitors therapy.

Rara asociación entre la enfermedad de Vogt-Koyanagi-Harada y la artritis reumatoide. Reporte de un caso clínico de la consulta multidisciplinar de uveítis / Rare association between Vogt-Koyanagi-Harada disease and rheumatoid arthritis: Report of a clinical case from the unit of multidisciplinary uveitis

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The effectiveness of adalimumab treatment for non-infectious uveitis.

Uveitis, which is a major cause of blindness worldwide, is defined as intraocular inflammation that affects the iris, ciliary body, vitreous, retina and choroid. Tumor necrosis factor-alpha (TNF-α) is a key cytokine involved in the pathogenesis of many inflammatory diseases including uveitis. Corticosteroids and immunosuppressive agents are the conventional therapy to treat non-infectious uveitis. In cases that are resistant to these therapies, anti-TNF agents are added. An anti-TNF-α agent, adalimumab, was recently approved for the treatment of refractory non-infectious uveitis. In this review, we provide an introduction to uveitis and summarize the effectiveness and safety of adalimumab in the treatment of non-infectious uveitis.

Descolamento seroso de coroide como manifestação tardia da síndrome de Vogt-Koyanagi-Harada / Serous choroidal detachment in chronic stage of Vogt-Koyanagi-Harada syndrome

Resumo Relatamos um caso atípico de uma paciente de 40 anos com apresentação completa da Síndrome de Vogt-Koyanagi-Harada (SVKH) que após 17 anos do diagnóstico inicial evoluiu com descolamento seroso de coroide. A paciente procurou atendimento com queixa de dor em olho esquerdo (OE). O exame oftalmológico revelou acuidade visual (AV) igual a de movimento de mãos, à biomicroscopia foi observada reação inflamatória granulomatosa na câmara anterior, a tonometria foi igual a 0 mmhg, e a fundoscopia indevassável pela pouca midríase e turvação de meios em OE. O descolamento seroso de coroide foi avaliado através de ultrassonografia ocular. A abordagem terapeutica intituida para paciente consistiu em prednisona 1mg/kg/dia via oral, dexametasona 1mg/mL e atropina 1% colírios. A evolução do quadro foi satisfatória, com melhora da AV para 20/40, ausência de reação inflamatória em câmara anterior, normalização da pressão intraocular e resolução do descolamento seroso de coroide em OE. Concluimos que a fase crônica da SVKH, apesar da manifestação classicamente descrita ser uveíte anterior, pode ter outras apresentações e o descolamento seroso da coroide é uma rara complicação.

Abstract We report an atypical case of a 40-year-old woman with complete presentation of Vogt-Koyanagi-Harada Syndrome (VKH) who presented with unilateral serous choroidal detachment 17 years after the diagnosis. The patient complained of pain in the left eye, the ophthalmologic examination revealed visual acuity (VA) equal to hand motion; biomicroscopy revealed a granulomatous inflammatory reaction in the anterior chamber, tonometry was equal to 0 mmhg, and the fundoscopy was impracticable. Serous choroidal detachment was assessed by ocular ultrasonography. The therapeutic approach proposed for the patient consisted of prednisone 1mg / kg / day orally, dexamethasone 1mg / mL and atropine 1% eye drops. The evolution of the condition was satisfactory, with VA improvement to 20/40, absence of inflammatory reaction in anterior chamber, normalization of intraocular pressure and resolution of serous choroidal detachment in OS. We conclude that the chronic phase of VKH, although classically described as anterior uveitis, may have other presentations and the serous choroid detachment is a rare complication.

Vogt-Koyanagi-Harada Disease Associated with Hepatitis B Vaccination.

Purpose: To report a case of Vogt-Koyanagi-Harada (VKH) disease associated with hepatitis B vaccination. Methods: Case report. Results: A 43-year-old Caucasian male presented with a three-week history of blurry vision, pain, photophobia, and redness in both eyes. Three days prior to the onset of symptoms, he had received the hepatitis B virus vaccine. Clinical evaluation revealed multifocal placoid lesions in the posterior pole, choroidal thickening, and serous macular detachment. Targeted laboratory investigations were negative for infectious or autoimmune markers. After treatment with oral corticosteroids, the patient had resolution of symptoms with near-total recovery of visual function. The patient later reported systemic findings of hearing loss, tinnitus, and integumentary changes. A diagnosis of VKH disease was made and inflammation was managed with oral corticosteroids followed by methotrexate for long-term disease control. Conclusions: VKH disease is an inflammatory condition primarily affecting the choroid, retinal pigment epithelium, and outer retina. The underlying etiology is unclear, but it can be associated with a viral prodrome suggesting an infectious trigger in a genetically susceptible individual. Our case suggests that hepatitis B vaccination may trigger a similar inflammatory response.

Vogt-Koyanagi-Harada disease in a patient of chronic myeloid leukemia.

This case report describes the concurrent development of Vogt-Koyanagi-Harada (VKH) disease in a 39 year old male patient of chronic myeloid leukemia (CML). The patient being reported was a known case of CML in remission with history of painless sudden loss of vision in both eyes. Cases of leukemia can present with visual loss due to multiple ocular manifestations of leukemia itself or side effects of modern drugs used for its treatment. Clinical examination and multimodal imaging of our patient were suggestive of concurrent development of VKH. The patient was started on oral steroids, to which he showed a good response. Thus, the cases of CML may rarely develop concurrent ocular disorders not related to leukemia. These associated ocular disorders need to be distinguished from the ocular manifestations of leukemia itself. Our case highlights the concurrent development of VKH as the etiology of visual loss in a case of CML.

[Vogt-Koyanagi-Harada disease]. / La maladie de Vogt-Koyanagi-Harada.

Vogt-Koyanagi-Harada (VKH) disease is defined as a severe bilateral, chronic granulomatous panuveitis associated with serous retinal detachments, disk edema, and vitritis, with central nervous system, auditory, and integumentary manifestations. It is an autoimmune inflammatory condition mediated by T cells that target melanocytes in individuals genetically susceptible to the disease. Vogt-Koyanagi-Harada disease presents clinically in 4 different phases: prodromal, acute inflammatory, chronic, and recurrent, with extraocular manifestations including headache, meningitis, hearing loss, poliosis, and vitiligo. Optical coherence tomography (OCT) allows earlier diagnosis of VKH disease by revealing heterogeneous exudative detachments of the retina in the acute stage and choroidal thickening, and by demonstrating choroidal thinning in the chronic stage. Treatment of this disease is initially with intravenous corticosteroids, with, if needed, a transition to immunosuppressant drugs for long-term control. Patients with VKH disease can have good final visual outcomes if treated promptly and aggressively.

[Clinical features, risk factors and progresses on treatment of recurrent Vogt-Koyanagi-Harada disease].

Vogt-Koyanagi-Harada disease(VKH) is a bilateral, granulomatous panuveitis associated with central nervous system, auditory, and integumentary manifestations. Clinically, VKH usually responds well to early aggressive glucocorticosteroid treatment and may be cured without any clinically significant sequelae. Some patients, however, may enter the chronic recurrent phase, which may result in marked loss of vision due to complications such as complicated cataract, secondary glaucoma and maculopathy. Recurrent VKH is mainly characterized by anterior uveitis associated with thickening of the choroid. Initial poor visual acuity, severe anterior chamber reaction, choroidal folds,rapid tapering of systemic corticosteroids or inadequate duration of treatment, and development of extraocular manifestations may be risk factors of disease recurrence. Prolonged glucocorticosteroid treatment has been suggested as effective strategy for recurrence of VKH. The positive effects of other immunosuppressive agents and biologic agents on treatment of chronic recurrent and refractory VKH have been gradually recognized by the uveitis community. (Chin J Ophthalmol, 2017, 53: 317-320).

Vogt-Koyanagi-Harada-like Syndrome Complicating Pembrolizumab Treatment for Metastatic Melanoma.

Vogt-Koyanagi-Harada (VKH) syndrome is a rare condition implicating systemic immune reaction against melanocytes. The pathophysiology is unclear. A genetic predisposition has been suggested as HLA-DR4/DRB1*04 is more common among VKH patients. Drug induced VKH syndrome has been reported in advanced melanoma patients receiving immunotherapy, including ipilimumab and adoptive cell transfer of Tumor-Infiltrating Lymphocyte associated with IL-2. To date, no case of anti PD-1 -induced VKH syndrome has been described. We report here the case of a HLA-DR4/DRB1*04 patient successfully treated with anti PD-1 for advanced melanoma who developed a systemic immune reaction against melanocytes for whom we discuss a VKH-like syndrome diagnosis in a potentially genetically predisposed patient.

Genetic analysis of innate immunity in Behcet's disease identifies an association with IL-37 and IL-18RAP.

Interleukin-1 (IL-1) and the IL-1 receptor (IL-1R) family play an important role in the pathogenesis of inflammatory diseases. This study aimed to investigate the association between single nucleotide polymorphisms (SNP) of IL-1 and IL-1R family genes with Vogt-Koyanagi-Harada (VKH) and Behcet's disease (BD) in Han Chinese. The case-control study was divided into two stages and included 419 VKH cases, 1063 BD cases and 1872 healthy controls. The MassARRAY platform (Sequenom), iPLEX Gold Assay and TaqMan SNP assays were used to score genotypes of 24 SNPs. The expression of IL-37 and IL-18Rap was measured by ELISA and real-time PCR in genotyped healthy individuals. A significantly lower frequency of the AG genotype, and a higher frequency of the GG genotype and G allele of IL-37/rs3811047 were observed in BD as compared to controls. AA genotype and A allele frequency of IL-18RAP/rs2058660 was significantly decreased in BD as compared to controls. Functional studies performed in healthy controls showed that rs3811047 AG genotype carriers had a higher IL-37 gene expression in peripheral blood mononuclear cells (PBMCs) than GG carriers. GG carriers showed a higher cytokine expression as compared to AG carriers. No association was detected between the tested SNPs and VKH.

Cutaneous manifestations associated with melanoma.

Melanoma is a malignancy most commonly arising from the skin; therefore, primary melanoma characteristics are usually the first cutaneous manifestations of melanoma. Cutaneous metastases, which can occur locally or diffusely, are important to detect in a timely manner as treatments for advanced melanoma that impact survival are now available. Melanoma can be associated with local or diffuse pigmentation changes, including depigmentation associated with the leukodermas and hyperpigmentation associated with diffuse melanosis cutis. The leukodermas occur frequently, illustrate the immunogenic nature of melanoma, and may impact prognosis. Paraneoplastic syndromes in association with melanoma are rare, though can occur.