Hipoacusia en el síndrome de Vogt-Koyanagi-Harada: reporte de caso y revisión de la literatura / Hearing loss in Vogt-Koyanagi-Harada syndrome: case report and literature review

El síndrome de Vogt-Koyanagi-Harada (VKH) es una rara enfermedad granulomatosa multisistémica caracterizada por aparición de panuveítis grave bilateral y desprendimiento seroso de retina; puede acompañarse de un amplio espectro de síntomas extraoculares como los auditivos, y la afección más frecuente es la hipoacusia neurosensorial. Su etiología se reconoce como respuesta autoinmune mediada por células T contra antígenos de melanocitos presentes en coroides, meninges, cóclea y piel. Asimismo, factores genéticos del huésped se han identificado como predisponentes para su aparición, y es la presencia del alelo HLA-DR4, en particular el subtipo HLA-DRB1 0405, el más estudiado hasta la fecha. El tratamiento se basa en administración de corticosteroides sistémicos en dosis altas, sin embargo, es escasa la evidencia que evalúa específicamente la eficacia de estos medicamentos sobre sus manifestaciones audiovestibulares. Este artículo expone un caso de síndrome de VKH con compromiso auditivo concomitante y realiza una breve revisión narrativa de la literatura.

Vogt-Koyanagi-Harada syndrome (VKHS) is a rare multisystemic granulomatous disease, characterized by severe bilateral panuveitis and serous retinal detachment; it can be associated with a wide spectrum of extraocular symptoms, such as auditory symptoms, and the most common condition is sensorineural hearing loss. Its etio-logy is recognized as a T-cell-mediated autoimmune response against melanocyte antigens present in the choroid, meninges, cochlea, and skin. Likewise, host genetic factors have been identified as predisposing for its development, specifically the pre-sence of the HLA-DR4 allele, the HLA-DRB1 0405 subtype is the most studied up to date. Treatment is based on the administration of high doses of systemic corticos-teroids, however, there is not much evidence that specifically evaluates the efficacy of these medications on their audiovestibular manifestations. This article presents a clinical case of VKH syndrome with concomitant hearing impairment and carries out a short narrative review of the literature.

Hepatotoxicidade induzida por azatioprina em portadora da síndrome de Vogt-Koyanagi-Harada / Azathioprine-induced hepatotoxicity in a Vogt-Koyanagi-Harada syndrome patient

Este relato teve como objetivo apresentar um caso de hepatotoxicidade colestática induzida por azatioprina em portadora da síndrome de Vogt-Koyanagi-Harada. À admissão, apresentava icterícia +3/+4, acolia fecal e colúria, além de aumento de marcadores hepáticos, sendo compatível com síndrome colestática, cuja etiologia foi confirmada após exclusão de outras causas possíveis e retirada da azatioprina. A paciente evoluiu, após 1 semana de retirada do fármaco, com diurese livre de coloração menos escura e evacuação presente, sem acolia. Além disso, houve melhora nos exames que precederam a alta hospitalar

This report aimed at presenting a case of azathioprine-induced cholestatic hepatotoxicity in a patient with Vogt-Koyanagi-Harada syndrome. On admission, she presented with jaundice +3/+4, acholic feces, and choluria, as well as increased hepatic markers, all consistent with cholestatic syndrome, the etiology of which was confirmed after other possible causes were ruled out and azathioprine was discontinued. After 1 week of the drug discontinuation, the patient progressed with free diuresis of lighter color and defecation, with no acholia. In addition, tests performed before discharge were improved.

Achados audiológicos na Síndrome de Vogt-Koyanagi-Harada / Audiological findings in the Vogt-Koyanagi-Harada Syndrome

RESUMO A síndrome de Vogt-Koyanagi-Harada (SVKH) é rara, multissistêmica e autoimune. Atinge principalmente os olhos, provocando uma panuveíte crônica bilateral, porém traz afecções em outras áreas e tecidos que são ricos em melanócitos, como olhos, orelha interna, meninges e a pele. Sua origem ainda não é totalmente conhecida. Geralmente, a SVKH atinge indivíduos de origem hispânica, do Oriente Médio, indianos, nativos americanos e asiáticos. Descrição dos aspectos audiológicos acometidos pela síndrome e as possíveis intervenções fonoaudiológicas para um caso específico. Paciente de 53 anos, sexo feminino, compareceu à Clínica de Fonoaudiologia, Faculdade de Odontologia de Bauru (FOB) com queixas audiológicas e diagnóstico médico da SVKH. A paciente apresentou perda auditiva sensório-neural bilateralmente, emissões otoacústicas evocadas ausentes e queixas vestibulares de vertigem postural e desequilíbrio ao andar, bem como queixa de zumbido agudo contínuo. O caso apresentado mostrou perda auditiva sensório-neural, vertigem, zumbido e acometimento ocular bilateral. Apesar do tratamento com corticoesteroide, a perda auditiva se manteve. Desta forma, precedente à indicação do AASI, o fonoaudiólogo deve atentar-se para o acompanhamento audiológico do caso, realização ou não de tratamento medicamentoso e ocorrência de sintomas sugestivos da síndrome, favorecendo o encaminhamento para o médico e participando ativamente do processo terapêutico envolvendo a audição.

ABSTRACT The Vogt-Koyanagi-Harada syndrome (VKHS) is a rare, multisystemic and autoimmune disease. The syndrome mainly affects the eyes, followed by bilateral chronic panuveitis, however, the syndrome may also affect the melanocytes tissues, for example, the eyes, inner ear, meninges and skin. The syndrome origin mechanism is not yet completely known. Commonly, the specific ethnic groups that are affected by the VKHS are as follows: Hispanics, Asians, Indians, Native Americans and ethnic groups from the Middle East. The audiological characteristics of the syndrome and the possible audiologist interventions for a specific case will be reported. The patient was attended at the Clinic of Speech Therapy, Faculdade de Odontologia de Bauru (FOB). She is 53 years old and presented audiological complaints. She was diagnosed with VKHS by a specialist doctor. Throughout the audiologist assessment, she presented bilateral sensorineural hearing loss, absent otoacoustic evoked emissions, complaints about postural vertigo and acute tinnitus. The specific case reported presented sudden sensorineural hearing loss, vertigo, tinnitus and bilateral ocular disease. Even though drug treatment was performed, the hearing loss remained. Therefore, before the hearing aid (HA) fitting, the audiologist should perform the hearing management, investigate if the patient takes the drug treatment and the occurrence of suggestive symptoms of the syndrome. These are some points that help in the reference to the specialist doctor and the audiologist strongly participates in what concerns the hearing.

Vogt-Koyanagi-Harada disease. Case report and review of the literature / Enfermedad de Vogt Koyanagi Harada. Reporte de un caso y revisión de la literatura

ABSTRACT Vogt Koyanagi Harada disease affects several parts of the body, such as eyes, meninges, ears, and skin. The progressive course of the disease can lead to blindness and deafness. The case is presented of a Hispanic woman (mixed-race) with visual alterations, headache, tinnitus, hearing loss, and posterior uveitis with serous detachments of the retina in both eyes, as well as lymphocytic meningitis. The aim of the present study is to review the literature, the diagnostic strategies, and the appropriate treatment, as well as to update the immunogenetic pathogenesis of the disease.

RESUMEN La enfermedad de Vogt Koyanagi Harada compromete múltiples órganos tales como ojos, meninges, oídos y piel. El curso progresivo de la enfermedad puede llevar a ceguera y cofosis. Se describe un caso de esta enfermedad en mujer hispana (mestiza) con alteraciones visuales, cefalalgia, tinnitus e hipoacusia a quien se le encuentra uveítis posterior con desprendimientos serosos de retina en ambos ojos y meningitis linfocitaria. El objetivo del presente estudio es, mediante una revisión de la literatura, actualizar la patogénesis inmunogenética, conocer las estrategias diagnósticas y el tratamiento apropiado.

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.

The comparison of optic disc parameters and the thickness of circumpapillary retinal nerve fiber layer between acute Vogt-Koyanagi-Harada syndrome and acute central serous chorioretinopathy / 中华眼底病杂志

Objective To compare the differences of optic nerve head (ONH) parameters and the thickness of circumpapillary retinal nerve fiber layer (CP-RNFL) between acute Vogt-Koyanagi-Harada syndrome (VKH) and acute central serous chorioretinopathy (CSC) patients.Methods Retrospective clinical case control analysis.This study included 38 eyes of 20 acute VKH patients (VKH group) and 37 eyes of 37 acute CSC patients (CSC group).Seventy five eyes of 57 normal healthy subjects,matching patients with age and gender,were collected as control group.The disc RPE angle,the thickness of average CP-RNFL,the nasal,superior,temporal and inferior quadrant CP-RNFL thickness,and ONH parameters including optic disc area,cup area,rim area,C/D area ratio,linear CD ratio (CDR),vertical CDR were measured by 3D-OCT.Analysis of variance was performed for comparison among three groups.Minimum significant difference t test was performed for comparison between two groups.Results The differences of ONH parameters between VKH group and CSC group:29 eyes of VKH group appeared retinal detachment next to disc,only 12 eyes appeared in CSC group.Twenty one eyes of VKH group appeared optic disc hyperemia while none in CSC group.The three groups' disc RPE angles were (138.62± 11.96)°,(154.09±5.85)° and (153.41 ±5.77)°.VKH group were significantly smaller than CSC group (t=-2.05,P=0.00) and control group (t=-1.68,P=0.00),while there was no significant difference between CSC group and control group (t=-1.88,P=0.72).The optic cup area and rim area were significantly bigger in VKH group than in CSC group (t=4.61,2.71;P=0.00,0.01),and the thickness of mean CP-RNFL,all quadrants of CP-RNFL were significantly thicker in VKH group than in CSC group (t=6.25,4.40,3.53,5.48,2.69;P=0.00,0.00,0.00,0.00,0.01).Conclusion Compared with the acute CSC,VKH patients are likely to appear retinal detachment next to disc,their disc RPE angles are smaller,their optic cup area and rim area are bigger,and their CP-RNFL thickness are thicker.

Síndrome de Vogt-Koyanagi-Harada: Avaliação da fase da doença na qual os pacientes recebem o primeiro atendimento em serviço especializado / Vogt-Koyanagi-Harada syndrome: evaluation of the disease phase in which patients receive the first specialized attendance

Resumo Objetivo: Avaliar em qual fase da síndrome de Vogt-Koyanagi-Harada (SVKH) os pacientes recebem o primeiro atendimento em serviço especializado. Métodos: Foram analisados prontuários de 14 pacientes atendidos no Setor de Uveítes do Hospital Universitário Clementino Fraga Filho da UFRJ no período de janeiro de 2014 a março de 2017. Nesta análise, foram observados o sexo, a idade, a fase da doença e a acuidade visual destes pacientes com ao menos doença provável da SVKH. Resultados: Observamos que 35,4% dos pacientes apresentavam a doença ainda na fase uveítica e que 78,5% destes pacientes apresentava acuidade visual igual ou pior que 0,05. Destes pacientes, 78,5% eram do sexo feminino e 21,5% do sexo masculino e a mediana de idades foi de 34 anos. Conclusão: Os pacientes analisados obtiveram dificuldade em ter acesso precoce a um setor especializado, afetando assim, diretamente o tratamento e prognóstico visual.

Abstract Objective: To evaluate in which phase of Vogt-Koyanagi-Harada (VKH) syndrome the patients receive the first attendance in specialized service. Methods: A retrospective study was conduted to evaluate medical records of 14 patients with VKH in the Clementino Fraga Filho University Hospital of the Federal University of Rio de Janeiro from January 2014 to March 2017. In this analysis, gender, age, stage of disease and visual acuity of these patients with at least probable VKH were recorded. Results: Of these patients, 78.5% were female and 21.5% male and the median age was 34 years. We observed that 35.4% of the patients had the disease still in the uveitic phase and that 78.5% of these patients had visual acuity equal to or worse than 0.05. Conclusion: There is a delay in the admission of these patients to a specialized sector, thus affecting directly the treatment and visual prognosis.

The changes in optic disc parameters of Vogt-Koyanagi-Harada syndrome and optic neuritis with optic disc edema using three-dimensional optical coherence tomography / 中华眼底病杂志

Objective To compare the differences of optic disc morphology and optic nerve head parameters between Vogt-Koyanagi-Harada (VKH) syndrome and optic neuritis (ON) with optic disc edema. Methods This is a retrospective study including 21 first-onset VKH patients (35 eyes) as VKH group and 22 first-onset ON patients with optic disc edema (27 eyes) as ON group. The differences of age (t=-1.11) and gender (χ2=0.20) between two groups were not significant (P>0.05). Sixty-two eyes of 43 age and gender-matched healthy subjects were enrolled in this study as control group. All subjects underwent three dimensional optical coherence tomography (3D-OCT) examinations. The difference of optic disc morphology between two groups was observed. The parameters included average thickness of entire circumpapillary retinal nerve fiber layer (CP-RNFL), thickness of nasal, superior, temporal and inferior quadrant of CP-RNFL, disc area, disc cup area, rim area, cup/disc (C/D) area ratio, C/D horizontal diameter ratio and C/D vertical diameter ratio. The disc retinal pigment epithelium (RPE) angle was observed too. Results Among 35 eyes in VKH group, 31 eyes (88.57%) had retinal detachment next to the disc, 3 eyes (8.57%) had serrated inner limiting membranes of the disc. Twenty eyes (64.52%) had highly reflective points, lines, or membrane-like structures in the retinal detachment areas. No such signs appeared in ON patients. Compared with ON group, the optic cup area, C/D area ratio, C/D horizontal diameter ratio and C/D vertical diameter ratio were bigger, the thickness of mean CP-RNFL and the superior, inferior quadrants of CP-RNFL were thinner, disc RPE angles was smaller in VKH group (P<0.05). Compared with control group, the disc area, optic cup area, rim area were bigger, C/D vertical diameter ratio was smaller, the mean CP-RNFL and 4 quadrants CP-RNFL were thicker, disc RPE angles was smaller in VKH group (P<0.05); the disc area, optic cup area, C/D area ratio, C/D horizontal diameter ratio and C/D vertical diameter ratio were smaller, the mean CP-RNFL and 4 quadrants CP-RNFL were thicker, disc RPE angles was bigger in VKH group (P<0.05). Conclusions VKH patients have smaller disc RPE angles and more chance to develop retinal detachment next to disc than ON patients. The C/D area ratio, C/D horizontal diameter ratio and C/D vertical diameter ratio are bigger, the mean CP-RNFL and the superior, inferior quadrants of CP-RNFL are thinner in VKH eyes.

The changes in optic disc parameters and thickness of circumpapillary retinal nerve fiber layer in acute uveitis of Vogt-Koyanagi-Harada syndrome with different degrees of optic disc edema / 中华眼底病杂志

Objective To compare the differences of optic disc parameters and the thickness of circumpapillary retinal nerve fiber layer (CP-RNFL) in acute uveitis Vogt-Koyanagi-Harada (VKH) syndrome with different degrees of optic disc edema. Methods This is a retrospective study including 40 eyes of 23 VKH patients. The eyes were divided into 2 groups according to the results of fluorescein fundus angiography (FFA). The discs with hyperfluorescence but no leakage were in mild optic disc edema group (group A, 13 patients and 25 eyes), and the discs with hyperfluorescence and leakage were in severe optic disc edema group (group B, 10 patients and 15 eyes). The patients were significantly older in group B than in group A (t=-2.17, P<0.05). The differences of gender, diseased time (t=-1.67) and corrected visual acuity (t=-0.76) between 2 groups were not significant (P>0.05). Eighty eyes of 46 normal healthy subjects, matching group A and group B with age and gender, were divided into group C (26 subjects and 50 eyes) and group D (20 subjects and 30 eyes) respectively.All subjects underwent three dimensional optical coherence tomography examinations. The parameters included average thickness of entire circumpapillary retinal nerve fiber layer (CP-RNFL), thickness of nasal, superior, temporal and inferior quadrant of CP-RNFL, disc area, disc cup area, rim area, cup/disc (C/D) area ratio, C/D horizontal diameter ratio and C/D vertical diameter ratio. Results The disc area, disc cup area and rim area were bigger, the thickness of mean CP-RNFL and the nasal and temporal quadrants of CP-RNFL were thicker in group A than those in group C (P<0.05). The disc area and rim area were bigger, the thickness of mean CP-RNFL and the nasal, superior, temporal and inferior quadrant of CP-RNFL were thicker, C/D area ratio and C/D diameter ratio were smaller in group B than those in group D (P<0.05). The disc area was bigger, disc cup area, C/D area ratio and C/D diameter ratio were smaller, the thickness of mean CP-RNFL and the nasal , superior and inferior quadrants of CP-RNFL were thicker in group B than those in group A (P<0.05). Conclusions Acute VKH uveitis with mild optic disc edema has thicker CP-RNFL in the nasal and temporal quadrants; with severe optic disc edema has thicker CP-RNFL in all 4 quadrants. Acute VKH uveitis also has smaller C/D area ratio and C/D diameter ratio.

The changes in optic disc parameters of Vogt-Koyanagi-Harada syndrome and optic neuritis with optic disc edema using three-dimensional optical coherence tomography / 中华眼底病杂志

Objective To compare the differences of optic disc morphology and optic nerve head parameters between Vogt-Koyanagi-Harada (VKH) syndrome and optic neuritis (ON) with optic disc edema. Methods This is a retrospective study including 21 first-onset VKH patients (35 eyes) as VKH group and 22 first-onset ON patients with optic disc edema (27 eyes) as ON group. The differences of age (t=-1.11) and gender (χ2=0.20) between two groups were not significant (P>0.05). Sixty-two eyes of 43 age and gender-matched healthy subjects were enrolled in this study as control group. All subjects underwent three dimensional optical coherence tomography (3D-OCT) examinations. The difference of optic disc morphology between two groups was observed. The parameters included average thickness of entire circumpapillary retinal nerve fiber layer (CP-RNFL), thickness of nasal, superior, temporal and inferior quadrant of CP-RNFL, disc area, disc cup area, rim area, cup/disc (C/D) area ratio, C/D horizontal diameter ratio and C/D vertical diameter ratio. The disc retinal pigment epithelium (RPE) angle was observed too. Results Among 35 eyes in VKH group, 31 eyes (88.57%) had retinal detachment next to the disc, 3 eyes (8.57%) had serrated inner limiting membranes of the disc. Twenty eyes (64.52%) had highly reflective points, lines, or membrane-like structures in the retinal detachment areas. No such signs appeared in ON patients. Compared with ON group, the optic cup area, C/D area ratio, C/D horizontal diameter ratio and C/D vertical diameter ratio were bigger, the thickness of mean CP-RNFL and the superior, inferior quadrants of CP-RNFL were thinner, disc RPE angles was smaller in VKH group (P<0.05). Compared with control group, the disc area, optic cup area, rim area were bigger, C/D vertical diameter ratio was smaller, the mean CP-RNFL and 4 quadrants CP-RNFL were thicker, disc RPE angles was smaller in VKH group (P<0.05); the disc area, optic cup area, C/D area ratio, C/D horizontal diameter ratio and C/D vertical diameter ratio were smaller, the mean CP-RNFL and 4 quadrants CP-RNFL were thicker, disc RPE angles was bigger in VKH group (P<0.05). Conclusions VKH patients have smaller disc RPE angles and more chance to develop retinal detachment next to disc than ON patients. The C/D area ratio, C/D horizontal diameter ratio and C/D vertical diameter ratio are bigger, the mean CP-RNFL and the superior, inferior quadrants of CP-RNFL are thinner in VKH eyes.

The changes in optic disc parameters and thickness of circumpapillary retinal nerve fiber layer in acute uveitis of Vogt-Koyanagi-Harada syndrome with different degrees of optic disc edema / 中华眼底病杂志

Objective To compare the differences of optic disc parameters and the thickness of circumpapillary retinal nerve fiber layer (CP-RNFL) in acute uveitis Vogt-Koyanagi-Harada (VKH) syndrome with different degrees of optic disc edema. Methods This is a retrospective study including 40 eyes of 23 VKH patients. The eyes were divided into 2 groups according to the results of fluorescein fundus angiography (FFA). The discs with hyperfluorescence but no leakage were in mild optic disc edema group (group A, 13 patients and 25 eyes), and the discs with hyperfluorescence and leakage were in severe optic disc edema group (group B, 10 patients and 15 eyes). The patients were significantly older in group B than in group A (t=-2.17, P<0.05). The differences of gender, diseased time (t=-1.67) and corrected visual acuity (t=-0.76) between 2 groups were not significant (P>0.05). Eighty eyes of 46 normal healthy subjects, matching group A and group B with age and gender, were divided into group C (26 subjects and 50 eyes) and group D (20 subjects and 30 eyes) respectively.All subjects underwent three dimensional optical coherence tomography examinations. The parameters included average thickness of entire circumpapillary retinal nerve fiber layer (CP-RNFL), thickness of nasal, superior, temporal and inferior quadrant of CP-RNFL, disc area, disc cup area, rim area, cup/disc (C/D) area ratio, C/D horizontal diameter ratio and C/D vertical diameter ratio. Results The disc area, disc cup area and rim area were bigger, the thickness of mean CP-RNFL and the nasal and temporal quadrants of CP-RNFL were thicker in group A than those in group C (P<0.05). The disc area and rim area were bigger, the thickness of mean CP-RNFL and the nasal, superior, temporal and inferior quadrant of CP-RNFL were thicker, C/D area ratio and C/D diameter ratio were smaller in group B than those in group D (P<0.05). The disc area was bigger, disc cup area, C/D area ratio and C/D diameter ratio were smaller, the thickness of mean CP-RNFL and the nasal , superior and inferior quadrants of CP-RNFL were thicker in group B than those in group A (P<0.05). Conclusions Acute VKH uveitis with mild optic disc edema has thicker CP-RNFL in the nasal and temporal quadrants; with severe optic disc edema has thicker CP-RNFL in all 4 quadrants. Acute VKH uveitis also has smaller C/D area ratio and C/D diameter ratio.

Adalimumab como alternativa terapéutica en el s¡ndrome de vogt koyanagi harada refractario al infliximab: reporte de caso / Adalimumab, therapeutic alternative in the vogt koyanagi harada syndrome refractory to infliximab: case report

El síndrome de Vogt Koyanagi Harada (VKH) consiste en una panuveitis bilateral que forma parte de los síndromes uveomeníngeos.El tratamiento en estadio crónico es difícil por presentar pobre respuesta a la inmunomodulación, por lo que se recurre a opcionesterapéuticas como agentes biológicos tipo anti-TNF alfa. Se describe el caso de una paciente con VKH severo y resistencia al infliximab,quien mostró respuesta al adalimumab. El adalimumab es un anticuerpo monoclonal humanizado efectivo en casos de resistenciaal infliximab en pacientes con síndrome de VKH crónico persistente. El caso es de interés por ser infrecuente la resistencia a estemedicamento en la práctica clínica, y el uso del activador de plasminógeno tisular contribuyó significativamente en la mejoría visual.

Vogt Koyanagi Harada syndrome (VKH) is a bilateral panuveitis included in the uveomeningeal syndromes. Treatment of its chronicstage is difficult because of poor response to immunomodulation. Other therapeutic options include biological agents such as antiTNFalpha. We present the case of a patient with severe VKH resistant to infliximab that responded to adalimumab. Adalimumab isa humanized monoclonal antibody effective when there is resistance to infliximab in patients with chronic persistent VKH syndrome.The case presented is interesting because of uncommon resistance to this drug in the clinical practice; the use of tissue plasminogenactivator contributed significantly to visual improvement.

Echographic findings in the late stages of Vogt-Koyanagi-Harada disease in mexican population / Resultados ecográficos nas fases atrasadas da doença de Vogt-Koyanagi-Harada na população mexicana

Purpose: To correlate clinical findings of Vogt-Koyanagi-Harada disease with standardized echography findings in a cross-sectional, descriptive and observational study. Methods: Patients with Vogt-Koyanagi-Harada disease in the convalescent and recurrence phases were evaluated with standardized ocular echography. Eyes with opaque media were excluded. Clinical findings were correlated with echographic data. Results: Thirty-seven eyes of 25 patients were included. Best corrected visual acuity was in average 20/100 (0.70 logMAR). Clinical findings included: sunset glow fundus (92%), pigment migration (92%), nummular chorioretinal depigmented scars (68%) and subretinal fibrosis (64.8%). Standardized echography was able to recognize all the cases with subretinal fibrosis (n=24) described clinically. Standardized echography showed a 100% sensitivity and specificity of finding subretinal fibrosis. Subretinal fibrosis in patients with Vogt-Koyanagi-Harada represents a risk factor for low vision. In our patients’ eyes, presence of subretinal fibrosis had a 2.5 time relative risk of having a visual acuity equal or worst to 20/70. Conclusions: Standardized echography represents a useful tool in patients with VKH in the chronic (convalescence and recurrence) phase of the disease. Subretinal fibrosis, a sight threatening complication in the convalescence and recurrent phases of Vogt-Koyanagi-Harada, can be diagnosed with ocular echography, with characteristic images. Knowledge of these images can be useful in cases with opaque media and bilateral anterior segment granulomatous inflammatory disease. .

Objetivo: Correlacionar achados clínicos da síndrome de Vogt-Koyanagi-Harada com resultados ecográficos padronizado da doença em um estudo transversal, descritivo e observacional. Métodos: Pacientes com a doença de Vogt-Koyanagi-Harada, o convalescente e recorrência em fases padronizadas foram avaliados com ecografia ocular. Olhos com material opaco foram excluídos. Achados clínicos foram correlacionados com dados ecográficos. Resultados: Um total de 25 pacientes e trinta e sete olhos foram incluídos no estudo. A acuidade visual (AV) 20/100 foi em média 0.70 logMAR. Os achados clínicos incluídos: sunset glow fundus (92%), pigmento migração (92%), numular despigmentado cicatrizes coriorretinianas (68%) e fibrose sub-retiniana (64,8%). A ecografia padronizada foi capaz de reconhecer todos os casos de fibrose sub-retiniana (n= 24) descrito clinicamente. A ecografia revelou um padrão 100% de sensibilidade e especificidade do diagnóstico fibrose sub-retiniana. Sub-retiniana em pacientes com fibrose Vogt-Koyanagi-Harada representa um fator de risco para a baixa visão. Em nossos pacientes olhos, presença de fibrose subretiniana tinham um risco relativo 2,5 hora de ter uma acuidade visual igual ou pior para 20/70. Conclusão: Ecografia padronizadarepresenta uma ferramenta útil em pacientes portadores da doença na fase crônica (convalescença, e recidiva). Fibrose sub-retiniana, uma visão ameaçadora e complicação na convalescença e recorrentes nas fases da Síndrome de Vogt-Koyanagi- Harada, podem ser diagnosticados com ecografia ocular, com imagens características. O conhecimento dessas imagens pode ser útil em casos com material opaco e segmento anterior bilateral da doença inflamatória granulomatosa. .

Vogt-Koyanagi-Harada syndrome: 5 cases report with clinical and neuroimaging features / 中华神经科杂志

Objective To investigate the clinical and neuroimaging features of Vogt-KoyanagiHarada syndrome ( VKH ).Methods Cerebrospinal fluid ( CSF ), neuroimaging examination, clinical manifestation and pharmacotherapy features were investigated in 5 patients diagnosed as VKH. ResultsAll 5 patients were diagnosed as uveitis in the early stage of disease.All patients suffered “ headache”.Meningeal irritation sign was appeared in 3 cases. The MRI enhanced scan of all 5 cases showed abnormal enhancement of meninges. CSF examination showed increased leukocyte number ((4--196) × 106/L). All patients were alleviatedwith combination therapyof high dose of steroid with cyclophosphamide.ConclusionsVKH is a systemic disease that usually involving the uvea, central nervous system, internal ear and the skin. MRI and CSF examination are valuable for diagnosis. High dose of steroid combined with cyclophosphamide is an effective therapeutic strategy.

Síndrome de Vogt-Koyanagi-Harada e o seu acometimento multissistêmico / Vogt-Koyanagi-Harada's syndrome and its multisystem involvement

A síndrome de Vogt-Koyanagi-Harada é uma enfermidade rara que atinge os tecidos que contêm melanócitos, como os olhos, sistema nervoso central, orelha interna e pele. Alguns grupos étnicos têm maior propensão para desenvolver a doença, como os asiáticos, indianos e latino-americanos >e o gênero mais acometido é o feminino. O método realizado foi a revisão bibliográfica em livros, artigos publicados na internet e trabalhos disponíveis nos bancos de dados online MEDLINE, LILACS e SciELO. Foram selecionados os textos que abordassem a doença de forma abrangente, ressaltando suas manifestações otorrinolaringológicas. Revisão da literatura: A doença apresenta provável etiologia autoimune em que ocorre agressão à superfície dos melanócitos promovendo reação inflamatória com predomínio de linfócitos T. O alelo HLA DRB1*0405 é o mais associado à doença. As manifestações clínicas dividem-se em quatro estágios: prodrômico, uveítico, crônico e de recorrência. As manifestações otorrinolaringológicas ocorrem na fase uveítica e são caracterizadas por perda auditiva sensorioneural bilateral, zumbido e sintomas vestibulares. O diagnóstico é realizado através dos critérios diagnósticos da doença. O tratamento é realizado principalmente com corticoides. Considerações finais: É necessário que a síndrome de Vogt-Koyanagi-Harada seja uma doença reconhecida pelas diversas especialidades médicas, pois o atraso em seu diagnóstico pode resultar em sequelas oculares e cutâneas.

Vogt-Koyanagi-Harada's syndrome is a rare disease that affects tissues containing melanocytes such as eyes, central nervous system, inner ear and skin. Some ethnic groups have a higher probability of developing the disease like Asians, Indians and Latin Americans and most affected is the female gender. Methods: Literature was reviewed in books, articles published on the internet and papers available in the online databases MEDLINE, LILACS and SciELO. Texts were selected focusing on the otorhinolaryngological symptoms. Literature review: The disease probably has an autoimmune etiology in which aggression occurs on the surface of melanocytes by promoting inflammatory reaction with predominance of T lymphocytes. The HLA DRB1*0405 allele is the most associated with the disease. Clinical manifestations are divided into four stages: prodromal, uveitic, chronic and recurrent. The otorhinolaryngological symptoms occur at the uveitic stage characterized by bilateral sensorioneural hearing loss, tinnitus and vestibular symptoms. Diagnosis is made following diagnostic criteria of the disease. Treatment consists mainly of corticosteroids. Conclusions: Different specialities must recognize the importance of the Vogt-Koyanagi-Harada's syndrome.

New insights into Vogt-Koyanagi-Harada disease / Novos conhecimentos sobre a doença de Vogt-Koyanagi-Harada

Vogt-Koyanagi-Harada disease (VKH), a well-established multiorgan disorder affecting pigmented structures, is an autoimmune disorder of melanocyte proteins in genetically susceptible individuals. Several clinical and experimental data point to the importance of the effector role of CD4+ T cells and Th1 cytokines, the relevance of searching a target protein in the melanocyte, and the relevance of the HLA-DRB1*0405 in the pathogenesis of the disease. Vogt-Koyanagi-Harada disease has a benign course when early diagnosed and adequatey treated. Full-blown recurrences are rare after the acute stage of Vogt-Koyanagi-Harada disease is over. On the other hand, clinical findings, such as progressive tissue depigmentation (including sunset glow fundus) and uveitis recurrence, indicate that ocular inflammation may persist after the acute phase. Additionally, indocyanine green angiography findings suggest the presence of choroidal inflammation in eyes without clinically detectable inflammation. The aim of this paper is to review the latest research results on Vogt-Koyanagi-Harada disease pathogenesis and chronic/convalescent stages, which may help to better understand this potentially blinding disease and to improve its treatment.

A doença de Vogt-Koyanagi-Harada (VKH) afeta vários órgãos que têm em comum a presença de pigmento. É doença autoimune que agride os melanócitos de indivíduos geneticamente susceptíveis. Inúmeras evidências clínicas e experimentais demonstram a importância de células T CD4+ como células efetoras da resposta imune celular, das citocinas pró-inflamatórias Th1, da procura da proteína-alvo dentro do melanócito, e da relevância do HLA-classe II DRB1*0405 na patogênese desta doença. A doença de Vogt-Koyanagi-Harada apresenta bom prognóstico visual desde que o diagnóstico seja precoce e o tratamento instituído seja adequado. Recidivas com acometimento do segmento posterior são raras após a fase aguda da doença. No entanto, achados clínicos como a progressiva despigmentação do fundo, incluindo o aspecto em por do sol, e as recidivas da uveíte indicam que a inflamação ocular pode persistir mesmo após a fase aguda da doença. Os achados da angiografia com indocianina verde também sugerem a presença de inflamação da coróide mesmo em olhos sem inflamação clinicamente detectável. O objetivo do presente trabalho é rever os mais recentes estudos sobre a patogênese da doença Vogt-Koyanagi-Harada e sobre os aspectos clínicos da fase crônica e/ou convalescente da doença, permitindo melhores conhecimentos sobre esta doença potencialmente mórbida e oferecendo terapias mais adequadas.

MRI findings of Vogt-Koyanagi-Harada syndrome in eye / 中华放射学杂志

Objective To characterize the ocular findings on MRI in patients with Vagt-Koyanagi-Harada syndrome (VKHS)and its value for diagnosis. Methods The MRI findings of eyes in 14 patients (7 males, 7 females, age ranged 10-62 years) with VKHS were retrospectively analyzed. Results Choriodai thickening was found bilaterally in all 14 patients with isointense signal on T2 and T1 weighted images. Exudative retinal detachment was found in 6 patients (12 eyes) and 5 cases (10 eyes) showed abnormal thickening and enhancement of iris. Two cases were accompanied with optic neuritis. Homogeneous enhancement of lesions after administration of gadopentetate was observed in 11 patients. Conclusion M RI can characterize the ocular lesions and their extent in patients with VKHS, which makes MRI as a useful method to diagnosis and the follow-up of these patients.

Síndrome de Vogt-Koyanagi-Harada: revisão de literatura / Vogt-Koyanagi-Harada's disease: literature review

Introdução: A síndrome de Vogt-Koyanagi-Harada é uma doença rara que atingem tecidos contendo melanócitos como nos olhos, sistema nervoso central, pele e ouvido interno. Apresenta predominância nos asiáticos, indianos e latinoamericanos e no sexo feminino. Objetivo: Realizar uma revisão de literatura sobre os diversos aspectos da Síndrome de Vogt-Koyanagi-Harada, enfatizando a sua etiopatogenia bem como as manifestações clínicas otorrinolaringológicas através dos bancos de dados on line Cochrane, LILACS, MEDLINE, OMIM e SciELO. Revisão de Literatura: A etiologia é incerta, mas há indícios de processo auto-imune contra antígenos na superfície dos melanócitos determinando uma resposta inflamatória imune com predomínio de linfócitos T. O alelo HLA-DRB1*0405 é o mais associado à doença. As manifestações clínicas são divididas em quatro estágios: prodrômico, uveítico, crônico e de recorrência. As manifestações otorrinolaringológicas se desenvolvem na fase uveítica. Há hipoacusia do tipo neurossensorial bilateral e rapidamente progressiva associada a zumbidos. O comprometimento do componente vestibular leva a vertigem, nistagmo horizontal e alteração do reflexo óculo-vestibular.

Introduction: Vogt-Koyanagi-Harada's disease is a rare syndrome that affects tissues with melanocytes like eyes, central nervous system, skin and inner ear. It affects primarily Asians, Indians and Latin Americans and also women.

The proportion changes of CD4+CD25+ regulatory T cells in the periphery blood of patients with Vogt-Koyanagi-Harada disease / 中华眼底病杂志

Objective To observe the proportion changes of CD4+CD25+FOXP3+ T cells in peripheral blood of patients with Vogt-Koyanagi-Harada disease(VKH)before and after one month of treatment. Methods The peripheral blood samples from 15 patients with VKH disease before and after one month of treatment by glucocorticoid,and from 15 healthy volunteers were collected,and lymphoeytes were separated from them.CD4+CD25+regulatory T cells were Iabeled by antibodies of cell surface marker CD4、CD25 and transcription factor FOXP3.The proportion of CD4+CD25+FOXP3+ T cells were detected by flow cytometry. Results Before the treatment,the percentage of CD4+ CD25+FOXP3+ T cells in periphery blood was(0.30±0.19)%of CD4+ cell in VKH patients,and(1.41±0.52)%in control group,the difference was statistically significant(t=7.665,P＜0.01);after one month of treatment,the VKH patients group was(1.28±0.54)%which close to the control group.However there were two patients whose CD4+ CD25+ T cells inereased extraordinarily after one month of treatment. Conclusions The proportion of CD4+ CD25+ FOCP3+ T cells in periphery blood in VKH patients were lower than control group obviously before treatment,but were close to eontrol group after treatment.Those results indicated that VKH diseases may be associated with the decreased proportion of CD4+ CD25+ regulatory T cells.

Síndrome de Vogt-Koyanagi-Harada incompleta associada a HLA DRB1*01 em criança de quatro anos de idade: relato de caso / Incomplete Vogt-Koyanagi-Harada syndrome associated with HLA DRB1*01 in a 4-year-old child: case report

A síndrome de Vogt-Koyanagi-Harada é doença crônica, sistêmica e auto-imune, com manifestações oculares, nervosas, auditivas e tegumentares. Descrevemos aqui o caso de uma criança com início dos sintomas aos quatro anos e dois meses de idade, com positividade para o HLA DRB1*01.

Vogt-Koyanagi-Harada syndrome is chronic systemic autoimmune disease with ocular, nervous, auditory and tegumental manifestations. We report here the case of a child with onset of symptoms at four years and two months of age, with positive HLA DRB1*01.