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Frontiers in Medicine 2021Uveitis associated with Vogt-Koyanagi-Harada (VKH) disease is a bilateral, chronic, granulomatous autoimmune disease associated with vitiligo, poliosis, alopecia, and... (Review)
Review
Uveitis associated with Vogt-Koyanagi-Harada (VKH) disease is a bilateral, chronic, granulomatous autoimmune disease associated with vitiligo, poliosis, alopecia, and meningeal and auditory manifestations. The disease affects pigmented races with a predisposing genetic background. Evidence has been provided that the clinical manifestations are caused by a T-lymphocyte-mediated autoimmune response directed against antigens associated with melanocytes in the target organs. Alongside of T lymphocytes, autoreactive B cells play a central role in the development and propagation of several autoimmune diseases. The potential role of B lymphocytes in the pathogenesis of granulomatous uveitis associated with VKH disease is exemplified within several studies. The early initial-onset acute uveitic phase typically exhibits granulomatous choroiditis with secondary exudative retinal detachment and optic disc hyperemia and swelling, subsequently involving the anterior segment if not adequately treated. The disease eventually progresses to chronic recurrent granulomatous anterior uveitis with progressive posterior segment depigmentation resulting in "sunset glow fundus" appearance and chorioretinal atrophy if not properly controlled. Chronically evolving disease is more refractory to treatment and, consequently, vision-threatening complications have been recognized to occur in the chronic recurrent phase of the disease. Conventional treatment with early high-dose systemic corticosteroids is not sufficient to prevent chronic evolution. Addition of immunomodulatory therapy with mycophenolate mofetil as first-line therapy combined with systemic corticosteroids in patients with acute initial-onset disease prevents progression to chronic evolution, late complications, vitiligo, and poliosis. Furthermore, patients under such combined therapy were able to discontinue treatment without relapse of inflammation. These findings suggest that there is a therapeutic window of opportunity for highly successful treatment during the early initial-onset acute uveitic phases, likely because the underlying disease process is not fully matured. It is hypothesized that early and aggressive immunosuppressive therapy will prevent remnant epitope generation in the initiation of the autoimmune process, the so-called primary response. B cell depleting therapy with the anti-CD20 monoclonal antibody rituximab is effective in patients with refractory chronic recurrent granulomatous uveitis. The good response after rituximab therapy reinforces the idea of an important role of B cells in the pathogenesis or progression of chronic recurrent uveitis associated with VKH disease.
PubMed: 34869409
DOI: 10.3389/fmed.2021.705796 -
Annals of Indian Academy of Neurology 2021Vogt-Koyanagi-Harada (VKH) syndrome is an immune-mediated granulomatous disease which affects melanin-rich organs like eyes, skin, nervous system, and ears. Neurological...
Vogt-Koyanagi-Harada (VKH) syndrome is an immune-mediated granulomatous disease which affects melanin-rich organs like eyes, skin, nervous system, and ears. Neurological and auditory manifestations usually precede the involvement of other sites. Patients may manifest with "complete" or "incomplete" syndrome. We report two patients who presented with acute headache and impaired vision. Fundus examination revealed optic disc hyperemia and exudative retinal detachment which provided a clue for the diagnosis at the bedside. Fundus fluorescein angiogram (FFA) revealed abnormal dye leakage, whereas B scan showed choroid thickening. Cerebrospinal fluid (CSF) pleocytosis contrasted with unremarkable brain magnetic resonance imaging and lack of meningeal signs. Melanophagocytosis was evidenced by melanin-laden macrophages in CSF and skin biopsy. This finding is specific for VKH syndrome and helps to clinch the diagnosis even when the complete syndrome is not present cross-sectionally. VKH syndrome should be suspected in patients with aseptic meningitis if tests for common infectious and immune-mediated diseases are negative.
PubMed: 34447006
DOI: 10.4103/aian.AIAN_405_20 -
Journal of Clinical Medicine Jul 2021Immunotherapy with checkpoint inhibitors significantly improves the outcome for stage III and IV melanoma. Cutaneous adverse events during treatment are often reported.... (Review)
Review
Immunotherapy with checkpoint inhibitors significantly improves the outcome for stage III and IV melanoma. Cutaneous adverse events during treatment are often reported. We herein aim to review the principal pigmentation changes induced by immune check-point inhibitors: the appearance of vitiligo, the Sutton phenomenon, melanosis and hair and nail toxicities.
PubMed: 34300213
DOI: 10.3390/jcm10143047 -
BMC Ophthalmology Oct 2020East and South East Asian subjects as well as Amerindians and Hispanic subjects are predominantly affected by Vogt-Koyanagi-Harada disease. In Europe, only few studies...
BACKGROUND
East and South East Asian subjects as well as Amerindians and Hispanic subjects are predominantly affected by Vogt-Koyanagi-Harada disease. In Europe, only few studies have described the clinical features and treatment of this disease, especially in France.
METHODS
This retrospective case series was based on data collected from patients with a VKH disease diagnosed from January 2000 to March 2017, provided by three French Tertiary Centers.
RESULTS
Forty-one patients (16 men and 25 women) were diagnosed: average age at diagnosis was 38.7 years. Patients were mainly from Maghreb (58%), but ethnic origins were multiple. Pleiocytosis was observed in 19 cases (63%) and 17 out of 41 patients showed audio vestibular signs (41%), and 11 showed skin signs (27%). Thirty-four were treated with corticosteroids (83%), 11 with an immunosuppressant treatment (27%) and 5 with biological therapy drugs (13%). Relapse was observed in 41% patients, even though final average visual acuity had improved. We did not find any significant clinical difference in the population from Maghreb compared to other populations, but for age and sex trends, since there was a majority of younger women.
CONCLUSION
We report here the second largest French cohort reported to date to our knowledge. The multiethnicity in our study suggests that VKH disease should be evoked whatever patients' ethnicity.
Topics: Female; France; Humans; Immunosuppressive Agents; Male; Retrospective Studies; Uveomeningoencephalitic Syndrome; Visual Acuity
PubMed: 33028239
DOI: 10.1186/s12886-020-01656-x -
La Clinica Terapeutica 2020To better understand the real prevalence of cutaneous manifestations, in Neurofibromatosis type 1. (Review)
Review
OBJECTIVE
To better understand the real prevalence of cutaneous manifestations, in Neurofibromatosis type 1.
MATERIALS AND METHODS
We reviewed all clinical charts of 1102 NF1 patients followed by February 1983 to February 2020 at the "Sapienza" University of Rome, Italy. NF1 patients are seen usually every year by a dermatologist.
RESULT
Café-au-lait macules were shown in 1063 patients (96.5%), axillary and inguinal freckling in 991 (90%) and neurofibromas in 861 (78.1%). Other skin manifestations included: lipoma (6.2%), nevus anemicus (3.9%), psoriasis (3.4%), spilus nevus (3.2%), juvenile xanthogranuloma (3.2%), vitiligo (2.3%), Becker's nevus (1.9%), melanoma (0.7%) and poliosis (0.5%).
CONCLUSION
Neurofibromatosis type 1 is a multisystem disorder primarily involving the skin and nervous system. The clinical manifestations are extremely variable even within a family. This study was performed to delineate the prevalence of cutaneous manifestations in NF1.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Humans; Italy; Male; Middle Aged; Neurofibromatosis 1; Prevalence; Skin Diseases; Young Adult
PubMed: 32901776
DOI: 10.7417/CT.2020.2242 -
Veterinary and Animal Science Dec 2020Low serum level of vitamin D has been linked to numerous diseases. The Akita breed of dog shows a high incidence of immune-mediated diseases such as uveodermatologic...
Low serum level of vitamin D has been linked to numerous diseases. The Akita breed of dog shows a high incidence of immune-mediated diseases such as uveodermatologic (UVD) syndrome and sebaceous adenitis (SA). Furthermore, in Japanese Akita dogs, skin depigmentation often appears after birth at different ages, in healthy dogs, and without any other symptoms. In humans poliosis is associated to low vitamin D level. The aim of this survey was to evaluate serum 25-hydroxyvitamin D (25(OH)D) levels in Japanese Akita dogs. One hundred and three Akita blood samples were collected for the 25(OH)D evaluation. Age, sex, current disease, presence and location of skin depigmentation, and diet were reported on a medical record. Based on history and clinical examination, dogs were classified according their health status as healthy (HE) or pathological (PA). The overall mean of 25(OH)D concentration was 82.42 ± 26.14 ng/mL, whereas the concentrations in the healthy dogs were significantly higher (84.90 ± 3.36 ng/mL) in comparison with the dogs with diseases (72.13 ± 4.09 ng/mL) ( < 0.01). In this study, the depigmented healthy dogs showed low level of 25(OH)D and very similar to the sick group. The appearance of depigmented areas associated with low levels of vitamin D could be considered as an alert sign in Akitas as well as in humans. However, clinical trials should also be carried out to establish whether vitamin D supplementation could be an effective preventive treatment to limit the onset of immune-mediated diseases in Japanese Akita dogs.
PubMed: 32875143
DOI: 10.1016/j.vas.2020.100139 -
American Journal of Ophthalmology Case... Sep 2020To report asymptomatic progressive fundus depigmentation and choroidal thinning in the absence of intraocular inflammation in a patient treated with checkpoint...
PURPOSE
To report asymptomatic progressive fundus depigmentation and choroidal thinning in the absence of intraocular inflammation in a patient treated with checkpoint inhibitors.
OBSERVATIONS
A 69-year-old woman with metastatic cutaneous melanoma, treated with checkpoint inhibition (nivolumab, ipilimumab and pembrolizumab), developed asymptomatic progressive fundus depigmentation associated with choroidal thinning in both eyes over 26 months. Serial multimodal imaging was obtained over the study period including fundus photography, fundus autofluorescence and optical coherence tomography (OCT). Over 26 months, the central choroidal thickness decreased by 34% (from 270μm to 92μm, mean between both eyes). Concurrently, central retinal thickness remained stable (206μm to 214μm, mean between both eyes). There were no findings of intraocular inflammation, subretinal fluid or retinal pigment epithelium disturbance. The patient reported no visual symptoms and maintained a visual acuity of 20/25+ in the right eye and 20/30 in the left eye throughout the observation period. Concurrently, cutaneous vitiligo and poliosis, inclusive of her periorbital dermis and eyelashes also developed.
CONCLUSIONS AND IMPORTANCE
Progressive fundus depigmentation and choroidal thinning can be observed with checkpoint inhibition in the absence of intraocular inflammation.
PubMed: 32637735
DOI: 10.1016/j.ajoc.2020.100799 -
Journal of the American Academy of... Mar 2021
Topics: Adult; Age of Onset; Aged; Diagnosis, Differential; Female; Hair Color; Hair Diseases; Humans; Male; Middle Aged; Pigmentation Disorders; Retrospective Studies; Tuberous Sclerosis; Young Adult
PubMed: 32416202
DOI: 10.1016/j.jaad.2020.05.038 -
Molecular Vision 2019The and genes are said to be associated with multiple autoimmune diseases. This study investigated the association between these genes and VogtKoyanagiHarada (VKH)...
PURPOSE
The and genes are said to be associated with multiple autoimmune diseases. This study investigated the association between these genes and VogtKoyanagiHarada (VKH) syndrome in Han Chinese.
METHODS
A two-stage case-control study was performed on three single nucleotide polymorphisms ([SNPs] rs4750316, rs11258747, and rs947474) of the gene and three SNPs (rs842647, rs702873, and rs13031237) of the gene using PCR-restriction fragment length polymorphism (PCR-RFLPs) in a total of 859 patients with VKH syndrome and 1,542 healthy controls. Variables such as extraocular presentations were assessed. The data were analyzed using chi-square analysis, and corrected for multiple comparisons with the Bonferroni method.
RESULTS
We found a decreased frequency of the GC genotype and the C allele of rs4750316 in patients with VKH syndrome when the GG genotype or G allele was used as a reference, respectively (GC genotype: =2.45e-10, odds ratio [OR]=0.37, 95% confidence interval [CI]=0.28-0.51; C allele: =8.79e-10, OR=0.41, 95% CI=0.31-0.55). The genotypic and allelic frequencies of rs11258747, rs947474, rs842647, rs702873, and rs13031237 were not statistically significantly different between patients with VKH syndrome and controls. Stratification analysis indicated that the rs4750316 polymorphism was associated with patients with VKH syndrome experiencing headache, alopecia, poliosis, tinnitus, and dysacusia, but no statistically significant association of the other five SNPs was found.
CONCLUSIONS
The rs4750316 polymorphism may be a susceptibility factor for VKH syndrome pathogenesis and extraocular presentations, indicating that may be involved in the pathogenesis and extraocular presentations of VKH syndrome through the T-cell receptor (TCR) signaling pathway.
Topics: Adult; Asian People; Case-Control Studies; Ethnicity; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Male; Polymorphism, Single Nucleotide; Protein Kinase C-theta; Uveomeningoencephalitic Syndrome
PubMed: 31908401
DOI: No ID Found -
Case Reports in Medicine 2019Vogt-Koyanagi-Harada (VKH) syndrome is a multisystemic autoimmune disease of uncertain pathogenesis. Infectious aetiology has been proposed which is suggested to lead to...
BACKGROUND
Vogt-Koyanagi-Harada (VKH) syndrome is a multisystemic autoimmune disease of uncertain pathogenesis. Infectious aetiology has been proposed which is suggested to lead to the loss of melanocytes in the skin, inner ear, meninges, and uvea in those who are genetically predisposed. Information regarding VKH syndrome is scanty among the African population.
CASE PRESENTATION
We report a 28-year-old HIV-uninfected Ugandan woman who had previously been well and presented with chronic bilateral panuveitis; symmetrical vitiligo patches on the head, trunk, and upper limbs; tinnitus; and poliosis of the scalp hair, eyelashes, and eyebrows. A flu-like syndrome preceded this. Several weeks of prednisolone and azathioprine therapy resulted in remarkable improvement of the ocular and inner ear symptoms.
CONCLUSION
A high index of suspicion is required in diagnosing VKH syndrome, even in sub-Saharan Africa where the disease is reported to be rare. Initiation of prompt and appropriate treatment prevents blindness and other complications.
PubMed: 31636673
DOI: 10.1155/2019/5192754