RESUMO
Immune checkpoint inhibitors (ICIs) activate anti-tumor activity by inhibiting immune checkpoint molecules that suppress inflammatory T-cell activity. However, ICIs can initiate excessive immune responses, thereby causing immune-related adverse events (irAEs). ICI-associated uveitis (ICIU) is an irAE that affects the eyes. Although Vogt-Koyanagi-Harada disease (VKH)-like uveitis is a common form of ICIU, it is unclear which factors determine the ICIU form. We retrospectively reviewed the medical records of nine ICIU cases treated with ICIs for malignancies. We also performed HLA typing in seven cases to investigate the association between HLA and disease type. Fisher's exact test was used for the statistical analysis. Five of the ICIU cases were VKH-like ICIUs, and four were non-VKH-like ICIUs. No association was found between mean age, sex, primary disease, ICI, time to onset, and disease type. Four patients with VKH-like uveitis underwent HLA genotyping and were all positive for HLA-DRB1*04:05. All 3 patients with non-VKH-like uveitis were negative for HLA-DRB1*04:05. Statistical analysis showed that HLA-DRB1*04:05 was significantly associated with developing VKH-like ICIU (P = 0.029). In ICIU, HLA-DRB1*04:05 was associated with the pathogenesis of VKH-like uveitis, suggesting that ICI-associated VKH-like uveitis has a similar pathogenesis to VKH.
Assuntos
Cadeias HLA-DRB1 , Síndrome Uveomeningoencefálica , Humanos , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/metabolismo , Inibidores de Checkpoint Imunológico , Estudos Retrospectivos , Síndrome Uveomeningoencefálica/induzido quimicamente , Síndrome Uveomeningoencefálica/genéticaRESUMO
PURPOSE: To clarify the proportion of ocular sarcoidosis with severe, refractory, and prolonged inflammation and their association with ocular complications and visual prognosis. STUDY DESIGN: Multicenter, retrospective, longitudinal cohort study. METHODS: Three hundred and twenty-three eyes of 164 patients (45 men; 119 women) with ocular sarcoidosis who visited Hokkaido University Hospital and Yokohama City University Hospital from 2010 to 2015. We newly defined severe, refractory, and prolonged inflammation in ocular sarcoidosis, and investigated their proportions, ocular complications and final visual acuity from medical records of our sarcoidosis patients. RESULTS: The eyes with severe inflammation numbered 72/323 (22.3%), with refractory inflammation, 80/323 (24.8%), and with prolonged inflammation, 91/323 (28.2%). The number of eyes having neither severe, refractory, nor prolonged inflammation (defined as none) was 114/323 (35.3%). The numbers of eyes that reached irreversible visual dysfunction were 6/72 (8.3%) of those with severe inflammation, 10/80 (12.5%) with refractory inflammation, 12/91 (13.2%) with prolonged inflammation, and 4/114 (6.2%) with none. As complications, cataract (62.2%), glaucoma (28.5%), epiretinal membrane (24.1%), cystoid macular edema (22.6%), vitreous hemorrhage (2.8%), choroidal atrophy (2.5%), macular degeneration (1.2%), macular hole (0.9%) and retinal detachment (0.3%) were identified. Among them, secondary glaucoma (16 eyes) and macular degeneration (4 eyes) were major complications related to irreversible visual dysfunction. CONCLUSIONS: Although most of the patients with ocular sarcoidosis had a relatively good visual prognosis, some developed severe, refractory, and/or prolonged inflammation related to the development of ocular complications, that resulted in poor visual prognosis.
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Endoftalmite , Glaucoma , Edema Macular , Sarcoidose , Endoftalmite/complicações , Feminino , Glaucoma/complicações , Humanos , Inflamação/complicações , Estudos Longitudinais , Edema Macular/etiologia , Masculino , Estudos Retrospectivos , Sarcoidose/complicações , Sarcoidose/diagnóstico , Sarcoidose/epidemiologia , Transtornos da VisãoRESUMO
BACKGROUND: In recent years, numerous studies have reported the development or exacerbation of sarcoidosis due to interferon therapy. However, ocular lesions rarely present as initial symptoms. Herein, we describe a rare case of interferon-α-induced sarcoidosis with uveitis as the initial symptom, and present a review of the relevant literature. CASE PRESENTATION: This case involved a 62-year-old-Japanese woman with a history of a combination treatment of pegylated interferon-α-2a, ribavirin, and simeprevir, after which she developed granulomatous panuveitis. She was subsequently diagnosed with sarcoidosis following histological examination of skin biopsy specimens. In addition to reporting this case, we performed a literature review of 27 cases (24 case reports) of histopathologically diagnosed interferon-α-induced sarcoidosis published between January 2009 and November 2018. CONCLUSIONS: Among the reviewed cases, 23 (85.1%) cases developed skin lesions and 19 (70.1%) had lung lesions. Only three cases (11.1%) had accompanying eye lesions. Interferon-α therapy was discontinued in 16 cases (52.9%), and the majority exhibited improvement after systemic corticosteroid treatment. There are few reported cases of interferon-α-induced sarcoidosis with uveitis as the initial symptom. However, if uveitis develops during or after interferon-α treatment, it might represent an initial symptom of interferon-α-induced sarcoidosis, as observed in the present case.
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Pan-Uveíte , Sarcoidose , Uveíte , Antivirais/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Pan-Uveíte/induzido quimicamente , Pan-Uveíte/tratamento farmacológico , Ribavirina/efeitos adversos , Sarcoidose/induzido quimicamente , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico , Uveíte/induzido quimicamente , Uveíte/diagnósticoRESUMO
PURPOSE: Although infliximab (IFX) decreases the risk of blindness due to refractory uveitis in patients with Behçet's disease (BD), there are no standard criteria for IFX switching or withdrawal. To evaluate the effect of IFX switching in patients with BD in long-term remission, a prospective, single-arm intervention trial was conducted, switching from IFX to cyclosporine A (CYA). STUDY DESIGN: A prospective open-label study. METHODS: Eligible patients met the following criteria: administration of IFX without concomitant immunosuppressants for more than 5 years with no episodes of ocular attacks, no retinal vasculitis on fluorescein fundus angiography, negative C-reactive protein in serum, and no extraocular lesions at the time of IFX withdrawal. CYA 5 mg/kg/day was administered from 6 weeks after IFX withdrawal. The primary outcome was the rate of readministration of tumor necrosis factor inhibitors at 1 year after IFX withdrawal. RESULTS: Three of 45 BD patients treated with IFX for refractory uveitis were included in the study. At 1 year after withdrawal of IFX, no patient had experienced any ocular attacks or needed readministation of IFX. However, extraocular lesions, such as recurrent oral ulcers, folliculitis, and recurrent fevers, occurred in all patients. Liver or renal dysfunction, which may have been caused by CYA, was also observed in all patients. CONCLUSIONS: Although no ocular attacks were observed for at least 1 year after IFX withdrawal, this prospective study indicates that IFX withdrawal should be considered carefully, even for patients in long term remission of ocular and extraocular lesions.
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Síndrome de Behçet , Uveíte , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamento farmacológico , Ciclosporina , Humanos , Infliximab , Estudos Prospectivos , Resultado do Tratamento , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Uveíte/etiologiaRESUMO
Sarcoidosis is a genetically complex systemic inflammatory disease that affects multiple organs. We present a GWAS of a Japanese cohort (700 sarcoidosis cases and 886 controls) with replication in independent samples from Japan (931 cases and 1,042 controls) and the Czech Republic (265 cases and 264 controls). We identified three loci outside the HLA complex, CCL24, STYXL1-SRRM3, and C1orf141-IL23R, which showed genome-wide significant associations (P < 5.0 × 10-8) with sarcoidosis; CCL24 and STYXL1-SRRM3 were novel. The disease-risk alleles in CCL24 and IL23R were associated with reduced CCL24 and IL23R expression, respectively. The disease-risk allele in STYXL1-SRRM3 was associated with elevated POR expression. These results suggest that genetic control of CCL24, POR, and IL23R expression contribute to the pathogenesis of sarcoidosis. We speculate that the CCL24 risk allele might be involved in a polarized Th1 response in sarcoidosis, and that POR and IL23R risk alleles may lead to diminished host defense against sarcoidosis pathogens.
Assuntos
Quimiocina CCL24/genética , Sistema Enzimático do Citocromo P-450/genética , Predisposição Genética para Doença , Receptores de Interleucina/genética , Sarcoidose/etiologia , Alelos , Quimiocina CCL24/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Feminino , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Japão , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Receptores de Interleucina/metabolismo , Sarcoidose/diagnóstico , Sarcoidose/metabolismoRESUMO
PURPOSE: Angiotensin-converting enzyme (ACE) is conventionally used as a biomarker in the diagnosis of uveitis associated with sarcoidosis, but its sensitivity is relatively low. In this study, we investigated whether serum soluble interleukin-2 receptor (sIL-2R) is also useful as a diagnostic marker, in addition to ACE, in the detection of uveitis associated with sarcoidosis. PATIENTS AND METHODS: Data were analyzed from 126 patients with uveitis (52 sarcoidosis and 74 non-sarcoid uveitis) and 12 with primary intraocular lymphoma (PIOL) who had their serum sIL-2R and ACE levels measured. RESULTS: Serum sIL-2R level was elevated in 69.2% of patients with sarcoid uveitis, 5.4% of those with non-sarcoid uveitis, and 16.7% of those with PIOL. The sensitivity and specificity of an elevated sIL-2R level for the detection of sarcoidosis were 69.2% and 93.0%, respectively. In contrast, serum ACE levels were elevated only in patients with sarcoid uveitis, with a sensitivity of 44.2% and specificity of 100%. Furthermore, serum sIL-2R and/or ACE level was elevated in 75.0% of patients with sarcoid uveitis, which is higher than those who had elevated serum ACE level only (44.2%, P = 0.0025). The sensitivity and specificity of elevated sIL-2R and/or ACE in detecting sarcoid uveitis were 75.0% and 93.0%, respectively. The PPV was 0.87, and the NPV was 0.86. CONCLUSION: Compared with the sensitivity of serum ACE levels alone, combined measurement of both serum sIL-2R and ACE levels improves sensitivity in the detection of uveitis associated with sarcoidosis. Nevertheless, serum ACE alone remains useful thanks to its high specificity in the differentiation of uveitis patients, with sarcoidosis from those without sarcoidosis.
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BACKGROUND: Neurosarcoidosis is a rare complication, and cranial neuropathy is the most frequent manifestation of this disease. However, few cohesive reports have discussed multiple cranial neuropathies in Japanese patients with sarcoidosis. The present report discusses the case of a patient with sarcoid uveitis and multiple neurological findings. We further review relevant literature regarding Japanese patients with multiple cranial nerve palsies published within the past 34 years (from January 1982 to December 2016). CASE PRESENTATION: We report findings associated with the case of a 56-year-old Japanese woman with granulomatous pan-uveitis who was later diagnosed as having sarcoidosis by skin and transbronchial lung biopsies. She presented right-sided Bell's palsy and was treated with orally administered prednisolone. However, while prednisolone was tapered, she developed facial (VII) and vagus (X) nerve palsies, followed by brain parenchyma lesions, which were not associated with any additional neurological symptoms. Furthermore, she exhibited increased intraocular pressure in her right eye, and she underwent trabeculectomy. Our review of the literature revealed that 64 Japanese patients with sarcoidosis experienced multiple cranial nerve palsies between 1982 and 2016. The most commonly affected cranial nerves were the facial (VII) (73.4%) and glossopharyngeal/vagus (IX/X) nerves (48.4%). Palsies of two distinct cranial nerves were found in 40.6% of the patients, followed by palsies of three (23.4%) and four (18.8%) nerves. Almost all patients (98.3%) received systemic steroid therapy, and total or partial remission was achieved in almost all patients (96.5%). CONCLUSIONS: According to the literature, patients with multiple cranial nerve palsies associated with sarcoidosis respond well to orally administered steroid therapy. However, our findings suggest that careful follow-up is necessary for patients with neurosarcoidosis due to potential aggravation of neuropathy.
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Granuloma/patologia , Pan-Uveíte/patologia , Sarcoidose Pulmonar/patologia , Dermatopatias/patologia , Feminino , HumanosRESUMO
PURPOSE: Sarcoidosis is a major cause of granulomatous uveitis but rarely manifests as multiple choroidal granulomas. This report describes the use of enhanced depth imaging optical coherence tomography (EDI-OCT) to visualize changes occurring in multiple choroidal granulomas during treatment. METHODS: The patient was a 36-year-old Japanese man with histopathologically confirmed sarcoidosis, who was examined using EDI-OCT and showed multiple yellowish-white subretinal lesions in the peripapillary region and the arcade of the right eye. RESULTS: EDI-OCT revealed homogeneous hyporeflective choroidal lesions with choriocapillaris thinning, consistent with a diagnosis of choroidal granulomas. Subretinal fluid adjacent to one of the peripapillary choroidal lesions was also apparent. EDI-OCT during oral prednisolone administration revealed a decrease in lesion size at as early as 3 weeks and complete resolution of the lesions after 6 months of treatment. However, 2 months after prednisolone discontinuation, EDI-OCT revealed recurrence of choroidal granulomas in the peripapillary region and the arcade of the right eye. After injection of triamcinolone acetonide into the posterior sub-Tenon's capsule (sub-Tenon's injection), EDI-OCT demonstrated a reduction in granuloma lesion size within 3 months of the injection. CONCLUSION: EDI-OCT allowed detailed morphologic visualization of the choroidal granulomas caused by sarcoidosis. This imaging technique was useful for monitoring changes in granuloma size in response to steroid administration and for early detection of recurrence. Injection of triamcinolone acetonide into the posterior sub-Tenon's capsule was as effective as oral prednisolone for the treatment of choroidal granulomas.
Assuntos
Doenças da Coroide/diagnóstico , Granuloma/diagnóstico por imagem , Sarcoidose/complicações , Adulto , Corioide/patologia , Doenças da Coroide/tratamento farmacológico , Granuloma/tratamento farmacológico , Humanos , Masculino , Tomografia de Coerência Óptica/métodos , Triancinolona Acetonida/administração & dosagemRESUMO
We here describe three different clinical manifestations of tubulointerstitial nephritis and uveitis (TINU) syndrome. We examined and diagnosed the following 3 patients: a 15-year-old boy with bilateral anterior uveitis (Case 1), a 14-year-old girl with bilateral papilledema (Case 2), and a 49-year-old woman with panuveitis (Case 3). The findings are presented herein. Case 1: The patient had bilateral anterior uveitis. Urinalysis revealed markedly increased ß2-microglobulin and N-acetyl-ß-D-glucosaminidase levels. As the patient was pathologically diagnosed with tubulointerstitial nephritis (TIN), we diagnosed TINU based on the presence of both uveitis and TIN. He was treated with oral corticosteroids. Case 2: This patient showed anterior uveitis and papilledema in both eyes. On initial examination, the urine test results did not show any abnormality. Three months later, high ß2-microglobulin and N-acetyl-ß-D-glucosaminidase levels were detected. As the patient was clinically diagnosed with TIN, we subsequently diagnosed TINU. Both the ocular and renal findings improved without treatment. Case 3: The patient developed bilateral panuveitis, retinal vasculitis, and macular edema, which were initially suspected to be sarcoidosis. However, she was pathologically diagnosed with TIN 12 months before the onset of uveitis; therefore, she was finally diagnosed with TINU. She recovered with local corticosteroid administration only. TINU may present with fundal features in addition to anterior uveitis. Detailed history taking and urinalysis are important to determine the presence of tubular disorders in similar patients.
Assuntos
Glucocorticoides/uso terapêutico , Túbulos Renais/patologia , Nefrite Intersticial/diagnóstico , Uveíte/diagnóstico , Adolescente , Biópsia , Feminino , Angiofluoresceinografia , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/tratamento farmacológico , Disco Óptico/patologia , Síndrome , Uveíte/tratamento farmacológicoRESUMO
INTRODUCTION: A Case Control Etiology of Sarcoidosis Study (ACCESS) sarcoidosis organ assessment instrument has been used for more than a decade to establish uniform standards for the probability of sarcoidosis organ involvement. The ACCESS instrument has become increasingly outdated as new technologies have been developed. Furthermore, the ACCESS instrument failed to address all possible organs involved with sarcoidosis. For these reasons, the World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG) developed a new sarcoidosis organ assessment instrument. METHODS: Clinical sarcoidosis experts assessed various clinical manifestations for the probability of sarcoidosis organ involvement. Two criteria were required to apply this assessment: 1) histologic evidence of granulomatous inflammation of unknown cause in an organ that was not being assessed; 2) the clinical manifestation being addressed required that alternative causes other than sarcoidosis had been reasonably excluded. Clinical manifestations were assessed as either: a) highly probable: likelihood of sarcoidosis causing this manifestation of at least 90%.; b) probable: likelihood of sarcoidosis causing this manifestation of between 50 and 90%; c) possible: likelihood of sarcoidosis causing this manifestation of less than 50%. The sarcoidosis experts voted on the likelihood of sarcoidosis causing each manifestation using Delphi study methodology where at least 70% agreement of the experts was needed for consensus. RESULTS: Various clinical manifestations were classified as highly probable, at least probable, possible, or indeterminate when no consensus could be reached. CONCLUSION: An instrument was developed by expert opinion that may be useful for the clinician and researcher in establishing criteria for sarcoidosis organ involvement.
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Sarcoidose/diagnóstico , Granuloma , Humanos , Sociedades MédicasRESUMO
PURPOSE: To report a case of corneal endotheliitis following the mumps parotitis. METHODS: A 46-year-old man noticed ciliary infection and visual loss in the right eye after mumps parotitis. To determine the cause of the disease, reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify mumps virus RNA in samples from the aqueous humor. RESULTS: RT-PCR revealed mumps virus RNA in an aqueous humor sample. Although full recovery of vision was achieved within 1 month of the onset, corneal endothelial cells were severely damaged. CONCLUSIONS: The authors have detected mumps virus in the aqueous humor by RT-PCR for the first time.
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Endotélio Corneano/virologia , Infecções Oculares Virais/virologia , Ceratite/virologia , Vírus da Caxumba/genética , Caxumba/virologia , RNA Viral/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Humor Aquoso/virologia , Diagnóstico Diferencial , Endotélio Corneano/patologia , Infecções Oculares Virais/diagnóstico , Humanos , Ceratite/diagnóstico , Masculino , Pessoa de Meia-Idade , Caxumba/diagnósticoRESUMO
PURPOSE: Sarcoidosis is a heterogeneous and multisystem granulomatous disorder. The etiology still is uncertain, but the disease currently is thought to be triggered by various genetic as well as environmental factors. Recently, an association between sarcoidosis and the butyrophilin-like 2 (BTNL2) gene located in close proximity to the HLA-DRB1 gene was reported. The purpose of our study was to verify the relationship between BTNL2 and HLA risk alleles for the susceptibility to sarcoidosis, and to assess whether the BTNL2 association is independent of the HLA risk alleles. METHODS: In our study, 11 single nucleotide polymorphisms (rs28362677, rs2076533, rs2076530, rs2076529, rs2294881, rs3763304, rs2076523, rs28362682, rs3806156, rs9268499, rs3763317), including the functional rs2076530 (G > A) of the BTNL2 gene, and HLA-DRB1 and -DQB1 alleles, were genotyped in 237 Japanese patients diagnosed with sarcoidosis and 287 healthy Japanese control subjects. RESULTS: In the patient group, the HLA-DRB1*08:03 (P = 6.15 × 10(-5), odds ratio [OR] = 2.43) and BTNL2 rs2076530_A (P = 6.90 × 10(-6), OR = 1.84) were associated with disease susceptibility. Upon stratification analysis in search for a synergistic effect given the extensive linkage disequilibrium between BTNL2 rs2076530_A and HLA-DRB1*08:03, our results suggested that the risk-bearing allele of these two loci interact negatively. No significant differences were observed in allele frequencies for alleles in patients with ocular and other systemic sarcoidosis. CONCLUSIONS: Our studies implicated that the HLA-DRB1 allele is a major contributing genetic factor in the development of sarcoidosis in Japan. However, further studies are needed to verify how HLA or BTNL2 alleles confer the disease phenotype, severity of sarcoidosis.
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Povo Asiático/genética , Povo Asiático/estatística & dados numéricos , Cadeias HLA-DRB1/genética , Glicoproteínas de Membrana/genética , Sarcoidose/etnologia , Sarcoidose/genética , Adulto , Idoso , Butirofilinas , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Cadeias beta de HLA-DQ/genética , Humanos , Japão/epidemiologia , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
PURPOSE: To investigate whether interleukin 10 (IL10) gene polymorphisms are associated with the development of sarcoidosis in Japanese patients. METHODS: Two hundred and eighty-eight Japanese sarcoidosis patients and 310 Japanese healthy controls were recruited. We genotyped 9 single-nucleotide polymorphisms in IL10 and assessed the allelic diversity between cases and controls. RESULTS: No significant differences in the frequency of IL10 alleles, genotypes, and haplotypes in the sarcoidosis cases compared to the controls were detected. CONCLUSIONS: Our results suggest that IL10 polymorphisms are not significantly related to the pathogenesis of sarcoidosis in the Japanese population.
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Povo Asiático , Olho/metabolismo , Interleucina-10/genética , Polimorfismo de Nucleotídeo Único/genética , Sarcoidose/genética , Regiões 5' não Traduzidas , Alelos , Estudos de Casos e Controles , Impressões Digitais de DNA , Olho/patologia , Frequência do Gene , Genótipo , Humanos , Íntrons , Desequilíbrio de Ligação , Sarcoidose/patologiaRESUMO
PURPOSE: Patients with Behçet's disease often need intraocular surgeries for the treatment of secondary cataract or glaucoma. This study aims to report the clinical course before and after the intraocular surgeries of 5 patients who were systematically treated with infliximab. METHODS: Retrospective case series. RESULTS: Seven eyes of 5 male patients with Behçet's disease, who underwent intraocular surgery while under systemic infliximab therapy at Yokohama City University Hospital from 2007 to 2009, were included in the study. The mean age at surgery was 44.2 years. Phacoemulsification was performed on 4 eyes, and trabeculectomy was done on the remaining 3 eyes. The mean duration since the onset of the ocular symptoms was 107 months. Control of the ocular attacks with the use of other systemic medications was difficult for all patients; however, the use of infliximab enabled adequate control of the attacks. The visual acuity status during the preoperative stage did not worsen during the postoperative period. No infectious complication was observed in all cases. CONCLUSIONS: Our results suggest that infliximab treatment does not complicate any subsequent intraocular surgery. Patients with Behçet's disease in need of intraocular surgery can benefit from control of attacks with infliximab treatment.
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PURPOSE: Sarcoidosis is a systemic inflammatory disease characterized by the formation of non-caseating granulomas, with varied clinical manifestations. The common etiology of sarcoidosis is uncertain, but it is thought to be triggered by an exogenous antigenic stimulus, such as some bacterial proteins. Toll-like receptors (TLRs) recognize microbial components and elicit innate as well as adaptive immune responses. It has been reported that polymorphisms in TLR2 might be important in a small group of Caucasian sarcoidosis patients. The present study aimed to establish whether these findings are relevant to the Japanese population. METHODS: We genotyped 5 single-nucleotide polymorphisms (SNPs) in TLR2 and assessed the allelic diversity between 257 Japanese sarcoidosis patients and 193 Japanese healthy controls. RESULTS: No significant differences in the frequency of TLR2 alleles and haplotypes in the sarcoidosis cases were found in comparison with the controls. However, marginal associations were observed for TLR2 at rs3804099 and rs3804100 in sarcoidosis patients with cutaneous manifestations. CONCLUSIONS: Our results suggest that TLR2 polymorphisms are not significantly related to the pathogenesis of sarcoidosis in the Japanese population.
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Povo Asiático/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Sarcoidose/genética , Receptor 2 Toll-Like/genética , Estudos de Casos e Controles , Frequência do Gene/genética , Genética Populacional , Humanos , Inflamação/complicações , Inflamação/genética , Japão , Desequilíbrio de Ligação/genética , Sarcoidose/complicaçõesRESUMO
PURPOSE: Toll-like receptors (TLRs) are pattern-recognition receptors that play an important role in innate and adaptive immune responses to microbial pathogens. Among TLRs, TLR4 recognizes lipopolysaccharides of Gram-negative bacteria. Genetic polymorphisms within the TLR4 gene have been reported to be associated with various inflammatory diseases; therefore, TLR4 appears to be a susceptibility gene for sarcoidosis. Although sarcoidosis has various clinical manifestations, its association with uveitis is more common in Japan than in other countries. The aim of this study was to investigate whether TLR4 polymorphisms were associated with sarcoidosis-related uveitis in a Japanese population. METHODS: Two hundred twenty-three patients with sarcoidosis and 206 healthy control subjects were recruited at seven sites in Japan. Eight single-nucleotide polymorphisms (SNPs) in TLR4 were genotyped with a TaqMan assay, and allelic and phenotypic diversity were assessed in affected and control subjects. RESULTS: We found no association with susceptibility to sarcoid-related uveitis for any of the SNPs analyzed. Strong linkage disequilibrium was observed among all the SNPs analyzed (D'>/=0.78), which were located in one haplotype block. CONCLUSION: TLR4 polymorphisms do not play an important role in the development of uveitis in Japanese patients with sarcoidosis.
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Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Sarcoidose/complicações , Sarcoidose/genética , Receptor 4 Toll-Like/genética , Uveíte/complicações , Uveíte/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Haplótipos/genética , Humanos , Desequilíbrio de Ligação/genética , MasculinoRESUMO
PURPOSE: To delineate features of ocular sarcoidosis. METHODS: Comparison of the old and new Japanese guidelines for diagnosing ocular sarcoidosis by review of the medical records of 100 sarcoidosis patients and 147 patients with non-sarcoidosis uveitis. RESULTS: The overall diagnostic sensitivity and specificity for the old guidelines were 80.0% and 45.6%; sensitivity and specificity for the new guidelines were 84.0% and 83.0%. Positive and negative predictive values and the likelihood ratios for a positive and negative test result improved. The new guidelines achieved more than 80% specificity for all categories. CONCLUSION: The new guidelines allow easier distinction of ocular sarcoidosis.
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Oftalmopatias/diagnóstico , Guias de Prática Clínica como Assunto/normas , Sarcoidose/diagnóstico , Humanos , Funções Verossimilhança , Prontuários Médicos , Oftalmologia/tendências , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Uveíte/diagnóstico , Uveíte/etiologiaRESUMO
OBJECTIVE: To report a case of neurosarcoidosis with rapid progression of visual field defects. CASE: A 28-year-old woman presented with bilateral uveitis and was diagnosed as having sarcoidosis after skin and cervical lymph node biopsy. Since bilateral excavations of the optic nerve head and visual field defects were observed, endocranial lesion was suspected. However, a computed tomography (CT) scan of the head detected nothing abnormal. It was regarded as a case of sarcoidosisaccompanied by normal-tension glaucoma and treatment was initiated with latanoprost. Four months later, the patient's visual field deteriorated rapidly. A CT scan showed a pituitary mass. Neurologicalfindings and hypopituitarism were found which improved with systemic prednisolone therapy. Diabetes insipidus developed after the start of treatment, and was treated with intranasal desmopressin therapy. After 6 weeks, head magnetic resonance imaging (MRI) showed a remarkable reduction of the enhanced regions. CONCLUSIONS: Although ocular sarcoidosis is often accompanied by secondary glaucoma or optic nerve atrophy, the progression of neurosarcoidosis can lead to visual field defects. Central nervous system (CNS) sarcoidosis is rare, but a precise examination with enhanced MRI should be considered when the visual field defect progresses rapidly.