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JAMA Ophthalmology Aug 2023Idiopathic multifocal choroiditis (MFC) is poorly understood, thereby hindering optimal treatment and monitoring of patients.
IMPORTANCE
Idiopathic multifocal choroiditis (MFC) is poorly understood, thereby hindering optimal treatment and monitoring of patients.
OBJECTIVE
To identify the genes and pathways associated with idiopathic MFC.
DESIGN, SETTING, AND PARTICIPANTS
This was a case-control genome-wide association study (GWAS) and protein study of blood plasma samples conducted from March 2006 to February 2022. This was a multicenter study involving 6 Dutch universities. Participants were grouped into 2 cohorts: cohort 1 consisted of Dutch patients with idiopathic MFC and controls, and cohort 2 consisted of patients with MFC and controls. Plasma samples from patients with idiopathic MFC who had not received treatment were subjected to targeted proteomics. Idiopathic MFC was diagnosed according to the Standardization of Uveitis Nomenclature (SUN) Working Group guidelines for punctate inner choroidopathy and multifocal choroiditis with panuveitis. Data were analyzed from July 2021 to October 2022.
MAIN OUTCOMES AND MEASURES
Genetic variants associated with idiopathic MFC and risk variants associated with plasma protein concentrations in patients.
RESULTS
This study included a total of 4437 participants in cohort 1 (170 [3.8%] Dutch patients with idiopathic MFC and 4267 [96.2%] controls; mean [SD] age, 55 [18] years; 2443 female [55%]) and 1344 participants in cohort 2 (52 [3.9%] patients with MFC and 1292 [96.1%] controls; 737 male [55%]). The primary GWAS association mapped to the CFH gene with genome-wide significance (lead variant the A allele of rs7535263; odds ratio [OR], 0.52; 95% CI, 0.41-0.64; P = 9.3 × 10-9). There was no genome-wide significant association with classical human leukocyte antigen (HLA) alleles (lead classical allele, HLA-A*31:01; P = .002). The association with rs7535263 showed consistent direction of effect in an independent cohort of 52 cases and 1292 control samples (combined meta-analysis OR, 0.58; 95% CI, 0.38-0.77; P = 3.0 × 10-8). In proteomic analysis of 87 patients, the risk allele G of rs7535263 in the CFH gene was strongly associated with increased plasma concentrations of factor H-related (FHR) proteins (eg, FHR-2, likelihood ratio test, adjusted P = 1.1 × 10-3) and proteins involved in platelet activation and the complement cascade.
CONCLUSIONS AND RELEVANCE
Results suggest that CFH gene variants increase systemic concentrations of key factors of the complement and coagulation cascades, thereby conferring susceptibility to idiopathic MFC. These findings suggest that the complement and coagulation pathways may be key targets for the treatment of idiopathic MFC.
Topics: Humans; Male; Female; Middle Aged; Complement Factor H; Multifocal Choroiditis; Genome-Wide Association Study; Proteomics; Polymorphism, Single Nucleotide; Choroiditis; Proteins
PubMed: 37410486
DOI: 10.1001/jamaophthalmol.2023.2557 -
Journal of Medical Case Reports Oct 2023Behçet's disease (BD) is a chronic systemic disease characterized by vasculitis as the basic pathological change. BD is rare, and gastrointestinal involvement occurs in... (Review)
Review
BACKGROUND
Behçet's disease (BD) is a chronic systemic disease characterized by vasculitis as the basic pathological change. BD is rare, and gastrointestinal involvement occurs in 3% to 25% of affected patients. This article describes a rare case of intestinal BD along with a literature review of intestinal involvement in BD.
CASE PRESENTATION
A 50-year-old Han woman from China presented with a > 6-month history of distending pain in the right upper abdomen. Because of mechanical obstruction secondary to stricture formation from an ileocecal ulcer, she underwent radical right colon resection, and postoperative pathologic examination indicated an ileocecal ulcer. The patient was readmitted to the hospital 6 months postoperatively for recurrence of the same symptoms. Colonoscopy indicated obvious narrowing of the anastomosis with an oval-shaped deep ulcer that could not be passed by the endoscope. Pathologic examination showed acute and chronic inflammation of the anastomotic mucosa and granulation tissue. In addition, gastroscopy showed a 3.0- × 4.0-cm giant ulcer at the junction of the descending bulb along with a sinus tract. Moreover, total gastrointestinal computed tomography angiography showed significant thickening of the intestinal wall near the transverse colon, forming a sinus tract at the junction of the antrum and duodenum with a length of about 1.3 cm and width of about 0.2 cm. Further inquiry regarding the patient's medical history revealed that she had developed repeated oral ulcers 3 years previously and repeated eye inflammation 5 years previously. Specimens of the right half of the colon removed 6 months previously were sent to Run Run Shaw Hospital Affiliated to Zhejiang University for consultation. The pathologic examination revealed vasculitis in the submucosa and subserosa, and the patient was finally diagnosed with BD. She began treatment with adalimumab, and repeat gastroenteroscopy revealed that the intestinal ulcer had significantly improved.
CONCLUSIONS
An oval-shaped deep intestinal ulcer is a characteristic lesion in patients with BD and may involve the intestinal muscle layer. This case emphasizes that BD is a vasculitis affecting multiple organs and can present with a single, deep, clean-edged intestinal ulcer that penetrates the bowel wall to form a sinus tract. Therefore, careful examination and differential diagnosis should be carried out to prevent a poor prognosis. Adalimumab is effective for patients with intestinal BD.
Topics: Female; Humans; Middle Aged; Behcet Syndrome; Ulcer; Adalimumab; Intestinal Diseases; Inflammation; Vasculitis
PubMed: 37798676
DOI: 10.1186/s13256-023-04148-w -
International Ophthalmology Apr 2024To review all studies reporting the onset of white dot syndromes following COVID-19 vaccines. (Review)
Review
PURPOSE
To review all studies reporting the onset of white dot syndromes following COVID-19 vaccines.
METHODS
Our protocol was registered prospectively on PROSPERO [registration number: CRD42023426012]. We searched five different databases including PubMed, Scopus, Web of Science, Google Scholar, and Science Direct up to May 2023. All the studies that reported the occurrence of white dot syndrome following COVID-19 vaccines were included. All statistical tests were conducted with a 95% confidence interval and a 5% error margin. A p value of less than 0.05 was considered statistically significant. The methodological quality of included studies was performed using the IHE Quality Appraisal Checklist for Case Series studies and JBI Critical Appraisal Checklist for Case Reports.
RESULTS
Fifty studies involving seventy-one subjects were included. Multiple evanescent white dot syndrome (MEWDS) was the most common disease (n = 25, 35.2% %), followed by acute macular neuroretinopathy (AMN) (n = 22, 31.0%) and acute posterior multifocal placoid pigment epitheliopathy (APMPPE) (n = 4, 5.6%). They were mostly unilateral (n = 50, 70.4%). The presenting symptoms were blurred vision (n = 26, 36.6%), paracentral scotoma (n = 19, 26.8%), visual field disturbance, and photopsia (n = 7, 9.9%). The mean duration for follow-up was 10.15 ± 14.04 weeks. Nineteen subjects (29.69%) received steroids with improvement reported in 68.4%. Eleven subjects (17.19%) were managed by observation only with reported full recovery and improvement.
CONCLUSION
White dot syndromes are very rare entities. Our findings highlight a possible association between COVID-19 vaccines and the occurrence of white dot syndromes. However, larger studies with good quality should be implemented to confirm these findings.
Topics: Humans; COVID-19; COVID-19 Vaccines; SARS-CoV-2; Tomography, Optical Coherence; White Dot Syndromes
PubMed: 38652153
DOI: 10.1007/s10792-024-03119-4 -
Investigative Ophthalmology & Visual... Oct 2023To explore the mechanism underlying IL-8-induced neutrophil extracellular trap (NET) formation in patients with ocular-active Behçet's disease (BD) and the effect of...
IL-8 Triggers Neutrophil Extracellular Trap Formation Through an Nicotinamide Adenine Dinucleotide Phosphate Oxidase- and Mitogen-Activated Protein Kinase Pathway-Dependent Mechanism in Uveitis.
PURPOSE
To explore the mechanism underlying IL-8-induced neutrophil extracellular trap (NET) formation in patients with ocular-active Behçet's disease (BD) and the effect of inhibiting NET formation on the severity of inflammation in experimental autoimmune uveitis (EAU) mice.
METHODS
The serum extracellular DNA and neutrophil elastase (NE) and IL-8 levels in patients with ocular-active BD, the expression of myeloperoxidase, NE, and histone H3Cit in IL-8-induced neutrophils isolated from healthy controls, and the effects of NETs on HMC3 cells were detected. Female C57BL/6J mice were immunized with IRBP651-670 to induce EAU and EAU mice received intravitreal injection of the CXCR2 (IL-8 receptor) antagonist SB225002 or PBS. The serum levels of extracellular DNA, NE, and keratinocyte-derived chemokine (the mouse ortholog of human IL-8) and expression of myeloperoxidase, NE, and histone H3Cit in mouse retinas were detected. Disease severity was evaluated by clinical and histopathological scores.
RESULTS
Serum keratinocyte-derived chemokine expression levels in EAU mice and IL-8 expression levels in patients with ocular-active BD increased. IL-8 notably increased NET formation in a dose-dependent manner through an nicotinamide adenine dinucleotide phosphate oxidase and mitogen-activated protein kinase pathway dependent mechanism. IL-8-induced NET formation damaged HMC3 cells in vitro. Pretreatment with SB225002 notably ameliorated the production of NETs in EAU mice.
CONCLUSIONS
Our data confirm that NET formation is induced by IL-8. IL-8-induced NET formation was found to be related to mitogen-activated protein kinase and nicotinamide adenine dinucleotide phosphate pathways. Pretreatment with the CXCR2 antagonist SB225002 alleviated neutrophil infiltration and suppressed NET formation in EAU mice.
Topics: Animals; Female; Humans; Mice; Behcet Syndrome; DNA; Extracellular Traps; Histones; Interleukin-8; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; NADP; Neutrophils; Peroxidase; Uveitis
PubMed: 37824136
DOI: 10.1167/iovs.64.13.19 -
Revista de Neurologia Jul 2023Limbic encephalitis (LE) can have a wide range of etiologies, most frequently infectious (especially viral) or autoimmune. Behcet's disease (BD) can present with... (Review)
Review
INTRODUCTION
Limbic encephalitis (LE) can have a wide range of etiologies, most frequently infectious (especially viral) or autoimmune. Behcet's disease (BD) can present with heterogeneous neurological manifestations. However, LE is not considered a typical presentation of neuro-Behcet's disease (NBD).
CASE REPORT
A 40-years-old male presented with new-onset subacute headaches, memory problems and apathy. A review of systems revealed an unrecorded past history of recurrent oral sores for years, recent malaise and fever, as well as an episode of bilateral panuveitis four months before presentation. His general and neurologic examination revealed slight fever, an isolated oral aphtha, anterograde amnesia and signs of bilateral retinal vasculitis. Brain magnetic resonance imaging displayed a pattern of limbic meningoencephalitis, and his cerebrospinal fluid showed mononuclear inflammation. The patient met BD diagnostic criteria. Considering LE is a very rare presentation of NBD, alternative etiologies were thoroughly assessed and excluded, including infectious, autoimmune and paraneoplastic encephalitis. Therefore, he was diagnosed with NBD, and he recovered well after immunosuppression.
DISCUSSION
Only two cases of NBD presenting with LE have been previously reported. We report a third case of this rare presentation and compare it with the previous two. We aim to highlight this association and contribute to enlarge the rich clinical spectrum of NBD.
Topics: Humans; Male; Adult; Behcet Syndrome; Limbic Encephalitis; Brain; Magnetic Resonance Imaging; Headache
PubMed: 37403244
DOI: 10.33588/rn.7702.2022049 -
Experimental and Clinical... Jan 2024HLA molecules play a crucial role in transplantation. The best treatment modality in patients with end-stage renal disease is renal transplant. HLA mismatches between...
OBJECTIVES
HLA molecules play a crucial role in transplantation. The best treatment modality in patients with end-stage renal disease is renal transplant. HLA mismatches between patients and donors can prolong time for renal transplant therapy, reduce graft survival, and increase mortality. HLA region is the most polymorphic genetic region and is essential for antigen presentation. The main target of the recipient's immune system is HLA molecules on the surface of donor cells. HLA-B*51 is associated with Behcet disease, a rare multisystemic disease characterized by autoimmunity and inflammatory processes. In transplant recipients, inflammation and vasculitis are immunologic mechanisms that are responsible for damage of graft tissue. In this retrospective study, we aimed to investigate the frequency of HLA-B*51 in patients diagnosed with end-stage renal disease and in controls and to investigate correlations with rejection episodes.
MATERIALS AND METHODS
Patients who applied to Baskent University Adana Dr. Turgut Noyan Research and Medical Center (between 2010 and 2022) with end-stage renal disease (n = 1732) and a control group (n = 5277) received HLA typing for class I (HLA-A, HLA-B). Sequence-specific primers or sequencespecific oligonucleotides were used. Among patients diagnosed with end-stage renal disease, 321 had kidney transplant.
RESULTS
Frequency of HLA-B*51 was 25.92% in patients and 25.22% in controls. No significant differences were found between patients and controls in the frequency of HLA-B*51. Among kidney transplant recipients with HLA-B*51 (n = 72), 38.89% had rejection episodes and 61.11% had no rejection. No significant association was found between HLA-B*51 allele positivity and rejection.
CONCLUSIONS
No significant relationship was shown between patients diagnosed with end-stage renal disease and HLA-B*51 positivity. Previous studies support frequency of the HLA-B*51 allele in the control group. Although Behçet disease is known to cause renal vasculitis, HLA-B*51 positivity alone was not associated with vasculitis or inflammation.
Topics: Humans; Behcet Syndrome; Graft Rejection; Graft Survival; Histocompatibility Testing; Inflammation; Kidney Failure, Chronic; Retrospective Studies; Tissue Donors; HLA-B51 Antigen
PubMed: 38385410
DOI: 10.6002/ect.MESOT2023.P76 -
Progress in Retinal and Eye Research Mar 2024Punctate inner choroidopathy (PIC) is an uncommon idiopathic inflammatory condition characterized by multifocal chorioretinopathy that primarily affects young adults,... (Review)
Review
Punctate inner choroidopathy (PIC) is an uncommon idiopathic inflammatory condition characterized by multifocal chorioretinopathy that primarily affects young adults, with a predilection for myopic females. Clinically, it manifests as small, yellowish-white lesions in the inner choroid and outer retina, often associated with inflammatory changes. Accurate diagnosis remains a challenge due to its resemblance to other posterior uveitic entities, necessitating an astute clinical eye and advanced imaging techniques for differentiation. Multimodal imaging plays a crucial role by offering valuable insights, as it enables the visualization of various abnormalities related to uveitis. The pathogenesis of PIC is still a subject of debate, with a complex interplay of genetic, immunological, and environmental factors proposed. Managing PIC presents multiple challenges for clinicians. Firstly, variable disease severity within and among patients requires diverse treatments, from observation to aggressive immunosuppression and/or anti-VEGF therapy. Secondly, treatment must distinguish between primary causes of vision loss. New or worsening PIC lesions suggest active inflammation, while new neovascular membranes may indicate secondary neovascular processes. Thirdly, deciding on maintenance therapy is complex, balancing PIC prognosis variability against immunosuppression risks. Some patients have long periods of inactivity and remission, while others face sudden, vision-threatening episodes during quiescent phases. Through a systematic review of the literature, this paper sheds light on the current understanding of PIC, its challenges, and the prospects for future research. By synthesizing existing knowledge, it aims to aid clinicians in accurate diagnosis and guide treatment decisions for improved visual outcomes in individuals affected by PIC.
Topics: Female; Young Adult; Humans; Fluorescein Angiography; Visual Acuity; White Dot Syndromes; Choroid; Choroid Diseases; Tomography, Optical Coherence
PubMed: 38181975
DOI: 10.1016/j.preteyeres.2023.101235 -
European Review For Medical and... Sep 2023The aim of this retrospective cohort study was to investigate complete blood count parameters in patients with Behçet's disease (BD) who present with oral ulcers and...
OBJECTIVE
The aim of this retrospective cohort study was to investigate complete blood count parameters in patients with Behçet's disease (BD) who present with oral ulcers and patients with recurrent aphthous stomatitis (RAS) in order to determine whether they could be used as discriminatory biomarkers.
PATIENTS AND METHODS
This study was conducted between January 2019 and January 2023. The study population consisted of three groups: patients with BD who had oral ulcer manifestation (n=85, BD-Group), patients with idiopathic RAS (n=186, RAS-Group) and healthy controls (n=90, HC-Group). All data about participants, on their first application, including sociodemographic and clinical data, comorbidity status, laboratory results were collected retrospectively from the hospital computer records and patients' charts.
RESULTS
The groups were similar in terms of age (p=0.235) and sex distribution (p=0.450). Mean platelet volume (MPV) and plateletcrit values of the BD-Group were significantly lower, while platelet distribution width (PDW) was significantly higher, compared to the other two groups (p<0.001 for all). Low MPV (<9.15) (56.47% sensitivity and 90.86% specificity), high PDW (≥15.75) (75.00% sensitivity and 94.96% specificity) and low plateletcrit (<0.237) (55.29% sensitivity and 79.46% specificity) could significantly distinguish BD patients with oral ulcer onset from patients with RAS.
CONCLUSIONS
PDW, MPV, and plateletcrit may be useful biomarkers in the differential diagnosis of oral ulcers when distinguishing between BD and RAS. However, these results need to be supported by further comprehensive studies.
Topics: Humans; Stomatitis, Aphthous; Behcet Syndrome; Oral Ulcer; Retrospective Studies
PubMed: 37782165
DOI: 10.26355/eurrev_202309_33774 -
Comparative Medicine Aug 2023Chronic asymptomatic and acute symptomatic anterior uveitis are forms of ocular inflammation associated with juvenile idiopathic arthritis (JIA) Chronic JIA-associated...
Chronic asymptomatic and acute symptomatic anterior uveitis are forms of ocular inflammation associated with juvenile idiopathic arthritis (JIA) Chronic JIA-associated uveitis is characterized by young age of onset, female predilection, oligoarthritis, and antinuclear antibody (ANA) positivity. Acute JIA-associated uveitis predominantly affects older male juveniles who also develop enthesitis. A type I collagen-derived peptide (melanin-associated antigen [MAA]) induces anterior uveitis in rodents. In this study, we evaluated MAA-induced uveitis in rats as a potential model for JIA-uveitis. We characterized MAA-induced uveitis by assessing its relationship to age and sex; tracking the occurrence of arthritis, enthesitis, and ANA positivity; and measuring vitreous fluid inflammatory biomarkers. Juvenile and adult and male and female Lewis rats () were inoculated with MAA. Slit-lamp biomicroscopy, indirect ophthalmoscopy, and joint examinations were performed 3 times weekly. Rats were euthanized at 4 wk after MAA inoculation, and plasma ANA testing, vitreous inflammatory biomarker assays, and globe histopathology assessments were conducted. Uveitis, arthritis, ANA status, levels of inflammatory biomarkers, histopathology, and joint tomographic images were assessed in relation to age and sex and compared with nonuveitic controls. All MAA-immunized rats developed uveitis characterized by anterior chamber fibrin, iridal vessel dilation, and miosis, and uveal and choroidal lymphocytic infiltration. Levels of the vitreous fluid biomarker CCL5 were higher in uveitic rats compared with control rats. Time to uveitis onset, clinical uveitis scores, and biomarker levels did not differ based on age or sex. None of the MAA-exposed rats had arthritis, enthesitis, or ANA. None of the rats inoculated with MAA that had been treated with matrix metallopeptidase 1 had clinical, histologic, or immunohistochemical evidence of ocular inflammation. In contrast to JIA-associated uveitis in humans, MAA-induced uveitis in rats is not associated with age or sex predilections and MAA is not arthritogenic.
Topics: Humans; Male; Female; Rats; Animals; Child; Arthritis, Juvenile; Collagen Type I; Rats, Inbred Lew; Uveitis; Uveitis, Anterior; Biomarkers; Inflammation
PubMed: 37550056
DOI: 10.30802/AALAS-CM-22-000129 -
Ophthalmology and Therapy Oct 2023We investigated the frequency of uveitic macular edema (UME) in patients with different types of noninfectious uveitis and present the primary treatment methods for UME...
INTRODUCTION
We investigated the frequency of uveitic macular edema (UME) in patients with different types of noninfectious uveitis and present the primary treatment methods for UME at a specialized eye center in Shaanxi Province, China.
METHODS
We conducted a retrospective, noninterventional, observational survey involving 1946 patients with noninfectious uveitis (2816 eyes). The collected data included sex, age of uveitis onset, age of UME onset, anatomical classification of uveitis, and the treatment administered to UME patients.
RESULTS
Of the 1946 patients with noninfectious uveitis, 929 (47.74%) were male and 1017 (52.26%) were female. The average age of all participants in the study was 42.19 ± 15.34 years, with average age at uveitis onset of 39.50 ± 15.52 years. Among the patients, 1003 (51.54%), 239 (12.28%), 410 (21.07%), and 294 (15.11%) had anterior uveitis, intermediate uveitis, posterior uveitis, and panuveitis, respectively. UME was observed in 134 (6.89%) of the uveitis patients. The average age of UME patients was 47.33 ± 17.17 years, with average age at uveitis onset of 45.78 ± 17.20 years. Out of the 134 UME patients, 3 (0.30%), 15 (6.28%), 47 (11.46%), and 69 (23.47%) had anterior uveitis, intermediate uveitis, posterior uveitis, and panuveitis, respectively. Among them, 37 were lost to follow-up, 44 received adalimumab (ADA) combined with low-dose prednisone and with or without conventional immunosuppressants, 19 received interferon-α2a therapy, 14 received intravitreal corticosteroid injections (such as dexamethasone implant or fluocinolone acetonide), 11 received low-dose corticosteroids combined with conventional immunosuppressants, 5 received only oral prednisone, and 4 received repeated peribulbar or subconjunctival injections of triamcinolone acetonide.
CONCLUSIONS
At our tertiary ophthalmic center in Shaanxi Province, China, only 6.89% of patients with noninfectious uveitis were diagnosed with UME. The primary treatment modality for UME in our center is ADA, in accordance with treatment guidelines and the Chinese medical insurance reimbursement system.
PubMed: 37440091
DOI: 10.1007/s40123-023-00763-4