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Clinical Immunology (Orlando, Fla.) Aug 2023Almost 90% of Behçet's patients present with oral and/or genital ulcers which influence the disease outcome. We hypothesised that the dysregulation of the oral and...
UNLABELLED
Almost 90% of Behçet's patients present with oral and/or genital ulcers which influence the disease outcome. We hypothesised that the dysregulation of the oral and genital microbiome, coupled with dysregulation of the immune response, contributes to the aetiopathogenesis of Behçet's Disease (BD) and drives disease activation.
METHOD
152 BD patient samples; 70 matched oral and genital samples plus 12 unmatched samples (Female: Male, 58:12; mean age, 42 ± 13.9: 39.3 ± 10.3) to profile microbial community high-throughput sequencing of the microbiome using 16 s rRNA sequencing targeting the V1/V2 and V3/V4 hyper variable regions were used and results reviewed in relation to disease severity, Work and Social Adjustment Scale (WSAS) outcomes and medication.
RESULTS
Alpha and beta diversity were significantly decreased in genital compared to oral samples; p value<0.05. However, grouping the samples as to whether ulceration was present was not significant. Escherichia-Shigella was the only Amplicon Sequence Variants (ASVs) in the V1/V2 region that was shared between the oral mucosa with ulcer (O_U) and genital mucosa with ulcer (G_U) groups. This was in contrast to the V3/V4 region which indicated that Lachnospiraceae, Saccharimonadales, and Coriobacteriales were shared between the O_U and G_U groups. In addition, gender had no impact on the bacterial abundance in V1/V2 analysis of the oral and genital samples. V3/V4 analysis of genital samples demonstrated that Lactobacilli and Gardnerella were significantly increased in females (20 times) compared to the males in samples; p-adj <0.05. Interestingly in BD patients, Rothia which is commonly found in the mouth was present in both oral and genital samples. Streptococci were significantly increased while Veillonella significantly decreased in the presence of oral ulceration in the BD cohort. The clinical phenotype had no effect on V1/V2 and V3/V4 on the bacterial abundance of oral samples. However, medication e.g. colchicine had a significant effect on the oral microbial abundance (V1/V2; P = 0.020, V3/V4; P = 0.003). There was no relationship between colchicine and the presence/absence of genital ulcers. BD patients with active disease had higher WSAS scores, and their bacterial abundance differed significantly from the non-active BD patients (ADONIS, R2 = 0.05, p value =0.029).
CONCLUSION
The presence of the microbes Streptococcus, Veillonella, Gardnerella, Lactobacillus, Atopobium, Peptoniphilus, Corynebacterium and Staphylococcus may provide early evidence of BD patients are with active disease.
Topics: Male; Female; Humans; Behcet Syndrome; Ulcer; Microbiota; Genitalia; Bacteria; Mucous Membrane; Colchicine
PubMed: 37257548
DOI: 10.1016/j.clim.2023.109654 -
International Journal of Ophthalmology 2024To determine the common causes and visual outcome after treatment among uveitis and scleritis patients.
AIM
To determine the common causes and visual outcome after treatment among uveitis and scleritis patients.
METHODS
This is a retrospective cohort observational study. All consecutive clinical records of patients with newly diagnosed uveitis and scleritis over a 4-year period, from Jan. 1, 2017 to Dec. 31, 2020, were analysed. Data was collected at the presentation and included a follow-up period of one year.
RESULTS
A total of 288 patients were recruited during the study period. Anterior uveitis was the most common anatomical diagnosis (50.0%) followed by panuveitis (25.0%), scleritis (13.5%), posterior uveitis (6.9%), and intermediate uveitis (4.5%). Viral Herpes was the most common cause of infectious cases, while Vogt-Koyanagi-Harada (VKH) disease and human leucocyte antigen (HLA) B27 spondyloarthropathy were the leading causes of identifiable non-infectious cases. Majority of patients presented with unilateral, non-granulomatous uveitis with an absence of hypopyon. Anatomical locations like posterior uveitis and panuveitis, and visual acuity worse than 3/60 at presentation were the factors associated with poor visual outcomes (<0.05). About 60% of patients had an identifiable cause for the uveitis and scleritis, with nearly equal distribution of infectious (=85, 29.5%) and non-infectious causes (=84, 29.2%). About 14.5% of patients were clinically blind at 1y of follow-up. The most common complication in our uveitis patients was glaucoma (47.5%), followed by cystoid macula oedema (18.9%) and cataract (13.9%).
CONCLUSION
Uveitis and scleritis are important causes of ocular morbidity. They are potentially blinding diseases which can have a good outcome if diagnosed and treated early.
PubMed: 38721518
DOI: 10.18240/ijo.2024.03.14 -
Frontiers in Immunology 2023Non-infectious uveitis is a complex disease characterized by intraocular inflammation of the uveal area and the leading cause of vision impairment and blindness in young...
PURPOSE
Non-infectious uveitis is a complex disease characterized by intraocular inflammation of the uveal area and the leading cause of vision impairment and blindness in young people globally. However, what triggers inflammation and contributes to its recurrence remains unclear. The complement system has been linked to various immunological and inflammatory conditions. In the present study, we have systematically evaluated the role of the alternative complement pathway in the pathogenesis of non-infectious uveitis.
METHODOLOGY
Quantitative PCR was done in the peripheral leukocytes to study the expression of genes and regulatory miRNA in both anterior and posterior uveitis (n=28 in each category). Multiplex ELISA was performed to measure alternative pathway complement components, such as C3b, factor B, and CFH, and aqueous humor of infectious and non-infectious uveitis patients and non-inflammatory controls (n=10 each). Western blotting was done to validate the ELISA findings in a subset of patients and controls.
RESULTS
Downregulation of and mRNA in the peripheral blood was shown by quantitative PCR in the group of anterior uveiits (AU), while the opposite result was found in the group of posterior uveitis (PU). ELISA levels of C3b and CFH proteins were significantly higher in aqueous humor of infectious and non-infectious uveitis (*p = 0.03 and **p = 0.0007 respectively) as compared to the control group. Western blotting further validated (VitH) the activation of the complement cascade in the aqueous (AH) and vitreous humor of patients with non-infectious uveitis, with an increased level of C3b (n=6) and CFH (n=4) in aqueous humor. C3b level was significantly increased while CFH was reduced relative to controls in the vitreous humor (VitH) of posterior uveitis patients compared to controls (n=27 in each category). A C3b to CFH ratio was computed to assess the regulation of complement activation and this index was several folds higher in both anterior and posterior uveitis (n=10 each). The expression of miRNA-hsa-miR-146a and miRNA-hsa-miR-155-5p that regulates CFH was downregulated and nicely correlated with the increased complement proteins in both anterior and posterior uveitis (n=10 each).
CONCLUSION
Our results demonstrate a clear role of CFH and the activation of the alternative complement pathway in the pathogenesis of non-infectious uveitis; however, its therapeutic potential warrants further investigations.
Topics: Humans; Adolescent; Complement Pathway, Alternative; Uveitis; Uveitis, Posterior; MicroRNAs; Inflammation
PubMed: 38187376
DOI: 10.3389/fimmu.2023.1222998 -
Indian Journal of Ophthalmology Jul 2024Acute Zonal Occult Outer Retinopathy (AZOOR) is characterized by sudden visual impairment, often presenting with scotoma and photopsia in young to middle-aged adults,... (Review)
Review
Acute Zonal Occult Outer Retinopathy (AZOOR) is characterized by sudden visual impairment, often presenting with scotoma and photopsia in young to middle-aged adults, showing a female predominance. This condition, distinct from genetic disorders like retinitis pigmentosa, lacks a hereditary basis and exhibits unique fundus changes and imaging features indicative of outer retinal dysfunction. Recent advancements have broadened our understanding, identifying variants like Acute Annular Outer Retinopathy (AAOR) and Multizonal outer retinopathy and retinal pigment epitheliopathy (MORR), each with specific clinical presentations and imaging characteristics. The diagnosis of AZOOR and its variants primarily relies on excluding other conditions through comprehensive evaluation, including imaging and serological testing. Treatment approaches, including the use of corticosteroids and immunosuppressives, remain debated, with some evidence suggesting benefits in the early stages. The prognosis of AZOOR varies, with most patients experiencing stabilization, although complications like choroidal neovascularization may occur, requiring targeted therapy. This manuscript elucidates the complexity of AZOOR, emphasizing the necessity of high clinical suspicion and the role of advanced imaging in diagnosis and management.
Topics: Humans; White Dot Syndromes; Scotoma; Tomography, Optical Coherence; Fluorescein Angiography; Fundus Oculi; Visual Acuity; Visual Fields; Electroretinography
PubMed: 38454854
DOI: 10.4103/IJO.IJO_3228_23 -
Journal of Ophthalmic Inflammation and... Sep 2023Uveitic macular edema is a complication of acute or chronic uveitis. Current treatment regiments frequently have numerous side effects, often requiring supplemental...
BACKGROUND
Uveitic macular edema is a complication of acute or chronic uveitis. Current treatment regiments frequently have numerous side effects, often requiring supplemental treatment. This study investigates the efficacy of dexamethasone (DEX) intravitreal implants as monotherapy for treatment of macular edema in non-infectious intermediate, posterior or panuveitis.
METHODS AND RESULTS
Retrospective chart review of thirty patients with intermediate, posterior and panuveitis treated with DEX. Outcomes measured were central retinal thickness (CRT) and best corrected visual acuity (BCVA). Baseline measurements of CRT and BCVA were measured within 1 month prior to intravitreal DEX implant and follow up measurements were collected until 1 year post implant. 48 implants on 39 eyes of 30 patients were included in this study; 64.1% of patients had an improvement in BCVA and 65.4% had a reduction in CRT. BCVA improved from 0.285 logMAR (SD: 0.312) at baseline to 0.175 logMAR (SD: 0.194) at 1 month and was sustained thereafter. Preliminary CRT data showed a decrease from 392 [Formula: see text] (SD: [Formula: see text]) at baseline to 303 [Formula: see text] (SD: [Formula: see text] at 1 month and 313 [Formula: see text] (SD: [Formula: see text] at 12 months.
CONCLUSIONS
The DEX implant as monotherapy for macular edema in non-infectious uveitis was associated with a reduction in CRT and improvement in BCVA. The DEX implant, used as a monotherapy in eyes with intermediate, posterior and panuveitis, has the potential to treat uveitis without oral corticosteroid or other immunomodulatory therapy.
PubMed: 37721556
DOI: 10.1186/s12348-023-00360-3 -
Journal of Ophthalmic Inflammation and... Jun 2024To report a case of Purpureocillium lilacinum endophthalmitis.
PURPOSE
To report a case of Purpureocillium lilacinum endophthalmitis.
METHODS
The case of a fungal endophthalmitis caused by Purpureocillium lilacinum documented in an immunocompetent patient with no apparent trigger.
RESULTS
A 64-year-old male with a two-month history of panuveitis in his left eye was referred to our hospital. Initially misdiagnosed as sympathetic ophthalmia due to a previous surgery on his right eye 4 months before the onset of the left ocular picture, the patient received corticosteroid treatment, leading to a rapid deterioration of the left eye condition. An urgent exploratory vitrectomy was performed to identify the underlying cause, revealing endophthalmitis. Microbiological investigation yielded Purpureocillium lilacinum as the causative agent. Despite intensive treatment, including intravitreal antibiotics and antifungals, along with another surgical intervention, clinical evolution remained unfavourable, ultimately leading to the evisceration of the affected eye.
CONCLUSIONS
Purpureocillium lilacinum poses a rare yet sever threat as a causative agent of fungal endophthalmitis. Managing such cases is challenging due to the delayed identification, fungus's resistance to common antifungals, and its association with prior corticosteroid misuse in most patients. This case underscores the crucial importance of heightened clinical suspicion, early diagnosis, and the exploration of alternative treatment strategies in addressing Purpureocillium lilacinum endophthalmitis. The challenges posed by this rare fungal pathogen emphasize the need for a multidisciplinary approach and continued research to improve outcomes in these complex cases.
PubMed: 38867117
DOI: 10.1186/s12348-024-00412-2 -
BMC Ophthalmology Aug 2023Cat-scratch disease typically presents with various ocular manifestations such as uveitis, vitritis, retinitis, retinochoroiditis, and optic neuritis. However, fundus...
BACKGROUND
Cat-scratch disease typically presents with various ocular manifestations such as uveitis, vitritis, retinitis, retinochoroiditis, and optic neuritis. However, fundus nodular lesions was rarely reported. In our study, we reported a case of Cat-Scratch disease with binocular fundus nodular lesions.
CASE PRESENTATION
An 11-year old male presented with uveitis in the right eye and bilateral fundus nodular lesions after indirect contact with unvaccinated cats. Comprehensive ancillary examinations including wide-angle fundus photography, ultrasonography, fluorescein fundus angiography, optical coherence tomography, and orbital magnetic resonance imaging were performed to elucidate the multidimensional features of the binocular lesions. Metagenomics next-generation sequencing was utilized to confirm the diagnosis of Cat-scratch disease. The patient's condition showed improvement after a 6-month combination treatment regimen involving systemic administration of doxycycline hyclate and methylprednisolone tablets, as well as local application of mydriatic and corticosteroid eye drops.
CONCLUSIONS
We firstly reported a case of Cat-scratch disease presenting simultaneously with uveitis and fundus nodular lesions caused by Bartonella henselae infection in a child. Timely diagnosis and treatment with antibiotics and corticosteroids showed promising outcomes for the prognosis of these ocular disorders.
Topics: Male; Humans; Cat-Scratch Disease; Bartonella henselae; Fundus Oculi; Retinitis; Chorioretinitis
PubMed: 37544996
DOI: 10.1186/s12886-023-03063-4 -
The Korean Journal of Internal Medicine Sep 2023The short- and long-term effects of adalimumab (ADA) on Korean patients with intestinal Behcet's disease (BD) for remain unclear. Therefore, a multicenter study was...
Real-world effectiveness and safety of adalimumab in Korean patients with intestinal Behcet's disease: a Korean Association for the Study of Intestinal Diseases (KASID) multicenter study.
BACKGROUND/AIMS
The short- and long-term effects of adalimumab (ADA) on Korean patients with intestinal Behcet's disease (BD) for remain unclear. Therefore, a multicenter study was performed to evaluate the efficacy and safety of ADA in Korean patients with intestinal BD in a real-world setting.
METHODS
The medical records of 67 patients with BD prescribed ADA between January 2012 and December 2020 at five referral centers in Korea were retrospectively analyzed and the safety and efficacy of ADA within 52 weeks were assessed. To evaluate the clinical efficacy of ADA, the Disease Activity Index for Intestinal BD (DAIBD) and representative blood biochemical markers were compared at 0, 12, 24, and 52 weeks of ADA treatment.
RESULTS
During the follow-up period of 52 weeks, 46 patients continued ADA treatment. The cumulative drug survival rate was 83.5%. The DAIBD score decreased over the study period (p < 0.001). Moreover, the erythrocyte sedimentation rate, serum C-reactive protein levels, and serum albumin levels significantly improved at 12, 24, and 52 weeks of ADA treatment (all, p <0.05).
CONCLUSION
As ADA is effective for refractory intestinal BD with few safety concerns in real-world situations, it is a potential treatment option for Korean patients with intestinal BD.
Topics: Humans; Adalimumab; Behcet Syndrome; Retrospective Studies; Intestinal Diseases; Treatment Outcome; Republic of Korea
PubMed: 37491721
DOI: 10.3904/kjim.2022.394 -
Medical Science Monitor : International... May 2024Behçet uveitis poses significant management challenges, owing to its intricate pathogenesis and the severe prognosis it harbors, frequently culminating in irreversible... (Review)
Review
Behçet uveitis poses significant management challenges, owing to its intricate pathogenesis and the severe prognosis it harbors, frequently culminating in irreversible visual impairment and an elevated risk of blindness. This review synthesizes contemporary insights into personalized immunosuppressive strategies for Behçet uveitis, emphasizing the necessity for a customized approach in recognition of the disease's heterogeneity and the variable responsiveness to treatment. This discourse elaborates on the application, efficacy, and safety profiles of traditional immunosuppressants, highlighting a paradigm shift toward integrative combination therapies aimed at diminishing reliance on glucocorticoids and mitigating their associated adverse effects. This thorough evaluation seeks to enlighten clinical practices and spearhead future investigations aimed at refining the management of Behçet uveitis, championing a personalized, multidisciplinary strategy to amplify therapeutic efficacy and enhance patient quality of life.
Topics: Humans; Behcet Syndrome; Uveitis; Immunosuppressive Agents; Precision Medicine; Quality of Life
PubMed: 38711247
DOI: 10.12659/MSM.943240 -
Reumatologia Clinica Apr 2024To develop multidisciplinary recommendations based on available evidence and expert consensus for the therapeutic management of patients with refractory Behçet's...
OBJECTIVE
To develop multidisciplinary recommendations based on available evidence and expert consensus for the therapeutic management of patients with refractory Behçet's syndrome (BS) (difficult to treat, severe resistant, severe relapse) to conventional treatment.
METHODS
A group of experts identified clinical research questions relevant to the objective of the document. These questions were reformulated in PICO format (patient, intervention, comparison and outcome). Systematic reviews of the evidence were conducted, the quality of the evidence was evaluated following the methodology of the international working group Grading of Recommendations Assessment, Development, and Evaluation (GRADE). After that, the multidisciplinary panel formulated the specific recommendations.
RESULTS
4 PICO questions were selected regarding the efficacy and safety of systemic pharmacological treatments in patients with BS with clinical manifestations refractory to conventional therapy related to mucocutaneous and/or articular, vascular, neurological parenchymal and gastrointestinal phenotypes. A total of 7 recommendations were made, structured by question, based on the identified evidence and expert consensus.
CONCLUSIONS
The treatment of most severe clinical manifestations of BS lacks solid scientific evidence and, besides, there are no specific recommendation documents for patients with refractory disease. With the aim of providing a response to this need, here we present the first official Recommendations of the Spanish Society of Rheumatology for the management of these patients. They are devised as a tool for assistance in clinical decision making, therapeutic homogenisation and to reduce variability in the care of these patients.
Topics: Behcet Syndrome; Humans; Immunosuppressive Agents
PubMed: 38614885
DOI: 10.1016/j.reumae.2023.12.006