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Thrombosis and Haemostasis Jul 2022To evaluate the relevance of plasma homocysteine (HC) in Behcet's disease (BD) and its clinical manifestations. (Meta-Analysis)
Meta-Analysis
AIM
To evaluate the relevance of plasma homocysteine (HC) in Behcet's disease (BD) and its clinical manifestations.
METHODS
Systematic review of EMBASE and PubMed databases according to PRISMA guidelines from inception to July 2021; random-effects meta-analyses for continuous outcomes.
RESULTS
The search strategy retrieved 48 case-control (2,669 BD and 2,245 control participants) and 5 cohort studies (708 BD participants). Plasma HC was higher in BD than in controls ( < 0.0001) with wide heterogeneity ( = 89.7%) that remained unchanged after sensitivity analysis according to year of article publication, age of BD participants, study size, study quality, method of HC determination, and male/female ratio >1.5; some pooled ethnicities explained a small part of the heterogeneity ( = 16.3%). Active BD participants had higher HC than inactive ones ( < 0.0001), with moderate heterogeneity = 49.2%) that disappeared after removal of an outlier study with very high disease activity. BD participants with any vascular involvement had higher HC than those without ( < 0.0001) with wide heterogeneity ( = 89.7%); subgroup analysis on venous thrombosis only changed neither effect size ( < 0.0001) nor heterogeneity ( = 72.7%). BD participants with ocular involvement had higher HC than those without ( < 0.0001) with moderate heterogeneity ( = 40.3%).
CONCLUSION
Although causality cannot be inferred, the consistency of the elevation of plasma HC in BD, particularly in patients with active disease, with vascular and ocular involvement suggests an intrinsic involvement of HC in these clinical manifestations.
Topics: Behcet Syndrome; Case-Control Studies; Female; Homocysteine; Humans; Male; Venous Thrombosis
PubMed: 34996122
DOI: 10.1055/s-0041-1740637 -
Seminars in Arthritis and Rheumatism Feb 2022Mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome is characterized by overlapping features of relapsing polychondritis (RP) and Behcet's disease (BD). To...
OBJECTIVE
Mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome is characterized by overlapping features of relapsing polychondritis (RP) and Behcet's disease (BD). To date, no studies have defined the clinical spectrum of disease in a cohort of patients with MAGIC syndrome.
METHODS
Adult patients within an ongoing prospective, observational cohort study in RP were clinically assessed for MAGIC syndrome. A systematic review was conducted to identify additional cases of MAGIC syndrome by searching four databases: PubMed (US National Library of Medicine), Embase (Elsevier), Scopus (Elsevier) and Web of Science: Core Collection (Clarivate Analytics). The inclusion criteria used were: [1] patients of any age or gender who were diagnosed with MAGIC syndrome, or both RP and BD; [2] case report or case series study; [3] published from 1985 - July 2020; and [4] in English language. Risk of bias was assessed using a checklist developed by the authors and based on the Consensus-based Clinical Case Reporting (CARE) Guidelines. Search results screening, article inclusion, data extraction and risk of bais assessment was performed independently by two investigators. Clinical characteristics, particularly BD-related features, were compared between patients with MAGIC syndrome and cases of non-MAGIC RP. The performance characteristics of different criteria to classify MAGIC syndrome were also evaluated.
RESULTS
Out of 96 patients with RP, 13 (14%) patients were diagnosed with MAGIC syndrome. For the systematic review, 380 articles were retrieved of which 90 were screened at title and abstract levels. Of these screened, 60 were excluded and 30 proceeded to full text review where an additional 8 were excluded. Twenty-two articles were included in our review and from which 27 additional cases of MAGIC syndrome were identified. Pooling all 40 cases together and comparing them with non-MAGIC RP, there was a significantly higher prevalence of ocular involvement (28% vs 4%, p<0.01), cutaneous involvement (35% vs 1%, p<0.01), GI involvement (23% vs 4%, p<0.01), and CNS involvement (8% vs 0, p = 0.04) in MAGIC syndrome. A higher prevalence of aortitis (23% vs 1%, p<0.01), Raynaud's phenomenon (54% vs 11%, p<0.01), and elevated anti-collagen II antibodies (50% vs 9%, p = 0.04) were observed in MAGIC syndrome. Fulfillment of either McAdam's or Damiani's Criteria for RP plus the International Criteria for Behçet's Disease had excellent sensitivity (98%) to classify cases of MAGIC syndrome.
CONCLUSION
A substantial proportion of patients with RP can be clinically diagnosed with MAGIC syndrome. These patients have features of RP, BD, and other unique features including aortitis, Raynaud's phenomenon and elevated anti-collagen II antibodies.
Topics: Adult; Behcet Syndrome; Cartilage; Genitalia; Humans; Mouth; Observational Studies as Topic; Prospective Studies; Ulcer; United States
PubMed: 34972595
DOI: 10.1016/j.semarthrit.2021.10.007 -
Autoimmunity Reviews Mar 2022Vasculitis are severe systemic autoimmune diseases which may involve different organs and systems. Conversely, muscles do not represent an organ commonly involved by... (Review)
Review
Vasculitis are severe systemic autoimmune diseases which may involve different organs and systems. Conversely, muscles do not represent an organ commonly involved by systemic vasculitis and myositis is not include among any classification or diagnostic criterion of vasculitis. In this regard, we aimed to review the literature in order to report all the available evidence concerning the inflammatory involvement of muscle in patients affected by systemic vasculitis. We collected a total of 108 papers, for a sum of 395 patients affected by muscle vasculitis. Most of them suffered from medium and small vessels vasculitis (mainly polyarteritis nodosa and ANCA-associated vasculitis) or from vasculitis secondary to rheumatoid arthritis. Conversely, muscle involvement in case of large vessel vasculitis occurred seldom, while only few papers reported such occurrence in Kawasaki or Behçet's disease. Histological findings may differ, but the most common ones displayed a necrotizing vasculitis of perimysium vessels, while granulomatous vasculitis was assessed only in case of ANCA-associated vasculitis patients. Creatine kinase were usually within normal range, seldom elevated, while imaging findings were generally undistinguishable from the ones found in idiopathic inflammatory myopathies: magnetic resonance imaging displays signal hyperintensity in T2 and STIR scans, while few data exist for positron emission tomography. The presentation of the disease may be fearsome and severe, sometimes life-threatening, but an overall good response to conventional immunosuppressants and/or glucocorticoids has been reported.
Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Arteritis; Behcet Syndrome; Humans; Muscles; Polyarteritis Nodosa
PubMed: 34971804
DOI: 10.1016/j.autrev.2021.103029 -
Survey of Ophthalmology 2022Cytomegalovirus (CMV) anterior uveitis is the most common form of ocular manifestation of CMV in immunocompetent individuals. The difficulty in diagnosing CMV anterior... (Meta-Analysis)
Meta-Analysis Review
Cytomegalovirus (CMV) anterior uveitis is the most common form of ocular manifestation of CMV in immunocompetent individuals. The difficulty in diagnosing CMV anterior uveitis may delay adequate treatment and affect outcomes. We sought to review systemically the overall clinical characteristics and compare treatment outcomes in CMV anterior uveitis and endotheliitis. A literature search was performed, and studies describing clinical characteristics, treatment regimens, and outcomes that included more than 5 treated eyes were included. In these 23 studies, acute CMV anterior uveitis commonly presented with high intraocular pressure (95.31%, 95% CI 90.45-98.60) and mild anterior chamber inflammation (cells >2+ = 3.18%, 95% CI 0.21-0.54). About two-thirds of CMV endotheliitis cases presented with high intraocular pressure and coin-shaped corneal lesions. Acute CMV anterior uveitis showed good clinical response to topical 0.15% ganciclovir (GCV) gel or oral valganciclovir (VGCV) (90%, 95% CI 74-100% and 95%, 95% CI 88-100%, respectively). For chronic CMV anterior uveitis, both topical GCV and oral VGCV yielded comparable results. Topical 0.5-2% GCV or a combination of topical and oral VGCV for CMV endotheliitis both resulted in good clinical response. Recurrence of inflammation was common after cessation of maintenance therapy. Overall, topical GCV resulted in an optimal outcome for CMV anterior uveitis. Escalated concentration and frequency of usage are needed for chronic CMV anterior uveitis and endotheliitis. Adequate induction and maintenance phases of anti-CMV treatment seem necessary to prevent recurrences.
Topics: Antiviral Agents; Aqueous Humor; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Eye Infections, Viral; Ganciclovir; Glaucoma; Humans; Inflammation; Treatment Outcome; Uveitis, Anterior; Valganciclovir
PubMed: 34954093
DOI: 10.1016/j.survophthal.2021.12.006 -
Genetics in Medicine : Official Journal... Mar 2022This study aimed to systematically review and summarize gene therapy treatment for monogenic retinal and optic nerve diseases. (Review)
Review
PURPOSE
This study aimed to systematically review and summarize gene therapy treatment for monogenic retinal and optic nerve diseases.
METHODS
This review was prospectively registered (CRD42021229812). A comprehensive literature search was performed in Ovid MEDLINE, Ovid Embase, Cochrane Central, and clinical trial registries (February 2021). Clinical studies describing DNA-based gene therapy treatments for monogenic posterior ocular diseases were eligible for inclusion. Risk of bias evaluation was performed. Data synthesis was undertaken applying Synthesis Without Meta-analysis guidelines.
RESULTS
This study identified 47 full-text publications, 50 conference abstracts, and 54 clinical trial registry entries describing DNA-based ocular gene therapy treatments for 16 different genetic variants. Study summaries and visual representations of safety and efficacy outcomes are presented for 20 unique full-text publications in RPE65-mediated retinal dystrophies, choroideremia, Leber hereditary optic neuropathy, rod-cone dystrophy, achromatopsia, and X-linked retinoschisis. The most common adverse events were related to lid/ocular surface/cornea abnormalities in subretinal gene therapy trials and anterior uveitis in intravitreal gene therapy trials.
CONCLUSION
There is a high degree of variability in ocular monogenic gene therapy trials with respect to study design, statistical methodology, and reporting of safety and efficacy outcomes. This review improves the accessibility and transparency in interpreting gene therapy trials to date.
Topics: Color Vision Defects; Genetic Therapy; Humans; Optic Nerve Diseases; Retina; Retinal Dystrophies
PubMed: 34906485
DOI: 10.1016/j.gim.2021.10.013 -
Journal of Gastroenterology and... Apr 2022Behcet's disease is a systemic vasculitis that can involve gastrointestinal tract. This is a systematic review and meta-analysis evaluating the efficacy and safety of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIM
Behcet's disease is a systemic vasculitis that can involve gastrointestinal tract. This is a systematic review and meta-analysis evaluating the efficacy and safety of anti-tumor necrosis factor (TNF) agents in treating patients with intestinal Behcet's disease.
METHODS
We conducted searches on PubMed, Embase, and Cochrane. Data from eligible studies were used to calculate the pooled estimate of proportions of clinical remission, mucosal healing at Months 3, 6, 12, and 24 as well as the pooled incidence of adverse drug reactions. And subgroup analysis based on the specific type of anti-TNF agents was performed.
RESULTS
Of the 828 studies initially identified, 13 were included finally, all of which were single-arm cohort studies. The pooled proportions of clinical remission at Months 3, 6, 12, and 24 were 0.61 (95%CI 0.48-0.78), 0.51 (95%CI 0.40-0.66), 0.57 (95%CI 0.48-0.67), and 0.38 (95%CI 0.16-0.88), respectively. The pooled proportions of mucosal healing at Months 3, 6, 12, and 24 were 0.66 (95%CI 0.50-0.86), 0.82 (95%CI 0.48-0.98), 0.65 (95%CI 0.51-0.81), and 0.69 (95%CI 0.39-1.00), respectively. The pooled estimate of proportion of overall adverse drug reactions for infliximab was 0.22 (95%CI 0.07-0.69).
CONCLUSIONS
Anti-TNF agents, including infliximab and adalimumab, were an efficient therapy for intestinal Behcet's disease. The safety of anti-TNF agents used in the treatment of intestinal Behcet's disease was acceptable.
Topics: Adalimumab; Behcet Syndrome; Humans; Infliximab; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha
PubMed: 34894004
DOI: 10.1111/jgh.15754 -
International Ophthalmology Feb 2022To provide an overview of the ocular features of rheumatoid arthritis (RA) and of the ophthalmic adverse drug reactions (ADRs) that may be associated with the... (Review)
Review
PURPOSE
To provide an overview of the ocular features of rheumatoid arthritis (RA) and of the ophthalmic adverse drug reactions (ADRs) that may be associated with the administration of antirheumatic drugs.
METHODS
A systematic literature search was performed using the PubMed, MEDLINE, and EMBASE databases. In addition, a cohort of 489 RA patients who attended the Authors' departments were examined.
RESULTS
Keratoconjunctivitis sicca, episcleritis, scleritis, peripheral ulcerative keratitis (PUK), and anterior uveitis were diagnosed in 29%, 6%, 5%, 2%, and 10%, respectively, of the mentioned cohort. Ocular ADRs to non-steroidal anti-inflammatory drugs are rarely reported and include subconjunctival hemorrhages and hemorrhagic retinopathy. In patients taking indomethacin, whorl-like corneal deposits and pigmentary retinopathy have been observed. Glucocorticoids are frequently responsible for posterior subcapsular cataracts and open-angle glaucoma. Methotrexate, the prototype of disease-modifying antirheumatic drugs (DMARDs), has been associated with the onset of ischemic optic neuropathy, retinal cotton-wool spots, and orbital non-Hodgkin's lymphoma. Mild cystoid macular edema and punctate keratitis in patients treated with leflunomide have been occasionally reported. The most frequently occurring ADR of hydroxychloroquine is vortex keratopathy, which may progress to "bull's eye" maculopathy. Patients taking tofacitinib, a synthetic DMARD, more frequently suffer herpes zoster virus (HZV) reactivation, including ophthalmic HZ. Tumor necrosis factor inhibitors have been associated with the paradoxical onset or recurrence of uveitis or sarcoidosis, as well as optic neuritis, demyelinating optic neuropathy, chiasmopathy, and oculomotor palsy. Recurrent episodes of PUK, multiple cotton-wool spots, and retinal hemorrhages have occasionally been reported in patients given tocilizumab, that may also be associated with HZV reactivation, possibly involving the eye. Finally, rituximab, an anti-CD20 monoclonal antibody, has rarely been associated with necrotizing scleritis, macular edema, and visual impairment.
CONCLUSION
The level of evidence for most of the drug reactions described herein is restricted to the "likely" or "possible" rather than to the "certain" category. However, the lack of biomarkers indicative of the potential risk of ocular ADRs hinders their prevention and emphasizes the need for an accurate risk vs. benefit assessment of these therapies for each patient.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Glaucoma, Open-Angle; Humans; Iatrogenic Disease; Rituximab
PubMed: 34802085
DOI: 10.1007/s10792-021-02058-8 -
Modern Rheumatology Oct 2022This study aimed to determine the clinical efficacy of apremilast for oral ulcers (OUs), extra-oral manifestations, and overall disease activity in patients with... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This study aimed to determine the clinical efficacy of apremilast for oral ulcers (OUs), extra-oral manifestations, and overall disease activity in patients with Behçet's disease (BD).
METHODS
A systematic literature search was performed in PubMed, Embase, Cochrane Library, and Web of Science Core Collection. Studies assessing the treatment effects of apremilast in BD were included. The odds ratios (ORs) of being symptom-free for individual manifestations and mean difference (MD) of Behçet's Disease Current Activity Form (BDCAF) scores were calculated with 95% confidence intervals (CIs) at 12 and 24 weeks using a random-model meta-analysis.
RESULTS
Of 259 screened articles, eight were included. After 12 weeks of apremilast treatment the OR of symptom-free was as followings: OUs, 45.76 (95% CI, 13.23-158.31); genital ulcers, 4.56 (95% CI, 2.47-8.44); erythema nodosum, 3.59 (95% CI, 1.11-11.61); pseudofolliculitis, 2.81 (95% CI, 1.29-6.15); and arthritis, 3.55 (95% CI, 1.71-7.40). Furthermore, BDCAF scores at 12 weeks were significantly reduced (MD=-1.38; -1.78 to -0.99). However, the proportion of oral-ulcer-free patients increased at 24 weeks (OR = 14.88; 4.81 to 46.07).
CONCLUSIONS
The currently accumulated data indicate an improvement in mucocutaneous and articular symptoms by short-term apremilast treatment in patients with BD.
Topics: Arthritis; Behcet Syndrome; Genitalia; Humans; Oral Ulcer; Skin Ulcer; Thalidomide; Ulcer
PubMed: 34752620
DOI: 10.1093/mr/roab098 -
Clinical and Experimental Rheumatology 2021Children and adults may develop Behçet's disease (BD), often with ocular involvement such as uveitis. This study aimed to determine the prevalence and type of ocular... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Children and adults may develop Behçet's disease (BD), often with ocular involvement such as uveitis. This study aimed to determine the prevalence and type of ocular manifestations in childhood and adult BD.
METHODS
Medline, Web of Science and Cochrane databases were searched from inception to October 5, 2018 to identify publications related to Behçet's disease comprising minimum twenty patients and providing the frequency of ocular manifestations (OC). Random effects models were used to combine the prevalence of OC in adults and children with BD. Heterogeneity was evaluated using I2.
RESULTS
The search resulted in 3129 articles, of which 51 were included in meta-analysis. OCs were slightly more frequent in childhood onset BD with the mean [95% Confidence Interval] frequency of 45 [34-56%] compared to 36 [29-43%] in adults, however, this difference was not statistically significant (p=0.198). In both children and adults, posterior uveitis (children 27% vs. adults 25%, and retinal vasculitis in adults 16%) was the most common ocular manifestation, followed by anterior uveitis (children 18% vs. adults 23%). When comparing the distribution of OC in Behcet's in adults, there was geographic variation where OC were higher in Turkey and the Middle East 42%, followed by Europe and North America (36%), North Africa 26% and East Asia 25% but not significantly (p=0.27).
CONCLUSIONS
Ocular manifestations, predominantly uveitis; are common in BD. Ocular manifestations are not proportionately more frequent in adults with BD along the ancient Silk Road.
Topics: Adult; Behcet Syndrome; Child; Humans; Prevalence; Retinal Vasculitis; Uveitis; Uveitis, Posterior
PubMed: 34596037
DOI: 10.55563/clinexprheumatol/pt60bc -
Clinical Ophthalmology (Auckland, N.Z.) 2021Noninfectious pediatric uveitis is a potentially blinding disease often associated with systemic conditions. In cases of chronic anterior uveitis without adequate... (Review)
Review
PURPOSE
Noninfectious pediatric uveitis is a potentially blinding disease often associated with systemic conditions. In cases of chronic anterior uveitis without adequate response to steroids and immunosuppressants, biological response modifiers would be viable therapeutic options. Still, evidence is lacking on the safety of the long-term use of these drugs in children. Therefore, this study aimed to evaluate the efficacy and safety of biological therapy to treat noninfectious pediatric uveitis.
METHODS
A systematic review was performed to identify original studies involving biological therapy for children diagnosed with noninfectious uveitis. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) classification system.
RESULTS
Nine studies involving 526 children were eligible. Adalimumab was superior to placebo in reducing inflammatory activity (risk ratio (RR) 3.21 [95% confidence interval (CI) 1.65-6.27]; P = 0.0006; I = 0%) and steroid use (RR 2.27 [95% CI 1.03-4.99]; P = 0.04; I = 0%, low-certainty evidence). There was no difference between adalimumab and placebo in the occurrence of systemic adverse events (RR 2.51 [95% CI 0.74-8.54]; P = 0.14; I = 48%) and local events (RR 1.15 [95% CI 0.46-2.88]; P= 0.76; I = 1%). There was no difference between adalimumab and infliximab in response to treatment (RR 1.18 [95% CI 0.69-2.03]; P= 0.55; I = 91%, very low-certainty evidence) and in the occurrence of adverse effects (RR 0.84 [95% CI 0.41-1.73]; P= 0.64; I = 18%, low-certainty evidence).
CONCLUSION
There is low to very-low evidence that biological therapy is effective and safe in managing noninfectious pediatric uveitis. Future large randomized trials may provide more substantial evidence to confirm these results.
PubMed: 34522080
DOI: 10.2147/OPTH.S322445