Analysis of the potential relationship between COVID-19 and Behcet's disease using transcriptome data.

To investigate the potential role of COVID-19 in relation to Behcet's disease (BD) and to search for relevant biomarkers. We used a bioinformatics approach to download transcriptomic data from peripheral blood mononuclear cells (PBMCs) of COVID-19 patients and PBMCs of BD patients, screened the common differential genes between COVID-19 and BD, performed gene ontology (GO) and pathway analysis, and constructed the protein-protein interaction (PPI) network, screened the hub genes and performed co-expression analysis. In addition, we constructed the genes-transcription factors (TFs)-miRNAs network, the genes-diseases network and the genes-drugs network to gain insight into the interactions between the 2 diseases. We used the RNA-seq dataset from the GEO database (GSE152418, GSE198533). We used cross-analysis to obtain 461 up-regulated common differential genes and 509 down-regulated common differential genes, mapped the PPI network, and used Cytohubba to identify the 15 most strongly associated genes as hub genes (ACTB, BRCA1, RHOA, CCNB1, ASPM, CCNA2, TOP2A, PCNA, AURKA, KIF20A, MAD2L1, MCM4, BUB1, RFC4, and CENPE). We screened for statistically significant hub genes and found that ACTB was in low expression of both BD and COVID-19, and ASPM, CCNA2, CCNB1, and CENPE were in low expression of BD and high expression of COVID-19. GO analysis and pathway analysis was then performed to obtain common pathways and biological response processes, which suggested a common association between BD and COVID-19. The genes-TFs-miRNAs network, genes-diseases network and genes-drugs network also play important roles in the interaction between the 2 diseases. Interaction between COVID-19 and BD exists. ACTB, ASPM, CCNA2, CCNB1, and CENPE as potential biomarkers for 2 diseases.

Frail Silk: Is the Hughes-Stovin Syndrome a Behçet Syndrome Subtype with Aneurysm-Involved Gene Variants?

Hughes-Stovin syndrome is a rare disease characterized by thrombophlebitis and multiple pulmonary and/or bronchial aneurysms. The etiology and pathogenesis of HSS are incompletely known. The current consensus is that vasculitis underlies the pathogenic process, and pulmonary thrombosis follows arterial wall inflammation. As such, Hughes-Stovin syndrome may belong to the vascular cluster with lung involvement of Behçet syndrome, although oral aphtae, arthritis, and uveitis are rarely found. Behçet syndrome is a multifactorial polygenic disease with genetic, epigenetic, environmental, and mostly immunological contributors. The different Behçet syndrome phenotypes are presumably based upon different genetic determinants involving more than one pathogenic pathway. Hughes-Stovin syndrome may have common pathways with fibromuscular dysplasias and other diseases evolving with vascular aneurysms. We describe a Hughes-Stovin syndrome case fulfilling the Behçet syndrome criteria. A MYLK variant of unknown significance was detected, along with other heterozygous mutations in genes that may impact angiogenesis pathways. We discuss the possible involvement of these genetic findings, as well as other potential common determinants of Behçet/Hughes-Stovin syndrome and aneurysms in vascular Behçet syndrome. Recent advances in diagnostic techniques, including genetic testing, could help diagnose a specific Behçet syndrome subtype and other associated conditions to personalize the disease management.

Clinical course of COVID-19 infections in patients with Behçet's disease in The Netherlands.

OBJECTIVES: The aim of this study is to investigate the cumulative incidence and the severity of COVID-19 infections in patients with Behçet's disease. METHODS: A retrospective cohort study of patients with Behçet's disease was conducted. We obtained the data systematically from electronic patient files and through telephone interviews between February 2020 and May 1, 2021. Main outcomes were COVID-19 infection, disease duration, hospitalisation, intensive care admission and mortality. Secondary outcome was adherence to quarantine measures as recommended by the government. RESULTS: 185 Behçet's disease patients were included (mean age 42.2 years, 54% female); 58% of the patients were receiving colchicine, 30% anti-TNFα, 16% azathioprine and 8% systemic steroids. 30 patients (16.2%) were positive for COVID-19. Within our cohort, the cumulative incidence of COVID-19 was therefore 16.2% (95% CI 11.2-22.3%), which is significantly increased when compared to the general Dutch population (8.7% (95% CI 8.72-8.73%)) (p < 0.001). Four out of 30 (13%) patients were admitted to the hospital. There was no COVID-19 related mortality observed. Patients adhered to government measures; except in the period between the 1st of June and the 28th of September, this cohort received more visitors than in period 1 and 3. CONCLUSIONS: In this cohort, Behçet's disease patients have a higher risk for COVID-19 infection, without an increase of virus-related mortality. The course of COVID-19 disease in this cohort is relatively mild, with a lower admission rate than expected of patients using immunosuppressive medication.

Effects of anti-SARS-CoV-2 vaccination on safety and disease exacerbation in patients with Behçet syndrome in a monocentric cohort.

AIM: Vaccination represents a cornerstone in mastering the coronavirus disease 2019 (COVID-19) pandemic. There is a paucity of data regarding the safety of COVID-19 vaccines in patients with rheumatic diseases such as Behçet syndrome (BS). The present study aimed to investigate the side-effects and post-vaccine disease exacerbation rates of COVID-19 vaccines in a BS cohort. METHODS: We retrospectively evaluated 450 BS patients followed in our clinic who met the criteria of the International Study Group. COVID-19 vaccination status, type of vaccine received (Pfizer-BioNTech vs CoronaVac), post-vaccine side-effects and exacerbations were evaluated by interviewing patients over the phone or face to face. Behçet's Disease Current Activity Form (BDCAF) scores were calculated for BS symptoms before and after vaccination. RESULTS: In all, 287 patients received at least one dose of the COVID-19 vaccine. Of the total number of COVID-19 vaccines (n = 639), 379 (59%) were Pfizer-BioNTech vaccines and 257 (41%) were CoronaVac vaccines. The number of side-effects after first, second, third and fourth vaccine doses were 151 (52.6%), 135 (49.4%), 29 (42.6%), and 3 (30%), respectively. BS exacerbation after first, second, third, and fourth vaccine doses were 151 (52.6%), 135 (49.4%), 16 (23.5%), and 3 (30%), respectively. Injection site pain/swelling was the most common side-effect at all vaccine doses followed by fatigue and arthralgia. CONCLUSION: COVID-19 vaccines are well tolerated in patients with BS, and more side-effects develop after mRNA vaccines. Regardless of the vaccine type, exacerbations after the COVID-19 vaccine are common, predominantly mucocutaneous and articular involvement, and exacerbations in the form of other organ involvement are rare.

Behçet's syndrome: one year in review 2022.

This review highlights publications on different aspects of Behçet's syndrome (BS) that appeared in 2021 and provides a critical view. These publications include works on the epidemiology of BS across different continents, newly developed instruments to assess damage in BS, studies highlighting the immunopathogenesis, genetics and epigenetic factors, histopathology of the pathergy lesion, clinical and imaging aspects of vascular involvement, and safety and efficacy of therapeutic agents including tocilizumab, apremilast and direct oral anticoagulants.

Behçet's disease in Wales: an epidemiological description of national surveillance data.

OBJECTIVES: Behçet's disease is a rare, chronic, incurable, multisystemic disease. It causes significant morbidity, with patients experiencing symptoms including mucous membrane ulcers, and joint pain and swelling. It is an important cause of avoidable blindness due to ocular involvement. The aetiology is unknown. The aims were to identify population prevalence of Behçet's disease in Wales in comparison to other endemic and non-endemic regions, and provide an epidemiological profile of a case series of adult patients. This is the first analysis of data from the Adult Rare Diseases Surveillance Registry for Wales, established in 2020 as part of the COVID-19 pandemic response. RESULTS: Between 1995 and 2020, 347 adults and 5 children were recorded in Wales with a diagnosis of Behçet's disease. Population prevalence was calculated as 11.1 per 100,000 population. Of the adult cases, 76.9% were female, and 6.6% died before the end of the study period. When comparing genders, there were no statistically significant differences in age at diagnosis, mortality or socioeconomic status. There was no evidence that the age at which cases were diagnosed had changed over time. Survival analyses showed no significant differences in durations of survival between genders or individuals residing in different WIMD 2019 quintiles. Age at diagnosis was the only factor significantly and independently associated with poorer durations of survival (p < 0.001).

Physical activity and psychosomatic status in patients with Behçet's disease during coronavirus disease pandem.

OBJECTIVE: The aim of this study is to examine the changes in physical activity level, fatigue, depression, and sleep quality in patients with Behçet's disease during the COVID-19 pandemic. METHODS: The study was designed as an online questionnaire applied to individuals who are being followed up with the diagnosis of Behçet's disease in the rheumatology department. Data were collected using multiple scales including International Physical Activity Questionnaire (IPAQ), Fatigue Severity Scale (FSS), Beck Depression Inventory (BDI), Pittsburg Sleep Quality Index (PSQI), and Visual Analogue Scale (VAS) to evaluate physical activity level, fatigue, depression, sleep quality, and pain, respectively. RESULTS: Sixteen patients diagnosed with Behçet's disease were included in the study. No statistically significant difference was observed between the IPAQ, FSS, BDI, PSQI, and VAS assessment scores before COVID-19 and during COVID-19 period (P > .05 for all). CONCLUSION: Thinking of the negative effects of aggressive clinical symptoms, Behçet's disease patients should be supported in physical activity and psychosocial status.

A multicenter evaluation of antibacterial use in hospitalized patients through the SARS-Cov-2 pandemic waves (preprint)

Background: Excessive use of antibiotics has been reported during the SARS-CoV-2 pandemic. We evaluated trends in antibiotic use and culture positive Gram-negative (GN)/Gram-positive (GP) pathogens in US hospitalized patients before and during the SARS-CoV-2 pandemic. Methods: : This multicenter, retrospective study included patients from 271 US facilities with >1-day inpatient admission with discharge or death between July 1, 2019, and October 30, 2021, in the BD Insights Research Database. We evaluated microbiological testing data, antibacterial use, defined as antibacterial use ≥24 hours in admitted patients, and duration of antibacterial therapy. Results: : Of 5,518,744 patients included in the analysis, 3,729,295 (67.6%) patients were hospitalized during the pandemic with 2,087,774 (56.0%) tested for SARS-CoV-2 and 189,115 (9.1%) testing positive for SARS-CoV-2. During the pre-pandemic period, 36.2% were prescribed antibacterial therapy and 9.3% tested positive for select GN/GP pathogens. During the SARS-CoV-2 pandemic, antibacterial therapy (57.8%) and positive GN/GP culture (11.9%) were highest in SARS-CoV-2-positive patients followed by SARS-CoV-2-negative patients (antibacterial therapy, 40.1%; GN/GP, pathogens 11.0%), and SARS-CoV-2 not tested (antibacterial therapy 30.4%; GN/GP pathogens 7.2%). Multivariate results showed significant decreases in antibacterial therapy and positive GN/GP cultures for both SARS-CoV-2-positive and negative patients during the pandemic, but no significant overall changes from the pre-pandemic period to the pandemic period. Conclusions: : There was a decline in both antibacterial use and positive GN/GP pathogens in patients testing positive for SARS-CoV-2. However, overall antibiotic use was similar prior to and during the pandemic. These data may inform future efforts to optimize antimicrobial stewardship and prescribing.

Adamantiades-Behçet disease: from clinical heterogeneity to diagnosis during the COVID-19 pandemic.

Adamantiades-Behçet disease (ABD) is a systemic disease with vasculitis, characterized by recurrent oral aphthosis and ocular, cutaneous, articular, vascular, cardiopulmonary manifestations and it is mainly found in the territories of the antique "silk road". ABD pathogenesis remains unknown although genetic, infectious and environmental factors seem to be implicated in the development of the disease, which is considered an auto-inflammatory condition. COVID-19 infection can present some symptoms, in particular at the level of oral and pulmonary mucosa, which require a differential diagnosis with ABD. Furthermore, the immunological alterations of this disease, and the drugs used for its treatment could influence the infection by COVID-19, and its clinical evolution. Nevertheless, vaccination anti-COVID-19 is recommended in ABD patients. The most commonly used diagnostic criteria for ABD are those established in 2014 by the International Team for the Revision of the International Criteria for BD (ITR-ICBD). Furthermore, criteria for disease severity according to the Overall Damage Index of Behçet's Syndrome (BODI) have recently been proposed in order to quantify the severity of the disease as well as the evolution during follow-up. In ABD patients it is mandatory to investigate on the presence of active/latent tuberculosis, because of the common organ involvement, such as eyes and bowel. ABD has a high morbidity and low mortality, sometimes linked to the rupture of an arterial aneurysm and/or neurological complications. This article is based on a general review on ABD ranging from the history of ABD to possible causes and clinical manifestations. A specific section has been dedicated to the COVID-19 pandemic.

Higher antibody responses after mRNA-based vaccine compared to inactivated vaccine against SARS-CoV-2 in Behcet's syndrome.

There are limited data about humoral response to vaccine in Behçet's syndrome (BS). We compared SARS-CoV-2 antibody response after two doses of inactivated (Sinovac/CoronaVac) or mRNA (Pfizer/BioNTech) vaccines in patients with BS and healthy controls (HCs). We studied 166 (92M/74F) patients with BS (mean age: 42.9 ± 9.6 years) and 165 (75M/90F) healthy controls (mean age: 42.4 ± 10.4 years), in a single-center cross-sectional design between April 2021 and October 2021. A total of 80 patients with BS and 89 HCs received two doses of CoronaVac, while 86 patients with BS and 76 HCs were vaccinated with BioNTech. All study subjects had a negative history for COVID-19. Serum samples were collected at least 21 days after the second dose of the vaccine. Anti-spike IgG antibody titers were measured quantitatively using a commercially available immunoassay method. We found that the great majority in both patient and HC groups had detectable antibodies after either CoronaVac (96.3% vs 100%) or BioNTech (98.8% vs 100%). Among those vaccinated with CoronaVac, BS patients had significantly lower median (IQR) titers compared to HCs [36.5 (12.5-128.5) vs 102 (59-180), p < 0.001]. On the other hand, antibody titers did not differ among patients with BS and HCs who were vaccinated with BioNTech [1648.5 (527.0-3693.8) vs 1516.0 (836.3-2599.5), p = 0.512). Among different treatment regimen subgroups in both vaccine groups, those who were using anti-TNF-based treatment had the lowest antibody titers. However, the difference was statistically significant only among those vaccinated with CoronaVac. Among patients vaccinated with BioNTech, there was no statistically significant difference between different treatment regimen groups. Compared to inactivated COVID-19 vaccine, mRNA-based vaccine elicited higher antibody titers among BS patients. Only in the CoronaVac group, patients especially those using anti-TNF agents were found to have low titers compared to healthy subjects. BS patients vaccinated with BioNTech were found to have similar seroconversion rates and antibody levels compared to healthy controls. Further studies should assess whether the low antibody titers are associated with diminished protection against COVID-19 in both vaccine groups.

One year in review 2021: Behçet's syndrome.

This review aims to provide a critical digest of the recent studies that enhance our understanding of Behçet's syndrome by evaluating time trends, differences in disease course between men and women, and between patients with an early and late disease onset, progress in disease assessment, novel findings on immunopathogenesis and genetics, clinical features and differential diagnosis of eye, vascular, nervous system and gastrointestinal system involvement, and new data on treatment modalities including TNF-alpha, IL-17 and IL-6 inhibitors, tofacitinib, and apremilast, as well as surgical interventions.

Prevalence and clinical course of SARS-CoV-2 infection in patients with Behçet's syndrome.

OBJECTIVES: We aimed to assess the prevalence of SARS-CoV-2 infection among Behçet's syndrome (BS) patients, evaluating the possible association between demographic and clinical features and the risk of infection. Moreover, we aimed to evaluate the possible association between BS disease activity and treatment, and the risk of SARS-CoV-2 infection. METHODS: A survey was conducted on BS patients followed at the Behçet's Centre of the Careggi University Hospital, Florence, Italy. We further evaluated the possible association between BS disease activity and treatment, and the risk of SARS-CoV-2 infection. RESULTS: Out of 335 BS patients contacted, fourteen cases of SARS-CoV-2 were identified between April 1st, 2020 and February 9th, 2021, suggesting a prevalence of SARS-CoV-2 infection among BS patients of 4.2%, in line with the data of the general population in Italy (4.4%). When comparing clinical features between SARS-CoV-2 cases and matched SARS-CoV-2 negative BS patients, we found that the presence of different disease manifestations did not significantly differ between the two groups. SARS-CoV-2 cases and controls were also comparable in terms of immunosuppressive therapy, with the only exception of corticosteroids (71.4% vs. 35.7%, p=0.030), whose daily dose was significantly higher in cases than controls [5mg/day (IQR 0-10,) vs. 0 mg/day (IQR 0-5), p=0.005], suggesting that the right timing of usage and the more appropriate dosage of corticosteroid are a key question for the better management of these patients. CONCLUSIONS: Based on our results, patients with BS do not seem to be at a greater risk of SARS-CoV-2 infection or severe complications compared with the general population.

Safety of SARS-CoV-2 vaccination in patients with Behcet's syndrome and familial Mediterranean fever: a cross-sectional comparative study on the effects of M-RNA based and inactivated vaccine.

Most of the published data relate to classical forms of rheumatic diseases (RD) and information on rare inflammatory disorders such as Behçet's syndrome (BS) and familial Mediterranean fever (FMF) is limited. We studied the frequency of side effects and disease flares after COVID-19 vaccination with either Pfizer/BioNTech or Sinovac/CoronaVac in 256 patients with BS, 247 with FMF, and 601 with RD. Telephone interviews were conducted using a questionnaire survey in a cross-sectional design in patients with BS, FMF, and RD followed by a single university hospital. Study participants were vaccinated either with CoronaVac (BS:109, FMF: 90, and RD: 343,) or BioNTech (BS: 147, FMF: 157 and RD: 258). The majority have received double dose (BS: 94.9%, FMF 92.3% and RD: 86.2%). BioNTech ensured a significantly better efficacy than CoronaVac against COVID-19 in all patient groups (BS: 1.4% vs 10.1%; FMF: 3.2% vs 12.2%, RD:2.7% vs 6.4%). Those with at least one adverse event (AE) were significantly more frequent among those vaccinated with BioNTech than those with CoronaVac (BS: 86.4% vs 45%; FMF: 83.4% vs 53.3%; and RD: 83.3% vs 45.5%). The majority of AEs were mild to moderate and transient and this was true for either vaccine. There were also AEs that required medical attention in all study groups following CoronaVac (BS: 5.5%, FMF: 3.3%, and RD:2.9%) or BioNTech (BS: 5.4%, FMF: 1.9%, and RD: 4.7%). The main causes for medical assistance were disease flare and cardiovascular events. Patients with BS (16.0%) and FMF (17.4%) were found to flare significantly more frequently when compared to those with RD (6.0%) (p < 0.001). This was true for either vaccine. BS patients reported mainly skin-mucosa lesions; there were however, 11 (4.3%) who developed major organ attack such as uveitis, thrombosis or stroke. Flare in FMF patients were associated mainly with acute serositis with or without fever. Arthralgia/arthritis or inflammatory back pain were observed mainly in the RD group. Our study demonstrates that BS and FMF patients vaccinated with either CoronaVac or BioNTech demonstrated similar AE profile and frequency compared to RD patients. AEs that required physician consultation or hospitalization occurred in all study groups after either CoronaVac or BioNTech. Increased frequency of flares in BS and FMF compared to that seen in RD might reflect defects in innate immunity and deserves further investigation. Caution should be required when monitoring these patients after vaccination.

Chronic thromboembolic pulmonary hypertension secondary to Behçet's disease: an extremely rare pediatric case.

Chronic thromboembolic pulmonary hypertension is an uncommon condition in the children. It almost always accompanies a hypercoagulable state. We described a rare case of Behçet's disease presenting with chronic thromboembolic pulmonary hypertension and initially misdiagnosed as coronavirus disease 2019 pneumonia.

COVID-19 related acute genital ulcer: a case report.

Acute vulvar ulcer (Lipschütz's ulcer) is a rare lesion with local hyperimmunoreactivity triggered by infection, which is characterized by acute, painful, and necrotic ulcerations. This condition is usually found in non-sexually active adolescents, and it resolves spontaneously. We report a case of a 35-year-old woman who was diagnosed with COVID-19 who did not have severe symptoms, but had high levels of D-dimer for 9 days. The COVID-19 diagnosis was followed by the appearance of an acute, necrotic, extremely painful vulvar ulcer, although symptoms caused by COVID-19 had improved. We emphasize the importance of the differential diagnosis to exclude diseases such as Behçet's syndrome, Sexually Transmitted Infections, as well as the presence of viruses that generally trigger Lipschütz's ulcer, such as Epstein-Barr virus and cytomegalovirus. No treatment is usually necessary, however, in the present report due to the pain experienced by the patient, we successfully used oral prednisone.