Organ damage is a major determinant of work productivity impairment in Behçet's Syndrome: a post-hoc analysis of the BODI validation study.

OBJECTIVES: To evaluate the prevalence, magnitude, and potential determinants of work productivity impairment in patients with Behçet's Syndrome (BS), focusing on the role of irreversible organ damage. METHODS: A post-hoc analysis of the BS overall damage index (BODI) prospective validation study was performed. Demographics and clinical features were recorded in all patients. The Work Productivity and Activity Impairment: General Health (WPAI: GH) questionnaire was administered to assess the work limitation and the BODI to measure organ damage. The independent effect of BS features on WPAI: GH outcomes was evaluated by regression analysis. RESULTS: Out of 148 patients, 34.5% were unemployed, with age (OR 1.035) and BODI score (OR 1.313 for 1-unit increase) as the only factors significantly (p< 0.05) associated with the unemployment state. An overall work impairment was reported in about 64.2% of the employed patients. Indeed, 22.7% reported missing work h due to their health (absenteeism), with a mean time loss of 34.4%; whereas 60.2% declared a reduced performance at work because of their health (presenteeism), with a mean productivity impairment of 45.4%. Ocular damage was associated with absenteeism (ß 0.225); female sex (ß 0.260), physician global assessment of disease activity (ß 0.502) and an increased BODI score (ß 0.166 for 1-point increase) with presenteeism; fibromyalgia (ß 0.246), physician global assessment (ß 0.469), and musculoskeletal damage (ß 0.325) with overall work impairment. CONCLUSIONS: Disease activity and organ damage accrual remarkably affect work productivity in BS patients. Achieving remission and preventing damage accrual are crucial and complementary objectives.

Accrual of organ damage in Behçet's syndrome: trajectory, associated factors, and impact on patients' quality of life over a 2-year prospective follow-up study.

BACKGROUND: This study aimed to investigate the trajectory of damage accrual, associated factors, and impact on health-related quality of life (HR-QoL) in a multicenter cohort of patients with Behçet's syndrome (BS) over 2 years of follow-up. METHODS: Patients recruited in the BS Overall Damage Index (BODI) validation study were prospectively monitored for 2 years and assessed for damage accrual, defined as an increase ≥1 in the BODI score, and HR-QoL was evaluated by the SF-36 questionnaire. Logistic and multiple linear regression models were built to determine factors associated with damage accrual and impairment in the different SF-36 domains. RESULTS: During follow-up, 36 out of 189 (19.0%) patients had an increase ≥1 in the BODI score with a mean (SD) difference of 1.7 (0.8) (p <0.001). The incidence rate of damage accrual was stable over time, regardless of the disease duration. Out of 61 new BODI items, 25 (41.0%) were considered related to glucocorticoid (GC) use. In multivariate analysis, duration of GC therapy (OR per 1-year 1.15, 95% CI 1.07-1.23; p <0.001) and occurrence of ≥1 disease relapse (OR 3.15, 95% CI 1.09-9.12; p 0.038) were identified as predictors of damage accrual, whereas the use of immunosuppressants showed a protective effect (OR 0.20, 95% CI 0.08-0.54, p<0.001). Damage accrual was independently associated with the impairment of different physical domains and, to a greater extent, in emotional domains of the SF-36 questionnaire. Female sex, higher disease activity, and fibromyalgia were also significantly associated with impairment in HR-QoL. CONCLUSION: In BS, organ damage accrues over time, also in long-standing disease, resulting in an impairment of the perceived physical and mental health. Adequate immunosuppressive treatment, preventing disease flares and minimizing exposure to GCs have a crucial role in lowering the risk of damage accrual.

Predictive Factors of Severe Behçet's disease: A Longitudinal, Prospective Cohort Followed Between 1981-2020.

INTRODUCTION: Behçet's disease (BD) is a systemic vasculitis of unknown cause. The spectrum of the disease ranges from mucocutaneous manifestations to other organ diseases with relevant morbidity. Associations between disease severity and male sex, earlier age at onset, and the presence of erythema nodosum have been described. OBJECTIVES: To evaluate clinical factors associated with manifestations of severe disease in a single-center cohort. METHODS: A longitudinal, prospective, unicentric cohort study with patients followed in a specialized outpatient clinic between 1981 and 2020. Severe BD was defined as a Krause total clinical severity score >4 points. RESULTS: We included 243 patients, of whom 31% were male, with an average follow-up time of 14.6 years. Regarding organ manifestations, all patients had mucous manifestations (N=243, 100%), 133 (55%) skin, 104 (43%) joint, 71 (29%) ocular, 48 (20%) vascular, 47 (19%) neurological, 22 (9%) gastrointestinal and 1 (0.4%) cardiac involvement by BD. One hundred fifty-six (64%) patients were classified as having severe BD. Severe BD was more frequent in men (OR=2.004, p=0.024), increasing with age (OR=1.021 per year, p=0.037), in the presence of skin manifestations (OR=4.711, p<0.001), specifically erythema nodosum (OR=8.381, p<0.001), and pseudofolliculitis (OR=2.910, p<0.001). In the multivariate model, variables independently associated with severe BD were male gender (Adjusted OR=1.961, p=0.047), erythema nodosum (Adjusted OR=8.561, p<0.001) and pseudofolliculitis (Adjusted OR=2.372, p=0.007). DISCUSSION: Male gender, erythema nodosum, and pseudofolliculitis were independently associated with severe BD forms and therefore should serve as warning signs to the clinician.

Predictive Factors of Severe Behçet's disease: A Longitudinal, Prospective Cohort Followed Between 1981–2020 / Factores predictivos de la enfermedad de Behçet grave: una cohorte prospectiva longitudinal seguida entre 1981-2020

Introduction: Behçet's disease (BD) is a systemic vasculitis of unknown cause. The spectrum of the disease ranges from mucocutaneous manifestations to other organ diseases with relevant morbidity. Associations between disease severity and male sex, earlier age at onset, and the presence of erythema nodosum have been described. Objectives: To evaluate clinical factors associated with manifestations of severe disease in a single-center cohort. Methods: A longitudinal, prospective, unicentric cohort study with patients followed in a specialized outpatient clinic between 1981 and 2020. Severe BD was defined as a Krause total clinical severity score >4 points. Results: We included 243 patients, of whom 31% were male, with an average follow-up time of 14.6 years. Regarding organ manifestations, all patients had mucous manifestations (N=243, 100%), 133 (55%) skin, 104 (43%) joint, 71 (29%) ocular, 48 (20%) vascular, 47 (19%) neurological, 22 (9%) gastrointestinal and 1 (0.4%) cardiac involvement by BD. One hundred fifty-six (64%) patients were classified as having severe BD. Severe BD was more frequent in men (OR=2.004, p=0.024), increasing with age (OR=1.021 per year, p=0.037), in the presence of skin manifestations (OR=4.711, p<0.001), specifically erythema nodosum (OR=8.381, p<0.001), and pseudofolliculitis (OR=2.910, p<0.001). In the multivariate model, variables independently associated with severe BD were male gender (Adjusted OR=1.961, p=0.047), erythema nodosum (Adjusted OR=8.561, p<0.001) and pseudofolliculitis (Adjusted OR=2.372, p=0.007).Discussion: Male gender, erythema nodosum, and pseudofolliculitis were independently associated with severe BD forms and therefore should serve as warning signs to the clinician.(AU)

Introducción: La enfermedad de Behçet (EB) es una vasculitis sistémica de causa desconocida. El espectro de la enfermedad abarca desde manifestaciones mucocutáneas hasta otras enfermedades de órganos con morbilidad relevante. Se han descrito asociaciones entre la gravedad de la enfermedad y el sexo masculino, la edad de inicio más temprana y la presencia de eritema nudoso. Objetivos: Evaluar los factores clínicos asociados con las manifestaciones de enfermedad grave en una cohorte de un solo centro. Métodos: Estudio de cohorte longitudinal, prospectivo y unicéntrico con pacientes seguidos en una clínica ambulatoria especializada entre 1981 y 2020. La EB grave se definió como una puntuación Krause total clinical severity score≥4 puntos. Resultados: Se incluyeron 243 pacientes, de los cuales el 31% eran varones, con un tiempo de seguimiento medio de 14,6 años. En cuanto a las manifestaciones orgánicas, todos los pacientes presentaron manifestaciones mucosas (n=243, 100%), 133 (55%) piel, 104 (43%) articular, 71 (29%) ocular, 48 (20%) afectación vascular, 47 (19%) neurológica, 22 (9%) gastrointestinal y 1 (0,4%) cardiaca por EB; 156 (64%) pacientes fueron clasificados como con EB grave. La EB severa fue más frecuente en hombres (OR=2,004, p=0,024), aumentando con la edad (OR=1,021 por año, p=0,037), en presencia de manifestaciones cutáneas (OR=4,711, p<0,001), específicamente eritema nodosum (OR=8,381, p<0,001) y pseudofoliculitis (OR=2,910, p<0,001). En el modelo multivariado, las variables asociadas de forma independiente con el EB grave fueron el sexo masculino (OR ajustado=1,961, p=0,047), eritema nudoso (OR ajustado=8,561, p<0,001) y pseudofoliculitis (OR ajustado=2,372, p=0,007). Discusión: El sexo masculino, el eritema nudoso y la pseudofoliculitis se asociaron de forma independiente con formas graves de DB y, por lo tanto, deberían servir como signos de advertencia para el médico.(AU)

Corynebacterium striatum Cardiac Device-Related Infective Endocarditis: The First Case Report in a Patient With a Cardiac Resynchronization Therapy Defibrillator Device and Review of the Literature.

Corynebacterium striatum (C. striatum) is a skin commensal agent, rarely described as a cause of infective endocarditis. We describe a case of a 48-year-old man, with multiple comorbidities with cardiac resynchronization therapy defibrillator (CRT-D) device implanted 1 year before. A cardiac device-related infective endocarditis (CDRIE) due to C. striatum, with vegetations in the tricuspid valve adjacent to the electrode lead and concomitant lumbar spondylodiscitis were diagnosed. The patient was treated initially with a 6-week course of vancomycin with sterile blood cultures and reduction of inflammatory parameters. Surgery was refused at this stage. Six weeks later, he was readmitted due to C. striatum bacteriemia recurrence, with vegetations adhering to the electrode wire, being treated with daptomycin 10mg/kg body weight, after presenting renal toxicity to vancomycin. CRT-D device was removed with implantation of epicardial cardiac resynchronization therapy pacemaker (CRT-P). To our knowledge, this might be the first description of C. striatum CDRIE in a patient with a CRT-D. In the five cases described in the literature of CDRIE by this agent, early removal of the pacemaker was performed with good results. In this case, the device was removed only after failure of medical treatment alone.

Immunoglobulin G4 Related-Disease: A Rare Presentation With Secondary Hypereosinophilic Syndrome and Eosinophilic Ascites.

Immunoglobulin G4 related-disease (IgG4-RD) is a multisystemic immune-mediated fibroinflammatory disease, with a strong predilection for salivary and lacrimal glands, pancreas, biliary tree, lungs, kidneys, aorta, and retroperitoneum. In the case of pancreatic involvement, it manifests as autoimmune pancreatitis. Patients with IgG4-RD usually have mild to moderate eosinophilia in the peripheral blood, however, they may present a secondary hypereosinophilic syndrome (HES). Although there are cases described with severe eosinophilia (> 5,000/µL), the 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-RD considers peripheral eosinophilia above 3,000/µL as an exclusion criterion, although stating that assessment for the presence of exclusion criteria should be individualized depending on a patient's clinical scenario. Here, we describe the clinical case of a 30-year-old woman who presented with chronic diarrhea and abdominal pain. The diagnostic workup revealed eosinophilic ascites, severe peripheral blood eosinophilia (> 5,000/µL), IgG4 elevation (> 2 × upper normal limit), and also diffuse swelling in the body and pancreatic tail (computed tomography (CT) scan). There was a prompt response to corticosteroid therapy with clinical resolution and continued remission under therapy. The patient was diagnosed with IgG4-RD with secondary HES, explaining the gastrointestinal tract and peritoneum damage in the form of enterocolitis and ascites. Exclusion of alternative diagnosis was made.

Sarcoidosis Presenting as Cranial Multinevritis.

A 29-year-old woman presented to the emergency department with red eyes and hypoacusia since the previous weeks associated with a sudden right facial palsy. Ophthalmologic examination revealed bilateral uveitis and lumbar puncture was compatible with aseptic meningitis. Thoracic computed tomography scan showed pulmonary nodules and mediastinal and hilar lymphadenopathy. Bronchoalveolar lavage revealed a CD4/CD8 ratio of 8, and lymph node biopsy confirmed non-caseating granulomas. The diagnosis of sarcoidosis with ocular, pulmonary, and neurologic involvement was made. Due to sarcoidosis severity at presentation, the patient was started on systemic steroids and methotrexate with improvement. Sarcoidosis involvement of the central nervous system is a rare condition (5-10%) but can be the first manifestation of the disease. Its presentation can be heterogeneous; therefore, symptoms are frequently devalued by patients and physicians, leading to a late diagnosis and permanent damage. Clinicians' awareness is crucial to early diagnosis and treatment.

Predictive Factors of Severe Behçet's disease: A Longitudinal, Prospective Cohort Followed Between 1981-2020.

INTRODUCTION: Behçet's disease (BD) is a systemic vasculitis of unknown cause. The spectrum of the disease ranges from mucocutaneous manifestations to other organ diseases with relevant morbidity. Associations between disease severity and male sex, earlier age at onset, and the presence of erythema nodosum have been described. OBJECTIVES: To evaluate clinical factors associated with manifestations of severe disease in a single-center cohort. METHODS: A longitudinal, prospective, unicentric cohort study with patients followed in a specialized outpatient clinic between 1981 and 2020. Severe BD was defined as a Krause total clinical severity score >4 points. RESULTS: We included 243 patients, of whom 31% were male, with an average follow-up time of 14.6 years. Regarding organ manifestations, all patients had mucous manifestations (N=243, 100%), 133 (55%) skin, 104 (43%) joint, 71 (29%) ocular, 48 (20%) vascular, 47 (19%) neurological, 22 (9%) gastrointestinal and 1 (0.4%) cardiac involvement by BD. One hundred fifty-six (64%) patients were classified as having severe BD. Severe BD was more frequent in men (OR=2.004, p=0.024), increasing with age (OR=1.021 per year, p=0.037), in the presence of skin manifestations (OR=4.711, p<0.001), specifically erythema nodosum (OR=8.381, p<0.001), and pseudofolliculitis (OR=2.910, p<0.001). In the multivariate model, variables independently associated with severe BD were male gender (Adjusted OR=1.961, p=0.047), erythema nodosum (Adjusted OR=8.561, p<0.001) and pseudofolliculitis (Adjusted OR=2.372, p=0.007). DISCUSSION: Male gender, erythema nodosum, and pseudofolliculitis were independently associated with severe BD forms and therefore should serve as warning signs to the clinician.

Discordance between patient and physician global assessment of disease activity in Behçet's syndrome: a multicenter study cohort.

BACKGROUND: To compare the patients' and physician's global assessment of disease activity in Behçet's syndrome (BS) and investigate the frequency, magnitude, and determinants of potential discordance. METHODS: A total of 226 adult BS patients with a median (IQR) age of 46.9 (35.6-55.2) years were enrolled across Italy, Greece, Portugal, and Spain. Demographic, clinical, and therapeutic variables, as well as the patient reported outcomes, were collected at the recruitment visit. The physical (PCS) and mental (MCS) component summary scores of the Short Form Questionnaire 36 (SF-36) and the Behçet's syndrome Overall Damage Index (BODI) were calculated. Disease activity was assessed by the patients' (PtGA) and physician's global assessment (PGA) in a 10-cm visual analog scale, as well as the Behçet Disease Current Activity Form (BDCAF). Discordance (∆) was calculated by subtracting the PGA from the PtGA and defined as positive (PtGA>PGA) and negative (PtGA 80%) of disagreements were due to patients rating higher their disease activity. Higher values of BDCAF were associated to increased rate of positive discordance. When BDCAF = 0, the median (IQR) values of PtGA and PGA were 0.2 (0-2) and 0 (0-1), respectively. PCS (adjusted odds ratio (adjOR) 0.96 per unit, 95% CI 0.93-0.98, p = 0.006) and MCS (adjOR 0.96 per unit, 95% CI 0.93-0.99, p = 0.003) were independently associated with positive discordance using both cutoffs. Active ocular involvement emerged as a potential determinant of negative discordance (adjOR 5.88, 95% CI 1.48-23.30, p = 0.012). CONCLUSIONS: PtGA and PGA should be considered as complementary measures in BS, as patients and physicians may be influenced by different factors when assessing active disease manifestations. Particularly, PtGA may be a useful tool in the assessment of BS disease activity, as it carries a low risk to misclassify an inactive disease, and may allow to capture aspects of the patient's health that negatively affect his well-being and the treatment.

Development and preliminary validation of the Behçet's syndrome Overall Damage Index (BODI).

OBJECTIVE: To develop and validate the evidence-based and consensus-based Behçet's Syndrome Overall Damage Index (BODI). METHODS: Starting from 120 literature-retrieved preliminary items, the BODI underwent multiple Delphi rounds with an international multidisciplinary panel consisting of rheumatologists, internists, ophthalmologists, neurologists, and patient delegates until consensus was reached on the final content. The BODI was validated in a cross-sectional multicentre cohort of 228 patients with Behçet's syndrome (BS) through the study of (a) correlation between BODI and Vasculitis Damage Index (VDI) and (b) correlation between BODI and disease activity measures (ie, Behçet's Disease Current Activity Form (BDCAF), Physician Global Assessment (PGA), Patient Global Assessment (PtGA)), c) content and face validity and (d) feasibility. RESULTS: The final BODI consists of 4 overarching principles and 46 unweighted-items grouped into 9 organ domains. It showed good to excellent reliability, with a mean Cohen's k of 0.84 (95% CI 0.78 to 0.90) and a mean intra-class correlation coefficient of 0.88 (95% CI 0.80 to 0.95). Overall, 128 (56.1%) patients had a BODI score ≥1, with a median score of 1.0 (range 0-14). The BODI significantly correlated with the VDI (r=0.693, p<0.001), demonstrating to effectively measure damage (construct validity), but had greater sensitivity in identifying major organ damage and did not correlate with disease activity measures (ie, BDCAF: p=0.807, PGA: p=0.820, PtGA: p=0.794) discriminating damage from the major confounding factor. The instrument was deemed credible (face validity), complete (content validity) and feasible by an independent group of clinicians. CONCLUSIONS: Pending further validation, the BODI may be used to assess organ damage in patients with BS in the context of observational and controlled trials.