Clinical significance of Angiopoietin-1 in Behcet’s disease patients with vascular involvement

Behcet’s disease (BD) is a chronic multisystem inflammatory disorder of unclear etiology. Vascular inflammation, endothelial dysfunction and angiogenesis may be in part responsible for the pathogenesis of BD. Angiopoietin-1 (Ang-1) is a recent angiogenic mediator. The aim of the present study was to assess Ang-1 in the plasma of BD patients as well as to analyze its association with clinical, and laboratory parameters of the disease. The present study included 47 BD patients and 30 age- and gender-matched healthy controls. Demographic, clinical, disease activity and severity were prospectively assessed. Plasma Ang-1 levels were measured using enzyme-linked immunosorbent assay. The plasma level of Ang-1 in BD patients was significantly lower than healthy controls (p = 0.005). Plasma Ang-1 level in patients with vascular affection was significantly lower than those without vascular affection (p = 0.045). Levels of Ang-1 showed a significant positive correlation with steroid dose. Patients who received cyclophosphamide or steroids showed a significant increase in plasma Ang-1 level. This was further confirmed by the results of the multivariate analysis. There was no significant association between plasma Ang-1 levels and other clinical manifestations or disease activity and severity. Plasma Ang-1 levels were diminished in our BD patients especially in patients with vascular involvement. Larger studies with further investigations of the precise role of Ang-1 in the pathogenesis of BD are needed and might lead to novel therapies for the clinical management of BD     

Pattern and outcome of vascular involvement of Omani patients with Behcet��s disease

The objective of the study is to study the pattern, frequency and outcome of vascular events in Omani patients with Behcet’s disease (BD). Forty BD patients were recruited. Clinical data parameters were recorded, including age at onset, disease duration, current disease activity, and the vascular manifestations of the disease (current and past events). Disease activity was assessed by ESR, CRP and also clinically. For venous and arterial thrombotic events, imaging studies, such as Doppler ultrasonography, angiography, MRI, CT, and echocardiography were performed. Nine patients had vascular events (23%). The mean age of these patients at diagnosis of the vascular event was 24 years (range 15–37) and the mean disease duration at onset of the vascular event was 3.8 years (range 3–5); this was significant when compared with patients without thrombosis (P = 0.001, Mann–Whitney test). In these patients with vascular involvement, two patients (22%) had venous lesions, three (33%) patients had arterial lesions and four patients (44%) had mixed lesions. Two patients (22%) had pulmonary artery aneurysm (PAA) and concomitant intracardiac thrombus, and further one patient also had PAA. Immunosuppressive therapy resulted in the resolution of PAA and intracardiac thrombous. In conclusion, the frequency of vascular complications of BD in our patients is similar to those reported around the world. We found younger male patients with short disease duration are at a greater risk of developing thrombosis. Medical treatment with immunosuppressive therapy without anticoagulation seems successful in treating PAA and intracardiac thrombus.     

Behcet’s disease and cardiovascular involvement: our experience of asymptomatic Behcet’s patients

Behcet’s disease is generally defined by oral and genital ulcers and uveitis. It is also known as a recurrent multisystemic and inflammatory disease. It is mostly seen in Mediterranean countries and the Far East.The aetiology of Behcet’s disease is associated with viral, toxic, bacterial and immunological factors. It was defined in 1963 as an auto-immune disease caused by auto-antibodies against the oral mucosa. Vascular involvement is 2–7% and it is usually seen in patients between the ages of 20 and 40 years.Behcet’s disease is a non-specific arterial and venous vasculitis.1-8 Proximal and distal anastomotic aneurysm formation after surgery is not rare one to 12 months postoperatively. Recurrent surgical interventions increase the risk of mortality and morbidity.9,10 Cardiovascular involvement in Behcet’s disease includes pericarditis, coronary arterial disease, cardiomyopathy and valvular dysfunction.11 The aim of this study was to report our experience of cardiovascular involvement with asymptomatic Behcet’s disease.     

Elevated white blood cell counts in Cushing’s disease: association with hypercortisolism

Background

Glucocorticoid receptors are expressed in white blood cells (WBC’s) and are known to play a role in cell adhesion and WBC’s recruitment from bone marrow. In Cushing’s disease leukocytosis is frequently mentioned as laboratory finding. However, there is no data on the prevalence of this finding among patients, or correlation with disease severity.

Purpose

To investigate the prevalence of leukocytosis in patients with Cushing’s disease, alterations in other blood count parameters and correlation with degree of hypercortisolism.

Methods

Data of 26 patients diagnosed and followed for Cushing’s disease at our clinic was reviewed. Two patients had disease relapse after complete remission and were studied as 2 separate events.

Results

Of the 26 patients, 17 were women (71 %), with a mean age of 39.8 ± 12.7 years. Mean baseline WBC count was 10,500 ± 2,600 cells/μl and dropped to 8,400 ± 1,900 cells/μl (p < 0.05) after treatment, mean neutrophil count at baseline was 7,600 ± 2,600 cells/μl and dropped to 5,300 ± 1,700 cells/μl (p < 0.05), lymphocyte count was 2,000 ± 600 cells/μl and raised to 2,300 ± 600 cells/μl (p < 0.05), hemoglobin was 13.7 ± 1.2 g/dl and dropped to 12.8 ± 1.4 g/dl (p < 0.05), and platelet number did not change. Elevated WBC count was present in 11/28 cases (40 %). Those patients with normal baseline WBC (mean 9,000 ± 1,500 cells/μl) dropped also to 7,700 ± 1,300 cells/μl after treatment (p < 0. 05). There was a significant positive correlation between decrease in UFC secretion and change in WBC’s following treatment (r = 0.67, p < 0.01).

Conclusions

Patients with Cushing’s disease present with leukocytosis in approximately 40 % of cases. In most cases, including those without elevated baseline count, the WBC’s decreased with disease remission, demonstrating the effect of glucocorticoids on these blood cells.     

Endoscopic findings of gastrointestinal involvement in Chinese patients with Behcet’s disease

AIM:To report the incidence,clinical features and outcomes of gastrointestinal(GI)involvement in Behcet’s disease(BD).METHODS:A total of 168 consecutive patients with BD were screened and upper and lower GI endoscopies were performed in 148 patients.Four hundred age-and sex-matched controls were enrolled for comparison.RESULTS:Fifty-two(35.1%)patients had GI lesions.After a mean follow-up of 10 mo,ileocecal ulcers had been confirmed in 20 patients,including active ulcer(s)in 18 patients,but no ileocecal ulceration was found in controls.GI symptoms were present in 14 patients with active ulcer(s),while 4 patients with smaller ulcer were asymptomatic.Endoscopic features of ileocecalulcer were:a single ulcer(50%),larger than 1 cm in diameter(72.2%),and round/oval or volcano-type in shape(83.3%).Compared with patients without GI involvement,less ocular lesions,lower levels of albumin,erythrocyte count and hemoglobin,and higher levels of C-reactive protein and erythrocyte sedimentation rate were confirmed in the intestinal BD group.Four patients had esophageal ulcers in the BD group but no case in controls.The other endoscopic findings were similar between the two groups.The prevalence of Helicobacter pylori infection was similar in both groups.Most patients received an immunomodulator and responded well.CONCLUSION:GI lesions commonly occur in Chinese BD patients.The most frequently involved area is the ileocecal region.Esophageal ulcer might be a rare but unique lesion.     

Lack of association of tumor necrosis factor-alpha gene polymorphisms with disease susceptibility and severity in Behçet’s disease

Although it has been reported that the MHC class I molecule, HLA-B51, is a risk factor for Behçets disease (BD), contribution of the tumor necrosis factor (TNF) genes, which are located in the vicinity of the HLA-B locus, to the genetic susceptibility for BD has yet to be elucidated. The purpose of this study was to analyze the effect of TNF- promoter polymorphisms at positions –308, –238 and –376 on the susceptibility, severity and clinical features of BD. The TNF- gene sequences from 107 patients with BD and 102 healthy subjects were amplified by the polymerase chain reaction. Sequence analysis of the TNF- gene locus, which contains promoter polymorphisms at positions –376, –308, and –238, was performed with a DNA sequencing kit on automated sequencer. The patients were classified according to disease severity and clinical features. Serum TNF- level in the study groups was measured by sandwich enzyme immunoassay. In patients with BD the frequencies of TNF- –308 (19.4% vs 18.4%), –238 (3.7% vs 5.9%), and –376 (0.9% vs 2.9%) gene polymorphisms were not found to be significantly different from those in healthy subjects. The TNF- gene polymorphisms did not show any association with disease severity or clinical features. Serum TNF- level was significantly higher in patients with BD than in healthy controls (3.10±1.45 pg/ml vs 2.43±1.94 pg/ml, P < 0.01). Serum TNF- level was not found to be significantly associated with disease severity, activity, clinical findings and TNF- genotypes. The results of this study suggest that the TNF- gene polymorphisms are unlikely to play an important role in the pathogenesis and severity of BD.     

Possible association of proinflammatory cytokines including IL1β and TNFα with enhanced Th17 cell differentiation in patients with Behcet’s disease

Clinical Rheumatology - We have reported that helper T type 17 (Th17) cells increased in patients with Behcet’s disease (BD). It remains obscure how Th17 cells increase in the patients. We...     

Pure red cell aplasia and adult-onset Still’s disease

Pure red cell aplasia (PRCA) associated with adult-onset Stills disease (AOSD) is very rare. In this report a 28-year-old woman was admitted with fever, skin rash, jaundice and anemia. She was diagnosed as having AOSD with PRCA by bone marrow examination. Treatment with high-dose prednisolone and intravenous immunoglobulin resulted in remission of the PRCA and a good response of the AOSD.Abbreviations ANA Antinuclear antibodies - AOSD Adult-onset Stills disease - PRCA Pure red cell aplasia - RF Rheumatoid factor     

Comparison of different onset ages in patients with Behcet’s disease

Clinical Rheumatology -     

Clinical characteristics of conduction disturbance in patients with Behcet’s disease

Clinical Rheumatology - To summarized clinical features of Behcet’s patients with conduction disturbances and explore the underlying risk factors. A retrospective case-control study was...     

Serum levels of natriuretic peptides in patients with Behcet’s disease

The objective of our study was to elucidate serum levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) in Behcet’s disease (BD) patients with active and inactive period. The multicenter study included 53 patients with active (n = 28) and inactive (n = 25) BD (mean age, 34.3 ± 9 years; 15 men and 38 women) satisfying the International Study Group criteria and 26 healthy controls (mean age, 34.4 ± 6.1 years; seven men and 19 women) matched for age and gender from a similar ethnic background. Serum natriuretic peptides levels were determined by enzyme immunoassay kit. Mean serum ANP concentrations in the active patients (4.01 ± 1.21 ng/ml) were significantly lower than in the healthy controls (5.76 ± 1.99 ng/ml, p = 0.004). Mean serum BNP levels were found to be significantly higher in both the active (6.19 ± 2.97 ng/ml) and inactive (6.49 ± 2.88 ng/ml) BD groups compared with the control group (3.82 ± 1.1 ng/ml, p = 0.004 and p = 0.001, respectively). Mean serum CNP concentrations in the active patients (0.49 ± 0.12 ng/ml) were significantly lower than in the inactive patients (0.65 ± 0.2 ng/ml, p = 0.017) and the healthy controls (0.8 ± 0.27 ng/ml, p < 0.001). Our results suggest that changes in natriuretic peptide levels may be associated with vasculitis that play role in the etiopathogenesis of the BD.     

Chronicle of a death foretold: a case of catastrophic vascular Behcet’s disease

A 20-year-old man with Behcet's disease characterized by recurrent arterial aneurysms presented with a new aortic root aneurysm. This patient previously had aneurysms of the coronary arteries and vein, as well as ruptured renal artery aneurysm. Chronic maintenance immunosuppressive therapy was recommended due to the catastrophic nature of the disease, which the patient refused to take. The patient died shortly after admission. This case demonstrates the unique catastrophic natural history of vascular Behcet's disease with recurrent life-threatening arterial events, and this case stresses the therapeutic dilemma of maintenance immunosuppressive therapy in selected patients.     

Clinical features of Behcet’s disease in Egypt

Behcet's disease (BD) is a chronic relapsing multisystem disease of unknown etiology. Ethnic origin is one of the factors that may modulate the prevalence and the expression of BD. To study the clinical characteristics of Egyptian patients with BD, and compare the pattern of the disease in Egyptians with studies from other countries. Sixty-three patients with BD were studied over a 4-year period. A rheumatologist, dermatologist, neurologist and other specialists as indicated assessed the patients clinically. Laboratory and radiological examinations were done to confirm the diagnosis to rule out any condition that may mimic BD. Sixty-one patients were men, two were women, the mean age of the patients was: 32.8 +/- 8.3 years, age of onset of the disease varied between 17 and 37.4 years. The initial presenting manifestation was oral ulcers in 39.7% of patients, followed by orogenital ulcers in 23.8%, followed by deep venous thrombosis in 7.9% Throughout the study period, the commonest manifestation was oral ulcers (100%), followed by genital ulcers (96.8%), vascular lesions (57.1%), cutaneous (55.5%), ocular (47.6%), joint (36.5%), neurological (34.9%), gastrointestinal (19%) and cardiac (6.3%). BD in Egyptians shows higher male-to-female ratio and higher incidence of vascular and neurological lesions.     

Coronavirus disease 2019 in patients with Behcet’s disease: a report of 59 cases in Iran

Clinical Rheumatology - To present the clinical characteristics, disease course, management, and outcomes of COVID-19 infection in patients with Behcet’s disease (BD). In this retrospective...     

Certolizumab Pegol treatment in Behcet’s disease with different organ involvement: A multicenter retrospective observational study

Objectives: The purpose of the present study was to describe our experience with the recombinant Fab’ antibody fragment against TNF-α Certolizumab Pegol (CZP) in patients with Behçet’s disease (BD) refractory to standardized therapies and previous biologic agents.

Methods: Retrieved data including demographic characteristics, clinical manifestations, and previous treatments were collected in three different specialized Rheumatologic Units in Italy. In order to evaluate disease activity, the BD current activity form (BDCAF) has been used before starting CZP therapy and at each visit during treatment.

Results: Thirteen BD patients (mean age 42.6?±?8.8 years) with a disease duration of 8.80?±?6.9 years, underwent CZP treatment for 6.92?±?3.52 months. Six patients (46.15%) experienced a worsening of symptoms after 4.16?±?1.21 months, whereas a satisfactory response was achieved in seven patients (53.84%) who were still on CZP therapy at the last follow-up visit (after 9.28?±?3.03 months of treatment). The mean decrease of BDCAF between the first and last visit was 0.308?±?1.84 without reaching significant difference (mean 8.3?±?1.3 and 8?±?2.08, respectively; p= .51). During the whole study period, CZP was well tolerated in all patients except one who developed a generalized cutaneous reaction after the third administration.

Conclusions: These results suggest that despite an improvement of clinical manifestations has been observed in more than half of the patients, it is not possible to draw firm conclusions about the effectiveness of CZP in BD and further studies with larger cohorts of patients are warranted. Whether the increase of CZP dosage may ensure a better clinical response remains an unsolved issue that needs to be considered.     

IgA nephropathy in association with Crohn’s disease

Background Urological complications of inflammatory bowel disease are seen in up to 25% of patients, but renal parenchymal disease is rarely reported.Case report The authors describe a case of a 29-year-old man with clinical and radiological features of ileocaecal Crohns disease. He had previously been investigated for painless macroscopic haematuria and a renal biopsy had revealed IgA nephropathy. Despite medical treatment, regular exacerbations of Crohns disease were associated with deterioration in renal function and the development of haematuria. The patient eventually underwent surgical resection of the terminal ileum and caecum. His renal disease has remained quiescent for the last 5 years following resection.     

Serum homocysteine level is higher in Behçet’s disease with vascular involvement

Objective Behçets disease (BD) is a multisystemic inflammatory disorder of unknown etiology that is sometimes associated with thrombosis. However, the mechanism of hypercoagulability is not known. In this study, we investigated whether hyperhomocysteinemia, being a well-known risk factor for thrombosis, is also a contributing risk factor to venous and arterial thromboses of BD.Methods Forty-five patients with BD and 40 healthy subjects were included in the study. Sixteen patients had vascular involvement. Serum homocysteine levels were determined by fluorescence polarization immunoassay.Results In male patients, the frequency of vascular involvement was significantly higher than in females (46.7% vs 13.3%, P<0.05). Serum homocysteine levels were significantly higher in patients with BD than healthy controls (P<0.01), in patients with vascular involvement than those with mucocutaneous involvement (P<0.01) and healthy controls (P=0.001), and in male patients than in female patients (P<0.001). There was no significant difference in homocysteine levels between the BD patients with mucocutaneous involvement and healthy subjects. In multiple regression analysis, serum homocysteine level was independently associated with thrombosis (odds ratio 1.29, P<0.01), but male sex was not.Conclusions This preliminary study suggests that elevated serum homocysteine levels may play some role in the development of venous and arterial thromboses in BD.     

Analysis of 27 cases of large vascular lesions in 161 cases of Behcet’s disease: clinical manifestations and treatment outcome

Very little is known about the features of Behcet’s disease (BD) with vascular lesions, especially in Chinese population. This study reports the incidence, pattern, and clinical features of vascular lesions in BD patients in China. A total of 161 patients with BD were screened, and 27 patients with vessel involvement were identified. The clinical and laboratory data of the 27 BD patients with vessel involvements were retrospectively analyzed. Of 161 enrolled patients with BD, 27 had large blood vessel damage (16.77 %), with 24 males and 3 females, indicating clear prevalence in males. The average age of onset was 26.2 years old. Seven patients involved arteries only, 15 had vein damage, and 5 showed damage to both arteries and veins. Although vein lesions were more prevalent, arterial lesions were not rare (44.4 % of the vessel-affected BD patients) and could be life-threatening. All 27 patients received various treatments such as steroids, immunosuppressants, anticoagulants, and surgery, and most responded well as evidenced by resumed blood circulation and complete resolution. In conclusion, this study shows features of vessel that involved BD similar to those reported in literatures. Comprehensive treatments lead to significant improvement in BD patients.     

Behcet’s disease and IgA nephropathy

Although Beh?et’s disease (BD) is a kind of systemic disease, renal involvement is rare, especially IgA nephropathy (IgAN). Renal manifestations in BD range from mild urinary abnormalities to glomerulonephritis with persistent renal failure, which includes minimal change disease, proliferative glomerulonephritis, rapidly crescentic glomerulonephritis, renal amyloidosis and IgA nephropathy. Amyloidosis seems to be the most common type of renal lesion in BD, and several cases of nephrotic syndrome secondary to amyloidosis have been documented. Co-occurrence of BD and IgA nephropathy has only been reported in only few cases. We describe two patients with the rare association of BD and IgAN. We suggested that it is important to periodically perform renal function assessment in patients with BD, through urinalysis and measurement of serum creatinine for detecting any abnormality and providing an early adequate treatment.