Giant Cell Arteritis: Focusing on Current Aspects From the Clinic to Diagnosis and Treatment.

Giant cell arteritis (GCA) is a granulomatous arteritis involving large arteries, particularly the aorta and its major proximal branches, including the carotid and temporal arteries. GCA involves individuals over 50 years old. The etiopathogenesis of GCA may involve a genetic background triggered by unknown environmental factors (eg infections), the activation of dendritic cells as well as inflammatory and vascular remodeling. However, its pathogenetic mechanism still remains unclear, although progress has been made in recent years. In the past, inflammatory markers and arterial biopsy were considered as gold standard for the diagnosis of GCA. However, emerging imaging methods have been made more sensitive and specific for the diagnosis of GCA. Treatment includes biological and other modalities including interleukin-6 (IL-6) inhibitors.

Juvenile Adamantiades-Behçet Disease.

Adamantiades-Behçet disease (ABD) is a chronic, multisystemic, recurrent, inflammatory vascular disorder of unknown etiology. Patients with symptoms initially appearing at the age of 16 or less are considered as cases of juvenile-onset ABD (JABD). JABD is relatively rare compared to ABD of adults, and only case reports and case studies have been published regarding this subtype of the disease. Epidemiology, clinical features, diagnosis and treatment of JABD are discussed in this review.

Reduced pressure wave reflections in patients with active clinical status of Adamantiades-Behcet disease.

INTRODUCTION: Acute and chronic inflammation has a deleterious effect on arterial structure and function. Increased arterial stiffness and pressure wave reflections may provide a pathophysiological link between inflammation and increased cardiovascular risk. Adamantiades-Behcet disease (ABD), a relapsing inflammatory vasculitis, is associated with impaired arterial properties modulated by corticosteroids. The effect of inflammation on arterial properties during the active state of ABD is not well known. METHODS: In 47 subjects with ABD, under no corticosteroid treatment, we examined pressure wave reflections (augmentation index, AIx) and central pressures by pulse wave analysis, as well as local aortic stiffness and left ventricular function by high resolution ultrasound. Thirty subjects with similar cardiovascular risk factors served as a control group. RESULTS: Subjects with active ABD (n=11) had lower AIx and central systolic blood pressure (CSBP), but similar peripheral blood pressure, stroke volume, and slightly higher local aortic stiffness in comparison to patients with inactive ABD (n=36) (Alx: 12.6 +/- 11.4 vs. 23.2 +/- 19.1%, p=0.009; CSBP 104.2 +/- 12.4 vs. 115.4 +/- 15.7 mmHg, p=0.028). The arrival of the reflected pressure wave within the cardiac cycle was significantly delayed in subjects with active ABD. Low values of AIx (<10.5%) predicted with 73% sensitivity the presence of active ABD. CONCLUSIONS: Patients with ABD, not treated with corticosteroids, have decreased pressure wave reflections and CSBP in the presence of active disease, possibly due to peripheral arterial vasodilation, but not due to altered left ventricular or aortic function. The underlying pathophysiological mechanisms and the role of low AIx in the presence of systemic inflammation need to be investigated further.

Role of polymorphisms in Adamantiades-Behçet's disease.

OBJECTIVE: We previously showed that Adamantiades-Behçet's disease (A-BD) is associated with a lower incidence of malignancy compared with the general population. Transforming growth factor-beta (TGF-beta) has been shown to play a role in cartilage regeneration and is increased in patients with A-BD. We also found 2 functional polymorphisms of the TGF-beta pathway, TGFBR1*6A and TGFB1*CC, that are associated with risk of malignancy. We tested whether incidence of these polymorphisms would differ in patients with A-BD compared with healthy controls of similar age and geographic location. METHODS: We performed a case-control study including 139 cases and 128 controls from Greece. Cases and controls were genotyped for TGFBR1*6A and TGFB1*CC. RESULTS: We found that cases had lower incidence of TGFBR1*6A compared with controls (11.3% vs 13.3%, respectively). Also, the incidence of TGFB1*CC was lower in cases than controls (24.6% vs 27.0%, respectively). These differences were not statistically significant. CONCLUSION: Although there is a suggestion that the lower incidence of TGFBR1*6A in A-BD patients may play a protective role against development of malignancy, larger studies would be needed to fully evaluate the role of TGF-beta and its polymorphisms in A-BD.

Interrelated modulation of endothelial function in Behcet's disease by clinical activity and corticosteroid treatment.

Corticosteroids are commonly used in empirical treatment of Behçet's disease (BD), a systemic inflammatory condition associated with reversible endothelial dysfunction. In the present study we aimed to dissect the effects of clinical disease activity and chronic or short-term corticosteroid treatment on endothelial function in patients with BD. In a case-control, cross-sectional study, we assessed endothelial function by endothelium dependent flow mediated dilatation (FMD) at the brachial artery of 87 patients, who either were or were not receiving chronic corticosteroid treatment, and exhibiting variable clinical disease activity. Healthy individuals matched for age and sex served as controls. Endothelial function was also assessed in a prospective study of 11 patients before and after 7 days of treatment with prednisolone given at disease relapse (20 mg/day). In the cross-sectional component of the study, FMD was lower in patients than in control individuals (mean +/- standard error: 4.1 +/- 0.4% versus 5.7 +/- 0.2%, P = 0.003), whereas there was a significant interaction between the effects of corticosteroids and disease activity on endothelial function (P = 0.014, two-factor analysis of variance). Among patients with inactive BD, those who were not treated with corticosteroids (n = 33) had FMD comparable to that in healthy control individuals, whereas those treated with corticosteroids (n = 15) had impaired endothelial function (P = 0.023 versus the respective control subgroup). In contrast, among patients with active BD, those who were not treated with corticosteroids (n = 20) had lower FMD than control individuals (P = 0.007), but in those who were receiving corticosteroids (n = 19) the FMD values were comparable to those in control individuals. Moreover, FMD was significantly improved after 7 days of prednisolone administration (3.7 +/- 0.9% versus 7.6 +/- 1.4%, P = 0.027). Taken together, these results imply that although corticosteroid treatment may impair endothelial function per se during the remission phase of the inflammatory process, it restores endothelial dysfunction during active BD by counteracting the harmful effects of relapsing inflammation.

Pressure wave reflections, central blood pressure, and aortic stiffness in patients with Adamantiades-Behcet's disease: a cross-sectional case-control study underlining the role of chronic corticosteroid treatment.

BACKGROUND: Adamantiades-Behcet's disease (ABD) is a multisystemic inflammatory/autoimmune disease involving both microcirculation and macrocirculation. Aortic stiffness index and aortic augmentation index (AI) are indices for the estimation of arterial stiffness and pressure wave reflections, respectively. The effect of anti-inflammatory and immunosuppressive drugs used in ABD on these indices is unknown. METHODS: In this cross-sectional study we examined 74 subjects with ABD (aged 40.1 +/- 12.5 years, 24 men) and 24 control subjects by using the noninvasive technique of radial artery applanation tonometry and pulse wave analysis for assessment of aortic AI by application of transfer functions. Echocardiography was used for assessment of aortic stiffness index. Classic cardiovascular (CV) risk factors, left ventricular and endothelial function of the brachial artery, as well as intima-media thickness of carotid artery, were also assessed. RESULTS: Corticosteroids were the only drug having a negative and independent effect on aortic AI, but not on aortic stiffness. Patients taking corticosteroids had lower aortic AI and central systolic blood pressure (BP), but not aortic stiffness and peripheral systolic BP, when compared to those without corticosteroids (21+/-14% v 12+/-14%, P < .050). Medication, traditional CV risk factors, and functional or structural CV parameters were all comparable among the two groups. The AI was similar between the control group and patients with ABD taking corticosteroids. CONCLUSIONS: The AI, but not aortic stiffness, is lower in patients with ABD taking corticosteroids compared to patients not taking corticosteroids and similar to the control group. These results imply a role of inflammation or immunomodulatory mechanisms in the regulation of pressure wave reflections.