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Behçet's Disease: an Update on Pathogenesis, Diagnosis And Rheumatology Reports 2010; volume 2:e2 Behçet’s disease: an update on with cutaneous, musculoskeletal, vascular and nervous system manifestations.1 The etio- Correspondence: Kenneth T. Calamia, Depart- pathogenesis, diagnosis and pathogenesis of the disease remains obscure, ment of Rheumatology, Mayo Clinic Jacksonville, management of vascular although genetic predisposition, environmen- 4500 San Pablo Road, Jacksonville, Florida 32224, involvement tal factors and immunological abnormalities USA. E-mail: [email protected] have been implicated.2,3 It has recently been Key words: Behçet’s disease, vasculitis, venous Phaedon G. Kaklamanis,1 proposed that BD is an autoinflammatory dis- 4 5 thrombosis, arterial aneurysm, endothelial dys- 2 order, although there is no consensus. People Kenneth T. Calamia function, immunosuppressive agents, corticos- from the Far East, the Middle East and the 1 teroids. Emeritus Professor of Internal Medicine, Mediterranean basin are more commonly Athens Medical Center, Greece; affected than those from other parts of the 2 Contributions: PK and KC are both responsible Associate Professor of Medicine, Mayo 6 world. In Northern Europe, Central Africa and for and contributed to study conception and Clinic, Jacksonville, FL, USA the United States the disease is infrequent.7 design, and acquisition, analysis and interpreta- All ages may be affected, although the frequen- tion of data. Both authors contributed to the cy is higher in persons in the 3rd or 4th drafting of the article and revised it critically for decade. The sex predominance varies widely important intellectual content. Both authors are Abstract among the diseased population in different responsible for the final version to be published. geographical areas.6,7 Earlier studies suggested Received for publication: 22 June 2009. a male predominance in high prevalence The objective of this review is to summarize Revision received: 28 January 2010. reports of the prevalence, clinical presenta- areas, but more recent surveys indicate equal Accepted for publication: 28 January 2010. tion, diagnostic methodology and treatment of involvement of the sexes. In Western coun- vasculitic manifestations of Behçet’s disease tries, females predominate. This work is licensed under a Creative Commons (BD). We performed a literature search on vas- Behçet’s disease is included in the wide Attribution 3.0 License (by-nc 3.0). culitis in BD. Articles were selected which pro- spectrum of vasculitides.8 Vasculitis is a prin- ©Copyright P.G. Kaklamanis and K.T. Calamia, 2010 vided insight into the pathogenesis and clini- cipal pathological finding in BD and vessels of onlyLicensee PAGEPress, Italy cal aspects of vasculitis. Vasculitis underlies all sizes are involved, both in arterial and Rheumatology Reports 2010; 2:e2 many of the clinical features of BD. Small ves- venous systems. Large vessel vasculitis is not doi:10.4081/rr.2010.e2 sel vasculitis is often found in the pathology of a rare manifestation of BD and it was pro- the mucocutaneous manifestations of BD. posed that this be one of the diagnostic crite- Large vessel vasculitis has been reported in 15- ria of the disease.9 The prevalenceuse of large 40% of BD patients. Ultrasound, angiography vessel vasculitis varies according to the ing the vasculitic involvement of small vessels and tomography are applied to confirm the authors and the population. in BD. Petechiae of the nailfolds were diagnosis when venous involvement is sus- described in BD for the first time by Hashi- pected. Endothelial dysfunction plays a role in moto in 1973. The first nailfold capillaroscopic the pathogenesis of disease. Peripheral arteri- study was reported in 1984 on 30 patients with al involvement in BD occurs in the form of Materials and Methods BD.10 Periungual petechiae were recognized in arterial occlusion or aneurysms. Pulmonary 50% of patients. Pallor of the background, arterial involvement is often life-threatening. Small vessel vasculitis in in sludge, and abnormal appearance of the venous plexus with irregularly arranged The cause of cardiac vascular involvement Behçet’s disease requires an aggressive diagnostic approach. venules were also described. There was no cor- Corticosteroids and immunosuppressive In this paper, we review the prevalence, relation between the capillaroscopic findings agents have been used successfully in the clinical manifestations, diagnostic methodolo- and the disease duration. More severe damage early stage of large vessel disease and should gy, treatment and management of vasculitis in was demonstrated in patients with long dis- be used as an adjunct to surgery. An increasing BD. Specifically, we covered small vessel vas- ease duration and these findings correlated amount of data is available regarding the role culitis in BD, large vessel vasculitis, venous with skin and joint manifestations. Both stud- of anti-tumor necrosis factor (TNF) agents for involvement in BD, superficial throm- ies were open, without controls. Video capil- the treatment of BD. AnticoagulantNon-commercial therapy bophlebitis, deep vein thrombosis (DVT), infe- laroscopy, a non-invasive, reliable procedure, may be hazardous in patients with aneurysmal rior vena cava (IVC) thrombosis, Budd-Chiari may have diagnostic and prognostic value in dilatation of the pulmonary vascular tree and is Syndrome (BCS), portal vein thrombosis, the definition of the microvascular abnormali- not effective in the treatment of venous throm- superior vena cava (SVC) thrombosis, ties in patients with BD. A recent video capil- bosis. Inflammation of small and large vessels endothelium in BD, other possible contribu- laroscopic study in 15 BD patients and 16 is very frequent in BD. Both arteries and veins tions to thrombosis in BD, homocysteine, healthy subjects matched for age and sex was may be involved. Early recognition and appro- coagulation factors, peripheral arterial performed. Various nailfold abnormalities priate management of large vessel vasculitis in involvement, pulmonary manifestations, car- were found, including capillary dystrophies, BD is essential to reduce associated morbidity diac manifestations, pericarditis, myocardium numeric capillary abnormalities, sludging, and mortality. involvement, endocardium, coronary arteries, petechiae and pericapillary edema in a high cerebral vasculitis, cerebral venous thrombo- proportion of patients with BD. Similar find- sis, and cerebral arterial aneurysms. This is, ings, along with vessel microaneurysms, coil- to our knowledge, the first review which con- ing and kinking were also found in the con- Introduction siders the wide spectrum of vascular inflam- junctiva of these patients.11 In a recent study by mation found in patients with BD. stereo-microscopy, qualitative capillaroscopy Behçet’s disease (BD) is a chronic, relaps- was performed; the reported findings were ing, multisystemic disorder characterized by Results of literature review confirmed, showing high frequency of morpho- urogenital ulcers and ocular inflammation Few studies have been published concern- logical abnormalities (90%) in small vessels. [Rheumatology Reports 2010; 2:e2] [page 13] Review In a study of the histopathology of pathergy, around vessels and skin appendages. The aberrations observed in patients with BD.25 true vasculitis was not seen. Rather, an majority of the T lymphocytes were CD4+ and T cells play a pivotal role in the pathogene- intraepidermal pustule and polymorphonu- almost all expressed CD45RO. Neutrophils sis of BD. Several investigators have observed clear aggregates were found.12 In an electron constituted less than 5% of the infiltrating that T cells dominate in the involved tissues microscopic study, small dermal blood vessels cells.22 and their phenotypic characteristics have been were found to be filled by thrombus after stim- In Takayasu’s disease, large arteries, includ- studied. In BD uveitis, CD8+ CD56+ T cells were ulation of the skin with needle prick and in ing the aorta and its branches, and pulmonary found.26 In the histopathology of the pathergy erythema nodosum-like lesions in BD patients. arteries are affected. Transmural granuloma- reaction mononuclear cells predominate com- Excessive proliferation of endothelial cells tous inflammation and chronic intimal fibrosis posed of T lymphocytes and mononuclear caused vascular stenosis and the appearance with luminal obstruction is found. Granuloma macrophages. The majority of the T lympho- of degenerated cells.13 formation and giant cells are predominately cytes were CD4+ and almost all cells expressed On biopsy, mucous membrane and cuta- found in the media and adventia of the large CD45RO. In a recent study, the histology of neous lesions in BD patients may demonstrate elastic arteries. central nervous system lesions in BD was stud- small vessel inflammation, including lympho- In Giant Cell arteritis large arteries are also ied. In histological studies of acute neuro cytic and necrotizing vasculitis.14 Vasculitis involved, with mononuclear cells, macro- Behcet’s disease, the infiltration of mononu- and phlebitis have been found in 48% of skin phages and multinuclear giant cells. Giant clear cells around small vessels consisted of biopsies in BD patients, lymphocytic vasculitis cells are typically found at the junction CD45RO+ T lymphocytes and CD68+ monocytes, in 31% and leukocytoclastic vasculitis in 17%.15 between the intima and media. and few CD20+ B lymphocytes. Phenotypical A neutrophilic vascular reaction or lymphocyt-
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