Interleukin 8 in Behçet's Disease

Activated peripheral polymorphonuclear leukocytes (PMNs) and infiltration of PMNs into the lesions are characteristic findings of Behçet's disease (BD). A variety of cytokines, including interleukin 8 (IL-8), have been shown to activate PMNs. To investigate the role of IL-8 in the development of BD lesions, IL-8 production in vivo and in vitro was examined in 25 BD patients. IL-8 levels measured by ELISA in the non stimulated culture supernatants of peripheral mononuclear cells (MNCs) were higher in patients with active BD than in those with inactive BD or normal controls. Without LPS stimulation, IL-8 mRNA expression in incubated MNCs detected by Northern blot analysis was higher in active BD patients than in controls. Polarization assay confirmed the accelerated activity of PMN isolated from patients with active BD. However, these PMNs did not respond to IL-8 as strongly as to FMLP (an exogenous stimulator); a possible reason is that the PMNs of these patients are constantly exposed to IL-8 in vivo. Immunohistochemically, MNCs, endothelial cells and fibroblasts in BD lesions were positively stained by anti-IL-8 antibody. These data indicate that the production of IL-8 may be accelerated in inactive BD and that IL-8 may play an important role in the pathogenesis of BD.     

Clinical Spectrum of Behçet's Disease

Behçet's disease is a chronic systemic inflammatory disease involving mucous membranes, skin, eyes, the gastrointestinal tract, joints, blood vessels, and the neurologic system. Behçet's disease occurs endemically in the Middle East and Mediterranean regions. It is also distributed in the Central and Far Eastern Asian countries including Korea, Japan, and China. With the volume of clinical information obtained from over 5,000 patients who visited the Behçet's Disease Specialty Clinic, Severance Hospital, Yonsei University College of Medicine, informative and educational viewpoints of Behçet's disease including dermatologic and other systemic manifestations were introduced.     

Natural Cellular Cytotoxicity in Behçet's Disease

This study evaluated the cytotoxic activity of natural killer cells in the active and inactive stages of Behçet's disease (BD) and attempted to develop a new explanation for its immuno-pathogenesis. Blood samples were taken from 16 BD patients and compared with 11 healthy individuals. The lymphocyte fraction was separated and diluated in RPMI-1640. Candida as a target cell (T) was mixed with lymphocytes (E) (effector cells) in ratios of T:E 1/5 and T:E 1/25. After the numbers of colonies were counted with controls, the anticandidal index (natural cytotoxicity) was calculated. Natural cytotoxicity relatively decreased in the active stage and increased in the inactive stage of BD. Although the difference between the mean value of natural cytotoxicity in the active stage and in the inactive stage was significant, the difference between the averages of active stage and the control group was insignificant. However, the difference between inactive stage and the control group was remarkable. The increase of the natural cytotoxic activity in the inactive period of the disease may play a role together with other immune mechanisms in the aetiopathogenesis of BD.     

The histopathology of pathergy: a chronologic study of skin hyperreactivity in Behçet's disease

Background many patients with Behçet's disease (BD) demonstrate hyperreactivity (pathergy), and the induced skin lesions may serve as a model for the disease. Objective This study examined the sequence of histopathologic changes after needle prick trauma. Methods Eight patients fulfilling the International Study Group Criteria for Behçet's Disease, two patients with recurrent aphthous stomatitis, and two healthy controls each underwent intradermal injections with subsequent biopsies at 0, 4, 24, and 48 h. Hematoxylin and eosin sections were evaluated in a blinded fashion according to 11 histopathologic criteria. Results At time zero, normal skin was seen. By 4 h, neutrophils were present usually admixed with lymphocytes (8 out of 10). The inflammatory cell density peaked by 24 h in 8 out of 10 patients and at 48 h in 2 out of 10 patients. Sparse leukocytoclasis was identifiable from 4 to 48 h, but was not associated with fibrin. True vasculitis (as evidenced by fibrin within vessel walls and/or intraluminal thrombi) was not seen. Intraepidermal pustules (IEPs) and polymorphonuclear (PMN) aggregates within the needle tract were seen as early as 4 h. The control patients and three out of eight of the BD patients failed to develop clinical lesions. Among this group histopathologic IEPs were lacking in all but two BD patients. Conclusions These data suggest that early pathergy is mediated by PMNs and lymphocytes without vasculitis. Hyperchemotaxis may explain the rapid accumulation of PMNs along the injection site.     

Pathogenesis of Mucocutaneous Lesions in Behçet's Disease

Behcet's disease (BD) is characterized by recurrent oral aphthae, skin lesions, eye lesions, and genital ulceration. To determine the pathogenesis of BD, we performed histological and immunohistochemical studies of these mucocutaneous lesions, an assay of neutrophil activity, and HLA typing. Dense dermal or subcutaneous infiltrations of polymorphonuclear cells (PMN) without leukocytoclastic vasculitis were found in 28 of 57 lesions. Immunohistochemically, deposits of C3 on the vessels were found in 12 of 31 lesions. Deposits of immunoglobulin were not found except for one of IgM. C3 deposits and PMN infiltrations were significantly related (p<0.05). PMN activity by polarization was enhanced; however, the results did not show a significant relationship with the PMN infiltrations or the C3 deposits. The incidence of HLA-B51 was significantly high in BD, but no significant relationship was found between HLA-B51 and the results of other examinations. These results suggest that the pathogenesis of BD lesions differs from that of collagen diseases and that C3 deposits on the vessels may play an important role in the development of mucocutaneous lesions where PMN have mainly infiltrated.     

Encapsulated Necrosis Associated with Behçet's Syndrome

We reported a case of a 45-year-old woman with encapsulated necrosis associated with Behçet's syndrome. The lesions were characterized by multiple, small subcutaneous nodules on the extremities. Histologically, a nodule consisted of degenerative adipocytes encapsulated by fibrous tissue. A membranocystic lesion was also observed in the cavity of the nodule. The patient had a long-term history of Behçet's syndrome and suffered from erythematous subcutaneous nodules, resembling erythema nodosum on the extremities with a tendency to recurrence. These observations indicate that Behçet's syndrome could be implicated in the development of encapsulated necrosis as an underlying disease.     

Histopathologic Study of Cutaneous Lesions in Behçet's Syndrome

Light microscopic studies of 55 patients with complete and incomplete types of Behçet's syndrome were reviewed. We reported here 39 skin biopsies from 30 patients with cutaneous lesions of oral, and genital ulcers, folliculitis, erythema multiforme, and thrombophlebitis. Leukocytoclastic vasculitis was seen in 5 of 12 (42%) cases of oral ulcers and 2 of 7 (29%) of genital ones. Lymphocytic vasculitis was demonstrated in 3 of 12 (25%) cases of oral ulcers and 4 of 7 (57%) of genital ulcers. However, the vasculitis was observed only locally in the areas with moderate or severe inflammation. From the biopsy specimens of our cases with fully developed mucocutaneous lesions of Behçet's syndrome, it appears that the forms of vasculitis that are often emphasized in the literature are a phenomenon secondary to the intense inflammation seen in such cutaneous lesions.     

Granulocyte and monocyte adsorption apheresis for Behçet's disease in a pregnant woman

We present a 39‐year‐old pregnant woman with Behçet's disease who was treated successfully with granulocyte and monocyte adsorption apheresis (GMA). There were no complications or adverse effects during her pregnancy and delivery. The neonate manifested no abnormalities.     

Serum GDF‐15 level in Behçet's disease: relationships between disease activity and clinical parameters

Growth differentiation factor‐15 (GDF‐15), a member of the transforming growth factor‐β superfamily of cytokines, plays an important role in cell growth, signal transduction, and apoptosis regulation. The aim of this study was to evaluate serum GDF‐15 levels and their relationships with disease‐related variables in patients with Behçet's disease (BD). Forty‐six patients diagnosed with BD and 30 demographically matched healthy control subjects participated in the study. GDF‐15 levels were measured in blood samples from patients and controls. The Behçet's Disease Current Activity Form (BDCAF) was used to evaluate the disease activity of BD. There were no significant differences between the two groups in C‐reactive protein (CRP) level, mean erythrocyte sedimentation rate (ESR), age, body mass index, and mean GDF‐15 levels (P > 0.05). Serum GDF‐15 levels were positively correlated with findings for peripheral arthritis and CRP, and with BDCAF erythema nodosum, BDCAF arthralgia, and BDCAF arthritis scores. Patients with BD were divided into two groups according to the presence of peripheral arthritis; nine subjects (20%) were positive for peripheral arthritis. Serum ESR, CRP, white blood cell counts, and GDF‐15 levels were significantly higher in the group that was positive for peripheral arthritis (P < 0.05). GDF‐15 may play a role in the progression and pathway of Behçet's joint involvement and erythema nodosum that is independent of classic inflammatory response measures.     

Re-evaluation of the pathergy test in Beh?et's disease.

A positive pathergy test in patients with Beh?et's disease has been accepted as a diagnostic criterion by many authors, but in recent years it has been claimed that the test has a decreased positivity. We have examined the test in 92 proven cases of Beh?et's disease, using 20G and 26G disposable needles and evaluated them after 48 h. Maximum positivity was found to be 65% when we used needles of size 0.9 mm (20G), but the reactivity was considerably less when 0.3 mm diameter (26G) needles were used. The disposable needles used nowadays are less traumatic to initiate the reaction than were the non-disposable ones used in the pre-AIDS era.