Lesions Of Behcet's Disease Research Articles

Mucocutaneous manifestations of Behçet's disease: Pathogenesis and management from perspectives of vasculitis.

Behçet's disease (BD) is a systemic inflammatory disorder characterized by vasculitis affecting blood vessels of any caliber or type. It can present with a wide spectrum of vasculitic lesions, including erythema nodosum-like lesions and retinal vasculitis, and may also lead to larger vessel diseases, such as aortic aneurysm and deep vein thrombosis. The full etiology of BD remains unclear, but it is considered a polygenetic disease with multiple genetic risk factors that promote immune dysregulation and thrombophilia. Inflammation can be triggered by environmental factors, such as bacteria or viruses, and the dysregulation of innate and adaptive immune cell subsets. Neutrophils and lymphocytes are the primary players involved in BD pathogenesis, with specific innate (i.e., neutrophil-derived reactive oxygen species and neutrophil extracellular traps) and adaptive (i.e., anti-endothelial cell antibodies) processes inducing endothelial cell activation and chemotaxis of inflammatory cells, leading to coagulation and vasculitis. These inflammation-induced vasculitic or vasculopathic features are observed in most mucocutaneous BD lesions, although vasculitis per se is often pathologically evident only during a brief period of the disease process. Due to the multifactorial nature of BD-associated inflammation, broad-spectrum anti-inflammatory medications, including glucocorticoids and immunosuppressive drugs, have been the mainstay for managing BD. In addition, inhibitors of interleukin (IL)-1, tumor necrosis factor (TNF)-α, and IL-17, which target innate and adaptive immune functions dysregulated in BD, have emerged as promising new therapeutics. In this review, we discuss the muco-cutaneous manifestations of BD by focusing on the underlying vasculitic components in their pathologies, as well as the current array of treatment options.

Behçet's disease with intestinal involvement: case-based review.

Behçet's disease (BD) is a rare (especially in East Europe, Ukraine) systemic vasculitis of blood vessels of varying calibers throughout the body that affects various organs. The variability of the clinical features requires the involvement of doctors of different specialties in the management of such patients. The work was aimed to conduct a literature review of the intestine involvement and skin lesions in BD based on the clinical case with bloody diarrhea at the onset, and to assess the frequency of development of various clinical syndromes in intestinal BD. This is an attempt at describing a manifestation of BD with colitis and to emphasize the necessary revision of BD diagnostic criteria with special attention to early manifestations of BD with gastrointestinal tract involvement.

Cardiovascular Manifestations of Behçet Disease among Egyptian Patients

Abstract Background Behcet’s disease is an auto immune disease with multisystem affection, the most common manifestations are in the form of oral or genital ulcers, eye affection, recurrent thrombosis . Behcet’s disease is a chronic disease with many sequelae, sometimes fatal, the treatment is by immunosuppressive therapy which also had its implications on the long term, unfortunately it has no sure diagnostic tests and relies mainly on clinical criteria, there are few scores to assess behcet’s disease activity (Behcet's Disease Current Activity Form) BDCAF score is a reliable follow up tool with wide accreditation. BD can virtually involve any organ system, cardiac involvement is variable and sought to occur in the range of 7-46% of patients and may cause myocardial infarction, pericarditis, valve problems, aneurysms or congestive heart failure. Different types of vessels, predominantly veins, can be affected in BD. The frequency of vascular lesions in BD, such as superficial and deep venous thromboses, arterial aneurysms and occlusions, ranges between 7-29%. Aims To assess cardiovascular manifestations for patient diagnosed as Behçet disease (BD) and its correlation to disease activity. Methods This was a cross sectional study which was done on 40 Behcet’s disease patients within the year 2019, it was done for the assessment of cardiovascular manifestations for patient diagnosed as Behçet disease (BD) and its correlation with BDCAF score (Behcet’s disease current activity form). The study group was subjected to full history, clinical examination including activity which was assessed according to BDCAF score (BEHCET'S DISEASE CURRENT ACTIVITY FORM), Assessment of any activity regarding the eyes using fundus examination, routine laboratory investigations including Complete blood count (CBC), Erythrocyte sedimentation rate (ESR), Creactive protein (CRP), lipid profile, liver enzymes. Results it was found that there is a positive correlation between BDCAF (behcet's disease current activity form) and cardiovascular affection (especially valvular lesions and vascular venous affection).

Lesional activation of Tc 17 cells in Behçet disease and psoriasis supports HLA class I-mediated autoimmune responses.

Behçet disease (BD) presents with lymphocytic and neutrophilic vasculitis of unknown aetiology. HLA-B*51, the endoplasmic reticulum aminopeptidase 1 (ERAP1), and interleukin 23 receptor (IL23R)/IL12R are genetic risk factors. IL-23 regulates IL-17A, which controls the recruitment and activation of neutrophils. To determine pathological changes in BD skin lesions related to the complex genetic predisposition. We characterized the expression of IL-17A and IL-23A in various cell types by immunohistological double staining of sections from papulopustular skin lesions of acute attacks of BD and psoriasis vulgaris lesions, another HLA-class I-associated T-cell-mediated autoimmune disease in which excessive T-cell-derived IL-17A production promotes neutrophil activation. We found that in BD lesions, as in psoriasis, actively expanding CD8+ T cells were the predominant source of IL-17A. IL-17A+ CD8+ T (Tc 17) cells outnumbered infiltrating IL-17A+ CD4+ T cells. Unlike the epidermal localization of CD8+ T cells in psoriasis, Tc 17 cells in BD lesions mainly infiltrated the perivascular tissue and the blood vessel walls of dermis and subcutaneous tissue. They co-localised with a marked IL-23A expression by CD11c+ dendritic cells and CD68+ macrophages. IL-17A expression was associated with extensive recruitment of neutrophils around blood vessels that formed neutrophil extracellular traps (NETs). In BD, the genetic predisposition may mediate antigen-specific activation and differentiation of a Tc 17 response, possibly targeting endothelial (auto)antigens. Neutrophils recruited by IL-17A in this process may enhance tissue damage by extensive NET formation (NETosis). Thus, the IL-23/IL-17 axis presumably controls neutrophilic inflammation in BD vasculitis in the context of a predominant antigen-specific CD8+ T-cell response.

Value of colchicine as treatment for recurrent oral ulcers: A systematic review.

In oral medicine, colchicine is a therapeutic alternative for idiopathic recurrent aphthous stomatitis (RAS), Behçet disease (BD), periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome, and mouth and genitals ulcers with inflamed cartilage (MAGIC) syndrome. The present review aims to evaluate reliability of colchicine against recurrent oral ulcers. A systematic review was conducted, with the following PICO (Patient, Intervention, Control, Outcome) question: "In populations with idiopathic or secondary recurrent oral ulcers, is colchicine more effective in improving pain and accelerating healing, compared to other intervention or placebo?" Seven RCTs and 3 OCTs were considered eligible. Four RCTs focused on BD, two RCTs and three OCTs on RAS, and one RCT on PFAPA syndrome. Heterogeneity between RCTs prevented from meta-analysis. Regarding BD, no significant difference between colchicine and placebo was found in two of three placebo-controlled RCTs, whereas the third RCT showed benefit. A comparative RCT found ciclosporin more effective than colchicine for oral lesions of BD. One open-label RCT showed promising but partial results on colchicine in reducing PFAPA attacks, when compared to corticosteroids. Concerning RAS, colchicine appeared less effective than clofazimine, thalidomide and dapsone, and with outcomes similar to low-dosage corticosteroids but higher gastric discomfort than prednisolone. One OCT reported positive results compared with no treatment but a RCT found no difference with placebo. Role of colchicine as treatment for idiopathic or secondary recurrent oral ulcers is still controversial. Further standardized RCTs and crossover trials are needed.

The Clinical Features, Risk Factors, and Outcome of Aneurysmal Lesions in Behcet's Disease.

Objective To investigate the clinical features and potential risk factors of aneurysmal lesions in Behcet's disease (BD). Methods We retrospectively reviewed the clinical data of BD patients with aneurysmal lesions in our institute from 1997 to 2017 and compared them with 207 BD patients without aneurysmal lesions. The treatment and outcome of these patients were also analyzed. Results Sixty-nine patients were included with 117 aneurysmal lesions. The average period between BD onset and diagnosis of aneurysmal lesion was 5.4 ± 5.5 years. Thirty-three patients (47.8%) had multiple aneurysmal lesions. Ten patients developed 20 pulmonary artery aneurysms alone. For the other 97 aortic and/or peripheral artery aneurysms in 59 patients, the most commonly affected vessels were abdominal aorta (27/97, 27.8%), coronary artery (10/97, 10.3%), and superficial femoral artery (8/97, 8.2%). Multivariate analysis revealed pathergy reaction (OR = 3.78 (1.70-8.41)), arterial stenosis or occlusion (OR = 44.12 (11.56-168.35)), and arterial thrombosis (OR = 9.27 (2.33-36.93)) as independent predictors of aneurysmal lesions in BD. With a mean follow-up of 5.5 ± 4.0 years, 40 patients (58.0%) achieved clinical improvements, 15 patients (21.7%) relapsed, and 10 patients (14.5%) died. The respective estimated cumulative 1- and 5-year relapse-free rates were 91.3% and 76.3%, and the respective estimated 1- and 5-year survival rates were 95.0% and 87.2%. Conclusion Aneurysmal lesions are severe complications in BD. Pathergy reaction, arterial stenosis or occlusion, and arterial thrombosis are the risk factors of aneurysmal lesions in BD. Achieving BD remission and performing surgical or interventional procedures are both important in the treatment of these patients.

High-dose intravenous steroid pulse therapy in ocular involvement of Behcet's disease: a pilot double-blind controlled study.

To evaluate the efficacy of intravenous high-dose pulses of methylprednisolone (IVPM) for treatment of ocular involvement in Behcet's disease (BD). In a double-blind control study, we randomized BD patients with posterior uveitis (PU) and/or retinal vasculitis (RV) into two groups. They received either IVPM (1000 mg methylprednisolone) or placebo for 3 consecutive days. Both groups received combination therapy with IV cyclophosphamide, azathioprine and prednisolone for 6 months. Visual acuity (VA), Disease Activity Index (DAI) based on the inflammatory state of each section of each eye, total inflammatory (TIAI) and adjusted DAI (TADAI) for each patient were calculated. The comparisons were done by paired t- and Mann-Whitney U-test. Seventeen patients in each group completed the treatment. The mean VA improved from 0.5 to 0.8 (P < 0.000001) for the study and from 0.6 to 0.7 (P < 0.02) for the placebo group. The difference was significant (P = 0.01). The comparison showed no significant difference regarding DAI improvement in other items (P > 0.2): PU, 1.9 to 0.5 (P < 0.0006) versus 2.3 to 0.8 (P < 0.0002); RV: 4.0 to 1.1 (P < 0.0004) versus 3.1 to 1.1 (P < 0.0005); TIAI: 23 to 5.7 (P < 0.0002) versus 24.8 to 8.4 (P < 0.003); TADAI: 24.1 to 7.3 (P < 0.0002) versus 25.9 to 7.9 (P < 0.004). We had one flare in the study versus seven in the placebo group (P < 0.005). Adding high-dose intravenous steroid pulse therapy to conventional combination therapy for severe ocular lesions of BD may cause better improvement on VA and fewer flares during the first 6 months of treatment.

Eosinophilic Pustular Folliculitis in a Patient with Behçet’s Disease

Behcet's disease (BD) is a chronic multisystemic inflammatory disease with chronic wax and waning course. Eosinophilic pustular folliculitis (EPF) is characterized by pruritic follicular papules and pustules that may involve the face, trunk, and upper arms. The precise etiopathogenesis of EPF is not yet elucidated. Immunological aberrations have been suggested to play pivotal roles, as the most common type of EPF is associated with HIV infection. Herein, we describe a patient with BD who presented with multiple vesicopustular lesions that were pathologically proven to represent EPF, and further postulate that EPF may be considered as cutaneous lesions of BD, although further studies are necessitated.

Capsule Endoscopy for Differentiating Early Crohn's Disease from Behçet's Disease

Objective: Crohn's disease (CD) and Behcet's disease (BD) are two major causes of inflammatory lesions in the small bowel. For detecting such lesions, the most sensitive exam is small-bowel capsule endoscopy (CE), an imaging modality suitable for evaluating lesions of the small intestine, with a relatively low rate of capsule retention. However, few reports have employed CE to compare the small-bowel inflammation in early CD with that in early BD. Thus, the aim of our study was to obtain a systematic characterization of small-bowel lesions in early CD and BD by using CE. Methods: This retrospective single-center study included 22 patients with early CD and 16 patients with early BD. The patients underwent small-bowel CE for detection and characterization of small-bowel lesions. After reviewing the CE findings in each patient, we assessed the small-bowel mucosal inflammation using the Lewis score, an inflammatory biomarker (C-reactive protein), and the disease activity index. The CE findings (number, distribution, and shape of lesions), Lewis score, disease activity index, and C-reactive protein levels were compared between the groups of CD and BD patients. Results: Small-bowel lesions were observed in 90.9% of CD patients, and in 68.7% of BD patients. Regarding distribution, CD patients exhibited multiple concentrated ulcers, which were more severe distally, while BD patients mostly exhibited solitary ulcers. Regarding shape, linear and longitudinal ulcers were observed, respectively, in 68.2% and 50% of CD patients; however, no such ulcers were observed in BD patients. C-reactive protein levels and disease activity indices were poorly correlated with Lewis score for both diseases. Capsule retention during CE did not occur in any patient included in this study. Conclusion: CE is a valuable tool to assess the mucosal inflammation of the small bowel in early CD and BD. Greater mucosal inflammation in the distal small bowel, and presence of linear and longitudinal ulcers may be the key findings for the differential diagnosis of small-bowel inflammation between early CD and BD

Atteintes aortiques inflammatoires associées à la maladie de Behçet

The arterial lesions affect about 10% of patients with Behçet's disease (BD). Aortic inflammatory involvement includes predominantly aortic aneurysmal lesions affecting most often the abdominal aorta. They account for the severity of the disease and are a leading cause of death when they hit the aorta or pulmonary arteries. Within the arterial lesions of BD, aortic involvement is, with femoral lesions, the most common site involved (18–28% of patients with vascular disease). Unlike other large vessels vasculitis (i.e. giant cell arteritis and Takayasu's arteritis) diffuse aortitis is observed in less than 5% of patients with BD. Aortic lesions of BD may be asymptomatic (systematic imaging or occasionally associated with other vascular event) or be revealed by the occurrence of abdominal, thoracic or lumbar pain, or an aortic valve insufficiency. Fever is frequently associated. Increase in acute phase reactants is common in these patients. Histological analysis may show infiltration by lymphocytes, neutrophils and plasma cells in the media and adventitia and a proliferation of the vasa vasorum in the media as well as a fibroblastic proliferation. In the later phase, a fibrous thickening of the media and adventitia is observed as well as a proliferation and thickening of the vasa vasorum. The therapeutic management should always include a medical treatment for the control of inflammation (corticosteroids, immunosuppressive drugs and/or biotherapy) and often an endovascular or surgical treatment if the aneurysm is threatening. The choice between endovascular or surgical treatment is considered case by case, depending on the experience of the team, anatomical conditions and of the clinical presentation. In this review, we provide a detailed and updated review of the literature to describe the aortic inflammatory damage associated with Behçet's disease.

Immunopathogenic characterization of cutaneous inflammation in Behçet’s disease

Behçet's disease (BD) is a recurrent multisystemic inflammatory disease characterized by recurrent oral aphthous and genital ulcers, ocular lesions and cutaneous lesions. Although many studies of cytokine levels in sera of BD patients have been conducted, there are only limited number of studies about the cytokine expression and cellular infiltration in the BD-related skin lesions. To investigate the immunophenotypes and cytokine profiles of BD-related skin lesions. Twenty patients who fulfilled the diagnostic criteria for BD with BD-related skin lesions were enrolled in this study. We assessed the histopathological features of BD-related skin lesions by immunohistochemical studies with anti-human CD4, CD8, CD68, FoxP3, CD-11b, IFN-γ and IL-4 antibodies. Immunophenotyping of inflammatory infiltrating cells showed that CD68+ macrophages were the most common type of infiltrated cells in erythema nodosum-like lesions, erythema multiforme-like lesions and Sweet's syndrome-like lesions, whereas neutrophils were the main population of inflammatory infiltrating cells in papulopustular lesions. In all of the four types of BD-related skin lesions, the percentage of CD8+ T cells was higher than that of CD4+ T cells (P < 0.05), and IL-4 expression was stronger than IFN-γ expression (P < 0.05). In this study, we assessed the infiltrating inflammatory cells and cytokine expression of acute cutaneous lesions in BD through immunohistochemical staining of BD-related skin lesions. Further studies about the disease activity and the molecular biology underlying the cutaneous inflammation are needed to understand the detailed pathogenesis of BD.

Long-Term Outcome of Arterial Lesions in Behçet Disease

The vasculitis of Behçet disease (BD) is distinctive because of involvement of both arteries and veins of all sizes. The concept of vasculo-Behçet disease has been adopted for cases in which vascular manifestations are present and often dominate the clinical features. While venous manifestations are frequent and have been reported in many publications, data regarding arterial lesions in patients with BD are rare and often isolated. In this study, we report the main characteristics, treatment, and long-term outcome of 101 patients with arterial lesions among a cohort of 820 (12.3%) BD patients. Factors that affect prognosis were assessed by multivariate analysis. There were 93 (91.2%) male patients; the median (Q1-Q3) age at diagnosis of BD was 33 (27-41) years. Arterial lesions included aneurysms (47.3%), occlusions (36.5%), stenosis (13.5%), and aortitis (2.7%). Lesions mainly involved the aorta (n = 25) and femoral (n = 23) and pulmonary (n = 21) arteries. Patients with arterial lesions were more frequently male (91.2% vs. 62.4%, respectively; p = 0.017) and had higher rates of venous involvement (80.4% vs. 29.8%, respectively; p < 0.001) compared to patients without arterial manifestations. Thirty-nine (38.6%) patients achieved complete remission. In multivariate analysis, the presence of venous involvement (odds ratio [OR], 0.29; 95% confidence interval [CI], 0.08-1.11) and arterial occlusive lesions (OR, 0.13; 95% CI, 0.01-1.25) were negatively associated with complete remission. The use of immunosuppressants (OR, 3.38; 95% CI, 0.87-13.23) was associated with the occurrence of complete remission. The 20-year survival rate was significantly lower in BD patients with arterial involvement than in those without arterial lesions (73% vs. 89%, respectively; p < 0.0001). In conclusion, the long-term outcome of arterial lesions in BD is poor, especially in the case of occlusive lesions and associated venous involvement. The use of immunosuppressants improved the prognosis.

Spectrum of Cardiac Lesions in Behçet Disease

Cardiac abnormalities in patients with Behçet disease (BD) include pericarditis, myocarditis, endocarditis with valvular regurgitation, intracardiac thrombosis, endomyocardial fibrosis, coronary arteritis with or without myocardial infarction, and aneurysms of the coronary arteries or sinus of Valsalva. Data regarding the clinical spectrum, prevalence, and outcome of cardiac lesions in BD are lacking. In this study, we report the main characteristics, treatment, and long-term outcomes of 52 patients with cardiac lesions from a cohort of 807 (6%) BD patients. Forty-five (86.5%) patients were male, with a mean (±SD) age at BD diagnosis of 29.3 ± 10.3 years.Cardiac involvement was the first feature of BD in 17 (32.7%) patients. Cardiac lesions included pericarditis (n = 20; 38.5%), endocarditis (mostly aortic insufficiency) (n = 14; 26.9%), intracardiac thrombosis (n = 10; 19.2%), myocardial infarction (n = 9; 17.3%), endomyocardial fibrosis (n = 4; 7.7%) and myocardial aneurysm (n = 1; 1.9%). Patients with cardiac involvement were more frequently male (86.5% vs. 64.9%; p < 0.01) and had more arterial (42.3% vs. 11.1%; p < 0.01) and venous lesions (59.6% vs. 35.8%; p < 0.01) compared to those without cardiac manifestations. Factors associated with complete remission of cardiac involvement were treatment regimens with oral anticoagulants, immunosuppressants, and colchicine. The 5-year survival rate was 83.6% and 95.8% (p = 0.03) in BD patients with and without cardiac involvement, respectively. After a median (Q1-Q3) follow-up of 3.0 (1.75-4.2) years, 8 patients had died, in 3 cases directly related to cardiac involvement.In conclusion, cardiac lesions affected 6% of our large cohort of BD patients. The prognosis of cardiac involvement in BD is poor and improves with oral anticoagulation, immunosuppressive therapy, and colchicine.

Granulysin-producing cytotoxic T cells in the mucocutaneous lesions of Behçet disease: a distinct inflammatory response from erythema nodosum

Cytotoxic T lymphocytes (CTLs) have been recognized as an important effector cell in Behçet disease (BD). Granulysin is a cytolytic granule protein expressed by CTLs and natural killer cells. To evaluate the involvement of granulysin-producing T cells in the pathogenesis of BD. Using immunohistochemistry, lymphocyte subsets expressing granulysin were investigated in mucocutaneous lesions of BD. Serum granulysin levels were assayed by ELISA. Granulysin-positive cells were seen in specimens from oral ulcers, genital ulcers and acne-like eruptions, but not erythema nodosum-like lesions. Both CD4+ and CD8+ T cells expressed granulysin. Serum granulysin levels did not correlate with disease activity in BD. Immune reactions mediated by granulysin-positive CTLs may play an important role in the pathogenesis of acne-like eruptions, oral ulcers and genital ulcers in BD.

Critical role of IL-21 in modulating TH17 and regulatory T cells in Behçet disease

Behçet disease (BD) is a chronic systemic inflammatory disorder of unknown etiology. To determine the nature of T cells driving inflammatory lesions in BD. T cell homeostasis and cytokines production were analyzed in peripheral blood and brain inflammatory lesions from 45 adult patients with BD (active and untreated BD [n = 25] and patients in remission [n = 20]) and 20 healthy donors, using Luminex, flow cytometry, immunohistochemistry, and immunofluorescence analysis. We found a marked increase in T(H)17 cells and a decrease in the frequency of CD4(+) forkhead box P3(+) regulatory T cells (Tregs) in peripheral blood that were induced by IL-21 production and that correlate with BD activity. The addition of serum from patients with active BD in a sorted CD4(+) T cells culture of healthy donors induced a significant and dose-dependent production of IL-17A and a decrease in forkhead box P3 expression. We demonstrated the presence of IL-21- and IL-17A-producing T cells within the cerebrospinal fluid, brain parenchyma inflammatory infiltrates, and intracerebral blood vessels from patients with active BD and central nervous system involvement. The stimulation of CD4(+) T cells with IL-21 increased T(H)17 and T(H)1 differentiation and decreased the frequency of Treg cells. Conversely, IL-21 blockade with an IL-21R-Fc restored the T(H)17 and Treg homeostasis in patients with BD. We provided here the first evidence of the critical role of IL-21 in driving inflammatory lesions in BD by promoting T(H)17 effectors and suppressing Treg cells. IL-21 represents a promising target for novel therapy in BD.

Recurrent Aortic Aneurysms In Behçet Disease

The following is a case of a 22-year-old male with recurrent thoracic aneurysms with several constitutional symptoms, including gastrointestinal discomfort, irritable bowel syndrome, lactose intolerance, and a 2-week history of severe lower back pain. The patient underwent an initial thoracoabdominal repair of a visceral aneurysm followed by endovascular repair of a recurrent thoracic pseudoaneurysm. The etiology of the visceral aneurysm was initially hypothesized to be mycotic; however, further information revealed signs and symptoms consistent with the diagnostic criteria for Behçet disease (BD). We suggest that BD be considered in younger patients who present with an aortic aneurysm. Although open repair is the traditional approach for arterial lesions in BD, the role for endovascular intervention should be considered as it represents a surgical repair with a significant reduction in morbidity.

HSP 60 expression in recurrent oral ulcerations of Behçet's disease

The aim was to investigate heat shock protein 60 (HSP60) expression in oral ulcerations of Behçet's disease (BD). Biopsy specimens were obtained from patients with BD (n = 11), recurrent aphthous stomatitis (RAS) (n = 11), oral lichen planus (OLP) (n = 11) and healthy individuals (HI) (n = 11). Eight samples in BD and RAS groups were evaluable. All groups were analyzed by biotin streptavidin-aminoethylcarbazole using monoclonal mouse antibodies to HSP60 Ab-1 (clone LK1). Immunostaining indicative of HSP60 expression in BD and RAS were significantly higher than HI. No significant difference was found between BD and OLP except in the suprabasal layer of epithelium. Altered expression of HSP60 was found in ulcerative lesions of BD and RAS suggesting that HSP60 has an association with the etiology or chronicity of these inflammatory lesions.

Primary localized cutaneous amyloidosis intermingled with papulopustular lesions in a patient with Behçet’s disease

Primary localized cutaneous amyloidosis (PLCA) sometimes shows overlapping with collagen vascular diseases; however, association with Behçet's disease (BD) is rare. We herein report a case of PLCA developing intermingled with papulopustular lesions associated with BD. A 57-year-old woman visited our hospital, complaining of recalcitrant multiple oral aphthae. Further detailed physical examination revealed folliculitis-like small pustules with surrounding erythema on the upper back. Also, she stated past histories of genital ulcers 10 years ago and erythema nodosum on the lower legs 4 years ago. A biopsy specimen from the pustular lesion on the back showed neutrophilic abscess in the epidermis with a number of perivascular inflammatory cells in the upper dermis. Congo-red and Dylon stain revealed amyloid deposition in the papillary dermis. Although association of systemic amyloidosis with BD is occasionally found in the literature, co-occurrence of cutaneous amyloidosis and papulopustular lesions of BD is extremely rare.

Involvement of innate immunity in the pathogenesis of intestinal Behçet's disease

The involvement of excessive T helper 1 (Th1) cell functions in the pathogenesis of Behçet's disease (BD) has been reported. We therefore studied Toll-like receptor (TLR)-expressing cells, which play important roles in innate immunity in patients with BD. Peripheral blood mononuclear cells (PBMC) of BD and healthy controls, and tissue specimens of intestinal BD and Crohn's disease (CD) were analysed for messenger RNA (mRNA) and protein expressions by reverse transcription-polymerase chain reaction and immunostaining respectively. PBMC of BD expressed TLR-2 and TLR-4 mRNA almost comparable with healthy controls. Intestinal lesions of BD expressed TLR-2 and TLR-4 mRNA consistently. In contrast, TLR-4 mRNA was expressed preferentially and TLR-2 mRNA was expressed less frequently in CD lesions. In intestinal samples of BD, TLR-2 and TLR-4 mRNA were detected in ileocaecal ulcer lesions, but not in unaffected sites of the same sample, indicating the association of the TLR expression with the disease manifestation of intestinal BD. TLR-2-expressing cells which were simultaneously cluster of distribution (CD)68-positive produced interleukin (IL)-12 in the lesions, indicating the participation of TLR-2-expressing cells in the Th1 skewed responses in vivo. As a possible ligand of TLR-2, in BD self-heat shock protein 60 was expressed in peripheral blood lymphocytes and intestinal tissues. Collectively, TLR-2-expressing cells as well as TLR-4-expressing cells accumulated in the intestinal lesions of BD. IL-12 produced by TLR-2-expressing cells may contribute to the induction of Th1-dominant immune responses in intestinal BD.

Increased expression of interleukin-23 p19 mRNA in erythema nodosum-like lesions of Behçet’s disease

Behçet's disease (BD) is a multisystemic chronic inflammatory disease with unknown aetiology. Interleukin (IL)-12, which is involved in the pathogenesis of BD, is a 70-kDa cytokine made of p35 and p40 subunits. Recently, IL-23, which is composed of a p19 subunit and a shared p40 subunit of IL-12, was discovered; as a consequence, this raises the need to re-examine previous IL-12 reports to determine whether IL-23 is also involved in BD pathogenesis. To determine whether there are changes in IL-23 in skin lesions and sera of patients with BD. For quantitative reverse transcription-polymerase chain reaction, the total cellular RNA of erythema nodosum (EN)-like skin lesions from patients with BD, psoriasis skin lesions and skin biopsy samples from normal individuals was analysed. To determine cytokine levels, sera from patients with BD and normal individuals were analysed. Increased IL-23 p19 mRNA levels were observed for both EN-like lesions of patients with BD and skin lesions of patients with psoriasis compared with normal individuals. Although we observed an elevation of IL-12/23 p40 mRNA expression in the BD lesions, this was not significant. Moreover, the levels of IL-12 p35 mRNA in BD lesions were also not significantly different from the levels in normal control skin. In addition, no significant changes were detected in serum IL-12 and IL-23 levels between patients with BD and normal control individuals, or in patients with BD before and after treatment. Increased expression of IL-23 p19 mRNA in BD lesions suggests that IL-23 may be associated with the development of the EN-like lesions in patients with active BD.