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

BACKGROUND: 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. OBJECTIVES: To determine pathological changes in BD skin lesions related to the complex genetic predisposition. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Ulcerative IgA vasculitis in the setting of warfarin therapy.

Henoch-Schönlein purpura (HSP) is a small vessel vasculitis characterized by the presence of vascular immunoglobulin A deposition that usually presents as non-thrombocytopenic palpable purpura. It primarily affects children and is less common in adults. The incidence of hemorrhagic necrotic skin lesions increases with age, similarly to renal involvement. Warfarin is a widely used oral anticoagulant drug that has rarely been associated with leukocytoclastic vasculitis and allergic interstitial nephritis. We report a patient with HSP who presented with cutaneous ulcerative plaques and proteinuria in the setting of warfarin therapy. We would like to raise the awareness of this potential adverse effect of warfarin for prompt diagnosis.

Association of pyrin mutations and autoinflammation with complex phenotype hidradenitis suppurativa: a case-control study.

BACKGROUND: Hidradenitis suppurativa (HS) is a rare, debilitating neutrophilic dermatosis characterized by chronic inflammation of hair follicles. Many inflammatory conditions may accompany HS. OBJECTIVES: To investigate the association of variants of the MEFV gene with a complex HS phenotype. METHODS: Firstly, we identified the clinical characteristics of 119 patients with HS with a complex phenotype (Hurley stage III disease and/or additional inflammatory symptoms). Then, we searched for MEFV variants among these patients. The odds ratios (ORs) for pathogenic MEFV mutations were calculated using data from these patients with HS and 191 healthy controls. RESULTS: The male/female ratio was higher, and the mean age of onset was earlier, in our complex HS group compared with patients with HS in general. Five of the patients with HS (4·2%) had a diagnosis of familial Mediterranean fever (FMF) with a standardized morbidity ratio of 45 [95% confidence interval (CI) 16·50-99·84, P < 0·001] when compared with the frequency of FMF in the general Turkish population. Of the patients with complex HS, 38% were positive for pathogenic variants of MEFV. The OR for carrying a pathogenic MEFV allele was 2·80 (95% CI 1·31-5·97, P < 0·001). CONCLUSIONS: The frequency of MEFV mutations in the group of patients with complex HS was higher than that in healthy controls, suggesting that MEFV mutations may contribute to the pathogenesis of HS. Understanding the role of autoinflammation in HS is of fundamental importance for the development of novel therapies.

Soluble tumour necrosis factor receptors sTNFR1 and sTNFR2 are produced at sites of inflammation and are markers of arthritis activity in Behçet's disease.

OBJECTIVE: We analysed the production of soluble tumour necrosis factor receptors sTNFR1 and sTNFR2 at sites of inflammation and measured their plasma concentrations to evaluate them as biological markers of disease activity. METHODS: Plasma samples of 35 patients with Behçet's disease (BD) were collected prospectively at monthly intervals and grouped for inactive disease, active BD without arthritis, and active BD with arthritis. sTNFR1 and sTNFR2 concentrations were measured using immunoassays and compared with other biological disease activity parameters. Plasma sTNFR levels were compared to synovial fluid (SF) levels in seven patients. Sixteen tissue samples of mucocutaneous lesions were stained for TNFR2 expression by immunohistochemistry. RESULTS: sTNFR1 and sTNFR2 were found at increased plasma concentrations in active BD, with the highest concentration in active BD with arthritis (p<0.001). Concentrations of both sTNFRs were at least three times higher in SF of arthritic joints than in the corresponding plasma samples (p = 0.025). A change of more than 1 ng/mL of sTNFR2 plasma concentrations correlated with a concordant change in arthritic activity (96% confidence interval). Sensitivity to change was superior to that of sTNFR1, and other biological disease activity parameters such as erythrocyte sedimentation rate (ESR), immunoglobulin (Ig)G, IgA, and interleukin (IL)-10 plasma concentrations. A strong staining for TNFR2 was found in mucocutaneous lesions, where mast cells were identified as the major source for this receptor. CONCLUSIONS: This longitudinal study demonstrates that sTNFR2 plasma concentrations are closely linked with active BD, and especially with arthritis. Taken together with the expression of TNFR molecules in mast cells of mucocutaneous lesions, our results indicate a fundamental role for the TNF/TNFR pathway in BD.

Behçet's disease-like presentation of bullous pyoderma gangrenosum associated with Crohn's disease.

A 47-year-old woman presented with a 2-month history of generalized arthralgia and a 10-day history of oral aphthous ulcers. After hospitalization, papulopustular lesions and perianal ulcerations developed. Pathergy test was positive and ophthalmological examination was normal. The presence of oral aphthous ulcers, genital ulcerations, papulopustular lesions and arthralgia, and the positive pathergy test suggested the diagnosis of Behçet's disease (BD). In a few days, positive pathergy reactions and papulopustular lesions evolved into bullous lesions, which were diagnosed dermatopathologically as pyoderma gangrenosum. Two days after the presentation of papulopustular lesions, the patient experienced diarrhoea accompanied by bloody stools and mucus. Histopathological examination of biopsy specimens showed no vasculitis but revealed findings suggestive of Crohn's disease. The patient responded well to treatment with systemic steroids and 5-aminosalicylic acid. Our case demonstrates that the differential diagnosis of BD and inflammatory bowel disease may be perplexing and that these two diseases may be closely related.

The prevalence of Behçet's disease above the age of 10 years. The results of a pilot study conducted at the Park Primary Health Care Center in Ankara, Turkey.

PURPOSE: The aim of this study was to determine the prevalence of Behçet's disease above the age of 10 years by means of a population-based study. METHODS: The epidemiological investigation (cross-sectional study) was made between May 1997 and May 1998 at the Park Primary Health Care Center, which is one of the education and research divisions of the Department of Public Health, Faculty of Medicine, Ankara University. The research aimed to cover all 17,256 (49.2% male, 50.8% female) inhabitants over 10 years of age living in this area. The screening team first surveyed and selected patients with recurrent aphthous stomatitis. These patients were further examined, free of charge, in the Preventive Ophthalmology Unit of the Public Health Center, at Ibni Sina Hospital's Behçet Center or in other clinics if necessary. In this study the International Study Group For Behçet's disease Criteria were used. RESULTS: As the final result of the screening, 11 female and 5 male patients with Behçet's disease were found (female/male = 2.2). These patients represented 9 already known and 7 newly diagnosed cases of Behçet's disease. The prevalence of Behçet's disease over 10 years of age is 0.11%. CONCLUSION: The existing regional prevalance studies conducted in Turkey have indicated that the real number of Behçet's patients in our country is markedly higher than the number of registered patients. Therefore the National Behçet's Disease Commity and Surveillance System was founded by our research group in December 1999.

Treatment of epidermodysplasia verruciformis with a combination of acitretin and interferon alfa-2a.

Epidermodysplasia verruciformis (EV) is an autosomal recessive disease characterized by the lifelong eruption of disseminated verrucae-like lesions. Numerous treatment modalities have been used to treat EV without benefit. Recently, retinoid and interferon therapies have been found to be of value in the treatment of EV. We present a case of EV that was treated with a combination of acitretin and interferon alfa-2a.

Livedoid vasculopathy associated with heterozygous protein C deficiency.

Livedoid vasculopathy is characterized by recurrent painful ulceration of the feet, ankles and legs that heals with residual white atrophic scars. For many years, livedoid vasculopathy has been considered to be a primary vasculitic process. Recently, however, there has been a trend towards considering livedoid vasculopathy as an occlusive vasculopathy due to a hypercoagulable state. Livedoid vasculopathy (under the designation livedo vasculitis) was first reported to be associated with protein C deficiency in 1992. We describe an additional patient with livedoid vasculopathy associated with heterozygous protein C deficiency. This second reported case suggests that protein C deficiency may be one cause of the hypercoagulable condition in these patients and demonstrates the necessity for further investigation of thrombogenic factors underlying the disease.

Interaction of commonly used emollients with photochemotherapy.

BACKGROUND/AIM: Even though emollients are commonly used in combination with photochemotherapy, we still lack guidance for the selection of the appropriate emollient to be used in combination with photochemotherapy. The purpose of our study was to determine the interaction of commonly used emollients with photochemotherapy. METHODS: The study was carried on 75 healthy volunteers. In order to assess the effects of five different emollients--white petrolatum, 3% salicylic acid in white petrolatum, Balmandol, Decubal and Urederm hydro--the subjects were divided into five groups. Minimal phototoxic dose (MPD) was determined by irradiating two rows of six circular test fields on the back of the subjects with increasing doses of UVA. One of the emollients listed above was applied to the skin under the upper rows alternatively, whereas the lower rows served as control. RESULTS: Application of Urederm hydro and Decubal before exposure to UVA resulted in a statistically significant decrease in the MPD in all subjects. Even though application of white petrolatum and white petrolatum containing 3% salicylic acid decreased the MPD in most of the subjects and Balmandol application slightly increased the MPD, the results did not reach statistical significance. CONCLUSIONS: According to our findings, it is probable that the total dose of UVA needed to cause clearing of psoriasis would be decreased by application of Urederm hydro and Decubal prior to photochemotherapy. We noted a slight photoprotective effect of Balmandol in the UVA range, but this finding has to be further studied. Clinical studies are needed to clarify the effects of these emollients on the course and outcome of photochemotherapy.

Long-term effects of interferon alpha 2A treatment in Behçet's disease.

BACKGROUND: Between May 1995 and April 1996, 20 patients with Behçet's disease were successfully treated with interferon alpha(2a) (IFN-alpha(2a)) 9 million IU/day three times a week and 16 patients with colchicine 1.5 mg/day orally for 3 months. OBJECTIVE: To study the long-term effects of IFN treatment in Behçet's disease. METHODS: Between the years of 1996 and 1999, the patients were followed up every 3 months or whenever indicated. Retrospective evaluation was performed. RESULTS: In 56% of the patients with complete remission or partial remission at the end of IFN-alpha(2a) treatment, long-term remissions ranging from 36 to 48 months were observed. CONCLUSION: IFN-alpha(2a) treatment is an effective treatment modality in Behçet's disease with the advantage of inducing prolonged remissions.

The depression, anxiety, life satisfaction and affective expression levels in psoriasis patients.

OBJECTIVE: The aim of this study was to determine the effect of stressful life events on the onset and exacerbation of psoriasis, depression, anxiety, life satisfaction and affective expression levels in psoriasis patients and psychological risk factors related to psoriasis. METHOD: Fifty psoriasis patients were examined dermatologically and psychiatrically and then administered the Beck Depression Inventory (BDI), Spielberger State-Trait Anxiety Scale (STAI I-II), Life Satisfaction Scale (LSS), Courtauld Emotional Control Scale (CECS) and Body Image Satisfaction Scale (BIS). Symptom severity was measured by the Psoriasis Area Severity Index (PASI). RESULTS: Thirty-four patients declared that they had had a psychologically stressful life event in the last 3 months prior to the beginning of the illness. The mean PASI score was 1.75+/-1.65; BDI score 13.58+/-6.11; STAI-I score 39.54+/-9.18, STAI-II score 46.58+/-8.05; LSS score 9.18+/-4.39; CECS score 51.64+/-9.75; BIS score 93.74+/-16.67. CONCLUSION: Psoriasis patients reported significantly higher degrees of depression and more body cathexis problems than controls. In addition, the risk for developing psoriasis increased significantly in patients with moderate and severe depression. We also found a relationship between symptom severity and low affective expression and high BDI scores in this study. These findings suggest that the relationship between psoriasis and psychological problems can be reciprocal and requires further investigation.