Genital ulcer severity score and genital health quality of life in Behçet's disease

Background: Behçet's Disease (BD) is a chronic auto-inflammatory, multisystem relapsing/remitting disorder of unknown aetiology. Oro-genital ulceration is a key feature of the disease and has a major impact on the patients' quality of life. Other clinical manifestations include ocular inflammation, rheumatologic and skin involvement, while CNS and vascular complications can lead to considerable morbidity. The availability of a valid monitoring tool for BD activity is crucial in evaluating the impact of the disease on daily life activity. The aims of this study were to validate a novel tool for monitoring genital ulceration severity in BD and to assess the impact of genital ulcers on the Genital Health Quality of Life (GHQoL). Methods: Genital Ulcer Severity Score (GUSS) was developed using six genital ulcer characteristics: number, size, duration, ulcer-free period, pain and site. A total of 207 BD patients were examined, (137 females: mean age∈±∈SD: 39.83∈±∈13.42 and 70 males: mean age∈±∈SD: 39.98∈±∈11.95) from the multidisciplinary Behçet's Centre of Excellence at Barts Health NHS Trust. GUSS was used in conjunction with Behçet's Disease Current Activity Form (BDCAF). Results: The over-all score of GUSS showed a strong correlation with all genital ulcer characteristics, and the strongest correlation was with the pain domain (r∈=∈0.936; P∈2: 0.600; P∈<∈0.0001). Conclusions: This study established the practicality of GUSS as a severity monitoring tool for BD genital ulcers and validated its use in 207 patients. Genital ulcers of BD have a considerable impact on the patients GHQoL

Thrombosis in vasculitis: from pathogenesis to treatment

In recent years, the relationship between inflammation and thrombosis has been deeply investigated and it is now clear that immune and coagulation systems are functionally interconnected. Inflammation-induced thrombosis is by now considered a feature not only of autoimmune rheumatic diseases, but also of systemic vasculitides such as Behçet’s syndrome, ANCA-associated vasculitis or giant cells arteritis, especially during active disease. These findings have important consequences in terms of management and treatment. Indeed, Behçet’syndrome requires immunosuppressive agents for vascular involvement rather than anticoagulation or antiplatelet therapy, and it is conceivable that also in ANCA-associated vasculitis or large vessel-vasculitis an aggressive anti-inflammatory treatment during active disease could reduce the risk of thrombotic events in early stages. In this review we discuss thrombosis in vasculitides, especially in Behçet’s syndrome, ANCA-associated vasculitis and large-vessel vasculitis, and provide pathogenetic and clinical clues for the different specialists involved in the care of these patients

Pemphigus autoimmunity: Hypotheses and realities

The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus is to achieve and maintain clinical remission without corticosteroids. Recent advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve controversies, and open novel perspectives for treatment. Elucidation of intimate mechanisms of keratinocyte detachment and death in pemphigus has challenged the monopathogenic explanation of disease immunopathology. Over 50 organ-specific and non-organ-specific antigens can be targeted by pemphigus autoimmunity, including desmosomal cadherins and other adhesion molecules, PERP cholinergic and other cell membrane (CM) receptors, and mitochondrial proteins. The initial insult is sustained by the autoantibodies to the cell membrane receptor antigens triggering the intracellular signaling by Src, epidermal growth factor receptor kinase, protein kinases A and C, phospholipase C, mTOR, p38 MAPK, JNK, other tyrosine kinases, and calmodulin that cause basal cell shrinkage and ripping desmosomes off the CM. Autoantibodies synergize with effectors of apoptotic and oncotic pathways, serine proteases, and inflammatory cytokines to overcome the natural resistance and activate the cell death program in keratinocytes. The process of keratinocyte shrinkage/detachment and death via apoptosis/oncosis has been termed apoptolysis to emphasize that it is triggered by the same signal effectors and mediated by the same cell death enzymes. The natural course of pemphigus has improved due to a substantial progress in developing of the steroid-sparing therapies combining the immunosuppressive and direct anti-acantholytic effects. Further elucidation of the molecular mechanisms mediating immune dysregulation and apoptolysis in pemphigus should improve our understanding of disease pathogenesis and facilitate development of steroid-free treatment of patients

Immunopathologic features of pemphigus in the east mediterranean region of Turkey: A prospective study

PubMedID: 20839419Pemphigus, a life-threatening autoimmune disorder, is the most common autoimmune bullous disease in the Mediterranean region of Turkey. No studies have investigated the immunopathologic features of this geographic setting. To determine the immunopathologic features of pemphigus in the Eastern Mediterranean region of Turkey, the authors evaluated the histopathological, immunofluorescence (IF), and enzyme-linked immunosorbent assay (ELISA) results in a 4-year study. In this prospective study, tissue from 174 patients was analyzed by direct IF (DIF); 384 by indirect IF (IIF) from 61 patients with pemphigus; and 88 by ELISA for antibodies against desmoglein (Dsg) 1 and Dsg 3 from 50 of those 61 patients. Pemphigus vulgaris (PV) was the most commonly observed subtype (46 of 61 patients, 75.41%), followed by pemphigus foliaceus (9 of 61 patients, 14.75%), pemphigus erythematosus (5 of 61 patients, 8.2%), and pemphigus herpetiformis (1 of 61 patients, 1.64%). There was a significant correlation between clinical activity score (CAS) and IgG antibody titer in IF (P<.001) and ELISA tests (P=.024 for Dsg 1; P=.028 for Dsg 3). Antibody titers and C3 scale did not predict exacerbations and relapse. The commonest clinical subtype of pemphigus was PV in this region. Results indicate that IgG antibody titer in IF and ELISA tests of patients with pemphigus are correlated with CAS; however, they are not useful in predicting exacerbations and relapse of disease. © 2010 Pulse Marketing & Communications, LLC. All rights reserved

The clinical course of Behcet's disease in pregnacy: A retrospective analysis and review of the literature

WOS: 000184233700001PubMed ID: 12928538Although Behcet's disease is mainly diagnosed during the reproductive periods of life, we know little about the influence of pregnancy on the clinical course of Behcet's disease. Therefore, we analyzed the relationship between Behcet's disease and pregnancy retrospectively, in order to detect any possible interaction between the two multisystemic processes, particularly in regard to the influence of pregnancy on the clinical course of Behcet's disease. We studied 44 pregnancies in 28 women with Behcet's disease. The diagnoses were made according to the criteria of the International Study Group for Behcet's disease. The patients were observed during pregnancy and puerperium periods at monthly intervals. The existence and incidence of symptoms were recorded during these periods. There was remission of Behcet's disease during 23 (52.3%) pregnancies, although the disease had been in a stage of exacerbation before pregnancy. The disease became exacerbated during 12 (27.3%) pregnancies, although it had been in a stage of remission before pregnancy. There were no changes in the clinical course of Behcet's disease in 9 (20.4%) pregnancies. The most frequent manifestations of the clinical exacerbation were increases in the intensity and severity of outbreaks of oral ulcers during pregnancy. Outbreaks of genital ulcers, eye inflammations, and arthritis were other signs of exacerbation. Other than spontaneous abortion in three patients, we did not observe maternal or fetal complications. Although Behcet's disease tends toward remission during pregnancy, the influence of pregnancy on its clinical course is quite variable between patients and even during different pregnancies in the same patient. On the basis of our and previous results, we speculate that pregnancy in general does not seem to markedly affect the natural course of Behcet's disease

A case of lupus erythematosus profundus with unusual manifestations

PubMedID: 15934442We describe a 16-year old female with lupus erythematosus panniculitis with unusual manifestations. She had noted to have developed erythematous nodules and plaques in the right axilla and inguinal region at the age of one year. These lesions resolved gradually with scar formation. However, new lesions were noted at the same locations in the following years. Some of her lesions at the scalp and the left axillary regions developing within the last two years slowly enlarged showing an annular configuration and subsequently resulted in hair loss. The erythematous border of her lesion in the left axilla consisted of two parallel red lines. Histopathological and direct immunofluorescent findings were consistent with lupus erythematosus panniculitis. Similar clinical findings in the same locations were also observed in the mother. © 2005 Edward Arnold (Publishers) Ltd

Histological and immunofluorescence findings of non-follicular papulopustular lesions in patients with Behçet's disease

PubMedID: 12941085Background. Papulopustular lesions (PPL), the most common type of cutaneous lesions in Behçet's disease (BD), clinically may not be differentiated from ordinary acne. Disagreement exists as to the exact nature of these acneiform and folliculitis-like lesions and whether to include them as a major criterion. Objective. We investigated whether PPL can be a useful tool for the diagnosis of BD when non-follicular lesions over the trunk or extremities were selected, and were correlated with histological and/or immunofluorescence study. Methods. Seventeen patients with BD (five women, 12 men; mean ± SEM age, 32 ± 7.9 years), were enrolled in the study with blind histopathological and immunofluorescence studies. Biopsies of the PPL and adjacent (approximately 2 cm distant) normal-appearing skin were performed from the extremities and trunk. Follicle-based acneiform lesions and those lesions over face were excluded. Histological evaluation primarily included epidermal and dermal alterations, cellular infiltration and vascular changes. We also performed direct immunofluorescence studies, using polyclonal antibodies for IgA, IgG, IgM, C3 and fibrin. Results. Lesional specimens of the patients with BD revealed a significant leucocytoclastic vasculitis as compared with non-lesional skin (P < 0.05). The vessels of the lesional skin showed a higher IgM deposition than non-lesional skin (52.9% and 17.6%) (P < 0.05). IgG, C3 and fibrin deposits on the vessels of the lesional skin were also higher than non-lesional skin (35.3, 11.8%; 41.2, 17.6%; and 47.1, 17.6%, respectively), but the differences were not statistically significant. Conclusions. Our findings indicate that non-follicular PPL over the trunk or extremities are more specific, and immune complex-mediated vasculitis is likely to be the main feature of these lesions, as they are in other cutaneous lesions of BD