203 research outputs found
Beyond the skin: disease parameters in pemphigus
No full textPemphigus represents a group of rare autoimmune bullous diseases that affect the skin and mucous membranes. This group has a chronic course leading to high morbidity and mortality. Because of the painful chronic-recurring blisters and/or erosions on skin and mucosa, pemphigus can impair quality of life (QOL). Therapeutic modalities, anxiety and depression can also have an additional negative impact in the QOL of the pemphigus patients. Since the nature and course of the pathology and the fact that pemphigus worsens the quality of life of affected patients, scoring systems to objectively evaluate the clinical activity of the disease and to correlate that with the QOL are needed. Nowadays the most used global scales to assess the clinical activity of pemphigus are the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS), the Pemphigus Disease Area Index (PDAI) and the Pemphigus Visual Activity Scale (PVAS). To evaluate the patient's generic QOL the most used score is the Dermatology Life Quality Index (DLQI), but all the sponsered clinical trials in pemphigus are using ABQOL this rather than DLQI
Flightless I over-expression impairs skin barrier development, function and recovery following skin blistering
No full textAbstract not availableZlatko Kopecki, Gink N Yang, Ruth M Arkell, Jessica E Jackson, Elizabeth Melville, Hiroaki Iwata, Ralf J Ludwig, Detlef Zillikens, Dedee F Murrell and Allison J Cowi
Bullous pemphigoid: therapeutic algrorithm and practical management
No full textIntroduction: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucosae. BP typically affects the elderly and manifests with severe itch, localised or generalised eczematous, urticated and/or bullous lesions. Its morbidity and impact on the quality of life are important. The disease is significantly associated with neurological disorders, such as stroke, Parkinson disease, major cognitive impairment and multiple sclerosis. Diagnosis of BP critically relies on immunopathologic examinations, particularly direct immunofluorescence microscopy studies.
Areas covered: This paper looks at the evidence of therapies commonly used in bullous pemphigoid.
Expert opinion: Treatment of BP has been a challenge, given the relative rarity of the disease, lack of good quality randomised controlled trials, the presence of co-morbidities in the affected elderly population and the high mortality rate. Recent controlled studies have indicated that potent topical corticosteroids constitute a more effective therapy for BP when compared to oral corticosteroids in terms of control of the disease, side effect profile and overall survival. Other therapies have been employed with varying success, but are not validated yet. Improved knowledge of the pathophysiology of BP will hopefully allow the development of new immunomodulatory treatments for this debilitating disease
A lesson learned about predatory journals and their difference from peer-reviewed open-access publishing
No full textTopically applied flightless I neutralizing antibodies improve healing of blistered skin in a murine model of Epidermolysis Bullosa Acquisita
No full textData source: supplementary material, https://doi.org/10.1038/jid.2012.457Epidermolysis bullosa (EB) is a chronic inheritable disease that leads to severe blistering and fibrosis. Previous studies have shown that the actin cytoskeletal protein flightless I (Flii) impairs wound healing associated with EB. Using a mouse model of EB acquisita (EBA), the effect of ‘‘mopping up’’ Flii using Flii-neutralizing antibodies (FnAbs) before, during, and after blister formation was determined. FnAbs, incorporated into a cream vehicle and applied topically to the skin, penetrated into the basal epidermis and upper papillary dermis but were not detected in serum or other organs and did not alter neutrophil or macrophage infiltration into the blistered skin. Histological assessment of blister severity showed that treatment of early-stage blisters with FnAb cream reduced their severity and improved their rate of healing. Treatment of established blisters with FnAb cream also improved healing and restored the skin’s tensile strength toward that of normal skin. Repeated application of FnAbs to EBA skin before the onset of blistering reduced the severity of skin blistering. Independent of when the FnAbs were applied, skin barrier function and wound healing were improved and skin fragility was reduced, suggesting that FnAbs could potentially improve healing of patients with EB.Zlatko Kopecki, Nadira Ruzehaji, Christopher Turner, Hioraki Iwata, Ralf J. Ludwig, Detlef Zillikens, Dedee F. Murrell and Allison J. Cowi
Autoimmune Subepidermal Bullous Diseases of the Skin and Mucosae: Clinical Features, Diagnosis, and Management.
No full textAutoimmune subepidermal blistering diseases of the skin and mucosae constitute a large group of sometimes devastating diseases, encompassing bullous pemphigoid, gestational pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, and anti-p200 pemphigoid. Their clinical presentation is polymorphic. These autoimmune blistering diseases are associated with autoantibodies that target distinct components of the basement membrane zone of stratified epithelia. These autoantigens represent structural proteins important for maintenance of dermo-epidermal integrity. Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering disease of the skin and mucosae. Although the disease typically presents with a generalized blistering eruption associated with itch, atypical variants with either localized bullous lesions or "non-bullous" presentations are observed in approximately 20% of patients. A peculiar form of BP typically associated with pregnancy is pemphigoid gestationis. In anti-p200 pemphigoid, patients present with tense blisters on erythematosus or normal skin resembling BP, with a predilection for acral surfaces. These patients have antibodies targeting the 200-kDa basement membrane protein. Epidermolysis bullosa is a rare autoimmune blistering disease associated with autoantibodies against type VII collagen that can have several phenotypes including a classical form mimicking dystrophic epidermolysis bullosa, an inflammatory presentation mimicking BP, or mucous membrane pemphigoid-like lesions. Mucous membrane pemphigoid (MMP) is the term agreed upon by international consensus for an autoimmune blistering disorder, which affects one or more mucous membrane and may involve the skin. The condition involves a number of different autoantigens in the basement membrane zone. It may result in severe complications from scarring, such as blindness and strictures. Diagnosis of these diseases relies on direct immunofluorescence microscopy studies and immunoserological assays. Management of affected patients is often challenging. We will here review the clinical and immunopathological features as well as the pathophysiology of this group of organ-specific autoimmune diseases. Finally, we will discuss the diagnostic approach and the principles of management in clinical practice
Interventions for bullous pemphigoid
No full textBackground Bullous pemphigoid (BP) is the most common autoimmune blistering disease in the West. Oral steroids are the standard treatment.This is an update of the review published in 2005. Objectives To assess treatments for bullous pemphigoid. Search strategy In August 2010 we updated our searches of the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (Clinical Trials), MEDLINE, EMBASE, and the Ongoing Trials registers. Selection criteria Randomised controlled trials of treatments for participants with immunofluorescence-confirmed bullous pemphigoid. Data collection and analysis At least two authors evaluated the studies for the inclusion criteria, and extracted data independently. Main results We included 10 randomised controlled trials (with a total of 1049 participants) of moderate to high risk of bias. All studies involved different comparisons, none had a placebo group. In 1 trial plasma exchange plus prednisone gave significantly better disease control at 1 month (0.3 mg/kg: RR 18.78, 95% CI 1.20 to 293.70) than prednisone alone (1.0 mg/kg: RR 1.79, 95% CI 1.11 to 2.90), while another trial showed no difference in disease control at 6 months. No differences in disease control were seen for different doses or formulations of prednisolone (one trial each), for azathioprine plus prednisone compared with prednisone alone (one trial), for prednisolone plus azathioprine compared with prednisolone plus plasma exchange (one trial), for prednisolone plus mycophenolate mofetil or plus azathioprine (one trial), for tetracycline plus nicotinamide compared with prednisolone (one trial). Chinese traditional medicine plus prednisone was not effective in one trial. There were no significant differences in healing in a comparison of a standard regimen of topical steroids (clobetasol) with a milder regimen (RR 1.00, 95% 0.97 to 1.03) in one trial. In another trial, clobetasol showed significantly more disease control than oral prednisolone in people with extensive and moderate disease (RR 1.09, 95% CI 1.02 to 1.17), with significantly reduced mortality and adverse events (RR 1.06, 95% CI 1.00 to 1.12). Authors' conclusions Very potent topical steroids are effective and safe treatments for BP, but their use in extensive disease may be limited by side-effects and practical factors. Milder regimens (using lower doses of steroids) are safe and effective in moderate BP. Starting doses of prednisolone greater than 0.75 mg/kg/day do not give additional benefit, lower doses may be adequate to control disease and reduce the incidence and severity of adverse reactions. The effectiveness of adding plasma exchange, azathioprine or mycophenolate mofetil to corticosteroids, and combination treatment with tetracycline and nicotinamide needs further investigation.Gudula Kirtschig, Philippa Middleton, Cathy Bennett, Dedee F Murrell, Fenella Wojnarowska, Nonhlanhla P Khumal
Overexpression of the Flii gene increases dermal-epidermal blistering in an autoimmune ColVII mouse model of epidermolysis bullosa acquisita
No full textData source: Supporting information, http://onlinelibrary.wiley.com.access.library.unisa.edu.au/doi/10.1002/path.2973/abstract;jsessionid=B184518E13E3CE2B8D9CE19084C524FF.f04t03#footer-support-info
Link to a related website: https://openresearch-repository.anu.edu.au/bitstream/1885/64116/2/01_Kopecki_Overexpression_of_the__Flii__2011.pdf, Open Access via UnpaywallEpidermolysis bullosa (EB) is a severe genetic skin fragility syndrome characterized by blister formation. The molecular basis of EB is still largely unknown and wound healing in patients suffering from EB remains a major challenge to their survival. Our previous studies have identified the actin remodelling protein Flightless I (Flii) as an important mediator of wound repair. Here we identify Flii as a novel target involved in skin blistering. Flii expression was significantly elevated in 30 patients with EB, most prominently in patients with recessive dystrophic EB (RDEB) who have defects in production of type VII collagen (ColVII). Using an autoimmune ColVII murine model of EB acquisita (EBA) and an immunocompetent-ColVII-hypomorphic genetic mouse model of RDEB together with murine Flii alleles, we investigated the contribution of Flii to EB. Overexpression of Flii produced severe blistering post-induction of EBA, while decreased Flii reduced blister severity, elevated integrin expression, and improved ColVII production. Flii(+/-) blistered skin showed reduced α-SMA, TGF-β1, and Smad 2/3 expression, suggesting that decreasing Flii may affect fibrosis. In support of this, Flii-deficient fibroblasts from EBA mice were less able to contract collagen gels in vitro; however, addition of TGF-β1 restored collagen contraction, suggesting an interplay between Flii and TGF-β1. Elevated Flii gene and protein expression was further observed in the blisters of ColVII hypomorphic mice, a murine model of RDEB, suggesting that reducing Flii in blistered skin could be a potential new approach for treating patients with EB.Zlatko Kopecki, Ruth M Arkell, Xanthe L Strudwick, Misa Hirose, Ralf J Ludwig, Johannes S Kern, Leena Bruckner-Tuderman, Detlef Zillikens, Dedee F Murrell and Allison J Cowi
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