22 research outputs found

    Definitions and outcome measures for mucous membrane pemphigoid: Recommendations of an international panel of experts

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    Mucous membrane pemphigoid encompasses a group of autoimmune bullous diseases with a similar phenotype characterized by subepithelial blisters, erosions, and scarring of mucous membranes, skin, or both. Although knowledge about autoimmune bullous disease is increasing, there is often a lack of clear definitions of disease, outcome measures, and therapeutic end points. With clearer definitions and outcome measures, it is possible to directly compare the results and data from various studies using meta-analyses. This consensus statement provides accurate and reproducible definitions for disease extent, activity, outcome measures, end points, and therapeutic response for mucous membrane pemphigoid and proposes a disease extent score, the Mucous Membrane Pemphigoid Disease Area Index

    Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic non-inferiority randomised controlled trial

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    Background: Bullous pemphigoid (BP) is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline conveys acceptable short-term blister control whilst conferring long-term safety advantages over starting treatment with oral corticosteroids. Methods: Pragmatic multi-centre parallel-group randomised controlled trial of adults with BP (≥3 blisters ≥2 sites and linear basement membrane IgG/C3) plus economic evaluation. Participants were randomised to doxycycline (200 mg/day) or prednisolone (0·5 mg/kg/day). Localised adjuvant potent topical corticosteroids (<30 g/week) was permitted weeks 1-3. The non-inferiority primary effectiveness outcome was the proportion of participants with ≤3 blisters at 6 weeks. We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of noninferiority. The primary safety outcome was the proportion with severe, life-threatening or fatal treatment-related adverse events by 52 weeks. Analysis used a regression model adjusting for baseline disease severity, age and Karnofsky score, with missing data imputed. Results: 132 patients were randomised to doxycycline and 121 to prednisolone from 54 UK and 7 German dermatology centres. Mean age was 77·7 years and 68.4% had moderate to severe baseline disease. For those starting doxycycline, 83/112 (74·1%) had ≤3 blisters at 6 weeks compared with 92/101 (91·1%) for prednisolone, a difference of 18·6% favouring prednisolone (upper limit of 90% CI, 26·1%, within the predefined 37% margin). Related severe, life-threatening and fatal events at 52 weeks were 18·5% for those starting doxycycline and 36·6% for prednisolone (mITT analysis), an adjusted difference of 19·0% (95% CI, 7·9%, 30·1%, p=0·001). Conclusions: A strategy of starting BP patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control and significantly safer long-term

    Keratinocyte Interleukin-10 Expression Is Upregulated in Tape-Stripped Skin, Poison Ivy Dermatitis, and Sezary Syndrome, but Not in Psoriatic Plaques

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    Despite the highly diverse reaction patterns of benign and malignant skin diseases involving T lymphocytes, polymerase chain reaction analysis of cytokine mRNAs present in biopsy samples has revealed that many cutaneous responses can be categorized into essentially two discrete groups. One group exemplified by psoriasis is characterized by consistently detectable mRNAs for IL-2, IFN-[gamma], and TNF-[alpha], but not IL-4, IL-5, IL-10, thereby closely resembling the murine Th1-type cell-mediated response. The second group exemplified by tape-stripped skin, poison ivy dermatitis, and Sezary syndrome contains predominantly IL-4, IL-5, and IL-10 mRNAs resembling the Th2-type cytokine profile. Because of the growing interest in the immunoregulatory role of IL-10, which can suppress IFN-[gamma] production and inhibit cell-mediated reactions, we produced a rabbit antiserum that was used to immunohistochemically localize IL-10 in a total of 27 biopsies. The results revealed that in Th2-type skin diseases, IL-10 was predominantly identified throughout all levels of epidermis in the cytoplasm of keratinocytes (KCs), with accentuation of their membranes in upper level cells. In Sezary syndrome, T cells were also immunoreactive for IL-10, which was confirmed using the HUT 78 T cell line derived from a Sezary syndrome patient. While normal skin was devoid of IL-10 expression, KCs began expressing it as early as 6 hr following tape stripping or application of poison ivy antigen and became strongly and diffusely positive by 18-24 hr. In contrast, psoriatic plaques contained no IL-10 immunoreactivity in either the parakeratotic scale or the epidermal KCs. These results confirm the earlier IL-10 mRNA analysis using whole skin samples and immunolocalize IL-10 to epidermal KCs in the Th2 diseases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31273/1/0000179.pd
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