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BJD Editor’s Choice

        Ciclosporin compared with prednisolone therapy for patients with pyoderma gangrenosum: cost-effectiveness analysis of the STOP GAP trial

        These U.K. authors explain that pyoderma gangrenosum (PG) is a painful, ulcerating skin disease with poor evidence for its management. They state that prednisolone and ciclosporin are the most commonly used treatments, although they have not previously been compared within a randomized controlled trial. The full STOP GAP study was published elsewhere; the objective of this element of the study was to compare the cost-effectiveness of ciclosporin- and prednisolone-initiated treatment for patients with PG. The authors concluded that consistently with the clinical findings of the STOP GAP trial, patients with small PG lesions should receive treatment guided by the side-effect profiles of the drugs and patient preference – they state that neither strategy is clearly a preferred use of National Health Service resources. They go on to explain that ciclosporin-initiated treatment may be more cost-effective for patients with large lesions.
        Br J Dermatol 2017; 177: 1527–1536
        https://doi.org/10.1111/bjd.15561

        Smad7 knockdown leads to reduced keratinocyte growth: a potential novel therapeutic discovery for psoriasis

        These researchers from Rome explain that transforming growth factor (TGF)-β1 exerts inhibitory effects on keratinocyte proliferation. Their aim in this study was to examine whether Smad7, a known inhibitor of TGF-β1 signalling, is involved in psoriasis-associated keratinocyte hyperproliferation. They found that Smad7 was highly expressed in keratinocytes of patients with psoriasis and of mice treated with Aldara (imiquimod). In HaCaT cells, Smad7 knockdown inhibited cell growth, reduced keratin (K)6 and K16 expression and promoted accumulation of cells in the S-phase of the cell cycle. Smad7-deficient keratinocytes exhibited reduced levels of CDC25A protein, a phosphatase that facilitates progression of cells through the S-phase, and hyperphosphorylation of eukaryotic initiation factor-2α, a negative regulator of CDC25 protein translation. Consistently, Smad7 overexpression in HaCaT cells was followed by induction of K6 and K16 and increased cell proliferation. Topical application of Smad7 AS oligonucleotide to Aldara-treated mice reduced epidermal thickness. The authors concluded that their data showed that Smad7 is overexpressed in human and murine psoriasis, which suggests a key role of this molecule in the control of keratinocyte proliferation. Their translational message was that the findings described in this work, together with their recent demonstration that Smad7 AS-based therapy is safe and effective in patients with inflammatory bowel diseases, suggest that restoring TGF-β signalling through Smad7 knockdown may help to attenuate the pathological lesions in human psoriasis.
        Br J Dermatol 2017; 177: 1633–1643
        https://doi.org/10.1111/bjd.15703

        Are guidelines as high quality as they claim to be?

        Eady and colleagues set out to determine the quality of recently published acne treatment guidelines by utilizing the Appraisal of Guidelines for Research and Evaluation (AGREE) II Reporting Checklist, the U.S. Institute of Medicine’s (IOM) criteria of trustworthiness, the red flags of Lenzer et al. and CheckUp. They carried out systematic searches of bibliographic databases and guideline depositories and used Google to identify acne treatment guidelines published since 2013. Six assessors independently scored each guideline using the AGREE II reporting checklist. Guidelines were concomitantly assessed for trustworthiness using the IOM criteria and for the red flags of Lenzer et al., indicative of potential bias. Updates were screened using CheckUp. They found eight guidelines, two of which were updates. The lowest-scoring AGREE II domains across all guidelines were rigour (six poor,one fair, one average) and applicability (four poor, one fair, three average). Paradoxically, two of the three highest-scoring guidelines were developed using AGREE II. No guideline fully met each IOM criterion and all raised at least one red flag indicative of potential bias. One updated guideline did not address seven of 16 items on CheckUp and the other did not address four. Patient involvement in guideline development was minimal. The authors concluded that use of the AGREE II instrument during guideline development did not have as great an effect on guideline quality as might be expected. Thus, there is considerable room for improvement in acne treatment guidelines in order to satisfy the IOM trustworthiness criteria and avoid bias.
        Br J Dermatol 2017; 177: 1716–1725
        https://doi.org/10.1111/bjd.15777