Vanessa Venning

Reducing wound pain in venous leg ulcers with Biatain Ibu : A randomized, controlled double-blind clinical investigation on the performance and safety

Six out of 10 patients with chronic wounds suffer from persistent wound pain. A multinational and multicenter randomized double‐blind clinical investigation of 122 patients compared two moist wound healing dressings: a nonadhesive foam dressing with ibuprofen (62 patients randomized to Biatain Ibu Nonadhesive Coloplast A/S) and a nonadhesive foam without ibuprofen (60 patients to Biatain Non‐Adhesive—comparator). Patients were recruited from September 2005 to April 2006. The ibuprofen foam was considered successful if the pain relief on a five‐point Verbal Rating Scale was higher than the comparator without compromising safety including appropriate healing rate. Additional endpoints were change in persistent wound pain between dressing changes and pain at dressing change on days 1–5 (double blind) and days 43–47 (single blind). The primary response variable, persistent pain relief, was significantly higher in the ibuprofen‐foam group, as compared with the comparator on day 1–5, with a quick onset of action (p<0.05). Wound pain intensity was significantly reduced with the ibuprofen foam during day 1–5 with 40% from baseline, compared with 30% with the comparator (p<0.001). At day 43–47, the patients in the ibuprofen‐foam group had a significant (p<0.05) reemergence of persistent pain and pain at dressing change (p<0.05) when the active dressing was changed to the comparator. Wound healing was similar in the ibuprofen foam and comparator group. No difference in adverse events between the comparator and the ibuprofen foam with local sustained release of low‐dose ibuprofen was observed in this study. It was generally found that women reported less pain intensity than men, and pain intensity decreased with increasing age. In addition, pain intensity increased with initial pain intensity and increasing wound size. This study has demonstrated that the ibuprofen‐foam dressing provided pain relief and reduced pain intensity without compromising healing or other safety parameters.

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

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

Summary Background Bullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral corticosteroids. Methods We did a pragmatic, multicentre, parallel-group randomised controlled trial of adults with bullous pemphigoid (three or more blisters at two or more sites and linear basement membrane IgG or C3). Participants were randomly assigned to doxycycline (200 mg per day) or prednisolone (0·5 mg/kg per day) using random permuted blocks of randomly varying size, and stratified by baseline severity (3–9, 10–30, and >30 blisters for mild, moderate, and severe disease, respectively). Localised adjuvant potent topical corticosteroids (<30 g per week) were permitted during weeks 1–3. The non-inferiority primary effectiveness outcome was the proportion of participants with three or fewer blisters at 6 weeks. We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of non-inferiority. The primary safety outcome was the proportion with severe, life-threatening, or fatal (grade 3–5) treatment-related adverse events by 52 weeks. Analysis (modified intention to treat [mITT] for the superiority safety analysis and mITT and per protocol for non-inferiority effectiveness analysis) used a regression model adjusting for baseline disease severity, age, and Karnofsky score, with missing data imputed. The trial is registered at ISRCTN, number ISRCTN13704604. Findings Between March 1, 2009, and Oct 31, 2013, 132 patients were randomly assigned to doxycycline and 121 to prednisolone from 54 UK and seven German dermatology centres. Mean age was 77·7 years (SD 9·7) and 173 (68%) of 253 patients had moderate-to-severe baseline disease. For those starting doxycycline, 83 (74%) of 112 patients had three or fewer blisters at 6 weeks compared with 92 (91%) of 101 patients on prednisolone, an adjusted difference of 18·6% (90% CI 11·1–26·1) 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% (22 of 121) for those starting doxycycline and 36% (41 of 113) for prednisolone (mITT), an adjusted difference of 19·0% (95% CI 7·9–30·1), p=0·001. Interpretation Starting patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control in bullous pemphigoid and significantly safer in the long-term. Funding NIHR Health Technology Assessment Programme.

Association of autoimmunity and cicatricial pemphigoid : is there an immunogenetic basis ?

A group of 34 patients with cicatricial pemphigoid was investigated for the presence of autoimmune disorders. Thirty-two percent of patients had autoimmune disease compared with 7% in the control population, a highly significant difference (p less than 0.002). Circulating autoantibodies were also significantly more common in patients (p less than 0.05). Twenty-four patients with cicatricial pemphigoid were typed for HLA. A statistically significant increase in the frequency of DR4 and DQw3 antigens was observed in these patients. These findings suggest a possible genetic basis for the autoimmune association and predisposition for development of cicatricial pemphigoid.

Less pain with Biatain-Ibu: initial findings from a randomised, controlled, double-blind clinical investigation on painful venous leg ulcers

Six out of 10 patients with chronic wounds suffer from persistent wound pain. A multinational and multicentre, randomised, double‐blind clinical investigation of 122 patients compared two moist wound‐healing dressings, a non adhesive foam dressing with ibuprofen (62 patients randomised to Biatain‐Ibu non adhesive, Coloplast A/S) with a non adhesive foam without ibuprofen (60 to Biatain non adhesive).The ibuprofen‐foam was regarded successful, if the pain relief on a 5‐point verbal rating scale was higher than the comparator without compromising safety, including appropriate healing rate. Additional endpoints were change in persistent wound pain between dressing changes and pain at dressing change on days 1–5 and days 43–47. The primary response variable, persistent pain relief, was significantly higher in the ibuprofen‐foam group compared with the comparator on days 1–5, with a quick onset of action (P < 0·05). The patients in the ibuprofen‐foam group had a significant (P < 0·05) higher reduction in the persistent wound pain from baseline (40%) as the comparator (30%). Women reported less pain intensity than men, and pain intensity decreased with increasing age. In addition, pain intensity increased with increasing initial pain intensity and increasing wound size. Wound healing was similar in the ibuprofen‐foam group to that of the comparator group. No difference in adverse events between placebo and local sustained release of low‐dose ibuprofen was observed in this study. This study has demonstrated that the ibuprofen‐foam dressing provided pain relief and reduced pain intensity without compromising healing or other safety parameters. The full report of this study will be published in Wound Repair and Regeneration.

Linear IgA Disease: Clinical Presentation, Diagnosis, and Pathogenesis

Linear IgA disease is one of the rarer subepidermal blistering diseases. Linear IgA disease is a chronic, acquired, autoimmune blistering disease that is characterized by subepidermal blistering and linear deposition of IgA basement membrane antibodies. The disease affects both children and adults and, although there are some differences in their clinical presentations, there is considerable overlap with shared immunopathology and immunogenetics.

Management of Linear IgA Disease in Adults

Linear immunoglobulin A (IgA) disease is an acquired autoimmune blistering condition of the skin and mucous membranes, characterised by linear deposition of IgA along the dermoepidermal basement membrane zone. In adults, drug triggers should be considered and withdrawn if suspected. Dapsone is the systemic treatment of choice, but ineffective or poorly tolerated alternative treatments include sulphonamides, anti-inflammatory antimicrobials, systemic steroids or other immunosuppressives.