SummaryBackgroundBullous 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.MethodsWe 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.FindingsBetween 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.InterpretationStarting 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.FundingNIHR Health Technology Assessment Programme.
The expression of different keratin intermediate filaments has been used to define keratinocyte maturation and different phenotypic subtypes involved in acute wound (AW) healing. Immunohistochemistry with specific anti-keratin monoclonal and polyclonal antibodies was used to examine AW in normal healthy volunteers (n = 16). In all wounds examined, basal keratinocytes and cells at the leading edge of the wound expressed keratins K5 and K14. However, suprabasal cells had a more complex pattern of keratin expression, which was dependent on their position relative to the wound and location within the suprabasal compartment of the epidermis. In general, K10 was expressed in suprabasal keratinocytes at the wound edge, but not in keratinocytes covering the wound center, which expressed K6, K16, and K17 in a complex fashion. Ki67 expression, a marker of cell proliferation, was restricted to basal and immediate suprabasal layers at the wound edge. Keratinocytes populated the wound bed below the scab by migration, which was supported by keratinocyte proliferation in the surrounding epidermis both at and adjacent to the wound edge.
Staphylococcal scalded skin syndrome (SSSS) is a common disorder that is usually seen in infants and children and rarely seen in adults. SSSS usually presents with a prodrome of sore throat or conjunctivitis. Extremely tender flaccid bullae, which are Nikolsky sign-positive, develop within 48 hours and commonly affect the flexures; occasionally, large areas of the skin may be involved. The bullae enlarge and rupture easily to reveal a moist erythematous base, which gives rise to the scalded appearance. SSSS in adults is a rare disorder, though there are now over 50 documented cases. Usually SSSS occurs in predisposed individuals, but not all adults have an underlying illness. Whereas mortality in childhood SSSS is approximately 4%, the mortality rate in adults is reported to be greater than 60%. SSSS is caused by an infection with a particular strain of Staphylococcus aureus, which leads to blistering of the upper layer of the skin, by the release of a circulating exotoxin. It has recently been demonstrated that the exfoliative exotoxin responsible for SSSS leads to the cleavage of desmoglein 1 complex, an important desmosomal protein. The same toxins that are responsible for causing SSSS also cause bullous impetigo. There appears to be a relationship between the disease extent, the amount of toxin produced and whether the toxin is released locally or systemically. As a result there is likely to be a spectrum of disease and there are likely to be a number of milder cases of adult SSSS that go undiagnosed. Social improvements and hygiene have led to a dramatic fall in the number of cases of SSSS. Treatment is usually straightforward, when there is no coexistent morbidity and the presentation is mild, but can be demanding if the patient is particularly ill. SSSS is still associated with mortality, particularly when it occurs in adults.
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