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.
Leishmaniasis is a major World health problem, which is increasing in incidence. In Northern Europe it is seen in travellers returning from endemic areas. The protozoa is transmitted by sandflies and may produce a variety of clinical syndromes varying from a simple ulcer to fatal systemic disease. This review considers the management of simple cutaneous leishmaniasis. Patients usually have a single ulcer which may heal spontaneously, requiring only topical, or no treatment at all. Lesions caused by Leishmania braziliensis may evolve into the mucocutaneous form, 'espundia', and should be treated with systemic antimony. Sodium stiboglucoante 20 mg/kg/day i. v. for 20 days is the appropriate first line treatment in these cases. Although it may cause transient bone marrow suppression, liver damage, a chemical pancreatitis, and disturbances in the electrocardiogram, it appears to be safe. The success of treatment should be assessed 6 weeks after it has been completed and patients should be followed up for 6 months.
Summary We report six cases of Dermatobia hominis myiasis imported into the U.K. from Belize. With increasing international travel, myiasis may be encountered more frequently in countries in which the parasites are not indigenous. The life‐cycle of D. hominis is described, and scanning electron micrographs show the detailed appearance of the larva.
The efficacy of aminosidine was compared with sodium stibogluconate in an open, randomized study of parasitologically-proven cutaneous leishmaniasis in Belize. Aminosidine, 14 mg/kg/d (max. 1 g daily) for 20 d, healed 10 of 17 lesions and sodium stibogluconate, 20 mg/kg/d for 20 d, healed 15 of 17 lesions. Lesions caused by Leishmania braziliensis were relatively unresponsive to aminosidine. Aminosidine was well tolerated and toxicity was not observed. Sodium stibogluconate was not well tolerated and treatment was associated with bone marrow suppression and elevation of serum aminotransferases.
The clinical features of the Dowling-Meara variant of epidermolysis bullosa simplex (EBS-DM) can, in an infant, be indistinguishable from other severe forms of epidermolysis bullosa (EB). Two unrelated infants with no family history of skin disease are described who, within hours of birth, developed extensive blistering of skin and oral mucosae and who both subsequently developed hoarse cries. Despite this superficial resemblance to other forms of EB, electron microscopy revealed a basal cell rupture and keratin aggregates characteristic of EBS-DM in the skin of both infants and in the vocal cord epithelium of one. Molecular analysis confirmed the diagnosis by identification of mis-sense point mutations in basal cell keratin genes in both cases. One patient carries a point mutation in keratin 14 (converting arginine at position 125 to histidine) and the other has a novel point mutation in keratin 5 (converting serine at position 181 to proline). Hoarseness is not a well documented feature of EBS-DM and is usually associated with junctional EB. These two patients demonstrate that the presence of a hoarse cry in an infant affected by severe EB does not necessarily indicate a poor prognosis.
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