Gudula Kirtschig

Follicular and epidermal alterations in patients treated with ZD1839 (Iressa), an inhibitor of the epidermal growth factor receptor

We report the cutaneous side‐effects of ZD1839 (Iressa), a new anticancer agent that acts by inhibiting epidermal growth factor (EGF) receptor signal transduction. Three patients receiving ZD1839 developed an eruption consisting of follicular papules and pustules in an acneiform distribution as well as diffuse fine scaling of the skin. Additionally, hair growth abnormalities were noted in two patients. Histologically, a superficial purulent folliculitis and disordered differentiation with focal parakeratosis were seen. The follicular eruption appeared to respond favourably to treatment with tretinoin cream and minocycline. The cutaneous adverse effects of ZD1839 are similar to those of other EGF receptor‐targeted agents and result from direct interference with the functions of EGF receptor signalling in the skin.

Guidelines for the management of bullous pemphigoid

Summary These guidelines have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence‐based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines and a brief overview of epidemiological aspects, diagnosis and investigation. The guidelines reflect data available from Medline, Embase, the Cochrane library, literature searches and the experience of the authors of managing patients with bullous pemphigoid in special and general clinics for over 10 years. However, caution should be exercised in interpreting the data obtained from the literature because only six randomized controlled trials are available involving small groups of patients.

British Association of Dermatologists' guidelines for the management of bullous pemphigoid 2012.

British Association of Dermatologists’ guidelines for the management of bullous pemphigoid 2012 V.A. Venning, K. Taghipour, M.F. Mohd Mustapa, A.S. Highet and G. Kirtschig Department of Dermatology, Churchill Hospital, Old Road, Headington, Oxford OX3 7LJ, U.K. Department of Dermatology, Whittington Hospital, Magdala Avenue, London N19 5NF, U.K. British Association of Dermatologists, Willan House, 4 Fitzroy Square, London W1T 5HQ, U.K. York Hospital, Wigginton Road, York YO31 8HE, U.K. Vrije Universtiteit, PO Box 7057, Amsterdam NL-1007 MB, the Netherlands

Successful treatment of erosive vulvovaginal lichen planus with topical tacrolimus

SIR, The ichthyoses are a heterogeneous group of skin disorders of epidermal differentiation, with both inherited and acquired forms. This cornification disorder may be found isolated or in association with other genetic defects. In 1998, five siblings with congenital ichthyosis, follicular atrophoderma, hypotrichosis and hypohidrosis were described as a new genodermatosis by Lestringant et al. We report a 17-year-old Turkish patient with ichthyosis vulgaris, follicular atrophoderma, woolly hair and hypotrichosis as a second report on this syndrome. A 17-year-old-girl was admitted to our hospital because of woolly hair, sparse eyelashes and eyebrows, and a very dry skin. She was born at term after an uncomplicated pregnancy. Ichthyosis and baldness were present at birth, but there was no history of a collodion baby. She had almost no scalp hair until she was 4 months old. In the early childhood period, funnel-shaped round follicular depressions had appeared on the dorsal aspects of the hands. She stated that her scalp hair had improved and straightened with age. The patient was otherwise healthy and detailed ophthalmological, neurological and audiometric examinations were normal. There was no history of atopy. There was no family history of similar skin problems. Both her parents and paternal grandparents were first cousins. There was no maternal history of drug intake during pregnancy. On examination, there was diffuse ichthyosiform scaling sparing the major flexures and face as in ichthyosis vulgaris (Fig. 1). The ichthyotic skin was hypohydrotic but the axilla, palms and soles sweated normally. Follicular atrophoderma was observed on the backs of her hands (Fig. 2). She had diffuse and patchy non-scarring hypotrichosis with a receding frontal hairline. Her hair was normal in length, but was light brown in colour, coarse, curly and unruly, in contrast to the straight black hair of the rest of her family. Eyelashes and particularly eyebrows were sparse (Figs 3–4). Routine haematological, biochemical, immunological, thyroid and radiological investigations were normal. Osteopoikilosis was not present on the X-rays. Echocardiography and ECG were normal. Hair microscopy was normal apart from curling. Biopsy from ichthyotic skin showed orthokeratosis with focal hypogranulosis (Fig. 5). Electron microcopy showed normal tonofilaments. Based on clinical and laboratory findings a diagnosis of ichthyosis vulgaris associated with follicular atrophoderma, hypotrichosis and woolly hair was made. The patient was prescribed 10% urea cream and salicylic acid ointments. The ichthyotic lesions resolved within a few weeks. Ichthyosis is a feature of several genetic disorders. These are rare disorders and the associated ichthyosis may be mild. The following syndromes with ichthyosis may be considered

Autologous full-thickness skin substitute for healing chronic wounds

Background  Chronic wounds represent a major problem to our society. Therefore, advanced wound‐healing strategies for the treatment of these wounds are expanding into the field of tissue engineering.

Systematic review and meta-analysis of randomized controlled trials on topical interventions for genital lichen sclerosus

BACKGROUND Lichen sclerosus (LS) is a chronic inflammatory dermatosis that occurs mainly in the anogenital area and causes itching and soreness. Progressive destructive scarring may result in burying of the clitoris in females and phimosis in males. Affected people have an increased risk of genital cancers. OBJECTIVE We sought to assess the effects of topical interventions for genital LS. METHODS We undertook a systematic review and meta-analysis using the methodology of the Cochrane Collaboration. RESULTS We included 7 randomized controlled trials with a total of 249 participants covering 6 treatments. Clobetasol propionate 0.05% was better than placebo in treating genital LS (participant-rated improvement/remission of symptoms: risk ratio 2.85 [95% confidence interval {CI} 1.45-5.61]; investigator-rated global degree of improvement: standardized mean difference [SMD] 5.74 [95% CI 4.26-7.23]) as was mometasone furoate 0.05% (change in clinical grade of phimosis: SMD -1.04 [95% CI -1.77 to -0.31]). We found no evidence supporting the efficacy of topical androgens and progesterone. There were no differences between pimecrolimus and clobetasol propionate in relieving symptoms through change in pruritus (SMD -0.33 [95% CI -0.99 to 0.33]) and burning/pain (SMD 0.03 [95% CI -0.62 to 0.69]). However, pimecrolimus was less effective than clobetasol propionate in improving gross appearance (investigator-rated global degree of improvement: SMD -1.64 [95% CI -2.40 to -0.87]). LIMITATIONS Most of the included studies were small. CONCLUSIONS The current limited evidence supports the efficacy of clobetasol propionate, mometasone furoate, and pimecrolimus in treating genital LS. Further randomized controlled trials are needed.

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.

Evidence‐based (S3) guideline on topical corticosteroids in pregnancy

Women with skin conditions may need topical corticosteroids during pregnancy. However, little is known about the effects of topical corticosteroids on the fetus. A guideline subcommittee of the European Dermatology Forum was organized to develop an evidence‐based guideline on the use of topical corticosteroids in pregnancy (http://www.euroderm.org/edf/images/stories/guidelines/EDF‐Guideline‐on‐Steroids‐in‐Pregnancy.pdf). The evidence from a Cochrane Review suggested that the major possible adverse effects on the fetus of topical corticosteroids were orofacial clefts when used preconceptionally and in the first trimester of pregnancy, and fetal growth restriction when very potent topical corticosteroids were used during pregnancy. To obtain robust evidence, a large population‐based cohort study (on 84 133 pregnant women from the U.K. General Practice Research Database) was performed, which found a significant association of fetal growth restriction with maternal exposure to potent/very potent topical corticosteroids, but not with mild/moderate topical corticosteroids. No associations of maternal exposure to topical corticosteroids of any potency with orofacial cleft, preterm delivery and fetal death were found. Moreover, another recent Danish cohort study did not support a causal association between topical corticosteroid and orofacial cleft. The current best evidence suggests that mild/moderate topical corticosteroids are preferred to potent/very potent ones in pregnancy, because of the associated risk of fetal growth restriction with the latter.

Systematic review of the safety of topical corticosteroids in pregnancy

BACKGROUND Pregnant women may have skin conditions that require topical corticosteroids. However, little is known about their safety in pregnancy. OBJECTIVE We sought to evaluate the available evidence concerning the safety of topical corticosteroids in pregnancy. METHODS We systematically searched 17 databases and trial registers, and contacted pharmaceutical companies. Randomized controlled trials and cohort studies of topical corticosteroids in pregnant women, and case-control studies comparing maternal exposure to topical corticosteroids between patients and control subjects were included. The Newcastle-Ottawa Scale was used for quality assessment of included studies. RESULTS Seven studies, including two cohort and five case-control studies, were included. Most studies did not find significant associations of topical corticosteroids with congenital abnormality, preterm delivery stillbirth, and mode of delivery. One study found a significant association between first-trimester use of topical corticosteroids and orofacial cleft, and another study found a significant association between very potent topical corticosteroids and low birthweight. LIMITATIONS The available data were limited and mainly on orofacial cleft. The quality of evidence was generally low. CONCLUSIONS Currently limited and inconclusive data are unable to detect an association between topical corticosteroids and congenital abnormality, preterm delivery, or stillbirth. The current evidence shows no statistically significant difference between pregnant women who use and those who do not use topical corticosteroids. However, there does appear to be an association of very potent topical corticosteroids with low birthweight. Further cohort studies with comprehensive outcome measures, consideration of corticosteroid potency, dosage and indications, and a large sample size are needed.

Erosive lichen planus of the vulva: weak circulating basement membrane zone antibodies are present

The objective of this study was to investigate whether circulating basement membrane zone (BMZ) antibodies are present in erosive lichen planus (LP) of the vulva. In total, 56 consecutive women with biopsy‐confirmed erosive LP of the vulva were recruited from a vulval clinic in a district general hospital and teaching hospital in Oxfordshire. Indirect immunofluorescence (IgG and IgA) was performed on 56 sera, and 15 were tested to IgG subclasses (1–4). Immunoblotting was carried out on salt‐split and urea‐extracted epidermal skin extracts on 11. The main outcome measure was the presence or absence of staining at the BMZ. Of the 56 sera, 34 (61%) had weak (neat or 1 : 5) epidermal‐binding BMZ antibodies (25 had IgG, 5 had IgA, 4 had both IgG and IgA). All 15 sera tested to IgG showed epidermal binding to one or more IgG subclasses: IgG1 (7 sera), IgG2 (7), IgG3 (7) and IgG4 (0). Immunoblotting identified IgG antibodies to bullous pemphigoid (BP)180 (10/11) and BP230 (2/11). The majority (61%) of patients with vulval erosive LP had circulating serum IgG BMZ antibodies, chiefly reacting with BP180. There was subclass restriction of the IgG response to IgG1, 2 and 3. The significance of these antibodies is uncertain, but they may be a marker for the disease.