Showing papers in "British Journal of Dermatology in 2003"

Causes, investigation and treatment of leg ulceration

Abstract: Chronic ulceration of the lower leg is a frequent condition, with a prevalence of 3-5% in the population over 65 years of age. The incidence of ulceration is rising as a result of the ageing population and increased risk factors for atherosclerotic occlusion such as smoking, obesity and diabetes. Ulcers can be defined as wounds with a 'full thickness depth' and a 'slow healing tendency'. In general, the slow healing tendency is not simply explained by depth and size, but caused by an underlying pathogenetic factor that needs to be removed to induce healing. The main causes are venous valve insufficiency, lower extremity arterial disease and diabetes. Less frequent conditions are infection, vasculitis, skin malignancies and ulcerating skin diseases such as pyoderma gangrenosum. But even rarer conditions exist, such as the recently discovered combination of vasculitis and hypercoagulability. For a proper treatment of patients with leg ulcers, it is important to be aware of the large differential diagnosis of leg ulceration.

Guidelines for the management of alopecia areata.

Abstract: Summary These guidelines for management of alopecia areata 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.

Antibiotic-resistant acne: lessons from Europe.

Abstract: SummaryBackground Propionibacterium acnes and P. granulosum are widely regarded as the aetiological agents of inflammatory acne. Their proliferation and metabolism are controlled using lengthy courses of oral and/or topical antibiotics. Despite numerous reports of skin colonization by antibiotic-resistant propionibacteria among acne patients, accurate prevalence data are available only for the U.K. Objectives To determine the prevalence of skin colonization by antibiotic-resistant propionibacteria among acne patients and their contacts from six European centres. Methods Skin swabs were collected from 664 acne patients attending centres in the U.K., Spain, Italy, Greece, Sweden and Hungary. Phenotypes of antibiotic-resistant propionibacteria were determined by measuring the minimum inhibitory concentrations (MIC) of a panel of tetracycline and macrolide, lincosamide and streptogramin B (MLS) antibiotics. Resistance determinants were characterized by polymerase chain reaction (PCR) using primers specific for rRNA genes and erm(X), followed by nucleotide sequencing of the amplified DNA. Results Viable propionibacteria were recovered from 622 patients. A total of 515 representative antibiotic-resistant isolates and 71 susceptible isolates to act as control strains were characterized phenotypically. The prevalence of carriage of isolates resistant to at least one antibiotic was lowest in Hungary (51%) and highest in Spain (94%). Combined resistance to clindamycin and erythromycin was much more common (highest prevalence 91% in Spain) than resistance to the tetracyclines (highest prevalence 26·4% in the U.K.). No isolates resistant to tetracycline were detected in Italy, or in Hungary. Overall, there were strong correlations with prescribing patterns. Prevalence of resistant propionibacteria on the skin of untreated contacts of the patients varied from 41% in Hungary to 86% in Spain. Of the dermatologists, 25 of 39 were colonized with resistant propionibacteria, including all those who specialized in treating acne. None of 27 physicians working in other outpatient departments harboured resistant propionibacteria. Conclusions The widespread use of topical formulations of erythromycin and clindamycin to treat acne has resulted in significant dissemination of cross-resistant strains of propionibacteria. Resistance rates to the orally administered tetracycline group of antibiotics were low, except in Sweden and the U.K. Resistant genotypes originally identified in the U.K. are distributed widely throughout Europe. Antibiotic-resistant propionibacteria should be considered transmissible between acne-prone individuals, and dermatologists should use stricter cross-infection control measures when assessing acne in the clinic.

Epidemiology of cutaneous melanoma and non‐melanoma skin cancer in Schleswig‐Holstein, Germany: incidence, clinical subtypes, tumour stages and localization (epidemiology of skin cancer)

Abstract: Summary Background Population-based figures on skin cancer are essential for a realistic assessment of the personal disease burden, prevention modes and the need for caring. The Robert Koch Institute in Germany estimates the incidence of melanoma skin cancer as seven cases in 100 000 persons (age-standardized by the European standard rate). Population-based studies presumably show higher incidence rates of 10–16 cases in 100 000 persons. Few data exist for non-melanoma skin cancer (NMSC) as this is not systematically registered in Germany. Objectives To present the first population-based results from the Schleswig-Holstein (Germany) Cancer Registry on incidence, stage distribution, clinical types and localization of skin cancer and to compare the results with other studies. Methods The Cancer Registry of the Bundesland Schleswig-Holstein with 3500 registering institutions, 100 of which are dermatological institutions, investigates all notifiable incident cancer cases according to international standards. From the recorded data all melanoma and NMSC cases were identified and evaluated. Results Between 1998 and 2001, 1784 malignant melanoma (MM) and 12 956 NMSC cases underwent diagnostic and analytical evaluation. For MM, age-standardized incidence rates were 12·3 and 14·8 in 100 000 men and women, respectively, and the mean age of men was greater than that of women (56·6 vs. 54·9 years, P < 0·05). Superficial spreading melanoma was the most frequent clinical type (39·1%). The tumours were predominantly located on the trunk in men (46·8%) in contrast to leg and hip in women (39·5%). For NMSC, the age-standardized incidence rates were 100·2 and 72·6 in 100 000 men and women, respectively. More than 80% of all tumours were basal cell carcinoma. Conclusions The first population-based data from Schleswig-Holstein on the characteristics (age, sex, histological subtypes, localization and stage) of skin tumours agree well with the existing literature and may thus be regarded as representative. However, markedly higher incidences for MM and NMSC in the north of Germany compared with other parts of the country were observed. As the incidence rates from the north of Germany fit well into the European geographical pattern, we assume no regional increase. Therefore, the official German estimates on cutaneous tumours may largely depend on regional factors and may not be regarded as representative for all regions in Germany.

Normal keratinocytes express Toll-like receptors (TLRs) 1, 2 and 5: modulation of TLR expression in chronic plaque psoriasis

Abstract: SummaryBackground Toll-like receptors (TLRs) are part of the innate immune system involved in the response to microbial pathogens. TLR2 recognizes various ligands expressed by Gram-positive bacteria, while TLR3, TLR4 and TLR5 are specific for double-stranded RNA, Gram-negative lipopolysaccharides and bacterial flagellin, respectively. Objectives To determine, firstly, whether epidermal keratinocytes of normal skin express TLRs and, secondly, whether modulation of TLR expression occurs in psoriasis, an inflammatory skin disease associated with certain microorganisms such as streptococci, staphylococci and yeasts. Methods Eight samples of normal, and 15 samples of lesional and nonlesional psoriatic skin were stained with polyclonal antibodies specific for TLR1-5 using an avidin–biotin–peroxidase technique. Results Epidermal keratinocytes in normal skin constitutively expressed TLR1, TLR2 and TLR5, while TLR3 and TLR4 were, in most cases, barely detectable. Cytoplasmic TLR1 and TLR2 were expressed throughout the epidermis, with higher staining of the latter on basal keratinocytes, while TLR5 expression was concentrated in the basal layer. In contrast, in lesional epidermis from patients with psoriasis, TLR2 was more highly expressed on the keratinocytes of the upper epidermis than on the basal layer, while TLR5 was downregulated in basal keratinocytes compared with corresponding nonlesional psoriatic epidermis. In addition, nuclear TLR1 staining was observed in the upper layers of both nonlesional and lesional psoriatic epidermis, but not in that of normal skin. Conclusions These findings suggest that TLRs expressed by epidermal keratinocytes constitute part of the innate immune system of the skin. The relevance of altered keratinocyte TLR expression in psoriasis remains to be determined.

Oxidative stress in malignant melanoma and non‐melanoma skin cancer

Abstract: SummaryBackground Solar ultraviolet (UV) radiation is considered to be a major aetiological factor in melanoma and non-melanoma skin cancer. A growing body of evidence indicates that oxidative stress is involved in photocarcinogenesis. However, in vivo data for human skin are still lacking. Reactive oxygen species participate in a number of pathophysiological processes including DNA damage and lipid peroxidation (LPO) and are considered to be a key factor in tumour progression. Objectives We hypothesized that in human skin cancer the natural redox balance is disturbed and that this imbalance may result in an accumulation of LPO products. Methods To test this, skin biopsies of superficial spreading melanoma were compared with age-matched benign melanocytic naevi and young healthy controls. Additionally, non-melanoma skin cancers (basal cell carcinoma, squamous cell carcinoma) and actinic keratosis were investigated (n = 18 each). Expression of the antioxidant enzymes, copper–zinc superoxide dismutase, manganese superoxide dismutase and catalase was analysed by immunohistochemical techniques. To detect LPO products, protein-bound malondialdehyde (MDA) was visualized. Results In human melanoma biopsies, a significant overexpression of the antioxidant enzymes was found when compared with surrounding non-tumour tissue, benign melanocytic naevi, and young controls. Intriguingly, the LPO marker MDA was significantly increased in melanoma tissue. MDA was located not only in typical melanoma cells, but also occurred in surrounding keratinocytes. In contrast, a severely disturbed antioxidant balance with diminished antioxidant enzymes was found in non-melanoma tumours, whereas MDA was elevated only in squamous cell carcinomas. Conclusions These findings indicate that oxidative stress may play different roles in the pathogenesis of human skin cancers. In non-melanoma skin cancer, a diminished antioxidant defence caused by chronic UV exposure might contribute to multistep carcinogenesis, whereas melanoma cells exhibit increased oxidative stress which could damage surrounding tissue and thus support the progression of metastasis.

Guidelines for the management of pemphigus vulgaris

Abstract: These guidelines for management of pemphigus vulgaris 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.

Epidemiology, clinical presentation and diagnosis of onychomycosis

Abstract: Onychomycosis is a common nail disease, responsible for up to 50% of diseases of the nail. The distribution of different pathogens is not uniform; it depends on various factors such as climate, geography and migration. However, studies have revealed that two dermatophytes, Trichophyton rubrum and Trichophyton mentagrophytes, account for more than 90% of onychomycoses. Onychomycosis can be divided into four major clinical presentations: distal subungal (the most common form of the disease), proximal subungal (the most common form found in patients with human immunodeficiency virus infection), and superficial and total dystrophic onychomycosis. Onychomycosis is a multifactorial disease. Age has a very important effect on the occurrence of onychomycosis, with a correlation between increasing age and infection. Genetics has also been identified as a factor governing the epidemiology of onychomycosis; T. rubrum infection shows a familial pattern of autosomal dominant inheritance. Disease and lifestyle may also play a role in the epidemiology of fungal nail infections. Studies have shown that diabetes, acquired immunodeficiency syndrome and peripheral arterial disease may be independent predictors of onychomycosis. Because of the multifactorial nature of the epidemiology, accurate diagnosis, pertinent treatment and patient education must be paramount when treating the disease.

A 6-month prospective survey of cutaneous drug reactions in a hospital setting.

Abstract: Summary Background Few prospective studies are available on the incidence and analysis of the characteristics of adverse cutaneous drug reactions in hospital settings. Objectives A 6-month prospective study was managed in our hospital among hospitalized patients to: (i) evaluate the incidence of cutaneous allergic reactions from systemic drugs; (ii) study characteristics of patients with cutaneous drug reactions; (iii) describe the adverse cutaneous reactions; and (iv) evaluate drug reaction imputability and preventability. Methods All suspected allergic cutaneous reactions to systemic drugs were collected during a 6-month period (November 2000 to May 2001). Exhaustivity of recording was ensured by regular dissemination of information about this study to the practitioners; a simple method for inclusion by fax was established. Inclusion criteria were suspected cutaneous allergic reactions induced by systemic drugs responsible for hospitalization or developed during hospitalization. A physical examination was done by a dermatologist who completed a standardized questionnaire. Requested information included patient characteristics (associated disorders, severity score), drug intake (list and chronology of the drug intake during the 3 weeks preceding the adverse reaction) and characteristics of the skin reaction (type, course). A group comprising dermatologists and pharmacologists evaluated the drug imputability and preventability. Results Forty-eight cases were collected. A prevalence of 3·6/1000 among hospitalized patients was estimated. The prevalence rate was higher in patients hospitalized in medical departments (0·5%) than in surgical departments (0·01%) (P < 0·001). The cases were mostly recruited in departments of infectious diseases and dermatology. The most frequent associated disorders were: human immunodeficiency virus (HIV) infection (19%), connective tissue disease (10%) and viral or autoimmune hepatitis (12%). Of these patients, 31% had had a previous immunological drug reaction. Adverse cutaneous drug reactions were principally exanthematous (56%). Reactions were considered severe in 34% of cases because they were responsible for hospitalization (18%), increased the duration of hospitalization (14%) or were life threatening (2%). Principal imputable drugs were antibiotics, mainly penicillins. An imputability score was likely in 56% of cases, but it was only possible to conclude definitively in 44% of patients. In 15% of the cases, the side-effect was considered to be preventable. Conclusions This study finds a lower incidence than other studies that reported an incidence of 2% of cutaneous drug reactions in hospitalized patients, but only allergic adverse cutaneous reactions induced by systemic drugs were collected in this study. The previous studies were principally done in selected patients hospitalized only in general internal medicine or medical divisions. Our results confirm some data already known about skin drug reactions: HIV infection as a risk factor (P < 0·0001), high prevalence of adverse cutaneous reactions due to antibiotics, and difficulty in ascertaining the imputability of a drug. A high proportion (34%) of these reactions was severe and 15% were avoidable; these two facts justify the development of an intensive programme of clinical pharmacology.

Streptococcal throat infections and exacerbation of chronic plaque psoriasis: a prospective study

Abstract: Summary Background Guttate psoriasis has a well-known association with streptococcal throat infections but the effects of these infections in patients with chronic psoriasis remains to be evaluated in a prospective study. Objectives To determine whether streptococcal throat infections are more common in and can cause exacerbation in patients with chronic psoriasis. Methods Two hundred and eight patients with chronic plaque psoriasis and 116 unrelated age-matched household controls were followed for 1 year. At recruitment all patients were examined, their disease severity scored and throat swabs taken. Patients and corresponding controls were then re-examined and tested for streptococcal colonization whenever they reported sore throat or exacerbation of their psoriasis during the study period. Results The psoriasis patients reported sore throat significantly more often than controls (61 of 208 vs. three of 116, P < 0·0001), and β-haemolytic streptococci of Lancefield groups A, C and G (M protein-positive streptococci) were more often cultured from the patients than the controls (19 of 208 vs. one of 116, P = 0·003). A significant exacerbation of psoriasis (P = 0·004) was observed only if streptococci were isolated and the patients were assessed 4 days or later after the onset of sore throat. No difference was observed between groups A, C or G streptococci in this respect. Conclusions This study confirms anecdotal and retrospective reports that streptococcal throat infections can cause exacerbation of chronic plaque psoriasis. It is concluded that psoriasis patients should be encouraged to report sore throat to their physician and that early treatment of streptococcal throat infections might be beneficial in psoriasis. A controlled trial for assessing potential benefits of tonsillectomy in patients with severe psoriasis should also be considered.

Skin diseases associated with the cosmetic use of bleaching products in women from Dakar, Senegal.

Abstract: SummaryBackground The cosmetic use of bleaching products is considered a common practice in dark-skinned women from sub-Saharan Africa. However, there are few studies on this subject. Objectives To increase the knowledge about the dermatological consequences of this practice in Dakar, the capital of Senegal. Methods A representative sample of 368 adult women presenting at our dermatological centre was selected. Each woman was questioned about her cosmetic use of bleaching products. Next, the following data were recorded in 425 women who used bleaching products: names and types of products used; modalities of the skin bleaching practice; skin diseases motivating the dermatological visit, with recording of their clinical features; and results of a full skin examination. The active substances of the bleaching products were determined mainly by reading the indications on their packages; with products of unknown composition, a pharmacological analysis of samples was done. A statistical analysis was performed. Results Of the 368 women questioned, 194 (52·7%) were current users of bleaching products. Concerning the 425 users enrolled, products were applied on the whole body in 92% of users, with a median duration of use of 4 years. The active principles used included hydroquinone (used by 89% of users), glucocorticoids (70%), mercury iodide (10%) and caustic agents (17%); 13% of users used products of unknown composition. In the samples that were analysed, hydroquinone was found at concentrations of between 4% and 8·7%. Concerning steroids, superpotent (class 1) glucocorticoids predominated. The main skin complaints in bleaching products users included dermatophyte infections (n = 105) and scabies (n = 69), both often unusually extensive and severe; acne (n = 42), often severe; eczema (n = 41); irritant dermatitis (n = 14); and dyschromia (n = 26, including 14 cases of exogenous ochronosis). The skin examination noted features apparently disregarded by users: striae (noticed in 39% of users), and macular hyperchromia involving the face, mainly the periocular area (33%). The statistical analysis showed that glucocorticoid use was associated with the presence and severity of infectious skin diseases, and of acne. Conclusions More than half of the adult women presenting at our dermatology centre were using bleaching products. Most skin diseases observed in bleaching products users appeared to be induced, aggravated or modified by this practice. Superpotent topical glucocorticoids appeared to be the main agents responsible for the observed complications. The cosmetic use of bleaching products therefore has a major impact on our current dermatological practice.

Comparison of parent knowledge, therapy utilization and severity of atopic eczema before and after explanation and demonstration of topical therapies by a specialist dermatology nurse.

Abstract: Summary Background The failure of patients to take medicines in a way that leads to clinical benefit is a major challenge. A consensus has emerged that, on average, compliance sufficient to obtain therapeutic objectives occurs about half the time, with noncompliance contributing to therapeutic failure in the other half. These figures refer to simple oral regimens. There has been little work assessing compliance/concordance with complex treatment regimens for atopic eczema. Asthma schools led by specialist nurses have been shown to improve knowledge, use of therapies and clinical outcome. Objectives To determine the effect of education and demonstration of topical therapies by specialist dermatology nurses on therapy utilization and severity of atopic eczema. Methods Fifty-one children with atopic eczema attending a paediatric dermatology clinic were followed for up to 1 year. At each visit the parent's knowledge about atopic eczema and its treatment and therapy utilization was recorded. The severity of the eczema was recorded using the six area, six sign atopic dermatitis severity score (SASSAD) and parental assessment of itch, sleep disturbance and irritability. At the first visit a specialist dermatology nurse explained and demonstrated how to use all of the topical treatments. This education was repeated at subsequent visits depending on the knowledge of the parent. Results At baseline less than 5% of parents had received/recalled receiving any explanation of the causes of eczema or demonstration of how to apply topical treatments. The eczema was poorly controlled in all children (mean SASSAD 42·9). Of the children, 24% were not being treated with any emollient cream/ointment; the mean use was 54 g weekly. Of the children, 25% were being inappropriately treated with potent or very potent topical steroids. Following repeated education and demonstration of topical therapies by a specialist dermatology nurse, there was an 89% reduction in the severity of the eczema. The main change in therapy utilization was an 800% increase in the use of emollients (to 426 g weekly of emollient cream/ointment) and no overall increase in the use of topical steroids, accounting for potency and quantity used. Conclusions This study reinforces the importance of specialist dermatology nurses in the management of atopic eczema. It also confirms the opinion of patients, patient support groups, dermatologists and best practice guidelines that the most important intervention in the management of atopic eczema is to spend time to listen and explain its causes and demonstrate how to apply topical therapies.

Suggestions for uniform outcome variables when reporting treatment effects in hidradenitis suppurativa

Abstract: SIR, Mycosis fungoides (MF) is characterized by clonal helper ⁄ memory (CD4+ CD45RO+) T-cells in the epidermis, whereas follicular mucinosis or alopecia mucinosis has perifollicular T-cell infiltrates and may clinically resemble alopecia areata. Bexarotene is the first retinoid X receptor (RXR)-selective retinoid shown to be effective for cutaneous T-cell lymphoma. Bexarotene has recently been shown to induce T-cell apoptosis in vitro. Although bexarotene oral and topical gel are effective for MF, this is the first report, to our knowledge, of reversal of associated alopecia. Five patients with alopecia secondary to MF or follicular mucinosis were observed among a cohort of over 90 patients receiving bexarotene therapy at the M.D. Anderson Cancer Center. Their demographic data, degree of hair loss, skin biopsy results and drug administration are shown in Table 1. The location of the hair loss was confined to the scalp in four patients and to the extremities in a fifth. All of the skin biopsy specimens revealed atypical CD4+ CD8+ perifollicular lymphocytic infiltrates, and two showed mucin deposits consistent with follicular mucinosis. Three patients had scaling with negative fungal cultures. Patients with early stage MF were treated with topical bexarotene therapy and advanced stage patients with oral bexarotene. The MF as well as the alopecia improved in all five patients, irrespective of the route of delivery. Hair regrowth began within 2–9 months and full regrowth was evident by 1Æ5 years. Patient 1. A 77-year-old Native American woman presented with a 3-month history of a single patch of alopecia accompanied by pruritus and mild tenderness, generalized xerosis, fatigue and a 4Æ5-kg unintentional weight loss. Asthma and childhood eczema were noted. There was a 4 · 5 cm alopecia areata-like lesion with scaling on the scalp (Fig. 1a) and macular erythema of less than 1%. An atypical CD4+ CD8– clonal lymphocytic infiltrate and mucin deposits were present in the follicular epithelium. After applying 1% bexarotene gel daily to the leg and scalp lesions, partial hair regrowth was present at 3 months (Fig. 1b), with full regrowth of terminal grey hair covering the former patch of alopecia at 5 months (Fig. 1c). Patient 2. A 64-year-old Hispanic man with dermatitis for 30 years developed generalized exfoliative erythroderma, patchy alopecia, and a skin biopsy consistent with MF. He had increased fatigue, chills, night sweats and intense pruritus. On examination, he had generalized exfoliative erythroderma and lymphadenopathy. On the scalp, multiple round alopecia areata lesions, patches of white hair, and exclamation point hairs were observed (Fig. 2a,b). An atypical CD4+ CD8+ dermal infiltrate with epidermotropism and a clonal T-cell receptor gene rearrangement were observed in

Development and validation of a health-related quality of life instrument for women with melasma.

Abstract: Summary Background Melasma can have significant emotional and psychological effects on those affected with the condition. In the past, the impact of melasma on health-related quality of life (HRQoL) has been assessed using general measures of skin disease that equally weigh both the physical and psychosocial distress arising from the presence of a dermatological condition. Objectives Our purpose was to develop and validate a disease-specific HRQoL instrument to identify the areas of the patient's life most impaired by melasma as well as the effects of the condition on their level of functioning in correlation with disease severity: the Melasma Quality of Life scale (MELASQOL). Patients and methods A random sample of 102 women identified by an investigator as having melasma were evaluated by the investigator using the Melasma Area and Severity Index (MASI). The patients were then anonymously surveyed with the SKINDEX-16, the Fear of Negative Evaluation scale, the Dermatology Life Quality Index (DLQI), a skin discoloration evaluation questionnaire, and a measure of perceived life quality difference without melasma. The 10-item MELASQOL scale was devised from the comprehensive HRQoL assessment battery. Results The psychometric properties of the MELASQOL were comparable with the properties of the DLQI and the SKINDEX-16. The MELASQOL scores were highly correlated with the other HRQoL measures. The discriminatory ability of the MELASQOL is superior to the SKINDEX-16 and the DLQI for melasma. The three life domains most adversely affected by melasma (social life, recreation/leisure and emotional well-being) were highlighted by this instrument. These were the same three areas of life that patients believed would improve the most if they no longer were affected by the disease. Conclusions The MELASQOL can be used to evaluate objectively the effect of melasma on a patient's HRQoL. The high correlation with the DLQI, the SKINDEX-16 and the skin discoloration questionnaire suggests that the new scale is a valid instrument, which can be used to monitor the level of impairment individuals suffer due to their melasma. The MELASQOL scores can help guide treatment methods as well as track the improvement of patients' HRQoL.

Degradation of extracellular matrix components by defined proteinases from the greenbottle larva Lucilia sericata used for the clinical debridement of non-healing wounds.

Abstract: Summary Background Larvae of the greenbottle fly Lucilia sericata are used routinely for the clinical treatment of difficult necrotic and infected wounds. Degradation by proteinases contained in larval excretory/secretory (ES) products is thought to contribute to wound debridement by removal of dead tissue. However, proteinase activity may also affect host tissue remodelling processes. Objectives To identify proteolytic enzymes derived from L. sericata ES products with activities against fibrin and extracellular matrix (ECM) components. Methods Larval proteinase activities were assayed in vitro using class-specific substrates and inhibitors. Their action against fibrin and ECM components was examined using sodium dodecyl sulphate–polyacrylamide gel electrophoresis. Results Three classes of proteolytic enzyme were detected in the secretions using fluorescein isothiocyanate-labelled casein as a model substrate. The predominant activity belonged to serine proteinases (pH optima 8–9) of two different subclasses (trypsin-like and chymotrypsin-like), with a weaker aspartyl proteinase (pH 5) and a metalloproteinase (pH 9) with exopeptidase characteristics also present. Using skin-relevant ECM components as substrates L. sericata ES products solubilized fibrin clots and degraded fibronectin, laminin and acid-solubilized collagen types I and III. Hydrolysis of ECM macromolecules was inhibited by preincubating ES products with phenylmethylsulphonyl fluoride but not 4-amidinophenylmethylsulphonyl fluoride, indicating that degradation was due to the ‘chymotrypsin-like’ serine proteinase. Conclusions These data suggest that a combination of L. sericata ES proteinases involving chymotrypsin-like and trypsin-like activities could potentially influence wound healing events when maggots are introduced into necrotic and infected wounds, with the chymotrypsin-like activity involved in the remodelling of ECM components.

Joint British Association of Dermatologists and U.K. Cutaneous Lymphoma Group guidelines for the management of primary cutaneous T-cell lymphomas

Abstract: These guidelines were commissioned by the British Association of Dermatologists guidelines and therapeutics subcommittee. Members of the committee are N.H.Cox (Chairman), A.S.Highet, D.Mehta, R.H.Meyrick Thomas, A.D.Ormerod, J.K.Schofield, C.H.Smith and J.C.Sterling. Members of the U.K. Cutaneous Lymphoma Group who have contributed include C.Benton, R.Cowan, C.Deardon, B.Hancock, H.Lucraft and D.Slater. Disclaimer These guidelines have been prepared for dermatologists on behalf of the British Association of Dermatologists and the U.K. Cutaneous Lymphoma Group (UKCLG) and reflect the best data available at the time the report was prepared. Caution should be exercised in interpreting the data; the results of future studies may require alteration of the conclusions or recommendations in this report. It may be necessary or even desirable to depart from the guidelines in special circumstances. Just as adherence to guidelines may not constitute defence against a claim of negligence, so deviation from them should not be necessarily deemed negligent. Summary These guidelines for the management of cutaneous T-cell lymphoma have been prepared for dermatologists on behalf of the British Association of Dermatologists and the U.K. Cutaneous Lymphoma Group. 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.

Randomized comparison of photodynamic therapy with topical 5-fluorouracil in Bowen's disease.

Abstract: SummaryBackground Bowen's disease (BD; intraepithelial squamous cell carcinoma) is therapeutically challenging because lesions, which may be multiple, are frequently located at sites that heal poorly. There is a small risk of progression to invasive carcinoma. Photodynamic therapy (PDT) is an effective treatment for certain non melanoma skin cancers, but comparison studies with other, better-established therapies are limited. Objectives To compare the efficacy and tolerability of PDT and topical 5-fluorouracil (5-FU) in BD. Methods Forty patients from two centres were randomized to either topical PDT or 5-FU. The PDT group was treated with 20% 5-aminolaevulinic acid (ALA) applied 4 h before illumination with 100 J cm−2 narrowband red light (630 ± 15 nm). 5-FU was applied to lesions for 4 weeks. A repeat treatment cycle was performed after 6 weeks if required. Results Twenty-nine of 33 (88%) lesions treated with PDT initially responded completely, compared with 22 of 33 (67%) after 5-FU. After 12 months, two recurrences in the PDT group and six in the 5-FU group reduced complete clinical clearance rates to 82% and 48%, respectively. PDT was significantly more effective (P = 0·006, odds ratio 4·78, 95% confidence interval 1·56–14·62). In the 5-FU group, severe eczematous reactions developed around seven lesions, ulceration in three and erosions in two. No such reactions occurred following PDT. There was no difference in overall pain experienced during each therapy. Conclusions Topical ALA-PDT is more effective than topical 5-FU in the treatment of BD, with fewer adverse events. ALA-PDT should be considered one of the first-line therapeutic options for BD.

Onychomycosis in clinical practice: factors contributing to recurrence.

Abstract: The treatment of onychomycosis has improved in recent years and many patients can now expect a complete and lasting cure. However, for up to 25% of patients, persistent disease remains a problem, thus presenting a particular challenge to the clinician. For these patients, it is obviously important to ensure that a correct diagnosis of onychomycosis has been made, as misdiagnosis will inevitably jeopardize the perception of therapeutic effectiveness. Although onychomycosis accounts for about 50% of all nail diseases seen by physicians, nonfungal causes of similar symptoms include repeated trauma, psoriasis, lichen planus, local tumours vascular disorders and inflammatory diseases. Predisposing factors that contribute to a poor response to topical and/or oral therapy include the presence of a very thick nail, extensive involvement of the entire nail unit, lateral nail disease and yellow spikes. However, poor penetration of systemic agents to the centre of infection, or the inability of topical agents to diffuse between the surface of the nail plate and the active disease below, probably contributes to this. Other factors contributing to recurrence may be related to the patient's family history, occupation, lifestyle or underlying physiology. In addition, patients with concomitant disease (e.g. peripheral vascular disease, diabetes) or patients who are immunosuppressed (e.g. those with human immunodeficiency virus/acquired immunodeficiency syndrome) are more susceptible to onychomycosis. In the elderly, the prevalence of onychomycosis may be as high as 60%, and increases with age; in this population, physical trauma plays a major role in precipitating recurrence, especially in patients with faulty biomechanics due to underlying arthritis and bone abnormalities. It is also possible that recurrence in some cases is due to early termination of treatment or use of an inappropriate dose, and these possibilities should be eliminated before further investigations are undertaken. There is good evidence to suggest that a combination of oral and topical therapies, when given at the same time, yield excellent clinical outcomes, although there remains a need for more effective topical agents with greater nail penetration and more effective oral antifungal agents.

International consensus conference on atopic dermatitis II (ICCAD II) Clinical update & current treatment strategies

Abstract: C . E L L I S * A N D T . L U G E R † O N B E H A L F O F T H E I C C A D I I F A C U L T Y : D . A B E C K , R . A L L E N , R . A . C . G R A H A M B R O W N , Y . D E P R O S T , L . F . E I C H E N F I E L D , C . F E R R A N D I Z , A . G I A N N E T T I , J . H A N I F I N , J . Y . M . K O O , D . L E U N G , C . L Y N D E , J . R I N G , R . R U I Z M A L D O N A D O A N D J H . S A U R A T

Guidelines for treatment of onychomycosis.

Abstract: These guidelines for management of onychomycosis 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.

Association of SPINK5 gene polymorphisms with atopic dermatitis in the Japanese population.

Abstract: Background Netherton's syndrome (NS) is an autosomal recessive disorder characterized by trichorrhexis invaginata ('bamboo hair'), congenital ichthyosiform erythroderma and an atopic diathesis. NS has recently been shown to be due to a defect in the SPINK5 gene, encoding LEKTI, a 15-domain serine protease inhibitor. SPINK5 maps to chromosome 5q31-q32, and has been suggested to be a locus predisposing to atopy in general. Recently, coding polymorphisms in SPINK5 exons 13 and 14 have been reported to be associated with atopy, asthma and atopic dermatitis (AD). Objectives To examine whether these polymorphisms are also associated with AD in Japan. Methods We characterized eight polymorphisms in SPINK5 exons 13 and 14 in 124 Japanese patients with AD and 110 healthy controls. The polymorphisms we examined were IVS12-26C-->T, IVS12-10A-->G, 1103A-->G (Asn368Ser, in exon 13), 1156G-->A (Asp386Asn, in exon 13), 1188T-->C (His396His, in exon 13), IVS13-50G-->A, 1258G-->A (Glu420Lys, in exon 14) and IVS14+19G-->A. Results We found significant associations between seven of these polymorphisms and AD in Japanese patients. Conclusions This study confirms the previous suggestion of an association between SPINK5 and AD.

Long‐term safety aspects of systemic therapy with fumaric acid esters in severe psoriasis

Abstract: Summary Background Therapy with fumaric acid esters (FAE) has been shown to be safe and effective in patients with severe psoriasis in several clinical studies with limited follow-up periods. In view of the chronic character of psoriasis, long-term safety aspects are of major importance in determining the suitability of a drug during prolonged periods of treatment. Objectives To investigate adverse events of therapy with systemic FAE with follow-up periods of up to 14 years, in order to determine safety aspects of their long-term use in patients with severe psoriasis. Methods Current and/or past therapeutic use of FAE was reviewed in 66 patients with severe psoriasis. Results Forty-one of 66 patients had received FAE for at least 1 year, and 12 of these 41 patients had received FAE for between 10 and 14 years. Adverse events were reported in 73% of the patients. These were usually mild and mainly consisting of flushing (55%), diarrhoea (42%), nausea (14%), tiredness (14%) and stomach complaints (12%). A relative lymphocytopenia was observed in 76% of patients during therapy with FAE, resulting in a permanent discontinuation of therapy with FAE in four patients. A transient eosinophilia and moderate liver enzyme elevations were observed in 14% and 25% of patients, respectively. Conclusions The present study indicates that FAE can be considered as a safe long-term treatment in patients with severe psoriasis.

Androgenetic alopecia in men aged 40-69 years: prevalence and risk factors.

Abstract: Summary Background The epidemiology of androgenetic alopecia (AGA) is not fully understood. Although a strong genetic basis has long been identified, little is known of its non-genetic causes. Objectives To estimate the prevalence of and to determine risk factors for AGA in men aged 40–69 years in Australia. Methods Men (n = 1390) were recruited at random from the electoral rolls to serve as controls in a population-based case–control study of prostate cancer. All were interviewed in person and direct observations of AGA were made. Men were grouped into the following categories; no AGA, frontal AGA, vertex AGA and full AGA (frontal and vertex AGA). Epidemiological data collected from these men were used for an analysis of risk factors for each AGA category using unconditional logistic regression with AGA category as the response variable adjusting for age, education and country of birth. Results The prevalence of vertex and full AGA increased with age from 31% (age 40–55 years) to 53% (age 65–69 years). Conversely, the proportion of men with only frontal AGA was very similar across all age groups (31–33%). No associations were found between pubertal growth spurt or acne, reports of adult body size at time of interview, urinary symptom score, marital status, or current smoking status or duration of smoking and the risk of any form of AGA. The consumption of alcohol was associated with a significant increase in risk of frontal and vertex AGA but not full AGA. Men with vertex AGA had fewer female sexual partners but average ejaculatory frequency did not differ between men in different AGA categories. Reported weight and lean body mass at reaching maturity at about 21 years of age were negatively associated with vertex balding (P for trend < 0·05) but not with frontal AGA or full AGA. Conclusions Evidence for environmental influences on AGA remains very slight. Our study failed to confirm previously reported or hypothesized associations with smoking and benign prostatic hypertrophy. The associations that we found with alcohol consumption and with lean body mass at age 21 years would be worthy of further research if they were able to be replicated in other studies.

Topical methyl aminolaevulinate photodynamic therapy in patients with basal cell carcinoma prone to complications and poor cosmetic outcome with conventional treatment.

Abstract: Summary Background Conventional treatment of basal cell carcinoma (BCC) causes morbidity and/or disfigurement in some patients because of the location (e.g. mid-face) and size of the lesion. Objectives Following reports that such difficult-to-treat BCC lesions have been treated successfully with topical methyl aminolaevulinate (MAL) photodynamic therapy (PDT), a multicentre study was performed to determine the response of such BCC to MAL-PDT. Methods An open, uncontrolled, prospective, multicentre study was conducted comprising patients with superficial and/or nodular BCC who were at risk of complications, poor cosmetic outcome, disfigurement and/or recurrence using conventional therapy. Patients were given one or two cycles within 3 months of topical MAL-PDT, each consisting of two treatments 1 week apart. Tumour response was assessed clinically at 3 months after the last PDT, with histological confirmation of all lesions in clinical remission. The cosmetic outcome was rated. Patients with a BCC in remission will be followed up for 5 years for recurrence, of which the 24-month follow-up is reported here. Ninety-four patients with 123 lesions were enrolled and treated with MAL-PDT at nine European primary care and referral university hospitals. An independent blinded study review board (SRB) retrospectively excluded nine patients and a total of 15 lesions from the efficacy analysis, for not having a difficult-to-treat BCC according to the protocol. Results The lesion remission rate at 3 months was 92% (45 of 49) for superficial BCC, 87% (45 of 52) for nodular BCC, and 57% (four of seven) for mixed BCC, as assessed by clinical examination, and 85% (40 of 47), 75% (38 of 51), and 43% (three of seven), respectively, as assessed by histological examination and verified by the SRB. At 24 months after treatment, the overall lesion recurrence rate was 18% (12 of 66). The cosmetic outcome was graded as excellent or good by the investigators in 76% of the cases after 3 months follow-up, rising to 85% at 12 months follow-up, and 94% at 24 months follow-up. Conclusions Topical MAL-PDT is effective in treating BCC at risk of complications and poor cosmetic outcome using conventional therapy. MAL-PDT preserves the skin and shows favourable cosmetic results.

The patterns of melanosome distribution in keratinocytes of human skin as one determining factor of skin colour.

Abstract: Background: One determining factor of skin colour is the distribution pattern of melanosomes within keratinocytes. Melanosomes in keratinocytes of light skin as in Caucasians are distributed as membrane-bound clusters, whereas the melanosomes in keratinocytes of dark skin as in African/American individuals tend to be larger and distributed individually. It has been shown that melanin content, melanin composition and the size of melanosomes in the human epidermis vary considerably with both ethnicity and chronic sun exposure. Objectives: To assess quantitatively the distribution pattern of melanosomes that have been transferred to keratinocytes in the photoprotected (volar forearm) skin from normal Asian individuals and to compare these data with those from light-skinned Caucasian and dark-skinned African/American individuals. Methods: Electron microscopy was used. Results: We have demonstrated that melanosomes within keratinocytes of Asian skin are distributed as a combination of individual and clustered melanosomes with a proportion of 62.6% vs. 37.4%, respectively. This contrasts with dark and light skin keratinocytes where melanosomes are predominantly individual (88.9%) and clustered (84.5%), respectively. Analysis of mean +/- SD melanosome size also revealed a progressive variation in size with ethnicity, melanosomes in dark skin being the largest (1.44 +/- 0.67 microm(2) x 10-2) followed in turn by those in Asian skin (1.36 +/- 0.15 microm(2) x 10-2) and Caucasian skin (0.94 +/- 0.48 microm(2) x 10-2). In addition, it was shown that the melanosomes that are individually distributed tend to have a larger size than the clustered melanosomes. Conclusions: The present data indicate that there may be a size gradient of melanosomes encompassing the global complexion coloration and that the melanosome distribution in keratinocytes of Asian skin is intermediate between that in light Caucasian and dark African/American skin.

Pruritogenic mediators in psoriasis vulgaris: comparative evaluation of itch-associated cutaneous factors.

Abstract: Summary Background Although some patients with psoriasis vulgaris also complain of severe pruritus, the data available regarding pruritus in psoriasis are sparse. Objectives To clarify the mechanism and mediators involved in the pruritus of psoriasis vulgaris, we compared itch-associated factors in lesional skin from psoriatic patients vs. skin without pruritus quantitatively using a panel of histological and immunohistological parameters. Patients and methods Biopsied specimens were obtained from 38 patients with psoriasis vulgaris who were divided into two groups according to the presence or absence of pruritus. Results When compared with psoriatic patients devoid of pruritus, lesional skin from patients with pruritus showed the following characteristic features: (i) a rich innervation both in the epidermis and in the papillary dermis; (ii) an increase in neuropeptide substance P-containing nerve fibres in perivascular areas; (iii) decreased expression of neutral endopeptidase in the epidermal basal layer as well as in the endothelia of blood vessels; (iv) many mast cells showing degranulating processes in the papillary dermis; (v) a strong immunoreactivity for nerve growth factor (NGF) throughout the entire epidermis and an increased NGF content in lesional skin homogenates; (vi) an increase in the expression of high-affinity receptors for NGF (Trk A) in basal keratinocytes and in dermal nerves; (vii) an increased population of interleukin-2-immunoreactive lymphocytes; and (viii) a strong expression of E-selectin on vascular endothelial cells. A significant correlation was observed between the severity of pruritus and protein gene product 9.5-immunoreactive intraepidermal nerve fibres, NGF-immunoreactive keratinocytes, expression of Trk A in the epidermis and the density of immunoreactive vessels for E-selectin. These findings indicate that possible pruritogenic mediators in psoriatic lesional skin are neurogenic factors including innervation, neuropeptide substance P, neuropeptide-degrading enzymes and NGF, activated mast cells, one or more cytokines and endothelial–leucocyte adhesion molecules. Conclusions These data document for the first time itch-related local markers in psoriasis, and suggest complex and multifactorial mechanisms of pruritus in the disease. These results provide the groundwork for further studies to evaluate the efficacy of antipruritic treatment for psoriatic patients.

Basal cell carcinoma: a dermatopathological and molecular biological update

Abstract: The ideal classification of basal cell carcinoma (BCC) should be able to identify subtypes which correlate with clinical behaviour and treatment requirements Unfortunately, however, such a classification has yet to be defined In the interim, the currently most favoured classification is one based predominantly on histological growth pattern This classification contributes to the useful concept of low- and high-risk histological subtypes of BCC The latter are characterized by an increased probability of subclinical extension and/or incomplete excision and/or aggressive local invasive behaviour and/or local recurrence The Royal College of Pathologists has published a minimum dataset for the histopathological reporting of BCC and this has been written to be compatible with the British Association of Dermatologists' management guidelines Growth patterns to be reported include nodular, superficial, infiltrative/morphoeic and micronodular types, together with differentiation when of severely atypical or malignant squamous type (basosquamous carcinoma) Deep and peripheral excision margins will be reported to be either involved or clear The latter will include a comment of a clearance of less than 1 mm for close margins and a measured distance in whole millimetres for other excisions Clinical assessment and histology remain the 'gold standard' for evaluating BCC and cancers in general However, in the postgenomic era emphasis is changing from the gathering and archiving of genomic data to its analysis and use in guiding clinical practice In this context, a current goal is to define cancer phenotype in terms of molecular abnormalities and use this as a new gold standard One way to assess whether this goal is being achieved for BCC is to determine whether our knowledge of its molecular pathology has any relevance to the minimum dataset for histological reporting Knowledge of BCC molecular pathology has been fuelled by the recent discovery that deregulation of the Hedgehog (Hh) signalling pathway, a key player in embryonic patterning, appears to be fundamental to tumour growth But despite accrual of a large amount of data concerning Hh pathway molecular alterations in neoplasia, little is known about the functional consequences of these changes in BCC, how they lead to tumour development, or how they relate to non-Hh pathway alterations such as TP53 mutation Recent work suggests that the cellular localization of beta-catenin gives a degree of credence to the growth pattern classification of BCC Furthermore, it is possible that beta-catenin may have a pathogenetic role in the invasive behaviour of BCC This review draws on current evidence to discuss these issues and assess whether they are relevant to the minimum dataset

In vitro susceptibility testing of ciclopirox, terbinafine, ketoconazole and itraconazole against dermatophytes and nondermatophytes, and in vitro evaluation of combination antifungal activity.

Abstract: Summary Background With the development of newer antifungal agents with activity against both yeasts and filamentous fungi, there is an increased need to develop and standardize in vitro assays that will evaluate the activity of antimycotics against filamentous fungi. In vitro analysis of antifungal activity of these agents would also allow for the comparison between different antimycotics, which in turn may clarify the reasons for lack of clinical response or serve as an effective therapy for patients with chronic infection. Objectives To determine the in vitro susceptibility of fungal organisms to ciclopirox, terbinafine, ketoconazole and itraconazole and to evaluate the in vitro activity and mode of interaction of ciclopirox in combination with either terbinafine or itraconazole. Materials and methods In the minimum inhibitory concentration (MIC) study 133 strains were evaluated, including dermatophytes (110 strains; 98 from Trichophyton spp.), Candida spp. (14 strains) and nondermatophyte moulds (nine strains). In vitro susceptibility testing was conducted in microbroth dilutions based on the National Committee for Clinical Laboratory Standards (NCCLS) M27-A proposed standard. The testing MIC ranges were 0·003–2 μg mL−1 for ciclopirox and terbinafine, and 0·06–32 μg mL−1 for itraconazole and ketoconazole. For inoculum preparation, dermatophytes were grown on Heinz oatmeal cereal agar slants. Inoculum suspensions of dermatophytes were diluted in RPMI 1640 (Sigma-Aldrich) with the desired final concentration being 2–5 × 103 c.f.u. mL−1. Once inoculated, the microdilution plates were set up according to the NCCLS M27-A method, incubated at 35 °C, and read visually following 7 days of incubation. For azole agents, the MIC was the lowest concentration showing 80% growth inhibition; for terbinafine and ciclopirox, the MIC was the lowest concentration showing 100% growth inhibition. In the synergy studies, 29 strains from nondermatophyte species were evaluated using a checkerboard microdilution method. The concentrations tested were: 0 and 0·06–32 μg mL−1 for itraconazole, and 0 and 0·003–4 μg mL−1 for both terbinafine and ciclopirox. Modes of interaction between drugs were classified as synergism, additivism, antagonism or indifference based on fractional inhibitory concentration index values (FIC index). Synergism was defined as an FIC index of ≤ 0·50, additivity as an FIC index of ≤ 1·0, and antagonism as an FIC index of ≥ 2·0. The drug combination was interpreted as indifferent if neither of the drugs had any visible effect on the presence of the other drug. Results In the MIC study, the dermatophyte MIC values (μg mL−1) (mean ± SEM) were: ciclopirox (0·04 ± 0·02), terbinafine (0·04 ± 0·23), itraconazole (2·28 ± 7·42) and ketoconazole (0·83 ± 1·99). The yeast MIC values (μg mL−1) (mean ± SEM) were: ciclopirox (0·05 ± 0·02), terbinafine (1·77 ± 0·58), itraconazole (0·18 ± 0·27) and ketoconazole (0·56 ± 0·60). The non-dermatophyte fungi MIC values (μg mL−1) (mean ± SEM) were: ciclopirox (1·04 ± 2·62), terbinafine (1·04 ± 0·95), itraconazole (17·87 ± 16·75) and ketoconazole (10·69 ± 13·09). In the synergy study, with ciclopirox in combination with terbinafine, mainly a synergistic or additive reaction was observed; there were no cases of antagonism. For ciclopirox in combination with itraconazole, there were some instances of additivism or synergism, with indifference in the majority of instances; there were no cases of antagonism. Conclusions In vitro susceptibility testing indicates that ciclopirox may have a broad antimicrobial profile including dermatophytes, yeasts and other nondermatophytes. Terbinafine is extremely potent against dermatophytes. In vitro evaluation of activity of ciclopirox and terbinafine suggests many instances of synergy or additivism; for ciclopirox and itraconazole there may be indifference, synergy or additivism.

Direct stimulatory effect of low-intensity 670 nm laser irradiation on human endothelial cell proliferation.

Abstract: Summary Background Endothelial cell (EC) proliferation plays a key role in the process of tissue repair. Low-intensity laser irradiation has been demonstrated to accelerate wound healing and to improve microvascularization. Objectives The present study evaluated a possible stimulatory influence of low-intensity laser irradiation on human umbilical vein endothelial cell (HUVEC) proliferation in a systematic manner. Methods Subconfluent cultures of HUVEC were irradiated every other day with a 670-nm diode laser (intensity: 10–65 mW cm−2, dose: 2–8 J cm−2) during a period of 6 days. Cell proliferation was evaluated quantitatively by counting in a haemocytometer. Results Our data demonstrate a dose-dependent and intensity-dependent stimulatory effect of laser irradiation on HUVEC cell proliferation. Doses of between 2 and 8 J cm−2 induced statistically significant cell proliferation. Testing different intensities at a constant dose of 8 J cm−2, 20 and 65 mW cm−2 induced most pronounced cell proliferation. Conclusions Low-intensity laser irradiation influences EC proliferation and might thereby contribute to the increase in angiogenesis and the acceleration of wound healing in vivo.