Showing papers in "British Journal of Dermatology in 2009"

Objective scoring of hidradenitis suppurativa reflecting the role of tobacco smoking and obesity

Abstract: Summary Background Hidradenitis suppurativa (HS) is a long-standing disease with abscess and often fistula formation, predominantly in the axillae and groins. The disease is difficult to treat and has a severe impact on quality of life. A clinically relevant system for scoring disease severity is lacking in HS. Objectives To evaluate the modified Hidradenitis Suppurativa Score (HSS) and to study the impact of body mass index (BMI) and smoking habits on disease severity. Methods Two hundred and fifty-one consecutive patients with HS referred to a clinic with special interest in the disease were included, of whom 115 were scored. Points were given for regions involved, types of lesion (nodules, fistulas), total area involved and whether lesions were separated by normal skin. Background characteristics included BMI and smoking habits. Two hundred and forty-six patients completed the Dermatology Life Quality Index (DLQI). Results The median (interquartile range, IQR) HSS for all patients was 38 (18–66): women 38 (18–71) and men 37 (19–51). Median (IQR) HSS for smokers was 41 (22–75·5), former smokers 27 (16–53) and nonsmokers 22 (10–57). Median (IQR) HSS for patients with BMI < 25 kg m−2 was 32 (12–54), BMI 25–30 kg m−2 44 (22–56) and BMI ≥ 30 kg m−2 50 (18–86). Mean ± SD DLQI for the whole group of patients was 10·3 ± 7·5, median 9, and showed no significant differences between the groups studied. There was a significant positive correlation of fair degree between HSS and DLQI. There were significant differences in HSS between nonsmokers and smokers as well as between women of normal weight compared with obese women. Conclusions The modified HSS is simple and practical and it extracts important clinical information. A connection between disease severity and BMI as well as smoking habits in patients with HS is presented. The results suggest that the HSS may be a relevant outcome measure in future therapeutic trials in HS.

British Association of Dermatologists’ guidelines for biologic interventions for psoriasis 2009

Abstract: St John’s Institute of Dermatology, King’s College London and Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT U.K. *Department of Dermatology, Royal Gwent Hospital, Newport NP20 2UB, U.K. Department of Dermatology, Western Infirmary, Glasgow G11 6NT, U.K. The Dermatology Centre, Salford Royal Hospital, University of Manchester, Manchester Academic Health Science Centre, Manchester M6 8HD, U.K. §Psoriasis and Psoriatic Arthritis Alliance, PO Box 111, St Albans AL2 3JQ, U.K. –Department of Dermatology, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, U.K. **Royal National Hospital for Rheumatic Diseases, Bath BA1 1RL, U.K. Department of Dermatology, Belfast City Hospital, Belfast BT9 7AB, U.K. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, U.K. §§Department of Dermatology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB9 2ZB, U.K.

Epidemiology and clinical pattern of psoriatic arthritis in Germany: a prospective interdisciplinary epidemiological study of 1511 patients with plaque-type psoriasis

Abstract: Summary Background Because psoriatic arthritis (PsA) usually develops years after the first manifestation of skin symptoms, in many cases the initial diagnosis of PsA depends on the dermatologist. Objectives To investigate the prevalence and clinical pattern of PsA in a daily practice population of patients with psoriasis. Methods Patients were enrolled in an observational prospective cross-sectional cohort study at 48 community and academic centres. Demographic and medical parameters were recorded, including severity of skin symptoms (Psoriasis Area and Severity Index, PASI), previous and current treatments, concomitant diseases, and the impact of psoriasis on productivity and health-related quality of life (Dermatology Life Quality Index, DLQI). Patients with joint symptoms were referred to a rheumatologist for diagnosis and to record the activity and pattern of arthritis. Results Among 1511 patients 20·6% had PsA; in 85% of the cases PsA was newly diagnosed. Of these patients more than 95% had active arthritis and 53·0% had five or more joints affected. Polyarthritis (58·7%) was the most common manifestation pattern, followed by oligoarthritis (31·6%) and arthritis mutilans (4·9%). Distal interphalangeal involvement was present in 41·0% and dactylitis in 23·7% of the patients. Compared with patients without arthritis, patients with PsA had more severe skin symptoms (mean PASI 14·3 vs. 11·5), a lower quality of life (mean DLQI 11·6 vs. 7·7) and greater impairment of productivity parameters. Conclusions The findings are consistent with a high prevalence of undiagnosed cases of active PsA among patients with psoriasis seen by dermatologists. As many of these patients also have significant skin symptoms, treatment strategies are required that are equally effective in the control of skin and joint symptoms of psoriasis.

Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin.

Abstract: Summary Background Th17 cells are a lineage of proinflammatory T helper cells producing interleukin (IL)-17. The importance of Th17 cells in inflammation and autoimmunity has now been recognized. The IL-17 cytokine family consists of six isoforms (IL-17A–IL-17F) whereas five members of the IL-17 receptor (IL-17R) family have been identified (IL-17RA–IL-17RE). Objectives To characterize the expression of the IL-17 isoforms and receptors in lesional and nonlesional psoriatic skin. Methods Keratome and punch biopsies taken from patients with psoriasis were examined by enzyme-linked immunosorbent assay and quantitative reverse transcription–polymerase chain reaction in order to measure the IL-17 isoforms and receptors. Results We demonstrated significantly increased mRNA expression of IL-17A, IL-17C and IL-17F in psoriatic skin. In contrast, the mRNA expression of IL-17B and IL-17D was significantly decreased in lesional compared with nonlesional skin, while IL-17E mRNA was undetectable. The increased mRNA expression of IL-17A, IL-17C and IL-17F was paralleled by an increased protein accumulation of these cytokines in psoriatic skin. Analysis of the IL-17R mRNA expression revealed significantly impaired mRNA expression of IL-17RB, IL-17RC, IL-17RD and IL-17RE in lesional psoriatic skin, whereas the mRNA expression of IL-17RA was similar in lesional and nonlesional psoriatic skin. Conclusions This study characterizes the mRNA profile of the IL-17 isoforms and receptors in psoriatic skin lesions. Furthermore, we demonstrate for the first time augmented protein levels of IL-17A, IL-17C and IL-17F in psoriatic skin lesions, indicating a possible role for IL-17C in addition to IL-17A and IL-17F in the pathogenesis of psoriasis.

Prevention of non-melanoma skin cancer in organ transplant patients by regular use of a sunscreen: a 24 months, prospective, case-control study.

Abstract: Summary Background Skin cancers represent a major challenge within the ever growing group of long time surviving organ transplant recipients (OTR) world wide. Especially UV-induced non-melanoma skin cancers (NMSC) like invasive squamous cell carcinomas (SCC) and actinic keratoses (AK), and basal cell carcinoma (BCC), outnumber every other form of cancer in organ transplant recipients. Despite encouraging reports of protective effects of broad-spectrum sunscreens in immunocompetent patients, evidence for the prevention of NMSC in immunocompromised patients is still missing. Objectives To assess preventive effects of regular sun-screen use on AK, SCC and BCC in chronically immunocompromised organ transplant recipients. Methods Hundred and twenty matched (age, sex, skin type, graft, transplant duration, previous post-transplant skin malignancies) organ transplant recipients (40 heart, 40 kidney, 40 liver grafted) were recruited for this prospective, single-center study. Both groups received equally written and oral information on sun protection measures. Sixty patients were provided with a free broad spectrum study-sunscreen (SPF > 50, high-UVA absorption) for daily application of 2 mg cm−2 to the head, neck, forearms, and hands. Results All 120 patients completed the 24 months study. Within this 24 month study interval 42 of the 120 patients developed 82 new AK (−102 sun screen group vs. + 82 control; P < 0·01), 8 new invasive SCC (0 vs. 8; P < 0·01) and 11 BCC (2 vs. 9; ns). In spite of equal numbers of AK at baseline, a marked difference in favor of the intent-to-treat sunscreen group was recorded after 24 months (89 vs. 273; P < 0·01, mean difference 3·07 [1·76–4·36]) and the lesion count was significantly lower as compared to the initial visit (89 vs. 191; P < 0·01, mean difference 1·7 [0·68–2·72]). With an average of 5·6 applications per week throughout the 24 months the study sunscreen was generally well tolerated. Serum 25-hydroxy vitamin D levels as marker for vitamin D status were decreased in all patients without adequate substitution and 25(OH)D was found to be lower in the sunscreen-group as compared to the control group (mean value 53 ng mL−1 vs. 60 ng mL−1). Interpretation Regular use of sunscreens, as part of a consequent UV-protection strategy, may prevent the development of further AK and invasive SCC and, to a lesser degree, BCC in immune-compromised organ transplant recipients.

Hereditary angio-oedema in Denmark: a nationwide survey.

Abstract: Background Hereditary angio-oedema (HAE) is a rare disease caused by deficiency of complement C1 inhibitor (C1 inhibitor). The diagnosis is challenging as the disease can have a variety of clinical manifestations. In 2001 a national HAE comprehensive care centre was established and a search for these patients was initiated. Objectives To identify and characterize all patients with HAE in Denmark and increase awareness of the disease. Methods Patients were recruited from hospital departments, dermatologists in private practice, Centres for Rare Diseases, the Danish patient organization and the national reference laboratory. Family interviews were conducted and medical records were evaluated. Information was spread through lectures, articles in popular magazines and via television. National guidelines for diagnosis and treatment were published. Results Eighty-two patients were identified. The mean diagnostic delay was 16.3 years. Five patients had HAE type II. Forty-five patients reported a characteristic serpiginous rash (erythema marginatum). More than 90% of patients had noticed precipitating factors before skin and mucosal swellings. Four patients underwent a total of eight tracheotomies and five families recalled 11 relatives who died of HAE. Conclusions The minimal prevalence of HAE in Denmark is approximately 1.41 per 100 000 inhabitants. The risk of upper airway obstruction underlines the importance of diagnosing these patients. Precipitating factors, a preceding or concomitant serpiginous erythema and cutaneous swelling and/or abdominal pain attack and/or laryngeal oedema are clues to the diagnosis. As a consequence of this survey, information has been spread to patients, families and physicians.

Incidence of bullous pemphigoid and pemphigus in Switzerland: a 2-year prospective study.

Abstract: BACKGROUND: Bullous pemphigoid (BP), pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune bullous diseases characterized by the presence of tissue-bound and circulating autoantibodies directed against disease-specific target antigens of the skin. Although rare, these diseases run a chronic course and are associated with significant morbidity and mortality. There are few prospective data on gender- and age-specific incidence of these disorders. OBJECTIVES: Our aims were: (i) to evaluate the incidence of BP and PV/PF in Swiss patients, as the primary endpoint; and (ii) to assess the profile of the patients, particularly for comorbidities and medications, as the secondary endpoint. METHODS: The protocol of the study was distributed to all dermatology clinics, immunopathology laboratories and practising dermatologists in Switzerland. All newly diagnosed cases of BP and pemphigus occurring between 1 January 2001 and 31 December 2002 were collected. In total, 168 patients (73 men and 95 women) with these autoimmune bullous diseases, with a diagnosis based on clinical, histological and immunopathological criteria, were finally included. RESULTS: BP showed a mean incidence of 12.1 new cases per million people per year. Its incidence increased significantly after the age of 70 years, with a maximal value after the age of 90 years. The female/male ratio was 1.3. The age-standardized incidence of BP using the European population as reference was, however, lower, with 6.8 new cases per million people per year, reflecting the ageing of the Swiss population. In contrast, both PV and PF were less frequent. Their combined mean incidence was 0.6 new cases per million people per year. CONCLUSIONS; This is the first comprehensive prospective study analysing the incidence of autoimmune bullous diseases in an entire country. Our patient cohort is large enough to establish BP as the most frequent autoimmune bullous disease. Its incidence rate appears higher compared with other previous studies, most likely because of the demographic characteristics of the Swiss population. Nevertheless, based on its potentially misleading presentations, it is possible that the real incidence rate of BP is still underestimated. Based on its significant incidence in the elderly population, BP should deserve more public health concern.

Targeted treatment of pyoderma gangrenosum in PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome with the recombinant human interleukin-1 receptor antagonist anakinra.

Abstract: The triad of sterile pyogenic arthritis, pyoderma gangrenosum and acne is known by the acronym of PAPA syndrome. It is a rare autosomal dominant disease of early onset. The treatment of pyoderma gangrenosum is challenging as there is often only partial response to systemic glucocorticosteroids and immunosuppressive therapies. We report the rapid and lasting response of pyoderma gangrenosum to the targeted treatment with the recombinant human interleukin-1 receptor antagonist (rHuIL-1Ra) anakinra in a patient with PAPA syndrome.

Cutaneous adverse effects in patients treated with the multitargeted kinase inhibitors sorafenib and sunitinib

Abstract: Summary Background The multitargeted kinase inhibitors sorafenib and sunitinib have improved treatment of solid tumours including renal cell carcinoma and hepatocellular carcinoma by offering better clinical responses. However, sorafenib and sunitinib are commonly associated with cutaneous toxicity. Objectives We conducted this study to make a clinical assessment of the cutaneous toxicities induced by the oral multitargeted kinase inhibitors sorafenib and sunitinib. Methods Retrospectively, we reviewed medical records of patients receiving multitargeted kinase inhibitors, including 109 patients on sorafenib for the treatment of renal cell carcinoma or hepatocellular carcinoma and 119 patients receiving sunitinib for treatment of renal cell carcinoma or a gastrointestinal stromal tumour. Clinical data on cutaneous toxicities were collated. We describe the incidences and intensities of toxicities, and analyse the data statistically. Results The most common cutaneous toxicity was hand-and-foot skin reaction (HFSR). Other cutaneous toxicities included alopecia, stomatitis, skin discoloration (hair or face), subungual splinter haemorrhage, facial swelling, facial erythema and xerosis. HFSR and severe stomatitis required therapy modifications to relieve symptoms, but other cutaneous toxicities did not affect treatment course. HFSR was observed in 48% of patients treated with sorafenib and 36% of those treated with sunitinib. Median time to onset was 18·4 days in patients receiving sorafenib and 32·4 days in those receiving sunitinib. HFSR and stomatitis were early symptoms compared with other cutaneous toxicities. Patients with severe HFSR were likely to develop the symptoms at early phases of therapy. A significant correlation between the severity of HFSR and development of alopecia and stomatitis was found. Conclusions Multitargeted kinase inhibitors are associated with a significant risk of various cutaneous adverse events. HFSR is the commonest and most serious cutaneous toxicity in patients treated with these drugs.

Psoriasis and risk of incident myocardial infarction, stroke or transient ischaemic attack: an inception cohort study with a nested case-control analysis.

Abstract: BACKGROUND: Systemic inflammation may increase the risk for cardiovascular diseases in patients with psoriasis, but data on this risk in patients with early psoriasis are scarce. OBJECTIVES: To assess and compare the risk of developing incident myocardial infarction (MI), stroke or transient ischaemic attack (TIA) between an inception cohort of patients with psoriasis and a psoriasis-free population. METHODS: We conducted an inception cohort study with a nested case-control analysis within the U.K.-based General Practice Research Database. The study population encompassed 36,702 patients with a first-time recorded diagnosis of psoriasis 1994-2005, matched 1 : 1 to psoriasis-free patients. We assessed crude incidence rates (IRs) and applied conditional logistic regression to obtain odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Overall, the IRs of MI (n = 449), stroke (n = 535) and TIA (n = 402) were similar among patients with or without psoriasis. However, the adjusted OR of developing MI for patients with psoriasis aged > 60 years was 1.66 (95% CI 1.03-2.66) compared with patients without psoriasis, while the OR for patients aged 60 years, mainly with severe disease.

Increased stratum corneum serine protease activity in acute eczematous atopic skin.

Abstract: Summary Background Atopic dermatitis (AD) is a chronic inflammatory disease associated with changes in stratum corneum (SC) structure and function. The breakdown of epidermal barrier function in AD is associated with changes in corneocyte size and maturation, desquamation, lipid profiles, and some protease activities. Objectives The purpose of this study was: (i) to examine physiological changes in lesional (L) skin of acute eczematous AD, compared with nonlesional (NL) AD skin and healthy (H) skin, using sequential tewametry and SC protein analysis to estimate SC thickness; and (ii) to assess which serine proteases might be involved in pathogenesis. Methods Six subjects with H skin, six AD patients with NL skin and six AD patients with mild to moderate eczema (L skin) were enrolled. Skin was assessed using several noninvasive techniques but SC thickness was estimated using tewametry and SC protein content of D-Squame strippings. SC integrity was determined by sequential tape stripping (D-Squame) and infrared densitometry. Kallikreins, plasmin, urokinase and leucocyte elastase protease activities together with a novel SC tryptase-like enzyme activity were quantified. Results Transepidermal water loss (TEWL) levels after D-Squame stripping were elevated in L compared with NL and H skin at all sampling points (P < 0·05). Conversely, the amount of SC removed by sequential tape stripping was decreased in L skin, indicating increased intracorneocyte cohesion (P < 0·05). By correlating 1/TEWL values and SC removed as an estimate of SC thickness, a significantly thinner SC was observed in L compared with NL and H skin (P < 0·05). Elevated extractable serine protease activity was measured in AD skin in the order: SC tryptase-like enzyme (45×), plasmin (30×), urokinase (7·1×), trypsin-like kallikreins (5·8×) and chymotrypsin-like kallikreins (3·9×). Leucocyte elastase activity was not detected in H and NL skin but was observed in AD SC samples (L skin). All enzymes were elevated in the deeper layers of L SC compared with NL and H SC samples. All consistently elevated SC protease activities were significantly correlated with the bioinstrumental data. Conclusions We report increased serine protease activities in acute eczematous AD, especially in deeper layers of the SC, including SC tryptase-like enzyme, plasmin, urokinase and leucocyte elastase activities. These elevations in protease activities were associated with impaired barrier function, irritation, and reduced skin capacitance. Increased SC cohesion was apparent despite elevated TEWL during tape stripping, which would indicate reduced SC thickness in acute eczematous lesions of AD. Indeed, this was observed using an estimate of SC thickness.

Impact of dermoscopy and short‐term sequential digital dermoscopy imaging for the management of pigmented lesions in primary care: a sequential intervention trial

Abstract: Background Studies have shown the benign to malignant ratio of excised pigmented skin lesions is suboptimal in primary care. Objectives To assess the impact of dermoscopy and short-term sequential digital dermoscopy imaging (SDDI) on the management of suspicious pigmented skin lesions by primary care physicians. Methods A total of 63 primary care physicians were trained in the use of dermoscopy and SDDI (interventions) and then recruited pigmented lesions requiring biopsy or referral in routine care by naked eye examination. They were then given a dermatoscope and the option of a SDDI instrument, and change of diagnosis and management was assessed. Results Following the use of the interventions on 374 lesions a total of 163 lesions (43·6%) were excised or referred, representing a reduction of 56·4%. Of the 323 lesions confirmed to be benign, 118 (36·5%) were excised or referred, leading to a reduction of 63·5% (P < 0·0005) in those requiring excision or referral. The baseline naked eye examination benign to melanoma ratio was 9·5 : 1 which decreased to 3·5 : 1 after the diagnostic interventions (P < 0·0005). Of the 42 malignant lesions included in the study (34 melanoma, six pigmented basal cell carcinoma and two Bowen disease) only one in situ melanoma was incorrectly managed (patient to return if changes occur) resulting in the correct management of 97·6% and 97·1% of malignant pigmented lesions and melanoma, respectively. Conclusions In a primary care setting the combination of dermoscopy and short-term SDDI reduces the excision or referral of benign pigmented lesions by more than half while nearly doubling the sensitivity for the diagnosis of melanoma. © 2009 British Association of Dermatologists.

Frontal fibrosing alopecia: clinical presentations and prognosis

Abstract: Summary Background Frontal fibrosing alopecia is an uncommon condition characterized by progressive frontotemporal recession due to inflammatory destruction of hair follicles. Little is known about the natural history of this disease. Objectives To determine the clinical features and natural history of frontal fibrosing alopecia. Methods We studied the cases notes of patients diagnosed with frontal fibrosing alopecia from 1993 to 2008 at the Royal Hallamshire Hospital, Sheffield. Results There were 18 patients aged between 34 and 71 years. Three were premenopausal. All had frontotemporal recession with scarring. This was associated with partial or complete loss of eyebrows in 15 patients while four had hair loss at other sites. One had keratosis pilaris-like papules on the face, and one had follicular erythema on the cheeks. Three patients had oral lichen planus, of whom two also had cutaneous lichen planus affecting other sites of the body. Treatments given included intralesional triamcinolone acetonide, 0·1% tacrolimus ointment and oral hydroxychloroquine. Progression of frontotemporal recession was seen in some patients, but not all. In one patient the hair line receded by 30 mm over 72 months, whereas in another patient there was no positional change in the hair line after 15 years. Conclusions Frontal fibrosing alopecia is more common in postmenopausal women, but it can occur in younger women. It may be associated with mucocutaneous lichen planus. Recession of the hair line may progress inexorably over many years but this is not inevitable. It is not clear whether or not treatment alters the natural history of the disease – the disease stabilized with time in most of the patients with or without continuing treatment.

Genetic susceptibility to raised dermal scarring.

Abstract: Raised skin scars, such as keloid and hypertrophic scars mostly occur post-wounding in the human dermis. There is compelling evidence for a genetic component to these conditions, given the familial predisposition, varied incidence in different ethnic populations and the presence in twins. The aim of this study was to perform a systematic review of the literature regarding genetic susceptibility to raised dermal scarring. We identified relevant articles by a systematic search of relevant search engines. Key search terms included: keloid disease, hypertrophic scarring, fibrosis, linkage analysis, gene expression, human leucocyte antigen system (HLA), twins, families, case-control association study and congenital syndromes. Numerous candidate genes have been identified, along with potential linkage regions on different chromosomes. Recent data also suggest that carriers of specific major histocompatibility complex (MHC) alleles, in particular HLA-DRB1*15, HLA-DQA1*0104, DQB1*0501 and DQB1*0503, are at increased risk of developing keloid scarring. In addition, distinct immunophenotypical profiles can distinguish between keloid and hypertrophic scars. Keloid and hypertrophic scars are multifaceted aberrations of the healing process with as yet incompletely understood aetiologies. Current data suggest a genetic susceptibility with a strong immunogenic component to dermal fibrosis with MHC genes being implicated. It appears unlikely that a single gene is responsible for the development of raised dermal scars. A likely scenario may involve the interaction of several gene pathways in addition to environmental factors. The ability to assess accurately an individual's potential genetic susceptibility to raised scarring may lead to a more personalized approach to their management in the future.

Does chronic sunscreen use reduce vitamin D production to insufficient levels

Abstract: Summary Exposure to ultraviolet B radiation in sunlight provides the mechanism for more than 90% of the vitamin D production in most individuals. Concern has been expressed in recent years that the widespread use of sunscreens, particularly those with high sun protection factors, may lead to a significant decrease in solar-induced previtamin D3 in the skin, resulting in a vitamin D level which is considered insufficient for protection against a wide range of diseases. In this article the published evidence to support and to question this view is presented. It is concluded that, although sunscreens can significantly reduce the production of vitamin D under very strictly controlled conditions, their normal usage does not generally result in vitamin D insufficiency.

Hand eczema classification: a cross‐sectional, multicentre study of the aetiology and morphology of hand eczema

Abstract: Hand eczema is a long-lasting disease with a high prevalence in the background population. The disease has severe, negative effects on quality of life and sometimes on social status. Epidemiological studies have identified risk factors for onset and prognosis, but treatment of the disease is rarely evidence based, and a classification system for different subdiagnoses of hand eczema is not agreed upon. Randomized controlled trials investigating the treatment of hand eczema are called for. For this, as well as for clinical purposes, a generally accepted classification system for hand eczema is needed. The present study attempts to characterize subdiagnoses of hand eczema with respect to basic demographics, medical history and morphology. Clinical data from 416 patients with hand eczema from 10 European patch test clinics were assessed. A classification system for hand eczema is proposed. It is suggested that this classification be used in clinical work and in clinical trials. (Less)

Exclusive breastfeeding and incident atopic dermatitis in childhood: a systematic review and meta‐analysis of prospective cohort studies

Abstract: Summary Background Breastfeeding is undisputedly preferable to formula feeding for infant nutrition because of its nutritional, immunological and psychological benefits. However, studies on the association between breastfeeding and development of atopic dermatitis (AD) have shown inconsistent results. Objectives To examine the association between exclusive breastfeeding for at least 3 months after birth and the development of AD in childhood. Methods An electronic literature search of MEDLINE (January 1966–May 2008) and EMBASE (1980–May 2008) was conducted. Prospective cohort studies that met the predetermined criteria were independently assessed by three reviewers. The pooled effect estimate was calculated by random effects model. Heterogeneity across the studies was investigated by meta-regression analysis. Results Twenty-one studies with 27 study populations were included for meta-analysis. The summary odds ratio (OR) for the effect of exclusive breastfeeding on the risk of AD was 0·89 (95% confidence interval, CI 0·76–1·04). Heterogeneity was found across the studies (χ2 = 83·6, d.f. = 26; P < 0·001). Breastfeeding was associated with a decreased risk of AD (OR 0·70; 95% CI 0·50–0·99) when analysis was restricted to the studies comparing breastfeeding with conventional formula feeding. The pooled OR for study populations with atopic heredity was 0·78 (95% CI 0·58–1·05). Conclusions There is no strong evidence of a protective effect of exclusive breastfeeding for at least 3 months against AD, even among children with a positive family history.

In vivo thickness measurement of basal cell carcinoma and actinic keratosis with optical coherence tomography and 20-MHz ultrasound.

Abstract: Summary Background Accurate assessment of tumour size is important when planning treatment of nonmelanoma skin cancer (NMSC). Imaging with optical coherence tomography (OCT) has the potential to diagnose and measure depth of NMSC. Objectives To compare accuracy of mean tumour thickness measurement in NMSC tumours < 2 mm of depth using OCT and 20-MHz high-frequency ultrasound (HFUS). In addition, OCT morphology of NMSC was studied in OCT images and the influence of histological and colorimetric values on the quality and penetration depth in OCT images was estimated. Methods In total, 93 patients were scanned and 34 lesions [23 basal cell carcinoma (BCC) and 11 actinic keratosis (AK) lesions] < 2 mm thick and easily identified in OCT images were studied. OCT and HFUS were compared with biopsies. The influence of skin pigmentation and infiltration analgesia on OCT image quality was studied. Skin colour was measured with a colorimeter. Results OCT presented narrower limits of agreement than HFUS. Both methods overestimated thickness but OCT was significantly less biased (0·392 mm vs. 0·713 mm). No relation between OCT penetration depth and skin colour was found. Conclusions OCT appears more precise and less biased than HFUS for thickness measurement in AK and BCC lesions < 2 mm, but both OCT and especially HFUS tended to overestimate tumour thickness.

Guidelines for the management of contact dermatitis: an update

Abstract: These guidelines for management of contact dermatitis have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence-based guidance for investigation and treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, including details of relevant epidemiological aspects, diagnosis and investigation.

Photodynamic therapy of actinic keratoses with 8% and 16% methyl aminolaevulinate and home-based daylight exposure: a double-blinded randomized clinical trial.

Abstract: Summary Background Photodynamic therapy (PDT) is an effective but time-consuming andoften painful treatment for actinic keratosis (AK). Home-based daylight–PDT hasthe potential to facilitate treatment procedure and to reduce associated pain dueto continuous activation of small amounts of porphyrins. Moreover, a reducedmethyl aminolaevulinate (MAL) concentration may reduce associated inflamma-tion, making the treatment more tolerable for the patients.Objectives To compare response rates and adverse effects after PDT using conven-tional 16% and 8% MAL with home-based daylight exposure in treatment of AK.Methods Thirty patients with mostly thin-grade AK of the face or scalp were trea-ted with 16% and 8% MAL–PDT in two symmetrical areas after application ofsunscreen. Immediately after, patients left the hospital with instructions to spendthe remaining day outside at home in daylight. Patients scored pain during treat-ment and light exposure was monitored with an electronic wristwatch dosimeter.Results The complete response rate after 3 months was 76AE9% for 16% MAL and79AE5% for 8% MAL (P =0AE37). Patients spent a mean of 244 min outdoors andreceived a mean effective light dose of 30 J cm

Systematic review of dermoscopy and digital dermoscopy/ artificial intelligence for the diagnosis of melanoma

Abstract: Summary Background Dermoscopy improves diagnostic accuracy of the unaided eye for melanoma, and digital dermoscopy with artificial intelligence or computer diagnosis has also been shown useful for the diagnosis of melanoma. At present there is no clear evidence regarding the diagnostic accuracy of dermoscopy compared with artificial intelligence. Objectives To evaluate the diagnostic accuracy of dermoscopy and digital dermoscopy/artificial intelligence for melanoma diagnosis and to compare the diagnostic accuracy of the different dermoscopic algorithms with each other and with digital dermoscopy/artificial intelligence for the detection of melanoma. Methods A literature search on dermoscopy and digital dermoscopy/artificial intelligence for melanoma diagnosis was performed using several databases. Titles and abstracts of the retrieved articles were screened using a literature evaluation form. A quality assessment form was developed to assess the quality of the included studies. Heterogeneity among the studies was assessed. Pooled data were analysed using meta-analytical methods and comparisons between different algorithms were performed. Results Of 765 articles retrieved, 30 studies were eligible for meta-analysis. Pooled sensitivity for artificial intelligence was slightly higher than for dermoscopy (91% vs. 88%; P = 0·076). Pooled specificity for dermoscopy was significantly better than artificial intelligence (86% vs. 79%; P < 0·001). Pooled diagnostic odds ratio was 51·5 for dermoscopy and 57·8 for artificial intelligence, which were not significantly different (P = 0·783). There were no significance differences in diagnostic odds ratio among the different dermoscopic diagnostic algorithms. Conclusions Dermoscopy and artificial intelligence performed equally well for diagnosis of melanocytic skin lesions. There was no significant difference in the diagnostic performance of various dermoscopy algorithms. The three-point checklist, the seven-point checklist and Menzies score had better diagnostic odds ratios than the others; however, these results need to be confirmed by a large-scale high-quality population-based study.

Distinct patterns of brain activity evoked by histamine-induced itch reveal an association with itch intensity and disease severity in atopic dermatitis.

Abstract: Pruritus is a most distressing symptom in many dermatological and systemic disorders – the most notable being atopic dermatitis (AD).1 In its chronic form, pruritus profoundly impacts quality of life and constitutes an enormous burden to society. Pruritus is so central to AD that it may frequently be referred to as ‘the itch that rashes’.2 Currently, the understanding of the pathophysiology of pruritus is poor. Present data points towards an intricate interplay between peripheral and central mechanisms.3 Neuroimaging studies until recently were focused on brain imaging of histamine-induced itch in healthy human subjects. In healthy humans, acute histamine-induced itch coactivates the anterior cingulate cortex (ACC), the insular and primary somatosensory cortices, premotor and supplementary motor areas, cerebellum and thalamus.4–13 A recent study using positron emission tomography (PET) was the first to image brain processing of itch in patients with AD in remission and demonstrated similar areas of activation to those of healthy subjects, with higher activation in patients with AD in the contralateral thalamus, ipsilateral putamen and pallidum.14 However, as yet there is no study that has examined brain activation of itch in patients with active chronic itch. The neuroimaging of pruritus-related brain activity is a methodogical challenge. To date, studies have used PET and functional magnetic resonance imaging (fMRI) employing blood oxygen level dependent (BOLD) contrast.4,5,7,9,10,12 Although PET is fully quantifiable, radiation exposure and methodological complexities associated with this neuroimaging technique limit its routine use. In addition, the BOLD technique is suited to a biphasic stimulus model where sensory stimuli are turned on and off within a few seconds. However, the biphasic stimulus model is not suitable for experimentally induced itch, which usually takes a few minutes to reach peak intensity. Recent studies have been performed to overcome this limitation by manipulating the time course of itch with repeated itch induction with intermittent cooling or local anaesthetics.6,11 These experimental designs are rather complex to perform. The emerging technique of fMRI using arterial spin labelling (ASL) appears more suited to assess pruritus-related brain activity than the widely adopted BOLD method. Reasons include improved sensitivity for slow changes in neural activity (> 30 s) and better comparisons between different subject groups.15,16 In the present study we evaluated the central processing of histamine-induced pruritus in patients with AD with active disease and healthy subjects using the emerging technique of ASL fMRI. We show that the neural networks activated by pruritus differ in these two groups.

Itch characteristics in atopic dermatitis: results of a web‐based questionnaire

Abstract: Summary Background Itch significantly impairs the quality of life of patients with atopic dermatitis. However, only a few previous studies have examined the specific characteristics of itch in atopic dermatitis. Objective To examine the frequency, intensity and perceived characteristics of pruritus among individuals with atopic dermatitis. Methods Questionnaire reliability and validity were established in pilot testing. Survey participants completed the comprehensive, web-based ‘Characteristics of itch’ questionnaire. Participants provided anonymous demographic information and answered questions regarding itch intensity, frequency, timing, duration, location, associated symptoms and itch descriptors. Results A total of 304 individuals with atopic dermatitis completed the web-based questionnaire. Itch occurred at least once daily in 91% of the individuals surveyed. Of the 32 itch descriptors rated by survey participants, 31 demonstrated a statistically significant positive correlation with the participants’ ratings of itch intensity (P < 0·001). More than half the survey participants reported pain (59%) and heat sensation (53%) associated with itch. Conclusion The questionnaire was found to be a useful tool in characterization of itch. Pain appears to be an important component of atopic dermatitis. The strong correlation between itch descriptors and itch intensity suggests that such descriptors serve as strong indicators of the symptomatology in atopic dermatitis.

Cytokine imbalance with increased production of interferon-α in psoriasiform eruptions associated with antitumour necrosis factor-α treatments

Abstract: Summary Background Psoriasiform eruptions occur in association with antitumour necrosis factor (TNF)-α treatments in autoinflammatory diseases. The major reported clinical presentation is palmoplantar pustulosis, sometimes accompanied with plaque-like psoriasis. In some reports, histological findings suggest psoriasis whereas others favour a lichenoid drug reaction. We present a case series with a comprehensive clinical, histopathological and immunohistochemical study. Objectives To investigate the mechanism involved in psoriasiform eruptions in patients receiving anti-TNF-α inhibitors. Methods Between July 2004 and May 2008, 13 patients with psoriasiform eruptions arising under anti-TNF-α treatment were enrolled in the study. Punch biopsy specimens of lesions were processed for standard and immunohistochemical analyses using antibodies against CD3, CD4, CD8, CD20, CD1a, KP1, CXCR3, CXCL9, Tia1 and MxA, which is specifically induced by type I interferons (IFNs). Additionally, we analysed biopsies from lesional skin of patients with cutaneous discoid lupus erythematosus, lichen planus and psoriasis. Control biopsies were taken from unaffected skin. Results All patients developed psoriasiform plaques on the body accompanied with palmoplantar keratoderma or pustulosis in three patients. Histological and immunohistochemical findings showed a psoriasiform pattern with focal lichenoid and spongiotic features. We detected strong production of the MxA protein in inflammatory cells, indicating involvement of type I IFNs, and the expression was higher than in control psoriasis samples. Expression of MxA was closely associated with the recruitment of CXCR3+ lymphocytes in the skin bearing markers of cytotoxic capacity. Conclusions Results support the hypothesis that psoriasiform eruptions are a new model of drug reaction characterized by an increased expression of type I IFNs induced by anti-TNF-α.

Natural moisturizing factor components in the stratum corneum as biomarkers of filaggrin genotype: evaluation of minimally invasive methods

Abstract: Summary Background The carriers of loss-of-function mutations in the filaggrin gene (FLG) have reduced levels of natural moisturizing factor (NMF) in the stratum corneum. The concentration of NMF components which are formed by filaggrin protein breakdown in the stratum corneum might therefore be useful as a biomarker of the FLG genotype. Objectives To investigate the feasibility of different sampling methods for the determination of two NMF components, 2-pyrrolidone-5-carboxylic acid (PCA) and urocanic acid (UCA), in the stratum corneum as biomarkers for the FLG genotype. Methods PCA and UCA from the stratum corneum were sampled by using a tape stripping technique and an extraction technique using skin patches containing potassium hydroxide (KOH). The concentrations of PCA and UCA were measured by high-performance liquid chromatography. Eleven carriers of an FLG mutation and 10 individuals wild type for the two most common FLG mutations (R501X and 2282del4) were included in the study. Results The most significant difference between the FLG genotypes was found for PCA sampled by the tape stripping technique. The mean values of PCA obtained by the tape stripping technique were, respectively, 0·18, 0·50 and 1·64 mmol g−1 protein in homozygous (or compound heterozygous), heterozygous and wild-type genotypes (P < 0·005 homozygous vs. heterozygous; P < 0·0001 heterozygous vs. wild type). The tape stripping technique showed less intrasubject variation compared with the KOH patches, in particular when the concentrations of UCA and PCA on the tape strips were normalized for protein amount. Conclusions The concentration of PCA in the stratum corneum collected by tape stripping showed it to be a feasible biomarker of the FLG genotype.

Hand eczema and quality of life: a population‐based study

Abstract: Summary Background Hand eczema is a common disease in the population and is of interest from a public health perspective. Health-related quality of life (HRQoL) is increasingly being measured in dermatology. Objectives To investigate HRQoL in relation to hand eczema in the general population. Methods In the Public Health Survey of Stockholm County Council 2006, a questionnaire was sent to 57 009 randomly selected individuals aged 18–84 years. The response rate among persons of working age (18–64 years) was 58%. The questionnaire included a validated question concerning hand eczema and a generic instrument for measurement of HRQoL, the EQ-5D. Results The proportion of individuals reporting problems was significantly larger among those with than without hand eczema in all five dimensions of the EQ-5D. Gender differences were found in some age subgroups. The EQ-5D index was lower for individuals with hand eczema than for those without, and on the same level as for psoriasis and asthma. Beta regression showed that the strongest confounding factors were low back pain, depression and hay fever/asthma. Conclusions HRQoL was negatively affected in individuals with hand eczema irrespective of age. With the EQ-5D instrument it is also possible to detect certain gender differences. The EQ-5D index for hand eczema was of the same size as for psoriasis and asthma, all common diseases with an impact on public health. It is of importance to acknowledge the influence of hand eczema on daily life, in order to give the patients good care.

Pemphigoid gestationis: early onset and blister formation are associated with adverse pregnancy outcomes.

Abstract: Summary Background It is unclear whether clinical features of pemphigoid gestationis (PG), such as timing of onset and severity, may affect pregnancy outcomes or whether the adverse outcomes in pregnancies complicated by PG are related to or worsened by systemic corticosteroid treatment. Objectives To evaluate the associations of adverse pregnancy outcomes with clinical features, autoantibody titre of PG, and systemic corticosteroid treatment. Methods We conducted a retrospective cohort study recruiting 61 pregnancies complicated by PG from the St John’s Institute of Dermatology database which enrolled cases from dermatologists across the U.K., and two tertiary hospitals in the U.K. and Taiwan. Outcome measures included gestational age at delivery, preterm birth, birthweight, low birthweight (LBW, i.e. birthweight < 2500 g), small-for-gestational-age (i.e. birthweight below the 10th percentile for gestational age), fetal loss, congenital malformation, and mode of delivery. Results After controlling for maternal age and comorbidity, decreased gestational age at delivery was significantly associated with presence of blisters (P = 0·017) and disease onset in the second trimester (P = 0·001). Reduced birthweight was significantly associated with disease onset in the first and second trimesters (P = 0·030 and 0·018, respectively) as was also LBW [adjusted odds ratio (95% confidence interval) 13·71 (1·22–154·59) and 10·76 (1·05–110·65), respectively]. No significant associations of adverse pregnancy outcomes with autoantibody titre or systemic corticosteroid treatment were found. Conclusions Onset of PG in the first or second trimester and presence of blisters may lead to adverse pregnancy outcomes including decreased gestational age at delivery, preterm birth, and LBW children. Such pregnancies should be considered high risk and appropriate obstetric care should be provided. Systemic corticosteroid treatment, in contrast, does not substantially affect pregnancy outcomes, and its use for PG in pregnant women is justified.

Willingness-to-pay and quality of life in patients with vitiligo.

Abstract: Summary Background Vitiligo is a chronic pigmentary disorder of the skin, affecting 1–2% of the general population. Although not life threatening, vitiligo may considerably influence patients’ health-related quality of life (QoL) and psychological well-being. Willingness-to-pay (WTP) is a construct reflecting disease burden and QoL reduction which has not yet been used in vitiligo. Objectives To assess the WTP and the QoL of patients with vitiligo. Methods Patients with vitiligo were included in a nationwide German postal survey. WTP was assessed by two standardized items, and QoL was evaluated using the Dermatology Life Quality Index (DLQI) and the EuroQol (EQ-5D) questionnaire. QoL data were compared with n = 1511 patients from a national survey on psoriasis. Results The questionnaire was completed by 1023 patients (71·5% women, mean age 44·4 years, mean disease duration 20·3 years) with vitiligo. The mean DLQI was 7·0 (7·5 in women, 5·5 in men) compared with 8·6 in psoriasis. Of the patients with vitiligo, 24·6% had a DLQI > 10 which indicates severe QoL reductions, compared with 34·1% in patients with psoriasis. The highest mean DLQI value was observed in the patient group aged 20–29 years. EQ-5D mean score was 83·6 compared with 75·3 in psoriasis. Of the patients with vitiligo, 32·9% would pay more than 5000 Euro in order to achieve complete disease remission. WTP was highest among middle-aged patients (30–60 years). There was a significant correlation between DLQI scores and WTP (χ2 = 65·43, P < 0·001). Moreover, WTP significantly correlated with duration of disease, and with body surface area affected (P < 0·001). Conclusions Vitiligo causes substantial disease burden as reflected by QoL impairment and high WTP, especially in women. These results should draw the attention of physicians to this disease, as appropriate education and treatment are likely to improve the QoL of patients with vitiligo and may support patients’ compliance and empowerment.

Illness perceptions, coping and quality of life in patients with alopecia

Abstract: Background: Alopecia can have substantial psychological consequences, but there has been no research looking at patients' beliefs about their condition nor how they relate to quality of life (QoL). Objectives To investigate the relationships between illness perceptions, coping and QoL in patients with alopecia. Methods: The study employed a cross-sectional design. In total, 214 individuals with alopecia were recruited from four internet support groups. There were 171 women and 43 men (mean age 35 years). Participants completed an online questionnaire comprising the Revised Illness Perception Questionnaire, the Dermatology Life Quality Index and the brief COPE. Results: The findings indicate several areas in which alopecia impacted on individuals' QoL, particularly in relation to symptoms and feelings. Women reported poorer QoL compared with men. Impaired QoL was associated with a strong illness identity, beliefs in the serious consequences of alopecia and strong emotional representations. Hierarchical multiple regressions indicated that illness perceptions accounted for 35% of the variance in QoL after controlling for demographic and disease factors, with coping adding a further 7% to the regression model. Conclusions: Although alopecia is not a life-threatening condition, it can impair QoL by negatively impacting on self-awareness. The strong relationships found between patients' beliefs about their condition and QoL suggests that health professionals should recognize the psychological impact of alopecia and address negative beliefs and emotions surrounding the condition in treatment programmes.

Effect of folic or folinic acid supplementation on methotrexate-associated safety and efficacy in inflammatory disease: a systematic review.

Abstract: Summary Background Methotrexate is a folic acid antagonist widely used for the treatment of inflammatory disorders for more than 50 years. Methotrexate is a standard systemic therapy for severe psoriasis and rheumatoid arthritis. Folic acid supplementation has been advocated to limit the toxicity of methotrexate on blood cells, gastrointestinal tract and liver. However, there is still controversy regarding the usefulness of folic acid supplementation. Objectives We sought to assess the evidence for the efficacy of folic acid supplementation in patients treated with methotrexate for inflammatory diseases. We also investigated whether folic acid supplementation may decrease the efficacy of methotrexate. Methods Cochrane and MEDLINE databases were systematically searched. Randomized controlled trials in patients treated with methotrexate for rheumatoid arthritis or psoriasis with or without arthritis were included. Study selection, assessment of methodological quality, data extraction and analysis were carried out by two independent researchers. We selected double-blind randomized placebo-controlled trials. Analysis was performed for each subgroup of side-effects: gastrointestinal, mucocutaneous, haematological and hepatic. Results Six randomized controlled trials met the inclusion criteria, with a total sample of 648 patients. There were 257 patients in the placebo group, 198 patients treated with folic acid, and 193 patients treated with folinic acid. The statistical analysis showed a significant reduction of 35·8% of hepatic side-effects induced by methotrexate for patients with supplementation with folic or folinic acid (95% confidence interval −0·467 to −0·248). There was no statistical difference for mucocutaneous and gastrointestinal side-effects although there was a trend in favour of supplementation. The effect of supplementation on haematological side-effects could not be assessed accurately due to a low incidence of these events in the population studied. We were unable to analyse the effect of supplementation on the effectiveness of methotrexate, as markers of activity used in each study were not comparable. Conclusions Supplementation with folic acid is an effective measure to reduce hepatic adverse effects associated with methotrexate treatment. There is no difference between folinic acid and folic acid, but the lower cost of the latter promotes its use.