Showing papers in "British Journal of Dermatology in 2004"

Global perspectives of contemporary epidemiological trends of cutaneous malignant melanoma.

Abstract: During the past several decades, there has been a substantial increase in the incidence of cutaneous melanoma among all caucasian populations The number of deaths due to cutaneous malignant melanoma has also increased in most fair-skinned populations throughout the world in the past few decades Trends in melanoma incidence worldwide are examined The most recent data on the mortality from cutaneous melanoma are reported The role of different environmental, genetic and host factors in the aetiology of melanoma is discussed

Minoxidil: mechanisms of action on hair growth

Abstract: Summary We have known for over 30 years that minoxidil stimulates hair growth, yet our understanding of its mechanism of action on the hair follicle is very limited. In animal studies, topical minoxidil shortens telogen, causing premature entry of resting hair follicles into anagen, and it probably has a similar action in humans. Minoxidil may also cause prolongation of anagen and increases hair follicle size. Orally administered minoxidil lowers blood pressure by relaxing vascular smooth muscle through the action of its sulphated metabolite, minoxidil sulphate, as an opener of sarcolemmal KATP channels. There is some evidence that the stimulatory effect of minoxidil on hair growth is also due to the opening of potassium channels by minoxidil sulphate, but this idea has been difficult to prove and to date there has been no clear demonstration that KATP channels are expressed in the hair follicle. A number of in vitro effects of minoxidil have been described in monocultures of various skin and hair follicle cell types including stimulation of cell proliferation, inhibition of collagen synthesis, and stimulation of vascular endothelial growth factor and prostaglandin synthesis. Some or all of these effects may be relevant to hair growth, but the application of results obtained in cell culture studies to the complex biology of the hair follicle is uncertain. In this article we review the current state of knowledge on the mode of action of minoxidil on hair growth and indicate lines of future research.

Terahertz pulsed imaging of basal cell carcinoma ex vivo and in vivo

Abstract: Summary Background Terahertz radiation lies between the infrared and microwave regions of the electromagnetic spectrum and can be used to excite large amplitude vibrational modes of molecules and probe the weak interactions between them. Terahertz pulsed imaging (TPI) is a noninvasive imaging technique that utilises this radiaton. Objectives To determine whether TPI could differentiate between basal cell carcinoma (BCC) and normal tissue and to test whether it can help facilitate delineation of tumour margins prior to surgery. Methods A portable TPI system was used in the clinic to image 18 BCCs ex vivo and five in vivo. Results The diseased tissue showed a change in terahertz properties compared with normal tissue, manifested through a broadening of the reflected terahertz pulse. Regions of disease identified in the terahertz image correlated well with histology. Conclusions This study has confirmed the potential of TPI to identify the extent of BCC in vivo and to delineate tumour margins. Further clinical study of TPI as a surgical tool is now required.

The inflammatory response in mild and in severe psoriasis

Abstract: Summary Background Psoriasis is a chronic and recurrent inflammatory skin disease. The inflammatory response represents a fundamental ability of the organism to protect itself from infectious agents and from injury. Objectives To evaluate the inflammatory response in mild and in severe psoriasis, to evaluate the endogenous systems counterbalancing the deleterious effects of the inflammation products, and to establish values of prognostic significance. Methods The study was performed in a control group (n = 40) and in 60 patients with psoriasis vulgaris, half presenting with mild psoriasis, and the other half with severe psoriasis. We evaluated total and differential leucocyte count; elastase, lactoferrin and lipid peroxidation as markers of neutrophil activation; total plasma antioxidant capacity (TAS), transferrin, ceruloplasmin, α1-antitrypsin and α2-macroglobulin as markers of the endogenous antioxidant and antiprotease systems; and fibrinogen, erythrocyte sedimentation rate, C-reactive protein (CRP), haptoglobin, C3 and C4 complement proteins as markers of inflammation. Results Our data suggested that psoriasis is an inflammatory condition in which neutrophils seem to play a crucial role by contributing to the development of oxidative and proteolytic stress. The worsening of the disease seemed to be linked to the enhancement of the inflammatory response and of the imbalance between neutrophil activation products and their inhibitors. Conclusions We propose values for elastase, CRP, elastase/α2-macroglobulin, elastase/α1-antitrypsin, thiobarbituric acid/TAS and elastase/neutrophil ratios with prognostic significance for the worsening of psoriasis.

An update and guidance on narrowband ultraviolet B phototherapy: a British Photodermatology Group Workshop Report

Abstract: Summary These guidelines for use of narrowband (TL-01) ultraviolet B have been prepared for dermatologists by the British Photodermatology Group on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment of patients with a variety of dermatoses and photodermatoses, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of background photobiology.

Topical aminolaevulinic acid‐photodynamic therapy for the treatment of acne vulgaris: a study of clinical efficacy and mechanism of action

Abstract: Summary Background Acne affects 83–95% of 16-year-olds of both sexes, and many seek help from a clinician. Emerging problems with conventional acne treatments, specifically antibiotic resistance of Propionibacterium acnes and fears over the safety and tolerance of oral isotretinoin, create a demand for novel treatment modalities in acne. Objectives To study the efficacy of aminolaevulinic acid-photodynamic therapy (ALA-PDT) in the treatment of acne and to identify the mode of action, looking specifically at the effects on surface numbers of P. acnes and on sebum excretion. Methods Ten patients (nine men and one woman, age range 16–40 years) with mild to moderate acne on their backs were recruited. Each patient's back was marked with four 30-cm2 areas of equal acne severity. Each site was then randomly allocated to either ALA-PDT treatment, light alone, ALA alone or an untreated control site. At baseline, numbers of inflammatory and noninflammatory acne lesions were counted, sebum excretion measured by Sebutapes (CuDerm, Dallas, TX, U.S.A.) and surface P. acnes swabs performed. ALA cream (20% in Unguentum Merck) was applied under occlusion to the ALA-PDT and ALA alone sites for 3 h. Red light from a diode laser was then delivered to the ALA-PDT and light alone sites (635 nm, 25 mW cm−2, 15 J cm−2). Each patient was treated weekly for 3 weeks. At each visit acne lesion counts were performed and 3 weeks following the last treatment sebum excretion rates and P. acnes swabs were repeated. Results There was a statistically significant reduction in inflammatory acne lesion counts from baseline after the second treatment at the ALA-PDT site but not at any of the other sites. No statistically significant reduction in P. acnes numbers or sebum excretion was demonstrated at any sites including the ALA-PDT site. Conclusions ALA-PDT is capable of clinically improving acne. An alternative mode of action for ALA-PDT other than direct damage to sebaceous glands or photodynamic killing of P. acnes is suggested from the results of this study.

Mohs' micrographic surgery for treatment of basal cell carcinoma of the face--results of a retrospective study and review of the literature.

Abstract: Summary Background The incidence of skin cancer and especially basal cell carcinoma (BCC) has increased in the last decade and is still increasing. Many treatment modalities can be used to treat BCC; surgical excision is the most frequently used. Mohs' micrographic surgery (MMS) is an advanced excision technique which is often used to treat BCC in the U.S.A. In Europe it is practised less frequently. Objective The aim of this article was to evaluate the efficiency of MMS for the treatment of facial BCC. Methods In a retrospective study recurrence rates after the treatment of facial BCC by MMS were estimated by reviewing the records of all patients with BCCs (620 patients with 720 BCCs) treated by MMS in our department from April 1992 until December 1999. Results The 5-year recurrence rates estimated from this study were 3·2% for primary BCC and 6·7% for recurrent BCC. Prognostic factors for recurrence are: an aggressive histopathological subtype, more than four Mohs' stages, a large defect size and a recurrent BCC. Conclusion Based on the fact that MMS provides the lowest recurrence rates, it is the treatment of first choice for primary facial BCCs with an aggressive histopathological subtype and for recurrent BCCs in the face.

Improvement of malignant/benign ratio in excised melanocytic lesions in the ‘dermoscopy era’: a retrospective study 1997–2001

Abstract: Summary Background Because of the many limitations of studies based on the diagnostic setting of excised lesions, the impact of dermoscopy (epiluminescence microscopy, dermatoscopy) in melanoma screening during practice remains to be established. Objectives We assumed that effects of the use of dermoscopy on some indicators of diagnostic performance in melanoma screening should be traceable retrospectively; therefore, we analysed the impact of routine dermoscopy use on the malignant/benign ratio in excised melanocytic lesions. Methods Preoperative and histological diagnosis of 3053 melanocytic lesions [319 melanomas (10·4%)] consecutively diagnosed and excised at the Department of Dermatology, University of Florence in the period 1997–2001 inclusive were retrieved. Six dermatologists who selected the lesions to excise and who performed preoperative diagnosis were divided into two groups according to their use of dermoscopy in routine activity (n = 2 dermoscopy users and n = 4 nonusers). The study period was divided into a predermoscopy period (1997), a shift phase (1998) and a dermoscopy period (1999–2001). Results During the study period, the malignant/benign ratio improved in dermoscopy users only (from 1 : 18 to 1 : 4·3, P = 0·037). No significant difference was found for nonusers (from 1 : 11·8 to 1 : 14·4). Dermoscopy users were more likely to have a melanoma diagnosed within a series of excised lesions than nonusers, even taking into account potential confounders such as sex, age and study period by means of multivariate analysis (odds ratio 1·55, 95% confidence interval 1·17–2·01). The percentage of ‘problem’ naevi (naevi with architectural disorder with or without cytological atypia and Spitz or Reed naevi) over the total number of excised lesions was higher in dermoscopy users than in nonusers (year 2001, 51·6% vs. 40·9%, P = 0·014). Similar findings were obtained after exclusion from the data set of lesions excised for cosmetic reasons. Conclusions The adoption of dermoscopy in routine melanoma screening is followed by an improvement of the malignant/benign ratio in excised lesions, suggesting a more appropriate selection of pigmented lesions referred to surgery. Because of the possible limitations of a retrospective study design, future confirmation of this finding by means of a prospective, randomized study is advisable. The introduction of dermoscopy in routine practice may have major implications in large-scale melanoma screening with cost savings and a reduction of the dermosurgery workload.

Dermoscopy of Bowen's disease.

Abstract: Background Dermoscopy improves the diagnostic accuracy in pigmented skin lesions, but it is also useful in the evaluation of nonpigmented skin tumours as it allows the recognition of vascular structures that are not visible to the naked eye. Bowen's disease (BD) or squamous cell carcinoma in situ is usually nonpigmented, but may also rarely be pigmented.

Proinflammatory cytokine production by human keratinocytes stimulated with Propionibacterium acnes and P. acnes GroEL.

Abstract: BACKGROUND: Keratinocytes form the first line of defence in the skin and alert the host to danger by the production of a number of cytokines and chemokines. However, the interaction of commensal microorganisms with keratinocytes has not been well studied. OBJECTIVES: To investigate the effect of viable and nonviable cells of Propionibacterium acnes in both exponential and stationary growth phases, and of P. acnes GroEL on cytokine production by human primary keratinocytes. METHODS: Actively proliferating or contact-inhibited keratinocytes were cocultured with viable or formaldehyde-killed P. acnes cells in either the exponential or stationary phase of growth. Culture supernatants were assayed by enzyme-linked immunosorbent assay for the cytokines interleukin (IL)-1alpha, tumour necrosis factor (TNF)-alpha and granulocyte/macrophage colony-stimulating factor (GM-CSF). Keratinocytes were also stimulated with different concentrations of P. acnes GroEL and supernatants assayed for cytokines. RESULTS: Viable P. acnes in the stationary phase of growth stimulated keratinocyte monolayers to produce significantly higher amounts of IL-1alpha, TNF-alpha and GM-CSF than unstimulated keratinocytes. Viable exponential-phase bacteria stimulated production of significantly higher amounts of TNF-alpha and GM-CSF but these levels were significantly lower than those for stimulation with stationary-phase bacteria. Nonviable P. acnes from either growth phase was not able to stimulate cytokine production. P. acnes GroEL at concentrations in the range 0.05-1.0 micro g mL(-1) was able to induce increased production of cytokines by keratinocytes in a dose-dependent manner. This was analogous to stimulation with Escherichia coli GroEL. CONCLUSIONS: Stimulation of cytokine production by P. acnes and P. acnes GroEL may be important in the pathogenesis of inflammatory acne vulgaris and may have wider implications for the immunomodulation of the human immune system by commensal skin microorganisms.

Biological therapies in the systemic management of psoriasis: International Consensus Conference.

Abstract: Psoriasis is a chronic, immune-mediated disorder that usually requires long-term treatment for control. Approximately 25% of patients have moderate to severe disease and require phototherapy, systemic therapy or both. Despite the availability of numerous therapeutic options, the long-term management of psoriasis can be complicated by treatment-related limitations. With advances in molecular research and technology, several biological therapies are in various stages of development and approval for psoriasis. Biological therapies are designed to modulate key steps in the pathogenesis of psoriasis. Collectively, biologicals have been evaluated in thousands of patients with psoriasis and have demonstrated significant benefit with favourable safety and tolerability profiles. The limitations of current psoriasis therapies, the value of biological therapies for psoriasis, and guidance regarding the incorporation of biological therapies into clinical practice are discussed.

Quality of life and disease severity are correlated in children with atopic dermatitis.

Abstract: Summary Background Atopic dermatitis (AD) in children may affect their daily activities and normal development. It can have a negative impact on the child's behaviour. Little is known about the quality of life (QOL) in children and its relationship to disease severity, especially from a community-based study. Objectives To document the impact of AD on children's QOL and its relationship to disease severity. Methods The targeted population, before recruitment, comprised children with AD aged 5–10 years from a primary care setting. Their general practitioners identified potential patients and the U.K. diagnostic criteria for AD were used to verify the diagnosis. Eczema severity was assessed using the SCORAD (SCORing Atopic Dermatitis) index. The Children's Dermatology Life Quality Index (CDLQI) was used to quantify the impact of AD on children's QOL. These two parameters were evaluated on two occasions 6 months apart. The Spearman correlation coefficient and multiple regressions were used in statistical analysis. Results Of the 116 children attending the first QOL assessment visit, 78 (mean age 8·6 years, 44 girls and 34 boys) were able to complete the CDLQI. Of these 78 children, 71 (91%) attended the second visit, and were included in the analysis. The children's QOL was affected in 65 (92%) and 55 (77%) children attending the first and second visits, respectively. The CDLQI was significantly correlated with the SCORAD at the first and second visits (r = 0·52, P < 0·001 and r = 0·59, P < 0·001, respectively). Each unit change in the SCORAD was associated with a 0·12 (95% confidence interval 0·04–0·19, P = 0·004) unit change in the children's QOL. Conclusions We have shown a positive correlation between children's QOL and disease severity on cross-sectional and over time observation. This highlights the impact of AD on children's life. It also draws attention to the long-term effect on children's behaviour and development. In addition, these findings may imply that the CDLQI could be used as an extra measure of disease assessment in clinical practice and research studies.

Prevalence of symptoms experienced by patients with different clinical types of psoriasis

Abstract: Summary Background The main dermatology textbooks describe only in passing pruritus in psoriasis and rarely mention other symptoms. A quantification of the presence of symptoms is not available for clinical subgroups of psoriasis. Objectives To investigate the prevalence of symptoms experienced by patients with different clinical types of psoriasis. Methods The study was carried out in patients hospitalized for psoriasis between February 2000 and February 2002 at the inpatient wards of the Istituto Dermopatico dell'Immacolata, Rome, Italy. Symptoms were evaluated using the symptoms scale of Skindex-29. Clinical severity was assessed by the dermatologists using the Psoriasis Area and Severity Index (PASI), and by the patients completing the self-administered PASI. Psychiatric morbidity was evaluated using the 12-item General Health Questionnaire. Results In total, 936 eligible patients were analysed. The proportions of patients experiencing symptoms often or always in the 4 weeks before hospitalization were: 63·8% itching, 59·7% irritation, 46·1% burning/stinging, 39% sensitivity, 26% pain (from 10% in guttate psoriasis to 50% in arthropathic), 25·4% bleeding (17% pustular, 19% localized plaque, 36% palmoplantar), and 23·9% bothered by water (from 8·5% in the guttate form to 68% in palmoplantar). The prevalence of all symptoms was significantly higher in women and tended to increase with clinical severity. Conclusions Our study provides evidence of the high frequency of a number of symptoms in different subgroups of psoriasis patients determined by their sociodemographic characteristics, clinical type and disease severity. Symptoms represent a serious disabling factor in patients affected by psoriasis, including those with low levels of psychological distress. Dermatologists should include symptoms in the evaluation of disease severity both in clinical practice and in clinical trials.

Amelanotic/hypomelanotic melanoma: clinical and dermoscopic features

Abstract: Background Amelanotic malignant melanoma is a subtype of cutaneous melanoma with little or no pigment on visual inspection. It may mimic benign and malignant variants of both melanocytic and nonmelanocytic lesions.

Acneiform eruption induced by epidermal growth factor receptor inhibitors in patients with solid tumours

Abstract: progression and pulmonary haemorrhage. Primary or metastatic haematopoietic neoplasia along a needle tract or portal site has rarely been reported. Fisher et al. reported that mechanical, chemical or surgical trauma will promote the localization of intravenous or intra-arteriolar tumour cells at a trauma site. In our patient, the insertion of needles and the catheter must have produced unavoidable mechanical and surgical trauma, even though they had been removed 28 days prior to the clinical manifestation of the tumour cells. None the less, the possibility of minimal extravasation of blood along the puncture site of the cephalic vein or subclavian vein as a source of haematogenous spread cannot be ruled out. The distribution of the tumours along all the puncture sites suggests that the physical injury produced a favourable environment for metastatic spread during the creation of the needle or catheter tunnel. There is no clear explanation for tumour cell implantation and proliferation at the needle tract or portal site. One possible explanation is that a major disruption of the blood vessel walls with secondary bleeding into the skin and leakage of a sufficient quantity of soluble growth factors and cell mediators into the subcutaneous tissue would lead to a protected environment in which any viable atypical tumour cells could survive and proliferate. Another possible mechanism is associated with trauma-specific and cutaneousspecific tumour cell migration. Preferential expression of specific chemokine receptors on myeloma-derived leukaemic cells may account for migration to specific sites. Release of cytokines, related to trauma, may have played a role in chemokine-mediated recruitment and proliferation of leukaemic cells at these sites. It is possible that tumour cell subclones expressing specific chemokine receptors may have been selected during chemotherapy, resulting in the preferential trafficking of the leukaemic cells to the trauma sites. Swelling along the catheter tracts most commonly indicates a haematoma or an infection. If the index of suspicion for tumour implantation is low, the initial management may consist of an attempted aspiration after carefully preparing the area. The presence of blood in the aspirate suggests a haematoma, whereas an infection will be demonstrated by a positive culture. However, if blood is not obtained and an infection cannot be determined, a biopsy will be needed. In our patient, the tumour mass was somewhat harder on palpation than a normal haematoma, and aspiration and bacterial culture were both negative. Therefore, in a rapidly progressing disease with the presence of subcutaneous nodules elsewhere, as our patient, a biopsy will be necessary for making a differential diagnosis. As leukaemia cutis is considered to be a poor prognostic sign in patients with systemic leukaemia, accurate identification of leukaemia cutis is important for management of the disease. Conventional chemotherapy regimens are advocated in leukaemia cutis. Small skin lesions may be successfully treated by surgical removal or local radiotherapy. Whole body electron-beam radiation therapy is considered to be beneficial in widespread skin involvement. Our patient received combination chemotherapy different from the previous chemotherapeutic regimen, but there was no improvement. In conclusion, this case of secondary PCL is interesting due to the unusual skin lesions limited to the needle and catheter insertion sites. The tumour cell infiltrate appeared to have developed at these sites. Therefore, careful attention should be given to vascular access in such patients.

Human hair greying is linked to a specific depletion of hair follicle melanocytes affecting both the bulb and the outer root sheath

Abstract: Summary Background Although hair greying is a very common phenomenon characterized by loss of pigment in the hair shaft, the events that cause and control natural hair whitening with age in humans are still unclear Objectives To decipher the origin of natural hair whitening Methods Human hair melanocytes were immunohistochemically characterized at different stages of whitening Results Loss of hair shaft melanin was found to be associated with a decrease in both bulb melanin content and bulb melanocyte population Although few melanocytes were present in the bulbs of grey hair, they still expressed tyrosinase and tyrosinase-related protein-1, synthesized and transferred melanins to cortical keratinocytes as seen by the presence of melanin granules In white hair bulbs, no melanocytes could be detected either with pMel-17 or vimentin labelling Pigmented hair follicles are known to contain inactive melanocytes in the outer root sheath (ORS), and grey and white hairs were also found to contain some of these quiescent melanocytes However, their population was decreased compared with pigmented hair follicles, ranging from small to nil This depletion of melanocytes in the different areas of white hairs was detected throughout the hair cycle, namely at telogen and early anagen stages In contrast, the infundibulum and sebaceous gland of both pigmented and white hairs showed a similar distribution of melanocytes Furthermore, other distinct cell populations located in the ORS, namely putative stem cells, Merkel cells and Langerhans cells were equivalently identified in pigmented and white hairs Conclusions Thus, hair greying appears to be a consequence of an overall and specific depletion of bulb and ORS melanocytes of human hair

The effect of environmental tobacco smoke on eczema and allergic sensitization in children

Abstract: Summary Background The negative impact of environmental tobacco smoke (ETS) on airway diseases in children is well known. Whether there is an effect on atopic eczema is not clear. Objectives To determine the impact of ETS on atopic eczema, allergic sensitization and allergic airway diseases in 1669 school beginners. Methods The prevalence of atopy-related health outcomes was assessed by questionnaire, dermatological examination, skin prick testing and specific immunoglobulin E measurement. Exposure assessments were based on measurement of cotinine [expressed as cotinine to creatine ratio (CCR)] in spot urine samples (n = 1220) together with questionnaire and interview data on smoking behaviour of the parents. Results In the total study group, prevalence of atopic eczema diagnosed on examination was significantly associated with urinary CCR values. The odds ratio (OR) and 95% confidence interval (CI), calculated for an increase of 100 ng mg−1 CCR was 1·97 (95% CI 1·23–3·16). The prevalence of skin manifestations according to questionnaire data as well as a history of asthma, wheezing, and hay fever were positively although not significantly associated with ETS exposure. When genetically predisposed children (defined by the presence of parental atopy) were compared with children whose parents had no atopy, the ORs of allergic outcome variables were generally higher in the first group. In the group of predisposed children, significant associations with urinary CCR were found for allergic sensitization against house dust mites as measured by skin prick test (OR 3·10, 95% CI 1·63–5·90). Conclusions Children are at a higher risk of developing an atopic eczema when exposed to ETS and genetically predisposed children are at higher risk of developing a sensitization against house dust mites.

Photodynamic therapy of actinic keratosis at varying fluence rates: assessment of photobleaching, pain and primary clinical outcome.

Abstract: Summary Background Although photodynamic therapy (PDT) is becoming an important treatment method for skin lesions such as actinic keratosis (AK) and superficial basal cell carcinoma, there are still discussions about which fluence rate and light dose are preferable. Recent studies in rodents have shown that a low fluence rate is preferable due to depletion of oxygen at high fluence rates. However, these results have not yet been verified in humans. Objectives The objective was to investigate the impact of fluence rate and spectral range on primary treatment outcome and bleaching rate in AK using aminolaevulinic acid PDT. In addition, the pain experienced by the patients has been monitored during treatment. Patients/methods Thirty-seven patients (mean age 71 years) with AK located on the head, neck and upper chest were treated with PDT, randomly allocated to four groups: two groups with narrow filter (580–650 nm) and fluence rates of 30 or 45 mW cm−2, and two groups with broad filter (580–690 nm) and fluence rates of 50 or 75 mW cm−2. The total cumulative light dose was 100 J cm−2 in all treatments. Photobleaching was monitored by fluorescence imaging, and pain experienced by the patients was registered by using a visual analogue scale graded from 0 (no pain) to 10 (unbearable pain). The primary treatment outcome was evaluated at a follow-up visit after 7 weeks. Results Our data showed a significant correlation between fluence rate and initial treatment outcome, where lower fluence rate resulted in favourable treatment response. Moreover, the photobleaching dose (1/e) was found to be related to fluence rate, ranging from 4·5 ± 1·0 J cm−2 at 30 mW cm−2, to 7·3 ± 0·7 J cm−2 at 75 mW cm−2, indicating higher oxygen levels in tissue at lower fluence rates. After a cumulative light dose of 40 J cm−2 no further photobleaching took place, implying that higher doses are excessive. No significant difference in pain experienced by the patients during PDT was observed in varying the fluence rate from 30 to 75 mW cm−2. However, the pain was found to be most intense up to a cumulative light dose of 20 J cm−2. Conclusions Our results imply that the photobleaching rate and primary treatment outcome are dependent on fluence rate, and that a low fluence rate (30 mW cm−2) seems preferable when performing PDT of AK using noncoherent light sources.

Increased risk of skin cancer associated with the presence of epidermodysplasia verruciformis human papillomavirus types in normal skin.

Abstract: Background Human papillomaviruses (HPVs) are found in normal skin and in benign and malignant skin conditions. Epidermodysplasia verruciformis (EV) HPV types are those most plausibly linked to the development of squamous cell carcinomas of the skin.Objectives To assess the risk of nonmelanoma skin cancer (NMSC) associated with the presence of EV HPV in normal skin in immunocompetent (IC) individuals and renal transplant recipients (RTRs).Methods Using a degenerate and nested polymerase chain reaction technique, HPV DNA was sought in 124 normal skin samples from sun-exposed and nonsun-exposed sites, from 39 IC individuals and 38 RTRs, both with and without NMSC. Data were analysed using the Mantel-Haenszel test and by logistic regression analysis.Results HPV DNA was detected in 58/67 (87%) and 20/57 (35%) samples from renal transplant and IC patients, respectively. There was no difference in either the prevalence or spectrum of HPV types found in sun-exposed and nonsun-exposed normal skin. However, there was significant association between NMSC and the presence of EV HPV DNA. Multivariate analysis provided an odds ratio of 6.41 (95% confidence interval 1.79-22.9) for the association of EV HPV DNA in normal skin (irrespective of site) and NMSC status, even after stratifying for patient group and adjusting for the clustering effect of multiple sampling. Conversely, there was no association between skin cancer status and the presence of cutaneous or mucosal HPV types in either sun-exposed or nonsun-exposed skin.Conclusions HPV DNA is widespread in normal adult skin, particularly in transplant patients. In our study, the presence of EV but not cutaneous HPV DNA in normal skin was significantly associated with NMSC status and may prove to be of predictive value for skin cancer risk. These data provide reason to focus on EV HPV types as causal agents in skin cancer.

Cutaneous complications of intravenous drug abuse.

Abstract: Injection drug abuse is a world-wide problem responsible for numerous minor to life-threatening and fatal complications. The skin is the tissue most evidently affected by intravenous drug addiction. A wide spectrum of cutaneous complications may occur in intravenous drug users. These include acute or delayed local complications, hypersensitivity reactions, cutaneous manifestations of systemic infections or becoming the site of toxigenic infections. Between 1996 and 2001, in our institution in south-eastern France, we observed cutaneous complications after crushed buprenorphine tablet injections in 13 patients. This paper reviews and classifies adverse effects of parenteral drug abuse on the skin.

U‐serrated immunodeposition pattern differentiates type VII collagen targeting bullous diseases from other subepidermal bullous autoimmune diseases

Abstract: Background Epidermolysis bullosa acquisita (EBA) can be differentiated from other subepidermal bullous diseases by sophisticated techniques such as immunoelectron microscopy, salt-split skin antigen mapping, fluorescence overlay antigen mapping, immunoblot and enzyme-linked immunosorbent assay. Objectives To determine whether the diagnosis can also be made by routine direct immunofluorescence microscopy. Methods We studied frozen skin biopsies from 157 patients with various subepidermal immunobullous diseases. Results We found three distinct 'linear' fluorescence patterns at the basement membrane zone: true linear, n-serrated and u-serrated. The true linear pattern, often seen in conjunction with either the n- or the u-serrated pattern, was found in any subepidermal immunobullous disease with non-granular depositions. In bullous pemphigoid, mucous membrane pemphigoid, antiepiligrin cicatricial pemphigoid, p200 pemphigoid and linear IgA disease the n-serrated pattern was found, corresponding with depositions located in hemidesmosomes, lamina lucida or lamina densa. However, in EBA and bullous systemic lupus erythematosus the u-serrated staining pattern was seen, corresponding with the ultralocalization of type VII collagen in the sublamina densa zone. The diagnosis of EBA with IgG or IgA autoantibodies directed against type VII collagen was confirmed by immunoelectron microscopy, salt-split skin antigen mapping, fluorescence overlay antigen mapping or immunoblotting. Conclusions Using this pattern recognition by direct immunofluorescence microscopy we discovered several cases of EBA which would otherwise have been erroneously diagnosed as a form of pemphigoid or linear IgA disease.

Enhancement of topical 5-aminolaevulinic acid delivery by erbium:YAG laser and microdermabrasion: a comparison with iontophoresis and electroporation

Abstract: Summary Background 5-aminolaevulinic acid (ALA) is used as a protoporphyrin IX-precursor for the photodynamic therapy of superficial skin cancer and cutaneous metastases of internal malignancies. However, the permeability of hydrophilic ALA across the skin is very low. Objectives and methods The objective of this study was to optimize and enhance the in vitro skin permeation of ALA by two resurfacing techniques: erbium:yttrium-aluminium-garnet (Erb:YAG) laser and microdermabrasion. Light microscopic changes in pig skin caused by these techniques were also compared. The electrically assisted methods, iontophoresis and electroporation, were also used to facilitate ALA permeation across laser- or microdermabrasion-treated skin. Results Among the modalities tested in this study the Erb:YAG laser showed the greatest enhancement of ALA permeation. The laser fluence was found to play an important role in controlling the drug flux, producing enhancement ratios from 4-fold to 246-fold relative to the control. The skin permeation of ALA across microdermabrasion-treated skin was approximately 5–15-fold higher than that across intact skin. Both the ablated effect of the stratum corneum (SC) and ALA flux were proportional to the treatment duration of microdermabrasion. The application of iontophoresis or electroporation alone also increased the ALA permeation by approximately 15-fold and 2-fold, respectively. The incorporation of iontophoresis or electroporation with the resurfacing techniques caused a profound synergistic effect on ALA permeation. Conclusions This basic study has encouraged the further investigation of ALA permeation by laser or microdermabrasion.

Ciclosporin in psoriasis clinical practice: an international consensus statement.

Abstract: The main recommendations for the use of ciclosporin in the management of psoriasis are: (i) intermittent short courses (average of 12 weeks duration) of ciclosporin are preferable; (ii) ciclosporin should be given in the dose range 2.5-5.0 mg kg(-1) day(-1) (doses greater than 5.0 mg kg(-1) day(-1) should only be given in exceptional circumstances); (iii) treatment regimens should be tailored to the needs of each patient; (iv) selection of patients should take into account psychosocial disability, as well as clinical extent of disease and failure of previous treatment; (v) each patient's renal function (as measured by serum creatinine) should be thoroughly assessed before and during treatment; (vi) each patient's blood pressure should be carefully monitored before and during treatment; (vii) adherence to treatment guidelines substantially reduces the risk of adverse events; (viii) long-term continuous ciclosporin therapy may be appropriate in a subgroup of patients; however, duration of treatment should be kept below 2 years whenever possible; and (ix) when long-term continuous ciclosporin therapy is necessary, annual evaluation of glomerular filtration rate may be useful to accurately monitor renal function.

Cumulative meta-analysis of systemic antifungal agents for the treatment of onychomycosis.

Abstract: Background Onychomycosis is a common nail disease that is often chronic, difficult to eradicate, and has a tendency to recur. The most common oral therapies for dermatophyte toenail onychomycosis include terbinafine, itraconazole and fluconazole. Objectives A cumulative meta-analysis of the randomized controlled trials (RCTs) for antimycotic agents was performed to determine whether the pooled estimate of the cure rates has remained consistent over the years. Furthermore, for each agent we compared the overall meta-analytical average of both mycological and clinical response rates of RCTs vs. open studies. Methods We searched MEDLINE (1966 to November 2002) for relevant studies evaluating the efficacy of the oral antifungal agents terbinafine, itraconazole (pulse or continuous), fluconazole and griseofulvin for treating dermatophyte toenail onychomycosis. Studies included in this meta-analysis required a standard accepted dosage regimen, treatment duration and follow-up period. To determine the cumulative meta-analytical average, studies were sequentially pooled by adding one study at a time according to the date of publication (i.e. earliest to the most recent). Results There were 36 studies included in the analyses. For RCTs the change in efficacy of mycological cure rates from the first trial to the overall cumulative meta-average for each drug comparator is as follows (with 95% confidence interval): terbinafine, 78 +/- 6% (n = 2 studies, 79 patients) to 76 +/- 3% (n = 18 studies, 993 patients) (P = 0.68); itraconazole pulse, 75 +/- 10% (n = 1 study, 20 patients) to 63 +/- 7% (n = 6 studies, 318 patients) (P = 0.25); itraconazole continuous, 63 +/- 5% (n = 1 study, 84 patients) to 59 +/- 5% (n = 7 studies, 1131 patients) (P = 0.47); fluconazole, 53 +/- 6% (n = 1 study, 72 patients) to 48 +/- 5% (n = 3 studies, 131 patients) (P = 0.50); and griseofulvin, 55 +/- 8% (n = 2 studies, 109 patients) to 60 +/- 6% (n = 3 studies, 167 patients) (P = 0.41). The cumulative meta-analytical average of mycological cure rates when comparing RCTs vs. open studies was: terbinafine, 76 +/- 3% (n = 18 studies, 993 patients) vs. 83 +/- 12% (n = 2 studies, 391 patients) (P = 0.0028); itraconazole pulse, 63 +/- 7% (n = 6 studies, 318 patients) vs. 84 +/- 9% (n = 3 studies, 194 patients) (P = 0.0001); and fluconazole, 48 +/- 5% (n = 3 studies, 131 patients) vs. 79 +/- 3% (n = 3 studies, 208 patients) (P = 0.0001). Conclusions The cumulative meta-analysis of cure rates for RCTs suggests that over time, as new RCTs have been conducted, the efficacy rates have remained consistent. The efficacy rates of open studies are substantially higher compared with RCTs and may therefore overestimate cure rates.

Microfabricated silicon microneedles for nonviral cutaneous gene delivery

Abstract: Summary Background The skin represents an accessible somatic tissue for therapeutic gene transfer. The superficial lipophilic layer of the skin, the stratum corneum, however, constitutes a major obstacle to the cutaneous delivery of charged macromolecules such as DNA. Objectives To determine whether silicon-based microneedles, microfabricated via a novel isotropic etching/BOSCH reaction process, could generate microchannels in the skin of sufficient dimensions to facilitate access of lipid : polycation : pDNA (LPD) nonviral gene therapy vectors. Methods Scanning electron microscopy was used to visualize the microconduits created in heat-separated human epidermal sheets after application of the microneedles. Following confirmation of particle size and particle surface charge by photon correlation spectrocopy and microelectrophoresis, respectively, the diffusion of fluorescent polystyrene nanospheres and LPD complexes through heat-separated human epidermal sheets was determined in vitro using a Franz-type diffusion cell. In-vitro cell culture with quantification by flow cytometry was used to determine gene expression in human keratinocytes (HaCaT cells). Results The diffusion of 100 nm diameter fluorescent polystyrene nanospheres, used as a readily quantifiable predictive model for LPD complexes, through epidermal sheets was significantly enhanced following membrane treatment with microneedles. The delivery of LPD complexes either into or through the membrane microchannels was also demonstrated. In both cases considerable interaction between the particles and the epidermal sheet was observed. In-vitro cell culture was used to confirm that LPD complexes mediated efficient reporter gene expression in human keratinocytes in culture when formulated at the appropriate surface charge. Conclusions These studies demonstrate the utility of silicon microneedles in cutaneous gene delivery. Further studies are required to elucidate fully the influence of the physicochemical characteristics of gene therapy vectors, e.g. particle diameter and surface charge, on their diffusion through microchannels and to quantify gene expression in vivo.

Inflammation in acne scarring: a comparison of the responses in lesions from patients prone and not prone to scar

Abstract: Summary Background Many patients with inflammatory acne suffer from significant scarring, which is disfiguring and difficult to treat. A cell-mediated immune response is considered to be involved in the pathogenesis of acne, although the extent of this response has been found to differ among patients. Objective To assess whether there were differences in the cell-mediated immune responses at different time points in inflamed lesion development and resolution in patients who were prone (S patients) and those with the same degree of inflamed acne who were not prone (NS patients) to develop scarring. Methods Cellular and vascular markers were investigated using standard immunohistochemical techniques on biopsies of inflamed lesions of known duration, i.e. < 6 h (n = 14), 24 h (n = 14), 48 h (n = 10), 72 h (n = 10) and 6–7 days (n = 11) from the backs of acne patients. Results In early lesions from NS patients there was a large influx of CD4+ T cells, macrophages and Langerhans cells with a high number of cells expressing HLA-DR. Also there was significant angiogenesis and vascular adhesion molecule expression. Cell recruitment peaked in 48 h lesions, after which leucocyte numbers decreased and vascular activity returned to normal. Of the T cells, only 50% were memory/effector (CD45RO+) and naive (CD45RA+) cells, while the remainder were unclassified (CD45RO–, CD45RA–). In early lesions from S patients, CD4+ T cell numbers were smaller, although a high proportion were skin homing memory/effector cells. Langerhans cell numbers and cellular HLA-DR expression were low, while numbers of macrophages, blood vessels and vascular adhesion molecules were high. In resolving lesions angiogenesis remained high, with a further influx of macrophages and skin homing memory/effector cells and increased cellular HLA-DR expression. Conclusions The cellular infiltrate was large and active with a greater nonspecific response (few memory T cells) in early lesions of NS patients, which subsided in resolution. In contrast, a predominantly specific immune response was present in S patients, which was initially smaller and ineffective, but was increased and activated in resolving lesions. Such excessive inflammation in healing tissue is conducive to scarring and suggests that the use of topical anti-inflammatory treatments would be appropriate for these patients.

Melanomas detected with the aid of total cutaneous photography.

Abstract: Summary Background Early detection of melanoma results in excision of thinner melanomas, which are associated with better prognosis. Total cutaneous photography provides a temporal comparison of lesions, which allows clinicians and patients to recognize new and subtly changing lesions. Objectives We examined the utility of total cutaneous photography in detecting melanoma, identified the reason for biopsy of suspicious lesions and determined who detected new melanomas, the physician on follow-up examination or the patient on self-examination. Patients/methods The charts of the 576 patients in the total cutaneous photography database were reviewed. Twelve patients were identified who had melanoma diagnosed with photographic assistance. Baseline and prebiopsy photographs, dermatology clinic notes (115 patient visits) and pathology reports for each biopsied lesion were reviewed. Histological diagnosis, cause for biopsy, and whether the lesion was detected by the patient or physician, was recorded for each of the biopsied lesions. Also noted were all the lesions that concerned patients, the cause for concern, and whether these lesions were biopsied. Results A total of 93 lesions were biopsied in these patients. Twenty-seven (35%) of 77 melanocytic lesions were histologically diagnosed as melanoma. The thickest melanoma found measured 1·1 mm, indicating a favourable prognosis in our patients. Seventy-four per cent of the melanomas were biopsied due to changes from baseline and 19% were biopsied because they were new lesions. The changes noted were subtle and the lesions that proved to be melanoma did not satisfy the classical clinical criteria for melanoma. Eight (30%) of the melanomas were identified by patients on skin self-examination. Twenty-six per cent of the lesions that concerned patients were not biopsied after evaluation by a physician. Conclusions We found that photographically assisted follow-up helped detect new and subtly changing melanomas, which did not satisfy the classical clinical features of melanoma. In addition, photographically assisted follow-up helped detect nonmelanoma skin cancers. Patient skin self-examination proved to be valuable, in that it complemented physician follow-up examination in detecting melanomas. Photographic follow-up was also valuable in avoiding unnecessary biopsy in suspicious, but stable lesions. Total cutaneous photography therefore may be an effective way to increase the sensitivity and specificity for detecting melanoma.

Lichen planus and hepatitis C virus: a multicentre study of patients with oral lesions and a systematic review.

Abstract: Summary Background An association between hepatitis C virus (HCV) infection and lichen planus (LP) has been investigated, but results have been inconsistent. Objectives To investigate the relationship between LP and HCV seropositivity. Methods In a cross-sectional study we tested the sera of 303 consecutive newly diagnosed patients with histologically proven LP referred to three Italian centres for the presence of anti-HCV IgG. A comparable control group was also tested. Next, in a systematic review, studies were identified by searching different databases in April 2004. Inclusion criteria were: (i) analytical study design; (ii) clinical and histological diagnosis of LP; and (iii) serological test for anti-HCV antibodies as main outcome. The risk of bias was assessed on the basis of characteristics of the study group, appropriateness of the control group and study design. Pooled data were analysed by calculating odds ratios (ORs), using a random effects model. Results In the cross-sectional study, nearly one in five (19·1%) of the LP group was HCV positive, while a much lower prevalence of infection was found in the control group (3·2%) [OR 7·08; 95% confidence interval (CI) 3·43–14·58]. The systematic review yielded 25 relevant studies, six of which had a low risk of bias. There was a statistically significant difference in the proportion of HCV-seropositive subjects among patients with LP, compared with controls (OR 4·80; 95% CI 3·25–7·09). Following subgroup analyses, the variability of HCV prevalence in patients with LP seemed to depend on geographical area, but not on age. Conclusions Anti-HCV circulating antibodies are more common in patients with LP than in controls, although such an association may not be significant in some geographical areas.

Stratum corneum adhesive tape stripping: influence of anatomical site, application pressure, duration and removal

Abstract: Summary Background Tape stripping is a common method for investigating stratum corneum (SC) physiology as well as bioavailability and bioequivalence of topical drugs. Objectives To investigate the influence of procedures (anatomical site, pressure, pressure duration, tape removal rate) inherent in each stripping protocol on changes in skin physiology. Methods Tape stripping was performed using tapes on the forearm, forehead and back. On the forearm different pressures (165 and 330 g cm−2), durations of pressure (2 and 10 s), and removal rate (slow and rapid removal) were used. Changes in skin physiology were evaluated by measurement of transepidermal water loss (TEWL) and hydration. Results A significant influence of all parameters on the TEWL increase as a function of tape strip number was observed. The fastest increase was demonstrated on the forehead, followed by the back and, lastly, the forearm. Rapid removal produced a protracted increase in comparison with slow removal. Pressure for 10 s induced a faster increase in TEWL than 2 s pressure. Likewise, pressure at 330 g cm−2 induced an earlier increase than pressure at 165 g cm−2. Skin hydration was not influenced by the variables tested. Conclusions Tape stripping results are influenced dramatically by all investigated parameters. A dynamic SC stress test to investigate SC cohesion more closely is proposed based on the present observations.