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1.  Photoallergic reaction in a patient receiving vandetanib for metastatic follicular thyroid carcinoma: a case report 
BMC Dermatology  2015;15:2.
Background
Novel targeted agents have been increasingly developed and tested in clinical trials over the past 5–10 years, many with unknown and unanticipated side effects. We describe here a case of a patient with a history of metastatic follicular thyroid carcinoma that we believe developed vandetanib–associated photoallergic dermatitis while enrolled on a phase 1 clinical trial.
Case presentation
A 51-year-old Caucasian female with poorly differentiated, metastatic follicular thyroid carcinoma presented with a cutaneous eruption that developed over 3 to 4 days while treated on phase 1 clinical trial with vandetanib-based therapy. Given the concern for photoallergic dermatitis, vandetanib was discontinued and supportive care provided including topical and oral steroid administration. Her cutaneous eruption improved and she was successfully re-challenged with vandetanib.
Conclusion
Tyrosine kinase inhibitors, such as typo-vandetinib, with various therapeutic targets have come to the forefront of oncologic therapy in recent years. It is important to have a better understanding of the side effect profile and management in order to anticipate adverse events and maintain patient safety in future clinical trials.
doi:10.1186/s12895-015-0022-1
PMCID: PMC4336708
Photoallergic reaction; Vandetanib; Metastatic follicular thyroid carcinoma; Tyrosine kinase inhibitor; Investigational cancer therapeutics
2.  Exploring the association between Morgellons disease and Lyme disease: identification of Borrelia burgdorferi in Morgellons disease patients 
BMC Dermatology  2015;15(1):1.
Background
Morgellons disease (MD) is a complex skin disorder characterized by ulcerating lesions that have protruding or embedded filaments. Many clinicians refer to this condition as delusional parasitosis or delusional infestation and consider the filaments to be introduced textile fibers. In contrast, recent studies indicate that MD is a true somatic illness associated with tickborne infection, that the filaments are keratin and collagen in composition and that they result from proliferation and activation of keratinocytes and fibroblasts in the skin. Previously, spirochetes have been detected in the dermatological specimens from four MD patients, thus providing evidence of an infectious process.
Methods & Results
Based on culture, histology, immunohistochemistry, electron microscopy and molecular testing, we present corroborating evidence of spirochetal infection in a larger group of 25 MD patients. Irrespective of Lyme serological reactivity, all patients in our study group demonstrated histological evidence of epithelial spirochetal infection. Strength of evidence based on other testing varied among patients. Spirochetes identified as Borrelia strains by polymerase chain reaction (PCR) and/or in-situ DNA hybridization were detected in 24/25 of our study patients. Skin cultures containing Borrelia spirochetes were obtained from four patients, thus demonstrating that the organisms present in dermatological specimens were viable. Spirochetes identified by PCR as Borrelia burgdorferi were cultured from blood in seven patients and from vaginal secretions in three patients, demonstrating systemic infection. Based on these observations, a clinical classification system for MD is proposed.
Conclusions
Our study using multiple detection methods confirms that MD is a true somatic illness associated with Borrelia spirochetes that cause Lyme disease. Further studies are needed to determine the optimal treatment for this spirochete-associated dermopathy.
doi:10.1186/s12895-015-0023-0
PMCID: PMC4328066
Morgellons disease; Lyme disease; Borrelia burgdorferi; Spirochetes; Dermopathy
3.  Digital photography in skin cancer screening by mobile units in remote areas of Brazil 
BMC Dermatology  2014;14(1):19.
Background
Non-melanoma skin cancer (NMSC) is one of the most common neoplasms in the world. Despite the low mortality rates, NMSC can still cause severe sequelae when diagnosed at advanced stages. Malignant melanoma, the third most common type of skin cancer, has more aggressive behavior and a worse prognosis. Teledermatology provides a new tool for monitoring skin cancer, especially in countries with a large area and unequal population distribution.
This study sought to evaluate the performance of digital photography in skin cancer diagnosis in remote areas of Brazil.
Methods
A physician in a Mobile Prevention Unit (MPU) took four hundred sixteen digital images of suspicious lesions between April 2010 and July 2011. All of the photographs were electronically sent to two oncologists at Barretos Cancer Hospital who blindly evaluated the images and provided a diagnosis (benign or malignant). The absolute agreement rates between the diagnoses made by direct visual inspection (by the MPU physician) and through the use of digital imaging (by the two oncologists) were calculated. The oncologists’ accuracy in predicting skin cancer using digital imaging was assessed by means of overall accuracy (correct classification rate), sensitivity, specificity and predictive value (positive and negative). A skin biopsy was considered the gold standard.
Results
Oncologist #1 classified 59 lesions as benign with the digital images, while oncologist #2 classified 27 lesions as benign using the same images. The absolute agreement rates with direct visual inspection were 85.8% for oncologist #1 (95% CI: 77.1-95.2) and 93.5% for oncologist #2 (95% CI: 84.5-100.0). The overall accuracy of the two oncologists did not differ significantly.
Conclusions
Given the high sensitivity and PPV, Teledermatology seems to be a suitable tool for skin cancer screening by MPU in remote areas of Brazil.
doi:10.1186/s12895-014-0019-1
PMCID: PMC4302445  PMID: 25539949
Teledermatology; Skin cancer; Diagnosis; Public health; Accuracy; Verification bias
4.  [No title available] 
PMCID: PMC4289267  PMID: 25427661
5.  Association of variation in the LAMA3 gene, encoding the alpha-chain of laminin 5, with atopic dermatitis in a German case–control cohort 
BMC Dermatology  2014;14:17.
Background
Atopic dermatitis (AD) is a chronic inflammatory skin disorder caused by complex interaction of genetic and environmental factors. Besides mutations in the filaggrin gene, leading to impaired skin barrier function, variation in genes encoding additional skin proteins has been suggested to contribute to disease risk. Laminin 5, playing an important role in skin integrity, is composed of three subunits encoded by the LAMA3, LAMB3 and LAMC2 genes in which biallelic mutations cause epidermolysis bullosa junctionalis. We aimed at evaluating the role of variation in the LAMA3, LAMB3 and LAMC2 genes for AD pathogenesis.
Methods
29 single nucleotide polymorphisms (SNPs) were genotyped in the three genes in a German AD case–control cohort comprising 470 unrelated AD patients and 320 non-atopic controls by means of restriction enzyme digestion. Allele, genotype and haplotype frequencies were compared between cases and controls using chi-square testing and the Haploview software.
Results
Several SNPs in the LAMA3 gene showed significant association with AD in our cohort (p <0.01), while we did not detect association with variations in the LAMB3 and LAMC2 genes. Haplotype analysis additionally revealed several significantly associated haplotypes in the LAMA3 gene. Due to extensive linkage disequilibrium, though, we were not able to further differentiate the specific disease causing variation(s) in this region.
Conclusions
We established the LAMA3 gene as novel potential susceptibility gene for AD. Additional studies in independent cohorts are needed to replicate these results.
doi:10.1186/1471-5945-14-17
PMCID: PMC4221780  PMID: 25363238
Atopic dermatitis; Genetic factors; Laminin 5; LAMA3; Skin barrier function
6.  Testing the effectiveness of a self-efficacy based exercise intervention for adults with venous leg ulcers: protocol of a randomised controlled trial 
BMC Dermatology  2014;14:16.
Background
Exercise and adequate self-management capacity may be important strategies in the management of venous leg ulcers. However, it remains unclear if exercise improves the healing rates of venous leg ulcers and if a self-management exercise program based on self-efficacy theory is well adhered to.
Method/design
This is a randomised controlled in adults with venous leg ulcers to determine the effectiveness of a self-efficacy based exercise intervention. Participants with venous leg ulcers are recruited from 3 clinical sites in Australia. After collection of baseline data, participants are randomised to either an intervention group or control group. The control group receive usual care, as recommended by evidence based guidelines. The intervention group receive an individualised program of calf muscle exercises and walking. The twelve week exercise program integrates multiple elements, including up to six telephone delivered behavioural coaching and goal setting sessions, supported by written materials, a pedometer and two follow-up booster calls if required. Participants are encouraged to seek social support among their friends, self-monitor their weekly steps and lower limb exercises. The control group are supported by a generic information sheet that the intervention group also receive encouraging lower limb exercises, a pedometer for self-management and phone calls at the same time points as the intervention group. The primary outcome is the healing rates of venous leg ulcers which are assessed at fortnightly clinic appointments. Secondary outcomes, assessed at baseline and 12 weeks: functional ability (range of ankle motion and Tinetti gait and balance score), quality of life and self-management scores.
Discussion
This study seeks to address a significant gap in current wound management practice by providing evidence for the effectiveness of a home-based exercise program for adults with venous leg ulcers. Theory-driven, evidence-based strategies that can improve an individual’s exercise self-efficacy and self-management capacity could have a significant impact in improving the management of people with venous leg ulcers. Information gained from this study will provide much needed information on management of this chronic disease to promote health and independence in this population.
Trial registration
Australian New Zealand Clinical Trials Registry ACTRN12612000475842.
doi:10.1186/1471-5945-14-16
PMCID: PMC4188410  PMID: 25277416
Venous leg ulcers; Exercise; Randomised controlled trial; Self-efficacy; Protocol
7.  Tomotherapy concomitant with cetuximab, followed by cetuximab as single-agent therapy for unresectable squamous cell carcinoma of the skin: a case report 
BMC Dermatology  2014;14:15.
Background
Cutaneous squamous cell carcinoma (SCC) is the second most frequency of all skin tumors. Incidence of SCC has risen significantly due to an increased sun exposure and the number of immunodeficient patients. Cutaneous SCC is characterized by high Epidermal growth factor receptor (EGFR) expression with low frequency of RAS mutations. Generally, locoregional surgery is curative and systemic therapy is not indicated. We evaluated the activity and toxicity profile of tomotherapy concomitant with Cetuximab, followed by Cetuximab as single agent therapy in a patient affected by unresectable, locally advanced cutaneous SCC.
Case presentation
At our institution, on March 2012 we treated a 45 years-old patient affected by locally advanced, unresectable G1 SCC of the lumbar region. At our first observation, the patient was asthenic, with severe pain and functional limitations. There was also a superinfection due to Pseudomonas Aeruginosa resistant to antibiotics, and a G3 anemia secondary to the bleeding lesion. ECOG Performance Status was 2. Tomotherapy has been performed concomitant with the Cetuximab (400 mg/m2, followed by weekly doses of 250 mg/m2) at the total dose of 60 Gy (2 Gy/fx), followed by Cetuximab monotherapy.
The lesion reduced progressively until disappear even after the suspension of the treatment and the patient achieved complete response. Toxicity resulted in G1 cutaneous rash and G2 toxicity to the nails, appeared after 5 months of treatment, typical toxicity profile of the anti-EGFR therapies. After one month of therapy the Pseudomonas Aeruginosa superinfection totally disappeared. Quality of life resulted significantly improved with reduction until discontinuation of the anti-pain drugs, and progressive increase of the hemoglobin levels. At follow up of 15 months there was no evidence of active disease and the ECOG Performance Status was 0 (zero).
Conclusion
The treatment was effective and feasible. Considering these excellent results, further studies about concomitant tomotherapy with Cetuximab for advanced/inoperable SCC of the skin are needed.
doi:10.1186/1471-5945-14-15
PMCID: PMC4186952  PMID: 25270710
SCC; Cetuximab; Tomotherapy; Target therapy; Quality of life
8.  Employment is maintained and sick days decreased in psoriasis/psoriatic arthritis patients with etanercept treatment 
BMC Dermatology  2014;14:14.
Background
Psoriasis and psoriatic arthritis (PsA) impair quality of life, including reduction in employment or job duties. The PRESTA (Psoriasis Randomized Etanercept STudy in Patients with Psoriatic Arthritis) study, a randomized, double-blind, two-dose trial, examined the efficacy of etanercept treatment in patients with moderate-to-severe plaque psoriasis and PsA and the main results have been presented previously. This analysis examined employment status, job duties and sick days, pre-defined endpoints in PRESTA, among this patient population.
Methods
Participants (N = 752) were randomized to receive etanercept 50 mg twice weekly (BIW; n = 379) or 50 mg once weekly (QW; n = 373) for 12 weeks by subcutaneous injection. All participants then received open-label etanercept 50 mg QW for 12 additional weeks, while remaining blinded to the randomization. A pharmacoeconomic questionnaire was administered at baseline, week 12 and week 24 of treatment. The questionnaire included employment status and changing job responsibilities and sick time taken due to psoriasis or PsA. The statistical methods included analysis of covariance, t-test, Fisher’s exact test and McNemar’s test. Last-observation-carried-forward imputation was used for missing data.
Results
Employment was at least maintained from baseline to week 24 in both dose groups (56% [BIW/QW] and 60% [QW/QW] at baseline, 61% and 60%, respectively, at week 24). Among employed participants, the proportion of patients whose job responsibilities changed due to PsA decreased significantly from baseline to week 24 (17–23% to 5–8%; p < 0.01). Similar results were seen with job responsibility changes due to psoriasis (11–14% to 4%; p < 0.01). The number of monthly sick days also decreased from baseline to week 24 (2.4 days for both treatment groups to 0.7 (BIW/QW) and 1.1 (QW/QW); p ≤ 0.03 for each). No significant differences between the treatment groups were observed for any economic endpoint at any time point.
Conclusions
For patients with moderate-to-severe plaque psoriasis and PsA, etanercept treatment resulted in reducing job responsibility changes due to disease and in reducing sick time. Effective treatment of psoriasis and PsA may reduce missed work days.
doi:10.1186/1471-5945-14-14
PMCID: PMC4147874  PMID: 25091090
Psoriasis; Psoriatic arthritis; Pharmacoeconomics; Etanercept; Employment; Sick days
9.  Low rate of dermatology outpatient visits in Asian-Americans: an initial survey study for associated patient-related factors 
BMC Dermatology  2014;14:13.
Background
Asian-Americans represent the fastest growing minority group in the United States, but are under-represented patients in outpatient dermatology clinics. At the same time, skin cancer rates in individuals of Asian descent are increasing, but skin cancer detection appears to be delayed in Asian-Americans compared to white individuals. Some health-care provider related factors for this phenomenon have been reported in the literature, but the patient-related factors are unclear.
Methods
This exploratory study to identify patient-related factors associated with dermatology visits in Asian-Americans was performed after Institutional Review Board (IRB) approval. An anonymous, online survey utilizing validated items was conducted on adults who self-identified as Asian-American in Northern California. Univariate and multivariate logistic regression for dermatology visits as indicated by responses to the question of “ever having had skin checked by a dermatologist” were performed on survey responses pertaining to demographic information, socioeconomic factors, acculturation, knowledge of melanoma warning signs and SSE belief and practice.
Results
89.7% of individuals who opened the online survey completed the items, with 469 surveys included in the analysis. Only 60% reported ever performing a SSE, and only 48% reported ever having a skin examination by a dermatologist. Multivariate models showed that “ever performing SSE” (p < 0.0001), marital status (p = 0.02), family history of skin cancer (p = 0.03) and generation in the United States (p = 0.02) were significant predictors of the primary outcome of “ever had skin checked by a dermatologist”.
Conclusions
Identification of patient-related factors that associate with dermatology clinic visits in Asian-Americans is important so that this potential gap in dermatologic care can be better addressed through future studies.
doi:10.1186/1471-5945-14-13
PMCID: PMC4130701  PMID: 25085260
Dermatology; Skin cancer; Early detection; Acculturation; Asian-Americans; Skin self-examination; Dermatology visits; Prevention; Ethnic skin
10.  Two sisters reveal autosomal recessive inheritance of epidermodysplasia verruciformis: a case report 
BMC Dermatology  2014;14:12.
Background
Epidermodysplasia verruciformis is a rare genodermatosis characterized by a unique susceptibility to cutaneous human papillomaviruses infection. Most patients show autosomal recessive patterns of inheritance.
Case presentation
We report a case of two sisters with clinically epidermodysplasia verruciformis specific lesions on the face, neck, trunk, and extremities. PCR analysis indicated the presence of human papillomavirus type 5 in the lesions. Electron microscopic examination showed viral-like particles in keratinocyte nuclei and the stratum corneum of the epidermodysplasia verruciformis lesions. In addition, we examined the EVER1 and EVER2 genes using eight different primer pairs without finding any nonsense or frameshift mutations in the gDNA from lymphocytes of the elder sister.
Conclusions
In this report, the patient’s parents did not have epidermodysplasia verruciformis lesions or a consanguineous marriage. EV did not develop in the elder sister until five years of age, so the parents did not perceive EV as an inherited disease. The probability that EV developed in both sisters was only 6.25%. Thus, it is rare for both sisters to develop epidermodysplasia verruciformis lesions considering that the parents were presumed to be carriers and the disease reveal an autosomal recessive pattern of inheritance.
doi:10.1186/1471-5945-14-12
PMCID: PMC4110534  PMID: 25048734
Epidermodysplasia verruciformis; Hereditary pattern; Human papillomavirus; EVER1 and EVER2 genes; Electron microscopic examination
11.  A systematic literature review of pediculosis due to head lice in the Pacific Island Countries and Territories: what country specific research on head lice is needed? 
BMC Dermatology  2014;14:11.
Background
Lack of guidelines on control of pediculosis in the Solomon Islands led to a search for relevant evidence on head lice in the Pacific Island Countries and Territories (PICTs). The aim of this search was to systematically evaluate evidence in the peer reviewed literature on pediculosis due to head lice (Pediculus humanus var capitis) in the 22 PICTs from the perspective of its value in informing national guidelines and control strategies.
Methods
PubMed, Web of Science, CINAHL and Scopus were searched using the terms (pediculosis OR head lice) AND each of the 22 PICTs individually. PRISMA methodology was used. Exclusion criteria were: i) not on topic; ii) publications on pediculosis not relevant to the country of the particular search; iii) in grey literature.
Results
Of 24 publications identified, only 5 were included. Four related to treatment and one to epidemiology. None contained information relevant to informing national guidelines.
Conclusions
Current local evidence on head lice in the PICTs is minimal and totally inadequate to guide any recommendations for treatment or control. We recommend that local research is required to generate evidence on: i) epidemiology; ii) knowledge, attitudes and practices of health care providers and community members; iii) efficacy of local commercially available pharmaceutical treatments and local customary treatments; iv) acceptability, accessibility and affordability of available treatment strategies; and iv) appropriate control strategies for families, groups and institutions. We also recommend that operational research be done by local researchers based in the PICTs, supported by experienced head lice researchers, using a two way research capacity building model.
doi:10.1186/1471-5945-14-11
PMCID: PMC4078391  PMID: 24962507
Head lice; Pediculosis; Pediculus humanus var capitis; Pacific Island Countries and Territories; Systematic literature review; Papua New Guinea; Solomon Islands; French Polynesia
12.  Survey and online discussion groups to develop a patient-rated outcome measure on acceptability of treatment response in vitiligo 
BMC Dermatology  2014;14:10.
Background
Vitiligo is a chronic depigmenting skin disorder which affects around 0.5-1% of the world’s population. The outcome measures used most commonly in trials to judge treatment success focus on repigmentation. Patient-reported outcome measures of treatment success are rarely used, although recommendations have been made for their inclusion in vitiligo trials. This study aimed to evaluate the face validity of a new patient-reported outcome measure of treatment response, for use in future trials and clinical practice.
Method
An online survey to gather initial views on what constitutes treatment success for people with vitiligo or their parents/carers, followed by online discussion groups with patients to reach consensus on what constitutes treatment success for individuals with vitiligo, and how this can be assessed in the context of trials. Participants were recruited from an existing database of vitiligo patients and through posts on the social network sites Facebook and Twitter.
Results
A total of 202 survey responses were received, of which 37 were excluded and 165 analysed. Three main themes emerged as important in assessing treatment response: a) the match between vitiligo and normal skin (how well it blends in); b) how noticeable the vitiligo is and c) a reduction in the size of the white patches. The majority of respondents said they would consider 80% or more repigmentation to be a worthwhile treatment response after 9 months of treatment. Three online discussion groups involving 12 participants led to consensus that treatment success is best measured by asking patients how noticeable their vitiligo is after treatment. This was judged to be best answered using a 5-point Likert scale, on which a score of 4 or 5 represents treatment success.
Conclusions
This study represents the first step in developing a patient reported measure of treatment success in vitiligo trials. Further work is now needed to assess its construct validity and responsiveness to change.
doi:10.1186/1471-5945-14-10
PMCID: PMC4075774  PMID: 24929563
Vitiligo; Outcome measure; Patient-reported outcome; Randomised controlled trial
13.  HLA class II alleles may influence susceptibility to adult dermatomyositis and polymyositis in a Han Chinese population 
BMC Dermatology  2014;14:9.
Background
Polymyositis (PM) and dermatomyositis (DM) are idiopathic inflammatory myopathies. Genetic variability in human leukocyte antigen (HLA) genes plays an important role in the pathogenesis of PM and DM. However, few studies on the subject in Chinese populations have been reported thus far.
Methods
We studied the influence of HLA polymorphisms on DM and PM susceptibility by analyzing HLA-DRB1, HLA-DQA1, and HLA-DQB1 alleles in 71 adult DM patients, 20 adult PM patients, and 113 controls in a Han Chinese population.
Results
A positive association was found between HLA-DQA1*0104 and DM (p = 0.01; corrected p (pcorr) NS; odds ratio (OR) = 2.58; 95% confidence interval (CI): 1.18–5.64), while an inverse correlation was noted between HLA-DQB1*0303 and myositis patients with interstitial lung inflammation (p = 0.01; pcorr NS; OR = 0.25; 95% CI: 0.07–0.73). A positive relationship was also observed between HLA-DRB1*07 and DM (p = 0.01; pcorr NS; OR = 2.26; 95% CI: 1.12–4.59), while HLA-DRB1*03 seems to be protective against DM (p = 0.01; pcorr NS; OR = 0.26; 95% CI: 0.06–0.81). The lung complication was closely associated with HLA-DRB1*04 (p = 0.01; pcorr NS; OR = 2.82; 95% CI: 1.15–6.76) and HLA-DRB1*12 (p = 0.02; pcorr NS; OR = 2.52; 95% CI: 1.02–6.07). The frequency of HLA-DRB1*07 was significantly higher among myositis patients with dysphagia than among controls (p = 0.01; pcorr NS; OR = 4.78; 95% CI: 1.03–24.42). The putative haplotype DRB1*07-DQA1*01-DQB1*02 was positively correlated with DM (p = 0.03; pcorr NS; OR = 2.90; 95% CI: 1.02–8.93) and the lung complication (p = 0.02; pcorr NS; OR = 3.45; 95% CI: 1.04–11.58).
Conclusions
Our results demonstrate that HLA alleles may be involved in susceptibility to adult DM and PM in the Han Chinese population.
doi:10.1186/1471-5945-14-9
PMCID: PMC4062285  PMID: 24894810
Polymyositis; Dermatomyositis; HLA; Susceptibility; Chinese
14.  miR-125b induces cellular senescence in malignant melanoma 
BMC Dermatology  2014;14:8.
Background
Micro RNAs (miRs) have emerged as key regulators during oncogenesis. They have been found to regulate cell proliferation, differentiation, and apoptosis. Mir-125b has been identified as an oncomir in various forms of tumours, but we have previously proposed that miR-125b is a suppressor of lymph node metastasis in cutaneous malignant melanoma. Our goal was therefore to further examine this theory.
Methods
We used in-situ-hybridization to visualise miR-125b expression in primary tumours and in lymph node metastasis. Then using a miRVector plasmid containing a miR-125b-1 insert we transfected melanoma cell line Mel-Juso and then investigated the effect of the presence of a stable overexpression of miR-125b on growth by western blotting, flow cytometry and β-galactosidase staining. The tumourogenicity of the transfected cells was tested using a murine model and the tumours were further examined with in-situ-hybridization.
Results
In primary human tumours and in lymph node metastases increased expression of miR-125b was found in single, large tumour cells with abundant cytoplasm. A stable overexpression of miR-125b in human melanoma cell line Mel-Juso resulted in a G0/G1 cell cycle block and emergence of large cells expressing senescence markers: senescence-associated beta-galactosidase, p21, p27 and p53. Mel-Juso cells overexpressing miR-125b were tumourigenic in mice, but the tumours exhibited higher level of cell senescence and decreased expression of proliferation markers, cyclin D1 and Ki67 than the control tumours.
Conclusions
Our results confirm the theory that miR-125b functions as a tumour supressor in cutaneous malignant melanoma by regulating cellular senescence, which is one of the central mechanisms protecting against the development and progression of malignant melanoma.
doi:10.1186/1471-5945-14-8
PMCID: PMC4021480  PMID: 24762088
hsa-miR-125b; Melanoma; Senescence; In-situ-hybridization; Mel-Juso
15.  Dermoscopy as an adjuvant tool for detecting skin leiomyomas in patient with uterine fibroids and cerebral cavernomas 
BMC Dermatology  2014;14:7.
Background
Hereditary syndromes frequently need the cooperation of different specialties to increase diagnostic competence. Multiple cutaneous and uterine leiomyomatosis syndrome is a rare autosomal dominant disorder caused by the mutations of the fumarate hydratase gene, demonstrated in 80 to 100 percent of affected individuals. This can be linked to an increased risk of renal cancer in both sexes. The skin involvement is described to highlight the diagnostic role of the cutaneous counterpart in identifying this rare syndrome.
Case presentation
A 37-year-old woman suffering from several uterine fibroids presented multiple, painful, papulo-nodules on her left subscapular side, both forearms and legs. The patient underwent surgery on six lesions: five were leiomyomas, whilst one was a dermatofibroma. Genetic sequencing did not evidence known fumarate hydratase gene mutations. Dermoscopy showed a brown delicate pigmented network and included leiomyomas among the non-melanocytic benign skin tumours featuring a dermatofibroma-like pattern. Abdominal computerized-tomography scan did not reveal renal cancer, but brain magnetic resonance imaging showed one asymptomatic cerebral cavernoma. The patient benefited from the surgical removal of the five larger cutaneous lesions and from gabapentin, which relieved her pain.
Conclusions
This observation highlights the usefulness of dermoscopy in the diagnosis of cutaneous leiomyomas disclosing multiple cutaneous and uterine leiomyomatosis syndrome. Dermoscopy should be performed for non-melanocytic multiple lesions mimicking leiomyomas in a large number of patients, to establish a strict classification and identify false negative cases or evaluate them as dermatofibromas. In this case, the dermatologist recognized the risk of renal cancer and cerebral cavernomas.
doi:10.1186/1471-5945-14-7
PMCID: PMC4005830  PMID: 24739762
Cutaneous leiomyoma; Dermoscopic pattern; Dermatofibroma; Differential diagnosis
16.  Risk factors for eczema in infants born in Cuba: a population-based cross-sectional study 
BMC Dermatology  2014;14:6.
Background
There is a concern that allergic disease in childhood is higher than expected in Cuba. The aim of this study was to determine the risk factors for eczema of infants aged 12–15 months living in Havana.
Methods
We used a cross-sectional epidemiological study design. Data on eczema symptoms and a wide range of lifestyle factors were collected by researcher administered questionnaires.
Results
Data were collected on 1956 children (96% response rate), of whom 672 (34%) were reported as having had eczema. Independent risk factors for eczema included young maternal age (adjusted odds ratio (OR) 0.98 per additional year of age; 95% confidence interval (CI) 0.97-0.99), child’s weight (OR 1.13 per additional kg; 95% CI: 1.03-1.25), insect sting allergy (OR 2.11; 95% CI: 1.33-3.35), rodents in the home (OR 1.39; 95% CI: 1.10-1.76), attendance at childcare facilities (OR 1.34: 95% CI: 1.05-1.70) and self-reported mould in the home (OR 1.23; 95% CI: 1.07-1.41). Infant exposure to paracetamol was associated with an increased risk of eczema even after adjustment for wheeze (OR 1.22; 95% CI: 1.03-1.46).
Conclusion
Despite a very different culture and environment, the consistency of these findings with those from more economically developed countries suggests potential causal associations. The association with paracetamol, even after adjustment for wheeze, suggests that intervention studies are required in young infants, to ascertain if this commonly used anti-pyretic medication increases allergic disease.
doi:10.1186/1471-5945-14-6
PMCID: PMC3987161  PMID: 24666750
Eczema; Infants; Risk factor; Cuba; Paracetamol
17.  BMC Dermatology reviewer acknowledgement 2013 
BMC Dermatology  2014;14:2.
Contributing reviewers
The editors of BMC Dermatology would like to thank all our reviewers who have contributed to the journal in Volume 13 (2013).
doi:10.1186/1471-5945-14-2
PMCID: PMC3994478
18.  A laboratory-based study on patients with Parkinson’s disease and seborrheic dermatitis: the presence and density of Malassezia yeasts, their different species and enzymes production 
BMC Dermatology  2014;14:5.
Background
Seborrheic dermatitis (SD) and Parkinson’s disease (PD) are frequently associated conditions. Aims of this study were: to determine severity of SD, presence of different species and density of Malassezia yeasts; to assess yeast lipases and phosphatases production in vitro and to compare these results between SD patients with and without PD.
Methods
This case–control prospective study was conducted at the Dermatology and Neurology Units, Clinical Centre of Serbia and at the National Medical Mycology Reference Laboratory, University of Belgrade Medical School, Serbia. A total of 90 patients and 70 healthy controls (HC) were investigated: 60 patients with SD (SDN) and 30 patients with SD and PD (SDP). Culture-based mycological examination was carried out on lesional skin (LS) and non-lesional skin (NLS). A yeasts density was determined by counting the Malassezia colony forming units per tape (CFU/tape). Enzymes production by isolated Malassezia was investigated.
Results
The most patients with SD were male (76.7%; SDP and 63.3%; SDN) and the intensity of SD was dominantly severe or moderate (76.7%; SDP and 75%; SDN). The presence of Malasseziа was high on LS in both groups (87.3%; SDP and 86.7%; SDN) (p=0.667).
The highest yeasts density (mean CFU/tape=67.8) was detected on LS in 53% of SDP group and in 21.7% of SDN group (mean CFU/tape=31.9) (p < 0.01). The presence of negative cultures was lower in SDP group (13.3%) in comparison to HC and SDN groups (37% and 31.7%, respectively). Malassezia density on NLS in SDP group (mean CFU/tape=44.3) was significantly higher in comparison to SDN and HC (p=0.018). M. globosa was the most abundant species identified amongst isolates from the SDP group (42.3%) and exhibited high production of phosphatase and lipase in vitro.
Conclusion
From this laboratory-based study a positive correlation between SD, PD, M. globosa incidence, high yeast density and high phosphatase and lipase activity was established. Our data lead to conclusion that local skin performance of PD patient’s characterized with increased sebum excretion ratio play a role in SD by stimulation of yeasts replication and enzyme production.
doi:10.1186/1471-5945-14-5
PMCID: PMC3995588  PMID: 24628775
Seborrheic dermatitis; Parkinson’s disease; Malassezia species; Colony forming units; Enzymes
19.  Exploring patterns of recurrent melanoma in Northeast Scotland to inform the introduction a digital self-examination intervention 
BMC Dermatology  2014;14:4.
Background
Melanoma incidence is growing and more people require follow-up to detect recurrent melanoma quickly. Those detecting their own recurrent melanoma appear to have the best prognosis, so total skin self examination (TSSE) is advocated, but practice is suboptimal. A digital intervention to support TSSE has potential but it is not clear which patient groups could benefit most. The aim of this study was to explore cutaneous melanoma recurrence patterns between 1991 and 2012 in Northeast Scotland. The objectives were to: determine how recurrent melanomas were detected during the period; explore factors potentially predictive of mode of recurrence detection; identify groups least likely to detect their own recurrent melanoma and with most potential to benefit from digital TSSE support.
Methods
Pathology records were used to identify those with a potential recurrent melanoma of any type (local, regional and distant). Following screening of potential cases available secondary care-held records were subsequently scrutinised. Data was collected on demographics and clinical characteristics of the initial and recurrent melanoma. Data were handled in Microsoft Excel and transported into SPSS 20.0 for statistical analysis. Factors predicting detection at interval or scheduled follow-up were explored using univariate techniques, with potentially influential factors combined in a multivariate binary logistic model to adjust for confounding.
Results
149 potential recurrences were identified from the pathology database held at Aberdeen Royal Infirmary. Reliable data could be obtained on 94 cases of recurrent melanoma of all types. 30 recurrences (31.9%) were found by doctors at follow-up, and 64 (68.1%) in the interval between visits, usually by the patient themselves. Melanoma recurrences of all types occurring within one-year were significantly more likely to be found at follow-up visits, and this remained so following adjustment for other factors that could be used to target digital TSSE support.
Conclusions
A digital intervention should be offered to all newly diagnosed patients. This group could benefit most from optimal TSSE practice.
doi:10.1186/1471-5945-14-4
PMCID: PMC3984711  PMID: 24612627
Melanoma recurrence; Self-detected; Follow-up; Skin self-examination; Education
20.  Distribution of Malassezia species on the skin of patients with atopic dermatitis, psoriasis, and healthy volunteers assessed by conventional and molecular identification methods 
BMC Dermatology  2014;14:3.
Background
The Malassezia yeasts which belong to the physiological microflora of human skin have also been implicated in several dermatological disorders, including pityriasis versicolor (PV), atopic dermatitis (AD), and psoriasis (PS). The Malassezia genus has repeatedly been revised and it now accommodates 14 species, all but one being lipid-dependent species. The traditional, phenotype-based identification schemes of Malassezia species are fraught with interpretative ambiguities and inconsistencies, and are thus increasingly being supplemented or replaced by DNA typing methods. The aim of this study was to explore the species composition of Malassezia microflora on the skin of healthy volunteers and patients with AD and PS.
Methods
Species characterization was performed by conventional, culture-based methods and subsequently molecular techniques: PCR-RFLP and sequencing of the internal transcribed spacer (ITS) 1/2 regions and the D1/D2 domains of the 26S rRNA gene. The Chi-square test and Fisher’s exact test were used for statistical analysis.
Results
Malassezia sympodialis was the predominant species, having been cultured from 29 (82.9%) skin samples collected from 17 out of 18 subjects under the study. Whereas AD patients yielded exclusively M. sympodialis isolates, M. furfur isolates were observed only in PS patients. The isolation of M. sympodialis was statistically more frequent among AD patients and healthy volunteers than among PS patients (P < 0.03). Whether this mirrors any predilection of particular Malassezia species for certain clinical conditions needs to be further evaluated. The overall concordance between phenotypic and molecular methods was quite high (65%), with the discordant results being rather due to the presence of multiple species in a single culture (co-colonization) than true misidentification. All Malassezia isolates were susceptible to cyclopiroxolamine and azole drugs, with M. furfur isolates being somewhat more drug tolerant than other Malassezia species.
Conclusions
This study provides an important insight into the species composition of Malassezia microbiota in human skin. The predominance of M. sympodialis in both normal and pathologic skin, contrasts with other European countries, reporting M. globosa and M. restricta as the most frequently isolated Malassezia species.
doi:10.1186/1471-5945-14-3
PMCID: PMC3975586  PMID: 24602368
Identification; Malassezia spp; PCR-RFLP; Sequence analysis; Drug susceptibility
21.  Comparison of publication trends in dermatology among Japan, South Korea and Mainland China 
BMC Dermatology  2014;14:1.
Background
We previously showed that the number of publications in dermatology is increasing year by year, and positively correlates with improved economic conditions in mainland China, a still developing Asian country. However, the characteristics of publications in dermatology departments in more developed Asian countries such as Japan and South Korea are unknown.
Methods
In the present study, publications from 2003 through 2012 in dermatology in Japan, South Korea and mainland China were characterized. All data were obtained from http://www.pubmed.com.
Results
Dermatology departments in Japan published 4,094 papers, while mainland China and South Korea published 1528 and 1,758 articles, respectively. 48% of articles from dermatology in Japan were original research and 36% were case reports; The number of publications in Japan remained stable over time, but the overall impact factors per paper increased linearly over the last 10 year period (p < 0.05). In mainland China, 67% of articles from dermatology were original research, while 19% were case reports; The number of publications and their impact factors per paper increased markedly. In South Korea, 65% of articles from dermatology were original research and 20% were case reports. The impact factors per paper remained unchanged, despite of the fact that the number of publications increased over the last 10 year period (r2 = 0.6820, p = 0.0032). Only mainland China showed a positive correlation of the number of publications with gross domestic product per capita during this study period.
Conclusions
These results suggest that the total number of publications in dermatology correlates with economic conditions only in developing country, but not in more developed countries in Asia. The extent of economic development could determine both the publication quantity and quality.
doi:10.1186/1471-5945-14-1
PMCID: PMC3893556  PMID: 24405832
Publication; Dermatology; Gross domestic product; China; Japan; South Korea
22.  Protocol for a randomised trial on the effect of group education on skin-protective behaviour versus treatment as usual among individuals with newly notified occupational hand eczema – the Prevention of Hand Eczema (PREVEX) Trial 
BMC Dermatology  2013;13:16.
Background
The incidence of occupational hand eczema is approximately 0.32 per 1,000 person years. The burden of the disease is high, as almost 60% has eczema-related sick leave during the first year after notification, and 15% are excluded from the workforce 12 years after disease onset. New treatments and prevention strategies are needed.
Methods/Design
Trial design: The PREVEX trial is a randomised, parallel-group, superiority trial.
Participants: All individuals from the Capital Region of Denmark and Region Zealand with a suspected occupational skin disorder notified to the National Board of Industrial Injuries between June 2012 and December 2013 are invited to participate in the trial. Inclusion criteria are: self-reported hand eczema and informed consent. Exclusion criteria are: age <18 years or >65 years; permanent exclusion from the workforce; inability to understand the Danish language; any serious medical condition; and lack of written informed consent. We plan to randomise 742 participants. Interventions: The experimental intervention is an educational course in skin-protective behaviour and written information about skin care related to the participants' specific occupation. Also, a telephone hotline is available and a subgroup will be offered a work-place visit. The experimental and the control group have access to usual care and treatment. All participants are contacted every eighth week with questions regarding number of days with sick leave or other absence from work. 12 months after randomisation follow-up is completed. Objective: To assesses the effect of an educational course versus treatment as usual in participants with newly notified occupational hand eczema. Randomisation: Participants are centrally randomised according to a computer-generated allocation sequence with a varying block size concealed to investigators. Blinding: It is not possible to blind the participants and investigators, however, data obtained from registers, data entry, statistical analyses, and drawing of conclusions will be blinded. Outcomes: The three co-primary outcomes, assessed at 12 months, are: total number of self-reported days with sick leave; health-related quality of life; and subjective assessment of hand eczema severity. Explorative outcomes are: self-reported eczema-related sick leave, absence from work registered by the DREAM-register and by self-report, risk behaviour, knowledge of skin protection and performance management (self-efficacy; and self-evaluated ability to self-care).
Discussion
The PREVEX trial will be the first individually randomised trial to investigate the benefits and harms of group-based education in patients with newly notified occupational hand eczema.
Trial registration
ClinicalTrials.gov Identifier: NCT01899287
doi:10.1186/1471-5945-13-16
PMCID: PMC4225615  PMID: 24245553
Occupational hand eczema; OHE; Occupational contact dermatitis (OCD); Prevention; Work related; Intervention
23.  Hematological and hepatic effects of vascular epidermal growth factor (VEGF) used to stimulate hair growth in an animal model 
BMC Dermatology  2013;13:15.
Background
Alopecia areata is the hair loss usually reversible, in sharply defined areas. The treatment of alopecia using growth factors shows interesting activity in promoting hair growth. In this concept, VEGF (vascular endothelial growth factor) is a marker of angiogenesis, stimulating hair growth by facilitating the supply of nutrients to the hair follicle, increasing follicular diameter. The aim of this study was the evaluation of a topical gel enriched with VEGF liposomes on the hair growth stimulation and its toxicological aspects.
Methods
Mesocricetus auratus were randomly divided into three groups. Control group was treated with Aristoflex® gel, 1% group with the same gel but added 1% VEGF and 3% group with 3% VEGF. Biochemical, hematological and histological analyses were done.
Results
At the end of the experiment (15th day of VEGF treatment) efficacy was determined macroscopically by hair density dermatoscopy analysis, and microscopically by hair diameter analysis. They both demonstrated that hair of the VEGF group increased faster and thicker than control. On the other hand, biochemical and hematological results had shown that VEGF was not 100% inert.
Conclusions
VEGF increased hair follicle area, but more studies are necessary to confirm its toxicity.
doi:10.1186/1471-5945-13-15
PMCID: PMC3817933  PMID: 24168457
Alopecia; Experimental model; Growth factor
24.  Prevalence, incidence and predictive factors for hand eczema in young adults – a follow-up study 
BMC Dermatology  2013;13:14.
Background
Hand eczema is common in the general population and affects women twice as often as men. It is also the most frequent occupational skin disease. The economic consequences are considerable for society and for the affected individuals.
Methods
To investigate the prevalence and incidence of hand eczema and to evaluate risk factors for development of hand eczema in young adults. Subjects and methods; This is a prospective follow-up study of 2,403 young adults, 16 – 19 years old in 1995 and aged 29 – 32 years, 13 years later, in 2008. They completed a postal questionnaire that included questions regarding one-year prevalence of hand eczema, childhood eczema, asthma, rhino-conjunctivitis and factors considered to affect hand eczema such as hand-washing, washing and cleaning, cooking, taking care of small children and usage of moisturisers. These factors were evaluated with the multinominal logistic regression analysis.
Results
The one-year prevalence of hand eczema was 15.8% (females 20.3% and males 10.0%, p < 0.001). The incidence was 11.6 cases per 1000 person-years (females 14.3 and males 5.2, p < 0.001). Childhood eczema was the most important risk factor for hand eczema. The odds ratios were 13.17 when having hand eczema 1995 and 2008 compared to 5.17 in 2008 (p < 0.001). A high frequency of hand washing was important in predicting hand eczema only when having 1-year prevalence 2008, OR 1.02 (p = 0.038).
Conclusions
After 13 years an increased 1-year prevalence of hand eczema was found. The significant risk factors for hand eczema changed over time from endogenous to exogenous factors.
doi:10.1186/1471-5945-13-14
PMCID: PMC3819704  PMID: 24164871
Hand eczema; Childhood eczema; Prevalence; Incidence; Cohort; Gender; Skin care; Hand-wash
25.  Longitudinal, mixed method study to look at the experiences and knowledge of non melanoma skin cancer from diagnosis to one year 
BMC Dermatology  2013;13:13.
Background
Skin cancer is the most common type of cancer in humans and the incidence is increasing worldwide. Our objective was to understanding the needs, experiences and knowledge of individuals with Non Melanoma Skin Cancer (NMSC) from diagnosis up until one year.
Methods
Patients with NMSC completed questionnaires at diagnosis, treatment, 8 weeks post treatment and 12 months post diagnosis. Body image, psychological morbidity and Quality of Life (QOL) were assessed at each time point, with the exception of QOL that was not assessed at diagnosis. Knowledge of NMSC was assessed at baseline and 8 weeks. A sub-sample of participants was also interviewed to allow a more in-depth exploration of patients’ experiences.
Results
76 participants completed the initial questionnaire, of which 15 were interviewed. Patients were anxious about a diagnosis of skin cancer, however they were no more depressed or anxious than the general population. QOL significantly improved from diagnosis to 8 weeks and from diagnosis to one year. Knowledge of NMSC was poor and did not improve after treatment. Hairdressers were highlighted as playing an important role in raising awareness and encouraging individuals to seek medical help. Most participants were aware of the need to check their skin for suspicious lesions but were not sure what to look for. At one year participants had forgotten their experience and were not overly concerned about skin cancer.
Conclusion
There is a need to raise awareness of the signs and symptoms of NMSC. Information on skin cancer needs to be tailored to the individual both at the start of treatment and during the follow up months, ensuring that participants’ needs and expectations are met. Targeting education at individuals in the community who regularly come into contact with skin should help in early identification of NMSC. This is important since skin cancer caught early is easily treatable and delay in presentation leads to larger and more complex lesions which impacts in terms of increased morbidity and increased health care costs.
doi:10.1186/1471-5945-13-13
PMCID: PMC3819707  PMID: 24164857
Skin cancer; Non melanoma skin cancer; NMSC; Needs; Experiences; Knowledge

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