Pilonidal sinus disease: an intergluteal localization of hidradenitis suppurativa/acne inversa: a cross-sectional study among 2465 patients.

BACKGROUND: Hidradenitis suppurativa (HS), also referred to as acne inversa, is a debilitating skin disease characterized by inflammatory nodules, chronic abscesses and tunnels (fistulae and sinuses). The association with pilonidal sinus disease (PSD) is frequently reported but not well documented. OBJECTIVES: To determine the prevalence and characteristics of inflammatory skin lesions located in the intergluteal fold (IGF) of patients with HS. METHODS: This was an international multicentre retrospective cross-sectional study based on data collection from a large cohort of patients with HS with and without histopathology. Results From a total of 2465 patients with HS included in the study, 661 (27%) reported lesions in the IGF. These patients were significantly more often smokers and had more severe HS. Of the 238 patients with an available clinical diagnosis, intergluteal-HS (IG-HS) was diagnosed in 52 patients (22%) and PSD was diagnosed in 186 patients (78%). IG-HS was associated with the localization of HS in the proximity of the IGF, including the buttocks, genitals and the anus. There was a possibility of misclassification bias in this study as a clinical/image-based diagnosis or histopathology of the IGF lesions was not always available. CONCLUSIONS: The high prevalence of PSD suggests a strong link between both entities. Therefore, it may be useful to identify common pathophysiological mechanisms and develop common therapeutic strategies. What's already known about this topic? The occurrence of pilonidal sinus disease has not been clearly reported among patients with hidradenitis suppurativa/acne inversa. What does this study add? This is the first study that investigated the prevalence of pilonidal sinus disease among a large cohort of patients and identified the patient characteristics. Risk factors that might help to improve the management of patients were identified.

Clinical and dermoscopic characteristics of congenital melanocytic naevi.

BACKGROUND: Prompted by the limited data, we conducted this study to gather more information on dermoscopic features of CN in children, in order to optimize clinical care and management. MATERIALS AND METHODS: All children with congenital nevi (CN) attending our Pediatric Pigmented Skin Lesion Unit during a 2-year period were included in the study. Clinical data were collected, and all children underwent clinical and dermoscopic examination. Dermoscopic patterns and specific features were recorded. RESULTS: Three hundred and thirty CN were examined in a population of 276 children, aged from 6 months to 14 years. The majority (85.14%) had only one congenital naevus, and 43.12% had a family history of congenital nevi. Children with multiple congenital nevi were more likely to have a positive family history of a CN (P = 0.012). Only, in 23 children, neurological/developmental abnormalities were reported. Small CN were the commonest in our cohort (167) followed by the medium-sized (160), whereas large CN (>20 cm) were only three. Thirty-eight CN were located on the volar skin. The globular was the commonest dermoscopic pattern, followed by the reticular, whereas the parallel furrow pattern was the commonest pattern on palms and soles. CN on the trunk were more likely to be globular on the limbs, and reticular and homogeneous on the head and neck (P < 0.001). The commonest dermoscopic findings were haloed and target globules, blotches and perifollicular hypopigmentation, whereas globules and dots around cristae on volar skin. CN located on the limbs were more likely to demonstrate an atypical network (P = 0.001) and a target network with globules (P = 0.020), whereas haloed and target globules (P < 0.001), blotches (P = 0.023) and dots (P = 0.004) were found with an increased frequency in CN on the trunk. CONCLUSIONS: Given that there is much controversy on the management and accurate classification of CN, our findings may provide useful information.

Are VNTRs co-localizing with breast cancer-associated SNPs?

PURPOSE: Several common genetic variants (single-nucleotide polymorphisms, SNPs) have been shown to be associated with breast cancer (BC) risk in the general population, and to modify BC risk for BRCA1 and BRCA2 mutation carriers. Co-localization of variable number of tandem repeats (VNTRs) with these BC-associated SNPS has not been comprehensively studied. METHODS: Cross referencing of genome-wide VNTRs with the known BC genome-wide association studies (GWAS) SNPs significantly associated with increased risk for developing breast cancer was carried out. Analysis was based on the overlap between the VNTRs and 10-kb windows around these BC-susceptibility SNPs. RESULTS: Cross referencing of the 1.2 million TR with the 161 known BC-associated SNPs in the general population led to 690 matches. Of those, in 17 VNTRs, the SNP was within the VNTR. Analysis restricted to loci known to modify BC penetrance in BRCA1 (n = 31) and BRCA2 (n = 33) mutation carriers led to 139 and 170 co-localization matches, respectively. For these, none of the SNPs were within the VNTR. The distances between the SNPs and the VNTRs were not significantly different from what was expected to occur by chance alone (p = 0.61; p = 0.44; p = 0.25, respectively). CONCLUSION: There is no evidence that VNTRs co-localize with currently reported SNP tagged BC GWAS loci.

Low and high body mass index in hidradenitis suppurativa patients-different subtypes?

INTRODUCTION: Overweight is a well-established risk factor for hidradenitis suppurativa (HS). In this cross-sectional study, we compare HS patients with a high body mass index (BMI) with HS patients with a low BMI to investigate differences in disease characteristics. MATERIALS AND METHOD: Patients were recruited from 17 dermatological centres from four continents. A total of 246 patients with a BMI below 25 were compared to 205 patients with a BMI of above 35. RESULTS: Patients with a high BMI suffered more severe disease (Hurley, physician global assessment, number of areas affected and patient-reported severity (PRS), P < 0.001 for all). There was no difference in smoking (P = 0.783) nor in family history (P = 0.088). In both low and high BMI patients, early onset of HS was a predictor of positive family history (P < 0.001, for each). For low BMI patients, an increase in BMI significantly increased PRS (P < 0.001). For patients with a high BMI, number of pack-years significantly increased PRS (P = 0.001). Cluster analysis of eruption patterns was location specific for low BMI patients but severity specific for high BMI patients. DISCUSSION: Patients with a low and high BMI could represent two clinically different subtypes. We suggest a non-linear relationship between BMI and impact of HS. As patients go from a low BMI patient to a high BMI patient (or from high to low), eruption patterns and risk factors may change.

Patients with Spitz naevi in the Greek population: Epidemiologic, Clinical and Histopathological characteristics.

BACKGROUND: Spitz naevi may present with clinical and histopathological atypical features that do not affect patient prognosis but may become worrisome for patients ≥40 years presenting with newly appearing SN. OBJECTIVE: Patient characteristics and sun behaviour patterns were investigated in correlation with age. SN characteristics and histopathological attributes were also investigated in correlation with age. METHODS: Patients with histopathologically confirmed diagnosis of SN were invited for a clinical examination. Data such as skin type, number of banal/atypical naevi, sun exposure patterns and personal/family history were collected. Histopathology preparations were re-examined by two different histopathologists, and characteristics were collected based on a prespecified checklist. Patients were afterwards followed up every 6 months. RESULTS: A total of 110 patients with SN were identified and assigned to three age groups. The most common area of presentation was the trunk, for the ≥40 years age group, and the limbs for the other age groups. Patients ≥40 years had a higher possibility of presenting with a naevus count ≥50 and at least one atypical naevus compared to the other age groups. Patients ≥40 years presented more commonly with a history of painful sunburn (100%) before the appearance of the SN, used less sunscreen, had higher sun exposure times and more clinical signs of solar skin damage compared to the other age groups. Finally, patients ≥40 years presented more commonly with signs of histopathological atypia such as the presence of mitoses, cellular atypia and prominent nucleolus. CONCLUSION: Patients ≥40 were more likely to report a history of longer sun exposure times, of never using a sunscreen and of having a history of painful sunburn. However, the importance of this observation remains to be elucidated as these patients also presented more commonly with lesions located on non-sun-exposed areas (trunk) and higher naevus/atypical naevus counts.

Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium.

BACKGROUND: Advanced-stage mycosis fungoides (MF)/Sézary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. PATIENTS AND METHODS: This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). RESULTS: Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. CONCLUSION: This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach.

From basal cell carcinoma morphogenesis to the alopecia induced by hedgehog inhibitors: connecting the dots.

The deciphering of the hedgehog (Hh) signalling pathway implicated in the tumorigenesis of basal cell carcinoma (BCC) led to the development of targeted drug therapies, the Hh pathway inhibitors (HPIs) vismodegib and sonidegib. In the skin, physiological Hh signalling is activated in growing hair follicles (HFs), where it is required for proliferation of the epithelium of HFs during morphogenesis and for their postnatal growth. The effects of HPI treatment leading to the regression of BCC and the development of alopecia underpin the central role of the Hh pathway in BCC formation, as well as hair cycling. Given the fact that BCC is a follicular-driven tumour, it is a fine tuning of events that regulate hair cycling that may drive towards the formation of benign follicular hamartomas or malignant BCC neoplasms. Wnt/ß-catenin signalling interacts with the Hh signalling during HF morphogenesis, normal hair cycling and BCC development. The aim of this review is to present how key molecular events implicated in Hh pathway crosstalk in the HF are also involved in BCC pathogenesis and result in the alopecia developed by HPI treatment.

Psoriasis in patients with mycosis fungoides: a clinicopathological study of 25 patients.

BACKGROUND: It has been reported that patients with psoriasis are at increased risk for developing lymphoma including cutaneous T-cell lymphomas (CTCL). However, the comorbidity and the histopathologic correlation of psoriasis and mycosis fungoides (MF) have been less studied. OBJECTIVE: The objective of this study was to investigate the relation between MF and psoriasis. METHODS: We retrospectively reviewed and re-evaluated all MF cases diagnosed and followed in a 16-year period who carried both MF and psoriasis diagnoses. RESULTS: Forty-one of 321 MF patients was the rate of psoriasis' comorbidity according to medical records. Twenty-five patients (7.8%) finally met the inclusion criteria. The rest were excluded due to inadequate evidence. Twenty patients had psoriatic lesions at the time of MF diagnosis. In 23 patients, there was histological confirmation of both diseases. Six patients (24%) were diagnosed with folliculotropic MF, two were diagnosed with pustular psoriasis, and six patients were affected by palmoplantar and nail psoriasis. In four patients, there was a very short time interval between MF and psoriasis diagnosis. Fourteen patients with psoriasis had been previously treated with immunomodulatory regimens. Interestingly, in eight patients, typical histological findings of both diseases were detected in the same biopsy specimen. CONCLUSION: Our results support the opinion that the association between psoriasis and MF does exist. It is most possibly related to the chronic lymphocyte stimulation that occurs during psoriasis that eventually leads to a dominant clone and the evolution to CTCL. Our study suggests that apart from cases of early MF, which are being indeed misdiagnosed as psoriasis, there is another group of patients, where psoriasis truly coexists with - or even progresses to - MF.

Prognostic indicators for mycosis fungoides in a Greek population.

BACKGROUND: Mycosis fungoides (MF) is an indolent cutaneous lymphoma with excellent prognosis at early stages and much poorer outcome during disease progression. Old age, male sex and folliculotropism have been proposed as relevant prognostic factors; however, their exact effect remains debatable. OBJECTIVES: To evaluate MF prognostic indicators and survival rates in a Greek population. METHODS: Prognostic variables affecting survival rates were studied in 473 patients with MF diagnosed and treated by two academic referral centres in Greece. Kaplan-Meier estimates were used to determine survival rates and progression. The Cox proportional hazards regression model was used to assess prognostic factors. RESULTS: The mean age of diagnosis was 61·7 years (SD 16·33). Five-year disease-specific survival was 96% in patients with stage IA disease and 52% in patients with stage IIB disease. Univariate analysis certified that large-cell transformation, clonal rearrangements of the TCR gene, severe pruritus and presence of plaques were the most important prognostic factors. Folliculotropism altered disease progression only in patients with early-stage disease. The application of the Cutaneous Lymphoma International Prognostic Index (CLIPI) on our late-stage group failed to provide reliable evidence. The current Cutaneous Lymphoma International Consortium (CLIC) prognostic index can efficiently distinguish a low-risk from a high-risk group of patients. Tumour-Node-Metastasis-Blood (TNMB) staging was the most important prognostic factor for survival rates in multivariate analysis. CONCLUSIONS: In our study we validated the current prognostic indicators for MF in a Greek population and identified new potential prognostic factors for survival outcome. Our findings contribute to the ongoing investigation of prognostic indicators of MF, further validation of which is highly needed through prospective studies and among different populations.

Aberrant microRNA expression in tumor mycosis fungoides.

Herein, miRNA candidates relevant to mycosis fungoides were investigated to provide data on the molecular mechanisms underlying the pathogenesis of the disease. The miRNA expression profile of skin biopsies from patients with tumor stage MF (tMF) and normal donors was compared using miRNA microarrays. Overall, 154 miRNAs were found differentially expressed between tMF and the control cohort with the majority of them being up-regulated (57 %). Among the upregulated miRNAs, miR-3177, miR-514b-3p, miR-1267, and miR-1282 were exclusively detected in 70 % of tMF. Additional upregulated miRNAs included miR-34a, miR-29a, let-7a*, and miR-210, while miR-200c* was identified among the downregulated ones. Quantitative real-time polymerase chain reaction was used to further investigate the expression profiles of miR-34a and miR-29a and validated the overexpression of miR-34a. Enrichment studies revealed that the target genes of the differentially expressed miRNAs were important in several cancer-related signaling pathways. The overlapping relationship of the target genes among tMF, Sezary syndrome, and atopic dermatitis revealed several common and disease-specific genes. Collectively, our study modulated miR-34a as a candidate oncogenic molecule and miR-29a as a putative tumor suppressor highlighting their promising potential in the molecular pathogenesis of tMF.

Demographic, behavioural and physician-related determinants of early melanoma detection in a low-incidence population.

BACKGROUND: Knowledge of the factors that influence early detection of melanoma is important in developing strategies to reduce associated mortality. OBJECTIVES: To identify sociodemographic, behavioural and medical care-related factors associated with melanoma thickness in a low-incidence population but with a high case fatality. PATIENTS AND METHODS: In a multicentre, retrospective, survey-based study of 202 patients with a recent diagnosis of invasive melanoma (< 1 year), we collected data on demographic and behavioural factors, attitudes towards prevention, access to medical care, frequency of skin self-examination (SSE) and physician skin examination (PSE) in relation to melanoma thickness. RESULTS: Thinner tumours (≤ 1 mm, 80 melanomas) were associated with female sex (P ≤ 0.049), nonnodular (superficial spreading melanoma, lentigo maligna melanoma, acral lentiginous melanoma) histological subtypes (P < 0.001), absence of ulceration (P ≤ 0.001), and location other than lower extremity or trunk location (P ≤ 0.004). Patients married at the time of diagnosis or who performed SSE during the year prior to diagnosis were more likely to have thinner tumours than those who did not [odds ratio (OR) 3.45, 95% confidence interval (CI) 1.48-8.04 and OR 2.43, 95% CI 1.10-5.34, respectively]. Full-body skin examination by a physician was not significantly associated with thinner melanoma (OR 1.99, 95% CI 0.66-6.07). CONCLUSIONS: SSE was shown to be an important factor in the detection of thin melanoma, in contrast to partial or full-body PSE, which did not show any statistically significant effect on tumour thickness.

Stimulated human melanocytes express and release interleukin-8, which is inhibited by luteolin: relevance to early vitiligo.

Vitiligo is a disorder of depigmentation, for which the pathogenesis is as yet unclear. Interleukin (IL)-8 (CXCL8) is a key inflammatory chemokine. We investigated the regulation of IL-8 production in human melanocytes, and the IL-8 serum levels and skin gene expression in patients with vitiligo and in controls. Cultured melanocytes were stimulated for 24 h with tumour necrosis factor (TNF) 100 ng/mL and IL-1ß 10 ng/mL, with or without pretreatment with luteolin 50 µmol/L for 30 min, and IL-8 release was measured by ELISA. Serum cytokines were measured by a microbead array. Skin biopsies were taken from healthy subjects (n = 14) as well as from marginal lesional and nonlesional skin from patients with vitiligo (n = 15). IL-8 gene expression was evaluated by quantitative real time PCR. Both TNF and IL-1ß stimulated significant IL-8 release (P < 0.01) from melanocytes, whereas pretreatment with luteolin significantly inhibited this effect (P < 0.01). IL-8 gene expression was significantly increased in vitiligo compared with control skin (P < 0.05). IL-8 may be involved in vitiligo inflammation. Inhibition by luteolin of IL-8 release could be useful for vitiligo therapy.

The eminent dermatologist Moriz Kaposi (1837-1902) and the first description of idiopathic multiple pigmented sarcoma of the skin.

In 1872, the Hungarian born dermatologist Moriz Kaposi that was practicing in Vienna first described a rare endemic disease that bears his name, among elderly persons of Central European or Mediterranean origin named "idiopathic multiple pigmented sarcoma of the skin". Ten years later the Italian dermatologist Tommaso de Amicis confirms Kaposi's findings. For more than a century the disease was known as a rare low grade malignancy till the 1980s AIDS epidemic.

Serum neurotensin (NT) is increased in psoriasis and NT induces vascular endothelial growth factor release from human mast cells.

BACKGROUND: Psoriasis involves skin inflammation that often worsens with stress, but the mechanism of this effect remains obscure. We have shown that corticotropin-releasing hormone (CRH) is increased in the serum of patients with psoriasis. A peptide, neurotensin (NT), can trigger skin histamine release and augment the ability of CRH to increase skin vascular permeability. OBJECTIVES: To investigate the serum level of NT, and the expression of genes for NT and NT receptor-1 (NTR-1) in lesional and nonlesional skin of patients with psoriasis, compared with normal controls. Also, to study the effect of NT on human mast cell release of vascular endothelial growth factor (VEGF), which is increased in psoriatic skin. METHODS: Serum was obtained from patients with psoriasis (n = 56) and controls (n = 33); NT levels were measured with the Milliplex microbead assay. Biopsies were obtained from the lesional and nonlesional skin of patients with chronic plaque psoriasis (n = 40), who had not received any treatment for at least 15 days and were free of any systemic inflammatory diseases. Control skin samples were obtained from healthy subjects (n = 30). Expression of genes for NT and NTR-1 in the skin was evaluated by quantitative reverse transcriptase-polymerase chain reaction. LAD2 human mast cells were stimulated by NT (1 µmol L(-1)) for 24 h and VEGF was measured by enzyme-linked immunosorbent assay. RESULTS: Serum NT was increased in patients with psoriasis, while expression of genes for NT and NTR-1 in lesional skin was decreased compared with controls. NT induced VEGF release from mast cells and was augmented by interleukin-33. CONCLUSION: NT may play a role in psoriasis pathogenesis and its worsening by stress, at least in part through activation of skin mast cells.