The role of androgens and estrogens in Hidradenitis Suppurativa – a Systematic Review

Hidradenitis suppurativa (HS) is an inflammatory skin disease. Several observations imply that sex hormones may play a role in its pathogenesis. HS is more common in women, and the disease severity appears to vary in intensity according to the menstrual cycle. In addition, parallels have been drawn between HS and acne vulgaris, suggesting that sex hormones may play a role in the condition. The role of androgens and estrogens in HS has therefore been explored in numerous observational and some interventional studies; however, the studies have often reported conflicting results. This systematic review includes 59 unique articles and aims to give an overview of the available research. Articles containing information on natural variation, severity changes during menstruation and pregnancy, as well as articles on serum levels of hormones in patients with HS and the therapeutic options of hormonal manipulation therapy have all been included and are presented in this systematic review. Our results show that patients with HS do not seem to have increased levels of sex hormones and that their hormone levels lie within the normal range. While decreasing levels of progesterone and estrogen seem to coincide with disease flares in premenopausal women, the association is speculative and requires experimental confirmation. Antiandrogen treatment could be a valuable approach in treating HS, however randomized control trials are lacking.</p

In vivo microvascular imaging of cutaneous actinic keratosis, Bowen's disease and squamous cell carcinoma using dynamic optical coherence tomography

Background: A clear distinction between actinic keratosis (AK), Bowen's disease (BD) and squamous cell carcinoma (SCC) cannot reliably be made by clinical and dermoscopic evaluation alone. Dynamic optical coherence tomography (D-OCT) is a novel angiographic variant of OCT that allows for non-invasive, in vivo evaluation of the cutaneous microvascular morphology. Objective: To investigate the microvascular structures of AK, BD and invasive SCC using D-OCT in order to gain insights into the microvascular morphology of lesions in the spectrum of keratinocyte skin cancers. Methods: Forty-seven patients with a total of 54 lesions (18 AK, 12 BD and 24 SCC) were included in the study. D-OCT still images of AK, BD and SCC at three predefined skin depths were prepared and randomized, creating a study set of 162 D-OCT images. Three observers performed blinded evaluations of the randomized study set assessing multiple parameters including the different types of vascular morphology. Non-blinded quantitative measurements of vascular diameter were also performed. Results: The blinded observer analysis suggests that D-OCT evaluation of the vascular morphology may aid in distinguishing AK, BD and SCC lesions. We identified two vascular shapes that presented significantly differently across the lesion types, namely âblobsâ and âcurvesâ. A strong presence of blobs at 300 μm skin depth was characteristically seen in a third of BD cases, while not or only slightly present in AK and SCC lesions. Vascular curves were predominantly present in AK lesions. Conclusion: We identified various vascular D-OCT features that may aid in non-invasively differentiating subtypes within the keratinocyte skin cancer spectrum

In vivo differentiation of common basal cell carcinoma subtypes by microvascular and structural imaging using dynamic optical coherence tomography

The subtype of basal cell carcinoma (BCC) influences the choice of treatment. Optical coherence tomography (OCT) is a non-invasive imaging tool, and a recent development of an angiographic version of OCT has extended the application of OCT to image the cutaneous microvasculature (so-called dynamic OCT, D-OCT). This study explores D-OCT's ability to differentiate the common BCC subtypes by microvascular and structural imaging. Eighty-one patients with 98 BCC lesions, consisting of three subtypes: 27 superficial BCC (sBCC), 55 nodular BCC (nBCC) and 16 infiltrative BCC (iBCC) were D-OCT scanned at three European dermatology centres. Blinded evaluations of microvascular and structural features were performed, followed by extensive statistical analysis of risk ratio (RR) and multiple correspondence analysis. nBCC lesions displayed most characteristic structural and vascular features. Serpiginous vessels, branching vessels, vessels creating a circumscribed figure and sharply demarcated hyporeflective ovoid structures in the dermis were all associated with a higher risk of the subtype being nBCC. The presence of highly present lines and dark peripheral borders at the margin of ovoid structures was negatively associated with iBCC. Lastly, the finding of hyporeflective ovoid structures protruding from epidermis correlated with sBCC. We identified various microvascular and structural D-OCT features that may aid non-invasive identification of BCC subtypes. This would allow clinicians to individualize and optimize BCC treatment as well as aid follow-up of non-surgical treatment

Dynamic Optical Coherence Tomography in Dermatology

Optical coherence tomography (OCT) represents a non-invasive imaging technology, which may be applied to the diagnosis of non-melanoma skin cancer and which has recently been shown to improve the diagnostic accuracy of basal cell carcinoma. Technical developments of OCT continue to expand the applicability of OCT for different neoplastic and inflammatory skin diseases. Of these, dynamic OCT (D-OCT) based on speckle variance OCT is of special interest as it allows the in vivo evaluation of blood vessels and their distribution within specific lesions, providing additional functional information and consequently greater density of data. In an effort to assess the potential of D-OCT for future scientific and clinical studies, we have therefore reviewed the literature and preliminary unpublished data on the visualization of the microvasculature using D-OCT. Information on D-OCT in skin cancers including melanoma, as well as in a variety of other skin diseases, is presented in an atlas. Possible diagnostic features are suggested, although these require additional validation

Dynamic optical coherence tomography of blood vessels in cutaneous melanoma — correlation with histology, immunohistochemistry and dermoscopy

Dermoscopy adds important information to the assessment of cutaneous melanoma, but the risk of progression is predicted by histologic parameters and therefore requires surgery and histopathologic preparation. Neo-vascularization is crucial for tumor progression and worsens prognosis. The aim of this study was the in vivo evaluation of blood vessel patterns in melanoma with dynamic optical coherence tomography (D-OCT) and the correlation with dermoscopic and histologic malignancy parameters for the risk assessment of melanoma. In D-OCT vessel patterns, shape, distribution and presence/type of branching of 49 melanomas were evaluated in vivo at three depths and correlated with the same patterns in dermoscopy and with histologic parameters after excision. In D-OCT, blood vessel density and atypical shapes (coils and serpiginous vessels) increased with higher tumor stage. The histologic parameters ulceration and Hmb45- and Ki67-positivity increased, whereas regression, inflammation and PD-L1-positivity decreased with risk. CD31, VEGF and Podoplanin correlated with D-OCT vasculature findings. B-RAF mutation status had no influence. Due to pigment overlay and the summation effect, the vessel evaluation in dermoscopy and D-OCT did not correlate well. In summary, atypical vessel patterns in melanoma correlate with histologic parameters for risk for metastases. Tumor vasculature can be noninvasively assessed using D-OCT before surgery

In-vivo-Darstellung einer Sarcoptes-scabiei-Infestation mittels optischer Kohärenztomographie

&lt;b&gt;&lt;i&gt;Hintergrund: &lt;/i&gt;&lt;/b&gt;&lt;i&gt;Sarcoptes scabiei&lt;/i&gt; kann mit Hilfe verschiedener Darstellungsverfahren sichtbar gemacht werden. Mit der optischen Kohärenztomographie (OCT) lassen sich möglicherweise die bei Skabies-Infestation auftretenden Veränderungen der Hautmorphologie charakterisieren und der Parasit darstellen. &lt;b&gt;&lt;i&gt;Methoden:&lt;/i&gt;&lt;/b&gt; Fünf Patienten aus der Klinik für Dermatologie am Klinikum Augsburg und am Roskilde Hospital in Roskilde, Dänemark, wurden mit der optischen Kohärenztomographie (OCT; VivoSight®; Michelson Diagnostics Ltd., UK) untersucht. Der Nachweis der Milben erfolgte mittels Epilumineszenz; zur Bestätigung der Diagnose wurde eine lichtmikroskopische Untersuchung durchgeführt. &lt;b&gt;&lt;i&gt;Ergebnisse:&lt;/i&gt;&lt;/b&gt; Die OCT wies in vivo bei allen Patienten &lt;i&gt;S.-scabiei&lt;/i&gt;-Milben nach. Milben und Gänge wurden sichtbar gemacht und Einzelheiten des Ganginhalts dargestellt. &lt;b&gt;&lt;i&gt;Schlussfolgerung:&lt;/i&gt;&lt;/b&gt; Die OCT kann &lt;i&gt;S.-scabiei&lt;/i&gt;-Milben in vivo sichtbar machen, was dafür spricht, dass die OCT zur Untersuchung der Biologie der Milbe in vivo eingesetzt werden kann und eine frühzeitige Beurteilung einer gegen Krätzmilben wirkenden Therapie ermöglicht. Die OCT ist in der Lage, Strukturen in der Haut mit einer Auflösung von 8 µm darzustellen. Somit könnte dieses Verfahren eine rasche, nichtinvasive, In-vivo-Diagnose und -Untersuchung von Infestationen ermöglichen.</jats:p

Reflectance confocal microscopy for diagnosing cutaneous melanoma in adults

Background: Melanoma has one of the fastest rising incidence rates of any cancer. It accounts for a small percentage of skin cancer cases but is responsible for the majority of skin cancer deaths. Early detection and treatment is key to improving survival; however, anxiety around missing early cases needs to be balanced against appropriate levels of referral and excision of benign lesions. Used in conjunction with clinical or dermoscopic suspicion of malignancy, or both, reflectance confocal microscopy (RCM) may reduce unnecessary excisions without missing melanoma cases.Objectives: To determine the diagnostic accuracy of reflectance confocal microscopy for the detection of cutaneous invasive melanoma and atypical intraepidermal melanocytic variants in adults with any lesion suspicious for melanoma and lesions that are difficult to diagnose, and to compare its accuracy with that of dermoscopy.Search methods: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; and seven other databases. We studied reference lists and published systematic review articles.Selection criteria: Studies of any design that evaluated RCM alone, or RCM in comparison to dermoscopy, in adults with lesions suspicious for melanoma or atypical intraepidermal melanocytic variants, compared with a reference standard of either histological confirmation or clinical follow‐up.Data collection and analysis: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS‐2). We contacted authors of included studies where information related to the target condition or diagnostic threshold were missing. We estimated summary sensitivities and specificities per algorithm and threshold using the bivariate hierarchical model. To compare RCM with dermoscopy, we grouped studies by population (defined by difficulty of lesion diagnosis) and combined data using hierarchical summary receiver operating characteristic (SROC) methods. Analysis of studies allowing direct comparison between tests was undertaken. To facilitate interpretation of results, we computed values of specificity at the point on the SROC curve with 90% sensitivity as this value lies within the estimates for the majority of analyses. We investigated the impact of using a purposely developed RCM algorithm and in‐person test interpretation.Main results: The search identified 18 publications reporting on 19 study cohorts with 2838 lesions (including 658 with melanoma), which provided 67 datasets for RCM and seven for dermoscopy. Studies were generally at high or unclear risk of bias across almost all domains and of high or unclear concern regarding applicability of the evidence. Selective participant recruitment, lack of blinding of the reference test to the RCM result, and differential verification were particularly problematic. Studies may not be representative of populations eligible for RCM, and test interpretation was often undertaken remotely from the patient and blinded to clinical information.Meta‐analysis found RCM to be more accurate than dermoscopy in studies of participants with any lesion suspicious for melanoma and in participants with lesions that were more difficult to diagnose (equivocal lesion populations). Assuming a fixed sensitivity of 90% for both tests, specificities were 82% for RCM and 42% for dermoscopy for any lesion suspicious for melanoma (9 RCM datasets; 1452 lesions and 370 melanomas). For a hypothetical population of 1000 lesions at the median observed melanoma prevalence of 30%, this equated to a reduction in unnecessary excisions with RCM of 280 compared to dermoscopy, with 30 melanomas missed by both tests. For studies in equivocal lesions, specificities of 86% would be observed for RCM and 49% for dermoscopy (7 RCM datasets; 1177 lesions and 180 melanomas). At the median observed melanoma prevalence of 20%, this reduced unnecessary excisions by 296 with RCM compared with dermoscopy, with 20 melanomas missed by both tests. Across all populations, algorithms and thresholds assessed, the sensitivity and specificity of the Pellacani RCM score at a threshold of three or greater were estimated at 92% (95% confidence interval (CI) 87 to 95) for RCM and 72% (95% CI 62 to 81) for dermoscopy.Authors' conclusions: RCM may have a potential role in clinical practice, particularly for the assessment of lesions that are difficult to diagnose using visual inspection and dermoscopy alone, where the evidence suggests that RCM may be both more sensitive and specific in comparison to dermoscopy. Given the paucity of data to allow comparison with dermoscopy, the results presented require further confirmation in prospective studies comparing RCM with dermoscopy in a real‐world setting in a representative population

Optical coherence tomography for the diagnosis of skin cancer in adults

Background: Early accurate detection of all skin cancer types is essential to guide appropriate management and to improve morbidity and survival. Melanoma and squamous cell carcinoma (SCC) are high-risk skin cancers, which have the potential to metastasise and ultimately lead to death, whereas basal cell carcinoma (BCC) is usually localised, with potential to infiltrate and damage surrounding tissue. Anxiety around missing early cases needs to be balanced against inappropriate referral and unnecessary excision of benign lesions. Optical coherence tomography (OCT) is a microscopic imaging technique, which magnifies the surface of a skin lesion using near-infrared light. Used in conjunction with clinical or dermoscopic examination of suspected skin cancer, or both, OCT may offer additional diagnostic information compared to other technologies. Objectives: To determine the diagnostic accuracy of OCT for the detection of cutaneous invasive melanoma and atypical intraepidermal melanocytic variants, basal cell carcinoma (BCC), or cutaneous squamous cell carcinoma (cSCC) in adults. Search methods: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; EMBASE; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles. Selection criteria: Studies evaluating OCT in adults with lesions suspicious for invasive melanoma and atypical intraepidermal melanocytic variants, BCC or cSCC, compared with a reference standard of histological confirmation or clinical follow-up. Data collection and analysis: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). Our unit of analysis was lesions. Where possible, we estimated summary sensitivities and specificities using the bivariate hierarchical model. Main results: Five studies including 529 cutaneous lesions (273 malignant lesions) were included, providing nine datasets for OCT, two for visual inspection alone, and two for visual inspection plus dermoscopy. Studies were of moderate to poor quality using data driven thresholds for test positivity and giving poor accounts of reference standard interpretation and blinding. Studies may not be representative of populations eligible for OCT in practice, for example due to high disease prevalence in study populations, and may not reflect how OCT is used in practice, for example by using previously acquired OCT images. It is not possible to make summary statements regarding accuracy of detection of melanoma or of cSCC because of the paucity of studies, small sample sizes, and for melanoma differences in the OCT technologies used (high-definition versus conventional resolution OCT), and differences in the degree of testing performed prior to OCT (i.e. visual inspection alone or visual inspection plus dermoscopy). Pooled data from two studies using conventional swept-source OCT alongside visual inspection and dermoscopy for the detection of BCC estimated the sensitivity and specificity of OCT as 95% (95% CI: 91, 97%) and 77% (95% CI: 69, 83%), respectively. When applied to a hypothetical population of 1000 lesions at the mean observed BCC prevalence of 60%, OCT would miss 31 BCCs (91 fewer than would be missed by visual inspection alone and 53 fewer than would be missed by visual inspection and dermoscopy), and OCT would lead to 93 false positive results for BCC (a reduction in unnecessary excisions of 159 compared to using visual inspection alone and of 87 compared to visual inspection and dermoscopy). Authors' conclusions: Insufficient data are available on the use of OCT for the detection of melanoma or cSCC. Initial data suggests conventional OCT may have a role for the diagnosis of BCC in clinically challenging lesions, our meta-analysis showing a higher sensitivity and higher specificity when compared to visual inspection and dermoscopy. However the small number of studies and varying methodological quality means implications to guide practice cannot currently be drawn. Appropriately designed prospective comparative studies are required, given the paucity of data comparing OCT with dermoscopy and indeed other similar diagnostic aids such as reflectance confocal microscopy