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Background Pityriasis rosea (PR) is a common, self-limited, inflammatory papulosquamous skin disease with a possible viral etiology. Objective The goal of this study was to evaluate skin biophysical properties in patients with PR compared with uninvolved skin to better understand the pathogenesis of PR. Methods Stratum corneum hydration, transepidermal water loss, surface friction, pH, sebum, melanin, erythema, temperature, elasticity parameters (R0, R2, R5), thickness, and echodensity of the epidermis and dermis were measured on lesions of classic PR in 21 patients and compared with control sites (average of uninvolved perilesional and symmetrical skin) with a paired t test. Results Stratum corneum hydration (p

Idiopathic scrotal calcinosis is a rare condition, characterized by the idiopathic deposition of calcium in the scrotal dermis leading to the formation of a single nodule or multiple nodules of different sizes. Surgical excision of the nodules reduces symptoms and improves cosmesis. We present a case of idiopathic scrotal calcinosis that had an en bloc excision of scrotal skin nodules and primary closure of the scrotal skin. Handling each hemiscrotum as a separate entity and preserving the median raphe with its uninvolved skin improved the cosmesis. Reported outcomes of surgery were satisfactory with no postoperative complications. At 30 months of follow-up, the residual scrotal skin had regained its laxity and the scrotum its normal configuration. There is the risk of recurrence of the calcific nodules post excision, but these may be smaller in size and with regained scrotal configuration that could be amenable to excision with further preservation of the native scrotal skin.

Keratinocyte stress-response of the uninvolved psoriatic epidermis is known to be altered compared to healthy cells. Therefore, we aimed to reveal potential mechanisms underlying this alteration. We compared the expression of annotated cell-stress-related proteins between uninvolved psoriatic and healthy skin using the protein array method. Data were analyzed by the Reactome over-representation test. We found that p27/CDKN1B and cytochrome C showed at least a two-fold increase, while cyclooxygenase-2, indolamine-2,3-dioxygenase-1, serum paraoxonase 1, serum paraoxonase 3, serine-46-phosphorylated tumor protein p53, and superoxide-dismutase-2 showed a two-fold decrease in expression in the uninvolved skin. Over-representation analysis suggested the Forkhead-box protein O (FOXO)-mediated transcription as the most significant pathway affected by the differently expressed cell-stress-related proteins (DECSRPs). DECSRPs indicate increased FOXO-mediated transcription of cell-cycle genes and reduced interleukin-signaling in the psoriatic uninvolved skin. Nuclear positivity of the FOXO-signaling-related p27/CDKN1B and FOXO1 are negatively correlated with the disease severity and showed increased expression in the uninvolved epidermis and also in healthy primary keratinocytes, which were grown on cartilage oligomeric matrix protein-coated surfaces. Our results indicate a cell-cycle inhibitory process, as a stress-related compensatory mechanism in the uninvolved epidermis, that could be responsible for blocking keratinocyte hyperproliferation in the psoriatic uninvolved skin, thus maintaining the symptomless skin phenotype.

In recent years, a growing interest in the characterization of the molecular basis of psoriasis has been observed. However, despite the availability of a large amount of molecular data, many pathogenic mechanisms of psoriasis are still poorly understood. In this study, we performed an integrated analysis of 23 public transcriptomic datasets encompassing both lesional and uninvolved skin samples from psoriasis patients. We defined comprehensive gene co-expression network models of psoriatic lesions and uninvolved skin. Moreover, we collected, curated and exploited a wide range of functional information from multiple public sources in order to systematically annotate the inferred networks.The integrated transcriptomics analysis of public datasets shed light on a number of genes which are frequently deregulated in the psoriatic lesion compared with the unaffected skin in a large number of studies. In particular, CRABP2, LCN2, S100A12 and PDZK1IP1 were found to be deregulated in all of the datasets analyzed.Furthermore, the analysis of co-expression networks highlights genes showing aberrant patterns of connectivity in the lesional network as compared to the network inferred from unaffected skin samples. For instance, we identified co-expression patterns of SERPINB4, KYNU and S100A12 as being the most affected by the disease. Network analysis allowed us to identify YPEL1 and HUS1 as plausible, previously unknown, actors in the expression of the psoriasis phenotype. In addition, by exploiting topological properties of the network models, we highlighted a set of 250 non-deregulated genes, 223 of which have never been associated with the disease before, including CACNA1A, HADH, ATP5MC1 and CBARP among others.Finally, we characterized specific communities of co-expressed genes sustaining relevant molecular functions and specific immune cell types expression signatures playing a role in the psoriasis lesion. Overall, integrating experimental driven results with curated functional information from public repositories represents an efficient approach to empower knowledge generation about psoriasis and may be applicable to other complex diseases.

Psoriasis affects more than 125 million people worldwide, and the diagnosis and treatment efficacy evaluation of the disease mainly rely on clinical assessments that could be subjective. Our previous study showed that the skin erythema level could be quantified using diffuse reflectance spectroscopy (DRS), and the hemoglobin concentration of most psoriatic lesion was higher than that of its adjacent uninvolved skin. While the compromised epidermal barrier function has been taken as the major cause of clinical manifestation of skin dryness and inflammation of psoriasis, very few methods can be used to effectively evaluate this function. In this study, we investigate the near infrared spectroscopic features of psoriatic (n = 21) and normal (n = 21) skin that could link to the epidermal barrier function. From the DRS measurements, it was found that the water bonding status and light scattering properties of psoriasis are significantly different from those of uninvolved or normal skin. The connection between these parameters to the epidermal barrier function and morphology will be discussed. Our results suggest that objective evaluation of epidermal barrier function of psoriasis could be achieved using a simple DRS system.

Background The ability of Cutibacterium acnes strains to form biofilms has been correlated with their virulence. Objective This study examined biofilm and skin microbiota in acne patients in order to understand their role in the development of acne lesions. Methods Thin sections of punch biopsy specimens of (i) uninflamed comedones, (ii) inflammatory lesions, and (iii) uninvolved adjacent skin of acne patients were examined. Epiflourescence and confocal laser scanning microscopy were used for biofilm detection, and pyrosequencing with taxonomic classification of 16s rRNA gene amplicons was used for microbiota analysis. Results Of the 39 skin specimens from patients with mild-moderate acne (n = 13) that were studied, nine (23%) contained biofilm. Among these specimens, biofilm was most frequently detected in comedones (55.6%) and less frequently in inflammatory papules (22.2%) and uninvolved skin (22.2%). Comedones demonstrated the highest mean alpha diversity of all the lesion subtypes. The relative abundance of Staphylococcus was significantly higher in comedones (11.400% ± 12.242%) compared to uninvolved skin (0.073% ± 0.185%, P = 0.024). Conclusions The microenvironment of the comedone differs from that of inflammatory lesions and unaffected skin. The increased frequency of biofilm in comedones may account for the lack of host inflammatory response to these lesions.

Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disorder of unknown etiology, initially described in 1835. It is characterized by keratotic follicular papules, well-demarcated salmon-colored erythematous scaly plaques interspersed with distinct islands of uninvolved skin, and palmoplantar keratoderma. Is PRP a systemic disease? Skin is mainly affected in PRP. Despite its clinical heterogeneity, PRP could be associated with a variety of rheumatologic, infectious, neoplastic, and other extracutaneous manifestations. We accept the hypothesis of not only an association but also a causative relation between skin and systemic manifestations with possible common underlying pathomechanisms such as systemic immunologic processes and superantigen mimicry., SCOPUS: ar.j, info:eu-repo/semantics/published

Pseudoxanthoma elasticum (PXE) is a rare multisystemic autosomal recessive connective tissue disease. In most cases, skin manifestations of PXE are the first to develop, followed later by severe ocular and cardiovascular complications. In our present study, in addition to dermoscopy, we introduced novel techniques, autofluorescence (AF) and diffuse reflectance (DR) imaging for the assessment of affected skin sites of five PXE patients. PXE-affected skin areas in most skin sites showed a previously observed pattern upon dermoscopic examination. With the novel imaging, PXE-affected skin lesions displayed high AF intensity. During our measurements, significantly higher mean, minimum and maximum AF intensity values were found in areas of PXE-affected skin when compared to uninvolved skin. Conversely, images acquired with the use of 660 and 940 nm illumination showed no mentionable difference. Our results demonstrate that AF imaging may be used in the in vivo diagnostics and quantification of the severity of the skin lesions of PXE patients. In addition, it is a safe, fast and cost-effective diagnostic method. AF imaging may be also used to objectively monitor the efficacy of the possible novel therapeutic approaches of PXE in the future.

HHS Public Access Author manuscript Author Manuscript J Invest Dermatol. Author manuscript; available in PMC 2015 May 01. Published in final edited form as: J Invest Dermatol. 2014 November ; 134(11): 2843–2846. doi:10.1038/jid.2014.205. Abnormal Epidermal Barrier Recovery in Uninvolved Skin supports the Notion of an Epidermal Pathogenesis of Psoriasis Li Ye 1 , Chengzhi Lv 1 , George Man 2 , Shunpeng Song 1 , Peter M. Elias 2 , and Mao-Qiang Man 2 1 Dalian Skin Disease Hospital, Liaoning, P.R. China 2 Dermatology Author Manuscript Services, Veterans Affair Medical Center and University of California San Francisco, CA, USA Keywords Psoriasis; Stratum Corneum; Permeability Barrier; Hydration; pH; Transepidermal Water Loss To The Editor Author Manuscript Psoriasis is generally considered to be an immunologically-initiated disorder, which shares certain common susceptibility loci with autoimmune diseases (Zhang, 2012). Yet, both clinical experience (Gottlieb et al.,1990; Griffiths et al., 1995; Volden et al., 2001;) and recent molecular studies (Bergboer et al., 2012; Kim et al., 2011; Mischke et al., 1996; Vermeij et al., 2011) support an emerging concept that psoriasis could be ‘driven’ by a primary defect in epidermal permeability barrier function. Clinicians know well that psoriasis predictably flares during winter months (Park and Youn, 1998; Kwon et al., 2012), when the barrier is under additional stress due to low stratum corneum hydration, which accelerates transepidermal water loss (TEWL) rates (Lin, 2009; Muizzuddin et al., 2013). They also appreciate that sites vulnerable to epidermal trauma, such as the extensors of the extremities and the scalp, are preferentially involved in psoriasis. The Koebner phenomenon offers an additional, eloquent example of how psoriasis can be provoked by external perturbations. Finally, improvement of epidermal permeability barrier function by occlusion alone often alleviates psoriasis (e.g., Friedman, 1987). Author Manuscript Among psoriasis susceptibility genes, PSORS4 is located on chromosome 1q21, within the epidermal differentiation complex, which encodes numerous proteins required for epidermal differentiation and the formation of the cornified envelope (Mischke et al., 1996), a structure that is critical for the permeability barrier (Vermeij et al., 2011). Additionally, deletion of differentiation-related proteins, such as keratin1, whose levels are reduced in psoriasis (Thewes et al., 1991; Bata-Csorgo and Szell, 2012), not only compromises the permeability barrier, but also leads to upregulation of inflammatory genes and altered cytokine production Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms Address Correspondence To: Mao-Qiang Man, MD, Dermatology Service (190), 4150 Clement Street, San Francisco, CA 94121, USA, Tel: (415)750-2091, Fax: (415)750-2106, mqman@hotmail.com Or Chengzhi Lv, MD, dlpfb@126.com. All authors declare no conflicts of interest

Background In chronic spontaneous urticaria (CSU) mast cell activation together with inflammatory changes in the skin are well documented and may play an important role in mechanisms of tissue oedema. Objectives To confirm and extend these observations by measuring microvascular markers, leucocytes and mast cell numbers in lesional and uninvolved skin and to compare findings with a control group. Methods Paired biopsies (one from 4–8-h spontaneous weals and one from uninvolved skin) were taken from eight patients with CSU and nine control subjects and studied using immunohistochemistry and confocal microscopy using the lectin Ulex europaeus agglutinin 1 (UEA-1). Results Lesional skin in CSU contained significantly more CD31+ endothelial cells; CD31+ blood vessels, neutrophils, eosinophils, basophils and macrophages; and CD3+ T cells than nonlesional skin. Increased vascularity was confirmed by confocal imaging using the lectin UEA-1. Uninvolved skin from CSU contained significantly more CD31+ endothelial cells, CD31+ blood vessels and eosinophils compared with the control subjects. There was a threefold increase in mast cell numbers when CSU was compared with controls but no difference was observed between lesional and uninvolved skin. Conclusions Increased vascular markers together with eosinophil and neutrophil infiltration are features of lesional skin in CSU and might contribute to tissue oedema. Eosinophils and microvascular changes persist in uninvolved skin, which, together with increased mast cells, suggests that nonlesional skin is primed for further wealing.

SUMMARY A study of thirty-three patients with a clinical diagnosis of dermatitis herpetiformis (DH) referred to our DH clinic over the last 11 years is reported. Twenty-six were referred by other consultant dermatologists. The diagnosis had been made by the clinical features and response of the rash to dapsone. Seventeen patients were found to have IgA in the uninvolved skin (IgA positive) and in sixteen no IgA was found (IgA negative). The duration of the rash prior to referral to the DH clinic was 3 months to 19 years (mean 5.0 years) for the IgA negative patients and 2 months to 22 years (mean 5.2 years) for the IgA positive group. The length of follow-up was 3 months to 11 years (mean 5.0 years) for the IgA negative, and 2–11 years (mean 5.6 years) for the IgA positive group. During follow-up the rash cleared completely and required no treatment in seven of the sixteen IgA negative patients. Thirteen of these sixteen patients no longer required dapsone, but six patients were receiving alternative treatment. In the three patients still taking dapsone IgA has not been found on subsequent biopsy. Of the seventeen IgA positive patients only three were able to stop dapsone during follow-up and in these three the IgA was still detected in the skin. Small intestinal mucosa was abnormal in eight of eleven IgA positive patients, but was normal in all thirteen IgA negative patients in whom jejunal biopsies were performed. An alternative diagnosis to DH has subsequently been made in thirteen of the sixteen IgA negative patients. Although the significance of IgA in the skin in DH is not known it appears to be part of the disease process. Patients who have a rash suggestive of DH and which is dapsone responsive, but in whom IgA is not found in the uninvolved skin, usually turn out to have a dermatosis other than dermatitis herpetiformis. Referral to a unit with expertise in immunofluorescence techniques of skin biopsies would appear to be helpful.

SUMMARY IgA deposits in the skin in 53 patients with dermatitis herpetiformis (DH) have been studied in relation to treatment. In 19 patients the disorder was controlled by a gluten-free diet (GFD) alone, in 13 patients by dapsone and GFD and in 18 by dapsone alone. In 3 patients the skin disorder became insignificant and required no treatment. Of the patients taking a GFD alone, six had been clear of skin lesions for 7 years, 5 for 3–5 years, and 8 for periods of 6 months-3 years. IgA deposits were found in all patients in an initial biopsy and in a second biopsy after treatment for periods varying from I to 7 years. There was no difference in the quantity of IgA, as assessed by the amount of fluorescence, whether patients were controlled with a GFD alone, GFD and dapsone, dapsone alone, or in those in clinical remission. The C3 component of complement was present in the skin in 3 of the 19 patients (16%) controlled by a GFD alone, 6 of the 13 patients (46%) of those controlled by a GFD and dapsone, and in 12 of 18 (66%) of the patients taking dapsone alone, and in one of the patients in clinical remission.

Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer. The incidence of BCC is rising. The nodular, superficial spreading, and infiltrating variants are the three most commonly encountered types of BCC in descending order of prevalence. Superficial spreading basal cell carcinoma (SSBCC) accounts for 15-26% of all cases of BCC. It usually occurs on the trunk and upper extremities, but may be seen on the face. Surgical excision is the most commonly used treatment for BCC. Topical chemotherapy agents such as imiquimod or 5-fluorouracil (5-FU) may be various alternatives or adjuvants in the treatment of SSBCC. characteristically shows areas of uninvolved skin between tumor nests.[7].

Background: Ideal treatment for warts should be effective, safe, have less morbidity and provide long-lasting immunity against human papilloma virus. This can optimally achieved by the stimulation of the immune system against the virus. The autoimplantation of warts, autowart injection and quadrivalent vaccines have been used for this purpose. Autoimplanatation is a simple technique where the subcutis deep wart tissue is harvested as a donor and implanted into the uninvolved skin. However, this led to two wounds, at donor and recipient sites. Aim: The aim was to evaluate the safety and efficacy of a novel modification of autoimplantation therapy in the treatment of multiple, recurrent and palmoplantar warts. Subjects and Methods: Thirty-three patients with multiple, recurrent and palmoplantar warts were enrolled. Instead of taking a bit of the wart tissue, the donor tissue was harvested by paring the wart. The pared tissue was implanted deep into the subcutis by stab incision done using the same surgical blade no. 11. The resolution of all warts within 3 months after the procedure was considered successful. Patients with complete clearance were followed up for 1 month for any recurrence. Results: Out of 35 patients, 27 patients were available for follow-up. A total of 20 (74.1%) patients showed a complete clearance of warts within 3 months. Partial clearance was seen in 1 patient. Erythematous nodules developed at the site of implantation in 3 (11.1%) patients. There was relapse in one patient. Conclusion: A modified technique of autoimplantation of warts employing the pared stratum corneum tissue from the wart is a simple, effective, less traumatic and rapid procedure in the treatment of multiple, recurrent and palmoplantar warts.

Background: Recent studies have shown that human beta-defensin-1 (hBD-1) and (human beta-defensin-2 hBD-2), which are antimicrobial peptides produced by the skin, play a role in the pathogenesis of acne vulgaris (AV). Objective: The aim of this study was to determine the role of antimicrobial peptides in the pathogenesis of AV and enlighten the effects of doxycycline and isotretinoin in the expression of these defensins in AV. Materials and Methods: A total of 44 patients (22 patients in each group) with Grade 6 and 8 AV who were indicated doxycycline or isotretinoin for their treatment, and 20 healthy volunteers were included in this study. Pretreatment cutaneous samples were obtained from pustular lesions and uninvolved skin of AV patients and were repeated after the treatment. Only one biopsy was obtained from controls. Results: Cutaneous levels of hBD-1 and hBD-2 were significantly increased in AV patients when compared with healthy controls (P0.05). Conclusion: In the light of these results, it was reasonable to assume the role of hBD-1 and hBD-2 in the pathogenesis of AV. Our results showing a significant reduction in hBD-1 staining with doxycycline treatment and in hBD-2 with isotretinoin suggested that some part of their anti-acne effect worked through these mechanisms.

Vitiligo is one of the most striking of all human disease phenotypes, and it is perhaps the most common pigmentary disorder. The patchy loss of skin pigmentation and the marked contrast between involved and uninvolved skin particularly impacts persons of color, with consequent stigmatization that has long been recognized to result in significant social inequality and morbidity in affected individuals (Brito, 1885). Because of its visually evident cutaneous manifestations, vitiligo has been known for thousands of years. However, only relatively recently has there been real progress in understanding its pathobiological basis, which, it is hoped, may facilitate progress in vitiligo treatment and ultimately even prevention. Surprisingly, in several instances key discoveries seem to have been overlooked or discounted, only to be rediscovered and republished by others a decade or more later.

Evidence is now emerging for enhanced penetration of chemical solutes into uninvolved skin of atopic dermatitis patients. Along with the recent discovery of prevalent null mutations in the gene encoding filaggrin, a protein essential for stratum corneum formation, these data point to an innate epidermal-barrier defect in atopy.

The Köebner phenomenon (isomorphic response) is defined as the development of typical lesions of a dermatosis that occur in areas of trauma in previously uninvolved skin. Rare reports have suggested that striae are a form of injury to the skin that can result in koebnerization of psoriasis, vitiligo, and lichen planus. We herein report a 27-year-old female patient with plaque psoriasis who developed psoriatic lesions along striae distensae.

Background: MR spectroscopy of intact biopsies can provide a metabolic snapshot of the investigated tissue. The aim of the present study was to explore the metabolic pattern of uninvolved skin, psoriatic skin and corticosteroid treated psoriatic skin. Methods: The three types of skin biopsy samples were excised from patients with psoriasis (N = 10). Lesions were evaluated clinically, and tissue biopsies were excised and analyzed by one-dimensional 1H MR spectroscopy. Relative levels were calculated for nine tissue metabolites. Subsequently, relative amounts of epidermis, dermis and subcutaneous tissue were scored by histopathological evaluation of HES stained sections. Results: Seven out of 10 patients experienced at least 40% reduction in clinical score after corticosteroid treatment. Tissue biopsies from psoriatic skin contained lower levels of the metabolites myo-inositol and glucose, and higher levels of choline and taurine compared to uninvolved skin. In corticosteroid treated psoriatic skin, tissue levels of glucose, myo-inositol, GPC and glycine were increased, whereas choline was reduced, in patients with good therapeutic effect. These tissue levels are becoming more similar to metabolite levels in uninvolved skin. Conclusion: This MR method demonstrates that metabolism in psoriatic skin becomes similar to that of uninvolved skin after effective corticosteroid treatment. MR profiling of skin lesions reflect metabolic alterations related to pathogenesis and treatment effects. © 2013 Sitter et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Dear Editor: Koebner phenomenon, the appearance of preexisting skin lesions following trauma to previously uninvolved skin, is frequently seen with vitiligo, and the dermatological literature contains reports of various forms of trauma resulting in this phenomenon. However, the appearance of vitiligo coexistent with striae distensae as a form of Koebner phenomenon is rarely reported. A 14-year-old boy presented with vitiliginous macules that had coexisted with striae on both legs for the past 4 months. He had developed several scattered depigmented macules on the right pretibial skin 1 year prior, and the lesions progressed slowly and asymptomatically, so he ignored them and did not seek any treatment. Four months before seeking treatment, he noticed a relatively sudden onset of striae on both legs. Gradually he noticed rapidly developing white spots occurring throughout the striae, and he eventually sought treatment. The patient had no history of excessive exercise or obesity, and was no evidence of any endocrinopathy. His height and weight had increased over the past year, but he did not know by exactly how much. Physical examination showed an otherwise well developed and healthy boy. Striae were scattered across both legs and were surrounded by vitiliginous macules. Some fresh erythematous striae located on both the pretibial regions and the right peroneal region were not affected (Fig. 1). He was prescribed traditional Chinese medicine granules made for vitiligo treatment but failed to attend follow-up appointments. Fig. 1 Vitiligo on and around the striae distensae on the right (A) and left (B) pretibial regions; some fresh erythematous striae located on the right peroneal region (C) were not affected. Although vitiligo and striae are both common skin disorders, only two articles before now have reported this rare phenomenon1,2, and all the reported patients had preexisting vitiligo before the striae occurred, and striae were considered the initiating factor for the 'true Koebnerization' of vitiligo. In this case, although the patient had vitiligo for 1 year prior to seeking treatment, he was otherwise a healthy and well-developed 14-year-old, so the striae in both legs were caused by the onset of puberty. Unlike the other reported cases, his vitiliginous macules were not restricted to the areas with striae; rather, his history of preexisting vitiligo and onset sequence of the striae and the developed vitiliginous lesions were consistent with the clinical aspect of Koebner phenomenon3. As such, we propose that in this patient, the vitiligo on and around the striae is the Koebner phenomenon and not just a coincidence. Striae-induced Koebner phenomenon in vitiligo has not been studied at the cellular level. Striae are a form of dermal scarring in which the pathological changes occur in the sub-epidermis while the overlying epidermis remains normal. However, the pathological changes in vitiligo are in the basal layer of the epidermis, so it still remains a mystery as to how a sub-epidermal condition can initiate the spread of vitiligo4. Cause striae distensae and vitiligo are both common diseases in teenagers, but the two diseases occur together was rarely reported. It is important to document that striae are not only a common disfiguring cutaneous condition but may be a form of trauma that can initiate or precipitate the Koebner phenomenon in susceptible individuals with vitiligo. To the best of our knowledge, this is the first case of vitiligo coexistent with striae to be reported in China.

An 84-year-old man with keloids since early adulthood, was referred to our clinic because of the recent appearance of erythematous, tumid plaques upon the old keloids and upon uninvolved skin. The plaques were located mainly on the trunk in a linear distribution. On the back there were round, nodular, erythematous nodules and plaques, with central crusts, that had just appeared on normal skin. A skin biopsy was performed on the plaques that appeared over the older lesions. The histological appearance was consistent with keloid. Similar histology was found in a biopsy taken from a plaque that had erupted on normal skin.

Background The pathobiological dynamics of psoriatic lesions are complex and difficult to perceive by clinical inspection alone. Non-invasive bioengineering methods may prove to be useful in this field. Objective To identify some subtle capacitance variations in the stratum corneum of chronic psoriasis lesions. Method The newly developed method of skin capacitance imaging was used to provide non-optical images of the hydration of the superficial layers of the stratum corneum. Results Compared to the uninvolved skin, psoriatic lesions usually showed an overall lowered capacitance, admixed with foci of moderately higher capacitance. Still other sharply circumscribed blotches with higher capacitance were present. The latter aspect corresponded to inflammatory areas. Sweating appeared markedly impaired inside the lesions. The fingerprint of some patients was altered, thus potentially interfering with the current biometric security procedures using the same method. Conclusion Skin capacitance imaging is a non-invasive, non-optical method that distinguishes three contrasting levels of stratum corneum hydration in psoriatic lesions. The lowest capacitance level probably corresponded to xerotic orthokeratosis. The medium capacitance level presumably identified foci of parakeratosis and clumps of neutrophils. The highest capacitance level suggested exsudation at the site of prominent vessel dilation and dermal inflammation. Impaired sweating in the psoriatic lesions may potentially interfere with body thermoregulation.

Involved regions of the skin in atopic dermatitis (AD) patients have an altered barrier function. Whether uninvolved skin also has a diminished barrier is controversial. To assess the barrier function of uninvolved skin in AD patients, the percutaneous penetration of polyethylene glycols (PEGs) of various molecular sizes was determined in vivo in AD patients and control subjects using tape stripping of the stratum corneum (SC). The diffusion and partition coefficients were determined using Fick’ s second law of diffusion. The SC thickness was similar in both groups ; however, the trans-epidermal water loss was higher in atopic skin. The apparent diffusion coefficient of PEGs through atopic skin was twice as high as through normal skin, and decreased with increasing molecular weight (MW) in both groups. The partition coefficient in the skin of AD patients was half of that for normal skin but as for normal skin, there was no MW dependency. Although atopic skin exhibited altered barrier with respect to diffusion and partitioning, the permeability coefficients were nearly the same for atopic and normal skin. The results support the assumption of altered skin barrier of AD patients even in the skin that is visibly unaffected by disease.

Reactive oxygen species play an important role in inflammatory skin diseases such as psoriasis. Reactive oxygen species synthesis is catalysed by iron and some species are scavenged by ascorbic acid. The aim of this work was to assess iron and ascorbic acid in uninvolved and involved psoriatic dermis and to compare the corresponding concentrations in the dermis of healthy subjects. Microdialysis associated with atomic absorption spectrometry and gas chromatography-mass spectrometry was used to assess iron and ascorbic acid, respectively. Seven psoriatic patients and five healthy volunteers were studied. Iron concentrations in the involved (57.1 +/- 19.3 microg/l) and uninvolved (49.7 +/- 27.1 microgl/l) psoriatic dermis were higher than the corresponding value determined in the dermis of healthy subjects (21.8 +/- 2.4 microg/l) (p

Since Leyden et al showed in 1974 that 90% of patients with atopic dermatitis (AD) have their skin colonized with Staphylococcus aureus (SA), [1] the increased incidence of a carrier state of SA in patients with AD has been a subject of interest. Several studies in children and adults with AD have demonstrated an increased carrier state of SA in both involved and uninvolved skin. AD is reported to be exacerbated when the density of SA is greater than 10 CFU/cm (CFU, colony forming unit).

In 8 patients with psoriasis vulgaris, the cutaneous blood flow (CBF) was measured simultaneously in both involved and uninvolved psoriatic skin before (i.e., on the first day of hospitalization) and on the 3rd, 7th, 14th, and 28th days of treatment with tar. The 133Xe washout method was used after epicutaneous labeling and compared to the laser Doppler velocimetry (LDV) technique. Control experiments were performed in 10 normal individuals. Before treatment the mean CBF in involved psoriatic skin was 62.6 +/- 18.7 SD ml X (100 g X min)-1, which is significantly higher than CBF of uninvolved skin in psoriatic patients, 9.5 +/- 4.0 SD ml X (100 g X min)-1, (p less than 0.01) and is 13.6 times higher than CBF in the normal individuals (p less than 0.01). Fifty hours following onset of treatment (i.e., after only 2 applications of tar), mean CBF of the involved psoriatic skin had decreased significantly to 35.0 +/- 13.9 SD ml X (100 g X min)-1, (p less than 0.01), which was not statistically different from the CBF on the 7th day. During the following weeks, the CBF in involved psoriatic skin decreased at a more moderate rate than that observed during the first week and was 15.0 +/- 6.1 SD ml X (100 g X min)-1 on the 28th day. This value is not significantly different from the CBF of uninvolved skin in these patients. At the end of treatment, the CBF of the uninvolved skin had decreased significantly (p less than 0.05) in all the patients to values similar to those observed in the skin of normal individuals. A parallel decline was observed in a clinical psoriatic score index; however, it is not known whether the observed decrease in CBF was preceded or succeeded by the clinical improvement. A comparison of the 133Xe measurements and LDV measurements in the normal individuals by linear regression analysis yielded a correlation coefficient of -0.24 (N = 20, p greater than 0.05). In the skin of psoriatic patients the correlation coefficient was 0.01, (N = 47, p greater than 0.05) for unaffected skin, and 0.61 (N = 47, p less than 0.001) in the involved psoriatic skin sites. The LDV measurements did not reflect changes in the uninvolved skin in psoriatic patients during treatment and resulted in a remarkably high C.V. in the bilateral measurements of skin in normal individuals (43.8%) compared to the C.V. of 133Xe flow measurements (14.8%). It is concluded that while the LDV method gives a rough estimate of blood flow in cutaneous tissue with a high capillary perfusion rate, inaccurate measurements are made in skin areas with normal to twice the normal CBF range.

SUMMARY Four African female patients are described, who presented with the features of systemic sclerosis. Overlapping features of lupus erythematosus or dermatomyositis were present in three cases but were not prominent. Direct immunofluorescence of uninvolved skin revealed a particulate (or speckled) epidermal nuclear staining, with specificity for IgG. In view of the reported association between this finding and mixed connective tissue disease, these patients were treated with corticosteroids and marked improvement occurred in all cases. The usefulness of this investigation in making the distinction between systemic sclerosis and mixed connective tissue disease and in indicating a potentially effective form of therapy is discussed.

The in vitro growth characteristics of melanocytes obtained from uninvolved and perilesional skin of vitiligo vulgaris subjects have been investigated in comparison to those from healthy adult donors. Normal human melanocytes have been found to grow exponentially in the presence of 10(-11) M cholera toxin and 10 ng/ml of 12-O-tetradecanoylphorbol-13-acetate in routine tissue culture media. They could be trypsinized up to 3-4 passages. Melanocytes of the uninvolved skin of vitiligo subjects manifested a lag of 8-11 days for the onset of growth and they could not be passaged. Melanocytes obtained from both hypo- and hyper-pigmented perilesional skin failed to grow under these conditions. Only in a few cases where the perilesional skin was normally pigmented did the melanocytes manifest some growth after a lag of 15 days. The initial seeding capacity of the melanocytes from uninvolved and perilesional skin of vitiligo patients were, respectively, 50% and 25% of the normal individuals. Vitiligo lesions themselves gave rise to unidentified dendritic cells that survived for 10-15 days without manifesting any growth. Our results suggest that melanocytes of individuals with vitiligo are defective. This fact has to be taken into account in any theory on the etiology of vitiligo.

Records of 147 patients with primary cutaneous malignant melanoma treated at the Lahey Clinic from 1955--1979 were reviewed. Complete clinical follow-up data were obtained, and all pathologic material was reviewed. Proposed new risk categories based on a modification of the Clark and Breslow categorizations are outlined. The incidence of low-risk melanoma has dramatically increased (from 23--53%) and that of high-risk melanoma has decreased (from 34--10%) over the period of this study. Dermal punch biopsy gives accurate staging information and carries no increased risk of local recurrence, nodal metastases, or death from disease. Resection of a margin of clinically uninvolved skin measuring twice the diameter of the primary melanoma minimizes local recurrence (2.5% or less), does not adversely affect survival, and reduces the need for skin grafting. Arbitrary wide margins are not justified. Regional lymphadenectomy offers no improvement in survival in patients with low-risk and moderate-risk melanoma and can play only a minor role at most in improving survival for patients with high-risk melanoma.

The distribution and amount of fibronectin in both involved and uninvolved skin from scleroderma patients and controls were compared by indirect immunofluorescence. A marked increase in fibronectin was found in the deep dermis of involved scleroderma skin, while the subepidermal papillary regions of all specimens revealed little variation in fibronectin content. The districution of the accumulated fibronectin appeared to parallel that of the accumulated collagen in the involved reticular dermis.

1. A case of 33-year-old house wife with Senear-Usher syndrome was reported.2. Antiepithelial antibody in the sera of the patient was demonstrated by indirect IF staining technique. Bound IgG was present in the intercellular space of the prickle cell layer of the skin.3. IgG was significantly high in the cantharidin blister fluid induced from uninvolved skin of the patient while IgA and IgM remained slightly higher levels.4. Several immunological tests for lupus erythematosus gave negative results.5. These data indicate that the Senear-Usher syndrome should be classified as a form of pemphigus. However, more cases should be further accumulated and immunologically investigated as an aid to clarify the relationship between lupus erythematosus and this syndrome and to elucidate the pathogenesis of the syndrome.

From an examination of the concept that surface lipids of uninvolved skin areas in psoriasis are deficient in esterified sterols (1), it has become evident that misleading results can be obtained if studies of this type involve “casual” surface lipids (2). We have extended our investigations to other features of lipids from these skin sites. These features have been described in recent publications as typical of psoriasis and include the following : (i) Reduced “acid number” (1, 3, 4). (ii) Reduced amounts of unsaturated fatty acids (5). (iii) Increased amounts of long-chain (C18 or over) saturated acids in the FF A1 fraction including a C acid which was 10 times more abundant than in the same fraction from control subjects (6).

The effect of increasing doses from 1.25 to 10 ng/ml of PDGF was tested for chemotactic and mitogenic activity on psoriatic fibroblasts cultured from involved and uninvolved skin of five patients compared to normal fibroblasts from five matched control subjects. The chemotactic response of psoriatic fibroblasts from involved skin (p less than 0.05) and uninvolved skin (p less than 0.005) is significantly enhanced compared to normal fibroblasts. Similarly, PDGF in the presence of platelet poor human plasma is a more potent mitogenic agent in psoriatic fibroblasts than in normal fibroblasts. This increased sensitivity of psoriatic fibroblasts to PDGF may be related to the inflammatory and vascularization processes involved in psoriatic dermis.

In the present study we have compared cyclic nucleotide-phosphodiesterase activities and affinity of phosphodiesterase for substrates (Km) in enzyme preparations obtained from the involved and uninvolved skin of psoriatic patients. With crude skin homogenates we consistently obtained two Km values (high and low) for both the involved and uninvolved, and both Km values were nearly identical between the involved and uninvolved. The same conclusion is also drawn from the Km determinations with partially purified preparations. Cyclic AMP-phosphodiesterase activities with crude homogenates showed no statistically significant differences between the involved and the uninvolved skin. However, when cyclic AMP- and cyclic GMP-phosphodiesterase activities were compared with a highly sensitive assay method in "pure" epidermal samples, which were microdissected free from stratum corneum, dermis and skin appendages, the involved skin contained 40% more activity of the low Kin enzyme and 100% more of the high Km enzyme of both cyclic AMP- and cyclic GMP- phosphodiesterase. It is suggested that this may be due to a higher proportion of germinative cells in the lesional epidermis.

de Koning, Heleen D Kamsteeg, Marijke Rodijk-Olthuis, Diana van Vlijmen-Willems, Ivonne M J J van Erp, Piet E J Schalkwijk, Joost Zeeuwen, Patrick L J M Letter Research Support, Non-U.S. Gov't United States J Invest Dermatol. 2011 Jan;131(1):263-6. Epub 2010 Sep 23.

By the radioactive, freely diffusible, inert gas 133 Xenon we studied the cutaneous blood flow in 15 cases of fresh, untreated psoriasis and in 10 normal subjects. In normal skin and in uninvolved skin in psoriatics the blood flow proved to be approx. 6.5ml/100 g tissue per min, while in the psoriatic plaques it was twice this value, viz. , about 12ml/100 g tissue per min. It is concluded (1) that the gross erythema, the slightly elevated skin temperature (by 1.5° C), and the microscopic evidence of vascular changes in psoriatic lesions are in fact based upon increased blood flow, (2) that, according to the results of the present technique, the cutaneous tissue of uninvolved skin in psoriatics does not have a greater blood flow than cutaneous tissue of controls, and (3) that the present method of determining the cutaneous blood flow following intracutaneous injection of 133 Xenon, calculating from the first, rapidly falling slope of the flow curve, is well-suited for clinical use, as the measurement need not be done for more than 10–15 minutes in order to calculate the cutaneous blood flow during the traumatic phase immediately after the injection.

The possible relation between the therapeutic action and Langerhans cell (LC) depleting effect of psoralen photochemotherapy (PUVA) was investigated in 9 psoriatic patients by parallel recording of the clinical status, using the psoriasis area and severity index ( PASI ), and the epidermal LC counts of uninvolved skin, using light (ATPase staining) and electron microscopy (EM). Both light and electron microscopically recorded LC numbers decreased significantly during the PUVA course of, on the average, 21 exposures and a mean cumulative UVA dose of 77 J/cm2. At the end of the treatment period, both the PASI score and the light microscopically recorded LC density had reduced to about one-tenth of original, i.e., from 7.5 +/- 5.7 to 0.8 +/- 0.8 points and from 787 +/- 70 to 60 +/- 48 cells/mm2, respectively. After cessation of the PUVA course, the PASI scores remained low during the 3-7 week follow-up period, while the LC counts returned to normal, and even exceeded the starting value by 12%. Although a possible functional impairment of LC in the post-PUVA period cannot be excluded, the data are interpreted as speaking against the hypothesis that the therapeutic action of PUVA would be mediated through its LC effects.

The extent to which skin sterols occur in esterified form in healthy and in psoriatic subjects has been studied by various workers during the past twenty-five years (1, 2, 3, 4, 5). As a result, it is currently held that the clinically uninvolved skin in psoriasis has a surface film which is relatively poorer in sterol esters than normal skin, although one investigator reported no difference (5) and another claimed an increase (2). The concept of a deficiency in esterified sterols has become more meaningful since the recent report of the greatly reduced ability of uninvolved skin areas in psoriasis to esterify free cholesterol with labelled palmitic acid (6).

Epidermal cells from 8 patients with psoriasis (involved and uninvolved areas) and from 7 normal individuals, were propagated in vitro. DNA synthesis was determined autoradiographically by measuring the labeling index (1 hr) and a continuous labeling index (72 hr) on 8–10 day old cell cultures. No differences in these 2 kinetic parameters were obtained with respect to involved and uninvolved psoriatic cells. However, when psoriatic cells (involved and uninvolved) were compared to normal cells, the psoriatic cells exhibited a much higher labeling index and continuous labeling index, 200–300% and 60–70% respectively. These data clearly show that in vitro (1) epidermal cells from clinically uninvolved skin of psoriatics proliferate at a rate equal to that of involved psoriatic cells and (2) psoriatic epidermal cells proliferate at a rate greater than normal cells.

Extracts of involved and uninvolved skin from nine patients with untreated psoriasis were studied for chemotactic activity. Psoriatic plaque contains increased amounts of a complement-dependent chemotactic factor that is inhibited by diisopropyl fluorophosphate. This factor may be human skin serine proteinase.

The polyacrylamide SDS electrophoretic pattern of protein extracted from the stratum corneum obtained by scraping the surface of involved skin of patients with psoriasis was different from that of uninvolved skin and normal controls. The pattern from superficial scales was similar to that of whole stratum corneum in the case of involved psoriatic epidermis but different in uninvolved and normal epidermis. These data indicate that the changes which are observed in the structural proteins during normal keratinization are not seen in involved psoriatic epidermis. In addition, the relative proportion of keratin polypeptides was different in involved psoriatic epidermis compared to normal skin. That these changes are not specific for psoriasis was shown by finding similar electrophoretic patterns with stratum corneum proteins from patients with other keratinizing disorders.