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It is generally acknowledged that the first morphological change of hidradenitis suppurativa/acne inversa (HS/AI) consists of infundibular plugging of the folliculosebaceous apocrine apparatus, which is followed by acute and chronic inflammation, cysts with sinus formation, and fibrosis. Alternatively, it has been hypothesized that HS/AI is primarily a neutrophilic autoinflammatory disease and that the follicular plugging typical of this disease is secondary to inflammation.To review the sequence of the changes that mark the disease development, we have performed a histopathologic study on the surgical material from a series of axillary and inguinal/perineal cases.The histologic material from surgery on Hurley's second and third stage HS/AI was retrieved and collected with the patients' clinical images. The virtually uninvolved skin peripheral to the lesions was studied together with the main inflammatory foci on vertical sections stained with hematoxylin-eosin and immunohistochemistry for the follicle sheaths.The fully developed lesions showed acute and chronic, suppurative and granulomatous inflammation overlapping fibrosis, cysts, and sinuses. Instead, the skin adjacent to florid inflammation showed plugging and dysmorphic alterations of the hair follicles associated with immunopathological changes of the inner root sheath keratin expression.Our observations coincide with the classical pathological studies on the progressive changes of HS/AI; however, in our specimens, the virtually normal skin peripheral to the fully developed lesions show seemingly initial follicular changes that suggest development error. This finding would support the hypothesis of combined mutation-induced epithelial differentiative defects and immunological derangement in HS/AI pathogenesis.GRUNDLAGEN: Es wird allgemein akzeptiert, dass die ersten morphologischen Veränderungen einer Hidradenitis suppurativa/Acne inversa (HS/AI) infundibuläre Keratosen des apokrinen follikulosebaceösen Apparates darstellen. Dieser Verschluss der Ostien wird gefolgt von akuter und chronischer Entzündung, Zysten mit Sinusformationen und Fibrose. Alternativ wird die HS/AI als eine primär neutrophile autoinflammatorische Erkrankung angesehen, bei der die Infundibulumkeratosen als Sekundärphänomen auftreten.Wir führten eine histopathologische Untersuchung an chirurgischen Gewebeproben axillärer und anogenitaler HS/AI durch, um die Reihenfolge morphologischer Veränderungen im Verlauf der Erkrankung zu erfassen.Das Gewebematerial stammte von Patienten mit HS/AI im Hurley-Stadium II und III, die sich einer chirurgischen Behandlung unterzogen hatten. Klinische Abbildungen lagen ebenfalls vor. Wir analysierten sowohl klinisch gesunde Haut in der Peripherie der Exzidate als auch die verschiedenen inflammatorischen Läsionen mittels vertikaler Gewebeschnitte. Hierzu wurden Hämatoxylin-Eosin und immunhistologische Färbungen der Haarscheiden verwendet.Die vollausgebildeten Läsionen zeigten akute und chronische, suppurative und granulomatöse Entzündungszeichen, die sich mit Fibrose, Zysten und Sinusen überlappten. Die benachbarte scheinbar gesunde Haut wies Infundibulumverschlüsse und dysmorphe Veränderungen der Haarfollikel auf. Es fanden sich immunpathologische Alterationen der Keratinexpression der inneren Haarwurzelscheiden.Unsere Beobachtungen stimmen mit den klassischen Studien zu progredienten entzündlichen Veränderungen der HS/AI überein. Wir konnten jedoch auch initiale Alterationen der Haarfollikel in der scheinbar gesunden Haut finden, die auf eine Entwicklungsstörung hinweisen. Diese Befunde stützen die Hypothese einer Kombination von durch Mutationen bedingten Störungen der epithelialen Differenzierung und immunologischen Komponenten in der HS/AI-Pathogenese.

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

BACKGROUND Some skin diseases may modify epidermal barrier function. Psoriasis is a chronic multi-systemic inflammatory disease that affects the epidermal barrier. Phototherapy is an option for treating psoriasis, but little is known about how epidermal barrier function is modified by phototherapy in psoriatic patients. OBJECTIVES (a) To compare skin homeostasis between involved and uninvolved skin in psoriatic patients with healthy controls (b) To evaluate changes in the epidermal barrier function in psoriatic patients treated with phototherapy. METHODS Sixty patients with plaque-type psoriasis and sixty gender and age-matched healthy controls were enrolled. Temperature, transepidermal water loss (TEWL), stratum corneum hydration (SCH), pH, elasticity, erythema and melanin index were measured using non-invasive tools in the healthy control and involved and uninvolved psoriatic skin before and after phototherapy. RESULTS Healthy controls had lower TEWL and erythema index and higher SCH than psoriatic patients, both at uninvolved psoriatic skin and psoriasis plaques. TEWL was higher at psoriasis plaques than at uninvolved skin (19.20 vs 11.57 g/h/m2 ; 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.

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.

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.

Whole-body phototherapy is limited in that there can be needless exposure of uninvolved skin and no benefit to unexposed skin (such as the hair-covered scalp). In the last decade, various portable and lightweight handheld phototherapy units have become available for the treatment of localized psoriasis in the office and at home. These handheld devices, as compared with full-body irradiance in a booth or by a panel, have the added benefit of limiting skin exposure to UV light. The handheld devices are useful for the treatment of scalp psoriasis, as well as recalcitrant localized psoriasis plaques.

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.

Lichen planus pemphigoides (LPP) is a rare autoimmune blistering disease. It appears to be combination of lichen planus and bullous pemphigoid. We describe four new cases of LPP and discuss the epidemiological, clinical, pathological, and therapeutic features of this singular association through a review of the 74 published cases within the English literature. We report four cases of LPP (three women aged respectively 47, 51, and 53 years old, and a 53-year-old man). All patients presented with bullae on lichenoid and normal skin, predominately on the extremities. The diagnosis was confirmed by immunohistological findings. Our patients were treated with oral corticosteroids with a good response. Our review of the literature of 78 cases of LPP (65 adults and 13 children) showed that it involved adults (mean age: 54 years), with a slight female preponderance. A mean lag time between LP and the development of LPP was 8.3 months. LPP is characterized by developing blisters on lichenoid lesions and on uninvolved skin with more acral distribution of bullous lesions. Involvement of palms and soles was more frequent in children. The diagnosis is based on pathological and immunological confrontation. LPP is usually idiopathic, but some cases were reported in association with various drugs. There have also been reports of association with internal malignancy. Most cases of LPP are successfully treated with systemic corticosteroids. In most cases, the prognosis was good.

Uninvolved skin of psoriasis may not be entirely normal. The object was to characterize healthy, uninvolved psoriatic skin and lesional skin by biophysical methods.Involved and uninvolved psoriatic and age-gender matched healthy skin was measured objectively with a colorimeter and evaporimeter and subjectively with visual assessment in 14 subjects.Visual assessment of erythema (E), scaling (S) and induration (I) as well as the target lesion score at the involved psoriatic skin sites were significantly elevated (p0.05) above uninvolved psoriatic or healthy skin sites. No difference between uninvolved psoriatic and healthy skin was measured visually. Transepidermal water loss at involved psoriatic skinuninvolved psoriatic skinhealthy skin (p0.05). Objective assessment of skin color in 3 color scales, L*, a*, and b*, differentiated involved and uninvolved psoriatic skin from healthy skin sites. Involved psoriatic skin demonstrated higher (p0.01) a-scale values and lower (p0.01) L* and b* scale values than uninvolved psoriatic skin. Further, colorimeter L* and a* scale values at uninvolved psoriatic skin sites were lower and higher (p0.05), respectively, than healthy skin. The individual chromameter parameters (L*, a*, b*) correlated well with the visual parameters (E, S and I). Composite colorimeter description (L*× b*)/a* significantly differentiated healthy skin from both involved and uninvolved psoriatic skin.These collective data highlight that even visually appearing uninvolved psoriatic skin is compromised compared with healthy skin. These objective, noninvasive but differential capabilities of the colorimeter and evaporimeter will aid in the mechanistic quantification of new psoriatic drug therapies and in conjuction with biochemical studies, add to understanding of the multifactorial pathogenesis of psoriasis.

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].

Lichen planus pemphigoides (LPP) is a rare and controversial disease. It is characterized clinically by tense bullae arising both on lichen planus papules and on uninvolved skin, histologically by the demonstration of subepidermal bullae and by linear deposits of immunoglobulin G and C3 along the basement membrane zone on immunofluorescence of peribullous skin. Some authors consider LPP as the combination of lichen planus and bullous pemphigoid. Others think that it most likely encompasses a heterogeneous group of subepidermal autoimmune blistering disorders occurring in association with lichen planus. We present a child case that supports the heterogeneous condition of this disease triggered by varicella.

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.

Syndecan 4 (SDC4), a heparan sulfate proteoglycan, and neuropilin 1 (NRP1), a transmembrane receptor, are both involved in normal wound healing, but little is known about their possible role in venous leg ulcer pathogenesis. We aimed to investigate whether there are any expression abnormalities and/or gene polymorphisms of SDC4 and NRP1 associated with venous leg ulcer. SDC4 showed significantly lower mRNA and protein expression in the uninvolved dermis of venous leg ulcer patients (n=15) compared with controls (n=15; p=0.0136), while NRP1 showed no expression abnormalities. None of the examined SDC4 and NRP1 polymorphisms showed a difference in their allelic distribution between leg ulcer patients (n=92) and controls (n=92). We hypothesize that SDC4 may play an essential role not only in the inflammation and tissue formation phases of normal wound healing, but its expression abnormalities observed in the uninvolved dermis of venous leg ulcer patients may contribute to venous leg ulcer development.

Objective.To investigate skin elasticity using acoustic radiation force impulse (ARFI) quantification in systemic sclerosis (SSc), and compare the modified Rodnan skin score (mRSS) with measured shear wave velocity (SWV) and thickness of the skin.Methods.Fifteen patients with diffuse cutaneous SSc (dcSSc) and 15 age-matched and sex-matched healthy controls were evaluated. The SWV and thickness of skin were measured at 17 sites corresponding to those assessed in the mRSS in each participant. The SWV measurements of skin were compared between patients with dcSSc and healthy controls. The correlations between the mRSS and the skin SWV and thickness were explored using Spearman’s correlation.Results.The SWV values were higher in patients with dcSSc compared with healthy controls at right hand dorsum, right forearm, left hand dorsum, left forearm, right foot dorsum, and left foot dorsum (p < 0.05). In patients with dcSSc, the SWV values of uninvolved skin were higher than those of controls (p < 0.001), and the SWV values increased with increasing skin scores except for skin score 3 (p < 0.05). The sum of the SWV values correlated with total clinical skin score (r = 0.841, p < 0.001), and the sum of the skin thickness correlated with total clinical skin score (r = 0.740, p = 0.002).Conclusion.ARFI quantification is feasible and reliable for assessing the skin involvement in dcSSc. ARFI quantification could identify early skin change that may precede palpable skin involvement, and may be a valuable adjunct to skin evaluation in patients with SSc.

SUMMARY Electron microscopy of clinically uninvolved skin taken from a 12-month-old male child with biochemically proven angiokeratoma corporis diffusum showed characteristic lamellar lipid deposits within endothclial and perithelial cells of dermal blood vessels. Ultrastructural examination of skin may aid the early identification of males affected with Anderson-Fabry disease long before the development of specific skin lesions.

SUMMARY In uninvolved epidermis from nine psoriatic subjects, the mean phospholipase A2 activity was significantly greater (P

In recent years, research on the aetiology of psoriasis has focused on immune aetiopathogenesis. However, in the last few years, research on the immunoloogical changes in psoriasis has failed to mention the lymphatics. Also, studies emphasizing the importance of the dermal lymphatics have neglected the lymphatic changes seen in psoriasis. Therefore, we decided to put this matter back on the agenda. Skin biopsies from 20 patients with psoriasis vulgaris were examined lymphatically by light microscopy using the orcein stain. We found a considerable increase in both number and dilatation in the lymphatics of psoriatic plaques, compared with both the clinically uninvolved skin of the psoriatic patients and also the skin of the control group.

First described in 1877 as the appearance of psoriatic lesions in the uninvolved skin of psoriatic patients as a consequence of trauma, the Koebner phenomenon has since been described in numerous diseases. Other authors have tried to implicate either infections or parasitic causes as the pathogenesis of this phenomenon. Subsequent research by many authors have contributed to our poor understanding of this reaction in the hope of understanding the pathogenesis of psoriasis. We present a review of the literature covering the following topics as they relate to the Koebner phenomenon: diseases that koebnerize and their possible causes, predisposing and provoking factors, type, site, depth and degree of trauma, the all or none phenomenon, time lag, site preference, medications, inhibition of koebnerization and reverse koebnerization.

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.

BACKGROUND: An episode of guttate psoriasis can be an isolated event, can recur as guttate episodes, or develop into chronic plaque psoriasis (CPP). A previous study revealed that early-onset (before age 40�years) CPP is associated with inhibition of epidermal Langerhans cell (LC) migration. OBJECTIVES: To determine whether guttate psoriasis is also associated with abnormal LC mobilization. METHODS: Three groups of patients were recruited: current guttate episode (n�=�5); guttate psoriasis progressed to CPP (n�=�6); and resolved guttate psoriasis (n�=�2). Biopsies were taken from uninvolved skin and LC migration was measured ex vivo using an epidermal explant model. RESULTS: Patients with a current episode of guttate psoriasis displayed epidermal LC migration, although the extent was significantly lower than in skin from healthy controls (P�

In order to study the possible role of neuropeptide-Y (NPY) in the pathogenesis of vitiligo, the authors measured the levels of NPY in the plasma from 47 patients with vitiligo compared with 25 healthy volunteers, and the tissue fluids of skin lesions and uninvolved skin from 32 patients, employing a NPY 125I RIA Kit. The results showed that the levels of NPY in the patients with vitiligo of all of the generalized, local and segmental types were significantly higher than the normal controls. In both local and segmental type, the levels in progressive stage were significantly higher than those in stable stage, while in generalized type, there was no significant difference between those in progressive stage and stable stage. The levels of NPY in the tissue fluids from skin lesions were significantly higher than those from uninvolved skin in both the local type and segmental type, while in the generalized type, there was no significant difference between the NPY level in the tissue fluid from skin lesion and that from uninvolved skin. It is speculated that NPY may play certain roles in the pathogenesis of vitiligo, via neuro-immunity mechanism or neuronal affection on the melanocytes.

Studies suggest that moisturisers have a beneficial effect on psoriasis, and their use in preventive or adjuvant dermatological therapy is therefore of considerable clinical interest, although no classification of these products exists to guide their use. We have previously suggested a classification based on the ability of moisturisers to induce mechanical changes in normal skin. In psoriasis patients obvious objective differences exist between plaques and clinically uninvolved skin. This study was undertaken to investigate if these differences influence the mechanical response to moisturisers. Skin mechanics distension and hysteresis, Dermaflex® as well as capacitance Corneometer 812 CM® and moisturiser absorption were measured on psoriasis plaques and adjacent clinically uninvolved skin of 17 psoriasis patients. Three commonly available moisturisers, a barrier cream and a gel were tested. Baseline distensibility and capacitance were significantly lower for plaques (p < 0.0001), and all moisturisers increased distensibility in both lesions and adjacent skin. Hysteresis was generally affected to a greater degree by Locobase®. The gel caused greater increases in hysteresis outside plaques. Capacitance was significantly increased in plaques, except for areas treated with Locobase, while only Decubal® appeared to cause significant increases in uninvolved skin. Locobase showed better absorption in plaques than in control areas. No objective differences were found in the effects of moisturisers between psoriatic plaques and adjacent clinically uninvolved skin, suggesting that the significant clinical differences between lesional and paralesional skin do not influence the efficacy of moisturisers.

There are divergent opinions as to whether atrophoderma of Pasini and Pierini (APP) is a nosologic entity or a primary atrophic morphoea. In this study, we used high performance liquid chromatography to analyse the skin disaccharide contents of glycosaminoglycan (GAG) in two patients with APP and compared the results with those from a typical atrophic morphoea patient. Perilesional uninvolved skin was used as a control in each patient. In the atrophic phase morphoea, both the total amount of disaccharide per skin punch-biopsy and the amount of DeltaDi-4S(DS) - the main disaccharide unit of dermatan sulphate - per mg dry weight were increased. These changes were consistent with sclerotic phase morphoea. In contrast, the total amount of disaccharide per skin punch-biopsy was decreased and the amount of DeltaDi-4S(DS) per mg dry weight was decreased or unchanged in APP. Our results suggest that GAG metabolism in APP may be unique and quite different from that in morphoea.

Although the etiology of urticaria is mostly unclear, there are a number of recent new insights into the underlying pathomechanisms and causes. Dermal mast cell numbers and endothelial cell adhesion molecule and cytokine expression are also increased in uninvolved skin, while serum P-selectin levels are elevated, suggesting a systemic activation of the cutaneous inflammatory system in urticaria. In all adults, but not children with indolent mastocytosis, we found activating point mutations of c-kit, the mast cell growth factor receptor, in lesional cutaneous mast cells. In acute urticaria, IgE-dependent mechanisms are only rarely involved (0.9%), in contrast to generally held beliefs, whereas acute upper respiratory infections (39.3%) and drug intolerance (9.2%) are more frequent. In chronic urticaria, pseudoallergies to food (73%) and more rarely chronic inflammatory gastrointestinal diseases (11%) play a major role, with avoidance or elimination of the eliciting factors leading to long term remission. On the basis of recent findings, autoantibodies must be viewed mostly as secondary rather than causative in chronic urticaria.

The Koebner phenomenon originally described the appearance of psoriatic lesions in the uninvolved skin of patients with psoriasis as a consequence of trauma. We describe a case of concurrent lichen planus and sarcoidosis in the auditory canal, which represents an unusual manifestation of the Koebner phenomenon. This is the first case of concurrent lichen planus and sarcoidosis in the head and neck region and highlights the need for biopsy to allow accurate histopathological diagnosis and treatment.

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.

Background: Research has shown that involved as well as uninvolved skin of psoriatic subjects have an inherent defect that manifests, at a minimum, as nonapparent epidermal hyperplasia. Fibroblasts have been shown to regulate epidermal proliferation and differentiation; furthermore, fibroblasts from patients with psoriasis have altered growth, response, and mediator release when compared with normal. Objective: We conjectured that it might be possible to generate the enhanced epidermal proliferation inherent to psoriatic skin in vitro using a defined interactive culture system with cellular components from the skin of normal and psoriatic subjects. Methods: To reduce the variables whereby fibroblasts stimulate keratinocyte proliferation in vitro, a system was developed that does not permit direct contact between keratinocytes and fibroblasts, but does permit the exchange of media and mediators as well as an assessment of keratinocyte growth as a function of time. Fibroblasts from involved and uninvolved sites from biopsies of seven untreated psoriatic subjects were assessed for their effect on the growth of keratinocytes from normal subjects. Results: Analysis shows that five of seven fibroblast sources from involved sites and six of seven from uninvolved sites of psoriatic subjects induce normal keratinocytes to display enhanced outgrowth. Three of 14 fibroblast sources consistently do not induce this change. Fibroblasts from uninvolved sources are particularly effective, with a mean of 40 ± 8% (SD) more growth than with normal fibroblasts. Conclusion: It is concluded that fibroblasts from psoriatics can induce the phenotype of increased epidermal proliferation on normal keratinocytes via a soluble mediator in a defined system.

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.

Lasers are versatile instruments capable of treating an ever-increasing array of cutaneous conditions. Various vascular, pigmented, epidermal, and dermal lesions can be selectively destroyed without damaging normal uninvolved skin structures by utilizing lasers that correspond to the absorption characteristics of the intended target. Recently, lasers have been used with much success in the treatment of rhytides, photodamaged skin, and scarring. The rapid development of laser technology has made many lasers obsolete that only a few years ago were considered state of the art. Lasers are more reliable, emit light at higher energies with shorter pulse widths, and at faster delivery rates. As is typically the case with high-technology devices, lasers are becoming less expensive and more consolidated. For this reason, laser techniques will continue to evolve and new indications for their use will, no doubt, be discovered in the near feature. Physicians treating the skin are in a unique position to study the clinical and histological effects of lasers, as the skin remains an easy-access organ. Laser medicine and surgery will continue to be enhanced by the contributions made through the investigative efforts of laser surgeons treating the skin.

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.

We report on a male patient with mycosis fungoides (MF) with blisters mainly occurring on clinically uninvolved skin. This rare association has to be differentiated from other bullous diseases of the skin. The clinical picture has been known since the end of the last century and has been described as mycosis fungoides bullosa. The pathomechanism, however, has not yet been exactly identified. The different clinical and histological features of the disease are discussed.

In PUVA treatment of psoriasis, clinical observation suggests that uninvolved skin is more susceptible to PUVA erythema than lesions of psoriasis. If this is the case, then the efficacy of PUVA treatment might be increased by using localized high-dose UVA restricted to lesional skin. We have therefore studied the erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA and, for comparison, the erythemal response to UVB. In 14 patients, an area of psoriasis and adjacent uninvolved skin were exposed to a series of UVA doses (350 +/- 30 nm, 1-16J/cm2), using an irradiation monochromator. Six other patients were similarly phototested with a series of UVB doses (300 +/- 5 nm, 20-112 mJ/cm2) to both uninvolved and lesional skin. Erythema was judged visually at 72 h for psoralen-UVA, and at 24 h for UVB, and measured using a scanning laser-Doppler velocimeter. In 10 patients, PUVA therapy using high-dose UVA was subsequently given to lesional skin (8-16J/cm2 twice weekly) in addition to conventional whole-body PUVA. For psoralen-UVA, the minimal phototoxic dose within psoriasis was increased by a factor of 4 compared with non-lesional skin (P0.01, Wilcoxon signed-rank test). For UVB, the minimal erythema dose within psoriasis was higher than that for non-lesional skin (medians112 and 28 respectively, P0.05). Laser-Doppler measurements confirmed that the reduced erythemal sensitivity was not due to masking of response by pre-existing increased blood flux within psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)

The Koebner phenomenon is one of the most well-known entities in dermatology. It was first described by Heinrich Koebner in 1876 as the formation of psoriatic lesions in uninvolved skin of psoriatic patients after cutaneous trauma. This isomorphic phenomenon is now known to involve numerous diseases, among them vitiligo, lichen planus, and Darier disease. The pathogenesis of the Koebner phenomenon is still obscure but may involve cytokines, stress proteins, adhesion molecules, and autoantigens. This contribution reviews the clinical manifestations of Koebner phenomenon, its provocative factors, suggested pathogenesis mechanisms, and the various skin conditions that exhibit this unique response.

In the present study, an immunohistochemical analysis was made of the expression pattern of different macrophage markers such as 25F9, 27E10 and RM 3/1 on the surface of human keratinocytes (HK) in biopsies obtained from healthy volunteers and from patients with lichen planus, chronic cutaneous graft-versus-host reaction, mycosis fungoides, and purpura pigmentosa chronica. In biopsies from the healthy volunteers and from both clinically involved and uninvolved skin of the patients, the HK of the basal cell layer exhibited a specific peroxidase-positive reaction when the monoclonal antibody against 25F9 was used. Lesional HK from all patients studied displayed 25F9 and 27E10 in nearly the entire epidermis. The present findings provide further evidence that HK and macrophages share a number of common cell surface moieties.

Summary Pre-treatment plaque thickness determined the rate at which psoriasis responded to PUVA treatment, taking longer with thicker plaques. For dithranol, the rate of response to treatment was independent of pre-treatment plaque thickness. Plaques of psoriasis that showed the greatest evaporative water loss before treatment took longest to clear with PUVA. At the time of clinical clearing the water loss had returned to that of adjacent, uninvolved skin. With dithranol the evaporative water loss did not return to normal levels but remained considerably elevated when the plaque was clinically clear.

We report an unusual scleroderma case. A 45-year-old woman had recurrent morphea lesions over 10 times in 6 years. She had had preceding inactive systemic scleroderma. New morphea lesions developed cyclically on various portions of her body and improved within 2 years. Interestingly, new lesions have developed on once involved skin as well as uninvolved skin. No exacerbation of systemic scleroderma was induced by outbreaks of new morphea lesions. We could not find a similar case in the literature and named it "Palindromic morphea" because of its unique clinical course. D-penicillamine treatment had a limited effect. Minimal oral prednisolone (5 mg/day) completely suppressed the multiple recurrence of the morphea lesions and enhanced improvement of the sclerosis.

Intravital capillaroscopy using a video-microscopy system permits real-time imaging of the skin microvasculature with retrospective analysis of capillary dynamics. The addition of fluorescein angiography improves contrast and detects aspects of blood vessel behaviour, such as perfusion homogeneity and transcapillary solute diffusion, not detectable under native conditions. This study was performed to evaluate whether the method can be applied to the investigation of a skin disease and in particular the understanding of the role of the blood vessel in the pathogenesis of psoriasis. Results demonstrated clear differences between normal and psoriatic skin. More capillaries were red-cell perfused in both plaque and uninvolved skin compared to normal skin (P less than 0.001) and 0.01 less than P less than 0.02, respectively). The capillaries in psoriatic plaque skin were much larger than those in normal skin (P less than 0.001). The density of capillaries was not increased in plaque or uninvolved psoriatic skin, indicating expansion of existing vessels and not new vessel formation. The area of fluorescence seen around each capillary at 60 s was greater in plaque (P less than 0.001) and in uninvolved psoriatic skin (P less than 0.001) than in normal skin, indicating greater vessel transcapillary diffusion. This study confirms the value of video-microscopy as a non-invasive technique for the examination of the cutaneous microcirculation in vivo.

Background Psoriatic lesions are characterized by induration, scaling and erythema. Erythema is a result of inflammation and increased microvascular blood flow. Anthralin is the strongest topical antipsoriatic drug that causes clearing of psoriatic lesions and temporary remission. Objective The objective evaluation of skin perfusion might be a suitable way to gain a better insight in the pathophysiological process of this disease and to evaluate the response to antipsoriatic anthralin therapy. Methods We evaluated 21 psoriatic lesions (plaques, patches and pinpoint lesions) including 4 lesions in remission with anthralin induced erythema and 4 controls of healthy, uninvolved skin. We performed the measurements with a combined fluorescence and remission imaging (FRIS). The FRIS sensor is coupled with a touch screen industrial computer. The equipment consists of a white-light halogen lamp (20 W), two VIS-spectrometer modules (Zeiss) for remission detection and references. Imaging is realized by CCD-colour camera module and white light ring-lighting. Fluorescence emission was realized using an ultraviolet LED with a wavelength of 370 nm. The fluorescence detector is a highly sensitive MCS CCD (Zeiss) with an integration time of 2.5 sec. Results Spectral remission of psoriatic skin is characterized by a pronounced decrease (60–80%) of the haemoglobin double-peak compared to uninvolved skin. The NADH-fluorescence is diminished in lesional psoriatic skin including anthralin-treated areas with clinical remission. Conclusions Vascular perfusion is increased in psoriatic lesions as demonstrated by remission spectroscopy. NADH-fluorescence is reduced in lesional psoriatic skin and in anthralin-induced erythema. FRIS is a suitable tool for objective evaluation of the cutaneous response to antipsoriatic treatment.

Basic physiological characteristics were examined in the uninvolved skin of 39 patients with hand eczema and in 39 healthy controls. Susceptibility to sodium lauryl sulphate (SLS)-induced irritant dermatitis was evaluated by the application of a single 24-h SLS patch test to the upper arm. Transepidermal water loss (TEWL) was measured by an evaporimeter, skin thickness by ultrasound A-scan, blood flow by laser-Doppler flowmetry and skin colour by a chroma meter using the L*a*b* system of the Commission Internationale de l'Eclairage (CIE). No difference in basal TEWL values was found between patients and controls. A decreased skin thickness was found in those with hand eczema as compared to the controls. The hand eczema patients had significantly increased L* and decreased b*-values compared to controls, indicating a more 'fair' skin. Susceptibility to SLS was increased only in patients with acute eczema, indicating that the presence of an active eczema increases the reactivity to irritants of distant uninvolved skin.

Summary Using different monoclonal anti-cytokeratin antibodies (broad spectrum, cytokeratin 7, 8, 18, 19) and the antibody A55-A/A9 until now characterized only by immunohistology the staining of ductual structures and some cells within the lobulae of dermal cylindromata was demonstrated. In regard to the cytokeratin polypeptide patterns of the adnexes in uninvolved skin an exact histogenetic correlation by our findings is not possible, but the pattern is consistent with the conception of the glandular origin of the tumours.

Summary Background Fluorescence lifetime imaging (FLIM) is a novel imaging technique that generates image contrast between different states of tissue due to differences in fluorescence decay rates. Objectives To establish whether FLIM of skin autofluorescence can provide useful contrast between basal cell carcinomas (BCCs) and surrounding uninvolved skin. Methods Unstained excision biopsies of 25 BCCs were imaged en face with FLIM following excitation of autofluorescence with a 355 nm pulsed ultraviolet laser. Results Using FLIM we were able to distinguish areas of BCC from surrounding skin in an ex vivo study. Significant reductions in mean fluorescence lifetimes between areas of BCC and areas of surrounding uninvolved skin were demonstrated (P