Fluorescence optical imaging for the detection of potential psoriatic arthritis in comparison to musculoskeletal ultrasound.

OBJECTIVE: Comparison of fluorescence optical imaging (FOI) with grayscale (GS) and power Doppler ultrasound (PDUS) to detect joint inflammation in patients with confirmed or suspected psoriatic arthritis (PsA). METHODS: Patients (n = 60) with psoriasis and tenderness and/or swelling of joints were separated into two groups: diagnosis confirmed by the treating dermatologist before the start of the study (n = 26), and suspected PsA (n = 34). GS/PDUS of the hand most clinically affected was performed with a dorsal/palmar view (wrist, MCP, PIP, DIP2-5). FOI examination was carried out in a standardized manner by analyzing the predefined Phases 1-3. RESULTS: FOI was found to be more sensitive than ultrasound (US) for detection of inflammation in PIP/DIP joints (p = 0.035). Confirmed PsA patients showed more findings in FOI P2 and P3, while suspected PsA patients showed more findings in P1. In the confirmed PsA group, most involved joints were MCP joints, while in the suspected PsA group, more involved wrist joints and DIP joints (p = 0.006) were detected with FOI. CONCLUSIONS: The differences between the confirmed and suspected groups indicate that FOI is helpful in the detection of early PsA since P1 may correspond to acute inflammation, whereas P2 and P3 enhancement reflect chronic inflammation. Fluorescence optical imaging might therefore be a novel diagnostic tool for early PsA diagnosis.

MMP8 Is Increased in Lesions and Blood of Acne Inversa Patients: A Potential Link to Skin Destruction and Metabolic Alterations.

Acne inversa (AI; also designated as hidradenitis suppurativa) is a chronic inflammatory disease with still unknown pathogenesis that affects the intertriginous skin of perianal, inguinal, and axillary sites. It leads to painful nodules, abscesses, and fistulas with malodorous secretion and is frequently associated with metabolic alterations. Here, we demonstrate that one of the most highly upregulated molecules in AI lesions is matrix metalloproteinase 8 (MMP8), an enzyme specialized in the degradation of extracellular matrix components and the HDL component apolipoprotein A-I. Granulocytes, which were present in AI lesions, secreted high amounts of MMP8 especially after TNF-α stimulation. Furthermore, activated fibroblasts but not keratinocytes were found to express MMP8. The high lesional MMP8 levels were accompanied by elevated blood levels that positively correlated with TNF-α blood levels and disease severity assessed by Sartorius score, especially with the number of regions with inflammatory nodules/abscesses and fistulas. Additionally, we found a negative correlation between blood MMP8 and HDL-cholesterol levels, suggesting a contributory role of MMP8 in metabolic alterations in AI. In summary, we demonstrate elevated MMP8 levels in AI lesions, suggest their role in skin destruction and metabolic alterations, and recommend the use of MMP8 as blood biomarker for AI disease activity assessment.

Influence of Topical, Systemic and Combined Application of Antioxidants on the Barrier Properties of the Human Skin.

BACKGROUND: The formation of free radicals in human skin by solar ultraviolet radiation is considered to be the main reason for extrinsic skin aging. The antioxidants in human tissue represent an efficient protection system against the destructive action of these reactive free radicals. In this study, the parameters of the skin, epidermal thickness, stratum corneum moisture, elasticity and wrinkle volume, were determined before and after the treatment with antioxidant- or placebo-containing tablets and creams. METHODS: The study included 5 groups of 15 volunteers each, who were treated for 2 months with antioxidant-containing or placebo tablets, creams or a combination of antioxidant-containing tablets and cream. The skin parameters were measured at time point 0 and at week 8 utilizing ultrasound for the determination of epidermal thickness, a corneometer for stratum corneum moisture measurements, skin profilometry for quantifying the wrinkle volume and a cutometer for determining the elasticity. RESULTS: The verum cream had a positive influence on epidermal thickness, elasticity and skin moisture, but the verum tablets improved the epidermal thickness only. The combined application of verum tablets and creams led to a significant improvement of all investigated skin parameters, whereas the application of placebo tablets or cream did not influence any parameters. CONCLUSION: The topical and oral supplementation of antioxidants can be an instrument to improve several skin parameters and potentially counteract or decelerate the process of extrinsic skin aging.

Aggressive epidermotropic cutaneous CD8+ lymphoma: a cutaneous lymphoma with distinct clinical and pathological features. Report of an EORTC Cutaneous Lymphoma Task Force Workshop.

AIMS: Aggressive epidermotropic cutaneous CD8(+) lymphoma is currently afforded provisional status in the WHO classification of lymphomas. An EORTC Workshop was convened to describe in detail the features of this putative neoplasm and evaluate its nosological status with respect to other cutaneous CD8(+) lymphomas. METHODS AND RESULTS: Sixty-one CD8(+) cases were analysed at the workshop; clinical details, often with photographs, histological sections, immunohistochemical results, treatment and patient outcome were discussed and recorded. Eighteen cases had distinct features and conformed to the diagnosis of aggressive epidermotropic cutaneous CD8(+) lymphoma. The patients typically present with widespread plaques and tumours, often ulcerated and haemorrhagic, and histologically have striking pagetoid epidermotrophism. A CD8(+) /CD45RA(+) /CD45RO(-) /CD2(-) /CD5(-) /CD56(-) phenotype, with one or more cytotoxic markers, was found in seven of 18 patients, with a very similar phenotype in the remainder. The tumours seldom involve lymph nodes, but mucosal and central nervous system involvement are not uncommon. The prognosis is poor, with a median survival of 12 months. Examples of CD8(+) mycosis fungoides, lymphomatoid papulosis and Woringer-Kolopp disease presented the typical features well documented in the CD4(+) forms of those diseases. CONCLUSIONS: Aggressive epidermotropic cutaneous CD8(+) lymphoma is a distinct lymphoma that warrants inclusion as a distinct entity in future revisions of lymphoma classifications.

T-cell receptor gene rearrangement analysis of sequential biopsies in cutaneous T-cell lymphomas with the Biomed-2 PCR reveals transient T-cell clones in addition to the tumor clone.

Detection of a dominant T-cell clone by T-cell receptor (TCR) gene rearrangement analysis is often essential for the diagnosis of cutaneous T-cell lymphomas (CTCL). The occurrence of T-cell clones in addition to the diagnostic T-cell clone during the course of CTCL has been reported, but the data of these studies have been contradictory. We retrospectively evaluated the data of 114 lesional skin biopsies from 26 patients with Mycosis fungoides and two patients with primary cutaneous anaplastic large cell lymphoma, which were analysed with the standardized Biomed-2 PCR for the TCRγ and TCRß locus. A dominant T-cell clone was repetitively detected in 93% (26/28) of patients. Additional T-cell clones appeared temporarily in 39% (11/28) of patients. Correlation with the clinical data did not show an association of the presence of additional T-cell clones with age, number of treatments, progression of disease or survival. Our findings demonstrate that a persistent T-cell clone, most likely the disease causing tumor clone, is detectable in almost all CTCL patients. In addition, transiently appearing T-cell clones frequently occur during the course of disease. The biological relevance of these additional clones has still to be determined. However, it is important to take the possibility of additional T-cell clones into account for diagnostic analyses.

Comparative study of hair follicle morphology in eight mammalian species and humans.

BACKGROUND: The objective of the present study was the investigation of hair follicle morphology in eight mammalian species in order to evaluate the species-specific contribution of hair follicles to skin penetration particularly with regard to the utilization of the different animal species as skin models for human skin. METHODS: Cyanoacrylate skin surface biopsy method (CSSB), light microscopy and also digital photography were used for the measurements of hair follicle morphology. RESULTS: The results revealed species-specific differences regarding the pattern of hair follicle distribution and also differences with regard to hair follicle parameters and characteristics. The results also showed that hair follicles generally possess enormous reservoir capacities, regarding the follicular volume. In all examined species, hair follicles reached at least one-fifth of stratum corneum storage capacity. The results were compared with human data obtained in a previous study. CONCLUSION: With regard to hair follicle morphology and skin structure, the porcine skin seems to be the most appropriate skin model for human skin analog to previous investigations, whereas the skin of dog, cat, and rabbit showed the most significant differences.

Evaluation of optical coherence tomography as a non-invasive diagnostic tool in cutaneous wound healing.

BACKGROUND: The monitoring of wound-healing processes is indispensable for the therapeutic effectiveness and improved care of chronic wounds. Histological sections provide the best morphological assessment of wound recovery, but cause further tissue destruction and increase the risk of infection. Therefore, it is reasonable to apply a diagnostic tool that allows a non-invasive and reliable observation of morphological changes in wound healing. METHODS: Optical coherence tomography (OCT) is an imaging technique for in vivo evaluation of skin diseases with a resolution close to histopathology. The aim of this study was to investigate whether OCT is suited to display the phases of wound healing. For this purpose, six patients with chronic wounds were objectively characterized by OCT during a period of 2 weeks. RESULTS: Comparable results between histological findings and OCT were achieved. OCT allowed the detection of partial loss of the epidermis, vasoconstriction, vasodilatation and epithelialization. CONCLUSION: Consequently, OCT could be a potential non-invasive diagnostic tool for the characterization and monitoring of cutaneous wound-healing processes over time.

Palmoplantar erythrodysesthesia-like skin symptoms in patients under various chemotherapeutics: preventive and therapeutic options.

BACKGROUND/AIMS: The palmoplantar erythrodysaesthesia (PPE) is an inflammatory cutaneous side effect in patients under chemotherapy with pegylated liposomal doxorubicin (PLD), with indications that also other chemotherapeutics induce similar side effects. Recently, it has been demonstrated that PLD escapes with the sweat onto the skin inducing radical-forming processes that damage the skin. The topical application of antioxidants with a high radical protection factor has proven to be a very efficient prevention strategy for PLD-treated patients. METHODS: 68 patients, who had been treated with 12 different chemotherapeutics and experienced side effects similar to PPE, were treated with a meanwhile commercially available ointment. RESULTS: At the beginning of the therapy, 46 patients suffered from a PPE of severity grade III, while in 22 patients a PPE of severity grade II was diagnosed. The application of the ointment resulted in a significant improvement of the clinical symptoms and the skin status in all these patients; their chemotherapies could be continued. CONCLUSION: The obtained results suggest that radical-forming processes play an essential role in a great number of chemotherapeutics which induce dermal side effects. The topical application of the antioxidant-containing ointment proved to be a good therapeutic option which needs further evaluation.

Efficient prevention strategy against the development of a palmar-plantar erythrodysesthesia during chemotherapy.

BACKGROUND: Pegylated liposomal doxorubicin (PLD) is a highly efficient chemotherapeutic; however, it induces dermal side effects such as palmar-plantar erythrodysesthesia (PPE) in up to 80% of cases, probably by being emitted with the sweat onto the skin surface. AIM: The aim of the present study was to examine whether a topically applied ointment containing antioxidants with a high radical protection factor is able to prevent the formation of PPE. METHODS: Twenty patients suffering from ovarian carcinoma and treated with PLD were observed. RESULTS: 60% of the patients tolerated the regular application of the cream and developed no PPE. The remaining 40% interrupted the application. Six of them developed PPE and resumed ointment application thereafter. In these cases the PPE disappeared or was strongly reduced. CONCLUSION: The results of the observation clearly demonstrate that topical application of the ointment is an efficient strategy against the development of PPE during chemotherapy with PLD.

Antioxidants in Asian-Korean and caucasian skin: the influence of nutrition and stress.

BACKGROUND: The antioxidant status of the human skin provides protection against the destructive action of free radicals. Most antioxidants cannot be synthesized by the human organism itself, but have to be ingested with a healthy nutrition rich in fruit and vegetables. The Korean cuisine is known to be one of the healthiest worldwide. This binational study investigated the cutaneous carotenoid concentrations in German subjects, South Korean subjects and immigrant Korean subjects resident in Germany and examined whether dietary- and lifestyle-related differences are reflected in the cutaneous carotenoid concentrations. METHODS: Measurements of the carotenoid concentrations of 714 healthy volunteers were performed using a non-invasive spectroscopic measurement system based on reflectance spectroscopy. RESULTS: In the present study South Korean residents showed a significantly higher antioxidant status than both native German residents and Korean immigrants living in Germany (p < 0.001). The first generation of Korean immigrants to Germany over the age of 50 mostly preserved Korean dietary habits, showing significantly higher concentrations (p < 0.001) than the German-born second and third Korean generations under the age of 50. CONCLUSION: The results of the study indicate that a healthy nutrition alone does not provide a high antioxidant status unless the stress exposure can be reduced simultaneously.

Approach towards developing a novel procedure to selectively quantify topically applied substances in the hair follicles of the model tissue porcine ear skin.

Hair follicles represent reservoirs for localized drug therapy and transport pathways for systemic drug delivery. This study describes an approach towards developing a novel procedure for quantifying topically applied substances located in the hair follicles of porcine ear skin, a model for human in vivo skin, using a fluorescent dye. Approximately 5% of the topically applied dye was recovered from the hair follicles, which is in accordance with a previous study.

Deficiency of IL-22 contributes to a chronic inflammatory disease: pathogenetic mechanisms in acne inversa.

Overexpression of the T cell cytokine IL-22 is linked to the development of some chronic diseases, but little is known about IL-22 deficiency in humans. As demonstrated in this study, acne inversa (AI; also designated as Hidradenitis suppurativa) lesions show a relative deficiency of IL-22 and IL-20, but not of IL-17A, IL-26, IFN-γ, IL-24, or IL-1ß. Moreover, AI lesions had reduced expression of membranous IL-22 and IL-20 receptors and increased expression of the natural IL-22 inhibitor, IL-22 binding protein. AI is a chronic inflammatory skin disease with prevalence up to 4% of the population and in which cutaneous bacterial persistence represents an important pathogenetic factor. Accordingly, we also found a relative deficiency of antimicrobial proteins (AMPs) in AI lesions and a positive correlation between lesional IL-22 and IL-20 versus AMP levels. IL-22, like its tissue cell downstream mediator IL-20, upregulated AMPs in reconstituted human epidermis and was critical for increased AMP levels under inflammatory conditions. The relative IL-22 deficiency in AI was not linked to lesional T cell numbers or Th22/Th1/Th17 subset markers and -inducing cytokines. However, IL-10 was highly expressed in AI lesions and correlated negatively with IL-22 expression. Moreover, IL-10 inhibited IL-22 but not IL-17 production in vitro. The IL-10 overexpression, in turn, was not associated with an elevated presence of regulatory T cells but with the enhanced presence of an IL-10-inducing cytokine. We conclude that IL-22 deficiency may contribute to the pathogenesis of certain chronic disorders as postulated in this paper for AI.

Influence of finishing textile materials on the reduction of skin irritations.

BACKGROUND: An increasing number of people is reported to have sensitive skin. Consequently, the development of textile materials with comfortable wearing properties has become a major interest. One method to create a pleasant sensation of textile materials on the skin is to coat them with silk proteins. This technologically complex procedure requires both optimization and control. METHODS: The present study was aimed to characterize the subjective perception of different textiles and to objectively assess their influence on skin morphology with non-invasive optical techniques like optical coherence tomography (OCT), laser scanning microscopy (LSM) and optical surface profilometry (OP). Furthermore, optical methods were used to characterize surface properties of different textile fabrics. RESULTS: In the present study it could be shown that optical non-invasive methods, as applied in cosmetology and dermatology are suited to characterize the structural properties of fabrics and the effects that textile materials have on the skin. Here, both unfinished textile materials and fabrics finished with silk protein coating were investigated by OCT, LSM and OP. In addition, volunteers were interviewed about their subjective sensation when these fabrics were in contact with their skin. CONCLUSION: The study showed that optical methods could be applied to compare textile materials in vitro, which permit the wearing comfort to be predicted and in vivo perception on the skin.

Depression is a frequent co-morbidity in patients with acne inversa.

BACKGROUND: Acne inversa (AI) is a common chronic inflammatory disease that has a profound impact on the patientsí quality of life. We hypothesized a higher level of depression in AI patients compared to controls. OBJECTIVES: We studied depression in patients with AI and control subjects. Additionally, we evaluated whether the severity of the disease, anxiety, sexual distress and acute inflammation may have an influence on depression. PATIENTS AND METHODS: The Hospital Anxiety and Depression Scale (HADS) was given to 90 voluntary study participants to assess depression in AI patients and in age-, gender-, and BMI-matched controls. Moreover, the correlation between depression and conjectural influencing factors was evaluated. RESULTS: This study demonstrated that AI patients have a higher depression score than matched controls. Importantly, 38.6% of AI patients are affected by depression compared to 2.4% of the control subjects. In contrast to the duration of the disease and the AI patientsí age, anxiety and sexual distress showed a strong correlation with the degree of depression. CONCLUSIONS: Patients with AI have a higher risk of developing depression. Physicians should be alert to the possible development of depression when treating patients with this disorder.

In vivo skin treatment with tissue-tolerable plasma influences skin physiology and antioxidant profile in human stratum corneum.

The antimicrobial treatment of wounds is still a major problem. Tissue-tolerable electrical plasma (TTP) is a new approach for topical microbial disinfection of the skin surface. The aim of the present study was to investigate the influence of TTP on a carotenoid profile in relation to skin physiology parameters (epidermal barrier function, stratum corneum (SC) hydration, surface temperature and irritation parameters). We were interested in the interaction of TTP and the antioxidative network, as well as the consequences for skin physiology parameters. These parameters are also indicative of TTP safety in vivo. For plasma application, 'Kinpen 09' was used (surface exposure 30-43°C) for 3 s. Beta-carotene and water profiles were assessed by in vivo Raman microspectroscopy (skin composition analyzer 3510). Skin physiology parameters were measured with Tewameter TM 300, Corneometer CM 825, skin thermometer and Chromameter CR 300. All parameters were assessed non-invasively on seven healthy volunteers before and after plasma application in vivo. We could show that TTP application leads to a decrease in beta-carotene especially in the superficial SC. Skin-surface temperature increased by 1.74°C, while the transepidermal water loss (TEWL) increase indicated an impaired barrier function. SC hydration decreased as seen in water profile especially in the superficial layers and capacitance values. A slight increase in skin redness was measurable. The induction of reactive oxygen species is probably the major contributor of TTP efficacy in skin disinfection. Skin physiology parameters were influenced without damaging the skin or skin functions, indicating the safety of TTP under in vivo conditions.

Incidence of spontaneous remission in patients with CD25-positive mycosis fungoides/Sézary syndrome receiving placebo.

BACKGROUND: Spontaneous remission is recognized in mycosis fungoides (MF) and Sézary syndrome (SS). OBJECTIVE: We analyzed the outcome of 44 patients with previously treated CD25-positive (CD25+), recurrent/persistent MF/SS randomly assigned to receive placebo as part of a phase III trial. METHODS: This trial investigated the efficacy and safety of two doses of denileukin diftitox in patients with MF/SS who had received up to 3 prior therapies. The primary end point was overall response rate. Multivariate regression analyses were used to assess the relationship between baseline covariates and clinical outcomes. RESULTS: The overall response rate was 15.9% for placebo recipients (complete response: 2.3%; partial response: 13.6%), reflecting the baseline rate of disease remission that can be expected in a clinical trial. The median progression-free survival (PFS) in the placebo arm was moderately short at 4.4 months compared with the active-agent arm but important to consider in the context of recent single-arm phase II studies of other therapies for MF/SS that report PFS of approximately 6 months. Multivariate analyses identified no significant effects of any baseline factors on either overall response rate or PFS, although there was a trend toward poorer PFS with advanced age. Because sepsis occurred significantly more often in the placebo arm versus the active-treatment arm, the role of antibiotics in causing remission cannot be discounted (6.8% vs 0%; P < .05). LIMITATIONS: This study had a relatively small sample size, yielding a wide 95% confidence interval. CONCLUSION: The results may serve as a useful comparator for other active-treatment studies of MF/SS that lack a placebo-control arm.

Profound disturbances of sexual health in patients with acne inversa.

BACKGROUND: Acne inversa (AI) leads chronically to painful eruptions and extensive scarring in predominantly intimate areas. We hypothesized an impairment of sexual life caused by the disease. OBJECTIVES: By means of validated questionnaires, sexual health and quality of life were assessed in patients with AI and in healthy control subjects. METHODS: A self-administered questionnaire was given to 85 voluntary study participants. In all, 45 women (24 patients vs 21 control subjects) and 40 men (20 patients vs 20 control subjects) were enrolled in the study. The Female Sexual Function Index, the International Index of Erectile Function, and the Frankfurt Self-Concept Scale for Sexuality were used to assess sexual health. Quality of life was measured with the Dermatology Life Quality Index. RESULTS: This study demonstrated, for the first time to our knowledge, that patients with AI have sexual dysfunctions and sexual distress in comparison with matched control subjects. Sexual distress was particularly higher in female than in male patients with AI. Surprisingly, severity of cutaneous alterations correlated neither with sexual dysfunctions nor with sexual distress. However, the sexual dysfunction and sexual distress negatively correlated with the quality of life in female patients with AI who had a lower quality of life compared with gender-matched control subjects and male patients. LIMITATIONS: Small sample size is the main limitation of this study. CONCLUSIONS: Sexual health is diminished in patients with AI. We underscore the need for physicians to implement attention on the impact of AI on sexual health and quality of life when treating patients for this disease.

Evaluation of scientific programs at a large-scale academic congress: lessons from the 22nd World Congress of Dermatology.

BACKGROUND: The organization of a scientific program and the arrangement of the speakers require a considerable amount of time and effort. However, little is known about how to reinforce the participants' satisfaction with scientific programs at a large-scale academic congress with multiple parallel sessions. OBJECTIVES: This study had three main purposes: (1) to create a reference for future congresses, (2) to determine session popularity and participation rate, and (3) to identify which characteristics of sessions can affect the perception of the audience. METHODS: A total of 216 scientific sessions during the 22nd World Congress of Dermatology were evaluated using printed evaluation surveys. RESULTS: The average scores for all sessions and speakers were relatively high. There were significant differences in the numbers of total session scores, collected surveys and speakers for each session category. The number of speakers at each session was not related to the session results. It was found that among the three different session grades (excellent, fair and poor), the proportion of speakers of each grade especially contributed to the perceived quality of the poor-grade sessions. CONCLUSIONS: This survey will help to organize scientific sessions and improve the quality of academic congresses.