Detection of asymptomatic enthesitis in psoriasis patients: An onset of psoriatic arthritis?

Presence of asymptomatic joint involvement is recognized in patients with psoriasis. However, it remains elusive whether such patients develop psoriatic arthritis (PsA). The aim of the present study was to examine the incidence of asymptomatic joint lesions, in particular, enthesitis in patients with psoriasis vulgaris (PsV) and to further assess the clinical features. Eighteen PsV and 28 PsA patients were enrolled for examination by positron emission tomography/computed tomography (PET/CT) using ¹⁸F‐fluorodeoxyglucose (FDG). Any nail, scalp and intergluteal involvements were reported. Levels of serum C‐reactive protein (CRP), white blood cell (WBC) counts and erythrocyte sedimentation rate (ESR) were examined. All of the PsA patients showed FDG accumulation in the affected joints. Notably, asymptomatic enthesitis was detected in six out of 18 PsV patients (33%), and they were diagnosed as having subclinical PsA. Incidences of scalp, intergluteal and nail psoriasis in subclinical PsA patients were 100%, 83% and 64%, respectively, which were higher than those in PsV patients (67%, 25% and 40%, respectively). CRP, WBC counts and ESR were invariable between PsV and subclinical PsA groups. PET/CT imaging could discover asymptomatic enthesitis. Our data suggested that the subpopulation of subclinical PsA was much higher than expected. Higher prevalence of nail, scalp and intergluteal psoriasis confirmed the risk of PsA as previously described.     

Extracorporeal shockwave: mechanisms of action and physiological aspects for cellulite,body shaping,and localized fat—Systematic review

Extracorporeal Shockwave Therapy (ESWT) has had a wide use in rehabilitation, and has presented positive effects in the treatment of unaesthetic affections. The objective of the present study was to search, in the literature, the mechanisms of action and the physiological aspects of shockwaves acting on the biological tissue to improve the condition of cellulite and localized fat. The systematic review of the literature was carried out in the period of September 2016 to February 2017 based on the bibliographic databases such as Lilacs, Medline, PubMed, and SciELO. Fifteen articles were identified in that systematic review, three of which were excluded as they did not make the complete access to the article available or the theme investigated did not encompass the objective of the study. The revision demonstrated that extracorporeal shockwaves present relevant effects on the biological tissue, which leads to the restructuring of skin properties and subcutaneous tissue, thus clinically improving the aspects of cellulite and localized fat.     

Number of cell layers of the stratum corneum in normal skin – relationship to the anatomical location on the body, age, sex and physical parameters

Abstract We counted the number of cell layers in the stratum corneum (SC) of normal skin taken from different anatomical locations of the body of 301 individuals of various ages. Frozen 6 μm thick sections were stained with a 1% aqueous solution of safranin and observed under a microscope after application of 2% KOH solution. There were great variations in the number of SC cell layers (mean ± SD) according to location and among different individuals. The smallest number was found in genital skin (6 ± 2), followed in order by skin of the face (9 ± 2), neck (10 ± 2), scalp (12 ± 2), trunk (13 ± 4), extremities (15 ± 4) and the palms and soles (47 ± 24). The heel showed the largest number (86 ± 36). No definite correlation was found between the number of corneocyte layers and sex of the individual, whereas there was a slight increase in the number of SC layers with age in the skin of the cheek and back, particularly in male individuals. Comparison of these data with those from functional assessments of the SC of the skin from various locations of healthy adults showed that transepidermal water loss, an indicator of SC barrier function, reflected the number of corneocyte cell layers. In contrast, high-frequency conductance, an indicator of the hydration state of the outer SC, did not seem to be under the influence simply of the number of SC cell layers. Received: 4 January 1999 / Received after revision: 11 June 1999 / Accepted: 17 June 1999     

Serum levels of interleukin-8, tumor necrosis factor-α and γ-interferon in Egyptian psoriatic patients and correlation with disease severity

Psoriatic plaques have been shown to contain increased levels of pro-inflammatory cytokines. Also, serum levels of several cytokines have been reported elevated in psoriatic patients. It is postulated that changes in cytokine production both locally and systemically could be useful in monitoring disease activity. The aim of this study was to evaluate serum cytokine profile of interleukin (IL)-8, γ-interferon (IFN-γ) and tumor necrosis factor-α (TNF-α) in Egyptian psoriatic patients by enzyme-linked immunosorbent assay (ELISA) technique and to correlate these levels with disease severity. We analyzed serum samples from 60 Egyptian patients (31 females and 29 males) with a mean age of 40.2 ± 17.4 years with active psoriasis, and 21 healthy volunteers for major T-helper type 1 cytokines using the ELISA technique. The disease severity, including erythema, induration and scales, was assessed by Psoriasis Area and Severity Index (PASI) score. TNF-α and IFN-γ were markedly elevated in all sera from psoriatic patients. TNF-α was found a more efficient predictor for disease severity than IL-8 and IFN-γ using three receiver-operator curves with accuracy. IL-8 was also moderately elevated and correlated with the age of patients (r = 0.28). We have obtained evidence that TNF-α in our study was found to be more useful than the other two tested cytokines, IL-8 and IFN-γ as a follow-up marker for monitoring disease severity in Egyptian psoriatic patients. A positive correlation between lL-8 and the age of the patients was also noted.     

Serum concentration of IL-6, IL-2, TNF-α, and IFNγ in Vitiligo patients

Background:

Vitiligo is an acquired depigmenting disorder characterized by the loss of functional melanocytes from the epidermis. Although the etiology of vitiligo is unknown, over the last few years, substantial data from clinical research has greatly supported the ‘Autoimmune theory’ and this is supported by the frequent association of vitiligo with disorders that have an autoimmune origin, including Hashimoto''s thyroiditis, Graves disease, type 1 insulin-dependent diabetes mellitus, and Addison''s disease. As cytokines are important mediators of immunity, there is evidence to suggest that they play a major role in the pathogenesis of autoimmune diseases.

Aim:

Keeping this in view we have assayed sera for cytokine IL-6, IL-2, Tumor necrosis factor (TNF)-α, and IFNγ in 80 cases of vitiligo and compared it with healthy subjects, in order to find out whether they play a role in the pathogenesis of vitiligo or not.

Materials and Methods:

Serum IL-6, IL-2, TNF-α, and IFNγ were done by the indirect enzyme linked immunosorbent assay (ELISA).

Results:

The mean serum IL-6 and IL-2 levels in the patient group were significantly higher when compared with those of the normal controls. The mean serum IFNγ level in patients with vitiligo was significantly lower than that in the control group. There was no significant difference in the serum level of TNF-α between vitiligo and healthy controls.

Conclusion:

An increase in the production of proinflammatory cytokines such as IL-6 and IL-2 in vitiligo patients may play an important role in melanocytic cytotoxicity. Thus, we speculate that the cytokine production of epidermal microenvironment may be involved in vitiligo.     

Organ culture of psoriatic skin: effect of TGF-α and TGF-Β on epidermal structure in vitro

Summary Normal skin and uninvolved and involved psoriatic skin specimens were maintained in vitro in organ culture. The 3–4 mm punch-biopsied skin specimens were put freely into the culture medium with or without fetal calf serum, under an atmosphere of 95% O₂ plus 5% CO₂, and rotated at 60 rpm at 37C. In the serum-free culture medium (vitamin A-free) granular layers appeared in the involved psoriatic epidermis in culture. Addition of TGF- caused normal skin and uninvolved and involved psoriatic skin specimens to become acanthotic and to degenerate easily almost to the full thickness of the epidermal layer in proportion to increasing concentrations of TGF- as well as with the duration of the culture, but without disappearance of their granular layers. TGF- caused the normal skin and uninvolved psoriatic skin specimens to become thinned without disappearance of granular layers, but caused the involved psoriatic skin specimens to be thinned without appearance of granular layers in serumcontaining medium or with their disappearance in the serum-free medium. TGF- also antagonized the acanthotic and degenerative effect of TGF-. The results suggest that TGF- and TGF- may partially be related to the induction of psoriatic epidermal lesions.     

Clinical,microbiological, immunological and imaging characteristics of tunnels and fistulas in hidradenitis suppurativa and Crohn’s disease

Hidradenitis suppurativa (HS) tunnels and Crohn's disease (CD) fistulas are a challenge to treat. Although pathogenic similarities have been described between HS and CD, recent studies indicate that clinical, microbiological, immunological and imaging characteristics differ between these diseases. This review highlights the differences between HS tunnels and CD fistulas. Next-generation sequencing studies demonstrate a microbiome in HS tunnels dominated by Porphyromonas spp., Prevotella spp. whereas no specific bacteria have been associated with cutaneous CD. Immunologically, TNF has been found upregulated in HS tunnels along with various interleukins (IL-8, IL-16, IL-1α and IL-1β). In CD fistulas, Th1, Th17, IL-17, IFN-ɤ, TNF and IL-23 are increased. US imaging is an important tool in HS. US of HS tunnels depict hypoechoic band-like structure across skin layers in the dermis and/or hypodermis connected to the base of a widened hair follicle. In CD, MR imaging of simple perianal fistulas illustrates a linear, non-branching inflammatory tract relating to an internal opening in the anus or low rectum and an external opening to the skin surface. An increased awareness of the immediate potential differences between HS tunnels and CD fistulas may optimize treatment regimens of these intractable skin manifestations.     

Etanercept in the treatment of psoriasis and psoriatic arthritis with concomitant hepatitis C virus infection: clinical and virological study in three patients

Treatment of patients with psoriasis and concomitant hepatitis-C virus (HCV) infection poses a therapeutic challenge because most systemic drugs are associated with potential hepatotoxicity, either due to direct liver damage or to immunosuppression. Among newly available drugs for the treatment of psoriasis and psoriatic arthritis, studies investigating the effect of anti-tumour necrosis factor-α in such patients are still limited. We describe three psoriatic patients with HCV, one with concomitant alcoholic hepatitis, who were treated with etanercept monotherapy for six months. We obtained good clinical responses for both psoriasis and arthritis in all three patients. While no significant changes in viral load and transaminases were observed in two patients, alanine aminotrasferase and gamma-glutamyltransferase levels were raised during treatment in the patient with concomitant alcoholic hepatitis. At baseline, one patient was negative and two were positive for mixed-type cryoglobulins. During treatment, none of the patients developed cryoglobulinemia-related clinical symptoms, and one of the two patients positive at baseline was negative for cryoglobulins at the end of follow-up. Our results add to accumulating data suggesting that etanercept represents a valuable therapeutic option for treatment of HCV-positive psoriatic patients, with an acceptable safety profile in the short-term. However, etanercept treatment of HCV cases with concomitant alcoholic hepatitis must be undertaken with caution.     

High levels of endothelial progenitor cells and circulating endothelial cells in patients with Behcet’s disease and their relationship to disease activity

Background: Behcet’s disease is a multisystemic vasculitis, associated with vascular endothelial dysfunction. Currently, the prognosis is unpredictable, because there is still no valid laboratory marker indicating the disease activity in Behcet’s disease. Endothelial progenitor cells and circulating endothelial cells are newly introduced hematological markers which are presumed to take part in the pathogenesis of vasculitis.Objectives: To evaluate the levels of endothelial progenitor cells and subtypes and circulating endothelial cells in patients with Behcet’s disease and to describe their relationship with the disease activity.Methods: A total of 45 patients with Behcet’s disease and 28 healthy controls were included in the study. Endothelial progenitor cells (CD34+CD133+KDR+ as early endothelial progenitor cells and CD34+KDR+ as late endothelial progenitor cells), and circulating endothelial cells (CD34+CD133+) were measured by flow cytometry.Results: The mean plasma level of endothelial progenitor cells and circulating endothelial cells, vascular endothelial growth factor, matrix metalloproteinase-9, C-reactive protein, and erythrocyte sedimentation rate were significantly higher in patients with Behcet’s disease. All of these parameters except circulating endothelial cells were also found to be higher in patients with active disease than in patients with inactive disease. Early endothelial progenitor cells showed significant correlations with C-reactive protein and circulating endothelial cells.Study limitations: The cross-sectional nature of the study and patient characteristics such as being under treatment, which can affect endothelial progenitor cells numbers.Conclusion: The increase in endothelial progenitor cells may play an essential role in the repair of endothelial injury in Behcet’s disease, especially in the active period of the disease. Thus, endothelial progenitor cells can indicate the disease activity. In addition, endothelial progenitor cells and circulating endothelial cells can be used as endothelial repair and injury markers for Behcet’s disease, respectively.     

Podoplanin expression in wound and hyperproliferative psoriatic epidermis: regulation by TGF-β and STAT-3 activating cytokines, IFN-γ, IL-6, and IL-22

Background

Podoplanin (PDPN)/T1α/aggrus/PA2.26 antigen, a transmembranous glycoprotein, is a well-known lymphatic endothelial marker. Recent evidence indicates that PDPN is also expressed in keratinocytes especially of sebaceous glands.

Objective

To verify expression-pattern and the regulatory mechanism of PDPN in human epidermal keratinocytes.

Methods

PDPN-expression pattern was analyzed in normal and psoriatic epidermis by immunostaining. The regulatory mechanism of PDPN-expression of keratinocytes by cytokines was analyzed using specific inhibitors, siRNA, and adenoviral shRNA of signaling pathways.

Results

In normal skin, PDPN was expressed on the basal cell layer of sebaceous glands and on the outer root sheath of hair follicles. While no expression was detected in the normal interfollicular epidermis, PDPN was detected in the basal cell layer of wound and hyperproliferative psoriatic epidermis, where the granular layer is lacking. TGF-β1 and IFN-γ independently upregulated PDPN-expression of keratinocytes via TGF-β receptor-Smad pathway and JAK-STAT pathway, respectively. IL-6 and IL-22 also stimulated PDPN-expression of keratinocytes accompanied by STAT-3 phosphorylation. siRNA of STAT-1, inhibitors of STAT-3 signaling, AG490, STAT-3 inhibitor VI, and si/shRNA of STAT-3 inhibited the PDPN-expression of keratinocytes induced by IFN-γ, IL-6 and IL-22 but not by TGF-β1.

Conclusion

These results indicate that TGF-β1, IFN-γ, IL-6, and IL-22 induce PDPN-expression of keratinocytes, which might be significantly involved in the wound healing process as well as in the pathomechanism of hyperproliferative psoriatic epidermis.     

Willingness to pay and time trade-off: sensitive to changes of quality of life in psoriasis patients?

BACKGROUND: Willingness to pay (WTP) and time trade-off (TTO) have been used successfully as quality of life (QOL) measurements in dermatology. However, until now there have been no studies available individually comparing these measures pre- and post-treatment. OBJECTIVES: To check sensitivity to changes for WTP and TTO (i). pre- to post-treatment, and (ii). to a 6-month follow-up period. METHODS: We performed a prospective multicentre study in outpatients with psoriasis vulgaris treated with synchronous balneo-phototherapy (simultaneous application of narrowband ultraviolet B and bathing in 10% Dead Sea salt solution). Besides WTP and TTO, the Psoriasis Disability Index (PDI) and the Psoriasis Area and Severity Index (PASI) were monitored. RESULTS: One hundred and ninety-four patients participated in the pretreatment survey, of whom 138 (71%; 84 men, 54 women; mean age 43.9 years) also returned the post-treatment questionnaire. WTP (percentage of monthly income) was shown to be independent of patients' income. During treatment, mean +/- SD WTP fell from 13.8 +/- 19.2% to 11.5 +/- 15.9% (relative improvement 16.7%; P < 0.05), TTO (h per day) from 2.7 +/- 3.8 to 2.3 +/- 3.6 (relative improvement 15%; P < 0.001), PDI improved from 29.8 +/- 18.6 to 23.5 +/- 18.9 (relative improvement 21.1%; P < 0.001) and PASI (available for 113 patients) from 14.9 +/- 7.7 to 5.6 +/- 5.0 (relative improvement 62.4%; P < 0.001). Changes in WTP, PDI and PASI were statistically significantly correlated. Ninety-one of 138 patients (66%) also completed a third survey after a follow-up period: no further changes in PDI, WTP and TTO were found, indicating a stable QOL post-treatment. CONCLUSIONS: Correlation analysis indicated that WTP, assessed as percentage of monthly income, seems to be an appropriate way to measure QOL, unbiased by income of patients. WTP, TTO and PDI were correlated and were sensitive to changes during treatment. WTP and TTO therefore also seem to be appropriate tools for assessment of QOL in interventional studies, especially for pharmacoeconomic analyses.     

Assessment of serum homocysteine, endothelin-1, and nitric oxide levels in behçet's disease

Background:

Some prominent features of Behçet’s disease (BD) are arterial and venous thromboses as a result of endothelial dysfunction. Hyperhomocysteinemia is responsible for vascular endothelial injury due to an increased frequency of thrombogenesis. Endothelin-1 (ET-1) is a vasoconstrictor whereas nitric oxide (NO) is an endothelial vasorelaxing peptide that is responsible for the inhibition of platelet adhesion.

Aim:

To evaluate serum levels of homocysteine (Hcy) and determine whether hyperhomocysteinemia is considered as a contributing risk factor for venous and arterial thromboses of BD, and to correlate serum levels of ET-1 and NO with disease activity.

Materials and Methods:

We measured serum levels of Hcy, ET-1, and nitrite (NO₂⁻) in 25 patients who fulfilled the criteria of the International Study Group for BD, and compared them to those of 15 healthy control subjects. Levels of Hcy and ET-1 were measured by using enzyme-linked immunosorbent assay (ELISA), whereas serum nitrite (NO₂⁻) levels were measured by using Griess reaction as an indicator for NO production. All the patients were screened for a history of venous thrombosis and subdivided into thrombotic and nonthrombotic subgroups according to their thrombotic history. Patients with BD were divided into two subgroups, active and inactive, according to their clinical and laboratory findings.

Results:

There were significant increases in serum levels of Hcy, ET-1, and nitrite in BD patients compared to those in controls. There was a significant increase in serum Hcy levels in thrombotic compared to nonthrombotic subgroups. Positive correlations were detected between the serum ET-1 and nitrite levels with disease activity in BD patients.

Conclusion:

Hyperhomocysteinemia may play some role in the development of venous and arterial thromboses in BD. Increased NO production might ave critical biological activities that are relevant to pathological events in the active period of the disease.     

Coexistence of bullous pemphigoid, vitiligo, and thyroid disease: a multiple autoimmune syndrome?

Bullous pemphigoid is the most common autoimmune blistering skin diseases. The significance of the association of bullous pemphigoid with other autoimmune diseases is still unknown. There have been reports of an association with many autoimmune skin diseases. We report the simultaneous occurrence of bullous pemphigoid and thyroid disease in a 76-year-old patient who also suffered from vitiligo. It is possible that there is a common underlying pathogenic mechanism involved in the co-existence of these three diseases. The association adds to the documentation of bullous pemphigoid co-existing with other autoimmune disorders. This association is probably not fortuitous and suggests a pathogenic relationship.     

The focal nature of Darier's disease lesions: calcium pumps, stress, and mutation?

Haploinsufficiency of the ATP2A2 gene product, SERCA2, underlies most cases of Darier's disease. Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase isoform 2 (SERCA2) is an intracellular Ca2+ pump that replenishes ER Ca2+, and it seems likely that the disease manifests in stress-induced lesions because SERCA levels become limiting as extra demands are made on the pump in times of stress. However, Müller and colleagues (2006) present a radical new proposal invoking somatic mutation as the basis for Darier lesions. Using a novel animal model for depleted keratinocyte SERCA-gated Ca2+ stores, the authors show that keratinocytes from Darier-like lesions retain their distinctive phenotype after culture, suggesting heritable defects. Mechanistically linking stress, calcium levels, mutation, and disease pathogenesis is complicated, and the proposal is likely to be controversial. However, recent reports of age- and stress-dependent tumor formation in the mouse model for SERCA2 haploinsufficiency (ATP2A2 heterozygous mouse) support the proposal that deficiency in SERCA-gated ER Ca2+ replenishment may be linked to mutation accumulation.