Nonlesional Skin (nonlesional + skin)

Distribution by Scientific Domains


Selected Abstracts


Modulation of the atopy patch test: tacrolimus 0.1% compared with triamcinolone acetonide 0.1%

ALLERGY, Issue 5 2006
J. M. Oldhoff
Background:, The atopy patch test (APT) is an in vivo model to study the induction of eczema by inhalant allergens in atopic dermatitis patients. We studied the effect of pretreatment with topical tacrolimus 0.1% on APT in nonlesional skin of patients with atopic dermatitis. Methods:, Nonlesional skin of the back of patients with atopic dermatitis (n = 8) was treated once daily for 3 weeks with tacrolimus 0.1% ointment. Cetomacrogol ointment (placebo) was used as a negative control and triamcinolone acetonide 0.1% ointment as positive control. Twenty-four hours after the last APT application, samples were taken from the three treated areas (t = 0 and 24 h) for immunohistochemical analysis. Results:, Pretreatment with tacrolimus ointment did not suppress nonlesional skin infiltrate, in contrast to triamcinolone acetonide. Furthermore, tacrolimus did not inhibit the induction of the APT macroscopically (t = 24 h). An equal influx of T cells, eosinophils, dendritic cells, CD64+ and Fc,RI-positive cells was present compared with placebo. Only CD36+ and CD68-positive cells were inhibited compared with placebo. All cell types were significantly inhibited in triamcinolone acetonide-treated sites compared with placebo. Conclusions:, Pretreatment with tacrolimus 0.1% ointment does not inhibit the APT reaction in patients with atopic dermatitis. [source]


Temperature modulated histamine-itch in lesional and nonlesional skin in atopic eczema , a combined psychophysical and neuroimaging study

ALLERGY, Issue 1 2010
F. Pfab
Abstract Background: Itch is the major symptom of many allergic diseases; yet it is still difficult to measure objectively. The aim of this study was to use an evaluated itch stimulus model in lesional (LS) and nonlesional (NLS) atopic eczema (AE) skin and to characterize cerebral responses using functional magnetic resonance imaging (fMRI). Methods: Thermal modulation was performed on a histamine stimulus in randomized order on LS or NLS in rapid alternating order from 32°C (warm) to 25°C (cold). Subjective itch ratings were recorded. Additionally, fMRI measurements were used to analyze the cerebral processing (n = 13). Healthy skin (HS) of age-matched volunteers served as control (n = 9). Results: Mean VAS itch intensity was significantly (P < 0.0001) higher during the relative cold [55.2 ± 8.3% (LS); 48.6 ± 8.2% (NLS)] compared to the relative warm blocks [36.0 ± 7.3% (LS); 33.7 ± 7.6% (NLS)]. Compared to HS, the itch response was delayed in LS and NLS. Itch intensity was perceived highest in LS, followed by NLS and HS. For NLS, fMRI revealed at the beginning of the itch provocation a cerebral deactivation pattern in itch processing structures (thalamus, prefrontal, cingulate, insular, somatosensory and motor cortex). During the course of stimulation, the cerebral deactivation was reduced with time and instead an activation of the basal ganglia occurred. In contrast LS showed an activation instead of deactivation pattern already at the beginning of the stimulation in the above mentioned structures. Conclusions: Moderate short-term temperature modulation led to a reproducible, significant enhancement of histamine-induced itch with the strongest effect in LS. The differences in itch perception and itch kinetics between healthy volunteers and NLS in patients point towards an ongoing central inhibitory activity patients with AE, especially at the beginning of the itch provocation. [source]


Modulation of the atopy patch test: tacrolimus 0.1% compared with triamcinolone acetonide 0.1%

ALLERGY, Issue 5 2006
J. M. Oldhoff
Background:, The atopy patch test (APT) is an in vivo model to study the induction of eczema by inhalant allergens in atopic dermatitis patients. We studied the effect of pretreatment with topical tacrolimus 0.1% on APT in nonlesional skin of patients with atopic dermatitis. Methods:, Nonlesional skin of the back of patients with atopic dermatitis (n = 8) was treated once daily for 3 weeks with tacrolimus 0.1% ointment. Cetomacrogol ointment (placebo) was used as a negative control and triamcinolone acetonide 0.1% ointment as positive control. Twenty-four hours after the last APT application, samples were taken from the three treated areas (t = 0 and 24 h) for immunohistochemical analysis. Results:, Pretreatment with tacrolimus ointment did not suppress nonlesional skin infiltrate, in contrast to triamcinolone acetonide. Furthermore, tacrolimus did not inhibit the induction of the APT macroscopically (t = 24 h). An equal influx of T cells, eosinophils, dendritic cells, CD64+ and Fc,RI-positive cells was present compared with placebo. Only CD36+ and CD68-positive cells were inhibited compared with placebo. All cell types were significantly inhibited in triamcinolone acetonide-treated sites compared with placebo. Conclusions:, Pretreatment with tacrolimus 0.1% ointment does not inhibit the APT reaction in patients with atopic dermatitis. [source]


Expression of p53 in lesions and unaffected skin of patients with plaque-type and guttate psoriasis: A quantitative comparative study

THE JOURNAL OF DERMATOLOGY, Issue 6 2007
Ayça Cordan YAZICI
ABSTRACT Psoriasis is a common inflammatory and hyperproliferative skin disease characterized by hyperproliferation of keratinocytes. The pathogenesis of psoriasis has yet to be determined. The control of cell growth is a delicately balanced process, regulated by external signals or the internal genetic program of an individual cell. In psoriasis, these processes are disturbed and some candidate genes like p53 are suspected of being involved in the pathogenesis of the disease. The p53 protein is essential for the regulation of cell proliferation. The study was performed on 32 patients with psoriasis (24 plaque type, eight guttate type). Biopsy specimens for immunohistochemical determination of p53 protein expression were collected from both the lesional and the nonlesional skin sites that were not exposed to sun in all of the patients (n = 32). Taking the ultraviolet (UV) exposure of the skin into consideration, a third skin sample was taken from each patient (n = 7) who had lesions on the sun-exposed areas. Immunohistochemical assessment of p53 expression in skin was determined as p53 protein expression per 1000 cells (keratinocytes). The statistical analysis revealed that the expressions of p53 per 1000 cells were higher in non-sun-exposed lesional skin than the non-sun-exposed nonlesional skin, also in plaque-type psoriasis than guttate-type psoriasis (P = 0.000, P = 0.046, P = 0.037, respectively). There was a positive correlation between the p53 expression in non-sun-exposed lesional skin versus expression in sun-exposed lesional skin (cubic centimeters = 0.811, P = 0.027). Our results show a stronger association of elevated p53 expression with chronic rather than acute inflammatory psoriasis. This may indicate a mechanistic difference between plaque-type and guttate psoriasis. Alternatively, this could reflect a chronological course as the disease transitions from an acute to a chronic phase. [source]


Lesional and nonlesional skin from patients with untreated juvenile dermatomyositis displays increased numbers of mast cells and mature plasmacytoid dendritic cells

ARTHRITIS & RHEUMATISM, Issue 9 2010
Sheela Shrestha
Objective To investigate the distribution of mast cells and dendritic cell (DC) subsets in paired muscle and skin (lesional/nonlesional) from untreated children with juvenile dermatomyositis (DM). Methods Muscle and skin biopsy samples (4 skin biopsy samples with active rash) from 7 patients with probable/definite juvenile DM were compared with muscle and skin samples from 10 healthy pediatric controls. Mast cell distribution and number were assessed by toluidine blue staining and analyzed by Student's t -test. Immunohistochemical analysis was performed to identify mature DCs, myeloid DCs (MDCs), and plasmacytoid DCs (PDCs) by using antibodies against DC-LAMP, blood dendritic cell antigen 1 (BDCA-1), and BDCA-2, respectively. Myxovirus resistance protein A (MxA) staining indicated active type I interferon (IFN) signaling; positive staining was scored semiquantitatively and analyzed using the Mann-Whitney U test. Results Both inflamed and nonlesional skin from patients with juvenile DM contained more mast cells than did skin from pediatric controls (P = 0.029), and comparable numbers of mast cells were present in lesional and nonlesional skin. Interestingly, mast cell numbers were greater in skin than in paired muscle tissue from patients with juvenile DM (P = 0.014) and were not increased in muscle from patients with juvenile DM compared with control muscle. Both muscle and skin from patients with juvenile DM showed more mature PDCs and MxA staining than did their corresponding control tissues (P < 0.05). In both muscle and skin from patients with juvenile DM and in pediatric control muscle, there were fewer MDCs than PDCs, and the distributions of MDCs and PDCs were similar in pediatric control skin samples. Conclusion The identification of mast cells in skin (irrespective of rash) from patients with juvenile DM, but not in paired muscle tissue, suggests that they have a specific role in juvenile DM skin pathophysiology. In skin from patients with juvenile DM, increased numbers of PDCs and increased expression of type I IFN,induced protein suggest a selective influence on T cell differentiation and subsequent effector function. [source]


Comparison of skin barrier function and sensory nerve electric current perception threshold between IgE-high extrinsic and IgE-normal intrinsic types of atopic dermatitis

BRITISH JOURNAL OF DERMATOLOGY, Issue 1 2010
T. Mori
Summary Background, Two types of atopic dermatitis (AD) have been proposed, with different pathophysiological mechanisms underlying this seemingly heterogeneous disorder. The extrinsic type shows high IgE levels presumably as a consequence of skin barrier damage and feasible allergen permeation, whereas the intrinsic type exhibits normal IgE levels and is not mediated by allergen-specific IgE. Objectives, To investigate the relationship between pruritus perception threshold and skin barrier function of patients with AD in a comparison between the extrinsic and intrinsic types. Methods, Enrolled in this study were 32 patients with extrinsic AD, 17 with intrinsic AD and 24 healthy individuals. The barrier function of the stratum corneum was assessed by skin surface hydration and transepidermal water loss (TEWL), and pruritus perception was evaluated by the electric current perception threshold (CPT) of sensory nerves upon neuroselective transcutaneous electric stimulation. Results, Skin surface hydration was significantly lower and TEWL was significantly higher in extrinsic AD than intrinsic AD or normal controls. Although there was no statistically significant difference in CPT among extrinsic AD, intrinsic AD and normal controls, CPT was significantly correlated with skin surface hydration and inversely with TEWL in intrinsic AD and normal controls, but not extrinsic AD. Finally, CPT was correlated with the visual analogue scale of itch in the nonlesional skin of patients with extrinsic but not intrinsic AD. Conclusions, Patients with extrinsic AD have an impaired barrier, which increases the pre-existing pruritus but rather decreases sensitivity to external stimuli. In contrast, patients with intrinsic AD retain a normal barrier function and sensory reactivity to external pruritic stimuli. [source]


Interleukin-20 plays a critical role in maintenance and development of psoriasis in the human xenograft transplantation model

BRITISH JOURNAL OF DERMATOLOGY, Issue 2 2009
K. Stenderup
Summary Background, Interleukin (IL)-20 is a recently discovered cytokine displaying increased levels in psoriatic lesions. Interestingly, IL-20 levels decrease with antipsoriatic treatment, correlating with clinical improvement. However, the role of IL-20 in the aetiology of psoriasis is unknown. Objectives, In this study, we investigate the effects both of blocking IL-20 signalling in psoriatic plaques and of adding IL-20 to nonlesional psoriasis skin. Methods, We employed the human skin xenograft transplantation model in which psoriatic plaques and nonlesional keratome skin biopsies obtained from donors with moderate to severe plaque psoriasis were transplanted on to immuno-deficient mice. The transplanted mice were treated with anti-IL-20 antibodies or recombinant human IL-20. Results, We demonstrate that blocking IL-20 signalling with anti-IL-20 antibodies induces psoriasis resolution and inhibits psoriasis induction. We also demonstrate that continuous IL-20 infusion, together with injection of additional nonactivated leucocytes, promotes induction of psoriasis in nonlesional skin from patients with psoriasis. Conclusions, The results suggest that IL-20 plays a critical role in the induction and maintenance of psoriasis, and IL-20 is suggested as a new possible specific target in psoriasis treatment. [source]


Reduced expression of nicotinic , subunits 3, 7, 9 and 10 in lesional and nonlesional atopic dermatitis skin but enhanced expression of , subunits 3 and 5 in mast cells

BRITISH JOURNAL OF DERMATOLOGY, Issue 4 2008
F. Kindt
Summary Background, The skin cholinergic signalling system is modulated in atopic dermatitis (AD). Objectives, To investigate of the role of nicotinic acetylcholine receptors (nAChRs) in the pathogenesis of AD. Methods, We investigated the expression and localization of nAChR , subunits in AD by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry of biopsies from lesional and nonlesional areas of AD skin and of skin biopsies from healthy control persons. Results, Our data demonstrate the presence of mRNA and protein of the nAChR , subunits 3, 5, 7, 9 and 10 in keratinocytes and mast cells in healthy and AD skin. Expression of the , subunits 3, 7, 9 and 10 was generally reduced in the skin of patients with AD whereas mast cells in AD but not in healthy skin showed ,3 and ,5 subunit immunoreactivity. Differences in the subunit mRNA levels between lesional and nonlesional skin were obtained for the , subunits 3, 9 and 10 with higher levels of ,3 but lower levels of ,10 subunit mRNA in lesional areas. No differences in the expression of the , subunits was found between the groups of extrinsic, intrinsic or mixed AD types, between genders and between smokers and nonsmokers. Conclusions, This supports the idea that the cholinergic system is dysregulated independently from inflammation in AD and that inflammation further modulates individual nAChR subunits. [source]


Microarray analysis of aberrant gene expression in actinic keratosis: effect of the Toll-like receptor-7 agonist imiquimod

BRITISH JOURNAL OF DERMATOLOGY, Issue 6 2007
A. Torres
Summary Background, The molecular events leading to actinic keratosis (AK) are not well understood. Objective, To identify and compare gene expression changes in AK lesions and in sun-exposed nonlesional skin and to determine the effect of imiquimod 5% cream on these changes. Method, A double-blind, vehicle-controlled, randomized study was conducted to evaluate the molecular changes in AK treated with imiquimod. Seventeen male subjects with , 5 AK lesions on the scalp applied vehicle or imiquimod three times a week for 4 weeks. Gene expression analysis using Affymetrix® oligonucleotide arrays was performed on shave biopsies of lesions taken before and after treatment. Confocal microscopy was performed on the study area as an adjunctive diagnostic procedure. Results, We identified gene expression changes which occur in sun-exposed, nonlesional skin as well as in AK lesions. These changes include, but are not limited to, the overexpression of oncogenic and proliferative genes and diminished expression of tumour suppressor genes. The gene expression changes observed in AK lesions and in sun-exposed, nonlesional skin were consistent with the confocal microscopy observations, which showed abnormalities in the sun-exposed, nonlesional skin, similar in nature but less pronounced than abnormalities seen in AK. Imiquimod partially or totally reversed the aberrant expression of some of the genes observed in AK, consistent with clearing of lesions and normalization of confocal cellular images. Conclusions, The data show that profound gene expression changes occur in sun-exposed, nonlesional skin which progress further in AK lesions. The data also suggest that imiquimod may play a role in normalizing gene expression and cellular morphology in sun-damaged skin. [source]


Perforin expression is upregulated in the epidermis of psoriatic lesions

BRITISH JOURNAL OF DERMATOLOGY, Issue 4 2004
M. Ka, telan
Summary Background, There are currently very few data regarding the role of cell-mediated cytotoxicity in psoriasis. Both cytotoxic T lymphocytes and natural killer (NK) cells mediate cytotoxicity reactions, mainly by two distinct pathways, the perforin/granzyme and the Fas/Fas ligand pathway. Objectives, To study the expression and distribution of perforin, T- and NK-cell subsets in psoriatic lesional and nonlesional skin. Methods, Skin biopsy specimens from both lesional and nonlesional skin of 11 patients with chronic plaque psoriasis and eight healthy controls were analysed by immunohistochemistry. Results, We found a significant increase in CD4+ and CD8+ cells in psoriatic lesions compared with nonlesional and healthy skin. The expression of CD16+ NK cells was significantly lower in lesions compared with healthy skin. Perforin expression was significantly enhanced in the epidermis of psoriatic lesions. Conclusions, Perforin expression is upregulated in the epidermis of psoriatic lesions, suggesting a potential role for perforin in the creation of the psoriatic plaque. [source]


Immunophenotyping of inflammatory cells in lesional skin of the extrinsic and intrinsic types of atopic dermatitis

BRITISH JOURNAL OF DERMATOLOGY, Issue 1 2004
N-K. Rho
Summary Background There is a subgroup of atopic dermatitis (AD) patients with normal total and specific IgE levels and negative skin tests towards common allergens. This form of the disease has been referred to as the ,intrinsic' form of AD. Although previous studies have demonstrated differences in the cytokine profile between the extrinsic and intrinsic subtypes, the pathogenesis of both subtypes of AD remains unclear. Objectives To compare the inflammatory micromilieu in both forms of AD. Methods Immunophenotyping of the inflammatory cells was performed in lesional and nonlesional skin from 18 patients with extrinsic and 17 with intrinsic AD. Results Immunohistochemical analysis revealed a high proportion of CD4+ T cells in the dermis, with a similar CD4/CD8 ratio in the two groups. The expression levels of other T-cell markers and epidermal Langerhans cells were increased in both forms of AD. Although the T-cell repertoires in the two subtypes were similar, dermal infiltration of eosinophils and eosinophil granular proteins was more prominent in the extrinsic type than in the intrinsic type. Eotaxin immunoreactivity was also significantly higher in the extrinsic subtype. Conclusions The data suggest that although the overall inflammatory microenvironment in the two subtypes appears to be similar, differences in T-cell cytokine production might contribute to the differential tissue eosinophilia in these subtypes. [source]


Immunohistochemical investigation of mid-dermal elastolysis

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 2 2004
T. Gambichler
Summary We report a 31-year-old Caucasian woman presenting with remarkable wrinkling on her trunk and proximal extremities. Diagnosis of mid-dermal elastolysis (MDE) was confirmed by Van Gieson's staining. Immunohistochemical investigations revealed enhanced expression of CD34+ and CD68+ cells accompanied by slightly increased expression of CD3+ and CD4+ lymphocytes in lesional skin. Furthermore an elevated cellular expression of matrix metalloproteinase (MMP)-1 and slightly increased presence of MMP-12 positive cells combined with a decrease of tissue inhibitor of metalloproteinases 1 (TIMP-1) positive cells was observed in lesional skin as compared with a control specimen obtained from nonlesional skin. Our data may indicate inflammatory processes and an altered balance between MMPs and TIMPs in MDE. Furthermore CD34+ dendritic fibroblasts and/or histiocytes are possibly involved in the pathogenesis of MDE. [source]