Interleukin-1 Gene Polymorphisms and their Relation with NFκB Expression and Histopathological Features in Psoriasis

Background:

Psoriasis is a chronic inflammatory disease driven by exaggerated production of pro-inflammatory cytokines and interleukins. Various genetic polymorphisms including IL-1 are implicated in pathogenesis of psoriasis. The exact role of IL-1 gene polymorphisms and their interaction with NFκB is not yet determined. We aimed to study various genetic polymorphisms of IL-1 in psoriasis and their influence on NFκB and histopathological features.

Materials and Methods:

112 newly diagnosed cases of psoriasis vulgaris were included in this prospective study. Histology was done on sections and genotyping was done for the IL-1β and IL-1 receptor antagonist (IL-1RA) genetic polymorphisms. In addition, NFκB immunostaining was performed on 89 sections and the intensity of staining was evaluated in the epidermis, basal cells, and the lymphocytes.

Results:

A strong association of IL-1β 511 C/T polymorphism was found with both genotypes and alleles in psoriasis. A strong correlation was also detected between the IL-1β genotype and the grade of NFκB immunostaining in the epidermis (P = 0.012). The grade of NFκB lymphocyte staining showed a strong correlation with the IL-1RA genotype (P = 0.025) but not with the IL-1β genotype (P = 0.226). The genetic polymorphisms did not show any correlation with the histological features.

Conclusions:

IL-1 genetic polymorphisms may not play a very direct role in pathogenesis of psoriasis. However, their interaction with NFκB appears to be a significant factor in this direction as NFκB is activated by pro-inflammatory genetic polymorphisms and therefore may influence the severity of psoriasis.     

A Comprehensive Study of Tumor Necrosis Factor-Alpha Genetic Polymorphisms,its Expression in Skin and Relation to Histopathological Features in Psoriasis

Background:

Tumor necrosis factor-alpha (TNFα) is an important inflammatory mediator in psoriasis and several genetic polymorphisms of this cytokine have been reported. Majority of studies have focused on the increased G– A polymorphism at the –308 position in psoriasis. There has been no comprehensive study evaluating the genetic polymorphisms, TNFα expression in the skin and histopathology. We are undertaking this study to outline TNFα genetic polymorphisms, its skin expression and histopathological correlation to help determine its role at the genetic and protein level.

Materials and Methods

112 patients of psoriasis and 243 healthy controls were included in this prospective study. 5 ml of peripheral blood was collected to study the TNFα genetic polymorphisms by polymerase chain reaction and restriction fragment length polymorphism analysis. Histopathological analysis of biopsies from the 112 patients were done using visual analogue scale and correlated with the findings. 61 of these cases were analyzed for TNFα expression by immunohistochemistry. The results of study were statistically analyzed using SPSS 13.0 statistical package program.

Results:

A strong association of TNFα –308 G/A polymorphism in psoriasis cases was detected. The A allele of the TNFα –308 G/A polymorphism occurs rarely in the Indian population, however there is an over representation of this allele in psoriatic patients. There was no association seen between TNFα genotype and histopathological severity of psoriasis.

Conclusion:

The study emphasized the central role of TNFα in the pathogenesis of psoriasis. TNFα genotyping may be helpful in identifying subjects in whom anti-TNFα therapeutic strategies may be tried.     

Prevalence of Metabolic Syndrome In South Indian Patients with Psoriasis Vulgaris and the Relation Between Disease Severity and Metabolic Syndrome: A Hospital-Based Case-Control Study

Background:

Psoriasis is a chronic inflammatory disease of the skin and joints with an increased cardiovascular risk. Previous studies have shown a higher prevalence of metabolic syndrome (MS) in psoriatic patients.

Objective:

To investigate the prevalence of MS in patients with psoriasis and healthy controls, and to determine the relation between disease severity and the presence of MS.

Materials and Methods:

We performed a hospital-based case-control study on 118 adult patients with psoriasis vulgaris and 120 controls matched for age, sex and body mass index. MS was diagnosed by the presence of three or more of the South Asian Modified National Cholesterol Education Program''s Adult Panel III criteria.

Results:

MS was significantly more common in psoriatic patients than in controls (44.1% vs. 30%, P value = 0.025). Psoriatic patients also had a higher prevalence of triglyceridemia (33.9% vs. 20.8%, P value = 0.011), abdominal obesity (34.7% vs. 32.5%, P value = 0.035) and elevated blood sugar. There was no difference in the high density lipoprotein (HDL) levels and presence of hypertension among patients with psoriasis and normal controls. There was no correlation between the severity and duration of psoriasis with MS.

Conclusion:

MS is frequent in patients with psoriasis. We have found no relationship between disease severity and presence of MS. Hence, we suggest that all patients must be evaluated for the MS, irrespective of the disease severity.     

Immunomodulatory Mechanisms of Action of Calcitriol in Psoriasis

Background:

Calcitriol is well known for its therapeutic efficacy in psoriasis, but its mechanism of action is still unclear. In this study, we tried to elucidate the precise mechanism of calcitriol for its therapeutic efficacy in psoriasis.

Materials and Methods:

Proliferation and apoptosis studies were done to determine the effect of calcitriol on normal human epidermal keratinocytes (NHEKs) and T lymphocytes. To elucidate the effect of Calcitriol on relevant chemokines and epidermal proteins of psoriasis, real-time polymerase chain reaction were done on the modified reconstructed human epidermis (RHE) an in vitro model of psoriasis. All experiments were done in triplicate. Results were expressed as mean ± standard error of mean.

Results and Conclusions:

In vitro, Calcitriol showed significant inhibition of NHEKs and T lymphocyte proliferation by inducing apoptosis of these cells. Moreover, in an in vitro model of psoriasis (RHE), Calcitriol significantly inhibited relevant gene expression of chemokines (Interleukin-8, Regulated upon Activation Normal T-cell Expressed and Secreted [RANTES]) and psoriasin (S100A7). Here, we observed that Calcitriol inhibits critical pathological events associated with the inflammatory-proliferative cascades of psoriasis. Calcitriol induced apoptosis of NHEKs and T lymphocytes as well as inhibited gene expression of relevant chemokines and epidermal proteins in the in vitro model of psoriasis.     

Zinc-responsive acral hyperkeratotic dermatosis—A novel entity or a subset of some well-known dermatosis?

Background:

We are reporting a series of interesting cases, which presented to us with psoriasiform lesions distributed over the acral regions of the body. The cases are unusual because they were resistant to conventional treatment modalities like topical corticosteroids, tacrolimus and oral methotrexate but showed significant improvement on oral zinc therapy.

Materials and Methods:

Ten patients with characteristic clinical features of distinctive hyperkeratotic plaque in the acral areas, who were resistant to treatment by different modalities including potent topical steroids and oral methotrexate, were included for detailed investigations. A proper history was taken and relevant laboratory investigations were done which included blood count, urine, liver function, renal function, hepatitis-C virus serology and serum zinc levels. Patients were followed up every 2 weeks. Histopathological examinations of the lesional tissue were done at baseline and after 6 weeks of therapy. Patients were given oral zinc daily and no other treatment during the 6 weeks course.

Results:

All our patients were non-reactive to hepatitis-C. Of the ten patients only one patient (10%) showed low titer of serum zinc, another (10%) showed higher zinc level, while the rest of the patients had normal zinc level. Five of our patients had chronic renal failure, one had Grave''s disease and the remaining had no associated systemic illness. Histopathology mostly showed hyperkeratosis, acanthosis, prominent granular layer, spongiosis and dermal infiltrate. After 6 weeks of follow up, all patients showed rapid and remarkable therapeutic response with zinc.

Conclusions:

We here report a series of patients, discernible because of their uniform clinical presentation of acral hypekeratotic plaques and in showing a noticeable response to zinc. Clinical, histopathological and laboratory investigations were done to rule out diseases of similar morphology including psoriasis, acral necrolytic erythema and lichen simplex chronicus. Authors understand that further studies with greater number cases and more detailed investigations are required to establish exact etio-pathogenesis and nomenclature of this distinct subset of patients.     

Apoptosis and Clinical Severity in Patients with Psoriasis and HCV Infection

Background:

It has been proposed that hepatitis C virus (HCV) antigens are involved in the pathogenesis of psoriasis and may contribute to severity of the disease. Increased expression of the apoptosis-regulating proteins p53 and tTG and decreased levels of bcl-2 in the keratinocytes of the skin of psoriatic patients have been reported.

Aim:

This study aims to identify the serum levels of apoptosis-regulating proteins in patients with psoriasis and without HCV infection and to study the relation between clinical severity of psoriasis and the presence of HCV infection.

Materials and Methods:

Disease severity was assessed by psoriasis area severity index score (PASI) of 90 patients with psoriasis grouped as mild (n = 30), moderate (n = 30) and severe (n = 30); 20 healthy individuals were used as controls. All groups were subjected for complete history taking, clinical examination, and tests for liver function and HCV infection. The serum levels of apoptosis related proteins: p53, tTG and bcl-2 were estimated by enzyme linked immune sorbent assay (ELISA).

Results:

There was a statistically significant (P < 0.001) correlation between clinical severity of psoriasis and presence of HCV antibodies and HCV-mRNA. In addition, significantly (P < 0.001) raised serum p53 and tTG, and reduced bcl-2 were observed among HCV-positive patients as compared to HCV-negative patients and control patients.

Conclusion:

These results conclude that clinical severity of psoriasis is affected by the presence of HCV antibodies and overexpression of apoptotic related proteins. In addition, altered serum levels of apoptosis-regulating proteins could be useful prognostic markers and therapeutic targets of psoriatic disease.     

Lichen Planus: A Clinical and Immuno-Histological Analysis

Background:

Direct immunofluorescence examination is an important technique in the diagnosis of cutaneous inflammatory disorders including lichen planus, especially in clinically and histopathological doubtful cases.

Objective:

To study the diagnostic utility of intensity, number, and subtypes of positive immuno-reactants found in lichen planus.

Materials and Methods:

A detailed analysis of clinical as well as immuno-histological features of lichen planus cases was carried out.

Results:

The male to female ratio was 1:1.1. The largest number of patients was in 31-50 year age group. Itching was the most common presenting symptom. Papular lesions were seen in 53% cases. Remaining had hypertrophic (6), follicular (3) and mucosal (9) variants. Clinico-pathological discrepancies were observed in 3 patients. The characteristic histopathological changes including basal cell vacuolization, band-like lymphocytic infiltrate at dermo-epidermal junction were seen in all the biopsies while Civatte bodies were detected in 29% cases. The overall positive yield of direct immunofluorescence microscopy was 55%. Immune deposits at Civatte bodies and dermo-epidermal junction were detected in 47% and 8% of cases, respectively. Immunoglobulin M was the most common immunoreactant followed by immunoglobulin G.

Conclusions:

There was no correlation found between the number and intensity of Civatte bodies with clinical variants of disease and also between the number of positive immunoreactants and clinical severity of the disease. The frequency, number, and arrangement of Civatte bodies in clusters in the papillary dermis as well as multiple immunoglobulins deposition at the Civatte bodies on direct immunofluorescence of skin biopsies are important features distinguishing lichen planus from other interface dermatitis.     

Evaluation of topical 0.1% tazarotene cream in the treatment of palmoplantar psoriasis: an observer-blinded randomized controlled study

Background:

Palmoplantar psoriasis is a frequently encountered variant of psoriasis. It is difficult to treat and even more difficult to maintain remission as it is exacerbated by friction and trauma of the patient''s daily activities. Existing topical modalities of treatment are often inadequate and show unpredictable response.

Aim:

To study the efficacy and safety of a newer retinoid, tazarotene, as 0.1% cream in the treatment of palmoplantar psoriasis.

Materials and Methods:

Thirty adult patients with palmo-plantar psoriasis were randomized to therapy with once daily application of topical tazarotene cream (0.1%) or once daily application of clobetasol propionate cream (0.05%) for 12 weeks. The patients were assessed every 2 weeks for improvement in Erythema, Scaling, Fissures and Induration (ESFI) score and Physicians Global Assessment Scale.

Results:

At 12 weeks, the tazarotene group showed mean ESFI reduction to 1.12 (83.2%) from 6.65 at baseline. Complete clearance was noted in 52.9% of the patients. Clobetasol propionate group showed mean ESFI reduction to 0.62 (89.1%) from 5.69 at baseline, with complete clearance in 61.5% of the patients. Differences between the two groups were statistically insignificant. Side effects observed were initial irritation (41%) in the tazarotene group and hypopigmentation (53.8%) in the steroid-treated patients.

Conclusion:

Tazarotene is as effective as clobetasol propionate and provides a good alternative for the treatment of palmo-plantar psoriasis where hypopigmentation limits the use of clobetasol propionate cream.     

Determinants of quality of life in psoriasis patients: a cluster analysis of 50 patients

Background:

Although psoriasis generally does not affect survival, it certainly has a number of major negative effects on patients, demonstrable by a significant detriment to quality of life.

Aims:

We have done a study with the objective of assessing the clinical variables adversely affecting quality of life in patients diagnosed with psoriasis.

Materials and Methods:

This study is a cluster analysis of 50 consecutive consenting patients with psoriasis, of both sexes, aged over 18 years, attending the dermatology outpatient department of a tertiary care center. We measured the clinical severity using psoriasis area severity index and health-related quality of life using psoriasis disability index (PDI). Statistical analysis was performed using unpaired independent student''s t-test, analysis of variance (and Scheffe''s post hoc test as appropriate) and Pearson''s correlation coefficients.

Results:

There was a significant correlation between the physician-rated severity of psoriasis and the extent of impact of psoriasis on physical disability as measured by the PDI. We have identified that a younger age at onset of disease and self-reported stress exacerbators suffer greater disability in most aspects of quality of life.

Conclusions:

On the basis of this study, we would recommend that psoriasis patients especially with severe disease require a more holistic treatment approach that encompasses both medical and psychological measures.     

PASI AND PQOL-12 SCORE IN PSORIASIS: IS THERE ANY CORRELATION?

Background:

Psoriasis, a common papulo-squamous disorder of the skin, is universal in occurrence and may interfere with the quality of life adversely. Whether extent of the disease has any bearing upon the patients’ psychology has not much been studied in this part of the world.

Aims:

The objective of this hospital-based cross-sectional study was to assess the disease severity objectively using Psoriasis area and severity index (PASI) score and the quality of life by Psoriasis quality-of-life questionnaire-12 (PQOL-12) and to draw correlation between them, if any.

Materials and Methods

PASI score denotes an objective method of scoring severity of psoriasis, reflecting not only the body surface area but also erythema, induration and scaling. The PQOL-12 represents a 12-item self-administered, disease-specific psychometric instrument created to specifically assess quality-of-life issues that are more important with psoriasis patients.PASI and PQOL-12 score were calculated in each patient for objectively assessing their disease severity and quality of life.

Results:

In total, 34 psoriasis patients (16 males, 18 females), of age ranging from 8 to 55 years, were studied. Maximum and minimum PASI scores were 0.8 and 32.8, respectively, whereas maximum and minimum PQOL-12 scores were 4 and 120, respectively. PASI and PQOL-12 values showed minimal positive correlation (r = +0.422).

Conclusion:

Disease severity of psoriasis had no direct reflection upon their quality of life. Limited psoriasis on visible area may also have greater impact on mental health.     

Pilot study of sexual dysfunction in patients with psoriasis: influence of biologic therapy

Background:

Psoriasis is a chronic skin disease that affects 1 to 3% of the population in most industrialized countries. It is commonly associated with a variety of psychological problems including low self-esteem, depression, suicidal thoughts, and sexual dysfunction.

Materials and Methods:

We have performed a pilot study in which we have tried to assess the impact on sexual dysfunction in patients with psoriasis who have started treatment with biological therapy using validated indexes in Spanish: International Index of Erectile Function for men and female sexual function index in women.

Results:

Considering the men and women from our study, an improvement in FSFI by an average of 9.5 and 6.3 points is observed, respectively.

Conclusion:

We considered our series as a first step for a more detailed approach to the study of sexual function in patients with psoriasis.     

Morphometry and epidermal fas expression of unexposed aged versus young skin

Background:

Identifying the molecular mechanisms of intrinsic aging is critical in developing modalities for reversal of cutaneous aging.

Objective:

The objective was to evaluate the expression of epidermal Fas, epidermal thickness, collagen, and elastic fibers degeneration in unexposed skin of aged individuals compared with young ones.

Materials and Methods:

Skin biopsies were taken from normal skin of the back of 22 old subjects (age range: 48-75 years) and 15 young subjects (age range: 18-28 years). Skin sections were stained with hematoxylin and eosin, Masson trichrome, orcein. Epidermal thickness was measured with image analyzer and scoring was done for collagen and elastic fiber degeneration. Fas immunostaining was done. Quantitative and qualitative data were compared statistically between the old and young subjects.

Results:

A statistically significant decreased epidermal thickness was found in old compared with young skin (P<0.05). A statistically significant number of patients showed decreased epidermal thickness, density, and fragmentation of both collagen and elastic fibers in old compared with young skin (P<0.001). Epidermal Fas expression was detected in 19 of 22 old subjects (86.4%) compared with 2 of 15 young subjects (13.3%) (P<0.001). There was no statistically significant correlation between age of old subjects and each of epidermal thickness, collagen, and elastic fiber degeneration.

Conclusion:

The decreased epidermal thickness and morphological alteration of collagen and elastic fibers are not correlated with aging and Fas-mediated apoptosis could be involved in thinning of the epidermis in unexposed aged skin.     

Dermal vasculature in psoriasis and psoriasiform dermatitis: a morphometric study

Background:

Vascular proliferation in the papillary dermis is considered to be an important and probably an early feature of psoriasis. Few morphometric studies have attempted to analyze the vascular changes. However, no study was found in the available literature comparing vascular changes between psoriasis and psoriasiform dermatitis.

Materials and Methods:

Skin biopsies from 25 cases each of psoriasis and psoriasiform lesions were immunohistochemically stained for CD34 (endothelial marker). Microvessel density (MVD), microvessel length density and ratio of microvessel area to papillary dermal area were calculated using image analysis software.

Results:

Skin biopsies from psoriasis showed higher staining for CD34 on light microscopy. Using morphometric techniques, microvessel length density was significantly higher in psoriasis compared to psoriasiform lesions (P value <0.05). MVD was also higher in psoriasis, though the difference was not significant. The ratio of microvessel area to dermal area was almost similar in both the groups.

Conclusion:

Our results indicate that vascular tortuousity and dilatation is significant only in psoriatic lesions. These results may assist in automated diagnosis of skin biopsies.     

Genital/Perigenital Inflammatory Linear Verrucous Epidermal Nevus: A Case Series

Background:

Inflammatory linear verrucous epidermal nevus (ILVEN) is a distinct variety of keratinocytic epidermal naevus. In contrast to non-inflammatory epidermal naevi, ILVEN are far less common, usually erythematous and intractably pruritic. ILVEN usually appears at birth or early childhood and has a linear distribution following the Blaschko lines. Genital/perigenital involvement is relatively rare.

Objectives:

To describe the clinical features of 9 children with ILVEN localized to the genital and perigenital areas.

Method:

A retrospective study of 9 children with ILVEN presenting to a tertiary care Dermatology Clinic between 2007 and 2014 was undertaken. The clinical and histopathological features were reviewed.

Results:

Nine children (6 females, 3 males) were included in the study based on their characteristic clinicopathological features. The lesions were associated with severe itching in all cases. The mean age at presentation was 4 years (range 1-11 years). Onset of lesions was before 6 months of age in 8 patients. Left sided involvement was twice as common as the right sided one. Male patients had penoscrotal and groin involvement while all the female children had vulvar lesions. None of the children had any extracutaneous abnormalities. The children were treated with topical agents with variable relief or symptoms.

Conclusions:

The possibility of ILVEN should be considered in every linear genital lesion in children. We have presented the largest series of perigenital ILVEN reported in English literature.     

Spectrum of non-infectious erythematous, papular and squamous lesions of the skin

Background:

Dermatopathologists base their diagnostic approach on the tissue reaction pattern. This study mainly includes the interpretation of two major tissue reaction patterns, the psoriasiform and the lichenoid reactions, with clinicopathological correlation.

Aims:

To analyze the spectrum of non-infectious erythematous papular and squamous lesions of the skin at our institute, study the age, sex and anatomic distribution pattern and classify the lesions into major categories; determine the incidence of each subcategory.

Materials and Methods:

Study period: two years; prospective, sample size: 161 cases, proforma filled.

Results:

The lesions comprised 15.80% of the total load of surgical pathology and 30.99% of total number of skin biopsies. The highest percentage was in the 30-40 year age group (28.6%) with a male preponderance of 60.25%. The extremities were most frequently involved (67.79%). Lichenoid lesions were the commonest (46.57%) with lichen planus 26.7% and psoriasis vulgaris-19.88% being the most frequent. There were 5.6% seropositive cases. Correlation with the histopathological diagnosis was positive in 97.52% cases and negative in 2.48% cases.

Conclusion:

The contribution of histopathology to the final diagnosis was significant. It confirmed the diagnosis in 92.55% and gave the diagnosis in 4.97% cases.     

Hla-a and hla-B alleles associated in psoriasis patients from mumbai, Western India

Background:

Psoriasis, a common autoimmune disorder characterized by T cell-mediated keratinocyte hyperproliferation, is known to be associated with the presence of certain specific Human Leukocyte Antigen (HLA) alleles.

Aim:

To evaluate distribution of HLA-A and HLA-B alleles and hence identify the susceptible allele of psoriasis from patients in Western India.

Materials and Methods:

The study design included 84 psoriasis patients and 291 normal individuals as controls from same geographical region. HLA-A and HLA-B typing was done using Serology typing. Standard statistical analysis was followed to identify the odds ratio (OR), allele frequencies, and significant P value using Graphpad software.

Results:

The study revealed significant increase in frequencies of HLA-A2 (OR-3.976, P<0.0001), B8 (OR-5.647, P<0.0001), B17 (OR-5.452, P<0.0001), and B44 (OR-50.460, P<0.0001), when compared with controls. Furthermore, the frequencies of HLA-A28 (OR-0.074, P=0.0024), B5 (OR-0.059, P<0.0001), B12 (OR-0.051, P=0.0002), and B15 (OR-0.237, P=0.0230) were significantly decreased in psoriasis patients.

Conclusion:

This study shows the strong association of HLA-A2, B8, and B17 antigens with psoriasis conferring susceptibility to psoriasis patients from Western India, while the antigens HLA-A28, B5, and B12 show strong negative association with the disease.     

Plantar warts treated with topical adapalene

Background:

Treatment of plantar warts caused by human papilloma virus (HPV) strain types 1, 2 and 4 is often difficult and a challenging problem. Various therapeutic modalities available for treating this problem have not been uniformly successful.

Purpose:

The purpose of present study is to evaluate the efficacy of adapalene applied locally with occlusion in plantar warts.

Materials and Methods:

A total of 10 patient with 118 plantar warts were included in an open study. All were treated by applying adapalene gel 0.1% after paring of warts if needed followed by occlusive dressing with polythene paper in each patient. The effects of the treatment were evaluated every week till the clearance of all warts.

Findings:

Adapalene was used in 10 patient having 118 plantar warts. All the warts cleared in 39±15.07 days. There was no side effects like scar formation, irritation, erythema or infection with adapalene.

Conclusion:

Adapalene clears the plantar warts faster compared to other modalities available.

Limitation:

Need trial with large number of patients.     

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.     

Caveolin-1 Expression in Different Types of Psoriatic Lesions: Analysis of 66 Cases

Background:

Caveolin-1 is a key structural and functional protein. Caveolin-1 is known to modulate multiple signal-transducing pathways involved in cell differentiation and proliferation. Psoriasis is viewed as a multifactorial pathology characterized by keratinocyte hyperproliferation and abnormal cell maturation.

Objectives:

To examine the expression of caveolin-1 in skin biopsies from normal subjects, patients, and subjects with the three respective isoforms of psoriasis (psoriasis vulgaris, localized pustular psoriasis, and erythrodermic psoriasis). The expression level of caveolin-1 was compared among psoriasis vulgaris, localized pustular psoriasis, erythrodermic psoriasis, and normal subjects.

Materials and Methods:

Using immunohistochemical methods, caveolin-1 protein expression was assayed in four groups. An analysis was conducted on skin samples obtained from 22 normal subjects and 28 patients with psoriasis vulgaris, 22 patients with localized pustular psoriasis, and 16 patients with erythrodermic psoriasis. The statistical analysis of the scoring criteria reflecting the level of Caveolin-1 immunostaining between different groups was determined using the Mann–Whitney U-test.

Results:

In the normal skin, intense and consistent caveolin-1 staining was present in 22 cases. The Caveolin-1 protein was significantly reduced and showed very weak or absent staining within the tissues of psoriasis vulgaris, localized pustular psoriasis, and erythrodermic psoriasis (respective P < 0.001). Caveolin-1 protein expression in psoriasis vulgaris was higher than that in localized pustular psoriasis and erythrodermic psoriasis (respective P < 0.05). Caveolin-1 protein expression was no different in localized pustular psoriasis and erythrodermic psoriasis (P > 0.05).

Conclusion:

The finding of this study was consistent with a downregulation of Caveolin-1, which might serve as an etiological factor in the development of psoriasis vulgaris, localized pustular psoriasis, and erythrodermic psoriasis. Further mechanistic investigations are required to prove that Caveolin-1 protein has the potential and may be a novel target for therapy of psoriasis vulgaris, localized pustular psoriasis, and erythrodermic psoriasis.     

Polyamine Metabolism Changes in Psoriasis

Introduction:

Polyamines – putrescine, spermidine and spermine are polycationic compounds ubiquitous for all living organisms. They are essential for the cell growth and differentiation, the control of cell cycle progress, apoptosis, and cancerogenesis. Accumulated scientific evidence suggests the central role of polyamines in the process of keratinocytic proliferation, differentiation, and regulation.

Objective:

To elucidate the polyamine metabolic changes that occur in benign keratinocytic proliferation. Fifty eight patients were enrolled in the study, 31 with plaque-form of psoriasis vulgaris, which had been referred to as a model of benign keratinocytic proliferation, and 27-healthy controls.

Materials and Methods:

An original, innovative chromatographic method was used to detect the levels of putrescine, spermidine, and spermine in all skin samples.

Results:

Were significantly proven (P < 0.05). No difference was found between the polyamines levels of non-lesional psoriatic skin and healthy controls. Psoriatic lesions showed a two-time higher concentration of all polyamines in lesional, compared to non-lesional skin. Spermine had the highest concentration and highest proliferation trend, which demonstrated the importance of propylamine synthesis in the pathogenesis of psoriasis. Spermine highest concentrations suggested the leading role of adenosine methionine decarboxylase (AMDC) in the pathogenesis of benign keratinocytic proliferations.

Conclusions:

Non-lesional skin in psoriatic patients did not show latent changes in polyamine metabolism. Psoriatic lesions demontrated two-time higher levels of the most essential biogenic polyamines compared to healthy controls. The highest level of spermine proved the crucial role of AMDC in the polyamine metabolism changes in psoriasis. Future therapeutic approaches should be focused on reduction of exogenic spermine intake, utilizing new spermine blockers, and synthesis of AMDC inhibitors.