The role of glucose-dependent insulinotropic polypeptide 3 (G1P-3) and nucleolar phosphoprotein-1 (NPM1) in pathogenesis of psoriasis.

Background Psoriasis is a multifactorial, hyperproliferative, chronic inflammatory skin disease affecting males and females equally. Aims To study the expression of certain non-coding RNAs, Interferon Alpha Inducible Protein 6 (IFI6), previously named Glucose-dependent Insulinotropic Polypeptide 3 (G1P-3), and nucleolar phosphoprotein (in serum and tissue), and to attempt to elucidate their role in the pathogenesis of psoriasis, which in turn might help in treatment. Methods Twenty patients with psoriasis and 20 healthy subjects were included in this study. Serum and skin biopsies were obtained from all participants. Molecular biology techniques were employed to estimate the expression levels of long noncoding G1P-3 and nucleolar phosphoprotein in serum and skin biopsy. Results Psoriasis patients had a mean age of 41.85 ± 12.29. The median serum G1P-3 level of the patients' group (3.330) was significantly higher than that of the control group (1.085) (P ≤ 0.001). Tissue G1P-3 level of the patients' group (6.495) was also significantly higher compared to that of controls (1.040) (P ≤ 0.001). Similarly, for nucleolar phosphoprotein, the median serum level of patients' group (2.030) was significantly higher than that of controls (1.040) (P ≤ 0.001) and median tissue level (5.425) was also significantly higher than that of controls (1.040) (P ≤ 0.001). Limitations In this study, only outpatients were included and follow-up was not well-handled. For future work, follow-up can be considered. Conclusion Long non-coding G1P-3 as well as nucleolar phosphoprotein may be considered as genetic markers for psoriasis susceptibility. In future, these might provide a novel direction for advances in psoriasis treatment.

Is cutaneous microbiota a player in disease pathogenesis? Comparison of cutaneous microbiota in psoriasis and seborrheic dermatitis with scalp involvement.

Background Knowledge about cutaneous microbiota in psoriasis vulgaris and seborrheic dermatitis is limited, and a comparison of microbiota in the two diseases was not yet previously undertaken. Aims/Objectives This study aimed to compare the scalp lesional and non-lesional microbiota in psoriasis vulgaris and seborrheic dermatitis with that in a healthy control group. Methods Fifty samples were taken with sterile swabs from patients' and controls' scalps, and 16S rRNA gene sequencing analyses were performed. Results Alpha and beta diversity analyses showed that bacterial load and diversity were significantly increased in psoriasis vulgaris and seborrheic dermatitis lesions compared to the controls. As phyla, Actinobacteria decreased and Firmicutes increased, while as genera, Propionibacterium decreased; Staphylococcus, Streptococcus, Aquabacterium, Neisseria and Azospirillum increased in lesions of both diseases. Specifically, Mycobacterium, Finegoldia, Haemophilus and Ezakiella increased in psoriasis vulgaris and Enhydrobacter, Micromonospora and Leptotrichia increased in seborrheic dermatitis lesions. Mycobacterium, Ezakiella and Peptoniphilus density were higher in psoriasis vulgaris compared to seborrheic dermatitis lesions. The bacterial diversity and load values of non-lesional scalp in psoriasis vulgaris and seborrheic dermatitis lay between those of lesional areas and controls. Limitations The small sample size is the main limitation of this study. Conclusion Higher bacterial diversity was detected in lesions of both psoriasis and seborrheic dermatitis compared to the controls, but similar alterations were observed when the two diseases were compared. Although these differences could be a result rather than a cause of the two diseases, there is a need to analyze all members of the microbiota and microbiota-host interactions.

Diagnostic utility of plasmacytoid dendritic cells in dermatopathology.

Differentiating cutaneous diseases that mimic each other clinically and histopathologically can at times be a challenging task for the dermatopathologist. At the same time, differentiation of entities with overlapping features may be crucial for patient management. Although not seen in normal skin, plasmacytoid dendritic cells usually infiltrate the skin in several infectious, inflammatory/autoimmune and neoplastic entities. Plasmacytoid dendritic cells can be identified in tissue using specific markers such as CD123 and/or blood-derived dendritic cell antigen-2. Plasmacytoid dendritic cells are the most potent producers of type I interferons and their activity may therefore be assessed indirectly in tissue using human myxovirus resistance protein A, a surrogate marker for type I interferon production. In recent years, accumulating evidence has established the utility of evaluating for specific plasmacytoid dendritic cell-related parameters (plasmacytoid dendritic cell content, distribution and clustering and/ or human myxovirus resistance protein A expression) as a diagnostic tool in differentiating cutaneous diseases with overlapping features such as the alopecias, lupus and its mimics, and neoplastic entities. In this review, we provide an update on the current evidence on this topic and on the contexts where this can be a useful adjunct to reach the histopathological diagnosis.

Expression of pigment epithelium-derived factor in psoriasis, verrucae, squamous cell carcinoma and normal skin: An immunohistochemical study.

BACKGROUND: Preservation of homeostasis status in the skin needs an equilibrium of keratinocyte proliferation, differentiation, necrosis and apoptosis. Disturbance of these regulatory mechanisms may lead to keratinocyte neoplastic and hyperproliferative diseases. Pigment epithelium-derived factor is a glycoprotein that is endogenously produced in different tissues and has a variety of biological effects in different diseases. OBJECTIVE: To evaluate the keratinocyte expression of pigment epithelium-derived factor in normal skin and three epidermal hyperproliferative diseases, namely, psoriasis, verrucae and squamous cell carcinoma. METHODS: This study included skin biopsy samples from 80 participants who were divided into four equal groups; each containing 20 samples. The first group included skin biopsies from normal skin, the second group from psoriatic lesions, the third group from verruca vulgaris and the fourth group from squamous cell carcinoma. All tissue samples were stained with hematoxylin and eosin stain and later immunohistochemically for pigment epithelium-derived factor expression. RESULTS: Scores of pigment epithelium-derived factor expression were lower in squamous cell carcinoma and verruca and psoriasis than normal skin with a significant difference (P = 0.04). In addition, the pattern of pigment epithelium-derived factor expression was mainly cytoplasmic in normal skin with a significant difference with that seen in psoriasis, squamous cell carcinoma and verruca vulgaris (P = 0.001). CONCLUSION: Pigment epithelium-derived factor may play a role in keratinocyte differentiation.

Case Report: Leprosy and Psoriasis: A Rare Coexistence.

Leprosy presents with erythematous or pigmented patches, plaques, and nodules with loss of sensation and nerve thickening. Psoriasis presents as sharply demarcated erythematous plaques with overlying silvery scales. The controversial relationship between both has existed since biblical times when psoriasis was considered to be a form of leprosy. Records of leprosy patients have depicted a rarity of the coexistence of psoriasis, leading to a hypothesis that both rarely develop in the same patient. We report a rare coexistence of both diseases.

Schwann cells as underestimated, major players in human skin physiology and pathology.

Schwann cells (SCs) have long been recognized for their ability to support repair and promote axon regeneration following injury to the peripheral nervous system. In response to nerve injury, they rapidly dedifferentiate into a precursor-like state, secrete an array of inflammatory mediators and growth factors, proliferate, undergo epithelial-to-mesenchymal-like transformation to facilitate migration, phagocytose cellular debris and remodel the extracellular environment to promote regeneration of axons through the site of injury. However, even though a cutaneous role for SCs is becoming increasingly recognized, we argue in this Viewpoint essay that the likely complex functions of SCs in skin physiology and pathology beyond skin sensation and nerve repair deserve more attention and systemic research than they have received so far. For example, SCs promote wound healing, disseminate infection in leprosy, support the growth of neurofibromas/schwannomas and facilitate/accelerate the growth and invasion of melanoma. Despite representing a major dermal cell population, comparatively little is still known about the role of SCs in other dermatoses. To quintessentially illustrate the opportunities that promise to arise from a new skin research focus on SCs, we focus on two dermatoses that are not traditionally associated with SCs, that is, psoriasis and atopic dermatitis (AD), since both show distinct SC changes along with continuous nerve fibre degeneration and regeneration, and an impact of denervation on skin lesions. Specifically, we critically discuss the hypothesis that repeated activation of the SC repair programme occurs in and contributes to psoriasis and AD and delineate experimental approaches how to probe this clinically relevant hypothesis.

Ultrasound assessment of enthesis thickness in psoriasis and psoriatic arthritis: A cross-sectional study.

BACKGROUND: The inflammatory involvement of the enthesis in the course of psoriasis is accompanied by structural abnormalities detectable by ultrasound. The most common of these abnormalities is the thickening of the tendon at the insertion site. AIMS: The aim of the present study was to compare the thickness of entheses of patients with psoriatic arthritis, only skin psoriasis, and healthy controls. METHODS: A cross-sectional study was conducted in a cohort of patients affected with either only skin psoriasis or psoriatic arthritis as well as in a control group. Eight entheses sites were scanned by ultrasound bilaterally. The following entheseal characteristics were collected and recorded in a predefined database: entheseal thickness, bone erosions, enthesis calcifications (enthesophytes), presence of blood flow, and presence of bursitis. All the detected entheseal changes were scored, and the data was statistically analyzed. RESULTS: The major differences in enthesis thickness between only skin psoriasis and psoriatic arthritis patients were found at the following sites: (i) olecranon tuberosity, (ii) superior pole of the patella, and (iii) medial epicondyle of femur. The thickness of the medial collateral ligament at the site of the femoral origin was increased in psoriatic arthritis, but not in both only skin psoriasis and healthy controls. The score obtained by adding the thickness of all the 8 examined entheses for each patient showed significant differences among the three groups (psoriatic arthritis: 81.3; only skin psoriasis 74.4; Controls: 67.6; P < 0.0001). Interestingly, we found that in psoriatic arthritis patients, the highest enthesis thickening was seen in entheses affected by bone erosions. LIMITATIONS: The small sample of patients studied is a limiting factor in this study. CONCLUSIONS: Our data demonstrated that the ultrasound measurement of the enthesis thickness enables a distinction between patients with psoriatic arthritis from those with only skin psoriasis. It is a useful method to improve diagnostic accuracy, especially in patients without clear clinical signs of enthesitis.

A study of the histopathology of palmo-plantar psoriasis and hyperkeratotic palmo-plantar dermatitis.

BACKGROUND AND OBJECTIVES: Palmo-plantar psoriasis and dermatitis show several overlapping clinical features. We undertook this retrospective study to elucidate and compare the histological findings in these two dermatoses. MATERIALS AND METHODS: Biopsies of 31 clinically diagnosed cases of palmo-plantar psoriasis and 24 cases of hyperkeratotic palmo-plantar dermatitis, with concomitant presence of representative lesions at other body sites, were retrieved and analysed. RESULTS: Histologically, confluent parakeratosis, suprapapillary thinning and dermal edema were observed in significantly greater number of palmo-plantar psoriasis biopsies while an inflammatory infiltrate confined to the papillary dermis only, was a significant feature in palmo-plantar dermatitis. The two conditions could not be differentiated on the basis of features like focal parakeratosis, presence of neutrophils and fibrin globules in the stratum corneum, hypogranulosis, acanthosis, spongiosis, rete ridge pattern, or vascularity. CONCLUSION: Histopathology of palmo-plantar psoriasis and dermatitis can have several overlapping features. In our study, we found only few features as strong pointers towards psoriasis.

Anti-proliferative and anti-inflammatory effects of 3ß,6ß,16ß-Trihydroxylup-20(29)-ene on cutaneous inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: 3ß,6ß,16ß-Trihydroxylup-20(29)-ene (TTHL) is a triterpene isolated from the flowers of Combretum leprosum, a plant used in folk medicine in the north of Brazil for the treatment of skin disorders. AIM OF THE STUDY: In the present study, TTHL was evaluated as a potential topical anti-inflammatory and anti-proliferative agent through in vivo and in vitro models. MATERIAL AND METHODS: Anti-inflammmatory and anti-proliferative effects of TTHL were assessed using Swiss mice in acute and chronic models of skin inflammation induced by 12-O-tetradecanoylphorbol-acetate (TPA) application. Anti-proliferative activity was proved through in vitro experiments with the HaCaT human keratinocyte cell line. RESULTS: Treatment with TTHL inhibited inflammatory parameters such as oedema formation and cellular infiltration in acute and chronic models. In the chronic model, TTHL also inhibited epidermal hyperproliferation, as evidenced by reduction of epidermis thickness and proliferating cell nuclear antigen expression. The anti-proliferative effect was confirmed by the capability of TTHL in reducing the proliferation and inducing cell apoptosis of HaCaT cells. Suggesting a mechanism of action, TTHL showed activation of corticosteroid receptors, but without the induction of corticosteroid-related cutaneous side effects. CONCLUSION: Our results demonstrate consistent anti-inflammatory and anti-proliferative activity and assign TTHL as a valuable tool in the development of a new treatment for skin inflammatory and proliferative diseases, such as psoriasis.

Severe combined immunodeficiency mouse-psoriatic human skin xenograft model: a modern tool connecting bench to bedside.

Psoriasis is a multifactorial chronic inflammatory disease. Research into the pathogenesis of this disease is hindered by the lack of a proper animal model. Over the past two decades, many scientists were involved in the development of animal models that nearly mirror the immunopathogenesis of psoriasis. One such model, which has opened doors to the study of molecular complexities of psoriasis as well as its treatment, is the severe combined immunodeficiency (SCID) mouse-human skin chimera model. This model not only mirrors the clinical and histopathological features of psoriasis but also help in the study of cell proliferation, angiogenesis, function of T cells, neurogenic inflammation and cytokines involved in inflammatory reactions. In this article, we have reviewed the prospects and the limitations of the SCID mouse model of psoriasis.

Matched case-control study to examine association of psoriasis and migratory glossitis in India.

BACKGROUND: Psoriasis is a multifactorial disease. Genetic and environmental factors, which determine the disease epidemiology and clinical spectrum, are heterogeneous in different populations. A few case-control studies from other countries have shown an association between psoriasis and migratory glossitis (MG). The characteristics of the association (e.g. relationship with gender, severity of psoriasis, early- versus late-onset psoriasis, etc.) have not been clearly defined. AIM: To investigate the association of psoriasis and MG by conducting a matched case-control study in India. METHODS: The study was conducted on 600 patients with psoriasis and 800 age- and sex-matched controls. Patients were examined for oral lesions and psoriasis severity was assessed by overall severity index (OSI) and psoriasis area and severity index (PASI). We compared the proportions of patients and controls with oral lesions, proportions of male and female patients who had MG, psoriasis severity scores of patients with or without MG, and proportions of early- and late-onset psoriasis patients who had MG. RESULTS: Significantly, more patients had oral lesions than controls (P=0.0013). There was a strong association between psoriasis and MG (P<0.0001). MG and fissured tongue (FT) occurring in the same patient were also strongly associated with psoriasis (P=0.0003). There was a weak association of psoriasis with FT (P=0.0456). Significantly, higher proportion of male patients had MG compared to female patients (P=0.0246). Patients with MG had more severe psoriasis compared to those without the tongue lesions (P<0.0001). Similar proportions of patients with type 1 and type 2 psoriasis had MG (P=0.7268). CONCLUSIONS: The results suggest that MG is a rare manifestation of psoriasis which occurs more commonly in male patients and in those with severe disease, and that it occurs with equal frequency in early- and late-onset psoriasis. It will be interesting to follow those patients who have MG, but not psoriasis, to see whether they develop psoriasis phenotype in future.

Psoriatic alopecia - fact or fiction? A clinicohistopathologic reappraisal.

BACKGROUND: The incidence of psoriatic alopecia in psoriatic patients is underwhelming, given the prevalence of psoriasis in the North American population. Recently, a 60-year-old Albanian female, lacking a significant medical history for psoriasis, presented to our clinic with a 1-year history of "dandruff" associated with itch, hair thinning, and histopathologic evidence consistent with prior reports of "psoriatic alopecia." AIMS: The absence of preceding or concomitant psoriasis suggests that the patient's alopecia is an antecedent manifestation of psoriasis, thus prompting this retrospective study to ascertain better the relationship between alopecia and psoriasis. METHODS: We performed a retrospective review of 33 scalp biopsies on 31 patients having histopathologic diagnosis of psoriasis belonging to 31 patients seen between 2007 and 2010. RESULTS: Alopecia was a presenting feature in 48% of cases with definitive clinical and/or histopathologic diagnosis of psoriasis (scale crust with neutrophils, psoriasiform epidermal hyperplasia, and hypogranulosis). The most common follicular-related changes were infundibular dilatation (87%) followed by perifollicular fibrosis (77%), perifollicular lymphocytic inflammation (68%), thinning of the follicular infundibulum (55%), and fibrous tracts (28%). Of interest, sebaceous glands were absent in 60% and atrophic in 25% of cases. CONCLUSION: While a major limitation of this study is that it is a retrospective one, given that these changes are common to varying degrees in all lymphocytic scarring alopecias, we posit that psoriatic alopecia likely represents a secondary clinical change to a primary process and is not a unique histopathologic entity. A prospective study with a control group that includes lymphocytic scarring alopecias from non-psoriatic patients is required to support our findings.

Comparative efficacy of narrow-band ultraviolet B phototherapy alone and its combination with topical 8-methoxypsoralen in psoriasis.

BACKGROUND: Very few studies using the combination of topical 8-methoxypsoralen (8-MOP) and narrow-band ultraviolet B (NBUVB) have been performed, especially in Indian patients. A combination of oral psoralen with NBUVB has been shown to have a superior efficacy as compared with NBUVB alone in psoriasis. AIMS: Comparison of the efficacy of topical psoralen NBUVB (combination) versus NBUVB alone in psoriasis. METHODS: Thirty patients with plaque psoriasis were taken up for the study and NBUVB phototherapy was given twice weekly. The target lesions on one side were treated with 0.1% topical 8-MOP 15 min before the irradiation. The treatment period was 12 weeks or 24 exposures. RESULTS: The number of treatment sessions and cumulative NBUVB doses were lower in the combination therapy as compared with NBUVB monotherapy, although the differences were not statistically significant. CONCLUSION: To conclude, topical 8-MOP enhances the therapeutic effects of NBUVB therapy without increasing the incidence of adverse effects.