Psoriasis: Association of interleukin-17 gene polymorphisms with severity and response to treatment.

Psoriasis is a chronic, inflammatory disease with a complex pathogenesis that is not yet fully understood. Although it is a multifactorial disease, the genetic factor has a major role in the pathogenesis of psoriasis. Genome wide association studies have identified over 50 genetic loci associated with psoriasis risk. Beside TNF-α or IL-23, the IL-17 family is a newer group that has proven implications in the pathogenesis of psoriasis. The most important members of the family, with pro-inflammatory qualities, are IL-17A and IL-17F. These interleukins are produced by a varied number of cells, but by far the most important are Th17 cells. Of the patients 20-30% present moderate-to-severe psoriasis, therefore, systemic medication (phototherapy, methotrexate, cyclosporine, acitretin or biologic agents) is mandatory. The necessity of an individualized treatment plan, for each patient, is imperative in order to establish the best strategy for non-responders to classical treatment or to other biologic treatments. The discovery of Th17 pathway improved the treatment and prognosis of psoriasis. Anti-psoriatic agents against IL-17 or its receptors are a novel group of biologic agents; these include ixekizumab, secukinumab and brodalumab. Polymorphisms of IL-17 family have been correlated with the severity and response to treatment in psoriasis, and also with the risk of inflammatory, infectious, autoimmune or neoplastic pathologies. The significant difference in the presence or absence of susceptibility loci in different population is due to genetic background and environmental factors that have a major impact on disease predisposition. In this study, we reviewed the importance and influence of the IL-17 polymorphisms as predictors of response to treatment and severity of the disease.

Relationship between etanercept and thyroid function in patients with psoriasis vulgaris.

BACKGROUND AND AIM: Psoriasis vulgaris, a chronic inflammatory skin disease, requires a long term medication, in order to avoid relapsing episodes. TNF-alpha, one of the targeted molecule in psoriasis therapy, seems to be also involved in thyroid disorders etiopathogenesis. The aim of this study was to evaluate the relationship between anti TNF-alpha therapy and thyroid parameters: serum level of triiodothyronine (T3), free thyroxine (FT4), thyroid-stimulating hormone (TSH) and antithyroidperoxidase antibody (AbTPO) in psoriasis treated population. METHODS: The study was performed on 44 patients with psoriasis vulgaris (20 patients under antiTNF-alpha treatment (etanercept), 24 patients with no previous systemic therapy). Serum concentrations of hormones, AbAntiTPO and TNF-alpha were measured and a thyroid ultrasonographic evaluation was performed for each patient. RESULTS: The mean serum level of FT4 was significantly higher in patients with no systemic treatment (p<0.05). The patients treated with etanercept had a significantly higher level of TNF-alpha (p<0.05). No significant difference was observed for the other evaluated parameters. Also, we found a significant negative correlation between TNF-alpha and TSH levels (r=-0.366, p=0.015). CONCLUSIONS: We only found that the mean level of FT4 was significantly higher in patients with no systemic treatment. Also, a negative strong correlation was seen between serum level of TSH and TNF-alpha. Based on our data, comparison with other anti TNF-alpha therapies might be of interest in future studies.

Patterns of clinical nail appearances in patients with cutaneous psoriasis.

BACKGROUND AND AIM: Nail manifestations are often an overlooked aspect in psoriatic disease, cutaneous and joint involvement being far more often reported and investigated. The reported prevalence of nail changes varies in literature, specific fingernail clinical features having different degrees of occurrence. The aim of this study was to describe specific clinical patterns of fingernail alterations in adult patients with plaque-type psoriasis in a university hospital in the North-West of Romania. METHODS: Clinical data of 35 patients with fingernail psoriasis were collected and analyzed. Psoriasis Area and Severity Index (PASI) and Nail Psoriasis Severity Index (NAPSI) scores were used to quantify disease extension in each patient. RESULTS: PASI score proved linearly correlated with NAPSI score (p<0.05). The age of onset of fingernail psoriasis was positively correlated with age of onset cutaneous psoriasis (p<0.0001). Furthermore, the duration of cutaneous involvement and NAPSI proved significantly related (p<0.05). The third fingernail in the right hand and first fingernail in the left hand were in most of the cases severely affected. The most common observed nail pattern was pitting, followed by salmon patches and subungual hyperkeratosis. CONCLUSION: Important nail changes appear even in moderate forms of cutaneous psoriasis. Particular localization of specific fingernail psoriasis pattern enables the possibility of detecting early stage disease.

Hair loss and regeneration performed on animal models.

Research in the field of reversal hair loss remains a challenging subject. As Minoxidil 2% or 5% and Finasteride are so far the only FDA approved topical treatments for inducing hair regrowth, research is necessary in order to improve therapeutical approach in alopecia. In vitro studies have focused on cultures of a cell type - dermal papilla or organ culture of isolated cell follicles. In vivo research on this topic was performed on mice, rats, hamsters, rabbits, sheep and monkeys, taking into consideration the advantages and disadvantages of each animal model and the depilation options. Further studies are required not only to compare the efficiency of different therapies but more importantly to establish their long term safety.

The role of hormones in the pathogenesis of psoriasis vulgaris.

Psoriasis vulgaris is a chronic, common skin disease, which affects the patient's quality of life to the highest degree. Several exogenous factors and endogenous hormonal changes may act as triggers for psoriasis. The skin possesses a true endocrine system, which is very important in multiple systemic diseases. A number of conditions are associated with psoriasis, and its severity can also be influenced by hormones. Even though the sex hormones and prolactin have a major role in psoriasis pathogenicity, there are a lot of other hormones which can influence the psoriasis clinical manifestations: glucocorticoids, epinephrine, thyroid hormones, and insulin.

VEGF involvement in psoriasis.

Vascular endothelial growth factor (VEGF) is a key growth factor, regulating the neovascularization, during embryogenesis, skeletal growth, reproductive functions and pathological processes. The VEGF receptors (VEGFR) are present in endothelial cells and other cell types, such as vascular smooth muscle cells, hematopoietic stem cells, monocytes, neurons, macrophages, and platelets. Angiogenesis is initiated by the activation of vascular endothelial cells through several factors. The excess dermal vascularity and VEGF production are markers of psoriasis. The pathological role of VEGF/VEGFR signaling during the psoriasis onset and evolution makes it a promising target for the treatment of psoriasis. Antibodies and other types of molecules targeting the VEGF pathway are currently evaluated in arresting the evolution of psoriasis.

Ultrasonography in psoriatic disease.

Psoriasis represents a common, chronic inflammatory disease involving the skin, nails and joints. Nail psoriasis in usually investigated and diagnosed by clinical examination. New insights support ultrasonography as being a non-invasive reliable imaging technique for studying nail and skin involvement in patients with psoriasis. Power Doppler frequency, higher than 10MHz enables a very sensitive detection and semiquantitative assessment of the blood flow at the dermal level and in the nail bed. In this review we will present the main US findings in skin and nail psoriasis, and discuss the importance of ultrasonography in diagnosing and monitoring psoriasis vulgaris.