Optimizing Secukinumab Treatment in Psoriasis with Concomitant Methotrexate Administration: Minireview and A Case Report.

The introduction of biologic drugs for the treatment of moderate-to-severe psoriasis resulted in a significant improvement in patients' health. Moreover, treatment regimens in psoriatic patients should be tailored to meet specific needs based on disease severity, impact on quality of life, response to previous therapies and presence of comorbidities. Combination therapy of biologic agents with conventional systemic drugs has been proposed to optimize psoriasis treatment outcomes in unresponsive or partial responsive severe psoriatic patients. We report the case of a patient with a long-standing recalcitrant plaque psoriasis and psoriatic arthritis who was administered secukinumab combined with methotrexate. The patient had previously been treated with several topical and systemic therapies associated with loss of efficacy or adverse event occurrence. Approximately 24 weeks after starting the combined regimen, significant clearance of psoriasis and reduction of arthritis ensued, with no drug side effects.

Oral features in patients with psoriasis: an observational study.

BACKGROUND: The aim of this study was to investigate and compare the prevalence of oral mucosal lesions in a group of psoriatic patients and healthy subjects. METHODS: 120 psoriatic patients were enrolled in this observational study. Clinical examination, panoramic X-ray, magnetic nuclear resonance of temporo-mandibular joint, parodontal evaluation, oropharyngeal buffer and incisional biopsies by scalpel, as applicable, were done in order to value the patients. The control group was formed by 201 non-psoriatic patients attending the hospital for dental conditions. Oral clinical evaluation of these patients was performed, to assess the presence of any oral manifestation that can be related to psoriasis: fissured tongue, geographic tongue, parodontitis, temporo-mandibular joint disorders and oral candidiasis. After the observational analysis, a statistical examination was conducted using the chi-square test (2-sided). RESULTS: A percentage of 78.34% of patients belonging to the case group presented oral manifestations, while in the control group the 35.3% of the individuals presented any oral lesions. Especially geographic and fissured tongue showed a strong correlation with psoriasis. CONCLUSIONS: Some oral mucosal lesions, such as geographic and fissured tongue, are strongly associated with psoriasis. Although these lesions are non-pathognomonic to psoriasis, their precise relationship needs to be clarified and further investigated.

Correlation between plasmatic levels of vitamin D and PASI score.

BACKGROUND: Psoriasis is a common, inflammatory, chronic, relapsing skin disease. The pathogenesis is multifactorial and it is involved both innate and acquired immunity. Several studies have shown the important role of vitamin D in the pathogenesis of this disorder. In this study we have evaluated a possible correlation between vitamin D and clinical severity of psoriasis calculated using the Psoriasis Area Severity Score (PASI) score. METHODS: In this case control study we included 141 Caucasian subjects affected by moderate to severe psoriasis and 62 healthy controls. We have calculated PASI score and serum levels of vitamin D. RESULTS: Psoriatic patients had significantly lower serum levels of 25(OH)D than healthy controls. Using no parametric Spearman's coefficient test between serum levels of vitamin D and the PASI score we found a statistical significant correlation. However, the statistical significance was not reached analyzing separately the patients with psoriatic arthritis, while it was confirmed for patients without an articular involvement. CONCLUSIONS: The present study confirm that serum levels of vitamin D are significantly lower in psoriatic patients and correlate with the clinical severity of psoriasis; these data suggest that psoriatic patients could be screened for vitamin D insufficiency for a more comprehensive management.

Safety and efficacy of anti-tumor necrosis factors α in patients with psoriasis and chronic hepatitis C.

Up to date, in literature, it is still debated the role of anti-tumor necrosis factors (TNF)-α treatments in hepatitis C virus (HCV) patients. TNF-α performs a lot of functions, it is an important pro-inflammatory cytokine and it is involved in the host's immunity. Since TNF-α is implicated in the apoptotic signaling pathway of hepatocytes infected by HCV, anti TNF-α therapy may increase the risk of viral replication or their reactivation. However the treatment of anti TNF-α could have a healthful role because TNF-α appears to be engaged in the pathogenesis of liver fibrosis, inducing apoptotic pathways. We describe the case of a patient with plaque-type psoriasis and concomitant chronic HCV, who was treated successfully with anti-TNF agents simultaneously to cyclosporine without sign of reactivation of HCV and increase of liver enzymes. Our personal experience shows that anti-TNF-α agents are not only effective but also safe. Furthermore the combination therapy of cyclosporine and anti-TNF-α appears to be well-tolerated and able to reduce the amount of liver enzymes as well as HCV-viral-load. However systematic, large-scale studies with long follow-ups will be needed to confirm our results, in association with close liver function monitoring.

Psoriasis and bone mineral density: implications for long-term patients.

Psoriasis is a chronic inflammatory disease associated with several comorbidities. Osteoporosis is defined as a reduction in bone mineral density with impaired bone microarchitecture. Several mechanisms may be implicated as a possible cause for the association between psoriasis and osteoporosis, such as systemic inflammation, anti-psoriatic drug intake and joint dysfunction for psoriatic arthritis (PsA). The aim of the present study was to assess bone mineral density (BMD) in patients with psoriasis, correlating the prevalence of osteopenia/osteoporosis with Psoriasis Area and Severity Index (PASI) score, mean duration of psoriatic disease, PsA and previous treatments for psoriasis. Forty-three consecutive patients with psoriasis, 19 of whom were affected by the arthropathic form, were enrolled. We evaluated the severity of psoriasis as measured by PASI score, the CASPAR criteria and ultrasounds of the joints to verify the diagnosis of PsA and the age of psoriasis onset to estimate mean disease duration. Patients underwent a bone density scan of the lumbar spine and femoral neck by dual-energy X-ray absorptiometry to measure BMD. Patients with osteopenia/osteoporosis showed a statistically significant longer average duration of psoriatic disease (17 years), compared to patients affected by psoriasis with normal T-score (8.8 years) (P = 0.04). The linear logistic regression confirms a significant relation between mean psoriatic disease duration and BMD alterations (P = 0.04). Our results suggest the necessity of an early diagnostic evaluation of bone metabolism in patients with psoriasis, especially if characterized by longer disease duration.

New patents on topical anesthetics.

Anesthesia is defined as a total or partial loss of sensation and it may be general, local or topical, depending on the method of drug administration and area of the body affected. General anesthesia is a reversible state of unconsciousness produced by anesthetic agents, characterized by amnesia, muscle relaxation and loss of sensitivity to pain of the whole body. General anesthetic drugs can be classified into two main groups according to their predominant molecular pharmacological effects: volatile and intravenous agents. Local anesthesia produce a reversible loss of sensation in a portion of the body and it reversibly block impulse conduction along nerve axons and other excitable membrane. All local anesthetics (LA) are membrane stabilizing drugs; they reversibly decrease the rate of depolarization and repolarization of excitable membranes. They act mainly by inhibiting sodium influx through sodium-specific ion channels in the neuronal cell membrane, in particular the voltage-gated sodium channels. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is inhibited. The main local anesthetic (LA) agents for skin anesthesia are benzocaine (aminoester), prilocaine and lidocaine (aminoamides) which are commercially available as gels, ointments and creams (benzocaine and eutectic mixture of lidocaine and prilocaine) or as a bioadhesive (lidocaine) with different compositions (vehicles and excipients) for adults or pediatric use. Topical anesthetics decrease anxiety, pain and discomfort during cutaneous procedures and provide effective analgesia with rapid onset, prolonged duration and minimal side effects. This article outlines the different classes of topical anesthetics available and gives an overview of the mechanism of action, metabolism of each different class, of the possible complications that can occur because of their use and their possible treatment options and new patents.

Importance of regulatory T cells in the pathogenesis of psoriasis: review of the literature.

Psoriasis is a common chronic relapsing inflammatory cutaneous disease; the main role in the inflammation of this condition is played by lymphocyte Th1, Th17 and their cytokines. The activity of these cells is modulated by a particular kind of T cells recently described: the T regulatory cells (Treg). These are able to inhibit the immunological response and to maintain the cutaneous immunological homeostasis, thus preventing autoimmunity against self antigens. Few data are available in the literature as to Treg in psoriasis; several studies demonstrate that the function of these cells is impaired in this condition and treatments for psoriasis may increase the number and activity of Treg. The role of these cells in the pathogenesis of psoriasis is very important to understand how they may contribute to the development of this cutaneous disorder. In the near future it would be possible to target therapies at these defects, improving the activity of these cells and maintaining cutaneous homeostasis, preventing psoriasis or other inflammatory cutaneous conditions.

Serum levels of functional T-regs in vitiligo: our experience and mini-review of the literature.

Vitiligo is an acquired depigmentary skin disorder due to the loss of cutaneous melanocytes or alteration in melanocyte function, affecting over 0.5% of the world population. The exact cause of melanocyte loss in non-segmental vitiligo is still debatable, but many observations have pointed to the main role of cellular immunity. Earlier evidence has shown that depigmenting vitiligo skin is accompanied by CD8+ T cytotoxic lymphocytes infiltrates at the dermal-epidermal junction. Dysregulation of Tregs may be one of the factors that can break tolerance to melanocyte self-antigens and contribute to the pathogenesis of vitiligo. The objectives of the present study were to provide evidence of the presence of a functional defect and decrease of peripheral regulatory T cells in patients affected by vitiligo, supporting the hypothesis of their involvement in the pathogenesis of the disease, opening new possibilities to advance therapeutic approaches.

Psoriasis: new insight about pathogenesis, role of barrier organ integrity, NLR / CATERPILLER family genes and microbial flora.

Psoriasis is a common, inflammatory, chronic, relapsing skin disease. New insight about the etiology of this disease shows the important role played by the epidermal barrier function, its integrity and pathogen responses in combination with microbial environmental factors. A pivotal role in the management of this balance is played by NLR genes, also known as NBD-LRR or CATERPILLER, that encode important mediators of innate immunity and provide the first line of defense against pathogens. The polymorphism of these genes is implicated in the pathogenesis of several immunological diseases and might be of importance in the pathogenesis of barrier organ disorders. Crohn's disease is considered archetypal of these kinds of disorders; similarities between Crohn's disease and psoriasis and their similar pathogenetic mechanisms may support the concept of psoriasis as a barrier organ disorder and common genetic ground lying behind these illnesses. Considering psoriasis as a "barrier organ disease" is not only a mere mental exercise; this consideration may, in fact, open new prospects in the treatment of these disorders just by preventing alterations of microbial flora or regulating the response of the host to infective diseases.

Gemcitabine-induced extensive skin necrosis.

An 82-year-old woman presented with oedema and extensive necrotic ulcerative lesions on the back side of her lower limbs, emerging after the second cycle of chemotherapy consisting of Gemcitabine for metastatic pancreatic cancer. The absence of any convincing argument in favor of cardiovascular or autoimmune disease led us to attribute the onset of skin necrosis to chemotherapy administration. Although skin ischemia has also been described as a paraneoplastic syndrome, in this case we could observe a temporal and causal relationship to Gemcitabine infusion. Recently, this drug has been associated with important vascular side effects; its vascular toxicity is in fact higher than previously estimated. To our knowledge, careful attention should be reserved to neoplastic patients candidated to Gemcitabine administration, especially if previously affected by arterial vascular disease, venous thromboembolism, or collagenoses.