Exclusive and Solitary Facial Porokeratosis: Pathogenesis and Literature Reappraisal of a Rare Entity.

Porokeratosis is a group of well-known clinically distinct entities, characterised by different clinical aspects, but sharing a single common histological aspect, namely the cornoid lamella. Usually, porokeratosis occurs in the limbs and trunk, while it rarely involves the face, especially as an exclusive, single, and solitary lesion. We report the case of a 52-year-old Caucasian woman, with an 11-month history of a 2-cm slowly growing solitary, keratotic lesion on her left cheekbone. The patient did not present other cutaneous lesions on the face, as well as in other body sites. A cutaneous biopsy showed epidermal hyperplasia with multiple, sharply defined cornoid lamella, associated with an underlying attenuation of the granular layer and scattered dyskeratotic cells in the spinous layer. The superficial dermis underneath showed a mild lymphocytic infiltrate and fibrosis with remodelled collagen bundles. A final diagnosis of solitary facial porokeratosis was made.

Systemic immunobiological, immunosuppressant, and oncologic agents for the treatment of dermatologic diseases during the SARS-CoV-2 (COVID-19) pandemic emergency: A quick review for a quick consultation.

The precision medicine era has helped to better manage patients with immunological and oncological diseases, improving the quality of life of this class of patients. Regarding the management of these patients and positivity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), currently, limited data are available and information is evolving. In this quick review, we have analyzed the mechanisms of action and related infective risk of drugs used for the treatment of immune-mediated and oncologic skin conditions during the daily clinical practice. In general, immunosuppressant and antineoplastic agents for dermatologic treatments do not require suspension and do not require special measures, if not those commonly observed. In the case of a coronavirus disease (COVID-19) patient with complications (such as pneumonia, respiratory failure), treatment suspension should always be considered after taking into account the general condition of the patient, the risk-benefit ratio, and the pathophysiology of COVID-19 infection. The COVID-19 emergency pandemic does not imply undertreatment of existing skin conditions, which together with the SARS-CoV-2 infection may jeopardize the patient's life.

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.

Vitamin D and melanoma: state of the art and possible therapeutic uses.

Despite the presence of several studies in literature, the real connection between vitamin D serological levels, vitamin D receptor and melanoma remains unclear, probably because of the complex correlation between vitamin D and melanoma. Indeed, UV radiations are not reported as the main risk factor for melanoma in non-sun-exposed, while systemic immunosuppression, anatomical and physiological features may contribute to malignancy. Therefore, the correlation between melanoma cells in sun-exposed areas and vitamin D, as well as vitamin D receptor could be different from the one in melanoma of sun-shielded sites. These differences may also explain the controversial results reported in the literature regarding the correlation between melanoma and vitamin D, as well as the different outcomes in melanoma patients treated with vitamin D as adjuvant therapy. The aim of this review is to highlight the most recent findings about vitamin D and melanoma, focusing on the anatomic site of the primary tumor as well as on the possible therapeutic uses of vitamin D in melanoma patients.

Mast cells and cancer.

Mast cells (MCs) are a potent proangiogenic factor in tumors, they product several pro-angiogenic factors such as fibroblast growth factor 2 (FGF-2), vascular epithelial growth factor (VEGF), tryptase and chymase. Tryptase is a serine protease classified as α-tryptase and ß-tryptase, both produced by MCs. Tryptase degrades the tissues, playing an important role in angiogenesis and in the development of metastases. Serum tryptase increases with age, with increased damage to cells and risk of developing a malignancy and it could be considered the expression of a fundamental role of MCs in tumor growth or, on the contrary, in the antitumor response. Many biomarkers have been developed in clinical practice for improving diagnosis and prognosis of some neoplasms. Elevated tryptase levels are found in subgroups of patients with haematologic and solid cancers. In the current review, we want to update the perspectives of tryptase as a potential biomarker in daily practice in different neoplasms.

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.

HaCaT Cells as a Reliable In Vitro Differentiation Model to Dissect the Inflammatory/Repair Response of Human Keratinocytes.

Cultured primary human keratinocytes are frequently employed for studies of immunological and inflammatory responses; however, interpretation of experimental data may be complicated by donor to donor variability, the relatively short culture lifetime, and variations between passages. To standardize the in vitro studies on keratinocytes, we investigated the use of HaCaT cells, a long-lived, spontaneously immortalized human keratinocyte line which is able to differentiate in vitro, as a suitable model to follow the release of inflammatory and repair mediators in response to TNFα or IL-1ß. Different treatment conditions (presence or absence of serum) and differentiation stimuli (increase in cell density as a function of time in culture and elevation of extracellular calcium) were considered. ELISA and Multiplex measurement technologies were used to monitor the production of cytokines and chemokines. Taken together, the results highlight that Ca2+ concentration in the medium, cell density, and presence of serum influences at different levels the release of proinflammatory mediators by HaCaT cells. Moreover, HaCaT cells maintained in low Ca2+ medium and 80% confluent are similar to normal keratinocytes in terms of cytokine production suggesting that HaCaT cells may be a useful model to investigate anti-inflammatory interventions/therapies on skin diseases.

Psoriasis, vitamin D and the importance of the cutaneous barrier's integrity: An update.

Psoriasis is a common, inflammatory, chronic, relapsing skin disease. Despite several hypotheses having been postulated to explain the pathogenesis of this disorder, nowadays it is considered as a T-cell-mediated disease; in this context an important role is played by vitamin D. The role of this micronutrient is important for many reasons: it is able to modulate the immune system; it is implicated in keratinocyte turnover; and it is involved in the integrity of the cutaneous barrier. In psoriasis, this molecule plays an important role due to its ability in the modulation of innate and adaptive immunity and by its antiproliferative and pro-differentiative effects on keratinocytes. Alteration of the metabolism of vitamin D may alter the cutaneous barrier integrity and favor an infective and inflammatory condition. The importance of vitamin D in the pathogenesis of psoriasis is not a mere mental exercise but may open further perspectives in the treatment of this disorder just preventing alterations of immune homeostasis, modulating the proliferation of keratinocyte, regulating the microbial flora and the response of the host to infective diseases.

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.

Mutational profiling in melanocytic tumors: multiple somatic mutations and clinical implications.

In this study, we analyzed multiple somatic mutations in 10 genes relevant in melanoma tumorigenesis and targeted therapies. Overall, 45% of the tumors showed mutations and, in particular, 33% had multiple mutations. Based on our results, we conclude that the assessment of mutation status of multiple genes, including CDKN2A, could provide a genetic profile that can be useful as a prognostic and therapeutic marker in melanocytic tumors.

A-1012G promoter polymorphism of vitamin D receptor gene is associated with psoriasis risk and lower allele-specific expression.

Psoriasis is caused by a combination of genetic, immunologic, and environmental factors. The vitamin D receptor (VDR) is involved in antiproliferative and prodifferentiation pathways in keratinocytes and exerts immunosuppressive effects. We aimed to investigate possible associations between VDR polymorphisms and psoriasis susceptibility and to evaluate functional effects of potential psoriasis-associated polymorphisms. We genotyped 108 patients with psoriasis and 268 healthy controls at 5 VDR polymorphisms (A-1012G, FokI, BsmI, ApaI, and TaqI) by TaqMan allelic-discrimination real-time polymerase chain reaction. We found a significant increased overall risk of psoriasis for the VDR A-1012G promoter polymorphism (odds ratio [OR]=2.43, 95% confidence interval [CI]: 1.15-5.13; p=0.05). A significant higher frequency (p=0.035) of the A allele was found in psoriatic cases compared with controls. In a case-case analysis, a statistically significant association between A-1012G and family history emerged (p=0.033). Furthermore, a significant association of A-1012G risk genotypes with a lower expression of VDR mRNA emerged (p=0.0028). Our data show that VDR promoter A-1012G polymorphism is associated with psoriasis risk and suggest that this polymorphism may modulate psoriasis risk by affecting VDR expression.

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.

Imiquimod 5% cream use in dermatology, side effects and recent patents.

Imiquimod is an immune response modifier that stimulates the patient's own immune system to release various chemical substances, such as interferon and interleukin-12. Although, approved by the United States Food and Drug Administration since 1997 as a topical treatment for genital and perianal warts, investigators have found that this product may offer an alternative treatment for a wide variety of medical conditions, such as for actinic keratoses, molluscum contagiosum, genital herpes, and various skin tumours. Clinical trials are now demonstrating the beneficial effects that its administration may have in treating other immune-related, dermatologic disorders. Understanding the pharmacology of this kind of drug is another step to fully understanding the power of the human immune system. Local reactions occur most frequently and include itching, burning, pain, soreness, flaking, erosions, and crusting. Since, it is administered locally; only a small amount of drug should reach systemic circulation, if used correctly. However, uncommon systemic side effects have been reported including headache, flu-like symptoms, fatigue, nausea, and myalgia. This article reviews imiquimod use in dermatology including its off-label use, side effects, future developments, new molecules related to dermatology and relevant patents.