Giovanni Paolino

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 hosts 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.

Superficial basal cell carcinoma successfully treated with ingenol mebutate gel 0.05

Basal cell carcinoma (BCC) is the most common cancer in the world (1). It is typically slow growing and rarely metastatic, usually effectively managed with surgery. However, BCC in some patients is unsuitable for surgery; whereas in other cases, patients may prefer a nonsurgical treatment, especially when they have several lesions (2). Among other already known topical treatments, topical ingenol mebutate gel, a derivate of Euphorbia peplus plant, recently arrived in the Italian market, has begun to show effectiveness in superficial BCC (BCCs). We describe a case of a 79-year-old Caucasian man, skin phototype II, referred to our clinic complaining of severe sun-damaged skin and multiple nonmelanoma skin cancers; he had several actinic keratosis (AKs) for which we chose ingenol mebutate gel 0.05% and we decided to apply this also on the bigger BCCs on his back (FIG. 1). We directly applied the gel for 2 days and we observed only a light erythema on the first day, worsened already on the second day. From the third day, he experienced severe flaking/scaling/dryness extending beyond the application site (FIG. 2). Nonsevere, potentially treatment-related events included: erythema extending beyond the application site, application-site pain, and headache; the local reaction lasted almost 2 weeks and then we observed almost completed resolution that persisted after 3 months from the treatment (FIG. 3). The incidence of nonmelanoma skin cancers is undergoing a drastic global increase. The continuous search for noninvasive treatments has encouraged the development of new therapeutic agents. An understanding of the history, mechanism of action, and recent trial evidence for the emerging therapy can assist physicians in counseling patients on available treatment options and in selecting appropriate therapy. Ingenol mebutate is a new topical drug extract from the latex sap of a plant E peplus that acts by chemoablative and immune-stimulatory properties (3). The sap from E peplus, commonly known as petty spurge in the UK or radium weed in Australia, has been used as a traditional treatment for a number of cancers (4). The incidence of local skin reactions is high, although clinical studies have proven it to be safe and efficacious, leading to the Address correspondence and reprint requests to: Carmen Cantisani, MD, Professor, Department of Dermatology. “Sapienza” University of Rome, Viale del Policlinico 155, 00186 Rome, Italy, or email: carmencantisanister@gmail.com; cantisanicarmen@gmail.com.

Successful use of etanercept in a case of toxic epidermal necrolysis induced by rituximab.

and triglycerides in asteatotic eczema. Pemetrexed predominantly inhibits thymidylate synthetase and other folate enzymes, which are involved in the synthesis of purines and pyrimidines. To the best of our knowledge, these enzymes were not implicated in the epidermal lipids nor in sebum production. Xerosis and eczema craquel e were not associated with folate deficiency and other antifolate drugs (e.g. methotrexate, trimethoprim). Therefore, we postulate that this rare skin toxicity is not directly related to the antifolate mechanism. In conclusion, our case demonstrated that generalized eczema craquel e can be induced by pemetrexed. Further investigation (e.g. patch test) is needed to elucidate the underlying pathomechanism.

Immunohistochemical expression of VDR is associated with reduced integrity of tight junction complex in psoriatic skin

Cell junctions are crucial for the formation and maintenance of the paracellular barrier and for cell polarity in simple epithelia and endothelia. Altered localization and formation of tissue junction proteins in the epidermis have been described in plaque‐type psoriasis. Vitamin D receptor (VDR) is a nuclear hormone involved in anti‐proliferative and pro‐differentiation pathways in keratinocytes. However, still to date, vitamin D/VDR signalling involved in tissue barrier related to psoriasis remains largely unknown.

Biliopancreatic Diversion: When a Cure Becomes a Disease

Phrynoderma is a type of follicular hyperkeratosis located primarily on the extensor surfaces of the extremities. It is most commonly seen in Africa and Southeast Asia, where it is correlated with malnutrition; however, it is rare in developed countries, where it is often the result of malabsorption secondary to pancreatic insufficiency, colectomy, chronic giardiasis, and bariatric surgery. Here, we report a case of a 51-year-old white male patient, who presented to our Institute with a 1-year history of diffuse, reddish-brown asymptomatic papules associated with follicular nodules. In association with cutaneous symptomatology, the patient complained of also having night blindness. The patient, 4 years before, underwent a bariatric surgical treatment, which included a biliopancreatic diversion. Histologic examination of skin biopsy revealed hyperkeratosis and irregular acanthosis of the epidermis in association with dilated follicular infundibulum filled with keratinous material, whereas the laboratory investigations showed hypovitaminosis A. Based on the patients history and cutaneous biopsy, a final diagnosis of phrynoderma was made. The steady increase of obesity in developed countries results in a relative increase in bariatric surgery. This must involve a multidisciplinary team to manage nutrition deficiencies and prevent possibly important complications, as mentioned in this report.

Successful treatment of pyoderma gangrenosum with anakinra in a patient with Wiskott-Aldrich syndrome

Dear Editor, Pyoderma gangrenosum (PG) is a rare, chronic, inflammatory disease, characterized by painful papules or pustules that rapidly evolve into ulcers with irregular, undermined, and overhanging violaceous borders (Gameiro, Pereira, Cardoso, & Gonçalo, 2015). PG is more frequent on lower extremities and in women between 20 and 50 years of age (Gameiro et al., 2015). Up to 70% of PG patients show an underlying systemic disease, including inflammatory bowel diseases, arthritis, and hematological malignancies (Gameiro et al., 2015). Wiskott–Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by severe immunodeficiency, thrombocytopenia, and eczema (Buchbinder, Nugent, & Fillipovich, 2014). The WAS gene (Xp11.22–p11.23) encodes the WAS protein, involved in actin polymerization and associated coupling of receptor engagement, signaling events, and cytoskeletal rearrangement (Buchbinder et al., 2014). A 14-year-old Caucasian male presented to our Institute with a 5month history of PG lesions (Figure 1a,b). His personal medical history was positive for WAS. Whole genome sequencing detected the mutation inv(X)g.5721–11840, a rare inversion in WAS gene. In addition, the patient medical history was also positive for arthritis, Henoch– Sch€ onlein purpura, and a Crohn-like colitis, that led to subtotal colectomy and ileostomy. Several therapies were started to manage PG, including systemic metil-prednisolone (5 mg/kg/day), minocycline (100 mg twice daily), cyclosporine (5 mg kg/day), and adalimumab (80 mg at week 0, 40 mg at week 1, followed by 40 mg every 15 days). However, no PG improvement was observed. Therefore, we decided to start anakinra 100 mg once a day. Two months after a complete

Non Melanoma Skin Cancer Pathogenesis Overview

(1) Background: Non-melanoma skin cancer is the most frequently diagnosed cancer in humans. The process of skin carcinogenesis is still not fully understood. However, several studies have been conducted to better explain the mechanisms that lead to malignancy; (2) Methods: We reviewed the more recent literature about the pathogenesis of non-melanoma skin cancer focusing on basal cell carcinomas, squamous cell carcinoma and actinic keratosis; (3) Results: Several papers reported genetic and molecular alterations leading to non-melanoma skin cancer. Plenty of risk factors are involved in non-melanoma skin cancer pathogenesis, including genetic and molecular alterations, immunosuppression, and ultraviolet radiation; (4) Conclusion: Although skin carcinogenesis is still not fully understood, several papers demonstrated that genetic and molecular alterations are involved in this process. In addition, plenty of non-melanoma skin cancer risk factors are now known, allowing for an effective prevention of non-melanoma skin cancer development. Compared to other papers on the same topic, our review focused on molecular and genetic factors and analyzed in detail several factors involved in non-melanoma skin cancer.

Resolution of Benign and Malignant Sebaceous Neoplasms, in a Renal Transplant Patient Treated With Everolimus.

Nonmelanoma skin cancers are the most common malignancies in transplant recipients under immunosuppression; nevertheless, appendage tumors also may appear. The onset of several cutaneous neoplasms in transplant patients can cause deterioration in quality of life of these patients. A 62-year-old white woman patient developed several malignant and benign sebaceous neoplasms during an immunosuppressive treatment for a renal transplant. The genetic study showed a mutation in MSH6-eson 1 (c116G>A), without mutations in MLH1 gene and MSH2. A final diagnosis of multiple sebaceous tumors in an immunosuppressed patient without Muir -Torre syndrome was made. The spreading of further cutaneous neoplasms led to a change in immunosuppression: namely, that clinicians suspended tacrolimus and add everolimus. After 2 months, all tumor lesions on the face and on the limbs have disappeared, and no further lesions occurred. Everolimus could represent a valid therapeutical treatment for transplant patients at high risk for cutaneous tumors. A genetic consult and a consequent study of the genetic profile should be performed on each of these patients, to avoid risks of recurrent cutaneous tumors and negative effects on the quality of life.

MAL Daylight Photodynamic Therapy for Actinic Keratosis: Clinical and Imaging Evaluation by 3D Camera.

Non-melanoma skin cancer is the most common skin cancer with an incidence that varies widely worldwide. Among them, actinic keratosis (AK), considered by some authors as in situ squamous cell carcinoma (SCC), are the most common and reflect an abnormal multistep skin cell development due to the chronic ultraviolet (UV) light exposure. No ideal treatment exists, but the potential risk of their development in a more invasive form requires prompt treatment. As patients usually present with multiple AK on fields of actinic damage, there is a need for effective, safe, simple and short treatments which allow the treatment of large areas. To achieve this, daylight photodynamic therapy (DL-PDT) is an innovative treatment for multiple mild actinic keratosis, well tolerated by patients. Patients allocated to the PDT unit, affected by multiple mild−moderate and severe actinic keratosis on sun-exposed areas treated with DL-PDT, were clinically evaluated at baseline and every three months with an Antera 3D, Miravex© camera. Clinical and 3D images were performed at each clinical check almost every three months. In this retrospective study, 331 patients (56.7% male, 43.3% female) were treated with DL-PDT. We observed a full clearance in more than two-thirds of patients with one or two treatments. Different responses depend on the number of lesions and on their severity; for patients with 1–3 lesions and with grade I or II AK, a full clearance was reached in 85% of cases with a maximum of two treatments. DL-PDT in general improved skin tone and erased sun damage. Evaluating each Antera 3D images, hemoglobin concentration and pigmentation, a skin color and tone improvement in 310 patients was observed. DL-PDT appears as a promising, effective, simple, tolerable and practical treatment for actinic damage associated with AK, and even treatment of large areas can be with little or no pain. The 3D imaging allowed for quantifying in real time the aesthetic benefits of DL-PDT’s increasing compliance.