Antonio Giovanni Richetta

Total Spontaneous Regression of Advanced Merkel Cell Carcinoma after Biopsy: Review and a New Case

The clinical behavior is characterized by high incidence of local recurrence (27%–60%), of lymph node metastases (45%–91%), and of distant metastases in the liver, bone, brain, lung, or skin (18%–52%). The incidence of disease-related death is as high as 35% to almost 50%. Despite its highly malignant nature, spontaneous regression has occasionally been reported. The first recorded case of spontaneous regression (CSR) of MCC was described in 1986; since then, other such cases have been reported, bringing the total to 14. Of the total number of 14 cases, 12 cases can be classified as complete spontaneous regression after only the performance of a biopsy.

Imiquimod 5% Cream Use in Dermatology, Side Effects and Recent Patents

Imiquimod is an immune response modifier that stimulates the patients 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.

Lisch nodules of the iris in neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disease. The Lisch nodule represents one of the most common NF1 ocular manifestations. Several studies have reported that the Lisch nodule is a melanocytic hamartoma but its pathogenesis is still debated. We have studied the histopathological and ultrastructural features of a Lisch nodule of a 50‐year‐old woman biopsied during an intracapsular cataract extraction. Our researches revealed that it was composed of three main cytotypes: pigmented cells, fibroblast‐like cells and mast cells, showing a pattern similar to a neurofibroma. Furthermore, we hypothesize that Lisch nodules are compatible with neurofibromas.

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.

CD4+ CD25+ T-regulatory cells in psoriasis. Correlation between their numbers and biologics-induced clinical improvement

BACKGROUND Regulatory T-cells (T-reg) play a central role in the immunopathogenesis of psoriasis. T-reg cells are both functionally and numerically impaired in psoriasis and they are up-regulated by drug therapy. OBJECTIVE To analyse the circulating CD4+CD25 bright FOXP3+ subset in 14 patients with vulgaris/arthropathic psoriasis treated with biological drugs and to investigate their relationship with the clinical response. METHODS The CD4+ CD25 bright FOXP3+ expression was determined in peripheral blood by flow cytometry at baseline and during treatment. RESULTS A response was obtained in 10/14 patients with increased CD4+ CD25 bright FOXP3+ (T-reg) in peripheral blood after the first month and then 4 months after therapy with biological drugs. This increase is associated with the achievement of a clinical response and with a reduction in the Psoriasis Activity and Severity Index (PASI) score. 2/14 patients showed a decrease in T-reg after drug therapy and this decrease correlated with a worsening of the clinical skin. CONCLUSION Biological drugs induce circulating T-reg up-regulation in psoriatic patients; such an increase is an early predictive marker of clinical response.

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.

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.

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.

Treatment of erythrodermic psoriasis in HCV+ patient with adalimumab

Erythrodermic psoriasis is a severe and disabling variant of psoriasis. The authors present the case of a 48‐year‐old man with psoriasis and hemophilia presented with a history of hepatitis C virus (HCV) infection treated with pegylated interferon alpha‐2a and ribavirin therapy. At the end of antiviral therapy, skin manifestation progressively worsened, becoming erythrodermic, with lack of efficacy of steroid therapy. The authors decided to start biological therapy with induction dose of adalimumab (Humira, Abbott Laboratories, Abbott Park, Chicago, IL) 80 mg at Week 0 and 40 mg weekly. In our case, this resulted in a highly effective and safe treatment.

Treating psoriasis with etanercept in Italian clinical practice: Prescribing practices and duration of remission following discontinuation

AbstractBackground: Conventional antipsoriatic therapies are often administered until remission, with treatment resumed in the case of relapse, in order to reduce the likelihood of cumulative, dose-dependent toxicities. Biological agents have been safely used in continuous therapy. Objective: To assess the use of etanercept for psoriasis in clinical practice in Italy. Methods: This was an observational study carried out in 13 dermatological centres across Italy in patients with plaque psoriasis (with a Psoriasis Area and Severity Index [PASI] score ≥10) treated with etanercept. The study comprised a treatment and subsequent discontinuation period. Patients were eligible if they had plaque psoriasis and had begun treatment with etanercept between 1 September 2007 and 1 April 2008. Patients were evaluable for the duration of discontinuation analysis if they achieved a PASI reduction ≥50% (PASI50) and a PASI score <10 at the end of treatment. Etanercept treatment was restarted if the PASI score reached ≥10 or the patient had a clinical relapse. Data were collected retrospectively up to June 2008 and prospectively between July 2008 and January 2009. Patients received etanercept during the treatment period, followed by no etanercept treatment (other psoriasis treatment permitted) during the discontinuation period, and etanercept again during re-treatment. The main outcome measures were: PASI scores (type A responders: PASI reduction ≥75% [PASI75]; type B responders: PASI50 and PASI final score <10), Dermatology Life Quality Index (DLQI) scores and body surface area (BSA) involvement. Time from discontinuation to retreatment was evaluated. Use of other antipsoriatic medications was recorded throughout. Results: Eighty-five patients were evaluable for the treatment period. Overall, 55 (64.7%) of these patients were prescribed etanercept 50 mg twice weekly. The mean treatment duration was approximately 25 weeks. In total, 79 patients (92.9%) were considered type B responders and 77 of these patients were evaluable for the duration of discontinuation analysis. Overall, 68/85 (80%) were type A responders. During the treatment period, 7/85 (8.2%) patients received other antipsoriatic therapies. Improvements in mean DLQI score (−71.5%) and mean BSA involvement (−79.2%) were also observed. Etanercept was well tolerated. During the discontinuation period, 40/77 (51.9%) patients used other antipsoriatic medications (group 1) and 37/77 (48.1%) did not (group 2). The mean duration of discontinuation was significantly longer in group 1 (174 days) than in group 2 (117 days, log-rank test: p = 0.0013). Conclusion: In clinical practice, the duration of discontinuation from etanercept was in accordance with previously reported data, and was longer in patients who received other antipsoriatic drugs during discontinuation of etanercept than in those who did not. High rates of PASI50 and PASI75 response were obtained with etanercept, and these rates were higher than those observed in controlled clinical studies. Etanercept treatment was flexible, effective and well tolerated, and was associated with improved quality of life.