Francesca Prignano

Traumatic eosinophilic granuloma of the oral mucosa: a CD30+(Ki-1) lymphoproliferative disorder?☆

Traumatic eosinophilic granuloma of the oral mucosa, also known as eosinophilic ulcer, is considered to be a reactive lesion of unknown aetiology. It usually presents as a tongue ulcer and injury has been considered to play a role in its cause. We present a 72-year-old man who had suffered multiple episodes of recurrent eosinophilic ulcers of the oral mucosa which underwent self-healing. Biopsy specimens (including fresh tissue) were studied with a combination of histology, electron microscopy and immunohistochemistry. A dense cell infiltrate composed of eosinophilis, lymphocytes and large mononuclear cells was constantly shown. Immunostains showed that the infiltrate was mainly composed of CD3+,CD4+,CD8-T-cells and CD1a + dendritic cells. Approximately 70% of the T-cells expressed CD30 (Ki-1) antigen. On the basis of the clinical behaviour, histology and antigenic features, it seems reasonable to suggest that traumatic eosinophilic granuloma of the oral mucosa may represent the oral countpart of primary cutaneous CD30 (Ki-1)-positive lymphoproliferative disorders. This group of cutaneous lymphomas are indeed characterised by non-aggressive clinical behaviour (sequential evolution in ulceration, necrosis and self-regression) and expression of CD30 antigen by the infiltrating large T-cells.

Prurigo nodularis and lichen simplex chronicus

ABSTRACT:  Emotional tensions in predisposed subjects may play a key role in inducing a pruritic sensation, leading to a scratching that, becoming a self‐perpetuating pathomechanism, may represent the main feature of two distinct cutaneous clinical entities: prurigo nodularis and lichen simplex chronicus. Psychogenic factors play a relevant role in both conditions, and they are often associated with depression and dissociative experiences. Hence, the importance of the evaluation of these patients from the point of view of psychodermatology, which may analyze the relationship between skin disease and psychological factors. Patients with real or perceived imperfections in particular areas of the body (face, scalp, hands, and genital area) are more prone to psychologic distress, whereas cutaneous diseases may lead to experience a heightened level of distress. As psychosomatic factors have been estimated to be present in at least one‐third of dermatologic patients, effective management of skin conditions involves consideration of the associated emotional factors.

Fractional CO2 laser: a novel therapeutic device upon photobiomodulation of tissue remodeling and cytokine pathway of tissue repair

Minimally ablative fractional laser devices have gained acceptance as a preferred method for skin resurfacing. Notable improvements in facial rhytides, photodamage, acne scarring, and skin laxity have been reported. The aim of the present work was to compare how different CO2 laser fluences, by modulating the secretory pathway of cytokines, are able to influence the wound‐healing process, and how these fluences are associated with different clinical results. Eighteen patients, all with photodamaged skin, were treated using a fractional CO2 laser (SmartXide DOT, Deka M.E.L.A., Florence, Italy) with varying laser fluences (2.07, 2.77, and 4.15 J/cm2). An immunocytochemical study was performed at defined end points in order to obtain information about specific cytokines of the microenvironment before and after treatment. The secretory pathway of cytokines changed depending on the re‐epithelization and the different laser fluences. Different but significant improvements in wrinkles, skin texture, and hyperpigmentation were definitely obtained when using 2.07, 2.77, and 4.15 J/cm2, indicating fractional CO2 laser as a valuable tool in photorejuvenation with good clinical results, rapid downtime, and an excellent safety profile.

Tumour necrosis factor-α antagonists in patients with concurrent psoriasis and hepatitis B or hepatitis C: a retrospective analysis of 17 patients.

Introduction  Tumour necrosis factor (TNF)‐α antagonists are effective for the treatment of plaque‐type psoriasis and psoriatic arthritis, but concerns remain about the safety of these agents in the presence of chronic infections, including past hepatitis B (HBV) and chronic hepatitis C virus (HCV) infections.

Guidance for the management of patients with latent tuberculosis infection requiring biologic therapy in rheumatology and dermatology clinical practice

Since the introduction of biologics for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and psoriasis (Pso) an increased risk of tuberculosis (TB) reactivation in patients with latent tuberculosis infection (LTBI) has been recorded for anti-TNF agents, while a low or absent risk is associated with the non-anti-TNF targeted biologics. To reduce this risk several recommendation sets have been published over time, but in most of them the host-related risk, and the predisposing role to TB reactivation exerted by corticosteroids and by the traditional disease-modifying anti-rheumatic drugs has not been adequately addressed. Moreover, the management of the underlying disease, and the timing of biologic restarting in patients with TB occurrence have been rarely indicated. A multidisciplinary expert panel, the Italian multidisciplinary task force for screening of tuberculosis before and during biologic therapy (SAFEBIO), was constituted, and through a review of the literature, an evidence-based guidance for LTBI detection, identification of the individualized level of risk of TB reactivation, and practical management of patients with TB occurrence was formulated. The literature review confirmed a higher TB risk associated with monoclonal anti-TNF agents, a low risk for soluble receptor etanercept, and a low or absent risk for non-anti-TNF targeted biologics. Considering the TB reactivation risk associated with host demographic and clinical features, and previous or current non-biologic therapies, a low, intermediate, or high TB reactivation risk in the single patient was identified, thus driving the safest biologic choice. Moreover, based on the underlying disease activity measurement and the different TB risk associated with non-biologic and biologic therapies, practical indications for the treatment of RA, PsA, AS, and Pso in patients with TB occurrence, as well as the safest timing of biologic restarting, were provided.

The involvement of Smac/DIABLO, p53, NF-kB, and MAPK pathways in apoptosis of keratinocytes from perilesional vitiligo skin: Protective effects of curcumin and capsaicin.

Oxidative stress has been suggested as the initial pathogenetic event in melanocyte degeneration in vitiligo. Our previous results indicate that keratinocytes from perilesional skin show the features of damaged cells. In the present study, biopsies were taken from the perilesional skin of 12 patients suffering from nonsegmental vitiligo. The intracellular pathways involved in keratinocyte damage and apoptosis and the antioxidant protection of curcumin and capsaicin in these cells were investigated. In keratinocytes from perilesional vitiligo skin, we observed high levels of activated p38, NF-kB p65 subunit, p53, and Smac/DIABLO proteins. In contrast, low levels of ERK phosphorylation were present. To investigate the relationship between these pathways, we used specific inhibitors and evaluated the alteration of each pathway. For the first time, our study demonstrates the pivotal role of p38 MAP kinase as an upstream signal of perilesional keratinocyte damage, and the important contribution of p38 and NF-kB on p53 accumulation. Curcumin and capsaicin also increase ERK phosphorylation, thus inhibiting apoptosis. Moreover, pretreatment with such natural antioxidants inhibited caspase activation, increased total antioxidant capacity, repressed intracellular ROS generation and lipid peroxidation, and improved mitochondrial activity. These results suggest that antioxidants might represent an alternative approach to protect against vitiligo progression.

Ultrastructural and functional alterations of mitochondria in perilesional vitiligo skin

BACKGROUND Vitiligo is a chronic acquired hypomelanotic disorder affecting 0.5-2% of the worlds population. The two major pathogenetic hypotheses are focused on immune-mediated or toxic-mediated cell damage primarily directed at melanocytes. Recent experimental data underline the complex interactions that exist between melanocytes and other cells found in the skin. OBJECTIVE Among these cells, keratinocytes are able to influence both the survival and the functional activity of melanocytes. In order to gain insights into the involvement of different types of epidermic cells in the pathogenesis of vitiligo, we have performed an ultrastructural study on lesional, perilesional and normal skin from 12 patients. All these patients suffered from non-segmental vitiligo, with a similar clinical history in terms of lesion extension and duration of the disease. METHODS We have therefore grown cultures of keratinocytes from lesional, perilesional and healthy skin, evaluating the presence of oxidative damage and apoptotic markers in the cells. RESULTS Taken together, our results indicate that keratinocytes from perilesional skin show features of damaged cells. CONCLUSION Our data, besides considering the achromic patch as the terminal event of a chain of biological processes that take place in the perilesional skin, highlight keratinocytes as having an important role in the development of vitiligo.

HBV Reactivation in Patients Treated with Antitumor Necrosis Factor-Alpha (TNF-α) Agents for Rheumatic and Dermatologic Conditions: A Systematic Review and Meta-Analysis

Introduction. Antitumor necrosis factor-alpha (TNF-α) agents are widely used for treatment of rheumatic and dermatological diseases. We conducted the systematic review and meta-analysis to assess the prevalence of HBV reactivation among patients treated with anti-TNF-α. Methods and Findings. A comprehensive literature search of MEDLINE, Scopus, and ISI Web of Knowledge databases was conducted. From 21 studies included in the systematic review, 9 included patients with occult chronic HBV infection and 6 included patients with overt infection while 6 addressed both groups. Based on 10 studies eligible for meta-analysis we report pooled estimate of HBV reactivation of 4.2% (95% CI: 1.4–8.2%, I 2: 74.7%). The pooled prevalence of reactivation was 3.0% (95% CI: 0.6–7.2, I 2: 77.1%) for patients with occult infection, and 15.4% (95% CI: 1.2–41.2%, I 2: 79.9%) for overt infection. The prevalence of reactivation was 3.9% (95% CI: 1.1–8.4%, I 2: 51.1%) for treatment with etanercept and 4.6% (95% CI: 0.5–12.5%, I 2: 28.7%) for adalimumab. For subgroup of patients without any antiviral prophylaxis the pooled reactivation was 4.0% (95% CI: 1.2–8.3%, I 2: 75.6%). Conclusion. Although HBV reactivation rate is relatively low in patients treated with anti-TNF-α for rheumatic and dermatological conditions, the antiviral prophylaxis would be recommended in patients with overt chronic HBV infection.

Psoriasis and body mass index

Recently, it has emerged a strong association between increased adiposity, obesity, and psoriasis. Body Mass Index (BMI) is a simple index of weight‐for‐height that is commonly used to classify underweight, overweight and obesity in adults. Psoriasis has also been associated with systemic obesity‐related disorders including type 2 diabetes, hypertension, ischemic heart disease, and combined hyperlipidemia, as a part of metabolic syndrome. Not only the obesity may be associated with higher psoriasis incidence and activity, and prevalence of obesity‐related syndromes, but it may also influence the therapeutic approach to disease and the clinical response to systemic treatment. Consequently, the approach of the experienced dermatologist will take into account all the aspects of the patient clinical conditions including the analysis of BMI for the choice of the best suitable therapy.

Infliximab efficacy in nail psoriasis. A retrospective study in 48 patients.

Background  Nail psoriasis occurs in up to half of psoriatic patients and can lead to significant physical impairment and pain. To date, patients and clinicians are actually dissatisfied by current therapeutic approaches.