Leonardo Pescitelli

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.

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.

Deficiency of serum concentration of 25-hydroxyvitamin D correlates with severity of disease in chronic plaque psoriasis

To the Editor: We read with interest the article by Orgaz-Molina et al regarding the vitamin D status in patients with chronic plaque psoriasis. The authors report a high prevalence (25.6%) of vitamin D deficiency [25(OH)D levels\20 ng mL ] in a cohort of 43 psoriatic patients, independently of age, sex and Psoriasis Area and Severity Index (PASI) score. Low 25(OH)D levels were negatively associated with markers of inflammatory activation (C-reactive protein) and body mass index (BMI). We conducted a case-control study over 4months ( fromSeptember to December) including 68 patients affected by chronic plaque psoriasis and 60 healthy controls. 25(OH)D serum levels were measured in a centralized laboratory using the LIAISON 25OH Vitamin D TOTAL Assay. Logistic regression analysis of the relationship of 25(OH)D levels to demographic data (age, sex and body mass index), alcohol consumption and smoking habit data, exposure time to sunlight, dairy intake, disease duration and severity was performed. Psoriatic patients had significantly lower serum levels of 25(OH)D than healthy controls (P \ .05) with 68% and 97% being vitamin D deficient (\20 ng/mL) and insufficient (\30 ng/mL), respectively (Fig 1). In the logistic regression analysis, vitamin D deficiency was associated with psoriasis independently of age, sex, BMI, alcohol consumption, and smoking habit. Interestingly, serum 25(OH)D had significant negative correlations with PASI score (P\ .001), which signifies a possible link between the extent of vitamin D deficiency and the degree of the severity of psoriasis (Fig 2). Recently, vitamin D deficiency has been implicated as a potential environmental factor triggering some immune-mediated disorders. Our study confirms that vitamin D deficiency may be common in patients with psoriasis and adds some important information concerning a possible link between this deficit and the severity of disease. We conclude that psoriatic patients could be screened for vitamin D insufficiency for a more comprehensive management. Future studies looking at a potential role of oral supplementation of vitamin D in the treatment of psoriasis are warranted.

Etanercept restores a differentiated keratinocyte phenotype in psoriatic human skin: a morphological study.

Tumor Necrosis Factor‐α (TNF‐α) plays a pivotal role in psoriasis, an immuno‐mediated and genetic skin disease. Anti‐TNF‐α inhibitors, such as etanercept, are widely used in clinical practice. By immunofluorescence, we investigated the expression of junctional transmembrane proteins in desmosomes (desmocollin‐1, Dsc1; desmoglein‐1, Dsg1), adherens junctions (E‐cadherin), tight junctions (occludin), biomarkers of keratinocyte differentiation (keratin‐10, K10; keratin‐14, K14; keratin‐16, K16; involucrin), epithelial proliferation and apoptosis in psoriatic skin before/after etanercept treatment (n = 5) and in control skin samples (n = 5). Occludin, K14, K16 and involucrin expressions were altered in psoriatic epidermis, while Dsc1, Dsg1, E‐cadherin and K10 localisations were comparable to controls. Etanercept promoted the restoration of the physiological condition as suggested by a more differentiated keratinocyte phenotype and a reduced epidermal proliferation rate.

Development of MGUS in psoriatic patients: a possible undiagnosed event during anti-TNF-α-treatment

Background  Monoclonal gammopathies are haematological conditions characterized by the clonal proliferation of plasma cells which produce a monoclonal immunoglobulin that accumulates in the blood. They have already been reported during treatment with a range of drugs but never before during treatment with the anti‐TNF‐α treatments: adalimumab, etanercept and infliximab currently used in the therapy of moderate‐severe psoriasis and psoriatic arthritis.

Treatment of severe nail psoriasis with acitretin: an impressive therapeutic result

Nail psoriasis is common in adult psoriatic patients. Although several new drugs have recently been introduced for the treatment of skin psoriasis, treatment of nail psoriasis still remains a challenge. Topical treatments (e.g., corticosteroids, tazarotene, 5‐fluorouracil, calcipotriol) are the first line in the management of skin psoriasis. The efficacy of these drugs in nail disease, however, is limited, mainly due to the difficulty in penetrating the nail bed and nail matrix. In cases of nail disease resistant to topical treatment, methotrexate, ciclosporin, acitretin, or biological agents can be used. The present authors introduce a 73‐year‐old patient affected by impressive psoriatic nail disease involving all her fingernails and toenails treated by acitretin, a traditional systemic treatment. After 2 months of treatment there was a marked improvement. The clinical improvement of the nails was progressive and 6 months later it was stable and satisfactory. The remarkable response to treatment in this case suggests that oral acitretin, in association to urea nail lacquer, might be useful in the management of disabling severe nail psoriasis even in absence of severe cutaneous involvement.

Development of monoclonal gammopathy in 12 patients receiving efalizumab treatment for chronic plaque psoriasis

REFERENCES 1. Mendenhall WM, Mendenhall CM, Werning JW, Reith JD, Mendenhall NP. Cutaneous angiosarcoma. Am J Clin Oncol 2006;29:524-8. 2. DeMartelaere SL, Roberts D, Burgess MA, Morrison WH, Pisters PW, Sturgis EM, et al. Neoadjuvant chemotherapy-specific and overall treatment outcomes in patients with cutaneous angiosarcoma of the face with periorbital involvement. Head Neck 2008;30:639-46. 3. Skubitz KM, Haddad PA. Paclitaxel and pegylated-liposomal doxorubicin are both active in angiosarcoma. Cancer 2005;104:361-6. 4. Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007;357:2666-76. 5. Koontz BF, Miles EF, Rubio MA, Madden JF, Fisher SR, Sher RL, et al. Preoperative radiotherapy and bevacizumab for angiosarcoma of the head and neck: two case studies. Head Neck 2008;30:262-6.

Retrospective analysis of systemic treatments for psoriasis patients attending a Psocare center in Florence. Relevance of biological drugs use and comorbidities

Background  Psoriasis is a chronic inflammatory skin condition associated with several risk factors and comorbidities.

Interleukin 22 early affects keratinocyte differentiation, but not proliferation, in a three-dimensional model of normal human skin

Interleukin (IL)-22 is a pro-inflammatory cytokine driving the progression of the psoriatic lesion with other cytokines, as Tumor Necrosis Factor (TNF)-alpha and IL-17. Our study was aimed at evaluating the early effect of IL-22 alone or in combination with TNF-alpha and IL-17 by immunofluorescence on i) keratinocyte (KC) proliferation, ii) terminal differentiation biomarkers as keratin (K) 10 and 17 expression, iii) intercellular junctions. Transmission electron microscopy (TEM) analysis was performed. A model of human skin culture reproducing a psoriatic microenvironment was used. Plastic surgery explants were obtained from healthy young women (n=7) after informed consent. Fragments were divided before adding IL-22 or a combination of the three cytokines, and harvested 24 (T24), 48 (T48), and 72 (T72)h later. From T24, in IL-22 samples we detected a progressive decrease in K10 immunostaining in the spinous layer paralleled by K17 induction. By TEM, after IL-22 incubation, keratin aggregates were evident in the perinuclear area. Occludin immunostaining was not homogeneously distributed. Conversely, KC proliferation was not inhibited by IL-22 alone, but only by the combination of cytokines. Our results suggest that IL-22 affects keratinocyte terminal differentiation, whereas, in order to induce a proliferation impairment, a more complex psoriatic-like microenvironment is needed.