Certolizumab for the treatment of psoriasis and psoriatic arthritis: a real-world multicentre Italian study.

BACKGROUND: Certolizumab, a pegylated tumour necrosis factor-α inhibitor, reduced disease activity in randomized trials of patients with psoriasis and psoriatic arthritis. Real-life data are missing. OBJECTIVE: To confirm the effectiveness and safety of certolizumab in patients with psoriasis and psoriatic arthritis in routine clinical practice. METHODS: In this retrospective study involving 11 Italian sites, patients with psoriasis and psoriatic arthritis received subcutaneous certolizumab (400 mg loading dose at 0, 2 and 4 weeks, followed by 200 mg every 2 weeks) for up to 52 weeks. Primary outcomes included mean change from baseline in Psoriasis Area and Severity Index (PASI) and modified Nail Psoriasis Severity Index (mNAPSI) scores, and the proportion of patients achieving a 75%, 90% or 100% reduction in PASI score. Other endpoints included Disease Activity Score computed on 44 joints correlated with the erythrocyte sedimentation rate during the first hour (DAS44-ESR), Tender Joint Count (TJC), Swollen Joint Count (SJC), pain [visual analogue scale (VAS) score], inflammatory markers and quality of life (QOL). RESULTS: In the study were enrolled 153 patients (mean age: 55 years). Certolizumab reduced the mean PASI score from baseline by 4.45, 6.30 and 7.58 at weeks 12, 24 and 52, respectively (P < 0.001 for all). At weeks 24 and 52, 69.6% and 83.3% of patients had a PASI score ≤3. DAS44-ESR, TJC, SJC and mNAPSI scores, and pain VAS were also all significantly improved from baseline at each time point. C-reactive protein levels decreased during treatment, being significant at week 24. On multivariate analysis, psoriasis duration, baseline PASI, mNAPSI and pain VAS scores were found to be predictive of the improvement in PASI score at week 12. CONCLUSION: Certolizumab displayed also in the real-life encouraging results in both psoriasis and psoriatic arthritis patients.

The role of the dermatologist in the immune-mediated/allergic diseases - position statement of the EADV task force on contact dermatitis, EADV task force on occupational skin diseases, UEMS-EBDV subcommission allergology and European Dermatology Forum.

BACKGROUND: The members of the Task Force on Contact Dermatitis and the Task Force on Occupational Dermatoses of the European Academy of Dermatology and Venereology (EADV), of the European Dermatology Forum (EDF), and the members of the UEMS Section of Dermatology-Venereology (UEMS-EBDV) we want to vindicate the fundamental role that the specialist in Dermatology has in the diagnosis and management of Immuno-mediated /allergic Diseases. OBJECTIVE: In disagreement with the blueprint paper of the UEMS section of Allergology (2013), in which dermatologists are excluded from one of their core activities it was decided to write this consensus paper. DISCUSSION: The skin occupies a crucial place in the broad spectrum of allergic diseases; there is no other organ with such a multitude of different clinical conditions mediated by so many pathogenetic immune mechanisms. Subsequently, dermatologists play a fundamental role in the management of immune-mediated diseases including among others contact dermatitis, atopic dermatitis, urticaria and angioedema or cutaneous adverse drug, food and arthropod reactions. The essential role of dermatology in the diagnostic, therapeutic and preventive management of immune mediated /allergic diseases which is crucial for patient management is justified from both the academic and professional point of view. CONCLUSION: Based on the best care of the patient with cutaneous immune allergic disease a multidisciplinary approach is desirable and the dermatologist has a pivotal role in patient management. Be so good and no one will not ignore you, dermatologist. Ideally Dermatology should be governed according the following Henry Ford statement: "Arriving together is the beginning; keeping together is progress; working together is success."

A new T helper 17 cytokine in hidradenitis suppurativa: antimicrobial and proinflammatory role of interleukin-26.

BACKGROUND: Interleukin (IL)-26 is a signature T helper 17 cytokine described as a proinflammatory and antimicrobial mediator. So far, IL-26 has been reported in several immune-mediated inflammatory diseases, but its involvement in inflammatory skin disorders is poorly known. OBJECTIVES: To investigate the role of IL-26 in hidradenitis suppurativa (HS), through its involvement in antimicrobial activity. METHODS: IL-26 was assessed in patients with HS through gene expression and protein analysis at skin and circulating levels. Ex vivo HS organ skin cultures, together with IL-26 antibody treatment, were performed to determine the IL-26 activity. Peripheral blood mononuclear cells (PBMCs) from patients with HS and healthy controls were either silenced or not with IL-26 small interfering (si)RNA in order to measure its antimicrobial, cytotoxic and phagocytic activities against Staphylococcus aureus. RESULTS: Firstly, we observed that IL-26 is able to modulate the proinflammatory response at the immune cell level. IL-26 was increased in the plasma of patients with HS compared with healthy controls. Subsequently, we explored the bactericidal, cytotoxic and phagocytic activities of PBMCs against S. aureus in patients with HS and healthy controls. These activities were lower in patients with HS than in controls. Remarkably, the killing activities were reduced when healthy control PBMCs were transfected with IL-26 siRNA. However, the transfection did not affect the killing activity of HS PBMCs, supporting the idea that IL-26 lacks efficacy in HS. CONCLUSIONS: Our findings suggest that infection susceptibility in HS might be related to IL-26. Although the role of bacteria remains controversial in HS, this paper supports that there is a defect of antimicrobial response in these patients. What's already known about this topic? Interleukin (IL)-26 is a T helper 17 cytokine described as an antimicrobial and proinflammatory mediator. IL-26 has been reported in immune-mediated inflammatory diseases, but its involvement in inflammatory skin disorders remains unclear. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder characterized by deficiency of IL-20 and IL-22 (a close homologue of IL-26), which causes antimicrobial peptide pauperization leading to severe and recurrent skin infections. What does this study add? IL-26 plasma levels are higher in patients with HS than in healthy control individuals. The antimicrobial activity of IL-26 might be ineffective in patients with HS. What is the translational message? Cutaneous antimicrobial incompetence in HS could be related to IL-26.

Understanding the role of haptoglobin in psoriasis: effects of ultraviolet B.

BACKGROUND: Haptoglobin (Hp) is one of the acute phase proteins, whose main function is to bind free haemoglobin (Hb) and transport it to the liver for degradation and iron recycling. In addition to its role as an Hb scavenger, Hp has been shown to behave as an anti-inflammatory, antioxidant and angiogenic factor. We previously investigated the role of Hp in the pathogenesis of psoriasis, and found that it displays some structural modifications that might be associated with protein function in the disease. Phototherapy is an efficacious treatment for psoriasis, although the biological mechanisms by which phototherapy improves psoriasis are still unclear. AIM: To investigate the effects of ultraviolet (UV)B on Hp to clarify the role of Hp in psoriasis. METHODS: Expression of the genes encoding Hp, interleukin (IL)-6 and IL-10 was assessed in UVB-irradiated and unirradiated HaCaT cells. The biological significance of Hp modulation of UVB treatment was confirmed by ELISA and Western blotting. The Hp gene and protein expression in the skin of patients with psoriasis was also investigated. RESULTS: In vitro results showed that UVB modulated IL-6 and IL-10 gene expression and Hp gene and protein expression in HaCaT cells. The in vivo data also showed that Hp levels were increased in the skin of patients with psoriasis compared with healthy controls. CONCLUSIONS: UVB irradiation was able to modulate Hp production in immortalized keratinocytes. The higher levels of Hp in vivo in both lesional and nonlesional skin suggest that it might have a role in the pathogenesis of the disease.

Nicotinamide downregulates gene expression of interleukin-6, interleukin-10, monocyte chemoattractant protein-1, and tumour necrosis factor-α gene expression in HaCaT keratinocytes after ultraviolet B irradiation.

Ultraviolet (UV) radiation has profound effects on human skin, causing sunburn, inflammation, cellular-tissue injury, cell death, and skin cancer. Most of these effects are mediated by a number of cytokines produced by keratinocytes. In this study we investigated whether nicotinamide (NCT), the amide form of vitamin B3, might have a protective function in reducing the expression of interleukin (IL)-1ß, IL-6, IL-8, IL-10, monocyte chemoattractant protein (MCP)-1 and tumour necrosis factor (TNF)-α in UV-irradiated keratinocytes. HaCaT cells were treated with UVB in the presence or absence of NCT, and cytokine mRNA levels were examined by quantitative real-time PCR. NCT significantly downregulated IL-6, IL-10, MCP-1 and TNF-α mRNA expression, whereas it did not exert any significant effect on IL-1ß or IL-8 expression. Because of its ability to decrease these cytokine mediators after UV exposure, NCT is a possible therapy to improve or prevent conditions induced or aggravated by UV light.

Climate change and skin.

Global climate appears to be changing at an unprecedented rate. Climate change can be caused by several factors that include variations in solar radiation received by earth, oceanic processes (such as oceanic circulation), plate tectonics, and volcanic eruptions, as well as human-induced alterations of the natural world. Many human activities, such as the use of fossil fuel and the consequent accumulation of greenhouse gases in the atmosphere, land consumption, deforestation, industrial processes, as well as some agriculture practices are contributing to global climate change. Indeed, many authors have reported on the current trend towards global warming (average surface temperature has augmented by 0.6 °C over the past 100 years), decreased precipitation, atmospheric humidity changes, and global rise in extreme climatic events. The magnitude and cause of these changes and their impact on human activity have become important matters of debate worldwide, representing climate change as one of the greatest challenges of the modern age. Although many articles have been written based on observations and various predictive models of how climate change could affect social, economic and health systems, only few studies exist about the effects of this change on skin physiology and diseases. However, the skin is the most exposed organ to environment; therefore, cutaneous diseases are inclined to have a high sensitivity to climate. For example, global warming, deforestation and changes in precipitation have been linked to variations in the geographical distribution of vectors of some infectious diseases (leishmaniasis, lyme disease, etc) by changing their spread, whereas warm and humid environment can also encourage the colonization of the skin by bacteria and fungi. The present review focuses on the wide and complex relationship between climate change and dermatology, showing the numerous factors that are contributing to modify the incidence and the clinical pattern of many dermatoses.

A preterm infant with benign neonatal hemangiomatosis and persistent patent ductus arteriosus: a curious comorbidity.

A female infant had been delivered prematurely at 33 weeks to a gravida 1, para 0, 32-year-old mother following normal spontaneous vaginal delivery. Because of persistent patent ductus arteriosus the new born underwent surgery after 30 days. Four months later, when the infant arrived at our observation, approximately 13 red, nodular hemangiomas ranging from 0.5 to 30 mm in diameter were scattered over the scalp, trunk, abdomen, and extremities. Laboratory and instrumental tests investigating visceral involvement were all negative. Our diagnosis was of benign neonatal hemangiomatosis. Benign neonatal hemangiomatosis is a condition with multiple congenital hemangiomas limited to the skin. The incidence in the newborn population is between 1.0% and 4% with females 4 times more affected than males. Solitary hemangiomas occur more frequently in premature neonates with a reported incidence, inversely proportional to birth weight. Although the exact mechanism for hemangioma development remains unknown, vascular growth factors seem to play a role in the pathogenesis. Proliferation most likely results from an imbalance between positive and negative angiogenic factors expressed by the hemangioma and adjacent normal tissue. Patency of the ductus arteriosus is a common complication of preterm birth. During the immediate postpartum period, a loss of vasodilatory stimuli and activation of intrinsic contractile mechanisms facilitates ductus lumen occlusion. The imbalance of these forces, linked to premature birth, interrupts the normal maturation process, leaving the immature ductus patent. Our case is the first one of benign neonatal hemangiomatosis and patency ductus arteriosus described.

Modification of osteopontin and MMP-9 levels in patients with psoriasis on anti-TNF-α therapy.

Psoriasis is a chronic skin inflammatory disease in which a pleiotropic cytokine, tumor necrosis factor alpha (TNF-α), plays a central role, as demonstrated by the clinical success of anti-TNF-α therapy. Among the multiple effects of TNF-α on keratinocytes, the induction of matrix metalloproteinase-9 (MMP-9), a collagenase implicated in joint inflammation, might be one of the key mechanisms in psoriasis pathogenesis. Interestingly, MMP-9 expression can be enhanced also by osteopontin (OPN), a glycosylated protein whose levels are increased in skin and peripheral blood mononuclear cells (PBMC) of psoriasis patients. The aim of the current study is to investigate the relationship between OPN, MMP-9 and TNF-α in psoriasis. Our survey identified high levels of both OPN and MMP-9 in PBMC as well as skin of psoriatic patients with respect to healthy controls. Significant reduction of OPN and MMP-9 levels in PBMC, plasma and lesional skin of psoriasis patients was observed after 24 weeks of anti-TNF-α therapy. Moreover, OPN and MMP-9 were enhanced by TNF-α and down-regulated by anti-TNF-α treatment in healthy PBMC. These findings may suggest that OPN and MMP-9 may be regulated by TNF-α, indicating a possible role in the pathogenesis of psoriasis.

Psoriasis and melanocytic naevi: does the first confer a protective role against melanocyte progression to naevi?

BACKGROUND: Some of the cytokines that have effects on melanogenesis are also reported to be involved in psoriasis. OBJECTIVES: We therefore studied the relationship between psoriasis and melanocytic naevi. In particular, the aim of our study was to investigate the number of melanocytic naevi in patients with psoriasis vs. controls. METHODS: We performed a prospective case-control study, analysing 93 adult patients with psoriasis and 174 adult aged-matched controls. For each participant a questionnaire was completed to establish personal data, personal medical history, and personal and familial history of skin cancer and psoriasis. We analysed interleukin (IL)-1α, IL-6 and tumour necrosis factor (TNF)-α gene expression at the peripheral blood mononuclear cell level in patients with psoriasis and in controls. RESULTS: In our study, patients with psoriasis presented a lower number of areas with naevi in comparison with controls (P < 0·0001). Nobody had ever had squamous cell carcinoma or melanoma in the psoriatic group; moreover, there was a significant difference in familial history of melanoma between the two groups (none in the psoriatic group vs. 8% in the control group; P < 0·05). IL-1α, IL-6 and TNF-α expression levels were higher in patients with psoriasis. CONCLUSIONS: People with psoriasis had fewer melanocytic naevi. This suggests that the proinflammatory cytokine network in psoriasis skin might inhibit melanogenesis, melanocyte growth and/or progression to naevi.

Telediagnosis and face-to-face diagnosis reliability for melanocytic and non-melanocytic 'pink' lesions.

BACKGROUND: Telemedicine is a worldwide healthcare practice that, during the last years, has dramatically reduced the time of consultation for patients. Teledermoscopy aids in the current management of skin cancers in general and particularly of melanoma; telemedicine and teledermoscopy give the chance to provide consultations with experts also by long distance. OBJECTIVE: The purpose of this study is to determine the diagnostic reliability, according to interobserver agreement, between clinical and dermoscopic diagnosis of lesions with poor and/or absent pigmentation, comparing face-to-face diagnosis and telediagnosis. MATERIALS AND METHODS: Forty-four lesions were examined by two different dermatologists with good and similar experience in the clinical field and dermoscopy. A store-and-forward teledermatological system, based on clinical and dermoscopic images, was done by the two skilled dermatologists. RESULTS: Our results underline that teledermoscopy of 'pink' lesions does not provide a similar degree of diagnostic accuracy as otherwise in face-to-face diagnosis perhaps due to the absence of typical criteria. Atypical skin lesions are characterized by the absence of typical dermoscopic patterns, and their teleconsultation does not always increase the diagnostic accuracy.

Hemosiderotic dermatofibroma: report of one case.

Dermatofibroma (DF) is a common benign fibrohistiocytic lesion which presents with a wide variety of clinicopathological features. Generally, the clinical diagnosis is easy, but differentiating it from other cutaneous tumors could be difficult in atypical cases and rare variants. We may find at least four different histopathological variants of DF; more than one of which may be present in a single tumor. Hemosiderotic DF is a variant composed of numerous small vessels, extravasated erythrocytes, and intra- and extracellular hemosiderotic deposits. The differential diagnosis may comprise melanoma as well as other melanocytic and nonmelanocytic tumors. We report the case of a 38-year-old man who presented with a hemosiderotic DF on the abdomen.