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- IL-31 and IL-8 in Cutaneous T-Cell Lymphoma: Looking for Their Role in ItchPublication . Abreu, Maria; Miranda, Marta; Castro, M; Fernandes, Iolanda; Cabral, Renata; Santos, Ana Helena; Fonseca, Sonia; Rodrigues, João; Leander, Magdalena; Lau, Catarina; Freitas, Inês; Coimbra, Susana; Santos-Silva, Alice; Lima, MargaridaThe itch associated with cutaneous T-cell lymphoma (CTCL), including Mycosis Fungoides (MF) and Sézary syndrome (SS), is often severe and poorly responsive to treatment with antihistamines. Recent studies have highlighted the possible role of interleukins in nonhistaminergic itch. We investigated the role of IL-31 and IL-8 in CTCL, concerning disease severity and associated itch. Serum samples of 27 patients with CTCL (17 MF and 10 SS) and 29 controls (blood donors) were analyzed for interleukin- (IL-) 31 and IL-8; correlations with disease and itch severity were evaluated. IL-31 serum levels were higher in CTCL patients than in controls and higher in SS than in MF. Also, serum IL-31 levels were higher in patients with advanced disease compared to those with early disease, and they correlated positively with lactate dehydrogenase and beta 2-microglobulin levels, as well as with the Sézary cell count. Itch affected 67% of CTCL patients (MF: 47%; SS: 100%). Serum IL-31 levels were higher in itching patients than in controls and in patients without itching. There was no association between serum IL-8 and disease severity, nor with itching. Serum IL-8 levels correlated positively with peripheral blood leukocyte and neutrophil counts in CTCL patients. Our study suggests a role for IL-31 in CTCL-associated itch, especially in advanced disease and SS, offering a rational target for new therapeutic approaches. Increased serum IL-8 observed in some patients may be related to concomitant infections, and its role in exacerbating itch by recruiting neutrophils and promoting the release of neutrophil proteases deserves further investigation
- Diagnosis, Screening and Treatment of Patients with Palmoplantar Pustulosis (PPP): A Review of Current Practices and RecommendationsPublication . Freitas, Egídio; Rodrigues, Maria Alexandra; T, TorresPalmoplantar pustulosis (PPP) is a rare, chronic, recurrent inflammatory disease that affects the palms and/or the soles with sterile, erupting pustules, which are debilitating and usually resistant to treatment. It has genetic, histopathologic and clinical features that are not present in psoriasis; thus, it can be classified as a variant of psoriasis or as a separate entity. Smoking and upper respiratory infections have been suggested as main triggers of PPP. PPP is a challenging disease to manage, and the treatment approach involves both topical and systemic therapies, as well as phototherapy and targeted molecules. No gold standard therapy has yet been identified, and none of the treatments are curative. In patients with mild disease, control may be achieved with on-demand occlusion of topical agents. In patients with moderate-to-severe PPP, phototherapy or a classical systemic agent (acitretin being the best treatment option, especially in combination with PUVA) may be effective. Refractory patients or those with contraindications to use these therapies may be good candidates for apremilast or biologic therapy, particularly anti-IL-17A and anti-IL-23 agents. Recent PPP trials are focusing on blockage of IL-36 or IL-1 pathways, which play an important role in innate immunity. Indeed, IL-36 isoforms have been strongly implicated in the pathogenesis of psoriasis. Therefore, blockage of the IL-36 pathway has become a new treatment target in PPP, and three studies are currently evaluating the use of monoclonal antibodies that block the IL-36 receptor in PPP: ANB019 and spesolimab (BI 655130). In this review, we explore the diagnosis, screening and treatment of patients with PPP.
- Update on Atopic DermatitisPublication . Torres, T.; Ferreira, E.; Gonçalo, M.; Mendes-Bastos, P.; Selores, M.; Filipe, P.With an increasing prevalence during the past decades, atopic dermatitis has become a global health issue. A literature search following a targeted approach was undertaken to perform this non-systematic review, which intends to provide an overview of the epidemiology, pathophysiology, clinical features, comorbidities, and current therapies for the treatment of atopic dermatitis. In sum, this is a heterogeneous skin disorder associated with variable morphology, distribution, and disease course. Although not completely understood, its pathogenesis is complex and seems to result from a combination of genetic and environmental factors that induce skin barrier dysfunction, cutaneous and systemic immune dysregulation, skin microbiota dysbiosis, and a strong genetic influence. Diagnosis is based on specific criteria that consider patient and family history and clinical manifestations. Overall disease severity must be determined by evaluating both objective signs and subjective symptoms. Therapeutic goals require a multistep approach, focusing on reducing pruritus and establishing disease control. Patients should be advised on basic skin care and avoidance of triggers. Topical anti-inflammatory agents should be considered in disease flares or chronic/recurrent lesions. In case of inadequate response, phototherapy, systemic immunosuppressants and, more recently, dupilumab, should be added. Nevertheless, the treatment of moderate-to-severe atopic dermatitis remains challenging and novel, efficacious, safe and targeted treatments are urgently needed. In conclusion, although the last few years have seen important improvement in the understanding of the disease, future research in atopic dermatitis will continue exploring gene-environment interactions and how it affects pathophysiology, disease severity, and treatment outcomes.
- Ustekinumab in Real-Life Practice: Experience in 116 Patients with Moderate-To-Severe PsoriasisPublication . Raposo, I.; Bettencourt, A.; Leite, L.; Selores, M.; T, TorresUstekinumab is a monoclonal antibody directed against the p40 subunit common to both IL-12 and IL-23 cytokines. Although the evidence of ustekinumab efficacy and safety in clinical trials is extensively recognized, data on its use in clinical practice is limited. Our objective is to report on the real-life experience of two Portuguese dermatology departments with ustekinumab in patients with moderate to severe psoriasis, and to identify the clinical characteristics associated with a weaker clinical response.
- Papuloerythroderma of Ofuji: First Case Report in PortugalPublication . Raposo, I.; Sanches, M.; Ferreira, S.; Selores, M.
- BlepharochalasisPublication . Machado, Á.; Machado, S.; Selores, M.
- Spotlight on risankizumab and its potential in the treatment of plaque psoriasis: evidence to datePublication . Machado, Á; Torres, T.Psoriasis is a common chronic immune-mediated skin disease, with systemic involvement and significant impact in patients' quality of life. Several highly specific treatments have been developed over the years, such as tumor necrosis factor-α inhibitors, a nonselective IL-23 inhibitor (ustekinumab), and most recently IL-17 inhibitors. Risankizumab is a monoclonal antibody which targets IL-23p19 without binding IL-12. This novel therapeutic approach is expected to have advantages over the recently approved anti-IL-17 agents, such as the avoidance of Candida infections and neutropenia. In addition, unlike ustekinumab, the selective inhibition of IL-23 may preserve IL-12-dependent functions such as protection against infections and tumor immune surveillance. Risankizumab showed an excellent efficacy when compared to placebo and ustekinumab, with higher Psoriasis Area Severity Index (PASI) 75, PASI 90, and PASI 100 rates, along with a convenient every 12-week maintenance dosing regimen. Overall, risankizumab was well tolerated and the most common adverse event was upper respiratory tract infection. In the near future, further data will be available not only in psoriasis but also in Crohn's disease and psoriatic arthritis fields. Head-to-head trials comparing risankizumab with other IL-23 inhibitors and with IL-17 inhibitors will be crucial to reveal the role of risankizumab in the treatment of psoriasis.
- Photo Rounds: Rapid-onset rash in childPublication . Matos, R.; Torres, T.Our patient's pruritic rash was spreading throughout his trunk and arms. An acute infection 10 days earlier shed light on the diagnosis.
- The successful treatment with ixekizumab in a multi-failure psoriasis patientPublication . Azevedo, A.; Torres, T.We report a patient with severe psoriasis who failed to respond to phototherapy, conventional systemic treatment and four biologic agents (etanercept, ustekinumab, adalimumab and secukinumab). Combination of a higher-dose secukinumab regimen with phototherapy had no success. Remarkably, ixekizumab, an IL-17A inhibitor, provided almost complete psoriasis clearance after 24 weeks of treatment. The reason for the success of ixekizumab after the failure to respond to a biologic with same mechanism of action is still unknown. Interestingly, failure of secukinumab does not preclude future therapeutic success with a second IL-17A-inhibitor.
- Biosimilar Agents for Psoriasis Treatment: The Perspective of Portuguese PatientsPublication . Azevedo, A.; Bettencourt, A.; Selores, M.; Torres, T.INTRODUCTION: Biosimilars are highly similar copies of previously approved original biologic medicines. Their introduction on the market may yield cost reduction. The aim of this study was to evaluate the perspectives of psoriasis patients on biosimilar medications. MATERIALS AND METHODS: We conducted a 14 questions survey of psoriasis patients receiving biological therapy and followed-up in a dermatology department of a Portuguese tertiary care hospital. RESULTS: From a total of 108 patients included, 70.4% of patients did not know the definition of biosimilar agent and 76.6% of patients showed partial or total interest in using a biosimilar drug. Nearly 80% of patients partially or totally agreed in using a biosimilar drug in order to reduce healthcare costs with psoriasis treatment. However, the lack of studies in the European population and in psoriatic patients led most of the patients (72.2% and 75.0%, respectively) to somewhat or completely oppose to the use of biosimilars. Demographic variables, household income and type of current biologic therapy did not affect patient preferences. DISCUSSION: Despite of the unfamiliarity of the respondents with biosimilars, most patients seem receptive to their use. Nevertheless, there are two issues of concern: i) the use of biosimilars that are not tested in a European population, and ii) its approval for psoriasis without trials in this disease. Thus, an immediate need exists for patient education about biosimilars. CONCLUSION: Biosimilars may increase patient access to biologic therapies. Improved communication and the involvement of patients in decision-making regarding biosimilars may increase their acceptance in future.