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AIM: To assess the impact of non-surgical periodontitis treatment over conventional dermatological treatment on the severity and extent of psoriasis in patients affected by comorbid psoriasis and periodontitis. METHODS: Seventy-four patients affected by both psoriasis and Stages I-IV periodontitis were randomized to receive either Steps 1-2 (non-surgical) of periodontal therapy (test group; n = 37) or no treatment (control group; n = 37). The two groups were balanced in terms of psoriasis medications, with the majority of the included patients undergoing biologics (74.0%) as monotherapy, while minor proportions were under systemic medications (13.7%) or none/topical/phototherapy (12.3%). The psoriasis area severity index (PASI) was regarded as the primary outcome. The Body Surface Area (BSA) and the Dermatology Life Quality Index (DLQI) were additionally considered as dermatological outcomes. Probing pocket depth, recession depth, clinical attachment level, periodontal inflamed surface area, and full-mouth plaque and bleeding scores were also measured. [Correction added on July 5, 2024, after first online publication: The preceding sentence has been revised]. RESULTS: Periodontal therapy in the test group led to statistically significant lower PASI scores at 10 weeks (mean = 3.15; standard deviation [SD] = 3.78) compared to the control group (mean = 7.11; SD = 6.09) (mean difference [MD] = -4.0; 95% confidence interval [CI]: -6.3, -1.6; p = .001). The test group also showed improvements in BSA (MD = -4.3) and periodontal parameters compared to the control group. DLQI only showed a non-statistically significant tendency (MD = -2.0). CONCLUSION: Steps 1-2 of periodontal therapy showed an additional effect over conventional dermatological treatment in reducing the severity and extent of psoriasis (Clinicaltrials.gov: NCT05311501).
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Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent and painful nodules and abscesses in intertriginous skin areas, which can progress to sinus tract formation, tissue destruction, and scarring. HS is highly debilitating and severely impairs the psychological well-being and quality of life of patients. The therapeutic approach to HS is based on medical therapy and surgery. First-line medical therapy includes topical antibiotics, systemic antibiotics, and biologics. Main surgical procedures include deroofing, local excision, and wide local excision. Despite the availability of multiple therapeutic options, the rates of disease recurrence and progression continue to be high. In recent years, the possibility of combining biologic therapy and surgery has raised considerable interest. In a clinical trial, the perioperative use of adalimumab has been associated with greater response rates and improved inflammatory load and pain, with no increased risk of postoperative infectious complications. However, several practical aspects of combined biologic therapy and surgery are poorly defined. In June 2022, nine Italian HS experts convened to address issues related to the integration of biologic therapy and surgery in clinical practice. To this purpose, the experts identified 10 areas of interest based on published evidence and personal experience: (1) patient profiling (diagnostic criteria, disease severity classification, assessment of response to treatment, patient-reported outcomes, comorbidities); (2) tailoring surgery to HS characteristics; (3) wide local excision; (4) presurgery biologic treatment; (5) concomitant biologic and surgical treatments; (6) pre- and postsurgery management; (7) antibiotic systemic therapy; (8) biologic therapy after radical surgery; (9) management of adverse events to biologics; and (10) management of postoperative infectious complications. Consensus between experts was reached using the Estimate-Talk-Estimate method (Delphi Method). The statements were subsequently presented to a panel of 27 HS experts from across Italy, and their agreement was assessed using the UCLA Appropriateness Method. This article presents and discusses the consensus statements.
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BACKGROUND: UVA-1 phototherapy was first used to treat atopic dermatitis and afterwards to several other skin diseases. The contribution of UVA-1 in human photocarcinogenesis, skin photoaging, immune suppression, and hyperpigmentation is now well established. The actual contribution of UVA-1 radiation to the development of malignant melanoma (MM) in humans cannot be excluded. PURPOSE: The aim of the study is to evaluate the risk of developing skin cancers (non-melanoma skin cancers (NMSCs) and MM) in patients treated with UVA-1 phototherapy with a 5-year dermatological follow-up. METHODS: We conducted a retrospective cohort study with 31 patients with morphea and atopic dermatitis treated with medium dose UVA-1 phototherapy (34 J/cm2). All enrolled patients underwent an oncologic prevention visit annually with a 5-year follow-up with clinical evaluation of the entire skin surface. RESULTS: During the 5-year follow-up, we recorded a case of basal cell carcinoma (BCC) in the cervical region and one case of MM on the back (pT1a). In both cases, the patients were female and affected by morphea. The Glogau 3 group is prevalent (42%), which is consistent with moderate to severe aging; the data appear to be compatible with the age. CONCLUSIONS: This study attests that medium-dose UVA-1 phototherapy does not increase the risk of developing skin tumors and that UVA-1 phototherapy is not a worsening factor of facial photoaging. The main limitation of the study is the small sample size, avoiding to obtain statistically significant values. It was not possible to analyze individually the actual daily sun exposure during the 5-year observation period and to correlate it in terms of time and tumor development. Further studies with large sample sizes will be needed to confirm our data. Our study reaffirms how the dermatological examination performed annually is essential in the follow-up of patients undergoing this type of therapy.
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Carcinoma Basocelular , Melanoma , Neoplasias Cutâneas , Terapia Ultravioleta , Humanos , Feminino , Estudos Retrospectivos , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/epidemiologia , Pessoa de Meia-Idade , Adulto , Carcinoma Basocelular/etiologia , Melanoma/epidemiologia , Terapia Ultravioleta/efeitos adversos , Masculino , Dermatite Atópica , Idoso , Esclerodermia Localizada/etiologia , Seguimentos , Neoplasias Induzidas por Radiação/etiologia , Raios Ultravioleta/efeitos adversosRESUMO
OBJECTIVES: Actinic keratosis have a high risk of progression to a squamous cell carcinoma. Insulin-like growth factor 1 and its receptor play a relevant role in restoring repair of ultraviolet-induced cell damage. This pathway is reduced in patients older than 65 years. Ablative fractional laser resurfacing could normalize insulin-like growth factor 1 (IGF-1) secretion in elderly by recruiting new fibroblasts. The aim of the study is to evaluate restoration of IGF1 values by PCR in senescent fibroblasts after ablative fractional laser resurfacing. METHODS: We enrolled 30 male patients with multiple actinic keratosis on the scalp, equally divided into two mirror areas of up to 50 cm2 , treating only the right one. We performed one skin biopsy for each area 30 days after treatment. Real-time PCR in fibroblasts was performed to assess the change in IGF1. At baseline and after 6 months, in vivo reflectance confocal microscopy examination was performed in all patients. RESULTS: IGF1 values were increased in the treated side by about 60%. The right areas had fairly complete resolution of actinic keratosis at the last follow-up visit after 6 months with no appearance of new lesions. The mean number of actinic keratosis in the right area was reduced by more than 75% at four- and six-follow-up visits compared to the left area. The improvement in the right area was also evidenced by lower values of the mean AKASI (actinic keratosis area and severity index) score. Reflectance confocal microscopy showed a reduction of keratinocytic disarray and scales after treatment. DISCUSSION: Taken together, all the clinical, laboratory, and in vivo results of our study allowed us to confirm that ablative fractional laser resurfacing is a valuable tool for the treatment of actinic keratosis and cancerization field, both for the management of clinically evident lesions and for preventing the occurrence of squamous cell carcinoma.
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Carcinoma de Células Escamosas , Ceratose Actínica , Humanos , Masculino , Idoso , Ceratose Actínica/tratamento farmacológico , Fator de Crescimento Insulin-Like I/uso terapêutico , Dióxido de Carbono/uso terapêutico , Couro Cabeludo , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Lasers , Resultado do TratamentoRESUMO
Nail psoriasis (NP) is often considered disfiguring for patients with a relevant impact on quality of life (QoL). It is also difficult to treat for dermatologists who are often frustrated by the scarcity of effective therapeutic alternatives in this particular location. Topical therapies are often used as the first-line treatment for mild NP, but efficacy is the modest. Conventional disease-modifying antirheumatic drugs (cDMARDs) (e.g., cyclosporine, methotrexate, acitretin, and dimethyl fumarate) are generally avoided in NP without general cutaneous involvement. Biologics represent, to date, a concrete possibility for the management of these patients. The data from the clinical trials are encouraging, although there are still few data in real-life. Here, we report a study conducted at Siena University Hospital on 20 patients with NP on both hands and feet treated with anti-IL23 for 52 weeks. No differences were evaluated from baseline to week 4 of anti-IL-23 treatment. NAPSI greatly improved at week 24 with almost 60% of patients reaching NAPSI75 and 40% NAPSI50. At week 52, almost 75% of patients reached NAPSI90. No adverse effects were reported in the patients in the study. The clinical response observed in these patients suggests that treatments that target interleukin-23 may be an effective option for NP, especially when refractory to conventional therapies.
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Doenças da Unha , Psoríase , Acitretina/uso terapêutico , Humanos , Metotrexato/uso terapêutico , Doenças da Unha/tratamento farmacológico , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Qualidade de Vida , Resultado do TratamentoRESUMO
Psoriasis vulgaris is a chronic immune-mediated dermatological condition, resulting from an interaction between environmental triggers and genetic susceptibilities. Alteration in the production of the inflammatory mediators plays a pivotal part in the pathogenesis of the disease. Genes encoding the mediators of these inflammatory pathways can dictate susceptibility to psoriasis. These genes have a wide range of functions that involve innate immunity (IFIH1, TRAF3IP2, CARD14, c-REL, DDX58), antigen presentation (HLA-Cw6), T-cells development, maturation, and polarization (RUNX1, RUNX3, STAT3), cytokine signaling (IL12Bp40, IL23Ap19, IL23R, JAK2), and immune regulators (TNIP1, TNFAIP3, IL36RN, SOCS1, ZC3H12C, NFKBIA). The risk alleles of these genes can contribute to the overall state of susceptibility to psoriasis by lowering the threshold of the innate immune response that can eventually provoke the pathogenic adaptive immune responses capable of inducing psoriasis. The investigations on genetic associations of psoriasis may allow the discovery of new diseases modifying targets and possibly open a path for the advancement of personalized medicine. They also allow us to discover new aspects of human skin biology.
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Proteínas Adaptadoras de Sinalização CARD , Imunogenética , Psoríase , Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Predisposição Genética para Doença , Guanilato Ciclase/genética , Humanos , Imunidade Inata/genética , Interleucinas/metabolismo , Proteínas de Membrana/metabolismo , Psoríase/genética , Psoríase/metabolismo , Pele/metabolismoRESUMO
Erytrhodermic psoriasis (EP) is a rare subset of psoriasis that is considered a dermatologic emergency. Due to its limited clinical evidence, pathogenesis is largely unknown and its treatment represents a challenge. Conventional therapies such as methotrexate, cyclosporine, and acitretin are still considered first-line of treatment but it is necessary to study the efficacy and safety of biologics, including antitumor necrosis factor (TNF), anti-interleukin (IL)-23, and anti-IL17 agents to define new guidelines of treatment. Here, we report two cases of patients with EP treated with ixekizumab.
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Produtos Biológicos , Fármacos Dermatológicos , Psoríase , Anticorpos Monoclonais Humanizados/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Humanos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: Phototherapy is a mainstay for the treatment of MF. However, there is scarce evidence for its use, mostly due to the lack of a unified schedule. AIMS: The primary aim of this study was to establish the first structured, expert-based consensus regarding the indications and technical schedules of NB-UVB and PUVA for MF. The secondary aim was to determine the consensus level for each specific item. MATERIALS & METHODS: E-delphi study. Item-specific expert consensus was defined as the number of "Totally Agree" results to ≥80% of the panelists. Cronbach alpha index ≥0.7 was used as a measure of homogeneity in the responses among questions related to the same topic. RESULTS: Overall, there was a high homogeneity among responders (0.78). On specific topics, the highest grade was observed for technical items (0.8) followed by indications for early (0.73) and advanced stages (0.7). CONCLUSIONS: Items related to the most canonical indications of phototherapy and to treatment schedules showed the highest agreements rates. There is consensus about the use of standardized treatment schedules for the induction and consolidation phases for NB-UVB and PUVA in MF.
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Micose Fungoide , Neoplasias Cutâneas , Consenso , Técnica Delphi , Humanos , Micose Fungoide/tratamento farmacológico , Terapia PUVA , Neoplasias Cutâneas/tratamento farmacológicoAssuntos
Granuloma/patologia , Imunoglobulina A/sangue , Mieloma Múltiplo/patologia , Pioderma/patologia , Dermatopatias Vesiculobolhosas/patologia , Assistência ao Convalescente , Idoso , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/uso terapêutico , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/uso terapêutico , Biópsia/métodos , Medula Óssea/patologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Dapsona/administração & dosagem , Dapsona/uso terapêutico , Quimioterapia Combinada , Granuloma/complicações , Humanos , Hiperpigmentação/patologia , Masculino , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Dermatopatias Vesiculobolhosas/complicações , Dermatopatias Vesiculobolhosas/diagnóstico , Resultado do TratamentoRESUMO
Background: The risk of developing non-melanoma skin cancers (NMSCs) in patients with psoriasis is highly debated, and, to date, there is no unambiguous consensus opinion. Psoriasis is known to be related to an increased likelihood of other comorbidities such as psoriatic arthritis, obesity, metabolic syndrome, depression, and cardiovascular disease. Regarding cancer risk, previous studies have reported a greater tendency for the development of cutaneous T-lymphomas and colon, breast, kidney, and lung cancers. Furthermore, data from network meta-analyses have shown that patients with psoriasis have a higher risk of developing squamous cell carcinomas (SCCs) and/or basal cell carcinomas (BCCs). Multiple factors may contribute to the development of NMSCs in psoriatic patients, ranging from immunosuppression induced by biologic agents to previous phototherapy. However, the extent to which each factor may impact this risk has not been entirely assessed. The aim of this study was to evaluate the risk of developing NMSCs in patients with psoriasis observed for at least 5 years, by directly comparing patients only treated with phototherapy and patients treated with anti-tumor necrosis factor α (TNFα) agents, naive to other systemic treatments or phototherapy. Methods: We conducted a single-center retrospective study at Siena University Hospital, Italy, on 200 adult patients with psoriasis divided into two groups: (i) group 1, including 100 patients treated with narrow-band UVB phototherapy (nb-UVB), and (ii) group 2, including 100 patients treated with anti-TNFα. The patients included in group 2 had to be naive to cDMARDs and biologics and treated with anti-TNFα continuously for 5 years without loss of efficacy. All patients were observed for 5 years and underwent annual dermatologic examinations to assess for the occurrence of BCC or SCC. Results: A total of 34 out of 100 patients treated with phototherapy had one BCC or one SCC and 10 out of 34 developed two skin cancers. In particular, five had both types (one BCC and one SCC), and five had two BCCs. Conclusions: The results of our study highlight how the risk of developing NMSCs is greater in patients undergoing phototherapy compared to those treated with anti-TNFα. It also draws attention to the consideration that patients with scalp psoriasis might need closer follow-up as they could be more at risk of developing NMSCs.
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Psoriasis is an inflammatory skin disease with a chronic relapsing course and an often-detrimental impact on patients' quality of life. Thanks to incredible advances in research over the past few decades, the therapeutic armamentarium of psoriasis is now reasonably broad and structured, with several therapeutic agents that have demonstrated successful long-term control of this condition. However, there are still unfulfilled gaps resulting from the inherent limitations of existing therapies, which have paved the way for the identification of new therapeutic strategies or the improvement of existing ones. A great deal of attention has recently been paid to the JAK/STAT pathway, playing a crucial role in chronic inflammatory skin diseases, including psoriasis. Indeed, in a disease with such a complex pathogenesis, the possibility to antagonize multiple molecular pathways via JAK/STAT inhibition offers an undeniable therapeutic advantage. However, data from clinical trials evaluating the use of oral JAK inhibitors in immune-mediated disorders, such as RA, have arisen safety concerns, suggesting a potentially increased risk of class-specific AEs such as infections, venous thromboembolism, and malignancies. New molecules are currently under investigation for the treatment of psoriasis, such as deucravacitinib, an oral selective inhibitor that binds to the regulatory domain of TYK2, brepocitinib (PF-06700841) and PF-06826647 that bind to the active site in the catalytic domain. Due to the selective TYK2 blockade allowing the inhibition of key cytokine-mediated signals, such as those induced by IL-12 and IL-23, anti-TYK2 agents appear to be very promising as the safety profile seems to be superior compared with pan-JAK inhibitors. The aim of our review is to thoroughly explore the rationale behind the usage of JAK inhibitors in PsO, their efficacy and safety profiles, with a special focus on oral TYK2 inhibitors, as well as to provide a forward-looking update on novel therapeutic strategies targeting the TYK2 pathway in psoriasis.
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Psoriasis is a chronic inflammatory cutaneous condition characterized by several comorbidities, including musculoskeletal disorders. While the association with psoriatic arthritis has been widely addressed in literature, the aim of the present systematic review was to identify all available evidence on the relationship between psoriasis and fibromyalgia, a musculoskeletal syndrome primarily characterized by chronic widespread pain. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and MedLine and Web of Science (WOS) databases were searched for literature up to March 2023. After the removal of duplicate records, a total of 11 articles were deemed eligible for inclusion in a qualitative synthesis. Our results suggested that psoriatic patients had a higher prevalence of fibromyalgia (8-30%), with a very high impact on symptoms of psoriasis. Moreover, fibromyalgic patients had a slightly increased prevalence of psoriasis (2.2-6.7%) compared to the control groups. Finally, several studies demonstrated the substantial impact of fibromyalgia on psoriatic outcome measures in patients with concomitant psoriatic arthritis. In conclusion, available data support a potential interplay between psoriasis and fibromyalgia, but further research is encouraged in this area.
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Background: Psoriatic disease, a chronic immune-mediated systemic inflammatory condition, significantly impairs patients' quality of life. The advent of highly targeted biological therapies has transformed treatment strategies, emphasizing the importance of selecting the most effective and cost-efficient option. Secukinumab, an IL-17A inhibitor, has demonstrated efficacy and safety in treating moderate-to-severe plaque psoriasis (PsO). However, long-term real-world data on its effectiveness and persistence rate are limited. Methods: This retrospective study, conducted across eight Italian dermatology centers, aimed to evaluate the 6-year persistence rate and effectiveness of secukinumab in patients with PsO. Additionally, the study investigated the onset of psoriatic arthritis during treatment. Results: Overall, 166 adult patients were analyzed. Their median age was 53.9 years. The mean BMI was 26.5. Of the 166 patients, 64 were bio-experienced while 102 were bio-naïve. A progressive reduction in PsO severity measured by PASI scores over 6 years of treatment was revealed: the PASI score decreased from a baseline value of 18.1 (±9.1) to 0.7 (±1.6) after 6 years of follow-up. Adverse events, including mucocutaneous fungal infections and cardiovascular disturbances, were reported in 19.9% of patients. The persistence rate was 86.8% at 24 months, decreasing to 66.4% at 72 months. Psoriatic arthritis onset during treatment was observed in 15 (9.0%) of patients. Conclusions: This study highlights the sustained effectiveness and favorable safety profile of secukinumab over 6 years, providing valuable real-world evidence. Understanding the long-term persistence rate and predictors of discontinuation could help clinicians optimize treatment decisions and improve patient outcomes in PsO management. We found that the absence of scalp PsO, no involvement of the genital area and normal weight were the best factors of persistence in secukinumab treatment in the long term.
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BACKGROUND: Tirbanibulin 1% ointment is approved for the field treatment of Olsen grade I actinic keratoses (AKs) of the face and scalp. METHODS: We performed a multicenter retrospective study involving 15 dermatologic units in Italy to investigate the efficacy and tolerability of tirbanibulin in a real-life setting. 250 patients were enrolled. Tirbanibulin, 1% ointment, was applied daily for five consecutive days. The efficacy of treatment was measured with modifications of the Actinic Keratosis Area and Severity Index (AKASI). A satisfactory response was defined by complete (100% reduction in the number of lesions) or partial clearance (75-99%) of treated AKs. RESULTS: Overall, the AKASI score was significantly reduced in the studied population (mean, from 4.1 ± 2.7 to 1.4 ± 1.5; P < 0.001). A satisfactory response was observed in 222 (88.8%) cases. The proportion of satisfactory responses was higher when follow-up was performed after 8 weeks (34/35, 97.1%). The reduction in AKASI was significant in patients with Olsen grade II or III lesions (from 5.3 ± 2.8 to 1.6 ± 1.6; P < 0.001). A satisfactory response was observed in 91/104 (87.5%) cases. AKASI reduction was also significant in patients with trunk or limb AKs (from 7.0 ± 1.3 to 2.0 ± 1.6; P = 0.018) since a satisfactory response was observed in 7/8 (87.5%) cases. Tirbanibulin was well tolerated; all adverse events (AEs) included transient local reactions at the site of treatment. Overall, 231 patients had at least one AE. Only 7 (2.8%) grade 4 AEs were recorded. CONCLUSION: Our retrospective study confirmed that tirbanibulin 1% ointment is effective and well tolerated in a real-life setting and is also promising for Olsen grade II and grade III AKs and AKs localized on difficult-to-treat areas.