Oral Diseases During Systemic Psoriatic Drugs: A Review of the Literature and Case Series.

INTRODUCTION: The oral health of psoriatic patients seems to be compromised compared to that of control individuals: many published studies have investigated the relationship between psoriatic disease and gingivitis, periodontitis, and missing teeth. However, data from these studies are not consistent nor exhaustive. Moreover, no study has considered the possible specific effects of conventional and biological systemic psoriatic treatments. OBJECTIVE: We report a narrative review of the literature about the possible link between anti-psoriatic drugs and oral disease onset and present case series of patients that have experienced oral disease during systemic therapy for psoriasis. METHODS: This is a narrative review. The literature search was performed using the MEDLINE database. From the selected articles, additional references were identified by a manual search among the cited literature. RESULTS: Oral adverse events during psoriatic therapies can be found in sporadic cases. The specific mechanisms of interplay between oral anatomic structures and the pathway targeted by the systemic agents will be investigated in depth. CONCLUSION: All psoriatic patients who are candidates for conventional or biological systemic therapy should have regular oral health check-ups with a dentist and a dermatologist to prevent oral complications. Dermatologists and oral medicine specialists should be ready to recognize and manage this increasing number of oral adverse drug reactions during systemic treatments for psoriatic disease so as to provide patients with sufficient information about this risk and to stress the fundamental importance of regular dental assessments and good oral hygiene.

Cannabidiol exerts multitarget immunomodulatory effects on PBMCs from individuals with psoriasis vulgaris.

Introduction: The involvement of endocannabinoid system (ECS) in the inflammatory cascade, and the ability of phytocannabinoids, endocannabinoids and their synthetic analogues to modulate it has become an interesting research area for new therapeutic approaches in inflammatory skin diseases. Cannabidiol (CBD) appears to be the most promising among phytocannabinoids, due to the lack of psychotropic effects and low toxicity profile. Its anti-inflammatory action has been highlighted in different preclinical models, ranging from experimental colitis to arthritis and neuroinflammation. Our aim was to evaluate CBD immune-modulatory effects in peripheral blood mononuclear cells (PBMC) of psoriasis individuals with particular attention to both innate and adaptative immune arms. Methods: We performed in vitro immune functional experiments to analyze CBD action on various immune cells active in psoriatic lesions. Results: The results showed that CBD produced a shift from Th1 to Th2 response, while boosting cytotoxic activity of Natural Killer (NK) cells. Furthermore, it also exerted a potent action on monocyte differentiation as, after CBD treatment, monocytes from psoriatic individuals were unable to migrate in response to inflammatory stimuli and to fully differentiate into mature dendritic cells. Finally, a M2 skewing of monocyte-derived macrophages by CBD also contributed to the fine tuning of the magnitude of immune responses. Conclusions: These data uncover new potential immunomodulatory properties of this cannabinoid suggesting a possible therapeutic action in the treatment of multiple inflammatory skin diseases.

Oral Lesions and Oral Health-Related Quality of Life in Adult Patients with Psoriasis: A Retrospective Chart Review.

Psoriasis is a widespread chronic inflammatory skin disease, that negatively affects physical and emotional well-being and quality of life, as shown by the generally low Dermatology Life Quality Index (DLQI). Psoriasis is burdened by associated comorbidities and some patients manifest concurrent oral lesions, although the existence of oral psoriasis remains controversial. Psoriasis-specific and nonspecific oral lesions and Oral Health-Related Quality of Life (OHRQoL), self-assessed using the Oral Health Impact Profile-14 (OHIP-14) questionnaire, were retrospectively reviewed in adult untreated psoriasis patients with ≥15 teeth, who were non-smokers and had no dental or periodontal infections. Sample (age, gender, comorbidities) and descriptive variables (Body Surface Area-BSA, Psoriasis Area and Severity Index-PASI, Dermatology Life Quality Index-DLQI, severity of psoriasis, distribution of lesions and predominant involvement, years since diagnosis) were correlated with DLQI and OHIP-14 and compared by baseline DLQI and OHRQoL classes. Charts from 90 participants were included. No oral lesions were detected, and excellent/good OHRQoL was found in 94% of the participants. DLQI scores displayed positive significant associations with PASI and BSA, while OHIP-14 with hypertension and IMID, and age. PASI and BSA were significantly higher in participants with DLQI > 10 and also differed significantly among OHQRoL ranks, as well as mucosal involvement and comorbidities. Specifically, among subjects revealing an Excellent OHQRoL, 92.6% were non-IMID, 75% non-hypertensive, 89.7% non-diabetic subjects, 86.8% of non CVD-subjects.

Dupilumab therapy reduces urinary biopyrrin levels in atopic patients: a new possible biomarker of oxidative status in atopic dermatitis.

BACKGROUND: Accumulating evidence suggests that oxidative stress is involved in the inflammatory process of atopic dermatitis (AD). Biopyrrins are the end products of the oxidative reaction of bilirubin with reactive oxygen species. The aim of our study was to explore the correlation between urinary biopyrrin levels and AD severity as well as to assess the possible modification of them in AD patients during biologic therapy with human monoclonal antibody dupilumab. METHODS: For this purpose, 25 adult patients with moderate-severe AD who were candidates for dupilumab therapy independently from the study, and 15 healthy control subjects, matched by sex and age, were enrolled. Morning urine samples were collected from all study participants. For AD patients, a collection was planned before starting therapy with dupilumab (WO), after 8, 16, 52 weeks (W8, W16, W52, respectively), and two years (Y2) of treatment. The analysis of urinary levels of biopyrrins was performed by ELISA assay. RESULTS: Our results demonstrated that urinary biopyrrin levels were significantly augmented in AD patients, and interestingly they correlated with disease severity. Furthermore, dupilumab therapy decreased levels of urinary biopyrrins in AD patients after eight and 16 weeks, maintaining the result after 52 weeks as well as after two years of treatment. The correlation analysis showed a statistically significant positive correlation between the urinary concentration of biopyrrins and EASI Index, circulating total IgE as well as plasma C reactive protein levels. CONCLUSIONS: Dupilumab therapy was able to ameliorate oxidative state in AD patients.

Efficacy, tolerability and patient's satisfaction for the treatment of moderate to severe plaque psoriasis with apremilast in the real-life setting of Campania region, Italy.

BACKGROUND: Little information is available from real-life studies evaluating the efficacy of apremilast in moderate-to-severe psoriasis. METHODS: In this real-life study, we retrospectively examined a database of 231 patients with moderate-to-severe psoriasis treated with apremilast (30 mg twice/day) and followed up for 52 weeks. Disease severity and treatment response were assessed by the Psoriasis Area and Severity Index (PASI) at baseline and after 16, 24, and 52 weeks. Quality of life was assessed by the Dermatology Life Quality Index (DLQI). RESULTS: PASI score decreased from 14.6 at baseline to 4.1 and 1.2 at 16 and 24 weeks. At 24 weeks, 86.7% of patients achieved a PASI score of ≤3 and this improved up to 52 weeks, where all patients had a PASI score of ≤3. At 24 weeks, PASI 75, 90 and 100 responses were achieved in 92%, 83.2% and 36.3% of patients, respectively. At 52 weeks, PASI 75, 90 and 100 response were achieved in 97%, 89.3% and 62% of patients, respectively. DLQI score was 12.4 at baseline and decreased to 2 at week 24, and close to 0 at week 52. No serious adverse event was reported during the treatment with apremilast. CONCLUSIONS: In patients with moderate-severe chronic psoriasis in a real world-setting apremilast was shown to be effective and safe up to 52 weeks.

Oral Human Papillomavirus Benign Lesions and HPV-Related Cancer in Healthy Children: A Systematic Review.

The present systematic review aimed to assess the prevalence of oral HPV-related lesions, categorized as benign (verruca vulgaris "VV", squamous cell papilloma "SP", condyloma acuminata "CA", and focal epithelial hyperplasia "FEH") and malignant (oral squamous cell carcinoma "OSCC"), in descending order of occurrence in pediatric subjects (≤18 years of age). The secondary objectives were to evaluate the frequency and types of oral lesions described in relation to HPV genotypes and the HPV vaccine type (if any). The study protocol, compliant with the PRISMA statement, was registered at PROSPERO (CRD42022352268). Data from 60 studies, of which quality was assessed using the ROBINS-I tool, were independently extracted and synthesized. Along with seven poorly described benign HPV-related oral lesions that could not be categorized, a total of 146 HPV-related oral lesions, namely 47.26% (n = 69) VV, SP, and CA, 51.37% (n = 75) FEH, and 1.37% (n = 2) OSSC, were diagnosed in 153 pediatric subjects (M:F ratio = 1:1.4) with a mean age of lesion onset of 8.46 years. The viral genotypes detected were HPV-13 (30.61%), -6 (20.41%), -11 (16.33%), HPV-2 (12.24%), -32 (10.20%), -57 (6.12%), and -16 (4.08%). No HPV vaccination was reported in any case. Further studies should be conducted to evaluate the prevalence of HPV-related benign and malignant lesions and the potential role of HPV and associated vaccination in oral carcinogenesis in pediatric subjects.

Oxidative Stress in Atopic Dermatitis and Possible Biomarkers: Present and Future.

Oxidative stress is important in the pathogenesis of atopic dermatitis (AD); it can damage keratinocytes, increase dermal inflammation, and reduce skin barrier function, the hallmarks of atopic dermatitis pathogenesis. Measuring oxidative stress is possible by identifying peripheral markers, which could have a predictive value of disease severity, disease progression and response to therapy, with a potentially significant impact on patient management. Our review explored this fascinating field of research, focusing on old and new possible biomarkers that may represent an effective tool to investigate the inflammatory-oxidative axis in AD, adding clinically important information to patient care.

Prevalence, Features and Degree of Association of Oral Lesions in COVID-19: A Systematic Review of Systematic Reviews.

Regardless of rapidly emerging findings on oral lesions described in adult SARS-CoV-2-positive subjects, the evidence level remains quite low and rather contrasting; therefore, the present systematic review of systematic reviews primarily aims to point out the overall prevalence of diagnosed cases. Secondary aims are to estimate the degree of association between oral lesions and SARS-CoV-2 infection and to grade, based on the reported frequency, the primary oral lesions, with related clinical presentations and microscopic features, in relation to COVID-19 forms. A study protocol compliant with the PRISMA statement was developed. Twelve studies were included, reporting highly heterogeneous and incomplete findings, thus precluding a meta-analysis. Further studies should be conducted to assess the overall prevalence of cases diagnosed with oral lesions among adult SARS-CoV-2-positive subjects, especially considering novel viral variants, and to determine their degree of association with SARS-CoV-2 infection and COVID-19 forms. Moreover, the reported findings noticed the need to evaluate the putative role both of SARS-CoV-2 in oral lesions genesis and of periodontitis and periodontal microbiome in COVID-19 worsening and re-activations. Deeper insights into oral lesions in adult SARS-CoV-2-positive subjects could enhance the comprehension of illness pathogenesis, natural history and clinical presentation, thus improving the preparedness of health professionals in the inter-disciplinary management of COVID-19.

Immuno-Pathogenesis of Chronic Inflammatory Skin Diseases: Novel Molecular Targets and Biomarkers.

Chronic inflammation has a crucial pathogenetic role in many diseases, including cutaneous chronic inflammatory disorders, such as psoriasis, atopic dermatitis, hidradenitis suppurativa, and chronic urticaria [...].

Hepatitis Virus Reactivation in Patients with Psoriasis Treated with Secukinumab in a Real-World Setting of Hepatitis B or Hepatitis C Infection.

BACKGROUND AND OBJECTIVE: Biologics for psoriasis, especially anti-tumor necrosis factor-α therapies, may reactivate hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, as well in inactive carriers or patients with occult infection. However, some biologics, including anti-interleukin-17 therapies such as secukinumab, seem to be less likely to cause hepatitis reactivation. This study assessed the safety of secukinumab treatment in patients with psoriasis with HBV or HBC infection. METHODS: This was a retrospective cohort study of patients with moderate-to-severe psoriasis treated with secukinumab at seven Italian centers. Patients serologically positive for one or more of the following viral hepatitis markers were included: HCV antibody (± HCV-RNA positivity) and/or hepatitis B surface antigen, and/or HBV core antibody and/or HBV surface antibody (± HBV-DNA positivity). Patients received secukinumab 300 mg subcutaneously at week 0/1/2/3/4 then every 4 weeks; prophylactic therapy before starting secukinumab was prescribed where indicated. The primary study endpoint was the reactivation of hepatitis viral infection, defined as conversion to HBV-DNA or HCV-RNA positivity, with or without elevation of transaminases. RESULTS: Sixty patients (17 with concomitant psoriatic arthritis) were included. Thirteen subjects were hepatitis B surface antigen positive, 19 were HBV core antibody positive, and 30 were positive for the HCV antibody; however, all were HCV-RNA negative. After 53.5 ± 37.5 weeks of secukinumab therapy, hepatitis reactivation occurred in only one patient, who had a reactivation of both hepatitis B and hepatitis C. This patient had not undergone hepatitis B prophylaxis or hepatitis C treatment before secukinumab. CONCLUSIONS: These real-world data support the safety of secukinumab in patients with positive markers of HBV or HCV infection, when administered together with dedicated prophylaxis.

In this retrospective cohort study, 60 patients with moderate-to-severe psoriasis were treated with secukinumab at seven Italian centers. Secukinumab is a fully human monoclonal antibody targeting interleukin-17A, a key cytokine associated with the development of psoriatic disease. All patients had markers of hepatitis B and/or C. Where appropriate, patients received prophylactic antiviral therapy before starting secukinumab at the standard dose for treating psoriasis in Italy. Secukinumab was administered at the labeled dose. After a mean duration treatment of 53.5 weeks, hepatitis reactivation (both B and C) occurred in one patient. This patient had not undergone hepatitis B prophylaxis or hepatitis C treatment before receiving secukinumab. The study is important, as some biologics for psoriasis, especially anti-tumor necrosis factor-α therapies, have been shown to reactivate both hepatitis B virus or hepatitis C virus infections in inactive carriers, patients with occult hepatitis B virus infection, or patients with hepatitis C virus infections. However, there is evidence that second-generation biologic therapies, including those with anti-interleukin-17 activity, are less likely to cause hepatitis reactivation. This study supports the safety of secukinumab treatment in patients with psoriasis with hepatitis B and/or C.

Clinical predictors of psoriatic arthritis and osteoclast differentiation.

Psoriasis and psoriatic arthritis (PsA) are interrelated inflammatory diseases. Psoriasis usually precedes PsA onset and represents a well-established risk factor for PsA development. Bone erosion is a hallmark of PsA, and the contribution of cutaneous psoriatic inflammation in this process has been demonstrated. However, little is still known on the pathogenetic mechanisms that link psoriatic skin to joint damage. Clinical features of psoriatic disease, including specific body site involvement, seem to be important risk predictors of PsA. The aim of this pilot research study was to investigate if psoriatic cutaneous inflammation, affecting these anatomical predictive sites for PsA, could be linked to osteoclast differentiation and activity. Our results showed that psoriasis skin localizations were positively related to the osteoclastogenic profile in psoriatic patients. These results provide new insights into the fascinating skin-joint axis concept.

Anti-IL-17 therapy rapidly decreases osteoclast activity in psoriatic patients: a novel quality in addition to its efficacy and safety.

BACKGROUND: Psoriasis is a chronic, immune-mediated, inflammatory skin disease where interleukin-17 plays an important role in the underlying pathogenesis. IL-17A is a key driver of pro-osteoclastogenic process, that is abnormal in psoriatic patients. Aim of this study was to investigate in vivo the capability of secukinumab to influence the osteoclastogenesis in psoriatic patients reporting also our experience regarding the effectiveness and safety profile of this biological treatment. METHODS: Efficacy and tolerability of secukinumab were evaluated after the induction period and 12 weeks. Moreover, to investigate how the cutaneous clinical improvement impacted also on the osteoclastogenic profile of psoriatic patients, the osteoclastogenic assay was performed in 5 secukinumab-treated psoriatic patients, not including psoriatic arthritis, before and after 5 weeks of therapy. RESULTS: In line with clinical trials, our results confirmed the efficacy, speed of achievement and safety of secukinumab for the treatment of psoriatic patients. CONCLUSIONS: Moreover, in our experiments secukinumab has demonstrated speed of action also on osteoclastogenic process, reducing the number and activity of osteoclasts only after five weeks of treatment.

Atopic Dermatitis: Epidemiology and Clinical Phenotypes.

Atopic dermatitis (AD) is a chronic, lifelong, relapsing condition. The wide spectrum of the possible clinical presentations, depending on patient' s age, age of onset of disease, topography and morphology of dermatitis, limits the epidemiologic information on its prevalence and incidence. A clear definition of the different clinical AD phenotypes and epidemiology is essential for an appropriate patient's treatment and management, in particular for adults. This review summarizes the most recent epidemiologic data from the 21st century, on AD prevalence and incidence rates either in children or adults, with a special focus on their trends in Europe. Moreover, an effort to categorize diverse AD clinical expressions, has been made, aiming to facilitate differential diagnosis and speed up the start of the correct therapy.

Patients' demographic and socioeconomic characteristics influence the therapeutic decision-making process in psoriasis.

BACKGROUND: Knowledge regarding differences in care for psoriatic patients is limited. The aim of this study was to investigate factors influencing prescription of systemic treatments for patients with psoriasis with a special focus on socioeconomic factors. METHODS AND FINDINGS: This was a non-interventional, cross-sectional study, conducted in 18 Italian University and/or hospital centers with psoriasis-specialized units. Questionnaires evaluating demographic and socioeconomic characteristics were administered to participants. Overall, 1880 consecutive patients affected by mild-to-severe psoriasis were recruited. Univariate and multivariable logistic regression analyses of systemic therapy prescription, with a special focus on biologics, accounting for the above mentioned characteristics were performed. Our analysis showed that all analyzed patients' characteristics were significantly associated with biological therapy compared to non-biological systemic one. Particularly, women were less likely to receive biologics than men (OR = 0.66; 95% CI, 0.57-0.77). Elderly patients (≥65 years) and subjects with a BMI ≥30 had lower odds to receive biologics respect to adults (≥35-64 years) (OR = 0.33; 95% CI, 0.25-0.40), and subjects with BMI≥25<30 (OR = 0.64; 95% CI, 0.53-0.77), respectively. Northern and Southern patients were both less likely to receive biologics than Central patients (OR = 0.75; 95% CI, 0.63-0.89, and OR = 0.56; 95% CI,0.47-0.68, respectively). Lower economic profile and never reading books were both associated with decreased odds of receiving biological therapy. CONCLUSIONS: This study shows that sex, age, comorbidities, and socioeconomic characteristics influence the prescription of systemic treatments in psoriasis, highlighting that there are still unmet needs influencing the therapeutic decision-making process that have to be addressed.

Photosensitivity and cancer immune-targeted therapies.

The novel group of immunological agents used for solid tumors has importantly improved the quality of life and the survival rate of oncologic patients. Compared to conventional chemotherapy agents, they are more effective and less toxic. However, adverse cutaneous effects are commonly observed, and in some cases, they may induce treatment discontinuation, with heavy impact on patient prognosis. Among these, photosensitive reactions, either phototoxic or photoallergic, are increasing. Much remains to be clarified on the understanding of their prevention, diagnosis, and management. We have reviewed the literature about photosensitive reactions occurring during oncologic immunotherapies. Early dermatological diagnosis and adequate management, with oncologist's cooperation, is fundamental.