Safety of omalizumab in chronic urticaria during pregnancy: a real-life study.

BACKGROUND: Managing a pregnant patient with chronic spontaneous urticaria (CSU) is often challenging. Recent data have shown that most CSU treatments in pregnant patients are second-generation H1 antihistamines (sgAHs), while data on the safety of omalizumab are scant. OBJECTIVES: To evaluate, in a routine clinical practice setting, the efficacy and safety of omalizumab in patients with severe CSU refractory to sgAHs who either became pregnant during treatment or who started the drug during pregnancy. METHODS: We conducted a retrospective study of women aged ≥ 18 years who were pregnant, who received one or more doses of omalizumab at any time during their pregnancy or who were taking omalizumab at the time of, or in the 8 weeks before, conception. RESULTS: Twenty-nine pregnant patients were evaluated: 23 (79%) conceived a child while taking omalizumab (group A), while 6 (21%) started omalizumab treatment during pregnancy (group B). Among patients in group A, we observed 23 births (21 liveborn singletons and 1 liveborn twin pair) and 1 miscarriage. Fifteen (65%) patients discontinued omalizumab after confirming their pregnancy, while eight (35%) were exposed to omalizumab during their entire pregnancy. In group B, omalizumab was introduced at a mean (SD) 10.83 (3.60) weeks' gestation and all patients were exposed to it until the end of pregnancy. In this group, there were seven liveborn infants (five singletons and one twin pair). No adverse events, pregnancy complications or congenital anomalies in newborns were recorded in either group. CONCLUSIONS: Omalizumab for CSU treatment before and during pregnancy does not appear to have negative effects on maternal or fetal outcomes.

Short-, mid- and long-term efficacy of dupilumab in moderate to severe atopic dermatitis: a real life multicenter Italian study on 2576 patients.

BACKGROUND: The efficacy and safety of dupilumab in atopic dermatitis (AD) have been defined in clinical trials but limited real-world evidence on long term treatment outcomes are currently available to inform clinical decisions. OBJECTIVES: to describe long-term effectiveness and safety of dupilumab up to 48 months in patients with moderate-to-severe AD. METHODS: a multicenter, retrospective, dynamic cohort study was conducted to assess long term effectiveness and safety of dupilumab in patients with moderate to severe AD in a real-world setting. Predictors of minimal disease activity (MDA) optimal treatment target criteria (defined as the simultaneous achievement of EASI90, itch NRS score ≤1, sleep NRS score ≤1 and DLQI ≤1) were investigated. RESULTS: 2576 patients were enrolled from June 2018 to July 2022. MDA optimal treatment target criteria were achieved by 506 (21.91%), 769 (40.63%), 628 (50.36%), 330 (55.37%) and 58 (54.72%) of those that reached 4, 12, 24, 36 and 48 months of follow-up, respectively. Logistic regression revealed a negative effect on MDA achievement for conjunctivitis and food allergy at all timepoints. Adverse events (AE) were mild and were observed in 373 (15.78%), 166 (7.02%), 83 (6.43%), 27 (4.50%) and 5 (4.55%) of those that reached 4, 12, 24, 36 and 48 months of follow-up. Conjunctivitis was the most frequently reported AE during the available follow-up. AE led to treatment discontinuation in <1% of patients during the evaluated time periods. CONCLUSION: High long-term effectiveness and safety of dupilumab were confirmed in this dynamic cohort of patients with moderate to severe AD, regardless of clinical phenotype and course at baseline. Further research will be needed to investigate the effect of Th2 comorbidities and disease duration on the response to dupilumab and other newer therapeutics for AD.

Differential diagnosis of contact dermatitis: A practical-approach review by the EADV Task Force on contact dermatitis.

The diagnosis of eczema ('dermatitis') is mostly clinical and depends on the clinical history and exploratory objective findings (primary lesions, patterns). Contact dermatitis remains as an important condition in the group of eczematous disorders, with important socioeconomic and occupational relevance. Although irritant and allergic contact dermatitis have a different pathogenesis, both are characterized by a rather typical morphology, are triggered by external factors and tend to occur primarily in the area of contact with the exogenous agent. In addition, allergic and irritant dermatitis may also co-exist. The importance of diagnosing contact dermatitis, especially when allergic in nature, is both due to the possibility of avoiding the trigger, and due to its role in aggravating other skin conditions. Nevertheless, the heterogeneity of clinical presentations in daily practice may pose an important challenge for the suspicion and correct diagnosis of contact dermatitis. Furthermore, other conditions, with different pathogenesis and treatment, may clinically simulate contact dermatitis. The Task Force aims to conduct a review of the unifying clinical features of contact dermatitis and characterize its main clinical phenotypes, and its simulators, in order to contribute to an early suspicion or recognition of contact dermatitis and enable a correct differential diagnosis.

Age affects drug survival rates of interleukin (IL)-17 and IL-23 inhibitors in patients with plaque psoriasis: Results from a retrospective, multicentric, multi-country, cohort study.

BACKGROUND: Scarce data related to the drug survival of biologic agents in psoriasis patients aged ≥65 years is available. OBJECTIVES: To evaluate the drug survival of interleukin (IL)-23 or the IL-17 inhibitors approved for the treatment of moderate-to-severe psoriasis in elderly patients (aged ≥65 years), compared with younger adult patients (aged <65 years), and to identify clinical predictors that can influence the drug survival. METHODS: This retrospective multicentric cohort study included adult patients with moderate-to-severe psoriasis, dissecting two-patient subcohorts based on age: elderly versus younger adults. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. RESULTS: We included 4178 patients and 4866 treatment courses; 934 were elderly (1072 treatment courses), and 3244 were younger patients (3794 treatment courses). Drug survival, considering all causes of interruption, was higher in patients aged <65 years than in elderly patients overall (log-rank p < 0.006). This difference was significant for treatment courses involving IL-23 inhibitors (p < 0.001) but not for those with IL-17 inhibitors (p = 0.2). According to both uni- and multi-variable models, elder age was associated with an increased risk of treatment discontinuation (univariable analysis: HR: 1.229, 95% CI 1.062-1.422; p < 0.006; multivariable analysis: HR: 1.199, 95% CI 1.010-1.422; p = 0.0377). Anti-IL-23 agents were associated with a reduced likelihood of treatment discontinuation after adjusting for other variables (HR: 0.520, 95% CI 0.368-0.735; p < 0.001). Being previously treated with IL-17 inhibitors increased the probability of discontinuation. CONCLUSION: Elderly patients with psoriasis have an increased risk of biologic treatment discontinuation compared with younger adult patients, particularly, if being treated with IL-23 inhibitors. However, in stratified analyses conducted in elderly patients, IL-23 inhibitors showed higher drug survival rates than IL-17 inhibitors.

Association between maternal dupilumab exposure and pregnancy outcomes in patients with moderate-to-severe atopic dermatitis: A nationwide retrospective cohort study.

BACKGROUND: There is limited epidemiological evidence on outcomes associated with dupilumab exposure during pregnancy; monitoring pregnancy outcomes in large populations is required. OBJECTIVE: To investigate the potential association between exposure to dupilumab in pregnant women with atopic dermatitis and any adverse pregnancy, neonatal, congenital and post-partum outcomes. METHODS: We performed a multicentre retrospective cohort study across 19 Italian tertiary referral hospital. Childbearing women were eligible if aged 18-49 years and carried out the pregnancy between 1 October 2018 and 1 September 2022. RESULTS: We retrospectively screened records of 5062 patients receiving dupilumab regardless of age and gender, identifying 951 female atopic dermatitis patients of childbearing age, 29 of whom had been exposed to the drug during pregnancy (3%). The median duration of dupilumab treatment prior to conception was 22.5 weeks (range: 3-118). The median time of exposure to the drug during pregnancy was 6 weeks (range: 2-24). All the documented pregnancies were unplanned, and the drug was discontinued in all cases once pregnancy status was reported. The comparison of the study cohort and the control group found no significant drug-associated risk for adverse pregnancy, congenital, neonatal or post-partum outcomes. The absence of a statistically significant effect of exposure on the event was confirmed by bivariate analysis and multivariate analysis adjusted for other confounding factors. CONCLUSIONS: This cohort of pregnant patients exposed to dupilumab adds to the existing evidence concerning the safety of biologic agents in pregnancy. No safety issues were identified regarding the primary outcome assessed. In clinical practice, these data provide reassurance in case of dupilumab exposure during the first trimester. However, the continuous use of dupilumab throughout pregnancy warrants further research.

New Perspectives in the Management of Chronic Hand Eczema: Lessons from Pathogenesis.

Chronic hand eczema (CHE) is a common inflammatory skin condition that significantly impacts the quality of life. From work-related disabilities to social embarrassment, pain, and financial costs, the burden on society is substantial. Managing this condition presents challenges such as long-term treatment, poor patient compliance, therapy side effects, and economic feasibility. As a result, significant efforts have been made in this field in recent years. Specifically, the broader understanding of CHE pathogenesis has led to the development of new drugs, both topical and systemic. The aim of this narrative review is to summarize the current available data on hand eczema pathophysiology and explore the resulting developments in drugs for its treatment. A comprehensive search on PubMed and the other main scientific databases was conducted using keywords related to CHE and its pathogenesis. The most relevant pathways targeted by therapies include the JAK-STAT cascade, IL-4, and IL-13 axis, phosphodiesterase 4 enzyme, and chemo-attractant cytokines. In the near future, physicians will have a plethora of therapeutic alternatives. Consequently, they should be well-trained not only in how to use these alternatives but also how to combine these treatments to address the ongoing challenges related to efficacy, tolerability, and safety.

A Familial Novel Putative-Pathogenic Mutation Identified in Plaque-Psoriasis by a Multigene Panel Analysis.

Psoriasis is a chronic multifactorial skin disorder with an immune basis. It is characterized by patches of skin that are usually red, flaky and crusty, and that often release silvery scales. The patches appear predominantly on the elbows, knees, scalp and lower back, although they may also appear on other body areas and severity may be variable. The majority of patients (about 90%) present small patches known as "plaque psoriasis". The roles of environmental triggers such as stress, mechanical trauma and streptococcal infections are well described in psoriasis onset, but much effort is still needed to unravel the genetic component. The principal aim of this study was to use a next-generation sequencing technologies-based approach together with a 96 customized multigene panel in the attempt to determine if there are germline alterations that can explain the onset of the disease, and thus to find associations between genotypes and phenotypes. To this aim, we analyzed a family in which the mother showed mild psoriasis, and her 31-year-old daughter had suffered from psoriasis for several years, whereas an unaffected sister served as a negative control. We found variants already associated directly to psoriasis in the TRAF3IP2 gene, and interestingly we found a missense variant in the NAT9 gene. The use of multigene panels in such a complex pathology such as psoriasis can be of great help in identifying new susceptibility genes, and in being able to make early diagnoses especially in families with affected subjects.

Therapeutics targeting the IL-23 and IL-17 pathway in psoriasis.

Psoriasis is a chronic inflammatory disease characterised by sharply demarcated erythematous and scaly skin lesions accompanied by systemic manifestations. Classified by WHO as one of the most serious non-infectious diseases, psoriasis affects 2-3% of the global population. Mechanistically, psoriatic lesions result from hyperproliferation and disturbed differentiation of epidermal keratinocytes that are provoked by immune mediators of the IL-23 and IL-17 pathway. Translational immunology has had impressive success in understanding and controlling psoriasis. Psoriasis is the first disease to have been successfully treated with therapeutics that directly block the action of the cytokines of this pathway; in fact, therapeutics that specifically target IL-23, IL-17, and IL-17RA are approved for clinical use and show excellent efficacy. Furthermore, inhibitors of IL-23 and IL-17 intracellular signalling, such as TYK2 or RORγt, are in clinical development. Although therapies that target the IL-23 and IL-17 pathway also improve psoriatic arthritis symptoms, their effects on long-term disease modification and psoriasis-associated comorbidities still need to be explored.

Sociodemographic, clinical and therapeutic factors as predictors of life quality impairment in psoriasis: A cross-sectional study in Italy.

Psoriasis is a chronic inflammatory skin disease showing a high burden due to its aesthetic, social, psychological, and quality of life (QoL) implications which also affect patient-physician relationship and, consequently, the adherence to treatments. Limited data on the natural history of psoriasis and factors predicting its prognosis are available. The aim of this study was to investigate patients' global characteristics, including treatments, associated with QoL impairment in psoriasis. Questionnaires evaluating sociodemographic features and Dermatology Life Quality Index (DLQI) were administered to patients. Multiple regression analysis was performed to evaluate factors associated with a large effect on patient's life (DLQI > 10), moderate effect on patient's life (DLQI ≥ 6 ≤ 10), small effect on patient's life (DLQI ≥ 2 < 6), and no effect on patient's life (DLQI < 2). Overall, 1052 consecutive patients affected by mild-to-severe psoriasis were recruited. Our logistic regression analysis showed that the influencing factors for a large effect on QoL were living in Southern Italy, depression, psoriatic arthritis, and psoriasis localization on facial, intertriginous, palmoplantar, trunk and scalp regions. For a moderate effect on patient's life, phototherapy and non-biological systemic therapies resulted to be the predictive factors. Mild psoriasis, living in social housing and the isolated involvement of scalp psoriasis had a small effect on QoL. Lastly, mild psoriasis and current biological therapies including anti-IL-12/23, anti-IL-17, and anti-TNF-α were positively associated with no life quality impairment. Perceived quality of life impairment in psoriasis not only depends on the skin disease but rather on patients' global characteristics. Therefore, the individual background of these patients should be respected in the selection of treatment options.

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.

Secukinumab Improves Patient Perception of Anxiety and Depression in Patients with Moderate to Severe Psoriasis: A Post hoc Analysis of the SUPREME Study.

This study evaluated whether secukinumab treatment for patients with moderate to severe plaque psoriasis correlates with improvements in symptoms of anxiety and depression. SUPREME was a 24-week, phase IIIb, multicentre, prospective study conducted across 50 centres in Italy with an extension period of up to 72 weeks. Assessments used were: Psoriasis Area Sever-ity Index (PASI), Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A), and HADS - Depression (HADS-D) scores and Dermatology Quality Life Index (DLQI). Compared with baseline, a significantly greater proportion of patients who reported moderate to severe clinical symptoms of anxiety or depression (HADS-A or HADS-D ≥ 11) were free of moderate to severe symptoms at weeks 16 and 48. The PASI and DLQI scores reduced over time with secukinumab treatment. Psoriasis treatment with secukinumab for 48 weeks resulted in significantly improved skin clearance and a parallel improvement in symptoms of anxiety and depression, assessed by HADS.

European Surveillance System on Contact Allergies (ESSCA): Characteristics of patients patch tested and diagnosed with irritant contact dermatitis.

BACKGROUND: Irritant contact dermatitis (ICD) is caused by the acute locally toxic effect of a strong irritant, or the cumulative exposure to various weaker physical and/or chemical irritants. OBJECTIVES: To describe the characteristics of patients with ICD in the population patch tested in the European Surveillance System on Contact Allergies (ESSCA; www.essca-dc.org) database. METHODS: Data collected by the ESSCA in consecutively patch-tested patients from January 2009 to December 2018 were analyzed. RESULTS: Of the 68 072 patients, 8702 were diagnosed with ICD (without concomitant allergic contact dermatitis [ACD]). Hand and face were the most reported anatomical sites, and 45.7% of the ICD was occupational ICD (OICD). The highest proportions of OICD were found in metal turners, bakers, pastry cooks, and confectionery makers. Among patients diagnosed with ICD, 45% were found sensitized with no relevance for the current disease. CONCLUSIONS: The hands were mainly involved in OICD also in the subgroup of patients with contact dermatitis, in whom relevant contact sensitization had been ruled out, emphasizing the need for limiting irritant exposures. However, in difficult-to-treat contact dermatitis, unrecognized contact allergy, or unrecognized clinical relevance of identified allergies owing to incomplete or wrong product ingredient information must always be considered.

Is there any association between psoriasis, psoriatic arthritis and thyroid autoimmunity?

BACKGROUND: Autoimmune diseases share a significant part of their genetic background and tend to coexist in the same patient. Some studies have investigated the possible association between autoimmune thyroiditis and psoriasis or psoriatic arthritis (PsA), with conflicting results. This study aimed to investigate the prevalence of autoimmune thyroiditis in psoriatic patients with (PsA) or without (PsC) joint involvement. METHODS: 208 patients with psoriasis and/or PsA were recruited. These patients were divided into two groups: psoriasis patients (without PsA) (PsC group: 100 patients; mean age of 50.1 ± 11.7 years) and subjects with psoriasis and psoriatic arthritis (PsA group: 108 subjects: mean age of 39.8 ± 10.8 years). Assessment of psoriasis severity was conducted using the Psoriasis Area and Severity Index (PASI) score. The diagnosis of psoriatic arthritis was made according to CASPAR criteria. All patients had thyroid evaluation through evaluation of thyroid function, thyroperoxidase antibodies and thyroid ultrasound examination. RESULTS: A statistically significant difference was found between the prevalence of autoimmune thyroiditis in the PsA group than the PsC group (25.9 vs 9.0 %; P = 0.018) with higher trends to hypothyroidism in the PsA group compared to the PsC group (13.9% vs 2.0%, P = 0.0018). CONCLUSIONS: The higher prevalence of autoimmune thyroiditis in the PsA group may be due to an immune dysfunction pathway in patients with psoriatic arthritis with a higher risk to develop other autoimmune diseases. This evidence confirms that psoriatic arthritis is an autoimmune disease with an overactive immune system that can involve multiple organs. Thyroid function evaluation should be part of the clinical and laboratory examination of patients with psoriatic arthritis.

Long-term efficacy and safety of apremilast in psoriatic arthritis: Focus on skin manifestations and special populations.

Few real-life studies evaluated long-term apremilast therapy in the variable spectrum of clinical-anamnestic features which can be found in psoriatic arthritis (PsA) patients. This real-life retrospective observational study aimed to assess long-term efficacy, safety, and tolerability of apremilast among patients with PsA and concomitant cutaneous psoriasis. A stratified analysis was performed on special populations, defined as (a) number (≤1 vs >2) of comorbidities, presence or absence of: (b) history of malignancy, and (c) previous exposure to biologics. Patients attending three Italian University and Hospital centers, who received at least one dose of apremilast and had at least one follow-up visit were included. Ninety-six patients with PsA were identified. Psoriasis Area and Severity Index (PASI), Body Surface Area, 28-joint Disease Activity Score, and Dermatology Life Quality Index scores improved during treatment, already at week 4, relative to baseline. More than 2 comorbidities, history of malignancy and previous biologic treatment negatively influenced PASI responses. At least one adverse event was experienced by 56/96 patients, and 11/56 events required drug withdrawal. In conclusion, this study confirm efficacy and safety of apremilast on joints and skin involvement of PsA, highlighting which patients could have less favorable treatment response.

A case of erythrodermic psoriasis successfully treated with ixekizumab.

Erythrodermic psoriasis (EP) is the most severe form of psoriasis, resulting in significant morbidity and mortality. International guidelines on EP treatment are lacking, with most of the biologic drugs being used basing on case reports or small case series. Ixekizumab, a fully human anti-interleukin (IL)-17A monoclonal antibody, is approved for moderate to severe plaque psoriasis while its use in EP is off label. However, two studies conducted on eight Japanese EP patients have showed ixekizumab as an efficacious and well tolerated therapy up to 24 and 52 weeks, respectively. To date, no case reports on Caucasian patients have been described. We report the case of a 66-year-old Caucasian female with EP successfully treated with ixekizumab, reaching PASI 100 after only 6 weeks of therapy and still maintaining this response at week 24. Our case report suggests ixekizumab as a highly efficacious treatment in EP, presenting also a very rapid action which leads to complete resolution of the disease after 6 weeks. Further studies are warrant to confirm our data, with controlled trials specifically dedicated to EP being strictly needed in order to verify the role and efficacy of the new biologics in EP.

Psoriatic cutaneous inflammation promotes human monocyte differentiation into active osteoclasts, facilitating bone damage.

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy that can be associated with focal bone erosions. Psoriasis usually precedes the psoriatic arthritis onset by an average of 10 years, but this relation is not yet fully elucidated. Pro-inflammatory cytokines, such as IL-33, OPN, IL-17, and TNF-α are involved in both psoriasis and PsA pathogenesis as well as in bone homeostasis. In this study, we have demonstrated that IL-33, OPN, IL-17, and TNF-α induced the release of a wide range of pro-osteoclastogenic factors from the skin, such as RANKL, that promote monocyte differentiation in osteoclasts. The addition of osteoprotegerin, a RANKL inhibitor, to monocyte cultures treated with supernatant from stimulated skin did not completely deplete osteoclast formation, suggesting that skin produced several additional pro-osteoclastogenic mediators, which could act in a RANKL-independent manner. Moreover, we have found that RANKL serum levels as well as osteoclast number and activity in psoriatic patients with and without arthritis, was influenced by severity of cutaneous disease. Our data demonstrate that psoriatic cutaneous inflammation contributes to bone damage.

IL-26 in allergic contact dermatitis: Resource in a state of readiness.

In this study, we investigated the role of IL-26 in allergic contact dermatitis (ACD), highlighting its' contribute in the cytotoxic mechanism responsible for the tissue injury. IL-26 is a signature Th17 cytokine, and immune cells are its predominant sources. Recently, it has shown that Th17 cell-derived-IL-26 functions like an antimicrobial peptide. Here, we hypothesized that IL-26 could be involved in cytotoxicity mechanism that underlies ACD. Indeed, we have attributed a role to IL-26 in this context, through PBMC cytotoxicity assays vs HaCat. To demonstrate that IL-26 was effectively involved in this activity, we performed the assay using transfected ACD PBMCs by siRNA for IL-26. Indeed, we demonstrated that these cells were less able to kill keratinocytes compared with ACD PBMCs (P < .01). In conclusion, our findings support the idea that this emergent cytokine, IL-26, is implicated in the killing mechanisms of KC observed during ACD.