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.

Down syndrome and biological treatments in dermatology: Efficacy and safety in our real-life experience and review of literature.

Down syndrome (DS) is the most common chromosomal disorder; several dermatological conditions are common in these patients; among them, psoriasis and atopic dermatitis can be frequently encountered. From 2017 to today, we retrospectively identified 4 adults and 3 under 18-year-old patients treated with biological drugs, from our research database. The first endpoint of this study was to evaluate whether the biological drugs work in these special population, and a secondary endpoint was to evaluate any loss of efficacy or any side effects during follow-up. All patients were treated with biological drugs experience resolution of their psoriasis. Mean PASI (Psoriasis Area Severity Index), BSA (Body Surface Area) and DLQI (Dermatology Life Quality Index) at baseline were 20, 16.5 and 25. At week 4, mean PASI, BSA and DLQI decreased, respectively, to 8, 6 and 12, while at week 24, mean values were, respectively, 3, 1.3 and 1. The patients that started therapy earlier, at week 52, do not have signs of recurrence and side effects. We highlighted that no official guidelines exist to approach these patients, from a literature evaluation the most employed drugs are anti-TNFα and in particular adalimumab. In our experience, the new anti-interleukin drugs seem to be well-tolerated, with no sides effect, good compliance and no loss of efficacy.

Cutaneous Melanoma Arising in Congenital Melanocytic Nevus: A Retrospective Observational Study.

BACKGROUND: Congenital melanocytic nevi (CMN) are benign proliferations of melanocytes usually present at birth. The magnitude of the melanoma risk for CMN is controversial, generating an ongoing debate on the best approach to manage these lesions. OBJECTIVE: To perform a retrospective, observational study with the aim to evaluate the prevalence of CMN-associated melanomas in tertiary referral centers, as well as the eventual correlation between clinical, dermoscopic, and histological features of CMN-associated melanomas. METHODS: A single-center retrospective observational study was performed on all clinical and dermoscopic images of histologically confirmed melanomas arising on CMN over a 14-year period (January 2005 to March 2019). RESULTS: Our database included 2,159 melanomas in the considered period. Of those, 27 (1.3%) were CMN-associated melanomas. The mean age of patients with CMN-associated melanoma was 33 years (range, 11-70 years). The mean diameter of CMN-associated melanoma was 18 mm (range, 6 mm to 20 cm), and 56% were located on the back. Twenty-one (77.8%) of CMN-associated melanomas arose on small CMN (<1.5 cm), 5 (18.5%) on medium-sized CMN (1.5-19.9 cm), and 1 (3.7%) on a large/giant type (≥20 cm). The majority of CMN-associated melanomas (63%) exhibited a globular dermoscopic pattern in their benign part, while a blue-white veil and irregular blotches were the most frequent dermoscopic features in the malignant part. About three quarters of melanomas occupied 10-50% of the nevus surface. Breslow thickness was higher in melanomas involving less than 10% of nevus surface (mean thickness, 1 mm) than in those affecting 10-50 and >50% of the nevus surface (0.8 and 0.7 mm, respectively). CONCLUSIONS: In our series, small CMN was the most frequent type of CMN-associated melanoma. Although the risk of melanoma is increasing by the increasing size of CMN, our finding is definitely related to the much higher prevalence of small CMN in the general population as compared to the prevalence of intermediate-sized and large CMN. LIMITATIONS: Small sample size, single-center experience, retrospective design.

Dupilumab improves clinical manifestations, symptoms, and quality of life in adult patients with chronic nodular prurigo.

BACKGROUND: Chronic nodular prurigo (CNPG) is a multifactorial skin disease characterized by itchy papules and nodules, usually resistant to standard treatment and associated with markedly impaired quality of life. OBJECTIVE: To describe dupilumab effectiveness and tolerability in treating adult patients with CNPG refractory to both topical and systemic therapies. METHODS: Retrospective, multicenter study including adult patients affected by CNPG, who were treated with dupilumab for at least 16 weeks. RESULTS: Twenty-seven CNPG patients showed clinical improvement in terms of skin lesions, itch, sleeplessness, and quality of life. A consistent proportion of patients (24/27; 88.9%) had at least 16-week continuous treatment and achieved Investigator Global Assessment score 1 (11/24; 45.8%). An increased number of patients achieved at least a 2-grade reduction in Investigator Global Assessment score (19/24; 79.2%). Numeric rating scale values for itch and sleeplessness decreased from 8.9 to 2.7 and from 8.2 to 1.7, respectively (P < .001) after 16-week therapy. Ten patients achieved 36 weeks of continuous treatment while maintaining clinical efficacy. LIMITATIONS: Major limitations included lack of validated assessment tools at the initial data collection, a limited cohort of treated patients, and a short-term observation period. CONCLUSION: Dupilumab was proven effective in reducing itch and improving CNPG skin lesions.

Lung Disease in Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is an acquired prothrombotic condition characterized by vascular thrombosis and/or obstetric complications, in the persistent positivity of circulating antiphospholipid antibodies (aPLs). The clinical spectrum of manifestations associated with aPL positivity is progressively expanding, including the description of several lung manifestations. The most common pulmonary involvement related to aPL positivity is pulmonary embolism (PE), which has been reported to occur in 14.1% of APS patients during disease course. PE acknowledges a purely thrombotic etiology and thus might be accounted as a criterion for APS, making imperative to test aPL in young subjects with unprovoked PE. Pulmonary hypertension (PH) can manifest in APS patients, being the second most common lung complication of the syndrome, with a prevalence ranging between 1.8 and 3.5%. aPL-positive patients might present PH following a PE, might develop pulmonary arterial hypertension associated with connective tissue disease, or might present pulmonary venous hypertension due to Libman-Sacks endocarditis. Additional lung manifestations, such as diffuse alveolar hemorrhage, acute respiratory distress syndrome, and pulmonary fibrosis, are rarely described in APS patients; it is still not clear whether in these settings aPLs exert a pathogenic role or is a mere epiphenomenon. Hereby we discuss impact, clinical presentation, histopathologic findings, etiology, and treatment of each aPL-associated lung manifestation.

Plasma radiofrequency ablation for treatment of benign skin lesions: Clinical and reflectance confocal microscopy outcomes.

BACKGROUND: In the latest few years, plasma radiofrequency ablation has turned out a good option for treatment of several benign skin lesions. The technique can be easily performed to treat skin lesions with limited tissue invasion and no residual scars or hypo/hyperpigmentation areas. OBJECTIVE: The aim of this study was to assess the effects of plasma radiofrequency ablation in treatment of benign skin lesions, through clinical and reflectance confocal microscopy outcomes. METHODS: Six patients who presented benign skin lesions underwent long-wave plasma radiofrequency ablation treatment with DAS medical device (Technolux, Italia). Reflectance confocal microscopy analysis was performed at baseline and after 1 month. RESULTS: The treatment was well tolerated; only a slight erythema and a thin crust on the treated area were referred for 3-7 days after treatment. After one month from treatments, we observed the complete disappearance of the lesions and no significant signs of inflammation, redness, hypo/hyperpigmentation, or scars on the site of the treated areas; these clinical data were also confirmed by reflectance confocal microscopy analysis. CONCLUSIONS: Long-wave plasma radiofrequency ablation actually can be considered a well-tolerated, painless, safe, effective, and low-cost procedure for skin treatments.

Real-Life Effectiveness and Safety of Guselkumab in Patients with Psoriasis Who Have an Inadequate Response to Ustekinumab: A 3-Year Multicenter Study.

Background: Guselkumab is the first approved human IgG1λ monoclonal antibody selectively targeting the p19 subunit of IL23. Its effectiveness and safety were widely reported by clinical trials. However, these results must be confirmed in real life since its safety deals with more complicated subjects with respect to trials. Currently, real-life data on the use of guselkumab following treatment failure with ustekinumab are limited, and existing studies usually show a small cohort and/or a reduced follow-up period. In this context, the aim of our study was to evaluate the use of guselkumab in patients who previously did not respond to ustekinumab after up to 3 years of treatment. Methods: A multicenter retrospective study was performed. The study enrolled patients affected by moderate-to-severe plaque psoriasis undergoing treatment with guselkumab who were attending the Psoriasis Center of nine different centers in the Campania region of Italy. Demographic and clinical features were collected for each patient at baseline. Moreover, data on psoriasis severity and adverse events (AEs) were collected at each follow-up visit (week (W)16-W36-W52-W104-W156). Results: A total of 112 patients (70 male, 62.5%; mean age 54.8 ± 11.7 years old) were enrolled. Of these, 48 (42.9%), 34 (30.4%), and 16 (14.3%) reached 1, 2, and 3 years, respectively, of follow-up under guselkumab. A statistically significant clinical improvement was observed since W16, and sustained effectiveness was reported at each timepoint up to W156. No serious AEs were collected. Moreover, a sub analysis on the body mass index, involvement of difficult-to-treat areas, and presence of psoriatic arthritis (PsA) showed that the presence of PsA or palmoplantar psoriasis was associated with a reduced clinical improvement at W16 and W36, without differences from W52. In contrast, the efficacy of guselkumab does not seem to be affected by the BMI, involvement of fingernails, or location in the genital or scalp area. Conclusions: To sum up, our long-term real-life multicenter retrospective study confirmed the efficacy and safety of guselkumab following ustekinumab discontinuation up to 156 weeks of treatment.

Incidence and Clinical Relevance of Incidental Papillary Carcinoma in Thyroidectomy for Multinodular Goiters.

INTRODUCTION: Patients undergoing a total thyroidectomy for multinodular goiter typically have a long clinical history of the disease. They often come to surgery for compression symptoms, with no suspicion of neoplastic disease. For these patients, the incidence of microcarcinomas is high, even though we know that this does not affect subsequent therapies and long-term survival. On the other hand, when a true incidental carcinoma is present, the patient requires specific therapy and long-term follow-up. The purpose of the study was to identify the incidence of incidental carcinomas in the high prevalence region of goiter, the clinical-pathological characteristics of the tumor, and the therapeutic implications. METHOD: This is a retrospective study, from January 2010 to December 2020, on a case series of 1435 total thyroidectomies for goiters. All patients had a preoperative diagnosis of a benign disease. Gender, mean age, and mean duration from the initial diagnosis of goiter were evaluated along with the number and frequency of fine needle aspirations carried out. On the basis of the histological examination, the incidence of incidental carcinoma was then assessed (diameter ≥ 10 mm) as well as the incidence of microcarcinoma (diameter < 10 mm), the pathological characteristics (multifocality, capsular invasion), and the subsequent prescribed therapies. RESULTS: Patients with incidental carcinoma numbered 41 (2.8%%), 34 women and 7 men. The mean age was 53.5 years, while the patients diagnosed with microcarcinoma were 88 (6.1%). The mean duration of the disease from initial diagnosis was 7.8 years. On average, these patients underwent 1.8 fine needle aspirations during the course of the disease, almost exclusively in the first four years. The mean diameter of the tumor was 1.35 cm (±0.3). Multifocality was present in six patients, while only one patient presented capsular invasion. The chi-square test delivered a significant dependence on gender in terms of the incidental diagnosis after Yates correction (chi-stat = 5.064; p = 0.024), highlighting a higher incidence in the female population. All patients underwent subsequent metabolic radiotherapy. The mean follow-up was 6.3 years and in the 35 patients examined, none displayed any recurrence of the disease. CONCLUSIONS: Incidental carcinoma is not uncommon in patients who have undergone total thyroidectomy for goiters. It must be differentiated from microcarcinoma for its therapeutic implications and the follow-up of the patient. Statistical analysis has shown that the only significant variable is gender. In a goiter area, the careful monitoring of patients is required to highlight suspicious clinical-instrumental aspects that may appear even several years after the initial diagnosis.

Laparoscopic deroofing in large hepatic cyst with alcohol sclerotherapy. Analysis of three cases.

Hepatic cysts have become increasingly frequent findings thanks to the improvement in diagnostic investigations. Distinction has to be made between congenital hepatic cysts (like liver cyst, PLCD) and acquired forms (such as a parasitic cyst and a cyst occurring as part of a neoplastic process) (1). When a simple hepatic cyst becomes symptomatic, when its size is > 4 cm or when there is some radiological suspicion of malignancy (thick wall, peripheral enhancement on CT/MRI) surgical management is indicated and relies on a variety of techniques (2). Presently the two most common techniques are percutaneous aspiration with sclerotherapy and laparoscopic fenestration. The use of laparoscopic approach has achieved, in the last years, some great results, for it shortens hospital stay, involves minimal invasiveness and offers low recurrence rate. We report three cases of symptomatic hepatic cysts successfully treated by using laparoscopic procedure. KEY WORDS: Laparoscopic deroofing, Sclerotherapy, Simple hepatic cysts.

Topical and Conventional Systemic Treatments in Atopic Dermatitis: Have They Gone Out of Fashion?

Atopic dermatitis is a Th2 disease, due to relapse of IL-4 and IL-13 by Th2 cells. Despite the approval by FDA of dupilumab, the first monoclonal antibody for the severe forms, traditional drugs remain a milestone for the treatment of this dermatosis. Dermatologists need a good knowledge of all therapies for an integrated and personalized management of patients.

Is Apremilast a Safe Option in Patients with History of Melanoma? A Case Series and a Review of the Literature.

Background: Recently it has been reported that apremilast might promote melanogenesis and it would therefore not be safe to use this drug in patients with psoriasis who have a history of melanoma. Methods: From January 2017 to December 2020, we retrospectively identified, within a cohort of 635 patients in follow-up care for melanoma, 16 cases of patients with psoriasis treated with apremilast and history of melanoma. Patients were monitored at our unit for a mean duration of 36 months of follow up. Results: The use of apremilast, in our case series was, thus, effective in managing psoriasis without causing recurrence of previous melanoma or any new suspicious lesions which would need removal. Discussion: It has been speculated that apremilast might not be safe in patients who have a history of melanoma as it would be involved in the stimulation of melanogenesis and consequent possibility of recurrence of previous melanoma. Conclusion: Our data show that none of the patients treated with apremilast developed recurrence of melanoma at 36 months of follow-up. Further studies are necessary to confirm the safety of apremilast in a larger number of patients with concurrent malignancies, specifically melanoma, and for a longer follow-up period.

Are we born and do we die without nevi? A cross-sectional study.

BACKGROUND: It is well known that the number of nevi varies with age. However, there are a few data in the literature concerning total nevus count at different ages. The aim of this study was to assess and compare the total nevus count among different age groups. METHODS: The total nevus count was assessed in consecutive patients belonging to nine age groups. Median nevus count was calculated and compared for each age group. Multivariate logistic regression analysis was used to define the influence of sex and phototype on the association between nevus count and age. RESULTS: We enrolled 900 patients (461, 51.2% females), with a median age of 46 years and a total of 18,136 nevi. Significant differences were found in the median total nevus count among all age groups (P < 0.001), with a significant increase in the first two decades and a significant decrease after the age of 50 years. A similar trend was also observed in subgroups. The differences observed in the total body nevus count among age groups were independent of sex and phototype. CONCLUSIONS: We demonstrate that the total nevus count significantly increases during childhood and gradually decreases in the elderly.

A systematic review on shared biological mechanisms of depression and anxiety in comorbidity with psoriasis, atopic dermatitis, and hidradenitis suppurativa.

BACKGROUND: Mental disorders in comorbidity with chronic skin diseases may worsen disease outcome and patients' quality of life. We hypothesized the comorbidity of depression, anxiety syndromes, or symptoms as attributable to biological mechanisms that the combined diseases share. METHODS: We conducted a systematic review based on the Preferred Reporting Items for Systematic Review and Meta-Analysis statement searching into PubMed, PsycInfo, and Scopus databases. We examined the literature regarding the comorbidity of psoriasis (Ps), atopic dermatitis (AD), or hidradenitis suppurativa with depression and/or anxiety in adults ≥18 years and the hypothetical shared underlying biological mechanisms. RESULTS: Sixteen studies were analyzed, mostly regarding Ps and AD. Brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling and nuclear factor kappa-light-chain-enhancer of activated B cells/p38 mitogen-activated protein kinase pathways arose as shared mechanisms in Ps animal models with depression- and/or anxiety-like behaviors. Activated microglia and neuroinflammatory responses emerged in AD depressive models. As to genetic studies, atopic-dermatitis patients with comorbid anxiety traits carried the short variant of serotonin transporter and a polymorphism of the human translocator protein gene. A GA genotype of catechol-O-methyltransferase gene was instead associated with Ps. Reduced natural killer cell activity, IL-4, serotonin serum levels, and increased plasma cortisol and IgE levels were hypothesized in comorbid depressive AD patients. In Ps patients with comorbid depression, high serum concentrations of IL-6 and IL-18, as well as IL-17A, were presumed to act as shared inflammatory mechanisms. CONCLUSIONS: Further studies should investigate mental disorders and chronic skin diseases concurrently across patients' life course and identify their temporal relation and biological correlates. Future research should also identify biological characteristics of individuals at high risk of the comorbid disorders and associated complications.

Current and emerging biologics for the treatment of juvenile idiopathic arthritis.

INTRODUCTION: The management of a child with juvenile idiopathic arthritis (JIA) requires a combination of pharmacological, physical, and psychosocial therapies in order to induce disease remission, by controlling articular and systemic inflammation. This review aims to provide a comprehensive discussion on the biological therapies currently in use in the treatment of JIA referring to existing recommendations and clinical evidence. We also discuss on the emerging biological drugs actually under consideration. AREAS COVERED: Recent findings on immunological mechanisms involved in the pathogenesis of the disease allowed us to identify several specific targets for biologic therapies. A systematic literature review was conducted between January 1997 and January 2020 on PubMed including national and international guidelines and recommendations, trials and case-control studies. EXPERT OPINION: There is now a plethora of therapies that are directed against variable targets, and the physician has to choose the most appropriate available medication in order to achieve early and sustained remission with as few side effects as possible. Research is advancing very fast in order to be more and more specific in suppressing inflammatory pathways without harming natural defenses. Finally, pharmacoeconomic considerations will also be very important to deal with, considering the high cost of most of these molecules.

CMV Infection: A Clinical Challenge in Biological Therapy? The Case of Asymptomatic Patients with Persistent Positive Immunoglobulin M Anti-CMV Treated with Secukinumab.

The use of biological therapy is now common practice in the treatment of immune-mediated inflammatory diseases (IMID). Currently, there are no guidelines related to the management of cytomegalovirus (CMV) infections or reactivation during therapy with biological agents. Furthermore, there is a lack of guidance on the management of asymptomatic patients with persistent positive immunoglobulin (Ig)M anti-CMV after an extended period and who have to undergo therapy with biological agents. We report the case of a patient in this situation for whom treatment with biological drugs for psoriasis was indicated. A good clinical response was obtained with secukinumab and maintained during 6 months of follow-up. No infectious disease or reactivation of CMV infection occurred. We suggest some possible guidelines for the management of such cases.