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.

Probiotics and Prebiotics Orally Assumed as Disease Modifiers for Stable Mild Atopic Dermatitis: An Italian Real-Life, Multicenter, Retrospective, Observational Study.

The role of the skin-gut axis in atopic dermatitis (AD) remains a subject of debate, limiting non-pharmacological interventions such as probiotics and prebiotics. To improve understanding of their potential as a monotherapy for stable mild cases, we conducted a real-life, multicenter, retrospective observational study in Italy. We administered three selected bacteria (Bifidobacterium animalis subsp. lactis BS01, Lactiplantibacillus plantarum LP14, and Lacticaseibacillus rhamnosus LR05) orally to patients with mild atopic dermatitis without a placebo control group, following up for 12 weeks. Clinical assessments using the Scoring Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI), and Three-Item Severity (TIS) score were conducted on 144 enrolled patients (average age: 25.1 ± 17.6 years). Notably, both pruritus and AD-related lesions (erythema, edema/papules, excoriation) exhibited significant clinical and statistical improvement (p < 0.001) after 12 weeks of exclusive probiotic and prebiotic use. These preliminary results suggest a potential link between the skin-gut microbiome and support the rationale for using specific probiotics and prebiotics in mild AD, even for maintenance, to reduce flares and dysbiosis.

Biological therapy in patients with psoriasis: What we know about the effects on renal function.

Psoriasis is a chronic inflammatory dermatosis affecting 2%-3% of the general population. The link between psoriasis and renal dysfunction has been investigated, demonstrating a common pro-inflammatory pathogenesis. This study is aimed at evaluating renal function in patients with moderate-to-severe chronic plaque psoriasis treated with biological therapy. We analyzed 92 patients, correlating PASI and serum creatinine levels at baseline, after 6 months and after 1 year of continuous treatment with biological therapy. Data were analyzed using paired t-test and the linear mixed model for PASI and serum creatinine levels correlation, whereas the analysis of variances (ANOVA) was used for creatinine levels assessment between the baseline, the 6-months and, 1-year later evaluation. We observed a significant mean decrease in comparing serum creatinine levels after 1 year of biological therapy (p < 0.001). Interestingly, PASI reduction is correlated with creatinine decrease, and the renal function improvement is greater when complete psoriasis remission is attained. Our data suggest that a drop in systemic inflammation, secondary to biological therapy administration, might improve renal function. Future research is needed to confirm and expand our findings.

Refractory palmo-plantar discoid lupus erythematosus successfully treated with mycophenolate mofetil: Unusual localization and literature review.

Palmo-plantar lesions in discoid lupus erythematosus (DLE) can be considered a very distinct rarity, generally refractory to conventional treatments. We present a 47-year-old African female patient with a 6-month clinical history of palm and soles erosions. Clinical examination revealed painful multiple, well defined, erosions with an erythematous and scaly central area and peripherical post-inflammatory hyperchromic border bilaterally distributed on the palmo-plantar surfaces. Pterygium inversum unguis involved all nails of both hands. Histological analysis and direct immunofluorescence study confirmed palmo-plantar DLE. Therapy with mycophenolate mofetil (MMF) was initiated with a progressive clearing of palmo-plantar lesions and a drastic reduction of pain. Therapy was well tolerated, neither side effects nor altered laboratory investigations were observed. Our case and literature review confirm that MMF may be an effective approach for the management of refractory palmo-plantar DLE with a safer profile than Azathioprine regarding adverse effects and cutaneous malignancies risk.

Therapeutic approaches and targets for treatment of autoimmune bullous diseases.

Autoimmune bullous diseases are a heterogeneous group of diseases characterized by the development of cutaneous and mucosal vesicles, blisters, and finally erosions. The common pathogenetic mechanism is the presence of autoantibodies targeting structural proteins of the skin and mucous membranes (demosomes and hemidesmosomes): in the case of pemphigus, the antigens are intraepidermal, whereas in the case of pemphigoid, dermatitis herpetiformis, and epidermolysis bullosa acquisita they are subepidermal. Mucosal involvement typically affects the oral and ocular mucosa, but in some cases, the upper airways or the upper digestive tract are affected. The burden on patients' lives could be severe due to the impairment of normal feeding or breathing. In other cases, they may represent paraneoplastic syndromes. Since autoimmune bullous diseases may result in significant morbidity and mortality, depending on the grade of cutaneous and mucosal involvement, a prompt therapeutic approach is mandatory and, in recalcitrant cases, may be challenging. The first line therapy consists of corticosteroids, both topical and systemic. Once remission or control of the acute phase is obtained, adjuvant therapies need to be introduced in order to spare the corticosteroid load and minimize side effects such as iatrogenic diabetes or osteoporosis. Herein, we describe all current therapeutic approaches to autoimmune bullous diseases, also including emerging therapies.

Comorbid diseases associated with pemphigus: a case-control study.

BACKGROUND AND OBJECTIVES: Pemphigus has been associated with physical and psychiatric comorbid diseases. This study aims to further investigate these associations in patients with pemphigus, and to analyze the relationships of comorbid conditions with sex and age, pemphigus disease area index score, diagnostic delay and cutaneous/mucous involvement. PATIENTS AND METHODS: Patients with pemphigus were matched by age, gender and area of residence with eight controls each. The odds of comorbid conditions in patients vs. matched controls was determined using univariate conditional logistic regression models. Comorbid diseases significantly associated with the diagnosis of pemphigus at P < 0.05 in univariate models were subsequently included in a multivariable conditional logistic regression model with a forward procedure. RESULTS: The study sample included 163 patients with pemphigus. Cardiovascular diseases, hyperlipidemia, autoimmune thyroid disorders, dermatological autoimmune/inflammatory conditions and cancer were the most prominent conditions at the time of diagnosis. In the multiple conditional regression analysis, the two diagnoses independently associated with patients with pemphigus were cancer and dermatological autoimmune/inflammatory conditions. In sensitivity analyses excluding four patients with paraneoplastic pemphigus, these associations were still significant. CONCLUSIONS: Cancer and dermatological autoimmune/inflammatory conditions may represent possible triggering conditions for pemphigus and should be considered as early warning signs for the disease.

Komorbidität bei Pemphigus: eine Fall-Kontroll-Studie.

HINTERGRUND UND ZIELE: Pemphigus ist mit physischen und psychischen Erkrankungen assoziiert. Diese Studie soll derartige Zusammenhänge bei Patienten mit Pemphigus näher untersuchen sowie die Komorbidität nach Geschlecht, Alter, dem Pemphigus Disease Area Index, der Diagnoseverzögerung und der Beteiligung von Haut/Schleimhaut analysieren. PATIENTEN UND METHODEN: Jedem Pemphigus-Patienten wurden acht Kontrollen mit ähnlichem Alter, Geschlecht und Wohnsitz zugeordnet. Die Wahrscheinlichkeit für Begleiterkrankungen bei Patienten und Kontrollpersonen wurde anhand univariater konditionaler Regressionsmodelle bestimmt. Begleiterkrankungen, die in den univariaten Modellen mit P < 0,05 mit der Diagnose Pemphigus assoziiert waren, wurden dann in einem Vorwärtsverfahren in ein multivariates konditionales Regressionsmodell eingefügt. ERGEBNISSE: Die Studie umfasste 163 Patienten mit Pemphigus. Die hauptsächlichen Erkrankungen zum Diagnosezeitpunkt waren kardiovaskuläre Erkrankungen, Hyperlipidämie, Autoimmunerkrankungen der Schilddrüse, autoimmune/entzündliche Dermatosen und Krebs. In der multivariaten konditionalen Regressionsanalyse waren Krebs und autoimmune/entzündliche Dermatosen unabhängig mit Pemphigus assoziiert. In Sensitivitätsanalysen, in denen vier Patienten mit paraneoplastischem Pemphigus ausgeschlossen wurden, waren diese Assoziationen ebenfalls signifikant. SCHLUSSFOLGERUNGEN: Krebs und autoimmune/entzündliche Dermatosen sind möglicherweise auslösende Faktoren für Pemphigus dar und sollten als frühe Warnsignale für diese Erkrankung angesehen werden.

The unforeseen during biotechnological therapy for moderate-to-severe psoriasis: How to manage pregnancy and breastfeeding, infections from Mycobacterium tuberculosis, hepatitis B virus, hepatitis C virus, and HIV, surgery, vaccinations, diagnosis of malignancy, and dose tapering.

The use of biotechnological therapies for moderate-to-severe psoriasis is ever-expanding and it is becoming increasingly more frequent to encounter different unforeseen events during their use, such as fertile patients becoming pregnant and breastfeeding, development of infections due to personal habits like tuberculosis, hepatitis B virus, hepatitis C virus, or HIV, scheduling of surgical procedures, need of vaccinations, development of malignancy, and evaluation of dose tapering. As any clinician may experience at least one of these unexpected events, it should be good practice to know how to manage them. Thus, a practical analysis has been proposed in this study.

Erosive pustular dermatosis of the scalp: Clinical, trichoscopic, and histopathologic features of 20 cases.

BACKGROUND: Erosive pustular dermatosis of the scalp is a chronic eruption that leads to scarring alopecia. OBJECTIVE: The clinical, dermoscopic, and histopathological features and the course of the disease in 20 patients were reviewed and compared with the reports in the literature. METHODS: Gender, age at diagnosis, age at onset, duration, topography, predisposing factors, concomitant diseases, trichoscopy, histology, treatment, and outcome were taken into consideration. RESULTS: The mean age was 59.4 years. Androgenetic alopecia was present in 12 patients, 6 of whom showed actinic damage. Trauma was reported in 9 patients. Four patients were affected by autoimmune disorders. The vertex was the most common location. In all 20 patients trichoscopy showed an absence of follicular ostia with skin atrophy. Histopathology revealed 3 different features, depending on the disease duration. A reduction of inflammatory signs was observed in 14 patients treated with topical steroids and in all 3 patients treated with topical tacrolimus 0.1%. LIMITATIONS: The rarity of this disease is a limitation. CONCLUSIONS: The relatively high number of patients allowed us to identify a better diagnostic approach, using trichoscopy, and a more effective therapeutic strategy, with high-potency steroids or tacrolimus, which should be considered as first-line treatment.