Factors Associated with Affective Symptoms and Quality of Life in Patients with Atopic Dermatitis.

The aim of this study was to detect demographic and clinical factors associated with affective symptoms and quality of life in patients with severe atopic dermatitis. First, one-way analyses of variance and correlations were performed to compare a large set of qualitative and quantitative clinical variables. Three final multivariable regression models were performed, with depression/anxiety subscales and Dermatology Life Quality Index scores as dependent variables, and the factors that were statistically significant on univariate analyses as independent ones. More severe anxiety symptoms and poorer quality of life (p < 0.01) were significantly associated with more severe depressive symptoms. Female sex and disturbed sleep (p = 0.03) were significantly associated with more severe anxiety. Finally, previous treatment with cyclosporine (p = 0.03) or methotrexate (p = 0.04), more severe depressive symptoms (p < 0.01), itch (p = 0.03), impaired sleep (p < 0.01) and perceived severity of dermatological illness (p < 0.01) were significant predictors of low quality of life. This study shows a complex interplay between the severity of atopic dermatitis, poor quality of life and presence of clinically relevant affective symptoms. These results will help dermatologists to identify patients who need psychiatric consultation within the framework of a multidisciplinary approach.

Quality of life in patients with allergic and immunologic skin diseases: in the eye of the beholder.

Allergic and immunologic skin diseases negatively impact the quality of life (QoL) of affected patients with detrimental consequences. Nonetheless, in everyday clinical practice the evaluation of QoL is often overlooked. Considering the increasing prevalence of atopic dermatitis, allergic contact dermatitis, hereditary angioedema, cutaneous mastocytosis, and urticaria, it is essential to determine the effects of allergic and immunologic skin diseases on QoL. A joint meeting (GET TOGETHER 2021) of the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC) and the Italian Society of Allergological, Occupational and Environmental Dermatology (SIDAPA) aimed to summarize the features of the main QoL tools used in these diseases and to describe the extent of QoL impairment as well as the impact of treatments on QoL, particularly biologic therapies. The assessment of QoL in patients with allergic and immunologic skin diseases relies on generic, organ-specific and disease-specific questionnaires. While generic and organ-specific questionnaires allow comparison between different diseases, disease-specific questionnaires are designed and validated for specific cohorts: the QoL Index for Atopic Dermatitis (QoLIAD) and the Childhood Atopic Dermatitis Impact Scale (CADIS) in atopic dermatitis, the ACD-11 in allergic contact dermatitis, the Angioedema QoL Questionnaire (AE-QoL) and the Hereditary Angioedema QoL questionnaire (HAE-QoL) in hereditary angioedema, the Mastocytosis QoL Questionnaires (MCQoL e MQLQ) in cutaneous mastocytosis, and the Chronic Urticaria QoL questionnaire (CU-Q2oL) in urticaria. Among the many factors that variably contribute to QoL impairment, pruritus can represent the leading cause of patient discomfort. Biologic therapies significantly ameliorate QoL in atopic dermatitis, hereditary angioedema, mastocytosis and chronic urticaria. In general, adequate management strategies are essential for improving QoL in patients with allergic and immunologic skin diseases.

Assessment of Patient-Reported Outcomes at 48 Months of Treatment with Dupilumab for Severe Atopic Dermatitis: A Single-Center Real-Life Experience with 126 Patients.

BACKGROUND: The main objective was to analyze patient-reported outcomes (PRO) trends over a four-year period in severe atopic dermatitis (AD) patients treated with dupilumab. METHODS: data from 126 severe patients receiving dupilumab for at least 48 months were collected. The clinical scores assessed included the Eczema Area and Severity Index (EASI), Pruritus Numerical Rating Scale (NRS), Sleep NRS, Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), and Atopic Dermatitis Control Tool (ADCT). RESULTS: the study compellingly demonstrates dupilumab's effectiveness in reducing EASI and improving PROs, with sustained enhancements observed beyond the initial twelve months of treatment. Univariate and multivariate regression analyses show that baseline factors do not significantly increase the risk of adverse outcomes related to Pruritus NRS, POEM, or ADCT at T48. The robust correlation between ADCT and other PROs suggests closely aligned changes. CONCLUSION: Dupilumab's benefits endure beyond the first year, emphasizing its long-term efficacy, and consistently improves AD outcomes regardless of individual characteristics or clinical variables. ADCT appears to be a practical and versatile tool for the streamlined assessment of AD treatment outcomes.

Which Factors Are Associated with Persistence of Depressive and Anxiety Symptoms in Patients Affected by Atopic Dermatitis despite 2-Year Treatment with Dupilumab?

Background: Atopic Dermatitis (AD) is a prevalent inflammatory skin disease whose course is often complicated by the presence of concomitant anxiety and depressive disorders. Dupilumab has been demonstrated to be largely effective in AD. The aims of the present study were to (1) to verify the effectiveness of 2-year dupilumab treatment on the depressive and anxiety symptoms of patients affected by AD and (2) to identify predictors of the persistence of psychiatric symptoms despite maintenance treatment with dupilumab. Methods: A total of 331 patients with severe AD were assessed at baseline and at different times over 2 years by a large set of rating scales, including the Eczema Area and Severity Index (EASI), the Hospital Anxiety and Depression Scale (HADS), and the Dermatology Life Quality Index (DLQI). Paired sample t-tests were performed to verify the effectiveness of dupilumab on the severity of AD and mental health items. Two binary logistic regression models were then used to identify the predictors of the persistence of clinically significant depression and anxiety, defined by a score ≥ 8 on each sub-scale of the HADS. Results: After 2 years of treatment with dupilumab, the patients benefited, showing a significant improvement in both the dermatological disease and comorbid depression/anxiety (p < 0.001 for all scales). Overall, 17.5% and 13% of patients, respectively, reported residual depressive and anxiety symptoms after the 2-year treatment with dupilumab. The baseline predictors of the persistence of clinically significant depressive symptoms after the 2-year treatment with dupilumab were found to be a higher body mass index (BMI) (p = 0.012), a lower impact of dermatological disease on quality of life (p = 0.015), and more severe depressive symptoms (p < 0.01), while for anxiety, the only predictor was found to be female gender (p = 0.03). Conclusions: Using a multidisciplinary approach, at baseline, dermatologists should more closely monitor patients who are at a greater risk of maintaining residual psychiatric symptoms despite therapy, such as those with more severe depressive symptoms and those who are overweight.

Mental health in patients affected by atopic dermatitis: which effects of treatment with dupilumab?

Atopic dermatitis (AD) is an inflammatory skin disease. Patients with AD are prone to develop anxiety and mood disorders. Aim of this study is to investigate if treatment with dupilumab may improve mental health status of patients affected by AD. A total of 66 patients with severe AD were included: 24 subjects were candidate or have just started (one month) treatment with dupilumab, and 42 have been in treatment for one year. 25.8%, 30.3%, and 45.5% of the total sample showed, respectively, clinically significant anxiety, depression, and symptoms of Internet addiction. Patients with anxiety symptoms resulted to have more severe AD, more sleep problems ( P  = 0.028), less quality of life ( P  = 0.001), more severe depressive symptoms ( P  < 0.001), to be more frequently women ( P  = 0.016), to be less frequently treated with dupilumab for one year ( P  = 0.025). Similarly, patients with clinically significant depressive symptoms resulted to have more severe AD, more sleep problems ( P  = 0.003), less quality of life ( P  < 0.001), more severe anxiety symptoms ( P  < 0.001), to be less frequently treated with dupilumab for one year ( P  = 0.008). Patients with AD treated for one year with dupilumab showed a better mental health profile in terms of less severe anxiety and depression with respect to their counterparts.

Peristomal Skin Complications: Detailed Analysis of a Web-Based Survey and Predictive Risk Factors.

Patients with a stoma are at risk of developing peristomal skin complications (PSCs) that can negatively impact their quality of life. This study aims to identify potential risk factors for dermatitis, pruritis/xerosis, infections, and ulcerations among patients with a stoma and evaluate preventive measures. This cross-sectional study involved data regarding 232 Italian patients with a stoma. A questionnaire was used to collect patient characteristics, comorbidities, and stoma management data. The most frequent PSCs observed were dermatitis and pruritis/xerosis in approximately 60% of patients. Psoriasis was strongly correlated with dermatitis, while being overweight or obese increased the risk of pruritis/xerosis. Class 2 obesity and atopic dermatitis were associated with an increased risk of infections. Being underweight, completely nonautonomous, and having inflammatory bowel disease were associated with a higher risk of ulcerations, while radiotherapy was a strong risk factor for ulceration. Preventive measures such as using hydrocolloid barriers, TNT gauze cleansing, and low pH detergent were effective in preventing dermatitis. Appropriate stoma care and maintenance, including the use of protective film and careful monitoring of weight and comorbidities, are crucial in minimizing the risk of complications associated with a stoma.

Remission of Alopecia Universalis after 1 Year of Treatment with Dupilumab in a Patient with Severe Atopic Dermatitis.

Alopecia areata (AA), an autoimmune disease with a relapsing-remitting course, represents the second cause of non-scarring alopecia worldwide and is associated with several comorbidities, notably atopic dermatitis (AD). In particular, AD is related to its more severe forms alopecia totalis (AT) and alopecia universalis (AU) [Nat Rev Dis Primers. 2017;3:17011]. Considering that AA has been classified as T helper 1-driven disease, whereas AD is the prototypical T helper 2 (Th2)-driven skin disorder, recent studies suggest that these forms may underlie a different chemokine expression resulting in a Th2 skewing as a key pathomechanism that could explain this association [JAMA Dermatol. 2015 May;151(5):522-8]. Several reports showed that dupilumab, a fully human monoclonal antibody targeting the interleukin 4α receptor and thus downregulating Th2 response, led to an improvement of AA associated with AD; most of these patients were females with AT or AU, early-onset AD, and atopic comorbidities [Exp Dermatol. 2020 Aug;29(8):726-32]. We report here a case to further support this hypothesis.

Elevation of peripheral blood eosinophils during dupilumab treatment for atopic dermatitis is associated with baseline comorbidities and development of facial redness dermatitis and ocular surface disease.

INTRODUCTION: Transient eosinophilia is not uncommon in patients with moderate-to-severe atopic dermatitis (AD) treated with dupilumab. METHODS: A retrospective, single center, observational study was conducted to assess the difference in terms of absolute eosinophil count (AEC) change at 4 months and at 12 months, relative to the baseline, in predefined subgroups of patients affected by moderate-to-severe AD treated with dupilumab. RESULTS: Complete data for 373, 289 and 210 patients were available at the baseline, 4 months and 12 months, respectively. Patients with a history of conjunctivitis (n = 152) had greater increases in AEC at 4 months as compared with those (n = 137) who did not (+16%vs0%,p = 0.01). Patients with food allergies (n = 46) showed similar increases (+39%vs + 5%, p = 0.01). Patients experiencing facial redness dermatitis on dupilumab (n = 46) had greater increases in AEC at 4 months than those (n = 243) who did not (+40%vs + 5%, p = 0.03). Patients that had dupilumab-induced ocular surface disease (n = 44) had greater increases in AEC at 4 months than those (n = 245) who did not (+43%vs + 5%, p = 0.01). CONCLUSIONS: Atopic comorbidities are associated with a paradoxical increase in AEC at 4 months in AD patients treated with dupilumab. Patients experiencing dupilumab-related ocular surface disease or facial redness dermatitis also have remarkable increases in AEC at 4 months.

Capryloyl glycine and soy isoflavonoids in hypertrichosis: An experimental and placebo-controlled clinical study.

BACKGROUND: The management of acquired hypertrichosis (HT) is based on the search of the causes and subsequent specific treatment. However, simultaneous hair removal is important. No single method for hair removal is appropriate for all patients and skin areas. Treatment options are actually limited and clinical results are often unsatisfactory. Ornithine decarboxylase 1 (ODC1), an enzyme present in hair follicles, is considered as a potential target to inhibit hair growth. Only eflornithine hydrochloride, an inhibitor of ODC1, showed to be partially effective in the management of acquired HT. AIMS: The aim of our study was to evaluate the potential inhibition of ODC1 activity by a cream containing 4% capryloyl glycine, an ODC1 inhibitor, and 1% glycine soy-fermented extract (soy isoflavonoids). Furthermore, we present the results of a placebo-controlled clinical study that evaluated the efficacy and tolerability of this cream. METHODS: The ODC1 activity was detected by measuring absorbance at 340 nm. In the presence of ODC1 inhibitors, absorbance decreases as a function of inhibition. Difluoromethylornithine (DFMO) was provided as an inhibitor control. ODC1 activity inhibition was expressed as percentage of control (untreated sample). All data were presented as mean ± standard deviation of three independent experiments. To determine if statistically significant differences between treatments were present, a t test analysis was performed. The differences between groups were considered significant at p < 0.05. Twelve Caucasian female adult patients, with HT located on the forearms, were enrolled. The study cream (product A) was applied twice/day for four months on the right forearm. A placebo cream (product B) was applied twice/day for four months on the left forearm. Clinical efficacy was evaluated by means of macrophotography. RESULTS: The cream significantly inhibited ODC1 activity (35.1 ± 0.5% inhibition, equivalent to a 64.9 ± 0.5% ODC1 activity). DFMO completely abolished the enzymatic activity (100 ± 5% inhibition, equivalent to 0 ± 5% ODC1 activity). All patients were considered evaluable. In 11 out of 12 patients (91.7%), who were treated with product A, an improvement was observed. No improvement was observed in patients treated with product B. The global assessment showed good efficacy in 7 patients (58.3%) and moderate efficacy in 5 patients (41.7%) treated with the product A. No efficacy was detected in patients treated with product B. CONCLUSIONS: The study cream showed to be effective in Caucasian, adult, female patients with hypertrichosis located on the forearms.

Skin barrier status during dupilumab treatment in patients with severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common chronic-relapsing inflammatory skin disease hallmarked by epidermal barrier dysfunction, increased transepidermal water loss (TEWL) and decreased skin hydration. Recent findings on the T helper 2 (Th2)-driven pathogenesis of AD have led to the development of dupilumab, a monoclonal antibody directed against interleukin-4 and interleukin-13 that has been demonstrated to be effective in the treatment of moderate-to-severe AD. The effect of dupilumab on skin barrier dysfunction, however, has not yet been adequately investigated. OBJECTIVES: The primary endpoint of this study was to assess the status of the skin barrier in nonlesional skin of patients with severe AD treated with dupilumab, by evaluating the association between the relative variation of TEWL and the achievement of a 75% reduction of EASI (EASI75) over time. METHODS: TEWL was measured below the antecubital fossae by means of the Vapometer® at baseline, at week 4 (T4), at week 16 (T16) and at week 32 after dupilumab starting. EASI and NRS-itch were measured at the same time points. RESULTS: Seventy-eight patients with severe AD treated with dupilumab were enrolled. Median TEWL relative variation respect to baseline was significantly higher in patients who achieved EASI75 as compared with those who did not achieve EASI75 at T16 and at T32, but not at T4. CONCLUSION: During dupilumab treatment, TEWL on nonlesional skin tends to significantly improve 4 months after treatment initiation and could be a good tool for monitoring response to therapy.

Endolimax nana and urticaria.

Endolimax nana is a commensal protozoan of the colon. We report a case of chronic urticaria associated with E. nana in a 34-year-old Italian woman. The patient suffered from abdominal pain, diarrhoea and weight loss. The disease appeared after a trip to Vietnam. Laboratory examinations showed mild blood eosinophilia. Three coproparasitological examinations were positive for cysts of E. nana. The patient was successfully treated with two courses of metronidazole (2 g/day for 10 days each). No antihistamines were used. Three coproparasitological examinations, carried out at the end of the therapy, were negative. Follow up (six months) was negative. E. nana can be responsible for very rare cases of abdominal pain, diarrhoea, polyarthritis and urticaria.

Efficacy of Dupilumab on Different Phenotypes of Atopic Dermatitis: One-Year Experience of 221 Patients.

BACKGROUND: The clinical features of adult-onset atopic dermatitis (AD) are heterogeneous and the diagnosis can be a challenge. A new biologic drug (dupilumab) has been approved for moderate to severe AD in adult patients. The efficacy and safety have been demonstrated in clinical trials, but these studies do not reflect conditions in daily practice and do not consider the different clinical manifestations of AD. OBJECTIVES: Analyzing the dupilumab activity in a real-world setting and comparing its efficacy on different AD phenotypes. METHODS: We retrospectively evaluated 221 AD patients treated with dupilumab, stratified into six clinical phenotypes: classic, generalized eczema inflammatory and lichenoid patterns, prurigo, nummular eczema, and erythroderma. At baseline and at weeks 4, 16, and 52, the disease severity was assessed through the Eczema Area and Severity Index (EASI) and the quality of life was assessed through the Dermatology Life Quality Index (DLQI) questionnaire, Peak Pruritus Numerical Rating Scale (itch NRS), and Peak Sleep NRS. RESULTS: We found a significant improvement after 16 weeks of treatment (p < 0.0001) in all six phenotypes for all the assessed scores mentioned above, persisting up to week 52. The best improvement was seen in the more severe phenotypes, particularly the erythrodermic one. CONCLUSIONS: The present study confirmed the efficacy and safety of dupilumab in the treatment of severe AD. Its strength was in the stratification of AD patients in six different phenotypes based on their clinical presentation, all of whom markedly improved in terms of both clinically evident and reported symptoms, as well as their quality of life.

Clinical Response and Quality of Life in Patients with Severe Atopic Dermatitis Treated with Dupilumab: A Single-Center Real-Life Experience.

Dupilumab is an anti-interleukin-4 receptor monoclonal antibody that was recently approved for the treatment of atopic dermatitis (AD). In this single-center retrospective study, clinical baseline data of 117 severe AD patients treated with dupilumab were collected. At baseline and at weeks 4 and 16, disease severity was assessed through the Eczema Area and Severity Index (EASI) and quality of life through the Dermatology Life Quality Index (DLQI) questionnaire, Patient-Oriented Eczema Measure (POEM), Hospital Anxiety and Depression Scale (HADS), Peak Pruritus Numerical Rating Scale (NRS-itch), and VAS-sleep. Response to dupilumab was defined as an improvement of ≥75% in EASI from baseline (EASI75). At multivariate analysis, AD onset before 18 years [OR, 2.9; 95% CI, 1.2-7.2; p = 0.0207] and absence of hypereosinophilia [OR, 2.24; 95% CI, 1.03-4.86; p = 0.0412] were identified as significant predictive parameters for response to dupilumab in terms of EASI75 at week 4 but not at week 16. Significant reductions in EASI, DLQI, POEM, HADS, NRS-itch, and VAS-sleep were found between week 4 versus baseline (p < 0.0001 for all) and week 16 versus baseline (p < 0.0001 for all). Early AD onset and absence of hypereosinophilia may be suggested as predictive markers of early response to dupilumab. We confirmed the efficacy and safety of this agent along with the improvement of life quality in severe AD patients.

Malignancies in bullous pemphigoid: A controversial association.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disorder that has been reported to be associated with malignancies. Some authors described several cases of pemphigoid associated with malignancies (PAM); however, the evidence of this correlation still remains controversial. Several theories have been postulated to explain the relationship between malignant neoplasms and BP; the main theory suggests that antibodies directed against tumor-specific antigens of malignant cells may cross-react with antigens (like BP antigens) in the basement membrane zone leading to the formation of blisters. We performed an extensive review of the English published work focusing on the epidemiology, the pathogenetic theories and the clinical and histological aspects of the disease. We identified 40 cases of PAM: of these, seven cases were associated with hematological malignancies and 33 with solid tumors. Physicians should be aware of the existence of PAM and we suggest an oncological screening in early-onset pemphigoid, in patients with a former oncological history, in those with signs and symptoms that could be related to a neoplasm and in BP refractory to common immunosuppressive therapy.