Gender differences in adult atopic dermatitis and clinical implication: Results from a nationwide multicentre study.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease that affects both children and adults. However, limited research has been conducted on gender differences in AD. OBJECTIVES: This study aimed to assess gender differences in adult AD patients, focusing on demographic and clinical features, comorbidities and treatment approaches. METHODS: In this multicentre, observational, cross-sectional study, we enrolled 686 adult patients with AD (357 males and 329 females). For each patient, we collected demographic data (age and sex), anthropometric measurements (weight, height, hip circumference, waist circumference and waist-to-hip ratio), clinical information (onset age, disease duration, severity, itching intensity, impact on quality of life) and noted comorbidities (metabolic, atopic and other). We recorded past and current topical and systemic treatments. We analysed all collected data using statistical techniques appropriate for both quantitative and qualitative variables. Multiple correspondence analysis (MCA) was employed to evaluate the relationships among all clinical characteristics of the patients. RESULTS: We found no differences in age at onset, disease duration, severity and quality of life impact between males and females. Males exhibited higher rates of hypertriglyceridaemia and hypertension. No significant gender differences were observed in atopic or other comorbidities. Treatment approaches were overlapping, except for greater methotrexate use in males. MCA revealed distinct patterns based on gender, disease severity, age of onset, treatment and quality of life. Adult males with AD had severe disease, extensive treatments and poorer quality of life, while adult females had milder disease, fewer treatments and moderate quality of life impact. CONCLUSIONS: Our study reveals that gender differences in adult AD patients are largely due to inherent population variations rather than disease-related disparities. However, it highlights potential undertreatment of females with moderate AD and quality of life impact, emphasizing the need for equitable AD treatment. JAK inhibitors may offer a solution for gender-based therapeutic parity.

Geographic tongue clinical response in moderate-to-severe psoriatic patients undergoing secukinumab: a real-life, multicenter retrospective observational study.

Geographic tongue (GT), a form of inverse psoriasis, is frequently linked to plaque psoriasis. The objective of the study is to evaluate IL-17 blocker (secukinumab) effect on GT severity. This reallife, multicenter, retrospective observational pilot study evaluated patients with plaque psoriasis and concomitant GT that started in label treatment with secukinumab. Patients were evaluated twice (T0=baseline and T1=after 16 weeks) by a dentist and a dermatologist collecting data on cutaneous Psoriasis Area Severity Index (PASI) and oral statuses using Hume's classification of the Geographic Tongue Severity Index (GTASI). Twenty-nine psoriatic patients with GT treated with secukinumab were enrolled for the study. Seventeen patients display type I GT, 6 type II and 6 type III with an overall GTASI of 25.52±9.57 at the baseline (T0). No correlation was found between delta GTASI and delta PASI (r=-0.27, p=0.1551). GTASI decrement from T0 to T1 was statistically significant ([95%CI -26.64 to -19.56], t=-13.36, p<0.0001). Secukinumab may enter in GT therapeutic armamentarium as the first biologic IL-17 blocker in patients with concomitant moderate-to-severe plaque psoriasis.

Cutaneous and oral comorbidities in patients with geographic tongue: a multicenter multidisciplinary cross-sectional observational study.

Geographic tongue (GT) represents a localized type of psoriasis inversa and its burden of dermatological and oral comorbidities frequently conditions its severity and diagnosis. Currently, no epidemiological studies have evaluated GT muco-cutaneous comorbidities. We aimed to study oral and dermatological comorbidities in a large sample of GT patients. In this multicenter, cross-sectional study, involving 4 primary referral centers in Italy, we evaluated adult GT patients, who were assessed by board certified dermatologists and dentists for 5 months and collected demographics and medical history. GT was evaluated using Hume's classification together with Geographic tongue severity index (GTASI) to score its severity. The prevalence of oral and dermatological comorbidities was recorded. In the sample we enrolled 137 GT patients (M/F= 5:1) with a mean age of 48,2 ± 14,7 yoa and 33.6% had GT family history. The clinical evaluation found 96 (70.1%) GT type I, 7 (5.1%) type II, 13 (9.5%) type IIIa, 19 (13.9%) type IIIb, 2 (1.5%) type IV, following Hume's classification. The mean GTASI score was 23,7 ± 14,2 and the vast majority displayed a severe form of GT. Eighty-nine patients had oral comorbidities (burning mouth syndrome, caries, parulid and lichen planus) and 80 had dermatological concurrent conditions (plaque psoriasis, inverse psoriasis and atopic dermatitis). In GT patients, both dermatological and dental evaluation should be mandatory to identify previously undiagnosed mucocutaneous comorbidities.

Dupilumab therapy of atopic dermatitis of the elderly: a multicentre, real-life study.

BACKGROUND: Treatment of moderate-to-severe atopic dermatitis (AD) in the elderly may be challenging, due to side-effects of traditional anti-inflammatory drugs and to comorbidities often found in this age group. Furthermore, efficacy and safety of innovative drugs such as dupilumab are not yet well known. OBJECTIVES: A multicentre retrospective, observational, real-life study on the efficacy and safety of dupilumab was conducted in a group of patients aged ≥65 years and affected by severe AD. Their main clinical features were also examined. METHODS: Data of elderly patients with severe (EASI ≥24) AD treated with dupilumab at label dosage for 16 weeks were retrospectively collected. Treatment outcome was assessed by comparing objective (EASI) and subjective (P-NRS, S-NRS and DLQI) scores at baseline and after 16 weeks of treatment. RESULTS: Two hundred and seventy-six patients were enrolled in the study. They represented 11.37% of all patients with severe AD. Flexural eczema was the most frequent clinical phenotype, followed by prurigo nodularis. The coexistence of more than one phenotype was found in 63/276 (22.82%) subjects. Data on the 16-week treatment with dupilumab were available for 253 (91.67%) patients. Efficacy of dupilumab was demonstrated by a significant reduction of all the scores. No statistically significant difference regarding efficacy was found in elderly patients when compared to the group of our AD patients aged 18-64 years, treated with dupilumab over the same period. Furthermore, only 18 (6.52%) patients discontinued the drug due to inefficacy. Sixty-one (22.51%) patients reported adverse events, conjunctivitis and flushing being the most frequent. One (0.36%) patient only discontinued dupilumab due to an adverse event. CONCLUSIONS: Therapy with dupilumab led to a significant improvement of AD over a 16-week treatment period, with a good safety profile. Therefore, dupilumab could be considered as an efficacious and safe treatment for AD also in the elderly.

Photoadaptation to ultraviolet B TL01 in psoriatic patients.

BACKGROUND: In the biologic era, narrow-band ultraviolet B (NB-UVB) phototherapy still remains a valuable, effective, inexpensive, safe anti-psoriatic treatment. Patients can lose response to NB-UVB over time due to photoadaptation. This phenomenon is the tendency of the skin to respond to ultraviolet (UV) exposure by undergoing changes that may result in a decreased future response to an equivalent dose of radiation, thus leading to the need for an increased exposure during phototherapy course. AIM: To characterize and quantify the determinants of photoadaptation in NB-UVB treated psoriatic patients. METHODS: We enrolled 57 adult patients with moderate plaque psoriasis. Patients underwent 24 sessions of NB-UVB phototherapy delivered thrice a week. Dosing was started with 70% of the minimal erythema dose (MED) with percentage-based dose increments every two treatments. MED as well as change in the erythema and melanin index (MI) were measured at baseline and at the end of phototherapy course. Moreover, an adaptation factor (AF) was calculated for each patient. RESULTS: Adaptation factor was not influenced by both baseline MED and skin type. We found a weak correlation between higher cumulative dosages and the initial MED (Spearman's rho = 0.32, P = 0.0154) as well as with the mean initial MI (Spearman's rho = 0.25, P = 0.0624, statistically borderline). Clearance and mean number of treatments were correlated (Spearman's rho = 0.48, P < 0.001). CONCLUSION: Photoadaptation is a physiological skin response that negatively influences NB-UVB responsiveness and is not predictable by the baseline MED and skin type. Thus, starting with more aggressive protocols and increasing rapidly dosage progression to prevent AF may increase NB-UVB response.

Predictors of response to omalizumab and relapse in chronic spontaneous urticaria: a study of 470 patients.

BACKGROUND: Chronic spontaneous urticaria (CSU) is defined as spontaneous occurrence of wheals and/or angioedema for ≥6 weeks. Omalizumab is a monoclonal anti-IgE antibody effective in refractory CSU, but its mechanism of action and markers predictive of response remain not completely defined. OBJECTIVES: To correlate baseline levels of two proposed biomarkers, total IgE (bIgE) and d-dimer (bd-dimer), and clinical parameters to omalizumab response and to relapses after drug withdrawal. METHODS: In this retrospective Italian multicentre study, clinical data were collected in 470 CSU patients, and bIgE and bd-dimer were measured in 340 and 342 patients, respectively. Disease activity was determined by Urticaria Activity Score 7 (UAS7) at week 1 and 12 after omalizumab starting. Relapses were evaluated during a 2- and 3-month interval after a first and a second course of treatment, respectively. RESULTS: bIgE correlated to a good response to omalizumab since levels were significantly higher in responders than non-responders (P = 0.0002). Conversely, bd-dimer did not correlate to response. There was no correlation between both bIgE and d-dimer and either first or second relapse. Disease duration was significantly longer in patients who experienced either first or second relapse (P < 0.0001 and P = 0.0105, respectively), while baseline UAS7 correlated only to first relapse (P = 0.0023). CONCLUSIONS: Our study confirms bIgE as a reliable biomarker predicting response to omalizumab in CSU, while it does not support the usefulness of bd-dimer unlike previous findings. CSU duration before omalizumab and baseline UAS7 may be clinical markers of relapse risk.

Clinical epidemiology of hand eczema in patients accessing dermatological reference centres: results from Italy.

BACKGROUND: Data on the epidemiological impact and clinical characteristics of chronic hand eczema in Southern Europe are lacking. OBJECTIVES: To estimate the prevalence of chronic hand eczema in its different stages of severity and refractoriness to standard therapy in patients accessing Italian dermatological reference centres, and to evaluate sociodemographic and clinical factors associated with each stage. METHODS: A cross-sectional multicentre study was conducted. Adult patients with hand eczema, consecutively accessing 14 centres over a 6-month period, were enrolled. Patients were classified according to disease duration, severity and response to standard therapy with potent topical corticosteroids. Logistical regression was performed to investigate the relationship between sociodemographic and clinical data with different stages of eczema. RESULTS: The total number of participants was 981. Hand eczema was chronic in 83·5% of patients; 21·3% had severe eczema, with 62·0% of these patients refractory to standard therapy. Food processing and related work, the health professions, craft and related trade works (building, plumbing, electrical), hairdressing/beauty and handicraft work were most frequently associated with chronic hand eczema. Severe chronic hand eczema was more likely to be seen in men, older patients and those with less education. Severe and refractory hand eczema was also more likely among the unemployed and patients with allergic rhinitis and/or atopic dermatitis. CONCLUSIONS: Chronic hand eczema is frequent among patients with hand eczema accessing dermatology centres. Many patients were severe and refractory to standard therapy. The appropriate identification of hand eczema is the first step in implementing effective and efficient treatments.

Development of a clinical score system for the diagnosis of photoallergic contact dermatitis using a consensus process: item selection and reliability.

BACKGROUND: Photoallergic contact dermatitis (PACD) is an uncommon condition, and there is a lack of validated criteria for its diagnosis. OBJECTIVE: To identify a set of relevant criteria to be considered when suspecting a diagnosis of PACD and to assess the reproducibility of these criteria. METHODS: This was a diagnostic item selection and reliability study performed between July 2012 and October 2012. A panel of seven recognized experts was invited to consecutive rounds of a Delphi survey and to a conclusive face-to-face meeting with the aim of obtaining an agreement on criteria for the diagnosis of PACD. The panel was also provided with a series of 16 reports of suspected PACDs to be classified according to a five-point likelihood scale. Identified criteria with the weights attributed by experts were used to develop a score system for the diagnosis of PACD. Consensus was measured by calculating the Intraclass Correlation Coefficient (ICC). The performance of the score system was evaluated in terms of overall classification accuracy. RESULTS: Seven criteria were identified by experts as relevant for the diagnosis of PACD. The criteria were related to the type of skin lesions, accompanying symptoms, skin area involved, general medical history, modality of exposure to the culprit substance, history of exposure to the sun or other light sources and photopatch test results. Experts reached a moderate agreement on PACD cases classification, with ICC = 0.69 (95% Confidence Interval, CI, 0.50-0.86). The score system enabled discrimination of probable and definite PACD cases from possible and unlikely or excluded ones, with a nearly perfect agreement being observed between the score system classification and judgment by experts. CONCLUSION: A diagnostic score was proposed. The score should receive a comprehensive validation on a larger series of cases and with multiple evaluators.

Conctact dermatitis: some important topics.

Allergic contact dermatitis (ACD) is a type IV delayed hypersensitivity reaction. The gold standard for diagnosis is patch testing. The prevalence of positive patch tests in referred patients with suspected ACD ranges from 27 to 95.6%. The relationship between ACD and atopic dermatitis (AD) is complicated with conflicting reports of prevalence in the literature; however, in a patient with dermatitis not responding to traditional therapies, or with new areas of involvement, ACD should be considered as part of the work-up.

Management of chronic spontaneous urticaria: practical parameters.

Chronic urticaria (CU) is a skin disorder characterized by transient, pruritic wheals persisting for longer than 6 weeks. According to the European Academy of Allergy and Clinical Immunology (EAACI) guidelines, CU can be categorized into two main types: chronic spontaneous urticaria (CSU), in which the wheals appear spontaneously, and inducible urticaria, that is triggered by physical agents. CSU may be due to triggering factors such as food allergens or infections, but in at least 40% of cases it is autoimmune in origin, caused by circulating autoantibodies anti-FcεR1 or anti-IgE, or autoreactive. In the present paper, re-evaluating the EAACI guidelines, we have developed a document containing some practical indications which are useful for diagnosis and management of CSU in the context of the Italian situation. Concerning CSU treatment, second generation antihistamines are the first-line treatment; these drugs can be used, as second-line treatment, at a higher than licensed dose in patients who do not respond adequately at licensed doses. The third-line treatment includes leukotriene receptor antagonists which, however, do not have a specific indication for the treatment of CSU, cyclosporine, whose use in this disease is still off-label, and omalizumab. The latter is a recombinant monoclonal IgG antibody that binds free IgE, down regulates mast cell function and induces eosinophil apoptosis. Recently, it has emerged as an effective and safe treatment for antihistamine-unresponsive CSU of both autoimmune/autoreactive and non-autoimmune/non-autoreactive, and has been officially approved for use against this disease.

Probiotics: immunomodulatory properties in allergy and eczema.

In the last decades the prevalence of allergic diseases and eczema raised significantly, and today they are the most common chronic pathologies affecting children. It has been shown that a functional intestinal mucosa provides a defensive barrier to the host against potential dangerous antigens, regulating the tolerance to them. Some inflammatory diseases of the gut weaken the barrier causing an increase in the mucosa permeability and in antigenic transition. As a consequence, there is an aberrant immune response and the release of pro-inflammatory cytokines further compromises the barrier functionality. It has been demonstrated that a correlation between allergy and eczema onset and the intestinal microflora composition exists, and in particular, it has been showed that some microorganisms are able to influence the immune response. For these reasons it has been hypothesized that probiotics may have a beneficial role in preventing and treating allergies and eczema. However, the benefits of this treatment depend on many factors, such as the bacterial strain, the duration of administration, the pathology, the patient characteristics (age, diet, allergy predisposition). The aim of this work was to review the present knowledge about the use of probiotics in allergic diseases and eczema, highlighting their role in the aforementioned pathologies.

Clinical evaluation of photoprotective effect by a topical antioxidants combination (tocopherols and tocotrienols).

BACKGROUND: Vitamin E is among the earliest recognized antioxidants. Recent findings suggested that tocotrienols have superior activity than tocopherols. Moreover, vitamin A is well-known in dermatology for its actions, including the ultraviolet radiation absorbing property. OBJECTIVES: In view of experimental evidence for the photoprotective properties of these antioxidants, we evaluated in 30 patients with photosensitivity, the prophylactic efficacy of a new topical agent, containing tocopherols 10% and tocotrienols 0.3%, compared with retinol, simple vehicle and untreated areas. METHODS: After determination of the minimal UVB erythema dose (MED), two areas of 2 × 2 cm were selected on the buttocks of each subject, one of which was treated with the antioxidant formulation whereas the other field did not undergo any treatment. Therefore, both areas were irradiated with a twofold MED. As further controls, other two similar areas, selected on the forearm of 15 patients, were photo-irradiated similarly, 30 min after application of the simple vehicle to a field and of vitamin A in the same vehicle to the other. Reactions (erythema/oedema/itch/vesciculation) assessment was carried out assigning scores indicative of their intensity; then, mean values +DS of scores were calculated. RESULTS: The pre-treatment with the vitamin E formulation highly protects against photosensitivity, and all reactions to irradiation were significantly lower in the areas treated with the topical vitamin E formulation compared to those treated with the simple vehicle or vitamin A. CONCLUSIONS: The use of a new topical formulation containing significant concentrations of tocotrienols and tocopherols represents a promising strategy to reduce the photo-induced skin damage.

Psoriasis and oral lesions: multicentric study of Oral Mucosa Diseases Italian Group (GIPMO).

OBJECTIVE: This is a multicentric, observational and controlled study designed to verify the existence of a significant association between plaque-type psoriasis and oral lesions, such as geographic tongue and/or fissured tongue. STUDY DESIGN: during a period of 9 months all consecutive patients with plaque-type psoriasis were enrolled using simple nonrandom (sequential) sampling. The control group included healthy subjects presenting to the same Dermatology centers to monitor pigmented skin lesions; the patients were matched for age and sex. All patients were examined for oral lesions. RESULTS: Out of a total of 535 psoriatic patients and 436 control group patients, oral mucosal lesions were detected in 188 (35.1%) and 86 (19.7%) cases, respectively, and the difference is statistically significant. Fissured tongue (FT) and geographic tongue (GT), which were most frequently detected, were seen more frequently in psoriatic patients (FT: 22.6%; GT: 9.1%) than the control group (FT: 10.3%; GT: 5.2%) (p<0.05). CONCLUSIONS: On the basis of the similar studies reported in the literature and the large number of patients involved in our study, we can conclude that FT and GT can be clearly suggested as oral manifestations of plaque-type psoriasis, although the reason for this association is not clear.

Comorbidities and treatment patterns in adult patients with atopic dermatitis: results from a nationwide multicenter study.

Adult atopic dermatitis (adult AD) is a systemic inflammatory disorder, whose relationship with immune-allergic and metabolic comorbidities is not well established yet. Moreover, treatment of mild-to-moderate and severe atopic dermatitis needs standardization among clinicians. The aim of this study was to evaluate the distribution of comorbidities, including metabolic abnormalities, rhinitis, conjunctivitis, asthma, alopecia and sleep disturbance, according to severity of adult AD, and describe treatments most commonly used by Italian dermatologists. Retrospective, observational, nationwide study of adult patients over a 2-year period was performed. Clinical and laboratory data were obtained through review of medical records of patients aged ≥ 18 years, followed in 23 Italian National reference centres for atopic dermatitis between September 2016 and September 2018. The main measurements evaluated were disease severity, atopic and metabolic comorbidities, treatment type and duration. Six-hundred and eighty-four adult patients with AD were included into the study. Atopic, but not metabolic conditions, except for hypertension, were significantly associated with having moderate-to-severe AD in young adult patients. Disease duration was significantly associated with disease severity. Oral corticosteroids and cyclosporine were the most widely used immunosuppressant. Our study seems confirm the close relationship between adult AD and other atopic conditions, further long-term cohort studies on patients affected by adult AD need to be performed to evaluate the complex relationship between adult AD disease severity and metabolic comorbidities.

Real-life experience on effectiveness and safety of dupilumab in adult patients with moderate-to-severe atopic dermatitis.

BACKGROUND: Dupilumab, a fully human monoclonal antibody targeting the alpha subunit of IL-4 was recently approved for the treatment of moderate-to-severe atopic dermatitis (AD) in adult patients. OBJECTIVE: To assess dupilumab effectiveness and safety in adults with moderate-to-severe AD in a real-life Italian multicentre retrospective cohort. METHODS: Adult moderate-to-severe AD patients, referring to 39 Italian centers, received dupilumab in the context of a national patient access program. Disease assessment was performed at baseline, after 4 and 16 weeks of treatment using Eczema-Area-and-Severity-Index (EASI) score, itch and sleep numerical-rating-score (itch-NRS, sleep-NRS) and Dermatology-Life-Quality-Index (DLQI). RESULTS: A total of 109 (71 M/38F) patients was studied. There was a significant reduction in EASI score, itch-NRS, sleep-NRS and DLQI from baseline to week 4 and a further significant decline to week 16. EASI 50, EASI75 and EASI90 were achieved by 59.6%, 28.4% and 9.3% of patients at 4 weeks and by 87.2%, 60.6% and 32.4% of them at 16 weeks, respectively. Adverse events were experienced by 19.2% (21/109) of the patients and they were all mild in intensity, being conjunctivitis the most common side effect. CONCLUSIONS: Dupilumab significantly improved disease severity, pruritus, sleep loss and quality of life with an acceptable safety profile.