Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials.

BACKGROUND: Many patients with chronic spontaneous urticaria (CSU) do not achieve complete control of their symptoms with current available treatments. In a dose-finding phase 2b study, ligelizumab improved urticaria symptoms in patients with H1-antihistamine (H1-AH) refractory CSU. Here, we report the efficacy and safety outcomes from two ligelizumab phase 3 studies. METHODS: PEARL-1 and PEARL-2 were identically designed randomised, double-blind, active-controlled and placebo-controlled parallel-group studies. Patients aged 12 years or older with moderate-to-severe H1-AH refractory CSU were recruited from 347 sites in 46 countries and randomly allocated in a 3:3:3:1 ratio via Interactive Response Technology to 72 mg ligelizumab, 120 mg ligelizumab, 300 mg omalizumab, or placebo, dosed every 4 weeks, for 52 weeks. Patients allocated to placebo received 120 mg ligelizumab from week 24. The primary endpoint was change-from-baseline (CFB) in weekly Urticaria Activity Score (UAS7) at week 12, and was analysed in all eligible adult patients according to the treatment assigned at random allocation. Safety was assessed throughout the study in all patients who received at least one dose of the study drug. The studies were registered with ClinicalTrials.gov, NCT03580369 (PEARL-1) and NCT03580356 (PEARL-2). Both trials are now complete. FINDINGS: Between Oct 17, 2018, and Oct 26, 2021, 2057 adult patients were randomly allocated across both studies (72 mg ligelizumab n=614; 120 mg ligelizumab n=616; 300 mg omalizumab n=618, and placebo n=209). A total of 1480 (72%) of 2057 were female, and 577 (28%) of 2057 were male. Mean UAS7 at baseline across study groups ranged from 29·37 to 31·10. At week 12, estimated treatment differences in mean CFB-UAS7 were as follows: for 72 mg ligelizumab versus placebo, -8·0 (95% CI -10·6 to -5·4; PEARL-1), -10·0 (-12·6 to -7·4; PEARL-2); 72 mg ligelizumab versus omalizumab 0·7 (-1·2 to 2·5; PEARL-1), 0·4 (-1·4 to 2·2; PEARL-2); 120 mg ligelizumab versus placebo -8·0 (-10·5 to -5·4; PEARL-1), -11·1 (-13·7 to -8·5; PEARL-2); 120 mg ligelizumab versus omalizumab 0·7 (-1·1 to 2·5; PEARL-1), -0·7 (-2·5 to 1·1; PEARL-2). Both doses of ligelizumab were superior to placebo (p<0·0001), but not to omalizumab, in both studies. No new safety signals were identified for ligelizumab or omalizumab. INTERPRETATION: In the phase 3 PEARL studies, ligelizumab demonstrated superior efficacy versus placebo but not versus omalizumab. The safety profile of ligelizumab was consistent with previous studies. FUNDING: Novartis Pharma.

Real-world data on the effectiveness of brodalumab in patients with moderate-to severe plaque psoriasis in the Greek clinical setting (the BrIDGE study).

BACKGROUND: Despite that brodalumab's efficacy and safety have been assessed in randomized clinical trials, real-life data remain scarce. BrIDGE was an observational, prospective, single-cohort, multicentre study that recruited patients with moderate-to severe plaque psoriasis in Greece. OBJECTIVES: The primary objective was to assess the proportion of patients who achieved Psoriasis Area and Severity Index (PASI)100 after 24 weeks. Other endpoints included: the maintenance of PASI90/100 through to 104 weeks, the short-term response [PASI75/90/100 and static Physician's Global Assessment (sPGA) 0/1] to brodalumab at 12-16 weeks and time to complete clearance. Moreover, we explored the change in quality of life [Dermatology Life Quality Index (DLQI) 0/1] and adherence to brodalumab. METHODS: Two hundred patients who were initiating treatment with or switching to brodalumab, were recruited. Analyses were conducted using the as observed data and three imputation approaches were also applied for the missing data (last observation carried forward, 'worst case' and 'best case' scenario). Continuous variables were reported using summary statistics, whereas categorical variables were reported in frequency tables. RESULTS: Based on the 'as observed data', 42.0% of patients achieved PASI100 at Week 24 after 25.9 ± 3.5 weeks and 65% of patients attained PASI100 at Week 104. In total, 70.2%, 47.5% and 32.0% achieved PASI75/90/100, respectively, whereas 72.6% of patients achieved sPGA 0/1, at Weeks 12-16. With respect to sPGA status 82.8%, 89.2% and 92.5% of patients achieved sPGA 0/1 at Weeks 24, 52 and 104, respectively. The time to achieve PASI100 at Weeks 12-16 was 13.7 ± 1.3, 52.1 ± 3.4 weeks at Week 52 and 105.5 ± 4.8 weeks at Week 104. Mean DLQI and Psoriasis Symptom Inventory (PSI) scores decreased by 11.4 ± 7.0 and 15.4 ± 6.5 points from baseline to Week 104, respectively. Adherence to treatment was equal to 98.9%. CONCLUSIONS: Brodalumab confers rapid and durable responses, as well as improvements in the quality of life of moderate-to-severe psoriasis patients.

Adalimumab-Induced Paradoxical Psoriasis Treated with Biologics Targeting the IL-17/IL-23 Axis in Patients with Hidradenitis Suppurativa.

BACKGROUND: Paradoxical psoriasis (PP) has been mainly described in patients receiving tumor necrosis factor-α (TNFα) inhibitors for inflammatory bowel disease or psoriasis vulgaris, while such data in the context of hidradenitis suppurativa (HS) are scarce. The purpose of this study was to demonstrate the course of PP and the underlying HS upon switching from adalimumab to a biologic agent targeting the interleukin (IL)-17/IL-23 axis. METHODS: The electronic medical database of the outpatient department for HS of a tertiary hospital for skin diseases was searched to identify patients with moderate-to-severe HS under treatment with adalimumab, who developed PP and were switched to biological therapy with an IL-17 or IL-23 inhibitor between February 2016 and January 2022. Disease assessment scores were evaluated at baseline, at time of PP development, as well as six and 12 months thereafter. RESULTS: Among the 83 patients who received adalimumab for the treatment of HS between February 2016 and January 2022, 10 patients (12%) developed paradoxical psoriasiform skin reactions after a median time of seven (range, 2-48) months. There were four females (40%) and six males (60%) with a median age of 42.5 (range, 33-56) years. Five patients presented with plaque psoriasis and five with palmoplantar pustulosis, while four had intertriginous and three nail involvement. In most of the patients, HS responded well to adalimumab at onset of PP. Eight patients were changed to secukinumab, one to ustekinumab, and one to risankizumab. HS further improved in all but 2 patients, one receiving secukinumab and one receiving risankizumab. In addition, all patients achieved improvement of PP. CONCLUSION: Despite the small number of patients, this study provides support that patients with adalimumab-induced PP may benefit from biologics targeting the IL-17/IL-23 axis. Further studies are needed to establish the optimal therapeutic strategy of the anti-TNFα-induced PP in the context of HS.

Brodalumab in plaque psoriasis: Real-world data on effectiveness, safety and clinical predictive factors of initial response and drug survival over a period of 104 weeks.

BACKGROUND: Brodalumab, a fully human IgG2k antibody blocking the receptor of IL17, is characterized by a rapid onset of action with high skin clearance rates in clinical trials. Since setting PASI90/100 or absolute PASI ≤ 3 as treatment goals have become attainable, evaluating the effectiveness and safety profile of biologic agents, such as brodalumab, in a real-world setting is essential. OBJECTIVE: The aim of this study was to evaluate the effectiveness and safety profile of brodalumab over a period of 104 weeks in everyday practice. Clinical predictive factors of initial (week 12/16) response to treatment and long-term drug survival were also investigated. METHODS: In this monocentric, retrospective study, PASI90/100 and absolute PASI ≤ 1/3 were assessed in 91 patients with moderate-to-severe skin psoriasis under brodalumab at weeks 12/16, 24, 52 and 104 of treatment. At week 12/16, patients with an absolute PASI ≤ 3 were defined as 'initial responders' and ≤1 as 'super-responders'. Clinical parameters, such as age, gender, BMI, comorbidities and previous systemic treatment, were assessed in order to predict 'super-responders'. Drug survival and its prognostic factors were also evaluated. RESULTS: PASI90/100 has reached 81.1/66.0% in week 12/16. This response rate increased at week 104, where 87.1/80.7% had PASI90/100 and 84.9% had absolute PASI ≤ 1. The presence of >3 comorbidities, prior treatment with >2 systemic agents and obesity tended to be negative predictive factors of 'super-response'. Previous exposure to IL17 inhibitors had no impact on both PASI < 1 and PASI < 3 initial response. One- and two-year drug survival probability was 87.6% and 77.32%, respectively. 'Initial responders' and anti-IL17 drug-naïve patients had better drug survival. Drug discontinuation occurred in 24.2%, mostly due to secondary failure, and arthralgia was the most common adverse event that led to discontinuation. CONCLUSIONS: Our study confirms the high effectiveness and good safety profile of brodalumab in the real-world setting.

Sub-population analysis of patients with plaque psoriasis treated with calcipotriol/betamethasone aerosol foam; effectiveness and patient satisfaction, according to baseline disease severity and prior psoriasis treatment experience, in a Greek population.

Fixed combination calcipotriol/betamethasone (Cal/BD) aerosol foam has been shown to be effective in psoriasis treatment in clinical trials, but real-world evidence is currently sparse. The real-world CELSUS study in Greece found that Cal/BD aerosol foam treatment was effective and associated with satisfaction in psoriasis patients. Patients from the CELSUS study (N = 400) were stratified by baseline disease severity according to physician's global assessment (PGA) score (mild vs. moderate vs. severe) and by previous psoriasis treatment (naïve vs. treatment-experienced). Proportions of patients achieving treatment success (clear/almost clear [PGA 0/1]) after 4 weeks' treatment with Cal/BD aerosol foam were reported for each subgroup. Psoriasis area and severity index (PASI) and patient-reported itch, itch-related sleep loss, scaling, dry skin, and erythema numerical rating scores were reported by subgroup. At baseline, 216 (54%) patients were systemic-or-topical psoriasis treatment-naïve and 184 (46%) were treatment experienced. By disease severity, there were 135 versus 89 patients with mild, 69 versus 83 with moderate and 12 versus 12 with severe disease in the treatment-naïve versus treatment-experienced groups, respectively. In the treatment-naïve group, treatment success was achieved by 72.6%, 56.5%, and 66.7% of patients with mild, moderate, and severe disease, respectively, while the proportions in the treatment-experienced group were 60.7%, 42.2%, and 25%, respectively. Reduction from baseline in psoriasis symptoms was observed in all patient groups. The greatest reductions were observed in treatment-naïve patients with severe disease. Clinically relevant benefits were observed with Cal/BD aerosol foam in psoriasis patients, regardless of prior treatment-experience and disease severity at baseline.

Real world experience of brodalumab treatment in patients with moderate-to-severe plaque psoriasis in the Greek population: Results from an interim analysis of the BrIDGE study.

Brodalumab's clinical efficacy and favorable safety profile have been demonstrated during controlled clinical trials, but real-world data remain scarce. BrIDGE, an ongoing 104 week, observational, prospective, multicenter study conducted in Greece, enrolled moderate-to-severe plaque psoriasis patients, with body surface area (BSA) > 10 or psoriasis area severity index score (PASI) > 10 and dermatology life quality index (DLQI) > 10, based on European consensus, initiating brodalumab treatment as per routine clinical practice. This interim analysis includes evaluations 12-16 weeks following treatment initiation. Key efficacy endpoints included proportion of patients achieving static Physician's Global Assessment (sPGA) score of "clear/almost clear" (0/1) and a reduction ≥75%, 90%, 100% from baseline in PASI (PASI75, PASI90, and PASI100) at weeks 12-16. Other endpoints included time to achieve PASI100, changes in self-reported DLQI and psoriasis symptom inventory (PSI) at weeks 12-16. From 200 patients (mean age 51.4 years, 70% male, mean disease duration 13.8 years) enrolled, 72.8% achieved sPGA of 0/1, whereas 70.2%, 47.5%, and 32.0% achieved corresponding PASI75, PASI90, and PASI100 responses following 12-16 weeks of brodalumab treatment, according to the "as-observed" analysis. The mean time to achieve PASI100 was 13.7 ± 1.2 weeks for the 32% who achieved PASI100. Concurrent decreases in mean DLQI and PSI were observed. Furthermore, 90% adherence to brodalumab was noted and nine adverse events were reported. Brodalumab confers substantial clinical improvements short-term as reflected by high levels of skin clearance in moderate-to-severe plaque psoriasis patients within 12-16 weeks of treatment under everyday clinical conditions, followed by improvements in symptoms and quality of life and a favorable safety profile.

Patient characteristics, treatment patterns and disease outcomes in patients with psoriatic arthritis followed in a combined Dermatology-Rheumatology clinic: a retrospective real-world study.

The aim of this study was to assess the patient characteristics, treatment patterns and disease outcomes in patients with psoriatic arthritis (PsA) referred to a combined Dermatology-Rheumatology (Derm-Rheum) Clinic. This was a retrospective study of patients seen in a combined Derm-Rheum Clinic (February 2018 to June 2020) in a Tertiary University Hospital. Consecutive patients with suspicious musculoskeletal symptoms or a known diagnosis of PsA referred to the Derm-Rheum Clinic were examined and followed simultaneously by experienced dermatologists and rheumatologists. Among 151 patients with psoriasis (PSO) with suspicious musculoskeletal complaints, 129 (85%) with a final diagnosis of PsA were included (56% females, mean age: 55 years, median disease duration: 14.2 years). In 62% of these patients (n = 94), PsA was diagnosed for the 1st time. At initial evaluation, 95% had peripheral arthritis, 45% nail involvement, 23% axial involvement, 12% enthesitis and 6% dactylitis with a median DAPSA and PASI scores of 20.5 and 1.6, respectively. 31% of the patients were not receiving any systemic treatment, 45% were on biologics, 29% on non-biologics and 10% on targeted synthetic agents (apremilast). At last visit (median interval time: 15 months), only 8% did not receive any systemic therapy (p < 0.001 compared to 1st visit), 62% were on biologics (p = 0.009 compared to 1st visit), 46% on non-biologics (p = 0.01 compared to 1st visit) and 10% remained on apremilast. The median DAPSA and PASI scores decreased significantly to 5.3 and 0, respectively. In conclusion, about 2/3 of patients with PSO and musculoskeletal complaints referred to a combined Derm-Rheum Clinic were diagnosed for the 1st time with PsA. During follow-up, the percentage of PsA patients on systemic therapies significantly increased with major improvement of disease activity indices. These data emphasize the value of combined Derm-Rheum Clinics for earlier referral, diagnosis, and more effective treatment of PsA patients.

Occupational contact allergy of construction workers in Greece: Trends during 2009-2018.

BACKGROUND: Recent trends in the sensitization of construction workers show a decrease in potassium dichromate and an increase in epoxy resin sensitization. OBJECTIVES: To present the trends of occupational contact allergy of construction workers in Greece from 2009 to 2018. METHODS: We retrospectively reviewed the files of patients with eczema patch tested in our Contact Dermatitis Clinic who were construction workers. RESULTS: A total of 191 construction workers initially reported contact dermatitis. Of these, 138 had occupation-relevant allergic contact dermatitis (ACD) or irritant contact dermatitis (ICD). All patients were men. After being patch tested, 98 (71.0%) were diagnosed with ACD and 40 with ICD. Median duration of occupation till onset of ACD was 2 years (interquartile range [IQR] 0.8-7). The hands were the most common location for ACD (73.5%), followed by the trunk (39.8%), the legs (38.8%), and the face (11.2%). Of the patients, 74.6% had lesions affecting multiple body sites. Potassium dichromate (67%) was the most frequent allergen, followed by thiuram mix (37.4%) and cobalt chloride (31.8%). Sensitization to epoxy resins was lower (12.1%). CONCLUSION: The sensitization pattern of Greek construction workers does not follow the trends in Central or Northern Europe, rather sharing attributes with less industrialized countries.

Immune checkpoint-mediated psoriasis: A multicenter European study of 115 patients from the European Network for Cutaneous Adverse Event to Oncologic Drugs (ENCADO) group.

BACKGROUND: Immune checkpoint inhibitor (ICI)-mediated psoriasis poses significant diagnostic and therapeutic challenges. OBJECTIVE: To report data on ICI-mediated psoriasis, emerging from the largest cohort to date, to our knowledge, and to propose a step-by-step management algorithm. METHODS: The medical records of all patients with ICI-mediated psoriasis were retrospectively reviewed across 9 institutions. RESULTS: We included a cohort of 115 individuals. Grade 1, 2, and 3 disease severity was reported in 60 of 105 (57.1%, 10 missing data), 34 of 105 (32.4%), and 11 of 105 (10.5%), respectively. The ratio between exacerbation and de novo cases was 1:4.3. The most common systemic therapy was acitretin (23 patients, 20.1%), followed by systemic steroids (8 patients, 7%), apremilast (7 patients, 6.1%), methotrexate (5 patients, 4.3%) and biologics (4 patients, 3.6%). Overall, 29 of 112 patients (25.9%) interrupted and 20 of 111 (18%) permanently discontinued ICIs because of psoriasis. Body surface area of greater than 10% at baseline had a 3.6 increased risk for ICI treatment modification (odds ratio, 3.64; 95% confidence interval, 1.27-10.45; P = .03) and a 6.4 increased risk for permanent discontinuation (odds ratio, 6.41; 95% confidence interval, 2.40-17.11; P < .001). Guttate psoriasis and grade 2 or 3 disease were significant positive predictors for antitumor response of ICI, whereas pruritus was a negative predictor. LIMITATIONS: Retrospective design. CONCLUSION: Acitretin, apremilast, and methotrexate are safe and effective modalities for ICI-mediated psoriasis. In most cases, ICI can be completed unhindered. A therapeutic algorithm is proposed.

Occupational and non-occupational allergic contact dermatitis to hair dyes in Greece. A 10-year retrospective study.

BACKGROUND: Oxidative hair dyes are an important source of chemical exposure and a major risk factor for the development of occupational and non-occupational allergic contact dermatitis (ACD) worldwide. OBJECTIVE: To identify the frequency of common allergens associated with occupational and non-occupational ACD to hair dyes during the last 10 years, in Greece. METHODS: We retrospectively reviewed the medical records of patients with suspected ACD to hair dyes from 2010-2019. All patients with patch-test-confirmed ACD to hair dyes were evaluated. RESULTS: Out of 501 patients with suspected ACD to hair dyes, 362 had at least one positive reaction to hair dye allergens (62.4% were customers and 37.6% were hairdressers). The mean age of customers and hairdressers was 43.8 years and 30.8 years, respectively. Of the customers, 58.9% were exposed to dyes for >10 years and 61% of hairdressers for <5 years. The most common site of ACD among customers was the scalp (85%) and among hairdressers the hands (90%). p-Phenylenediamine (PPD) was the most common contact allergen (52.2%), followed by toluene-2,5-diamine, p-aminophenol, m-aminophenol, and ammonium persulfate. CONCLUSIONS: Sensitization prevalences for PPD and cross-reacting allergens have increased in Greece during the last decade, regardless of occupational or non-occupational exposure to hair dyes.

Recommendations for the definition, evaluation, and treatment of nail psoriasis in adult patients with no or mild skin psoriasis: A dermatologist and nail expert group consensus.

Nail involvement in psoriasis is common, and the severity of it does not always parallel the intensity of cutaneous disease. We created a consensus group, of which the aim was to provide practical recommendations for the treatment of nail psoriasis in patients without skin psoriasis or with mild skin lesions with no indication for a systemic treatment. This collaborative process was conducted by an international panel of dermatologists with special expertise in nail disorders, using formal consensus methods. During this process, the panel strived to establish an agreement regarding the definition of nail psoriasis, the severity of nail psoriasis, and treatment response. Treatment recommendations are provided regarding nail psoriasis severity and matrix or bed involvement. Few-nail disease was considered as nail psoriasis affecting ≤3 nails. In the case of matrix involvement only, intralesional steroid injections were considered the treatment of choice. Topical steroids alone or in combination with topical vitamin D analogues were suggested for nail psoriasis limited to the nail bed. For the systemic treatment of nail psoriasis acitretin, methotrexate, cyclosporine, small molecules, and biologics may be employed.

Patients' self-esteem before and after chemical peeling procedure.

INTRODUCTION: Chemical peeling is a safe method, widely used to treat a variety of skin conditions and reduce the aging effects. This study aims to evaluate self-esteem among adolescents who undergo chemical peelings. MATERIAL AND METHODS: One hundred and twenty six patients constituted the study group. Sixty seven individuals had undergone chemical peeling for therapeutic reasons and 59 individuals for cosmetic reasons. To assess patients' self-esteem, the Rosenberg's Self-esteem Scale (RSES) was used before and after treatment. The control group included 71 healthy, age- and sex-matched volunteers from the general population. They were also asked to complete the RSES, after the same time interval as the patients. RESULTS: The healthy controls (23.01 ± 3.12) presented statistically significantly higher self-esteem than both the groups of individuals who would be submitted to chemical peeling. Furthermore, patients who would undergo peeling for therapeutic reasons (21.58 ± 3.20) had statistically significantly higher self-esteem than those who would undergo the procedure for cosmetic reasons (18.97 ± 3.36). After the chemical peeling sessions, the self-esteem of patients treated for therapeutic reasons (23.48 ± 2.43) and of patients treated for cosmetic reasons (22.83 ± 3.34) improved statistically significantly, while the self-esteem of the healthy controls remained stable, as expected. CONCLUSION: Patients who undergo chemical peelings tend to have low levels of self-esteem. Although facial lesions in skin diseases such as acne, acne scars, rosacea, and melasma seem to have negative effect on individuals' self-consciousness, patients who would be submitted to chemical peeling in order to treat wrinkles, loss of radiance, and skin tone clarity have even lower self-esteem. Chemical peelings were shown to favorably affect patient's self-esteem since all patients showed an increase in self-esteem after treatment, while the control group experienced no change.

Psoriasis is associated with risk of obstructive sleep apnea independently from metabolic parameters and other comorbidities: a large hospital-based case-control study.

PURPOSE: Obstructive sleep apnea (OSA) represents a breathing disorder during sleep with significant health consequences. Few studies have examined the prevalence of OSA in psoriatic patients and whether OSA may be associated with psoriasis risk. We aimed to explore: (1) the inverse relationship, that is whether psoriasis might represent an independent predictor of OSA and its severity considering important predisposing factors and (2) the psoriatic phenotype related to severe OSA. METHODS: In a large hospital-based case-control study, we examined a total of 253 patients with OSA and a control group of 104 subjects without OSA, who underwent full nocturnal polysomnography and dermatologic examination. RESULTS: The prevalence of psoriasis was significantly greater in OSA patients than in controls (p = 0.03). Psoriasis was associated with OSA risk (p = 0.04) but not severity of OSA, sleepiness severity or sleep efficiency, independently from age, gender, anthropometric features, and significant comorbidities. The phenotype of a psoriatic patient suffering from severe OSA is not different from that of a patient with severe OSA and is not associated with psoriasis severity indexes. OSA psoriatic patients were not compliant with CPAP treatment in comparison with OSA patients without psoriasis. CONCLUSION: Psoriasis may represent an independent risk factor for OSA above and beyond significant comorbidities, anthropometric and metabolic parameters. Physicians should be aware of the bi-directional association of psoriasis and OSA. Managing psoriasis may be a potential target for preventing OSA as well as the potential cardiovascular mortality related to OSA and psoriasis.

Onychomycosis in patients with nail psoriasis: a point to point discussion.

Onychomycosis is the most common nail disease and affects large parts of the population. Psoriasis is a frequently encountered skin disorder with nail involvement being found in up to 80% of the patients at some time of the course of the disease. It has been postulated that onychomycosis occurs more frequently in patients with nail psoriasis, but the results of studies in the literature are controversial. Moreover, onychomycosis could exacerbate psoriasis through Koebner phenomenon and the treatment of psoriasis could predispose to onychomycosis. Finally, the differential diagnosis could be a real challenge due to many same clinical signs, the high prevalence and the possible coexistence of the two diseases. This article attempts to enlighten all these different aspects of a very close relationship.

Cross sectional questionnaire-based internet study: Self-perception and clinical course of drug allergy in Greece.

BACKGROUND: Data on self perception of drug allergy in the general population are lacking. Epidemiological studies focus either on specific populations or document adverse drug reactions in general. Our objective was to document self-reported drug allergy in Greece, through a simple, informative internet-based questionnaire. METHODS: A questionnaire on drug allergy was accessible online for a 3-month period. Participants voluntarily answered 28 questions referring to: suspected drug, clinical manifestations, concomitant factors, received treatment, reaction's re-occurrence. RESULTS: A total of 2528 questionnaires were included in study analysis. Beta-lactams and non-steroidal anti-inflammatory drugs were the most prevalent culprit agents (53% and 27.5% respectively) while half of the participants acknowledged skin manifestations as the most common symptoms. One out of three reported subsequent exposure to the drug presumed to be responsible for the reaction and 74.5% of those stated a new reaction upon re-exposure. Only 26.7% underwent allergological evaluation. Reactions manifested with respiratory or cardiovascular symptoms, parenteral administration of the culprit drug and personal history of allergy to agents of >1 different pharmacological categories were associated with increased risk of hospitalization. CONCLUSIONS: Allergic reactions to drugs are adverse events difficult to define and diagnose. A remarkable proportion of presumed as hypersensitivity reactions are not referred to allergists; therefore these patients may be either re-exposed to potentially noxious drugs, or needlessly avoid whole classes of drugs as b-lactams for more costly or less appropriate treatments. Internet-based questionnaires may contribute to awareness programs concerning drug allergy and help improve proper referral.

E-cadherin/α-catenin deregulated co-expression in thyroid carcinoma based on tissue microarray digital image analysis.

PURPOSE: Deregulation of cell-to-cell adhesion molecules is a common and also critical genetic event in epithelial malignancies leading to an increasing metastatic potential. Among them, e-cadherin and catenins--especially α and ß--, act as oncogenes during the carcinogenetic process affecting specific signaling transduction pathways (i.e. Wnt/ b-catenin). Concerning thyroid carcinoma, decreased or loss of expression in these proteins seems to affect the biological behavior of the neoplasm increasing its aggressiveness. The aim of this study was to investigate the deregulation of e-cadherin/α-catenin complex in thyroid carcinomas. METHODS: Thirty-five paraffin-embedded tissue samples including thyroid carcinomas (N=20) and also 15 cases of benign follicular nodules were cored at 1 mm diameter and transferred to a microarray block. Immunohistochemistry (IHC) was performed using anti-e-cadherin/α-catenin antibodies. Digital image analysis was also implemented for measuring the corresponding protein expression levels. RESULTS: E-cadherin/α-catenin protein expression demonstrated a significant progressive decrease regarding benign and malignant lesions (p=0.001). Simultaneous e-cadherin/α-catenin reduced or loss of expression was observed in 10/20 (50%) cancer cases correlated to advanced stage (especially nodal metastasis) of the examined tumours (p=0.02). Concerning the histological type, combined loss of e-cadherin/α-catenin expression was predominantly associated with follicular and anaplastic histology (p=0.001). Interestingly, α-catenin protein expression pattern was significantly correlated with the grade of differentiation of the examined malignancies (p=0.01). CONCLUSIONS: Progressive loss of e-cadherin mainly and also α-catenin expression is associated with an aggressive phenotype (low differentiation, increased metastatic activity/advanced stage) in thyroid carcinomas. Based on their aberrant protein expression, novel agents have been developed for restoring their normal function.

Molecular assays in detecting EGFR gene aberrations: an updated HER2-dependent algorithm for interpreting gene signals; a short technical report.

Purpose: Among oncogenes that have already been identified and cloned, Epidermal Growth Factor Receptor (EGFR) remains one of the most significant. Understanding its deregulation mechanisms improves critically patients' selection for personalized therapies based on modern molecular biology and oncology guidelines. Anti-EGFR targeted therapeutic strategies have been developed based on specific genetic profiles and applied in subgroups of patients suffering by solid cancers of different histogenetic origin. Detection of specific EGFR somatic mutations leads to tyrosine kinase inhibitors (TKIs) application in subsets of them. Concerning EGFR gene numerical imbalances, identification of pure gene amplification is critical for targeting the molecule via monoclonal antibodies (mAbs). In the current technical paper we demonstrate the main molecular methods applied in EGFR analyses focused also on new data in interpreting numerical imbalances based on ASCO/ACAP guidelines for HER2 in situ hybridization (ISH) clarifications.