Maria Esposito
@Discab.univaq.it
University of L’Aquila
Biotechnological and Applied Clinical Sciences
RESEARCH INTERESTS
Clinical Research in inlammatory skin diseases
Scopus Publications
Scopus Publications
Andrea Chiricozzi, Anna Balato, Gabriella Fabbrocini, Lucia Di Nardo, Graziella Babino, Mariateresa Rossi, Maria Esposito, Alberto Maria Bertoldi, Giampiero Girolomoni, Alessio Gambardella,et al.
Elsevier BV
Federico Salfi, Giulia Amicucci, Michele Ferrara, Daniela Tempesta, Andrea De Berardinis, Andrea Chiricozzi, Ketty Peris, Maria Concetta Fargnoli, and Maria Esposito
Springer Science and Business Media LLC
AbstractAtopic dermatitis (AD) is a common inflammatory chronic skin disease typically associated with atopic comorbidities and other non-atopic conditions such as sleep disturbances, and mood/anxiety disorders. A growing literature proposed a crucial role of sleep disturbances in the development of mental health problems in AD. We tested this assumption by mediation model analyses in adult AD patients.A total of 57 patients (mean age ± std. dev., 34.28 ± 13.07 years; 27 males; range 18–67 years) diagnosed with AD participated in a cross-sectional study. We evaluated self-perceived severity of AD, insomnia, depression, and anxiety symptoms using validated questionnaires: the Patient-Oriented Eczema Measure (POEM), the Insomnia Severity Index (ISI), the Beck Depression Inventory-second edition (BDI-II), and the Generalized Anxiety Disorder-7 scale (GAD-7), respectively. Two mediation models were performed, testing the mediation effect of insomnia symptoms on the relationship between AD severity and depression (model 1) and anxiety (model 2). AD symptoms, as expressed by POEM, were positively associated with insomnia, depression, and anxiety severity. Insomnia fully mediated the effect of AD severity on depression and anxiety. Specifically, insomnia accounted for 81.64% of the relationship between atopic eczema severity and depression, and for 81.84% of the effect of AD severity on anxiety symptoms. The present study proposed a critical role of insomnia in predisposing adult AD patients to experience depression and anxiety. Early interventions focused on treating sleep disturbances could indirectly be beneficial on mental health of patients with AD, counteracting the onset and exacerbation of anxiety and depression disorders.
Luca Stingeni, Leonardo Bianchi, Elettra Antonelli, Elena Sofia Caroppo, Silvia Mariel Ferrucci, Carlotta Gurioli, Michela Ortoncelli, Gabriella Fabbrocini, Eustachio Nettis, Donatella Schena,et al.
Wiley
Alfonso Troisi, Roberta Croce Nanni, Alessandro Giunta, Valeria Manfreda, Ester Del Duca, Silvia Criscuolo, Luca Bianchi, and Maria Esposito
Springer Science and Business Media LLC
AbstractThe aim of this study was to estimate the contribution of adult attachment style and alexithymia to cutaneous body image in patients with psoriasis while controlling for the confounding effects of disease severity and depressive symptoms. Participants were 107 consecutive patients (60% women) with a diagnosis of plaque-type psoriasis. Cutaneous body dissatisfaction was measured with the Cutaneous Body Image Scale (CBIS) and disease severity with the Psoriasis Area and Severity Index (PASI). Depressive symptoms, attachment style and alexithymia were assessed with the Beck Depression Inventory (BDI), the Attachment Style Questionnaire (ASQ) and the Toronto Alexithymia Scale (TAS-20), respectively. Hierarchical regression analysis showed that, independently from the severity of skin disease and depressive symptoms, patients with an insecure-avoidant attachment style and higher levels of alexithymia reported greater cutaneous body dissatisfaction. Because of the cross-sectional design, the causal relationship between avoidant attachment, alexithymia and cutaneous body image cannot be determined. There was no control group. Clinical assessment of patients with psoriasis should include attachment style and alexithymia among the psychological variables related to cutaneous body dissatisfaction.
L. Sacchelli, F. Filippi, A. Balato, R. Balestri, F. Bellinato, N. Bernardini, L. Bianchi, M. Burlando, A. Campanati, M. A. Chessa,et al.
Wiley
Anna Balato, Francesca Ambrogio, Martina Burlando, Carlo Giovanni Carrera, Andrea Chiricozzi, Maria Esposito, Stefano Piaserico, Miriam Teoli, and Paolo Gisondi
Springer Science and Business Media LLC
Luca Stingeni, Andrea Chiricozzi, Piergiacomo Calzavara-Pinton, Maddalena Napolitano, Ketty Peris, Donatella Schena, Cataldo Patruno, Mariateresa Rossi, Caterina Foti, Maria C. Fargnoli,et al.
Springer Science and Business Media LLC
Emanuele Vagnozzi, Manfredo Bruni, Maria Esposito, and Maria Concetta Fargnoli
Informa UK Limited
Hidradenitis suppurativa (HS) is a chronic autoinflammatory follicular disease, affecting body areas that are rich in apocrine glands. Moderate-to-severe HS may severely impair patients' quality of life also because the available therapies are often unsatisfactory. Several lines of evidence suggest that inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-17 play a pivotal role in the physiopathology of HS. TNF-α inhibitors have long been used with benefit in moderate-severe forms of HS. However, several monoclonal antibodies against IL-17 isoforms are currently being investigated for HS. We report the case of a 50-year-old man with long-standing HS and concomitant palmo-plantar psoriasis treated with brodalumab after failure of various TNF-α inhibitors. The HS lesions and the patient's quality of life improved steadily over time until week-136. Interestingly, the clinical benefit was confirmed by radiological improvement with MRI evaluation. Our case report demonstrates the long-term efficacy and safety of brodalumab in HS encouraging the use of drugs to inhibit the T helper-type 17 immune axis, especially in cases of HS refractory to therapy with TNF-α inhibitors.
Luca Stingeni, Andrea Chiricozzi, Piergiacomo Calzavara-Pinton, Maddalena Napolitano, Ketty Peris, Donatella Schena, Cataldo Patruno, Mariateresa Rossi, Caterina Foti, Maria C. Fargnoli,et al.
Springer Science and Business Media LLC
Cataldo Patruno, Gabriella Fabbrocini, Giuseppe Lauletta, Valeria Boccaletti, Cristiana Colonna, Riccardo Cavalli, Iria Neri, Michela Ortoncelli, Donatella Schena, Luca Stingeni,et al.
Informa UK Limited
Background: Dupilumab has been shown to be a safe and effective drug for the treatment of atopic dermatitis (AD) in children from 6 months to 11 years in randomized clinical trials. Aim: The aim of this real-life study was to determine the effectiveness in disease control and safety of dupilumab at W52 in moderate-to-severe AD children aged 6-11 years.Methods: All data were collected from 36 Italian dermatological or paediatric referral centres. Dupilumab was administered at label dosage with an induction dose of 300 mg on day 1 (D1), followed by 300 mg on D15 and 300 mg every 4 weeks (Q4W). Treatment effect was determined as overall disease severity, using EASI, P-NRS, S-NRS and c-DLQI at baseline, W16, W24, and W52. Ninety-six AD children diagnosed with moderate-to-severe AD and treated with dupilumab were enrolled.Results: Ninety-one (94.8%) patients completed the 52-week treatment period and were included in the study. A significant improvement in EASI score, P-NRS, S-NRS and c-DLQI was observed from baseline to weeks 16, 24 and 52.Conclusions: Our real-life data seem to confirm dupilumab effectiveness and safety in paediatric patients. Moreover, our experience highlighted that patients achieving clinical improvement at W16 preserved this condition over time.
Marco Carotenuto, Giovanni Messina, Maria Esposito, Claudia Santoro, Diego Iacono, and Karen Spruyt
Frontiers Media SA
BackgroundNeurofibromatosis type 1 (NF1) is a genetic disease that alters neurodevelopment. We aimed to analyze the sleep macrostructure of a sample of children affected by NF1 without neurocognitive co-morbidities and MRI reports of unidentified bright objects (UBOs).MethodsA 100 pre-pubertal children participated in the cross-sectional study: 50 subjects were children diagnosed with NF1 and 50 subjects were typically developing healthy children (TDC). All participants underwent polysomnographic evaluation through which conventional sleep parameters were collected: Total sleep time (TST), Sleep latency (SOL), first REM latency (FRL), number of stage shifts/h (SS/h), number of awakenings/h (AWN/h), wake after sleep onset (WASO%), sleep efficiency percentage (SE%), percentage of sleep time spent in sleep stages 1 (N1%) and 2 (N2%), slow-wave sleep (N3%), and REM sleep (REM%). Additionally, nocturnal respiratory events such as apnea/hypopnea index (AHI), oxygen desaturation index (ODI), and periodic limb movement index (PLMI) were recorded.ResultsNeurofibromatosis type 1 children showed a reduction in sleep duration parameters (TST; p < 0.001), sleep efficiency (SE%; p < 0.001), and stage N2% (p < 0.001). Moreover, the number of awakenings per hour (AWN/h), wake after sleep onset (WASO%), and respiratory events such as AHI, ODI, and PLMI resulted higher in NF1 vs. TDC children.ConclusionThe data showed that the sleep macrostructure differs between NF1 and TDC children. These findings suggest that the evaluation of sleep may provide useful support in corroborating the diagnosis and offers additional therapeutic management perspectives in NF1 and genetic neurodevelopmental disorders in general.
Piero Ruscitti, Maria Esposito, Ilenia Di Cola, Cristina Pellegrini, Andrea De Berardinis, Mirco Mastrangelo, Camilla Gianneramo, Antonio Barile, Maria Concetta Fargnoli, and Paola Cipriani
Frontiers Media SA
BackgroundThe idea of psoriatic disease continuum has been progressively prompted based on the advances of the knowledge about the pathogenic steps underpinning the occurrence of psoriasis (PSO) and psoriatic arthritis (PSA). To evaluate biomolecules (inflammatory cytokines, inflammatory chemokines, cell adhesion and cellular mediators) in naïve patients with PSO, PSA with PSO, and PSA sine PSO. To stratify the results considering the presence of psoriatic nail involvement, extensive skin disease and obesity evaluating all involved patients.MethodsBy multiplex technology, 20 serum biomolecules were assessed with the inclusion of pro-inflammatory cytokines (GM-CSF, IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-12p70, IL-17A, IL-23, TNF), anti-inflammatory cytokines (IFN-α, IL-4, IL-10, IL-13), inflammatory chemokines (IP-10, MCP-1, MIP-1α, MIP-1β), cell adhesion and cellular mediators (ICAM-1, E-selectin, P-selectin). The assessment of possible statistical differences between the means of the three groups was performed by One-Way ANOVA. In addition, by non-parametric T-tests, we stratified the results according to selected clinical characteristics (psoriatic nail involvement, PASI ≥ 10, BMI ≥ 30).ResultsIn 80 assessed naïve patients, patients with PSO showed significant increases of E-selectin (p=0.021) and IL-8 (0.041) than other groups. In patients with PSA with PSO, significant higher levels of ICAM-1 were observed (p=0.009) than other groups. We did not observe further differences comparing pro-inflammatory and anti-inflammatory cytokines, inflammatory chemokines, and cell adhesion and cellular mediators in patients with PSO, PSA with PSO, and PSA sine PSO. Patients with psoriatic onychopathy showed significant increased levels of ICAM-1 (p=0.010) and IP-10 (0.030) than others. In patients with PASI ≥ 10, significantly enhanced values of IL-8 (p=0.004), TNF (p=0.013), E-selectin (p=0.004), MIP-1α (p=0.003), and MIP-1β (p=0.039). In patients with BMI ≥ 30, significantly higher levels of E-selectin were pointed out (p=0.035) than others.ConclusionOur findings may suggest that a similar cytokine profile may characterize naïve patients with PSO, PSA with PSO, and PSA sine PSO, reinforcing the concept of psoriatic disease continuum. However, some differences may be also shown, underlying possible pathogenic differences and leading to the clinical heterogeneity of these patients.
Kristina Callis Duffin, Luis Daniel Mazzuoccolo, María Julia Cura, Maria Esposito, Anthony P. Fernandez, Paolo Gisondi, Alessandro Giunta, Tom Hillary, Stefano Piaserico, James A. Solomon,et al.
The Journal of Rheumatology
ObjectiveOur aim was to summarize and evaluate the current quality of evidence regarding the efficacy of therapies for cutaneous psoriasis (PsO) in patients with psoriatic arthritis (PsA).MethodsA literature search of MEDLINE, Embase, Cochrane Library databases, and conference abstracts was conducted to identify interventional randomized controlled trials in patients with PsA between February 2013 and December 2021. Studies were included if PsO outcomes included achieving at least 75% improvement in the Psoriasis Area and Severity Index and the blinded comparison period was ≥ 10 weeks. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was employed to assess quality of the evidence to inform and update the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations.ResultsA total of 116 studies and 36 abstracts identified in the initial search were screened. A total of 37 studies (40 treatment arms) met the criteria for final inclusion. Phosphodiesterase 4 inhibitors, Janus kinase inhibitors, and tyrosine kinase 2 inhibitors, interleukin 17 inhibitors (IL-17i), IL-12/23i, IL-23i, and tumor necrosis factor inhibitors (TNFi) had high-quality data broadly supporting the efficacy of each class for plaque PsO over placebo. Head-to-head studies with high-quality data supported both IL-17i and IL-23i over TNFi.ConclusionSeveral pharmacologic therapeutic classes have high-quality evidence demonstrating efficacy for cutaneous PsO in the PsA population. The findings will be integrated into the 2021 GRAPPA treatment recommendations, intended to guide selection of a therapeutic class where efficacy in 1 or more cutaneous or musculoskeletal domains is required.
Maria Esposito, Andrea De Berardinis, Rocco Totaro, and Maria Concetta Fargnoli
Elsevier BV
P. Gisondi, M. Maurelli, A. Costanzo, M. Esposito, and G. Girolomoni
Springer Science and Business Media LLC
Piero Ruscitti, Maria Esposito, Camilla Gianneramo, Ilenia Di Cola, Andrea De Berardinis, Andrea Martinese, Gerard Nkamtse Tochap, Alessandro Conforti, Carlo Masciocchi, Paola Cipriani,et al.
Springer Science and Business Media LLC
Abstract Purpose To characterize nail and enthesis abnormalities using high frequency ultrasound (HFUS) in patients with psoriasis (PSO), psoriatic arthritis (PSA) with PSO, and PSA sine PSO. Material and Methods Patients with PSO, PSA with PSO, and PSA sine PSO were evaluated and compared in a cross-sectional single centre study. Nail and enthesis abnormalities were evaluated by HFUS using high frequency probes (27 MHz). After a descriptive assessment, Brown University Nail Enthesis Scale (BUNES) and Madrid Sonography Enthesitis Index (MASEI) were used to assess nail and enthesis, respectively. Results Fifty-nine patients were enrolled (19 PSO, 22 PSA with PSO, 18 PSA sine PSO). In patients with PSO and in those with PSA and PSO, HFUS evaluation identified the following nail alterations characterised by thickened matrix, inhomogeneous echogenicity of the nail bed, and increased blood flow by power Doppler. In 38.9% patients with PSA sine PSO, a subclinical nail involvement was described. No difference was observed comparing BUNES values in three groups. In PSA patients with PSO and in those with PSA sine PSO, HFUS assessment of entheses mainly showed a hypoechoic aspect and thickness of the tendon, focal cortical erosion, and ossification. A subclinical enthesis involvement in 47.4% patients with PSO was observed. No difference was reported comparing MASEI values in three groups. Conclusion Qualitative and quantitative abnormalities of nail and enthesis were demonstrated by HFUS in patients with PSO, PSA with PSO, and PSA sine PSO, suggesting a practical additional tool to be used in clinical settings. Furthermore, HFUS highlighted a subclinical nail involvement in patients with PSA sine PSO and enthesis subclinical alterations in patients with PSO.
Cristina Pellegrini, Maria Esposito, Ernesto Rossi, Paolo Gisondi, Stefano Piaserico, Paolo Dapavo, Andrea Conti, Alessio Gambardella, Martina Burlando, Alessandra Narcisi,et al.
Springer Science and Business Media LLC
L. Stingeni, L. Bianchi, E. Antonelli, E.S. Caroppo, S.M. Ferrucci, M. Ortoncelli, G. Fabbrocini, E. Nettis, D. Schena, M. Napolitano,et al.
Wiley
Moderate‐to‐severe atopic dermatitis (AD) in the adolescence is a high burden disease, and its treatment can be very challenging due to paucity of approved systemic drugs for this age and their side‐effects. Dupilumab was recently approved for treatment of adolescent AD.
A. Campanati, T. Bianchelli, R. Gesuita, C. Foti, G. Malara, G. Micali, P. Amerio, F. Rongioletti, M. Corazza, A. Patrizi,et al.
Springer Science and Business Media LLC
A. Campanati, T. Bianchelli, R. Gesuita, C. Foti, G. Malara, G. Micali, P. Amerio, F. Rongioletti, M. Corazza, A. Patrizi,et al.
Springer Science and Business Media LLC
AbstractAdult 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.
Francesca PERINO, Alice FATTORI, Alfredo PICCERILLO, Luca BIANCHI, Maria C. FARGNOLI, Pasquale FRASCIONE, Giovanni PELLACANI, Anna CARBONE, Elena CAMPIONE, Maria ESPOSITO,et al.
Edizioni Minerva Medica
BACKGROUND
Diclofenac 3% gel is a widely used topical treatment with proven efficacy in reducing the burden of Actinic Keratosis (AK), however clinical benefit might not fully translate in clinical practice as non-adherence is substantial for prolonged treatment regimens. We evaluated the efficacy of an integrated low-intensity intervention program versus standard-of-care on treatment adherence among patients with multiple AK receiving diclofenac in hyaluronic acid gel 3%.
METHODS
We designed an open label, randomized, parallel group, interventional, multicenter, longitudinal cohort study including patients with multiple, grade I/II AKs. Visits were scheduled for end of treatment (T4), follow-up 1 (T5) and follow-up 2 (T6) at 90, 180 and 365 days from baseline, respectively. Patients in the intervention group received additional visits at 30 and 60 days from baseline, a brief health education intervention, an enhanced patient-physician communication, a weekly SMS reminder to medication prescriptions.
RESULTS
Patients were equally allocated between intervention (intervention group [IG], N=86) and control group (CG, N=86); at baseline, both groups had similar socio-demographic and clinical characteristics. Change scores from baseline showed a slight increment in quality of life related to AK in both groups (CG: ΔT4 - T1=-0.079; IG: ΔT4 - T1=-0.006; p=0.39) and in quality of physicianpatient interaction reported by IG (ΔT3 - T2=0.18; p<.0001). Adherence rate was not statistically different between IG and CG (28.4% vs 40.7%; p=0.11). Patients reported similar satisfaction for effectiveness, convenience and side effects of treatment. Clinical conditions improved over time and results did not differ between groups; complete clearance rate at 1 year was 18% and 29% for CG and IG, respectively.
CONCLUSIONS
Our findings showed no difference in adherence rate between the two groups, suggesting that enhanced follow-up interventions and health care education may not be sufficient drivers to promote adherence among this clinical population. Further studies are needed to explore barriers to adherence with treatments for AKs.
Maria Esposito, Anna Campanati, Alessandro Giunta, Gianluca Calianno, Luca Bianchi, Federico Diotallevi, Anna Maria Offidani, and Maria Concetta Fargnoli
Springer Science and Business Media LLC
K. Hansel, A. Zangrilli, L. Bianchi, K. Peris, A. Chiricozzi, A. Offidani, F. Diotallevi, M.C. Fargnoli, M. Esposito, P. Amerio,et al.
Wiley
The long-term efficacy and safety of the IL-23 inhibitor risankizumab, has been demonstrated in clinical trials, and only in a few real-world studies. We recently reported an Italian multicentre 16-week real-life experience in 57 adult patients with moderate-to-severe psoriasis treated with risankizumab. Herein, we report an extension analysis of our study beyond 16 weeks, collecting data on effectiveness of risankizumab on psoriasis characteristics (PASI, PGA, DLQI, NRS itch, NRS pain) after 36 and 52 week treatment.
Marco Galluzzo, Marina Talamonti, Nicoletta Bernardini, Andrea Chiricozzi, Clara De Simone, Claudio Bonifati, Pierluigi Bruni, Federico Diotallevi, Maria Esposito, Dario Graceffa,et al.
Informa UK Limited
ABSTRACT Background Real-world data on guselkumab, especially at times >6 months, are limited. Research design and methods We performed a longitudinal, retrospective analysis on 307 patients with moderate–severe chronic plaque psoriasis (Psoriasis Area Severity Index [PASI] >10) treated with guselkumab for up to 12 months. Main outcome measures PASI 75, PASI 90, and PASI 100 were assessed at baseline and at 4, 12, 20, 28, 36, 44, and 52 weeks. Results At 12 weeks, PASI 75, PASI 90, and PASI 100 were achieved in 56.4%, 33.6%, and 24.1% of patients, respectively. At 52 weeks, PASI 75, PASI 90, and PASI 100 were achieved in 82.7%, 68.7%, and 51.1% of patients, respectively. Patients without comorbidities and those naïve to previous biological therapy had better responses. The mean Dermatology Life Quality Index score decreased from 14.0 at baseline to 3.1 at 12 weeks and 1.6 at 6 months, which was maintained at later times. Similar improvements were seen in pruritus visual analog scale. Conclusions Guselkumab maintains its efficacy for up to 12 months among responders in a real-world cohort of patients with moderate–severe plaque psoriasis, confirming data from prior real-world studies with smaller cohorts and shorter duration of follow-up.
Maria Mannino, Pietro Sollena, Maria Esposito, Maria Concetta Fargnoli, Ketty Peris, and Eduardo Nagore
S. Karger AG
<b><i>Background:</i></b> Cutaneous melanoma accounts for the majority of skin cancer-related deaths. Readily identifiable phenotypic characteristics and total body nevus count (TBNC) &#x3e;50 are among the most important risk factors for cutaneous melanoma. Implementation of nevus self-count procedures and self-assessment of phenotypic traits as part of skin self-examination could be an excellent screening tool for identifying an at-risk target population. <b><i>Objectives:</i></b> Objectives of the study were to assess the skills of a central Italian and eastern Spanish population sample to recognize their skin lesions via the submission of a self-assessment questionnaire and to explore which self-assessment questionnaire item combination best predicts the high-risk condition of TBNC &#x3e;50. <b><i>Methods:</i></b> Patients aged ≥18 years filled a self-assessment questionnaire, autonomously and prior to the dermatological visit. Subsequently, dermatologists performed total body skin examination and reported patients’ skin lesions on a separate questionnaire. <b><i>Results:</i></b> We reported fair to moderate patient-dermatologist agreement for skin lesion self-assessment. The item number of nevi on the back was the single questionnaire item most accurately predicting TBNC &#x3e;50. The high-sensitivity and high-specificity classification and regression tree models for the prediction of TBNC &#x3e;50 displayed different items combinations; the item nevus on the back was always the first and most important predictor in both our models. <b><i>Conclusions:</i></b> Patients were partially able to provide correct estimation of their whole-body nevus self-count. The item nevi on the back seems to be the first and most important predictor of TBNC &#x3e;50 across our models. Delivery of high-sensitivity and high-specificity prediction models based on our questionnaire item combination may help defining a high-risk target population.