@IT2020: An innovative algorithm for allergen immunotherapy prescription in seasonal allergic rhinitis.

BACKGROUND: Allergen immunotherapy (AIT) is the only disease-modifying treatment in patients with seasonal allergic rhinoconjunctivitis (SAR). Its efficacy depends on the precise identification of the triggering allergen. However, diagnostics based on retrospective clinical history and sensitization to whole extracts (SWE) often leads to equivocal results. OBJECTIVES: To assess the usability and impact of a recently established algorithm for a clinical decision support system (@IT2020-CDSS) for SAR and its diagnostic steps [anamnesis, SWE (skin prick test or serum IgE), component resolved diagnosis, CRD, and real-time digital symptom recording, eDiary] on doctor's AIT prescription decisions. METHODS: After educational training on the @IT2020-CDSS algorithm, 46 doctors (18 allergy specialists, AS, and 28 general practitioners, GP) expressed their hypothetical AIT prescription for 10 clinical index cases. Decisions were recorded repeatedly based on different steps of the algorithm. The usability and perceived impact of the algorithm were evaluated. RESULTS: The combined use of CRD and an eDiary increased the hypothetical AIT prescriptions, both among AS and GP (p < .01). AIT prescription for pollen and Alternaria allergy based on anamnesis and SWE was heterogeneous but converged towards a consensus by integrating CRD and eDiary information. Doctors considered the algorithm useful and recognized its potential in enhancing traditional diagnostics. CONCLUSIONS AND CLINICAL IMPLICATIONS: The implementation of CRD and eDiary in the @IT2020-CDSS algorithm improved consensus on AIT prescription for SAR among AS and GP. The potential usefulness of a CDSS for aetiological diagnosis of SAR and AIT prescription in real-world clinical practice deserves further investigation.

IgE antibody repertoire in nasal secretions of children and adults with seasonal allergic rhinitis: A molecular analysis.

BACKGROUND: There is growing interest both in testing IgE in nasal secretions (NS) and in molecular diagnosis of seasonal allergic rhinitis (SAR). Yet, the reliability of nasal IgE detection with the newest molecular assays has never been assessed in a large cohort of pollen allergic patients. OBJECTIVE: To investigate with microarray technology and compare the repertoires of specific IgE (sIgE) antibodies in NS and sera of a large population of children and adults with SAR. METHODS: Nasal secretions were collected with an absorbent device (Merocel 2000® , Medtronic) and a minimal dilution procedure from 90 children and 71 adults with SAR. Total IgE (tIgE) (ImmunoCAP, Thermo Fisher Scientific (TFS)) and sIgE antibodies against 112 allergen molecules (ISAC-112, TFS) were measured in NS and serum. RESULTS: Nasal sIgE was detectable in 68.3% of the patients. The detected nasal sIgE antibodies recognized airborne (88%), vegetable (10%), and animal food or other (<1%) allergen molecules. The prevalence and average levels of sIgE in NS and serum were highly interrelated at population level. A positive nasal sIgE antibody to a given molecule predicted the detection of the same antibody in the patient's serum with a specificity of 99.7% and a sensitivity of 40%. CONCLUSIONS: The concentration of sIgE is much lower in nasal secretions than in the serum. sIgE assays with very high analytical sensitivity and sampling methods with minimal dilution will be therefore needed to validate nasal secretions as alternative to serum in testing the sIgE repertoire.

Adherence to Prescribed E-Diary Recording by Patients With Seasonal Allergic Rhinitis: Observational Study.

BACKGROUND: Complete diagnosis and therapy of seasonal allergic rhinoconjunctivitis require evidence that exposure to the sensitizing pollen triggers allergic symptoms. Electronic clinical diaries, by recording disease severity scores and pollen exposure, can demonstrate this association. However, patients who spontaneously download an e-diary app show very low adherence to their recording. OBJECTIVE: The objective of our study was to assess adherence of patients with seasonal allergic rhinitis to symptom recording via e-diary explicitly prescribed by an allergist within a blended care approach. METHODS: The @IT-2020 project is investigating the diagnostic synergy of mobile health and molecular allergology in patients with seasonal allergic rhinitis. In the pilot phase of the study, we recruited Italian children (Rome, Italy) and adults (Pordenone, Italy) with seasonal allergic rhinitis and instructed them to record their symptoms, medication intake, and general conditions daily through a mobile app (Allergy.Monitor) during the relevant pollen season. RESULTS: Overall, we recruited 101 Italian children (Rome) and 93 adults (Pordenone) with seasonal allergic rhinitis. Adherence to device use slowly declined during monitoring in 3 phases: phase A: first week, ≥1267/1358, 90%; phase B: second to sixth week, 4992/5884, 80% to 90%; and phase C: seventh week onward, 2063/2606, 70% to 80%. At the individual level, the adherence assessed in the second and third weeks of recording predicted with enough confidence (Rome: Spearman ρ=0.75; P<.001; Pordenone: ρ=0.81; P<.001) the overall patient adherence to recording and was inversely related to postponed reporting (ρ=-0.55; P<.001; in both centers). Recording adherence was significantly higher during the peak grass pollen season in Rome, but not in Pordenone. CONCLUSIONS: Adherence to daily recording in an e-diary, prescribed and motivated by an allergist in a blended care setting, was very high. This observation supports the use of e-diaries in addition to face-to-face visits for diagnosis and treatment of seasonal allergic rhinitis and deserves further investigation in real-life contexts.

A new molecular multiplex IgE assay for the diagnosis of pollen allergy in Mediterranean countries: A validation study.

BACKGROUND: The identification of the primary sensitizing pollen is difficult in Southern European patients with Seasonal Allergic Rhinitis (SAR) if sensitized to various pollen sources with overlapping seasonality. A more precise diagnosis is obtained by IgE assays to allergen molecules, currently available as singleplex or microarrays. OBJECTIVES: To test the analytical performance of a multi-parameter immunoblot molecular "Pollen Test" specifically designed to test IgE antibodies to pollen extracts and molecules clinically relevant in Southern Europe. METHODS: Sera were obtained from 101 children and 98 adults with SAR and tested with a customized multiplex immunoblot assay (EUROLINE Southern European Pollen Profile [ESEP]; EUROIMMUN AG, Luebeck, Germany) containing a comprehensive panel of allergen extracts and molecules. ESEP's outcomes were then compared in selected sera (ESEP positive to negative = 2:1) with those of singleplex IgE assays (ImmunoCAP; ThermoFisher Scientific, Uppsala, Sweden). For each of the examined reagents, qualitative (sensitivity, specificity, accuracy), semi-quantitative (classes) and quantitative (Spearman's rank correlation, Bland-Altmann plots) comparisons were performed. RESULTS: Compared to ImmunoCAP, cumulative ESEP's sensitivity and specificity were 87% (95% CI 84%-90%) and 88% (83%-93%) for extracts and 99% (98%-100%) and 87% (83%-91%) for molecules. Cohen's kappa coefficients (κC ) ranged for extracts from 0.18 (Pellitory) to 0.50 (Cypress) and for molecules from 0.21 (Ole e 1) to 0.68 (Phl p 7). The quantitative outcomes of the two diagnostic tests were highly correlated, with Spearman's rank correlation coefficients always exceeding 0.80. Bland-Altmann plots showed a tendency of ESEP to overestimate serum specific IgE levels, when compared to ImmunoCAP. CONCLUSIONS AND CLINICAL RELEVANCE: Sensitivity and specificity of ESEP in testing serum IgE antibodies against pollen allergen extracts and molecules, in Italian patients with SAR, both exceeded 85%. The advantages and limitations of a multiplex customized immunoblot assay, in the routine clinical use of molecular diagnostics in Southern European pollen allergic patients, deserve to be tested.

Potential Indications of Dupilumab in Th-2 Inflammatory Disease.

Dupilumab is a fully humanized IgG4 monoclonal antibody, inhibiting IL-4 and IL-13 signaling, which are the main cytokines involved in type 2 inflammatory diseases. Its introduction was a breakthrough in the treatment of moderate-to-severe atopic dermatitis, but it is also used in other inflammatory diseases, including asthma, eosinophilic esophagitis and chronic rhinosinusitis with nasal polyposis. Recent advances in the understanding of inflammatory pathways have revealed that Th2-type inflammation is involved in a wider range of diseases than previously thought. The aim of our review is to examine off-label therapeutic indications of dupilumab, including bullous dermatoses (pemphigus, bullous pemphigoid) and alopecia areata, and to investigate its potential applications in cancer patients on anti-PD1 therapy.

Combining Reflectance Confocal Microscopy, Optical Coherence Tomography and Ex-Vivo Fluorescence Confocal Microscopy for Margin Assessment in Basal Cell Carcinoma Excision.

INTRODUCTION: Recent developments of noninvasive, high-resolution imaging techniques, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), have enhanced skin cancer detection and precise tumor excision particularly in highly aggressive and poorly defined basal cell carcinomas (BCCs). OBJECTIVES: The aim of this pilot study is to assess the feasibility and reproducibility of a systematic clinical workflow combining noninvasive (RCM-OCT) and invasive fluorescence confocal microscopy (FCM) imaging modalities in pre- and intra-surgical evaluations of the lateral and deep margins of BCC. METHODS: Superficial incisions were made 2 mm beyond the clinical-dermoscopic BCC margins. Lateral margins were then explored with OCT and RCM. In positive margins, a further cut was made 2 mm distal from the previous. A final RCM/OCT-based double-negative margin was drawn around the entire perimeter of the lesion before referring to surgery. The freshly excised specimen was then examined with FCM (ex-vivo) for the evaluation of the deep margin. Histopathologic examination eventually confirmed margin involvement. RESULTS: The study included 22 lesions from 13 patients. At the end of the study, 146 margins-106 negative (73%) and 40 positive (27%) at RCM/OCT-were collected. The RCM/OCT margin evaluation showed an overall sensitivity of 100% and a specificity of 96.3%. The overall positive margins diagnostic accuracy was 98.2%. Reproducibility was evaluated on recorded images and the raters showed a substantial inter-observer agreement on both RCM (κ = 0.752) and OCT images (κ = 0.724). CONCLUSIONS: The combined RCM/OCT/FCM ex-vivo approach noninvasively facilitates the presurgical and intrasurgical lateral and deep margin assessment of poorly defined BCCs.

A Machine Learning Algorithm Applied to Trichoscopy for Androgenic Alopecia Staging and Severity Assessment.

INTRODUCTION: Androgenic alopecia (AGA) staging is still based on macroscopic scales, yet the introduction of trichoscopy is gradually bringing an important change, even though it remains an eye-based method. However, recently developed artificial intelligence-assisted programs can execute automated count of trichoscopic patterns. Nevertheless, to interpret data elaborated by these programs can be complex. Machine learning algorithms might represent an innovative solution. Among them, support vector machine (SVM) models are among the best methods for classification. OBJECTIVES: Our aim was to develop a SVM algorithm, based on three trichoscopic patterns, able to classify AGA patients and to calculate a severity index. METHODS: We retrospectively analyzed trichoscopic images from 200 AGA patients using Trichoscale Pro® software, calculating the number of vellus hair, empty follicles and single hair follicular units. Then, we elaborated a SVM model, based on these three patterns and on sex, able to classify patients as affected by mild AGA or moderate-severe AGA, and able to calculate the probability of the classification being correct, expressed as percentage (from 50% to 100%). This probability estimate is higher in patients with more AGA trichoscopic patterns and, thus, it might serve as a severity index. RESULTS: For training and test datasets, accuracy was 94.3% and 90.0% respectively, while the Area Under the Curve was 0.99 and 0.95 respectively. CONCLUSIONS: We believe our SVM model could be of great support for dermatologists in the management of AGA, especially in better assessing disease severity and, thus, in prescribing a more appropriate therapy.

A new combination of molecules for the treatment of androgenetic alopecia and telogen effluvium: a double-blind randomized, monocentric, placebo-controlled study.

BACKGROUND: Androgenetic alopecia (AGA) is the most frequent form of alopecia. Telogen effluvium (TE) is a common form of diffuse hair loss mainly observed in women. The aim of our study was to evaluate the efficacy of a topical trichological treatment containing a new combination of molecules for the treatment of AGA and TE. METHODS: In-vitro tests were performed analyzing different combinations and concentrations of arginine, zinc and a third enzymatically neutral substance called AA on human follicles dermal papillae cells. These tests evaluated the capability of inhibiting the 5α-reductase (5-AR) enzyme and the 5-AR gene expression. We also performed an in-vivo study. Forty individuals affected by AGA and TE were divided into two groups. One group was administered a combination of zinc and arginine (lotion A), whilst the other placebo (lotion B). Therapy duration was 23 consecutive weeks. Follow-up examinations and pull tests occurred at baseline, after 6 weeks and at the end of the therapy. On 20 randomly selected patients we also performed noninvasive phototrichograms. RESULTS: In-vitro tests showed that the combination had a strong statistically significant inhibitory activity on 5-AR of dermal papillae cells. Number of hairs removed by pull-test significantly decreased at T0, T1 and T2 in patient treated with lotion A. We also observed an increase in the percentage of anagen hair and a decrease in telogen hairs. Concerning phototrichograms, all objective parameters evaluated showed better results in the lotion A group when compared with the placebo group. CONCLUSIONS: Based on our results, the combination of arginine and zinc tested in our study could represent a good therapeutic option for the treatment of AGA and TE and it might represent a valid alternative to finasteride.

Recommendations on trichological treatments during COVID-19 pandemic.

COVID-19 is an infectious disease caused by the novel coronavirus SARS-CoV-2, which rapidly spreads via respiratory droplets and is the cause of the current pandemic. In this alarming situation, it is a delicate matter how to visit patients safely and how to manage their chronic treatments. The aim of this paper is to examine in detail the potential impact on SARS-CoV-2 infection of treatments routinely used in trichology and to provide a useful guide for the therapeutic management of trichological patients in this new COVID-19 era.

Clinical and Trichoscopic Graded Live Visual Scale for Androgenetic Alopecia.

Introduction: Currently, the mostly used classifications of androgenetic alopecia (AGA) only provide a macroscopic and subjective description of this disorder, without evaluating trichoscopic features. Objectives: The aim of this study is to elaborate a graded live visual AGA severity scale including macroscopic and microscopic (trichoscopic) pictures, and to determine the most frequent trichoscopic characteristics associated to each grade. Methods: A retrospective observational study was conducted on 122 patients (50 females and 72 males) affected by AGA. Macroscopic and trichoscopic photographs were taken at standardized scalp points. Results: Each picture was ranked from AGA stage I to VII, according to Hamilton scale for men and Sinclair scale for women, and the most representative images of each severity degree were collected to produce a graded live visual scale. In males, 2 live visual scales, 1 for the anterior and 1 for posterior region of the scalp were created. In females, only 1 scale of the anterior region was realized. For each stage of severity, the corresponding trichoscopic parameters were statistically analyzed. Conclusions: We realized new macroscopic and trichoscopic graded live visual scales for male and female patients affected by AGA, which could help physicians in giving an objective evaluation of the disease and in better managing it.

Efficacy of a new combination of a microemulsion and oral supplementation for androgenetic alopecia: an interventional multicentric study.

BACKGROUND: The aim of this study was to study new therapeutic options for the treatment of female and male androgenetic alopecia (AGA) and to assess the efficacy of a possible new coadjuvant oral and topical therapy, containing a complex of natural substances. METHODS: Sixty individuals affected by mild-to-moderate female and male AGA were enrolled in the study and underwent the oral and topical treatment with a microemulsion formulation for 6 months. At baseline and at 3- and 6-month follow-up, global photographs were taken and three expert operators evaluated photographs using the 7-point scale. On a subgroup of our sample, non-invasive phototrichograms with TrichoScan® HD at baseline and follow-ups were performed to collect the trichological parameters of total number of hairs, hair density/cm2, vellus hair density/cm2, terminal hair density/cm2 and hair thickness. One-way ANOVA and Unpaired Student t-test were performed to analyze the data. RESULTS: Using the 7-point scale, a clinically visible improvement of hair loss was observed after three and six months of treatment. A statistically significant increase of all TrichoScan® trichological parameters was observed at both 3- and 6 month-follow-up. CONCLUSIONS: The complex of natural and active substances tested in this work showed good efficacy in improving both male and female hair loss. These new products could represent a valid alternative or coadjuvant therapy of AGA, increasing the efficacy of conventional treatments such as minoxidil or finasteride.

Validation Parameters of Patient-Generated Data for Digitally Recorded Allergic Rhinitis Symptom and Medication Scores in the @IT.2020 Project: Exploratory Study.

BACKGROUND: Mobile health technologies enable allergists to monitor disease trends by collecting daily patient-reported outcomes of allergic rhinitis. To this end, patients with allergies are usually required to enter their symptoms and medication repetitively over long time periods, which may present a risk to data completeness and quality in the case of insufficient effort reporting. Completeness of patient's recording is easily measured. In contrast, the intrinsic quality and accuracy of the data entered by the patients are more elusive. OBJECTIVE: The aim of this study was to explore the association of adherence to digital symptom recording with a predefined set of parameters of the patient-generated symptom and medication scores and to identify parameters that may serve as proxy measure of the quality and reliability of the information recorded by the patient. METHODS: The @IT.2020 project investigates the diagnostic synergy of mobile health and molecular allergology in patients with seasonal allergic rhinitis. In its pilot phase, 101 children with seasonal allergic rhinitis were recruited in Rome and instructed to record their symptoms, medication intake, and general conditions daily via a mobile app (AllergyMonitor) during the relevant pollen season. We measured adherence to daily recording as the percentage of days with data recording in the observation period. We examined the patient's trajectories of 3 disease indices (Rhinoconjunctivitis Total Symptom Score [RTSS], Combined Symptom and Medication Score [CSMS], and Visual Analogue Scale [VAS]) as putative proxies of data quality with the following 4 parameters: (1) intravariation index, (2) percentage of zero values, (3) coefficient of variation, and (4) percentage of changes in trend. Lastly, we examined the relationship between adherence to recording and each of the 4 proxy measures. RESULTS: Adherence to recording ranged from 20% (11/56) to 100% (56/56), with 64.4% (65/101) and 35.6% (36/101) of the patients' values above (highly adherent patients) or below (low adherent patients) the threshold of 80%, respectively. The percentage of zero values, the coefficient of variation, and the intravariation index did not significantly change with the adherence to recording. By contrast, the proportion of changes in trend was significantly higher among highly adherent patients, independently from the analyzed score (RTSS, CSMS, and VAS). CONCLUSIONS: The percentage of changes in the trend of RTSS, CSMS, and VAS is a valuable candidate to validate the quality and accuracy of the data recorded by patients with allergic rhinitis during the pollen season. The performance of this parameter must be further investigated in real-life conditions before it can be recommended for routine use in apps and electronic diaries devoted to the management of patients with allergic rhinitis.

A Case Report of Monkeypox in an Adult Patient from Italy: Clinical and Dermoscopic Manifestations, Diagnosis and Management.

Monkeypox infection is an emerging problem and a new challenge for modern medicine. With an increasing number of new cases worldwide, new data regarding the clinical manifestations, characteristics of the patients, risk factors and treatment options are coming to light. Knowing more about the disease will allow to elaborate new helpful methods to facilitate its diagnosis. Special attention should be paid to the careful dermatologic and dermoscopic examination of the patient. The analysis of available data also suggests possible strategies for the prevention of Monkeypox virus spread; the vaccine against Smallpox seems to be an effective solution. This case report describes the diagnostic approach and management of a non-vaccinated adult patient with several risk factors and a history of sexually transmitted disease. The patient had no history of travel abroad. Even though a clinical diagnose of Monkeypox can be challenging due to its similarities with skin rashes caused by other Orthopoxviral infections, there are fine differences between the rashes which can be helpful in their differentiation, although laboratory analysis is required for a definitive identification. A careful study of the characteristics of the rash, such as diameter, its presence on palms and soles and its evolution in time, provided important clues for the diagnosis of Monkeypox infection. The lack of vaccinations in the history of the patient was another crucial finding in the diagnostic process.

Are dissecting cellulitis and hidradenitis suppurativa different diseases?

Although dissecting cellulitis (DC) and hidradenitis suppurativa (HS) are classified separately, they share many clinical, dermatoscopic, pathogenetic, and histologic aspects, as well as therapeutic options. The association between DC, HS, and acne conglobata represents the follicular occlusion triad or follicular occlusion tetrad, which may include a pilonidal sinus. DC, also known as "folliculitis et perifolliculitis capitis abscendes et suffoidens," is classified as a secondary cicatricial and neutrophilic alopecia. It occurs with perifolliculitis of the scalp, dermal abscesses, sinus tract development, and secondary scarring alopecia. HS, sometimes known as acne inversa, is a chronic relapsing inflammatory disease afflicting apocrine gland-rich areas of the body with painful nodules and abscesses, sinus tracts, and scarring. Given the overlap between the clinical features and the pathogenesis of DC and HS, it would be more appropriate to consider these conditions as two different localizations of the same disease rather than two different pathologies, being a follicular occlusion disease occurring on the scalp and on the apocrine gland-rich areas of the body.

Recurrence of alopecia areata after covid-19 vaccination: A report of three cases in Italy.

BACKGROUND: Common COVID-19 vaccines side effects are pain at the injection site, muscle pain, fever, headaches, fatigue. Possible immune-related side effects in predisposed individuals have not been established so far. MATERIALS AND METHODS: We report three cases of recurrence of alopecia areata (AA) occurred after the first dose of COVID-19 vaccine. RESULTS: All patients had previous episodes of AA with total hair regrowth and stable remission during the months preceding the vaccination. Rapid hair loss occurred 2-3 weeks after BNT162b2 mRNA (patient 1) and AZD1222/ChAdOx1 vaccine (patient 2 and 3), with widespread hair loss in two cases and a single patch of the vertex in one case, with typical trichoscopic features of AA. DISCUSSION: Both BNT162b2 mRNA and AZD1222/ChAdOx1 vaccines share the same goal of inducing the immune system, with antibodies production and Th1 cells activation with release of pro-inflammatory cytokines. Thus, in patients with pre-existing inflammatory dysregulated pathways, the interaction between the immune system and vaccines may enhance other autoimmune mechanisms. In our cases, we speculate that vaccine may have induced the hair loss focusing on components having a key role in both COVID-19 vaccination and AA pathogenesis. CONCLUSION: This report may help to collect new data concerning possible immune-related effects of vaccines. Certainly, only three cases are not sufficient to draw conclusion, thus a large-scale study is necessary. Immune-mediated side effects remain a rare event, thus the benefits of COVID-19 vaccines outweigh the risk of disease flares and we strongly recommend it in all eligible patients with AA.

An Open-label Study Comparing Oral Zinc to Lymecycline in the Treatment of Acne Vulgaris.

BACKGROUND: Acne is a chronic multifactorial skin disease with a high prevalence among adolescents. The therapeutic approach for mild to moderate papulopustular acne includes the use of systemic tetracycline. Increased risk of antibiotic resistance necessitates research into alternative therapeutic approaches, such as zinc sulphate. Efficacy of zinc sulphate in acne treatment is widely reported in the literature, but drug comparison studies are lacking. OBJECTIVE: We sought to compare the efficacy and safety of zinc sulphate to lymecycline for the treatment of mild to moderate papulopustular acne. METHODS: One hundred patients were equally randomized to receive either zinc sulphate or lymecycline. Acne severity was evaluated using the subjective Global Acne Grading System (GAGS) and the Acne-specific Quality of Life (AQoL) questionnaire at baseline and after four and 12 weeks. RESULTS: Both zinc sulphate and lymecycline induced a statistically significant reduction in GAGS scores at four and 12 weeks of treatment. The improvements in AQoL scores in patients treated with zinc sulphate were significantly higher than those in the lymecycline group. CONCLUSIONS: Our study suggests that zinc sulphate is a valid alternative therapeutic approach in the treatment of mild to moderate papulopustular acne relative to lymecycline in terms of clinical efficacy, tolerability, and the occurrence of side effects.