Mortality and prognostic factors in patients with bullous pemphigoid: a retrospective multicenter Italian study.

INTRODUCTION: Bullous pemphigoid is the most common autoimmune bullous dermatosis. In recent years several studies have tried to identify the main factors of the disease related with an increased risk of death. The aim of this multicenter Italian study was to assess the risk score of death considering epidemiologic, clinical, immunological, and therapeutic factors in a cohort of patients affected by bullous pemphigoid and try to identify the cumulative survival up to 120 months. METHODS: We retrospectively reviewed the medical records of patients with bullous pemphigoid who were diagnosed between 2005 and 2020 in the 12 Italian centers. Data collected included sex, age at the time of diagnosis, laboratory findings, severity of disease, time at death/censoring, treatment, and multimorbidity. RESULTS: A total of 572 patients were included in the study. The crude mortality rate was 20.6%, with an incidence mortality rate of 5.9 × 100 person/year. The mortality rate at 1, 3, 5, and 10 years was 3.2%, 18.2%, 27.4% and 51.9%, respectively. Multivariate model results showed that the risk of death was significantly higher in patients older than 78 years, in presence of multimorbidity, anti-BP180 autoantibodies >72 U/mL, or anti-BP230 > 3 U/mL at diagnosis. The variables jointly included provided an accuracy (Harrel's Index) of 77% for predicting mortality. CONCLUSION: This study represents the first nationwide Italian study to have retrospectively investigated the mortality rates and prognostic factors in patients with bullous pemphigoid. A novel finding emerged in our study is that a risk prediction rule based on simple risk factors (age, multimorbidity, steroid-sparing drugs, prednisone use, and disease severity) jointly considered with two biomarkers routinely measured in clinical practice (anti-BP230 and anti-BP180 autoantibodies) provided about 80% accuracy for predicting mortality in large series of patients with this disease.

Socioeconomic status and skin cancer incidence: a population-based, cohort study in the province of Ferrara, northern Italy.

To assess the impact of socioeconomic status (SES) on the occurrence of skin cancer in the population living in the province of Ferrara, Italy, a retrospective cohort of patients with squamous cell carcinoma (SCC), basal cell carcinoma (BCC) or malignant melanoma (MM), provided by the local cancer registry, was investigated. The SES was expressed through an ecological-based deprivation index. During the 8-year study period (2006-2013, total person-years 2 859 137), 6051 carcinomas (1535 SCCs, 4365 BCCs) and 459 MMs were diagnosed. Both crude and standardized (on the European population) rates and the standardized incidence ratio showed a direct correlation between BCC and SES. Multivariate analysis confirmed these results for BCC and also for MM, while it showed an excess of SCC incidence in the lowest SES subgroup. This study shows, for the first time, to our knowledge, opposite effects of SES on SCC and BCC occurrence. A role of environmental factors conditioned by SES may be hypothesized.

Pictorial Representation of Illness and Self-Measure to assess the perceived burden in patients with chronic inflammatory vulvar diseases: an observational study.

BACKGROUND: Chronic inflammatory vulvar diseases can have a huge detrimental impact on patient welfare. A few studies have addressed this issue so far, mainly measuring patients' quality of life or sexual dysfunction. OBJECTIVE: To assess the burden of suffering in patients with chronic inflammatory vulvar diseases using the Pictorial Representation of Illness and Self-Measure (PRISM), a visual, non-verbal instrument. We also assessed (i) the concordance between PRISM and the Dermatology Life Quality Index (DLQI), (ii) whether some variables, both patient-related and disease-related, affect the patient's suffering and quality-of-life impairment. METHODS: We evaluated for inclusion in this cross-sectional study all patients who attended our Vulva Unit over a 9-month period with histologically proven lichen sclerosus (LS), lichen planus (LP), lichen simplex chronicus (LSC), eczema, plasma cell vulvitis and psoriasis (at least five for each disease). Demographics and disease-related subjective and objective scores were recorded. The PRISM and DLQI were administered. RESULTS: We included 87 patients affected with LS, 13 with LSC and seven with LP. Median PRISM values (0-273 mm) ranged from 95 to 120 mm, depending on the disease, and median DLQI scores (0-30) were five for all three groups. Neither PRISM nor DLQI scores differed significantly among the three groups. Moderate coherence was found between PRISM and DLQI (ρ = 0.5455, P < 0.001). Global subjective score was the only variable significantly associated with the degree of suffering and quality-of-life impairment. CONCLUSIONS: Pictorial Representation of Illness and Self-Measure proved to be a valuable, highly reliable tool for measuring the perceived burden in these patients. In spite of a moderate correlation, PRISM resulted more sensitive in capturing patient distress than DLQI.

Dermoscopy of genital diseases: a review.

The male and female external genital regions are anatomical areas in which various types of skin disorders may occur. Although most of these conditions can be diagnosed by means of clinical examination and an accurate medical history, in most cases further investigations with time-consuming and/or invasive procedures are needed in order to reach the correct diagnosis. Dermoscopy, as a modern non-invasive tool, is able to better diagnose pigmented and non-pigmented skin tumours along with various inflammatory and infectious skin and appendage disorders. The aim of this paper was to provide a review of the use of dermoscopy in genital disorders based on published data and to include personal experience gained from real life, focusing on any possible gender difference and whether disease mucosal/semimucosal dermoscopy features may differ from those observed on the skin. In conclusion, genital dermoscopy should always be considered during clinical inspection in order to enhance the diagnosis or to rule out those conditions that may look similar but that show a different dermoscopy pattern, thus narrowing down the differential diagnoses and avoiding unnecessary invasive investigations.

Mechanical properties and metallurgical features of new and ex vivo used Reciproc Blue and Reciproc.

AIM: To compare the mechanical properties and metallurgic features of new and used Reciproc Blue and Reciproc instruments. METHODOLOGY: A total of 120 R25 Reciproc Blue and R25 Reciproc instruments were used. The morphological, chemical, mechanical, thermal and phase composition characteristics of new and ex vivo used files were investigated by scanning electron microscopy (FEG-SEM) with energy dispersive X-ray spectroscopy (EDS), focused ion beam analysis (FIB), micro-Raman spectroscopy, FEG-SEM metallography, X-ray diffraction (XRD), differential scanning calorimetry (DSC) and indentation tests. Usage-induce degradation was evaluated. Ten new and ten used instruments per type were run until fracture occurred in a stainless steel artificial canal (60° angle of curvature, 4-mm radius). Time to fracture and the length of the fractured fragment were recorded. Torque and angle of rotation at failure of ten new and ten used instruments for each type were measured according to ISO 3630-1. The fracture surface of each fragment was examined. Two-way analyses of variance was used to analyse the data statistically (α-level 0.05). RESULTS: SEM analysis revealed microcracks near the tip on both files after ex vivo usage tests. FIB imaging and micro-Raman spectroscopy confirmed the presence of an oxide layer on the Reciproc Blue surface. There was no thinning of the coating after use. XRD revealed a reduction of martensite and R-phase in Reciproc Blue after use. DSC analysis revealed different transformation temperatures for the instruments analysed. Reciproc Blue was significantly more flexible than Reciproc for both new and used samples (P < 0.05), and they were significantly more resistant to cyclic fatigue than Reciproc (P < 0.05). Ex vivo usage reduced the fatigue resistance of both files. Torsional resistance of Reciproc and Reciproc Blue was not reduced by simulated use (P > 0.05). CONCLUSIONS: The thermal treatment of Reciproc Blue was associated with a finer structure with smaller grains than Reciproc, which increased its fracture resistance and was also responsible for its reduced hardness and lower elastic modulus. Both files were safe during ex vivo usage in severely curved canals.

Clearance in vulvar lichen sclerosus: a realistic treatment endpoint or a chimera?

BACKGROUND: According to the current guidelines, the aim of vulvar lichen sclerosus (VLS) treatment was to improve symptoms and signs, not to cure. OBJECTIVE: To assess (i) the rate of patients with VLS who achieved complete clearance of symptoms or objective features, or both, with a 12-week pharmacological treatment and (ii) the predictive value of therapeutic response to the demographic and clinical features. METHODS: We retrospectively included patients with VLS who had undergone any topical treatment for 12 weeks; demographics, history, VLS-related symptoms and objective features recorded at baseline and on completion of treatment were collected and elaborated. The primary study endpoint was to assess the rate of patients achieving complete clearance of global subjective score (GSS), or in global objective score (GOS), and in both scores. RESULTS: One hundred and ninety-six patients were included; 24 (12.2%) were asymptomatic at baseline, and nine (4.6%) dropped out. After treatment, 78 patients (47.3%) achieved GSS = 0, 40 (21.4%) achieved GOS = 0, and 23 (13.9%) achieved complete clearance of both symptoms and signs. Lower symptom scores at baseline and shorter disease duration were associated with the achievement of symptom clearance at the end of the treatment. Earlier disease onset, diagnosis and beginning of study treatment as well as lower baseline GOS were significantly associated with complete recovery of VLS signs and clearance of both symptoms and signs. CONCLUSION: A relevant part of patients who undergo a 12-week topical treatment is not completely cured of VLS. It may be hypothesized that these patients, in spite of a significant improvement, may still have substantial residual disease and, as a result, its effect on their quality of life.

New insights into potential risk factors and associations in genital lichen sclerosus: Data from a multicentre Italian study on 729 consecutive cases.

BACKGROUND: Limited data are available on risk factors associated with lichen sclerosus and no data are available on gender differences in genital lichen sclerosus (GLS). OBJECTIVE: This multicentre study aimed at identifying potential risk factors for GLS, through data collection from a large, mixed-sex sample of patients comparing gender-related differences in relation to data from the general population. METHODS: This was a cross-sectional study on 729 subjects (53.8% females, 46.2% males) affected with GLS, consecutively observed within a network of 15 Italian dermatology units. The following information was collected: demographic data, anthropometric measures, comorbidities, family history of LS, clinical features and symptoms related to GLS. RESULTS: Overweight and obesity, blood hypertension, hypothyroidism and an educational attainment equal or above upper secondary school level were more frequent among the study patients than among the general Italian population. Moreover, a family history of GLS was reported more frequently than expected among GLS patients. These factors were similar in males and females. The disease tended to occur later in females than in males. CONCLUSIONS: Our findings suggest that metabolic factors, and possibly a sedentary lifestyle, may play a role in GLS pathogenesis in genetically predisposed patients, and that risk profile is similar in males and females despite some difference in the onset of symptoms.

Pyoderma gangrenosum and its syndromic forms: evidence for a link with autoinflammation.

Pyoderma gangrenosum is a rare inflammatory neutrophilic dermatosis manifesting as painful ulcers with violaceous, undermined borders on the lower extremities. It may occur in the context of classic syndromes like PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) and SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis), as well as in a recently described entity named PASH (pyoderma gangrenosum, acne and suppurative hidradenitis). Pyoderma gangrenosum has recently been included within the spectrum of autoinflammatory diseases, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T cells. In PAPA syndrome, different mutations involving the PSTPIP1 gene, via an increased binding affinity to pyrin, induce the assembly of inflammasomes. These are molecular platforms involved in the activation of caspase 1, a protease that cleaves inactive prointerleukin (pro-IL)-1ß to its active isoform IL-1ß. The overproduction of IL-1ß triggers the release of a number of proinflammatory cytokines and chemokines, which are responsible for the recruitment and activation of neutrophils, leading to neutrophil-mediated inflammation. In SAPHO syndrome, the activation of the PSTPIP2 inflammasome has been suggested to play a role in inducing the dysfunction of the innate immune system. Patients with PASH have recently been reported to present alterations of genes involved in well-known autoinflammatory diseases, such as PSTPIP1, MEFV, NOD2 and NLRP3. Pyoderma gangrenosum and its syndromic forms can be regarded as a single clinicopathological spectrum in the context of autoinflammation.

Clobetasol propionate vs. mometasone furoate in 1-year proactive maintenance therapy of vulvar lichen sclerosus: results from a comparative trial.

BACKGROUND: Twice-weekly proactive application of mometasone furoate 0.1% ointment (MMF) over 52 weeks was found to be an effective and safe therapy option in maintaining vulvar lichen sclerosus (VLS) remission and in preventing relapse. OBJECTIVE: To assess and compare the effectiveness and safety of two different topical corticosteroids, clobetasol propionate 0.05% ointment (CP) and MMF, administered twice weekly as a maintenance therapy of VLS previously stabilized with a topical corticosteroid course. METHODS: Forty-eight patients affected with VLS who had responded to therapy with either CP or MMF in an earlier 12-week randomized active treatment phase trial were enroled in a 52-week maintenance phase (MP) to apply their previous treatment twice weekly. The main efficacy parameters were the relapse rate, the mean time of relapse, and the change in symptom and sign severity throughout MP. RESULTS: By the end of the 52-week MP, 2 (8.33%) subjects among the CP patients and 1 (4.17%) among the MMF patients experienced a relapse; among relapsing patients the mean time to relapse was 30 weeks. Neither subjective nor objective scores changed significantly during MP among CP and MMF patients. No significant differences were found in any of the assessed efficacy endpoints between CP and MMF. Both treatments were well tolerated and the proactive regimen was judged as convenient by patients. CONCLUSIONS: Proactive application of the ultra-potent CP and the potent MMF was found to be an effective, safe and suitable maintenance treatment for long-term management of VLS. There were no differences between the two corticosteroids.

Continuous vs. tapering application of the potent topical corticosteroid mometasone furoate in the treatment of vulvar lichen sclerosus: results of a randomized trial.

BACKGROUND: Topical corticosteroids are the first-line treatment for vulvar lichen sclerosus (VLS). However, evidence on the most appropriate treatment regimen is lacking. OBJECTIVES: To compare the effectiveness and tolerability of tapering vs. continuous application of mometasone furoate (MMF) 0·1% ointment in the treatment of active VLS. METHODS: Sixty-four patients with VLS who enrolled in a 12-week active treatment phase were randomized to apply MMF either (i) once daily for 5 days per week for 4 weeks, then on alternate days for 4 weeks, then twice weekly for 4 weeks (group A) or (ii) for five consecutive days per week for the entire treatment duration (group B). The efficacy parameters were the response rate, the proportion of patients achieving an improvement from baseline of ≥ 75% in subjective and objective scores, and the mean reduction in subjective and objective scores. RESULTS: By the end of the active treatment phase, 27 patients (84%) were considered to be responders in group A, and 25 patients (78%) in group B; 69% and 47% of patients in group A and 62% and 28% in group B achieved ≥ 75% improvement in subjective and objective scores, respectively. The decreases in mean symptom and sign scores were significant compared with baseline with both regimens. No significant differences were found in any of the assessed efficacy end points between the two treatment protocols. Both regimens were well tolerated. CONCLUSIONS: Both tapering and continuous application of MMF showed similar efficacy and tolerability in the treatment of active VLS, without any difference in patient adherence to therapy.

Differences in clinicopathological features and distribution of risk factors in Italian melanoma patients.

BACKGROUND: No studies are available in the literature on the distribution of different melanoma features and risk factors in the Italian geographical areas. OBJECTIVE: To identify the differences in clinical-pathological features of melanoma, the distribution of risk factors and sun exposure in various Italian macro-areas. METHODS: Multicentric-observational study involving 1,472 melanoma cases (713 north, 345 centre, 414 south) from 26 referral centres belonging to the Italian Multidisciplinary Group for Melanoma. RESULTS: Melanoma patients in northern regions are younger, with thinner melanoma, multiple primaries, lower-intermediate phototype and higher counts of naevi with respect to southern patients; detection of a primary was mostly connected with a physician examination, while relatives were more involved in the south. Northern patients reported a more frequent use of sunbeds and occurrence of sunburns before melanoma despite sunscreen use and a lower sun exposure during the central hours of the day. CONCLUSIONS: The understanding of differences in risk factors distribution could represent the basis for tailored prevention programmes.

Comparative study on topical immunomodulatory and anti-inflammatory treatments for plasma cell vulvitis: long-term efficacy and safety.

BACKGROUND: Evidence on the treatment of plasma cell vulvitis (PCV) is scarce and comparative studies are lacking. OBJECTIVE: To assess and compare the effectiveness and safety, on a long-term basis, of three topical interventions for the treatment of PCV. METHODS: Retrospectively collected efficacy and safety data of a cohort of PCV patients treated with fusidic acid 2% and betamethasone valerate 0.1% cream fixed combination (FA/BM, 14 patients), clobetasol propionate 0.05% ointment (CP, six patients) and tacrolimus 0.1% ointment (TC, four patients) at different regimens between January 2000 and June 2013 were analysed. Treatment outcome was assessed according to Investigator Global Assessment (i) symptoms and (ii) signs, at 12, 24 and 52 weeks. RESULTS: After 12 weeks, 85% of all patients achieved satisfactory improvement in PCV-related symptoms and maintained the improvement across a 52-week observation period. About 45% achieved a satisfactory result in clinical signs after 12 weeks, without further improvement during the following 9 months. No statistical differences in response were found among treatment groups at 12, 24 and 52 weeks. All study treatments were significantly more effective in improving PCV symptoms rather than clinical signs. With regard to treatment tolerability, one patient (7.1%) in FA/BM group and one (25%) in TC group discontinued the treatment due to local side-effects. CONCLUSIONS: CP, FA/BM and TC are effective and safe in treating PCV, inducing both a rapid improvement of the disease, notably of symptoms, and stabilizing its control.

Avocado and soybean extracts as active principles in the treatment of mild-to-moderate vulvar lichen sclerosus: results of efficacy and tolerability.

OBJECTIVE: Limited evidence is available on the effectiveness of treatments alternative to corticosteroids for vulvar lichen sclerosus (VLS). The present study aimed to assess the efficacy and tolerability of avocado and soybean extracts (ASE) as active principles of both a topical product and a nutritional supplement in the treatment of active mild-to-moderate VLS. MATERIALS AND METHODS: Twenty-three patients were enrolled. Treatment consisted of a topical product containing ASE and other lenitive and anti-oxidant principles administered twice daily for 24 weeks, in association with a dietary supplement containing ASE, vitamin E and para-aminobenzoic acid for the first 12 weeks. The primary efficacy endpoint was the rate of patients achieving an improvement from baseline in global subjective score (GSS) and global objective score (GOS) of ≥ 75%. Secondary efficacy endpoint was the rate of patients achieving GSS50 and GOS50. Tertiary efficacy endpoint was the mean reduction in subjective and objective scores throughout the treatment. RESULTS: By the end of the 24-week treatment, 12 (70.5% of symptomatic patients) and 13 patients (72.2%) achieved an improvement of at least 75% in subjective and objective global scores, respectively; 100% and 88.9% reached GSS50 and GOS50, respectively. Mean symptom and sign scores decreased significantly after treatment. The treatment was well tolerated. CONCLUSIONS: Our results provide evidence that the topical and dietary supplements used in the study, which contain active principles exerting anti-inflammatory, anti-fibrotic, emollient and lenitive actions, are effective alternatives in the treatment of symptoms and signs of mild-to-moderate VLS.

First randomized trial on clobetasol propionate and mometasone furoate in the treatment of vulvar lichen sclerosus: results of efficacy and tolerability.

BACKGROUND: A 3-month topical application of clobetasol propionate (CP) represents the recommended and accepted first-line treatment for vulvar lichen sclerosus (VLS); however, to date, no randomized controlled trials have compared the efficacy and safety of CP with other topical corticosteroids. OBJECTIVE: To compare the effectiveness and tolerability of two different topical corticosteroids, CP 0·05% ointment and mometasone furoate (MMF) 0·1% ointment, in the treatment of VLS. METHODS: Fifty-four patients with VLS were enrolled in a 12-week active treatment phase (ATP) and randomized to apply either CP or MMF in a tapering regimen. The main efficacy parameters were the response rate, the rate of patients achieving an improvement from baseline of ≥ 75% in the subjective and objective scores, and the mean reduction in subjective and objective scores throughout the treatment. RESULTS: By the end of the 12-week ATP, 24 (89%) patients were considered to be responders among the CP patients and 24 (89%) among the MMF patients; 59% and 37% of patients in the CP group and 67% and 48% in the MMF group achieved an improvement of at least 75% in subjective and objective scores, respectively. The decrease in mean symptom and sign scores was significant compared with baseline with both treatments. No significant differences were found in any of the assessed efficacy endpoints between CP and MMF. Both treatments were well tolerated. CONCLUSIONS: Clobetasol propionate and MMF appeared similarly efficacious and well tolerated for the treatment of VLS and both may represent the first-line treatment for the disease.

Mometasone fuoroate 0.1% ointment in the treatment of vulvar lichen sclerosus: a study of efficacy and safety on a large cohort of patients.

BACKGROUND: Guidelines identify a 3-month topical application of an ultra-potent corticosteroid ointment as the mainstay of medical treatment for vulvar lichen sclerosus (VLS). However, there are no trials providing evidence that any specific corticosteroid is superior to another. OBJECTIVE: To assess the effectiveness and safety of a 12-week application of mometasone furoate (MMF) 0.1% ointment, with a tapering regimen, in achieving control of VLS signs and symptoms and to detect potential risk factors for VLS non-response. METHODS: 147 patients affected with VLS were enrolled in a 12-week active treatment phase (ATP) with topical 0.1% MMF. The primary efficacy endpoint was the rate of patients achieving clinical response, as defined by protocol parameters. The secondary efficacy endpoint was to assess the changes of mean VLS-related symptoms after the 12-week ATP compared with baseline. RESULTS: By the end of the ATP, 113 patients (80.7%) experienced a treatment response, whereas 27 women (19.3%) were judged as non-responders. Mean symptom scores decreased significantly in the study patients, regardless of their clinical response at the end of the ATP. Among all the epidemiological and clinical data considered, only the absence of previous medical therapies was found to be related to a significantly higher risk of non-response to treatment. CONCLUSIONS: Application of 0.1% MMF ointment for 12 weeks on a tapering regimen was found to be an effective and safe therapy option in the ATP of VLS and could represent an alternative first-line treatment to an ultra-potent molecule.