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.

Children with psoriasis and COVID-19: factors associated with an unfavourable COVID-19 course, and the impact of infection on disease progression (Chi-PsoCov registry).

BACKGROUND: The COVID-19 pandemic has raised questions regarding the management of chronic skin diseases, especially in patients on systemic treatments. Data concerning the use of biologics in adults with psoriasis are reassuring, but data specific to children are missing. Moreover, COVID-19 could impact the course of psoriasis in children. OBJECTIVES: The aim of this study was therefore to assess the impact of COVID-19 on the psoriasis of children, and the severity of the infection in relation to systemic treatments. METHODS: We set up an international registry of paediatric psoriasis patients. Children were included if they were under 18 years of age, had a history of psoriasis, or developed it within 1 month of COVID-19 and had COVID-19 with or without symptoms. RESULTS: One hundred and twenty episodes of COVID-19 in 117 children (mean age: 12.4 years) were reported. The main clinical form of psoriasis was plaque type (69.4%). Most children were without systemic treatment (54.2%); 33 (28.3%) were on biologic therapies, and 24 (20%) on non-biologic systemic drugs. COVID-19 was confirmed in 106 children (88.3%) and 3 children had two COVID-19 infections each. COVID-19 was symptomatic for 75 children (62.5%) with a mean duration of 6.5 days, significantly longer for children on non-biologic systemic treatments (P = 0.02) and without systemic treatment (P = 0.006) when compared with children on biologics. The six children who required hospitalization were more frequently under non-biologic systemic treatment when compared with the other children (P = 0.01), and particularly under methotrexate (P = 0.03). After COVID-19, the psoriasis worsened in 17 cases (15.2%). Nine children (8%) developed a psoriasis in the month following COVID-19, mainly a guttate form (P = 0.01). DISCUSSION: Biologics appear to be safe with no increased risk of severe form of COVID-19 in children with psoriasis. COVID-19 was responsible for the development of psoriasis or the worsening of a known psoriasis for some children.

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.

Profile of tofacitinib citrate and its potential in the treatment of moderate-to-severe chronic plaque psoriasis.

The outlook for patients with psoriasis has improved significantly over the last 10 years with the introduction of targeted therapies. Cytokines exert their effects by activating intracellular signaling and transcription pathways, among which there are Janus kinases (JAKs) and signal transducers and activators of transcription (STAT) pathways. JAKs are intracellular second messengers that are crucial for transmitting extracellular cytokine signals to the cell. JAK inhibition interrupts intracellular signaling and can suppress immune cell activation and inflammation in T-cell-mediated disorders, such as psoriasis. Consequently, JAKs are the subject of intensive research activity, since they represent possible therapeutic targets. Tofacitinib is an orally available compound belonging to a novel category of nonbiologic drugs, the "JAK inhibitors", which target JAKs. Recently, oral and topical formulations of tofacitinib have been demonstrated to be safe and effective for the treatment of plaque psoriasis in randomized clinical trials. In particular, a 10 mg bid dose of tofacitinib was shown to be noninferior to etanercept 50 mg subcutaneously twice weekly. Questions remain unresolved regarding the safety risk beyond the 5 mg bid dose. This review, assessing the available scientific literature, focuses on the profile of tofacitinib, as investigational compound in the treatment of plaque psoriasis. An overview of the efficacy and safety data from randomized clinical trials is provided. In addition, the authors highlight future potential applications of tofacitinib in other skin diseases, in particular alopecia areata and vitiligo.

Effectiveness and safety of cyclosporine in pediatric plaque psoriasis: A multicentric retrospective analysis.

BACKGROUND: Cyclosporine (CysA) is effective for psoriasis in adult patients but little data exist about its efficacy and safety in childhood and adolescence psoriasis. OBJECTIVES: To assess the effectiveness and safety of CysA for childhood and adolescence psoriasis. METHODS: Retrospective analysis of a group of children and adolescents (age < 17 years) with plaque psoriasis treated with CysA at several Italian dermatology clinics. RESULTS: Our study population consisted of 38 patients. The median age at the start of treatment was 12.3 years. Therapy duration varied from one to 36 months. The median maintenance dosage per day was 3.2 mg/kg (range 2-5 mg/kg). Fifteen patients (39,4%) achieved a complete clearance or a good improvement of their psoriasis defined by an improvement from baseline of ≥75% in the psoriasis area and severity index (PASI) at week 16. Eight patients (21.05%) discontinued the treatment due to laboratory anomalies or adverse events. Serious events were not recorded. CONCLUSIONS: In this case series, CysA was effective and well-tolerated treatment in a significant quote of children. CysA, when carefully monitored, may represent a therapeutic alternative to the currently used systemic immunosuppressive agents for severe childhood psoriasis.

Reflectance confocal microscopy for plaque psoriasis therapeutic follow-up during an anti-TNF-α monoclonal antibody: an observational multicenter study.

BACKGROUND: Psoriasis is a chronic recurrent inflammatory skin disease that affects 2-3% of the world population. Biologics are relatively new systemic treatments that block molecular steps important in the pathogenesis of psoriasis. In vivo Reflectance confocal microscopy (RCM) is a non-invasive, imaging technique already reported to be useful in the evaluation of the follow-up of PP under treatment with topical actives and phototherapy. No reports on systemic treatments have been proposed in literature so far. OBJECTIVE: The aim of this study was to evaluate the feasibility of RCM in the monitoring of microscopic response to a subcutaneous anti-TNF treatment, Adalimumab. METHODS: One target lesion with typical clinical aspect, from 48 psoriatic patients, was evaluated using RCM at baseline, after 4 and 8 weeks of treatment. RESULTS: Microscopic confocal changes were followed up during treatment. Results disclosed identification of early microscopic evidence of the anti-inflammatory activity of Adalimumab not detected at clinical examination. Confocal feature related to the effect of TNF-α on melanocytes activity has been also identified. CONCLUSION: Early detected RCM parameters related to Adalimumab activity could be used to identify an early response to the treatment. RCM seems to be able to give useful and practical information about follow-up in patients with PP under treatment with Adalimumab.

Linear and whorled naevoid hypermelanosis in a patient with trisomy 4 mosaicism.

Linear whorled naevoid hypermelanosis (LWNH) is a rare skin condition, characterized by swirls and whorls of hyperpigmented macules distributed in a reticulate pattern along the lines of Blaschko. We report a 2-year-old boy who presented with linear and whorled hyperpigmentation on his trunk and limbs, following the lines of Blaschko. Hyperkinesia and developmental speech-language impairment were also present. A biopsy specimen showed increased pigmentation within the basal keratinocytes without incontinentia pigmenti. No chromosomal abnormality was found in peripheral blood samples. Chromosomal analysis of skin fibroblasts detected trisomy 4 mosaicism. This case shows for the first time an association of LWNH with trisomy 4 mosaicism. LWNH should not be considered a single entity, but a cutaneous expression of mosaicism.

Familial aggregation of moderate to severe plaque psoriasis.

BACKGROUND: Psoriasis is a highly heritable disease. It has been suggested that psoriasis is preferentially transmitted from fathers. AIM: To evaluate the degree of familial aggregation of psoriasis; to determine the recurrence risk ratio (λR ) of psoriasis in first, second and third degree relatives of patients with psoriasis; and to investigate the transmission patterns of the disease and their relationships with the clinical profiles of patients. METHODS: A cross-sectional study on 640 consecutive, unrelated adult patients with chronic plaque psoriasis was performed. The prevalence of psoriasis in first, second and third degree relatives of the patients was determined, and the λR was calculated under the assumption of a population prevalence of 2%. Age of onset and presence of facial, hand and foot psoriasis were evaluated in probands with paternal vs. maternal transmission. RESULTS: A positive familial history of psoriasis was found in 380 patients (59.37%). Of these, 174 (27.18%) had at least one parent with psoriasis, with a λR of 13.59, while 106 patients (16.56%) had at least one second degree relative with psoriasis, and 34 patients (5.31%) had one third degree relative with psoriasis. No parent-of-origin effect in transmission of psoriasis from affected parent to offspring was observed, and there were no significant differences in the clinical profiles of the disease between patients grouped by transmission pattern of psoriasis. CONCLUSIONS: These results show a high familial recurrence risk of psoriasis, and suggest a balanced parental transmission of the disease.

Dermoscopic patterns of common facial inflammatory skin diseases.

BACKGROUND: Several common inflammatory dermatoses, such as rosacea, seborrheic dermatitis (SD), discoid lupus erythematosus (DLE) and granulomatous skin diseases manifest as erythematous macules or plaques on the facial skin. Although clinical examination represents the cornerstone of diagnosis, the broad variety of clinical features and uncommon presentations of these diseases may cause at times diagnostic and therapeutic uncertainty. Dermoscopy, in addition to its well-documented value in evaluation of skin tumours, is continuously gaining appreciation also in the field of general dermatology. OBJECTIVE: To describe and compare the dermoscopic patterns of common facial inflammatory skin diseases including SD, erythematotelangiectatic rosacea (ER), sarcoidosis, lupus vulgaris (LV), DLE and granuloma faciale (GF). METHODS: Dermoscopic images of lesions from patients with histopathologically confirmed diagnosis of SD, ER, sarcoidosis, LV, DLE or GF were retrospectively evaluated for the presence of several criteria. Selection of the dermoscopic variables included in the evaluation process was based on the data available in the literature and on our preliminary observations. RESULTS: One hundred and fifteen dermoscopic images were included in the study. SD was dermoscopically characterized by dotted vessels and yellow scales, whereas ER was typified by a characteristic pattern of vascular polygons. Sarcoidosis and LV very commonly exhibited orange-yellowish areas and linear branching vessels. Features related to follicle abnormalities and linear branching vessels were the most common dermoscopic criteria of DLE and GF. CONCLUSIONS: This study provides new insights into the dermoscopic variability in common facial inflammatory dermatoses.

Dermoscopy of discoid lupus erythematosus.

BACKGROUND: Dermoscopy is useful in evaluating skin tumours, but its applicability also extends into the field of inflammatory skin disorders. Discoid lupus erythematosus (DLE) represents the most common subtype of cutaneous lupus erythematosus. While dermoscopy and videodermoscopy have been shown to aid the differentiation of scalp DLE from other causes of scarring alopecia, limited data exist concerning dermoscopic criteria of DLE in other locations, such as the face, trunk and extremities. OBJECTIVE: To describe the dermoscopic criteria observed in a series of patients with DLE located on areas other than the scalp, and to correlate them to the underlying histopathological alterations. METHODS: DLE lesions located on the face, trunk and extremities were dermoscopically and histopathologically examined. Selection of the dermoscopic variables included in the evaluation process was based on data in the available literature on DLE of the scalp and on our preliminary observations. Analysis of data was done with SPSS analysis software. RESULTS: Fifty-five lesions from 37 patients with DLE were included in the study. Perifollicular whitish halo, follicular keratotic plugs and telangiectasias were the most common dermoscopic criteria. Statistical analysis revealed excellent correlation between dermoscopic and histopathological findings. Notably, a time-related alteration of dermoscopic features was observed. CONCLUSIONS: The present study provides new insights into the dermoscopic variability of DLE located on the face, trunk and extremities.