External Validation of the IHS4-55 in a European Antibiotic-Treated Hidradenitis Suppurativa Cohort.

BACKGROUND: Previously, a new dichotomous outcome was developed, calculated as 55% reduction in the International Hidradenitis Suppurativa 4 (IHS4-55) score. It was validated in datasets of adalimumab and placebo-treated HS patients. External validation is an important aspect of clinical outcomes. OBJECTIVES: We aimed to externally validate the novel dichotomous IHS4-55 in a non-biologic treated dataset of HS patients. METHODS: Data from a previously published European-wide prospective clinical study of antibiotic treatment of HS patients were used to assess the association of IHS4-55 achievement with individual reduction in inflammatory nodules, abscesses, and draining tunnels. Moreover, the associations between IHS4-55 positivity and achievement of the minimal clinically important differences (MCIDs) for Dermatology Life Quality Index (DLQI), Numerical Rating Scale (NRS) Pain, and NRS Pruritus were analyzed. RESULTS: Data were obtained from 283 individual patients, of which 36.4% (103/283) were treated with clindamycin and rifampicin and 63.6% (180/283) with tetracyclines for 12 weeks. Achievers of the IHS4-55 demonstrated a significant reduction the counts of inflammatory nodules, abscesses, and draining tunnels (all p < 0.001). Additionally, IHS4-55 achievers had an odds ratio for achieving the MCID of DLQI, NRS Pain, and NRS Pruritus of 2.16 (95% CI 1.28-3.65, p < 0.01), 1.79 (95% CI 1.10-2.91, p < 0.05), and 1.95 (95% CI 1.18-3.22, p < 0.01), respectively. CONCLUSIONS: This study shows the external validity of the novel IHS4-55 by demonstrating a significant association between IHS4-55 achievement and a reduction in inflammatory lesion counts as well as achievement of MCIDs for DLQI, NRS Pain, and NRS Pruritus in an antibiotic-treated cohort. These findings support the use of the IHS4-55 as a novel primary outcome measure in clinical trials.

Psoriatic patients with a history of cancer: A real-life experience with Apremilast treatment for 104 weeks.

Psoriasis is a multifactorial, chronic, auto- inflammatory disease, with a worldwide prevalence of around 2%, subtended by robust genetic predisposition and autoimmune pathogenic traits. The disease, mainly involving the skin and joints, is featured by erythemato-squamous lesions, with a chronic relapsing course and relevant systemic comorbidities. Apremilast is a novel oral agent that has recently been made available to dermatologists for the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis. Although it is considered as relatively safe molecule with few contraindications, experience with Apremilast in the real-world setting for cancer patients with moderate-to-severe plaque psoriasis is lacking. Hence, we report the real-life experience in patients with psoriasis and a history of cancer who underwent treatment with Apremilast for 104 weeks.

Adverse skin reactions to personal protective equipment during COVID-19 pandemic in Italian health care workers.

To avoid exposure to SARS-COV-2, healthcare professionals must use personal protective equipment (PPE). Their use has been related to a series of adverse effects; the most frequent adverse events were headache, dyspnoea, and pressure injuries. Skin adverse effects are very common, including contact dermatitis, itching, erythema, and acneiform eruptions. The objective of this study is to evaluate the skin problems caused by personal protection equipment (PPE) in health care workers (HCWs) and to individuate eventual risk factors. From May to June 2020 a retrospective observational multi-centric study conducted by an online survey sent by email, involving 10 hospital centers, was performed. We considered as independent variables gender and age, occupational group and sector, time of utilization, type and material of PPE. We tested 3 types of PPE: gloves, bonnet, and mask for different time of utilization (<1, 1-3, 3-6, >6 h). We performed a multiple logistic regression model to correlate them with skin adverse events occurrence. Among all the 1184 participants, 292 workers reported a dermatological pathology: 45 (15.41%) had psoriasis, 54 (18.49%) eczema, 38 (13.01%) acne, 48 (16.44%) seborrheic dermatitis, and 107 (36.64%) other. In our sample previous inflammatory dermatological conditions, female sex, prolonged use of PPE were significant risk factors for developing skin related adverse events considering all the PPE considered. The use of PPE is still mandatory in the hospital setting and skin adverse reactions still represent a global problem. Although data from Europe are limited, our study highlighted the importance of the problem of PPE skin reactions in a large sample of Italian healthcare professionals.

Hidradenitis Suppurativa in a Large Cohort of Italian Patients: Evaluation of the Burden of Disease.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually occurs after puberty with painful, deep-seated, inflamed nodules and sinus tracts in the apocrine gland-bearing areas of the body, most commonly the axillae and inguinal and anogenital regions, with a relevant impact on patients' quality of life (QoL). OBJECTIVE: To evaluate how the burden of HS disease impacts on patient well-being and working activities in a large Italian population over a period of 9 months. METHODS: A multicenter, prospective, epidemiologic cohort study was conducted in adult Italian patients with HS. HS severity was assessed through Hurley stage and HS Physician's Global Assessment (HS-PGA), clinical improvement by HS Clinical Response (HiSCR) and partial response, and disease burden through QoL questionnaires (HIDRAdisk, Skindex-16, Dermatology Life Quality Index [DLQI]), and Work Productivity and Activity Impairment - General Health (WPAI:GH). RESULTS: A total of 308 patients (56.2% women; mean age 35.2 ± 12.9 years) were enrolled in 27 dermatologic clinics. Men were older (37.4 years vs. 33.5), more smoking addicted (74.1% vs. 60.1%), and alcohol consumer (34.1% vs. 13.9%), while more women were obese (34.10% vs. 22.22%). At baseline, most patients had a Hurley severity stage of 2 (43.9%), a moderate HS-PGA score (57.1%), and poor QoL (HIDRAdisk: 65.7 ± 23.3, Skindex-16: 60.3 ± 26.9, and DLQI: 10.8 ± 8.1). Patients with more severe disease showed worse QoL. Mean values for the variables related to HS severity decreased during the study period. The achievement of HiSCR and partial response increased during the study. CONCLUSION: This study offers insight into the disease burden of HS in an Italian population. Our results underline the impact of QoL evaluation, also with the use of the HIDRAdisk, in clinical routine as a support to validated severity clinical and instrumental indexes for a "360-degree" assessment of HS patient's burden of disease.

The efficacy and tolerability of tetracyclines and clindamycin plus rifampicin for the treatment of hidradenitis suppurativa: Results of a prospective European cohort study.

BACKGROUND: Tetracyclines and clindamycin plus rifampicin combination therapy are both considered first-line therapy in current hidradenitis suppurativa guidelines. However, evidence for their efficacy is drawn from small studies, often without validated outcomes. OBJECTIVE: To assess the 12-week efficacy of oral tetracyclines and a combination of clindamycin and rifampicin. METHODS: A prospective, international cohort study performed between October 2018 and August 2019. RESULTS: In total, 63.6% of the included 283 patients received oral tetracyclines, and 36.4% were treated with clindamycin and rifampicin. Both groups showed a significant decrease in International Hidradenitis Suppurativa Severity Score System from baseline (both P < .001). The Hidradenitis Suppurativa Clinical Response (HiSCR) was achieved in 40.1% and 48.2% of patients, respectively (P = .26). Patient characteristics or disease severity were not associated with the attainment of HiSCR or the minimal clinically important differences for the Dermatology Life Quality Index and pain. LIMITATIONS: Cohort study. Respectively, 23.9% and 19.4% of patients had to be excluded from the HiSCR analysis for the tetracycline and combination therapy group because of a low abscess and nodule count at baseline. CONCLUSION: This study shows significant efficacy of both tetracycline treatment and clindamycin and rifampicin combination therapy after 12 weeks in patients with hidradenitis suppurativa. No significant differences in efficacy were observed between the 2 treatments, regardless of disease severity.

Role of CD 20+ T cells and related cytokines in mediating retinal microvascular changes and ocular complications in chronic-plaque type psoriasis.

OBJECTIVE: To assess the role of CD3+ CD20+ CD4- CD8- double-negative (DN) or CD3+CD20+ CD4/CD8+ T cells and the related pro-inflammatory cytokines in the humor aqueous, in mediating retinal microvascular changes in patients with chronic plaque-type moderate to severe psoriasis. DESIGN: A total of 76 patients (57.6 ± 11.7 years) with chronic plaque-type psoriasis were initially evaluated. Nineteen patients (19 eyes) and 19 healthy volunteers (19 eyes) were subjected to dermatological evaluation with Psoriasis Area Severity Index (PASI) and the Dermatology life quality index (DLQI). Retinal images were processed using an automatized software. On the same day, a venous sample was collected and analyzed using multiparametric flow cytometry. Three out of 6 patients who presented cataract, consented to perform surgery with humor aqueous collection. The samples were analyzed using a Multi-Analyte ELISA kit for the simultaneous quantification of IL1α, IL1ß, IL2, IL4, IL6, IL8, IL10, IL12, IL17A, IFNγ, TNF-α, GMCSF. RESULTS: The CD3+CD4+/CD8+CD20+CD56- T cells expression was greater in the psoriatic patients (+73.9%, P < 0.001) compared to controls, but not the DN T cells (-8.2%, P = 0.30). Ocular complications were diagnosed in 61.1% of patients, microvascular parameters including artero-venous ratio (P = 0.04), subfoveal choriocapillaris/Sattler's layer, and choroidal thickness (CT, both P < 0.001) were significantly altered in psoriasis subgroup. The increased circulating levels of the CD3+CD4+/CD8+CD20+CD56- T cells were associated with thinning of subfoveal CT (P = 0.03) and Haller's layer (P = 0.01). Instead, the DN T cells presented an inverse relationship with disease duration (P = 0.02), DLQI score (P = 0.02), and the use of biological therapy (P = 0.05). The related cytokine patterns possibly modified in this cellular context have been investigated. No significant differences were observed in cytokines levels between psoriasis and controls, the most significant difference was detected on IL-6, without reaching statistical significance (fold change of 1.4, P = 0.13). CONCLUSION: Our findings demonstrated that CD20+ T cell subpopulation is highly represented in psoriasis regardless of the use of immunomodulatory therapies, and the diffuse microvascular alterations suggested possible endothelial damage as mainstream for the genesis of psoriatic-mediated complications as further supported by the comparable concentrations of cytokines, at least as humor aqueous content, with respect to healthy eyes.

Efficacy and safety of systemic isotretinoin treatment for moderate to severe acne (insights from the real-life clinical setting).

Acne is a chronic inflammatory relapsing disease that affect predominantly adolescents, with scarring as a frequent sequele. Early and appropriate therapy allows better management of the disease, longer remission, scars risk reduction, and improvement of quality of life. According to therapeutic algorithm, systemic isotretinoin can be used in severe acne and also in moderate forms resistant to other systemic treatments. The aims of this real-life observational study were to determine and compare the effectiveness of isotretinoin evaluated by Global Acne Grading System and Acne Quality of Life in moderate and in severe acne, correlation between efficacy and cumulative dose of isotretinoin, tolerability, and recurrence rate. Moreover, the differences in efficacy and tolerability between male and female patients were compared. The treatment with systemic isotretinoin led to an improvement in acne severity and quality of life in all observed subjects.

Interleukin-17A affects extracellular vesicles release and cargo in human keratinocytes.

Psoriasis is a chronic inflammatory systemic disease caused by deregulation of the interleukin-23/-17 axis that allows the activation of Th17 lymphocytes and the reprogramming of keratinocytes proliferative response, thereby inducing the secretion of cyto-/chemokines and antimicrobial peptides. Beside cell-to-cell contacts and release of cytokines, hormones and second messengers, cells communicate each other through the release of extracellular vesicles containing DNA, RNA, microRNAs and proteins. It has been reported the alteration of extracellular vesicles trafficking in several diseases, but there is scarce evidence of the involvement of extracellular vesicles trafficking in the pathogenesis of psoriasis. The main goal of the study was to characterize the release, the cargo content and the capacity to transfer bioactive molecules of extracellular vesicles produced by keratinocytes following recombinant IL-17A treatment if compared to untreated keratinocytes. A combined approach of standard ultracentrifugation, RNA isolation and real-time RT-PCR techniques was used to characterize extracellular vesicles cargo. Flow cytometry was used to quantitatively and qualitatively analyse extracellular vesicles and to evaluate cell-to-cell extracellular vesicles transfer. We report that the treatment of human keratinocytes with IL-17A significantly modifies the extracellular vesicles cargo and release. Vesicles from IL-17A-treated cells display a specific pattern of mRNA which is undid by IL-17A neutralization. Extracellular vesicles are taken up by acceptor cells irrespective of their content but only those derived from IL-17A-treated cells enable recipient cells to express psoriasis-associated mRNA. The results imply a role of extracellular vesicles in amplifying the pro-inflammatory cascade induced in keratinocyte by pro-psoriatic cytokines.

Isotretinoin for the treatment of squamous cell carcinoma arising on an epidermoid cyst.

A 63-year-old man showed multiple concentric erythemato-nodular lesions of approximately 1.5-3 cm in diameter, located in the parietal and temporal region. The skin biopsy allowed histological diagnosis of infundibular epidermal cyst associated with chronic granulomatous flogosis; in one of these, a well-differentiated squamous cell carcinoma arising from the cyst wall was found. The patient received isotretinoin at the daily dosage of 0.5 mg/kg/day for 5 months. During 1-year follow-up, laboratory tests, computed tomography scans, and control histology were all in the normal range, with a good improvement of the lesions. Epidermal cysts and squamous cell carcinoma are both commonly encountered in practice. However, the association of epidermal inclusion cysts and squamous cell carcinoma in the skin is very rare. In some cases, including the present one, more potent chemopreventive strategies, such as the use of systemic retinoids, must be considered. Systemic retinoids are the most heavily researched chemopreventive agents and have shown promise for multiple types of cancer, including bladder and head and neck carcinomas. We would like to recommend the possibility to administer retinoids in a squamous cell carcinoma, achieving very satisfactory results; in our case, a complete remission of malignant lesion and an improvement of epidermal cysts were made, without the development of side effects associated with retinoids.

Cardiovascular risk in psoriatic patients detected by heart rate variability (HRV) analysis.

Patients affected by severe psoriasis have an increased prevalence of cardiovascular () diseases as documented by several studies. Heart rate variability (HRV) is a noninvasive method to evaluate the autonomic control of the sinus node. In this study, HRV analysis has been used to evaluate whether young patients with moderate cutaneous psoriasis have increased cardiovascular (CV) risk, in absence of CV comorbidities. Our data indicate an imbalance toward the sympathetic arm of the autonomic cardiac modulation. As the increase in sympathetic activity may be associated with a higher CV risk, moderate psoriasis could be considered to be an independent CV risk factor.