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.

Analysis of clinical factors as possible predictors of response to omalizumab and relapse after treatment discontinuation in chronic spontaneous urticaria.

Omalizumab is a monoclonal anti-IgE antibody which is effective in chronic spontaneous urticaria (CSU), although clinical response appears to be variable in the real-life setting. The aim of this study was to evaluate whether the response of CSU to omalizumab and disease relapse are associated with individual and/or clinical characteristics of patients. We retrospectively evaluated the clinical records of 124 patients treated with omalizumab for moderate to severe CSU refractory to antihistamines. Disease activity was assessed using the urticaria activity score over the last 7 days (UAS7). After 24 weeks of treatment, 91% of patients showed complete remission (UAS7 = 0) or good control (UAS7 < 7) of CSU. Omalizumab was re-administered in 45 patients because of recurrence of moderate to severe symptoms at week 8 after treatment discontinuation or later, and clinical results achieved with retreatment were similar to those observed in the first course. Among the parameters included in our analysis (age and sex of patients, documented history of atopy or autoimmune thyroid disease, CSU duration and baseline severity, concurrent angioedema, and association with chronic inducible urticaria), none was associated with response to omalizumab in our study population. Similarly, these parameters did not significantly differ between patients who experienced CSU relapse and those without relapse. Predictors of response to omalizumab treatment in CSU patients are still unclear, and further studies are needed to evaluate the presence of baseline factors that can influence treatment outcome.

Prevalence of HPV genital infection in patients with moderate-to-severe psoriasis undergoing systemic treatment with immunosuppressive agents or biologics.

Psoriasis is an immune-mediated inflammatory disease and its relationship with infection has been extensively investigated. Concern for the increased prevalence of human papilloma virus (HPV) infection in patients undergoing systemic immunomodulatory or immunosuppressive therapies for psoriasis has been gradually growing among clinicians. To evaluate the prevalence of HPV in a cohort of patients with psoriasis treated with currently available systemic, conventional and biotechnological drugs. A multi-centric prospective study was conducted in the main dermatological clinical centres of central and southern Italy. Data from 588 patients (366 males and 222 females) with moderate-to-severe psoriasis, aged ≥18 years and treated with conventional and biological drugs, were collected based on a documented history of HPV infection, a positive Papanicolaou test (Pap-test) when available, and clinical evidence of genital warts reported during consultation. Overall, 18 of 588 patients (3.6% [95% CI: 1.8-4.5]) were positive for HPV or had a history of cervical cancer. Considering anamnestic and demographic data, such as gender, age, smoking, weight and body mass index, no statistically significant differences between HPV+ and HPV- patients were found. Moreover, the eradication of HPV infection was successfully achieved using conventional treatments. The prevalence of HPV infection in patients with moderate-to-severe psoriasis, undergoing systemic treatment with immunosuppressive agents or biologics, appears to be the same as that in the general Italian population, indicating that the level of infection among such patients is acceptable.

Factitious Cushing's syndrome, hypopituitarism, and self-provoked skin lesions: when the skin mirrors the soul.

SUMMARY: Factitious Cushing's syndrome (CS) is a very rare form of Münchausen syndrome. Its presentation and course are extremely heterogeneous, and diagnosis is generally challenging. We report the case of a 52-year-old woman who was initially investigated because of the occurrence of cushingoid features. Nevertheless, endocrine work-up showed very low morning plasma ACTH and serum cortisol levels. In addition, it also demonstrated central hypopituitarism and hypogonadotropic hypogonadism. Head MRI showed a small pituitary mass. Based on these results, and probably overlooking the initial clinical suspicion, general practitioner (GP) referred the patient to our Endocrine Unit for hypopituitarism. At inspection, moon face, central obesity, and bruising were evident. Multiple ulcerative skin lesions were also concentrated in the right arm and leg. Dermatology evaluation suggested that the lesions were self-provoked. For several days, the patient denied the assumption of corticosteroids, but we finally discovered that the GP' nurse had prescribed betamethasone without the GP's knowledge for about 2 years. In conclusion, the surreptitious assumption of corticosteroids is very rare, but the physicians should be aware that pituitary function could be impaired by high doses of corticosteroids, mimicking hypopituitarism. In these patients, a multidisciplinary approach and environmental investigation can be useful to diagnose factitious CS. LEARNING POINTS: Surreptitious assumption of corticosteroids can cause heterogeneous presentation, ranging from Cushing's syndrome to multiple hypopituitarism. Suppression of ACTH and cortisol levels in a patient with cushingoid features firstly suggests surreptitious assumption of corticosteroids. A multidisciplinary approach can be extremely useful in patients with suspected factitious Cushing's syndrome. Sometimes, to prove surreptitious assumption of corticosteroids needs environmental investigation.

Circulating ILC precursors expressing CD62L exhibit a type 2 signature distinctly decreased in psoriatic patients.

Human CD117+ CRTH2neg innate lymphoid cells (ILC) comprise multipotent precursors (ILCp), which are able to differentiate into subtypes in response to different signals received in peripheral tissues. NKp46+ ILCp have been reported to associate with ILC3 whereas KLRG1+ ILCp with ILC2, although the latter can also generate other ILC subsets, thus, maintaining a substantial plasticity. We here showed that CD62L is expressed by ILCp exclusively within KLRG1+ population and its expression marks a loss of their broad differentiation potential. Analysis of cytokine production and relevant markers demonstrated that CD62L+ ILCp mainly differentiate into ILC2 whereas CD62Lneg counterpart can also differentiate into other ILC subsets depending on the signals they receive. Remarkably, in peripheral blood of psoriatic patients, where ILC3 are usually enriched, CD62L+ ILC were drastically reduced, whereas CD62Lneg ILC2 upregulated both RORγt and NKp46, thus, suggesting an ongoing conversion to ILC3. Therefore, CD62L now emerges as a potential marker to identify a skewing toward type 2 among ILCp.

DECISA Project (DErmatology Clinics in Italy: Survey on Alitretinoin): A real-life retrospective cohort multicenter study on 438 subjects with chronic hand eczema.

Alitretinoin is the only systemic agent approved to treat moderate-severe chronic hand eczema (CHE) unresponsive to potent topical corticosteroids. No nationwide Italian data regarding real-life efficacy, safety, and tolerability of treatment are available. The DECISA project (DErmatology Clinics in Italy: Survey on Alitretinoin) retrospectively examined data from a registry including 15 Dermatology Clinics authorized to prescription of alitretinoin for CHE patients. Disease severity was assessed at baseline, and after 3 and 6 months of treatment, using the 5-point Physician Global Assessment (PGA) and the modified Total Lesion-Symptoms-Severity (mTLSS) scores. Between November 2010 and July 2018, data of 248 male and 190 female patients (mean age 49.71 ± 13.20 years) treated with alitretinoin were collected. Of them, 43.2% had irritant contact dermatitis, 22.2% allergic contact dermatitis, 18.0% atopic dermatitis, 16.7% mixed (irritant/allergic) type of eczema. At 3 months, the 420 re-evaluated patients showed significantly reduced mTLSS and PGA (P < .0000001 vs baseline for both); PGA was clear/almost clear in 35.6% of cases. At 6 months, the 341 re-evaluated patients showed significant (P < .0000001) improvement of mTLSS and PGA vs baseline and 3 months (PGA clear/almost clear: 41.4%). Relapses occurred in 125 patients; 58 underwent an additional course of alitretinoin, with similarly good results. No relevant safety issues were reported; 86 patients experienced adverse effects, which forced 40 to prematurely stop treatment. The DECISA project results confirm the real-life efficacy, safety and tolerability of alitretinoin in the treatment of moderate to severe CHE refractory to standard topical therapies.

Characterization of Hidradenitis Suppurativa Phenotypes: A Multidimensional Latent Class Analysis of the National Italian Registry IRHIS.

In spite of the large heterogeneity, limited data exist on hidradenitis suppurativa (HS) phenotypes. To identify the HS phenotypes that best explain the disease heterogeneity, a cross-sectional study using latent class (LC) analysis was conducted on a cohort of patients examined at 17 dermatological centers participating in the Italian Registry of Hidradenitis Suppurativa and being enrolled between January 2015 and January 2020. Overall, 965 patients aged 32.0 ± 12.4 years (mean ± SD) were evaluated. A three-class model in LC analysis best fitted the data. Patients in LC1 (20.1%) were females, mostly obese, with a high probability of axillary‒groin (0.85) and mammary (0.59) lesions and the highest HS severity. Patients in LC2 (29.6%) were nonobese males, with moderate disease severity; with a high probability of gluteal (0.50) and genital (0.17) lesions, besides axillary‒groin involvement; and with acne and pilonidal cysts. Patients in LC3 (50%) were nonobese females with a milder disease mostly limited to axillary (0.52) and groin (0.66) areas. The stratification of patients with HS into a severe axillary‒mammary‒groin phenotype with predominantly anterior body involvement in females, an axillary‒gluteal‒groin phenotype of intermediate severity mainly affecting males in the posterior body areas, and an axillary‒groin phenotype with mildest clinical symptoms and limited skin involvement may help in optimizing HS management.

Novel Therapeutic Approaches and Targets for the Treatment of Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis Suppurativa (HS) is a chronic, recurrent and disabling inflammatory skin condition, clinically characterized by nodules, bullae, abscesses, fistulae, and draining sinus tracts mainly located in axillae, inguinal folds, inframammary region and buttocks, often leading to pain, scarring, disfigurement and decreased quality of life. Due to its complex nature, with still no completely elucidated etiology and pathogenesis, the management of HS can be challenging. In fact, many patients do not respond to the traditionally available systemic treatments, including antiinflammatories, antibiotics and surgery. Research has provided new insights into the mechanisms of HS, mainly investigating the inflammatory cytokine pathways underlying the disease. METHODS: We review the current knowledge on newer therapeutic approaches and targets for the treatment of HS, through a PubMed-based literature search. RESULTS: In this setting, studies on tumor necrosis factor-α, IL-1ß, IL-10, and the IL-23/T-helper (Th) 17 and IL12/Th1 axes in immune dysregulation in HS have helped in developing new regimens. Inhibitor of phosphodiesterase 4 and laser treatments have shown clinically meaningful efficacy with good short-term safety and tolerability. CONCLUSION: Target therapy has revolutionized the treatment of moderate to severe HS, based on the inhibition of specific molecular or cellular targets, directly involved in the pathogenesis of the condition.

Dermoscopic Findings in the Presurgical Evaluation of Basal Cell Carcinoma. A Prospective Study.

BACKGROUND: Surgery is the best treatment for basal cell carcinoma (BCC); however, incomplete excisions are possible. OBJECTIVE: Assessment of the accurateness of dermoscopy and clinical evaluation in the detection of borders of BCC and description of dermoscopic findings in clinically healthy tissue surrounding BCC. MATERIALS AND METHODS: Eighty-eight lesions with clinical dermoscopic diagnosis of BCC were examined clinically and dermoscopically, to delineate the correct site of surgical incision, demarcating the respective margins with colred dermographic pencils. Specific dermoscopic features were searched in the skin adjacent to the demarcated clinical margin. RESULTS: In 29 of 88 lesions, clinical and dermoscopic margins of the tumor coincided. In the remaining 59 (67%), 10 (16.9%) presented, in the lesion area identified under dermoscopy, classical criteria for BCC and 57 (96.6%) nonclassical criteria. Differences between clinical and dermoscopic margins were significantly more frequent in superficial BCCs (p = .006). The frequency was not significantly different (p = .85) in relation to body sites. CONCLUSION: Dermoscopy improves the identification of margins for surgical excision in BCC. The observation of nontraditional dermoscopic criteria of BCC, mainly pink-white areas and short telangiectasias in the area between clinically and dermoscopically detected margins, helps to define the actual tumoral margins and to achieve a really radical excision.

Characteristic of chronic plaque psoriasis patients treated with biologics in Italy during the COVID-19 Pandemic: Risk analysis from the PSO-BIO-COVID observational study.

Background: The susceptibility of patients with chronic plaque psoriasis and the risks or benefits related to the use of biological therapies for COVID-19 are unknown. Few data about prevalence, clinical course and outcomes of COVID-19 among psoriatic patients were reported. The aims of this study were 1) to assess the prevalence and severity of COVID-19 in psoriatic patients treated with biologic agents during the first phase of the emergency (22 February to 22 April 2020) in Italy, and 2) to report the clinical outcomes of patients who have been exposed to individuals with confirmed SARS-CoV-2 infection. Methods: Patients with moderate-to-severe chronic plaque psoriasis, aged ≥18 years and undergoing treatment with biologic agents as of 22 February 2020, were eligible to be included in PSO-BIO-COVID study. Demographic and clinical characteristics of patients using any biologic for psoriasis treatment between 22 February and 22 April 2020 were registered. Results: A total of 12,807 psoriatic patients were included in the PSO-BIO-COVID study. In this cohort 26 patients (0.2%) had a swab confirmation of SARS-CoV-2 infection. Eleven patients required hospitalization and two died. Conclusion: The incidence of COVID-19 observed in our cohort of psoriatic patients (0.2%) is similar to that seen in the general population (0.31%) in Italy. However, the course of the disease was mild in most patients. Biological therapies may likely lessen 'cytokine storm' of COVID-19, which sometimes lead to multiple organ failure, ARDS, and death.

Pityriasis rosea during omalizumab treatment for chronic spontaneous urticaria.

Pityriasis rosea (PR) is an exanthematous disease whose etiology is related to reactivation of herpes human herpesviruses 6 (HHV-6) and 7 (HHV-7). We observed two cases of PR arising during omalizumab therapy for chronic spontaneous urticaria (CSU). Here we report for the first time PR occurring during omalizumab treatment. After PR diagnosis, viral serology was performed. Data in literature about omalizumab mechanism of action, PR and HHV-6/7 infection were analyzed in order to identify possible correlations. In both our cases IgM against HHV-6 and HHV-7 were negative. The first patient presented altered IgG titers for both viruses (1:160 and 1:80, respectively) while only HHV-6 IgG (1:320) were detected in the second patient. From data in literature, we consider it presumable that apoptotic immune cells due to omalizumab immunomodulation could release viral proteins produced from integrated DNA. This could elicit cutaneous cross-reactivity and PR onset. In conclusion, we think there is a link between omalizumab therapy and PR occurring in patients with CSU. Our case history is too small to draw firm conclusions. Data collection of similar cases could be helpful to improve our knowledge.

Management of pernio-like cutaneous manifestations in children during the outbreak of COVID-19.

During the outbreak of COVID-19 many pernio-like lesions have been increasingly reported. The aim of the study is to describe our management of these skin manifestations and to evaluate a possible correlation to SARS-CoV-2 infection. All patients underwent clinical and laboratory tests to detect a possible underlying connective disease and also to specific SARS-CoV-2 investigations such as oropharyngeal swab and IgG-IgM serology. Nine patients aged between 5 and 15 years old were evaluated. Skin lesions observed were purplish, erythematous and oedematous, in some cases painful and itchy. Six out of nine had respiratory and systemic symptoms (cough, nasal congestion, chills, fever, and asthenia) that preceded cutaneous findings of approximately 2 weeks. Concerning blood exams, three out of nine had D-dimer weakly increased, four had ANA positivity: two with a title 1:160, one with 1:320, and one with 1:5120 and a speckled pattern. The latter patient had also ENA SS-A positive and RF positivity, confirmed at a second check, so as to allow us to make a diagnosis of connective tissue disease. Four out of nine had aPL positivity (IgM). Reactants acute phase were all negative. Oropharyngeal swabs and serology tests for SARS-CoV-2 was negative (borderline in one patient for IgM). No treatment was needed. Even if we do not have enough data to prove it, we hypothesize a correlation between pernio-like lesions and SARS-CoV-2 infection for an increased number of these lesions described during the pandemic and also because such manifestations appeared when temperatures were mild and patients were at home in isolation for the lockdown. Many questions remain open about interaction host-virus.

Patients' demographic and socioeconomic characteristics influence the therapeutic decision-making process in psoriasis.

BACKGROUND: Knowledge regarding differences in care for psoriatic patients is limited. The aim of this study was to investigate factors influencing prescription of systemic treatments for patients with psoriasis with a special focus on socioeconomic factors. METHODS AND FINDINGS: This was a non-interventional, cross-sectional study, conducted in 18 Italian University and/or hospital centers with psoriasis-specialized units. Questionnaires evaluating demographic and socioeconomic characteristics were administered to participants. Overall, 1880 consecutive patients affected by mild-to-severe psoriasis were recruited. Univariate and multivariable logistic regression analyses of systemic therapy prescription, with a special focus on biologics, accounting for the above mentioned characteristics were performed. Our analysis showed that all analyzed patients' characteristics were significantly associated with biological therapy compared to non-biological systemic one. Particularly, women were less likely to receive biologics than men (OR = 0.66; 95% CI, 0.57-0.77). Elderly patients (≥65 years) and subjects with a BMI ≥30 had lower odds to receive biologics respect to adults (≥35-64 years) (OR = 0.33; 95% CI, 0.25-0.40), and subjects with BMI≥25<30 (OR = 0.64; 95% CI, 0.53-0.77), respectively. Northern and Southern patients were both less likely to receive biologics than Central patients (OR = 0.75; 95% CI, 0.63-0.89, and OR = 0.56; 95% CI,0.47-0.68, respectively). Lower economic profile and never reading books were both associated with decreased odds of receiving biological therapy. CONCLUSIONS: This study shows that sex, age, comorbidities, and socioeconomic characteristics influence the prescription of systemic treatments in psoriasis, highlighting that there are still unmet needs influencing the therapeutic decision-making process that have to be addressed.

Diagnosis and treatment of melanoma bone metastasis: A multidisciplinary approach.

Bone is the fourth most common site of melanoma metastasis after lung, liver, and brain. Melanoma bone metastases typically occur in patients who already have widespread metastases in other organs. Current available approaches for bone metastases from melanoma include chemotherapy, radiotherapy, biological therapy, combination therapy, and surgery. In this narrative review, we describe the management of patients affected by melanoma bone metastases, discussing the diagnostic and treatment approaches as well as their impact on survival and quality of life. Despite the fact that clinical and surgical trials will be required to determine the most appropriate treatment, we do expect a newer and more important role of multidisciplinary approach in the management of melanoma patients with bone metastases in the next future.

Efficacy and safety of conventional versus daylight photodynamic therapy in children affected by multiple facial flat warts.

BACKGROUND: facial flat warts (FFWs) are a superficial viral skin disease, extremely common in childhood. Recently, conventional photodynamic therapy (C-PDT) has been used for the treatment of FFWs with good outcome. The efficacy of daylight photodynamic therapy (DL-PDT) has not yet been evaluated. OBJECTIVES: to investigate and assess the efficacy and safety of C-PDT versus DL-PDT using 10% aminolevulinic acid (ALA) in the treatment of recalcitrant FFWs in a paediatric setting. MATERIALS AND METHODS: 30 consecutive patients aged <18 years with FFWs of the face were included and randomly divided into two groups: group A (15 patients) was treated with C-PDT and group B (15 patients) with DL-PDT. Patients underwent treatments for three times with 1-month intervals. The response was assessed on week 4,812 and 24 (T4,T8,T12,T24) and scored as excellent (75-100% reduction of total wart count), very good (74-50% reduction), good (49-25% reduction), poor (<25% reduction or no response). Any adverse event occurring during/after ALA application/irradiation as well as pain intensity were recorded at each visit. RESULTS: at T4 and T8 no excellent response was achieved in both groups. At week 12, excellent response was observed in 53.3% of group A patients vs 0% of group B patients, although in the latter 66.7% of patients achieved a very good response. Excellent outcome raised to 73.3% and 80% in group A and B, respectively, at week 24. Poor response to therapy was observed in 26.7% of patients in group A and 20% in group B. Both treatment modalities were well tolerated, with transient pain, irritation and hyperpigmentation as main side effects. CONCLUSIONS: ALA-PDT is effective and safe for FFWs, with striking cosmetic results and no recurrence. Compared with conventional modality, DL-PDT is better tolerated, time-saving, nearly painless and greatly appreciated by young patients.

Topical tacalcitol as neoadjuvant for photodynamic therapy of acral actinic keratoses: An intra-patient randomized study.

BACKGROUND: photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) is a well described and widely practiced treatment for actinic keratoses (AKs) on the head and face. Less is known about its use for AKs on upper extremities, which can be challenging for the dermatologist. The aim of our study was to compare the combination of topical tacalcitol before 5-ALA-PDT vs conventional 5-ALA-PDT for acral AKs in a prospective, randomized, intra-individual clinical study. METHODS: patients with AKs of both upper extremities underwent keratolytic pretreatment with topical tacalcitol on the back of one hand and/or forearm (right vs left), randomly selected, for fifteen consecutive days before PDT. All patients underwent one session of 5-ALA-PDT. Visual analog scale for pain was assessed immediately after PDT session and any side effects were recorded after 3 days. Efficacy was evaluated with lesion count (LC) prior to treatment (V0) and 90 days (V1) after PDT. RESULTS: twenty-one patients with multiple acral AKs were enrolled and completed the study. At V1, neoadjuvant combination of topical tacalcitol plus PDT was significantly more effective than PDT alone (percentage reduction in total lesion count was 44.4 %. There was no significant difference in VAS pain score between the two treatment modalities. Mild erythema was the only local side effect reported for both treatment regimens (52.4 %, tacalcitol plus PDT vs 42.9 %, PDT alone). CONCLUSIONS: neoadjuvant use of topical tacalcitol might be useful to improve PDT efficacy, especially in hard-to-treat AKs on extremities.