Clinical Features and Response to Treatment in Elderly Subjects Affected by Hidradenitis Suppurativa: A Cohort Study.

Hidradenitis suppurativa (HS) is a chronic-relapsing inflammatory skin disease. It usually appears in the second and third decades, but a smaller proportion of patients develop late-onset HS. Geriatric HS, defined as the persistence or the development of HS after the age of 65 years, has been poorly explored. This study aimed to investigate the clinical features, treatment management and response to therapies of HS elderly subjects (≥65 years old). We designed a multicentric observational study, gathering data from seven Italian university hospitals. Demographic and clinical data of HS patients aged over 65 years were collected at baseline, week 12 and week 24. Overall, 57 elderly subjects suffering from HS were enrolled. At baseline, disease severity was predominantly moderate-to-severe, with 45.6% of patients classified as Hurley III. The gluteal phenotype was the most frequently observed; it also appeared to affect patients' quality of life more than other phenotypes. Gluteal involvement was detected in about half (49.1%) of cases and associated with severe stages of the disease. In terms of therapeutic response, Hurley III patients showed the persistency of higher values of mean IHS4, DLQI, itch- and pain-NRS scores compared to Hurley I/II. In conclusion, disease severity in this subpopulation appears high and treatment is often challenging.

Brodalumab in the Treatment of Plaque Psoriasis Localized in Difficult-to-Treat Areas: A Narrative Review.

INTRODUCTION: Psoriasis is a common chronic, immune-mediated, inflammatory skin disease that in certain localization results difficult to treat. Psoriatic lesions in difficult-to-treat areas might be hardly managed as no standardized therapeutic approach and the application of topical treatments might have great limitations. Systemic agents, including biologic therapies, have been proven effective in treating this subgroup of patients. In particular, current evidence has shown beneficial effects with the use of brodalumab, a fully human IgG2 monoclonal antibody antagonizing the IL-17 receptor A subunit (IL-17RA). OBJECTIVES: The aim of this narrative review was to collect published data about efficacy and safety of brodalumab in the treatment of psoriasis occurring in difficult-to-treat areas. METHODS: Data on brodalumab effectiveness and safety deriving from both trials and real-world setting that had been published in the last 15 years were collected for this review, together with clinical findings issued during international meetings. RESULTS: In phase 3 trials, brodalumab demonstrated to be effective in promoting a rapid response in scalp psoriasis as well as in generalized pustular psoriasis and erythrodermic psoriasis. Nail psoriasis demonstrated marked clinical improvement after treatment with brodalumab. Amelioration of palmoplantar psoriasis was also described in brodalumab-treated patients. Various retrospective real-world studies reported a complete clearance of psoriatic lesions in difficult-to-treat areas, including genitalia, through short-term brodalumab treatment. CONCLUSIONS: Brodalumab, combining rapid and sustained efficacy with a favorable safety profile, may be a valid therapeutic option for severe variants of psoriasis as well as for psoriasis localized in difficult-to-treat areas.

Similar Levels of Efficacy of Two Different Maintenance Doses of Adalimumab on Clinical Severity and Quality of Life of Patients with Hidradenitis Suppurativa.

Adalimumab is the only biologic agent approved for the treatment of moderate-to-severe hidradenitis suppurativa (HS) patients (i.e., with Hurley II or III), which is recommended in two different maintenance doses (i.e., 40 mg weekly or 80 mg every two weeks). We conducted a prospective multicentric study to measure outcomes related to the severity of disease and quality of life (QoL) of patients affected by moderate-to-severe HS, treated with adalimumab at a maintenance dosing of 40 mg or 80 mg. Assessments were performed at baseline (T0) and after 32 weeks of treatment (T32). We enrolled 85 moderate-to-severe HS Italian patients, 43 men (50.6%) and 42 women, aged between 16 and 62 years (median 31 years, interquartile range 24.4-43.8). Statistically significant improvements were observed for clinical status (with a mean reduction of 7.1 points for the International Hidradenitis Suppurativa Severity Score System (IHS4)), pain levels (3.1 mean decrease in VAS), and QoL (3.4 mean improvement in DLQI score). Patients with no comorbidities, and those with higher levels of perceived pain showed significantly greater improvement in QoL than their counterpart from T0 to T32. As for the proportion of patients who at follow-up reached the minimal clinical important difference (MCID) in QoL, significantly higher proportions of success were observed for age (patients in the 29-39 category), pain (patients with higher reported pain), and Hurley stage III. While both treatment regimen groups (i.e., 40 vs. 80 mg) improved significantly, no statistical differences were observed when comparing the two treatment dosages.

Skin immunity and its dysregulation in atopic dermatitis, hidradenitis suppurativa and vitiligo.

While the epidermis is the frontline defense against infections and indeed, it is a peripheral lymphoid organ, the same immunological mechanisms may initiate and sustain pathological conditions. Indeed, a deregulated action against exogenous pathogens could activate a T cell response in atopic dermatitis, hidradenitis suppurativa and vitiligo. Atopic dermatitis (AD) is a chronic inflammatory skin condition with a complex pathophysiology. Although T helper 2 immunity dysregulation is thought to be the main cause of AD etiopathogenesis, the triggering mechanism is not well understood, and the treatment is often difficult. As the AD, hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a dramatic impact on the quality of life of the affected patients. The exact pathophysiology of HS is still unclear, but many evidences report a follicular obstruction and subsequent inflammation with TNF-α, interleukin (IL)-1ß, IL-10, and IL-17 involvement. Vitiligo is an autoimmune epidermal disorder which consists of melanocytes destruction and skin depigmentation. Melanocytes destruction is mainly due to their increased oxidative-stress sensitivity with a consequent activation of innate first and adaptative immunity (CD8+ T cells) later. The understanding of the triggering mechanisms of AD, HS and Vitiligo is pivotal to outline novel therapies aimed at regaining the physiological immune homeostasis of healthy skin. The aim of this review is to provide new insight on the pathogenesis of these skin diseases and to highlight on the new therapeutic approaches adopted in the treatment of AD, HS and Vitiligo.

Skin immunity and its dysregulation in psoriasis.

The skin is a peripheral lymphoid organ, being the first immunological defense against infections as the initial interface between the organism and the external background. The maintenance of the skin immune homeostasis depends on a finely equilibrium of well-regulated relations between different cells and exogenous pathogens. Inflammatory skin diseases are directly linked to the dysregulation of this equilibrium. The present review discusses the role of the immune system, of T cells, in the etiopathogenesis of psoriasis, illustrating a potential rationale for innovative therapeutic intervention.

Clinical evidence on the efficacy and tolerability of a topical medical device containing benzoylperoxide 4%, retinol 0.5%, mandelic acid 1% and lactobionic acid 1% in the treatment of mild facial acne: an open label pilot study.

Background: Acne is a debilitating disorder that requires proper treatment depending on the clinical manifestations and pathogenetic factors, among which hyper-keratinization, seborrhea and bacterial proliferation. Combining active ingredients targeting the different mediators of acne pathogenesis may yield optimal outcomes. Purpose: The purpose of this study was to evaluate the clinical effectiveness, safety and tolerability of a new topical medical device in cream containing benzoylperoxide 4%, pure retinol 0.05%, palmitate retinol 0.5%, mandelic acid 1% and glycyrrhetic acid on patients with mild acne. Patients and methods: Twenty consecutive patients of both sexes with mild acne were included in the study. The topical treatment was self-applied twice a day for 12 weeks. Evaluations included: Global Acne Grading System (GAGS); inflammatory and non-inflammatory lesions count; reflectance confocal microscopy; seborrhea and hydration degree; photographic documentation; a questionnaire to assess tolerability. Results: The GAGS score showed a 39% reduction from T0 to T1 and 69.20% from T0 to T2. The count of comedonic lesions showed a 44% reduction from T0 to T1 and 65% from T0 to T2. The count of papular lesions diminished by 49.4% from T0 to T1 and by 62% from T0 to T2. The count of pustular lesions decreased by 43% from T0 to T1 and by 80% from T0 to T2. Improvement of hydration and a decrease of seborrhea degree were even observed. These clinical results were confirmed by reflectance confocal microscopy exam. Conclusion: The topical medical device has shown to be clinically effective and well tolerated for the treatment of mild acne. Side effects were mild, transient and well tolerated. The results of our study demonstrated a high tolerability of this new combination of benzoylperoxide 4% and retinol. Furthermore, our results suggested that the studied compound could be considered as a "maintenance treatment" after specific pharmacological treatment, even in more severe types of acne.

The efficacy and tolerability of 5-aminolevulinic acid 5% thermosetting gel photodynamic therapy (PDT) in the treatment of mild-to-moderate acne vulgaris. A two-center, prospective assessor-blinded, proof-of-concept study.

BACKGROUND: Acne vulgaris is a chronic inflammatory skin disease, commonly treated with topical or systemic drugs, according to the severity of the condition. Retinoids and antibiotic compounds are considered cornerstone approaches in this condition. However, low adherence to the therapy and the issue of bacterial resistance undermine the efficacy in the long term. Photodynamic therapy (PDT) with 20% aminolevulinic acid (ALA) has shown to be effective in the treatment of inflammatory acne. Skin tolerability, however, could be a limiting factor for a widespread use of this approach. A new formulation of 5% ALA in thermosetting gel has been recently available. This formulation allows a more convenient application procedure without occlusion and better and more efficient release of the active compound in comparison with traditional ALA formulations like creams or ointments. STUDY AIM: To evaluate in a two-center, assessor-blinded, prospective, proof-of-concept study, the efficacy, and tolerability of red-light (630 nm) PDT with a new 5-ALA "low-dose" topical gel formulation (5%) in the treatment of inflammatory mild-to-moderate acne vulgaris (AV). SUBJECTS AND METHODS: A total of 35 subjects with moderate AV of the face (mean age: 24 ± 8 years, 13 men and 22 women) were enrolled, after their written informed consent. The primary outcome was the evolution of GAG (Global Acne Grade System) score at baseline and after an average of three, 630-nm, 15-minute, PDT sessions, performed every 2 weeks. GAG score was also calculated in a follow-up visit 6 months after the last PDT session. Skin tolerability was assessed during PDT sessions with a patient-reported discomfort level evaluation score from 0 (no discomfort at all) to 3 (severe discomfort). RESULTS: At baseline, the GAG score was 21 ± 6. After the last PDT session, the GAG score evaluated in a blinded fashion (digital photographs) was significantly reduced to 6.5 ± 5.7, representing a 70% reduction (P = .0001, Wilcoxon test; mean difference 14.9; 95% CI of the difference: 12.1-17.6). At the follow-up visit, the GAG score was 6.7 ± 6.8. The 5% ALA thermosetting gel Red-light PDT was in general very well tolerated with a discomfort mean level score of 0.5 ± 1. CONCLUSION: This proof-of-concept study supports the efficacy of 5% ALA thermosetting gel red-light PDT in inflammatory acne of the face with a relevant clinical improvement of inflammatory lesions with a very good tolerability profile. Clinical improvement was maintained in the medium term (Trial Registration Number: ISRCTN66066651).

Clinical and confocal evaluation of avenanthramides-based daily cleansing and emollient cream in pediatric population affected by atopic dermatitis and xerosis.

BACKGROUND: Xerosis and atopic dermatitis (AD) are chronic skin conditions that occur in children and adults which can result in scaling, flaking and itching. Risk factors for xerosis include sunlight, friction, low humidity and use of soaps. Xerosis is also a symptom of cutaneous conditions such as psoriasis, dermatitis and ichthyosis. AD has a complex pathogenesis but there is increased evidence that a genetically-impaired skin barrier plays a primary role in its development. METHODS: The aim of this study is to evaluate the efficacy of the combination of a product for topical application to be used for daily cleansing and an emollient cream with colloidal oatmeal, avenanthramides, shea butter and oat oil in patients with xerosis and AD. Indeed, emollients play a key role in the treatment of xerosis and of mild to moderate AD because help to restore and maintain the skin barrier function. Topical emollients are considered first-line treatment in those conditions. Outcomes included Investigators' Global Assessment (IGA) (0=clear, 5=very severe), Eczema Area and Severity Index (EASI) composite score, Itch severity (0=none, 4=severe), and Infant's Dermatitis Quality of Life Index (IDQOL). The evaluation of the response to treatment was also measured through the use of photographic documentation and examination by Reflectance Confocal Microscopy (RCM) performed at baseline and after therapy. RESULTS: The evaluation of the response to treatment was also measured through the use of photographic documentation and examination by reflectance confocal microscopy (RCM) performed at baseline and after therapy. Our results showed improvement in epidermal thickness, skin dryness, itching and cracking after one month of use of the oat cleanser and lotion. CONCLUSIONS: Colloidal oatmeal has been shown to safely reduce itching and irritation associated with AD and the severity of dry skin. These benefits, mediated by colloidal oatmeal's natural components, help to restore and maintain skin barrier function. This compound is safe, well tolerated, and can be effective as adjuvant treatment in AD. Moisturizers can reduce the dependency on topical corticosteroids and their potential adverse effects.

Clindamycin versus clindamycin plus rifampicin in hidradenitis suppurativa treatment: Clinical and ultrasound observations.

BACKGROUND: Antibiotics are recognized as first-line treatments for hidradenitis suppurativa (HS), but the data on their efficacy are limited. OBJECTIVE: Evaluate the efficacy of oral clindamycin versus that of clindamycin plus rifampicin in patients with HS. METHODS: A total of 60 patients with mild-to-moderate-severe HS who were classified according to their International Hidradenitis Suppurativa Severity Score System (IHS4) and Hurley scores, were subdivided into 2 groups of 30 patients each (group A, the members of which received clindamycin plus rifampicin, and group B, the members of which were treated with clindamycin alone) and retrospectively studied. The main objective was to evaluate and compare the clinical and ultrasound responses between the groups after 8 weeks of treatment according to the Hidradenitis Suppurativa Clinical Response measure. RESULTS: After the treatment, 17 of 30 patients in group A and 19 of 30 in group B met the primary outcome. Both groups showed a similar improvement of IHS4 score, whereas the Dermatology Life Quality Index and pain Visual Analogue Scale scores improved more in group B. In particular, the reductions in nodule and abscess counts were similar between the 2 groups, whereas the number of draining tunnels decreased more in group B. The factors significantly associated with Hidradenitis Suppurativa Clinical Response score were age, body mass index, IHS4 score, and absence of axillary involvement. Disease-free survival was similar between the 2 groups. LIMITATIONS: The study was not randomized or placebo-controlled. CONCLUSION: Clindamycin may be a useful treatment alternative to antibiotic combination regardless of HS clinical stage.

Correction to: Certolizumab Pegol in the Treatment of Psoriasis and Psoriatic Arthritis: Preliminary Real-Life Data.

In the original publication, part Fig. 3b and c were interchanged. The correct versions are given below.

Certolizumab Pegol in the Treatment of Psoriasis and Psoriatic Arthritis: Preliminary Real-Life Data.

INTRODUCTION: We present the results of real-life tests conducted in adults affected by psoriatic arthritis (PsA) with mild cutaneous involvement to evaluate the efficacy of certolizumab pegol (CZP), an anti-tumor necrosis factor-alpha agent approved in Europe for the treatment of rheumatoid arthritis and PsA. METHODS: Assessments included an evaluation of the Psoriasis Area and Severity Index (PASI) and the Disease Activity Score computed on 44 joints (DAS-44) correlated to the erythrocyte sedimentation rate (ESR) (DAS44-ESR). A total of 41 patients (16 men, 25 women; mean age 59.8 ± 8 years) completed the study. Of these, 36 patients were affected by both PsA and psoriasis, and five patients were affected only by PsA. A total of 32 patients (group A) completed 3 months of treatment (W12), and 12 patients completed 6 months of treatment (W24) (group B). RESULTS: The clinical efficacy of CZP was consistent on both the cutaneous and rheumatic components of the treatment. The mean PASI score decreased from 4.4 ± 4.7 at baseline (BL) to 2.3 ± 3.7 at W12 (group A), and from 5.1 ± 5.7 at BL to 0.8 ± 1.2 at W24 (group B). The DAS44-ESR decreased from 4.4 ± 0.6 at BL to a mean of 2.2 ± 0.9 at W12 (group A) and from 4.1 ± 0.6 at BL to a mean of 1.9 ± 0.5 at W24 (group B). No adverse events were reported. CONCLUSION: Our results demonstrate that CZP can be used safely and effectively to treat both the cutaneous and joint components of PsA. However, long-term data are needed to confirm our preliminary observations.

Hepatitis B reactivation in psoriasis patients treated with anti-TNF agents: prevention and management.

The risk of hepatitis B virus (HBV) reactivation (HBVr) in chronic HBV carriers, in occult HBV patients or in acute HBV patients affected by psoriasis and treated with anti-tumor necrosis factor (TNF)-α agents is a clinical practice issue to face with, particularly if the treatment has a long-term maintenance finality. The aims of this review are to examine the current knowledge on HBVr incidence in chronic HBV carriers and potential occult carriers undergoing therapy with biologics for the treatment of psoriasis and psoriatic arthritis; analyze the prophylactic measure to prevent HBV reactivation and define how to manage HBVr in patients treated with biologics. We searched through PubMed, Google Scholar and Scopus databases and evaluated all published manuscripts concerning HBVr in psoriatic patients, both plaque-type and psoriatic arthritis, in treatment with any indicated anti-TNF-α. Although anti-TNFs are considered moderate immunosuppressive drugs, the incidence of HBVr in psoriatic patients is lower compared to patients affected by other immune-mediated diseases treated with TNF inhibitors. HBV prophylaxis should be probably reserved to anti-HBs+/anti-HBc+ patients with a viral load <2000 IU/mL and alterations in serum liver enzymes, in order to prevent HBVr.

Discrimination of Dysplastic Nevi from Common Melanocytic Nevi by Cellular and Molecular Criteria.

Dysplastic nevi (DNs), also known as Clark's nevi or atypical moles, are distinguished from common melanocytic nevi by variegation in pigmentation and clinical appearance, as well as differences in tissue patterning. However, cellular and molecular differences between DNs and common melanocytic nevi are not completely understood. Using cDNA microarray, quantitative RT-PCR, and immunohistochemistry, we molecularly characterized DNs and analyzed the difference between DNs and common melanocytic nevi. A total of 111 probesets (91 annotated genes, fold change > 2.0 and false discovery rate < 0.25) were differentially expressed between the two lesions. An unexpected finding in DNs was altered differentiation and activation of epidermal keratinocytes with increased expression of hair follicle-related molecules (keratin 25, trichohyalin, ribonuclease, RNase A family, 7) and inflammation-related molecules (S100A7, S100A8) at both genomic and protein levels. The immune microenvironment of DNs was characterized by an increase of T helper type 1 (IFNγ) and T helper type 2 (IL13) cytokines as well as an upregulation of oncostatin M and CXCL1. DUSP3, which regulates cellular senescence, was identified as one of the disease discriminative genes between DNs and common melanocytic nevi by three independent statistical approaches and its altered expression was confirmed by immunohistochemistry. The molecular and cellular changes in which the epidermal-melanin unit undergoes follicular differentiation as well as upregulation of defined cytokines could drive complex immune, epidermal, and pigmentary alterations.

A new therapeutic for the treatment of moderate-to-severe plaque psoriasis: apremilast.

Psoriasis is a common, chronic, inflammatory skin disease. Being a life-long condition, a prolonged and safe control of the disease is needed. Current anti-psoriatic treatments show some limits in terms of tolerability and route of administration. Recently, a new oral small molecule, apremilast, has been approved for the treatment of patients with moderate-to-severe plaque psoriasis. Apremilast is a phosphodiesterase 4 (PDE4) inhibitor that regulates the transduction of intracellular signals, including pro-inflammatory and anti-inflammatory pathways. Because of the favorable safety profile and the oral route of administration, apremilast may represent a promising therapeutic target for moderate-to-severe psoriasis. In this review, we report an updated overview about clinical trials testing apremilast in the treatment of psoriasis and seek to provide comprehensive information about this anti-psoriatic drug and a future perspective of the therapeutic algorithm for psoriasis.

Treatment adherence to different etanercept regimens, continuous vs. intermittent, in patients affected by plaque-type psoriasis.

Treatment adherence to anti-tumor necrosis factor alpha (anti-TNF-α) agents is marker of treatment success, but overall efficacy of anti-TNF-α therapy decreases over time leading to a progressive loss of adherence. The present observational study was conducted in order to estimate the long-term adherence to etanercept in patients affected by plaque-type psoriasis, evaluating differences among intermittent and continuous treatment regimen. Our findings reflect routine clinical practice in three academic referral centers and show high treatment adherence with etanercept in psoriatic patients. Treatment survival was consistently high in the short/medium term. The univariate analysis showed longer treatment duration in patients undergoing intermittent treatment regimen (mean 1,706 days) compared with continuous regimen (mean 1,249 days). Results showed that a flexible pulsed treatment with etanercept can be optimal in terms of clinical success and adherence.

Complete resolution of erythrodermic psoriasis in an HIV and HCV patient unresponsive to antipsoriatic treatments after highly active antiretroviral therapy (Ritonavir, Atazanavir, Emtricitabine, Tenofovir).

BACKGROUND: Psoriasis is a chronic, inflammatory disease affecting 2-3% of the worldwide population, and it may worsen with HIV or be detected as HIV cutaneous manifestation. HIV-related psoriasis shows a severe and prolonged clinical course with more frequent exacerbations. The management of this condition is challenging because immunomodulating and immunosuppressant agents may have variable and partial efficacy, and therefore, antiretroviral treatment represents a potential adjunctive therapeutic option. RESULTS: In the case we report, the HIV test was shown to be crucial for driving the therapeutic approach. Indeed, antiretroviral agents have been proven to be effective in the treatment of HIV+ psoriasis as first-line therapy. CONCLUSION: The HIV test should be considered in high-risk patients affected by severe psoriasis and resistant to conventional and biological treatments.