HIV positive patient treated with ixekizumab.

Abstract: Psoriasis is a immune-mediated, chronic, inflammatory skin dis-ease. In HIV positive (HIV+) patients we usually observe more serious clinical features and recalcitrant course. Furthermore, therapeutic man-agement of HIV+ patient is complex and requires collaboration with the infectious disease specialist. We report the case of a patient affected by severe psoriasis who contracted HIV infection during biological therapy and, subsequently, succesfully treated with ixekizumab.

A case of proliferative nodule arising within blue nevus.

Abstract: Blue nevi are a heterogeneous group of lesions that can display a variety of different clinicopathological characteristics. Although attempts are made to classify each lesion into defined subtypes, there can be overlap between the subtypes. The clinical , dermoscopic and histolopathologic features of a case of proliferative nodule arising within blue nevus is discussed. Running title: Blue nevi are an heterogeneous group of melanocytic lesions blue tinctorial properties. Proliferative nodules are rare benign lesions often present at birth as a component of a large congenital melanocytic nevi, congenital or acquired nevi. We first report a case of proliferative nodule arising within blue nevus.

Use of brodalumab for the treatment of chronic plaque psoriasis: a one-year real-life study in the Lazio region, Italy.

Background: Information is limited from real-life studies evaluating the efficacy and safety of brodalumab.Research design and methods: In this real-life study, we retrospectively examined a database of 90 patients with moderate-to-severe psoriasis treated with brodalumab (210 mg, s.c.) and followed for 1 year. Disease severity and treatment response were assessed by the Psoriasis Area and Severity Index (PASI) at baseline and after 4, 12, 24, 36, and 48 weeks. Predictors of a PASI response were evaluated by logistic regression.Results: After 48 weeks, 92.2% of patients (mean age 50.2 ± 15 years) treated with brodalumab achieved a PASI score of <3. PASI score decreased from 17.4 ± 10.3 at baseline to 1.7 ± 3.9 and 1.4 ± 3.7 at 12 and 24 weeks, and PASI 75, 90, and 100 response was achieved in 87.3%, 81.8%, and 72.7% of patients, respectively, at 48 weeks.Univariate regression revealed that previous exposure to anti-IL17A treatment was associated with poorer PASI response between 36 and 48 weeks. In difficult-to-treat cases previously having failed with other biologics, brodalumab significantly improved outcome, leading to complete remission.Conclusion: Brodalumab was observed to be effective and safe in patients with moderate-to-severe chronic psoriasis in a real-world setting.

How lockdown measures, during COVID-19 pandemic, matter on psoriatic patient's perception: Study on 600 patients on biologic therapy.

BACKGROUND: The outbreak of coronavirus disease-2019 (COVID-19) is a public health crisis of global proportion. In psoriatic patients treated with biologic agents, evidence is not yet available on susceptibility to infection with the novel SARS-CoV-2 coronavirus, and data about the perception of COVID-19 and its impact on these patients are lacking. AIMS: The aim of this observational, spontaneous study was the evaluation of the impact of anti COVID-19 measures in "fragile population" such as patients with a chronic inflammatory disease. Thus, we evaluated the impact of perceived risk on quality of life of patients with moderate to severe psoriasis, in our outpatient clinic, and how their perceptions changed before and after the adoption of Covid-19 emergency measures following the Italian Ministerial Decree in March 9, 2020. METHODS: Using a series of questions, our study surveyed adult patients with moderate to severe psoriasis receiving treatment with biologic agents (n = 591), before and after the adoption of COVID-19 emergency measures. RESULTS: Most patients (97%) had been sufficiently informed by healthcare staff about COVID-19 spread. A significant change was observed in social activity reduction before and after the adoption of the measures (18% vs. 90% of patients; P < 0.0001). Similarly, patients were more likely to suspend ongoing therapy after the measures were adopted than before (87% vs. 34% of patients; P < 0.0001). Following the measures, older patients were significantly more inclined to suspend therapy and reduce social activities than younger patients. CONCLUSIONS: Government COVID-19 emergency measures further curtailed already reduced social activities in psoriatic patients, and led to a greater inclination to suspend biologic therapy, more so in older patients, despite there being no evidence to support this suspension. These vulnerable patients may need support from clinicians in order to maintain treatment adherence.

PET-guided Switch from Immunotherapy to Targeted Therapy in a Metastatic Melanoma Patient: a personalized approach.

An early identification of non-responders in oncology is of crucial importance to rapidly switch treatment regimens. Here we report a positron emission tomography, (PET)-guided switch from immunotherapy to targeted therapy in a patient affected by metastatic melanoma. We describe the case of a 78-years-old male patient diagnosed with nodular melanoma, submitted to baseline PET/CT with 18fluorodeoxyglucose (18F-FDG) that showed cutaneous and skeletal metastases (stage IV). The patients started immunotherapy with pembrolizumab. A PET/CT performed 3 months after the start of immunotherapy demonstrated progressive metabolic disease both at skeletal and cutaneous level, confirmed also by the biopsy. As patients resulted positive for BRAF V600k mutation, treatment regimen was rapidly switched to combined anti-BRAF/MEK targeted therapy. The PET/CT performed 3 months later, showed almost complete metabolic response. Ten months after the beginning of targeted therapy, the patient continues to present a durable metabolic response. PET/CT with 18F-FDG may help in monitoring the response to treatment in metastatic melanoma thus defining personalized therapeutic pathways.

Benefit of a topic ointment as co-medication with biologic drugs for the management of moderate-severe psoriasis: a prospective, observational real-life study.

BACKGROUND: Psoriasis is a multifactorial chronic inflammatory skin disease characterized by erythemato-squamous lesions with a chronic relapsing course. The desease clinical activity (PASI) and the patient's quality of life (DLQI) are the main elements to assess for setting up a correct therapeutic management. OBJECTIVES: The aim of the study was to evaluate the management of the patient with moderate-severe psoriasis in therapy with biological drugs and to establish the difference in the achievement of PASI 90 and DLQI 0-1 between a group of patients treated with only biological drugs and a group of patients receiving biologic therapy in combination with a topical ointment. METHODS: We conducted a prospective, observational real-life study enrolling 60 patients with moderate to severe psoriasis and divided in two groups: Group A patients treated with biological drugs, Group B patiens treated with biological drugs in association with an ointment composed of betamethasone, salicylic acid and ammonium sulpho-ichtyolate, applied 2 times a day. PASI and DLQI were evaluated at study beginning (T0) for both study groups, after 12 weeks (T3) for sample in therapy with biological drugs and after 24 weeks (T6) for sample in co-medication therapy. RESULTS: The two-way ANOVA method was used to evaluate the standard deviations (SD): at T3 and T6 Group B obtained a significant PASI reduction and improvement of DLQI (* p value <0.05) compared to Group A. CONCLUSIONS: Our study shown that the patients treated with biologics in co-medication with topical therapy reached a significantly higher PASI and DQLI compared with those treated with only biologics. Furthermore we observed that the association with topical oinment showed more efficacy in the treatment of areas such as palm-plantar region, that is often difficult-to-treat region, even for biologic drugs.

Clinical and histopathological characterization of eczematous eruptions occurring in course of anti IL-17 treatment: a case series and review of the literature.

Background: Real-life data often highlight the side effects of certain drugs not previously reported in randomized controlled trials (RCTs).Objective: To describe cutaneous inflammatory eruptions in psoriatic patients treated with an anti IL-17A agent (secukinumab or ixekizumab).Methods: Retrospective analysis of a cohort of patients with chronic plaque psoriasis who started an anti IL-17A agent between September 2016-February 2019 and who developed cutaneous inflammatory eruptions during treatment. A systematic review of similar events reported in the literature was performed.Results: Data of 468 patients were reviewed and 27 cutaneous inflammatory eruptions of 27 (5.8%) patients were collected. The eruptions appeared after a mean of 16.9 ± 17.0 weeks of therapy showing a classical acute eczema in 11 patients (40.7%), an atopic dermatitis-like rash in 11 patients (40.7%) and a psoriasiform eruption in 5 patients (18.5%). Histopathology of 12/27 cases showed epidermal spongiosis in all these variants.Conclusion: We described the clinic-pathologic features of some eczematous eruptions occurring in psoriatic patients, 3-4 months after treatment initiation with an anti IL-17A agent. Further investigations are needed to explain this phenomenon, that might be defined a paradoxical adverse event, based upon the role of IL17 in eczema pathogenesis.

A case of hidradenitis suppurativa linked to trisomy 1q.

Hidradenitis suppurativa (HS) is a chronic relapsing disorder of the apocrine gland affecting mainly areas subjected to friction (e.g. the axillae, groin, perineum and medial aspects of the thighs). This condition can be linked to different comorbidities: autoimmune and inflammatory disease, hormone-related disorders, obesity and the metabolic syndrome, as well as rare syndromes such as Bazex-Dupré-Christol, Down's, KID, PAPASH, PASS, PASH, and SAPHO syndromes, or Dowling-Degos disease. We report a case of severe HS in a patient with Trisomy 1q;13, a very rare cytogenetic anomaly characterized by severe anomalies including dysmorphisms, multiple congenital malformations, heart defects and intellectual disability.

Psoriasis Area and Severity Index response in moderate-severe psoriatic patients switched to adalimumab: results from the OPPSA study.

BACKGROUND: Few studies have compared the efficacy of switching to adalimumab in the real-life setting in plaque psoriasis patients. OBJECTIVE: To evaluate the effect of adalimumab in psoriasis patients previously treated with other biologics. METHODS: In this multicentre study, psoriasis patients (N = 262) treated with an anti-TNF-alpha agent, ustekinumab or naïve to biologics then switched to adalimumab were included. Disease severity was assessed by the Psoriasis Area and Severity Index (PASI) at baseline and after 3, 6, 12, 24 and 36 months. The association between clinical risk factors and achievement of PASI response was evaluated by logistic regression. RESULTS: Adalimumab treatment resulted in a decrease in PASI (15.1 ± 6.2 at baseline vs. 2.7 ± 4.8 at 6 months, P < 0.0001), regardless of previous biologic treatment. Furthermore, adalimumab allowed 92.5%, 79% and 56% of patients to achieve PASI response (PASI 50, 75 and 90, respectively) and complete remission (PASI 100 response) in 48.4% of patients, by 6 months and maintained over 3 years, independent of prior biologic treatment. The absence of metabolic syndrome, dyslipidemia, hypertension and lower PASI and lower age at baseline was associated with achievement of PASI response at 3, 6 and 12 months, whereas at later time points (24 and 36 months), PASI 90 and PASI 100 response was associated with diagnosis of psoriasis/psoriatic arthritis. CONCLUSION: Adalimumab was effective at reducing PASI score over 3 years, irrespective of whether patients were biologic naïve or previously treated with a TNF-alpha or IL-12/23 inhibitor.

Efficacy and tolerability of a lotion containing triethyl citrate, ethyl linoleate, and GT peptide-10 in the adjuvant treatment of hidradenitis suppurativa: Real-life data.

Hidradenitis suppurativa (HS) is a chronic disorder of terminal follicular epithelium in the apocrine gland-bearing areas. The long term therapy is based mainly on topical and/or systemic antibiotic use that could result in antibiotic resistance. The aim of our study was to present the real-life experience based on the efficacy and tolerability of a novel lotion containing triethyl-citrate, ethyl-linoleate, and g-peptide-10 in the treatment of mild to moderate HS that has already shown effectiveness in acne treatment. This was an open-label study on 30 patients of both sexes affected by HS. Patients were divided into two groups: 15 with Hurley I and 15 with Hurley II-III. The subjects were treated with the topical lotion, three-times-daily for eight weeks, with control at 4 (T1 ) and eight weeks (T2 ). Any other concomitant treatment (both topical and/or systemic) was avoided during study period. Improvement was observed in both Sartorius score grading system and inflammatory and noninflammatory lesion counts. The novel lotion has proved to be effective and well-tolerated topical agent alone or in association with other topical and/or systemic tratments in HS, without side effects.

Effects of L-DOPA/benserazide co-treatment on colonic excitatory cholinergic motility and enteric inflammation following dopaminergic nigrostriatal neurodegeneration.

INTRODUCTION: The mainstay therapy for Parkinson's disease (PD) relies on L-3,4-dihydroxyphenylalanine (L-DOPA) plus a DOPA-decarboxylase inhibitor. However, their effects on colonic dysmotility and inflammation observed in PD are undetermined. This study examined the effects of L-DOPA plus benserazide (BE) on colonic motility and inflammation in rats with central nigrostriatal dopaminergic denervation. METHODS: Neurodegeneration was induced by 6-hydroxydopamine (6-OHDA) injection into the medial forebrain bundle (MFB). 6-OHDA animals were treated orally with L-DOPA/BE for 28 days, starting 28 days after 6-OHDA injection. At the end of treatment, in vivo colonic transit was evaluated by a radiologic assay. Electrically stimulated (ES) cholinergic contractions were recorded in vitro from colonic preparations, while acetylcholine release was measured in the incubation medium. Choline acetyltransferase (ChAT) and glial fibrillary acidic protein (GFAP) expression as well as eosinophil and mast cell density were examined in the colonic wall by immunohistochemistry. Colonic TNF and IL-1ß levels were also assayed. RESULTS: 6-OHDA animals displayed: 1) decrease in in vivo colonic transit; 2) impairment of ES-stimulated cholinergic contractions; 3) decreased acetylcholine release from myenteric nerves; 4) decrease in ChAT and increase in GFAP myenteric immunopositivity; 5) increase in eosinophil and mast cell density; 6) increase in TNF and IL-1ß levels. Treatment with L-DOPA/BE elicited an improvement of in vivo and in vitro colonic motor activity, a normalization of acetylcholine release, ChAT immunopositivity, as well as pro-inflammatory cytokine patterns, ganglionic GFAP levels, eosinophil and mast cell density. CONCLUSION: Under dopaminergic nigrostriatal denervation, treatment with L-DOPA/BE ameliorated colonic motility through a normalization of myenteric cholinergic neurotransmission, along with an improvement of colonic inflammation.

Intestinal dysfunction in Parkinson's disease: Lessons learned from translational studies and experimental models.

BACKGROUND: Symptoms of digestive dysfunction in patients with Parkinson's disease (PD) occur at all stages of the disease, often preceding the onset of central motor symptoms. On the basis of these PD-preceding symptoms it has been proposed that PD could initiate in the gut, and that the presence of alpha-synuclein aggregates, or Lewy bodies in the enteric nervous system might represent one of the earliest signs of the disease. Following this hypothesis, much research has been focused on the digestive tract to unravel the mechanisms underlying the onset and progression of PD, with particular attention to the role of alterations in enteric neurotransmission in the pathophysiology of intestinal motility disturbances. There is also evidence suggesting that the development of central nigrostriatal neurodegeneration is associated with the occurrence of gut inflammation, characterized by increments of tissue pro-inflammatory markers and oxidative stress, which might support conditions of bowel neuromotor abnormalities. PURPOSE: The present review intends to provide an integrated and critical appraisal of the available knowledge on the alterations of enteric neuromuscular pathways regulating gut motor activity both in humans and preclinical models of PD. Moreover, we will discuss the possible involvement of neuro-immune mechanisms in the pathophysiology of aberrant gastrointestinal gut transit and neuromuscular activity in the small and large bowel.

Role of cyclooxygenase isoforms in the altered excitatory motor pathways of human colon with diverticular disease.

BACKGROUND AND PURPOSE: The COX isoforms (COX-1, COX-2) regulate human gut motility, although their role under pathological conditions remains unclear. This study examines the effects of COX inhibitors on excitatory motility in colonic tissue from patients with diverticular disease (DD). EXPERIMENTAL APPROACH: Longitudinal muscle preparations, from patients with DD or uncomplicated cancer (controls), were set up in organ baths and connected to isotonic transducers. Indomethacin (COX-1/COX-2 inhibitor), SC-560 (COX-1 inhibitor) or DFU (COX-2 inhibitor) were assayed on electrically evoked, neurogenic, cholinergic and tachykininergic contractions, or carbachol- and substance P (SP)-induced myogenic contractions. Distribution and expression of COX isoforms in the neuromuscular compartment were assessed by RT-PCR, Western blot and immunohistochemical analysis. KEY RESULTS: In control preparations, neurogenic cholinergic contractions were enhanced by COX inhibitors, whereas tachykininergic responses were blunted. Carbachol-evoked contractions were increased by indomethacin or SC-560, but not DFU, whereas all inhibitors reduced SP-induced motor responses. In preparations from DD patients, COX inhibitors did not affect electrically evoked cholinergic contractions. Both indomethacin and DFU, but not SC-560, decreased tachykininergic responses. COX inhibitors did not modify carbachol-evoked motor responses, whereas they counteracted SP-induced contractions. COX-1 expression was decreased in myenteric neurons, whereas COX-2 was enhanced in glial cells and smooth muscle. CONCLUSIONS AND IMPLICATIONS: In control colon, COX-1 and COX-2 down-regulate cholinergic motility, whereas both isoforms enhance tachykininergic motor activity. In the presence of DD, there is a loss of modulation by both COX isoforms on the cholinergic system, whereas COX-2 displays an enhanced facilitatory control on tachykininergic contractile activity.

Efficacy of food supplement to improve metabolic syndrome parameters in patients affected by moderate to severe psoriasis during anti-TNFα treatment.

AIM: Psoriasis is a systemic inflammatory immune-mediated skin disease. Recently a relationship with metabolic syndrome in terms of psoriasis severity and response to therapy was observed. METHODS: We performed an open-label randomized controlled study to evaluate the role of a nutraceutical containing Q10 coenzyme, Krill-oil, lipoic acid, resveratrol, Vitis vinifera seed oil, vitamin E and selenium in addition to etanercept therapy for patients affected by psoriasis and metabolic syndrome. Forty patients were enrolled and divided into two arms, one receiving only etanercept, one other receiving also the neutraceutical. After a period of 3 months (T1) a second evaluation of the considered parameters was performed. RESULTS: At T1 statistically significant differences were detected in HDL cholesterol and triglycerides values both comparing the two arms and in the nutraceutical arm. CONCLUSION: Our results show that the dietary addiction of the nutraceutical to the etanercept therapy in patients affected by both psoriasis and metabolic syndrome could help to restore the normal lipid profile.

Embedding methods for poly(L-lactic acid) microfiber mesh/human mesenchymal stem cell constructs.

Fiber mesh scaffolds were recently investigated in tissue engineering as possible support for stem cell growth and differentiation, in order to repair lesion areas in clinical practice. In particular, the literature is focused on fiber mesh scaffolds constituted of biocompatible and resorbable polymeric structures, like poly(L-lactic acid) (PLLA). However, as regards the study of constructs constituted of PLLA microfibers and cells, only quantitative and SEM analyses were reported, lacking histological analysis. Histological evaluation of these constructs could give important information about cellular distribution in the scaffold, cell-scaffold interactions and extracellular matrix production. The purpose of our study was to find a valid method to analyze PLLA microfiber/cell constructs from both histological and histochemical angles. Biodegradable non-woven fiber meshes were prepared using hollow microfibers, based on PLLA. We first evaluated different embedding methods useable for histological analysis and the results showed that among the paraffin, Killik, and acrylic resin the only suitable medium was the latter. Then we employed the acrylic resin to embed the constructs made up of PLLA microfibers and bone marrow-derived human mesenchymal stromal cells, which we then analyzed with Toluidine Blue, PAS and Alcian Blue staining. These constructs, previously analyzed for cell viability by MTT and CCK-8 tests, showed viable/proliferating cells until 6 weeks of culture. The stainings performed on constructs confirmed viability data obtained with SEM and MTT/CCK-8 and supplied other information on the cell behaviors such as the distribution and organization onto the scaffold and the production of extracellular matrix molecules. In conclusion, this methodological study mainly suggests a suitable method to analyze PLLA microfiber/cell constructs, at the same time confirming and enriching the literature data on the compatibility between PLLA microfibers and hMSCs.

The beta3-adrenoceptor agonist SR58611A ameliorates experimental colitis in rats.

Beta(3)-adrenoceptor agonists protect against experimental gastric ulcers. We investigated the effects of the beta(3)-adrenoceptor agonist SR58611A on 2,4-dinitrobenzene sulphonic acid-induced colitis in rats and analysed the expression of beta(3)-adrenoceptors in the colonic wall. SR58611A was administered orally (1-10 mg kg(-1)) for 7 days, starting the day before induction of colitis. Colitis was assessed by macroscopic and histological scores, tissue myeloperoxidase activity, interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) levels. Reverse transcription-polymerase chain reaction and immunohistochemical analysis were used to examine the expression of beta(3)-adrenoceptors. SR58611A significantly reduced the severity of colitis as well as the tissue levels of TNF-alpha, IL-1beta and IL-6. Colitis was associated with a decreased expression of beta(3)-adrenoceptor mRNA in the mucosal/submucosal layer of distal colon and this reduction was not affected by SR58611A. Immunohistochemical analysis revealed beta(3)-adrenoceptors within the muscularis externa, in myenteric neurons and nerve fibres and in the submucosa. beta(3)-Adrenoceptor immunoreactivity was decreased in inflamed tissues compared to controls, particularly in the myenteric plexus; this reduction was counteracted by SR58611A. Amelioration of experimental colitis by the selective beta(3)-adrenoceptor agonist SR58611A suggests that beta(3)-adrenoceptors may represent a therapeutic target in gut inflammation.

Electrophysiological characterization of vagal afferents relevant to mucosal nociception in the rat upper oesophagus.

Emerging evidence indicates a nociceptive role of vagal afferents. A distinct oesophageal innervation in the rat, with muscular and mucosal afferents travelling predominantly in the recurrent (RLN) and superior laryngeal nerve (SLN), respectively, enabled characterization of mucosal afferents with nociceptive properties, using novel isolated oesophagus-nerve preparations. SLN and RLN single-fibre recordings identified 55 and 14 units, respectively, with none conducting faster than 8.7 m s(-1). Mucosal response characteristics in the SLN distinguished mechanosensors (n = 13), mechanosensors with heat sensitivity (18) from those with cold sensitivity (19) and a mechanoinsensitive group (5). The mechanosensitive fibres, all slowly adapting, showed a unimodal distribution of mechanical thresholds (1.4-128 mN, peak approximately 5.7 mN). No difference in response characteristics of C and Adelta fibres was encountered. Mucosal proton stimulation (pH 5.4 for 3 min), mimicking gastro-oesophageal reflux disease (GORD), revealed in 31% of units a desensitizing response that peaked around 20 s and faded within 60 s. Cold stimulation (15 degrees C) was proportionally encoded but the response showed slow adaptation. In contrast, the noxious heat (48 degrees C) response showed no obvious adaptation with discharge rates reflecting the temperature's time course. Polymodal (69%) mucosal units, > 30% proton sensitive, were found in each fibre category and were considered nociceptors; they are tentatively attributed to vagal nerve endings type I, IV and V, previously morphologically described. All receptive fields were mapped and the distribution indicates that the posterior upper oesophagus may serve as a 'cutbank', detecting noxious matters, ingested or regurgitated, and triggering nocifensive reflexes such as bronchoconstriction in GORD.