Extracellular vescicles in psoriasis: from pathogenesis to possible roles in therapy.

Psoriasis is a chronic inflammatory disease affecting skin and joints characterized by a chronically altered immune and inflammatory response. Several factors occur from the onset to the development of this disease due to different types of cells spatially and temporally localized in the affected area, such as, keratinocytes, macrophages, neutrophils and T helper lymphocytes. This scenario leads to the chronic release of high levels of inflammatory mediators (i.e., IL-17, IL-23, IL-22, TNF-α, S100 proteins, Defensins) and lastly parakeratosis and thickening of the stratum spinosum. Extracellular vesicles (EVs) are small double membraned biological nanoparticles that are secreted by all cell types and classified, based on dimension and biogenesis, into exosomes, microvesicles and apoptotic bodies. Their role as vessels for long range molecular signals renders them key elements in the pathogenesis of psoriasis, as well as innovative platforms for potential biomarker discovery and delivery of fine-tuned anti-inflammatory therapies. In this review, the role of EVs in the pathogenesis of psoriasis and the modulation of cellular microenvironment has been summarized. The biotechnological implementation of EVs for therapy and research for new biomarkers has been also discussed.

18F-FDG PET-CT Scans in Oncology Patients Treated with Hyaluronic Acid Filler: Not Always a Pitfall.

The use of hyaluronic acid (HA) fillers in oncology patients undergoing PET-CT scans is a topic of debate due to potential interference with imaging accuracy. A 54-year-old female, postmelanoma metastasectomy in the parotid region with subsequent facial nerve palsy (FNP), received HA filler injections for facial symmetry and functional restoration. Follow-up PET-CT scans showed no interference or artifacts attributable to HA injection, allowing for accurate imaging results. This case suggests that HA fillers administered in oncology patients may not universally pose challenges or disrupt PET-CT imaging interpretation. Due to the possible false positives induced by fillers, the inclusion of aesthetic treatments in patients' anamnesis is a crucial step to accurately interpret PET-CT images. Although maintaining high level of caution in interpreting PET-CT results after filler injection is essential, our case emphasizes the safety of this procedure in oncology patients undergoing follow-up PET-CT scans.

Successful Treatment with Bimekizumab of a Psoriatic Patient Undergoing Hemodialysis: A Case Report and Review of the Literature.

Background/Objectives: Treating psoriasis patients requires the consideration of potential underlying complications like latent viral infections and chronic kidney disease, which may influence therapy selection. Case presentation: A patient with end-stage kidney disease (ESKD) undergoing hemodialysis (HD) was successfully treated with bimekizumab, an IgG1 humanized monoclonal antibody inhibiting interleukin (IL)-17A and IL-17F. This case appears to be the first documented instance of effective anti-IL-17A/IL-17F antibody treatment in a psoriasis patient undergoing HD, with a sustained positive response for eight months. Discussion: Studies indicate the comparable pharmacokinetics, efficacy, and safety of certain psoriasis drugs in patients with chronic kidney disease (CKD) and those with normal renal function. The positive clinical outcome observed following treatment with bimekizumab aligns with the existing literature on this topic. However, further studies are needed to objectively evaluate the pharmacokinetics, efficacy, and safety of this drug in this specific setting. Conclusions: This documented case represents the first known use of bimekizumab to treat psoriasis in patients undergoing dialysis, suggesting its potential effectiveness and safety in this population.

The Prognostic Role of [18F]FDG PET/CT in Patients with Advanced Cutaneous Squamous Cell Carcinoma Submitted to Cemiplimab Immunotherapy: A Single-Center Retrospective Study.

Background: Baseline 2-deoxy-2[18F]fluoro-d-glucose ([18F]FDG) positron emission tomography (PET)-derived parameters and 12-week metabolic response were investigated as prognostic factors in advanced cutaneous squamous cell carcinoma (cSCC) submitted to cemiplimab immunotherapy. Materials and Methods: Clinical records of 25 cSCC patients receiving cemiplimab, submitted to [18F]FDG positron emission tomography/computed tomography (PET/CT) at baseline and after ∼12 weeks, were retrospectively reviewed. The Kaplan-Meier (KM) method was applied to analyze differences in event-free survival (EFS), and Cox regression analysis was employed to identify the prognostic factors. Results: At the 12-week PET/CT evaluation, 16 patients (64%) were classified as responders (complete or partial response) and 9 (36%) as nonresponders ("unconfirmed progressive metabolic disease") according to immune PET Response Criteria in Solid Tumors (iPERCIST). By KM analysis, baseline metabolic tumor volume (MTV) and total lesion glycolysis (TLG) significantly correlated with the EFS (p < 0.05). Furthermore, the KM analysis showed that the lack of metabolic response at 12 weeks was associated with meaningfully shorter EFS (7.2 ± 1 months in nonresponders vs. 20.3 ± 2.3 months in responders). In Cox multivariate analysis, metabolic response at 12 weeks remained the only predictor of the EFS (p < 0.05). Conclusions: Baseline tumor load (i.e., MTV and TLG) and metabolic response at 12 weeks may have a prognostic impact in cSCC patients treated with cemiplimab.

Rehabilitation After Total Laryngectomy: An Integrated Protocol Remotely Delivered During COVID-19.

The aim of this paper was to evaluate the results of an integrated treatment delivered remotely to laryngectomized patients with voice prosthesis. Eighteen laryngectomized patients were treated remotely in groups co-led by a speech therapist and a psychologist ("Online Group"). The results were compared with those of 17 patients ("In-Person Group") previously studied. The two groups obtained comparable results on all parameters of the INFVo perceptual rating scale, in the DEP, ANX, PHO and HOS areas of the Symptom Check List-90-Revised questionnaire, and in the areas investigated by the WHOQOL-B questionnaire. The "In-Person Group" obtained statistically better results on the Italian Self-Evaluation of Communication Experiences after Laryngeal Cancer questionnaire. Although the in-person treatment favored the acceptance of the new voice and the development of conversational skills, telerehabilitation guaranteed an adequate level of assistance in terms of voice acquisition, prevention of anxiety and depression, and recovery of a good QoL.

Supraorbital Basosquamous Carcinoma Treated with Cemiplimab Followed by Sonidegib: A Case Report and Review of the Literature.

Basal cell carcinoma (BCC) is a skin cancer with low local aggressiveness and a low tendency to metastasize. Basosquamous Carcinoma (BSC) represents an aggressive histological subtype of BCC with intermediate features between Squamous Cell Carcinoma (SCC) and BCC. Cemiplimab is currently approved as first-line therapy in SCC and second-line therapy in BCC patients who have progressed on or are intolerant of a Hedgehog pathway Inhibitor (HHI). Our study describes the case of a 59-year-old man with BSC who was successfully treated with 5 cycles of Cemiplimab as first-line therapy and Sonidegib as second-line therapy. Currently, the efficacy of Cemiplimab against BSC and other histopathological subtypes of BCC has not been fully elucidated, as has the role of sequential or combination therapy with Cemiplimab and HHI in the management of BSC. The aim of this case report is to highlight the need to outline the use of checkpoint inhibitors in BCCs and focus attention on the synergistic role of Cemiplimab and HHIs in such a controversial entity as BSC.

Psoriasis induced by first­line pembrolizumab in metastatic non­small cell lung cancer: A case report.

Therapeutic options for non-small cell lung cancer (NSCLC) have changed with the introduction of immune checkpoint inhibitors. Immunotherapy is generally well tolerated, but can also be associated with severe adverse events, such as the development of new autoimmune diseases. In patients without a history of autoimmune diseases, psoriasis caused by immunotherapy treatment is rarely described in the literature. The present study describes the case of a 68-year-old man with metastatic NSCLC that started chemoimmunotherapy with carboplatin plus pemetrexed plus pembrolizumab. After two cycles of therapy, the patient developed a G3 maculopapular rash. Biopsy confirmed psoriasis and pembrolizumab treatment was discontinued. At the last follow up, the patient was still on maintenance therapy with pemetrexed alone, which is well tolerated. Psoriasis has rarely been reported as an immune-related adverse event. Although the patient had to stop the immunotherapy treatment, the patient is still exhibiting a response to it. Notably, it has previously been described how skin toxicities are associated with a better outcome. Other studies need to be conducted to identify the risk and predictive factors associated with severe immune adverse events and objective response.

A Case of Psoriatic Disease and Hidradenitis Suppurativa in a Child with Chromosome 17q21.31 Microduplication Syndrome.

Psoriatic disease is a chronic, relapsing inflammatory disorder, characterized mostly by cutaneous erythematous scaly plaques sometimes associated with arthritis. Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory disease of the apocrine glands, characterized clinically by painful abscesses, sinus tracts and scars. It typically occurs after puberty, affecting mainly intertriginous areas of the body. There is a strong association between HS and psoriasis since they share the same pathogenic inflammatory pathway. The patient presented: low birthweight, microcephaly, facial dysmorphisms, lumbar hyperlordosis, walking difficulties, global psychomotor developmental delay and learning disabilities. A genetic evaluation revealed a 2.5 Mb de novo microduplication in the 17q21.31 chromosomal region. Dermatological examination revealed HS (Hurley stage II-HS) distributed in the genital area and inguinal folds, psoriatic plaques on the retroauricolar folds, on the elbows bilaterally and on the lateral aspect of the right ankle and psoriatic arthritis. The patient was treated with adalimumab, with a marked improvement of both conditions. To our best knowledge, we report the first case of coexisting Psoriatic Arthritis Disease and Hidradenitis Suppurativa in a child with chromosome 17q21.31 microduplication syndrome. We hypothesize that gene CRHR1 duplication included in the 17q21.31 chromosomal region might be involved in the pathogenesis of both diseases.

[18F]FDG PET/CT in a Case of Mycosis Fungoides Showing an Unusual Adverse Reaction to Mogamulizumab: Correlation Between Imaging and Histological Findings.

A 73-year-old female patient, affected by mycosis fungoides (MF), discontinued mogamulizumab, after initial clinical benefit, due to the onset of generalized erythema. Follow-up positron emission computed tomography (PET/CTs) carried out at 3 weeks and 6 months after therapy discontinuation showed, with respect to baseline PET/CT scan, a progressively increasing number of hypermetabolic enlarged lymph nodes suspected for a neoplastic involvement, but with histology indicative of an inflammatory reaction. After sequential therapy with corticosteroids and methotrexate, a complete remission was registered at 18F-fluorodeoxyglucose ([18F]FDG) PET/CT performed at 12 months after mogamulizumab interruption. The case we describe highlights the usefulness of serial examinations with [18F]FDG PET/CT in an MF patient presenting an unusual adverse reaction to mogamulizumab.

Guselkumab for the treatment of severe plaque psoriasis in a schizophrenia patient.

A wide range of comorbid conditions are associated with psoriasis, many studies have drawn attention to a higher prevalence of psychiatric comorbidities in psoriatic population. Herein, we present a case of a Caucasian 44-years-old man suffering from a severe schizophrenia, who received guselkumab (a human monoclonal antibody targeting the p40 subunit of IL-23) for the treatment of a moderate-to-severe plaque type psoriasis. After 3 months, the patient reached complete resolution of psoriasis without any side effects, maintained at 6 months follow up visit. Some studies have highlighted the hypothesis that an hyperactivation of immune response appears to be one of the main mechanisms underlying the increased risk of this association. In particular, the axis il-17/il-23 plays a central role in the pathogenesis of this disease. Further research will be needed to assess whether anti-IL23 drugs could be a more suitable therapeutic option in psoriatic patients with schizophrenia.

Long term efficacy, safety, and tolerability of tildrakizumab in epileptic patient with psoriasis and eczema.

Psoriasis is a chronic inflammatory disease which mostly affects skin. Tildrakizumab is a specific anti-interleukin -23p19 monoclonal antibody approved for the treatment of plaque psoriasis in adults. Herein, we report about a patient who came to our attention for a moderate-to-severe plaque psoriasis, involving primarily upper limbs, elbow, abdomen and knees (PASI 18 - DLQI 22). His medical history was relevant for epilepsy controlled pharmacologically. In addition, an eczematous and edematous appearance of the tibial area was detected; the histologic findings did not contradict the diagnostic hypothesis of subacute spongiotic dermatitis. The patient was treated with Tildrakizumab. After 12 weeks the clinical lesions improved significantly, and the eczematous component disappeared in the tibial area bilaterally. The clinical improvement was maintained even after one year of therapy. Tildrakizumab showed excellent results in the control of psoriasis, with an excellent safety profile. The promising results of clinical trials have been confirmed in a real-life setting. There are no reports about its safety in epileptic patients. In our case, neurological adverse events did not verify and tildrakizumab managed to control both the psoriatic and eczematous components.

A Case Report of Monkeypox in an Adult Patient from Italy: Clinical and Dermoscopic Manifestations, Diagnosis and Management.

Monkeypox infection is an emerging problem and a new challenge for modern medicine. With an increasing number of new cases worldwide, new data regarding the clinical manifestations, characteristics of the patients, risk factors and treatment options are coming to light. Knowing more about the disease will allow to elaborate new helpful methods to facilitate its diagnosis. Special attention should be paid to the careful dermatologic and dermoscopic examination of the patient. The analysis of available data also suggests possible strategies for the prevention of Monkeypox virus spread; the vaccine against Smallpox seems to be an effective solution. This case report describes the diagnostic approach and management of a non-vaccinated adult patient with several risk factors and a history of sexually transmitted disease. The patient had no history of travel abroad. Even though a clinical diagnose of Monkeypox can be challenging due to its similarities with skin rashes caused by other Orthopoxviral infections, there are fine differences between the rashes which can be helpful in their differentiation, although laboratory analysis is required for a definitive identification. A careful study of the characteristics of the rash, such as diameter, its presence on palms and soles and its evolution in time, provided important clues for the diagnosis of Monkeypox infection. The lack of vaccinations in the history of the patient was another crucial finding in the diagnostic process.

Italian Real-Life Experience on the Use of Mogamulizumab in Patients with Cutaneous T-Cell Lymphomas.

Mycosis fungoides and Sèzary syndrome are the most studied subtypes common cutaneous T-cell lymphomas. The current treatment objective is to improve the clinical manifestations of the disease in the affected areas, to relieve symptoms and to halt disease progression. Patients with early-stage mycosis fungoides are usually managed with skin-directed therapies, whereas patients with resistant or advanced-stage mycosis fungoides or Sèzary syndrome often require systemic drugs. Over the last decade, new drugs have been developed, increasing the breadth of treatment options for cutaneous T-cell lymphomas patients. Mogamulizumab is a first-in-class defucosylated humanized IgG1 κ monoclonal antibody, which exerts its anti-tumour action by selectively binding to C-C chemokine receptor 4 and increasing antibody-dependent cellular cytotoxicity activity against malignant T-cells. Several clinical trials showed that mogamulizumab is able to effectively control the cutaneous T-cell lymphomas in each site (skin, blood, lymph nodes and viscera), improving patients' symptoms, function and overall quality of life with a manageable safety profile. In this report, we discuss 12 cases of patients with mycosis fungoides or Sèzary syndrome successfully treated with mogamulizumab in real-life clinical practice in Italy.

Multidimensional voice assessment after Lee Silverman Voice Therapy (LSVT®) in Parkinson's disease.

Objective: To investigate the effectiveness of Lee Silvermann Voice Treatment (LSVT®) in improving prosody in patients with Parkinson's disease over medium-term follow-up. Methods: 15 patients with Parkinson's disease were assessed before LSVT®, within one week, and 3 and 6 months after treatment. Subjective and objective evaluation included: Voice Handicap Index - 10 (VHI-10), perceptual assessment by GRBAS scale and item 18 of the Unified Parkinson's Disease Rating Scale III (UPDRS III), maximum phonation time (MPT /s/) and acoustic analysis by means the Voice Range Profile (VRP) and the "Intonation Stimulability Protocol" of the Motor Speech Profile (MSP). Results: A significant increase of the mean values of Imax and rF0 was observed until 6 months post-therapy (p < 0.001), whereas Running Speech Standard Deviation (rSTD) (p = 0.004), Amplitude Variability (rVAm) (p = 0.02) and Frequency Variability (rvF0) (p = 0-01) improved significantly after 3 months, but returned to pre-therapy levels after 6 months. The score of item 18 of the UPDRS III increased significantly early post-therapy (p = 0.03), but did not maintain the improvement at 3 and 6 months. Median values of Grade (G), Asthenia (A) and mean values VHI-10 score significantly decreased at each post-therapy control (p < 0.05). Conclusions: In addition to the subjective and perceptual beneficial effect of LSVT®, we found a long-lasting increase of loudness and fundamental frequency. There was also improvement of acoustic parameters related to prosody, although it was temporary.

PSSD and biologic therapy: Real-life data in 417 patients with moderate to severe psoriasis.

BACKGROUND: Psoriasis is a chronic relapsing immune-mediated disease leading to a strong impact on patient's quality of life. The treatment of psoriasis has undergone a revolution with the advent of biologic therapies. Currently, Psoriasis Area and Severity Index [PASI] and Dermatology Life Quality Index [DLQI] scores are in use to assess the overall severity of pathology. A new self- administered questionnaire, the Psoriasis Symptoms and Signs Diary (PSSD), assesses severity of six psoriasis symptoms (itch, skin tightness, burning, stinging, and pain,) and five signs (dryness, cracking, scaling, shedding/flaking, redness, and bleeding). OBJECTIVE: To evaluate and compare the efficacy of biologic therapies through PSSD in patients with moderate to severe psoriasis Methods: The PSSD questionnaire was administered to all the patients at the beginning and after 6 months of biologic therapy (anti-TNFalpha, anti- IL17, anti-IL23, anti-IL12/23 and phhosphodiesterase-4 Inhibitors). RESULTS: The study population included 417 adult patients with moderate to severe psoriasis in treatment with biologic drugs. All the drugs contributed to a significant improvement of mean total PSSD at t 24; anti-IL17 and anti-IL23 led to a significantly greater reduction at t 24 mean PSSD when compared to other therapies. CONCLUSION: The PSSD, is a new validated instrument useful for capturing psoriasis patient's quality of life and evaluating treatments efficacy. In our study this score has been useful to put in evidence significant differences between biologic drugs.

Non-Melanoma Skin Cancer Clearance after Medical Treatment Detected with Noninvasive Skin Imaging: A Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTIVES: Non-melanoma skin cancer (NMSC) treated with nonsurgical therapies can be monitored with noninvasive skin imaging. The precision of dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) in detecting clearance is unclear. We aim to report the proportion of persisting tumors identified with noninvasive technologies available in the literature. METHODS: A systematic literature search was conducted on the PubMed and Cochrane Public Library Databases for articles published prior to November 2021. Statistical analyses were conducted with MedCalc 14.8.1 software. RESULTS: A total of eight studies (352 lesions) reporting noninvasive imaging for NMSC clearance following nonsurgical treatment were included. Most (n = 7) reported basal cell carcinoma (BCC), and one study reported squamous cell carcinoma (SCC) clearance. A meta-analysis of the BCC clearance revealed that the summary effect for RCM was higher, as compared to the other techniques. Interestingly, the sensitivity and specificity for OCT were 86.4% (95% CI: 65.1-97.1) and 100% (95% CI: 94.8-100.0), respectively, whilst, for RCM, they reached 100% (95%CI: 86.8-100) and 72.5% (95% CI: 64.4-79.7), respectively. CONCLUSIONS: Routine clinical examination and dermoscopy underperform when employed for NMSC clearance monitoring, although they represent the first approach to the patient. OCT and RCM seem to improve the detection of persistent BCC after medical treatment.