Fatal hyalohyphomycosis with cutaneous involvement caused by purpureocillium lilacinum in an immunocompromised patient with bullous pemphigoid

Emergent pathogen as Purpureocillium lilacinum are becoming cause of morbidity and mortality in our population, especially in immunocompromised patients. We describe a case of hyalohyphomycosis in a diabetic man under systemic steroid treatment for a bullous pemphigoid. Treatment with different antimycotic drugs were ineffective and infection spread diffusely, leading to deterioration of general conditions and ultimately death. The aim of this article is to increase awareness of clinicians about this uncommon, but frequently fatal refractory mycotic infection

Agricultural use of copper and its link to Alzheimer’s disease

Copper is an essential nutrient for plants, animals, and humans because it is an indispensable component of several essential proteins and either lack or excess are harmful to human health. Recent studies revealed that the breakdown of the regulation of copper homeostasis could be associated with Alzheimer’s disease (AD), the most common form of dementia. Copper accumulation occurs in human aging and is thought to increase the risk of AD for individuals with a susceptibility to copper exposure. This review reports that one of the leading causes of copper accumulation in the environment and the human food chain is its use in agriculture as a plant protection product against numerous diseases, especially in organic production. In the past two decades, some countries and the EU have invested in research to reduce the reliance on copper. However, no single alternative able to replace copper has been identified. We suggest that agroecological approaches are urgently needed to design crop protection strategies based on the complementary actions of the wide variety of crop protection tools for disease control

Laser treatment monitoring with reflectance confocal microscopy

Laser treatments have become popular in Dermatology. In parallel to technologic development enabling the availability of different laser wavelengths, non-invasive skin imaging techniques, such as reflectance confocal microscopy (RCM), have been used to explore morphologic and qualitative skin characteristics. Specifically, RCM can be applied to cosmetically sensitive skin areas such as the face, without the need for skin biopsies. For these reasons, apart from its current use in skin cancer diagnosis, our systematic review reveals how RCM can be employed in the field of laser treatment monitoring, being particularly suitable for the evaluation of variations in epidermis and dermis, and pigmentary and vascular characteristics of the skin. This systematic review article aims to provide an overview on current applications of RCM laser treatment monitoring, while describing RCM features identified for different applications. Studies on human subjects treated with laser treatments, monitored with RCM, were included in the current systematic review. Five groups of treatments were identified and described: skin rejuvenation, scar tissue, pigmentary disorders, vascular disorders and other. Interestingly, RCM can assist treatments with lasers targeting all chromophores in the skin and exploiting laser induced optical breakdown. Treatment monitoring encompasses assessment at baseline and examination of changes after treatment, therefore revealing details in morphologic alterations underlying different skin conditions and mechanisms of actions of laser therapy, as well as objectify results after treatment

"Your Skin Tells You" Campaign for Keratinocyte Cancers: When Individuals' Selection Makes the Difference

Background: Prevention campaigns for skin cancers have focused primarily on melanoma, and over time there has been increasing awareness of the need to select the population to be screened to maximize program effectiveness. Objectives: The objective of the study was to report the results of a free dermatological initiative, as part of an awareness campaign dedicated to keratinocyte cancers, targeting individuals pre-selected through a short questionnaire. Methods: One day of dermatological consultations was held at 15 dermato-oncology referral centers during May 22-June 30, 2021. For selection, individuals answered a telephone interview consisting of 7 yes/no questions on risk factors. Demographics, clinical characteristics of suspicious tumors, and histopathologic diagnosis of excised lesions were collected. Suspicion rate, detection rate, and positive predictive values (PPVs) for any skin cancer, basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma were calculated. Results: A total of 320 individuals (56.9% males; 43.1% females) with a median age of 69.6 (range 21-91) years qualified for the screening initiative. Overall, skin cancers and precancerous lesions were diagnosed in 65.9% of the patients. Suspicion rate was 28.7% for any skin cancer (92/320), 22.8% for BCC (73/320), 4.7% for cSCC (15/320), and 1.2% for melanoma (4/320). Detection rate was 23.4% for any skin cancer (PPV 93.7%), 18.1% for BCC (PPV 95.1%), 4.4% for cSCC (PPV 93.3%), and 0.9% for melanoma (PPV 75%). Conclusions: Selection of individuals at high risk is a cost-effective approach for early detection campaigns for keratinocyte cancers

Systemic epidermal nevus with involvement of the oral mucosa due to FGFR3 mutation

Our results show that activating FGFR3 mutations can also affect the oral mucosa and that extracutaneous manifestations of EN syndrome can be subtle. We highlight the theoretical risk of the patient having an offspring with thanatophoric dysplasia as gonadal mosaicism for the R248C mutation cannot be excluded

Cytokine Signature in Schnitzler Syndrome: Proinflammatory Cytokine Production Associated to Th Suppression

Background: Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterized by urticarial exanthema, bone and joint alterations, fever and monoclonal IgM gammopathy. Overactivation of the interleukin(IL)-1 system is reported, even though the exact pathophysiological pathways remain unknown. Objective: To determine ex vivo cytokine profiles of Peripheral Blood Mononuclear Cells (PBMCs) from SchS patients prior to treatment and after initiation of anti-IL-1 therapy (anakinra). The sera cytokine profile was studied in parallel. Methods: We collected blood samples from thirty-six untreated or treated SchS. PBMCs were cultured with and without LPS or anti-CD3/CD28. Cytokine levels were evaluated in serum and cell culture supernatants using Luminex technology. Results: Spontaneous TNFα, IL-6, IL-1β, IL-1α, and IL-1RA release by PBMCs of SchS patients were higher than in controls. LPS-stimulation further induced the secretion of these cytokines. In contrast, after T-cell stimulation, TNFα, IL-10, IFNγ, IL-17A, and IL-4 production decreased in SchS patients compared to healthy controls, but less in treated patients. Whereas IL-1β serum level was not detected in most sera, IL-6, IL-10, and TNFα serum levels were higher in patients with SchS and IFNγ and IL-4 levels were lower. Of note, IL-6 decreased after treatment in SchS (p = 0.04). Conclusion: Our data strengthen the hypothesis of myeloid inflammation in SchS, mediated in particular by IL-1β, TNFα, and IL-6, associated with overproduction of the inhibitors IL-1RA and IL-10. In contrast, we observed a loss of Th1, Th2, and Th17 cell functionalities that tends to be reversed by anakinra

A 48-week update of a multicentre real-life experience of dupilumab in adult patients with moderate-to-severe atopic dermatitis

The long-term efficacy and safety of dupilumab has been demonstrated in clinical trials and only in few real-world studies. We conducted an extension analysis from a previous 16-week study on 109 adult patients affected by moderate-to-severe atopic dermatitis treated with dupilumab. Eczema-Area-and-Severity-Index (EASI), itch numerical-rating-score (itch-NRS), Dermatology-Life-Quality-Index (DLQI) scores, drug survival rate and occurrence of adverse events after 24 and 48 weeks of dupilumab treatment were retrospectively collected. Dupilumab demonstrated sustained improvement of disease severity, pruritus, and quality of life in our series with an increasing percentage of patients gaining EASI75 and EASI90 response during the study period. Few patients interrupted treatment resulting in a very high drug survival rate. We also confirmed the favorable safety profile of the drug with absence of serious adverse events and serious infections throughout the 48-week period. The prevalence of conjunctivitis was low and mainly occurred in the mid-term with resolution of the majority of cases at 48 weeks

Folliculin interacts with p0071 (plakophilin-4) and deficiency is associated with disordered rhoa signalling, epithelial polarization and cytokinesis

Inherited mutations in the folliculin (FLCN) gene cause the Birt-Hogg-Dubé syndrome of familial hair follicle tumours (fibrofolliculomas), lung cysts and kidney tumours. Though folliculin has features of a tumour suppressor, the precise function of the FLCN gene product is not well characterized. We identified plakophilin-4 (p0071) as a potential novel folliculin interacting protein by yeast two-hybrid analysis. We confirmed the interaction of folliculin with p0071 by co-immunoprecipitation studies and, in view of previous studies linking p0071 to the regulation of rho-signalling, cytokinesis and intercellular junction formation, we investigated the effect of cell folliculin status on p0071-related functions. Folliculin and p0071 partially co-localized at cell junctions and in mitotic cells, at the midbody during cytokinesis. Previously, p0071 has been reported to regulate RhoA signalling during cytokinesis and we found that folliculin deficiency was associated with increased expression and activity of RhoA and evidence of disordered cytokinesis. Treatment of folliculin-deficient cells with a downstream inhibitor of RhoA signalling (the ROCK inhibitor Y-27632) reversed the increased cell migration phenotype observed in folliculin-deficient cells. Deficiency of folliculin and of p0071 resulted in tight junction defects and mislocalization of E-cadherin in mouse inner medullary collecting duct-3 renal tubular cells. These findings suggest that aspects of folliculin tumour suppressor function are linked to interaction with p0071 and the regulation of RhoA signalling

Age and gender influence on HIDRAdisk outcomes in adalimumab-treated hidradenitis suppurativa patients

Background Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory skin disease characterized by a significant impairment of patients' quality of life (QoL). It has been recently found that clinical severity of HS does not correlate well with QoL. Therefore, it is important to enhance the evaluation of severity considering the disease burden on QoL. Recently, a new graphical tool able to better describe HS burden, the so-called HIDRAdisk, has been introduced. Objective To investigate the utility of HIDRAdisk in clinical practice before and after treatment and to analyse whether specific factors such as age and gender may influence the outcomes in patients with moderate-to-severe HS. Methods A single-centre retrospective study on 24 patients (13F/11M, mean age 38 +/- 15 years) with moderate-to-severe HS was performed. Clinical data (disease severity and quality of life) were collected at baseline and after 12 weeks of adalimumab. Results HIDRAdisk showed significantly better improvements in males (69.8 +/- 6.2-49.6 +/- 10.8) compared to females (80.7 +/- 6.0-72.3 +/- 6.7), P <0.001. A significant correlation was found in the total population between HS severity values measured through the modified Sartorius score (mSS) and QoL measured through HIDRAdisk. As regards the relationship between disease outcomes and age, a trend for better HIDRAdisk outcomes in younger patients (<40 years) compared to older ones was observed. Conclusions HIDRAdisk appears as a complete and informative tool which can easily measure the global burden of HS, guiding treatment choice and evaluating its efficacy