Combined treatment of palmar hyperhidrosis with botulinum toxin type A and oxybutynin chloride: Results of a clinical, multicenter, prospective study.

Oxybutynin chloride and botulinum toxin type A (BTX-A) have demonstrated to be effective treatments for primary palmar hyperhidrosis (PPH); however, both of them are not completely free from local and/or generalized side effects. Primary aim of this study is to compare efficacy and safety of a sequencing administration of oral oxybutynin chloride after BTX-A injections vs oral oxybutynin chloride in monotherapy in patients with PPH. Secondary aim is to evaluate if the sequencing approach can allow the control of hyperhidrosis with lower dose of oral oxybutynin. Patients enrolled were compared for short- and long-term efficacy and safety of treatments. Effectiveness was evaluated through the Hyperhidrosis Disease Severity Scale (HDSS), and the Dermatology Life Quality Index (DLQI) score; safety was assessed through collection of the adverse events reported by patients both at baseline, at 24 and 52 weeks. Patients receiving sequencing treatment showed significant greater improvement than patients receiving oxybutynin chloride alone at T24 (HDSS P = .0076 and DLQI P = .0139) and T52 (HDSS P = .0387 and DLQI P = .0087). The dose of oxybutynin chloride useful to control hyperhidrosis was lower, and retention rate to the treatment was higher in patients receiving sequencing treatment (P = .001), than patients receiving monotherapy (P = .04). A sequencing therapeutic approach to palmar hyperhidrosis increases both efficacy and safety compared with the use of oral oxybutynin chloride alone, and allows clinicians to keep lower dosage of oxybutynin chloride reducing generalized side effects and increasing the retention rate to the treatment.

Two cases of Hidradenitis suppurativa and botulinum toxin type a therapy: A novel approach for a pathology that is still difficult to manage.

Hidradenitis suppurativa is a chronic skin disease with an intense inflammatory activation. It typically affects the intertriginous areas with cysts, fistulae, and scarring extremely painful. Patients suffer from severe psychological impact. HS still results in a high unmet medical need with several underdiagnosed cases, probably due to the incomplete knowledge of the pathogenesis of HS. The use of botulinum toxin a has recently been proposed as an effective therapy for HS.

Pathogenetic Characteristics of Mesenchymal Stem Cells in Hidradenitis Suppurativa.

Importance: Hidradenitis suppurativa (HS) is a disease of the terminal hair follicle in apocrine gland-enriched skin areas, where immunobiology dysregulation of mesenchymal stem cells (MSCs) may have a key role. Objective: To investigate the MSC profile in patients with HS and in healthy controls. Design, Setting, and Participants: In this prospective case-control study, patients with HS were recruited from the Dermatological Clinic at the Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy. Biopsy specimens were analyzed at the Histology Section of the Department of Clinical and Molecular Sciences. Participants included 11 patients with HS and 9 healthy controls, who were recruited into the study between January 20, 2015, and September 20, 2016, and underwent punch biopsy from axillary skin. None of the participants had received any antibiotics (systemic or topical therapy) within almost 12 weeks before the study. Main Outcomes and Measures: The immunophenotypic profile of MSCs was characterized following the minimal criteria established by the International Society for Cellular Therapy for the identification of MSCs. Levels of 12 cytokines belonging to helper T-cell subtypes 1, 2, and 17 pathways were examined on the secretome of isolated cells by enzyme-linked immunoabsorbent assay. Results: Skin MSCs were characterized in 11 patients with HS (8 women and 3 men; mean [SD] age, 35.8 [7.9] years) and 9 healthy controls (7 women and 2 men; mean [SD] age, 36.7 [6.9] years). The healthy controls were matched with patients with HS for body mass index. Mesenchymal stem cells isolated from patients with HS (HS-MSCs) and from healthy controls (C-MSCs) met the International Society for Cellular Therapy minimal criteria. Compared with C-MSCs, cytokine analyses of HS-MSCs revealed statistically significant overexpression of interleukin (IL) 6 (median [interquartile range {IQR}], 8765.00 [7659.00-9123.00] vs 2849.00 [2609.00-3001.00] pg/mL; P = .008), IL-10 (median [IQR], 29.46 [26.35-35.79] vs 21.36 [19.89-23.33] pg/mL; P = .004), IL-12 (median [IQR], 15.25 [13.27-16.25] vs 11.89 [10.73-12.33] pg/mL; P = .03), IL-17A (median [IQR], 15.24 [13.23-17.24] vs 11.24 [10.28-11.95] pg/mL; P = .008), tumor necrosis factor (median [IQR], 42.54 [42.20-43.94] vs 32.55 [31.78-33.28] pg/mL; P = .004), transforming growth factor ß1 (median [IQR], 1728.00 [1535.00-1979.00] vs 500.80 [465.00-634.50] pg/mL; P = .004), and interferon γ (median [IQR], 11.49 [10.71-12.35] vs 9.45 [9.29-10.01] pg/mL; P = .005). Conclusions and Relevance: Mesenchymal stem cells isolated from the skin of patients with HS seem to be activated toward an inflammatory status. The imbalance between proinflammatory and anti-inflammatory activities of MSCs favors the hypothesis of their pathogenic involvement in HS.

Botulinum Toxin Off-Label Use in Dermatology: A Review.

BACKGROUND: Botulinum toxin is a neurotoxin produced by the bacterium Clostridium botulinum which causes a flaccid muscle paralysis. It is currently used for aesthetic treatments and in the focal hyperhidrosis. Recently, botulinum toxin has also been used experimentally in many other dermatological conditions with good results. OBJECTIVE: To review and analyze the possible botulinum toxin off-label applications published. METHODS: A retrospective review of the published data was conducted. CONCLUSIONS: this potent drug can lead to several off-label indications of interest for dermatologists. Further clinical trials are still needed to better understand the real efficacy and safety of these applications and to standardize injection and dose protocols.

TNF-α inhibitors reduce the pathological Th1 -Th17 /Th2 imbalance in cutaneous mesenchymal stem cells of psoriasis patients.

Psoriasis is a disease characterized by an imbalance between Th1 and Th17 and Th2 inflammatory axes, in which cutaneous mesenchymal stem cells (MSCs) are early involved, as they show a greater relative expression of several genes encoding for Th1 and Th17 cytokines. Therapeutic implications of TNF-α inhibitors on differentiated skin cells have been largely described in psoriasis; however, their effects on MSCs derived from patients with psoriasis have been only partially described. The aim of this work was to evaluate the effect of TNF-α inhibitors on cytokine milieu expressed by MSCs isolated from the skin of patients with psoriasis. Resident MSCs from skin of patients with psoriasis and healthy subjects have been isolated, characterized and profiled by PCR and ELISA for the expression of 22 cytokines involved in Th1 , Th2 and Th17 pathways, both before and after 12 weeks therapy with TNF-α inhibitors. The administration of TNF-α inhibitors for 12-weeks acts on MSCs as follows: it reduces the expression of several Th1 -Th17 cytokines whose levels are elevated at baseline (IL-6, IL-8, IL-12, IL-23A, IFN-γ, TNF-α, CCL2, CCL20, CXCL2, CXCL5, IL-17A, IL-17C, IL-17F, IL-21, G-CSF). Similarly, it enhances the expression of several Th2 cytokines which are underexpressed at baseline (IL-2, IL-4, IL-5), reducing the expression of those overexpressed at baseline (TGF-ß and IL-13). TNF-α inhibitors could contribute to reduce the pathological imbalance between the Th1 -Th17 vs Th2 axis in MSCs of patients with psoriasis.

Role of mesenchymal stem cells in the pathogenesis of psoriasis: current perspectives.

Mesenchymal stem cells (MSCs) are multipotent nonhematopoietic stromal cells studied for their properties and importance in management of several skin diseases. This review collects and analyzes the emerging published data, which describe the function of MSCs in the pathogenesis of psoriasis.

The effect of etanercept on vascular endothelial growth factor production by cutaneous mesenchymal stem cells from patients with psoriasis.

OBJECTIVE: To evaluate prospectively the effect of etanercept (a tumour necrosis factor [TNF]-α inhibitor) on vascular endothelial growth factor (VEGF) production by mesenchymal stem cells (MSC) from patients with psoriasis. METHODS: MSCs from lesional and perilesional skin were isolated, cultured and characterized. VEGF production was evaluated at baseline and after 12 weeks' etanercept treatment. RESULTS: Etanercept treatment resulted in significant reductions in VEGF production compared with baseline in both lesional MSCs (256.42 ± 3.07 pg/ml per 106 cells at baseline vs 27.66 ± 2.03 pg/ml per 106 cells after treatment) and perilesional MSCs (235.03 ± 2.52 pg/ml per 106 cells vs 41.65 ± 4.72 pg/ml per 106 cells). CONCLUSIONS: Etanercept reduces the production of VEGF in MSCs, which may modulate angiogenesis and contributes towards preventing the start of the "psoriatic march".

Efficacy, safety and tolerability of field treatment of actinic keratosis with ingenol mebutate 0.015 % gel: a single center case series.

INTRODUCTION: Actinic keratosis (AK) is a cutaneous intraepithelial neoplasm appearing within areas referred as 'fields of cancerization'. AK can progress to invasive squamous cell carcinoma. Treatments that target both clinically visible and subclinical AKs in cancerization fields are able to reduce the risk of malignant progression. Ingenol mebutate gel is a new effective topical therapy for AK, used once daily for 2 or 3 days depending on the location of lesions. CASE DESCRIPTION: Three elderly patients with multiple non-hypertrophic AKs within a contiguous 25-cm(2) treatment area on the face or scalp were treated with ingenol mebutate 0.015 % gel once daily for three consecutive days and followed up over a period of 57 days. DISCUSSION AND EVALUATION: Although individual local responses to treatment varied, all patients had total clearance of AK lesions without any sign of recurrence. In addition, all patients said that they were satisfied with the effectiveness of ingenol mebutate treatment and the aesthetic outcome, and would be prepared to use this agent again to treat AK in the future, if necessary. CONCLUSIONS: These three cases demonstrate that ingenol mebutate 0.015 % gel is effective and well tolerated in a clinical setting, with effective clearance of AK lesions present on the face and scalp, and good patient acceptability.

Pseudoxanthoma elasticum and skin: Clinical manifestations, histopathology, pathomechanism, perspectives of treatment.

Pseudoxantoma elasticum (PXE), also known as Groenblad-Strandberg syndrome, is a rare heritable disease with an estimated prevalence of 1:50,000 in the general population. PXE is considered a prototype of multisystem ectopic mineralization disorders and it is characterized by aberrant mineralization of soft connective tissue with degeneration of the elastic fibers, involving primarily the eyes, the cardiovascular system, and the skin. Cutaneous lesions consist of small, asymptomatic, yellowish papules or larger coalescent plaques, typically located on the neck and the flexural areas. PXE is caused by mutations in the ABCC6 (ATP-binding cassette subfamily C member 6) gene that encodes a transmembrane ATP binding efflux transporter, normally expressed in the liver and the kidney; however, the exact mechanism of ectopic mineralization remains largely unknown. The histological examination of cutaneous lesions, revealing accumulation of pleomorphic elastic structures in middermis, is essential for the definitive diagnosis of PXE, excluding PXE-like conditions. PXE is currently an intractable disease; although the cutaneous findings primarily present a cosmetic problem, they signify the risk for development of ocular and cardiovascular complications associated with considerable morbidity and mortality. The purpose of this review is to present a comprehensive overview of this rare form of hereditary connective tissue disorders, focus on the pathogenesis, the clinical manifestation, and the differential diagnosis of PXE. Emphasis is also placed on the management of cutaneous lesions and treatment perspectives of PXE.