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.

The expression of genes encoding for Th1, Th2 and Th17 cytokines has been extensively evaluated in differentiated skin cells of psoriatic patients. The microenvironment exerts a control on the phenotype of resident mesenchymal stem cells (MSCs) into the skin of psoriasis patients. Aim of the study was to extensively evaluate the relative expression of 43 genes encoding for Th1, Th2 and Th17 cytokines in MSCs isolated from skin of psoriasis patients. MSCs resident into psoriatic skin were isolated, characterized and profiled by PCR array for the relative expression of genes encoding for cytokines involved in Th1, Th2 and Th17 pathways. MSCs isolated from the skin of healthy subjects were used as control. The MSCs isolated from skin of psoriasis patients showed a greater relative expression of the most part of the analyzed genes encoding for Th1 and Th17 cytokines: INF-γ, CCR5, CXCL9, CXCL10, IL6, IL8, TNF-α, IL23A, CCL2, CCL20, CXCL2, CXCL5, IL17C, IL17F, IL17RA, IL21, TLR2 than healthy subjects. On the contrary, the relative expression of genes encoding for Th2 cytokines: CCL1, CCL22, CXCL12, IL2, IL3, IL4, IL13B, IL 22, IL 27, TGF-β1, was similar between the MSCs isolated from psoriasis and healthy subjects. In conclusion, the MSCs isolated from psoriasis show an imbalance between the Th1-Th17 and Th2 pathways, which reflects the well-known abnormal balance observed in differentiated skin cells. This evidence could strengthen the hypothesis of an early involvement of resident MSCs in the pathogenesis of psoriasis.

The profile of MSCs obtained from patients with chronic AD retraces the Th1/Th17 cell environment observed in differentiated cells of chronic AD. This evidence could open a new scenario in the pathogenesis of AD, according to which the inflammatory process may involve MSCs early on.

focal hyperhidrosis, aesthetic medicine and neurological conditions with a strong efficacy and safety profile [1][2][3][4][5][6][7] . The enormous therapeutic potential of this drug contributed to a number of broad applications, especially in dermatological diseases. A large number of these indications are still lacking shared, approved protocols for dilution, doses, and timing of follow-up and retreatment. Also the injection techniques are still debated, depending on the operator's experience, angle of injection and depth. We have previously published a novel injection approach consisting in a needle adaptor that ensures a uniform administration of the toxin [3] . The aim of this review was to collect and analyze the published data concerning the most relevant off-label indications of BoNT-A. MethodsA PubMed search from 1950 to July 2016 was performed to identify any reports on the use of botulinum toxin in off-label indications concerning dermatology. We detected these articles using the terms "botulinum toxin dermatology," "botulinum toxin treatment," "botulinum toxin off-label," and meshed with a secondary search of studies pertaining to each indication. Only studies in English were reviewed. All studies that met the criteria were included and summarized in this review. KeywordsBotulinum toxin · Off-label therapy · Keloids · Hidradenitis suppurativa · Folds dermatitis Abstract 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.

Our results confirm that psoriasis patients with more severe disease, can have hyperhomocysteinaemia, without regard to disease duration or joint involvement. Hyperhomocysteinaemia is not influenced by a target therapy for psoriasis and it is as greater as psoriasis severity. However, limitation of our study is the relatively small number of cases. Homocysteine plasmatic levels should be advisable as a further independent risk factor for cardiovascular disease in psoriasis patients.