Dermatitis in community pharmacies: a survey on italian pharmacists’ management and implications on corticophobia

Community pharmacists represent an important resource for the promotion of a safer and more effective self-management of common skin diseases, as well as the provision of educational support on therapies prescribed by clinicians, ultimately improving patients’ adherence. In this study, a semi-structured survey was administered to 154 Italian community pharmacists, in order to acquire information on their counseling activity on dermatological disorders. Collected data provide an overview on the frequency and methodology of counseling offered in Italian community pharmacies, identifying knowledge gaps and misbeliefs. In particular, an overall negative opinion on topical corticosteroid therapy emerged among pharmacists, unveiling a phenomenon previously described as corticophobia. Starting from this observation, we discuss the risks for patients’ adherence, associated with corticophobia among pharmacists. Lastly, we briefly report on the main tools desired by pharmacists to improve their education on dermatology, envisioning their implementation with the aim of a more effective counseling

Safety review of phenoxyethanol when used as a preservative in cosmetics

Phenoxyethanol, or 2-phenoxyethanol, has a large spectrum of antimicrobial activity and has been widely used as a preservative in cosmetic products for decades. It is effective against various Gram-negative and Gram-positive bacteria, as well as against yeasts, and has only a weak inhibitory effect on resident skin flora. According to the European Scientific Committee on Consumer Safety, phenoxyethanol is safe for all consumers \u2013 including children of all ages \u2013 when used as a preservative in cosmetic products at a maximum concentration of 1%. Adverse systemic effects have been observed in toxicological studies on animals but only when the levels of exposure were many magnitudes higher (around 200-fold higher) than those to which consumers are exposed when using phenoxyethanol-containing cosmetic products. Despite its widespread use in cosmetic products, phenoxyethanol is a rare sensitizer. It can be considered as one of the most well-tolerated preservatives used in cosmetic products

Molecular signature of retinoic acid treatment in acute promyelocytic leukemia

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia characterized by a block of differentiation at the promyelocytic stage. APL patients respond to pharmacological concentrations of all-trans retinoic acid ( RA) and disease remission correlates with terminal differentiation of leukemic blasts. The PML/RAR oncogenic transcription factor is responsible for both the pathogenesis of APL and for its sensitivity to RA. In order to identify physiological targets of RA therapy, we analysed gene expression profiles of RA-treated APL blasts and found 1056 common target genes. Comparing these results to those obtained in RA-treated U937 cell lines revealed that transcriptional response to RA is largely dependent on the expression of PML/RAR. Several genes involved in the control of differentiation and stem cell renewal are early targets of RA regulation, and may be important effectors of RA response. Modulation of chromatin modifying genes was also observed, suggesting that specific structural changes in local chromatin domains may be required to promote RA-mediated differentiation. Computational analysis of upstream genomic regions in RA target genes revealed nonrandom distribution of transcription factor binding sites, indicating that specific transcriptional regulatory complexes may be involved in determining RA response

Cytokine and Chemokine Profile in Amicrobial Pustulosis of the Folds: Evidence for Autoinflammation

Autoinflammation has recently been suggested in the pathogenesis of neutrophilic dermatoses but systematic studies on their cytokine profile are lacking. Notably, amicrobial pustulosis of the folds (APF), classified among neutrophilic dermatoses, has been studied only in small case series.In our University Hospital, we conducted an observational study on 15 APF patients, analyzing their clinical and laboratory features with a follow-up of 9 months to 20 years. Skin cytokine pattern of 9 of them was compared to that of 6 normal controls.In all patients, primary lesions were pustules symmetrically involving the skin folds and anogenital region with a chronic-relapsing course and responding to corticosteroids. Dapsone, cyclosporine, and tumor necrosis factor blockers were effective in refractory cases. In skin samples, the expressions of interleukin (IL)-1\u3b2, pivotal cytokine in autoinflammation, and its receptors I and II were significantly higher in APF (P\u200a=\u200a0.005, 0.018, and 0.034, respectively) than in controls. Chemokines responsible for neutrophil recruitment such as IL-8 (P\u200a=\u200a0.003), CXCL 1/2/3 (C-X-C motif ligand 1/2/3) (P\u200a=\u200a0.010), CXCL 16 (P\u200a=\u200a0.045), and RANTES (regulated on activation, normal T cell expressed and secreted) (P\u200a=\u200a0.034) were overexpressed. Molecules involved in tissue damage like matrix metalloproteinase-2 (MMP-2) (P\u200a=\u200a0.010) and MMP-9 (P\u200a=\u200a0.003) were increased.APF is a pustular neutrophilic dermatosis with a typical distribution in all patients. The disorder may coexist with an underlying autoimmune/dysimmune disease but is often associated only with a few autoantibodies without a clear autoimmunity. The overexpression of cytokines/chemokines and molecules amplifying the inflammatory network supports the view that APF has an important autoinflammatory component

Paradoxical Autoinflammatory Skin Reaction to Tumor Necrosis Factor Alpha Blockers Manifesting as Amicrobial Pustulosis of the Folds in Patients With Inflammatory Bowel Diseases

The therapy of inflammatory bowel disease, particularly with tumor necrosis factor (TNF) blockers, may be associated with a number of cutaneous adverse effects, including psoriasis-like, eczema-like, and lichenoid eruptions. Other rare skin complications are neutrophilic dermatoses such as amicrobial pustulosis of the folds (APF), which is a chronic relapsing pustular disorder classified in this spectrum.The authors analyzed clinical, histopathologic, and cytokine expression profiles of 3 inflammatory bowel disease patients with APF triggered by adalimumab (patient 1) and infliximab (patients 2 and 3).All 3 patients presented with sterile pustules involving the cutaneous folds, genital regions, and scalp 6 months after starting adalimumab (patient 1) and 9 months after starting infliximab (patients 2 and 3). Histology was characterized by epidermal spongiform pustules with a dermal neutrophilic and lymphocytic infiltrate. Tumor necrosis factor blocker withdrawal associated with topical and systemic corticosteroids induced complete remission of APF in all 3 patients. The expressions of interleukin (IL)-1 beta and its receptors as well as TNF alpha and its receptors were significantly higher in APF than in controls. Also IL-17, leukocyte selectin, and chemokines, such as IL-8, [C-X-C motif] chemokine ligand 1/2/3 (C\u200a=\u200acysteine, X\u200a=\u200aany amino acid), [C-X-C motif] chemokine ligand 16 (C\u200a=\u200acysteine, X\u200a=\u200aany amino acid), and RANTES (regulated on activation, normal T cell expressed and secreted) were significantly overexpressed. Finally, the authors found significant overexpression of both metalloproteinases 2/9 and their inhibitors 1/2.The observation of 3 patients with APF following anti-TNF therapy expands not only the clinical context of APF but also the spectrum of anti-TNF side effects. Overexpression of cytokines/chemokines and molecules amplifying the inflammatory network supports the view that APF is autoinflammatory in origin