Search Results (11)

Vitiligo, an autoimmune disorder causing depigmented skin patches, includes two types, segmental (SV) and non-segmental (NSV). Previously, NSV was off-label treated using Calcineurine inhibitors (Tacrolimus and Pimecrolimus). In 2022, the FDA approved Ruxolitinib cream, targeting the JAK/STAT pathway for NSV treatment based on promising results. This research conducts a retrospective descriptive safety assessment of Tacrolimus, Pimecrolimus, and Ruxolitinib safety in vitiligo treatment, utilizing the FDA Adverse Event Reporting System (FAERS) database spanning the period from 2013 to 2023 and including patients aged 2 years and above, encompassing both brand and generic names. A total of 844 adverse event reports involving 388 patients were extracted and categorized into dermatological and systemic groups for analysis. Tacrolimus resulted in 12 hospitalizations, two life-threatening events, and four disabilities. Pimecrolimus exhibited urticaria and pigmentation disorders, with tooth fracture as the primary systemic event. Pericarditis was the predominant systemic side effect of Ruxolitinib, followed by anemia, headache, and urosepsis. Local dermatological side effects reported were generally mild, not warranting treatment cessation. In conclusion, vitiligo significantly impacts patients’ psychological well-being, necessitating continuous post-marketing safety monitoring for topical medications. Full article

The etiopathogenesis and treatment response of sensitive skin remain poorly understood. We used 4-tert-butylcyclohexanol (4-TBLH) and 1% pimecrolimus ointment to treat sensitive skin in mice models constructed using tape stripping, propylene glycol, and capsaicin. This study aimed to further investigate the sensitivity and responsiveness of this sensitive mouse skin model. Sensitivity and responsiveness were assessed by measuring transepidermal water loss (TEWL), skin hydration, skin flakes, vascular dilatation, itching, stinging, and histological changes, including mast cell, lymphocyte, and granulocyte infiltration, tumor necrosis factor-α (TNF-α) expression, and transient receptor potential vanilloid 1 receptor (TRPV1) expression. The application of 4-TBLH and pimecrolimus revealed distinct responses in skin sensitivity indicators, including TEWL, capillary dilation, and mass cell activity, depending on the treatment timing and substance used. The prophylactic and therapeutic applications of 4-TBLH revealed distinct responses in skin sensitivity indicators, including skin flakes, TEWL, itching, stinging, epidermal thickness, mast cell activity, TNF-α, and TRPV1 expression. The prophylactic and therapeutic applications of pimecrolimus ointment revealed distinct responses in skin sensitivity indicators, including skin flakes, skin water content, itching, epidermal thickness, mast cell activity, CD45, CD11b, TNF-α, and TRPV1 expression. The mouse sensitive skin model demonstrates robust sensitivity and responsiveness to different treatment factors, and the model can be applied to the development of prophylactic and therapeutic medications for sensitive skin. Full article

Tinea incognito is a dermatophyte infection with atypical features, due to the use of topical or systemic steroids or other immunosuppressive medications. Delayed diagnosis, spread of the infection to critical body surfaces, resistance to antifungal drugs, and increased costs due to prolonged hospitalization and multiple treatment regimens often complicate tinea incognito. It can affect individuals of all ages and genders, but it is more common in children. Atypical clinical appearance often necessitates differentiation from other diseases such as eczema, seborrheic dermatitis, lupus erythematosus, psoriasis, or other non-fungal skin conditions. The treatment of tinea incognito usually involves discontinuation of topical steroids or other immunosuppressive medications. Preventive measures and management of the underlying fungal infection are necessary and can be achieved with antifungal drugs. Patients should wear loose cotton clothes, use boiling water for laundry, and iron their clothing before wearing them. Additionally, they should avoid sharing bed linens, towels, clothes, and shoes. This review aims to raise awareness of tinea incognito among health practitioners, provide tips for detecting the disorder, include it in the differentials, and evaluate the available diagnostic procedures. Full article

The aim of this study was to investigate whether subtle differences in molecular properties affected polymeric micelle characteristics and their ability to deliver poorly water-soluble drugs into the skin. D-α-tocopherol-polyethylene glycol 1000 was used to prepare micelles containing ascomycin-derived immunosuppressants—sirolimus (SIR), pimecrolimus (PIM) and tacrolimus (TAC)—which have similar structures and physicochemical properties and have dermatological applications. Micelle formulations were prepared by thin-film hydration and extensively characterized. Cutaneous delivery and biodistribution were determined and compared. Sub-10 nm micelles were obtained for the three immunosuppressants with incorporation efficiencies >85%. However, differences were observed for drug loading, stability (at the highest concentration), and their in vitro release kinetics. These were attributed to differences in drug aqueous solubility and lipophilicity. Differences between the cutaneous biodistribution profiles and drug deposition in the different skin compartments pointed to the impact of differences in thermodynamic activity. Therefore, despite their structural similarities, SIR, TAC and PIM did not demonstrate the same behaviour either in the micelles or when applied to the skin. These outcomes indicate that polymeric micelles should be optimized even for closely related drug molecules and support the hypothesis that drugs are released from micelles prior to skin penetration. Full article

Seborrheic dermatitis (SD) is a relapsing inflammatory skin disorder that affects the seborrheic areas of the body. Its etiology is not completely elucidated; however, the link between disease exacerbations and the proliferation of Malassezia spp., along with the good response to antifungal agents, indicate the role of fungi in its pathophysiology. Sertaconazole nitrate is a relatively new imidazole antifungal agent with a particular structure, consisting in a benzothiophene ring similar to the indole ring of tryptophan, and it acts mainly through the inhibition of ergosterol synthesis and the formation of pores in the fungal cell membrane. The aim of our study was to evaluate the efficiency of sertaconazole 2% cream compared with other topical treatments in patients with SD. We performed an extensive literature search by browsing the PubMed database with the keyword combination “sertaconazole AND seborrheic dermatitis AND clinical trial”, which retrieved eight controlled clinical trials evaluating the effects of sertaconazole in SD. All of the clinical trials included a standard scoring index (SI). At 28 days since the beginning of the treatment, the sertaconazole regimen was associated with a significantly higher percentage of patients with mild SI and a lower percentage of patients with moderate or severe SI (odds ratio 0.51) than the other investigated treatments—hydrocortisone, ketoconazole, clotrimazole, metronidazole, pimecrolimus, and tacrolimus (odds ratio 1.95). In conclusion, treatment with sertaconazole 2% cream may represent an efficient alternative therapy for patients with SD. Full article

A high-performance liquid chromatography-tandem mass spectrometry method was established for the simultaneous determination of mycophenolic acid, mycophenolate mofetil, tacrolimus, rapamycin, everolimus and pimecrolimus in human whole blood by optimizing the QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) preparation method. Whole blood was extracted into ethyl acetate, salted out with anhydrous magnesium sulfate, and purified with ethylenediamine-N-propyl silane adsorbent. The supernatant was evaporated under nitrogen until dry and finally reconstituted in methanol. Chromatographic separation was performed on an Agilent Poroshell 120 EC-C18 column in methanol (mobile phase A)-water (optimized for 0.1% acetic acid and 10 mM ammonium acetate, mobile phase B) at a 0.3 mL·min⁻¹ flow rate. Electrospray ionization and positive ion multiple reaction monitoring were used for detection. The time for of analysis was 13 min. The calibration curves range of tacrolimus, rapamycin, everolimus and pimecrolimus were in the range of 1–100 ng·mL⁻¹, mycophenolate mofetil in the range of 0.1–10 ng·mL⁻¹ and mycophenolic acid at 10–1000 ng·mL⁻¹. All correlation coefficients were >0.993. The coefficients of variation (CV, %) for inter-day and intra-day precision were less than 10%, while the spiked recoveries were in the range of 92.1% to 116%. Our method was rapid, sensitive, specific, and reproducible for the simultaneous determination of six immunosuppressants in human whole blood. Importantly, our approach can be used to monitor drug concentrations in the blood to facilitate disease treatment. Full article

Background: Lichen sclerosus is the most common nonmalignant vulvar disease with morbidity in postmenopausal age. The first line of treatment is corticosteroid therapy. In case of insufficiency, tacrolimus or pimecrolimus can be provided. Photodynamic therapy (PDT) can be used as alternative way of treatment while symptoms recurrent despite other methods. Methods: the analyzed population of 182 women with diagnosis of lichen sclerosus treated using PDT was divided into three groups: patients with neoplastic disease or intraepithelial neoplasia; those with a positive family history of neoplastic disease; and a control group with no neoplastic disease and no familial history of neoplastic diseases. Results: Reduction of vulvar changes was assessed in the whole vulva in the groups as 21.9%, 21.2% and 21.8%, respectively. The most frequent symptom, itching, was reported to decrease in all groups, 39.3%, 35.5% and 42.5%, respectively. Improvement of quality of life was assessed in 91.3% of the whole group, stabilization of lichen sclerosus in 7.1% and progression in 1.6%. Conclusions: Photodynamic therapy gives positive results in most cases. Improvement after PDT is observed in objective vulvoscopic assessment and in subjective patients’ opinions. Neoplastic disease in the past can influence the effectiveness of PDT. Full article

Although pruritic external auditory canal (PEAC) is a relatively common symptom, particularly in the geriatric population, its pathophysiology and appropriate treatment remain to be elucidated. We compared the therapeutic efficacy of pimecrolimus, a topical calcineurin inhibitor (CI), and a moisturizing cream (MC) in patients with PEAC. Thirty-nine patients (73 ears) were prospectively enrolled and treated topically twice daily with the CI (n = 20, 39 ears) or the MC (n = 19, 34 ears) for two weeks. The change in itching sensation was evaluated subjectively using a self-questionnaire at immediately, one month, and two months after self-application, and objectively by changes in erythema grading. Although topical treatment with the CI resulted in a more rapid improvement than treatment with the MC in patients with PEAC, the final outcomes did not differ between the groups. Furthermore, similar improvements in erythema scores were noted. The results of this study suggest that the MC, which rejuvenates the normal physiological status of the ear canal skin, may greatly benefit those elderly patients more susceptible to PEAC, without any concerns about adverse events and underlying comorbidities. Expanding upon the understanding of the role of moisturizers in the treatment of pruritic ears merits attention, as this knowledge provides a good example of the clinical guidelines for the management of PEAC. Full article

A cyclic tetrapeptide Pro-Pro-Pheβ³ho-Phe (4B8M) was tested for immunosuppressive activity and potential therapeutic utility in several in vitro and in vivo mouse and human models. The tetrapeptide was less toxic for mouse splenocytes in comparison to cyclosporine A (CsA) and a parent cyclolinopeptide (CLA). The tetrapeptide demonstrated potent anti-inflammatory properties in antigen-specific skin inflammatory reactions to oxazolone and toluene diisocyanate as well to nonspecific irritants such as salicylic acid. It also inhibited inflammatory processes in an air pouch induced by carrageenan. In addition, 4B8M proved effective in amelioration of animal models corresponding to human diseases, such as nonspecific colon inflammation induced by dextran sulfate and allergic pleurisy induced by ovalbumin (OVA) in sensitized mice. The tetrapeptide lowered expression of EP1 and EP3 but not EP2 and EP4 prostaglandin E2 (PGE2) receptors on lipopolysaccharide-stimulated Jurkat T cells and ICAM-1 expression on human peripheral blood mononuclear cells (PBMC). Its anti-inflammatory property in the carrageenan reaction was blocked by EP3 and EP4 antagonists. In addition, 4B8M induced an intracellular level of PGE2 in a human KERTr keratinocyte cell line. In conclusion, 4B8M is a low toxic and effective inhibitor of inflammatory disorders with potential therapeutic use, affecting the metabolism of prostanoid family molecules. Full article

Plants of the genus Wikstroemia have long been used as traditional medicines to treat diseases like pneumonia, rheumatism, and bronchitis. This study was designed to determine the effect of chamaejasmine, a biflavonoid present in W. dolichantha, on atopic dermatitis (AD)-like skin lesions in a 2,4-dinitrochlorobenzene (DNCB)-induced murine model of AD. Initially, we examined the anti-allergic activities of ten flavonoids from W. dolichantha by measuring β-hexosaminidase release from RBL-2H3 cells. Subsequently, an SKH-1 hairless mouse model of AD was developed based on the topical application of DNCB. Chamaejasmine (0.5%) or pimecrolimus (1%, positive control) were applied to dorsal skins of DNCB-sensitized AD mice for two weeks. Serum IL-4 and IgE levels were determined using enzyme-linked immunosorbent assay kits and transepidermal water loss (TEWL) and skin hydration were measured using a Tewameter TM210 and a SKIN-O-MAT, respectively. Of the ten flavonoids isolated from W. dolichantha, chamaejasmine most potently inhibited DNP-specific IgE-induced degranulation in RBL-2H3 cells. Topical administration of chamaejasmine attenuated the clinical symptoms of DNCB-induced dermatitis (i.e., itching, dryness, erythema, and edema). Histological analyses demonstrated that dermal thickness and mast cell infiltration in dermis were significantly reduced by chamaejasmine. In addition, 0.5% chamaejasmine inhibited DNCB-induced increases in total IL-4 and IgE levels in serum, improved skin barrier function, and increased epidermis moisture. Our findings suggest chamaejasmine might be an effective therapeutic agent for the treatment of atopic diseases. Full article

While alkyl halides are valuable intermediates in synthetic organic chemistry, their use as bioactive motifs in drug discovery and medicinal chemistry is rare in comparison. This is likely attributable to the common misconception that these compounds are merely non-specific alkylators in biological systems. A number of chlorinated compounds in the pharmaceutical and food industries, as well as a growing number of halogenated marine natural products showing unique bioactivity, illustrate the role that chiral alkyl halides can play in drug discovery. Through a series of case studies, we demonstrate in this review that these motifs can indeed be stable under physiological conditions, and that halogenation can enhance bioactivity through both steric and electronic effects. Our hope is that, by placing such compounds in the minds of the chemical community, they may gain more traction in drug discovery and inspire more synthetic chemists to develop methods for selective halogenation. Full article