Alclometasone 0.05% cream

Neuroligins are synaptic cell adhesion proteins with a role in synaptic function, implicated in neurodevelopmental disorders. The autism spectrum disorder-associated substitution Arg451Cys (R451C) in NLGN3 promotes a partial misfolding of the extracellular domain of the protein leading to retention in the endoplasmic reticulum (ER) and the induction of the unfolded protein response (UPR). The reduced trafficking of R451C NLGN3 to the cell surface leads to altered synaptic function and social behavior. A screening in HEK-293 cells overexpressing NLGN3 of 2662 compounds (FDA-approved small molecule drug library), led to the identification of several glucocorticoids such as alclometasone dipropionate, desonide, prednisolone sodium phosphate, and dexamethasone (DEX), with the ability to favor the exit of full-length R451C NLGN3 from the ER. DEX improved the stability of R451C NLGN3 and trafficking to the cell surface, reduced the activation of the UPR, and increased the formation of artificial synapses between HEK-293 and hippocampal primary neurons. The effect of DEX was validated on a novel model system represented by neural stem progenitor cells and differentiated neurons derived from the R451C NLGN3 knock-in mouse, expressing the endogenous protein. This work shows a potential rescue strategy for an autism-linked mutation affecting cell surface trafficking of a synaptic protein.

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Lichen nitidus is a chronic skin disease characterized by scattered shiny papules and is common among relatively young individuals. We report a persistent rash covering the body of a 6-year-old boy, unresponsive to prior treatments like moisturizers and topical steroids. Clinical examination revealed small yellow papules predominantly distributed on the trunk, around the eyes, and clustered around the elbow and knee fossa. Histopathological analysis showed a localized infiltrate of lymphocytes and basal epithelial cells, along with giant cells. The overlining rete ridges extended to surround the inflammatory cells, resembling a claw clutching a ball image. Topical treatment with alclometasone dipropionate ointment was more effective compared to maxacalcitol. Remarkably, after about 3 months of treatment, the rash had completely disappeared. We summarized treatments of lichen nitidus in Japan. Maxacalcitol had never been tried. In this report, we demonstrated the effectiveness of the steroid ointment compared to maxacalcitol through the clinical course.

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This study reports the discovery and structural characterization of a novel polymorph, designated as Form III, of Alclometasone dipropionate, a corticosteroid commonly used in the treatment of inflammatory dermatoses. Form III was obtained by modifying the crystallization conditions reported in prior art and was thoroughly characterized using Powder X-ray Diffraction (PXRD), Fourier Transform Infrared (FT-IR) spectroscopy, melting-point determination, Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), including its first derivative (DTG), optical microscopy, and Scanning Electron Microscopy (SEM). In parallel, pure Form II, previously observed only in mixtures with Form I, was successfully isolated and characterized using the same analytical techniques. Both forms were compared in terms of structural, thermal, and morphological properties. PXRD analysis revealed that Form III crystallizes in a triclinic system; FT-IR spectroscopy revealed unique vibrational signatures, and microscopy showed rod-like crystal morphology. The discovery of Form III expands the current understanding of the solid-state landscape of Alclometasone dipropionate and opens opportunities for the identification of new industrial purification methods for the compound.

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The safety and efficacy of using topical corticosteroids (TCS) in the treatment of atopic dermatitis (AD) has long been established.1 A recent Cochrane review analyzing 291 randomized trials found that potent and very potent topical steroids are among the most effective treatments for improving patient-reported symptoms and clinician-reported signs of atopic dermatitis.2 An additional study by Guttman-Yassky et al. found that very high potency steroids had improved clinical outcomes compared to high potency steroids for the treatment of atopic dermatitis.3 The previously mentioned Cochrane review noted that skin thinning, a common concern with high potency topical steroids, was not associated with short-term use (<16 weeks) of any topical steroid potency.2 Despite this evidence, fear of topical steroids, particularly very high potency topical steroids, is widespread among parents and some providers. Use of steroid ladders for the treatment of atopic dermatitis is a common strategy used by dermatologists to employ high frequency, high potency topical steroids for a limited period of time during an atopic dermatitis flare, though little has been written about this approach in the literature. One article published in 2019 described the “Schachner Ladder,” which involves treatment with topical clobetasol twice daily for 3–5 days, triamcinolone twice daily for 3–5 days, and alclometasone twice daily for 3–5 days, followed by maintenance therapy with topical calcineurin inhibitors (TCI) and phosphodiesterase-4 (PDE-4) inhibitors.4 Despite its common clinical use, no outcome or safety data have been reported on the use of a steroid ladder for the treatment of atopic dermatitis. This article aimed to provide efficacy and safety data on the use of a well-established steroid ladder, referred to as the 5–10–15 plan, used in clinical practice at the University of Virginia when either a new or established pediatric/adolescent patient presents with a severe (IGA score 4) AD flare. The 5–10–15 plan includes a super high potency (Group 1) TCS twice daily for 5 days followed by a high potency (Group 2 or 3) TCS twice daily for 10 days, and finally a medium potency (Group 4) TCS twice daily for 15 days. The regimen is discussed in length with the patient and any family members present, and a printed handout with written instructions is provided at the end of the appointment (Figure 1). Only enough medication is provided to complete the protocol. After completing the 5–10–15 plan, response to treatment is assessed, and maintenance therapy (e.g., low potency TCS, TCI, PDE-4 inhibitor) is initiated depending on the severity of the disease. This single-center, retrospective study was approved by the local institutional review board (IRB #HSR220416). UVA's electronic medical records were searched for patients treated with the 5–10–15 plan from January 1, 2016 to October 31, 2022. Patients were excluded from the study based on the following criteria: those who initiated systemic therapy at the same time as the 5–10–15 plan, those with no follow-up data available, those who were prescribed the 5–10–15 plan but never initiated it, those with a diagnosis other than AD, those who were prescribed the 5–10–15 plan by an outside provider, and duplicate patients. Outcome and side effect data were collected from the original follow-up appointment at 1 month after completion of the 5–10–15 plan, at 2–7 months while on the maintenance regimen, and at the most recent follow-up appointment. Statistical analyses were performed between categorical variables using chi-squared analyses and numerical variables using t-test analyses. A p-value less than 0.05 was considered statistically significant. A total of 445 patients met the initial search criteria. Of those, 198 patients were excluded. This left 247 patients who had a 1-month follow-up appointment following the initiation of the 5–10–15 plan, 153 patients who had a 2- to 7-month follow-up appointment following the initiation of a steroid maintenance plan, and 129 patients who had additional long-term follow-up appointments. The age of the included patients ranged from <1 month to 22 years. Twenty-one variations of the 5–10–15 plan were utilized. The modifications of steroids utilized were based on variability in insurance approval. The most used regimen was halobetasol 0.05% ointment for 5 days, fluocinonide 0.05% ointment for 10 days, and triamcinolone 0.1% ointment for 15 days (107 patients). The second most used regimen included clobetasol 0.05% ointment for the first 5 days but was otherwise identical to the first regimen (103 patients). There were no statistically significant differences in safety or efficacy between these two regimens. In regard to efficacy, among the 247 patients who completed the 5–10–15 plan and attended their 1 month follow-up appointment, 209 patients (85%) improved, 28 patients (11%) improved initially then flared when they stepped down to a less potent steroid while on the 5–10–15 regimen, 6 patients (2%) did not experience any effect, and 4 patients (2%) worsened. Amongst the 153 patients who were placed on a 3-month topical steroid maintenance regimen following the 5–10–15 plan and attended their follow-up appointment, 114 patients (74.5%) continued to be stable on the maintenance regimen, while 39 patients (25.5%) worsened on the maintenance regimen. Of the patients who were not lost to follow-up, 62 patients (48%) were able to be maintained on topical therapy alone, while 67 patients (52%) were ultimately placed on systemic therapy. Based upon the authors' clinical experiences, systemic therapy was more easily approved by insurance companies for patients who had failed the 5–10–15 plan as there was now documentation of topical steroid treatment inefficacy. Amongst the 247 patients who completed the 5–10–15 plan and attended their 1-month follow-up appointments, 11 patients reported side effects. Five patients (2%) reported subjective skin atrophy at the site of application, though objective skin atrophy was not found for any patients during the provider's visual examination. Three patients (1%) reported burning with the application of the topical steroid, one patient (<1%) reported muscle spasms, one patient (<1%) reported agitation, and one patient (<1%) reported hair thinning. Of the 153 patients on the 3-month maintenance regimen, three patients reported side effects (one patient reported subjective atrophy, and two reported irritation/pruritus). Among the 62 patients on long-term topical steroid maintenance who attended their final follow-up, three patients reported side effects (one patient reported subjective atrophy and two reported burning with application). In conclusion, the 5–10–15 plan is a standardized approach that clinicians can safely and effectively utilize in their practice for the treatment of severe AD flares in pediatric and adolescent patients. Nicole Edmonds: Conceptualization; investigation; writing – original draft; methodology; validation; visualization; writing – review and editing; formal analysis; project administration; data curation; supervision. Patricia Zhao: Writing – original draft; writing – review and editing; investigation; conceptualization. Aaron D. Smith: Investigation; writing – review and editing. Monica Lawrence: Conceptualization; supervision; data curation; resources; project administration; writing – review and editing. Barrett J. Zlotoff: Conceptualization; writing – review and editing; project administration; data curation; supervision; resources. The authors have no conflict of interest to declare. The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer-review/10.1111/pai.70082.

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