Vitamin A and analogs are widely used in dermatology, with retinoids being natural and synthetic vitamin A derivatives. Topical retinoids (especially tretinoin and tretinoin precursors) can diminish photoaging and contribute to the thickening and restoration of skin collagen. Retinoids used as therapeutic agents include oral retinoids (eg, isotretinoin, acitretin, alitretinoin, and bexarotene) and topical retinoids (eg, isotretinoin, tretinoin, adapalene, tazarotene, and trifarotene). Although retinoids have traditionally been used for skin disorders of keratinization, such as psoriasis, pityriasis rubra pilaris, Darier disease, and ichthyoses, there is a variety of indications of retinoids for the treatment of skin diseases, including diseases of the pilosebaceous unit such as acne vulgaris, pigmentary disorders such as melasma, or cutaneous malignancies such as cutaneous T-cell lymphoma. Other retinoids with distinct routes of administration (oral or topical) and distinct dosing or safety profiles are recommended for different skin disorders. We discuss the mode of action and indications of retinoids used as pharmacologic agents in dermatology and provide an update on their use, effectiveness, and tolerability.

Chronic hand eczema (CHE) is a frequent and heterogeneous condition associated with long-lasting symptoms, functional impairment, and high psychosocial and socioeconomic burden. Diagnostic evaluation relies on detailed history taking, physical examination, and patch testing, which remains the gold standard for identifying relevant sensitizations. Disease severity can be assessed with clinician-reported instruments, such as the Hand Eczema Severity Index, and patient-reported outcomes, particularly the Quality of Life in Hand Eczema Questionnaire (QOLHEQ). Management requires a structured, stepwise approach integrating preventive measures with pharmacological interventions. Topical corticosteroids remain the first-line treatment, whereas phototherapy and systemic options, including alitretinoin and immunosuppressants, are indicated in refractory cases. Recently, novel agents such as topical delgocitinib and biologics like dupilumab have expanded the therapeutic armamentarium, particularly for atopic CHE. Preventive strategies, implemented at primary, secondary, and tertiary levels, are crucial for reducing recurrences and improving long-term outcomes. Despite these advances, there is still a lack of standardized diagnostic tools, validated severity measures, and evidence-based treatment algorithms. Future efforts should focus on patient-centered, multidisciplinary care and further research to optimize disease control and quality of life in CHE.

Novel approaches to sensitize latently infected cells to apoptosis may provide additional methods to eliminate latent reservoirs. Prior research identified several retinoids as potential drugs that increase the sensitivity of HIV-infected cells to cell death. Retinoids are derivatives of vitamin A that target retinoid receptors causing antiproliferative and proapoptotic activity. Several are FDA-approved or in clinical trials. The aim of this study was to evaluate the ability of vitamin A, three of its natural metabolites, and nine synthetic derivatives to sensitize HIV-infected CD4 T cells to NK natural cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC). From the retinoids tested, alitretinoin, tazarotene acid, and AM80 significantly enhanced NK natural cytotoxicity in the presence of IL-15. Mechanistically, these retinoids increased NK degranulation upon target recognition in an HLA-F/KIR3DS1-dependent manner. Furthermore, these retinoids enhanced ADCC by transcriptionally increasing CD16 expression on NK cells. In conclusion, our study has identified at least three retinoids capable of enhancing NK natural cytotoxicity and ADCC against HIV-infected cells. These or other retinoids could be used to reduce HIV persistent reservoirs.IMPORTANCEThis study highlights how retinoids, compounds derived from vitamin A, can help the immune system target HIV-infected cells more effectively. HIV often hides in immune cells, making it difficult to fully eliminate the virus. We found that certain retinoids, including alitretinoin, tazarotene acid, and AM80, improve the function of natural killer (NK) cells-key immune cells that target infected cells. These retinoids boost NK cell activity by increasing their ability to release toxic molecules that kill infected cells and by enhancing their response to antibodies targeting HIV. This makes the infected cells more vulnerable to being eliminated. Since some of these retinoids are already approved for medical use, they could offer a promising way to reduce persistent HIV reservoirs in the body and improve efforts to cure the infection.

Hand eczema is a common inflammatory dermatosis in primary care, characterized by erythema, pruritus, scaling, fissures, and functional impairment. It encompasses various clinical and etiological forms, either acute or chronic, related to irritant, allergic, or atopic mechanisms. When the condition persists for more than three months or recurs at least twice within one year, it is defined as chronic hand eczema. This represents one of the most prevalent dermatoses, with substantial clinical, occupational, and psychosocial impact. Its multifactorial pathogenesis involves genetic predisposition, barrier dysfunction, and environmental exposures, particularly to occupational irritants and allergens. In primary care, the family physician plays a key role in the early recognition of hand eczema, patient education on skin care and preventive measures, and in identifying alarm signs that warrant referral to a dermatologist. A focused history and clinical examination enable diagnostic orientation and allow the initiation, from the first consultation, of appropriate topical treatment, emollient use, and protection against triggering factors. Referral should be considered in severe, refractory cases or those with significant functional or occupational impact, in order to assess advanced therapies such as phototherapy, alitretinoin, dupilumab, oral JAK inhibitors, or topical delgocitinib.

Canada’s Drug Agency (CDA-AMC) recommends that Anzupgo be reimbursed by public drug plans for the treatment of moderate to severe chronic hand eczema (CHE), if certain conditions are met. WHICH PATIENTS ARE ELIGIBLE FOR COVERAGE? Anzupgo should only be covered to treat adults (aged ≥ 18 years) with moderate to severe CHE who have had an inadequate response to, or cannot use, topical corticosteroids (TCSs). Patients must have tried appropriate topical therapy (emollients with or without TCSs) before starting Anzupgo. WHAT ARE THE CONDITIONS FOR REIMBURSEMENT? Anzupgo should only be reimbursed for patients who have received an adequate trial of appropriate topical therapy, when prescribed by — or in consultation with — a dermatologist or clinician experienced in the management of CHE, and the cost of Anzupgo should not exceed the total drug cost of alitretinoin. WHY DID CDA-AMC MAKE THIS RECOMMENDATION? • Evidence from 3 phase III clinical trials (the DELTA 1, DELTA 2, and DELTA FORCE trials) demonstrated that Anzupgo significantly reduced eczema severity and improved symptoms and health-related quality of life (HRQoL) compared with an inactive cream, and also showed comparable or greater efficacy than alitretinoin, the only approved therapy for CHE in Canada. Anzupgo was generally well tolerated, with mostly mild local reactions and no systemic safety concerns. • Based on the CDA-AMC assessment of the health economic evidence, Anzupgo does not represent good value to the health care system at the public list price. The Canadian Drug Expert Committee (CDEC) determined that there is not enough evidence to justify a greater annual cost for Anzupgo compared with alitretinoin. • Clinical experts and patient groups confirmed a substantial unmet need for an effective nonsteroidal topical option that improves symptoms such as itch and pain, and preserves hand function. • The sponsor-submitted budget-impact analysis (BIA) was associated with major limitations that precluded an accurate estimation of the budget impact.

Chronic hand eczema (CHE) affects up to 10% of the general population and is associated with significant physical discomfort, impaired hand function, and reduced quality of life, yet effective long-term treatment options remain limited. Delgocitinib cream, a nonsteroidal topical pan-JAK inhibitor, has demonstrated high efficacy and safety in adult Phase 3 pivotal trials, significantly improving clinical signs, symptoms, and quality of life for patients across diverse CHE subtypes. Comparative studies suggest delgocitinib offers superior or similar benefits to systemic therapies like the oral retinoid alitretinoin and the biologic dupilumab, with negligible systemic exposure. These findings support delgocitinib cream as an innovative and promising topical therapy addressing a critical unmet need in CHE patient management.

Delgocitinib is a pan-Janus kinase (JAK) inhibitor that targets all four JAK isoforms. Delgocitinib 20 mg/g cream (Anzupgo[®] 20 mg/g), a non-steroidal therapy, is the first topical treatment indicated in the EU for moderate to severe chronic hand eczema (CHE) in adults for whom topical corticosteroids are inadequate or inappropriate. In two 16-week, double-blind, vehicle-controlled, multinational phase III trials, twice-daily delgocitinib 20 mg/g cream improved the signs and symptoms of CHE and improved health-related quality of life in adults with moderate to severe disease; efficacy was maintained with as-needed treatment in a subsequent 36-week open-label extension study. Moreover, an active-controlled trial demonstrated that delgocitinib 20 mg/g cream had superior efficacy and apparent improved tolerability versus oral alitretinoin in adults with severe CHE. Delgocitinib 20 mg/g cream was well tolerated locally in clinical trials, with low systemic exposure with topical application. In summary, current data show that delgocitinib 20 mg/g cream is an efficacious and well tolerated treatment for moderate to severe CHE in adults. As the first topical treatment specifically approved for CHE, it presents a valuable new non-steroidal option in patients for whom topical corticosteroids are inadequate or inappropriate.

In Malaysia, the study on autism spectrum disorders (ASD) is limited. Most studies only focus on gene neuroligin 3 (NLGN3), NLGN4X, neurexin 1 (NRXN1) and SH3. This study focuses on the N-methyl-D-aspartate (NMDA) that was believed to have a significant effect on ASD. In this study, potential compounds and drugs that can restore receptor function in autistic patients were analysed. This research used an effective in silico method known as drug-repurposing to discover and rediscover drugs and analyse the binding of potential compounds or drugs to the NMDA receptor. AMPA and DOCK4 were used as controls in this study. Using a trusted server, Drug ReposER, 13 potential compounds or drugs that bind to NMDAR were identified. Then, proceed to the docking of potential compounds or drugs that bind to the NMDA receptor using Autodock Vina, Autodock, Hdock and CB dock and three drugs were selected that have the best binding score to NMDA, AMPA and DOCK4. The drugs were alitretinoin, salicylic acid and indinavir, respectively. Next, molecular dynamics simulations were performed with all selected compounds to study drug-protein binding, with detailed analysis of bond stability using root-mean-square fluctuation (RMSF) oscillations. Finally, ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) predictions identify 4-androstenedione, tryptophan, carbocisteine and vitamin A as having minimal toxic effects. This study showed that alitretinoin, which was known to treat skin lesions from Kaposi's sarcoma, might have the ability to reverse the effect in ASD, particularly in NMDA receptors, potentially making a significant impact on the field of neurology and psychiatry.

Chronic hand eczema is a heterogeneous, fluctuating, and long-lasting disease affecting the hands and wrists that substantially affects quality of life. For severe chronic hand eczema, topical corticosteroids are often unsatisfactory and systemic treatment can be required. The aim of the head-to-head, phase 3 DELTA FORCE trial was to evaluate the efficacy and safety of topical delgocitinib cream versus oral alitretinoin, the only currently approved systemic drug for severe chronic hand eczema.