Rosacea is a chronic inflammatory skin disorder characterized by persistent erythema, flushing, papules, pustules, and telangiectasia, predominantly affecting the central face. Topical calcineurin inhibitors (TCIs), including tacrolimus and pimecrolimus, are approved for atopic dermatitis(AD) but have also been used off-label in rosacea and other facial inflammatory dermatoses. Evidence for their use in rosacea is limited and mixed. Some small uncontrolled studies have reported clinical improvement, particularly with pimecrolimus. In contrast, rosaceiform dermatitis has been reported during treatment with both tacrolimus and pimecrolimus, including cases with increased Demodex density. These reports highlight the need to distinguish primary rosacea from steroid-induced rosacea-like dermatitis(SIRD) and other rosaceiform eruptions associated with topical therapies. Tacrolimus and pimecrolimus have also been studied in different clinical settings, and the available evidence does not support treating them as interchangeable. Current guidelines and consensus statements provide no consistent recommendation for TCI use in primary rosacea. This review summarizes the clinical evidence for the potential benefits and adverse effects of TCIs in rosacea and discusses their possible role in selected clinical settings.

The lines of Blaschko represent epithelial cell migration during embryonic development. Rare forms of cutaneous lupus erythematosus may manifest along these lines, and lesions are termed Blaschko-linear lupus erythematosus (BLE). The purpose of this case study is to present a rare manifestation of linear cutaneous lupus erythematosus following the lines of Blaschko in a pediatric patient. To date, there are very few reports of BLE. We present a 17-year-old female with a 2-month history of a mildly tender growing lesion along the right nasofacial sulcus. The patient denied lesions elsewhere and any systemic, joint, or mucosal symptoms. A biopsy of the lesion was consistent with cutaneous lupus erythematosus. Given the distribution and pathology, the patient was diagnosed with BLE. The patient was treated with intralesional triamcinolone, topical pimecrolimus, and systemic hydroxychloroquine with an emphasis on strict photo-protection. Despite these therapies the patient's disease persisted.

Limited data indicate that amounts of systemically administered tacrolimus are low in breastmilk and probably do not adversely affect the breastfed infant. United States and European experts and guidelines consider tacrolimus to be probably safe to use for inflammatory bowel disease and after organ transplantation during breastfeeding.[1-8] Exclusively breastfed infants should be monitored if this drug is used during lactation, possibly including measurement of serum levels to rule out toxicity if there is a concern. Topical tacrolimus presents a low risk to the nursing infant because it is poorly absorbed after topical application and peak blood concentrations are less than 2 mcg/L in most patients. Ensure that the infant's skin does not come into direct contact with the areas of skin that have been treated. If the breast is to be treated, an alternate drug is preferred; do not apply to the nipple area while nursing.[9-11] A newer European guideline allows tacrolimus to be applied just after nursing, with the nipples cleaned gently and carefully before nursing.[12]

This study aimed to formulate and optimise a roflumilast loaded ultradeformable transethosomal gel for enhanced topical delivery in psoriasis management, addressing limitations of conventional topical preparations through an advanced vesicular drug delivery approach. Ultradeformable transethosomes were prepared by the ethanol injection technique and optimised using a Box-Behnken experimental design. Independent variables selected were Phospholipon 90G (400-500 mg), Poloxamer 188 (1-3% w/v), and ethanol (20-40% v/v). Dependent responses were vesicle size (Y1), entrapment efficiency (Y2), and zeta potential (Y3), targeting size minimisation, maximum drug entrapment, and optimal negative surface charge respectively. The optimised formulation was incorporated into a Sepineo P600 gel matrix and evaluated for physicochemical properties, in vitro drug release, ex vivo skin permeation, accelerated stability, dermal safety, and in vivo antipsoriatic efficacy using an imiquimod-induced psoriasis model in Wistar rats. Optimised formulation F11, comprising Phospholipon 90G (450 mg), Poloxamer 188 (2% w/v), and ethanol (30% v/v), exhibited vesicle size of 101.4 ± 2.9 nm, entrapment efficiency of 74.38 ± 1.2%, and zeta potential of - 30.21 ± 1.3 mV. Transmission electron microscopy confirmed spherical unilamellar vesicles. Transethosomal gel TG1 demonstrated cumulative drug release of 94.78% and skin permeation of 89.67% over 12 h, surpassing conventional gel. In vivo studies revealed significant PASI score reduction (3.50 ± 0.52 on day 7), enhanced inflammatory biomarker suppression, and improved epidermal repair versus pimecrolimus cream (4.50 ± 0.66, p < 0.01). The optimised roflumilast-loaded ultradeformable transethosomal gel demonstrated improved skin penetration, sustained drug release, and superior preclinical antipsoriatic activity. Further clinical studies are warranted to establish long-term safety and therapeutic efficacy.

Atopic dermatitis (AD) is a common chronic inflammatory condition of the skin that has increased dramatically over the past decade and significantly impacts individual quality of life. Corticosteroids are still the primary therapy for AD, but there are limitations to their continued use due to potential adverse effects, particularly when used in sensitive areas. Topical calcineurin inhibitors (CNIs), such as tacrolimus and pimecrolimus, are available as a safe, steroid-sparing alternative that directly inhibit calcineurin-mediated activation of T cells and have been shown to be efficacious according to varying clinical study designs including randomized controlled trials, registry studies and meta-analyses. Although there was controversy regarding the safety of CNIs subsequent to the FDA's black-box warning in 2006, the preponderance of evidence supports their continued safety when used as directed. In contrast to biologics and JAK inhibitors, CNIs occupy an inherently unique therapeutic niche for use in pediatric patients, have demonstrated historical efficacy, and can provide localized affordable treatment in sensitive areas including the face, eyelids and intertriginous surfaces. Furthermore, the role of CNIs in the context of precision dermatology continues to be defined through new innovations including barrier-repair strategies used in combination with topical medications, microneedle systems, and nanocarrier formulations. Hence, the role of CNIs in the current AD treatment paradigm is crucial and lies at the interface between topical corticosteroids and systemic immunomodulatory agents. The narrative review discusses recent advances in formulation strategies, combination approaches, and targeted delivery systems, underscoring how CNIs continue to bridge established practice and emerging therapeutic innovation in AD.

Lichen sclerosus (LS) is a chronic inflammatory dermatosis that is frequently underdiagnosed in pediatric patients, especially girls presenting with persistent urinary symptoms. We aimed to characterize the clinical features and treatment outcomes in children with LS who presented with urinary symptoms. This retrospective study evaluated 88 children diagnosed with LS at a pediatric nephrology center, all of whom presented with urinary symptoms. Diagnosis was based on clinical and dermatoscopic findings. The mean age at diagnosis was 6.0 years, with a median delay of 8 months. Dysuria (79.5%) and pyuria (87.5%) were the most common symptoms, although only 45.5% had confirmed urinary tract infections. Among 60 patients followed (mean duration = 16.8 months), topical pimecrolimus resolved symptoms in 88.3% and improved skin lesions in 66.6%. Lichen sclerosus should be included in the differential diagnosis for children with urinary symptoms. Clinical awareness and early diagnosis can lead to avoiding unnecessary investigations.

Coadministration of azithromycin (AZM) and acetaminophen (APAP) is associated with an increased risk of hepatotoxicity, the underlying mechanism for which remains unclear. Here, we demonstrate that combined AZM and APAP treatment induced liver injury in mice, as evidenced by exacerbated glutathione depletion, enhanced formation of the toxic metabolite, acetaminophen-cysteine, and hepatocellular necrosis. Mechanistically, the combination inhibited liver X receptor α (LXRα) and upregulated pregnane X receptor, leading to increased expression of phase I enzymes, CYP2E1 and CYP3A11, while downregulating phase II enzymes, UDP-glucuronosyltransferase 1A and sulfotransferase 2A1. Furthermore, the combined treatment disrupted the LXRα-lysophosphatidylcholine acyltransferase 3 axis, which acts as a central driver inducing endoplasmic reticulum and oxidative stress, ultimately promoting hepatocyte apoptosis. Pharmacological activation of LXR (using GW3965, LXR agonist) or inhibition of pregnane X receptor (using pimecrolimus) conferred significant protection against liver injury. The complete abolition of GW3965-mediated protection in Lxrα-knockout mice unequivocally established the central and obligatory role of LXRα in this synergistic mechanism. Our findings indicate that coadministration of AZM and APAP induces hepatotoxicity through a dual-pronged mechanism involving metabolic dysregulation via the LXRα-cytochrome P450/UDP-glucuronosyltransferase axis and aggravation of endoplasmic reticulum stress via the LXRα-lysophosphatidylcholine acyltransferase 3 pathway. Collectively, these findings underscore the need for extreme caution in the clinical coprescription of AZM and APAP and highlight LXRα as a potential target for preventing liver injury. SIGNIFICANCE STATEMENT: This study demonstrates that azithromycin synergizes with acetaminophen to induce liver injury by suppressing liver X receptor α (LXRα). This suppression disrupts metabolic balance via the LXRα-cytochrome P450/UDP-glucuronosyltransferase axis and exacerbates endoplasmic reticulum stress via the LXRα-lysophosphatidylcholine acyltransferase 3 pathway. Based on the finding of a critical drug-drug interaction, the study cautions against coadministration of azithromycin and acetaminophen and proposes LXRα as a promising target for preventing hepatotoxicity.

Topical retinoids are cornerstone therapies in the management of acne vulgaris, psoriasis, and photoaging. Tazarotene, a third-generation retinoid, is highly effective but is associated with cutaneous adverse effects, including irritation, photosensitivity, and epidermal barrier disruption. While most retinoid-induced reactions are self-limited and respond to conservative management, a subset of patients may develop persistent inflammatory skin changes refractory to standard therapy. We report the case of a 20-year-old man with severe acne vulgaris who developed bilateral photosensitive facial erosions following chronic tazarotene use in the setting of prolonged cumulative ultraviolet exposure. Despite discontinuation of tazarotene and extended treatment with emollients, photoprotection, and topical corticosteroids, the lesions persisted for six months. Laboratory evaluation for autoimmune and systemic inflammatory disease, including antinuclear antibody (ANA), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), was unremarkable. Subsequent treatment with pimecrolimus 1% cream resulted in progressive clinical improvement, with complete healing of erosions within three months. This case highlights topical calcineurin inhibition as an effective steroid-sparing strategy for persistent retinoid-associated inflammatory dermatoses and underscores the role of cumulative ultraviolet exposure as a potentiating factor.