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.

Lupus miliaris disseminatus faciei (LMDF) is a rare granulomatous rosacea characterized by multiple papular eruptions primarily affecting the central face, resulting in both physical discomfort and notable cosmetic concerns. Despite various proposed therapies, the optimal treatment for LMDF remains controversial. Photodynamic therapy (PDT) employs a photosensitizer, light source, and oxygen to generate reactive oxygen species (ROS) that selectively target and destroy abnormal tissue, and it has also been shown to reduce and prevent scar formation. However, data on PDT use in LMDF is limited. Here, we report two young male patients with LMDF presenting with multiple firm red papules on the face, both of whom had previously received four lines of treatment-including antibiotics (minocycline, doxycycline, clarithromycin), topical tacrolimus, and traditional Chinese medicine-without clinical improvement. Both patients subsequently underwent four sessions of 5-aminolevulinic acid-based PDT (5-ALA-PDT) combined with oral thalidomide. Following this combination therapy, the lesions showed marked resolution, leaving only minimal depressed scars, and no relapse occurred during a 24-month follow-up. These cases suggest that PDT combined with thalidomide may provide an effective option for refractory LMDF, with early intervention potentially minimizing scarring. Further studies and controlled trials are warranted to confirm the efficacy and safety of this therapeutic approach.

Psoriasis is a chronic immune-mediated inflammatory skin disease affecting millions of individuals worldwide. Pimecrolimus (PMS), a calcineurin inhibitor, suppress T-cell activation thereby interrupting the inflammatory cascade in psoriasis. However, its poor aqueous solubility limits topical delivery. Wrightia tinctoria oil (WTO), a traditionally used herbal remedy, is anticipated to act synergistically with PMS in ameliorating psoriatic inflammation. Thus, the present study aimed to harness the potential of PMS and WTO by developing WTO PMS co-loaded liquid lyotropic crystals (LLC) incorporated into film forming gel (FFG) for enhanced solubilization, skin permeation and therapeutic performance. WTO PMS co-loaded LLC exhibited a mean particle size of 173 ± 4 nm, polydispersity index of 0.225 ± 0.03, and zeta potential of -29.6 mV. In vitro drug release studies demonstrated a sustained release pattern across the dialysis membrane. The LLCs were further incorporated into FFG base, which exhibited shear-thinning and viscoelastic behaviour, thermal stability (activation energy: 1.414 kJ/mol), bioadhesive strength (0.121 ± 0.04 kg) and sustained drug release profile. Ex vivo permeation studies revealed a 12-fold increase in drug flux and a 2.5-fold enhancement in skin retention from FFG LLC compared to pure drug in FFG base. In vivo anti-psoriatic evaluation demonstrated marked lesion recovery, which was supported by histopathological observations and downregulation of inflammatory cytokines. Overall, the WTO-PMS co-loaded LLC-based film-forming gel presents a promising synergistic platform to overcome the solubility barrier of hydrophobic PMS and achieve effective topical management of psoriasis.

Which topical anti-inflammatory treatments are most effective and safe for managing atopic dermatitis?

Psoriasiform lichenoid dermatosis (PLD) is a rare lesion in dogs receiving calcineurin inhibitors, associated with staphylococcal infection.

This open-label, single-arm, multicenter clinical study evaluated the treatment satisfaction, efficacy, and safety of 0.5% delgocitinib ointment twice daily for 12 weeks, applied to face/neck lesions caused by ≥ 3 months use of topical steroids or tacrolimus ointment in patients with atopic dermatitis (AD). The primary endpoint was change in treatment satisfaction (Treatment Satisfaction Questionnaire for Medication-9 [TSQM-9]). Secondary endpoints included changes in modified Eczema Area and Severity Index (mEASI) and EASI scores, the numerical rating scale (NRS) for pruritus, the severity of side effects, skin condition at target lesions, disease control (Atopic Dermatitis Control Tool [ADCT]), and preference for delgocitinib ointment (Patient Preference Questionnaire [PPQ]). Overall, 38 patients (mean age 40 years) with a duration of AD of 30.7 years were included in the study. Scores of TSQM-9 for global satisfaction (Week 0: 58.8 ± 14.7; Week 4: 68.5 ± 16.6; Week 12: 73.2 ± 16.0), effectiveness (57.0 ± 14.1; 67.0 ± 12.6; 70.9 ± 13.4), and convenience (64.9 ± 15.0; 73.6 ± 12.7; 76.1 ± 13.6) (all cases p < 0.01), mEASI (Week 0: 1.31; Week 12: 0.68, p < 0.001) and NRS (4.53; 2.71, p < 0.001) scores, and ADCT (8.3; 5.6, p < 0.01) were improved significantly. Compared with that at Week 0, the incidence of ≥ mild skin atrophy, telangiectasia, and skin irritation decreased. The PPQ showed that approximately 80% of patients rated all queries as "strongly agree" or "agree." In addition, skin conditions were significantly improved for all items (dryness, feel, firmness/elasticity, and appearance) at 1-2 weeks and 12 weeks (p < 0.001). The present results demonstrate that delgocitinib ointment might be an effective option for switching treatment for face/neck AD in patients with skin lesions, or for those who are concerned about the development of side effects related to steroids or tacrolimus. Trial Registration: Japan Registry of Clinical Trials (jRCTs031230063).