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Skin exposure to solar ultraviolet radiation and pollutants causes several skin disorders, calling for protection methods such as sunscreen application. However, common sunscreen contains chemicals that have displayed toxicity when exposed to ultraviolet radiation. Therefore, alternatives approaches have been recently developed, such as the use of natural phytochemicals as active ingredients in photoprotection preparations. Here, we review skin protection with focus on the physics of ultraviolet radiation and photoprotection by ultraviolet filters. We present sensors for measuring ultraviolet radiation and ultraviolet radiation in ecosystems. We discuss the phototoxicity of drugs, preservatives, personal care products, and pollutants. Photocarcinogenesis, photoallergy, photostability, and toxicity of sunscreen ingredients and their impacts on human health and skin, are also reviewed. We observed that phytochemicals are promising for photoprotection due to their ability to absorb photon energy, and thus act as antioxidants.

At our body surface, the epidermis absorbs UV radiation. UV overexposure leads to sunburn with tissue injury and pain. To understand how, we focus on TRPV4, a nonselective cation channel highly expressed in epithelial skin cells and known to function in sensory transduction, a property shared with other transient receptor potential channels. We show that following UVB exposure mice with induced Trpv4 deletions, specifically in keratinocytes, are less sensitive to noxious thermal and mechanical stimuli than control animals. Exploring the mechanism, we find that epidermal TRPV4 orchestrates UVB-evoked skin tissue damage and increased expression of the proalgesic/algogenic mediator endothelin-1. In culture, UVB causes a direct, TRPV4-dependent Ca ²⁺ response in keratinocytes. In mice, topical treatment with a TRPV4-selective inhibitor decreases UVB-evoked pain behavior, epidermal tissue damage, and endothelin-1 expression. In humans, sunburn enhances epidermal expression of TRPV4 and endothelin-1, underscoring the potential of keratinocyte-derived TRPV4 as a therapeutic target for UVB-induced sunburn, in particular pain.

Although dupilumab is an effective treatment approach for chronic actinic dermatitis (CAD) in some cases, its effectiveness and safety in CAD have not been sufficiently assessed.BackgroundAlthough dupilumab is an effective treatment approach for chronic actinic dermatitis (CAD) in some cases, its effectiveness and safety in CAD have not been sufficiently assessed.Evaluation of the effectiveness and safety of dupilumab in patients with recalcitrant CAD was performed.PurposeEvaluation of the effectiveness and safety of dupilumab in patients with recalcitrant CAD was performed.We retrospectively reviewed the medical records of CAD patients treated with dupilumab. Data regarding demographics were collected, and disease severity scores were assessed using the following: Clinical Severity Score of CAD (CSS-CAD), Atopic Dermatitis Control Tool (ADCT), Dermatology Life Quality Index (DLQI), and Numeric Rating Scale (NRS)-itch scores.MethodsWe retrospectively reviewed the medical records of CAD patients treated with dupilumab. Data regarding demographics were collected, and disease severity scores were assessed using the following: Clinical Severity Score of CAD (CSS-CAD), Atopic Dermatitis Control Tool (ADCT), Dermatology Life Quality Index (DLQI), and Numeric Rating Scale (NRS)-itch scores.After 12 weeks of treatment, there was a significant decrease in disease severity scores of 16 CAD patients. Only one patient achieved a good response and most of the patients (62.5%, 10/16) had no significant symptom improvement after 4 weeks of treatment. However, after 12 weeks of treatment, 43.75% (7/16) of the patients reached excellent response (>75% improvement of CSS-CAD), 31.25% (5/16) good response (50%-75% improvement of CSS-CAD), 6.25% (1/16) partial response (25%-50% improvement of CSS-CAD), and only 18.75% (3/16) no response (<25% improvement of CSS-CAD). One patient complained of injection site reaction at the first injection.ResultsAfter 12 weeks of treatment, there was a significant decrease in disease severity scores of 16 CAD patients. Only one patient achieved a good response and most of the patients (62.5%, 10/16) had no significant symptom improvement after 4 weeks of treatment. However, after 12 weeks of treatment, 43.75% (7/16) of the patients reached excellent response (>75% improvement of CSS-CAD), 31.25% (5/16) good response (50%-75% improvement of CSS-CAD), 6.25% (1/16) partial response (25%-50% improvement of CSS-CAD), and only 18.75% (3/16) no response (<25% improvement of CSS-CAD). One patient complained of injection site reaction at the first injection.This study supports dupilumab as an effective and safe treatment option for patients with recalcitrant CAD. Patients may require at least 4 weeks of treatment before the partial response is noted.ConclusionThis study supports dupilumab as an effective and safe treatment option for patients with recalcitrant CAD. Patients may require at least 4 weeks of treatment before the partial response is noted.

The present review explores the underlying mechanisms of phytophotodermatitis, a non-immunologic skin reaction triggered by certain plants followed by exposure to ultraviolet radiation emitted by sunlight. Recent research has advanced our understanding of the pathophysiology of phytophotodermatitis, highlighting the interaction between plant-derived photosensitizing compounds (e.g., furanocoumarins and psoralens) and ultraviolet light leading to skin damage (e.g., erythema, fluid blisters, edema, and hyperpigmentation), identifying these compounds as key contributors to the phototoxic reactions causing phytophotodermatitis. Progress in understanding the molecular pathways involved in the skin’s response to these compounds has opened avenues for identifying potential therapeutic targets suitable for the management and prevention of this condition. The review emphasizes the importance of identifying the most common phototoxic plant families (e.g., Apiaceae, Rutaceae, and Moraceae) and plant species (e.g., Heracleum mantegazzianum, Ruta graveolens, Ficus carica, and Pastinaca sativa), as well as the specific phytochemical compounds responsible for inducing phytophototoxicity (e.g., limes containing furocoumarin have been linked to lime-induced photodermatitis), underscoring the significance of recognizing the dangerous plant sources. Moreover, the most used approaches and tests for accurate diagnosis such as patch testing, Wood’s lamp examination, or skin biopsy are presented. Additionally, preventive measures such as adequate clothing (e.g., long-sleeved garments and gloves) and treatment strategies based on the current knowledge of phytophotodermatitis including topical and systemic therapies are discussed. Overall, the review consolidates recent findings in the field, covering a diverse array of phototoxic compounds in plants, the mechanisms by which they trigger skin reactions, and the implications for clinical management. By synthesizing these insights, we provide a comprehensive understanding of phytophotodermatitis, providing valuable information for both healthcare professionals and researchers working to address this condition.

Caspofungin, the first FDA-approved echinocandin antifungal agent, plays a vital role in managing invasive fungal infections (IFIs). Despite its established efficacy, large-scale real-world safety evaluations remain limited. This study provides a comprehensive pharmacovigilance analysis of caspofungin's safety profile. Adverse drug events (ADEs) associated with caspofungin were extracted from the FDA Adverse Event Reporting System (FAERS), the Japanese Adverse Drug Event Reporting Database and the Canadian Vigilance Adverse Reaction Database (CVARD) databases. Signal detection utilized four methods: reporting odds ratio proportional reporting ratio Bayesian confidence propagation neural network and multiple gamma-Poisson shrinkage Time-to-onset (TTO) analysis was conducted using FDA Adverse Event Reporting System data, and network pharmacology approaches were employed to investigate potential molecular mechanisms, particularly in caspofungin-related liver injury. A total of 2,270, 161, and 128 ADE reports were retrieved from FAERS, JADER, and CVARD, respectively. \"Hepatobiliary disorders\" and \"infections and infestations\" are overlapping positive signals from three databases at the system organ class level. ADEs such as hypokalemia, sepsis, and drug ineffectiveness were consistent with the drug label. Unexpected signals included prolonged QT interval, cardiac arrest, septic shock, and cholestasis. Cross-database overlap included \"drug ineffective\" and \"toxic skin eruption\" between FAERS and JADER, and \"renal failure,\" \"photodermatitis\" between FAERS and CVARD. TTO analysis revealed that 89.95% of ADEs occurred within the first month, with a median onset time of 6 days. Network pharmacology identified PI3K/Akt and HIF-1 pathways as mechanisms underlying caspofungin-induced liver injury. This study highlights both expected and unexpected ADEs of caspofungin, emphasizing the importance of clinical vigilance and molecular research to enhance patient safety and therapeutic outcomes.

ObjectivesThis study aims to compare the differences among patients of different onset ages in various subtypes of lupus erythematosus (LE) and to draw a panorama of the clinical characteristics of patients with different onset ages.MethodSubjects were recruited from the Lupus Erythematosus Multicenter Case–control Study in Chinese populations (LEMCSC), grouped by the age of onset (childhood-onset: onset < 18 years, adult-onset: onset 18–50 years, late-onset: onset > 50 years). The data collected included demographic characteristics, LE-related systemic involvement, LE-related mucocutaneous manifestations, and laboratory results. All included patients were assigned into three groups: systemic LE (SLE) group (with systemic involvement, with or without mucocutaneous lesions), cutaneous LE (CLE) group (patients who were accompanied by any type of LE-specific cutaneous manifestations), and isolated cutaneous LE (iCLE) group (patients who were in CLE group without systemic involvements). Data were analyzed using R version 4.0.3.ResultsA total of 2097 patients were involved, including 1865 with SLE and 232 with iCLE. We also identified 1648 patients with CLE among them, as there was some overlap between the SLE population and CLE population (patients with SLE and LE-specific cutaneous manifestations). Later-onset lupus patients seemed to be less female predominance (p < 0.001) and have less systemic involvement (except arthritis), lower positive rates of autoimmune antibodies, less ACLE, and more DLE. Moreover, childhood-onset SLE patients presented a higher risk of LE family history (p = 0.002, vs adult-onset SLE). In contrast to other LE-nonspecific manifestations, the self-reported photosensitivity history decreased with the age of onset in SLE patients (51.8%, 43.4%, and 39.1%, respectively) but increased in iCLE patients (42.4%, 64.9%, and 89.2%, respectively). There was also a gradual increase in self-reported photosensitivity from SLE, CLE, to iCLE in both adult-onset and late-onset lupus patients.ConclusionsA negative correlation was suggested between the age of onset and the likelihood of systemic involvement, except for arthritis. As the age of onset increases, patients have a greater propensity to exhibit DLE compared to ACLE. Moreover, the presence of rapid response photodermatitis (i.e., self-reported photosensitivity) was associated with a lower rate of systemic involvement.Trial registrationThis study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2100048939) on July 19, 2021, retrospectively registered. Key Points• We confirmed some phenomena that have been found in patients with SLE, such as the highest proportion of females of reproductive age, the higher risk of LE family history in childhood-onset SLE patients, and the less self-reported photosensitivity in the late-onset SLE group. We also compared the similarities and differences of these phenomena in patients with CLE or iCLE for the first time.• In patients with SLE, the proportion of females peaked in adult-onset patients, but this phenomenon disappeared in iCLE patients: the female-male ratio tends to decrease from childhood-onset iCLE, adult-onset iCLE, to late-onset iCLE.• Patients with early-onset lupus are more likely to have acute cutaneous lupus erythematosus (ACLE), and patients with late-onset lupus are more likely to have discoid lupus erythematosus (DLE).• In contrast to other LE-nonspecific manifestations, the incidence of rapid response photodermatitis (i.e., self-reported photosensitivity) decreased with the age of onset in SLE patients but increased with the age of onset in iCLE patients.

Chronic actinic dermatitis (CAD) is a rare chronic immunological photo-dermatosis resulting in pruritic eczematous eruption on sun-exposed skin to ultraviolet (UV) light. The disease mechanism may include a delay-type hypersensitivity reaction to an endogenous photo-induced antigen, postulated to be UVR-altered DNA, but the exact pathophysiology is unknown. Minimum erythema dosing and patch testing are diagnostic tools of CAD. There are limited safe and effective treatment options for CAD. Herein, a case series of three patients with severe recalcitrant CAD is presented after being treated with dupilumab off-label. The patients in this study had persistent severe disease and taken the first-line management plan, which consists of topical calcineurin inhibitors (TCI), topical corticosteroids (TCS), and strict photoprotection. However, the above treatment options were not able to control the symptoms. The patients were treated with dupilumab 600 mg first dose, 300 mg biweekly subcutaneously (SC), and hydroxychloroquine. Dupilumab showed excellent clinical benefits, including safe and well-tolerated in chronic actinic dermatitis. Further studies are required to be carried out before being applied in clinical practice.

Actinic prurigo is a rare photodermatosis, usually occurring during childhood. Pruritic papulonodules on sun-exposed areas are frequently associated with cheilitis and conjunctivitis. The most widely accepted pathophysiology to date is a type IV hypersensitivity reaction triggered by ultraviolet radiation. This case report describes a 12-year-old boy suffering from refractory actinic prurigo, who was successfully treated with the janus kinase inhibitor upadacitinib.

Photo-contact dermatitis (PCD) describes the adverse cutaneous reaction that occurs in some patients as a result of simultaneous exposure to a contactant and to light. PCD can be subdivided into photo-allergic and photo-irritant dermatitis depending on whether the contactant respectively invokes an allergic or irritant reaction. Photo-irritant reactions are commonly caused by plants, psoralens, and medications taken internally, whereas photo-allergic reactions are commonly caused by sunscreens and topical nonsteroidal anti-inflammatory medications. The work-up of photo-contact dermatitis includes a thorough history and physical exam augmented by patch and/or photopatch testing, as the cornerstone of treatment for PCD is identification and avoidance of the irritating or allergenic chemical. Photo-contact dermatitis has the potential to significantly impact quality of life, so an informed approach to diagnosis and management is critical. Clinical mimics of PCD include polymorphic light eruption, solar urticaria, actinic prurigo, hydroa vacciniforme, cutaneous porphyrias, and systemic disorders with photosensitivity such as lupus and dermatomyositis. Herein, we review the clinical presentation, differential diagnosis (including the clinical mimics mentioned above), pathogenic mechanisms, diagnostic testing, and therapeutic considerations for PCD.

Reticular erythematous mucinosis (REM) is a rare dermatological condition characterized by erythematous, reticulated patches and plaques with a slightly infiltrated appearance. REM is classified among cutaneous mucinoses, which are characterized by the accumulation of mucin in the subcutaneous tissues, leading to the formation of characteristic reticulated patches on the skin. The pathogenesis is still debated, but the association with sun exposure seems to play an important role. We present the case of a 54‐year‐old individual with a history of recurrent erythema on the chest and back. The patient came to our attention in 2007 due to a worsening of symptoms after sun exposure. On clinical examination, the patient presented with pruritic, erythematous patches with a reticulated appearance. A biopsy was performed, which showed the presence of a moderate lymphocytic infiltrate in the dermis, with a perivascular and periappendageal distribution, consisting mainly of T lymphocytes, and deposits of mucin in the superficial dermis, dissecting the collagen bundles. A diagnosis of REM was made, and the patient began treatment with hydroxychloroquine 200 mg per day, with rapid improvement of symptoms. Considering the resolution of symptoms, the therapy was discontinued after 3 months. The patient remained in remission until the following summer when the condition recurred, requiring a new cycle of hydroxychloroquine therapy. The patient has experienced recurrences over the past 15 years during the summer, which responded to hydroxychloroquine therapy, consistently achieving rapid symptom resolution without ever experiencing loss of efficacy or side effects.