American Journal of Clinical Dermatology最新文献

Tumor-infiltrating lymphocyte (TIL) therapy is a type of personalized immunotherapy that harnesses the antitumor activity of endogenous immune cells. While TIL therapy has been in clinical investigation since the 1980s and shown promising signs of clinical activity in immunogenic solid tumors such as melanoma, more recent improvements in product manufacturing and characterization have demonstrated consistent efficacy and the feasibility of administering TIL therapy on a larger scale. Lifileucel was granted accelerated approval by the US Food and Drug Administration in February 2024 for the treatment of advanced melanoma, marking the first regulatory approval of a TIL product, and also the first approval of cellular therapy for the treatment of any solid tumor. Despite this landmark event, questions remain surrounding optimal TIL timing, sequencing with other treatment modalities, and the optimal TIL repertoire and phenotype. Innovations in cellular engineering are expected to improve the antitumor efficacy and safety profile of TIL therapy, advance our understanding of how best to deliver TIL therapy, and provide hope for paradigm-shifting approaches in the treatment of advanced melanoma as well as for other solid tumors.

Recent advancements in wound healing are reshaping clinical practice by integrating dermatology, cutaneous microbiome research, and technology. This article discusses new diagnostic tools, such as imaging devices and microbial composition analysis, that enhance our understanding of wound environments. It highlights the importance of wound bed preparation and explores innovative treatment methods for optimal wound healing, including debridement techniques like ultrasound-assisted methods, hydrosurgery, and larval therapy. The evolution of wound management is further illustrated through the use of cellular and acellular matrix products and cellular therapies involving whole blood products. We also present the latest insights on the wound microbiome and antimicrobial treatments, including advanced dressings and antibiofilm surfactants. Finally, the potential of gene therapy for complex conditions like epidermolysis bullosa is discussed as a promising model for advancing wound healing. This review synthesizes current research to improve dermatological practices and patient outcomes in wound care.

Acne vulgaris is a chronic inflammatory skin condition with a multifactorial pathogenesis involving follicular hyperkeratinization, sebaceous gland dysregulation, microbial dysbiosis—particularly involving Cutibacterium acnes and Staphylococcus epidermidis—and complex immune-mediated mechanisms, on which T helper cell 1 (T_h1) and T_h17 pathways are central players. This evolving understanding has led to the exploration of biologic therapies targeting cytokines such as tumor necrosis factor-alpha (TNFα), interleukin (IL)-1, IL-17, and IL-23. However, clinical trials to date have not demonstrated efficacy of biologics in moderate to severe acne. In contrast, some case reports and studies suggest clinical improvement with TNFα and IL-17A inhibitors in severe, treatment-resistant acne, although these presentations often overlap with hidradenitis suppurativa (HS), raising questions about diagnosis and underlying disease mechanisms. Furthermore, in various monogenic autoinflammatory syndromes where “acne-like” lesions are part of the clinical spectrum, biologic therapies have shown effectiveness. These observations suggest that in such contexts, the lesions may reflect HS or HS-like pathology rather than true acne, potentially explaining the therapeutic benefit of biologicals in this context. This review synthesizes current insights into the immunopathogenesis of acne and critically evaluates the rationale, evidence, and limitations of biologic therapy in its treatment. While biologics hold promise in defined inflammatory dermatoses, their role in the management of acne vulgaris remains unproven and may be limited to specific phenotypes that overlap with autoinflammatory or HS-related conditions.

The complex interplay between atopic dermatitis (AD) and cutaneous T cell lymphomas (CTCL) has been known as a matter of clinical concern. With the widespread use of dupilumab, a monoclonal antibody inhibiting interleukin-4 receptor alpha (IL-4Ra) and interleukin-13 receptor (IL-13R), potential association between dupilumab and developing CTCL has been reported in patients with AD. Disease progression has also been described in patients with known CTCL who were treated with dupilumab. Although population-based and pharmacovigilance data support an increased risk of CTCL with dupilumab use in patients with AD, it is a rare association, most likely occurring in predisposed patients. No evidence is available to support a direct oncogenic risk of transforming AD into lymphoma by the treatment, and current literature suggests the role of IL-4Ra/IL-13R inhibition in unmasking pre-existing malignant T cell clones through increased IL-13 availability. On the basis of a comprehensive literature review and our experience in a cutaneous lymphoma clinic at a tertiary cancer center, we provide practical clinical care recommendations for the use of dupilumab in patients with AD, CTCL, and non-skin lymphomas. We also highlight the need for further researching alternative diagnostic approaches to differentiate CTCL from AD and other inflammatory skin disorders and studying the roles of IL-13 and its receptors in CTCL and the effect of the newly available IL-13-inhibiting therapies.

Mastocytosis is characterized by the clonal infiltration and proliferation of neoplastic mast cells into target organs. Clinical features of mastocytosis are based in large part on dysregulated mast cell mediator release. Affected individuals may present with isolated skin involvement or multisystemic disease with a spectrum of symptoms including anaphylaxis, pathologic fractures, and chronic gastrointestinal, neurocognitive, musculoskeletal, and constitutional symptoms. The term “mastocytosis in the skin” refers to individuals with cutaneous infiltration and encompasses both localized and systemic forms of disease. Cutaneous involvement is further categorized into cutaneous mastocytoma, diffuse cutaneous mastocytosis, and maculopapular cutaneous mastocytosis based on morphology. In ~95% of patients with systemic mastocytosis, the disease is driven by the KIT D816V somatic variant. The aim of this clinical review is to highlight the diagnostic considerations, management complexities, and evolving treatment landscape that must be considered when evaluating a patient presenting with mastocytosis in their skin. Clinical manifestations, histopathology, and laboratory parameters are essential to diagnosis and determining the disease burden in those with known or suspected systemic mastocytosis. Once appropriately staged, both skin-directed therapy as well as novel systemic treatment options, including selective tyrosine kinase inhibitors, can be considered with the potential to improve patient outcomes.

Pigmented lesions of the oral cavity can present significant diagnostic challenges because of their diverse etiologies and similar clinical presentations. Understanding these lesions is crucial for correct diagnosis and management because the biologic behavior ranges from benign physiologic variations to aggressive malignancies. The spectrum of oral lesions can include melanin-associated and exogenous pigmented lesions such as physiologic pigmentation and an amalgam tattoo, reactive processes such as smoker’s melanosis and post-inflammatory pigmentation, benign neoplasms such as melanocytic nevi, and malignant conditions such as oral mucosal melanoma. Unlike cutaneous malignant melanomas, mucosal melanomas show distinct molecular profiles, with a lower prevalence of BRAF^V600E mutations and a higher prevalence of c-KIT (CD117) mutations, which impacts therapeutic approaches. While most oral pigmented lesions are benign, they require a careful clinical evaluation, and when indicated, a biopsy for definitive diagnosis. This comprehensive review enables clinicians to navigate the complicated spectrum of oral pigmented lesions for optimal patient care.

A subset of patients with moderate-to-severe psoriasis show long-term remission after drug withdrawal lasting well beyond several half-life times of the drug, particularly following effective treatment with modern biologics such as interleukin-23 inhibitors. Furthermore, evidence suggests that the development of comorbidities, including psoriatic arthritis, a key comorbidity causing irreversible damage, can be prevented or delayed in a subgroup of patients with psoriasis receiving these therapies. This implies that psoriasis treatments may alter the underlying disease mechanisms in some individuals, extending beyond their direct pharmacological effects. However, this concept of disease modification remains controversial, as predicting the natural clinical course of an individual patient with psoriasis is challenging, and typically, no permanent clinically detectable changes occur in psoriatic skin inflammation. This article aims to provide an overview of the current evidence on disease modification in psoriasis and discusses clinical and molecular markers that could be used to predict or monitor disease modification in psoriasis.