RESUMO
Members of the Janus kinase (JAK) superfamily, comprising tyrosine kinase 2 (TYK2) and JAK1, JAK2, and JAK3, mediate signaling by cytokines (eg, interleukin [IL]-23) involved in psoriasis pathogenesis. Binding of IL-23 to its receptor activates TYK2 and JAK2, which trigger signal transducer and activator of transcription (STAT) translocation to the nucleus to regulate target gene transcription, including genes of proinflammatory mediators such as IL-17. Physiologically, TYK2 solely mediates immune function, whereas JAK1,2,3 mediate broad systemic and immune functions. Inhibition of individual JAK family members is being evaluated in many dermatologic indications, including psoriasis. Selective TYK2 inhibition is therefore expected to be associated with few adverse effects in patients with psoriasis. People with genetic mutations leading to loss of function of TYK2 are protected from the development of psoriasis without an increased risk of infections or malignancies. In contrast, treatments with JAK1,2,3 inhibitors are associated with various systemic effects. We review the unique allosteric mechanism of action of the selective TYK2 inhibitor, deucravacitinib, which binds to the TYK2 regulatory (pseudokinase) domain, and the mechanisms of action of JAK1,2,3 inhibitors, which bind to the adenosine 5'-triphosphate-binding active (catalytic) site in the kinase domains of JAK1,2,3. Deucravacitinib, which is approved for the treatment of moderate to severe plaque psoriasis in adults in the United States and several other countries, represents a novel, targeted systemic treatment approach with a favorable safety profile. J Drugs Dermatol. 2024;23(8):645-652. doi:10.36849/JDD.8293.
Assuntos
Psoríase , TYK2 Quinase , Humanos , Psoríase/tratamento farmacológico , TYK2 Quinase/antagonistas & inibidores , TYK2 Quinase/metabolismo , TYK2 Quinase/genética , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Compostos HeterocíclicosRESUMO
There is a growing awareness among dermatology providers of ocular comorbidities in patients with the chronic inflammatory skin disease atopic dermatitis (AD). For example, the prevalence of ocular surface diseases (OSD) such as conjunctivitis is higher in patients with AD than in the general population, and the use of some AD treatments may be associated with OSD. In a recent review published in the Journal of the American Academy of Dermatology, dermatologists and ophthalmologists provided an overview of the different types, etiology, pathophysiology, and practical management of OSD associated with AD. This review included a suggested treatment algorithm that champions a partnership between dermatology providers and eye care providers for optimal screening, diagnosis, and care. In this podcast article, a dermatologist and ophthalmologist who were authors on this review are joined by a nurse practitioner moderator to discuss how these concepts can be adapted to clinical practice, inclusive of dermatologists, eye care providers, and relevant advanced practice providers. This podcast focuses on the authors' clinical experiences and highlights the key aspects of optimal care, including exploring additional questions to answer with future research.
RESUMO
Psoriasis is a chronic, immune-mediated disease characterized by itchy, scaly, and often painful plaques in the skin. Psoriasis can have significant psychosocial burdens and increased risks for numerous comorbidities, including diabetes, hypertension, and cardiovascular disease, particularly in patients with moderate-to-severe disease. Dermatology nurse practitioners and physician assistants are an important part of the healthcare team, contributing to all aspects of psoriasis management. This review reinforces the unique aspects of care that nurse practitioners and physician assistants provide to patients with psoriasis, such as facilitating conversations about managing disease, setting appropriate expectations, and considering treatment options, including when treatment response or tolerability is suboptimal. The importance of relationship building is stressed. Patient management topics discussed include helpful tips about assessing treatment options, initiating biologic therapy, optimizing patient adherence, and managing comorbidities. Also reviewed are how to deal with common barriers including lack of knowledge about psoriasis or making healthy lifestyle changes, fear of injections or side effect risks, lack of health insurance, and concerns about treatment costs. Overall, by forming meaningful relationships and engaging patients in their psoriasis care, nurse practitioners and physician assistants can help to optimize clinical efficacy outcomes and consistently manage moderate-to-severe psoriasis and its comorbidities over the patient's life course.
RESUMO
The role of sentinel lymph node biopsy (SLNB) as a prognostic indicator in melanoma patients has been controversial in the fields of surgical oncology and dermatology for decades. This minimally invasive surgical technique was introduced in 1990 for diagnosing melanoma lymphatic metastases and has been deemed the standard of surgical care of cutaneous malignant melanoma by the World Health Organization and the Sunbelt Melanoma Clinical Trial. Its usefulness as a prognostic indicator of metastases led to expanded applications for breast, colon, gastric, esophageal, head and neck, thyroid, and lung cancers. This article first provides an overview of cutaneous melanoma and staging methods and treatment modalities. A brief study of the lymphatic system and the SLNB procedure are reviewed, followed by a discussion of its usefulness in patients who have melanoma, including risks and benefits. This article also discusses nursing considerations for patients undergoing the procedure, and patient education tips. Lastly, future indications for SLNB and new prognostic indicators for melanoma are discussed.