Metastatic Merkel Cell Carcinoma After Simultaneous Pancreas-Kidney Transplantation: Fatal Outcomes.

Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous malignancy. Immunosuppression increases the risk of MCC and is associated with poor prognosis. Organ transplant recipients (OTR) have worse overall survival (OS) than patients with immunosuppression due to other causes. Treating MCC after organ transplantation is challenging, as checkpoint inhibitor immunotherapy, the standard of care for treating MCC, increases the risk of transplant rejection. This paper reviews the cases of two simultaneous pancreas-kidney transplant (SPKT) recipients with MCC and explores the role of immunosuppression in the development of MCC. Immunosuppression was discontinued and checkpoint inhibitor therapy was initiated in the first patient and considered by the second patient. In both cases, treatment failed, and the patients died shortly after developing metastatic MCC. These cases illustrate the need for improved multidisciplinary treatment regimens for MCC in OTRs. J Drugs Dermatol. 2024;23(5):376-377.     doi:10.36849/JDD.8234  .

Approach to diagnosis, evaluation, and treatment of generalized and nonlocal dysesthesia: A review.

Dysesthesia is an abnormal sensation in the skin that occurs in the absence of any extraordinary stimulus or other primary cutaneous disorders, excluding any delusions or tactile hallucinations. Clinicians have characterized dysesthesias to include sensations such as burning, tingling, pruritus, allodynia, hyperesthesia, or anesthesia. The etiology and pathogenesis of various generalized dysesthesias is largely unknown, though many dysesthesias have been associated with systemic pathologies including malignancy, infection, autoimmune disorders, and neuropathies. Dermatologists are often the first-line clinicians for patients presenting with such cutaneous findings, thus it is crucial for these physicians to be able to methodically work-up generalized dysesthesias to build a working differential diagnosis, follow up with key labs and/or imaging, and offer patients evidence-based treatment to relieve their symptoms. This broad literature review is an attempt to centralize key studies, cases, and series to help guide dermatologists in their assessment and evaluation of complaints of abnormal cutaneous sensations.

Emerging treatments for itch in atopic dermatitis: A review.

Atopic dermatitis is a chronic inflammatory skin condition with a high prevalence that is increasing. The most universal symptom in patients with atopic dermatitis is pruritus; it is often the most troublesome symptom. New insights on the mechanism of itch in patients with eczema have been elucidated, involving cross-talk between neural and immune systems, which have advanced our treatments significantly. In the last few years, there are emerging treatments currently undergoing investigation that yield a promising outlook in treating this symptom. In this review, we aimed to provide an updated overview of future treatments undergoing phase II and III clinical trials that may be used to treat pruritus of atopic dermatitis.

Evaluation of risk in chronic cutaneous inflammatory conditions for malignant transformation.

Skin carcinomas are the most common form of cancer, and every year thousands of people die from skin cancer-related malignancies. Chronic inflammation is linked to the development and progression of cancer in multiple organ systems - about 20% of all human cancers are a result of chronic inflammation - skin included. While acute inflammation under normal circumstances is a mechanism for host defence and tissue regeneration following insult by trauma or infection by pathogens, over the long term it can drive oncogenic transformation of epithelial cells and promote cancer development, growth and metastasis. Therefore, inflammatory conditions may put individuals at a higher risk to developing skin malignancies. Many skin conditions are characterized by chronic inflammatory processes. These conditions may be particularly susceptible to malignant transformation and predispose patients to develop skin malignancies. As more pathophysiology of chronic inflammatory skin conditions is unveiled, we find that many of these conditions are characterized by immune dysregulation and signalling that result in chronic activation and upregulation of pro-inflammatory chemokines and cytokines, leading to downstream processes that further exacerbate inflammatory processes and cause abnormal cell growth and apoptosis. Here, we review the major chronic cutaneous inflammatory diseases that may have an increased risk of skin malignancies, including atopic dermatitis, psoriasis, discoid lupus erythematosus, lichen planus, hidradenitis suppurativa, prurigo nodularis, lichen sclerosus, systemic sclerosis and morphea, chronic leg ulcers, seborrheic keratoses and basal cell carcinoma. We evaluate the evidence for increased incidence and prevalence, the risk factors associated, the populations at heightened risk and the best management practices.

The effect of fatty acids, vitamins, and minerals on pediatric atopic dermatitis: A systematic review.

BACKGROUND: A body of research has examined the role of fatty acid (FA), vitamin, and mineral supplementation as adjunctive treatment for atopic dermatitis (AD); however, results are conflicting and concrete recommendations are lacking. The objective of this study is to highlight the role of these nutrients in alleviating AD severity and provide the clinician with consolidated information that can be used to make recommendations to the pediatric patient and caretaker, where this topic is of high interest. METHODS: A review of the PubMed and Embase databases was conducted to identify and qualitatively analyze all randomized controlled trials, systematic reviews, and meta-analyses conducted within the last 21 years regarding use of these nutrients to alleviate symptoms of AD. Inclusion criteria include AD diagnosis, non-infant age groups, and AD severity outcomes; exclusion criteria include preventative studies, predominantly maternal or infant demographics, or nonclinical outcomes. RESULTS: Sixty-nine studies were included. Evidence regarding FA supplementation is inconclusive; however, targeting an ideal omega-3:omega-6 FA ratio may play a small role in alleviating AD symptoms. Studies results regarding vitamin/mineral supplementation are inconsistent and supplementation should not be advised unless the patient has a documented deficiency. CONCLUSION: Pediatric AD patients should lead a healthy lifestyle with an emphasis on consumption of wholesome foods. Nutritional supplementation can play a role in improving AD symptoms; however, this should be evaluated on a case-by-case basis. Limitations include heterogeneity of studies.

Update on mosquito bite reaction: Itch and hypersensitivity, pathophysiology, prevention, and treatment.

Mosquito bites are endured by most populations worldwide. Reactions to mosquito bites range from localized wheals and papules with associated pruritus to rare systemic reactions and anaphylaxis in certain populations. The mechanism of itch is due to introduction of mosquito saliva components into the cutaneous tissue, although the exact pathophysiology is unclear. Histamine is thought to be a key player through mosquito saliva itself or through activation of mast cells by IgE or through an IgE-independent pathway. However, other salivary proteins such as tryptase and leukotrienes may induce non-histaminergic itch. Some individuals have a genetic predisposition for mosquito bites, and people with hematologic cancers, HIV, and other conditions are susceptible to robust reactions. Prevention of mosquito bites is key with physical barriers or chemical repellents. Treatment consists of second-generation antihistamines and topical corticosteroids. Further research on topical treatments that target neural-mediated itch is needed.

Silicone barrier cream in treatment of atopic dermatitis: A literature review.

Atopic dermatitis (AD) is a complex skin disorder that requires multidisciplinary treatment modalities to best improve the results of the condition. Although silicone formulations have been used for the treatments of wounds, ulcers, and burns, we aim to highlight the use of a silicon solution for the treatment of eczema. Components of the silicone formula may enhance treatment for AD, such as in the wet wrap therapy, and can be a useful addition. In this report, we aim to discuss the use and properties of the wet wrap therapy with silicone and the potential benefits of applying this formula for the treatment of AD in the future.

An evaluation of abrocitinib for moderate-to-severe atopic dermatitis.

INTRODUCTION: Atopic dermatitis (AD) is a common itchy inflammatory skin condition that affects many individuals. For many years, the landscape of AD treatment remained unchanged; however, there has been developing therapies that directly target the underlying immunological mechanism of AD. Janus kinase (JAK) inhibitors are small molecules that have shown anti-inflammatory and anti-itch effects in AD. Recently, abrocitinib, an oral JAK 1 inhibitor, was approved by the Food and Drug Administration for atopic dermatitis. AREAS COVERED: By downregulating the immune cascade, abrocitinib has demonstrated the ability to curb symptoms of AD, including rapidly reducing pruritus in 2-3 days, and is safe and well-tolerated overall despite a low increased risk in infection. The data discussed was obtained from a comprehensive literature review utilizing PubMed. EXPERT OPINION: Abrocitinib has strong efficacy, likely due to its broader mechanism of action provided by the inhibition of key regulatory molecule, JAK. Results have demonstrated that it is more efficacious at curbing symptoms of AD than dupilumab, the current treatment of choice for refractory, moderate-to-severe AD. While abrocitinib provides a great alternative treatment, particularly for non-responders and AD subtypes, it also demonstrates a stronger side effect profile that must be considered.

Managing Atopic Dermatitis with Lebrikizumab - The Evidence to Date.

Atopic dermatitis is a prevalent, inflammatory skin disease that presents with an eczematous, itchy rash. As of late, there have been many emerging monoclonal antibody inhibitor and small molecule therapies that have changed the course of eczema treatment. One of the treatments in the pipeline for atopic dermatitis is interleukin 13 monoclonal antibody inhibitor, lebrikizumab. As interleukin 13 has been identified as a pro-inflammatory cytokine in the immunological cascade of eczema, it is thought that lebrikizumab can be a great treatment choice for patients with atopic dermatitis. Lebrikizumab is currently being investigated in several studies. Thus far, lebrikizumab for the treatment of eczema has been found to be efficacious; in particular, a rapid response of pruritus improvement has been demonstrated in as early as 2 days. Additionally, it is well tolerated and has an acceptable safety profile, with reports suggesting that are decreased risks of infection when compared to dupilumab. In this review, we aim to summarize the current understanding of lebrikizumab in terms of the mechanism of action, preclinical pharmacology, pharmacokinetics and metabolism, efficacy and safety, and drug indications.

Immunotargets and Therapy for Prurigo Nodularis.

Prurigo nodularis is a chronic inflammatory skin disease consisting of severely pruritic nodules that can be very debilitating for patients. The basis of this skin condition is immunological dysregulation and neural amplification, driven by T-lymphocytes, mast cells, eosinophilic granulocytes, macrophages, and cytokines mediating itchy processes. Further complicating this already taxing diagnosis is the lack of approved treatment and consensus on management; although there are off-label treatments utilized as therapy. Immunomodulators are the cornerstone of treatment for PN, and additional novel therapies targeting key players in the immunological cascade are currently undergoing investigation. In this review, we will highlight targets of the immune cascade and explore current immunomodulating treatments as well as immunotherapies on the horizon for the management of prurigo nodularis.

Nemolizumab for atopic dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disease that has emerging treatments targeting the underlying immunological mechanism. Interleukin-31 (IL-31) is associated with the pathobiological mechanism of AD, contributing to symptoms such as dermatitis and pruritus. Nemolizumab is an anti-IL-31 receptor α-chain (IL-31RA) monoclonal antibody agent that is efficacious in improving symptoms of AD in several phase II and phase III studies in recent years. Nemolizumab demonstrates great efficacy in reducing pruritus and to a lesser degree, dermatitis associated with AD. Additionally, one advantage of nemolizumab is its quick speed of action. Adverse effects are mild and transient in nature, including exacerbation of AD, nasopharyngitis, upper respiratory tract infections, elevated creatine kinase and peripheral edema. Severe adverse effects were not common and consisted of exacerbation of AD and asthma exacerbation. Therefore, nemolizumab has the potential to be an important treatment of choice for AD given its efficacy, mild side effect profile and rapid time of onset. In this review, we examine the preclinical and clinical studies of the novel drug nemolizumab for the treatment of AD with a focus on its mechanism of action, pharmacokinetics, safety, efficacy, indications and drug interactions.

Autoimmune Progesterone Dermatitis: A Systematic Review.

ABSTRACT: Autoimmune progesterone dermatitis (AIPD) is a cyclical, cutaneous reaction to endogenous progesterone that occurs throughout the menstrual cycle. The cutaneous manifestations of AIPD vary greatly from patient to patient, ranging anywhere from urticaria to erythema multiforme to anaphylaxis. As such, recognition, diagnosis, and management of this condition are difficult for clinicians. In the present article, we conducted a systematic review of 112 articles and 132 individual cases to summarize the clinical features and presentation of AIPD while also summarizing the successes and failures of different treatment plans. Despite the great variety in clinical presentations, it is clear from the data that ovulation-suppressing medical therapies and surgery have the greatest success in treating AIPD, whereas more commonly used therapies such as antihistamines and systemic corticosteroids frequently fail in providing any relief. Further research is necessary to determine the exact pathogenesis of AIPD and allow for more targeted treatment.

Current Clinical Options for the Management of Itch in Atopic Dermatitis.

Pruritus is the most burdensome and prevalent symptom in patients suffering from atopic dermatitis. Treating atopic itch has historically been a challenge due to multiple underlying mechanisms within its pathogenesis and an incomplete understanding of them. In recent years, our understanding of these mechanisms have increased tremendously and subsequently, new treatments have reached the market that target the pathophysiology of atopic itch from different angles. In addition, there are several promising new treatments currently in development and trials. In the current article, we discuss these currently available treatment options, their available evidence and efficacy, and highlight some of the more recent advancements in the field.