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.

Development of squamous cell carcinoma in the setting of chronic discoid lupus erythematosus may be associated with plasmacytoid dendritic cell inflammation.

Discoid lupus erythematosus (DLE) is the most common type of cutaneous lupus and is clinically characterized by alopecia, depigmentation, and scars on sun-exposed skin. Squamous cell carcinoma is a potential long-term complication. The most important risk factor for squamous cell carcinoma development in people with dark skin is chronic scarring and inflammation, such as those seen in long-standing discoid plaques. African Americans who develop squamous cell carcinoma in the setting of chronic scarring and inflammation have a greater risk of metastasis and recurrence compared to sun-induced squamous cell carcinoma seen in whites. Despite this, the pathogenesis of squamous cell carcinoma development in chronic DLE is not fully understood. Herein, we describe a case of an African American patient who developed squamous cell carcinoma on a long-standing discoid plaque. Analysis of the lesion revealed a null type pattern of p53 protein expression and abundant CD123+ plasmacytoid dendritic cells, as potential drivers of oncogenesis and inflammation, respectively. Dermatologists should be aware of the increased risk of squamous cell carcinoma development within long-standing discoid plaques for a prompt early diagnosis and active long-term surveillance.

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.

Lichen Simplex Chronicus Itch: An Update.

Lichen simplex chronicus is a form of chronic localized pruritus with a secondary dermatitis, and one of the most common types of chronic itch conditions, estimated to affect more than 10% of the general population. However, despite its prevalence and burden, there has been limited research into the pathogenesis and aetiology of lichen simplex chronicus, which, historically, made it a challenging condition to treat. In recent years, our understanding of this condition, along with that of pruritus and the itch-scratch cycle, has increased greatly, enabling a substantial increase in treatment options. In addition, there are several new promising treatments currently in development and trials. This article discusses the definition, epidemiology, clinical characteristics, pathophysiology, and current therapeutic options for lichen simplex chronicus, in order to highlight recent advancements in this field.

Antipruritic Effect of Topical Acetaminophen Gel in Histaminergic and Non-histaminergic Itch Provocation: A Double-blind, Vehicle-controlled Pilot Study.

There is a need for new topical antipruritics that are effective on many types of itch. This study examined the antipruritic efficacy of a new formulation of topical acetaminophen. In vitro skin permeability studies showed that 2.5% and 5% formulations are able to rapidly deliver an adequate amount of the drug into the skin. In a double-blind, vehicle-controlled, randomized study in 17 healthy volunteers, 1%, 2.5% and 5% acetaminophen gels and a vehicle gel were applied to the skin prior to histaminergic and non-histaminergic itch induction and assessment of thermal pain thresholds. The 2.5% and 5% gel formulations significantly reduced the itch intensity time course and the area under the curve for both histamine and cowhage itch. No effect was noted on heat pain thresholds and no adverse effects were observed. These results suggest that topical acetaminophen would be a safe and effective over-the-counter medication for itch.

Use of Oral Supplements and Topical Adjuvants for Isotretinoin-Associated Side Effects: A Narrative Review.

Acne is a chronic inflammatory disease of the pilosebaceous unit with a multifactorial etiology and is one of the most common conditions treated by dermatologists and primary care physicians. Within an extensive and evolving treatment landscape, oral isotretinoin has demonstrated efficacy for treatment of severe, recalcitrant acne. Several side effects of isotretinoin have been reported, including laboratory abnormalities, mucocutaneous, and musculoskeletal effects, which may reduce compliance and patient satisfaction with treatment. In this narrative review, we aim to review the efficacy and safety profile of oral supplements or topical adjuvant therapies in mitigating isotretinoin-associated mucocutaneous and musculoskeletal side effects. Oral supplements reviewed include omega-3 fatty acids, vitamin E, folic acid and vitamin B12, antihistamines, l-carnitine, biotin, and combined oral supplements. Topical adjuvants include a hyaluronic acid, biosaccharide gum-2, and glycerine gel-cream; a nongreasy, noncomedogenic, fragrance-free moisturizing cream; dexpanthenol; trichloroacetic acid; and a combination cream. Most of the supplements and topical adjuvants demonstrated efficacy with an adequate level of supporting evidence and no reported adverse events, indicating an adequate safety profile. Patients on isotretinoin may benefit from using oral supplements and topical adjuvants to minimize primarily mucocutaneous side effects, increase adherence to treatment, and thereby improve overall outcomes.

When Foods Cause Itch: Clinical Characteristics, Pathophysiology, and Recommendations for Food-Induced Skin and Mucosal Pruritus.

Itch occurs in various dermatologic and systemic conditions. Many patients report that certain foods instigate itch, although there is limited published information in dermatology on food-induced pruritus. In addition, itch severity is rarely mentioned. Food can induce pruritus through either ingestion or direct contact with skin or mucosal membranes. The most common type of itch provoked by food is acute urticaria, often through the classical immunoglobulin E (IgE)-mediated pathway. Other mechanisms include non-IgE-mediated, mixed (IgE-mediated and non-IgE-mediated), T-cell-mediated, and nonimmune reactions. For patients presenting with urticaria, generalized pruritus, oral pruritus, or dermatitis, a thorough history is warranted, and possible food associations should be considered and assessed. Although any food seems to have the potential to elicit an immune response, certain foods are especially immunogenic. Treatment includes avoidance of the trigger and symptom management. Careful consideration should be used as to avoid unnecessarily restrictive elimination diets.

How to get rid of itching.

Itch is an unpleasant sensation arising from a variety of dermatologic, neuropathic, systemic, and psychogenic etiologies. Various itch pathways are implicated according to the underlying etiology. A variety of pruritogens, or itch mediators, as well as receptors have been identified and provide potential therapeutic targets. Recent research has primarily focused on targeting inflammatory cytokines and Janus kinase signaling, protease-activated receptors, substance P and neurokinin, transient receptor potential-vanilloid ion channels, Mas-related G-protein-coupled receptors (MRGPRX2 and MRGPRX4), the endogenous opioid and cannabinoid balance, and phosphodiesterase 4. Periostin, a newly identified pruritogen, should be further explored with clinical trials. Drugs targeting neural sensitization including the gabergic system and P2X3 are other potential drugs for chronic itch. There is a need for more targeted therapies to improve clinical outcomes and reduce side effects.

When Foods Cause Itch: Clinical Characteristics, Pathophysiology, and Recommendations for Food-Induced Skin and Mucosal Pruritus.

ABSTRACT: Itch occurs in various dermatologic and systemic conditions. Many patients report that certain foods instigate itch, although there is limited published information in dermatology on food-induced pruritus. In addition, itch severity is rarely mentioned. Food can induce pruritus through either ingestion or direct contact with skin or mucosal membranes. The most common type of itch provoked by food is acute urticaria, often through the classical immunoglobulin E (IgE)-mediated pathway. Other mechanisms include non-IgE-mediated, mixed (IgE-mediated and non-IgE-mediated), T-cell-mediated, and nonimmune reactions. For patients presenting with urticaria, generalized pruritus, oral pruritus, or dermatitis, a thorough history is warranted, and possible food associations should be considered and assessed. Although any food seems to have the potential to elicit an immune response, certain foods are especially immunogenic. Treatment includes avoidance of the trigger and symptom management. Careful consideration should be used as to avoid unnecessarily restrictive elimination diets.

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.

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.