Prolonged Antipruritic Effect of Botulinum Toxin Type A on Cowhage-induced Itch: A Randomized, Single-blind, Placebo-controlled Trial.

Botulinum toxin type A (Botox) is thought to have antipruritic effects through inhibition of pruritic factors, including acetylcholine, substance P, and glutamate. The aim of this randomized, single-blind, placebo-controlled trial was to test the effect of botulinum toxin type A on cowhage, a non-histaminergic model for chronic itch. Botulinum toxin type A was injected into the arm of 35 healthy subjects, with a saline control injected into the contralateral arm. Thermal sensory parameters (warmth and heat thresholds and heat pain intensity) and itch intensity after cowhage application were examined on test areas. Botulinum toxin type A reduced itch intensity, overall perceived itch (area under the curve (AUC); percentage change from baseline), and peak itch intensity compared with the control at 1 week, 1 month, and 3 months. Botulinum toxin type A had no effect on thermal thresholds or heat pain intensity. In conclusion, botulinum toxin type A reduced cowhage itch for at least 3 months, which suggests that botulinum toxin type A is a potential long-lasting treatment for localized, non-histaminergic itch.

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.

Laser tattoo removal: laser principles and an updated guide for clinicians.

Tattoos have become ingrained in our society and have served varied purposes throughout human civilization. So long as tattoos have existed, there has been demand for their removal. Lasers are currently the modality of choice in the removal of tattoos, as they are more efficacious than previously used methods. The most common lasers are the 532 nm and 1064 nm neodymium-doped yttrium aluminum garnet lasers, the quality-switched 694 nm Ruby laser, and the quality-switched 755 nm alexandrite laser. However, picosecond lasers are rapidly gaining favor in tattoo removal. An in-depth understanding of laser principles and how they can be applied in the setting of tattoo removal is key. Also, a greater understanding of the origin of and colors within a tattoo, the presence of tattoo layering, and a patient's Fitzpatrick skin type increase the odds of satisfactory results. This review provides dermatologists with a comprehensive summary on laser fundamentals, an overview on treatment principles, and recent developments in the field of laser tattoo removal.

Large, linear pigmentation anomaly: an unusual dyspigmentation case.

Segmental pigmentation anomalies can be further divided into segmental pigmentation disorder (SPD) complex and café-au-lait macules (CALMs). Both are congenital skin conditions characterized by hyper- or hypopigmentation. Segmental pigmentation disorder is a rare entity, whereas CALMs are common skin lesions that may be associated with various genetic conditions, especially when several are present and the patient has other indicators of a genetic abnormality. When the CALM is segmental, segmental neurofibromatosis (type V) may be considered in the differential diagnosis. Herein we present a 48-year-old woman with a history of malignant melanoma who presented with a large, linear, hyperpigmented patch on her shoulder and arm, present since around birth. The differential diagnosis consisted of CALM versus hypermelanosis (a subtype of SPD). Given a family history of a similar lesion, in addition to a personal and family history of melanoma and internal cancers, a hereditary cancer panel was completed demonstrating genetic variance of uncertain significance. This case brings attention to a rare dyspigmentation disorder and questions a possible association with melanoma.

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.

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.

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.

Cholestatic Itch: Our Current Understanding of Pathophysiology and Treatments.

Hepatic pruritus is common in liver conditions, including cholestasis and nonalcoholic fatty liver disease. The pruritus can be severe enough to diminish sleep and decrease quality of life. The pathophysiology likely involves many molecules and receptors, including bile acids, bilirubin, lysophosphatidic acid (LPA), endogenous opioids, and serotonin. Recent advances suggest a significant role of Mas-related G protein-coupled receptor X4 (MRGPRX4) and autotaxin/LPA as key players in cholestatic pruritus. Further research is needed to develop increasingly targeted therapies with greater efficacy, especially given that many patients report itch refractory to various treatments. Cholestyramine was the only US FDA-approved drug for cholestatic pruritus until recent approval of ileal bile acid transporter (IBAT) inhibitors for use in the pediatric cholestatic conditions, progressive familial intrahepatic cholestasis and Alagille syndrome. Both medications decrease the bile acid pool. IBAT inhibitors are under investigation for broader use, and targeting LPA receptors and MRGPR4 are additional attractive options.

Nail Loss in Mild to Moderate Pemphigus Vulgaris.

Introduction: Symptoms of pemphigus vulgaris (PV) rarely include nail findings. When ungual involvement does occur, the most common manifestations are paronychia and onychomadesis. Onycholysis is very uncommon, and complete nail loss has not been reported in the literature. Ungual involvement is thought to be closely correlated with disease severity, with only severe PV cases demonstrating nail symptoms. Case Presentation: We report a case of a 34-year-old female presenting with mild to moderate PV yet severe onycholysis of her first toe leading to secondary nail loss in conjunction with paronychia of her bilateral thumbs. Oral tofacitinib and rituximab infusions led to strikingly rapid improvement in her nail symptoms. Discussion/Conclusion: This case illustrates the importance of a thorough history and physical exam, as a primary complaint of nail symptoms in these patients may lead to unrecognized PV by even the most skilled practitioners. Tofacitinib and rituximab in combination may rapidly improve nail involvement.

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.

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.