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.

Approach to the Patient with Chronic Pruritus.

Chronic pruritus (itch lasting ≥6 weeks) is a bothersome chief complaint that may present in a broad variety of diseases. Most itch-causing diagnoses fit into 1 of 5 categories (inflammatory, secondary to systemic disease, neuropathic, chronic pruritus of undetermined origin, and psychogenic itch) and this broad differential can be narrowed using key findings in the history and physical. In this article, we discuss which key findings are most pertinent for narrowing this differential and guiding further workup and treatment, as well as how to treat many itchy conditions.

Hydrolysed formula, delayed food introduction and fatty acids for atopic dermatitis prevention in infancy.

AIM: The role of nutrition in preventing atopic diseases including atopic dermatitis has recently gained interest in the medical community. Caregivers of infants and children at an increased risk for developing atopic dermatitis often employ exclusion diets or other measures in hopes of preventing the development of this burdensome disease. This paper reviews the current literature in regard to the role of preventative dietary measures in the context of atopic dermatitis, with a special focus on the topics of hydrolysed formula, early vs. delayed introduction of certain foods and fatty acid supplementation. METHODS: Literature pertaining to preventative dietary measures for infants at risk for atopic dermatitis was reviewed. RESULTS: Analysis of the literature suggests that hydrolysed formula should not be routinely offered to infants for prevention of atopic dermatitis. Formulas utilised should contain concentrations of polyunsaturated fatty acids similar to that in breast milk. Finally, infant caregivers should not delay or restrict introduction of food, which can be more harmful than helpful to the patient. CONCLUSION: Recommendations to caretakers providing for infants at risk for atopic dermatitis should include infant consumption of breast milk and avoid delayed introduction of foods.

A systematic review of evidence-based treatments for prurigo nodularis.

Prurigo nodularis is a chronic dermatologic condition involving the development of multiple cutaneous nodules in the setting of intractable pruritus. Given emerging treatment options for this difficult-to-treat condition, a current review of therapeutics is needed. A systematic review was performed for clinical studies investigating prurigo nodularis treatment published from 1990 to present including ≥5 subjects. A total of 35 articles were assigned a level of evidence according to the Oxford Center for Evidence-based Medicine. All 5 studies investigating topical agents, including corticosteroids, calcineurin inhibitors, calcipotriol, and capsaicin, conveyed some beneficial effect with level of evidence 2b or higher. Six of 8 reports investigating photo- and photochemotherapy achieved levels of evidence 2b or greater and showed good partial response rates. Thalidomide was studied by 6 reports providing evidence of good symptom response, only 2 of which were rated level 2b or greater. Cyclosporine and methotrexate have demonstrated benefit in 4 combined studies, albeit with level 4 evidence. Pregabalin, amitriptyline, paroxetine, fluvoxamine, and neurokinin-1 receptor antagonists have demonstrated promising evidence in 5 level 2b studies. Higher-powered studies and additional randomized controlled trials are needed for the evaluation of safe and efficacious systemic treatment options for prurigo nodularis.

Prurigo Nodularis and Its Management.

Prurigo nodularis occurs with chronic pruritus and the presence of single to multiple symmetrically distributed, hyperkeratotic, and intensively itching nodules. Diverse dermatologic, systemic, neurologic, or psychiatric conditions can lead to prurigo nodularis. Structural analysis demonstrated a reduced intraepidermal nerve fiber density and increased dermal levels of nerve growth factor and neuropeptides such as substance P and calcitonin gene-related peptide. Novel therapy concepts such as inhibitors at neurokinin-1, opioid receptors, and interleukin-31 receptors have been developed. The mainstays of prurigo nodularis therapy comprise topical steroids, capsaicin, calcineurin inhibitors, phototherapy, and the systemic application of anticonvulsants, µ-opioid receptor antagonists, or immunosuppressants.

Chronic Pruritus in the Geriatric Population.

Chronic pruritus (>6 week's duration) in the geriatric population (≥65 years old), is an increasing health care problem. The pathophysiologic predisposing factors are abnormalities of the epidermal barrier, immune system, and nervous system. Causes can be dichotomized into histaminergic and nonhistaminergic pruritus. Topical treatments are generally safe. Systemic treatments are chosen depending on the condition, comorbid diseases, and drug interactions. Treatment options are limited. Progress has been made in identifying itch-selective mediators over the last decade. Numerous new medications are currently undergoing clinical trials and they are anticipated to enter the clinics in the near future.

Diagnosis and Management of Neuropathic Itch.

Neuropathic pruritus is a challenging condition that can be caused by injury or dysfunction in any part of the nervous system. A vast array of clinical pictures exist, including both localized and generalized pruritus, and their principal entities are described in this article. Diagnosis is often difficult and depends on patient history, imaging, and neurophysiologic studies. Other causes of chronic itch should be excluded. The management of neuropathic itch is demanding and the majority of interventions are not curative. The best treatment options include anticonvulsants, topical anesthetics, and capsaicin.

Management of Itch in Atopic Dermatitis.

Atopic dermatitis (AD) is the most common itchy dermatosis that affects millions of children and adults worldwide. Chronic itch in this condition has significant impact on measures of quality of life, such as sleep. Treating itch in AD has been challenging for decades, but new drugs have emerged in the last year with significant anti-pruritic effect. The optimal treatment regimen for atopic itch addresses barrier dysfunction, inflammation, neural hypersensitivity, and the itch-scratch cycle. Topical moisturizers remain the foundation of treatment and should be used by all patients with AD-associated pruritus. Step-wise therapy, from topical anti-inflammatory creams to systemic monoclonal antibodies and immunosuppressants, is recommended. There are multiple adjuvant therapies that can be used, especially to target itch in the setting of minimal skin inflammation. Finally, patient education, sleep management, and stress relief are important components to optimize outcomes. This review assesses the latest advances and treatment recommendations for pruritus in AD. Finally, suggested therapeutic ladders and emerging treatments are discussed.

Current and Emerging Therapies for Itch Management in Psoriasis.

Pruritus is a common and significant symptom among patients with psoriasis. Pruritus is often present beyond the borders of psoriatic plaques, and frequently affects the scalp and genital regions. Psoriatic itch may be severe and can profoundly affect quality of life and sleep, even in the context of mild-to-moderate disease. These features often make the treatment of psoriatic pruritus challenging. However, there are a variety of effective topical and systemic treatment modalities available to address this symptom. While there remains a need for treatments that specifically target psoriatic itch, newly licensed therapies including secukinumab, ixekizumab and apremilast have been shown to rapidly and effectively mediate itch reduction.

Mediators of Chronic Pruritus in Atopic Dermatitis: Getting the Itch Out?

For centuries, itch was categorized as a submodality of pain. Recent research over the last decade has led to the realization that itch is in fact a separate and distinct, albeit closely related, sensation. Chronic itch is a common complaint and has numerous etiologies. Various receptors (TRPA1, TRPV1, PAR2, gastrin-releasing peptide receptor (GRPR), Mas-related G proteins), secreted molecules (histamine, nerve growth factor (NGF), substance P (SP), proteases), and cytokines/chemokines (thymic stromal lymphopoietin (TSLP), IL-2, IL-4, IL-13, and IL-31) are implicated as mediators of chronic pruritus. While much remains unknown regarding the mechanisms of chronic itch, this much is certain: there is no singular cause of itch. Rather, itch is caused by a complex interface between skin, keratinocytes, cutaneous nerve fibers, pruritogenic molecules, and the peripheral and central nervous systems. Atopic dermatitis is one of the most itchy skin dermatoses and affects millions worldwide. The sensation of atopic itch is mediated by the interplay between epidermal barrier dysfunction, upregulated immune cascades, and the activation of structures in the central nervous system. Clinicians are in possession of an arsenal of different treatment options ranging from moisturizers, topical immunomodulators, topical anesthetic ion channel inhibitors, systemic immunomodulators, as well as oral drugs capable of reducing neural hypersensitization. Emerging targeted therapies on the horizon, such as dupilumab, promise to usher in a new era of highly specific and efficacious treatments. Alternative medicine, stress reduction techniques, and patient education are also important treatment modalities. This review will focus on the mediators of chronic pruritus mainly associated with atopic dermatitis (atopic itch), as well as numerous different therapeutic options.

Current topical and systemic therapies for itch.

Itch is a common distressing symptom which may be caused by multifactorial aetiologies including inflammatory skin diseases, systemic diseases, neuropathic conditions and psychogenic disorders. Itch is a term used synonymously with pruritus and is defined as acute if it lasts less than 6 weeks or chronic if it persists for more than 6 weeks. It can have the same impact on the quality of life as chronic pain and shares many of the same pathophysiological pathways. Depending on the aetiology of the itch, different pathogenic mechanisms have been postulated with a number of mediators identified. These include histamine, leukotrienes, proteases, neuropeptides, cytokines and opioids, which may activate peripheral itch-mediating C-fibres via receptors on the nerve terminals and central neuronal pathways. Therefore, there is no single universally effective anti-itch treatment available. First-line treatments for itch include topical therapies, such as emollients, mild cleansers (low pH), topical anaesthetics, steroids, calcineurin inhibitors and coolants (menthol). Treatment with systemic therapies can vary according to the aetiology of the chronic itch. Non-sedating antihistamines are helpful in conditions such as urticaria where the itch is primarily histamine mediated. Although the itch of eczema is not mediated by histamine, sedating antihistamines at night are helpful to break the itch-scratch cycle. Chronic itch may also be treated with other systemic therapies, such as anticonvulsants, antidepressants as well as mu-opioid antagonists, kappa-opioid agonists and phototherapy, depending on the cause of the itch. This article summarises the topical and systemic therapies available with our current understanding of the pathophysiology of itch.

Topical TrkA Kinase Inhibitor CT327 is an Effective, Novel Therapy for the Treatment of Pruritus due to Psoriasis: Results from Experimental Studies, and Efficacy and Safety of CT327 in a Phase 2b Clinical Trial in Patients with Psoriasis.

Pruritus is an important symptom in psoriasis with no targeted treatment. Tropomyosin-receptor kinase A (TrkA) is associated with pruritus and psoriatic plaque formation. We report the efficacy of a TrkA inhibitor, CT327, on pruritus in psoriasis. A randomised, double-blind, vehicle-controlled Phase 2b clinical trial was conducted in 160 subjects. No effect was found on psoriasis severity using Investigator's Global Assessment (primary endpoint). However, clinically and statistically significant reductions in pruritus were observed in the 108 patient subset reporting at least moderate pruritus at baseline (37.1 mm visual analogue scale improvement (95% CI [-37.5, -6.2], p = 0.0067) for lowest dose; secondary endpoint). Significant modified Psoriasis Area and Severity Index reductions were found in this subset (p < 0.05). Experiments exploring capsaicin-mediated calcium influx, important in pruritus signalling, were performed in sensory neurons. CT327 inhibited capsaicin responses, indicating action at the nerve growth factor-TrkA-TRPV1 pathway. TrkA is a key target in pruritus, and CT327 has potential to become an effective and safe first-in-class treatment.

Somatosensory pleasure circuit: from skin to brain and back.

The skin senses serve a discriminative function, allowing us to manipulate objects and detect touch and temperature, and an affective/emotional function, manifested as itch or pain when the skin is damaged. Two different classes of nerve fibre mediate these dissociable aspects of cutaneous somatosensation: (i) myelinated A-beta and A-delta afferents that provide rapid information about the location and physical characteristics of skin contact; and (ii) unmyelinated, slow-conducting C-fibre afferents that are typically associated with coding the emotional properties of pain and itch. However, recent research has identified a third class of C-fibre afferents that code for the pleasurable properties of touch - c-tactile afferents or CTs. Clinical application of treatments that target pleasant, CT-mediated touch (such as massage therapy) could, in the future, provide a complementary, non-pharmacological means of treating both the physical and psychological aspects of chronic skin conditions such as itch and eczema.

A randomised trial evaluating the effects of the TRPV1 antagonist SB705498 on pruritus induced by histamine, and cowhage challenge in healthy volunteers.

BACKGROUND: Transient receptor potential vanilloid type 1 (TRPV1) is a non-selective cation channel widely expressed in skin tissues, and peripheral sensory nerve fibres. Activation of TRPV1 releases neuropeptides; the resulting neurogenic inflammation is believed to contribute to the development of pruritus. A TRPV1 antagonist has the potential to perform as an anti-pruritic agent. SB705498 is a TRPV1 antagonist that has demonstrated in vitro activity against cloned TRPV1 human receptors and when orally administered has demonstrated pharmacodynamic activity in animal models and clinical studies. OBJECTIVES: To select a topical dose of SB705498 using the TRPV1 agonist capsaicin; to confirm engagement of the TRPV1 antagonistic action of SB705498 and assess whether the dose selected has an effect on itch induced by two challenge agents. METHODS: A clinical study was conducted in 16 healthy volunteers to assess the effects of 3 doses of SB705498 on skin flare induced by capsaicin. Subjects with a robust capsaicin response were chosen to determine if the selected topical formulation of SB705498 had an effect on challenge agent induced itch. RESULTS: Following capsaicin challenge the greatest average reduction in area of flare was seen for the 3% formulation. This dose was selected for further investigation. Itch intensity induced by two challenge agents (cowhage and histamine) was assessed on the Computerised Visual Analogue Scale. The difference in average itch intensity (Weighted Mean Over 15 Mins) between the 3% dose of SB705498 and placebo for the cowhage challenge was -0.64, whilst the histamine challenge showed on average a -4.65 point change. CONCLUSIONS: The 3% topical formulation of SB705498 cream was clinically well tolerated and had target specific pharmacodynamic activity. However there were no clinically significant differences on pruritus induced by either challenge agent in comparison to placebo. SB705498 is unlikely to be of symptomatic benefit for histaminergic or non-histaminergic induced itch. TRIAL REGISTRATION: ClinicalTrials.gov NCT01673529.

A comparative study of clinical characteristics, work-up, treatment, and association to malignancy in dermatomyositis between two tertiary skin centers in the USA and Singapore.

BACKGROUND: To date, no study has compared the clinical characteristics, malignancy associations, and treatment of dermatomyositis in predominantly Caucasian vs. Asian populations. MATERIALS AND METHODS: This prospective study was conducted to compare clinical characteristics of dermatomyositis, its relationship to malignancy, and treatment between two tertiary medical centers in the USA and Singapore. A total of 19 newly-diagnosed patients in the USA and 15 patients in Singapore were enrolled. Dermatomyositis or amyopathic dermatomyositis were diagnosed based on clinical assessment, skin and muscle biopsies, and muscle testing. RESULTS: Ninety-five percent of patients in the USA group were of Caucasian descent, while 93% of patients in the Singapore group were of Chinese descent. Both groups were predominantly female. Pruritus was the most common initial symptom reported in both groups, while periungual erythema and Gottron's papules were the most common skin presentations. Heliotrope eruption was more common in the Singapore group, occurring in 80% of patients vs. 32% of patients in the USA group (P = 0.007). Three patients in the Singapore group developed a malignancy, with two of these patients having nasopharyngeal carcinoma. None of the USA patients developed malignancies in a follow- up period of 2-5 years. Immunosuppressive steroid sparing therapy with hydroxychloroquine was more frequently used in Singapore, while topical tacrolimus was more frequently used in the USA. CONCLUSION: The clinical presentations of dermatomyositis vary among different ethnic populations. Chinese patients with dermatomyositis have a significant risk for nasopharyngeal carcinoma.

Holistic approach to treatment of intractable central neuropathic itch.

Central neuropathic itch can be a lifelong debilitating condition and treatment challenge. We report a patient with a traumatic brain injury with severe intractable pruritus who failed extensive pharmacologic and nonpharmacologic treatment but responded to a holistic approach using healing touch. We discuss the complexity of this type of neuropathic itch and present a holistic approach as an adjunct to therapy in reducing itch intensity. This case presentation along with the literature discussed suggests a therapeutic strategy for the management of complicated central neuropathic itch.

Contact dermatitis: a common adverse reaction to topical traditional Chinese medicine.

BACKGROUND: Over the past decade, there has been an increase in the use of topical traditional Chinese medicine (TTCM). The most common adverse event seen in the use of TTCM is contact dermatitis. This retrospective study was designed to determine the types of commonly used TTCM in Singapore causing contact dermatitis. METHODS: We retrospectively reviewed the case notes of 10 patients seen at the National Skin Centre over a 4-month period with a diagnosis of adverse cutaneous reactions to TTCMs. RESULTS: A total of 10 patients were diagnosed with contact dermatitis to TTCM at our institution over a 4-month period. The clinical manifestation ranged from eczematous lesions to urticarial plaques and blisters. Five of these patients were patch-tested to our standard series, our in-house TTCM series, as well as to the TTCM they had used. The other five patients declined patch testing. The results of patch testing confirmed the diagnosis of allergic contact dermatitis in three of the tested patients. Negative patch testing results inferred the diagnosis of irritant contact dermatitis to TTCM in the other two patients. Two of the patients with positive patch tests also had a positive reaction to balsam of peru and fragrance mix. The three positive patch tests were all caused by medicated oils. CONCLUSIONS: These results suggest it is likely that essential oils present as constituents of the medicated oils could be the possible allergen. The study also confirms that contact dermatitis is a common adverse event associated with the use of TTCM.

The management of chronic pruritus in the elderly.

The elderly in North America represent the fastest growing segment of the population and the most common skin complaint in this age group is pruritus. The multitude of variables that come with advanced age means that the management of pruritus in the elderly poses a particular therapeutic challenge. Pruritus in advanced age may result from a variety of etiologies, although xerosis is the most common. In addition, certain cutaneous and systemic diseases that are associated with pruritus are more prevalent in the elderly. At present, there is no universally accepted therapy for pruritus. Currently, management of pruritus in the elderly must take an individualistically tailored approach with consideration of the patient's general health, the severity of symptoms, and the adverse effects of treatment. Physical and cognitive limitations, multiple comorbid conditions, and polypharmacy are some aspects that can influence the choice of treatment in this age group.