The use of topical coconut oil application for itch relief has been studied in the contexts of atopic dermatitis and uremic itch.^7,8 Coconut oil is rich in medium-chain fatty acids, making it an excellent emollient and occlusive agent. In vitro studies have also found coconut oil to have anti-inflammatory and antioxidant properties that can help improve skin barrier function.⁹ Coconut oil also contains monolaurin, a short-chain fatty acid compound with antimicrobial properties.¹⁰

In a study by Muliani et al, topical application of virgin coconut oil was found to be effective in reducing symptoms of pruritus in patients on hemodialysis for chronic kidney disease.⁷ A randomized clinical trial studying the effects of topical virgin coconut oil in pediatric patients with atopic dermatitis also found that treatment with virgin coconut oil decreased pruritus scores in patients and also improved skin barrier function.¹¹ Another study found that 3 months of treatment with topical coconut oil with vitamins A and E decreased pruritus severity scores in pediatric patients with cholestatic liver disease.¹²

Sweet almond oil contains essential fatty acids including oleic, linoleic, palmitic, and stearic acids.¹³ These essential fatty acids reduce itching and inflammation and protect the skin, and deficiencies in essential fatty acids are thought to play a role in the pathogenesis of pruritus.¹³ In a randomized control trial involving 42 patients with uremic pruritus on hemodialysis, topical application of sweet almond oil for two weeks was found to significantly reduce uremic pruritus symptoms.¹³

In another study of 20 patients with pruritus related to end-stage renal disease, massage with a mixture of mint, lavender, and tea tree oils diluted to 5% in sweet almond oil was found to relieve symptoms of pruritus.¹⁴ Furthermore, a study of 80 patients with uremic pruritus found that aromatherapy massage with lavender, tea tree, almond, and jojoba oils significantly reduced pruritus severity.¹⁵ However, since these studies did not investigate the effects of sweet almond oil in isolation, the effects of the treatment can not be credited with certainty to the sweet almond oil in the mixture.

Clove, a fragrant plant prevalent in tropical climates, is high in antioxidants and has gained widespread attention for its many applications including utility in perfume, food, and health industries.¹⁶ In dermatology, clove oil has been of interest due to its anti-inflammatory and wound-healing effects. Eugenol, one of its active ingredients, is thought to reduce itch by inhibition of COX-2 expression and subsequent reduction in synthesis of inflammatory mediators.¹⁶

A clinical trial was conducted by Ibrahim et al to investigate clove oil’s potential utility in relieving pruritus. Fifty patients who had been diagnosed with chronic pruritus resulting from a range of diseases, such as renal, hepatic, and diabetic were divided into two groups of 25 participants each. Group II applied petrolatum topically, and Group I was instructed to moisturize their skin before applying topical clove oil.¹⁷ The 5-D itch scale was used to evaluate treatment efficacy. Results indicated a significant improvement in all of the individual parameters on the 5-D itch scale for clove oil users. No significant treatment effect was seen in the petrolatum group. A comparison of total scores on the 5-D itch scale between the two groups indicated a significantly greater improvement with clove oil than with the placebo/petrolatum (P>.05).¹⁷

Peppermint, a flowering herb native to North America and Europe, has a long history of medical use.¹⁸ The oil, obtained from fresh leaves via steam distillation, has several benefits including antibacterial and anti-inflammatory properties as well as the ability to modulate psychosocial stress. Peppermint oil has also been shown to affect the physiology of the esophagus, stomach, small intestine, and gallbladder.¹⁸ In the context of itch, peppermint oil is thought to reduce the sensation of itch by cooling the skin and activating A-delta and k-opioid receptors, creating a mild analgesic effect.¹⁹ Despite the popularity of topical peppermint oil treatments in dermatology, published research on the subject remains scarce.²⁰

Elsaie et al conducted a study to evaluate the efficacy of topical peppermint oil in treating chronic pruritus stemming from hepatic, renal, or diabetic causes.²⁰ The 5-D itch scale (5D-IS) was used to assess outcomes. Results indicated that topical peppermint oil treatment resulted in a significant reduction in pruritus compared to the control group across all domains measured—duration, degree, direction, disability, and distribution (P-value <0.05).²⁰ In another study by Akhavan Amjadi et al, twice daily topical application of peppermint oil was shown to decrease severity of itching associated with pregnancy (pruritus gravidarum).¹⁹ The efficacy of this treatment has also been studied in the context of treating pruritus associated with burn-induced hypertrophic scars.²¹ In a study by Wu et al, daily application of a formula containing peppermint oil, menthol, and methyl salicylate was found to significantly reduce pruritus severity in 74 patients with severe intractable pruritus due to burn-induced hypertrophic scars.²¹

Oatmeal is a natural substance with a high safety profile and a long history of treating dermatological diseases due to its antioxidant and anti-inflammatory properties.²² The anti-itch properties of oat-derived treatments are thought to be mediated by phytochemicals known as avenanthramides.^10,23 Avenanthramides inhibit activation of NF-kB, thereby reducing local inflammation and associated itch.^10,23 In a study by Sur et al using a murine itch model, topical application of isolated avenanthramides effectively reduced oxazolone-induced contact hypersensitivity, resiniferatoxin-induced neurogenic inflammation, and histamine-mediated itch.²³

Oats can be used as a topical treatment for pruritus in various ways, including oatmeal baths, oat oil, and oat oil-based creams.¹⁰ The oatmeal bath treatment contains 100% natural colloidal oatmeal, which is produced by grinding and boiling oats to extract a mixture mainly consisting of starch (65-85%), protein (15-20%), lipids (3-11%), fiber (5%), and beta-glucans (5%).²² 15-20 minutes of soaking in a bath containing this colloidal oatmeal substance cleans and soothes sensitive skin.²² Oatmeal baths have been shown in numerous trials to be effective in reducing pruritus. Matheson et al conducted a comparative study to determine the efficacy of two bath and shower oils in relieving pruritus in burn patients. One product had liquid paraffin and 5% colloidal oatmeal, whereas the other only contained liquid paraffin. The formulation including colloidal oatmeal considerably reduced itching and resulted in a significant decrease in antihistamine use among patients.²⁴ Oat oil-based lotion has also been shown to improve symptoms of itch, as demonstrated in a study by Southall et al. in which 29 patients with severe xerosis and itch underwent a 2-week treatment course with daily topical oat oil-based lotion application.²⁵

Throughout history, cannabis has been utilized for industrial, medical, and recreational purposes. The medicinal applications of cannabinoids have been gaining public attention in recent years, resulting in a subsequent increase in clinical trials and research. The biologically active compounds in cannabis, known as cannabinoids, are divided into three main groups: endocannabinoids, phytocannabinoids, and synthetic form.²⁶ Endocannabinoids are naturally produced in the human body and play a crucial role in maintaining skin homeostasis. Phytocannabinoids are naturally derived from Cannabis plants, and synthetic cannabinoids are produced chemically in laboratories.²⁶

Cannabinoids are ligands for cannabinoid receptors CB1R and CB2R. Previous studies have shown that both receptors are present in various skin components, such as keratinocytes, mast cells, hair follicles, and sensory nerve fibers. Generally, increased activity at these receptors has been associated with a reduction in pruritus.^26,27

In a study by Yuan et al, 60 patients with asteatotic eczema were enrolled in a double-blind randomized controlled trial. After 4 weeks of treatment with an emollient cream containing 0.3% N-palmitoylethanolamine (PEA) and 0.21% N-acetylethanolamine (AEA), the majority of patients experienced significant improvements specifically in the part of the Eczema Area and Severity Index assessing itch severity.²⁸

An observational cohort study of 2456 pediatric and adult patients with atopic eczema also demonstrated that treatment with a cream containing PEA led to “very much improved” or “improved” intensity of itch in 82.5% of patients.²⁹ In another study of 21 patients with uremic pruritus on hemodialysis, 3 weeks of treatment with a cream containing PEA and AEA was shown to significantly decrease pruritus, with 8 patients experiencing total resolution of pruritus.³⁰

Chamomile is one of the oldest medicinal herbs known to mankind. Chamomile tea and herbal extracts are prepared from the dried flowers of Matricaria species, containing numerous terpenoids and flavonoids that contribute to its medicinal properties.³¹ Chamomile is thought to have anti-pruritic effects via inhibition of pro-inflammatory cytokines, improvement of skin hydration and barrier function, effects on the metabolism of arachidonic acid, and interaction with sensory nerve endings that modulate itch signal transmission.^32,33 Chamomile has also been shown to have anti-allergic properties via inhibition of mast cell degranulation and decrease in histamine release.³⁴

In a randomized study with 72 patients observing the effects of a proprietary chamomile extract-containing cream on the symptoms of atopic eczema, a 2-week treatment course with the cream was shown to be more effective than both placebo and hydrocortisone 0.5% cream in relieving pruritus.³² Studies have also shown that topical application of 8% chamomile gel was effective in reducing itch in patients with dermatitis secondary to radiation treatment for head and neck cancer, and the use of twice daily chamomile compresses was more effective than 1% hydrocortisone ointment in relieving itch associated with peristomal skin lesions in colostomy patients.^35,36

Calendula officinalis, otherwise known as marigold, is an herbaceous flowering plant with a long history of medicinal use in a variety of contexts including digestive problems, headaches, wounds, menstrual irregularities, and more.³³ In the treatment of skin conditions, Calendula has been recognized for its anti-inflammatory, immunomodulatory, healing, antibacterial, and antifungal properties.³³ The flowers, roots, and leaves of Calendula contain many bioactive compounds including terpenes, phenols, and alkaloids.³³ While the mechanism by which Calendula relieves pruritus has not yet been elucidated, Calendula is thought to improve skin barrier function due to its high fatty acid content and attenuate inflammation.³³

Studies have investigated the use of topical Calendula in various formulations including creams, oils, and gels. While studies on the impacts of Calendula on itch in particular remain limited, Calendula has been reported to decrease itch severity in patients with vaginal dystrophy associated with menopause, bacterial vaginosis, xerosis with pruritus, and diabetes-related foot injuries/infections.^37–40

Aloe vera is a green cactus-like plant from the Liliaceae family that produces a colorless, mucilaginous gel, which is widely used for both medicinal and cosmetic purposes.⁴¹ Because aloe vera possesses anti-inflammatory, antibacterial, and wound-healing qualities, it has long been used to treat digestive problems and skin injuries like burns, wounds, insect bites, and eczema.⁴²

Mahboub et al conducted a study to compare the effects of silver sulfadiazine cream and aloe vera gel on first- and second-degree burns.⁴³ While both groups’ wounds healed fully in two weeks, the wounds of patients in the group being treated with aloe vera gel healed more quickly. Interestingly, both groups’ wound itching peaked on day seven, but drastically decreased 30 minutes after using aloe vera gel, revealing the plant’s powerful calming properties.⁴³ Aloe vera was also shown in a double blind, placebo-controlled clinical trial to significantly reduce pruritus and scaling in 58% of patients with seborrheic dermatitis.⁴⁴ Studies have also reported that topical aloe vera decreases itching in psoriasis, atopic dermatitis, and xerosis.³³

Black tea is made by soaking the oxidized leaves of Camellia sinensis in hot/boiling water and has been suggested to have anti-inflammatory properties.⁴⁵ Since facial skin is thinner and more susceptible to topical corticosteroid-related skin atrophy, black tea dressings are commonly used in Germany as a non-steroidal topical intervention for facial dermatitis.⁴⁵ While the mechanisms by which black tea dressings reduce itch are still unclear, astringent compounds found in black tea like tannins and flavonoids are thought to play a role.⁴⁵ The therapeutic effects of black tea dressings can also be further enhanced by the subsequent application of emollient cream to help repair epidermal barrier damage and reduce inflammation.⁴⁵ A small study on the effects of treatment with black tea dressings and subsequent cold cream (mixture of peanut oil, water, cetyl palmitate, and yellow wax) application in 22 patients with facial dermatitis found that this treatment regimen significantly decreased pruritus by day 3 of treatment.⁴⁵ One adverse event (eczema herpeticum) was reported, however, this was determined not to be related to the black tea dressing treatment.⁴⁵

Similarly, green tea baths have been studied and suggested to be an effective treatment for itch in atopic dermatitis, specifically AD associated with Malassezia sympodialis infection.⁴⁶ Green tea is rich in catechins, which have been found to have antioxidant, antimutagenic, antibacterial, and antitumor properties.⁴⁶ In a small clinical study of four pediatric patients with Malassezia-related atopic dermatitis, bathing in green tea (700 mL of 5% extract in 150 L of filtered water at 37º C) for 30 minutes 3 times a week for 4 weeks led to a marked decrease in pruritus and no serious adverse effects were reported during the study.⁴⁶

St. John’s wort (Hypericum perforatum), a flowering plant native to Europe and Asia, has been primarily used as an over-the-counter antidepressant for many years. Additionally, it exhibits anti-inflammatory and anti-neoplastic properties due to its anthraquinone content.⁴⁷ The use of St. John’s wort in dermatological applications has been explored in several clinical trials and pilot studies.^48,49

In one such study, Mansouri et al conducted a double-blind, placebo-controlled pilot study involving twenty patients with mild to moderate plaque-type psoriasis. Participants were treated with St. John’s wort ointment and a placebo, each applied to opposite sides of the body twice daily for four weeks. Clinical evaluations and two punch biopsies from symmetrically preferred lesions on both sides were performed to assess and compare treatment outcomes. The results showed a significant reduction in overall disease severity after one month of treatment with the St. John’s wort ointment, with pronounced decreases in thickness, scaling, and pruritus scores.⁴⁸

In another study, Schempp et al conducted a placebo-controlled, double-blind clinical trial involving twenty-one patients to assess the efficacy of a cream containing St. John’s wort extract, standardized to 1.5% hyperforin (verum), in comparison to a placebo for treating subacute atopic dermatitis. Treatment with either verum or placebo was randomly assigned to either the right or left side of the body, and patients were treated twice daily for four weeks. The group receiving the St. John’s wort extract/verum treatment reported significant improvements in eczematous lesions, and the treatment was well-tolerated.⁴⁹

Originating from the root of the Glycyrrhiza glabra plant, licorice has been valued for its extensive range of therapeutic benefits since ancient times, particularly as a traditional herbal medicine in China.^50,51 It is traditionally used to treat gastrointestinal and liver diseases, as well as oral and skin diseases. Human intestinal microflora converts the active component, glycyrrhizin, into glycyrrhetinic acid, which inhibits 11β-hydroxysteroid dehydrogenase (11β-HSD) and mimics the effects of corticosteroids.⁵¹

Due to licorice’s renowned anti-inflammatory properties, its effectiveness has been explored in treating various skin conditions. Saeedi et al conducted a double-blind clinical trial with 60 patients to investigate the impact of licorice extract (1% and 2%) vs. a base gel applied topically on atopic dermatitis.⁵² Reduction in erythema scores was 35.02% for the 1% licorice extract and 60.76% for the 2% licorice gel. Additionally, oedema scores decreased by 56.64% with the 1% licorice group and 83.76% with the group receiving the 2% formulation. Itching scores also saw significant reductions, dropping 44.1% for the 1% gel and 72.53% for the 2% gel by the conclusion of the study.⁵² In another study, treatment with shampoo containing glycyrrhetinic acid was shown to significantly decrease pruritus in patients with seborrheic dermatitis.⁴⁴

Turmeric is a yellow-colored spice used in cooking, cosmetics, and as a natural medicine.⁵³ The active phytochemical in turmeric, curcumin, has been shown to have anti-inflammatory, antimicrobial, antioxidant, and anti-neoplastic properties.⁵³ Turmeric can be used both orally and topically in the treatment of a variety of diseases including dermatologic conditions like skin eruptions and infections.⁵³ Studies have also demonstrated topical turmeric formulations’ efficacy in treating symptoms of itch/pruritus in atopic dermatitis, uremic pruritus, and itch related to external cancerous lesions.^53,54 The biochemical mechanism used by turmeric to alleviate itch remains unknown, however it has been hypothesized that turmeric reduces itch by acting on TNF-a, IL-4, IgE-antigen complexes, and compound 48/80.³³

Sangre de drago (Dragon’s blood) is a natural resin from the Amazonian dragon tree (Croton lechleri) that reduces neurogenic cutaneous inflammation via the inhibition of substance P release.⁵⁵ Sangre de drago is used both topically and orally as a natural medicine by indigenous cultures of the Amazon River basin for a number of afflictions including hives, sore throat, insect bites, wound healing, hemostasis, and diarrhea, but few scientifically rigorous studies have investigated the mechanisms and efficacy of this natural medicine.^56,57 While rodent studies have shown that the use of Sangre de Drago may decrease itch, clinical studies in human participants are severely lacking.⁵⁵ A small clinical study on the effects of a commercially available Sangre de Drago balm formulation on symptoms of insect bites/stings and other skin conditions in 10 pest control workers did find that all 10 participants reported itch relief with the use of the active balm, while the placebo balm offered itch relief in none of the cases.⁵⁶ Interestingly, symptom relief was reported to occur rapidly in less than two minutes on average, suggesting that the active compounds likely act on sensory afferent nerves.⁵⁶

Vitamin B12 has been shown to be an effective nitric oxide (NO) scavenger.⁵⁸ Excess nitric oxide (indicated by high levels of nitric oxide synthase in the skin) has been shown to be implicated in the pathogenesis of psoriasis and atopic dermatitis, which suggests that vitamin B12 may be useful in the treatment of these conditions.⁵⁸

In a randomized placebo-controlled trial with 49 patients with atopic dermatitis, twice daily topical application of vitamin B12 cream (0.07% cyanocobalamin DAB) was found to reduce symptoms of atopic dermatitis with significant superiority over placebo.⁵⁸ The treatment was well tolerated with low safety risk, with only 6 cases of skin irritation being reported during the study (two “possible” and four “probable” cases related to the B12 cream treatment).⁵⁸

Vitamin E is a natural phenolic antioxidant often found as an ingredient in skincare products thought to provide dermatologic benefits via stabilization of lipid bilayers of the stratum corneum and inhibition of lipid peroxidation.⁵⁹ Vitamin E is also thought to upregulate the expression of genes that drive keratinocyte differentiation, suggesting that vitamin E may provide therapeutic benefit in the treatment of atopic dermatitis.⁵⁹

In a clinical study of 30 pediatric patients with atopic dermatitis, 12 weeks of treatment with a topical cream containing vitamin E in the form of α-, β-, γ-, and δ- tocopherols and tocotrienols and 3-O-ethyl ascorbic acid was found to significantly decrease pruritus intensity/severity, with a relative reduction of 46.3% over the 12-week treatment course.⁵⁹ The treatment was very well tolerated, with no reported adverse reactions.⁵⁹

Coal tar is rich in phenols, polycyclic aromatic hydrocarbons and heterocyclic compounds and has been proven to have antimicrobial, anti-inflammatory, and antipruritic effects.^60,61 Coal tar is thought to exert these effects via restoration of filaggrin expression and activation of the aryl hydrocarbon receptor (AHR), thus counteracting Th2-mediated downregulation of skin barrier function.⁶² Coal tar for topical use is often compounded with glucocorticoids, but steroid-free formulations using petrolatum or unguentum leniens are also available.⁶⁰ Coal tar is a second-line treatment for atopic dermatitis, and studies have also demonstrated efficacy in the treatment of psoriasis.^60,61

Coal tar does have a variety of side effects that may limit its use including burning, local irritation, contact dermatitis, folliculitis, and phototoxicity.⁶⁰ Furthermore, its strong odor, tendency to stain skin and clothing, and poor cosmetic acceptance may deter patients from this treatment option and/or negatively impact patient compliance.^61,62 Overall, topical coal tar application is a long-standing treatment with moderate efficacy, but declining use in clinical practice.⁶²

Honey has long been used as a natural medicine in the treatment of various ailments. Honey has been shown to reduce inflammation, possess anti-microbial properties, promote wound healing, stimulate tissue regeneration, and more.^63,64

In a study of 21 patients with moderate-to-severe atopic dermatitis or psoriasis vulgaris, topical application of a honey, beeswax, and olive oil mixture was shown to be effective in reducing symptoms of pruritus.⁶⁴ The treatment was also very well tolerated, with no side effects being reported during the course of the study.⁶⁴ In another study on 29 patients with recurrent cold sores, treatment with a medical grade honey-based formula was found to be more effective than conventional treatments in reducing itching.⁶³ Furthermore, the honey-based formula was preferred over conventional treatment by 100% of patients.⁶³ Lastly, in a study of 28 patients who had received split-thickness skin grafts on the scalp or face, treatment with an ointment containing 70% honey, 20% aloe vera, and 10% peppermint was shown to effectively reduce pruritus and was also associated with significantly better treatment satisfaction in comparison to standard treatment (petroleum jelly).⁶⁵

Vinegar, aside from its culinary utility, is also renowned for its antimicrobial properties and is produced through a two-step fermentation process involving yeast and Acetobacter, which converts sugars to ethanol and then acetic acid, resulting in a solution of acetic acid and water.^66,67 Historically, its dermatological applications date back to 420 BC when Hippocrates used it to treat wounds. Over the years, numerous clinical trials have explored its benefits in dermatology.⁶⁶

In one such trial, Nakhaee et al studied 23 hemodialysis patients suffering from uremic pruritus, dividing them into three groups. The first group applied Avena sativa lotion twice daily for two weeks; the second group used diluted vinegar (30 mL synthetic white vinegar 5% in 500 ml of water); and the third group was treated with hydroxyzine tablets over the same period. Following a three-day washout period, the treatments were crossed over.⁶⁸ The effectiveness of each treatment was measured using a pruritus scale and a visual analogue scale before and after the interventions. The results showed that both vinegar and hydroxyzine significantly reduced all pruritus scale scores, providing strong evidence of vinegar’s potential to treat pruritus.⁶⁸

Sericin is a high molecular weight biopolymer derived from the silkworm (Bombyx mori) that functions as a moisturizer with anti-inflammatory properties.⁶⁹ Serine, the predominant amino acid in natural moisture factor (NMF), comprises 32% of sericin and contributes to its moisturizing properties.⁶⁹ Sericin is also thought to reduce inflammation by decreasing levels of TNF-α and IL-1β.⁶⁹

In a study of 47 patients with uremic pruritus on hemodialysis, 6 weeks of treatment with a topical sericin cream significantly decreased symptoms of itching (from moderate to severe pre-treatment to mild post-treatment) and led to increased quality of life.⁶⁹

Alkaline baths, particularly ones containing sodium bicarbonate, have long been utilized in the Mediterranean region to treat psoriasis. While the exact mechanism by which sodium bicarbonate baths reduce pruritus remain unknown, it is hypothesized that an alteration of pH may inactivate molecules or pathways involved in the pathogenesis of diseases associated with pruritus.⁷⁰ Sodium bicarbonate baths are also thought to have some keratolytic activity, as demonstrate by their efficacy in reducing hyperkeratosis in patients with psoriasis.⁷⁰

In a study by Verdolini et al involving thirty-one patients with mild to moderate psoriasis, sodium bicarbonate baths (350-500 g of sodium bicarbonate dissolved in average 85 L of bath water) every other day for 3 weeks were found to result in considerable improvement at the end of the trial.⁷⁰ Participants noted improvements in itching and irritation and expressed intentions to use the treatment even after the study.⁷⁰

While sodium bicarbonate baths have been reported to be effective in the prevention of aquagenic pruritus in some studies, other studies have documented treatment failure or loss of treatment efficacy over time.^71,72 While evidence for the efficacy of sodium bicarbonate for aquagenic pruritus is mixed, it is a safe and low-cost intervention that may provide symptomatic relief.⁷¹

Cooling the skin via the application of ice, cold air, or other cooling agents such as menthol has been shown to be effective in decreasing the sensation of itch.^73,74 Cooling the skin has been hypothesized to provide symptomatic relief of pruritus via vasoconstriction of blood vessels and subsequently decreased local release of pruritogens.⁷⁴ Cooling the skin is also thought to attenuate nerve membrane excitability and facilitate interactions between itch-mediating C fibers and cold-mediating Aδ fibers that may decrease the sensation of itch.⁷⁴

In a study of 15 healthy volunteers, cold exposure (achieved by exposing the skin to CO2 snow-cooled air at ~8.2º C or topical 1% menthol solution application) was found to rapidly attenuate itch sensation in the setting of experimental histamine-induced itch.⁷⁴ Furthermore, in a study of 60 patients with pruritus secondary to chronic kidney disease on hemodialysis, treatment with a self-operated ice roller was found to significantly decrease pruritus severity as well as distribution of pruritus-associated body parts.⁷⁵ Given that cooling the skin via the application of ice is a simple, accessible, and low-risk treatment with proven efficacy, this alternative/integrative treatment may improve symptomatic relief in patients with pruritus, especially when utilized in combination with other conventional and/or integrative therapies.

270219 Table 1.