Skin Disorders

Skin Disorders

1 Introduction

Summary and Quick Facts

  • Even though it gets very little recognition, the skin is our largest organ. It directly interacts with our body’s internal and external environments. As such, there are lots of opportunities for things to go wrong with it, and skin disorders are extremely common.
  • This protocol will help you understand the skin and how internal and external factors can contribute to problems. Learn how various common problems are diagnosed and medically treated. Also discover several natural ways to support skin health from the inside and the outside.
  • Because many skin disorders involve inflammatory processes, getting the right amounts of vitamin D can help support the body’s inflammatory response for helping to keep skin healthy.

The skin is one of the largest organs in the body and communicates directly with both the external and internal environments. As a result, it is prone to a wide range of disorders. In fact, skin disorders such as dermatitis, eczema, infections, and non-cancerous growths are among the most common reasons people visit a doctor (Kerr 2010; Awadalla 2008). Although many common skin conditions are not life-threatening, they can cause substantial discomfort and emotional distress, especially in chronic cases (Rubsam 2015; Huynh 2013).

Inflammation, chronic stress, infection, changes in the skin microbiome, and nutritional imbalances can contribute to common skin disorders (Kim, Cho 2013; de Graauw 2015; Huynh 2013). Changes in the immune system that occur during the aging process—called immune senescence —can also increase susceptibility to skin problems (Vukmanovic-Stejic 2011; Loo 2004; Berger 2011).

Typical conventional treatments for common skin disorders include topical and/or systemic anti-inflammatory or immunosuppressive medications, anti-microbial agents, and minor surgical techniques (Wollenberg 2013; Cevasco 2010; NLM 2017b). However, these approaches can leave much to be desired in terms of efficacy and potential side effects (Rubsam 2015).

Integrative therapies can also aid in the treatment of some skin conditions. Nutritional supplements such as zinc, vitamin C, fish oil, and vitamin D help restore skin integrity and normalize immune function (Gupta 2014; Piotrowska 2016; Moores 2013; Telang 2013; Bjorneboe 1987). Topical herbal therapies such as tea tree oil, garlic, and green tea extract have antimicrobial, anti-inflammatory, immune-modulating, and wound-healing properties. In addition, a growing body of evidence suggests that the health of the microbial community present on the skin—the skin microbiome—exerts significant influence over general skin health, highlighting a potential role for probiotics in managing skin disorders.

This protocol will examine the nature of several common skin disorders, broadly categorized as inflammatory, infectious, and neoplastic (growing abnormally). Brief descriptions of each skin disorder and the most common conventional treatments will be described. You will also learn about many natural, integrative interventions and emerging medical therapies that may improve skin health. For more general information about skin health, refer to the Skin, Hair, and Nail Health protocol.

NOTE: Because this protocol covers many skin disorders, you should refer to the table of contents to help locate information of interest to you.

Table of Contents

2 Skin: Basic Structure and Function

The skin serves many critical functions (MacNeal 2016a). Not only is it a barrier against the external environment, it is also an active part of the immune system (Jafferany 2016), regulates body temperature, helps maintain water and electrolyte levels, shields against solar radiation, and makes vitamin D with adequate sun exposure (MacNeal 2016a).

Skin is made up of three layers: the epidermis (superficial/outer layer), dermis (middle layer), and subcutaneous tissue (deep layer). The epidermal structural protein, keratin, and the oily secretion, sebum, give skin a tough surface that is relatively waterproof, protects against injury, and prevents entry of foreign substances. The dermis houses sweat and sebaceous glands, hair follicles, nerve endings, and capillaries. Its fibrous and elastic tissues give skin strength and flexibility. The subcutaneous layer, made up of fat cells and fibrous tissue, provides insulation, padding, and energy storage (MacNeal 2016b).

The Skin Microbiome

An estimated one million bacteria from hundreds of species reside on every square centimeter of skin surface (Egert 2016; Dreno 2016; Barnard 2017). Collectively, these bacteria comprise the skin microbiome, which plays an important role in skin immune function (Chen 2013). Alterations in the composition of the skin microbiome are linked to both inflammatory and infectious skin disorders (Biedermann 2015; Pasparakis 2014; Chen 2013).

The recognition of the important role bacteria play in skin integrity and immune function has led to intriguing new research avenues. For instance, we now have evidence that certain probiotic strains can reduce colonization by pathogenic microorganisms such as methicillin-resistant Staphylococcus aureus (MRSA) and other antibiotic-resistant bacteria (Hafez 2013; Sikorska 2013). Probiotics are also a promising treatment option for atopic dermatitis (Seite 2017).

3 Assessing Skin Problems

The skin is exposed to many irritants—external and internal—and is very physiologically active; thus, it can be affected by a wide array of disorders. A thorough medical history and physical exam are essential to ensure accurate diagnosis (Rajan 2012). The diagnostic exam takes into account the location of the lesion within the layers of skin, pattern of distribution of lesions on the body, and physical characteristics of the lesions. Microscopic exam, culture, and biopsy can be helpful in confirming an uncertain diagnosis. In some cases, blood and urine tests are used to investigate possible underlying systemic disease. Skin prick and patch tests may be used to identify allergens (Marks 2013; Ashton 2014).

Skin Manifestations of Insulin Resistance

Insulin plays an important role in skin health, regulating the growth and development of keratin-producing cells that support structural integrity. Insulin resistance can disrupt normal skin cell function (Napolitano 2015; Boehncke 2012), and has been associated with several skin disorders:

  • Acanthosis nigricans, a chronic skin condition characterized by patches of thick, darkened skin, is among the most common skin manifestations of insulin resistance (Napolitano 2015). Metformin, a first-line diabetes medication, has been shown to benefit patients with acanthosis nigricans. In one intriguing case of an adolescent with insulin resistance and extensive acanthosis nigricans, two years of metformin therapy resulted in complete remission of the acanthosis nigricans (Giri 2017).
  • Acne has been increasingly linked with metabolic disturbances involving insulin resistance (Kumari 2013; Del Prete 2012).
  • Psoriasis appears to be closely linked to insulin resistance (Napolitano 2015).
  • Skin tags are common in obese individuals and may be associated with insulin resistance (Napolitano 2015; Barbato 2012).

More information about insulin resistance and maintaining healthy blood glucose metabolism is available in the Diabetes and Glucose Control protocol.

4 Bacterial Skin Infections

Bacterial skin infections are usually caused by Staphylococcus aureus, but a range of other bacteria can also infect the skin (Rajan 2012). The rising prevalence of antibiotic-resistant bacterial strains, including methicillin-resistant Staphylococcus aureus (MRSA), poses a serious treatment challenge (Hartman-Adams 2014; McClain 2016).

Impetigo

Impetigo is a skin infection that causes small pimple-like red sores, which may rupture and form a crust. The rash may itch, but scratching can spread the infection (NLM 2017a). Impetigo is usually caused byStaphylococcus aureus or, less commonly, Streptococcus pyogenes, or both (Stevens 2016). These bacteria are frequent colonizers of healthy skin but can cause infection in susceptible skin. Impetigo is often a complication of insect bites, allergic skin reactions, and other types of skin infections. Other conditions that increase susceptibility are skin trauma, hot and humid climate, poor hygiene, malnutrition, diabetes, and other health problems (Hartman-Adams 2014).

Because of impetigo’s contagious nature, hygienic practices including hand washing, regular bathing, avoiding contact with other infected people, and prompt cleaning of minor skin injuries are important for preventing the spread of infection (Hartman-Adams 2014).

Folliculitis, Furuncles, and Carbuncles

Folliculitis is a superficial infection of the hair follicles, usually caused by Staphylococcus aureus. If the infection spreads to the tissue surrounding the hair follicle, it forms a pocket known as a furuncle, or a boil. A carbuncle is formed when these pockets of infection coalesce into a larger connected area of infection. Regular applications of warm compresses may promote drainage of furuncles, but larger and deeper infections may require incision and drainage (Cevasco 2010; Rajan 2012).

Erysipelas and Cellulitis

Erysipelas is an infection that involves the superficial skin layer and lymph vessels, while cellulitis involves rapidly-spreading infection and inflammation of the skin and subcutaneous tissues. These infections are usually caused by Streptococcus pyogenes or Staphylococcus aureus and can be complications of traumatic injuries, burns, surgery, injection drug use, and other skin diseases and infections (Stevens 2016; Badour 2017).

Conventional Treatment of Bacterial Skin Infections

Antibiotics

The global emergence of antibiotic-resistant bacteria over the last two decades makes the treatment of bacterial skin infections ever more difficult, and strategies to reduce antibiotic use in dermatology are needed (Colsky 1998; Chon 2012; Bangert 2012). Nevertheless, the mainstays of conventional treatment for bacterial skin infections are topical and oral antibiotics. Intravenous antibiotics may be necessary to control severe spreading infections (Cevasco 2010; Rajan 2012).

Newer antibiotic agents with low levels of known resistance and efficacy against MRSA and other treatment-resistant strains are currently being developed and tested; however, the expense of these new medications can be a deterrent (McClain 2016).

Integrative Treatment of Bacterial Skin Infections

Zinc

Of all tissues in the body, the skin has the third-highest abundance of zinc (Ogawa 2016). Zinc is useful in an array of infectious skin disorders due to its important roles in immune activity and wound healing (Gupta 2014). Chronic zinc deficiency is associated with increased susceptibility to skin infections (Bae 2010; Gupta 2014; Livingstone 2015).

In laboratory studies, zinc has demonstrated antibacterial activity against Staphylococcus aureus and Streptococcus pyogenes, the major causes of impetigo, erysipelas, and folliculitis (Chen 2016; Ong 2014; Ong 2015). Newer topical zinc oxide preparations using nanoparticle technologies have shown potential in combatting Staphylococcus aureus, including MRSA (Ansari 2012; Mohandas 2015; Pati 2014; Dizaj 2014). The use of nanoparticle-based systems in dermatology has emerged in recent years as a growing research area and a promising therapeutic approach (Desmet 2017; DeLouise 2012). Nanoparticle use in dermatology faces many unanswered questions and therapeutic challenges, including toxicological and environmental safety considerations, which need to be addressed in future, much-needed studies (DeLouise 2012; Papakostas 2011).

Vitamin D

Vitamin D is an important factor in skin barrier function (Piotrowska 2016). Vitamin D is involved in the production of antimicrobial peptides in the skin that help protect against cutaneous infections (Muehleisen 2012). Subjects with MRSA infections were found in one study to have lower vitamin D levels than subjects without MRSA infections (Thomason 2015). Several studies have noted a relationship between low vitamin D levels and nasal colonization with Staphylococcus aureus, including MRSA, which increases the risk of skin and soft tissue infections (Matheson 2010; Olsen 2012; Singh, Johnson 2016). In a controlled clinical trial, a reduction in nasal Staphylococcus aureus colonization was seen in 24 participants with atopic dermatitis who were treated with 2000 IU per day of oral vitamin D, potentially reducing their risk of secondary bacterial skin infections (Udompataikul 2015).

Garlic

Garlic’s (Allium sativum) broad antimicrobial properties give it a potential role in skin infection prevention and treatment. In one laboratory study, allicin (an active constituent of garlic) was effective at clearing all tested strains of MRSA, including those that were resistant to the antibiotic mupirocin (Bactroban), which is used to treat MRSA (Cutler 2004). In another laboratory study, garlic oil was found to inhibit immune-evading strategies by bacteria that frequently cause infections in burn patients (Nidadavolu 2012). In one small clinical trial, supplemental garlic extract increased circulation in the small blood vessels of the skin in ten healthy volunteers (Wohlrab 2000). Although this study did not examine effects on immune parameters or infection risk, better circulation in the skin may enhance the ability of immune cells to reach sites of infection to combat pathogens.

Probiotics

Given the increasing presence of treatment-resistant infectious microbes, evidence supporting the role of probiotics in preventing and treating skin infections is especially welcome (Wong 2013; Hafez 2013). Several probiotic bacteria have been shown to inhibit the growth of Staphylococcus aureus strains, including MRSA (Hafez 2013; Sikorska 2013). The subcutaneous injection of Lactobacillus plantarum prevented infections and promoted healing in burn wounds in laboratory mice (Valdez 2005), and its local application on the burn wound was beneficial in a clinical study of human burn patients (Peral 2009). Another probiotic strain, Lactobacillus reuteri, protected skin cells from the harmful effects of Staphylococcus aureus in a laboratory study (Prince 2012). Intriguing new research has highlighted the potential role of probiotics in the gut to promote skin immunity through the interconnectivity of the gut and skin immune systems. Immune cells in the gut called dendritic cells can modulate the systemic immune response to food-based antigens, which may influence skin issues related to food sensitivities or allergies (Friedrich 2017). More research in this area is needed to determine which probiotics may benefit skin conditions.

Honey

Honey’s broad antimicrobial and wound-healing actions are well established. It has been used historically as a topical treatment for non-healing wounds and ulcers, boils, and various skin infections, and its benefits have been attributed to its acidity, hydrogen peroxide content, nutrient and antioxidant content, and immune-modulating activity (Al-Waili 2011). Honey collected from different parts of the world has demonstrated antibacterial actions against both hospital-acquired and community-acquired MRSA cultures (Maeda 2008). In laboratory studies, New Zealand manuka honey worked synergistically with antibiotics to clear certain strains of Staphylococcus aureus, including MRSA (Liu 2014; Muller 2013). In a clinical trial, children with bacterial abscesses related to a condition called pyomyositis were treated with surgery and oral antibiotics; following surgery, their wounds were packed with gauze soaked with either honey or a commonly used antiseptic. Those treated with honey had faster wound-healing and shorter hospital stays (Okeniyi 2005). In a case report, topical honey effectively cleared a MRSA skin infection in an immunosuppressed patient (Natarajan 2001).

Topical Essential Oils

Essential oils have well known antimicrobial properties. Tea tree oil, the essential oil of Melaleuca alternifolia, has demonstrated antibacterial effects in laboratory research against bacteria involved in skin conditions, such as Streptococcus pyogenes (Tsao 2010), Staphylococcus aureus, and MRSA (Loughlin 2008; Halcon 2004; Brady 2006). In a clinical trial involving 224 hospitalized patients, a regimen using tea tree oil, as a 10% cream and 5% body wash, was more effective than a standard antibiotic regimen for clearing MRSA from the skin (Dryden 2004). Of note, tea tree oil may cause an allergenic reaction in some people, so should be used judiciously by those who have not used it before (Christoffers 2014). If you suspect you are prone to react to tea tree oil, your dermatologist may be able to perform a skin patch test for confirmation (Rutherford 2007). Other essential oils exhibiting antibacterial effects against skin-relevant bacteria include orange and coriander oils (Casetti 2012; Muthaiyan 2012).

Vitamin C

Vitamin C plays an important role in the synthesis of collagen (a structural protein found in skin and other connective tissues) and skin healing (Moores 2013; Telang 2013). It has shown antibacterial activity against Staphylococcus aureus (Kallio 2012), and a study that enrolled human participants with recurrent furuncles and decreased neutrophil function found that taking 1 gram oral vitamin C daily for 4‒6 weeks significantly improved the function of the participants’ neutrophils (Levy 1996).

Tea

Tea (Camellia sinensis) leaves are a source of polyphenolic compounds, including catechins, which have anti-microbial and immune-stimulating properties (Rosen 2012). A laboratory study showed that green tea extract and epigallocatechin gallate (EGCG), a primary active constituent of green tea, inhibited the growth of multidrug-resistant bacteria that can infect the skin. The researchers concluded that green tea extract and EGCG may have potential as adjunct topical antimicrobial treatments for skin infections caused by drug-resistant bacteria (Jeon 2014). In a controlled trial, a topical lotion made with black tea extract was comparable to antibiotics in treating impetigo (Sharquie 2000).

5 Fungal Skin Infections

Fungal skin infections involving a group of fungi known as dermatophytes are one of the most common infections in humans worldwide. Other frequent causes of fungal skin infections include Candida albicans and Malassezia furfur (White 2014).

Note : this section focuses on fungal infections of the skin; more general information about fungal infections, including systemic candidiasis, is available in the Fungal Infections (Candida) protocol.

Dermatophytosis

This very common condition includes a set of superficial infections of the skin, hair, and nails caused primarily by three groups of fungi known as dermatophytes: Trichophyton, Microsporum, and Epidermophyton. Tinea corporis (ringworm), tinea pedis (athlete’s foot), and tinea cruris (jock itch) are examples of dermatophytoses (Cevasco 2010; Sahoo 2016).

Cutaneous candidiasis

Cutaneous candidiasis is an infection of the skin and/or nails by Candida albicans or other Candida species. It is most common in individuals treated with antibiotics, diabetics, immunocompromised patients, and those with other skin afflictions (Aaron 2015; Cevasco 2010).

Tinea (or pityriasis) versicolor

Tinea versicolor, also known as pityriasis versicolor, is a fungal infection affecting skin pigmentation and involving species of the fungus Malassezia, such as Malassezia furfur.It is more common in hot, humid climates and may be associated with oral contraceptives, oral corticosteroids, immunosuppression, and malnutrition. The characteristic patches seen in tinea versicolor are either hypopigmented (white) or hyperpigmented (pink, tan, brown, or black) (Cevasco 2010; White 2014).

Onychomycosis (nail fungus)

Fungal infections of the toenails or fingernails are quite common, affecting about 10% of the general US population, with toenail infections being more prevalent than fingernail infections. In addition to disfiguring the nail(s), onychomycosis may cause pain and interfere with physical activity. The most common causative organism in onychomycosis isTrichophyton rubrum; other causal organisms include Trichophyton mentagrophytes and Epidermophyton floccosum. Ninety percent of toenail fungal infections involve dermatophytes. Treatment may involve topical and/or systemic antifungal medications, depending on the extent and location of the infection. Importantly, in nearly half of cases abnormal nail appearance is not due to fungal infection, so seeing a doctor for testing to identify the causal agent is fundamental to treatment planning (Bodman 2017; Westerberg 2013). More detailed information about onychomycosis is available in the Skin, Hair, and Nail Health protocol.

Conventional Treatment of Fungal Skin Infections

Topical antifungal agents are generally effective against certain common fungal infections (Sahoo 2016). Common examples of medications in this class include ketoconazole and econazole. In cases of more extensive fungal skin infections, oral antifungal drugs may be prescribed; these may include oral ketoconazole or oral micronized griseofulvin (Cevasco 2010). More care is needed with oral antifungal drugs because several may cause side effects or interact with other drugs. It is important to note that, like pathogenic bacteria, dermatophytes are becoming increasingly resistant to conventional treatments. Much attention has, as a result, been focused on natural products with antifungal properties for treating fungal skin infections (Lopes 2017).

For onychomycosis, topical treatment options include ciclopirox olamine 8% and efinaconazole 10% solutions. Often, topical treatments alone are not sufficient to eradicate the underlying infectious agent and cure the nail infection, so systemic medication is frequently indicated. Oral antifungal agents that may be used to treat onychomycosis include itraconazole (Sporanox) and terbinafine (Lamisil) (Kreijkamp-Kaspers 2017). The cure rates for systemic medications range from about 50% to about 75%. Side effects of oral antifungal agents used to treat onychomycosis include flu-like symptoms, gastrointestinal distress, infections, headaches, elevation of liver enzymes, and altered metabolism of other drugs (Bodman 2017; Westerberg 2013; Kreijkamp-Kaspers 2017).

Integrative Treatment of Fungal Skin Infections

Topical Zinc

In a four-week controlled trial, a topically applied powder made with 20% zinc undecylenate and 2% undecylenic acid improved symptoms and reduced the presence of fungi in patients with tinea pedis (athlete’s foot) (Chretien 1980). Topical 1% zinc pyrithione solutions are often used successfully to treat tinea versicolor, and a 15% topical zinc sulfate solution has also shown promise for this condition (Gupta 2014). Preparations of zinc oxide nanoparticles have demonstrated activity against Candida albicans (Khan 2014; Mohandas 2015).

Garlic

Garlic and its active constituents have antifungal effects against certain dermatophytes (Aala 2014), and have been effective against a variety of skin pathologies in early research (Pazyar 2011). In a pilot trial, a cream with 0.4% ajoene, a sulfur-containing compound from garlic, led to complete resolution of tinea pedis in 27 of 34 (79%) study participants after seven days, and in all participants after 14 days (Ledezma 1996). In another trial, 1% ajoene cream was as effective as the antifungal medication terbinafine in treating tinea pedis (Ledezma 2000). An animal model of a fungal infection showed that garlic consumption enhanced the immune response to the fungal pathogen in infected mice (Burian 2017). In an in vitro study, the garlic constituent allicin inhibited the growth of the common dermatophyte Trichophyton rubrum, which can infect the skin (Aala 2014).

Essential Oils

Essential oils from plants such as tea tree, eucalyptus, juniper, cedar, and lavender have a long history of use as topical treatments for fungal skin and nail infections. Laboratory studies have shown that various essential oils, their constituents, and combinations of essential oils have strong antifungal properties against common dermatophytes and Candida species (Baptista 2015; Takao 2012; Zuzarte 2012; Cavaleiro 2006). Findings from one such study suggest the addition of salt could increase the anti-dermatophyte activity of essential oils combined in a hot water bath (Inouye 2007). Experimental evidence also suggests essential oil constituents may enhance the activity of the antifungal medication fluconazole (Diflucan) against drug-resistant fungal strains (Khan 2011). Topical essential oils have been found to be helpful in sheep and horses affected by tinea corporis (ringworm) (Pisseri 2009; Mugnaini 2013).

Clinical trials show that topical tea tree oil can combat fungal infections (Martin 2004). In one trial, 25% and 50% tea tree oil preparations were more effective than placebo in patients with tinea pedis (athlete’s foot), but caused temporary skin irritation in some participants (Satchell 2002b). Topical tea tree oil was found in another trial to be as effective as the topical antifungal medication clotrimazole 1% (Lotrimin) in patients with fungal nail infections after six months of twice-daily treatment (Buck 1994).

6 Viral Skin Infections

Among the most common manifestations of viral skin infections are warts caused by strains of human papilloma virus (HPV) (Cardoso 2011). Another common viral skin infection, molluscum contagiosum, is caused by a virus in the poxvirus family. Skin is also a target of herpes simplex viruses, which cause oral and genital herpes. Reactivation of the chickenpox virus ( Varicella zoster virus) causes shingles (Cevasco 2010). Additional information is available in the Herpes and Shingles protocol.

In general, viral skin infections are more common in immune-compromised individuals, who are also more likely to experience severe and recurrent outbreaks and complications (Cardoso 2011; Bader 2013; Sauerbrei 2016).

Warts

HPV-related warts affect an estimated 10% of the population. Fleshy papules (raised areas) are common. Other types of warts include plane (flat) warts, plantar warts (affecting the soles of the feet), and condyloma acuminatum (cauliflower-like growths, usually affecting the genital area) (Cevasco 2010; Kollipara 2015). Although the vast majority of warts are benign, some HPV strains have the potential to cause malignant growths (Cardoso 2011).

Molluscum contagiosum

Molluscum contagiosum, which typically manifests as multiple wart-like lesions, affects nearly 5% of the population. Infection is frequent in children, people with compromised immune systems, and sexually active adults (Cevasco 2010). Molluscum cantagiosum resolves without treatment, but typically persists for 6 to 12 months and may last as long as five years (Butala 2013).

Conventional Treatment of Viral Skin Infections

Prevention is key in the battle against HPV-induced viral skin infections. The HPV vaccine can prevent genital warts: a large study conducted in Denmark reported that three injections provide complete protection (Thappa 2016; Blomberg 2015). The vaccine targets HPV subtypes associated with genital warts and cancers of the cervix and oropharynx (mid-throat) (Kim 2016).

Warts are most frequently treated with destructive (eg, cryosurgery), anti-proliferative, or antiviral agents applied topically or intralesionally (injected into the wart) (Cevasco 2010; Thappa 2016). Topical and intralesional treatments require multiple applications over a period of weeks. In general, side effects of these therapies include local irritation, burning, redness, and pain (Kollipara 2015; Thappa 2016). Topical imiquimod (Aldara), an immune-modulator that stimulates antiviral and antitumor immune activities, is approved for use in treating anogenital warts (Hanna 2016). The usefulness of imiquimod and other immunotherapies in the treatment of cutaneous warts is still being explored (Thappa 2016).

Cimetidine is an over-the-counter heartburn drug with interesting immune-modulating properties. Cimetidine has been shown to be an effective treatment for viral warts. One study showed that treatment with cimetidine alone for four months led to complete remission in 19 of 55 people with multiple viral warts. The drug produced partial remission in another 13 individuals. This study found that higher doses of cimetidine (30–40 mg/kg/day) were more effective than lower doses (less than 20 mg/kg/day). Although the precise mechanism by which cimetidine treats warts is not clear, the previously described study found that treatment with the drug increased levels of some immune-stimulating cytokines and activated a subset of T cells involved in antiviral defense (Mitsuishi 2003). Overall, data regarding the efficacy of cimetidine in treating viral warts are somewhat mixed, and larger, well-controlled studies are needed. Some studies and case reports to date have shown success in children with viral warts (Kharfi 2002; Chern 2010; Franco 2000), but evidence for efficacy in adults is less convincing (Rogers 1999).

Surgical removal of warts is sometimes preferred, but may require repeated surgery (NLM 2017b; Cevasco 2010).

Intralesional injections of microbial antigens and photodynamic therapy are new and promising treatments for genital and non-genital warts. These approaches are discussed in the Novel and Emerging Therapies section.

Integrative Treatment of Viral Skin Infections

Garlic

In a controlled trial, 28 patients with at least two warts that were unresponsive to prior treatment were treated topically with either a water extract or a lipid extract of garlic (Allium sativum), applied twice daily. Five patients with warts served as the control group and were treated with the lipid solvent with no garlic. Complete resolution was seen within two week in all participants with warts treated with the lipid extract of garlic. Slower and less complete improvements were seen in those treated with the water extract, and no improvement was seen in the control group. Garlic use was associated with several side effects, including redness, burning, and blistering of the surrounding skin, but the side effects usually subsided in one to two weeks (Dehghani 2005). Another study used a similarly prepared lipid garlic extract on warts that had not responded to other treatments in 25 participants. Another 25 participants served as controls and were treated with saline. The duration of treatment was until the warts cleared or up to four weeks. Complete responses, defined as disappearance of the wart and return of normal-appearing skin, were achieved in 96% of subjects treated with the lipid garlic extract. No side effects were reported during lipid garlic extract treatment in this study (Kenawy 2014).

Zinc

Low serum zinc levels were found in one study to correlate with persistent, progressive, and recurrent warts (Raza 2010). In a clinical study, a topical 10% zinc sulfate solution was more effective than placebo for treating plane and common warts (Sharquie 2007). Other clinical trials indicate oral zinc sulfate, at a daily dose of 10 mg/kg body weight, may also lead to successful resolution (Mun 2011; Al-Gurairi 2002). In one of these studies, 10 mg/kg zinc sulfate daily led to complete wart resolution in two months of treatment in half of participants that completed the study (Mun 2011). A study in children ages five to 11 showed that four weeks of treatment with a topical preparation containing zinc oxide and colloidal oatmeal extract led to partial or complete remission in all participants (Safa 2010).

Vitamin D

Topical preparations made with vitamin D analogs have benefited patients with viral warts (Imagawa 2007; Moscarelli 2011). In addition, one study examined the effect of vitamin D3 injections into plantar warts. In 20 subjects with one or more plantar warts, 16 (80%) experienced complete resolution and one experienced partial resolution (Aktas 2016). One report described a case of an anogenital wart in an infant treated successfully with a topical vitamin D3 derivative (Rind 2010).

Green Tea

A number of studies have demonstrated positive outcomes using topical preparations with 10% and 15% green tea (Camellia sinensis) extract in patients with external genital and perianal warts (Gupta 2015; Scheinfeld 2013b). In two randomized controlled trials, green tea ointment, applied three times daily for up to 16 weeks, was more effective than placebo in clearing external anogenital warts (Hoy 2012). This evidence led the US Food and Drug Administration (FDA) to approve the use of a green tea catechin ointment called polyphenon E (Veregen) for treatment of HPV-related external anogenital warts (Stockfleth 2014).

Multi-Nutrient Formula

In a clinical trial, 172 subjects with one or more warts were treated with standard therapy alone (salicylic acid plus lactic acid or liquid nitrogen cryotherapy) or standard treatment plus a four-month oral supplement regimen that included probiotics, methionine, echinacea, zinc, and other immune-stimulating nutrients. After six months, the group that received the supplements had fewer warts and a higher remission rate than the standard treatment group. Complete remission was achieved in 86% of subjects treated with the standard therapy plus oral supplements (Cassano 2011).

Emerging Therapy: Microbial Antigens

Microbial antigen therapy involves the injection of microbial antigens directly into warts (intralesional injections) to stimulate a strong local immune response. Extracts made from Mycobacterium w,Candida albicans, Bacillus Calmette-Guerin, and Trichophyton species, as well as tuberculin protein and the measles, mumps, and rubella vaccines have been used in early research against both genital and non-genital warts. Common side effects associated with this treatment include pain, redness, and swelling at the injection site, and systemic flu-like symptoms (Thappa 2016; Aldahan 2016). Some intralesional injection preparations are currently available, and are indicated in people with persistent, recurrent, or extensive warts, or in those with warts in hard-to-treat locations (Thappa 2016; Mulhem 2011).

7 Common Inflammatory Skin Disorders

Skin inflammation may be a sign of allergic, autoimmune, or infectious conditions. Atopic dermatitis, contact dermatitis, and urticaria (hives) are examples of allergic skin conditions (Wollenberg 2013); dermatitis herpetiformis and lichen planus are examples of autoimmune-mediated inflammatory skin diseases (Usatine 2011; Antiga 2015; Jiang 2015). Seborrheic dermatitis and rosacea appear to involve inflammatory reactions to skin microorganisms (Clark 2015; Lucas 2010). Psoriasis and acne are also considered primarily inflammatory in nature; more information about these conditions can be found in the Psoriasis and Acne protocols.

Eczema is a term that encompasses a subset of inflammatory skin disorders that are characterized by itchy rashes. Some conditions included in this group are atopic dermatitis, seborrheic dermatitis, and contact dermatitis. The term is sometimes used interchangeably with atopic dermatitis, which is the most prevalent condition in this group (Weston 2014; Gaby 2011b).

The likely contribution of multiple factors, such as genetics and environmental influences, to inflammatory skin disorders adds complexity to their satisfactory diagnosis and treatment (Nutten 2015; Dessinioti 2013). In addition to allergic, autoimmune, and antimicrobial processes, emotional stress may contribute to skin inflammation (Huynh 2013; Kim, Cho 2013). Anxiety, depression, and other mental health disorders are commonly associated with inflammatory and other skin problems (Yaghmaie 2013; Orion 2014; Dalgard 2015; Jafferany 2016; Marshall 2016). If you or a loved one have a skin disorder and a mental health disorder, consider reviewing additional relevant Life Extension protocols: Depression, Anxiety, Stress Management.

Inflammatory skin disorders frequently respond to dietary and stress-reducing interventions, including food sensitivity testing and avoidance, relaxation, and meditation. For more information about these interventions, see the Diet and Lifestyle section of this protocol.

Atopic Dermatitis

Atopic dermatitis is a chronic inflammatory skin condition affecting up to 20% of children and up to 3% of adults, and research suggests its prevalence worldwide is increasing. A family history of atopic dermatitis or allergies is a risk factor (Wollenberg 2013; Nutten 2015).

Although atopic dermatitis is commonly associated with allergic conditions such as asthma and hay fever, it is still unclear whether allergies are a cause or consequence of atopic dermatitis (Nutten 2015). Alterations in microbial communities and decreased skin microbial diversity have been noted in individuals with atopic dermatitis, and may contribute to an altered inflammatory response (Biedermann 2015; Dybboe 2017). Stress, which may disturb the skin microbiome, damage barrier function, and alter immune function, is another important factor in the initiation and aggravation of atopic dermatitis (Kim, Cho 2013; Bailey 2016; Holmes 2015).

Conventional treatments. Atopic dermatitis is typically treated with topical anti-inflammatory agents such as corticosteroids and calcineurin inhibitors in combination with emollient therapies and antimicrobial therapies (Wollenberg 2013; Clark 2015; Del Rosso 2016). It is important to note that long-term use of topical corticosteroids can have a number of negative effects, including damaging skin structure, interfering with skin repair, and increasing susceptibility to infections (Wollenberg 2013; Ashton 2014; Clark 2015; Dey 2014).

Immunotherapies appear promising in the treatment of atopic dermatitis. This topic is explored in the Novel and Emerging Therapies section.

Integrative treatments. Zinc has an important role in skin immune function (Brocard 2011; Gupta 2014). Inflammatory skin problems are a well-known result of zinc deficiency. One study showed that red blood cell zinc levels were lower in subjects with atopic dermatitis than in controls, and that dermatitis severity increased with lower red blood cell zinc levels (Karabacak 2016). In another study, zinc supplementation raised low hair zinc levels and decreased itching in children with atopic dermatitis (Kim, Yoo 2014).

Topical zinc may also have a role in managing atopic dermatitis. One interesting study found that sleeping in garments made with a zinc oxide-impregnated material for three consecutive nights reduced symptom severity and itching, and led to improved sleep in individuals with atopic dermatitis (Wiegand 2013). In a randomized controlled trial, 47 subjects with chronic hand eczema were treated with either a cream containing the high-potency corticosteroid clobetasol (Clobederm, 0.05%) plus zinc sulfate (2.5%) or clobetasol (0.05%) alone twice daily for two weeks. The clobetasol plus zinc cream was more effective at relieving symptoms and was associated with fewer recurrences at an eight-week follow-up (Faghihi 2008).

Vitamin D receptors in skin cells participate in the regulation of immune and inflammatory responses (Piotrowska 2016). A meta-analysis concluded that individuals with atopic dermatitis have lower vitamin D levels than their healthy counterparts, and pooled findings from four randomized controlled trials using 1000–1600 IU vitamin D daily for one to two months showed that vitamin D supplementation was effective for reducing the severity of atopic dermatitis (Kim, Kim 2016). In one study, the relationship between low vitamin D levels and atopic dermatitis severity was significant only in those participants whose condition involved food sensitivities, suggesting vitamin D supplements may be particularly helpful in such cases (Lee 2013).

In a randomized controlled trial in 20 atopic dermatitis patients, symptom scores were lower after four weeks of treatment with 2000 IU vitamin D daily. In addition, colonization with Staphylococcus aureus decreased with vitamin D supplementation (Udompataikul 2015). Staphylococcus aureus is a common cause of secondary infections and is thought to be a trigger of chronic inflammation in atopic dermatitis (Piotrowska 2016).

Probiotics have demonstrated effectiveness in animal models of atopic dermatitis in clinical trials (Shin 2016; Choi, Iwasa 2016; Choi, Konkit 2016; Yeom 2015; Kim, Park 2013; Inoue 2014; Wang 2015; Kim, Ah 2014). A meta-analysis concluded that supplements containing mixed strains of probiotic bacteria plus prebiotic fibers have a positive impact on atopic dermatitis severity in children (Chang 2016).

In a 12-week controlled clinical trial in 48 atopic dermatitis patients, a probiotic supplement containing Lactobacillus salivarius LS01 plus Bifidobacterium breve BR03 decreased symptom severity and improved quality of life. In addition, participants taking the probiotic supplement had less inflammatory activity and improved gut barrier function as reflected in reduced movement of bacteria across the gut mucosa (Iemoli 2012). In other clinical studies, Lactobacillus salivarius LS01 (Drago 2011), Lactobacillus acidophilus L92 (Inoue 2014), Bifidobacterium animalis subspecies lactis LKM512 (Matsumoto 2014), and a combination of Lactobacillus salivarius LS01, Streptococcus thermophilus ST10, and tara gum (a viscous material made from natural carbohydrate complexes) (Drago 2014) have all been found to reduce atopic dermatitis severity.

Also, probiotics may improve skin barrier function, which is disrupted in atopic dermatitis. In one study, an experimental candy prepared with extracts from Lactobacillus plantarum, derived from traditional Korean kimchi, was compared to a candy with no probiotic extracts in 41 participants with dry skin. After eight weeks, those using the experimental candies had better skin hydration, less water loss via the skin, and diminished thickness of the outermost layer of skin affected by dryness. These same Lactobacillus plantarum enzymes were also found to restore skin integrity in a mouse model of atopic dermatitis (Kim, Kim 2015).

Evening primrose oil, a rich source of the omega-6 fatty acid gamma-linolenic acid (GLA), has been found to be helpful in several clinical trials. Studies in patients with skin disorders have shown that evening primrose oil supplementation can increase blood levels of phospholipids that help modulate the inflammatory response. In eczema patients, evening primrose oil reduced concentrations of the inflammatory interleukin-2 receptor (Horrobin 2000). Borage oil, another high-GLA oil, has also proven helpful in some clinical trials (Foster 2010). One study showed that supplementation with GLA in adults with dry skin and mild atopic dermatitis improved skin barrier function, possibly via production of anti-inflammatory metabolites (Kawamura 2011).

Fish oil and its omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may help people with atopic dermatitis. In one trial, 31 atopic dermatitis patients received either 10 grams of fish oil daily, providing 1.8 grams EPA, or a placebo containing olive oil daily. After 12 weeks, the fish oil-treated subjects had reductions in scaling, itching, and overall severity (Bjorneboe 1987). In an eight-week controlled trial involving 53 subjects with atopic dermatitis, 5.4 grams per day of DHA reduced symptom severity and the production of allergy-related antibodies more than a placebo fatty acid blend (Koch 2008).

Research suggests other oils may have positive impacts on atopic dermatitis. Hempseed oil, a source of essential fatty acids as well as GLA, reduced dryness and itchiness when taken at 30 mL (two tablespoons) per day for eight weeks (Callaway 2005). A daily dose of 4.76 grams (about a teaspoon) of sunflower oil, a rich source of linoleic acid, was more effective than both fish oil and an olive oil placebo in one 12-week study with 48 participants affected by severe atopic dermatitis (Gimenez-Arnau 1997).

Topical colloidal oatmeal (a water suspension of oats [Avena sativa]) has been used historically to relieve skin itching and irritation. Colloidal oatmeal has anti-inflammatory and soothing properties, and has been found to improve skin barrier function (Pazyar 2012; Cerio 2010; Reynertson 2015) and may be beneficial in the treatment of atopic dermatitis (Fowler 2014). A set of two studies reported together found that topical application of a colloidal-oatmeal-containing cream reduced itchiness and improved skin hydration in subjects with mild-to-moderate atopic dermatitis (Lisante 2017).

French maritime pine bark extract (Pycnogenol) has been shown to counteract inflammatory skin conditions. For instance, in one study in patients with moderate-to-severe plaque psoriasis, Pycnogenol plus standard care outperformed standard care alone. Subjects took 50 mg of Pycnogenol three times daily for 12 weeks. Subjects who took Pycnogenol took fewer other drugs and incurred less treatment-related costs (Belcaro 2014). Several studies have evaluated mechanisms by which Pycnogenol may improve skin health. Some possibilities include improved skin barrier function (Grether-Beck 2016), better hydration (Marini 2012), and enhanced resilience to photodamage (Furumura 2012; Saliou 2001).

Emerging Therapies for Atopic Dermatitis

Allergen-specific immunotherapy involves repeated exposure to gradually increasing doses of allergens, usually administered sublingually or through subcutaneous injection (Tam 2016). An analysis of data from 217 atopic dermatitis patients treated with allergen-specific immunotherapy for three years or more noted improvement in 88% of subjects, with near-complete or complete remission in almost 64% (Lee 2016). A clinical study examined the effects of subcutaneous immunotherapy in 251 subjects affected by atopic dermatitis and dust allergy. The overall response rate was nearly 74%, and the response rate in those with severe disease was almost 91% (Nahm 2016).

Crisaborole is a topical non-steroidal anti-inflammatory medication that interferes with the local production of inflammatory chemicals by inhibiting the action of the enzyme phosphodiesterase. A review of four phase I and II clinical trials found a 2% crisaborole ointment was safe and effective for reducing symptoms of mild-to-moderate atopic dermatitis (Zane 2016). Two identically designed randomized controlled trials were then undertaken, enrolling a total of 1522 participants for 28 days of treatment with 2% crisaborole ointment or placebo. Crisaborole treatment resulted in greater reduction in itching and more overall improvement compared with placebo (Paller 2016). The FDA approved crisaborole in 2016 for use in the treatment of atopic dermatitis (FDA 2016).

Monoclonal antibodies. Randomized controlled trials have shown that dupilumab (Dupixent), an antibody against receptors for the pro-inflammatory cytokine interleukin-4, can reduce itching, relieve symptoms of anxiety and depression, and improve quality of life in individuals with moderate-to-severe atopic dermatitis (Simpson 2016). In 2017, the FDA approved dupilumab (Dupixent) for moderate-to-severe atopic dermatitis not adequately controlled by topical therapies (Blakely 2016; FDA 2017). Omalizumab (Xolair), an antibody that binds to IgE receptors and thereby blocks allergic reactions, is currently under investigation for its potential to treat atopic dermatitis. In a case series, four of eight atopic dermatitis patients treated with 300 mg subcutaneous omalizumab every four weeks had a good or excellent response to treatment. The researchers went on to review other reports and found that 74% of 174 reported patients experienced some degree of positive response to omalizumab (Holm 2017). Omalizumab is FDA approved to treat allergic asthma and chronic urticaria (a recurring skin reaction involving hives and wheals) (Genentech USA 2017).

Seborrheic Dermatitis

Seborrheic dermatitis causes itchy, scaly, flaky, reddened patches of skin primarily on the scalp and face and, to a lesser extent, on other areas of the body such as the chest (Sampaio 2011). It occurs in approximately 1–3% of the general population, but has a higher prevalence in immune-compromised individuals. It is more common in cold, dry climates and is often related to stress (Clark 2015). Seborrheic dermatitis may be caused by an inflammatory immune reaction to Malassezia yeast, despite the widespread presence of Malassezia on healthy skin. Individual factors allowing for the transformation of Malassezia into a pathogen and/or triggering an altered immune response are being explored (Clark 2015; Dessinioti 2013).

Conventional treatments. Like atopic dermatitis, seborrheic dermatitis is generally treated with topical anti-inflammatory agents in combination with emollient and antimicrobial therapies (Wollenberg 2013; Clark 2015; Del Rosso 2016). Because long-term use of topical corticosteroids can damage skin integrity, they should be used judiciously (Wollenberg 2013; Ashton 2014; Clark 2015; Dey 2014). Selenium sulfide, zinc pyrithione, and tar (from pine or coal) are antifungal compounds found in topical preparations and shampoos used to treat seborrheic dermatitis. Patients with seborrheic dermatitis may also benefit from topical treatments like salicylic acid, sulfur, and tar that soften and reduce the buildup of lipids and keratin on the skin surface (Clark 2015; Barnes 2016; Paghdal 2009; Reeder 2011; Van Cutsem 1990).

Integrative treatments. Deficiencies of the B vitamins biotin, riboflavin (vitamin B2), and pyridoxine (vitamin B6) can manifest as seborrheic dermatitis or a similar skin dysfunction, possibly due to the importance of these B vitamins in fatty acid and protein metabolism (Stone 1989; Higdon 2013; Schwartz 2006; Anonymous 1952; Bonjour 1977; Mock 1991). Biotin deficiency in infants can cause a form of infantile seborrheic dermatitis of the scalp that generally resolves without treatment. Biotin injections and intravenous biotin have been reported to be helpful in more extensive cases (Messaritakis 1975). It has been reported that a water-soluble cream with 10 mg of pyridoxine per gram, used topically four times daily, was beneficial in seborrheic dermatitis patients, suggesting a possible defect in skin metabolism of vitamin B6 leading to an increased need locally (Schreiner 1952; Anonymous 1952).

Tea tree oil has been studied for its possible role in treating seborrheic dermatitis (Mayo Clinic 2014a). In one clinical trial, 126 participants with dandruff presumed to be related to seborrheic dermatitis of the scalp used either a 5% tea tree oil shampoo or placebo daily for four weeks. The tea-tree oil-treated group had greater improvements in itchiness, greasiness, and overall dandruff severity (Satchell 2002a). Tea tree oil should be used carefully due to its potential to cause skin irritation when used in high concentrations and allergic reactions in some individuals (Hammer 2006).

Honey has been used traditionally to promote wound healing and prevent infections (Pereira 2016; Al-Waili 2001). In a clinical study, 30 subjects with seborrheic dermatitis of the scalp, face, and chest applied diluted crude honey (90% honey diluted in water) on their lesions every other day for four weeks. The honey was gently rubbed into the skin for two to three minutes and then left in place for three hours before being rinsed off. Patients showed improvement in itching, scaling, and the subjective evaluation of hair loss. Patients who showed improvement were included in a second phase lasting for six months. During this second phase, none of the 15 participants who continued weekly applications of diluted honey had any relapses, while 12 of the remaining 15 who did not continue treatment experienced relapses (Al-Waili 2001).

Contact Dermatitis

Contact dermatitis is a localized skin reaction to an irritant or allergen. Chemicals in soaps, cosmetics, and fragrances; jewelry metals such as nickel; and plants such as poison ivy are among the many triggers of contact dermatitis (Mayo Clinic 2014b; Torres 2009; Baer 1986).

Conventional treatment. Antihistamines are sometimes effective for temporary relief of itching, but identifying and avoiding allergens is critical to long-term management (Jafilan 2015).

Integrative treatments. Oxidative stress may be one of the important factors involved in contact dermatitis and, therefore, therapies that restore the balance between oxidant and antioxidant systems could have a role in treatment (Nakai 2012; Eisen 2004; Schempp 2012). In two clinical studies, participants with known reactivity to p-phenylenediamine, a common irritant found in hair dye, had decreased reactions when their skin was treated with topical vitamin C and then exposed to the chemical (Basketter 2016; Coenraads 2016). A 1% mixture of the biological antioxidant nicotinamide adenine dinucleotide (NADH) in petroleum jelly was reported to be effective for the treatment of contact dermatitis in adults (Wozniacka 2003). Animal research suggests that several additional natural antioxidants and anti-inflammatory agents may protect the skin against topical irritants. These include:

  • topical rutin (a flavonoid found in citrus and other plants) (Choi 2013)
  • silymarin (a mixture of flavonoids from milk thistle) (Han 2007)
  • grape seed proanthocyanidins (Tang 2012)
  • carotenoids (Sakai 2011)
  • coenzyme Q10 (Li 2016)

Quercetin is a flavonoid that has been shown to inhibit mast cells, which are the immune cells that are central to allergic, inflammatory, and autoimmune conditions. In 10 volunteers sensitive to contact with nickel, taking 2 grams per day of quercetin for three days reduced their nickel reactions: eight subjects had 50% reductions and two had 100% reductions in their reactions (Weng 2012).

In an animal model of contact dermatitis, topical colloidal oatmeal reduced skin inflammation (Fowler 2014). In experimentally induced contact dermatitis, tea tree oil reduced dermatitis in response to provocation with nickel in patients with a known nickel allergy (Wallengren 2011). Because tea tree oil may cause an allergenic reaction in some people, it should be used judiciously by those who have not used it before (Christoffers 2014). If you suspect you are prone to react to tea tree oil, your dermatologist may be able to perform a skin patch test for confirmation (Rutherford 2007). One small clinical study found that a cream containing Calendula officinalis L. extract reduced contact dermatitis in response to sodium lauryl sulfate when the cream and the sodium lauryl sulfate were applied at the same time (Fuchs 2005). Wearing medicated gloves containing aloe vera gel resulted in decreased skin redness and wrinkling and improved skin integrity on the hands of workers with dry skin and contact dermatitis related to occupational exposures (West 2003). In a study in 22 subjects, ginkgo biloba extract in combination with a chemically modified beta glucan reduced contact dermatitis. The participants applied the ginkgo-containing formulation twice daily for two weeks before being challenged with an allergen under experimental conditions. Sixty-eight percent of experts who judged the severity of the reactions to the irritants determined that reactivity was diminished in areas treated with the ginkgo-containing formulation compared with those treated with a placebo (Castelli 1998).

Urticaria

Urticaria, commonly referred to as hives, is mediated by allergy-related immune cells (eg, eosinophils) and chemicals (eg, histamine) (Wang 2016; de Graauw 2015). Urticaria can be acute or chronic, and while it may involve a known trigger, urticaria is far more often idiopathic, which is without a known cause (Jafilan 2015; Wang 2016; Deacock 2008). In such cases, patch testing may be useful for identifying allergies to metals and chemicals (Hession 2012). Chronic urticaria may reduce quality of life, and is frequently associated with anxiety, depression, and other psycho-emotional disorders (Wang 2016). Urticaria often presents with angioedema, which refers to the sudden swelling of the skin, mucous membranes, or both; may be life-threatening; and requires emergency medical attention, such as taking the patient to the emergency department for evaluation (Schaefer 2017; Kanani 2011; Kaplan 2008).

Conventional treatments. Antihistamines and other anti-inflammatory medications are sometimes used to relieve urticarial symptoms (Jafilan 2015; Wollenberg 2013). In some cases, short-duration adjunctive therapy with corticosteroids or leukotriene receptor blockers may help control symptoms (Schaefer 2017).

Integrative treatments. Vitamin D insufficiency (blood levels of 25-hydroxyvitamin D <30 ng/mL) and deficiency (<20 ng/mL) have been associated with chronic urticaria (Oguz Topal 2016; Boonpiyathad 2014; Movahedi 2015; Woo 2015). In addition, decreasing vitamin D status has been associated with increasing symptom severity and duration (Woo 2015). In a case-control study, supplementation with 20,000 IU vitamin D2 per day for six weeks resulted in decreased symptoms and improved quality of life in participants with chronic urticaria and vitamin D insufficiency who were also being treated with antihistamines (Boonpiyathad 2014). Similar results were seen in another clinical study in which subjects with chronic urticaria and vitamin D insufficiency added 300,000 IU vitamin D3 per month to their standard therapy for three months (Oguz Topal 2016). In one study, 4000 IU daily of vitamin D3 led to benefits after 12 weeks in chronic urticaria patients being treated with standard medications; however, no effects were seen with 600 IU per day (Rorie 2014). Findings from other research suggest vitamin D3 plus standard therapy may be more effective than either vitamin D or standard therapy alone (Rasool 2015).

Low levels of vitamin B12 have been observed in individuals with chronic idiopathic urticaria (Mete 2004; Wu 2015). The effects of B12 supplements in chronic urticaria have not been studied thoroughly, but some old papers report success using intramuscular injections (Simon 1951; Simon 1964). More research in this area is needed.

Low iron or ferritin levels have also been observed in some patients with chronic urticaria; iron supplementation may be useful in these cases (Guarneri 2014; Wu 2015).

In some individuals with celiac disease and chronic urticaria, the urticaria responded to a gluten-free diet (Haussmann 2006; Caminiti 2005; Peroni 2010; Ludvigsson 2013).

Rosacea

Rosacea is characterized by persistent or episodic acne-like lesions and redness, often affecting the face; the lesions are sometimes accompanied by burning or stinging (Mikkelsen 2016). The cause of rosacea is multifactorial: environmental factors such as sun exposure and heat, food and chemical sensitivities, and microbial factors have all been reported to trigger the immune responses that occur in certain individuals with rosacea (Vemuri 2015).

Conventional treatments. The rosacea rash is typically treated with topical agents that have both anti-inflammatory and antimicrobial properties, such as certain antibiotics and azelaic acid (Azelex) (Mikkelsen 2016; Cardwell 2016; Schulte 2015). Brimonidine (Mirvaso), a topical gel that stimulates vascular constriction, is sometimes used to treat rosacea’s redness. Laser and light-based therapies may be used to treat dilation of superficial blood vessels (Micali 2016).

Integrative treatments. In a controlled trial, 138 participants with rosacea were treated with either a 90% kanuka honey cream (a New Zealand honey closely related to manuka honey) in a 10% glycerin base or a placebo cream. After eight weeks of twice daily application, more of those receiving the honey cream than the placebo cream had significant reductions in rosacea severity (Braithwaite 2015). Phytochemicals such as licochalcone (from Glycyrrhiza inflata, licorice), silymarin (from Silybum marianum, milk thistle), and epigallocatechin gallate (EGCG, from Camellia sinensis, green tea) have shown promise as topical treatments for rosacea (Saric 2017; Fisk 2015). A 1% NADH cream in a petrolatum base was also reportedly helpful in treating rosacea (Wozniacka 2003).

Dermatitis Herpetiformis

Dermatitis herpetiformis is a skin manifestation often associated with celiac disease that causes small, itchy blisters typically on the buttocks, arms, and legs. Celiac disease is an autoimmune-mediate disorder of the digestive tract triggered by exposure to gluten, a protein in wheat and some other grains (Reunala 2015; Antiga 2015). If dermatitis herpetiformis is suspected, tests for the presence of IgA transglutaminase antibodies in blood and IgA deposits in the skin are helpful for making the diagnosis (Antiga 2015). More general information about celiac disease is available in the Celiac Disease protocol.

Conventional treatments. Dermatitis herpetiformis can be successfully treated with a gluten-free diet (Reunala 2015), but oral corticosteroid therapy is sometimes used to manage the itching and burning sensations (Antiga 2015). Oral corticosteroids have many negative side effects, which are more serious with prolonged use. These include adrenal suppression, decreased immune activity, metabolic disturbances, cardiovascular disease, bone loss, and psychiatric problems (Liu 2013).

Integrative treatments. Certain nutrients may aid in recovery either through a therapeutic role or by repairing deficiencies due to malabsorption. These include zinc, magnesium, selenium, iron, and vitamins B3, B12, and folic acid (Gaby 2011a).

Lichen Planus

Lichen planus is an autoimmune disorder that affects as much as 4% of the general population. It can affect the skin, hair, nails, and mucous membranes. On the skin, lichen planus usually develops on areas prone to flexural movement such as the wrists, and causes small, flat-topped lesions that may itch. The lesions appear most commonly on the surfaces of the wrists, forearms, and legs, but may also occur on the oral mucosa, genital mucosa, nails, and scalp (Usatine 2011). Most cases resolve on their own in six to 18 months (Chuang 2017).

Conventional treatments. Lichen planus is often treated aggressively, using the high-potency topical corticosteroid clobetasol and the calcineurin inhibitor tacrolimus (Protopic), as well as oral immunosuppressant medications as needed (Usatine 2011). Self-care measures are recommended in lichen planus, including tub soaking with colloidal oatmeal, cool compresses, over-the-counter hydrocortisone cream, and avoidance of scratching (Mayo Clinic 2017c).

Integrative treatments. Because of its autoimmune nature, it is possible that integrative treatments used to treat some other autoimmune conditions will be helpful in lichen planus. These include anti-inflammatory supplements such as omega-3 fatty acids from fish oil (Lorente-Cebrian 2015) and curcumin (Abdollahi 2017; Kunnumakkara 2016) as well as immune modulators such as reishi (Ganoderma lucidum) (Bhardwaj 2014; Xi Bao 2006) and vitamin D (Lucas 2014). A number of botanical therapies appear to be beneficial in the treatment of lichen planus lesions of the oral mucosa and may be helpful in treating its skin lesions as well. These include topical chamomile (Lopez Jornet 2016), aloe vera (Ali 2016), and grape skin anthocyanins (Rivarola de Gutierrez 2014), as well as oral curcuminoids from turmeric (Chainani-Wu 2007; Chainani-Wu, Collins 2012; Chainani-Wu Madden, 2012) and total glucosides of peony (Zhou 2016).

Acne Inversa (Hidradenitis Suppurativa)

Acne inversa, also known as hidradenitis suppurativa, is a severe type of chronic, recurrent folliculitis marked by intense pain and scarring. It is much overlooked and often misdiagnosed despite its prevalence of at least 1% and up to 4% worldwide (Dufour 2014; Tolaas 2009; Mi 2011). It is more common in women than men (AAD 2017). Acne inversa likely results from both impaired immunity in the hair follicles and an excessive response to certain skin bacteria (Scheinfeld 2013a), and is often associated with and worsened by obesity and smoking (Scheinfeld 2013a; Tolaas 2009; Dufour 2014).

Conventional treatments. Mild cases may be effectively treated with topical antibiotics, but more widespread or severe cases require oral or intravenous antibiotics, or possibly surgery (Gulliver 2016; Scheinfeld 2013a). Because acne inversa is multifactorial, a range of approaches and combinations of therapeutics may be helpful (Napolitano 2017). Vitamin A analogs (Verdolini 2015; Brown 1988; Hogan 1988), hormonal therapies, and immunosuppressive medications are among the treatments that may help patients with acne inversa. Pain management is an important consideration (Scheinfeld 2013a; Gulliver 2016; Blok 2013). Adalimumab (Humira) is an anti-inflammatory biologic medication FDA-approved to treat acne inversa. According to expert opinion, adalimumab is likely to deliver good results with weekly 40 mg subcutaneous injections in patients with inflamed lesions, but is unlikely to be effective for those with non-inflamed, non-scarring lesions (Zouboulis 2016).

Integrative treatments. In a small clinical study, 15 mg of oral elemental zinc (as 90 mg zinc gluconate) per day led to improvements in 100% of patients with acne inversa that were unresponsive to other treatments; out of 22 subjects, eight had complete resolution and 14 had partial remission (Brocard 2007).

Vitamin D is important for skin immune function, and vitamin D deficiency has been found to be widespread in people with acne inversa. In 14 acne inversa patients treated with vitamin D for six months at doses determined by their vitamin D levels, participants had an at least 20% decrease in the number of nodules and an at least 20% reduction in flare-up frequency, and those who experienced greater increases in vitamin D levels had greater positive effects (Guillet 2015).

Pityriasis rosea

Pityriasis rosea is an inflammatory skin rash characterized by patches on the skin; it sometimes follows a flu-like illness with symptoms such as fever, sore throat, fatigue, and headache. Although the cause is unknown, the involvement of infectious agents such as viruses and bacteria, as well as noninfectious causes such as autoimmunity, have been discussed (Mahajan 2016; Ozyurek 2014).

Conventional treatments. Pityriasis rosea typically resolves without treatment in one to three months; however, topical or oral corticosteroids and antihistamines may be helpful in some cases (Mayo Clinic 2015a; Chuh 2007). There is some evidence that the antiviral medication acyclovir (Zovirax) and the antibiotic erythromycin may each effectively decrease severity of symptoms and shorten duration of pityriasis rosea (Chuh 2016; Amatya 2012); however, other research suggests lack of efficacy for these medications (Singh, Tiwary 2016; Pandhi 2014).

Integrative treatments. Zinc oxide cream is sometimes used to relieve the symptoms of pityriasis rosea (AAFP 2004). Because of its inflammatory nature and possible connection to infection, immunomodulatory therapies such as reishi (Xi Bao 2006), vitamin D (Lucas 2014), and astragalus (Jin 2014) may be helpful.

Several studies have looked at the effect of light therapy in patients with pityriasis rosea. In one study, UV-B therapy for five days led to reductions in itching and extent of the condition in about half of 20 symptomatic participants, and seemed most effective when used within the first week of appearance of the rash (Arndt 1983). A similar study in 17 participants noted that UV-B therapy five times per week for two weeks reduced severity of the pityriasis rash, but did not affect itching or the course of the condition (Leenutaphong 1995).

Miliaria (Heat Rash or Prickly Heat)

Miliaria, often called heat rash or prickly heat, is a skin rash that comes on during hot, humid weather and is caused by perspiration trapped under the skin’s surface. Miliaria may be preventable by avoiding heavy sweating and overheating in general (Mayo Clinic 2015b).

Conventional treatments. Miliaria usually resolves without treatment. Symptoms are treated with cold compresses and ice packs, and patients are instructed to avoid further sweating and wear loose clothing. Anhydrous lanolin may be helpful in preventing future lesions by keeping sweat ducts open. In addition, topical steroids may be used to relieve symptoms in more severe cases, and antibiotics may be required in cases of secondary infection (Oakley 1997; Mayo Clinic 2015b).

Integrative treatments. Colloidal oatmeal, with its soothing, anti-inflammatory, and anti-itch effects (Fowler 2014), may be helpful in relieving symptoms of miliaria.

8 Common Skin Growths

Skin tags, epidermoid cysts, sebaceous hyperplasia, and seborrheic keratosis are common benign skin neoplasms (growths). These skin growths all occur more frequently with age, and although they are not typically associated with health problems, it is sometimes preferable to remove them (Luba 2003). Actinic keratosis is a precancerous skin growth caused by chronic sun exposure and for which treatment is recommended (Cantisani 2013; Costa 2015).

Benign Skin Growths

Skin tags. Also known as acrochordons, skin tags are superficial growths affecting an estimated 25% of adults, and are especially prevalent in obese people (Luba 2003). Skin tags are permanent unless removed (HHP 2013) and commonly recur even after removal (Luba 2003).

Epidermoid (or inclusion) cysts. Epidermoid cysts are pockets under the skin surface in which keratin and skin cells are trapped. Although epidermoid cysts are sometimes incorrectly referred to as sebaceous cysts, they do not involve sebaceous glands. Epidermoid cysts may resolve without treatment, but sometimes become inflamed or infected, requiring incision and drainage (Luba 2003).

Sebaceous hyperplasia. Sebaceous hyperplasia is a benign enlargement of sebaceous glands. The cause of sebaceous hyperplasia is not known, but transplant patients taking cyclosporine (an immune-suppressing medication) and dialysis patients have a higher risk of sebaceous hyperplasia (Luba 2003).

Seborrheic keratosis. Seborrheic keratosis is characterized by pigmented growths that are said to appear “stuck on” to the skin surface. In rare cases, a sudden onset or increase in number of seborrheic keratoses can indicate an underlying malignancy such as stomach, colon, or breast cancer (Luba 2003).

Conventional Treatment of Benign Skin Growths

Benign skin growths are typically treated if they are a site of chronic irritation, discomfort, or concern to the patient (Ingraffea 2013; Costa 2015; NLM 2017b). Excision (surgical removal) or cryotherapy using liquid nitrogen are common techniques for removal (NLM 2017b; Rao 2007). Electrodessication is sometimes used along with excision (NLM 2017b). Laser therapy and photodynamic therapy can also be used to treat skin growths, but these techniques can cause scarring and pigmentation changes that are especially problematic in darker skin (Alexis 2013). Photodynamic therapy is discussed in more detail in the Novel and Emerging Therapies section.

In a clinical study in 20 subjects with sebaceous hyperplasia, treatment with isotretinoin (Accutane) at 1 mg/kg of body weight per day for two months was effective in 100% of participants at reducing the number of lesions and caused no severe side effects. The average number of lesions per subject dropped during the trial from 24 to two. Two years after the end of treatment, few lesions had recurred, and the average number of lesions per subject was four (Tagliolatto 2015).

Integrative Treatment of Benign Skin Growths

Studies using vitamin D3 to treat seborrheic keratosis have yielded promising results (Asagami 1996; Lu'o'ng 2013). In 116 individuals with seborrheic keratosis treated with topical vitamin D3 ointment for three months or longer, nearly 77% showed at least a 40% reduction in volume, and no side effects were observed (Mitsuhashi 2005).

Actinic Keratosis

Actinic keratosis is a precancerous lesion caused by ultraviolet light exposure from sunlight or tanning beds. It manifests as rough, scaly skin patches, typically on the face, ears, backs of the hands, forearms, scalp, and neck (Mayo Clinic 2017a). In addition to older age, risk factors for actinic keratosis include a history of outdoor work, male gender, baldness, fair complexion, tendency to develop sunburns, evidence of sun damage to skin (eg, wrinkles), and prolonged immune weakness (Flohil 2013; Green 2015; Speight 1994; Cox 1994; Trakatelli 2016). Unlike benign skin growths, chemical or surgical treatment is strongly recommended for actinic keratosis (Cantisani 2013; Costa 2015). Importantly, a small percentage of actinic keratoses may develop into skin cancer, so consultation with a dermatologist is important (Mayo Clinic 2017b). For more information about protecting skin and preventing skin cancer, please refer to the Skin, Hair, and Nail Health and Skin Cancer protocols.

Conventional treatments. Although many actinic keratoses disappear on their own, they often return with subsequent sun exposure. Also, since it is challenging to determine which lesions will progress to skin cancer, the lesions are usually removed as a precaution (Mayo Clinic 2017b).

Topical salicylic acid (Acnevir and various others) is an exfoliant and peeling agent used to treat actinic keratosis and other types of sunlight damage on the skin (Arif 2015; Uhlenhake 2013; Chetty 2015). Other treatment options are topical imiquimod (Aldara), an immune-modulator, and 5-fluorouricil (5-FU), an anti-proliferative agent (Hanna 2016; Kaur 2010; Werschler 2008). These treatments typically cause side effect such as localized redness, dryness, burning, itching, and swelling (Thappa 2016; Arif 2015; Costa 2015). In rare cases, salicylic acid overdose may occur, leading to dangerous and potentially fatal central nervous system toxicity (Arif 2015).

Retinoids, natural and synthetic vitamin A derivatives, may also be used for treatment or prevention of actinic keratosis. Retinoids are used in the prevention and treatment of non-melanoma skin cancer, but their use in actinic keratosis is less firmly established because fewer studies specifically on actinic keratosis have been conducted. Some studies have shown that organ transplant patients using retinoids to prevent skin cancer have a lower rate to actinic keratosis development compared with those treated with placebo. It is not clear whether topical or systemic retinoids are preferable for actinic keratosis prevention; both routs of administration have reduced the number of actinic keratosis lesions in small studies (although many of the studies have design or methodology limitations). Systemic retinoids may cause several side effects such as dry eyes and dry skin, and less frequently systemic side effects such as elevation of liver enzymes and cholesterol may occur. Importantly, retinoids may cause birth defects, so should not be used be women expecting to become pregnant (Ianhez 2013).

Integrative treatments. In a study that enrolled nine actinic keratosis patients, an analog of vitamin D3 was applied topically on half of the affected area of the face or scalp and the base cream without the vitamin D3 analog was used on the other half for 12 weeks. The number of actinic keratoses decreased where the vitamin D3 analog was used but did not change where the base cream alone was used (Seckin 2009).

Photodynamic therapy is one of the most effective treatments for actinic keratosis, but recurrences due to treatment-related immunosuppression or DNA damage are an ongoing concern. One study found that actinic keratosis patients who received an oral supplement containing an extract from the fern Polypodium leucotomos for six months after photodynamic treatment had fewer recurrences than those treated with photodynamic therapy alone (Auriemma 2015).

9 General Dietary and Lifestyle Considerations

Proper nutritional intake is essential for skin health, and nutritional status disorders such as obesity and malnutrition often lead to skin problems (Liakou 2013; Park 2015; Pappas 2016). Excess glucose and insufficient protein can interfere with normal healing processes, and a balance of fatty acids is needed to maintain epidermal integrity and regulate inflammation and immune activity in skin (Nicolaou 2013; Kawahito 2009; Molnar 2014; Anderson 2012; Alexander 2014). Vitamins A, C, D, and E, B-complex vitamins, and the trace minerals zinc, copper, and selenium, all have important roles in protecting skin health, and deficiencies have been linked to specific skin disorders (Park 2015; Pappas 2016). Carotenoids and polyphenols from plant-based foods protect the skin against free radical damage (Pappas 2016).

In general, a healthy eating pattern that emphasizes fruits, vegetables, and foods that are low in sugar and saturated fat is associated with healthy skin and can be broadly recommended to people with skin disorders (Katta 2014). Lower rates of atopic dermatitis have been correlated with consumption of rice, fermented vegetables, and coffee in Korean populations (Park, Choi 2016; Park, Bae 2016) and consumption of fresh fruits and legumes in a Colombian population (Cepeda 2015).

Food allergy may play a role in atopic dermatitis, with eggs, cow’s milk, wheat, soy, and peanuts all being likely culprits. In atopic dermatitis patients with known food allergies, elimination of the allergenic foods from the diet can be helpful (Greenhawt 2010; Mohajeri 2014). Removing certain food additives, such as sorbic acid and tartrazine, from the diet may reduce symptoms in some patients with atopic dermatitis (Mohajeri 2014). In some individuals with nickel allergy, urticaria can be triggered by exposure to nickel that occurs naturally in foods or that has leached into food from stainless steel cookware. For these individuals, a low-nickel diet may be helpful (Antico 1999; Buyukozturk 2015; Abeck 1993; Zirwas 2009).

It is widely assumed that water intake has a positive effect on skin health, and a study published in 2015 has given additional support to this notion. In the study, 49 healthy women were randomly assigned to drink either less than or more than 3200 mL of water per day for one month. In general, the women assigned to the high water intake group increased their water intake by about 2 liters per day. At the end of the study, deep and superficial skin hydration and tests of skin physiology had improved in women drinking extra water (Palma 2015).

The well-established connection between the skin and mind is the basis of an emerging field called psychodermatology (Jafferany 2016). Hormones involved in the stress response stimulate inflammatory signaling in the skin (Kim, Cho 2013), and stress may affect the skin and gut microbiotas, further contributing to disturbed immune function and inflammation (Bailey 2016). Emotional stress can precipitate or exacerbate inflammatory skin disorders such as acne, atopic dermatitis, seborrheic dermatitis, psoriasis, rosacea, and urticaria (Jafferany 2016; Huynh 2013). Psychotherapy, cognitive behavioral therapy, relaxation training, hypnosis, stress management, biofeedback, and guided imagery have all been used successfully to treat skin disorders (Jafferany 2016). You can read more about healthy ways to handle stress in the Stress Management protocol.

Photodynamic Therapy for Skin Disorders

Photodynamic therapy involves the application of a topical photosensitizing agent (usually aminolevulinic acid or methyl aminolevulinate) and light to induce oxidative damage in the skin being treated. Although photodynamic therapy has long been used in the treatment of actinic keratosis, it has recently been proposed to have benefits in infectious and inflammatory skin disorders (Kim, Jung 2015; Wan 2014).

Researchers have found that photodynamic therapy can be effective for eradicating genital warts and persistent warts on the palms and soles (Kim, Jung 2015). It has also shown efficacy in treating sebaceous hyperplasia, particularly when combined with laser therapy (Simmons 2015). Preclinical research and early studies in humans suggest photodynamic therapy may be effective against fungal skin infections such as those caused by dermatophytes and by Malassezia and Candida species (Baltazar, Ray 2015). Intriguingly, preclinical research suggests curcumin, an anti-inflammatory and antimicrobial compound from turmeric ( Curcuma longa) (Mahmood 2015), may be an effective photosensitizer against dermatophytes (Brasch 2017; Baltazar, Krausz 2015).

Photodynamic therapy can cause an array of local adverse side effects, including redness, swelling, burning, prickling, ulceration, and pain that is often severe (Kim, Jung 2015). One strategy for reducing pain is to use daylight as the light source. In some studies, daylight in combination with photosensitizing methyl aminolevulinate cream appeared to be a promising approach in terms of effectiveness in treating actinic keratosis, and was accompanied by less pain compared with other forms of photodynamic therapy (Fitzmaurice 2016).

Disclaimer and Safety Information

This information (and any accompanying material) is not intended to replace the attention or advice of a physician or other qualified health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a physician or other qualified health care professional. Pregnant women in particular should seek the advice of a physician before using any protocol listed on this website. The protocols described on this website are for adults only, unless otherwise specified. Product labels may contain important safety information and the most recent product information provided by the product manufacturers should be carefully reviewed prior to use to verify the dose, administration, and contraindications. National, state, and local laws may vary regarding the use and application of many of the therapies discussed. The reader assumes the risk of any injuries. The authors and publishers, their affiliates and assigns are not liable for any injury and/or damage to persons arising from this protocol and expressly disclaim responsibility for any adverse effects resulting from the use of the information contained herein.

The protocols raise many issues that are subject to change as new data emerge. None of our suggested protocol regimens can guarantee health benefits. Life Extension has not performed independent verification of the data contained in the referenced materials, and expressly disclaims responsibility for any error in the literature.

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