Atopic Dermatitis - An Itchy Subject

What is atopic dermatitis?

Atopic dermatitis, also known as eczema, is a chronic and/or relapsing inflammatory skin condition, which often begins in childhood and persists into adulthood.^[1-3] According to the World Allergy Association, the term “atopic” refers to the genetic predisposition to develop an allergic reaction and produce IgE antibodies in response to the exposure to an allergen, usually proteins.^[1-2,4] Eczema is associated with a number of atopic conditions, such as food allergies, seasonal allergies, and asthma, which suggests a common pathogenesis, and is more likely to occur in people with a family history of these conditions.^[1,3] However, not all eczematous rashes are atopic such as the rash from poison ivy or the rash from contact with a chemical/irritant (both contact dermatitis). For the purposes of this article, atopic dermatitis and eczema will be used interchangeably.

Although the rashes can occur anywhere on the body, eczema typically affects babies on their cheeks and outer limbs, while children and adults commonly experience the rash on the flexural surfaces of the body, such as the neck, elbow and knee creases.^[3] Signs and symptoms of eczema include dry skin, redness, rash, scaling, swelling, oozing, intense itching, and skin thickening from chronic scratching of lesions. Eczema can lead to intractable scratching causing bleeding, sleep loss, poor concentration, psychological distress and self-esteem issues.^[1-3] Other red flag symptoms include rashes with any eye involvement, secondary bacterial infections from scratching, or rare conditions like exfoliative dermatitis (widespread rash with massive scaling), all of which require immediate referral. Diagnosis is typically made from clinical evaluation and disease history, and severity of the condition is evaluated using the SCORAD (scoring of atopic dermatitis) or SASSAD (six area, six sign atopic dermatitis) indexes.^[3] Eczema is usually made worse by dry weather conditions, hot bathing/showering, rough materials like wool, and studies have even suggested that stress and sleep deprivation decrease skin barrier function, leading to higher incidences of eczema.^{[1, 5]}

Eczema is a very common condition with worldwide prevalence, affecting up to 20% of children and 3% of adults, with rising incidence particularly in developed countries.^[4] The economic burden associated with treating eczema is comparable to treatment associated with epilepsy, emphysema, and other chronic diseases.^[1] Although there are a number of conventional treatments, these typically only address the symptoms of eczema.Thus, prevention and effective resolution of eczema are paramount for reducing the burden of this condition. In the next part of this series, we will investigate the potential causes of this common condition.

What are the causes of eczema?

To sanitize or not to sanitize? The Hygiene hypothesis

While staying germ-free has helped prevent the spread of disease and infection in the industrialized world, epidemiological data has shown that there has been an increased incidence of atopic diseases, such as eczema. Coined the term “hygiene hypothesis” by researcher Strachan in the early 90s, he observed that smaller family size, and thus less exposure to infectious agents, correlated to higher incidence of allergic disease.^[6-7] In developing countries where good health standards do not exist and parasitic infections predominate, the prevalence of allergic diseases remains low.^[8] Migration studies have also showed that people migrating from countries of low-incidence, to countries with high-incidence of allergies, had the next generation born with a high incidence of allergies.^[8] The hypothesis suggests that there is an imbalance between adaptive immune cells, the Th1 and Th2 responses. The lack of bacterial/viral burden in early childhood, which normally favors a strong Th1-biased response, redirects the immune system to a predominantly Th2-biased response which also happens to down-regulate the Th1 cells, ultimately predisposing the person to atopic conditions.^[6-8] Essentially, infections in childhood prime the immune system to favor one type of immune response over the other. However, this hypothesis does not fully explain all the immune mechanisms at play, or the concurrent increases of Th1-mediated autoimmune diseases like Crohn’s and multiple sclerosis.

Gut bugs: The Microbial hypothesis

Outnumbering our own cells 10-to-1, human intestinal bacteria represent the most significant microbial exposure to the developing infant.^[9] Under normal conditions, these friendly or commensal bacteria have a number of functions in the human gastrointestinal system, such as breakdown of undigested dietary fibers, the release of essential vitamins, and control of gut cell growth and differentiation.^{[9, 10]} One of the most important functions that intestinal microbes have is the stimulation of our largest immune organ, the gut-associated lymphoid tissue (GALT), while at the same time promoting tolerance to benign substances, including foods. This stimulation occurs throughout a person’s life, but is thought to be most critical during the prenatal and postnatal stages.^[10] Colonization by these friendly bacteria occurs immediately after birth, and is influenced by type of delivery, the maternal microbes, genes, breast feeding and other environmental factors.^{[10, 11]} Several epidemiological studies have demonstrated the relationship between intestinal microbes and the prevalence of eczema and allergies, but like the hygiene hypothesis, the microbial hypothesis falls short in explaining all the mechanisms involved in the development of eczema and other atopic conditions.

The role of the filaggrin gene

The largest organ of the body, the skin’s primary function is to act as a protective barrier between the external environment and the host, minimizing water loss and preventing pathogens and allergens from entering the system.^[12] One of the key genes involved in the formation of a functional skin barrier is filaggrin (FLG) and it encodes for proteins in the skin which prevent water loss and entry of microbes. Numerous human studies have shown that mutations in this gene correlate with a defective skin barrier, leading to dry, itchy skin and higher incidences of eczema.^[13] Researchers are now suggesting that this defect in functional skin barrier is what sets the stage for allergic sensitization and eventually eczema.^[12,13] We will examine the role of stress in the exacerbation of eczema.

Stress and the skin: the role of psychoneuroimmunology

Although it is generally accepted that stress is a relevant contributing factor to a number of chronic diseases, including eczema, the field of psychoneuroimmunology (PNI) is now providing evidence about the ways stressors create physiological changes in the body. Psychoneuroimmunology is a field that studies the complex interaction between the central nervous system (CNS), the endocrine system and the immune system.^[14] Psychological stress is broadly defined as an event or environmental demand, real or imagined, which exceeds a person’s perceived ability to cope, and can be further subdivided into acute and chronic stressors.^[14] Acute stress can be adaptive in some cases, such as during a “fight or flight” response, where the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS) prepare the body to deal with the threat by increasing heart and breathing rate, increasing blood flow to skeletal muscles and increasing blood sugar levels.^[15] On the other hand, chronic stress has more deleterious effects, that is, increasing susceptibility and severity of infection, slowing wound healing, and substantially increasing the production of pro-inflammatory cytokines.^[14] The skin, which contains a network of numerous sensory fibers, expresses many of the same neurotransmitters and receptors as the central nervous system (CNS), including serotonin, corticotrophin-releasing hormone and substance-P.^[16] The skin is also intimately connected with the immune, nervous and endocrine systems and has 2-way communication with these systems via chemical messengers.^[16] Dysregulation of these chemical messengers has been shown to uniquely contribute to the pathophysiology of eczema.

In one study, researchers took patients with an without eczema and exposed them to a psychosocial stress test, where participants had to do a speech and arithmetic tasks in front of an audience. The results showed that the people with eczema had significant circulating levels of eosinophils after the test, which are considered to play pivotal roles in chronic allergic inflammation and eczema.^[17] In addition, the results showed that eczema patients had significantly elevated circulating IgE antibodies for 24 hours after exposure to the stressor. IgE has been shown to be a key molecule in eczema pathology as it stimulates basophils and mast cells which contribute to the immediate hypersensitivity reaction.^[17] Furthermore, IgE enables other cells to activate a Th2-mediated immune response. In another study, researchers investigated how stress affects the barrier function of the skin. Subjects were evaluated during an initial low-stress period (following winter vacation), followed by a high-stress period (during February final exams), and finally 4 weeks after the stressful period.^[18] Using an evaporimeter, as well as the Profile of Mood States (POMS) and the Perceived Stress Scale (PSS), researchers were able to show that subjects who experienced the highest perceived stress had the greatest reduction in skin barrier function, with increased trans-epidermal water loss (TEWL) and exacerbation of skin lesions following a physical insult to the epidermis.^[18] The authors concluded that this study demonstrates the clinical relevance of the role of stress on initiating or exacerbating common inflammatory skin disorders such as eczema.

Naturopathic approaches for the management of eczema

Probiotics

With considerable evidence-based research, probiotics have garnered much attention as therapy for numerous conditions, including the prevention and treatment of eczema. According to the World Health Organization (WHO), probiotics are “live micro-organisms, which when administered in adequate amounts, confer a health benefit on the host”.^[19] Several randomized-control trials (RCTs) have shown that supplementation of probiotics during the prenatal and postnatal periods significantly reduced the cumulative incidence of eczema by age 2 years.^[20-25] Furthermore, breastfeeding has been shown to have important immune-regulatory factors which can help protect against the development of allergic disease, and studies have shown that exclusive breastfeeding for at least 6 months significantly decreased the risk of developing eczema in high-risk infants.^{[19, 26]} Finally, a meta-analysis of the impact of maternal probiotic supplementation showed a significantly reduced risk of eczema development in children by 2-7 years of age with the use of lactobacilli compared to placebo.^[27] Preventative effects were found with the following strains: Lactobacillus rhamnosus GG, L. acidophilus ,L. sakei, L. salivarius, L fermentum, B. lactis, and B. Bifidum.^[19] Similarly, probiotics have shown to be effective in the treatment of eczema. A 2012 study showed that children aged 1-3 years with a history of eczema supplementing for 8 weeks using a combination of B. Bifidum, L. acidophilus, L. casei, and L. salivarius had significant reductions in SCORAD, serum IgE, and cytokines associated with allergy compared to placebo.^[19] A similar study by Drago et al showed that adults supplementing with L. salivarious LS01 for 16 weeks resulted in significantly lowered SCORAD and Th1/Th2 cytokine ratios compared to placebo.^[19] However, based on systematic reviews and meta-analyses, efficacy of probiotic treatment for eczema remains inconclusive. A reason for this could be due to the heterogeneity between studies, both in study populations as well as the selection of probiotic strains used.

Hypoallergenic diet

Many clinicians believe that nutritional allergens may be important triggers of eczema, with sensitivities to cow’s milk, eggs, wheat and soy being the top offenders.^[28] The hypoallergenic diet removes common food allergens for a period of time, anywhere from 3 weeks to months, and slowly re-introduces the offending food items to determine if exacerbations occur. There are a handful of studies that have been published on egg- and cow’s milk-free diets, with the greatest reduction of eczema symptoms occurring with an egg-free diet in infants with established allergy to eggs.^[28] According to the German EAACI position paper, the administration of a hypoallergenic diet over a period of at least 3 weeks can be helpful in severe eczema.^[29] Furthermore, a pilot study of 100 infants and children found that elimination of some allergenic foods resulted in a significant reduction in severity of eczema, as measured by the SCORAD index.^[30] Finally, a more recent study in adults demonstrated that recommendation of a hypoallergenic diet for a period of 3 weeks resulted in significant reduction in severity of subjective parameters and all objective SCORAD parameters, except lichenification.^[31] Sadly, the hypoallergenic diet is criticized due to insufficient rigorous human RCTs and the concern that eliminating food groups may induce malnutrition, especially in growing children. In any case, there is adequate theoretical and observational evidence with which to prescribe a trial hypoallergenic diet for at least 3 weeks to determine whether food allergies play a role in a patient’s presentation of eczema, with clinicians closely monitoring their diet and supplementing where nutrients may be inadequate.

Specific nutrients for skin

Several nutrients have been found to promote the barrier function of the skin, reduce inflammation, and treat the symptoms associated with eczema. Topical therapy remains fundamental to the management of eczema symptoms, such as skin dryness, inflammation and itch. Hypoallergenic emollients help to reduce transepidermal water loss (TEWL), maintain epidermal ceramide levels, and can help reduce itching.^[32] A recent double-blind placebo-controlled trial found that topical vitamin B12 significantly reduced eczema lesions after 2 and 4 weeks of use.^[33] Studies also suggest that omega-3 fatty acids EPA and DHA are incorporated into epidermal ceramides thus decreasing skin permeability, reducing dryness and itching, and reducing inflammatory activity in the skin.^[34] Studies have also shown that use of 500mg evening primrose oil (EPO) containing 40mg GLA and 10mg vitamin E significantly reduced eczema symptoms in children after 16 weeks.^[35] Finally, supplementation with 1600 IU vitamin D3 and 600 IU vitamin E (α-tocopherol) resulted in significantly reduced SCORAD scores in patients with eczema after 60 days of treatment.^[36]

Given the complexity of eczema, Naturopathic Doctors should utilize a variety of treatment methods and aim to address both symptoms and causes of this condition.