The American Autoimmune Related Diseases Association estimates that in the United States alone, more than 50 million individuals have autoimmune diseases, with women representing more than 80% of autoimmune patients. These diseases affect a wide range of organs and tissues in the body, including the body’s largest organ, the skin. Because the skin is so visible and important to overall function, autoimmune skin disorders can significantly impact individuals’ physical and mental well-being. With an increasing understanding of the gut-skin axis, the connection between hormones, gut health, and autoimmune skin disorders is gaining interest as a potential avenue for managing these conditions.

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What Are Autoimmune Skin Disorders?

The immune system consists of cells, tissues, and organs that defend the body against pathogens and foreign invaders to prevent infection and disease. A properly functioning immune system is able to discern the difference between the body’s own cells and foreign cells, a concept called immune tolerance. In autoimmune diseases, the immune system loses self-tolerance and begins to attack the body’s own tissues. While the exact causes of autoimmunity are not completely understood, it is believed to involve a combination of genetics and environmental factors. Genetic predisposition can make certain individuals more susceptible to autoimmune diseases, while various triggers, including infections, chemical exposures, and hormone imbalances, may initiate or exacerbate the autoimmune response. (35)

Autoimmune diseases vary in terms of which organs or tissues are affected, extending to skin involvement. Some autoimmune diseases exclusively target the skin and mucous membranes, while others can affect multiple organs or systems, including the skin. Some common autoimmune disorders affecting the skin include:

1. Psoriasis
2. Vitiligo
3. Scleroderma
4. Systemic lupus erythematosus (SLE) 
5. Dermatomyositis
6. Lichen sclerosus
7. Alopecia areata

The Gut-Skin Axis

Certain digestive disorders increase the risk of developing skin disorders. For instance, psoriasis, atopic dermatitis, and rosacea have been observed to be more prevalent in inflammatory bowel disease, highlighting the bidirectional relationship that exists between these two systems, known as the “gut-skin axis.” Emerging research suggests that the health of the gut has a significant impact on the health of the skin and vice versa. The gut and skin even share commonalities in terms of structure and function. Both are physical barriers, serving as first-line defenders of the immune system. Furthermore, they each are home to immune cells, neuroendocrine connections, and a unique composition of microorganisms collectively known as the microbiome. These similarities underscore the interconnectedness between these two bodily systems. (​​19)

The gut’s microbiome performs many functions, including preventing infection from pathogens and synthesizing important nutrients and short-chain fatty acids (SCFA’s). Each person’s microbiome is unique and is influenced by factors like diet, stress, and environmental exposures. 70-80% of the immune system resides in the gut, where it interacts with the microbiome. This interaction influences the development and activity of immune cells. 

Certain commensal bacteria strains stimulate immune cells, called regulatory T cells, that help to maintain balance in the immune system and self-tolerance. Others can stimulate immune cells that increase the production of inflammatory mediators. Molecules associated with the microbiome, such as bile acid metabolites, SCFA’s, and endotoxins (lipopolysaccharide or LPS), also influence the activity of the immune system.

The gastrointestinal tract ideally functions as a physical barrier preventing the absorption of pathogens and other unwanted molecules. When this barrier becomes compromised, as observed in a condition called intestinal permeability or leaky gut, this barrier deteriorates. Consequently, it permits the unwanted absorption of these molecules, allowing them to interact with the immune system. This interaction triggers immune system activity and systemic inflammatory responses. 

Systemic inflammation, often identified by elevations in biomarkers like c-reactive protein (CRP) and interleukin-6 (IL-6), is an underlying imbalance often seen in autoimmune conditions. (63, 65) Many factors, including stress and disruptions to the composition of the microbiome, referred to as dysbiosis, contribute to the development of intestinal permeability. (48) Both dysbiosis and intestinal permeability have been associated with the development of autoimmune disorders in general, as well as skin conditions specifically. (9, 18, 57)  

This is not solely a one-directional relationship. UV exposure to the skin can increase the diversity of the gastrointestinal microbiome. An impaired skin barrier, as seen in conditions like atopic dermatitis, also increases the risk of food allergy. (19)

Hormones and Skin Health

Hormones are chemical messengers in the body, regulating important physiological processes. Hormones impact numerous aspects of skin health, including the regulation of sebum production, the maintenance of the skin's protective barrier function, the promotion of collagen synthesis for skin elasticity, the control of sweat production, and the regulation of hair growth. Given the extensive array of functions they govern, hormonal imbalances can have a substantial impact on the overall health and appearance of the skin. 

Excess sebum production is one underlying cause of acne. Androgens, like testosterone and DHEA, increase sebum production. This connection is exemplified in the case of polycystic ovarian syndrome (PCOS), a condition in which women have elevated androgen levels and often experience acne as a result. (25) 

Hormonal factors appear to play a role in other skin conditions like rosacea, an inflammatory skin disorder primarily affecting the face. Studies suggest that women undergoing hormone therapy and those using oral contraceptives are at a higher risk of developing rosacea, while postmenopausal women, who typically have lower estrogen levels, seem to have a lower risk, implying a potential contribution of estrogen to this condition. (77) 

Hormones can modulate immune activity, including in the skin, which can impact the disease course of autoimmune skin conditions. This dynamic is seen in psoriasis, where periods of reproductive hormone fluctuation like puberty, pregnancy, and menstruation influence symptoms. (10, 30) 

A higher prevalence of hypothyroidism is also seen in autoimmune conditions like vitiligo, alopecia areata, and lichen sclerosus. Although the mechanism behind this association is not fully understood, thyroid hormone can act directly on various skin cells, like keratinocytes, sebaceous glands, and vascular endothelial cells, as well as various immune cell types, which might help to explain the connection. (29, 52)

Triggers and Aggravators: Diet, Stress, and More

Having already discussed that genetics, microbiome composition, intestinal permeability, and hormonal fluctuations influence the development of autoimmune skin diseases, we will now delve deeper into additional triggers and exacerbating factors in these conditions.

Stress

Stress has been identified as a possible precipitating factor in the development of certain autoimmune skin conditions like psoriasis, vitiligo, and alopecia areata. (5, 26)  When individuals are under higher amounts of stress, it stimulates a neuroendocrine response. The hypothalamic-pituitary-adrenal (HPA) axis releases hormones like corticotropin-releasing hormone (CRH) and cortisol, and the nervous system releases neuropeptides like substance P. 

The skin also has its own peripheral HPA axis that is stimulated by central HPA axis activity. There are receptors for CRH on the skin, allowing it to trigger mast cell (a type of immune cell) activation and increasing inflammation, interrupting barrier function in the skin. (43)

Dietary Triggers

A Western diet is thought to be one contributing factor to the increasing prevalence of autoimmune diseases. This style of diet is one with an overabundance of processed sugars and foods, salt, refined grains, and saturated fats, and is limited in fiber, vitamins, minerals, and antioxidants. A Western diet directly stimulates inflammatory responses and can negatively impact the gut microbiome composition. Food sensitivities might also play a role in the development of autoimmune diseases in certain individuals. (11, 55) 

Gluten, a protein found in grains like wheat, can directly cause autoimmune diseases like celiac disease and dermatitis herpetiformis. Individuals with autoimmune diseases have also been found to have a higher prevalence of food-sensitivity reactions on serum antibody testing.

Environmental Toxins

Exposure to environmental toxins contributes to microbiome disruption, intestinal permeability, immune system dysregulation, and inflammation, increasing the risk of autoimmunity. Furthermore, certain environmental toxins, called endocrine-disrupting chemicals (EDCs), can cause hormone imbalances, further disrupting the gut-hormone-skin relationship. Autoimmune conditions affecting the skin, such as psoriasis, alopecia, SLE, and vitiligo, have been found to be associated with a variety of toxic compounds like pesticides, air pollution, heavy metals, cigarette smoke, and household chemicals.  (6, 38, 51, 81)

Lab Testing to Investigate the Gut-Hormone-Skin Connection

The human body operates as an interconnected system in which the health of one system significantly influences the functionality of another. When managing autoimmune skin conditions, an understanding of the relationship between the gut, hormones, and skin must be fully understood to provide comprehensive, holistic treatment. Functional medicine tests offer practitioners a means to evaluate the function of both the endocrine and gastrointestinal systems to understand their reciprocal impact on one another as well as their collective influence on skin health.

Diagnosing Autoimmune Skin Conditions

Although the characteristic appearance of skin lesions may be suggestive of a particular skin disorder, a biopsy is generally needed for a definitive diagnosis of an autoimmune skin disease. Doctors may also use swabs and skin cultures to assess for infections of the skin.

Blood tests for autoimmunity can be ordered, like antinuclear antibodies (ANA). Nonspecific tests for inflammation, such as c-reactive protein (CRP) might also be considered. (3)

Intestinal Permeability Screen

Cyrex’s Array 2, also known as Intestinal Antigenic Permeability Screen, measures antibodies against specific proteins associated with the gastrointestinal lining. Elevations in these antibodies indicate gut barrier damage, indicative of intestinal permeability. 

Food Sensitivity Tests

Cyrex’s Array 10, known as the Multiple Food Immune Reactivity Screen, assesses IgG and IgA antibody reactions to foods in various forms (raw, cooked, and modified), along with food enzymes, lectins, and artificial additives. In contrast to many other food sensitivity tests that exclusively target raw foods, this panel ensures that reactions are not overlooked due to cooking, modification, or ingredient combinations.

Environmental Exposures

An Environmental Pollutants Profile can identify exposures to heavy metals, like mercury and cadmium.

Hormone Panels

HPA Axis function is assessed thoroughly by including a 4-point cortisol measurement throughout the day to identify any deviations from the normal circadian rhythm. 

The Thyroid Panel by BostonHeart Diagnostics measures TSH, T4, T3, free T4, free T3, reverse T3, and thyroid antibodies. This provides a thorough picture of thyroid function to identify any conditions like hypothyroidism or autoimmune thyroid disorders that are associated with skin conditions.

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Healing from the Inside Out

Embracing a holistic skincare approach is about recognizing that true skin health is more than skin deep. It involves delving beneath the surface to address the underlying causes of skin issues rather than merely treating superficial symptoms. Holistic skincare strategies take into account the importance of achieving optimal hormone balance and supporting the gut-skin axis when selecting appropriate therapies and lifestyle changes.

Nutrition

A whole-food, nutrient-dense, and high-fiber diet can support optimal hormone balance, immune system function, microbiome diversity, and overall gut health. Vitamins, minerals, and phytonutrients found in fruits and vegetables help support hormone production and metabolism as well as immune system function. (46, 66) Oxidative stress is a contributing factor in at least some autoimmune skin conditions (53, 54). Incorporating plenty of fruits and vegetables ensures an adequate intake of antioxidants to combat free radicals and oxidative stress.

The Mediterranean Diet is an eating pattern that emphasizes the intake of vegetables, fruit, legumes, nuts, and healthy fats from foods such as olive oil and fish. This style of eating can help to reduce inflammation and support a healthy microbiome. Studies have shown its benefit in some autoimmune diseases, including psoriasis. (50)

Individuals who either have diagnosed or suspected food sensitivities might need to work closely with their healthcare provider to customize a personalized elimination diet. In an elimination diet, all potentially problematic foods are removed for at least several weeks. If desired, individual foods can then be reintroduced one at a time over the course of a few days to see if any problematic symptoms arise. Any foods that provoke unwanted symptoms are then removed for a longer period of time before any attempts for reintroduction are made again. The goal of an elimination diet is to remove foods that promote inflammation, thereby improving gut and immune health in the patient. Including a reintroduction phase allows patients to transition to a more diverse diet over time if no adverse reactions are experienced. 

Stress Management

Stressful life events can serve as precipitating and exacerbating factors in autoimmune diseases. Additionally, autoimmune skin conditions increase feelings of stress, anxiety, and depression. (27) Mind-body therapies support the body’s relaxation response to counteract the negative effects of stress and restore equilibrium to the nervous system and hormones. Some of these techniques include mindfulness, meditation, yoga, deep breathing, progressive muscle relaxation, and biofeedback.

Prebiotics & Probiotics

Prebiotics are non-digestible dietary compounds, typically carbohydrates or fiber, that serve as a nutritional source for beneficial gut bacteria, promoting their growth and activity. Prebiotics can be found naturally in some foods like certain fruits, vegetables, whole grains, and legumes or can also be taken in supplemental form. Common prebiotic supplements available include fructooligosaccharides (FOS), inulin, resistant starch, and galactooligosaccharides (GOS).

Probiotics are supplements containing live microorganisms, usually beneficial bacteria or yeast, that help restore balance to the microbiome. They inhibit the growth of potentially problematic organisms in the gut while simultaneously supporting the growth of beneficial commensal organisms. The probiotics themselves can also act directly on immune cells to help modulate inflammatory responses. (37)

Serum-Derived Bovine Immunoglobulins (SBI)

Immunoglobulins are proteins produced by immune cells to recognize and remove foreign substances from the body. Serum-derived bovine immunoglobulins (SBI) are immunoglobulin preparations derived from the serum of bovine animals. These supplements contain a mixture of antibodies, particularly immunoglobulin G (IgG), to help support various aspects of immune function. In the gut, immunoglobulins bind to pathogens and endotoxins and improve microbial diversity, which helps to reduce gastrointestinal inflammation and permeability. (13, 49, 70)

Curcumin

Curcumin is a compound found in turmeric. In the gastrointestinal tract, it can modulate the microbiome inflammatory cytokines and provide antioxidant protection. Outside of the gastrointestinal tract, it also decreases systemic inflammation and skin inflammation. (45, 69)

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Summary 

The gut-skin axis exerts a profound influence over autoimmune skin conditions. Hormones interact with both of these systems, thereby affecting this axis. An integrative approach to autoimmune skin disorders addresses skin health holistically from the inside out. Utilizing functional medicine tests provides a comprehensive assessment of gut and hormone health simultaneously to create personalized protocols, strengthening the synergy between these systems.