Understanding Vitiligo: a concise review and a Functional Medicine perspective

Vitiligo is an autoimmune disease characterised by the formation of patches of colourless skin due to a loss of function of melanocytes, the skin cells responsible for pigmentation. Melanocytes are a specialised type of skin cell that produces melanin, the pigment responsible for skin colour. A person with vitiligo has problems with their melanocytes due to multiple factors, including cellular stress and autoimmunity.

Vitiligo is the most common form of de-pigmenting skin disorder, and there are two major types of vitiligo: non-segmental vitiligo (NSV) and segmental vitiligo (SV). People with vitiligo have random patches of white and non-scaly skin that have lost all their melanocytes or become non-functional.

At the Australian Centre for Functional Medicine, we treat skin conditions like vitiligo and other autoimmune conditions with an innovative approach to Functional Medicine.

As practiced by the Australian Centre for Functional Medicine, functional medicine aims to treat the underlying problems behind your symptoms.

Essential Epidemiology of Vitiligo

Prevalence – Vitiligo is an autoimmune disease estimated to affect up to 2% of the world’s population, reaching people from all ethnicities and skin types. Research has revealed, however, significant geographical variation in the prevalence rates of this condition. For example, a recent review of more than 50 worldwide studies found that vitiligo prevalence ranged from 0.06% to 2.28%. Another study reported rates as high as 8.8% for some regions of India. These large differences in prevalence may be explained by inconsistency in disease classification, understanding and reporting of the disease, studies suggest¹.

Males and females are equally affected by this autoimmune disease, although studies show that women and girls more often seek medical advice for this condition^1-2.

While this disease can develop at any age, it is most common in certain age ranges^3-4, for example, for NSV:

About 25% of vitiligo patients first develop this condition before the age of 10 years.
About 50% develop the disease before the age of 20 years and
Between 70–80% of patients develop vitiligo before the age of 30 years

In contrast, SV usually occurs at a younger age, compared to NSV⁵:

About 87% of cases occur before the age of 30 years
More than 41% occur before the age of 10 years

Key Pathogenesis

Vitiligo is an autoimmune disease influenced by multiple factors, ultimately leading to a significant loss of functional melanocytes. Common factors known to influence the development of vitiligo include:

genetics
autoimmune responses
metabolic abnormalities
dysfunctions of the immune system
oxidative stress
generation of inflammatory mediators
melanocyte detachment mechanisms

However, each of these factors alone cannot explain the onset of vitiligo in all patients. The contribution of each to the pathology of this autoimmune disease is still under research⁶. Learn more about the immune system here.

How does Vitiligo develop? – The key characteristic of vitiligo is the loss of functional melanocytes. In other words, melanocytes are destroyed, or they stop functioning. This occurs on patches of skin, where the lack of functional melanocytes leads to melanin deficiencies and the typical skin decolouration that characterises the disease. The question of how/why melanocytes lose function is still under research. Still, it is thought to be due to multiple factors, including metabolic abnormalities, oxidative stress, generation of inflammatory mediators, cell detachment and autoimmune responses.

While the contribution of each of these factors is not fully understood, a consensus model is that the intrinsic defects in the melanocytes are the initial event. Under this model, oxidate stress in the melanocytes leads to a localised inflammatory response and the activation of certain immune processes, leading to autoimmunity in people with certain genetic predispositions. This autoimmunity can lead to melanocyte-specific cytotoxic immune attacks, ending in melanocyte loss of function⁶.

What occurs in the body?

The skin of a person with vitiligo develops patches of white colouration, because of the dysfunction of melanocytes in the area. Over time, these patches of discoloured skin can grow bigger. Vitiligo can occur on any part of the body, as well as on the hair or the inside of the mouth or nose.

Typical Vitiligo symptoms include:

Patchy loss of skin colour – usually starting on the hands, face, and areas around body openings and genitals
Premature whitening or greying of the hair on the scalp, eyelashes, eyebrows, or beard
Loss of colour in the inside of the mouth and nose

How does Vitiligo affect the skin?

There are various types of vitiligo, each affecting the skin in different degrees. For example:

Universal Vitiligo

When this type of vitiligo occurs, nearly all skin surfaces are affected by discolouration.

Generalized Vitiligo

With this type of vitiligo, multiple parts of the body are affected, and the disease progresses from these sites in a symmetrical way (on corresponding parts of the body).

Segmental Vitiligo

This occurs when vitiligo affects only one part or side of the body. Typically, this form of vitiligo affects younger people, lasts for 1-2 years and then disappears.

Localised Vitiligo

Where only one or a few areas of the body are affected.

Acrofacial Vitiligo

This is a type of vitiligo that only affects the face and hands, including the skin around body openings, such as the eyes, nose and ears.

In all forms of vitiligo, the characteristic pathology is the formation of white patches of skin. These white patches are skin where melanocytes are dysfunctional.

The immune system connection

Two key factors involved with vitiligo development are cellular stress and the immune system. Melanocytes can suffer from cellular stress, likely mediated by increased levels of reactive oxygen species (ROS), which are well known molecules that can cause damage to DNA, RNA and proteins in the cell.

Stressed melanocytes send out stress signals that are picked up by the immune system, resulting in an immune response that is ultimately translated into an autoimmune response against melanocytes. Support for the role of autoimmunity in vitiligo has been obtained by research showing that skin areas affected by this condition show:

presence of antibodies against melanocytes
association with polymorphisms at immune loci
presence of specific T cells and cytokine expression

Also, vitiligo is associated with other immune conditions, such as autoimmune thyroiditis and type 1 diabetes mellitus, two conditions that involve cellular stress, innate immunity and adaptive T cell responses. Vitiligo has also been associated with autoimmune thyroid diseases, including autoimmune thyroiditis, Grave’s disease, Addison’s disease and autoimmune adrenal insufficiency. In the context of thyroid diseases, this link suggests an association of vitiligo with polyglandular autoimmune diseases.

Overall, these observations provide further evidence for the role of autoimmunity in the pathology of this vitiligo.

Beyond immunity, another important factor influencing vitiligo is the human microbiota.

Focus on: Microbiota and Vitiligo

The human body is covered by microbes, inside and out, including bacteria, viruses, fungi and other microorganisms. These microorganisms live inside our gastrointestinal tract and all over our skin and other places in the body. One of their primary functions is to protect our body from external pathogens, but they also have other functions. The skin and gut microbiota, for example, interact with environmental factors and have important roles in influencing the function of the immune system. For example, a recent study showed that children who play outside have a healthier skin microbiota and a stronger immune system. Read all about this study here.

The skin microbiota also influences the health of the skin. In one study, patients with vitiligo were found to have reduced microbial diversity in affected skin patches affected. The study also found a specific distribution of bacterial taxa in their patients:

Bacteria from the Actinobacteria group primarily populate skin areas not affected by vitiligo.
Skin areas affected by vitiligo, in contrast, are dominated by bacterial members of the Firmicutes and Proteobacteria groups⁷.

Another study that compared the skin and gut microbiome (another common name for the gut microbiota) of vitiligo patients with those of healthy controls found comparable results. The study found that the gut microbiota of vitiligo patients had reduced diversity and a distinct taxa distribution compared to healthy controls. In particular, the study found that the gut of patients with vitiligo had a higher Firmicutes/Bacteroidetes ratio compared to healthy people. The skin microbiota was also found to host significantly different microbiota. Skin areas affected by vitiligo had low levels of the protective Bifidobacterium and enriched in Terenicutes, Streptococcus, Mycoplasma⁸.

These changes in gut microbiota composition may influence the development of vitiligo. So far, some evidence supporting this idea has been reported in mice. A recent study in mouse models of vitiligo found that treatment with antibiotics like ampicillin promoted vitiligo-like depigmentation and caused gut dysbiosis, characterised by a massive reduction in diversity and an overgrowth of a single bacterial species: Pseudomonas⁹.

These findings point toward a role of gut microbes influencing the progression of vitiligo and hint at the importance of considering environmental factors that may influence the pathology of vitiligo through their influence on the gut and skin microbiota.

Evidence for the role of gut microbes in skin health has been reported in recent studies. For example, metabolites released by gut bacteria can sometimes enter the bloodstream and reach the skin. One study found that the metabolites free phenol and p-cresol, produced by the bacterium Clostridium difficile, can reach the circulatory system and accumulate in the skin of mice¹⁰. Another study found that these two metabolites can reduce the expression of genes found in keratinocytes, the most common type of skin cell. Alterations to the optimal function of these cells can lead to altered epidermal differentiation and barrier function of the epidermis¹¹. Learn more about how the skin microbiota affects our health. Please read our article on this topic.

The influence of gut microbes on skin health through the metabolite they produce point towards another important concept: intestinal permeability.

Intestinal Permeability and Skin Health

The gut, and more specifically, the intestines, function as a protective barrier against invading pathogens from the environment. Those pathogens that manage to enter our body through the mouth and nose, manage to avoid the stomach’s gastric juices, are usually stopped at the intestines, preventing their entrance into the bloodstream.

However, sometimes, malfunctions in the gut can lead to increased intestinal permeability, which means pathogens and other potentially harmful substances can enter the bloodstream and reach any part of the body.

Some studies have found evidence linking intestinal permeability with skin disorders. One study, for example, found that patients with acne reacted to the presence of a bacterial toxin called LPS, whereas healthy controls never showed any reaction to this toxin. A positive reaction to the LPS toxin can be considered evidence of significant intestinal permeability in acne patients¹². Similar mechanisms may exist linking intestinal permeability to vitiligo.

Diagnosis and standard treatment

Vitiligo is normally diagnosed following an inspection of the typical skin lesions. Sometimes, a skin biopsy or a blood test may be conducted.

The standard treatments for vitiligo are focused on treating the symptoms and usually consist of medications and light-based therapies aimed at restoring skin colour. However, the outcomes of these treatments are somewhat unpredictable, and results vary from patient to patient. While drugs are also available, there is no medication that cures vitiligo. Some common drugs used in vitiligo patients include corticosteroid creams to ease inflammation and calcineurin inhibitor ointments, which target the immune system. Light therapy involve exposure to ultraviolet light (UVB), with the goal of slowing down or stopping progression of vitiligo. For more information about these standard treatments see this link.

Functional medicine Australia: a more efficient approach to Vitiligo

At the Australian Centre for Functional Medicine, we take a comprehensive look at all factors influencing and driving the development and worsening of vitiligo. We employ a Modern approach to Functional Medicine Australia, merging standard medical protocols with cutting edge, research-backed approaches, evidence-based natural treatments and extensive diagnostic testing.

Optimal skin health requires a careful combination of multiple factors, including an optimal composition of the gut and skin microbiota, optimal immune function, reduced cellular stress and many other factors. At the Australian Centre for Functional Medicine, we follow a constantly updated practice based on current research findings. Our goal is to understand the underlying factors affecting your skin and apply the best research-backed treatments to restore the health of your skin (as well as your overall health).

Our modern approach to Functional Medicine Australia offers an effective alternative to the standard model of clinical practice. The Australian Centre for Functional Medicine employs leading clinical testing approaches, evaluating biomarkers found in your blood, stool, urine, and breath. Genomic-based tests, for example, are used to inform us about genetic susceptibilities, mutational defects or other factors that may influence treatment efficacy and health. We also test the composition of your gut and skin microbiota to identify any instances of dysbiosis. This is the comprehensive approach of modern Functional Medicine.

This comprehensive testing is used to obtain a solid understanding of your physical health and garner evidence of any malfunctions that potentially affect your health. All this information will ultimately allow us to design a personalised treatment based on your specific needs. This unique approach to Functional Medicine will guarantee the best possible treatment and the best possible outcomes for your condition.

…and begin your path towards healthy skin and a healthier life with modern Functional Medicine.

To learn more about Functional Medicine and the many health conditions we treat, download our health e-Book now.

References

Ezzedine K, Eleftheriadou V, Whitton M, van Geel N. Vitiligo. Lancet. 2015 Jul 4;386(9988):74-84. doi: 10.1016/S0140-6736(14)60763-7. Epub 2015 Jan 15. PMID: 25596811. Read it!
Bergqvist C, Ezzedine K. Vitiligo: A Review. Dermatology. 2020 Mar 10:1-22. Read it!
Sehgal VN, Srivastava G. Vitiligo: compendium of clinico-epidemiological features. Indian Journal of Dermatology, Venereology, and Leprology. 2007 May 1;73(3):149. Read it!
Lee H, Lee MH, Lee DY, Kang HY, Kim KH, Choi GS, Shin J, Lee HJ, Kim DH, Kim TH, Lee AY. Prevalence of vitiligo and associated comorbidities in Korea. Yonsei medical journal. 2015 May 1;56(3):719-25. Read it!
Hann SK, Lee HJ. Segmental vitiligo: clinical findings in 208 patients. Journal of the American Academy of Dermatology. 1996 Nov 1;35(5):671-4. Read it!
Picardo, M., Dell’Anna, M., Ezzedine, K. et al. Vitiligo. Nat Rev Dis Primers 1, 15011 (2015). Read it!
Ganju P, Nagpal S, Mohammed MH, Kumar PN, Pandey R, Natarajan VT, Mande SS, Gokhale RS. Microbial community profiling shows dysbiosis in the lesional skin of Vitiligo subjects. Scientific reports. 2016 Jan 13;6:18761. Read it!
Bzioueche H, Sjodin KS, West CE, Khemis A, Rocchi S, Passeron T, Tulic MK. Deep skin dysbiosis in vitiligo patients: link with mitochondrial and immune changes. medRxiv. 2020 Jan 1. Read it!
Dellacecca ER, Cosgrove C, Mukhatayev Z, Akhtar S, Engelhard VH, Rademaker AW, Knight KL, Le Poole IC. Antibiotics drive microbial imbalance and vitiligo development in mice. Journal of Investigative Dermatology. 2020 Mar 1;140(3):676-87. Read it!
Ramírez-Boscá A, Navarro-López V, Martínez-Andrés A, Such J, Francés R, de la Parte JH, Asín-Llorca M. Identification of bacterial DNA in the peripheral blood of patients with active psoriasis. JAMA dermatology. 2015 Jun 1;151(6):670-1. Read it!
Miyazaki K, Masuoka N, Kano M, Iizuka R. Bifidobacterium fermented milk and galacto-oligosaccharides lead to improved skin health by decreasing phenols production by gut microbiota. Beneficial Microbes. 2014 Jun 1;5(2):121-8. Read it!
Juhlin L, Michaëlsson G. Fibrin microclot formation in patients with acne. Acta dermato-venereologica. 1983 Jan 1;63(6):538-40. Read it!