What is Non-Segmental Vitiligo?

Non-Segmental Vitiligo (NSV) is a condition that causes depigmentation of parts of the skin. It's generalized and symmetrical. It occurs when melanocytes, the cells responsible for skin pigmentation, detach from the basal membrane and exfoliate in the upper epidermis (melanocytorrhagy). Basically, NSV is a genetic predisposition to dysfunctional melanocyte adhesion, and it can be triggered by an internal or external "severe" event. Shifting the contemporary research paradigm, new studies point to the fact that NSV is not caused by a dysfunctional immune system.

Melanocytes have 2 adhesion mechanisms: (1) the main one: Integrin alpha5-beta1 and (2) the contingent one: CCN3→DDR1→Colagen-IV. The latter seems to be faulty in a genetically NSV predisposed person.  The former is easily affected by physical traumas, oxidative stress, and stress hormones in any person, what is critical for NSV sufferers since they do not have the contingent mechanism working properly, as shown below.  The upper picture shows both mechanisms.  The lower picture shows a disruption in the main adhesion mechanism (a5b1), but made up by the contingent mechanism.

A genetically NSV predisposed person may live a whole life without triggering the disease. However, once Vitiligo is triggered it becomes hard to cure (not impossible) because melanocyte's main adhesion mechanism will constantly be threatened  (1) by the action of friction and trauma in certain regions like knees, elbows, hands, feet, wrists, around the eyes, forehead and around the mouth, (2) facilitated by oxidative stress, and (3) accelerated by stress hormones. 

After NSV is triggered, the Koebner phenomenon or isomorphic response (mimetism theory) may explain the development pattern of new patches on the frictioned and  traumatized areas, but otherwise normal skin, and these new patches are clinically identical to those in the diseased skin (see picture below). 

It would be reasonable to think that new patches would regularly appear after NSV was triggered,  because the human body learned how to detach (kill) melanocytes due to the "mimetism theory".  Recent researches have also defined it as "killing memory effect".

However, the truth is not exactly like this.  The mimetism theory and/or the "killing memory effect" are directly connected to the presence of a protein called MIA.  This protein is the exact organic compound that the human body  learned to produce improperly in NSV predisposed people. Its presence in the skin is what detaches melanocytes.  While the protein is there, the "killing memory effect will remain. 

MIA will be explained in detail in the "How Does NSV Present in Patients" section ahead, sub-item "Consequence".

How does NSV Present in Patients?

As a potential condition, NSV is caused by a combination of the Primary Cause (genetic defective melanocyte adhesion mechanism) and one or more Secondary Causes (both types described below). However, it only becomes a disease if triggered by a severe internal or external event. This is when white patches appear. NSV causes/trigger combinations are known, but vary from person to person. It's hard to understand the difference between the roles of triggers and causes.

Whilst a trigger is usually a single severe event, causes are systematic but not severe. A patient can trigger their vitiligo by a severe emotional trauma, while systematic physical traumas to a specific area spread the white patches. Alternatively, a patient can trigger the onset of vitiligo by a severe physical trauma, but it spreads because of systematic psychological stress or even oxidative stress. This understanding of initial onset makes NSV a complex disease. It's very important to identify this cause/trigger mechanism properly, in each case, in order to have a much better chance of determining a cure.

● PRIMARY CAUSE: Genetic predisposition to dysfunctional melanocyte adhesion (lack of one mechanism). Either by inheritance or fetal DNA formation. This PRIMARY CAUSE is enough to keep someone in a constant "potential NSV" status.

● SECONDARY CAUSE 1: Physical traumas (friction, injuries, itches, scratches, allergies, sun burns, impacts, violent moves, and others).

● SECONDARY CAUSE 2: Oxidative stress (excess of free radicals) in the skin.

→Oxidative stress is a complex concept. It's essentially an imbalance between the production of free radicals and the ability of the body to counteract or detoxify their harmful effects through neutralization by antioxidants. The major factors for consideration are: food allergy, poor diet, leaky gut and dysbiosis (parasites, candida, h-pylori, yeast, fungus, etc.).

→ Additionally, onset can be caused by toxic chemical compounds and pollutants within your body, hydrogenated fats, all kinds of pollution (air, water and food), oils that have been heated to very high temperatures, cigarette smoke (directly inhaled or secondhand), dehydration, too much sugar, too much animal protein in your diet, geophysical stress (like living near power lines or waste dumps), viral infections, preservatives in your food, drugs (over the counter and prescription), artificial food colorings and flavorings, plastics and phthalates, chemical cleaning supplies, chlorinated water (that you drink, shower or swimming), alcohol, pesticides in your food, radiation exposure, psychological and emotional stress, endurance exercise and, rather incredibly, physical traumas within the body (muscle damaging anaerobic training, trauma or injury to muscle, bone and skin).

→Oxidative stress causes defects in the membrane integrity, also causes lipid peroxidation, generates hydrogen peroxide in the skin that mutates mitochondrial DNA. All this weakens cell adhesion. NSV starts because people who are predisposed to have dysfunctional melanocytes, start having mutated melanocytes. Their cell adhesion becomes compromised.

● SECONDARY CAUSE 3: Psychological and emotional systematic stress.

Examples:

→ if you are a person who is feeling completely out of place.

→ you feel that you are no one in the group or you have no sense of belonging.

→ if you are a "yes-but" person.

→ if you are never satisfied with what you have / how you look / what you are.

→ if you feel that there is lack of joy in your life, etc.

● SECONDARY EXCEPTIONAL CAUSES: There are exceptional causes like hypothyroidism, Hashimoto disease, adrenal fatigue, liver toxicity, lead contamination, and others that might be correlated to vitiligo, the presence of which must be addressed before starting any treatment plan. These factors are usually linked to different types of vitiligo, other than NSV (e.g., Segmental Vitiligo).

● TRIGGER: This is the factor that awakens and initiates the patient’s genetic predisposition.

→It only happens if one or more secondary causes are present (usually they are present in all people).

→Although it varies from person to person, the trigger has the following facets: emotional, psychological, physical and environmental. Whatever the trigger type, it is always a severe event.

→Stress hormones play a big role in triggering vitiligo. This understanding makes emotional and psychological trigger facets the most relevant ones. A good lifestyle helps to prevent this trigger.

→Some trigger examples are: severe emotional or psychological trauma, severe skin sun burn, severe friction, severe chronic allergy, chemical intoxication, etc.

● UNTRIGGER: To "untrigger" means to revert to potential NSV status, and, consequently, halt the risk of vitiligo spreading.

→Anyone is able to untrigger vitiligo. However, it's necessary to follow a Functional Treatment regime that includes a good diet, detox, lifestyle change, vitamins, anti-fungals, anti-oxidants, UVB-NB, topical creams, and others (all at the same time).

→More about Functional Treatment...

→UNTRIGGERING = STOP SPREADING ‡ CURE.

→In order to achieve the cure, one has to untrigger it AND also reach full repigmentation in all existing white patches. Therefore, obtaining a state of cure is hard, but not impossible.

● CONSEQUENCE: After vitiligo is triggered, a certain protein called MIA starts being improperly produced.

→Its production is conduced by (1) systematic physical traumas (friction, injuries, itches, scratches, allergies, sun burns, impacts, violent moves, etc.), (2) systematic oxidative stress, and (3) stress hormones from systematic emotional and/or psychological stress.

→MIA protein comes from two dysfunctional cellular sources, which are: (1) melanocytes/keratinocytes in the skin, and (2) chondrocytes in the cartilages of the joints. Both types destroy alpha5beta1 integrin, compromising melanocytes adhesion to the basal membrane.

→More specifically, MIA detaches melanocytes causing white patches by disrupting integrin, which is the only adhesion mechanism left. As mentioned above, NSV sufferers possess genetically defective adhesion mechanism. The picture below shows the actual melanocyte adhesion scenario that considers only the main adhesion mechanism. MIA stays in the border of the white patches, like sentinels, detaching any melanocyte, what makes one perceive it as a "killing memory effect".

● SUMMARY:

→Oxidative stress, physical traumas, and stress hormones do the initial damage to the melanocyte adhesion.

→When vitiligo is triggered by a severe event (physical, emotional, psychological, environmental), MIA starts being produced as a consequence.

→When MIA goes to the scene of trauma it finds the perfect environment to do it's job, which is "Detaching Cells".

→Detached melanocytes exfoliate in the upper epidermis silently. It's important to note this process can be facilitated by oxidative stress and accelerated by stress hormones in a patient.

Brief Description About MIA

MIA (melanoma inhibitory activity) is a protein that is supposed to be produced in response to malignant melanoma (malignancy of melanocyte). It is known to play a key role in melanoma development, progression and tumor cell invasion. After its secretion, which is restricted to the rear pole of migrating cells, MIA protein directly interacts with cell adhesion receptors and extracellular matrix molecules. By this mechanism, MIA protein actively facilitates focal cell detachment from surrounding structures at the cell rear and strongly promotes tumor cell invasion and formation of metastases.

MIA was not supposed to be produced by non-malignant melanocytes in the skin, and non-differentiated chondrocytes in the cartilages of the joints. However, non-segmental vitiligo sufferers produce it, based on the fact that both these types of cells have become dysfunctionally active after vitiligo was triggered. So, while MIA is present in the epidermis, vitiligo will appear and stay as a "killing memory effect".  NSV may spread or it may not. A certain white patch of skin may remain stable in size for 10 years, however, regardless of stability, the MIA will still be present. If the patch is stable, it means that while the skin produces "x" new melanocytes, MIA detaches roughly the same amount of melanocytes. If the vitiligo is spreading, it means that MIA is detaching more than the skin's ability to produce and keep attaching new melanocytes. It's an endless battle. Reducing physical traumas, oxidative stress (specially food allergy and dysbiosis), and stress hormones will definitely help to fight against MIA activity. To win the war, we have to remove MIA from the white patches of skin. It is important to note the older the affected patch is, the more populated with MIA it is, and this is what makes old patches difficult to be reversed. 

Dr. Matteo Bordignon (the Italian researcher who discovered the role of MIA in non-segmental vitiligo) is currently trying to develop a cure based on the inhibition of the MIA protein. We really hope it will be available as soon as possible.

In the meantime, some creams are shown to have moderate success in "fighting" against MIA (though not neutralizing it). These are Elidel, and Protopic. How they work is not specifically known, but it seems that they help by reducing the microinflammation, caused by MIA, around the integrin (adhesion molecules) in the basal membrane. Another good cream is Pseudocatalase that helps to minimize the local oxidative stress. Last, but not least, UVB-NB phototherapy is an excellent option because it makes melanocyte's adhesion get stronger, as well as stimulates melanocyte stem cell production in the hair follicles of the skin.

More details at: www.vitiligomap.com

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