Main Cause of Unsegmented Vitiligo and Secondary Causes of it!

Un-segmental vitiligo (VNS) is a condition that causes depigmentation of parts of the skin. It is widespread and symmetric. It occurs when melanocytes, the cells responsible for skin pigmentation, detach from the basement membrane (melanoctorragia). Basically, NSV is a genetic predisposition to dysfunctional adhesion of melanocytes, and can be triggered by a serious internal or external event. Changing the paradigm of contemporary research, the new studies point to the fact that NSV is not caused by a dysfunctional immune system.

It is true that there is an interaction between the immune system and melanocytes, but only when they are being separated by another agent or when they try to rejoin the basement membrane. Melanocytes have 2 adhesion mechanisms: (1) the main one: Integrin alfa5-beta1 and (2) the contingent: CCN3 → DDR1 → Colagen-IV. The latter seems to be defective in a person genetically predisposed to VNS. The first is easily affected by physical trauma, oxidative stress and stress hormones in any person, which is essential for those suffering from NSV, since they do not have the contingent mechanism working properly. The two mechanisms work correctly under external factors in normal skin. The 2 images below show interruptions in the main mechanism of vitiliginous skin, as well as the incorrect behavior of the contingency mechanism. A person genetically predisposed to NSV can live a lifetime without triggering the disease. However, once Vitiligo is activated, it becomes difficult to cure (not impossible) because the main mechanism of adhesion of the melanocyte will be constantly threatened …

(1) By the action of friction and trauma in certain regions such as 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 the NSV is triggered, the Koebner phenomenon or the isomorphic response (mimicry theory) can explain the pattern of development of new patches in the fricted and traumatized areas, but in other aspects of normal skin, and these new patches they are clinically identical to those of the diseased skin image below). It would be reasonable to think that new patches would appear on a regular basis after the NPV was activated, because the human body learned how to separate (kill) the melanocytes due to the “mimicry theory.” Recent research has also defined it as “killer memory effect”. However, the truth is not exactly so. The theory of mimicry and / or the “murderous memory effect” are directly related to the presence of a protein called MIA.

“This protein is the exact organic compound that the human body learned to produce inappropriately in people predisposed to NSV”.

Its presence in the skin is what separates the melanocytes. While the protein is there, the “lethal memory effect will remain.

How does Unsegmented Vitiligo Occur 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 it is triggered by a serious internal or external event. This is when white spots appear. The cause / trigger combinations of NSV are known, but vary from person to person. It is difficult to understand the difference between the roles of the triggers and the causes. While a trigger is usually a single serious event, the causes are systematic but not serious. A patient can trigger their vitiligo due to severe emotional trauma, while systematic physical trauma in a specific area extends white spots. Alternatively, a patient can trigger the appearance of vitiligo due to severe physical trauma, but it spreads due to systematic psychological stress or even oxidative stress. This understanding of the initial appearance makes NSV a complex disease. It is very important to correctly identify these activation mechanisms, in each case, to have a better chance of determining a cure.

  • Main Cause:

Genetic predisposition to dysfunctional adhesion of melanocytes (lack of a mechanism). Either by inheritance or by fetal DNA formation. This MAIN CAUSE is enough to keep someone in a constant state of “NSV potential.”

  • Secondary Cause 1:

Physical traumas (friction, injuries, itching, scratches, allergies, sunburn, impacts, violent movements and others).

  • Secondary Cause 2:

Oxidative stress (excess free radicals) in the skin.

→ Oxidative stress is a complex concept. Essentially, it is an imbalance between the production of free radicals and the body’s ability to counteract or detoxify its harmful effects through the neutralization of antioxidants. The main factors to consider are: food allergy, poor diet, leaky gut and dysbiosis (parasites, candida, h-pylori, yeast, fungi, etc.).

→ In addition, the onset can be caused by toxic chemical compounds and pollutants inside 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 second-hand), dehydration, too much sugar, too much animal protein in your diet, geophysical stress (such as living near power lines or landfills), viral infections, food preservatives, medications (over-the-counter and prescription), dyes artificial foods and flavorings, plastics and phthalates, chemical cleaning products, chlorinated water (drinking, showering or swimming), alcohol, pesticides in your food, radiation exposure, psychological and emotional stress, resistance exercises and, quite incredibly ,Physical trauma within the body (anaerobic training harmful to muscles, trauma or injuries to muscles, bones and skin).

→ Oxidative stress causes defects in membrane integrity, also causes lipid peroxidation, and generates hydrogen peroxide in the skin that mutates mitochondrial DNA. All this weakens cell adhesion. NSV begins because people predisposed to dysfunctional melanocytes begin to have mutated melanocytes. Your cell adhesion is compromised.

  • Secondary Cause 3:

Systematic psychological and emotional stress.


if you are a person who feels completely out of place.

→ You feel that you are nobody in the group or that you have no sense of belonging.

→ If you are a person who says “yes, but”.

→ if you are never satisfied with what you have / how it looks / with what it is.

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

  • Secondary Exceptional Causes:

There are exceptional causes such as hypothyroidism, Hashimoto’s disease, adrenal fatigue, liver toxicity, lead contamination and others that could be related to vitiligo, whose presence must be addressed before beginning any treatment plan. These factors are generally linked to different types of vitiligo, other than NSV (eg, segmental vitiligo).

  • Trigger:

This is the factor that awakens and starts the genetic predisposition of the patient.

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

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

→ Stress hormones play an important role in the activation of vitiligo. This understanding makes the emotional and psychological triggering facets the most relevant. A good lifestyle helps prevent this trigger.

→ Some triggering examples are: severe emotional or psychological trauma, severe sunburn on the skin, severe friction, severe chronic allergy, chemical poisoning, etc.

  • Untrigger:

“Disconnecting” means reverting to the potential NSV status and, consequently, stopping the risk of vitiligo spreading.

→ Anyone is able to disconnect the vitiligo. However, it is necessary to follow a functional treatment regimen that includes a good diet, detoxification, lifestyle change, vitamins, antifungals, antioxidants, UVB-NB, topical creams and others (all at the same time).

→ More about functional treatment…


→ To achieve the cure, one must unleash it and also achieve complete repigmentation in all existing white patches. Therefore, obtaining a state of cure is difficult, but not impossible.

  • Consequences:

After vitiligo is activated, a certain protein called MIA begins to be produced improperly.

→ Its production is driven by (1) systematic physical traumas (friction, injuries, itching, scratches, allergies, sunburn, impacts, violent movements, etc.), (2) systematic oxidative stress and (3) systematic stress hormones Stress emotional and / or psychological.

→ The MIA protein comes from two dysfunctional cellular sources, which are: (1) melanocytes / keratinocytes in the skin and (2) chondrocytes in the cartilage of the joints. Both types destroy integrin alfa5beta1, compromising the adhesion of melanocytes to the basement membrane.

→ More specifically, MIA separates melanocytes causing white spots by disrupting integrin, which is the only adhesion mechanism left. As mentioned earlier, patients with NSV have a genetically defective adhesion mechanism. The following image shows the real scenario of melanocyte adhesion that considers only the main adhesion mechanism. MIA stays on the edge of the white spots, like sentries, separating any melanocyte, which makes one perceive it as a “killer memory effect”


→ Oxidative stress, physical trauma and stress hormones cause initial damage to the adhesion of melanocytes.

→ When vitiligo is triggered by a serious event (physical, emotional, psychological, environmental), MIA begins to occur as a consequence.

→ When MIA goes to the trauma scene, she finds the perfect environment to do her job, which is “Separate the cells”.

→ Separated melanocytes are exfoliated in the upper epidermis in silence. It is important to keep in mind that this process can be 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 (melanocyte malignancy). It is known to play a key role in the development of melanoma, progression and invasion of tumor cells. After its secretion, which is restricted to the back pole of the migratory cells, the MIA protein interacts directly with the cell adhesion receptors and extracellular matrix molecules. By this mechanism, the MIA protein actively facilitates the detachment of focal cells from the surrounding structures at the back of the cell and strongly promotes the invasion of tumor cells and the formation of metastases. MIA was not supposed to be produced by non-malignant melanocytes in the skin and undifferentiated chondrocytes in the cartilage of the joints. However, people suffering from non-segmental vitiligo produce it, due to the fact that both types of cells have become dysfunctionally active after vitiligo was activated. Then, while MIA is present in the epidermis, vitiligo will appear and remain as a “deadly memory effect.” The NSV can spread or not. A certain white patch of skin may remain stable in size for 10 years; however, regardless of stability, the MIA will remain present. If the patch is stable, it means that while the skin produces “x” new melanocytes, MIA separates approximately the same amount of melanocytes.

If vitiligo is spreading, it means that MIA is detaching more than the skin. s ability to produce and continue joining new melanocytes. It is an endless battle. Reducing physical trauma, oxidative stress (especially food allergy and dysbiosis), and stress hormones will definitely help fight MIA activity. To win the war, we have to remove MIA from the white spots on the skin. It is important to keep in mind that the older the affected patch is, the more populated it is with MIA, and this is what makes it difficult to reverse the old patches. The Dr. Matteo Bordignon (Italian researcher who discovered the role of MIA in non – segmental vitiligo) is trying to develop a cure based on inhibition of protein MIA. We really hope it will be available as soon as possible. Meanwhile, it is shown that some creams have moderate success in “fighting” against MIA (although they do not neutralize it). These are Elidel, and Protopic. The way they work is not specifically known, but it seems that they help separate melanocytes to bind to the basement membrane, keeping the immune system away. Another good cream is pseudocatalase that helps minimize local oxidative stress. Last but not least, UVB-NB phototherapy is an excellent option because it causes melanocyte adhesion to become stronger and stimulates the production of melanocyte stem cells in the areas of the hair follicle of the skin.


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