We have some idea of what is happening in vitiligo but are less clear about why it is happening. We know that pigment cells are not functioning in the white patches although some of them do survive both in the skin and also in the hair follicles in the white patches. Many theories exist to explain the loss of pigment, the most popular is the autoimmune theory which means that the body’s own immune system is attacking the pigment cells.
It has also been recently established that genes play an important role in predisposing some people to vitiligo, especially those who have other autoimmune diseases, in particular thyroid disease, or who have family members who suffer from vitiligo or these diseases. This discovery strengthens the autoimmune theory.
Other theories which have been proposed include the neuronal theory which suggests that the nerves in the skin are implicated in the damage to pigment cells and the oxidative stress theory based on the break down of anti-oxidant defences in the skin or in the pigment cell itself. In addition, high levels of hydrogen peroxide which is toxic to pigment cells have been found in the skin of people with vitiligo.
It is also recognized that environmental factors such as psychological stress, hormonal changes including puberty and childbirth, trauma to the skin, and even exposure to certain chemicals may trigger the disease and could play an important role in its development and progression.
The specific cause of vitiligo is unknown but it is generally accepted to be an autoimmune disease where the individual’s own immune system destroys the melanocytes. The variety of clinical and experimental features along with different family histories suggests that vitiligo might be the end product of several pathological pathways. In all likelihood, vitiligo is a multifactorial disease with a combination of interrelating factors resulting in different degrees and rates of progression. It is thought that genetic factors, accumulation of toxic compounds, altered cellular environment, autoimmunity and impaired melanocyte function could all contribute to vitiligo.
There is much evidence to suggest that abnormalities in the immune system lead to the destruction of melanocytes in vitiligo patients. Antibodies are proteins, present in the blood, which the body produces in response to foreign objects, such as viruses and bacteria. The antibodies are like tags, which signal to other cells in the immune system to destroy the target. Patients with vitiligo usually have auto antibodies which complement their own melanocytes, a strong indicator that the immune system is attacking its own body cells.
Lymphocytes are the white blood cells which detect and destroy the targeted pathogens, often by releasing cytotoxic (cell-killing) chemicals or by engulfing them. Patients with active vitiligo have been discovered as having an increased number of these cells circulating in their blood. Furthermore, these lymphocytes in vitiligo patients are reactive to the antigens (molecule on the surface of a cell) on melanocytes. Studies have also shown an abundance of T-cells (a type of lymphocyte) in the areas affected by inflammatory vitiligo, some suggest that these specific T cells may mediate the destruction of melanocytes.
Vitiligo has been linked to a number of other autoimmune diseases, with vitiligo patients at greater risk of developing thyroid disease, diabetes mellitus, Addison’s disease, pernicious anemia, rheumatoid arthritis, psoriasis and Grave’s disease, among others.
There appears to be a genetic component to vitiligo, as 10% of patients have a family history of the condition and blood relatives have an increased risk of developing it. Multiple genes are likely to be involved, with different combinations inherited by different people. This is perhaps partially responsible for the extreme variability seen in vitiligo sufferers. Genes which could potentially be involved in the development of vitiligo include those responsible for autoimmunity regulation or melanin synthesis and degradation. The human leukocyte antigen (HLA) gene encodes many elements essential to immune system function in humans; this site is frequently associated with vitiligo.
Certain environmental conditions may interplay with the hereditary component of the disease, creating additional risk factors. Environmental triggers are not well-understood, though illness, emotional stress, severe sunburn and pregnancy have all been implicated as possible aggravating factors.
The pattern of lesions in one type of vitiligo, called ‘segmental vitiligo’, tend to correspond to underlying nerves. In such cases, it has been suggested that certain chemical mediators released from nerve endings may be toxic to melanocytes. Some vitiligo patients have been shown to have mild degenerative or regenerative changes in nerve cells beneath the depigmented areas.
Melanocytes possess a protective mechanism to eliminate toxic melanin precursors (e.g. dopa, dopachrome) and free radicals. Experts suggest that vitiligo may incorporate a disturbance of this mechanism, leading to an accumulation of toxic intermediates and free radicals which can damage melanocytes.
It has also been found that the red blood cells (erythrocytes) of vitiligo patients have lower levels of the antioxidant glutathione. Antioxidants mop up excess reactive oxygen species which can damage skin cells. It is thought that in the absence of sufficient glutathione, the reactive oxygen species produced by the body can damage or completely destroy the melanocytes.