Vitiligo is a multifactorial skin disease in which a faulty immune reaction attacks and kills off pigment cells known as melanocytes. The aftermath of the massacre leaves behind patches of white skin.
Even though it has been known about for at least 5000 years, little has been done to understand its causes or to evaluate possible treatments as it is not a painful or immediately life-threatening condition.
As someone who currently has various depigmented patches of skin running across my elbows, back and ankles, I have firsthand experience of the profound psychological and social impact it has on people diagnosed with the skin disease.
A (not-so) brief introduction to the pigmentation assassin
The disease often emerges in adolescence or later and is roughly estimated to affect ~1% of the general population — lucky me! It also seems highly likely that vitiligo is inherited: while the risk of a patient’s sibling later developing the disease is 6%, the percentage almost quadruples when it comes to an identical twin — a whopping 23%.
Oh, ancestors, what have you done to me?
In symmetrical vitiligo, the depigmented areas usually appear on both sides of the body equally and are often — you guessed it — symmetrical. The commonly affected areas include the face (especially around the eyes and mouth), hands and body creases (armpits and groins including genitals). For patients diagnosed with segmental vitiligo, white patches occur only on one side of the body.
But it’s important to note that the pigmentation assassins work in strange ways and depigmentation can occur literally anywhere on the body.
Vitiligo is considered an autoimmune disorder as patients and their relatives have an increased risk of developing other autoimmune diseases, such as autoimmune thyroiditis and type 1 diabetes.
As if that wasn’t scary enough: since melanocytes — pigment cells, in case I’ve lost you already — populate the inner ear, several tissues of the eyeball and a layer of the brain’s protective coating, there is a chance that us vitiligo patients can experience hearing loss, vision impairments and occasional neurological abnormalities. Fun.
The mystery of the assassins
While the earliest triggering events that lead to vitiligo are not yet fully understood, scientists have made headway on elucidating how pigment-producing cells are killed off at a molecular level.
A large percentage of genes linked to vitiligo play essential roles in the immune system. Scientists, therefore, believe that the skin disease may be regular immune surveillance in the skin which has maybe drunk a couple more cups of coffee than it should have.
The misguided T cells
Patients’ T-cells — cool, killer cells of the immunity system which hunt and destroy germs and cancerous cells — spearhead the massacre on pigment-producing cells entirely by mistake. A vicious cycle of destruction and depigmentation through a biochemical cascade is therefore triggered.
Treatment options available
#1 — Topical therapies
- Steroids — First-line treatment for localized vitiligo
In patients with localized vitiligo and, or an inflammatory component to their disease, a topical corticosteroid preparation is often the first-line treatment because of its ease of use and convenience. The steroid can be applied to the affected area(s) for months and tapered down if necessary, depending on the patient’s response.
Results of treatment have been moderately successful.
- Calcineurin inhibitors — Effective therapy when the disease involves the head and neck
When vitiligo affects the head and neck region, topical tacrolimus ointment (0.03% or 0.1%) and pimecrolimus cream are effective therapies. Calcineurin inhibitors can be used in combination with topical steroids.
Better treatment results may be obtained through augmenting topical calcineurin inhibitors with laser therapy or narrowband UV-VB (a form of phototherapy).
- Vitamin D analogs — Act on specific T-cell activation
Vitamin D analogs — particularly calcipotriol and tacalcitol — target the local immune response and act on specific T-cell activation. They prevent the biochemical cascade of destruction and depigmentation caused, in part, by interferon-gamma through the inhibition of the transition of T-cells.
However, the effectiveness of calcipotriol as a treatment for vitiligo remains controversial as certain studies have found it to improve repigmentation, while others have not. Nevertheless, the current, available scientific literature suggests that it should be used as a supplementary therapy rather than a stand-alone one.
#2 — Phototherapy
For the majority of patients diagnosed with early or localized vitiligo, phototherapy leads to satisfactory repigmentation. A treatment period of at least six months for phototherapy courses is usually encouraged to allow for more accurate assessment of the responsiveness to the treatment.
There are two main types of phototherapy: narrowband UV-B (NB-UVB) and PUVA: psoralen photochemotherapy, followed by UV-A radiation. NB-UVB has mostly replaced PUVA as the former has an overall better response, coupled with fewer adverse effects.
Additionally, NB-UVB wins out over PUVA with its shorter treatment times, cost, lack of nausea in patients, and the fact that patients don’t require subsequent photoprotection.
#3 — Janus kinase (JAK) inhibitor therapy
Rather than inhibiting the T cells, JAK inhibitors, as is suggested by their names, block JAK proteins — a different family of immune molecules which also provoke the body’s T cell attacks on itself.
After JAK inhibitors have suppressed normal immune activation, the affected areas need sunlight exposure to stimulate the pigment cells for repigmentation of the skin.
As far as treatments for vitiligo goes, JAK inhibitors have been described by most vitiligo experts to be the most promising.
#4 — Depigmentation therapy
Many of the current vitiligo treatment options have an anti-inflammatory or immunosuppressive effect: they target the immune factor in vitiligo but fail to have a direct impact on melanocyte differentiation, migration of proliferation. As a result, many treatment options fail to be efficient in the long-run once treatment is stopped — vitiligo eventually recurs over time.
Heck — did you say vitiligo recurs after treatment?
Yes, I did. White spots return at the same location, often just within a year of stopping treatment. But why? Maybe it’s because it bears grudges. Okay — not exactly.
It’s all because of “resident memory T cells.” These cells perform similar functions to normal memory cells that protect the skin from a second exposure to a viral infection.
As such, they stay on the surface even if normal coloration is achieved post-treatment. And they attack the pigment-creating cells once there’s an opportunity, or once unknowing patients cease treatment sessions.
How do we get rid of it for good?
Currently, no treatment can keep vitiligo away for long. But there’s hope.
An in-vivo study on mouses shows that the much-dreaded, disease-causing memory T-cells can be effectively wiped out with the injection of a particular antibody. This antibody blocks a specific type of protein in the body that is essential for the survival of the memory cells.
As you and I know, we are not mouses or mice. But this study paves the way for human clinical trials in the future.
And I’m beyond excited.