June 25 is the anniversary of Michael Jackson's death and World Vitiligo Day because the singer suffered from the autoimmune disease. For a long time, the disease with the typical white spots was considered a purely cosmetic problem. However, the psychological burden on those affected is often great and new therapeutic approaches give hope.
Bright spots suddenly appear on the skin, often initially on the face, hands or feet, but other parts of the body can also be affected: the clearly defined white spots are the hallmark of vitiligo. This chronic and often relapsing autoimmune disease is not contagious, is described as harmless and is nevertheless a great burden for many sufferers, as a look at the relevant online forums shows.
"I don't want to show my hands anymore." "The funny looks and stupid questions bother me a lot." "I feel like a monster." In fact, numerous studies show what psychological consequences can be associated with vitiligo. For example, a meta-analysis published in the American Journal of Clinical Dermatology in 2021 reported that more than 50 percent of the patients in the studies evaluated suffered from depression, anxiety, social phobias, feelings of stigmatization, adjustment and sleep disorders, and avoidance and restriction behaviors.
"The extent and severity of these comorbidities and the resulting impact on the quality of life of patients with vitiligo go beyond what was previously dismissed as a cosmetic disease," the analysis concludes. In addition, other autoimmune diseases are also associated with vitiligo, including those of the thyroid gland and gastric mucosa, as well as circular hair loss (alopecia areata).
It is estimated that vitiligo affects about 0.5 to 2 percent of the world's population. Not everyone suffers equally from the skin changes, both in terms of the extent of the spots and their psychological consequences. For some time now, models with vitiligo have been seen more frequently in the media and advertising, which is intended to counteract the stigmatization of those affected.
The causes of vitiligo have not yet been sufficiently clarified. Among other things, an increased production of hydrogen peroxide in the skin, neurological factors or a dysregulation of the immune system are suspected. Likewise, at least the tendency to the disease seems to be genetically determined. Various studies report that in about one third of the cases a familial accumulation can be observed; According to a US study, the risk that a patient's siblings will develop the disease is six percent and in the case of identical twins it is 23 percent.
However, what happens in vitiligo is well understood: cytotoxic T cells (CD8 T cells), which as part of the immune system are actually there to destroy diseased cells, suddenly turn against melanocytes, i.e. pigment-forming cells in the skin. The loss of these melanocytes is reflected in the white, sun-sensitive patches. In addition, various pro-inflammatory messenger substances can be detected in active vitiligo skin, which mobilize the cytotoxic T cells and also activate keratinocytes. As part of the epidermis, these cells normally serve to protect the skin, but in the case of vitiligo they produce factors that further increase the inflammation.
Various triggers seem to promote the onset of vitiligo. Patients report that they noticed the first spots after a severe infection or great stress, during pregnancy or after skin injuries. In most cases, the disease occurs between the ages of ten and 30, although the individual course can be very different, not least depending on the type of vitiligo.
"We see the non-segmental type most frequently," says Michael Hertl, director of the Department of Dermatology and Allergology at the University Hospital in Marburg. This typically affects both sides of the body at the same time, often starting on the face and showing up as white patches around the eyes and mouth. "But the spots can also appear on the backs of the hands, forearms, feet, around the armpits, in the genital area and around the buttocks, all of which are of course very stigmatizing areas," lists the doctor, who is also President of the German Dermatological Society (DDG ) is.
There is also segmental vitiligo, which often occurs earlier and can be limited to one side of the body. However, this type is rare. And finally, mixed forms and non-classifiable forms would also be observed. It applies to all forms that the disease cannot be cured. "However, the earlier you start the treatment, the greater the chance of reactivating the pigment cells that are still present," emphasizes Hertl. In this context, the doctor refers to the S1 guideline "Diagnostics and Therapy of Vitiligo", which was published for the first time last year, in which the DDG, together with other specialist societies, lists the most important recommendations for treatment.
According to the DDG President, the treatment includes two approaches: inhibition of inflammation and repigmentation of the skin. Traditionally, strong glucocorticoids in cream form are used to reduce inflammation; internal administration is less common. "Since cortisone makes the skin thinner, it's not a long-term treatment. You're more careful with stronger corticosteroids, especially on your face," Hertl notes. Accordingly, glucocorticoids are sometimes replaced by topical immune modulators, so-called calcineurin inhibitors: "These are not as strong, but can be used over the longer term."
On the other hand, to repigment the skin, UV or sometimes laser therapy would be prescribed. "With this one induces the remaining pigment-forming cells, which can be found as small islands in the white spots or at their edges," describes the dermatologist. In very advanced Vitiligo cases, pigment cells with healthy skin could also be transplanted - but this is technically relatively complex. Likewise, melanocytes could be removed and used to grow cell cultures for transplantation. "However, this is also a very complex approach, which on the one hand does not always work and on the other hand is only suitable for a few smaller areas," says Hertl.
In the case of a very extensive vitiligo, there is finally the possibility of depigmenting the still pigmented skin in order to match it to the white areas. This treatment was probably also used by pop star Michael Jackson: He is considered one of the most famous sufferers, which is why World Vitiligo Day is celebrated every year on June 25th, the anniversary of the death of the singer who died in 2009.
All of the approaches described by dermatologist Hertl can be found as treatment options in the already mentioned DDG guideline, which also gives hope for new therapeutic approaches. For some time, research has been carried out into whether so-called Janus kinase inhibitors, which are already being used successfully in rheumatoid arthritis, psoriasis and moderate to severe neurodermatitis, could also provide relief in vitiligo. These JAK inhibitors are small molecules ("small molecules") that inhibit signaling pathways involved in the development of inflammatory processes. In concrete terms, they occupy receptors on the cell surface and thus ensure that several pro-inflammatory messenger substances cannot penetrate into the cell nucleus.
According to Michael Hertl, the small molecules can be easily accommodated in cream or tablet form, and according to several research papers, treatment with cream in particular would bring good results. In fact, in a Phase II study conducted at multiple US clinics, JAK 1/2 inhibitor cream improved facial skin disease in about 50 percent of patients versus 3 percent who received a placebo.
"Data like this shows that creams with a high concentration of JAK inhibitors can quickly and powerfully block the signaling pathways involved in inflammation," explains Hertl. The side effects are manageable when administered in cream form: the skin can become a little more sensitive, initially itchy or burn and in rare cases develop acne, while the internal administration of JAK inhibitors can certainly be associated with an increased risk of infection, for example of the bronchi or urinary tract.
However, JAK inhibitors are not a miracle cure, says Hertl, who expects their approval for the coming year: "Even small molecules cannot do more than inhibit inflammation, only that, unlike corticoids, they have a less skin-thinning effect." In addition, as with all other therapeutic approaches, patience is required because the treatments last several months. And finally, the DDG President recommends that those affected go to a dermatological practice as early as possible if they notice white spots: "The longer you wait to treat vitiligo, the more difficult it becomes."