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Topical Therapies for Vitiligo

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Topical Therapies for Vitiligo

There is no question that vitiligo is a difficult disease to treat. This is in part due to the unclear mechanisms that leads to the disease in the first place.[1] While vitiligo may not cause any harmful or serious physiological effects, the psychological consequences due to the cosmetically significant characteristics are important to address for those suffering from vitiligo.

Steroids

Topical steroids have been used as therapy for vitiligo with suboptimal results.[2] They may be more effective on small, depigmented (total lack of color) areas of recent onset.[3,4] Topical corticosteroids have been considered the preferred drug for localized vitiligo.[5]

While steroids have been effectively shown to pigment skin vitiligo, they can be associated with side effects.[5-7] Long-term use of topical steroids is especially associated with a variety of side effects.[3] These side effects frequently include itching, redness, telangiectasia (red marks on the skin due to widened blood vessels), hypertrichosis (excessive hair growth), and atrophy.[3,6]

It is important to monitor steroid usage and if there is no response to the topical therapy within a pre-determined time frame (for example 3 months), the doctor together with the patient may wish to consider a different treatment strategy.[4] If topical steroids help with repigmentation without bothersome side effects, steroid use can be continued but should still be closely monitored.[4]

Calcineurin Inhibitors

Calcineurin inhibitors are therapies that suppress the immune system. They may potentially replace the use of topical steroids for vitiligo due to fewer side effects.

These immunosuppressive topical creams, including tacrolimus and pimecrolimus, have been well tolerated in both children and adults.[2] Because abnormalities in the immune system may be an underlying cause of vitiligo, using immunosuppressive medications may be a good treatment strategy. Applying topical tacrolimus twice a day can help to induce repigmentation.[8,9] Furthermore, using topical tacrolimus showed repigmentation after only four weeks of treatment.[8] When applied on the face and eyelids twice daily, along with daily sunlight exposure for 5 to 10 minutes, repigmentation may be seen after 3 weeks leading up to complete repigmentation in 4 months following this topical therapy.[3] In clinical trials, side effects including burning, stinging, redness, or itchiness of the skin were minimal or not experienced at all.[3,8,9] There is a possibility that natural sunlight exposure in combination with tacrolimus ointment can result in even greater benefit of tacrolimus therapy.[9]

Vitamin D Analogues

Vitamin D affects melanocyte and keratinocyte growth. Calcipotriol is an analog of vitamin D shown to be effective in treating children and adults with vitiligo when combined with UV light exposure.[2] However, there have been mixed results because minimal repigmentation of the skin has also been observed using this treatment.[2] There is evidence that topical therapy of vitamin D analog is effective for children between the ages of 5 to 17 years with vitiligo.[10] When applied every evening, followed by exposure to sunlight the following day for 10 to 15 minutes, repigmentation of the skin starts occurring after 6 to 12 weeks of treatment.[10] Complete repigmentation may occur. It is also rare to find any side effects or irritation upon application of vitamin D analog.[10] In vitiligo patients ages 5 to 61, topical calcipotriol alone was effective in those who showed no benefit from topical steroids.[11] However, it is important to note that there is also conflicting evidence that topical calcipotriol alone is not an effective treatment of vitiligo.[1]

L-DOPA

Theories propose that L-DOPA is both a marker and defense mechanism against reactive oxygen and nitrogen elements that can harm the cells in your body.[12] This type of stress can cause melanocyte death which in turn shows up as vitiliginous skin.[13] Hence, there seems to be potential in applying L-DOPA as topical therapy to repigment skin from melanocyte damage in vilitgo. However, one study showed that topical application of levodopa cream may not produce significant repigmentation.[14] As of now, there is no clear cut evidence whether or not L-DOPA can be topically applied to repigment vitiliginous skin.[14]

To conclude, more research needs to be done on which topical therapies are the most efficacious for vitiligo yet exhibit the least side effects. As of now, the medications listed above are some that have been used and show some benefit in repigmenting vitiligo patches. Finding treatment modalities for vitiligo may be difficult due to its unclear mechanisms, but it is important to conduct research that will lead to development of topical therapeutic options.

Janus Kinase (JAK) Inhibitors

Studies exploring the use of JAK inhibitors in treatment of vitiligo have shown promising results. Cytotoxic CD8+ T lymphocytes have an important role in the pathogenesis of vitiligo. These immune cells can directly destroy melanocytes. Recruitment of cytotoxic T cells is regulated by the JAK-STAT pathway. Thus, there has been growing interest in the JAK-STAT pathway as a therapeutic target for patients with vitiligo.[18]

A pilot study explored the effects of 2% tofacitinib cream, a JAK inhibitor, twice daily along with narrowband ultraviolet B (NB-UVB) therapy 3 times weekly for 3 months. 11 patients were recruited to this study, and all of them had facial vitiligo that did not respond to topical corticosteroids or calcineurin inhibitors. Following the intervention, all patients in this pilot study showed good to excellent repigmentation of their lesions, as defined by the Vitiligo Area Severity Index (VASI).[19] Another pilot study that consisted of 16 patients with refractory vitiligo found that use of 2% tofacitinib cream improved vitiligo lesions on the face. However, JAK inhibitors were found to be less effective at treating non-facial vitiligo.[20]

Use of a topical JAK inhibitor is preferred over systemic JAK inhibitors because of the potentially lower cost and better safety profile. Systemic JAK inhibitors have an increased risk for infection, malignancy, and cytopenia.[19] Current research suggests that JAK inhibitors can be an effective treatment option, especially for those with facial vitiligo, but further research is needed on larger populations to better characterize its effects.

Table 1. Summary of Topical Therapies for Vitiligo

Medication

Evidence For Use in Vitiligo

Side Effects

Topical Steroids

Clinical trials have shown that highly potent or potent topical steroids can cause repigmentation in a proportion of patients.[15-17] However, these studies have been critiqued for being poorly conducted.[15]

 

Adverse effects are common if topical steroids are used for more than a few weeks.[15]

 

Long-term use is associated with itching, redness, telangiectasia (red marks on the skin due to widened blood vessels), hypertrichosis (excessive hair growth), and atrophy.[3,6]

Calcineurin inhibitors

When applied on the face and eyelids twice daily, along with daily sunlight exposure for 5 to 10 minutes, repigmentation may be seen after 3 weeks leading up to complete repigmentation in 4 months following this topical therapy.[3]

In clinical trials, side effects including burning, stinging, redness, or itchiness of the skin were minimal or not experienced at all.[3,8,9]

Vitamin D analogues

Research shows mixed results on efficacy of vitamin D analogues in treating vitiligo.[2]

 

Some studies have demonstrated that Calcipotriol, when combined with UV light exposure, is effective at treating adults and children with vitiligo. Other studies observed minimal repigmentation using this treatment.[2]

Rare to find any side effects or irritation upon application of vitamin D analog.[10]

JAK Inhibitors

JAK inhibitors shown to be effective in treating facial vitiligo in 2 pilot studies. Further studies needed to determine effects on non-facial vitiligo.[18-20]

Acne-like papules on face reported by patient on one pilot study. Subtle skin contour changes reported by another patient.[20] Further studies needed to better characterize side effects.

 

* This Website is for general skin beauty, wellness, and health information only. This Website is not to be used as a substitute for medical advice, diagnosis or treatment of any health condition or problem. The information provided on this Website should never be used to disregard, delay, or refuse treatment or advice from a physician or a qualified health provider.

References

  1. Chiaverini C, Passeron T, Ortonne JP. Treatment of vitiligo by topical calcipotriol. J Eur Acad Dermatol Venereol.2002;16(2):137-138; PMID: 12046816 https://www.ncbi.nlm.nih.gov/pubmed/12046816.
  2. Grimes PE. New insights and new therapies in vitiligo. JAMA.2005;293(6):730-735; PMID: 15701915 https://www.ncbi.nlm.nih.gov/pubmed/15701915.
  3. Travis LB, Weinberg JM, Silverberg NB. Successful treatment of vitiligo with 0.1% tacrolimus ointment. Arch Dermatol.2003;139(5):571-574; discussion 573; PMID: 12756092 https://www.ncbi.nlm.nih.gov/pubmed/12756092.
  4. Shaffrali F, Gawkrodger D. Management of vitiligo. Clin Exp Dermatol.2000;25(8):575-579; PMID: 11167964 https://www.ncbi.nlm.nih.gov/pubmed/11167964.
  5. Forschner T, Buchholtz S, Stockfleth E. Current state of vitiligo therapy--evidence-based analysis of the literature. J Dtsch Dermatol Ges.2007;5(6):467-475; PMID: 17537039 https://www.ncbi.nlm.nih.gov/pubmed/17537039.
  6. Whitton ME, Pinart M, Batchelor J, et al. Interventions for vitiligo. Cochrane Database Syst Rev.2015;10.1002/14651858.CD003263.pub5(2):CD003263; PMID: 25710794 https://www.ncbi.nlm.nih.gov/pubmed/25710794.
  7. Njoo MD, Spuls PI, Bos JD, et al. Nonsurgical repigmentation therapies in vitiligo. Meta-analysis of the literature. Arch Dermatol.1998;134(12):1532-1540; PMID: 9875190 https://www.ncbi.nlm.nih.gov/pubmed/9875190.
  8. Grimes PE, Soriano T, Dytoc MT. Topical tacrolimus for repigmentation of vitiligo. J Am Acad Dermatol.2002;47(5):789-791; PMID: 12399778 https://www.ncbi.nlm.nih.gov/pubmed/12399778.
  9. Tanghetti EA. Tacrolimus ointment 0.1% produces repigmentation in patients with vitiligo: results of a prospective patient series. Cutis.2003;71(2):158-162; PMID: 12635898 https://www.ncbi.nlm.nih.gov/pubmed/12635898.
  10. Parsad D, Saini R, Nagpal R. Calcipotriol in vitiligo: a preliminary study. Pediatr Dermatol.1999;16(4):317-320; PMID: 10469422 https://www.ncbi.nlm.nih.gov/pubmed/10469422.
  11. Ameen M, Exarchou V, Chu AC. Topical calcipotriol as monotherapy and in combination with psoralen plus ultraviolet A in the treatment of vitiligo. Br J Dermatol.2001;145(3):476-479; PMID: 11531840 https://www.ncbi.nlm.nih.gov/pubmed/11531840.
  12. Liu MC, Yasuda S, Idell S. Sulfation of nitrotyrosine: biochemistry and functional implications. IUBMB Life.2007;59(10):622-627; PMID: 17891604 https://www.ncbi.nlm.nih.gov/pubmed/17891604.
  13. Slominski A, Zmijewski MA, Pawelek J. L-tyrosine and L-dihydroxyphenylalanine as hormone-like regulators of melanocyte functions. Pigment Cell Melanoma Res.2012;25(1):14-27; PMID: 21834848 https://www.ncbi.nlm.nih.gov/pubmed/21834848.
  14. Woolfson H, Finn OA. Topical levodopa in vitiligo. Lancet.1972;1(7750):598; PMID: 4110084 https://www.ncbi.nlm.nih.gov/pubmed/4110084.
  15. Taieb A, Alomar A, Böhm M, et al. Guidelines for the management of vitiligo: the European Dermatology Forum consensus. Br J Dermatol. 2013;168(1):5-19. doi:10.1111/j.1365-2133.2012.11197.x
  16. Kandil E. Treatment of vitiligo with 0-1 per cent betamethasone 17-valerate in isopropyl alcohol--a double-blind trial. Br J Dermatol. 1974;91(4):457-460. doi:10.1111/j.1365-2133.1974.tb13086.x
  17. Clayton R. A double-blind trial of 0-05% clobetasol proprionate in the treatment of vitiligo. Br J Dermatol. 1977;96(1):71-73. doi:10.1111/j.1365-2133.1977.tb05188.x
  18. Karagaiah P, Valle Y, Sigova J, et al. Emerging drugs for the treatment of vitiligo. Expert Opin Emerg Drugs. 2020;25(1):7-24. doi:10.1080/14728214.2020.1712358
  19. McKesey J, Pandya AG. A pilot study of 2% tofacitinib cream with narrowband ultraviolet B for the treatment of facial vitiligo. J Am Acad Dermatol. 2019;81(2):646-648. doi:10.1016/j.jaad.2019.04.032
  20. Mobasher P, Guerra R, Li SJ, Frangos J, Ganesan AK, Huang V. Open-label pilot study of tofacitinib 2% for the treatment of refractory vitiligo. Br J Dermatol. 2020;182(4):1047-1049. doi:10.1111/bjd.18606
 
 
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