Faith Shongwe

With Roman physician, Celsus, first introducing the term in the first century, vitiligo has surfaced through the face of history with references obtained from the literature of various regions such as the Ebers Papyrus from Egypt in 1500 BCE, India in 1300 BCE and Greek literature from 450 BCE.¹ Such descriptions, references and research has led to our current understanding, marking vitiligo as a chronic autoimmune condition characterised by white, non-scaly patches that fluoresce under woodlamp examination, affecting up to 2% of the global population.^1-3

Figure 1:  Acrylic painting “African Vitiligo” by Help-Child

Treatment strategies have been developed to address the social stigmatisation, iritis (eye involvement), increased risk of sunburn and skin cancer in patients with vitiligo⁴. These include: topical steroids, which are useful for localised areas of vitiligo; topical calcineurin inhibitors (TCIs), such as topical tacrolimus 0,1% ointment and pimecrolimus 1% cream; phototherapy; and in cases of persistent lesions, surgical interventions ,including split-skin and mini/punch grafts, may be implemented.^5,6 However, there still remains no therapeutic panacea for vitiligo; and ~40% rate of depigmentation with available treatment strategies.⁵ Consequent development of Ruxolitinib, a Janus Kinas (JAK) STAT inhibitor, has been implemented by Rosmarin (et al)⁷ as a potential treatment strategy for the condition.⁷

Consider the proposed multifactorial pathogenesis of vitiligo for understanding of the mechanism of action the ruxolitinib: inherited genetic risks and environmental insults induce melanocytic stress. This, then, leads to the stimulation of T-cells, which secrete INF-λ – this is mediated by the transcription factors STAT 1 by JAK 1 and 2 (target of ruxolitinib). INF-λ leads to the transcription of CXC ligand 10 (CKCL10), which in combination to autoreactive CD8+ T cells (which express CXC chemokine receptor 3 (CXCR3)) leads to the destruction of melanocytes.^1,5,7 Other aetiologies of vitiligo include intrinsic defects of melanocytes and oxidative stress. ^5,8

Method

The study to determine the efficacy of topical ruxolitinib in patients with vitiligo consisted of two vehicle-controlled trials called the Topical Ruxolitinib Evaluation in Vitiligo Study 1 and 2 (TRuE 1 and 2). The trials employed patients 12 years and older with a diagnosis of nonsegmental vitiligo, scoring 0,5 or more on the facial vitiligo area scoring index (F-VASI). This scoring index ranges from 0-3, with higher scores indicative of greater depigmentation across the forehead to the hairline, cheek to jawline, and from the corners of the mouth to the tragus, nose, and eyelids. Furthermore, the patients were required to have scores of 3 or more on the total vitiligo area scoring index (T-VASI). Wherein scores range from 0-100, with higher scores representing greater areas of depigmentation across the head, neck, trunk, genitalia, upper limbs and lower limbs.⁷

Results

Of patients who had applied 1,5% ruxolitinib cream bidaily, 45% had at least 50% improvement in the F-VASI (this is expressed as F-VASI50) at the end of week 24, with some patients having at least 75% improvement in the F-VASI (F-VASI75) at 52 weeks. However, a T-VASI50 was observed in 20,6% of patients who applied the ruxolitinib cream, as compared to 5,1% with the vehicle cream.⁷

Adverse effects experienced by patients at 24 and 52 weeks of topical ruxolitinib in both trials⁷:

• Application-site pruritis
• Application-site Acne
• Nasopharyngitis
• Application-site pain
• Nausea and headache (least common, seen in one patient)
• Application-site eczema (also observed in one participant)

Conclusion

Variability in the presentation of the condition makes its management particularly difficult.² This may lead to adverse psychosocial effects contributing to a burden in quality of life experienced by patients with vitiligo.⁷ Ruxolitinib has shown superiority in repigmentation in vitiligo when compared to the vehicle cream.⁷ However, follow-up of patients on ruxolitinib is needed to determine the rate of depigmentation, if present, as well as added benefits and/or long-term adverse effects that may occur.

Bibliography

1. Norman RA, Shenefelt PD, Rupani RN. Integrative dermatology [internet]. Oxford University Press; 2014. [cited March 10, 2023]. Available from: https://ebookcentral-proquest-com.uplib.idm.oclc.org/lib/pretoria-ebooks/detail.action?docID=1602554
2. Kang S (2019). Fitzpatrick’s dermatology 9th ed McGraw-Hill Education; 2019. [cited March 10, 2023]. Available from: https://accessmedicine-mhmedical-com.uplib.idm.oclc.org/book.aspx?bookid=2570
3. Silverberg NB. The Epidemiology of Vitiligo. Curr Derm Rep4, 36–43 (2015). https://doi.org/10.1007/s13671-014-0098-6
4. Ahmed jan N, Masood S. Vitiligo. [Updated 2023 Feb 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559149
5. Bolognia J, Schaffe JV, Cerroni L. Dermatology. Elsevier; 2018. [cited March 10, 2023]. Available from: https://www-clinicalkey-com.uplib.idm.oclc.org/#!/browse/book/3-s2.0-C20131144449
6. American Academy of Dermatology Association. Vitiligo: Diagnosis and Treatment. https://www.aad.org/public/diseases/a-z/vitiligo-treatment
7. Rosmarin D, Passeron T, Pandya AG. Two phase 3, randomized, controlled trials of ruxolitinib cream for vitiligo. N Engl J Med 2022;387:1445-1455
8. Grimes PE, Tsao H, Corona R. Vitiligo: Pathogenesis, Clinical Features, and Diagnosis. In: Post TW, ed. UpToDate .Waltham, MA: UpToDate. https://www.uptodate.com/contents/vitiligo-pathogenesis-clinical-features-and-diagnosis.Last updated February 3, 2017.