Laboratory Workup of Vitiligo

Vitiligo is considered an autoimmune skin disorder characterized by patchy white depigmented spots on the skin, especially in individuals with darker skin. Oxidative stress, antioxidant insufficiency, environmental influences, metabolic abnormalities, and genetic factors may contribute (Khoshdel 2022).

Vitamin D insufficiency may trigger vitiligo and other autoimmune conditions and should be evaluated (Iraji 2024). Antioxidants, including those in coffee, tea, and red wine, may be protective and reduce vitiligo risk (Ni 2024).

Laboratory Assessment

Vitiligo assessment should include (Chang 2020, Chen J 2014, Rodríguez-Martín 2012, Shekar 2022, Tsai 2019):

• Antinuclear antibodies
• Anti-parietal gastric cell antibodies
• CBC count with differential
• Homocysteine
• MTHFR SNPs
• Thyroid panel with TSH, free T3, free T4, and anti-TPO antibodies

Investigate nutrient insufficiencies potentially associated with vitiligo (Huo 2020, Iraji 2024, Khoshdel 2022, Mogaddam 2017, Noland 2020):

• Copper
• Vitamin B12
• Vitamin C
• Vitamin D
• Vitamin E
• Zinc

Selenium may have a depigmenting effect, and higher serum levels may be a risk factor for vitiligo (Huo 2020). The 3-O-ethyl ascorbic acid (EAA) ether derivative of ascorbic acid also has a depigmenting effect and may be contraindicated in vitiligo (Chen S, 2021).

Research

A meta-analysis of 47 studies found significantly lower vitamin D, E, and zinc levels in subjects with vitiligo, but no difference in B12 or copper levels. They also found significantly higher levels of selenium and folic acid (Iraji 2024). Note that increased levels of unmetabolized folic acid, the synthetic supplement form, can jeopardize folate status and induce a functional folate deficiency with associated adverse effects (Fardous 2023).

Both copper and zinc were significantly lower in a single study of 117 vitiligo patients and 137 controls. Copper and zinc were also lower in generalized versus localized vitiligo, while general antioxidant status was lower in both generalized and local disease. Researchers note that some research finds higher copper in those with vitiligo, and subjects should be assessed individually (Khoshdel 2022).

Although some research has been conducted regarding vitamin D levels and vitiligo, a meta-analysis of 31 studies found significantly lower serum vitamin D in vitiligo patients compared to controls and lower serum vitamin D in vitiligo patients working indoors in an urban setting compared to vitiligo subjects working outdoors in a rural setting (Varikasuvu 2021).

A study of 196 vitiligo patients and 160 controls suggests that testing anti-TPO antibodies and anti-parietal gastric cell antibodies may assist in assessing vitiligo. Researchers also note a higher frequency of anxiety, chronic insomnia, depression, diabetes, and thyroid disease associated with vitiligo (Rodríguez-Martín 2012). It would be prudent to screen for and address these issues as well.

Optimal Takeaways

Potential contributors to vitiligo:

• Oxidative stress and antioxidant depletion
• Thyroid disease
• Genetic factors
• Nutrient deficiency
• Insufficiencies of
  • Antioxidants
  • Copper
  • Vitamins B12, C, D, E
  • Zinc
• Excess
  • Homocysteine
  • Selenium
  • Unmetabolized folic acid

Promising functional interventions include:

• Nutrition therapy
  • A healthy anti-inflammatory, whole-food, plant-based diet containing an abundance of antioxidants, phytonutrients, and omega-3 fatty acids may be beneficial.
  • Avoid trans fats, refined processed foods, and processed meats
  • Identify and address nutrient insufficiencies
• Phototherapy
• Natural medicine therapy
  • Ginkgo biloba
  • Polypodium leucotomos with phototherapy
  • Phenylalanine with UVA therapy
  • Topical
    • Shvitrahara lepa, Cucumis melo, curcumin, herbal extracts, vitamin D3 analogues, honey bee, Allium cepa, Avena sativa, and topical antioxidants
    • Psoralen, Psoralea corylifolia, khellin have some efficacy but may have adverse side effects.

References

Chang, Hua-Ching et al. “Association Between Methylenetetrahydrofolate Reductase Gene Polymorphisms and Risk of Vitiligo: A Systematic Review and Meta-Analysis.” Acta dermato-venereologica vol. 100,6 adv00087. 18 Mar. 2020, doi:10.2340/00015555-3448

Chen, J-X et al. “Genetic polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) and risk of vitiligo in Han Chinese populations: a genotype-phenotype correlation study.” The British journal of dermatology vol. 170,5 (2014): 1092-9. doi:10.1111/bjd.12845

Chen, Siang-Jyun et al. “The anti-melanogenic effects of 3-O-ethyl ascorbic acid via Nrf2-mediated α-MSH inhibition in UVA-irradiated keratinocytes and autophagy induction in melanocytes.” Free radical biology & medicine vol. 173 (2021): 151-169. doi:10.1016/j.freeradbiomed.2021.07.030

Fardous, Ali M, and Ahmad R Heydari. “Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review.” Nutrients vol. 15,21 4699. 6 Nov. 2023, doi:10.3390/nu15214699

Huo, Jing et al. “Serum level of antioxidant vitamins and minerals in patients with vitiligo, a systematic review and meta-analysis.” Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) vol. 62 (2020): 126570. doi:10.1016/j.jtemb.2020.126570

Iraji, Fariba, Sarah Seyedyousefi, and Asieh Heidari. "Serum vitamins and trace elements in vitiligo patients: A systematic review and meta‐analysis of observational studies." JEADV Clinical Practice (2024).

Khoshdel, Zahra et al. “Serum Copper and Zinc Levels Among Iranian Vitiligo Patients.” Dermatology practical & conceptual vol. 12,4 e2022140. 1 Oct. 2022, doi:10.5826/dpc.1204a140

Mogaddam, Majid Rostami et al. “Evaluation of the serum zinc level in patients with vitiligo.” Postepy dermatologii i alergologii vol. 34,2 (2017): 116-119. doi:10.5114/ada.2017.67073

Natarelli, Nicole, et al. "Topical Integrative Approaches to Vitiligo: A Systematic Review." Journal of Integrative Dermatology (2023).

Ni, Yao et al. “The effect of antioxidant dietary supplements and diet-derived circulating antioxidants on vitiligo outcome: evidence from genetic association and comprehensive Mendelian randomization.” Frontiers in nutrition vol. 10 1280162. 11 Jan. 2024, doi:10.3389/fnut.2023.1280162

Noland, Diana, Jeanne A. Drisko, and Leigh Wagner, eds. Integrative and functional medical nutrition therapy: principles and practices. Springer Nature, 2020.

Rodríguez-Martín, Marina et al. “When are laboratory tests indicated in patients with vitiligo?.” Dermato-endocrinology vol. 4,1 (2012): 53-7. doi:10.4161/derm.19200 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License.

Shekhar Neema, MD. Vitiligo. Jul 20, 2022. https://emedicine.medscape.com/article/1068962-workup?form=fpf

Tsai, Tsung-Yu et al. “Serum homocysteine, folate, and vitamin B12 levels in patients with vitiligo and their potential roles as disease activity biomarkers: A systematic review and meta-analysis.” Journal of the American Academy of Dermatology vol. 80,3 (2019): 646-654.e5. doi:10.1016/j.jaad.2018.08.029

Varikasuvu, Seshadri Reddy et al. “Decreased circulatory levels of Vitamin D in Vitiligo: a meta-analysis.” Anais brasileiros de dermatologia vol. 96,3 (2021): 284-294. doi:10.1016/j.abd.2020.10.002