Oxidative Stress in Vitiligo: Catalase Defects, H2O2 Burden, and Redox-Immune Crosstalk

Key Takeaways

Lesional skin shows elevated H₂O₂ with reduced antioxidant enzyme activity, notably catalase and glutathione peroxidase.
Redox stress perturbs MITF–melanogenesis, damages melanocyte organelles, and generates neo-epitopes/DAMPs that feed immune activation.
Nrf2/KEAP1 signaling is variably impaired; restoring antioxidant tone may support repigmentation with NB-UVB or targeted therapies.
Oxidative signals amplify the IFN-γ–CXCL9/10 axis, linking redox injury to autoimmunity and relapse.

Biochemical assays demonstrate accumulated H₂O₂ and altered redox couples (GSH/GSSG) in lesional vs non-lesional skin.
Markers of oxidative damage (lipid peroxidation, protein carbonyls, pteridine shifts) are increased in active disease.
Keratinocyte–melanocyte units show mitochondrial dysfunction and ER stress under oxidative load.

Table 1. Antioxidant enzyme changes in vitiligo (typical patterns).

Enzyme/system	Pattern	Implication
Catalase	↓ activity in epidermis	H₂O₂ accumulation; protein oxidation
Glutathione peroxidase (GPx)	↓ or dysfunctional	Less H₂O₂/lipid peroxide clearance
Superoxide dismutase (SOD)	↑/↔ (context-dependent)	Shifts O₂^•− → H₂O₂
Thioredoxin/peroxiredoxin	Compensatory activation	Insufficient under chronic stress

Impaired Nrf2 activation limits transcription of detox enzymes (GCLC, HO-1, NQO1), reducing resilience.
Redox stress suppresses MITF and tyrosinase/TYRP expression, stalling melanogenesis and repigmentation potential.
NB-UVB can upregulate melanogenic genes while normalizing inflammatory tone, partially restoring balance.

Oxidized melanocyte antigens and DAMPs enhance APC activation → IFN-γ production and CXCL9/10 chemokine release.
Keratinocyte redox stress augments STAT1 signaling, sustaining CXCR3⁺ CD8 T-cell recruitment.
Mechanical stress (Koebner) increases ROS and antigen release, predisposing to site-specific relapse.

Table 2. Interventions acting on redox and downstream nodes.

Strategy	Target	Clinical note
NB-UVB 311 nm	Redox & cytokines; melanogenesis	Backbone therapy; improves pigment islands
Topical calcineurin inhibitors	T-cell activation (indirect on redox)	Face/neck steroid-sparing; combine with NB-UVB
Topical JAK inhibitors	IFN-γ–JAK–STAT	Interrupts chemokine loop; facial endpoints
Antioxidant support	Nrf2/ROS buffering	Adjunctive only; align with guideline-based care

Table 3. Redox and clinical readouts to populate from studies.

Readout	Method	Expected pattern
H₂O₂ levels	Spectrophotometry/fluorescent probes	Higher in lesional skin
Catalase/GPx activity	Enzyme assays	Reduced vs control
Nrf2 target gene expression	qPCR/protein	Lower in active lesions
F-VASI/T-VASI change	Clinical scoring	Improves with NB-UVB ± immunomodulators

Biochemical studies of epidermal H₂O₂ accumulation and catalase/GPx deficiency in vitiligo.
Translational work linking Nrf2/KEAP1 and MITF regulation under oxidative stress.
Immunology papers on redox-driven amplification of IFN-γ–CXCL9/10 signaling.
Clinical series on NB-UVB effects on redox/inflammatory markers alongside repigmentation.