Photochemotherapy with topical 8-methoxypsoralen (8-MOP) can be used in patients with lesions covering less than 5 % body surface area and also in children less than 12 years of age (systemic PUVA is contraindicated). However, topical psoralens may lead to significant pruritus, erythema, edema, blisters, and skin necrosis even with minimum dosage. Thus, therapy with these agents mandates strict monitoring [1]. Application of 0.001 % 8-MOP or less, one to three times per week for 20–30 min, is recommended. The skin is then exposed to UVA radiation at 0.25–0.5 J/cm². The exposure time is increased by 15–30 s in subsequent sessions (maximum 10 min). This procedure has to be repeated until a dosage and exposure time are attained which produces erythema but not burning. Post-procedural advice is crucial to avoid untoward adverse effects. The patients should wash away the excess 8-MOP with soap and water immediately after the irradiation and apply UVA sunscreen to avoid additional environmental UVA exposure [44]. The advantage of topical PUVA is the need for fewer treatments and considerably smaller cumulative UVA doses, lower plasma levels, and reduced systemic and ocular phototoxicity [11].

Khellin is a furanochrome extract of the plant Ammi visnaga (5,8-dimethoxy-2 methyl-4,5-furo-6,7 chromone). KUVA refers to khellin followed by UVA. It has a stimulatory effect on melanogenesis and melanocyte proliferation when combined with UVA light. Khellin can be topically applied in a moisturizing cream or Carbopol gel (3–5 %). Topical “KUVA-sun” is still used in sunny countries. It has been studied and found that topical khellin followed by UVA (KUVA) does not provide any significant benefit in patients with vitiligo [45, 46]. It is rather effective when given orally, but it has been abandoned.

Since phenylalanine is an essential amino acid responsible for initiation of melanogenesis, it is used as a photosensitizer for topical and/or oral supplementation of natural or artificial UVA light phototherapy in the management of vitiligo. The best responders are patients with less than 25 % body surface area involvement, with onset of disease before 21 years of age, and those having generalized and symmetrical lesions [47]. Lotti et al. reported a significant repigmentation in 29.3 % of patients applying topical L-phenylalanine as monotherapy [48]. The addition of topical L-phenylalanine to oral L-phenylalanine and light therapy makes it even more effective [49, 50].

Recent advances in the etiopathogenesis of vitiligo suggest the role of reactive oxygen species (ROS) in the inhibition of melanogenesis. Therapy with antioxidants (topical and oral) leads to increased catalase activity and a decrease in ROS [58]. Combining oral and topical phenylalanine gives good results [59]. Moreover, Schallreuter et al. reported remarkable repigmentation on the face and hands of patients who were put on topical pseudocatalase with short-term UVB [60]. Sanclemente et al. concluded that topical catalase is as effective as 0.05 % betamethasone in vitiligo [61]. Side effects associated with the use of topical catalase/superoxide dismutase include transient erythema, pruritus, and peeling [61, 62].

Topical 5-FU has been studied for the treatment of vitiligo. It is hypothesized that direct overstimulation of melanocyte proliferation, inhibition of agents able to destroy melanocytes, and immunomodulation stabilizing the vitiligo disease could be responsible for the efficacy of 5-FU in vitiligo. However, topical application of 5-FU alone cannot induce any pigment spread in vitiligo patients; application on a dermabraded or ablated epidermis could cause a long-lasting and favorable pigment spread [7, 25, 63].

Piperine and its analogs, PIP [5-(3,4-methylenedioxyphenyl)-2,4-pentadienoylpiperidine], tetrahydropiperine [THP, 5-(3,4-methylenedioxyphenyl)-pentanoylpiperidine], a cyclohexyl analog of piperine [CHP, 5-(3,4-methylenedioxyphenyl)-2,4-pentadienoylcyclohexylamine], and reduced CHP [rCHP, 5-(3,4-methylenedioxyphenyl)-2,4-pentanoylcyclohexylamine], have been reported to stimulate melanocyte replication in vitro and may be useful in treating vitiligo [8]. Treatments with these compounds and concomitant cutaneous exposure to ultraviolet (UV) radiation are better in efficacy than UV radiation alone [64].

PGE2, by virtue of its growth-stimulatory effects, is capable of regulating the proliferation and maturation of melanocytes [65]. Kapoor et al. studied the efficacy and safety of topical PGE2 in the treatment of stable vitiligo (<5 % body surface area). Excellent response was seen in 55 % of patients. Side effects in the form of a transient burning sensation especially on the lips were reported in a few patients [66, 67].

Treatment with these antioxidants inhibits caspase-induced apoptosis, increases the total antioxidant capacity of the body, decreases the generation of ROS and lipid peroxidation, and improves mitochondrial activity. Moreover, C. melo extracts have shown superoxide dismutase and catalase-like activities [68]. Thus, topical capsaicin and extracts of C. melo might protect against vitiligo progression [69]. However, well-designed randomized clinical trials are needed to support the use of these extracts for vitiligo because of conflicting reports regarding its effectiveness and efficacy [67, 70].

Keeping in mind the significant psychosocial trauma associated with vitiligo, camouflage has a considerable role in the management [71]. There is a wide choice of self-tanning agents; stains; dyes; whitening lotions; tinted cover creams; compact, liquid, and stick foundations; fixing powders; fixing sprays; cleansers; semipermanent and permanent tattoos; and dyes for pigmenting facial and scalp white hairs [11]. The results are even more gratifying in cases of vitiligo in children [72]. Dihydroxyacetone (DHA), one of the most effective camouflage agents, is an active ingredient of sunless tanners. DHA is an easy and convenient option for patients who want to camouflage their vitiligo, because the stain lasts up to 10 days. It reacts with proteins of the stratum corneum and forms brown chromophores called melanoidins, which temporarily impart a golden brown color to the skin [73]. The amount of tanning is proportional to the concentration of DHA used [74]. Thus, it becomes easy for the patient to choose the concentration of DHA that most closely matches their skin color [75, 76].