Second-line therapies primarily focus on improving skin appearance with a combination of topical, systemic and UVB phototherapy treatments. Such treatment duration varies from 8 to 24 months of two- to trice-weekly treatments, with an average 65-75% success rate.

Narrowband UVB (NB-UVB) phototherapy is the treatment of choice for non-segmental, generalized vitiligo. NB-UVB produces better repigmentation than PUVA, with better color match and fewer side effects. NB-UVB therapy is also better tolerated, and could be used on expecting or nursing women, and children. Home therapy with portable NB-UVB devices is a viable alternative for most vitiligo patients; eligibility, protocols and precautions are essentially the same as for clinic-based treatments.

Combination interventions are superior to monotherapies, like NB-UVB with 0.1% tacrolimus ointment.

Intermittent oral administration of steroids like betamethasone ⁄ dexamethasone has been sparingly reported as an emergency tool to arrest the activity of fast spreading vitiligo. Within one to three months a progressive disease is usually stabilized, and within four months repigmentation is observed in the majority of patients. However, they are not effective in repigmenting a stable vitiligo, and long-term adverse effects contraindicate their common use. The drawback is a higher relapse when reducing these medications.