Late Complications of PUVA or Narrowband UVB Therapy in Patients With Vitiligo: Are Patients Who Have Received Large Doses of PUVA (More Than 150 Treatment Sessions) or Narrowband UVB (More Than 150 Treatment Sessions) at Increased Risk of Developing Premalignant or Malignant Skin Changes?
It is not uncommon for patients with vitiligo to be given large numbers of PUVA or UVB treatments, occasionally over a relatively short period. As the areas of vitiligo have no melanin they are particularly susceptible to the damaging effects of UVB (or PUVA) and may therefore be more susceptible to developing premalignant or malignant changes.
There is only one study on vitiligo in which the issue of chronic cutaneous damage with long-term PUVA is specifically assessed.
Harrist etal. followed up annually with a skin examination 596 patients with vitiligo treated with PUVA (230 for up to 55months) but did not include a control group. No skin cancers were observed, but vitiligo and perilesional skin showed dermal changes of chronic photodamage.
There is a paucity of studies of skin cancer in vitiligo, but there are retrospective reports from centres that have treated patients with vitiligo with phototherapies over long periods of time. Wildfang etal. reported no actinic keratoses, lentigines or skin cancer in a retrospective study on 59 patients with vitiligo treated with PUVA. Chuan etal. reported no actinic keratoses or skin cancer in 21 patients with vitiligo treated with PUVA followed for up to 7years. Westerhof and Schallreuter reported no skin cancer in >2500 patients (but not in a study). Halder etal. in a study of 326 patients with vitiligo treated with PUVA with 4years of follow up reported no actinic keratoses, cutaneous carcinomas or lentigines, but acknowledged that the follow-up period was almost certainly too short to detect an increase in skin cancer.
Reports of skin cancer in patients with vitiligo treated with PUVA are limited. Buckley and Rogers describe a patient who developed multiple invasive squamous cell carcinomas in areas of vitiligo which had failed to repigment despite a prolonged continuous course of PUVA. A similar patient had multiple squamous cell carcinomas in situ in vitiligo areas following PUVA therapy over a 9-year period. Multiple bizarre-looking lentigines were reported in a patient with vitiligo following years of topical and systemic PUVA, but with no malignancy and benign histology. Park etal. reported a patient with vitiligo who developed a squamous cell carcinoma in an area of vitiligo following long-term PUVA.
The risk of skin cancer in patients with vitiligo treated with PUVA is currently unclear. There is no long-term follow-up study of the type carried out by Stern and Lange which established the clear cancer risk for PUVA in patients with psoriasis. Despite some authors' claims that high doses of PUVA in vitiligo are safe, it is counterintuitive to believe that patients with vitiligo are at a lower risk of skin cancer with PUVA than patients who have psoriasis. Indeed, the absence of functional melanocytes could put patients with vitiligo at a greater risk. In the absence of persuasive evidence to the contrary, it is logical to recommend more stringent limits on PUVA for vitiligo than apply for psoriasis.
In view of uncertainty regarding the cancer risk, clinicians prescribing NB-UVB or PUVA should be cautious in prescribing these treatments in vitiligo. A clear explanation of the risks and benefits of treatment must be given before treatment, with a Patient Information Leaflet written in lay terms.
Grade of recommendation D Level of evidence 3
Patients treated with PUVA or UVB should have their treatment closely supervised by a consultant dermatologist and the treatment regimen for patients with skin types I-III should not exceed 200 treatments for NB-UVB and 150 treatments for PUVA. This recommendation is based on published evidence for patients with psoriasis. Evidence is lacking to define an upper limit for patients with skin types IV-VI for NB-UVB or PUVA.
Grade of recommendation D Level of evidence 4
In most patients, NB-UVB should be used in preference to PUVA.
Grade of recommendation A Level of evidence 1+
In view of the possible long-term risk of skin cancer with extended courses of NB-UVB or PUVA in patients with vitiligo, further research to define this potential risk is recommended.
The British Journal of Dermatology. 2008;159(5):1051-1076. © 2008 Blackwell Publishing
Cite this: Guideline for the Diagnosis and Management of Vitiligo - Medscape - Nov 01, 2008.