Background

The clinically relevant electromagnetic radiation emitted by the sun consists of UVB, 290 to 320 nm and UVA, 320 to 400 nm. BB-UVB units available in clinical practice emit broadly between 270 to 390 nm with a peak at 313 nm. NB-UVB refers to a radiation source with a sharp emission peak between 311 and 312 nm.

For a given dose, UVB at 300 nm is approximately 1000-fold more erythemogenic compared with UVA at 360 nm, but because of its shorter wavelength, UVB has less depth of penetration than UVA.

Treatment Schedule

Most centers recommend phototherapy 2 or 3 times a week; for practical convenience, twice-weekly phototherapy will clear the skin involvement, albeit it at a slower pace than 3 times a week. It is best to have the treatments given at least 48 hours apart. Phototherapy directions are usually those recommended for psoriasis. The starting dose can be determined from minimal erythema dose (MED) or skin type; MED is usually utilized only in the face of a history of sun sensitivity. Increments in the light dose are best determined by a percentage of the previous dose based on the skin type and any unexpected or undesired erythema. Different phototherapy centers target a different endpoint and different maintenance schedule after clearing, which makes it difficult to determine overall efficacy and duration of response. Patients on NB-UVB may not be able to tolerate less frequent treatments than every 10 days due to burning. The United States Cutaneous Lymphoma Consortium (USCLC) has developed guidelines for MF that will hopefully alleviate this issue.

Efficacy

In a review of the published literature for both BB-UVB and NB-UVB, a complete response (CR) was defined as at least 90% clearance. The CR rates have been shown not unexpectedly to be greater for patch (>80%) than plaque disease (≤50%), but the majority of patients relapsed after discontinuing therapy. BB-UVB has largely now been replaced by NB-UVB.

The published reported CR rates for NB-UVB have ranged from 54% to 90% in patients with Stage IA–IIA disease. As with BB-UVB, patients with patch-only disease did better than those with plaques, but patients with one B (IB) disease did much better with NB-UVB versus BB-UVB in 1 study (78% vs 44% respectively). The relapse rate without maintenance therapy (defined as continued treatment post near clearing) varied from approximately 30 to 100% versus 4% to 83% in those with maintenance.

The literature describing the use of NB-UVB in combination with other treatment modalities in MF is sparse, and comparative studies of mono versus combination therapy are lacking. Case reports of NB-UVB combined with bexarotene suggest efficacy in MF.

Background

Psoralen, taken orally or applied topically, conjugates and forms covalent bonds directly with DNA following exposure to UVA, resulting in the formation of DNA-psoralen cross-links with inhibition of DNA replication.

Treatment Schedule

An optimized form of methoxalen, or 8-MOP, called Oxsoralen-Ultra, is the current oral formulation available in the United States. This should be dosed at 0.5 mg/kg 1 to 1.5 hours before exposure to UVA. There is also a 1% topical formulation available for localized treatment. PUVA treatments are given 2 to 3 times a week in the United States, potentially more frequently elsewhere in the world. As with NBUVB, less frequent treatments take longer to achieve remission. The starting dose and incremental doses are based primarily on skin type as with psoriasis. Maintenance treatment is generally done as for NB-UVB, although it is possible for patients on PUVA to tolerate treatments even given as infrequently as once a month; there may be no need to reduce amount of UVL at a given treatment when decreasing the frequency.

Efficacy

Complete clearance rates in MF being 85% for stage IA, 65% for stage IB, and 85% for stage IIA disease. Based on the experience of experts, patches and thin plaques are known to respond better to PUVA than thick plaques. Most physicians treating patients with MF do use some sort of tapering frequency when the patient has achieved a maximum response. Although expert opinion reflects that most MF experts do use some kind of maintenance PUVA because of the feeling that it prolongs remission, the literature is not as clear-cut. Querfeld and colleagues reported the long-term outcome of 66 patients with early stage MF (IA-IIA) who achieved a CR, most (94%) patients were then put on continuous maintenance therapy. Although 50% of the patients experienced relapse, the time to relapse was 39 months (range 2–127 months), and the other 50% of the patients had a sustained remission of a median duration of 84 months (7 years) (range 5–238 months, ie, 0.5–20 years). There was another study that compared the follow-up data between a group of patients with and without maintenance treatment after initial clearing phase of PUVA; there was no significant difference in the relapse rate or in the time to relapse between the group of 25 early MF patients who stopped PUVA after clearing phase, and the group of 9 patients who received maintenance treatment for a further 15 treatments (range 0.3–10.5 months). The results of this study suggest that relatively short-term PUVA maintenance treatment may not necessarily slow disease recurrence.

PUVA is ineffective as a monotherapy for tumor-stage disease. Patients with erythroderma generally require a greater number of treatments to clear compared with patients with plaque-stage disease, but this may be because the dose of UVA utilized is much lower due to extreme photosensitivity. Blood involvement has been shown to be affected by PUVA therapy.

Combination therapy, primarily with retinoic acid receptor (RAR) retinoids, or bexarotene, a retinoid X receptor (RXR) retinoid, or alpha interferon, has been used in early disease to improve efficacy, possibly prolong remissions, or to treat those patients in whom lower response rates with PUVA alone are expected. Despite the fact that a combination of skin-directed and systemic treatment is usually considered more effective than either alone in MF, there are few studies to support this. A combination of PUVA with systemic therapy, however, may decrease the total UVA exposure and thus reduce long-term adverse effects. Although multimodality therapy including PUVA is frequently used in clinical practice, there are few published reports.