Topical corticosteroids are effective in controlling disease activity of early MF, which is characterized by papules, patches, or plaques with limited, if any, lymph node involvement and no visceral involvement. In a study done by Zackheim et al. with 79 patients, 63 % of patients with stage T1 disease who were treated with topical steroids demonstrated complete remission, while 31 % showed partial remission [2]. This study alone showed a 94 % total response rate in patients treated with topical steroids. However, persistent application can lead to skin atrophy and telangiectasias [3]. In more advanced stages of the disease or treatment-resistant MF, including tumor-stage plaques and nodules, topical steroids are used as adjuvant therapy, and intralesional corticosteroids can be used for thicker MF lesions [4].

Chemotherapeutic agents used in MF include mechlorethamine (nitrogen mustard or HN₂) and carmustine (BCNU), both of which have proven to be safe and effective in controlling disease activity, particularly in early MF.

Nitrogen mustard is an alkylating agent and can be used as an initial therapy for treatment of MF patches and plaques. In a study of 76 patients studied over a 4-year period who were treated with HN₂, 50 % were free of detectable disease [5]. It is available as either ointment or aqueous formulation. Studies on MF patients treated with nitrogen mustard have demonstrated a 65 % complete response rate, 45 % 10-year relapse-free survival, and 95 % 10-year disease-specific survival in patients with T1 disease [6].

Side effects of this therapy include skin irritation, xerosis, hyperpigmentation, and, in rare cases, bullous reactions, urticarial rashes, and Stevens–Johnson syndrome [3, 7]. Long-term use has also been reported to be associated with increased risk for development of skin cancer. However, in a study of 203 patients with stages I–III MF treated with topical nitrogen mustard as monotherapy, the incidence of nonmelanoma skin cancers in patients who use topical nitrogen mustard is extremely low and occurred in only 2 (1 %) patients [6].

Topical carmustine (BCNU) has also been shown to be effective for early stage MF, with complete response rates of 92 % in stage T1 disease (less than 10 % skin involvement) and 64 % in stage T2 disease [8]. The 5-year relapse-free survival rate was reported to be 35 % and 10 % for T1 and T2 patients, respectively [9]. Side effects of this treatment include erythema, telangiectasias, and irritant or allergic dermatitis [10]. It is important to monitor complete blood count (CBC) as treatment with BCNU can also result in myelosuppression [11].

Bexarotene has been approved by the US Food and Drug Administration (FDA) as a treatment option for early MF, in particular in those with refractory or persistent disease [2, 3]. Mechanistically, bexarotene is a rexinoid, a vitamin A-derived compound that binds to retinoid X receptors and ultimately alters gene transcription to enhance tumor apoptosis [12]. In patients with stage IA–IIA disease, application of topical bexarotene resulted in a response rate of 63 % and a complete clinical response of 21 % [13]. Complete clearance may take up to 16 weeks [14]. This therapy is generally well tolerated. Common side effects include pruritus, erythema, photosensitivity, and burning pain at the application site.

Ultraviolet light , including ultraviolet B (UVB), narrow band UVB (NB-UVB), and psoralen plus ultraviolet A (PUVA) are also used in the treatment of MF. PUVA first appeared in 1976 and is one of the skin-directed therapies commonly used in the treatment of stages IA, IB, and IIA MF [15]. PUVA can result in total skin clearance and long-term remission [15], with complete response rates of up to 90 %, and has become a standard therapy for the early stages of MF [16].

UVB can be broadband, ranging from 290 to 320 nm, or narrowband ranging from 311 to 312 nm. UVB is generally used to treat thin patches and plaques, as UVB rays have limited penetration [3]. PUVA (psoralen plus UVA) differs from UVB in a variety of ways. First, UVA penetrates deeper into the skin in comparison to UVB, and thus has improved efficacy for thicker plaques. Also, in PUVA, prior to receiving UVA phototherapy, patients receive a skin-sensitizing medication by mouth, 8-methoxypsoralen. Intercalation of psoralen into DNA preempts the cells to undergo apoptosis upon exposure to UVA, which crosslinks the psoralen with the DNA. Of note, 8-methoxypsoralen is associated with side effects such as nausea and vomiting, and with enough treatments, skin cancer [3, 11]. Both UVB and PUVA are given to the patients 2–3 times per week, and the dose is increased based upon the patients’ skin type until a complete response is achieved [11]. Once complete response is reached, PUVA can be given once every 2–4 weeks for several years on a maintenance basis [3].

Side effects associated with PUVA and UVB include skin erythema, hyperpigmentation, xerosis, pruritus, and even blistering. Long-term risks of phototherapy include photoaging and increased risk of melanoma and nonmelanoma skin cancers [11]. As such, phototherapy may not be appropriate in those with a history of UV-associated skin cancers.

PUVA can be used as a monotherapy or combination therapy. PUVA has been shown to result in higher response rates when combined with interferon alpha (IFN-α[alpha]). In early stage MF, PUVA in combination with IFN-α(alpha) has been associated with 100 % complete response rate [17]. Combination therapy has important implications for the tumor stage of MF, a stage that has been shown to be less responsive to PUVA monotherapy [2]. Another advantage of combination therapy is that the dosage of PUVA can be reduced to mitigate side effects. PUVA can also be combined with retinoids (RePUVA).