Mycosis Fungoides (MF) and Sézary syndrome (SS) are two common forms of primary cutaneous T-cell lymphomas (CTCLs) , which represent a heterogeneous group of non-Hodgkin lymphomas. In MF, an epidermotropic form of CTCL, malignant helper T lymphocytes invade the skin; while patients with SS, a leukemic form of CTCL experience erythroderma and neoplastic T lymphocytes in the blood [1]. MF is a rather rare disease that has an annual incidence of 6 cases per million, which is approximately 4 % of all non-Hodgkin lymphoma cases [2]. MF is observed in all age groups but is most common in older individuals ranging from 55 to 60 years old, with a male-to-female ratio of 2:1. It is also more common in black ethnicities than in Caucasians [3].

MF usually follows an indolent course and an orderly progression from limited to generalized cutaneous symptoms, and noncutaneous or visceral involvement. The cutaneous symptoms are varied and they include patches, plaque, generalized erythroderma, poikiloderma, and itchy skin, as well as papules and tumors [1, 4]. Noncutaneous involvement is uncommon but has been observed in regional lymph nodes, lungs, spleen, liver, gastrointestinal tract, and bone marrow [5, 6]. Diagnosis depends on the type and severity of skin manifestations and noncutaneous involvement [6]. Early diagnosis is difficult when initial patches and plaques are present because of similarities with other skin disorders such as dermatitis or possible mismatch between clinical and pathological findings [7, 8].

The treatment process of MF depends on the stage and biological aggression of the disease, which includes severity of skin manifestations, presence or absence of lymphadenopathy, and severity of visceral involvement. It is believed that only the early stages (IA, IB, IIA) can be fully treated. In these stages, treatment is skin directed and it consists of topical therapies, including steroids and topical chemotherapy agents, such as mechlorethamine and carmustine, radiotherapy, total skin electron beam therapy (TSEBT), and phototherapy [9–13]. On the other hand, direct topical skin treatments may have a number of side effects, such as increased risk of skin cancer due to long-term contact with topical psoralen and ultraviolet A (PUVA) therapy and chemotherapy. In advanced stages of MF, where the disease becomes tumorous (IIB) and erythrodermic (III) and visceral involvement often occurs, no satisfactory response to the aforementioned treatments has been achieved. The aim of treatment in these stages of MF is usually palliation, and various treatment methods are used to improve the patient’s quality of life.

Furthermore, clinicians have been looking for alternative, less invasive treatment regimens with the least possible side effects. For instance, interferon (IFN), an immune system regulator, was first tested in 1984 as a treatment for MF patients [14]. It has been shown to have a high rate of response during early stages of the disease [15]. Low doses of interferon-α(alpha) (three million units, three times a week) demonstrated 53 % complete remission (CR) in patients with stage I [15]. Some studies have looked at the possibility of combining PUVA with different doses of systemic interferon therapy in order to reduce the number and doses of PUVA treatments required to make a full recovery [16–18]. Even though at all stages of MF these treatment methods have been proven more effective than interferon monotherapy, their considerable toxicity justifies the search for alternative treatments, such as low-dose interferon, shorter PUVA application, and other maintenance therapies. Unfortunately, there are few studies in the literature that compare PUVA with other therapies or combination treatments. This may be due to the fact that only a few centers have the expertise and experience to deliver electron beam radiation treatment due to its considerable rates of acute and late complications, even though it can produce complete remission [19].

In this section of this book (see Chaps. 10 through 13), I will present the results of our previously unpublished study whose main purpose was to determine and compare the efficacy of two treatment methods, one being PUVA monotherapy and the other being PUVA combined with interferon-alpha-2a in MF patients referred to the Razi Dermatology Hospital in Tehran, Iran. Our efforts focused on the comparison of these two treatment regimens with respect to complete remission, partial remission, different phases of MF, and effect of gender.