Artificial UV radiation is frequently used as a second-line treatment for moderate-to-severe AD in adults [
24,
25]. By reducing the number of epidermal nerve fibers and the expression of axon guidance molecules, it is also considered a good therapeutic approach for AD-associated itch, relieving patients from this oppressive symptom [
26,
27]. Moreover, UV irradiation is also able to modulate the immune response of AD patients via upregulation of FoxP3-positive regulatory T cells, whose number is directly correlated with the degree of AD severity score improvements [
28]. Different artificial light sources are available against AD: broadband UVB (290–320 nm), narrow-band (NB) UVB (311–313 nm), excimer laser (308 nm), UVA-1 (340–400 nm), psoralens and UVA (PUVA), and combined UVA/UVB (280–400 nm). Their efficacy is linked to the ability to inhibit DNA synthesis and keratinocyte proliferation, suppression of the antigen-presenting function of the Langerhans’ cells, T lymphocyte apoptosis induction and antiinflammatory mediator production [
29]. A complete review of the published literature on this topic, including a total of 428 studies regarding the efficacy and safety of phototherapy [
30], as well as an up-to-date review on 19 randomized controlled trials (including 905 participants) [
31] confirmed that medium-dose UVA1 and NB-UVB phototherapies are the most effective and safe modalities for adult AD treatment as also observed in various randomized controlled trials and other studies [
24,
32‐
37]. As a rule, phototherapy is not indicated in the acute stage of AD (except UVA1, which is also effective in managing AD flares) [
38‐
40], but is more apt to treat chronic, pruritic, lichenified forms [
24,
35], and should not be prescribed in those patients who experience a worsening of their dermatosis during sun exposure as in the case of other common chronic inflammatory diseases such as psoriasis [
41]. In general, NB-UVB has been indicated for chronic-moderate forms of AD and is currently preferred to broadband UV because it is less erythemogenic; a recent study reported that the combination with UVA did not show any further benefits [
42]. On the other hand, medium-dose UVA1 appears to be similar to NB-UVB in terms of efficacy, as shown in different studies [
43,
44]. In summary, phototherapy can be used as both short- and long-term treatment with variable scheduling including a minimum of thrice weekly access [
45]. Nevertheless, it is considered a safe and well-tolerated therapeutic approach, it is limited by the inconvenience and possible adverse events, including limited access to in-office treatment, difficulty adhering to a thrice-weekly schedule, erythema, photodamage, actinic keratosis, blistering and herpes virus reactivation. On the other hand, long-term side effects such as premature photoaging and carcinogenesis have not been excluded [
35,
37]. Safe use of NB-UVB and medium-dose UVA1 has been well documented, and it was cited as the most commonly used wave length and modality of light-based therapy for AD [
30,
31,
34,
45]. UV can also be combined with a prior (oral or topical) administration of photosensitizing drugs such as psoralens (photochemotherapy). Psoralens are used with UVA (PUVA). Generally, photochemotherapy is not considered the first phototherapy modality of treatment, especially for oral PUVA, which may present several side effects including nausea, headache, fatigue, burning skin, itching and irregular skin pigmentation as well as a higher risk of skin cancer, so that the risk/benefit ratio of this treatment must be carefully weighed [
24,
31,
45]. Moreover, it should be also stated that most patients favor NB-UVB or UVA1 phototherapy as they are easier to perform and do not require the concomitant administration of a photosensitizer. However, studies on photochemotherapy used in adult AD patients are less numerous with respect to NB-UVB or UVA1. In a crossover study on 23 patients, Tzaneva et al. reported that 5-methoxypsoralen (MOP) PUVA was significantly better than medium-dose UVA1 for the reduction of SCORing Atopic Dermatitis (SCORAD) and the duration of remission [
46], while Uetsu et al. reported a large series of 113 Japanese subjects (mean age 27.5 years) with severe AD in which 8-methoxypsoralen (8-MOP) PUVA led to a reduction of 51% and 80% of the AD severity score at 4 and 8 weeks of treatment, respectively, without severe adverse effects [
47]. In addition, a study on 12 adult AD patients showed comparable efficacy between 8-MOP bath PUVA and NB-UVB when applied in threshold erythemogenic doses [
48]. The efficacy of 8-MOP bath PUVA was also reported by de Kort et al., suggesting that it may represent a most welcome addition to the existing therapies for extensive atopic eczema also because of the lack of systemic side effects with respect to oral PUVA [
49]. However, despite this evidence, photochemotherapy still remains a less frequently used and investigated treatment modality for adult AD with respect to NB-UVB and UVA1.