Phototherapy in the Age of Biologics

Daniel Walker, BS, and Heidi Jacobe, MD, MSCS

Dermatologists are presented with a diversity of therapeutic modalities for the treatment of
inflammatory, sclerosing, and neoplastic conditions, but with the development of various new
irradiation devices that utilize specific parts of the electromagnetic spectrum, phototherapy has
become a more viable, accessible, and efficacious option in the treatment of these conditions.
The ultraviolet (UV) range (10-400 nm) is further subdivided into UVA and UVB, each of which
has been particularly useful in a number of skin conditions. The most commonly used forms of
UV irradiation are UVA1, psoralen plus UVA (PUVA), and narrowband (NB) UVB. Each of these
modalities differ in their mechanism of action, indications, and side effect profiles, and it is
important that clinicians be familiar with these differences. Today, phototherapy is a valuable
option in the treatment of many nonpsoriatic conditions including atopic dermatitis, sclerosing
skin conditions such as morphea, vitiligo, and mycosis fungoides. Due to its relative safety,
phototherapy may be used in most populations, including children and pregnant women.
However, contraindications and side effects are known and should be considered before
patients begin a phototherapeutic regimen.
Semin Cutan Med Surg 30:190-198 © 2011 Elsevier Inc. All rights reserved.

KEYWORDS phototherapy, UVA1, narrowband UVB, PUVA, atopic dermatitis, morphea, vitil-
igo, mycosis fungoides

F or thousands of years, sunlight has been used to treat a

variety of skin conditions. Ultraviolet (UV) light has been
a mainstay in the treatment of psoriasis for more than 30
Photobiology
The electromagnetic spectrum can be divided into subgroups
years, but the development of new topical agents and novel on the basis of the biological effects of each wavelength (Fig. 1).
biological immunomodulators has provided dermatologists An extensive review of each portion of this spectrum is be-
with a whole new armamentarium in the treatment of psori- yond the scope of this review, and we limit our discussion to
asis. However, these drugs are limited by their availability, radiation within the ultraviolet range (10-400 nm). Ultravi-
cost, and side effect profiles1,2 and because of several advan- olet radiation (UVR) can be further divided into several sub-
tages to both patients and physicians, phototherapy remains types, which are, from shortest to longest wavelengths, UVC
an important therapeutic option for the treatment of psoriasis (200-290 nm), UVB (290-320 nm), and UVA (320-400 nm).
and other inflammatory skin conditions. In addition, within UVA can be further divided into UVA2 (320-340 nm) and
the last 2 decades, new phototherapeutic modalities have UVA1 (340-400 nm).
been developed. These devices expanded the use of photo- UVB is also referred to as mid-UV, or the sunburn spec-
therapy in the treatment of dermatologic disease. Now, pho- trum, because most UVB sunscreens work to prevent ery-
totherapy is an excellent treatment option for many thera- thema. Broadband (BB) UVB was one of the first photother-
peutically challenging dermatologic disorders. apy modalities used in the treatment of psoriasis. Today,
however, the more commonly used form of UVB is narrow-
band (NB) UVB, which has a peak emission at 311 nm. A
series of clinical trials have demonstrated its superiority in
Department of Dermatology, UT Southwestern Medical Center at Dallas,
Dallas, TX.
the treatment of psoriasis3,4 and other conditions when com-
Conflict of Interest Disclosures: The authors have completed and submitted the pared with BB UVB. Today, it has become a first-line therapy
ICMJE Form for Disclosure of Potential Conflicts of Interest and none in the treatment of psoriasis and other nonpsoriatic condi-
were reported. tions5 because of its many advantages. In addition, NB UVB
Address reprint requests to Heidi Jacobe, MD, MSCS, Assistant Professor
Dermatology Department, UT Southwestern Medical Center at Dallas,
treatment may be home or office based.6,7
5323 Harry Hines Blvd., Dallas, TX 75390-9069. E-mail: heidi. Unlike UVB radiation, UVA has the ability to penetrate to the
[email protected] deep dermis and subcutis.8 UVA1, because of its proximity to

190 1085-5629/11/$-see front matter © 2011 Elsevier Inc. All rights reserved.
doi:10.1016/j.sder.2011.08.004
Phototherapy in the age of biologics 191

Figure 1 The electromagnetic spectrum.

visible light on the far end of the UVA spectrum, does not induce T cells are highly susceptible to the effects of UV irradiation.14
erythema effectively, whereas UVA2, which resides at the lower The apoptotic effect of UVB is modulated via multiple
wavelengths of UVA, may be associated with effects similar to mechanisms, including the Fas/Fas ligand system, p53,
UVB,9 including acute sunburn. UVA is also the only type of UV and apoptotic proteases.16-18 The apoptotic effects of UVA1
radiation that is not filtered by window glass. The therapeutic are different from those associated with UVB and include 2
potential of UVA1 first emerged in 1992 in the treatment of independent caspase systems and an immediate apoptotic
atopic dermatitis10,11 and then in 1995 for the treatment of lo- effect that may target specific types of cells preferen-
calized scleroderma.12 UVA1 has been reported to have efficacy tially.19,20 UVR also inhibits and depletes the skin of Langer-
in a growing number of skin disorders. hans cells.21,22
Photochemotherapy is the use of psoralen combined with The major target for UVB radiation is nuclear DNA, which
broadband UVA irradiation, also known as psoralen UV absorbs UVB-generating pyrimidine dimers, inhibiting DNA
(PUVA). PUVA, in its modern form, was first used to treat vitil- synthesis.23 For PUVA the psoralen molecule intercalates into
igo in 1947.13 The most common PUVA regimen in the United the double strand of DNA. UVA irradiation then induces a
States uses 8-methoxypsoralen (8-MOP), which is administered DNA-psoralen crosslink, inhibiting DNA replication and
orally 2 hours before UVA irradiation. Bath PUVA is application causing cell cycle arrest.24
of a topical psoralen before UVA irradiation, either to the entire UVR alters the cellular cytokine profiles. UVA1 suppresses
body or limited areas (hands and feet). Advantages of bath proinflammatory cytokines25 tumor necrosis factor-␣ and in-
PUVA include shorter irradiation times and a lack of gastroin- terleukin (IL)-12 and decreases levels of interferon-␥ and
testinal side effects associated with oral psoralens, but its use is intercellular adhesion molecule-1, proinflammatory cyto-
limited by need for special facilities, patient inconvenience, and kines involved in lymphocyte migration into tissues.26-28
unpredictability (although this is minimal for localized topical UVA1 also causes phenotypic and functional maturation of
PUVA). Consequently, PUVA is usually administered via the use migrating dermal dendritic cells into potent antigen-present-
of oral psoralen. ing cells.29 UVB has also been shown to decrease proinflam-
matory cytokines26,27 interferon-␥ and IL-12 and increase
Mechanism of Action levels of the anti-inflammatory cytokine IL-10. UVR also has
a multitude of effects30-35 on diseased skin, many of which
UV radiation exerts a multitude of biological effects in the putatively exert the therapeutic benefit of phototherapy (Ta-
skin from mutagenic to immunologic. We present a brief ble 1).
overview here. The depth of penetration of the different light
sources used for medical therapy dictate which part of the
skin they exert their greatest effect. UVB has more energy Disease-Specific Therapy
than UVA (inverse relationship between wavelength and en-
ergy) but has less capability to penetrate beyond the superfi- Atopic Dermatitis
cial layers of the skin. Thus, UVB primarily affects Langer- Early investigators observed that many patients with atopic der-
hans cells and epidermal keratinocytes. UVA radiation, matitis (AD) improved in the summer, which prompted early
particularly UVA1, reaches the deep dermis and potentially reports36 on the use of phototherapy in the treatment of AD.
the subcutis, thereby impacting dermal fibroblasts, dendritic Multiple phototherapeutic modalities have been credited with
cells, lymphocytes, mast cells, and granulocytes.8,14 exerting a beneficial effect in AD. For the purposes of this re-
The ability to induce lymphocyte apoptosis is an important view, we concentrate on those that are most commonly used in
immunomodulatory effect of UVA and UVB phototherapy.15 modern phototherapeutic practice: NB UVB and UVA1.
192 D. Walker and H. Jacobe

Table 1 Effects of Ultraviolet Radiation on Diseased Skin Taken together, the current evidence suggests NB UVB is
Vitiligo NB UVB induces activation, proliferation, the preferred phototherapy option for the treatment of AD
and migration of inactive melanocytes both because of efficacy and safety. PUVA or UVA1 may be
to the epidermis,30 melanocyte considered second-line treatment in patients who fail NB
proliferation via cytokines, such as UVB. Recommendations for phototherapy for AD are sum-
basic fibroblast growth factor and marized in Fig. 2.
endothelin-1,31 and
immunosuppression32
Sclerosing skin UVA1 alters cytokine casecade,
Sclerosing Skin Conditions
conditions including increased collagenase33,34 UVA1 is a promising treatment for sclerosing skin conditions,
Skin flora UVB has an antimicrobial effect on local a therapeutically challenging group of disorders.
flora and Staphylococcus aureus35
Morphea (Localized Scleroderma)
Kerscher et al12 was among the first to report the benefit of
low-dose UVA1 for patients with morphea. The use of UVA1
NB UVB is likely the best option for patients with AD who phototherapy for morphea is now supported by level 1 evi-
require therapy above and beyond topical preparations. In a dence, making it second only to methotrexate in terms of
pilot case series, 5 patients with severe atopic eczema treated demonstration of efficacy. Table 3 highlights important tri-
with NB UVB showed significant improvement after 3 weeks als12,33,47-54 supporting the use of UVA1 for morphea. A series
of treatment.37 In a large randomized trial of 73 adults with of studies have investigated the ideal dosing regimen of UVA1
moderate-to-severe atopic dermatitis, investigators com- for morphea (low, medium, or high dose). Taken together,
pared NB UVB with UVA during a 12-week course and found these studies indicate low-dose UVA1 might be of some
NB UVB to be more effective in reducing disease severity.38 efficacy or similar to NB UVB, but medium- and high-dose
The use of UVA1 in the management of patients with acute UVA1 are likely more efficacious. This finding is similar to
exacerbations of atopic dermatitis was first described by Krut- reports in AD.
mann et al10 in the early 1990s. They were able to demonstrate Although controversial, UVA1 phototherapy appears to be
that high-dose UVA1 (130 J/cm2) was superior to combined equally efficacious in darker skin type patients despite its
UVA and UVB (UVAB). In another study, Krutmann et al39 ability to induce rapid pigmentation.55,56 Nonetheless, opti-
showed that high-dose UVA1 was superior to midpotency cor- mum dose, frequency, and duration of therapy have not been
ticosteroids in addition to UVAB. Von Kobyletzki et al40 inves- worked out for UVA1. In our practice, patients begin at 20-60
tigated the use of cold-light UVA1, an apparatus that was de- J/cm2 depending on Fitzpatrick skin type, and their dose is
signed to reduce the heat load generated by traditional UVA1 increased in 10-J/cm2 increments to a maximum of 60-100
and UVAB. They found cold-light UVA1 to be superior to both J/cm2 on the basis of skin type. Treatments are delivered 3-5
UVA1 and UVAB. Two trials have attempted to establish the times per week, patients are evaluated every 10-15 treat-
optimal dosing schedule for UVA1 in the treatment of acute AD. ments, and treatment is discontinued after 40-50 treatments
Tzaneva et al41 compared high-dose UVA1 with medium-dose at the point of maximal response. In our experience, only the
UVA1 and showed that there was no statistically significant dif- earliest, most inflammatory lesions clear whereas sclerotic
ference between the 2 regimens. Kowalzick et al42 conducted a lesions tend to improve in texture and mobility. As some of
comparative trial for acute AD in which they determined that the studies indicate, patients with active, inflammatory mor-
medium-dose UVA1 was superior to low-dose UVA1. Both UVA1 phea respond best. Patients with atrophic lesions will not
and NB UVB in the treatment of AD are supported by level 1 improve. Given the depth of penetration of UVA1, we do not
evidence, as defined by the U.S. Preventative Task Force Ser- advocate UVA1 as monotherapy for morphea profunda or
vices.43 This led investigators to conclude that UVA1 was the eosinophilic fasciitis. Appropriate candidates for therapy in-
preferred therapy for acute exacerbations of AD and that NB clude patients with progressive, active lesions of any subtype.
UVB was preferred for maintenance. The authors of a series of Because UVA1 is not widely available, NB UVB may be con-
recent studies directly comparing NB UVB with UVA1 have chal- sidered for superficial dermal lesions and UVA without pso-
lenged this notion. ralen for thicker dermal lesions (Table 4).57-59
In a recent study, Gambichler et al44 compared medium-dose
UVA1 to NB UVB in the treatment of both acute and chronic Scleroderma
atopic eczema. After a 6-week course, both modalities produced Skin disease associated with scleroderma is disabling and
significant clinical improvements with no difference between highly symptomatic (including significant pruritus). Unfor-
the 2 modalities. Majoie et al45 published similar results, con- tunately, there is no therapy with proven efficacy for the
cluding that NB UVB and medium dose UVA1 appeared equally treatment of scleroderma. Phototherapy, particularly UVA1,
effective in the treatment of moderate to severe AD. Most re- has been investigated in largely uncontrolled trials, where it
cently, Tzaneva et al46 published the results of a randomized appeared to show benefit. One small controlled trial60 (18
observer-blinded cross-over trial in which the authors found patients, 1 hand randomized to receive treatment) showed
that PUVA provided a better short- and long-term response than that both arms improved over the course of the study, with
medium dose UVA1 in patients with severe AD. A summary of no significant difference between the treated and untreated
these studies11,37-42,44-46 is found in Table 2. arm. These studies only addressed acrosclerosis. In one ret-
Phototherapy in the age of biologics 193

Table 2 Studies of Phototherapy for AD

Number of Phototherapy
Authors Study Type Patients Modality Dose Comment
Krutmann et al RCT 25 HD UVA1 130 J/cm2 HD UVA1 superior to
(1992)11 UVAB, and produced
results more quickly
UVAB Mean 28 mJ/cm2
UVB, 7 J/cm2
UVA
Kowalzick et Uncontrolled trial 22 MD UVA1 50 J/cm2 MD UVA1 superior to
al (1995)42 LD UVA1
LD UVA1 10 J/cm2
Krutmann et al Randomized 43 HD UVA1 130 J/cm2 HD UVA1 superior to
(1998)39 multicenter trial UVAB, corticosteroids
UVAB Mean 33 mJ/cm2
UVB, 6.8 J/cm2
UVA
0.5% fluocortolone Once daily
cream
von Kobyletzki Randomized 120 Cold-light UVA1 50 J/cm2 Cold-light UVA1 superior
et al comparative trial to UVA1, UVAB
(1999)40
UVA1 50 J/cm2
UVAB Mean 0.29 J/cm2
UVB, 7.9 J/cm2
UVA
Grundmann- Case series 5 NB UVB Variable* Significant improvement
Kollmann et in 3 wks
al (1999)37
Tzaneva et al Randomized bilateral 10 HD UVA1 130 J/cm2 No difference between
(2001)41 comparison study HD and MD UVA1
MD UVA1 65 J/cm2
Reynolds et al RCT 73 NB UVB Variable* NB UVB more effective
(2001)38 over 12-wk course
BB UVA 5-15 J/cm2
Gambichler et Randomized controlled 28 MD UVA1 50 J/cm2 Both modalities
al (2009)44 crossover study comparably good
NB UVB Variable*
Majoie et al Randomized half-sided 13 MD UVA1 Average of 45 Both modalities equally
(2009)45 comparison study J/cm2 effective in chronic AD
NB UVB Variable*
Tzaneva et al Randomized crossover 40 PUVA Variable† PUVA provides better
(2010)46 study response in severe AD
MD UVA1 70 J/cm2
AD, atopic dermatitis; BB, broadband; HD, high dose; LD, low dose; MD, medium dose; NB, narrowband; PUVA, psoralen plus UVARCT;
randomized control trial; UV, ultraviolet; UVAB, ultraviolet A plus ultraviolet B.
*Based upon minimal erythema dose, with incremental increase.
†Based upon minimal phototoxic dose, with incremental increase.

rospective case series61 the authors did assess total body im- ment. PUVA has also been reported62 to be of benefit in
provement via the modified Rodnan skin score and found scleroderma and may be an option where UVA1 is not avail-
total body improvement for these patients. In our experience, able. Table 5 provides an overview of other sclerosing skin
UVA1 appears to be of benefit to scleroderma patients who conditions reported to improve with UVA1 phototherapy.
have early inflammatory skin disease. We also noted great
improvement in the pruritus and salt and pepper pigmentary Vitiligo
change associated with scleroderma. Adequately powered
trials assessing total body improvement in early scleroderma Vitiligo produces depigmentation as a result of destruction of
are needed to further define the potential benefit of this treat- melanocytes. Potent topical steroids remain the first-line
194 D. Walker and H. Jacobe

PUVA was a mainstay of treatment for vitiligo until 1997

when Westerhof and Nieuweboer-Krobotava reported64 the
first use of NB UVB in vitiligo. In 1999, guidelines for the
treatment of vitiligo were published65 and they advocated NB
UVB as the first choice therapy for generalized vitiligo in
adults and as an alternative therapy, after class-III corticoste-
roids, in children. This recommendation was supported by a
single randomized double-blind trial66 comparing PUVA
with NB UVB, which showed that NB UVB was superior to
PUVA.
There is no universally accepted protocol for the treat-
ment of vitiligo with NB UVB; therefore, protocols differ
between studies. A summary of these studies has recently
been published.32 In general, sessions are performed 2-3
times per week, with doses ranging from 100 to 280 mJ/
Figure 2 Recommendations for phototherapy for AD. cm2, with doses stabilized and adjusted for each patient
thereafter on the basis of individual response and devel-
opment of erythema. Patient response to NB UVB therapy
treatment for limited areas of vitiligo, but phototherapy has been variable. More than 75% repigmentation has
should be considered when more than 20% of the body sur- been achieved in 12.5%67 to 75%68 of patients after ap-
face area is involved.63 Targeted phototherapy sources are an proximately 6 months to 1 year of treatment. The reason
option when ⬍20% body surface area is involved. for such variability is unclear; however, proposed causes

Table 3 Studies of UVA1 Phototherapy for Morphea

Number of Phototherapy
Authors Study Type Patients Modality Dose Comment
Kerscher et al Case series 10 LD UVA1 20 J/cm2 >80% lesion clearance
(1995)12
Stege et al Controlled trial 17 HD UVA1 130 J/cm2 Significant clearance in both
(1997)47 groups, HD UVA1 is superior
to LD UVA1
LD UVA1 20 J/cm2
Gruss et al Uncontrolled trial 5 LD UVA1 20 J/cm2 5/5 improved, 3/45 resolved,
(1997)33 normal skin thickness
Kerscher et al Uncontrolled trial 20 LD UVA1 20 J/cm2 Significant clinical improvement
(1998)48
Gruss Case series 3 LD UVA1 20 J/cm2 Highly effective in plaque
(2001)49 clearance
de Rie et al Controlled trial 8 MD UVA1 48 J/cm2 Overall improved sclerosis
(2003)50
Kreuter et al Randomized controlled 27 MD UVA1 50 J/cm2 MD UVA1 is superior to LD
(2006)51 study UVA1 and NB UVB, LD UVA1
equivalent to NB UVB
LD UVA1 20 J/cm2
NB UVB 0.1-1.5 J/cm2
Tuchinda et al Multicenter retrospective 34 MD UVA1 50-60 J/cm2 Greater clinical improvement in
(2006)52 study medium and medium to HD
UVA1
LD UVA1 20-30 J/cm2
MD to HD UVA1 50-120 J/cm2
Sator et al Randomized controlled 16 MD UVA1 70 J/cm2 All improved, no difference
(2009)53 trial between MD and LD UVA
LD UVA1 20 J/cm2
Suh et al Retrospective study 6 LD UVA1 20 J/cm2 Both effective in complete and
(2010)54 partial remission
HD UVA1 100 J/cm2
HD, high dose; LD, low dose; MD, medium dose; NB, narrowband; UV, ultraviolet.
Phototherapy in the age of biologics 195

Table 4 Studies of UVA Phototherapy for Morphea

Number of
Authors Patients Regimen Study Type Response
El-Mofty et al 15 20 sessions at 20 Controlled trial Softening of sclerotic lesions (90% cure in
(2000)57 J/cm2 early lesions, 50% cure of late lesions)
El-Mofty et al 67 20 sessions at 5, 10, Randomized control All doses with remarkable softening of
(2004)58 or 20 J/cm2 trial sclerotic lesions, no difference between
doses
El-Mofty et al 22 20 sessions at 10 or Controlled trial All improved, 18/22 with moderate or better
(2004)59 20 J/cm2 improvement, 10 J/cm2 was equivalent to
20 J/cm2
UVA, ultraviolet A.

are skin type, location of lesions, and lack of the use of a for higher stages (ⱖIIB), disease progression, or lack of ap-
uniform validated outcome measure. A minimum treat- propriate responses.71,73
ment period of 6 months is recommended with NB UVB PUVA has remained a valuable tool in the treatment of
with a maximum treatment period of 24 months or until MF over the years owing in part to the large number of
100% repigmentation.65 Facial lesions have been shown to clinical trials that have supported its use. A comprehensive
be significantly more responsive to treatment, whereas ac- list of these studies has been published recently.74 The rate
ral site (hands and feet) have shown minimal response.69 of complete remission with PUVA is estimated to be 90%
The duration of disease is thought to be inversely corre- with stage IA, 76% with stage IB, 78% with stage IIA, 59%
lated with the repigmentation percentage of responsive with stage IIB, and 61% with stage III71,74,75 in general, the
lesions, with earlier lesions responding better than old protocol for PUVA is similar to that used in psoriasis.76
ones.69,70 Some researchers have shown that patients who Bath PUVA is generally not accepted as the head is not
responded earlier to treatment (around 1 month) have a exposed to the topical psoralen and this is a likely source
greater level of posttreatment repigmentation, allowing of relapse.77 The choice to use maintenance phototherapy
physicians to better predict patients with a greater chance after clearance is still controversial. Although maintenance
of achieving satisfactory pigmentation earlier in the treat- therapy is likely beneficial in preventing relapse, it is well
ment course.67 The Excimer light source is a NB UVB documented that PUVA has been associated with carcino-
source that has been used for treating localized areas, such genesis. Therefore, a practical approach is to reserve main-
as the face, neck, and trunk. tenance for those patients who show signs of early relapse
(⬍6 months). Currently, there is no agreement on main-
Mycosis Fungoides tenance therapy duration, frequency, UVA dosing, and
Mycosis fungoides (MF) is the most common form (approx- scheduling, but a practical approach may be once weekly
imately 65%) of the cutaneous T-cell lymphomas. MF is char- treatments for 3-6 months without dose increments.
acterized by an epidermotropic infiltrate of T lymphocytes The first report of UVB phototherapy in the treatment of
with the phenotypic display of mature memory T cells.71 MF appeared in 1982.78 A number of studies followed in
Gilchrest et al72 first reported the efficacy of phototherapy in which authors confirmed the efficacy of UVB in the treatment
MF, when they treated 9 patients with PUVA. In this report, of MF. A comprehensive list of these studies has been pub-
all patients responded well to treatment, and complete remis- lished recently elsewhere.79 Today, NB UVB has largely re-
sion was achieved in 4 patients. Today, the most common placed the use of BB UVB and is the treatment of choice for
forms of phototherapy used in the treatment of MF are PUVA the management of stage I MF patients according to a recent
and both NB and BB UVB. Recently, treatment recommenda- survey among dermatologists using office-based photother-
tions and reviews have been published that provide a rational
apy.74 However, there is a lack of studies comparing NB UVB
approach to MF. It is now commonly accepted that early-
with PUVA. A widely accepted consensus is that patients with
stage MF should be treated with skin directed therapies,
patches and thin plaques should be preferentially treated
while systemic and aggressive treatments should be reserved
with NB UVB, whereas PUVA should be reserved for thicker
plaques. One comprehensive review74 concluded that NB
Table 5 Other Sclerosing Skin Conditions Reported to Im- UVB administered 3 times per week or PUVA 2-3 times per
prove With UVA1 week, continued until clearance (most commonly 3-4
Lichen Sclerosis et Atrophicus months), was an effective regimen in the initial clearing
Sclerodermoid GVHD stages of MF. On the basis of the results of one retrospective
Scleredema analysis, it has been proposed that because of its practical
Necrobiosis lipodica advantages, NB UVB might be a reasonable approach to treat
Nephrogenic systemic fibrosis early MF. PUVA may then be initiated in cases that fail to
GVHD, graft-versus-host disease. respond.80
196 D. Walker and H. Jacobe

Table 6 Other Cutaneous Conditions That Have Been Responsive to Phototherapy

UVA1 NB UVB PUVA
Cutaneous mastocytosis Acquired perforating dermatitis Alopecia areata
Dyshidrosis Chronic urticaria Cutaneous GVHD
Granuloma annulare Generalized granuloma annulare Dermatitis herpetiformis
Keloids Lichen planus Dyshidrotic eczema
Mycosis fungoides Lichen simplex chronicus Granuloma annulare
Pityriasis lichenoides Lymphomatiod papulosis Histiocytosis
Sarcoidosis Mastocytosis Lichen planus
Systemic lupus erythematosus Parapsoriasis Mastocytosis
Pityriasis lichenoides Morphea
Pityriasis rosea Palmoplantar psoriasis
Pruritis Pityriasis rosea
Seborrheic dermatitis Urticaria
Urticaris pigmentosa
GVHD, graft-versus-host disease; NB, narrow band; PUVA, psoralen UV; UVA1, ultraviolet A1; UVB, ultraviolet B.

Other Uses of Phototherapy those reported, the most common are erythema, pruritus,
Other skin disorders that may be responsive to UVA, UVB, and xerosis, which typically resolve after topical emollients.32
and PUVA are listed in Table 6. Chronic adverse effects include photoaging and possibly
photocarcinogenesis (although studies to date have failed to
identify significantly increased risk).
Phototherapy in Children Patients treated with UVA1 most commonly report no side
The use of phototherapy in children is limited by concern effects other than tanning and, less commonly, erythema and
about long-term carcinogenesis and photoaging.81 Con- pruritus. UVA1 has been reported to cause a polymorphic
versely, it is important to avoid exposing children to the risks light eruption85 and activation of herpes simplex infection.
of prebiologics and biologics whenever possible because of The side effects of the psoralen, 8-MOP, used in PUVA
their potential risks, which include infection, malignancy, therapy, include nausea and gastrointestinal upset. One strat-
bone marrow suppression, and renal toxicity.82 Thus, many egy for reducing the side effects of 8-MOP–induced nausea is
have considered phototherapy to be a safe alternative in chil- to decrease the dose and compensate by increasing the dose
dren requiring more than topical agents to control their dis- of UVA by the same percentage.23 8-MOP may also be sub-
ease. Pavlovsky et al83 recently published one of the largest stituted with 5-MOP, which is relatively equivalent in effi-
retrospective studies to date on the use of NB UVB in the cacy and produces fewer side effects. As mentioned previ-
pediatric population for psoriasis and AD. Their report in- ously, bath PUVA carries some inconveniences as compared
cluded results from 129 children followed during an 8-year with oral psoralen therapy. Despite these inconveniences,
period, concluding that this was a viable therapeutic option bath PUVA is preferential in patients with limited treatment
that should be used with caution in a carefully selected pop- areas, such as the hands and feet, and may also be considered
ulation. Another recent 15-year prospective study evaluating in patients who would otherwise have difficulty in tolerating
the use of NB UVB phototherapy in 116 children determined oral psoralen (when facilities are available). In addition, some
it to be an effective and well-tolerated treatment, with most patients treated with PUVA complain of a painful, burning
children only needing a single course.84 As with all patients itch that may persist for months after treatment. Currently,
who receive phototherapy, parents should be counseled on PUVA is the only phototherapeutic modality definitively
sun protection, sunscreen use, sun avoidance, and the need linked with the development of melanoma and nonmela-
for regular skin examinations. noma skin cancer in white patients.86,87
Various factors modulate the risk of carcinogenesis in each
patient before any exposure to phototherapy. These factors
Side Effects and include Fitzpatrick skin type, preexisting actinic damage,
Contraindications age, and personal habits and behavior (extensive outdoor
exposure, tanning bed use). These elevate the baseline risk
One of the primary advantages of UV phototherapy as com-
for carcinogenesis for each patient and therefore, additional
pared to systemic steroids, biologics, or other immunosup-
exposure to further risk is clearly contraindicated.
pressive medications, is its relative safety and lack of side
effects. Nonetheless, reported side effects range from mild to
severe and should be considered before a patient begins UV
phototherapy.
Conclusions
NB UVB is safe in almost any patient regardless of comor- Phototherapy represents an excellent option in several ther-
bidity, including children83 and pregnant women. Acute ad- apeutically challenging disorders by providing effective ther-
verse side effects during NB UVB treatment are infrequent. Of apy without systemic side effects. Although most commonly
Phototherapy in the age of biologics 197

associated with the treatment of psoriasis, phototherapy is a human T helper cell apoptosis is the basic mechanism of ultraviolet-A
valuable tool in the treatment of a large number of skin dis- radiation phototherapy. J Exp Med 186:1763-1768, 1997
21. Gruner S, Zwirner A, Strunk D, et al: The influence of topical derma-
orders, many of which are disabling or have significant im-
tological treatment modalities on epidermal Langerhans cells and con-
pact on life quality. This makes phototherapy relevant to tact sensitization in mice. Contact Dermatitis 26:241-247, 1992
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