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Clinics in Dermatology (2016) 34, 633–639

Phototherapy in children: Considerations


and indications
Cary S. Crall a , Jillian F. Rork, MD b , Sophia Delano, MD a , Jennifer T. Huang, MD a,⁎
a
Harvard Medical School, Dermatology Program, Division of Allergy and Immunology, Department of Medicine,
Boston Children's Hospital, Boston, MA
b
Department of Dermatology, University of Massachusetts School of Medicine, Worcester, MA

Abstract Phototherapy can be a safe and effective treatment for various skin diseases in children. Special
considerations governing the use of this treatment modality in pediatric populations include patient, family,
and facility-based factors that are oriented around heightened concerns with regard to safety and tolerability
of treatment. Although phototherapy has been found to be effective in a wide range of dermatologic condi-
tions affecting pediatric populations, including psoriasis, atopic dermatitis, pityriasis lichenoides, cutaneous
T-cell lymphoma, and vitiligo, there is need for additional research on other conditions in which photother-
apy has shown promise.
© 2016 Elsevier Inc. All rights reserved.

Introduction Special considerations in pediatric phototherapy

Phototherapy can be a well-tolerated and effective treat- Evaluation of the newborn


ment for various skin diseases in children; however, special
considerations should be taken when employing this mode of The most common use of phototherapy in the pediatric
therapy, particularly in young children. In this review, we pro- population is the treatment of unconjugated hyperbilirubine-
vide guidance regarding the evaluation and management of mia in preterm and term infants. The evaluation of an infant
pediatric candidates and review associated risks. We also dis- with elevated bilirubin is beyond the scope of this contribu-
cuss the most common dermatologic indications for photother- tion, but the provided sources may serve as references.1,2
apy in children, including psoriasis, atopic dermatitis,
pityriasis lichenoides, cutaneous T-cell lymphoma, and vitili- Evaluation of the child and adolescent
go. Our discussion focuses on modalities of phototherapy with
evidence-based efficacy. The reader should be mindful that da- Determining the ideal pediatric candidate for phototherapy
ta on safety and efficacy of phototherapy are limited in chil- is a multifactorial process and should involve both the patient
dren, emphasizing the need for future studies. and parents.
The evaluation should begin with a thorough history in-
cluding assessment of disease symptoms, previous failed treat-
⁎ Corresponding author: Tel.: +1 617 355 8937. ment therapies, and effects on quality of life. Clinicians should
E-mail address: Jennifer.huang@childrens.harvard.edu (J.T. Huang). ask questions about school day hours, after school activities,

http://dx.doi.org/10.1016/j.clindermatol.2016.05.018
0738-081X/© 2016 Elsevier Inc. All rights reserved.

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634 C.S. Crall et al.

parents’ employment, and mode of transportation, because described in infants with severe cholestatic jaundice or con-
these responses help determine treatment feasibility. genital porphyria.2
Age of initiation depends on the type of phototherapy and There have been conflicting studies suggesting that neona-
is based on conventional wisdom rather than data-driven tal blue light phototherapy (NBLP) may increase the risk of ac-
guidelines. Because psoralen plus ultraviolet A (PUVA) can quired melanocytic nevi in children and adolescents. A study
induce cataracts, and the ocular lens is more permeable at a from France evaluating nevi counts in 9-year-old children
younger age, oral PUVA is relatively contraindicated in chil- found no major role of NBLP.6 Other studies have suggested
dren younger than 12 years of age. The school-age child is a NBLP resulted in a significantly higher prevalence of cutane-
reasonable recommended starting age for UVB, but younger ous melanocytic lesions, including a twin study comparing
candidates may be considered. The child’s behavioral devel- those who received NBLP with those who did not.7–9 There
opment and temperament should be assessed, including sepa- are no data on the risk for melanoma in this population. A con-
ration anxiety, fear of enclosed spaces, and ability to remain troversial Letter to the Editor was published in Pediatrics in
still during treatments. 2007, suggesting NBLP could increase the risk of dysplastic
Absolute contraindications to phototherapy include both ac- nevus development; however, the study methodology and re-
quired and inherited disorders aggravated by ultraviolet light, sults have been criticized.10 Additional research is necessary
such as lupus erythematosus, dermatomyositis, xeroderma pig- to establish potential long-term adverse effects.
mentosum, porphyria, and basal cell nevus syndrome. Short-term risks of UVB phototherapy include erythema,
A history of polymorphous light eruption would necessitate blistering, and xerosis, accompanied by pruritus, photosensi-
a more gradual increase in fluence but would not be an abso- tive eruptions, and recurrent herpes simplex virus infections.
lute contraindication to phototherapy. Medications should be Provoking anxiety is another potential risk and should be dis-
reviewed to identify photosensitizing agents; in pediatrics, cussed.11 Long-term risks include photo-aging and cutaneous
these are commonly antimicrobials, antidepressants, and anti- carcinogenesis. The true carcinogenic potential in children re-
convulsants. Medications may present a relative contraindica- mains unclear. There was one potential report of a melanoma
tion to phototherapy, but decreased phototherapy doses can in situ in an 11-year-old psoriatic girl 11 months into narrow-
also be considered. A family history of skin cancer should be band ultraviolet B (NBUVB) phototherapy; however, it was
obtained, although it is not necessarily a contraindication. later concluded to be a Spitz nevus.12 Several studies in the
The pediatric physical examination is similar to the evalua- adult population have not detected a relationship between pho-
tion of an adult with categorization of Fitzpatrick skin phototype totherapy and nonmelanoma skin cancer or melanoma.13,14
and assessment of body surface area involved. Recording the lo- NBUVB may perhaps have an even smaller risk, although this
cation and size of any nevi by photography for the medical re- is a relatively new treatment, and thus long-term side effects
cord may be useful if the patient’s family later has concerns of have yet to be determined. Given the lack of data, additional
changes to the lesions during the course of phototherapy. weight should be given to the risk of skin cancer in children,
No specific laboratory tests are required, although some because patients could require UVB treatments for many years
would advocate checking for an antinuclear antibody before and may also receive subsequent immunosuppression.
starting phototherapy in patients with autoimmune conditions, The safety profile of PUVA is more concerning. Oral psor-
such as vitiligo, to screen for previously undiagnosed photosen- alens alone can cause nausea and vomiting. There has also
sitizing conditions like lupus erythematosus.3 Careful history been concern for hepatotoxicity, but several large-scale studies
taking of unexpected dermatitis after sun exposure and inabil- have found no significant laboratory findings.15,16 Short-term
ity to tolerate minimal sun exposure should suffice for most side effects of psoralens plus UVA include erythema, swell-
patients. ing, and blister formation. Because PUVA can induce cata-
racts and the ocular lens is more permeable at a younger age,
oral PUVA is relatively contraindicated in children younger
Associated risks than 12 years of age. Long-term photo-aging includes pigmen-
tary changes, rhytides, xerosis, actinic damage, and PUVA
Phototherapy for the management of neonatal jaundice has lentiginosis.16 Photocarcinogenesis is a major concern; an in-
been used in millions of infants for more than 30 years. Imme- creased risk of nonmelanoma skin cancer has been reported
diate side effects include transient erythematous eruptions, in children receiving PUVA treatment for psoriasis.17 The risk
loose stools, hyperthermia, and dehydration. Eyes of neonates of melanoma remains more controversial. In light of this side
should be sufficiently covered to eliminate exposure, because effect profile, PUVA is generally reserved for children with re-
animal studies indicate retinal degeneration may occur after fractory cases of palmoplantar psoriasis, with use of topical
24 hours of continuous exposure.4 Another immediate side ef- rather than systemic psoralens.
fect is “bronze baby syndrome,” where the skin, serum, and
urine have a dark, grayish-brown discoloration in some infants Office treatment strategies
with cholestatic jaundice.5 The condition gradually resolves
without sequelae within several weeks of discontinuing photo- With thorough orientation and support, children often have
therapy. Rarely, purpura and bullous eruptions have been very successful treatment courses with in-office phototherapy.

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Phototherapy in children 635

Orienting patients and families to the phototherapy suite and and irritation and should apply sunscreen and sun-protective
treatment process before the first session lays the foundation clothing once the child has had 10 to 15 minutes of unprotect-
for effective, safe, comfortable phototherapy sessions. Chil- ed exposure. Topical psoralens have been used anecdotally in
dren and their parents should have a chance to stand inside conjunction with natural sunlight therapy for vitiligo in chil-
the unit and learn how to exit the unit if needed. During their dren but should be used with caution because of their pro-
orientation, patient families should be reminded to alert staff longed photosensitizing effects.
to any new medications, such as antimicrobials or over-the- For children with potential need for long-term photothera-
counter medications, that the patient begins after starting pho- py, home phototherapy units are another treatment option.
totherapy to avoid a photosensitive reaction during treatment. Many NBUVB home phototherapy units have open panels
If the child will be wearing undergarments during treatment, that may be less intimidating than the enclosed units in most
keeping these clothes at the phototherapy clinic may be the in-office phototherapy clinics. Children may also be more
easiest way to ensure consistent use of the same clothing, de- comfortable receiving phototherapy in their home environ-
creasing the risk of burns on newly exposed skin. If a child ment. Home units typically require longer sessions, given their
does not need treatment on his or her face, this should be lower fluences, and close parental supervision to prevent mis-
shielded during phototherapy. Various shielding devices may use. Home units necessitate continued follow-up with the pre-
be used depending on the center’s standard practice and the scribing physician for codes allowing additional treatments,
child’s level of comfort. typically in units of 25 to 75 sessions.
Partnering with parents to help children manage photother-
apy sessions carries over to the actual treatment sessions. Dur-
ing treatment, parents may stay right outside the booth or have Common pediatric indications for phototherapy
the booth’s door left slightly ajar so that they can hold the
child’s hand during treatment. Children may be accompanied Psoriasis
by a parent in the photo booth with the goal of transitioning
to unaccompanied sessions.
Phototherapy for the pediatric patient may be complicated
by the patient’s recreational use of indoor tanning, an increas- Modalities NBUVB, broadband UVB (BBUVB), PUVA
ingly popular activity among teenagers. In 2011, approximate- Supporting Multiple large retrospective reviews
evidence
ly 13.3% of high school students in the United States engaged
Indications Potential first-line treatment for patients with
in some tanning behavior, with that incidence increasing to diffuse involvement, especially those with
29.3% among non-Hispanic young women.18 Some teenagers guttate psoriasis or thin plaque disease
may have already discovered indoor tanning helps their skin
condition. Tanning teens undergoing phototherapy are receiv-
ing unknown amounts of ultraviolet exposure and are at in- Phototherapy therapy is an effective treatment for pediatric
creased risk for adverse side effects such as irritation, patients with psoriasis (Table 1). NBUVB (311-313 nm) is the
erythema, and burns. Asking about and discouraging tanning most studied and commonly prescribed because of its relative-
behaviors, even infrequent use before events like a prom, ly positive safety profile, efficacy, and ease of administration.
should be a part of the intake and orientation of any teenager In the most recent and largest study, 88 pediatric patients with
to phototherapy. psoriasis, mean age of 12 ± 4 years, received NBUVB therapy
for 3.1 ± 2.26 months with an average cumulative dose of 46.5
Home treatment strategies J/cm2. In all, 92% of children treated with NBUVB had greater
than 75% improvement with full clearance achieved in 51%.12
Phototherapy outside of the clinic setting, either with limit- This response rate was similar to that of prior retrospective co-
ed exposure to natural sunlight or with home phototherapy de- hort studies (Table 1).
vices, is an alternative for pediatric patients whose schedule Other treatment modalities include broadband UVB
and temperament preclude frequent office visits and treatment (BBUVB, 290-320 nm) and UVA (320-400 nm) with topical
in a phototherapy booth. or systemic psoralens. In a series of 30 patients with psoriasis
Exposure to natural sunlight is also a cost-effective alterna- (mean age 11 ± 3.6 years) treated with BBUVB (mean treat-
tive during spring and summer months for patient families ment number 28.8 ± 13.3), 93.3% of participants had more
who are able to limit their child’s exposure time. Encouraging than 75% improvement. Seven patients with plaque or guttate
10 to 15 minutes of unprotected sun exposure to the affected type psoriasis were treated with PUVA and 83% improved by
areas around noon may help mild to moderate photosensitivity more than 75% after an average of 28 PUVA treatments.22
conditions, such as psoriasis, vitiligo, and atopic dermatitis. Phototherapy regimens that include adjuvant therapy with
Midday exposure is usually not obtainable for older children other topical and systemic agents have been studied with vari-
during the school year, but during the summer months, natural able results. Topical agents had efficacy in patients receiving
sunlight offers a potential respite from in-office phototherapy phototherapy include serous-based emollients (ie, mineral oil),
sessions. Parents should limit these sessions to prevent burning topical corticosteroids, vitamin D analogs (must be applied after

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636 C.S. Crall et al.

Table 1 Phototherapy efficacy in pediatric psoriasis


Study Modality N Mean age Mean no. of Mean cumulative Mean max dose/ Response
(years) treatments dose (mJ/cm2) treatment (mJ/cm2)
Pavlosky NBUVB 88 12 (8-16) 46,500 92% with N 75%
(2011)12 improvement
Tan (2010)19 NBUVB 38 11.3 (8.5- 27.8 (4-76) 20,370 (161.5-89,091) 1388 (15-2996) with 90% with N 75%
15.5) with median of 13,113 median of 490 improvement
Zamberk NBUVB 20 13 (5-17) Median 28 Median 40,841 (5992- 3000 (873-3000) 52% with N 90%
(2010)20 (10-59) 144,037) improvement in PASI
Kortuem Goeckerman 65 11.6 20 (8-37) NR NR 85% with N 80% clearance
(2010)21 treatment (0.25-18)
Ersoy-Evans NBUVB 28 12 ± 2.5 25.8 ± 10.6 20,000 (3000-85,000) 1000 (300-6000) 92.9% with N 75%
(2008)22 improvement
Jain NBUVB + 18 (5-14) 20.56 ± 2956 ± 1070 297 ± 100 100% with clearance of
(2008)23 mineral oil 3.06 disease
NBUVB 18 (5-14) 23.78 ± 4,088 ± 1236 395 ± 115
alone 3.14
Jury NBUVB 35 Median Median NR NR 63% with clearance or
(2006)11 12 (4-16) 17.5 (9-35) minimal residual disease
Pasic UVA + 20 9.5 (6-14) 19 (10-39) 6610 (2400-24,500) 340 (30-500) 45% excellent response
(2003)24 NBUVB 40% good-moderate
response
NBUVB, Narrowband ultraviolet B; PASI, Psoriasis Area and Severity Index; UVA, Ultraviolet A.

phototherapy), coal tar, or topical retinoids23,25–27; however, Academy of Dermatology lists both UVA and UVB as well-
topical salicylic acid may decrease the efficacy of photothera- tolerated and effective treatments for childhood AD, both as
py.26 Systemic retinoids have been reported to increase effica- monotherapy and in combination with emollients and topical
cy of UV therapy, whereas methotrexate should be used with steroids.31 Phototherapy is best considered after maximizing
caution because of the increased risk of photosensitivity.26,28 topical therapies and can be administered on a scheduled inter-
There is no established consensus on the position of photo- mittent basis over time or continuously as maintenance thera-
therapy on the pediatric psoriasis therapeutic ladder. In gener- py for patients with refractory disease.32 A recent review
al, phototherapy should be considered in older patients, those suggests phototherapy’s position on the therapeutic ladder is
with diffuse involvement, or those with contraindications to similar to systemic treatments, such as methotrexate, azathio-
systemic therapy.29,30 Phototherapy has also been found to prine, and mycophenolate mofetil after oral cyclosporine. Pho-
be more effective in treating guttate psoriasis and thin plaque totherapy might best be employed as a potential adjunctive
disease.30 It may also be considered a first-line treatment in pa- treatment in older children, especially those with chronic,
tients with diffuse or debilitating lesions. lichenified disease.33
In conclusion, NBUVB, BBUVB, and PUVA are effective There is strong evidence supporting the efficacy of photo-
treatments for pediatric psoriasis. Although many factors may therapy in pediatric populations with atopic dermatitis. In gen-
influence a clinician’s choice among these treatment modali- eral, NBUVB is the preferred modality for treatment of AD in
ties, we recommend NBUVB as the preferred regimen because pediatric populations. A review of multiple randomized con-
of its relatively positive safety profile, efficacy, and ease of trolled trials, spanning 905 participants with mean age of 32
administration. years (range 8-83 years), concluded NBUVB and medium-
dose UVA1 were the most well-tolerated and effective modal-
Atopic dermatitis ities of phototherapy for AD patients.34 In a prospective cohort
study of children ages 3 to 16 years with moderate to severe
AD, the efficacy of treatment with NBUVB was evaluated.
Modality NBUVB, BBUVB, PUVA, UVA All patients were optimized on topical treatment and offered
Supporting evidence Multiple randomized controlled trials phototherapy. The 29 who accepted treatment experienced a
Indications Second line after maximizing topical 61% reduction in mean Six Area, Six Sign Atopic Dermatitis
treatments ± oral cyclosporine (SASSAD) score, compared with 6% in the 26 patients who
deferred phototherapy. In addition, mean surface area involve-
Phototherapy should be considered as a second-line therapy ment at the end of treatment was 11% for the NBUVB cohort
in pediatric patients with moderate to severe atopic dermatitis versus 36% for the unexposed cohort. Subjective and quality-
(AD). A recent consensus statement by the American of-life scores showed significant differences between cohorts

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Phototherapy in children 637

at the end of treatment (P b .05). Objective scores remained There is no established consensus regarding the position of
significantly lower than in the unexposed cohort 3 months phototherapy on the PL therapeutic ladder. Although NBUVB
and 6 months after treatment.35 may be considered a first-line treatment for generalized or re-
current PL and second line for localized disease failing topical
Pityriasis lichenoides steroids or antimicrobials, a 2007 review of 124 children treat-
ed for PL at a large academic center reported only 11 were giv-
en NBUVB after failing other treatments.36,40 The authors of
Modality NBUVB this review cited difficulties in treatment delivery and uncer-
Supporting Multiple small case series tainty about long-term side effects as limiting factors in their
evidence utilization of phototherapy. Other authors note clearance is
Indications First line, especially in pityriasis lichenoides achieved after a relatively short number of treatments in PL
chronic and thin plaque disease compared with other disease entities, mitigating potential risk
for future malignancy.41 In all, because of its effectiveness
and tolerability, NBUVB should be considered alongside oral
Pityriasis lichenoides (PL), in both its acute form (pityriasis antimicrobials as a potential first-line treatment for childhood
lichenoides et varioliformis acuta; PLEVA) and chronic form PL, especially in the PLC subtype.
(pityriasis lichenoides chronica; PLC) is an inflammatory skin
condition that is often difficult to treat. Because of its rare na-
ture, evidence supporting the efficacy of phototherapy in pedi-
atric patients with PLEVA/PLC is limited to a few small case Cutaneous T-cell lymphoma
series. A review of five patients (two with PLEVA and three
with PLC) with PL treated with NBUVB found complete re-
mission in all five patients after therapy for an average of 21 Modality NBUVB, oral PUVA, topical PUVA
sessions (range 13-40 sessions), corresponding to an average Supporting evidence Multiple moderate-size
duration of therapy of 4 months (range 2-8 months). The aver- retrospective reviews
age cumulative dose was 21 J/cm2 (range 15-32 J/cm2). Each Indications First-line treatment for stage I MF,
patient maintained remission of the disease at follow-up visits especially hypopigmented type
at 3 and 6 months.36
Physicians considering treatment of pediatric PL with pho-
totherapy should take into account the reported high rate of re- Recent retrospective reviews establish both PUVA and
lapse and morphologic differences between PLEVA and PLC. NBUVB as effective treatments for stage I pediatric cutaneous
A 1990 review of 89 patients with PL reported UVB therapy T-cell lymphoma, with NBUVB preferred because of its rela-
was effective at alleviating symptoms and controlling erup- tive ease of administration.
tions in patients receiving this treatment; however, authors re- Phototherapy was used in 28 patients with mean age at pre-
ported phototherapy “did not modify the course of the disease” sentation of 11.6 ± 3.9 years. All patients had stage I disease
given its high rate of relapse.37 In a 2015 review, continuous (IA = 10, IB = 17, unknown = 1) with median follow-up after
phototherapy treatment might be necessary to combat disease diagnosis of 43 months (range 6-274 months). NBUVB was
recurrence, a treatment plan limited by the practical demands used as first-line treatment in 18 patients and PUVA was used
and safety concerns of long-term phototherapy use.38 Finally, in 8 patients. Complete or partial response was observed in 19
a small retrospective review found children with PLC of 22 patients (86%). A further course of phototherapy was re-
responded better to phototherapy than those with PLEVA, quired in 7 of 12 patients (58%) treated with NBUVB after a
suggesting this may be due to the inability of UV therapy to median of 4 months (range 4-29 months). A further course
penetrate the relatively thicker PLEVA lesions.24 of phototherapy was required in 4 of 8 patients (50%) success-
There has been no proven benefit of phototherapy as adju- fully treated with PUVA after a median of 45.5 months (range
vant therapy to systemic medications, such as corticosteroids, 30-87 months). No disease progression was noted over the
antibiotics, and antihistamines. A review of 70 patients with follow-up (median 43 months).41 These results confirmed pre-
a mean age of 25 ± 18 years (range 2-80 years) treated with vious studies’ findings of effective response to phototherapy
phototherapy, compared the clinical efficacies of NBUVB with tendency toward relapse. Finally, another review suggests
phototherapy, systemic therapy, and a combination of phototherapy may be especially effective in patients with the
NBUVB and systemic medication in the treatment of PL. hypopigmented form.42
Based on the 90% complete clearance in the cohort treated Limited evidence indicates topical PUVA is effective in
with NBUVB alone, monotherapy using NBUVB is effective early-stage cutaneous T-cell lymphoma. A 2002 case series
and well tolerated in eliminating the need for concurrent sys- of three pediatric patients treated with topical PUVA found
temic medication; 81.1% of patients treated with NBUVB 100% complete response with a favorable side effect profile.43
were relapse free at 20 weeks and the results held across all Further studies are warranted to establish the efficacy of this
age groups including the pediatric population.39 treatment modality.

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638 C.S. Crall et al.

Vitiligo versus-host disease (GVHD), although efficacy evaluation in


these conditions is limited to relatively few cases.24,51,52
Phototherapy has also been used to diminish manifestations
of various light-sensitive cutaneous eruptions, such as erythro-
Modality NBUVB, combination UVA1 and UVB, poietic protoporphyria and polymorphic light eruption. Such
excimer laser, topical PUVA photoprophylaxis or hardening has been reported to increase
Supporting Multiple large retrospective reviews subsequent sun tolerance in patients receiving this treatment,
evidence and phototherapy may be considered as prophylaxis in other
Indications Second line after maximizing topical treatments;
dermatologic conditions that are known to be light sensitive.53
consider first line in diffuse disease
Finally, phototherapy has not been found useful in all pedi-
atric skin conditions in which it has been tried. Two large ret-
NBUVB phototherapy, targeted phototherapy combining rospective studies have found the response rate to topical and
ultraviolet A1 (UVA1) and UVB, 308-nm excimer lamp pho- oral PUVA is no better than the spontaneous remission rate
totherapy, and topical PUVA have all been effectively used to in patients treated for alopecia areata.54,55 Because of the high
treat childhood vitiligo. relapse rates, lack of randomized controlled trials, and in-
NBUVB is the most studied modality in childhood vitiligo creased risk of skin malignancies with PUVA, a recent review
with multiple retrospective reviews. Most recently, in 2015, 71 of treatment options in alopecia areata found this line of thera-
patients ages 5 to 15 years and skin types IV to VI were treated py to be less favored.56
with these varying modalities, having a 74% good response
rate with NBUVB (14/19), 67% with combined UVB/UVA1
(26/39), 54% with excimer laser (10/19), and 53% with topical Conclusions
“paint” PUVA (13/25).44
Although treatment is often deferred in pediatric vitiligo, es- Current literature suggests children may be treated safely
pecially in children of lighter skin types, treatment for childhood and effectively with various forms of phototherapy for com-
vitiligo should be initiated early in the disease process because mon skin conditions, including psoriasis, atopic dermatitis,
response is more robust in illness of recent onset.45 Because this and vitiligo; however, larger prospective studies are needed
may lead to treating younger children, some groups recom- to further understand the long term risks of these therapies,
mend stopping treatment after 6 months if it is ineffective to particularly in young children.
limit the cumulative overall dose and mitigate risk for future
malignancy.46 Co-administration of topical tacrolimus 0.1%
may increase response to phototherapy.47 Topical corticoste-
roids also have a synergistic treatment benefit, whereas co- References
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For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
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