Phototherapy and photochemotherapy in childhood psoriasis

Abstract

Psoriasis affects approximately 2% of the general population and in approximately a third of patients psoriasis starts in the first two decades. Treatment of childhood psoriasis represents a special challenge, since many therapeutic agents are not approved and guidelines are frequently lacking for this age group. It is, however, suggested that calcipotriene with or without topical corticosteroids, followed by dithranol, should be used for topical treatment. For systemic treatment, methotrexate is the first choice followed by etanercept. Phototherapy can be employed without age restrictions if the child is mentally and psychologically able to tolerate the procedure and accepts eye protection. Topical photochemotherapy, such as psoralen plus UVA (PUVA)-bath or cream-PUVA, are preferred over oral PUVA, but should be restricted to those aged over 10 or 16 years, respectively. It is generally agreed upon that phototherapy and photochemotherapy in childhood is effective and well tolerated, but must be employed carefully in selected patients only. Concerns remain regarding long-term side effects. This article reviews available data on UVB phototherapy and photochemotherapy in childhood psoriasis and discusses guidelines consented by dermatologic societies in Europe and the USA. Specific recommendations for the use of UV therapy in childhood are given.

Keywords::

• childhood psoriasis
• NB-UVB
• oral PUVA
• photochemotherapy
• phototherapy
• PUVA-bath

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This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and Expert Reviews Ltd. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians.

Medscape, LLC designates this Journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 70% minimum passing score and complete the evaluation at http://www.medscape.org/journal/expertderm; (4) view/print certificate.

Release date: July 28, 2011; Expiration date: July 28, 2012

Learning objectives

Upon completion of this activity, participants should be able to:

• • Distinguish primary therapy for children with psoriasis

• • Identify the preferred form of phototherapy for psoriasis in children

• • Evaluate the risks and limitations of phototherapy among children

• • Assess practice recommendations for the use of phototherapy among children

Financial & competing interests disclosure

EDITOR

Elisa Manzotti,Editorial Director, Future Science Group, London, UK

Disclosure:Elisa Manzotti has disclosed no relevant financial relationships.

CME AUTHOR

Charles P Vega, MD,Associate Professor; Residency Director, Department of Family Medicine, University of California, Irvine, CA, USA

Disclosure:Charles P Vega, MD, has disclosed no relevant financial relationships.

AUTHOR

Erhard Hölzle,Department of Dermatology and Allergology, Oldenburg Clinic, Oldenburg, Germany

Disclosure:Erhard Hölzle has disclosed no relevant financial relationships.

Psoriasis is quite a common inflammatory disorder with a prevalence of approximately 2–3%. In approximately a third of patients, the onset of psoriasis is observed in childhood [1–3]. In most cases the children develop plaque-type psoriasis or guttate psoriasis. Pustular eruptions rarely occur. There are many options for the treatment of psoriasis; however, the treatment of moderate to severe disease in childhood is challenging. There are only few reported data on treatment outcomes in children and the majority of therapeutic agents used in adulthood are not licensed for use in childhood. There is, indeed, a need for valid recommendations to treat children and there are even less data on phototherapy and photochemotherapy in childhood [4,5].

This article evaluates available data on phototherapy and photochemotherapy in childhood and reports on a series of consensus opinions detailing the current practice in Europe and the USA. Finally, practical recommendations for phototherapy and photochemotherapy in children are presented.

Summary of studies

There are well-conducted studies describing the treatment with narrow band UVB (NB-UVB) (Table 1).

In 1996, Tay et al. performed an open-label study in ten patients, aged 14 months to 12 years with guttate and plaque-types psoriasis. Duration of treatment varied from 6 to 20 weeks; clearance was achieved in 100% of the patients [6].

Pasic et al., in 2003, retrospectively reviewed a case series in which NB-UVB was used in 20 patients with guttate psoriasis aging from 4 to 16 years. In total, 10–39 treatments were performed and Psoriasis Area and Severity Index (PASI) 90 was reached in 45% of patients; 65% reached PASI 70 and 85% reached PASI 50 [7].

Another retrospective study was conducted by Jury et al. in 2006 [8]. NB-UVB was employed using only 50% of the minimal erythema dose of the patients. The study comprised 35 children aged 12 to 16 years. Average clearance was reached in 63%, 88% reached >80% clearance, 9% showed no change and in 28% no results were given [8].

In an open-label study, in 2007, Jain et al. used NB-UVB in 20 children with guttate psoriasis aged 6–14 years [9]. Treatment was performed for 20 weeks. PASI 90 was archived in 60%; 15% reached 70–90% PASI reduction, 5% reached 15–17% PASI reduction and 10% reached less than 50% PASI reduction [9].

Al-Fouzan and Nanda, in 1995, retrospectively reviewed 25 patients with moderate-to-severe childhood psoriasis and skin type V aged 5–12 years [10]. They underwent treatment with UVB for about 7.6 weeks (range: 9–50). They observed 80% clearance in 88% of patients [10].

Reports on photochemotherapy (psoralen plus UVA [PUVA]) in childhood are available from three groups (Table 2). In 1987, Braun-Falco et al. published data on two patients aged 7 and 11 years suffering from erythema annulare centrifugum-type psoriasis. They received 15 and 21 treatments, respectively, and clearance was reached in both patients (100%) [11]. In 1998, Kim et al. reported on one patient, aged 17 years, with palmoplantar psoriasis who reached complete clearance after 18 treatments [12]. Another patient, aged 10 years, was reported in 2006 by Thappa and Laxmisha. The child suffered from guttate psoriasis and was treated by suit-PUVA for 4 weeks, with an 89% improvement observed [13].

As far as side effects are concerned, erythema was observed in two studies [8,9] and occurred in 10–30% of patients. One study mentioned anxiety as an adverse event in 6.75% of treated children [9]. In general, NB-UVB was very well tolerated. The reports on PUVA treatment did not mention any adverse events in the four patients reported [11–13].

From these studies, it appears that NB-UVB shows good results in the treatment of plaque and guttate psoriasis in childhood and has only minimal side effects, mainly erythema. Owing to the study type, mainly uncontrolled case reports, the level of evidence is rather low and the grade of recommendation is statistically limited. A firm conclusion about the use of PUVA cannot be drawn as only the data for four patients have been published.

Peculiar risks of UV phototherapy in childhood

Children’s skin, as compared with adult skin, shows an increased photosensitivity owing to the thin stratum corneum and the restricted ability to tan. In addition, skin in childhood is much more susceptible to photodamage than in later ages [3]. The UV exposure in childhood adds to the cumulative UV lifetime dose, which increases the risk for basal cell carcinoma, squamous cell carcinoma and photoaging in adulthood and senescence. Repeated acute photodamage before the age of 20 years is known to increase the risk for development of malignant melanoma and basal cell carcinoma later in life. It is, therefore, generally recommended to protect the skin in childhood and adolescence.

Although these theoretical aspects are well known, an increase in the risk of basal cell carcinoma, squamous cell carcinoma or melanoma following phototherapy or photochemotherapy in childhood has not been observed in practice, except for one case report [14]. This child, treated with oral PUVA from age 18 months to 8 years because of severe infantile psoriasis, developed two basal cell carcinomas at age 17 and 20 years, respectively. A total of 25 further children in this age-group also having been treated with oral PUVA (and at least five of those received comparably high UV doses) showed no increased carcinogenic or melanoma risk. The authors concluded that exposure to PUVA in childhood might increase the risk of basal cell carcinoma [14]. Up until now, further studies concerning this question are not available, but concerns remain regarding long-term side effects.

The profile of acute adverse events of UV treatment in childhood is similar to that seen in adults. Erythema, herpes simplex reactivation and polymorphous light eruption may be induced [9]. In 5–10% of children anxiety can be a problem [8]. It is recommended that the phototherapy units are rendered more ‘child-friendly’ [15].

International guidelines for UV therapy in childhood

Several national societies have addressed the issue of phototherapy and photochemotherapy in childhood (Table 3). In 1994 [16], and in an update in 2000 [17], the British Photodermatology Group recommended PUVA-bath and cream-PUVA in severe and moderate psoriasis of childhood without any age restriction. Oral PUVA was recommended as a second-line treatment in severe and moderate psoriasis above the age of 16 years and in patients older than 10 years of age suffering from severe psoriasis. NB-UVB is regarded the UV-therapy of choice in moderate-to-severe psoriasis of childhood, if indicated [18].

The American Academy of Dermatology issued guidelines in 1994 [19] and 2010 [20]. Regarding phototherapy in childhood there was no restriction mentioned. Oral PUVA or bath-PUVA was recommended under special conditions only.

In 2010, the French Society of Photodermatology recommended NB-UVB as the UV treatment of choice in children and adolescents with extensive, small and superficial plaques [21].

The German Working Group on Photodermatology issued guidelines in 2003 [22] and an update in 2010 [101]. As regards NB-UVB treatment in moderate and severe psoriasis, no restrictions are defined except for the recommendations described below. PUVA-bath and cream-PUVA should be used only in severe psoriasis, preferably in those aged over 10 years. Oral PUVA is recommended in severe psoriasis only, preferably above the age of 16 years. In any case, phototherapy or photochemotherapy should be performed in combination with topical treatment. In severe psoriasis, combination with systemic treatment should be considered.

The German guidelines also mention contraindications. Absolutely contraindicated are phototherapy and photochemotherapy only in genetic defects associated with photosensitivity. These include xeroderma pigmentosum, Hartnup’s syndrome, Rothmund–Thomson’s syndrome, Bloom’s syndrome, Cockayne’s syndrome, PIBIDS syndrome and albinism. Relative contraindications are the simultaneous medication with potentially photosensitizing drugs, photodermatoses, increased photosensitivity due to skin type, epilepsy and malignant tumors in patients’ history. Multiple and/or atypical melanocytic nevi also represent a relative contraindication. It has to be kept in mind, however, that phototherapy or photochemotherapy in childhood should be restricted to cases in which topical and/or other systemic treatment modalities by themselves are not sufficient to control moderate or severe psoriasis.

Management of childhood psoriasis

An algorithm for treatment of psoriasis in children is discussed by de Jager et al.[23]. Calcipotriene with or without topical steroids are regarded as first-line topical treatment in childhood psoriasis [23]. Dithranol should be used as second-line treatment. Methotrexate or etanercept can be considered as systemic treatment. In plaque-type or guttate psoriasis, NB-UVB or broad-band UV treatment could be added, if topical treatment by itself is insufficient or systemic treatment not feasible. As an alternative, PUVA-bath, preferably in those above the age of 10 years, could be used instead. Oral PUVA should be restricted to patients older than 16 years [23–25]. It is our own experience that, in pustular psoriasis of childhood, PUVA-bath or oral PUVA are superior to NB-UVB. It should, however, be used in combination with systemic steroids and/or retinoids. We lack experience with methotrexate or etanercept in this setting.

Because extensive studies on the risks of phototherapy and photochemotherapy in children are lacking, we have to rely on experience from treatment of adult patients and must extrapolate these data to estimate the acute and long-term risks for children. We know that after UVB phototherapy no enhanced risks for basal cell carcinomas or squamous cell carcinoma have been observed so far, and this was also confirmed for NB-UVB. Shortly after the introduction of systemic photochemotherapy in the 1970s and 1980s, the prospective American PUVA follow-up study [26], as well as clinical studies in Europe [27], have shown a significant risk of squamous cell carcinoma after PUVA with high cumulative doses or high numbers of treatment sessions, respectively. PUVA nowadays is, however, performed more carefully in several ways. Patients are strictly selected, treatment schedules are improved and by the use of combination therapy and avoidance of maintenance therapy the cumulative doses are substantially reduced. PUVA-bath does not seem to enhance carcinogenicity; although, such a risk would theoretically exist. Until more data are available, PUVA-bath should be employed with the same care as oral PUVA. The risk of PUVA therapy inducing malignant melanoma is still being debated but is probably very low [22,101].

Weighing these aspects one can conclude that UVB and even more so NB-UVB are rather safe treatment modalities and can also be employed in childhood. PUVA therapy, if performed in accordance with the special requirements defined below, can be an alternative in cases in which phototherapy or other means of treatment are not effective or not tolerated.

It is pointed out that, in childhood, the following recommendations must be strictly adhered to:

• • Patients have to be carefully selected; contraindications must be respected;

• • Phototherapy and even more so photochemotherapy should be given only if other treatment modalities are not sufficiently effective or not tolerated;

• • The child must be capable of cooperating with the protocol;

• • UV therapy is only possible if eye protection is assured;

• • UV doses should be in the suberythema range and high cumulative doses are to be avoided;

• • Combination with topical or systemic therapy is mandatory;

• • Maintenance treatment is not recommended;

• • UV treatment should be restricted to only two treatment courses per year.

Expert commentary

So far, risk assessments for phototherapy and photochemotherapy in children are not available nor valid, since only few observations on small patient groups or only case reports are published. However, it is felt by the author that long-term risks are largely overestimated in adults as well as children. If restrictions for the use of UV therapy, as defined in this review are followed, NB-UVB and PUVA are valuable treatment options, even in childhood. More data on long-term risks of phototherapy and especially photochemotherapy in childhood are needed. This will lead to more clear-cut recommendations for the use of UV therapy in children.

Five-year view

Other types of phototherapy, such as visible light in the blue range, may be used in atopic dermatitis and, perhaps, in psoriasis. Targeted phototherapy using lasers or high-intensity UV sources emitting in the range between 308 and 312 nm may replace whole-body irradiation and improve safety and efficacy of phototherapy. Conventional phototherapy or photochemotherapy may become obsolete in childhood, since new systemic drugs, such as biologics or targeting molecules, may replace or at least supplement our existing therapeutic strategies.

Table 1. Phototherapy in childhood.

Study (year)	Treatment	Diagnosis	Number of patients (age)	Duration of treatment	Outcome	Ref.
Tay et al. (1996)	NB-UVB	GP, PP	10 (14 months–12 years)	6–20 weeks	Clearance 100%	[6]
Pasic et al. (2003)	NB-UVB	GP	20 (4–16 years)	10–39 treatments	45% PASI 90	[7]
Jury et al. (2006)	NB-UVB MED 50%		35 (4–16 years)		Clearance 63%	[8]
Jain et al. (2007)	NB-UVB	GP	20 (6–14 years)	12 weeks	60% PASI 90	[9]
Al-Fouzan & Nanda (1995)	UVB	Psoriasis	25 (5–12 years)	7.6 weeks (25 treatments)	80% clearance in 88% of patients	[10]

GP: Guttate psoriasis; MED: Minimal erythematous dose; NB-UVB: Narrow band UVB; PASI: Psoriasis Area and Severity Index; PP: Plaque-type psoriasis.

Table 2. Photochemotherapy in childhood.

Study (year)	Treatment	Diagnosis	Number of patients (age)	Duration of treatment	Outcome	Ref.
Braun-Falco et al. (1987)	PUVA	EACP	2 (7 and 11 years)	15–21 treatments	Clearance 100%	[11]
Kim et al. (1998)	PUVA	PP	1 (17 years)	18 treatments	Clearance 100%	[12]
Thappa and Laxmisha (2006)	Suit PUVA	GP	1 (10 years)	4 weeks	89% improved	[13]

EACP: Erythema annulare centrifugum-type psoriasis; GP: Guttate psoriasis; PP: Plaque-type psoriasis; PUVA: Psoralen plus UVA.

Table 3. Guidelines for UV therapy in childhood.

Guideline (year)	Treatment	Indication	Age restriction	Comment	Ref.
British Photodermatology Group (1994, 2000, 2004)	UVB	Moderate-to-severe psoriasis		Second line	[16–18]
	Oral PUVA	Severe psoriasis Moderate psoriasis	>10 years >16 years	Second line
	PUVA-bath Cream-PUVA	Severe and moderate psoriasis	None	Recommended in childhood
American Academy of Dermatology (1994, 2010)	Phototherapy		None	Selected cases only	[19,20]
	PUVA-bath Cream-PUVA			Preferred over oral PUVA
	Oral PUVA			Under special conditions only
German Working Group on Photodermatology (2003, 2010)	NB-UVB	Moderate-to-severe psoriasis	None	In combination with topical treatment	[22,101]
	PUVA-bath Cream-PUVA	Severe psoriasis	Preferably >10 years	In combination with topical or systemic treatment
	Oral-PUVA	Severe psoriasis	Preferably >16 years	In combination with topical or systemic treatment
French Society of Photodermatology (2010)	NB-UVB	Extensive moderate psoriasis with small superficial plaques	Children and adolescents	First-line phototherapy	[21]

NB-UVB: Narrow band UVB; PUVA: Psoralen plus UVA.

Key issues

• • If topical therapy is not sufficient and systemic treatment not feasible, phototherapy or photochemotherapy can be employed as an additive treatment regimen.

• • Genetic disorders associated with photosensitivity are absolute contraindications.

• • At least for narrow band UVB (NB-UVB) efficacy and tolerability in childhood psoriasis are well documented and do not differ from the vast experience in treating adult patients. Experience in photochemotherapy is, however, scarce and long-term risks are not known, but may currently be overestimated.

• • For the time being, first-line treatment in childhood psoriasis is topical calcipotriene, if necessary in combination with topical steroids. If this treatment regimen is not effective, dithranol is recommended. Second-line treatment would be the combination of NB-UVB with topical or systemic treatment. PUVA, preferably PUVA-bath or cream-PUVA, would be the third-line treatment of choice.

• • For systemic treatment, methotrexate or etanercept are suitable.

• • There is theoretically no age restriction for NB-UVB, but the child must be capable of tolerating the procedure and wear eye protection. It is the general opinion that local PUVA should be used in those aged over 10 years and oral PUVA used in those aged over 16 years only.

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Phototherapy and photochemotherapy in childhood psoriasis

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1. A 12-year-old girl has developed plaque-type psoriasis of moderate severity. Which of the following treatments is considered a first-line therapy for this patient?

• □ A Dithranol

• □ B Methotrexate

• □ C Etanercept

• □ D Calcipotriene

2. She has a weak response to first- and second-line therapy, and you consider photo- and photochemo-therapy options for her. Which of the following of these treatment options is most preferred among children?

• □ A Bath psoralen UV therapy (PUVA)

• □ B Cream PUVA

• □ C Oral PUVA

• □ D Narrowband (NB)-UVB

3. What should you consider in regard to the potential risks and limitations of phototherapy for psoriasis in childhood?

• □ A Most phototherapy options are safe for children with genetic disorders associated with photosensitivity

• □ B Erythema is the most common side effect

• □ C There are no age restrictions with regard to treatment with local PUVA in international guidelines

• □ D Oral PUVA appears safe for children over 8 years of age

4. What else should you consider in prescribing phototherapy for this patient?

• □ A High cumulative doses are generally necessary for treatment effectiveness

• □ B Maintenance therapy with phototherapy is necessary for most children

• □ C UV treatment should be restricted to 2 treatment courses per year

• □ D Topical or systemic therapy is not necessary in combination with local PUVA in particular