Systemic and Light Therapies for the Management of Childhood Psoriasis: Part II
K. M. Cordoro, MD
Department of Dermatology, University of California, San Francisco, CA, USA
The choice of treatment for psoriasis in children, as in adults, is determined by disease
acuity, morphology, distribution, severity, and the presence of comorbidities, such as
psoriatic arthropathy. Fortunately, most patients present with mild disease that responds
adequately to topical medications. A minor subset of children will present with severe,
rapidly evolving disease that requires more aggressive interventions. Advanced medical
treatment with systemic and phototherapy is challenging and primarily anecdotal, as
these modalities are neither well-studied nor approved for use in children.
Part II of this
2-part series features an overview of systemic and light therapies including their varying
degrees of effectiveness, potential side-effects and applications in clinical practice.
antibiotics, biologics, children, cyclosporine, methotrexate, phototherapy, retinoids, UVA, UVB
The 3 most commonly used systemic treatments for psoriasis in children, as in adults,
are acitretin, methotrexate, and cyclosporine. None are US FDA labeled for this
indication in children nor have they undergone the scrutiny of randomized controlled
trials in the pediatric population. Accumulated data regarding the utility, benefits, and
risks of these agents for the treatment of psoriasis derives largely from long-term use
in children with disorders of cornification (retinoids), juvenile rheumatoid arthritis
(methotrexate), and transplanted organs (cyclosporine).
Treatment with systemic
agents is typically reserved for severe, refractory, widespread or incapacitating
disease, pustular or erythrodermic forms, and psoriatic arthropathy. Close clinical and
laboratory monitoring for associated toxicity is mandatory for all 3 agents.
Acitretin is a second generation aromatic retinoid that is US FDA-approved for
the treatment of severe psoriasis in adults. It is not immunosuppressive and has no
formal restrictions on duration of therapy. Acitretin is useful for intermittent rescue
therapy in children with generalized pustular flares or longer term treatment of older
children with pustular, erythrodermic or severe plaque psoriasis as monotherapy, or
in combination with other agents such as topicals and narrowband UVB (NB-UVB)
There are convincing data, from long-term clinical follow-up of
patients with disorders of cornification, that oral retinoids are safe in children, but
do require monitoring as in adults.3 Treatment should be initiated and maintained at
dosages at or below 0.5-1mg/kg/day to limit short- and long-term toxicities. The most
common adverse events are mucocutaneous (xerosis, cheilitis, skin fragility, epistaxis)
and minor reversible alterations in liver enzymes and lipids, which rarely necessitate
cessation of therapy.4
The most feared complications are teratogenicity and effects on bone. The use of acitretin in females of childbearing
potential should be avoided if possible. Pregnancy must be
avoided for 3 years following discontinuation of acitretin
because of the potential for irreversible esterification to
etretinate with ingestion of ethanol. Although effects on
bone similar to that observed in chronic vitamin A toxicity
have been rarely identified with long-term, high-dose use,5
available evidence does not substantiate a clear link between
radiologic skeletal abnormalities and long-term, low-dose
use.6 In children anticipated to be on long-term retinoid
therapy, baseline and serial or symptom-driven radiologic
evaluation of the long bones and spine, and close monitoring
of growth parameters are appropriate.
Methotrexate has been used for psoriasis since the 1950s
and remains the most widely prescribed drug for severe
psoriasis worldwide. Its use in children is reserved for
severe, recalcitrant, extensive or disabling disease, psoriatic
arthritis, or erythrodermic and generalized pustular forms
unresponsive to topical and phototherapy.
may be used to gain control in the acute phases or flares
of psoriasis followed by transition to more conventional
topical or light-based maintenance regimens. In children,
0.2-0.7mg/kg/week is the recommended therapeutic dose
range.7 In nonemergent situations, a test dose of 1.25mg
to 5mg, followed in 1 week by laboratory monitoring, is
recommended to detect early toxicity. Conservative dose
escalations of 1.25-5mg/week are advised until therapeutic
effect is obtained, followed by a slow taper to a beneficial
The drug is supplied as 2.5mg scored
tablets that can be split or crushed and given with nonmilk
food, and as an injectable preparation (2.5mg/mL and
25mg/mL supplied in 2mL vials) that can be given orally.
Side-effects, both short- and long-term, are observed in
children taking methotrexate for psoriasis, but are much
less frequent and severe than in adults, likely because of the
relative lack of comorbidities and concurrent medications
Regardless of age, methotrexate is associated
with a substantial number of potential side-effects and drug
interactions and requires vigilant clinical and laboratory
Folic acid supplementation increases
tolerability and reduces the risk of pancytopenia, nausea,
macrocytic anemia, and liver enzyme elevations without
Cyclosporine is an immunosuppressant that is US
FDA-approved for severe, recalcitrant psoriasis in
non-immunocompromised adults and for prevention and
treatment of transplant rejection in children >6 months of
age. In carefully selected and closely monitored patients,
cyclosporine can produce relatively rapid clinical effects
and can be effectively combined with topical and systemic
therapies to increase efficacy and reduce toxicity.
is limited by the risk of nephrotoxicity, hypertension,
and immunosuppression, and close laboratory and blood pressure monitoring prior to and throughout the treatment
period is required.11 Maximum dosing by US guidelines is
4mg/kg/day and total duration of therapy should not exceed
1-2 years.11,12 Onset of effect is rapid (4-8 weeks) and gradual
tapering should start after a 1-3 month period of stability and
adjusted according to clinical response. Rebounds during
taper or after withdrawal are not uncommon. Sequential
therapy (i.e., the addition of a second, less potentially toxic
agent, such as acitretin) in select situations allows gradual
tapering of cyclosporine and reduced total dose and duration
of both medications in an effort to maximize efficacy and
The risk of malignancy, skin cancer, and
lymphoproliferative disorders, as observed in the transplant
population, are a concern in children; however, evidence
suggests that risk is minimal if using 5mg/kg/day or less in
patients who are not on concomitant immunosuppressive
Cyclosporine is available as 25mg and 100mg
soft gelatin capsules and as a clear yellow liquid supplied in
50mL bottles containing 100mg/mL.
As the complex molecular mechanisms underlying the
pathogenesis of psoriasis become increasingly clear, targeted
therapies aimed at specific components of the inflammatory
cascade, such as tumor necrosis factor, are gaining popularity
and are in widespread use among adults with psoriasis and
psoriatic arthritis. Experience with their off-label use in
children with psoriasis is limited, and critical evaluation of
the potential risk of these agents in children with psoriasis
is difficult because of the small number of children treated
and the short follow-up period.
No specific guidelines exist
for dosing and laboratory monitoring in pediatric patients.
Enthusiasm for the efficacy, short-term safety, and ease of
use of anti-tumor necrosis factor alpha agents in children is
reasonably tempered by concerns about the risk of infection,
lymphoma, demyelinating disorders, and cost.15
Phototherapy is an excellent, safe, and appropriate treatment
for carefully selected patients with refractory plaque, guttate
and pustular disease, diffuse (>15%-20% body surface area)
involvement, or focal debilitating palmoplantar psoriasis.
To avoid burns and other light-associated complications, it
is essential to utilize a phototherapy unit with experienced
and well-trained personnel who are comfortable working
with children. Three main types of therapeutic light
options exist: broadband UVB (BB-UVB, 280-320nm),
NB-UVB (311-313nm) and UVA (320-400nm).
encompasses the most biologically active radiation in
sunlight and guttate psoriasis responds best, but plaque
psoriasis in children tends to be thinner and will respond
to higher doses and a longer duration of treatment. One
of the greatest advances in phototherapy for psoriasis is
the use of NB-UVB, which, at therapeutic doses, is less
erythemogenic than other wavelengths in the UVB range.16
Centered on 311-313nm, NB-UVB is safe and effective
for a number of photoresponsive dermatoses in children, including psoriasis.17-19 Short-term side-effects of UVB
phototherapy are usually mild and consist of xerosis,
erythema, pruritus, and photoactivation of herpesvirus.
Potential long-term effects include premature photoaging
and cutaneous carcinogenesis.20
Photochemotherapy (psoralen plus ultraviolet A, [PUVA])
is based on the interaction between UVA radiation and
psoralen, a photosensitizing chemical. In children less than
12 years, oral PUVA is rarely used and if so, is done with
extreme caution and should be restricted to psoriasis and
phototherapy centers staffed by well trained, experienced
physicians and nurses.
Many authors consider oral psoralen
relatively contraindicated in children less than age 12 and
prefer topical PUVA because of the many short- and longterm
toxicities associated with psoralen ingestion (e.g.,
nausea, vomiting, headache, hepatotoxicity, generalized
photosensitization requiring 24 hours of photoprotection,
ocular toxicity, acute risk of burning, and long-term risk
of skin cancer).21 In children, NB-UVB is more convenient
and may be less carcinogenic. Given the downsides of
using psoralens in children and adults, NB-UVB is now
considered first-line phototherapy.22
Antibiotics and Tonsillectomy
Ample clinical and laboratory evidence exist suggesting
precipitation, exacerbation, and persistence of guttate
and other forms of psoriasis by pharyngeal and perianal
streptococcal infections. Dermatologists often prescribe
empiric systemic antibiotics for recurrence or flares of
guttate psoriasis and occasionally recommend tonsillectomy
in patients with refractory psoriasis and recurrent tonsillitis.
Two recent exhaustive reviews assessed the evidence for
such interventions in the management of childhood psoriasis
and concluded that available evidence does not support the
efficacy of oral antibiotics or tonsillectomy.23,24
Treating children with psoriasis is both rewarding and
challenging. It requires a current, comprehensive knowledge
of available therapies including the mechanism of action,
clinical action spectrum, potential toxicity, and appropriate
monitoring. Combination, rotational, and sequential therapy
as introduced by Menter, Weinstein and White, and Koo,
respectively, are time honored methods which aim to
improve overall efficacy while reducing the individual
toxicity of the chosen medications.25
requires continued education and support of the patient
and the family. Advocacy and education groups such
as the National Psoriasis Foundation (www.psoriasis.org;
800-723-9166) are excellent resources and can serve as an
extension of your comprehensive care.
- Kopp T, Karlhofer F, Szepfalusi Z, et al. Successful use of acitretin in conjunction with narrowband ultraviolet B phototherapy in a child with severe pustular psoriasis, von Zumbusch type. Br J Dermatol 151(4):912-6 (2004 Oct).
- Lee CS, Koo J. A review of acitretin, a systemic retinoid for the treatment of psoriasis. Expert Opin Pharmacother 6(10):1725-34 (2005 Aug).
- Lacour M, Mehta-Nikhar B, Atherton DJ, et al. An appraisal of acitretin therapy in children with inherited disorders of keratinization. Br J Dermatol 134(6):1023-9 (1996 Jun).
- Brecher AR, Orlow SJ. Oral retinoid therapy for dermatologic conditions in children and adolescents. J Am Acad Dermatol 49(2):171-82 (2003 Aug).
- Katugampola RP, Finlay AY. Oral retinoid therapy for disorders of keratinization: single-centre retrospective 25 years’ experience on 23 patients. Br J Dermatol 154(2):267-76 (2006 Feb).
- Halverstam CP, Zeichner J, Lebwohl M. Lack of significant skeletal changes after long-term, low-dose retinoid therapy: case report and review of the literature. J Cutan Med Surg 10(6):291-9 (2006 Nov-Dec).
- Paller AS. Dermatologic uses of methotrexate in children: indications and guidelines. Pediatr Dermatol 2(3):238-43 (1985 Mar).
- Callen JP, Kulp-Shorten CL, Wolverton SE. Methotrexate. In: Wolverton SE, editor. Comprehensive dermatologic drug therapy. 2nd ed. Philadelphia: Saunders Elsevier; p163-81 (2007).
- Swords S, Lauer SJ, Nopper AJ. Principles of treatment in pediatric dermatology: systemic treatment. In: Schachner LA, Hansen RC, editors. Pediatric dermatology. 3rd ed. Philadelphia: Mosby (Elsevier); p133-43 (2003).
- Gisondi P, Fantuzzi F, Malerba M, et al. Folic acid in general medicine and dermatology. J Dermatolog Treat 18(3):138-46 (2007).
- Lebwohl M, Ali S. Treatment of psoriasis. Part 2. Systemic therapies. J Am Acad Dermatol 45(5):649-61 (2001 Nov).
- Pereira TM, Vieira AP, Fernandes JC, et al. Cyclosporin A treatment in severe childhood psoriasis. J Eur Acad Dermatol Venereol 20(6):651-6 (2006 Jul).
- Koo J. Systemic sequential therapy of psoriasis: a new paradigm for improved therapeutic results. J Am Acad Dermatol 41(3 Pt 2):S25-8 (1999 Sep).
- Ellis CN. Safety issues with cyclosporine. Int J Dermatol 36 Suppl 1:7-10 (1997 Dec).
- Cordoro KM, Feldman SR. TNF-alpha inhibitors in dermatology. Skin Therapy Lett 12(7):4-6 (2007 Sep).
- Kist JM, Van Voorhees AS. Narrowband ultraviolet B therapy for psoriasis and other skin disorders. Adv Dermatol 21:235-50 (2005).
- al-Fouzan AS, Nanda A. UVB phototherapy in childhood psoriasis. Pediatr Dermatol 12(1):66 (1995 Mar).
- Jain VK, Aggarwal K, Jain K, et al. Narrow-band UV-B phototherapy in childhood psoriasis. Int J Dermatol 46(3):320-2 (2007 Mar).
- Tay YK, Morelli JG, Weston WL. Experience with UVB phototherapy in children. Pediatr Dermatol 13(5):406-9 (1996 Sep-Oct).
- Pasic A, Ceovic R, Lipozencic J, et al. Phototherapy in pediatric patients. Pediatr Dermatol 20(1):71-7 (2003 Jan-Feb).
- Wolff K. Side-effects of psoralen photochemotherapy (PUVA). Br J Dermatol 122 Suppl 36:117-25 (1990 Jun).
- MacDonald A, Burden AD. Psoriasis: advances in pathophysiology and management. Postgrad Med J 83(985):690-7 (2007 Nov).
- Owen CM, Chalmers RJ, O’Sullivan T, et al. A systematic review of antistreptococcal interventions for guttate and chronic plaque psoriasis. Br J Dermatol 145(6):886-90 (2001 Dec).
- Wilson JK, Al-Suwaidan SN, Krowchuk D, et al. Treatment of psoriasis in children: is there a role for antibiotic therapy and tonsillectomy? Pediatr Dermatol 20(1):11-5 (2003 Jan-Feb).
- Lebwohl M. Combination, rotational and sequential therapy. In: Weinstein G, Gottlieb A, editors. Therapy of moderate to severe psoriasis. 2nd ed. New York: Marcel Dekker; p179-95 (2003).
In this issue:
- Systemic and Light Therapies for the Management of Childhood Psoriasis: Part II
- The Role of the Dermatologist in Identification and Treatment of the Early Stages of Psoriatic Arthritis
- Update on Drugs and Drug News - May 2008