Department of Dermatology, University of Würzburg, D Würzburg, Germany

Transcription

1 Clinics in Dermatology (2007) 25, Childhood psoriasis Sandrine Benoit, MD, Henning Hamm, MD* Department of Dermatology, University of Würzburg, D Würzburg, Germany Abstract In about one third of patients, psoriasis starts in the first or second decade of life. In the beginning, involvement is often atypical or mild, and a confident diagnosis may be difficult to establish. Plaque psoriasis is the most frequent type, also in children, but lesions are often smaller, thinner, and less scaly than in adults. Treatment can be a challenge because many therapeutic options have drawbacks or are not approved in childhood. Because psoriasis is a life-long disease, affected children and their parents need special support and guidance. We herein focus on the peculiarities of clinical presentations and of the management of psoriatic children and adolescents Elsevier Inc. All rights reserved. Epidemiology Although psoriasis is already a rather frequent condition in children, only limited epidemiologic data are available. An analysis of the medical history of 5600 patients who have psoriasis revealed that in 35%, the disease started before the age of 20 years. 1 Other studies yielded that 30% to 32% of adult patients had onset of disease before the age of 15 years and another 20% between 15 and 19 years. 2 The peak age of onset in childhood varied in different studies. In surveys from India and Denmark, most patients developed first symptoms at the ages of 6 to 10 years, 3,4 whereas other authors from the Middle East and Australia reported a peak of onset at the ages of 0 to 4 years. 5,6 A number of studies indicate that the risk of developing psoriasis is higher if relatives are affected, 7 although data concerning its familial aggregation are inconsistent. 6-8 Faber and Nall 1 from the United States reported that 36% of their patients had an affected family member, whereas Lomholt 9 even found at least one affected relative in 91% on the Faroe Islands. Recent studies from Germany revealed a 14% Corresponding author. Tel.: , (secr.); fax: address: hamm_h@klinik.uni-wuerzburg.de (H. Hamm). prevalence of psoriasis in individuals with parental involvement compared with 3% in persons without parental disease. 7 Compared with 37% in adult-onset patients, 49% of pediatric-onset patients had first-degree family members affected with psoriasis. 8 There were 38% and 14% of pediatric-onset patients compared with 32% and 8% of adultonset patients who had psoriatic second- and third-degree relatives, respectively. 8 Twin studies yielded a concordance of monozygotic twins in up to 75%. 7 Several attempts have been made to detect psoriasis susceptibility loci by linkage studies. Up to now, at least 9 loci are known (PSORS1-9). 7 Interestingly, a strong association exists in early-onset psoriasis for the HLA-Cw6 allele. 10 Clinical features The relative frequency of particular types of psoriasis and patterns of presentation differ between adults and children. Plaque psoriasis with its variants is the most frequent type, also in infancy and childhood. In a large series of over 1200 Australian patients, 34% of the children presented this type of manifestation. 6 Smaller childhood studies showed plaque type rates of 61%, 3 69%, 11 and 84%. 5 Lesions typically X/$ see front matter 2007 Elsevier Inc. All rights reserved. doi: /j.clindermatol

2 556 S. Benoit, H. Hamm consist of well-defined, erythematous papules and plaques of varying size with silvery scales. In contrast to adulthood, lesions are often smaller, less scaly, and thinner, thus hampering a definite diagnosis (Fig. 1A-C). Most affected children have pruritus. 3,8 Mechanical removal of the scales by scratching may result in small bleeding points, a diagnostic criterion known as Auspitz sign. Papular and plaque lesions appear most frequently on the scalp followed by the extensor surfaces of the extremities and the trunk. Scalp involvement with thick, adherent white scales surrounding the hair shafts and only little erythema known as tinea amiantacea can lead to temporary hair loss and may be severe enough to result in visible psoriatic alopecia (Fig. 2A, B). Involvement of the face and the flexural areas (inverse psoriasis) is also more common in children than in adults. In addition, variants of plaque psoriasis including follicular papules, annular, or figurated lesions occur. Linear psoriasis is a highly unusual form of psoriasis, the existence of which has been disputed. Erythematosquamous lesions following the lines of Blaschko are typically present since birth. Unlike inflammatory linear verrucous epidermal nevus, there is no or only mild pruritus, psoriasis phenomena can be elicited, the histology is psoriasiform, and the family history for psoriasis is often positive. 12 A special clinical variant in young children is psoriatic diaper rash, which usually occurs until the age of 2 years Fig. 1 A-C, Typical plaque psoriasis.

3 Childhood psoriasis 557 months, but most patients experience recurrence within the next years. 11 Pustular psoriasis is rare in children. Typically, multiple sterile pustules arise on erythematous skin either localized or generalized. Localized pustular psoriasis can be subdivided into acrodermatitis continua of Hallopeau with digital and nail involvement, palmoplantar pustular psoriasis (Barber- Koenigsbeck type) (Fig. 5), and plaque psoriasis with surface pustules. Generalized manifestations include acute generalized pustular psoriasis (von Zumbusch type) and an annular variant reminding of erythema annulare centrifugum (Fig. 6). Annular pustular psoriasis is characterized by gyrate or annular lesions with an erythematous, scaly, and pustular margin and occurs more frequently in children than in adults. 14 There is often overlap between the 2 generalized forms. Although Morris et al reported acropustulosis as the most frequent type of pustular psoriasis in children, other series indicate that acute generalized and annular forms are more common Clinical presentations that are less frequent in children than in adulthood include psoriatic erythroderma and psoriatic arthritis. Because of difficulties in diagnosis and classification of psoriatic arthritis, exact prevalence data are missing. The estimated prevalence of psoriatic arthritis in all patients with psoriasis differs from 5% to 7% 17 to even 30% 18 ; 8% to 20% of cases of childhood arthritis are diagnosed as psoriatic arthritis. 19 The peak of onset in childhood is between 9 and 12 years of age. 20 Nail changes Fig. 2 Scalp psoriasis. A, Scalp lesions with thick, adherent scales. B, Scalp lesions typically transgressing the frontal hair line. (Fig. 3). In contrast to irritant diaper dermatitis, it is sharply demarcated, brightly red, and involves the inguinal folds. Typically, symptoms respond poorly to conventional treatment of diaper dermatitis. Dissemination with widespread eruption of erythematosquamous lesions on the whole body may follow. In the series of Morris et al, 6 13% of the children presented with diaper rash with dissemination and 4% with localized psoriatic diaper rash. Interestingly, 26% of the remaining patients had a positive history for this special presentation. Nevertheless, it is still under discussion whether diaper rash represents true psoriasis. 6 Guttate psoriasis is another subtype often occurring in children (Fig. 4). Frequencies vary from 6.4%, 6 9.7%, 3 up to 44%. 4 It appears abruptly and often follows streptococcal pharyngitis or, less frequently, perianal streptococcal dermatitis. 13 Papular lesions of up to 1 cm in diameter are scattered symmetrically over the entire integument, predominantly on the trunk, the proximal parts of the extremities, as well as the face and scalp. Guttate psoriasis often resolves spontaneously after 3 to 4 Fig. 3 Psoriatic diaper rash in an 11-month-old infant.

4 558 S. Benoit, H. Hamm Fig. 6 Annular pustular psoriasis resembling erythema annulare centrifugum. are observed in up to 40% of children who have psoriasis. 3,5,11 Most common are nail pits, but all other types of nail involvement such as discoloration in terms of so-called oil drops, onycholysis, subungual hyperkeratosis, onychodystrophy, and splinter hemorrhages can be observed. Nail involvement can precede, coincide with, or succeed psoriasis and may even rarely appear isolated. Nail Fig. 5 Fig. 4 Widespread guttate psoriasis. Localized pustular psoriasis of the palms. abnormalities are more frequent in psoriatic arthritis and in digital skin involvement. Depending on the clinical type of psoriasis, differential diagnosis includes a large number of skin diseases, such as different types of eczema and fungal infections (Table 1). Triggering and exacerbating factors Precipitating factors are more important in pediatricthan in adult-onset psoriasis. 8 They largely include trauma, infections, drugs, and stress. The appearance of psoriatic lesions in uninvolved skin at sites of former trauma is known as isomorphic response or Koebner phenomenon. Any form of trauma including physical, chemical, thermal, surgical, or inflammatory trauma can result in exacerbation of psoriasis. Streptococcal pharyngitis or perianal streptococcal dermatitis typically provokes guttate psoriasis. Infection with human immunodeficiency virus can induce or exacerbate psoriasis. 13,21-23 Whereas the use of β- blocking agents and lithium is a well-known trigger of psoriasis in adult patients, antimalarials and withdrawal of oral or topical corticosteroids play a more important role in rebound or induction of childhood psoriasis In addition, several studies emphasize the influence of psychological and psychosomatic factors like stress or lack of social support in the course of psoriasis. 27 Psoriasis

5 Childhood psoriasis Table 1 Important differential diagnoses of different types of psoriasis in childhood Type of psoriasis Differential diagnosis Plaque psoriasis Nummular dermatitis Tinea corporis Seborrheic dermatitis Scalp psoriasis Tinea capitis Atopic dermatitis Seborrheic dermatitis Linear psoriasis Inflammatory linear verrucous epidermal nevus Psoriatic diaper rash Acrodermatitis enteropathica Irritant diaper rash Candidiasis Erythrasma Flexural psoriasis Candidiasis Erythrasma Tinea corporis Irritant/Allergic dermatitis Guttate psoriasis Lichen planus Pityriasis rosea Pityriasis rubra pilaris Pityriasis lichenoides chronica Secondary syphilis Pustular psoriasis Acute generalized exanthematous (generalized) pustulosis Staphylococcal scalded skin syndrome Pustular psoriasis (annular form) Pustular psoriasis (palmoplantar) Nail psoriasis was recently shown to have a great impact on quality of life in affected children. 28 Treatment General considerations Subcorneal pustular dermatosis Tinea corporis Erythema annulare centrifugum Sweet syndrome Tinea manuum Infected dyshidrotic dermatitis Tinea unguium Nail dystrophy Lichen planus Childhood psoriasis is a therapeutic challenge. Successful treatment requires compliance, which can be enhanced by detailed education of the child and their parents. Choice of treatment has to consider the patient's and the parents' attitude toward the disease; the type, severity, extent, and sites of psoriasis; as well as safety concerns and accessibility of treatment. Various therapies are available, but only a limited number of trials have studied the use of antipsoriatic agents in children, and guidelines are often missing in this age group. Many treatments are not licensed for use in children. The outcome can vary from improvement with maintenance of a cosmetically acceptable state to complete remission. Total clearance is desirable but not essential because few remaining lesions have no prognostic significance. Patients and their parents are initially often unaware and have to learn to accept that psoriasis is a chronic disease without permanent cure. Mostly, topical treatment is sufficient to control disease. Phototherapy, especially with narrowband UVB light, has been proven as effective therapeutic option for psoriasis in adults and might be an option in older children with widespread plaque psoriasis resistant to conventional treatment. Long-term adverse effects of UV light need to be considered in this age group in a special way. Systemic therapy is reserved for children with severe and otherwise treatment-refractory psoriasis. Besides moisturizers and emollients, coal tar preparations are useful in the treatment of psoriatic children. Application is often limited because of smell, color, and phototoxicity. Salicylic acid is helpful in psoriasis of the scalp and lesions in other sites with thick and adherent scaling; however, it should be avoided in infants and toddlers, and its use should be guarded and limited to restricted areas in older children because fatal cases of percutaneous salicylate intoxication have repeatedly been reported in children. 29 Acute guttate psoriasis and pustular psoriasis might be associated with streptococcal infections. 13,23 The benefit of antibiotic therapy and tonsillectomy is still controversially discussed because of missing studies. Considering the relatively benign side effects of these treatments compared with other therapeutic options for severe psoriasis, their use may be worth especially in patients with recurrent streptococcal disease. 30 Anthralin (dithranol) 559 Anthralin is an old and well-established effective treatment for plaque psoriasis and still represents an important therapeutic option in all age groups 31 ; nevertheless, its mode of action is not well understood. Cytotoxic effects and inhibition of mitosis have been discussed. 32 In contrast to hospital settings where anthralin in petrolatum base is still used as long-contact therapy, it is usually applied in outpatients in a short-contact regimen to reduce side effects like irritation, temporary perilesional staining of the skin, and permanent staining of clothing. Anthralin 0.1% to 3% in an easily washable formulation is applied to the psoriatic plaques for 10 to 60 minutes and then washed or showered off. For good therapeutic results, anthralin concentration and/or duration of contact should be increased every few days to maintain slight irritation of the skin. Because therapeutic outcome and side effects depend in a particular way on the correct application, good information and education of patients and parents are of paramount importance. Anthralin therapy can be combined with other topical treatments or UVB

6 560 S. Benoit, H. Hamm phototherapy to improve the response. Few large psoriatic plaques may also be treated with anthralin in zinc paste. Unlike petrolatum base and washable products, zinc paste containing anthralin should strictly be applied to the lesions only, and higher concentrations are needed. Vitamin D 3 analogues Calcipotriol, tacalcitol, and calcitriol are vitamin D 3 analogues that induce differentiation of keratinocytes and inhibit their proliferation. Particularly, calcipotriol is an effective and safe therapeutic option in children with mild to moderate plaque psoriasis involving less than 30% of the body surface. The most common side effects are burning sensations or irritation of the skin especially when used in the flexures and on the face. Application in these areas should be avoided. No serious side effects or influence on calcium and bone metabolism were observed when vitamin D 3 analogues were correctly used and the recommended age-depending maximum dose was not exceeded In adults, combination with topical corticosteroids or UVB phototherapy was shown to increase the efficacy of vitamin D 3 analogues Topical corticosteroids Because of availability, acceptance, ease of application, and fast improvement of psoriatic lesions, topical corticosteroids are often prescribed as first choice topical treatment in psoriatic children. Because of their antiinflammatory properties, or because of missing licensed alternatives for treatment of psoriatic lesions localized in flexures, they are particularly useful in treatment of highly pruritic lesions. Different preparations and strengths are available and should be adapted to sites of application. Generally prolonged use of highly potent corticosteroids should be avoided. Strategies to reduce the amount of corticosteroids used are intermittent or rotational therapy as well as combination with other treatments. Nevertheless, side effects of long-term use like skin atrophy and striae at the site of application must be considered, particularly in facial, flexural, and genital skin. In rare cases, suppression of the hypothalamic-pituitary-adrenal axis may occur after prolonged, widespread application of potent topical corticosteroids. Application should be slowly tapered off to avoid rebound of psoriasis after treatment with topical corticosteroids. Calcineurin inhibitors The topical application of calcineurin inhibitors like tacrolimus and pimecrolimus is a well-established treatment of atopic dermatitis but is not licensed for psoriasis. In several studies, topical calcineurin inhibitors also proved successful in adult psoriasis Because of absent atrophogenic risk, they are particularly helpful and effective in inverse psoriasis, as a recently published study in 13 psoriatic children confirmed. 42 Tazarotene Tazarotene is a topical retinoid approved for the treatment in psoriatic adults, but there is only little experience in children. Phototherapy Narrowband UVB light is the first-line phototherapy in adults with extensive plaque psoriasis, and trials in children indicated good results in children as well Because of potential early side effects like erythema and burning, longterm side effects like photoaging or carcinogenicity and the crampedness of the UV light cabinet phototherapy should only be considered for older children and adolescents with severe widespread disease in which topical treatments have failed. To reduce the cumulative UVB dose and therefore simultaneously the carcinogenic risk, combination with anthralin or vitamin D 3 analogues is reasonable. In some children with special clinical presentations like palmoplantar forms of pustular psoriasis, psoralen plus UVA phototherapy might be indicated. In these cases, psoralen plus UVA bath treatment should be preferred to oral photochemotherapy because of avoidance of gastrointestinal side effects, needlessness of eye protection, and shorter photosensitization time. Systemic treatment If control of disease cannot be obtained by topical treatment or phototherapy, systemic medication has to be considered. Classic antipsoriatic drugs like acitretin, methotrexate, or ciclosporine are also used in children, although clinical trials for this age group are missing. In addition, socalled biologics that are successfully used in severely affected psoriatic adults are getting more and more important also in childhood psoriasis. No published information is currently available for the use of fumaric acid in children. Acitretin Acitretin is an aromatic retinoid that influences epithelial differentiation and can favorably be used in severe, especially in severe pustular psoriasis It increases the effect of topical treatment and is, therefore, especially suited for combination therapy. 49,50 Besides its highly teratogenic potential, mucocutaneous adverse effects like cheilitis, xerosis, skin peeling, and hair loss have to be considered. In addition, increase of liver function enzymes and hyperlipidemia may occur. In children, long-term treatment can lead to premature epiphyseal closure and

7 Childhood psoriasis impaired bone growth. 51 Regular follow-up visits must be ensured. Depending on the type of psoriasis, treatment is started with a dose of 0.3 to 1 mg/kg acitretin per day. When significant improvement occurs, the initial dose should be gradually tapered until a dose of 0.2 mg/kg per day and therapy should be continued 2 months over remission. 52 Methotrexate Methotrexate inhibits the replication and functions of T and B lymphocytes and suppresses the secretion of several cytokines such as interleukin-1, interferon α, and tumor necrosis factor α. It was one of the first systemic drugs used in psoriasis and is widely used to treat adult patients. Although controlled studies concerning dosage and safety are lacking in pediatric patients, good clinical response was obtained in several cases. 15,53-55 Kumar et al 53 successfully treated 7 patients of 3 to 16 years of age with a dose of 0.2 to 0.4 mg/kg once a week. Except for nausea and vomiting, no major side effects occurred. The benefit of folate supplementation in methotrexate-treated patients to reduce side effects is still discussed controversially. 56 Nevertheless, regular monitoring is needed to prevent and identify acute hematotoxicity or hepatotoxicity. Cyclosporine Cyclosporine is another immunosuppressive agent that inhibits T cell activation via calcineurin inhibition. It is effective in severe forms of psoriasis such as pustular or erythrodermic psoriasis. 57 Again, there is only limited experience of its use in psoriatic children. 55,58,59 Usually, cyclosporine is administered in an initial dose of 3 to 5 mg/kg per day. 60,61 The dose should be tapered gradually to the lowest dose needed to maintain disease control. Considering major side effects like renal dysfunction or hypertension, cyclosporine therapy should be reserved for the most severe and therapy-resistant cases in childhood and adolescence. Biologics In the last years, better understanding of the pathogenesis of psoriasis and biotechnological progress led to the generation of novel drugs, the so-called biologics. This group of drugs includes antibodies and fusion proteins targeting cytokines like tumor necrosis factor α that play an important role in the pathogenesis of psoriasis. In contrast to psoriatic adults, biologics are not yet approved for psoriasis treatment in underage patients. Nevertheless, first case reports of successful and safe employment of infliximab and etanercept indicate new future therapeutic prospects in severely affected psoriatic children. 55,62-64 Conclusions Childhood psoriasis represents a special challenge. Besides proper treatment of the disease considering the clinical presentation and the age of the patient, management of these patients has to include supportive care and consider quality of life issues like psychosocial ostracism. Most children have mild to moderate psoriasis for which topical treatment is sufficient. Although spontaneous remission is more frequent in pediatric- than in adult-onset patients, clearance is often followed by recurrence. 8 Complete clearance of lesions has not to be achieved at any price because it has no prognostic significance. In most patients, intermittent therapy is sufficient to control the disease, but some children worsen with age and will require a more aggressive therapy. References Faber E, Nall M. The natural history of psoriasis in 5600 patients. Dermatologica 1974;148: Swanbeck G, Inerot A, Martinsson T, et al. Age at onset and different types of psoriasis. Br J Dermatol 1995;133: Kumar B, Jain R, Sandhu K, et al. Epidemiology of childhood psoriasis: a study of 419 patients from northern India. Int J Dermatol 2004;43: Nyfors A, Lemholt K. Psoriasis in children. A short review and a survey of 245 cases. Br J Dermatol 1975;92: al-fouzan AS, Nanda A. 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