Psoriasis in childhood and adolescence

Abstracts

A psoríase é doença inflamatória crônica, imunologicamente mediada, recorrente e de caráter universal. Aproximadamente um terço dos adultos acometidos refere início da doença antes dos 16 anos de idade. Quanto mais precoce, mais grave tende a ser a evolução do quadro. Em crianças, as lesões podem ser fisicamente desfigurantes, causando prejuízos psicológicos e evidente comprometimento da qualidade de vida. As medicações sistêmicas utilizadas na psoríase, bem como a fototerapia, têm indicação limitada na infância, devido aos efeitos cumulativos das drogas, à baixa aceitação e ao risco de teratogenicidade. Nesta seção, discutiremos as principais manifestações clínicas da psoríase na infância e na adolescência, bem como os diagnósticos diferenciais, opções terapêuticas e prognóstico.

Adolescente; Criança; Epidemiologia; Infância; Psoríase; Quadro clínico; Terapêutica

CONTINUING MEDICAL EDUCATION

Psoriasis in childhood and adolescence

Ricardo Romiti^I; Luciana Maragno^II; Marcelo Arnone^III; Maria Denise Fonseca Takahashi^IV

^IAssistant Physician. Department of Dermatology, Hospital das Clinicas, Universidade de Sao Paulo (USP) - Sao Paulo (SP), Brazil

^IIResident Physician. Department of Dermatology, Hospital das Clinicas, Universidade de Sao Paulo (USP) - Sao Paulo (SP), Brazil

^IIIAssistant Physician. Department of Dermatology, Hospital das Clinicas, Universidade de Sao Paulo (USP) - Sao Paulo (SP), Brazil

^IVAssistant Physician. Department of Dermatology, Hospital das Clinicas, Universidade de Sao Paulo (USP) - Sao Paulo (SP), Brazil

Mailing Address

ABSTRACT

Psoriasis is a chronic, immunologically mediated, recurrent and universal inflammatory disorder. Approximately one third of adults refer onset before 16 years of age. The sooner the onset, the worse is the prognosis. In children, lesions may be physically disfiguring, leading to psychological impairment and evident loss of quality of life. Systemic therapy used in psoriasis, as well as phototherapy, has limited use in children due to accumulative effects of drugs, low acceptance, and risk of teratogenicity. In this section, we discuss the main clinical aspects of psoriasis in childhood and adolescence, differential diagnosis, therapeutic options, and prognosis.

Keywords: Adolescent; Child; Clinical features; Epidemiology; Infancy; Psoriasis; Therapeutics

INTRODUÇÃO

Psoriasis vulgaris represents a rare dermatosis in childhood and corresponds to about 4% of all dermatosis observed in patients below the age of 16 years ¹. Psoriasis that starts in childhood has high family incidence. The most common type presented in infants is characterized by well-delimited erythematous plaques involving the genitals, gluteal and peri-umbilical region, which tends to be persistent and resistant to treatment (Figure 1). Facial affection is rare. As time goes by, new erythematous-squamous plaques show up, affecting primarily the trunk and the limbs.

Childhood psoriasis variants include peri-ungual affection with different levels of onycodystrophy present (Figure 2), as well as forms restricted to the scalp. Guttate psoriasis is rarely observed in children below the age of 5 years.

Treatment basically depends on severity, association with articular affections, presence of co-morbidities, patient age, previous therapies and adverse events. To present, there is no authorized systemic treatment for psoriasis in childhood approved by the Food and Drug Administration (FDA). In Brazil, acitretin and cyclosporine have indication for pediatric use in severe cases of psoriasis. As to methotrexate, the package insert does not include indication to children with psoriasis, but it refers to its use in the symptomatic control of recalcitrant, severe and disabling psoriasis, especially in cases that do not response well to other approaches.

HISTORY

The first historical report on psoriasis was made by Celsus (25AC-DC45). Hippocrates (460-375AC) described lesions similar to psoriasis that he classified as "squamous eruptions" and named them lopoi (from lepo, desquamation). Galenus (DC 133-200) created the word psoriasis, from Greek, psora, pruritus. However, palpebral affection associated with other psoriasiform lesions, as well as the presence of desquamation and pruritus in the original description of Galenus, suggest the hypothesis that his report referred in fact to seborrheic eczema.

In the end of 18th century, psoriasis and Hansen's disease were classified together and patients were treated based on the same prejudice and marginalization by the society. Willian, in the beginning of 19th century, made a careful and precise characterization of psoriasis and described all its different clinical variants. Only in 1841, psoriasis was definitely separated from Hansen's disease by Ferdinand von Hebra.

EPIDEMIOLOGY

Even though psoriasis is seldom reported in children, the real prevalence in this age range is unknown ². It is estimated that between 25 and 45% of the cases of psoriasis may start their course before the age of 16 years and about 2% of them before the age of 2 years 3. It may in some exceptional occasions be congenital or nevoid ⁴. Even though in the past there was greater prevalence of psoriasis in girls, but current studies indicate that both genders are equally affected, similarly to adults .^5,6

The risk of developing psoriasis is greater when one of the parents is affected. Among the patients who develop psoriasis in childhood, 49% have first degree relatives with the disease, whereas in patients who have the onset at adult age, this figure is 37%. Studies with twins have shown agreement between monozygotic twins of up to 75% ⁶.

ETIOPATHOGENESIS

Despite the advances in the last decade, the cause of psoriasis remains unknown. It is a chronic skin and joint inflammatory disease, immunomediated, with polygenic predisposition, characterized by complex modifications of growth and epidermal differentiation and multiple biochemical, immune and vascular abnormalities, in addition to the unexplained correlation with emotional episodes. In the past, keratonocyte disorder was the etiopathogenic basis of psoriasis; however, currently it is known that it is initially an immune affection mediated by type Th1 response ^5,7,8,9,10.

The genetic component involved in the etiology of psoriasis may be evidenced through studies about family incidence, incidence in cases of issues, level of concordance between twins and identify of histocompatibility antigens (HLA). Multiple HLA alleles have been associated with psoriasis, especially HLA-Cw6, HLA-B13, HLA-B17, HLA-B37, HLA-DR7, HLA-B46, HLA-B57, HLA-Cw1 and HLA-DQ9. Recent studies have revealed loci of susceptibility named Psors, located on chromosomes 6p, 17q, 4q, and 1q^5,6,11.

Populational studies with monozygotic twins have shown there is a participation of environment factors in the process, among which cutaneous trauma, infections (beta-hemolytic streptococcus, HIV), drugs (lithium, beta-blockers, antimalaric agents and interruption of corticoid therapy - in this case, it may lead to severe generalized pustular psoriasis and erythrodermia), vaccination, psychogenic/ emotional factors, endocrine and metabolic disorders, smoking, alcohol abuse and weather variations ¹². There is a possible exacerbation of psoriasis by the use of non-hormonal antiinflammatory drugs, tetracyclines and ACE inhibitors should be considered with care, because despite the high frequency of use of these drugs, there are few reports associating their use with worsening of psoriasis ¹³.

In pathogenesis, there is acceleration of epidermal germinative cycle, increase in proliferation cells and shortening of the time required for cell renovation on the epidermis, both of the lesion and the normal skin in patients with psoriasis. It is believed that hyperproliferation of keratinocytes is due to increase in amount of epidermal growth factor (EGF), alpha transformation growth (TGF-alpha) and the participation of proinflammatory cytokines (IL-1, IL-6, IFN-gamma), which would operate as mitogenic agents to these cells. Other implied mechanism would be failure of keratinocytes to respond to inhibitory cytokines (IFNµ, TNFa, TGFß) produced by CD8 lymphocytes in psoriasis lesions. To guttate psoriasis, there is induced self-immunity by cross-reaction to streptococcus antigens.

CLINICAL ASPECTS

Relative frequency of clinical types of psoriasis and the clinical presentations of the disease differ among adults and children. Plaque psoriasis is the most frequent clinical variant in children and adolescents (34-84%), apart from the form that affects the diaper region (psoriatic diaper rash)⁵.

Lesions are characterized by papules and well-delimited erythematous plaques of varied sizes and silver desquamation, frequently organized in a symmetric fashion. In childhood, psoriasis may present atypical characteristics, that is, single or few erythematous plaques that are slightly desquamative, affecting uncommon regions such as the face - including periorbital, perioral and nasal regions - many times hindering the correct diagnosis (Figure 3). What is characteristic in childhood psoriasis is follicular affection with variable pruritus, better detected in limb lesions (Figure 4A) ^14,15,16. There may also be alternate forms that mimic pityriasis alba (Figure 4B).

   

Psoriasis lesions frequently affect the scalp, followed by extremities and the trunk. There is frequent symmetric distribution of lesions and absence of pruritus (Figure 5A). Affection of hands, feet, genitals and flexion areas (Figure 5B), including the periumbilical area, is also common among children ^6,17.

   

The congenital form, defined as occurrence of any of the clinical variants of psoriasis at birth or during the first days of life, is extremely rare. It is normally expressed in the forms of plaque psoriasis. Cases of congenital or neonatal erythrodermic psoriasis are rare, severe and demand immediate intervention. Differential diagnosis in these cases include staphylococcal scalded skin syndrome, toxic shock syndrome, candidiasis, congenital ichthyosis, immunodeficiencies, such as Omenn syndrome, metabolic disorders, atopical and seborrheic dermatitis, pityriasis rubra pilaris and generalized mastocytosis ¹.

Scalp affection, with presence of white scales, adhered and thickened placed around hair follicles with mild erythema (pseudo-tinea amiantacea) may lead to temporary hair loss or even psoriatic alopecia. There may be single plaque lesion or poorly delimited and desquamative lesions, clinically indistinguishable from seborrheic dermatitis ^{17, 18}.

The characteristic topography in children is affection of diaper area (psoriatic diaper rash), which occurs in children up to the age of two years. Differently from diaper dermatitis (contact dermatitis), lesions have clearer and brighter erythema, well-delimited margins, and involve inguinal folds, with variable pruritus. Classically, these signs and symptoms respond poorly to conventional therapeutic approach to diaper dermatitis. After one or two weeks from onset of diaper erythema, some children develop the classical lesions of psoriasis on the face, scalp, trunk and limbs ¹⁷.

Guttate psoriasis is a clinical variant of psoriasis that affects children in frequencies that range from 6.4% to 44% 6. Skin presentation is sudden, normally preceded by streptococcal infection (56 - 85% of the cases),5 of the upper airways. Papular lesions of up to 1cm in diameter are symmetrically displaced all over the body surface, predominantly on the trunk and root of limbs. Guttate psoriasis normally regresses spontaneously within 3 to 4 months. Occasionally, lesions may persist and increase in size, taking the characteristics of plaque psoriasis ¹⁹. Within 10 years, between one and two thirds of patients with diagnosis of guttate psoriasis progress to chronic presentation in plaques.

Linear psoriasis, a rare form of psoriasis, is characterized by erythematous-squamous lesions following the lines of Blaschko. It may start in childhood or adult age and affect essentially the trunk or the limbs with variable extension and progression. It should be differentiated from inflammatory linear verrucous epidermal nevus (ILVEN), whose onset is in childhood and affects primarily inguinal-crural and genital regions, following the lines of Blaschko. Pruritus may be intense. Despite the fact that histopathology may evidence psoriasiform dermatitis, the chronicity of the lesion and resistance to any form of therapeutic intervention differentiate it from linear psoriasis ^{6, 20}.

Pustular psoriasis in children is rare. It is characterized by multiple sterile pustules, over erythematous basis. It may be generalized or localized. The generalized form (von Zumbusch) may be triggered in a patient with psoriasis vulgaris by interrupting systemic corticoid, hypocalcemia, infection or local irritants. In general, there is affection of overall status, high temperature and leukocytosis. Eruption is sudden and generalized, but commonly it persists for few weeks, reverting the previous presentation or transforming it into erythrodermic psoriasis (Figure 6). The localized form comprises three subforms: pustular plaque or annular psoriasis, continuous acrodermatitis of Hallopeau (pustules or pus lakes in fingers and more rarely on the toes, chronic course, no tendency to spontaneous remission), and palmar-plantar pustular (characterized by episodes of sterile pustules comprising palmar and plantar regions, symmetrically distributed and without other manifestations) ¹⁹. Rare complications of this form of psoriasis, described in children, are renal failure, cholestatic jaundice, bone lytic lesions, and sterile multifocal osteomyelitis 1. The annular form that is associated with erythematous-desquamative lesions and peripheral pustules seem to be exclusive to children (Figure 7) ². This variant may be followed by fever, aseptic osteomyelitis, and lung impairment.

When compared to adults, erythrodermic psoriasis and psoriatic arthritis are less frequent clinical presentations in children.

In erythordermic psoriasis, there is marked, universal edema with variable desquamation. There may be natural progression of the disease, or more frequently, after attempted therapies, interruption of systemic corticoid therapy, or in patients with AIDS. There is clear predominance of erythema over desquamation. There may be hyper or hypothermia and in long-term cases, there may be reduction of cardiac output and impairment of liver and renal function. The eminent risk of cardiovascular shock and septic shock transform these patients into extremely severe cases, requiring immediate hospitalization and therapeutic intervention associated with support measures.^1,16,21

Psoriatic arthritis is characterized as a form of seronegative arthritis found between 5 and 42% of the patients with psoriasis, but it is rare in childhood ²². Conversely, 8 to 20% of the cases of arthritis in childhood are diagnosed as psoriatic arthritis 6. The incidence peak is between 9 and 12 years and girls are slightly more affected than boys (F:M = 3:2) ¹. There may be ophthalmic affections associated with psoriatic arthritis in some occasions.

The most frequent form of psoriatic arthritis is asymmetrical mono or oligoarthritis, which affects primarily hand and feet joints. Other less frequent forms present symmetrical, axial impairment and are sometimes disabling. Arthritis may precede (19%) the skin lesion, be concomitant (16%) or appear after skin psoriasis (65%), on average 10 years later. Almost all forms of psoriasis may be concomitant with arthritis; in general, the more severe the cutaneous affection, the higher the prevalence of arthritis. Cutaneous and articular presentations are not related from the standpoint of activity and progression, Psoriatic uveitis, a previous asymptomatic form of uveitis, occurs in 14-17% of the children with juvenile psoriatic arthritis ^{22,23, 24}.

Ungual affections are observed between 10-40% of the children with psoriasis, which may precede the onset of cutaneous lesions and for years they may be the only manifestation of the disease. The level of involvement depends on the location of the psoriatic process in the ungual system, intensity and duration of the progression of the disease. The most frequent aspect is cupuliform depressions, also named ungual pits (thimble-shaped nails), by affection of proximal ungual fold. Onycolysis, subungual hyperkeratosis and "oil spots" are other evidenced affections and correspond to affections of ungual bed. Finally, affection of ungual matrix may lead to onycodystrophy and trachyonychia. These patterns tend to be similar in children and adults.

Acral affection with variable levels of onycodystrophy may be the only manifestation in children (Figure 8). Ungual involvement increases with age, with duration and extension of disease and the presence of psoriatic arthritis ²⁵. To confirm the diagnosis it is necessary to exclude onycomycosis by mycological exam. Bear in mind that they can coexist given that ungual psoriasis increases the likelihood of contamination by dermatophytes ^{26, 27}.

DIAGNOSIS

Diagnosis of psoriasis is mainly clinical. Through methodic curettage of Brocq, we may find the two typical clinical findings of this dermatosis: sign of stratification of scales and sign of bleeding points or Auspitz sign (small points of bleeding when the scale is removed) ¹⁸. Woronoff hale or ring (perilesional light zone) is highly characteristic of the disease, but it is rarely observed ¹⁹. Isomorphic phenomenon of Köbner manifests the onset of the dermatosis in healthy skin areas after different types of local trauma in patients genetically predisposed and affected by the disease. Psoriasis is characterized by the classical example of Köbner phenomenon, which occurs in 1/3 of the patients with psoriasis. The lesions appear between 10 and 14 days after the trauma. However, the onset of lesions after few days or even years has also been reported. The pathogenesis of this phenomenon remains controversial, focusing mainly on immune and vascular affections. The phenomenon may be evidenced in 50% of the children with psoriasis, and in 39% of the affected adults. Köbner-positive patients may become Köbner-negative and vice-versa, regardless of any therapeutic strategies used ^{16, 17}.

Another phenomenon that was recently described, named Renbök phenomenon, and also called reverse Köbner, expresses the situation in which any local trauma posed on the psoriatic plaque leads to the disappearance of the lesion and replacement by apparently healthy skin on the site. Classically, Köbner-positive patients do not have Renbök phenomenon, because they seem to be mutually exclusive ²⁰.

There is no specific laboratory exam to diagnose psoriasis 1. Histological presentation is not specific, but it is highly suggestive. The first modifications evidenced are vasodilation and perivascular inflammatory infiltrate. The infiltrate invades the epidermis, in which there is mild spongiosis, invasion of neutrophils and parakeratosis. In a defined lesion there is elongation of regular epithelial cones, with thinning of supra-papillary portion; papillae are enlarged and swollen, showing dilated and tortuous capillaries. In the epidermis, there is parakeratosis, disappearance of granular layer and presence of neutrophil groups (Munro microabscesses). Especially in pustular psoriasis, there may be the presence of cavities containing neutrophils, named spongioform pustules of Kogoj. Inflammatory infiltrate is mild and comprised by mononuclear cells, especially lymphocytes 5, 28. Differential diagnosis to be considered in childhood and adolescence include seborrheic dermatitis, eczemas, superficial mycosis, secondary syphilis, pityriasis rubra pilaris, lichen planus, lupus erythematous, chronic lichenoid pityriasis, ILVEN, enteropathic acrodermatitis, erythrodermic pemphigus foliaceus, drug erythrodermia, Sneddon-Wilkinson sub-corneum pustulosis, generalized acute exanthematic pustulosis and impetigo bullous (Chart 1) ^{16, 19}.

TREATMENT

Treatment of psoriasis intends to control the disease and improve quality of life of the patients. To determine the best therapeutic regimen, we should consider gender, age, clinical presentation, disease severity, associated signs and symptoms, co-morbidities, concomitant modification, previous treatment, adverse events and participation of parents or guardians in treatment. Initially we should clarify the patients and parents about the characteristics of the treatment and its course, as well as to guide them about the importance of sun exposure ². To some patients, psychotherapic follow-up may be necessary ²¹. For most pediatric patients, psoriasis may be treated with topical medication. Phototherapy is an option to more extensive and refractory cases. Systemic therapy is reserved to more severe and extensive cases (Figure 9) that cannot be controlled with topical treatment and/or phototherapy ^{1, 6, 19}. Therefore, specific therapies depend on form and extension of the disease ^28-32.

Topical Treatment

As monotherapy or combined regimen, the use of topical medications is normally enough to control mild forms of psoriasis. In the moderate to severe cases, topical treatment, when associated with phototherapy and/or systemic therapy, provides more comfort to patients, speeds up improvement and minimizes pruritus.

Emollients and/or humectants (ammonia lactate, Vaseline, ceramides or mineral oil) and, in hyperkeratosic lesions, keratolytic agents (salicylic acid - 3 to 6%, urea - 5 to 20%), should be included in all therapeutic regimen, be it supportive or alternated with active products, or even in asymptomatic stages. The options for topical use are the following described below.

Topical corticosteroids: they have antiinflammatory actions, anti-proliferative (anti-mitotic), immunosuppresant, vasoconstrictor and anti-pruriginous action. It is the most widely used topical therapy in cases of childhood psoriasis. Efficacy of response to topical corticosteroids range according to its clinical form, and it is high in inverted psoriasis, moderate in body psoriasis, and mild in palmar-plantar and ungual psoriasis. The location of the psoriasis lesion determines the potency of topical corticosteroids to be used owing to the risk of adverse events. Medium and high potency corticosteroids are indicated in scalp, limb and trunk lesions. Less powerful corticosteroids are indicated in lesions located on the face, periauricular regions, folds and genitals. After clinical improvement, we should try to replace them by low potency corticosteroids to avoid development of atrophy, strias, hypertrichosis and inhibition of hypothalamic-pituitary-adrenal axis, especially in children. Tachyphylaxis, that is, loss of efficacy as a result of continuous use of the medication and the need to use stronger and stronger drugs to control the disease, is a constant factor in this infirmity.

Coaltar (2-10%): the vehicle is Vaseline, cold cream or ointments. When used in isolation, it has moderate action on plaque psoriasis, but when associated with phototherapy, its action is maximized. It may be combined with salicylic acid 2-5% in hyperkeratosic lesions.

It represents a very effective and very low cost therapeutic option. On the scalp, it is used as liquor carbonis detergens (coaltar 20% in alcohol 95o, emulsified with quillaja extract, diluted in creams or emulsions), or as shampoo. Folliculitis is the most frequent adverse event in the use of coaltar. Among the inconveniences of its use, we may include low cosmetic acceptance. There is controversy about the carcinogenic potential of coaltar. Despite in vitro studies and animal models clearly showing its carcinogenic potential, epidemiological studies with coaltar in human beings have not demonstrated increase in incidence of neoplasms in the studied group ³³.

Göckerman Method: indicated for disseminated plaque psoriasis, not erythrodermic. It is the association of coaltar with UVB radiation. Coaltar ointment is applied on the patient, and it should remain in place as long as possible. UVB application is made in increasing doses, daily or in alternate days, without removing the ointment. After irradiation, a shower should be taken to remove the scales and reapply the ointment. Total of 20-30 applications until lightening of lesions.

Anthralin (or ditranol): It is believed that its effect is cytostatic, reducing the mitotic activity of psoriatic epidermal cells. It may be used in low concentrations (0.1% to 0.5%) during 24h or in high concentrations (1 to 3%) in applications of only 15 to 30 minutes. Prepared as creams, pastes or ointments. Skin lightening takes place 3 to 4 weeks after application. Irritating substance, it should be avoided in intertriginous areas, close to the eyes and mucosa and on healthy perilesional skin, where there may be erosion and blisters. It stains clothes, tiles and the skin around the lesions. There is practically no risk of systemic toxicity, presenting excellent safety profile in children. It is considered highly effective medication for psoriasis, leading to prolonged periods of remission and no tachyphylaxis ³⁴.

Calcipotriol: analog of vitamin D3 that reduces proliferation and induces differentiation of keratinocytes, in addition to modifying immune response. It is safe and, in monotherapy, it had moderate efficacy to treat mild and moderate episodes of psoriasis in adults. When used in combined regimens or in sequence with topical corticosteroids, they offer prolonged periods of remission, without rebound effect that is induced by corticosteroids in monotherapy. It should be applied at night and washed off in the morning.

Efficacy and safety of calcipotriol in treatment of pediatric patients are not fully defined yet. In different literature reports, calcipotriol ointment has been proved to be effective, well tolerated and safe in children with psoriasis, and local irritation is the most commonly reported adverse effect ^35-38. Even though there are no formal guidelines for its use in children, the use of up to 45 g/week/m2 in children does not seem to influence calcium serum levels ³⁶. It may cause skin irritation, especially on the face, where it should be avoided. In addition to pruritus, erythema and ardor, there may be folliculitis and pigmentation abnormalities on the applied sites.

Topical Immunomodulators: pimecrolimus and tacrolimus may be indicated to localized forms on the face, folds and mucosa, because they cause fewer adverse events than corticosteroids and analogs of vitamin D and they have better absorption in these areas. Efficacy is extremely variable. In Brazil, pimecrolimus is indicated in children as of 3 months of life and tracolimus as of 2 years. They should not be used if there are virus, bacterial or fungal infections present ³⁹.

Topical retinoids: The retinoid used in psoriasis patients is tazarotene, available in gel and concentrations at 0.01% and 0.05%. With mild to moderate efficacy, tazarotene is indicated to chronic plaque psoriasis. It is not approved for use in children with psoriasis, but there is indication for its use in acne for children older than 12 years. There are no studies referring to efficacy and safety of its use in children with psoriasis. It may cause irritation, burning sensation and local erythema. It should not be used on folds. It does not cause tachyphylaxis, and current it is not available in Brazil ³⁴.

Phototherapy and Systemic Treatment PUVA, broad band UVB (290-320 nm) and narrow band UVB (311 nm) phototherapy. It is a therapeutic option used in isolation or combined with other therapeutic modalities, either topical or systemic. The action mechanism of phototherapy is through anti-proliferative, antiinflammatory and immunosuppresant activity. Different forms of psoriasis may be treated with this method, but the best indication is to moderate psoriasis, with predominance of fine plaques. Patients with pustular or erythrodermic psoriasis should not be submitted to phototherapy and even sun exposure, owing to the risk of worsening and vasodilation. In children, treatment should be reserved to those that can understand and accept this therapeutic modality. The necessary frequency for satisfactory treatment is three times a week.

UVB radiation is highly effective also for the treatment of plaque and guttate psoriasis. It is used in isolation or associated with the use of coaltar (Göckerman method). The most common adverse effect is burns, and it has low risk for skin cancer. Contraindications to the method are photosensitivity and melanoma history. Protection glasses should be worn during the exposure. The anti-psoriatic effect is greater when using the 311nm range, which allows less time of exposure to narrow band. Satisfactory outcomes can normally be seen after 8 weeks of treatment.

PUVA method tends to be more effective and quick in inducing improvement when compared to UVB. Associated with 8-MOP systemic, topical or added by sun exposure. Systemic medication should be taken every two hours before light exposure and it has the disadvantage of requiring eye protection for 24 hours. The advocated dose is 20mg below 50Kg of weight, 30mg between 51-65Kg, 40mg between 66-80Kg and 50mg over 80kg. There are no studies showing safety of oral PUVA in children below the age of 8 years, but the method may be used in adolescents ^{2, 40, 41}.

Antibiotics: Even though there are evidences that antibiotic therapy modifies the natural progression of guttate psoriasis triggered by infection, children with this form of the disease and documented streptococcus infection should receive penicillin or erythromycin for seven to 14 days ¹.

Methotrexate (amethopterin): Antagonist of folic acid, with which it has structural similarity. It may be administered by oral, intramuscular or intravenous route, and it is essentially excreted by renal route. Bioavailability of the medication reduces with the intake of some foods, especially dairy foods; however, the drug does not have to be taken in fast. Methotrexate should be used in extensive and resistant cases of psoriasis in childhood, or in cases of arthropathic, erythordermic and generalized pustular psoriasis. The used dose for pediatric cases is 0.2-0.4 mg/kg/week, up to the weekly total dose of 12.5 to 20mg. It may be associated with folic acid (1 to 5 mg per os/ day). It has quick action. The youngest child treated with it in the literature was 4 years old and had severe psoriasis since the age of 2 years.

Recently, low doses of methotrexate have been associated with use of biologicals, especially infliximab, based on its inhibitory action in the production of antibodies ^{42, 43}. This association has not been assessed for the pediatric population to present. Hematological controls and periodical liver and renal function tests are mandatory. Clinically, one of the early signs of intolerance is the onset of aphthoid lesions on the oral mucosa, signaling significant leucopenia. The most frequent adverse effect is gastric intolerance. It has multiple drug interactions, Absolute contraindications are pregnancy and breastfeeding, liver cirrhosis, active liver infection and liver failure ^{44, 1}. Live or attenuated virus vaccine should be avoided.

Acitretin: derived from vitamin A (retinol), it is employed in the dose 0.5 to 1.0 mg/kg/d. Especially indicated in generalized pustular psoriasis, also used in generalized plaque psoriasis, and erythrodermic psoriasis (improvement is expected within 3-4 months from treatment). It represents a systemic therapeutic option most used in children with disseminated and resistant presentations to topical treatment and phototherapy. Adverse effects include mild cheilitis (dose-dependent), epistaxis, conjunctivitis, paronychia, alopecia, pruritus, dyslipidemia and teratogenia (etretinate persists in the body for two years, and it should be contraindicated in childbearing age women). Prolonged therapy with acitretin should be carefully considered in children because there are reports of premature closure of bone epiphysis, tendon and ligaments calcifications and delay in bon growth. Radiological exams should be performed annually. Efficacy of acitretin tends to be moderate and it is high when associated with phototherapy. Clinical response is delayed. Among absolute contraindications are pregnancy and willingness to get pregnant in near future, liver and renal failure and allergy to paraben contained in capsules ⁴⁶. The use of vaccines to the specific age range is not contraindicated.

Cyclosporine A: acts by inhibiting activated T-CD4 lymphocytes preventing IL-2 release. Even though it has been widely studied in patients with atopical dermatitis, there are no safety and efficacy studies for psoriasis in children. It should be reserved for severe cases, such as erythrodermic psoriasis and in cases rapidly progressive and without response to other therapeutic methods. Cyclosporine dose is 2-5 mg/Kg, daily, for 3-4 months, after which it should be gradually discontinued. Recurrences tend to happen as a result of dose tapering. Adverse effects include nephrotoxicity, hypertension, nausea, paresthesia feelings, gingival hyperplasia, hypertrichosis and increase in risk of neoplasms, but they do not seem to be more frequent in children than in adults with psoriasis. The drug requires renal, hepatic and hematological monitoring every 2-4 weeks. Contraindications to the use of cyclosporine are renal function abnormalities, uncontrolled systemic hypertension, malignancy and breastfeeding. Immunization with live or attenuated virus vaccine should be avoided during the period and between 3-12 months after its completion, depending on the dose ². Cyclosporine has multiple drug interactions, but it is one of the few treatments for psoriasis that may be used in pregnant women ⁴⁶.

Immunobiological agents: Immunobiological or simply biological agents represent a group of drugs that interfere in specific and timely manner over the immune system. They act by blocking or stimulating one or more immune response pathways. Despite their high complexity and structural variability, all biological agents represent proteins obtained from modern biotechnology techniques. The goal of these therapeutic agents includes the traffic of lymphocytes in skin microcirculation, antigenic presentation of antigen-presenting cells to lymphocytes and, finally, different cytokines ^6,47,48 They are extremely expensive drugs. To present, etanercept is the biological agent most carefully studied to be used in children with psoriasis.

It represents the soluble form of totally human tumor necrosis factor (TNF) receptor ^{49, 50, 51}. The drug was approved for the first time in 1998 for moderate to severe rheumatoid arthritis, and later it was approved for treatment of children and adolescents with juvenile rheumatoid arthritis (1999). In 2004, etanercept was approved to treat moderate to severe plaque psoriasis in adults ^52-54. In a recent study published in the literature, children aged 4 to 17 years with moderate to severe psoriasis responded favorably to the mediation at a dose of 0.8 mg/Kg/week (maximum of 50mg), cutaneous route, within a total of 48 weeks, which included serious adverse events (including pneumonia, gastroenteritis, dehydration and surgical removal of ovarian cyst), which were solved without sequels ⁵⁵. The medication is still waiting for approval in Europe and in the USA to be used in children with moderate to severe psoriasis.

PROGNOSIS

Most children present the mild form of psoriasis with favorable response to topical treatment. Even though regression of the picture may be followed by prolonged remission, a chronic and recurrent course is the most common progression. In many cases, there are changes to the psoriasis pattern. Some children get worse as they become older, requiring more aggressive treatments. ⁵⁶ Patients with guttate psoriasis tend to progress to remission of the disease or even progress to plaque psoriasis ^{15, 26}.

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*

Trabalho realizado no Departamento de Dermatologia do Hospital das Clínicas da Universidade de São Paulo (USP) - São Paulo (SP), Brasil.

Publication Dates

• Publication in this collection
  23 June 2009
• Date of issue
  Feb 2009