A systematic review on the treatment of pediatric severe alopecia areata by topical immunotherapy or Anthralin (contact sensitization) or low-level light/laser therapy (LLLT): focus on efficacy, safety, treatment duration, recurrence, and follow-up based on clinical studies.

INTRODUCTION: Alopecia areata (AA) in its extensive and severe forms is treatment-challenging, especially in pediatrics. METHOD: A PRISMA-compliant systematic review of seven electronic databases was searched by the terms "alopecia areata," "pediatric," "topical immunotherapy," "Anthralin," and "light therapy" from inception until March 2021. All the alternative names of the disease and therapies have been included in the search terms. 790 articles went to title abstract review by two independent reviewers. In the subsequent level, a review of the full text of studies was conducted. RESULTS: Finally, 10 relevant articles in terms of content structure, subject coverage, and purpose, were selected for further review. The highest percentages of complete hair regrowth were 79.6% and 63.61% by SADBE (topical immunotherapy) and laser therapy. By Anthralin (contact sensitization), the complete response rate was below 50% (between 30 and 35%). Regarding average response, the most effective methods were local immunotherapy (with an average effectiveness of 53.8%), laser therapy (52.55%), and the use of Anthralin-induced contact dermatitis (30.86%), respectively. However, recurrence rate-after treatment with induced contact dermatitis by topical medications like Anthralin (contact sensitization)-was lower (mean 43.53%) in comparison with local immunotherapy (57%). In topical immunotherapy, light base therapy, and contact sensitization, the highest percentage of complete hair regrowth and the average response rate were (63.61% and 52.55%), (79.6% and 53.8%) and (32% and 30.8%), respectively. These methods are considered safe in children. CONCLUSION: A high and more than 50% efficacy in hair regrowth could be expected by topical immunotherapy and light/laser therapy method. No serious side effects have been observed by these methods that are well tolerated in children. Therefore, a combination of local immunotherapy and light/laser therapy could be suggested for the treatment of extensive AA in children. The use of Anthralin could be associated with a lower but more durable response. These points are important for patient selection in individualized situations.

[Children and adolescents with psoriasis. What therapy is recommended?]. / Kinder und Jugendliche mit Psoriasis. Welche Maßnahmen werden empfohlen?

Juvenile psoriasis shows a cumulative incidence of 1.76% until the 18th year of life and thus is important for both pediatricians and dermatologists. In contrast to psoriasis in adults, the main trigger factors are infections, mechanical trauma and stress factors and to a much lesser extent medical and recreational drugs. Apart from the classical predilection sites, the diaper area, scalp and face are mainly involved. Guttate psoriasis following streptococcal infections is a specific clinical manifestation in childhood and adolescence. Psoriasis arthritis of childhood falls into the group of juvenile idiopathic arthritis and typically presents before or simultaneously with skin symptoms. All recommended childhood vaccinations should be administered, ideally when the disease is under remission. Therapy relies heavily on topical agents like dithranol, corticosteroids, and alternatively topical calcineurin inhibitors in addition to individually adapted skin moisturizing measures. In severe cases which do not adequately respond to topical therapy, systemic treatment with classical immunomodulatory agents like methotrexate, cyclosporin, retinoids and fumarates may be initiated but all usage is off-label. The only agent licensed for the treatment of psoriasis in patients above the age of 8 years is etanercept if classical treatment has failed. Rehabilitative measures in mountain and seaside areas are reasonable for maintaining improvement and helping patient learn to deal with disease.

Targeted 307 nm UVB-phototherapy in psoriasis. A pilot study comparing a 307 nm excimer light with topical dithranol.

BACKGROUND: Phototherapy is a cornerstone in treatment of moderate-to-severe psoriasis. Narrow-band UVB has been shown to be a potent therapeutic tool. To reduce the potential carcinogenic risk, targeted phototherapy has been developed using excimer lasers or excimer light devices (ELD). OBJECTIVE: The role of excimer light therapy in practice and modes of action are not completely understood. We wanted to investigate a 307 nm ELD for plaque psoriasis in comparison with topical dithranol therapy twice daily. METHODS: We conducted a pilot trial in 21 adult patients with moderate plaque-type psoriasis. Two target lesions of comparable size and plaque-modified Psoriasis Activity and Severity Index (PSI) scores were selected. Lesion A was treated three times using a newly developed 307 nm ELD. Lesion B was treated twice daily with dithranol ointment. The mean period of treatment was 9 days. Clinical evaluation included PSI scores, safety, time needed to treat, and patient's satisfaction. In addition, fluorescence-remission imaging technique was used for objective evaluation. RESULTS: Both treatments improved the PSI score (mean 3.0 points). The treatments were safe but ELD was more convenient for patients. The time needed to treat the target lesion was significantly shorter with ELD. Targeted UVB therapy normalized NADH fluorescence in lesional skin. CONCLUSIONS: The 307 nm excimer light therapy for plaque type psoriasis was equipotent to twice daily topical dithranol. Efficacy, safety, and convenience suggest that targeted UVB therapy with quasi monochromatic light is a new useful treatment option for patients with limited psoriatic plaques.

Childhood psoriasis: often favorable outcome.

(1) Plaque psoriasis is the most common form of psoriasis in children. Topical agents should be tried first, especially well-tolerated products such as emollients. Topical corticosteroids are sometimes useful during exacerbations but, given adverse effects, they should only be used for short periods; (2) UVB phototherapy is an option for extensive psoriasis refractory to local treatments, but it carries a long-term risk of skin cancer. Immunosuppressants have not been well assessed in this setting, but methotrexate has been better evaluated than the others.

[Classical topical therapy of psoriasis]. / Klassische Therapien der topischen Psoriasisbehandlung.

In most cases mild to moderate forms of psoriasis can be treated with topical therapy. In addition, topical agents are also routinely combined with UV or systemic therapy to treat severe forms of psoriasis. A variety of standard products are available. The oldest topical treatment is anthralin. Since 1952 the development of topical corticosteroids has revolutionized not only dermatological treatment in general but the treatment of psoriasis in particular. Through the continuous development of these compounds, a better risk-benefit profile has been achieved. Corticosteroids are the most frequently employed topical agent for psoriasis treatment worldwide.

Effectiveness and side effects of UVB-phototherapy, dithranol inpatient therapy and a care instruction programme of short contact dithranol in moderate to severe psoriasis.

The efficacy of UVB-phototherapy (UVB) and dithranol treatment for psoriasis is well established. However, well-conducted clinical trials on the efficacy of dithranol are not available, making comparison between these time-honoured treatments with currently available therapies impossible. We studied the effectiveness of dithranol in a care instruction programme using short time exposures (short contact treatment), UVB-phototherapy and dithranol treatment in an inpatient setting. In an open randomised study we included 250 patients with moderate to severe psoriasis. The intention to treat group existed of 238 patients. 100 patients were treated with short contact dithranol, 78 Patients were treated with UVB and 60 patients underwent inpatient dithranol treatment. We found UVB and dithranol treatment to be effective and safe in moderate to severe psoriasis. The efficacy of short contact dithranol treatment equals the efficacy of UVB-phototherapy. Dithranol treatment at the inpatient department showed superior efficacy in clinical response rate and treatment duration as compared to UVB and short contact treatment. The median number of days in remission was significantly longer after short contact treatment as compared to inpatient treatment. Although the use of dithranol is hampered by skin irritation and staining, the present study shows that dithranol treatment has an outstanding efficacy and safety profile. Comparison between different antipsoriatic treatments should, besides clearing capacity, reconcile duration of remission, safety, patient acceptability and costs.

Dithranol embedded in crystalline monoglycerides combined with phototherapy (UVB): a new approach in the treatment of psoriasis.

Treatment of psoriasis with dithranol as monotherapy or dithranol in combination with UVB phototherapy is an effective and safe approach for the management of psoriasis. Recently a new formulation of dithranol embedded in crystalline monoglycerides (Micanol) has become available. It was shown that this formulation combines adequate efficacy with low irritation and staining properties. The aim of the present study was to compare and contrast three treatment schedules with respect to clinical efficacy and tolerability: Micanol monotherapy, Micanol in combination with UVB phototherapy and placebo combined with UVB phototherapy. The study design was a partly open, partly double-blind, randomized, left-right comparison. In total 36 patients were included and 24 body halves were available for each of the three treatments. The combination of Micanol with UVB resulted in clearance of lesions in 54% of the patients (body halves). Combination therapies with Micanol and either of the two other therapies were highly effective. However, with the number of patients investigated, a statistically significant difference between the three therapeutic approaches with respect to efficacy could not be shown. The three treatments resulted in a grosso modo comparable clinical improvement. Severe irritation was observed in 8% and staining of the skin in 29% of the patients treated with the combination therapy Micanol/UVB, which is far less compared to the irritation and staining by the conventional short contact approaches. The efficacy and tolerability of Micanol make this active substance an important tool in the management of psoriasis.

Effects of antipsoriatic therapies on hepatic microsomal enzyme activity in patients with psoriasis.

OBJECTIVE: The influence of several antipsoriatic therapies on microsomal enzyme activity was assessed by comparing measurements of antipyrine kinetics prior to and two weeks after initiation of therapy. METHODS: Serum and urine analysis was carried out by means of high performance liquid chromatography (HPLC). Each form of therapy was examined separately. 10 patients were treated with etretinate. The groups treated with 8-methoxypsoralene (8-MOP) in combination with UVA irradiation (PUVA), etretinate in combination with PUVA (RePUVA), anthralin, or combined UVA and UVB irradiation (SUP) consisted of 7 patients each. RESULTS: Neither anthralin nor SUP therapy led to any significant changes in antipyrine kinetics. Antipyrine clearance under the other regimens was, however, reduced. It was 23% lower in PUVA-treated patients, 20% lower in those receiving retinoids and 28% lower in those under RePUVA (p<0.05 - 0. 01). CONCLUSIONS: PUVA, etretinate and RePUVA inhibit microsomal enzyme activity in the liver. Possible drug interactions with other P subset450 inducing or inhibiting agents should be considered in the therapy of psoriatic patients.

Low-dose narrow-band UVB phototherapy combined with topical therapy is effective in psoriasis and does not inhibit systemic T-cell activation.

BACKGROUND: Psoriasis is a chronic T-cell-mediated inflammatory skin disease which can be treated with topical medication, phototherapy or systemic medication. A subgroup of psoriatic patients does not respond to monotherapy and needs combination therapy. We used low-dose narrow-band UVB phototherapy, combined with balneotherapy, short-contact anthralin, liquor carbonis detergens and calcipotriol for treatment of psoriatic patients in our day care centre. OBJECTIVE: Our purpose was to study the efficacy, induction of erythema and effect on systemic T-cell activation of this combination therapy. METHODS: Skin reflectance spectrophotometry was used to measure skin erythema. The Psoriasis Area and Severity Index (PASI) was used to evaluate psoriatic patients. Serum soluble IL-2 receptor (sIL2-R) levels were measured by an ELISA. RESULTS: The possible erythematogenic effect of low-dose narrow-band UVB irradiation was studied (skin reflectance spectrophotometer) in a control group of psoriatic patients (n = 11). No induction of skin erythema was seen. Subsequently, this low-dose irradiation regimen was used in combination with topical medication in 26 psoriatic patients. A 90% decrease in the PASI was seen after a mean number of 35 treatment sessions. Seventeen patients (65%) remained in remission during the following 6 months. Serum sIL-2R levels were elevated in all patients (mean 913 U/ml) and did not change during treatment. CONCLUSION: Our data indicate that low-dose narrow-band UVB can be used successfully, in combination with topical treatment, in a day care setting to treat psoriatic patients. Since sIL-2R serum levels were not decreased, it can be speculated that this treatment does not induce systemic immunosuppression.

Clinical studies with a novel dithranol formulation (Micanol) in combination with UVB at day-care centres.

The clinical effect, side effects, cosmetic properties and the patients preference between Micanol and other dithranol formulations were investigated in three separate studies combining UV-B phototherapy and a short contact dithranol regimen. Good clinical results without difference between Micanol and other dithranol formulations were obtained. Side effects, cosmetic properties and preferences were mostly in favor of Micanol. Therefore, a high patient compliance can be obtained with the new dithranol formulation.

Epidermal keratin levels during oral 1-alpha-hydroxyvitamin D3 treatment for psoriasis.

Recently the treatment of psoriasis with vitamin D3, its metabolites or analogues, has been reported to be clinically effective and free from side effects. We have quantified the changes in the levels of epidermal lesional keratins in 15 psoriatic patients receiving oral 1 alpha(OH)D3 treatment. Lesions were sampled before treatment commenced and at monthly intervals for 4-6 months. Clinical resolution occurred in 7 patients within this time; 3 other patients showed incomplete lesion resolution and the remaining 5 patients showed a complete lack of response within the treatment period. Lesion resolution, as judged by clinical criteria, was accompanied by significant changes in the levels of three of the keratin polypeptides and smaller changes in others. Keratin 2 increased to levels greater than those in normal epidermis, while keratins 16 and 18 decreased to normal levels. Changes in the levels of keratins 1 and 5 were small and those of keratins 7, 10 and 14 minimal. These changes were compared with values found during lesion resolution with other therapies used in psoriasis, i.e. topical dithranol, PUVA, oral etretinate and hydroxyurea and were highly reminiscent of those observed during PUVA therapy but contrasted with those during etretinate treatment. The decrease in level of keratin 16, a hyperproliferation marker, suggests that 1 alpha(OH)D3 inhibits keratinocyte proliferation, but at the same time the overproduction of keratin 2, a major keratin of the granular cells, indicates that there is an increase in the number of cells in the later stages of differentiation.

Chemically induced inflammation in rat oral mucosa.

The toxic, irritative, and sensitizing effects of topically applied sodium lauryl sulfate (SLS), dithranol triacetate (DTA), nonanoic acid in methyl- or propyl ester (NAM, NAP) in the buccal mucosa were investigated in a Sprague-Dawley rat model. Semi-quantitative evaluations of cellular infiltrates were performed in routine histologic preparations. The toxic potential was tested with 2% and 0.2% solutions. All substances, except 0.2% SLS, caused an increased cellularity, mainly of a mononuclear cell type. The low dose of NAM induced stronger inflammatory reactions than the high dose. Repeated applications of 2% solutions decreased the response compared to one application, except for NAM, where a clear irritative potential was observed. Pre-exposure of dorsal skin prior to buccal painting resulted in an enhanced reaction to NAM and NAP, whereas no sensitizing capacity was noted in SLS or DTA in this model.

Irritant potential of dithranol.

The minimal irritation dose (MID) for dithranol in 5% salicylic acid vaseline was determined by open patch testing. From the MID, the irritation dose 50 (ID50) was evaluated. It was 0.057% in 100 controls and 0.046% in 100 psoriatic patients, which is not statistically different due to the great differences between individuals. 20 other patients claimed a dithranol hyperreactivity in their history. Only 13 of them, however, showed a decrease in the MID, which was between 0.01 and 0.02% (means = 0.014%), i.e. outside the confidence interval found in the 100 psoriatic patients. 8 of these 13 reacted with blister formation after exposure to 0.1-0.16% dithranol. An allergic contact dermatitis was excluded as the cause of the hyperreactivity. The tolerance to increasing dithranol concentrations after beginning with the MID up to clearance of the lesions, as well as the predominance of granulocytes as compared to lymphocytes in blisters due to dithranol testing, suggest an irritant inflammatory mechanism. In such hyperreactive cases therapy should be started with the MID established in the open patch test.

[Effect of coal tar on cignolin erythema--1 hour treatment of psoriasis with high-dose cignolin with and without tar]. / Einfluss von Steinkohlenteer auf das Cignolinerythem-die hochdosierte Cignolin-Einstundentherapie der Psoriasis mit und ohne Teerzusatz.

Coal tar applied simultaneously showed a suppressive effect on anthralin erythema. This effect was demonstrated by an epicutaneous test 24 hours (27 patients) and 1 hour (46 patients) after application of various concentrations of anthralin combined with tar 3%. In a clinical study on 9 patients, anthralin 3% alone or combined with tar 10% were administered in a right and left comparison on symmetrical chronic psoriatic lesions for 1 hour daily. Anthralin plus tar exhibited a stronger anti-psoriatic effect than anthralin alone did. Tar reduced the anthralin erythema in the perilesional skin. These findings favor the combination of coal tar and anthralin in the 1-hour treatment schedule of psoriasis.

[Dithranol and combined treatment procedures: pro and con]. / Dithranol und kombinierte Behandlungsverfahren: Pro und Contra.

The combination of different antipsoriatics or treatment regimens should increase the therapeutic effect and reduce the adverse reactions. The combination of dithranol and tar (cignolin-salicyl-vaseline + tar, CSVT) reduces dithranol erythema and increases the antipsoriatic effect. CSVT treatment is highly effective, but patients tend to accept it less than other treatment regimens. On the other hand, Goeckerman therapy (tar + UV irradiation) is more accepted but less effective. Combinations of dithranol with UV irradiation or with tar and UV irradiation (Ingram regimen) are not advantageous. Dithranol and Goeckerman therapy are relatively secure treatment regimens, as they have been applied for more than 50 years without knowledge of significant late defects. PUVA therapy, although highly effective, is not superior to dithranol therapy. Even though PUVA therapy is more easily accepted than dithranol treatment, PUVA therapy should be applied only in severe cases. The combinations of aromatic retinoid with (selective) UVB irradiation (ReSUP) or with PUVA therapy (RePUVA) are highly effective. Retinoids can reduce the UV doses and most likely limit the risk of late damage. For routine treatment, ReSUP is preferable to RePUVA therapy.