J. I. Youn

Efficacy and safety of ustekinumab for the treatment of moderate-to-severe psoriasis: a phase III, randomized, placebo-controlled trial in Taiwanese and Korean patients (PEARL).

BACKGROUND Ustekinumab has been evaluated in Caucasian patients with psoriasis, but no studies have been conducted in Asian patients. OBJECTIVE To assess the efficacy and safety of ustekinumab in Taiwanese and Korean patients with moderate-to-severe psoriasis. METHODS In this 36-week, multicenter, double-blind, placebo-controlled study, 121 patients with moderate-to-severe psoriasis were randomized (1:1) to receive subcutaneous injections of ustekinumab 45mg at weeks 0, 4, 16 or placebo at weeks 0, 4 and ustekinumab 45mg at weeks 12, 16. Efficacy endpoints at week 12 included the proportion of patients achieving at least 75% improvement from baseline in Psoriasis Area and Severity Index (PASI 75; primary endpoint), proportion of patients with Physicians Global Assessment (PGA) of cleared or minimal, and change from baseline in Dermatology Life Quality Index (DLQI). RESULTS At week 12, the proportion of patients achieving PASI 75 was 67.2% and 5.0% in the ustekinumab 45mg and placebo groups, respectively (p<0.001). PGA of cleared or minimal was achieved by 70.5% (ustekinumab) and 8.3% (placebo; p<0.001), and median DLQI changes were -11.0 and 0.0, respectively (p<0.001). Efficacy was maintained through week 28 in ustekinumab-treated patients. Adverse event (AE) profiles at week 12 were similar between the ustekinumab and placebo groups: 65.6% and 70.0%, respectively, had at least one reported AE. Through week 36, no disproportionate increase in AEs was observed, with the exception of abnormal hepatic function, which was related to concomitant isoniazid treatment for latent tuberculosis. Injection-site reactions were rare and mild. No deaths, malignancies, or cardiovascular events were reported. CONCLUSIONS Treatment with subcutaneous ustekinumab 45mg offers a favorable benefit/risk profile for Taiwanese and Korean patients with moderate-to-severe psoriasis. The efficacy and safety profile is consistent with the global phase III studies of ustekinumab in psoriasis.

Electrical measurement of moisturizing effect on skin hydration and barrier function in psoriasis patients

Transepidermal water loss (TEWL) in psoriatic skin lesions seems to be related to the severity of the psoriasis, and the electrical capacitance and conductance of the skin are indicators of the hydration level of the stratum corneum. We compared the characteristics of these electrical measurements, in assessing the persistent effect of a moisturizing cream on skin hydration and barrier function in psoriasis patients. Seventeen Korean psoriasis patients were recruited. Their right leg was treated with the moisturizer twice daily for 6 weeks, while their left leg was used as the control site. For each patient, one psoriatic plaque on each leg was selected as the involved psoriatic lesion. Uninvolved psoriatic skin was regarded as the apparently healthy looking skin 4–5 cm away from the periphery of the psoriatic lesion. The TEWL, electrical capacitance and conductance were measured, in order to evaluate the barrier function and hydration level of the stratum corneum. The clinical and biophysical data for each patient were recorded at the start of the study and after 2, 4 and 6 weeks. The degree of skin dryness at the applied area improved progressively. The electrical capacitance at the treated psoriatic lesion increased significantly after 2 weeks, and this improvement was maintained during the entire study period. However, no noticeable change was observed in the electrical conductance. The TEWL showed an inverse pattern to that of the skin capacitance, decreasing during the study period. The skin capacitance and TEWL exhibited good correlation with the visual assessment of skin dryness, but the skin conductance did not. Our data suggest that electrical capacitance and TEWL may be useful in the evaluation of the effect of a moisturizer on the hydration status and barrier function of psoriatic skin.

Relationship between skin phototype and MED in Korean, brown skin

The Fitzpatrick skin classification has been a useful method to categorize cutaneous sensitivity to ultraviolet radiation (UVR), although it was based originally on responses in white skin. Because the relevance of this phototype in brown skin is in question, we investigated skin phototypes of university students by a self‐reporting questionnaire and measured their MEDs in Korean, brown skin. After studying our explanation of the definition of Fitzpatrick skin types, 707 Korean university students answered the questionnaire. We then measured UVB MEDs in 156 randomly selected male students. The order of frequency of skin type was type III (55.0%), IV (29.0%), and V (12.3%) by the questionnaire, with the sun sensitive categories (types I and II) reported only for 3.7%. There was no significant difference in MEDs between types IV and V, and the mean MED of each skin type did not show a monotonic increase with increasing skin type. Subjects with MEDs of 70–90 mJ/cm2 (corresponding to the MED of skin type V, as proposed by Pathak & Fitzpatrick) represented about half or more of the subjects in all categories, even types II and III. Subjects with MEDs lower than 60 mJ/cm2 were more prevalent in types II and III compared with types IV and V We suggest that there is at best a weak relationship between the skin types, by the Fitzpatrick method, and MEDs in Korean, brown skin.

Polymorphisms of tumor necrosis factor (TNF) α and β genes in Korean patients with psoriasis

To evaluate the association of TNF-α (TNFA) and TNF-β (TNFB) polymorphisms with psoriasis in the Korean population, we investigated TNF-α −238 and −308 promoter region and TNF-β NcoI polymorphism using PCR-RFLP in 103 Korean psoriasis patients and 125 normal controls. The carriage and allele frequencies of TNFB*2 were significantly increased in patients with psoriasis compared with normal controls. However, TNFB*1/1 homozygote and TNFB*1 allele were significantly decreased in the patients. There were no significant differences in the polymorphism of TNF-α promoter −238 and −308 between the patients and controls. We also analyzed the frequencies of TNFB alleles according to the clinical characteristics of the psoriasis patients, but no significant differences were found. However, female patients with early-onset psoriasis showed an association with the TNFB*2 allele. In conclusion, our results suggest that polymorphisms of the TNFB gene may contribute to a predisposition to psoriasis in the Korean population.

A pilot study to assess the safety and efficacy of topical calcipotriol treatment in childhood psoriasis.

Abstract: Childhood psoriasis is more extensive and severe compared with that of adults. Therefore an effective and safe treatment modality is needed. Although a few studies of childhood psoriasis indicate that treatment with calcipotriol is safe and effective, short‐term studies cannot reflect the exact effect of calcipotriol on systemic calcium homeostasis. Our purpose was to study the long‐term efficacy and safety of calcipotriol for childhood psoriasis. An uncontrolled pilot study, with long‐term follow‐up for as long as 106 weeks, using open‐label calcipotriol ointment was conducted in 12 psoriasis patients less than 15 years of age. Response to treatment was assessed by the psoriasis area and severity index (PASI) and serum 25‐hydroxyvitamin D3 and 1,25‐dihydroxyvitamin D3 levels, as well as routine laboratory analyses including serum calcium and phosphate, which were measured before and after the course of treatment. At the end of the study, the patients showed significant improvement in PASI scores compared with the baseline level. No serious side effects, including those related to calcium homeostasis, were detected. The mean values of 1,25‐dihydroxyvitamin D3, however, were decreased and half of the patients had levels below the normal range. In conclusion, it is thought that calcipotriol ointment is an effective treatment modality for long‐term use in childhood psoriasis. However, although not lowering serum calcium and phosphate levels, the long‐term use of calcipotriol in childhood may possibly decrease the serum values of endogenous vitamin D. Therefore monitoring of vitamin D metabolites may be necessary during calcipotriol therapy. More investigative studies are needed to resolve this issue.

Photoprotective effect of calcipotriol upon skin photoreaction to UVA and UVB

It has been shown that 1,25‐dihydroxyvitamin D3 has a photoprotective effect against UVB injury in mouse skin and cultured rat keratinocytes by induction of metallothionein (MT). Calcipotriol is a synthetic analogue of 1,25‐dihydroxyvitamin D3 with equipotent cell regulating properties, but with a lower risk of calcium‐related side effects. The aim of the present study was to see whether calcipotriol has a photoprotective property both in vitro and in vivo. We examined the effect of calcipotriol on UV‐induced damage of cultured human keratinocytes through a cell viability assay, and measurement of DNA synthesis by cultured keratinocytes, on UV‐induced damage of mouse skin and on minimal erythema dose (MED). We found that calcipotriol was protective against UVB‐induced reduction in DNA synthetic activity of cultured keratinocytes in relatively low doses (20 and 40 mJ/cm2) of UVB. With phototesting following application of calcipotriol, five subjects among 10 healthy volunteers and three among six psoriasis patients showed an increase in MED compared with the vehicle‐treated site. These findings imply that calcipotriol may be photoprotective and that more extensive studies with various doses of UV irradiation and modes of calcipotriol delivery are required.

Vitamin D receptor genotypes are not associated with clinical response to calcipotriol in Korean psoriasis patients

Abstract. Conflicting results have been reported on the association between BsmI restriction fragment length polymorphism (RFLP) at the vitamin D receptor gene (VDR) locus and the clinical response of psoriasis patients to calcitriol or calcipotriol therapy. We evaluated RFLPs of the VDR gene by analyzing the restriction pattern of polymerase chain reaction products in 55 Korean psoriasis patients receiving topical calcipotriol therapy, and evaluated the clinical response. Of the 55 patients, 43 completed the 8-week treatment protocol, and the response was evaluated as excellent in 9 patients, good in 20, and poor in 14. Thus, in our 43 patients BsmI and ApaI polymorphism in the VDR gene did not correlate with response to calcipotriol. The marked predominance of the b allele in the Korean population precludes the possibility that BsmI polymorphism is associated with clinical response to calcipotriol. The pattern of prevalence of the VDR genotypes in the Korean population is very different from that in Western populations. There were no differences in VDR genotype between controls and psoriasis patients at the BsmI site, but there were significant difference in terms of ApaI RFLP as previously reported. In conclusion, polymorphism analysis of the VDR gene with BsmI and ApaI restriction enzymes in psoriasis patients was not helpful in predicting clinical response to calcipotriol.

Neutrophilic dermatoses associated with myeloid malignancy.

The neutrophilic dermatoses are significantly associated with myeloid malignancies. We now describe the clinical and histological features of 11 patients with these disorders, namely Sweets syndrome in three cases, pyoderma gangrenosum in two, and neutrophilic eccrine hidradenitis in one; there were also five others which could not be categorised as recognised entities. Our observations, as well as those from a review of the literature, support the hypothesis that in the neutrophilic dermatoses associated with myeloid malignancy, a common mechanism may he involved.

Epidermolysis bullosa acquisita in childhood – a case mimicking chronic bullous dermatosis of childhood

Epidermolysis bullosa acquisila (EBA) is rarely reported in childhood, hut we mm describe a 6‐year‐old Korean girl with the condition. She presented with multiple tense bullae annularly distributed on the perioral, periorbital and genital areas, and was successfully treated with dapsoae. The clinical and histological features were similar to those of chronic bullous dermatosis of childhood. We review seven previously reported childhood EBA cases and contrast their features with those of adult EBA. We suggest that some childhood EBA is different from the adult form and shares features with chronic bullous dermatosis of childhood.

EFFICACY AND TOLERABILITY OF ITRACONAZOLE IN PATIENTS WITH FINGERNAIL ONYCHOMYCOSIS: A 6-WEEK PILOT STUDY

Abstract Twenty-one patients (6 men, 15 women) with fingernail onychomycosis participated in this open-label trial. They received 200-mg itraconazole once daily for 6 weeks and were followed up for 12 weeks after stopping treatment. All patients had fungal elements detected by using microscopic examination of potassium hydroxide (KOH) smear of their fingernail scrappings at the start of the trial. Cultures revealed that 7 patients were infected with Trichophyton rubrum ; 6 with yeasts; and 1 with Fusarium species. At the end of treatment (week 6), 42.9% of patients were free of fungal colonization, as assessed by using KOH smear and fungus culture results. At the end of the follow-up period (week 18), 81.0% were clinically completely clear of lesion with a negative KOH smear and fungus culture, and an additional 9.5% were markedly improved, with a minimal residual lesion and a negative KOH smear and fungus culture. Three (14.3%) of 21 patients reported mild adverse events. The results of this trial confirm that a regimen of 200-mg itraconazole once daily for 6 weeks is effective and well tolerated in the treatment of patients with fingernail onychomycosis caused by either dermatophytes or yeasts.