Association of HLA class II gene polymorphisms and expression levels of ORAI1/STIM1 genes in HIV-1‒positive patients with HIV-related dermatoses in Latvia.

INTRODUCTION: This study explores the immunogenetic associations of human leukocyte antigens (HLA) and the calcium release-activated calcium modulator 1 (ORAI1) and stromal interaction molecule 1 (STIM1) genes in HIV-1‒positive patients with HIV-related skin disorders. METHODS: This study assessed the distribution of variants of HLA class II alleles and expression levels of ORAI1 and STIM1 genes in the blood between HIV-1‒positive patients with HIV-related skin disorders and the control group with no HIV within the Latvian population. RESULTS: The research group comprised 115 HIV-1‒positive patients with HIV-related skin disorders, and the control group included 80 healthy individuals. Risk alleles (HLA- DQB1*02:01-0301 and HLA-DQA1*01:01-0501) and protective alleles (HLA-DRB1*07-13, DRB1*01-13, DRB1*04-11, and HLA-DQA1*05:01-0501) showed statistical significance in the groups. In 38 out of 115 patients, higher expression levels of ORAI1 and STIM1 genes were detected in the blood at the beginning of treatment. A significantly higher level of the microribonucleic acid (mRNA) ORAI1 gene was also found in the control group. CONCLUSIONS: The results demonstrate that HLA class II alleles are associated with a trend toward risk/protection concerning HIV-related skin disorders in HIV-1‒positive patients. It was also shown that a low level of ORAI1 mRNA and the risk allele HLA-DQB1*0201-0301 were simultaneously present in the research group.

Contact dermatitis: etiologies of the allergic and irritant type.

The term contact dermatitis describes an inflammatory process of the skin that occurs in response to contact with exogenous substances and involves pruritic and erythematous patches. Approximately 80% of all contact dermatitis is primary irritant contact dermatitis (ICD), whereas allergic contact dermatitis (ACD) makes up only 20% of contact dermatitis cases, the estimated prevalence of contact dermatitis in the United States being 1.4%. Among patch-tested patients, nickel has been identified as the most common allergen. Cobalt is the second most common metal allergen and is found in various dental alloys, paints, and coloring components of porcelain and glass. The average prevalence of dermatitis due to p-phenylenediamine (PPD) was found to be 4.3% in Asia, 4.0% in Europe, and 6.2% in North America. Rubber gloves are a major cause of occupational ACD in healthcare workers. Occupations involving frequent handwashing, between 20 and 40 times per day, have shown an increased incidence in cumulative ICD. The prevalence of occupational hand dermatitis was 69.7% in workers that reported a handwashing frequency exceeding 35 times per shift. The use of alcohol-based sanitizers is much more prevalent among today's healthcare workers than frequent handwashing. Both allergic and ICD are worldwide problems.

Plasma sublimation for the treatment of xanthelasma palpebrarum.

INTRODUCTION: Xanthelasma palpebrarum (XP) is a common xanthomatous lesion of the eyelid and periorbital skin. Several methods of treatment have been reported in the literature, each having its own indications and risks. We present a new treatment method for removing XP using a plasma exeresis device (Plexr®, GMV, Italy). METHODS: Fifteen patients with a total of 27 treated XPs were assessed and clinically identified by the treating dermatologist. Patients were photographed and assessed by a dermatologist prior to and immediately after treatment. A patient survey was conducted 12 months after the procedure, which assessed the outcome of the procedure (redness, pigmentation disorders, and scars). RESULTS: After just a single treatment session using a plasma sublimation, all 27 XPs showed complete clearance. There were no reports of scars, pigmentary alteration, or recurrence of lesions up to 12 months. CONCLUSIONS: We present plasma sublimation as a new method for the treatment of XP. During the procedure, the method allows to control the depth of tissue destruction and the presence of xanthoma tissue, and to minimize pain and trauma, making it particularly ideal for treating areas around the eye.

Hailey-Hailey disease: a diagnostic challenge.

Hailey-Hailey disease (HHD) is an autosomal-dominant genodermatosis characterized by crusted macerated erosions, as well as velvety, dry, fissured plaques in the intertriginous areas. No predilection for sex or ethnic group has been reported. The typical age of onset is in the third decade of life. Diagnosis of HHD is suggested based on clinical morphology, location of lesions, family history, and histology demonstrating a characteristic dilapidated brick wall appearance of the epidermis. However, HHD often is misdiagnosed due to lack of knowledge of this uncommon disorder and its resemblance to other dermatoses. We describe an unusual presentation of HHD with a late age of onset and involvement of nonintertriginous regions.

Long-term efficacy and tolerability of tacrolimus 0.03% ointment in infants:* a two-year open-label study.

BACKGROUND: Tacrolimus ointment is effective for treatment of moderate to severe atopic dermatitis (AD) in children aged ≥2 years (Br J Dermatol, 2004; 150: 554). Here, efficacy and tolerability of tacrolimus 0.03% ointment were evaluated in 50 infants aged <2 years at start of treatment. METHODS: Infants with AD previously enrolled in a tacrolimus ointment pharmacokinetics trial were eligible for a 24-month open-label phase II study. Tacrolimus 0.03% ointment was applied to affected areas until clearance. In cases of exacerbation or clinical worsening, patients restarted treatment. RESULTS: Mean ± SD Eczema Area and Severity Index (EASI) score improved, from 11.2 ± 10.5 baseline to 2.6 ± 4.1 at endpoint (24 months); mean affected body surface area decreased from 25.2 ± 21.1% to 5.1 ± 9.0%, with improvement on all items of the Physicians' Assessment of Individual Signs. The Physicians' Global Evaluation of Clinical Response showed a result of "cleared"/"excellent" for 63.3% of patients; 85.7% of parents/guardians assessed symptoms as "much better." Treatment was well tolerated, with common, nonserious respiratory infections and gastroenteritis the most frequently reported adverse events. The most common application-site events were infections and pruritus. Over 98% of blood samples showed tacrolimus concentrations <1.0 ng/ml; >40% showed concentrations below the lower limit of quantification (0.0250 ng/ml). CONCLUSIONS: Over a period of two years, tacrolimus 0.03% ointment was associated with substantial clinical improvement of AD in infants aged <2 years. Treatment tolerability was similar to that seen in older children.

The pharmacokinetics of tacrolimus after first and repeated dosing with 0.03% ointment in infants with atopic dermatitis.

BACKGROUND: In adults and children aged > 2 years, systemic absorption of tacrolimus from tacrolimus ointment is very low. In this study, the pharmacokinetics of tacrolimus 0.03% ointment were investigated in infants aged 3-24 months. METHODS: The pharmacokinetics of tacrolimus after first and repeated topical application of tacrolimus 0.03% ointment were evaluated in 53 infants (age, 3-24 month) with atopic dermatitis requiring treatment with mid-potency topical corticosteroids. Patients were grouped according to percentage of body surface area affected (Group 1: 5-20%; Group 2: > 20-40%; Group 3: > 40%). After stratification, patients were randomized (double-blind) to receive once-daily or twice-daily tacrolimus 0.03% ointment. RESULTS: Blood samples taken on days 1 and 14 (first and last application) showed minimal systemic tacrolimus exposure. Overall, 97% of blood samples assayed contained tacrolimus concentrations < 1 ng/ml, and 20% were below the lower limit of quantification (0.025 ng/ml). Systemic tacrolimus exposure was variable, but tended to increase as the treated body surface area increased. Mean apparent half-life of tacrolimus was 80 +/- 35 h (range: 25-175 h). Most patients experienced substantial clinical improvement in their atopic dermatitis. There were no clinically significant changes in laboratory values, and the most frequently reported adverse events were minor infections and local skin irritations. CONCLUSIONS: Tacrolimus 0.03% ointment in infants is associated with very low systemic exposure to tacrolimus. Treatment was well tolerated and led to considerable clinical improvement.

0.3% Tacrolimus gel and 0.5% Tacrolimus cream show efficacy in mild to moderate plaque psoriasis: Results of a randomized, open-label, observer-blinded study.

The efficacy and safety of 0.3% tacrolimus gel and 0.5% tacrolimus cream compared with calcipotriol ointment were evaluated in adults (n = 124) with mild to moderate plaque psoriasis. Treatment was twice daily for a maximum of 12 weeks. Clinical efficacy was assessed by the percentage change in the local psoriasis severity index of a target lesion between baseline and week 12. By week 12, the median percentage changes in local psoriasis severity index of the target lesions in the tacrolimus gel, tacrolimus cream and calcipotriol groups were 55.6%, 50.0% and 58.6%, respectively (no statistically significant differences). Clinical improvement was observed after one week and increased throughout the study. Tacrolimus-treated patients experienced more application site skin burning (tacrolimus gel and cream both 31.0% versus 7.5% for calcipotriol; p = 0.011). Skin burning was mostly mild in intensity and decreased substantially after 1 week of treatment. There were no differences in the nature and incidence of infections and no clinically relevant changes in laboratory values.

Pharmacokinetics of 0.1% tacrolimus ointment after first and repeated application to adults with moderate to severe atopic dermatitis.

The systemic exposure to tacrolimus after first and repeated application of 0.1% tacrolimus ointment was investigated in 32 adults with moderate to severe atopic dermatitis. Patients were allocated to treatment groups according to the size of the affected area to be treated: Group 13000 cm(2)6000 cm(2)

A multicenter study of the pharmacokinetics of tacrolimus ointment after first and repeated application to children with atopic dermatitis.

The pharmacokinetics of tacrolimus after first and repeated application of 0.1% tacrolimus ointment were evaluated in 39 children, aged 6-12 y, with moderate to severe atopic dermatitis. The patients were grouped according to the size of the affected body surface area to be treated: Group 1< or =1500 cm(2); Group 2 >1500 cm(2) < or =3000 cm(2); Group 3 >3000 cm(2) < or =5000 cm(2). Serial blood samples to calculate pharmacokinetic parameters taken on Day 1 (first ointment application) and Day 14 (last application) showed minimal systemic exposure to tacrolimus. Overall, 92% of the blood samples assayed contained tacrolimus concentrations below 1 ng per mL and 17% of samples were below 0.025 ng per mL, the lower limit of quantification. Systemic exposure to tacrolimus varied between patients and tended to increase proportionally as the size of the treated body surface area increased. Absorption decreased with time as the skin lesions healed and there was no evidence of systemic accumulation. The mean apparent half-life of tacrolimus (t(1/2, z)) was 66+/-27 h (range 19-125 h). Most patients experienced substantial clinical improvement in their atopic dermatitis. There were no clinically relevant changes in laboratory values, and the most frequently reported adverse event was skin burning, which resolved quickly as the skin condition improved.