Keratosis pilaris/ulerythema ophryogenes and 18p deletion: is it possible that the LAMA1 gene is involved?
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Biomedical subjects
Publications and source records attributed to H P Gollnick.
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Our objective was to determine patient attitudes to having genital warts, and their perceptions of their treatment with imiquimod and other therapies. As an adjunct to a clinical trial in which patients with external genital warts were treated with imiquimod 5% cream until their warts cleared or for up to 16 weeks, quantitative questionnaires consisting of multiple choice questions and 5-point rating scales were completed prior to, and at the end, of the study period. Pre-study and post-study questionnaires were completed by 902 and 629 patients, respectively. Patients expressed a definite concern about genital warts. The majority of patients (70%) had been previously treated for genital warts, and expressed dissatisfaction with their previous therapies. Of patients treated with imiquimod in this study, 82% reported that their warts decreased in size; this occurred within the first 4 weeks for 78% of patients. Sixty-one per cent of patients perceived that their warts completely cleared within the 16-week treatment period. Patients rated imiquimod 5% cream as better than other genital wart therapies in terms of overall satisfaction, time to clearance, convenience and lack of associated pain. In conclusion, patients rated imiquimod 5% cream as an effective treatment which clears warts in an acceptable length of time causing minimal pain and is convenient to use.
UV light exerts hazardous effects such as induction of skin cancer and premature skin aging. In this study we evaluated an assumptive anti-inflammatory effect of the nonsedative histamine H1-receptor antagonist, mizolastine, on UV-induced acute sunburn reaction. Therefore, a clinical, randomized, double-blind, four-arm, crossover study was conducted in healthy young female volunteers (skin type II) comparing the UV sensitivity under mizolastine, acetyl-salicylic acid (ASA), indomethacin or a mizolastine/ASA combination. Moreover, HaCaT keratinocytes were incubated with mizolastine under various UV treatment modalities in vitro to study its effect on the release of inflammatory cytokines, i.e. interleukin (IL)-1 alpha, IL-6 and tumor necrosis factor alpha (TNF-alpha). All three drugs were effective in suppressing the UVB-, UVA- and combined UVA/UVB-erythema. However, the strongest effects were observed using the combined treatment with both 250 mg ASA and 10 mg mizolastine. An inhibitory effect in vitro of 10 nM mizolastine upon UV-induced cytokine release from HaCaT keratinocytes was observed for IL-1 alpha at 24 h after 10 J/cm2 UVA1, for IL-6 at 48 h after 10 J/cm2 UVA1 and 30 mJ/cm2 UVB, and also for TNF-alpha at 4 h after 10 J/cm2 UVA, 10 J/cm2 UVA1 and 30 mJ/cm2 UVB, respectively. The combination of mizolastine and ASA can be strongly recommended as a protective measure against UV erythema development with a lower unwanted side effect profile than that of the hitherto treatment modality, i.e. indomethacin.
BACKGROUND: This paper reports the proceedings of the European Advisory Panel Meeting for tazarotene (Zoractrade mark), which took place in Cologne on May 7, 1998. AIM: The aim of this meeting was to discuss recommendations for the use of tazarotene based on the clinical data available and on the clinical experience of the Advisory Panel members, and to identify future research needs. RECOMMENDATIONS: Based on currently available data, tazarotene can be used for the treatment of chronic, stable, plaque-type psoriasis, on the trunk or limbs covering up to 20% of the body surface area. In clinical trials, patients generally experienced a clinical response within 4 weeks of starting tazarotene treatment, and improvement was maintained for up to 12 weeks after stopping therapy. Results from published and not yet published clinical trials show that the efficacy and tolerability of tazarotene can be enhanced by the addition of topical corticosteroids to the treatment regimen and that, when used in combination with broad-band UVB phototherapy, tazarotene reduces the amount of UV light required to treat plaques. Tazarotene gel is available in two concentrations, 0.05 and 0.1%. The Advisory Panel recommends that the choice of concentration should be based on factors such as the irritability of the patient's skin and the thickness of plaques. Irritation can be managed by reducing the concentration or frequency of application, or by adding a topical corticosteroid to therapy. Tazarotene shows promise as a treatment for psoriasis in special localisations, such as the scalp, face and skin folds, although clinical studies are required.
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The German Registry of Adamantiades-Behçet's disease was founded in 1990 in Berlin and it provides current data on the epidemiology, the clinical manifestations and the course of the disease in Germany on a continuous basis. A total of 218 patients, including 89 German and 100 Turkish patients, had been reported to the German Registry until October 1997. One hundred and ninety-six patients fulfilled the criteria of the Behçet's disease classification tree. The prevalence of the disease evaluated in Berlin-West was 1.68/100,000 in 1989 and had risen to 2.26/100,000 by 1994. The median age of onset was 25 years (range 5 to 66 years; German-Turks, ns). Juvenile disease was recorded in 6.9% of patients. The complete clinical picture according to the criteria of the International Study Group of Behçet's Disease developed in 15.5 months. The interval between onset of the disease and diagnosis was 35 months, which was significantly longer than the duration of the development of the complete clinical picture (p < 0.0001). The disease was diagnosed later in German (48.5 months) than in Turkish patients (25.5 months, p = 0.003). While German patients presented an equal male-to-female ratio, a male predominance was shown in Turkish patients (M:F 2.1:1, p = 0.022). Familial occurrence was detected in 2.0% of German and 15.9% of Turkish patients (p = 0.013). The frequencies of major clinical manifestations were: oral ulcers 99%, skin lesions 76%, genital ulcers 75%, ocular manifestations 59%, arthritis 59%, and positive pathergy test 52%. Clinical differences between German and Turkish patients were only found in the frequency of ocular lesions (48% vs. 66%, p = 0.025). Oral ulcers were with 72% the most common onset symptom of the disease followed by erythema nodosum (9%), uveitis (7%), arthritis (7%), genital ulcers (3%), superficial thrombophlebitis (2%) and papules/sterile pustules (2%). Uveitis and erythema nodosum as onset symptoms shortened the median interval to diagnosis to 1.5 and 15 months, respectively, while arthritis delayed diagnosis (43.5 months; p = 0.029). A severe course developed in 25% of the patients; irreversible retinal vasculitis to blindness in 15%, sterile meningoencephalitis in 8%, severe arthritis in 5%, hemoptysis in 2%, lethal outcome in 2% and bowel perforation in 1%. The relative risk of HLA-B5 positive German natives developing the disease. HLA-B5 was confirmed as a marker of severe prognosis. Cardiolipin autoantibodies were associated with cutaneous vasculitis and superficial thrombophlebitis was correlated with systemic vessel involvement.
Psoriasis is a disease of unknown aetiology, affecting approximately 1-3% of the population. In most cases involving relatively localized disease, patients are best managed with either topical therapy alone or topical therapy in combination with UV-phototherapy. However, approximately 35% of patients do not respond well to these conventional treatments or have moderate-to-severe disease requiring more aggressive forms of therapy. The second-generation retinoids, etretinate and its metabolite acitretin, are important additions to the armamentarium of agents used to treat these recalcitrant or severe forms of the disease. Generalized pustular psoriasis generally responds well to high-dose (0.7-1 mg/kg/day) oral retinoid monotherapy. In contrast, increasing small doses of the retinoid are recommended initially in erythrodermic psoriasis in order not to provoke the disease. Long-term clinical experience favours a combination treatment of the retinoid with either topical and/or UV irradiation in chronic plaque-like psoriasis. Both oral retinoids have comparable efficacy and tolerability profiles, and the relapse rates for both drugs are similar. The toxicities associated with both short- and long-term treatment with oral retinoids are significant and include mucocutaneous effects, adverse modulation of serum lipid chemistries, elevation of liver enzymes, and after long-term chronic dosing, skeletal and ligamentous calcification, and hyperostosis. Both etretinate and acitretin, like all retinoids, are known teratogens in animal models, and documented evidence exists for teratogenic activity in humans as well. Consequently, women of childbearing age are strongly advised to avoid pregnancy during treatment and up to 5 years following cessation of therapy with both etretinate and the carboxylic acid metabolite acitretin.
We conducted a randomized placebo-controlled double-blind study in 20 healthy young female students (skin type II + III, body mass index 18-22) in order to evaluate the efficacy of 10 weeks of moderate dose (30 mg/d) beta-carotene (BC) on plasma and skin beta-carotene levels during 12 days of time and intensity controlled sunlight exposure at sea level (30 degrees latitude, Red Sea, Eilath, Israel). After 12 days of controlled sun exposure (total UV dose of about 10.000J/cm2), plasma beta-carotene decreased in the placebo (p < 0.01) and beta-carotene group (not significant). In addition cutaneous beta-carotene decreased significantly in both groups. Plasma alpha-tocopherol decreased significantly (p < 0.01) during exposure time in both groups. In the supplemented group, however, the decrease of a-tocopherol was significantly greater (p < 0.01) than in the placebo group. We conclude that sunlight influences the beta-carotene and alpha-tocopherol content of blood and tissues.
Azelaic acid cream (20 percent) is a new topical treatment for acne with an additional therapeutic potential in rosacea and hyperpigmentation disorders. Azelaic acid (AzA; HOOC-(CH2)7-COOH) is a naturally occurring compound that interferes with acne pathogenesis by virtue of its antikeratinizing, antibacterial, and anti-inflammatory properties. Vehicle-controlled studies have verified that AzA exercises a significant and clinically relevant effect on both non-inflammatory and inflammatory acne lesions. Comparisons with clinically proven therapies have shown that 20 percent AzA cream is an effective monotherapy in mild to moderate forms of acne, with an overall efficacy comparable to that of tretinoin (0.05 percent), benzoyl peroxide (5 percent), and topical erythromycin (2 percent). In the treatment of moderate to severe acne, 20 percent AzA cream may be favorably combined with minocycline (90 percent good and excellent results), and may contribute towards reducing recurrences following discontinuation of systemic therapy (maintenance therapy with AzA cream). Particular advantages of AzA therapy include its favorable safety and side effect profile. It is non-teratogenic, is not associated with systemic adverse events or photodynamic reactions, exhibits excellent local tolerability, and does not induce resistance in Propionibacterium acnes.
Extracorporeal photochemotherapy (extracorporeal photopheresis, ECP) is going to become a new alternative in the treatment of cutaneous T cell lymphomas (CTCL), autoimmune disorders, and transplant rejections. After the first promising results in the treatment of CTCL reported in 1987 by Edelson et al. increasing numbers of CTCL patients in a growing number of ECP centers throughout the United States, Europe, and Japan have been successfully treated. Today, it seems that in particular Sézary's syndrome and the erythrodermic variant of mycosis fungoides (MF) respond very well to ECP. Compared to historical controls of MF with lymph node involvement, the median survival of the ECP-treated patients increased from 30 months to up to 60 months. It is our experience that the tumor stage of MF, however, cannot be treated with ECP alone, but is successfully controlled by combination regimens, for example with recombinant interferon alpha. CTCL patients heavily pretreated by polychemotherapy and severe endogenous or iatrogenic immunsuppression do not respond sufficiently and are not good candidates for ECP. The adverse reactions under ECP are well controlled and very low in number. In particular, general immunosuppression by ECP has not been reported so far.
Little is known about the composition of the cellular infiltrate in the early elicitation phase of contact allergy in atopic individuals. Therefore, we rechallenged ten presensitized disease-free atopic volunteers with their known contact allergen and performed biopsies at time 0 and after 6 and 24 h. Ten patients with acute exacerbated atopic dermatitis in the early stage were chosen as a control group. Skin biopsy specimens were processed for immunohistochemistry (APAAP) and evaluated by computer-assisted morphometry. CD4+ and CD45R0+ cells were found to be significantly increased after 6 (t6) and 24 h (t24), and this was accompanied by an enhanced TCR alpha/beta receptor expression at t6-CD45O+ cells showed a marked influx into the epidermis at t24. CD8+ cells infiltrated the basal layer of the epidermis, thus changing the CD4/CD8 ratio from 4.6:1 at t0 to 2.2:1 at t6. CD1a+ epidermal dendritic cells increased significantly from 811 +/- 240/mm2 at t0, to 1210 +/- 333/mm2 at t24 (P < 0.01). At t6 and t24, a so-called 'epitope CD1a+ shedding' was observed into the intercellular spaces of keratinocytes as well as an elongation and enlargement of the dendrites of CD1a+ cells. In the upper dermis, the number of CD1a+ cells increased from 1098 +/- 485/mm2 at t0 to 2388 +/- 740/mm2 at t24 (P < 0.01). In 7/10 volunteers, IgE+ dendritic cells increased significantly in number at t6 (P < 0.02). The activation markers HLA-DR and CD25 were expressed most distinctly at t24. Interestingly, expression of ICAM-1 on keratinocytes occurred only in four of the ten atopic volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)
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BACKGROUND/AIMS: The primary aim of the study was to establish the clinical efficacy and safety of a combined treatment consisting of topical 20% azelaic acid (AA) cream and the oral antibiotic minocycline in the therapy of severe inflammatory acne (nodular papulopustular acne and acne conglobata) in a comparison with oral isotretinoin therapy. The secondary aim was to establish the value of AA cream as maintenance therapy in the prevention of recurrent acne. METHODS: This open-label but randomised study involved 85 patients with nodular papulopustular acne or acne conglobata (Leeds grading scale > 4) who were treated for 6 months. In an immediately subsequent 3-month second phase, eligible patients from the initial combination group used the AA cream as maintenance therapy, while the eligible patients from the isotretinoin group served as untreated control. RESULTS: A 6-month course of treatment with topical 20% AA cream plus oral minocycline in 50 patients proved to be effective in nodular forms of acne (median reduction of facial comedones: 70%; of papules and pustules: 88%; of deep inflammatory acne lesions: 100%). Overall, the combined treatment was not quite as effective as treatment with oral isotretinoin (35 patients; reduction of comedones: 83%; of papules and pustules: 97%; of deep inflammatory acne lesions: 100%). In the 3-month maintenance therapy phase, about half of the patients who received AA monotherapy maintained the very good facial result achieved by the end of phase I. A similar rate was found in the patients of the isotretinoin group, who received no further active acne treatment. In the other 50% of patients, differences existed between the groups as regards the degree of deterioration: Marked deterioration occurred more frequently under AA treatment, while only slight deterioration was more frequent in the isotretinoin group. The combination was tolerated much better than isotretinoin. The incidence of local side effects observed under the combination of AA and minocycline (36.5%, mainly transient burning and itching of mild or moderate intensity) was considerably lower than that seen with isotretinoin (65.7%). The rate of local side effects of marked intensity observed under the combination, i.e. 6%, was well within the range of 5-10% previously reported for AA. The incidence of systemic side effects was lower (8%, mainly gastrointestinal symptoms) under the combined therapy than under isotretinoin (14.3%). CONCLUSION: The combination of topical 20% AA cream and oral minocycline is an highly effective treatment in severe forms of acne. It is better tolerated and associated with fewer risks than oral isotretinoin - in particular, there is no risk of teratogenicity. The combination can be regarded as a valuable alternative in patients for whom isotretinoin is not indicated, who do not wish to use or can not tolerate isotretinoin therapy and particularly in female acne patients of child-bearing potential. Topical 20% AA cream can be used successfully as maintenance therapy to prolong the recurrence-free interval.