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Biomedical subjects

S Reitamo

Publications and source records attributed to S Reitamo.

At least 37 records · Page 2Linked to original sources

Long-term follow-up of eczema patients treated with cyclosporine.

Cyclosporine is efficacious in short-term treatment of various eczematous disorders. In a follow-up study we have evaluated the long-term efficacy of cyclosporine in 75 patients, who in previous studies had been treated with cyclosporine for chronic actinic dermatitis (6 patients), atopic dermatitis (42 patients) and chronic hand eczema (27 patients), 4, 2 and 1 year after the initial treatment, respectively. Three out of 6 patients with chronic actinic dermatitis showed long-term efficacy. Two years after the initial treatment with cyclosporine (5 mg/kg/day for 1-2 treatment periods of 6 weeks) for atopic dermatitis the mean disease activity was significantly lower compared to baseline (58% decrease), and compared to the time of treatment stop no significant change had occurred. Of 37 evaluable patients 35 were still in remission. One year after the initial treatment with cyclosporine (3 mg/kg/day for 6 weeks) for chronic hand eczema the mean disease activity was significantly lower than at baseline (54% decrease), and compared to the time of treatment stop no significant change had occurred. Of 27 evaluable patients 21 patients were still in remission. The study suggests that long-term remissions are possible in eczematous diseases treated with cyclosporine, even for a relatively short treatment period. It must be stressed, however, that we did not have control groups for any of the studied patient groups.

Adult↗

A short-term trial of tacrolimus ointment for atopic dermatitis. European Tacrolimus Multicenter Atopic Dermatitis Study Group.

BACKGROUND: Tacrolimus (FK 506) is an effective immunosuppressant drug for the prevention of rejection after organ transplantation, and preliminary studies suggest that topical application of tacrolimus is effective in the treatment of atopic dermatitis. METHODS: We conducted a randomized, doubleblind, multicenter study that compared 0.03 percent, 0.1 percent, and 0.3 percent tacrolimus ointment with vehicle alone in patients with moderate to severe atopic dermatitis. The ointment was applied twice daily to a defined, symptomatic area of 200 to 1000 cm2 of skin for three weeks. The primary end point was the change in the summary score for erythema, edema, and pruritus between the first and last days of treatment. RESULTS: After three weeks of treatment, the median percentage decrease in the summary score for dermatitis on the trunk and extremities was 66.7 percent for the 54 patients receiving 0.03 percent tacrolimus, 83.3 percent for the 54 patients receiving 0.1 percent tacrolimus, 75.0 percent for the 51 patients receiving 0.3 percent tacrolimus, and 22.5 percent for the 54 patients receiving vehicle alone (P<0.001). The results for the face and neck were similar. The differences among the three tacrolimus groups were not statistically significant. A sensation of burning at the site of application was the only adverse event that was significantly more frequent with tacrolimus than with vehicle alone (P<0.001). Throughout the study, most patients in all three tacrolimus groups had blood concentrations of tacrolimus below 0.25 ng per milliliter. The highest concentration was 4.9 ng per milliliter, which was reported in the group receiving 0.3 percent tacrolimus. CONCLUSIONS: The short-term application of tacrolimus ointment is effective in the treatment of atopic dermatitis, with the sensation of burning being the main side effect.

Administration, Cutaneous↗

Comparison of the influence of cyclosporine and topical betamethasone-17,21-dipropionate treatment on quality of life in chronic hand eczema.

In a randomized, controlled parallel group study we have shown that cyclosporine at 3 mg/kg/day is as effective as topical betamethasone-17,21-dipropionate in the treatment of chronic hand eczema. In this study we compared the influence of these therapies on the quality of life. Forty-one patients were treated with either treatment for 6 weeks, after which patients with failure were switched to the other treatment for another 6 weeks. Quality of life was assessed with the Eczema Disability Index (EDI) at baseline and at the end of both treatment periods. The total EDI score decreased significantly and to the same degree in both groups, i.e. from the mean value of 30.5 to 20.9 in the cyclosporine group and from 27.2 to 18.9 in the betamethasone-17,21-dipropionate group. Irrespective of the dimension of the EDI (daily activity, school/work, personal relationship, leisure, treatment), the difference between the treatment groups at the end of the first treatment period was not significant. In the second part of the study a slight further decrease in total score was observed, but without any difference between the groups. There was a significant correlation between changes in the total EDI score and changes in all the clinical assessments, i.e. disease activity, extent of the disease, itch, sleep disturbances and use of emollients. Though the significant correlation between the total EDI and clinical assessments makes quality of life assessments in hand eczema questionable, the missing correlation between some clinical assessments and dimensions of the EDI suggests that EDI views aspects of the disease not covered by clinical measures.

Administration, Topical↗

Comparison of cyclosporin A pharmacokinetics of a new microemulsion formulation and standard oral preparation in patients with psoriasis.

Cyclosporin A (CyA) is a potent immunosuppressive drug which has shown efficacy in various skin disorders. The bioavailability of the oral CyA formulation (Sandimmun) is approximately 30%, showing high interpatient and intrapatient variability. The steady-state pharmacokinetics, efficacy and tolerability of CyA in two formulations: commercial Sandimmun soft gelatin capsules (CyA-SGC) and a newer oral formulation (Sandimmun Neoral: CyA-NOF), were compared in an open prospective study with a crossover between the two treatments in 19 patients with psoriasis. Each patient received a twice-daily treatment of CyA with a clinically effective dose of 2-5 mg/kg per day. The individual dosages were kept unchanged for at least 2 weeks before study entry and over the 42-day course of the study. At entry, patients were switched to CyA-NOF for 4 weeks and then back to CyA-SGC for another 2 weeks. Pharmacokinetic profiles were assessed at steady-state on day 14 while the patients were on CyA-NOF, and on day 42 while on CyA-SGC. Switching from CyA-SGC to CyA-NOF using 1:1 dose conversion resulted in an increased absorption of the drug. On average there was a 61% increase in maximum drug concentration (Cmax) and a 32% increase in the area under the steady-state blood concentration-time curve (AUC): Cmin was comparable in the two formulations. The increases in Cmax and AUC were associated with some increase in the clinical efficacy of the treatment. The number of adverse events reported by the patients and observed by the investigators were increased during CyA-NOF; the mean serum creatinine levels were not affected. An increased and a more consistent and predictable absorption of CyA is achieved with the new oral microemulsion formulation.

Administration, Oral↗

Treatment of lichen sclerosus with carbon dioxide laser vaporization.

We have treated 10 patients (five women and five men) with lichen sclerosus (LS), verified by histopathological studies from skin biopsies, with CO2 laser vaporization. All men studied had LS of the penile skin, of the women, three had extragenital lesions and two LS of the perineal skin. The mean follow-up time was 32 months (range 3-79 months). One man had both penile and urethral LS. All penile lesions of the five men were clinically cured by laser treatment: however, urethral lesions of one patient recurred despite three separate treatments. The two women with perineal LS improved after laser treatment. However, LS recurred on the treated are in one and on the margins of the treated area in another. Two women with LS on the skin of the breast became asymptomatic after treatment. One woman had several lesions on the skin of the trunk that improved after treatment but were not cured completely. The present study suggests that carbon dioxide vaporization may be an effective treatment of skin lesions in LS.

Adult↗

A study of 72 patients with contact allergy to tioconazole.

Over a 3 1/2 year period, from 1991 to 1994, we detected contact allergy to tioconazole in 72 patients by epicutaneous testing. During this period, tioconazole was included in the standard series of epicutaneous tests. Except for the first 6 months, the incidence of positive patch test reactions to tioconazole was over 1% of patients tested for contact allergy. As well as those tested with the standard series, 18 additional patients with tioconazole allergy were detected by direct testing with an imidazole patch test series. Of the various imidazole derivatives, tioconazole was the most important contact allergen. About half of patients with contact hypersensitivity to tioconazole, had additional contact allergies detected by the standard series. Men and women were equally affected. The present study suggests that tioconazole is an important contact allergen, which should be included into the patch test series in countries where it is used as a topical antifungal agent.

Adult↗

Delayed-type hypersensitivity in palmoplantar pustulosis: effect of cyclosporin A treatment on skin testing with recall antigens.

Delayed-type hypersensitivity reactions to skin antigens are an indirect measure of cellular immune response. We studied in a double-blind manner whether clinically effective doses of cyclosporin A in palmoplantar pustulosis would diminish delayed-type hypersensitivity reactions in vivo. For testing delayed-type hypersensitivity, we applied intradermally a standardized panel of seven recall antigens and a vehicle control in 30 patients with palmoplantar pustulosis, and 28 were tested both at baseline and after 4 weeks. For 4 weeks 14 patients were treated with 2.5 mg/kg/day cyclosporin A and 14 patients with placebo. Cyclosporin A but not placebo caused a significant decrease in clinical disease parameters. In contrast, no significant differences in delayed-type hypersensitivity reactions between treatment groups were observed. The results do not support the view that the efficacy of low-dose cyclosporin A in dermatological disorders can be entirely explained by cyclosporin A's inhibitory actions on effector T-cells.

Adult↗

Comparison of cyclosporine and topical betamethasone-17,21-dipropionate in the treatment of severe chronic hand eczema.

Topical corticosteroids are the standard treatment for hand eczema. However, in chronic forms of the disease they are often ineffective or lose their efficacy due to tachyphylaxis. In a previous open study cyclosporine showed efficacy in chronic hand eczema. The aim of this study was to compare oral cyclosporine at 3 mg/kg/day with topical 0.05% beta-methasone-17,21-dipropionate (BDP) cream in the treatment of chronic hand eczema. In a randomized, double-blind study 41 patients with chronic hand eczema resistant to conventional treatment were assigned to either cyclosporine or BDP for 6 weeks. Both cyclosporine and BDP improved the eczema. The total disease activity score decreased to 57% of baseline in the cyclosporine group (mean change -6, SD 4.3; p < 0.001) and to 58% of baseline in the BDP group (mean change -5.7, SD 4; p < 0.001) at the end of treatment. However, between the groups there was no significant difference. Adverse events occurred in 68% of the patients during cyclosporine and in 56% during BDP treatment. With cyclosporine no case of hypertension or increase in serum creatinine above normal levels was recorded. In two patients the serum creatinine levels increased to values 30% above their own baseline values. Relapses occurred to the same extent in both groups. Cyclosporine at 3 mg/kg/day is as effective as topical BDP in the treatment of chronic hand eczema. Low-dose cyclosporine could be useful as an alternative treatment for severe chronic hand eczema in patients unresponsive to conventional treatment.

Administration, Oral↗

Cyclosporin in atopic dermatitis: time to relapse and effect of intermittent therapy.

The efficacy of cyclosporin (CyA) in the induction of remission in atopic dermatitis has been documented in controlled studies. However, little information is available on the duration of remission after CyA treatment. We studied the length of remission in 43 patients with severe atopic dermatitis after a 6-week treatment period with CyA at 5 mg/kg per day. After a follow-up of 6-26 weeks, depending on the time-point of relapse, a second treatment period with CyA, identical to the first, was performed. Disease activity was evaluated bi-weekly, using six different parameters: 1, a total body disease activity score; 2, the extent of the disease; 3, the occurrence of itch; 4, the occurrence of sleep disturbance; 5, the use of topical emollients; and 6, the use of topical hydrocortisone. A significant decrease in disease activity was observed. The total body disease activity score decreased from the baseline score of 31 to 11.6 at the end of the first part and to 13.4 at the end of the second part of the study. An almost maximal response to treatment was already apparent after 2 weeks of treatment. All the other efficacy parameters studied also showed a significant response to CyA treatment. A similar response to CyA was seen when the patients were re-treated. After both treatment periods, approximately half of the patients relapsed after 2 weeks (42% first part; 54% second part). After 6 weeks follow-up, the relapse rates were 71 and 90%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Hypertension in cyclosporin A-treated patients is independent of circulating endothelin levels.

OBJECTIVES: To measure blood pressure (BP), plasma endothelin-1 (ET-1), atrial natriuretic peptide (ANP), antidiuretic hormone (ADH) and aldosterone (ALDO) concentration, and plasma renin activity (PRA) in patients treated with a low-dose cyclosporin A (CyA). DESIGN: An open study of patients with rheumatoid arthritis (RA) or palmoplantar pustulosis (PPP). SETTING: Out-patient clinics at the Central Hospital of Jyväskylä and Helsinki University Central Hospital. SUBJECTS: CyA was given to 25 patients with RA and to 10 patients with PPP. INTERVENTION: RA patients were given CyA at a dose of 2.5 +/- 0.13 mg kg-1 body weight (BW) to 3.47 +/- 0.79 mg kg-1 BW (mean values +/- SD) at the start of the study and after 6 months, respectively, and the CyA dose was 2.67 +/- 0.13 mg kg-1 BW decreasing to 2.07 +/- 0.96 mg kg-1 (P < 0.001) after 4 months in PPP subjects. RESULTS: Systolic (sBP) and diastolic blood pressure (dBP) increased from 127.8 +/- 13.6/79.7 +/- 8.4 mmHg to 140.0 +/- 19.8/83.8 +/- 9.7 mmHg during the study (P < 0.03). Plasma ET-1, ANP, ALDO and ADH concentration and PRA did not change during 4 to 6 months of CyA treatment. The plasma ANP concentration was constantly higher in CyA-treated RA patients (112 +/- 87 ng 1-1 to 118 +/- 78 ng 1-1) than in PPP patients (37.3 +/- 26 ng 1-1 to 47.7 +/- 39.9 ng 1-1; P < 0.02). The serum creatinine concentration remained within the normal range, but increased from baseline (76.7 +/- 11.9 mumol 1-1), to 90 +/- 15.4 mumol 1-1 (p < 0.001). The serum magnesium concentration decreased significantly (P < 0.005) after 6 months of CyA treatment in RA patients. No correlation was found between serum creatinine and plasma ET-1 concentration. CONCLUSIONS: Increased blood pressure during CyA treatment was independent of circulating ET-1 levels. A low dose of CyA did not induce increased ET-1 synthesis as judged from plasma samples. The high plasma ANP level observed in RA patients could be due to fluid retention caused by concomitant treatment with non-steroid anti-inflammatory drugs. Fluid retention and decreased magnesium levels could also be involved in the development of hypertension in CyA-treated subjects.

Adult↗

Interleukin 10 up-regulates elastin gene expression in vivo and in vitro at the transcriptional level.

In immune cells, such as T cells and monocytes, interleukin 10 (IL-10) has regulatory functions on a number of cytokines, including IL-1, IL-2, IL-8 and tumour necrosis factor-alpha expression. However, the effects of IL-10 have not previously been studied in detail in connective-tissue cells. In the present study, we show that recombinant human IL-10 at physiological concentrations has direct effects on the expression of the human elastin gene both in vivo and in vitro. Transgenic mice expressing a human elastin promoter/chloramphenicol acetyltransferase (CAT) reporter gene construct were injected subcutaneously with IL-10 (1-100 ng) and the site of injection was biopsied after 24 h. CAT assay revealed an increase of up to 3.5-fold in the promoter activity with 10 ng of IL-10. Transforming growth factor-beta 2 (TGF-beta 2) is known to up-regulate elastin gene expression in cultured fibroblasts. When IL-10 was added to such cultures, the effects of TGF-beta 2 on elastin mRNA levels were synergistically potentiated. These results suggest that IL-10 has an up-regulatory effect on elastin gene expression.

Animals↗

Cyclosporin A in the treatment of chronic dermatitis of the hands.

The efficacy of cyclosporin A (CyA) treatment was studied in seven patients with chronic dermatitis of the hands. CyA was started at a daily dose of 2.5 mg/kg in five patients, and 1.25 mg/kg in two patients. In patients who responded to the treatment at 2.5 mg/kg/day, the daily CyA dose was reduced stepwise, to the lowest maintenance dose of 1.25 mg/kg. In patients who did not respond, the dose was increased, to a maximum of 5 mg/kg/day. The patients were treated for 2-16 weeks. In six of the seven patients the dermatitis responded to CyA treatment within a few weeks. No response was seen with a starting dose of 1.25 mg/kg/day. In three of the five patients with a starting dose of 2.5 mg/kg/day, the daily CyA dose could be reduced to 1.25-2 mg/kg/day. After stopping CyA treatment, the dermatitis recurred during follow-up in three patients, three remained in remission, and one patient was not available for study. Treatment-related side-effects occurred in three patients. CyA treatment had to be stopped in one patient due to headache. The present study suggests that CyA could be a useful treatment for chronic dermatitis of the hands not responding to conventional therapy.

Adult↗

Interleukin-10 modulates type I collagen and matrix metalloprotease gene expression in cultured human skin fibroblasts.

IL-10, originally isolated from mouse helper T cells, is a cytokine with regulatory functions on a number of interleukins. In this study we show that recombinant human IL-10 affects the expression of several genes involved in extracellular matrix synthesis and remodeling in human dermal fibroblast cultures. As judged by Northern blot analyses, type I collagen gene expression was downregulated, while collagenase and stromelysin gene expression were markedly enhanced by IL-10. No effect on tissue inhibitor of metalloproteases mRNA levels was noted. Transient transfections of skin fibroblasts with type I collagen promoter/chloramphenicol acetyl transferase reporter gene constructs showed downregulation by IL-10, suggesting inhibition at the transcriptional level. When compared with control cultures, incubation with IL-10 resulted in a decrease in immunostaining of fibroblast cultures with antibodies to human type I collagen. In contrast, immunostaining of such IL-10-treated cultures with antibodies to human collagenase resulted in an increase in immunostaining. This study suggests a role for IL-10 in the breakdown and remodeling of the extracellular matrix.

Blotting, Northern↗

Contact allergy to corticosteroids.

Recent evidence shows that contact allergy to topical corticosteroids is more frequent than earlier believed. This review summarizes the current knowledge of this condition, including methods for clinical diagnosis.

Administration, Topical↗

Cyclosporin A in severe, therapy-resistant atopic dermatitis: report of an international workshop, April 1993.

Data on the use of oral cyclosporin A (CyA; Sandimmun) therapy for severe adult atopic dermatitis have accumulated since 1987. Details of over 200 adult patients who have received short-term CyA were presented at an international workshop in April 1993. Eighty-six of these patients had participated in three randomized, double-blind, placebo-controlled studies in which CyA was given for 6-8 weeks. The efficacy and safety of short-term CyA treatment in atopic dermatitis is established, provided that appropriate guidelines are observed. Evidence to date suggests that atopic dermatitis patients are no more prone to toxicity than patients with psoriasis, in whom more detailed and longer-term data are available. Early data also suggest that long-term CyA may be effective in atopic dermatitis, but there is concern regarding long-term safety, as experience is still limited. Careful monitoring of all CyA-treated patients is therefore mandatory. CyA should only be used under the direct and regular supervision of a hospital-based dermatologist who is knowledgeable in the use of cyclosporin A, and experienced in the management of severe skin disease and in the use of potentially toxic drugs.

Adult↗

Contact hypersensitivity to hydrocortisone-free-alcohol in patients with allergic patch test reactions to tixocortol pivalate.

It has been suggested that contact allergy to hydrocortisone alcohol is a frequent phenomenon. A recent study showed that all patients with allergic patch reactions to tixocortol pivalate reacted to intradermal hydrocortisone sodium phosphate. We studied patients with positive patch test reactions to tixocortol pivalate but negative to hydrocortisone alcohol, with penetration enhancers in hydrocortisone alcohol patch tests and oral challenges with hydrocortisone alcohol. Additionally, prick and intradermal tests with hydrocortisone sodium succinate were used. Using penetration enhancers and oral challenges enabled detection of more contact allergies to hydrocortisone alcohol compared to conventional patch testing alone. 9/12 patients with allergic reactions to tixocortol pivalate reacted to intradermal hydrocortisone sodium succinate. No immediate reactions were seen in prick or intradermal tests, suggesting that hydrocortisone contact hypersensitivity is probably not associated with immediate allergy to hydrocortisone. The present study suggests that allergic patch test reactions to tixocortol pivalate are caused by hypersensitivity to hydrocortisone alcohol itself or to one of its metabolites in the skin.

Anti-Inflammatory Agents↗

Cyclosporine in the treatment of palmoplantar pustulosis. A randomized, double-blind, placebo-controlled study.

BACKGROUND AND DESIGN: Palmoplantar pustulosis (PPP) is an inflammatory skin disease characterized by pustule formation, erythema, induration, and scaling of the affected skin of the palms and soles. Palmoplantar pustulosis is usually resistant to treatment. In a double-blind study (phase 1) of 4 weeks, 40 patients with PPP were randomized to receive oral cyclosporine, 2.5 mg/kg per day, or placebo. An open-label dose-finding phase 2 with cyclosporine doses of 1.25, 2.5, and 3.75 mg/kg per day was performed in the following 3 months. The patients were then followed for at least 2 months after termination of cyclosporine treatment. Response to treatment was judged by the number of fresh pustules. Patients displaying a reduction of 50% or greater in the number of pustules, compared with baseline, were defined as responders. RESULTS: Of the patients who completed phase 1, 17 of 19 patients in the cyclosporine group and four of 15 in the placebo group were classified as responders (P < .001). Cyclosporine, but not placebo, significantly reduced formation of new pustules (P = .001). In the subsequent open phase, a daily cyclosporine dose of 1.25 mg/kg appeared to be an effective treatment of PPP in approximately half of the treated patients. Many patients relapsed after initial success with cyclosporine. However, only one patient studied totally failed to respond to cyclosporine treatment. At the end of phase 3, most of the studied parameters had returned to pretreatment levels. The most common side effect was headache in the 2.5 mg/kg per day dosage group; no significant side effects were observed in the 1.25 mg/kg per day dosage group. CONCLUSIONS: Low-dose cyclosporine treatment (1.25 to 2.5 mg/kg per day) is effective in PPP.

Adolescent↗