Interferon-gamma in the treatment of systemic sclerosis: a randomized controlled multicentre trial.

We report the results of a randomized controlled multicentre study on interferon-gamma (IFN-gamma) treatment of systemic sclerosis as determined by skin sclerosis, renal and other organ involvement, global assessment, subjective symptoms and quality of life. Forty-four patients were enrolled into the trial, 27 in the treatment group and 17 in the control group. All patients presented with type I or type II scleroderma. Twenty-nine patients (64%) finished the study. The mean duration of Raynaud's phenomenon and skin sclerosis was 15.3 and 10.8 years, respectively. The skin scores tended to improve in the treatment group (P > 0.05). Mouth aperture increased significantly from 38.5 to 47.7 mm in the treatment group (P < 0.001). Subanalysis of IFN-gamma treated patients with normalized skin sclerosis scores >/=1 showed significant improvement in both skin involvement and subjective symptoms (P < 0.05). Organ involvement improved in eight of 18 treatment patients and in three of 11 control patients. It worsened in three of 18 treatment patients and in four of 11 control patients. One control patient died due to cardiorespiratory failure during the study. No deterioration of renal function occurred during IFN-gamma treatment. There was a significant improvement in quality of life parameters in the control group but not in the treatment group. Plasma levels of neopterin increased significantly during IFN-gamma treatment but not in the control group, whereas N-terminal procollagen III peptide levels did not change in either group. There was a high frequency of mild to moderate influenza-like adverse events during IFN-gamma treatment. Only four of nine drop-out patients, however, experienced symptoms most probably associated with IFN-gamma treatment. We conclude that IFN-gamma therapy has mild beneficial effects on skin sclerosis and disease-associated symptoms in type I and II scleroderma. IFN-gamma treatment was associated with acceptable tolerability and did not induce major renal dysfunction in our patients.

New treatment of atrophic acne scars by iontophoresis with estriol and tretinoin.

BACKGROUND: Common treatment of atrophic acne scars consists of invasive methods such as dermabrasion, chemopeeling, or implantation of bovine collagen. In our study a new noninvasive treatment method consisting of local iontophoresis is demonstrated. Local iontophoresis was performed with either estriol--a mainly topically active estrogen--or with tretinoin. PATIENTS AND METHODS: Eighteen women were treated with estriol iontophoresis twice weekly for a period of 3 months. In addition to photographic and clinical documentation of the skin, venous blood for determination of serum levels of prolactin and estradiol according to standard radioimmunoassay methods was obtained monthly. Tretinoin iontophoresis was performed according to the same time schedule in 28 patients (19 women and 9 men) with atrophic acne scars. RESULTS: Improvement of acne scars was observed in 93% of patients treated with tretinoin iontophoresis and in 100% of the group treated with estriol iontophoresis. No hormonal changes were noted in the estrogen group. Side effects involving the skin appeared in the tretinoin group in 4 cases and consisted of increased dryness and of retinoid dermatitis. CONCLUSION: Both treatments were shown to be clinically effective in decreasing acne scars and persistence of effects. This promising new therapeutic approach may thus replace invasive treatment methods in many patients.

Treatment of skin ageing symptoms in perimenopausal females with estrogen compounds. A pilot study.

A wide range of somatic symptoms of the perimenopausal female is due to the decrease of estrogen at that age. Minor attention has been paid hitherto to the involvement of estrogens in female skin ageing symptoms. In our study, the ageing skin of the face of perimenopausal females was treated with a 0.3% estriol cream (8 patients) or with a 0.01% estradiol cream (10 patients) for 6 months. Dermatologic follow-up was performed monthly. At each follow-up venous blood for radioimmuno assay determination of prolactin (PRL), follicle stimulating hormone (FSH) and estradiol (E2) was sampled. In addition, prior to and after 3 and 6 months of treatment, gynecological examinations for climacteric symptoms, mammary and colposcopic investigations and vaginal smears for cytology were performed. Both treatment groups showed improvement of the various skin ageing symptoms at the end of treatment. The effects of the group treated with topical estriol were slightly superior with regard to their extent and onset. No hormonal side effects were noted either clinically or by hormone monitoring. According to these preliminary results, local estrogen treatment appears to be a promising new approach for the treatment of skin ageing in perimenopausal females. However, for minimizing the risk of systemic hormonal side effects, concentrations and size of application field should be limited.

Pentoxifylline in vivo down-regulates the release of IL-1 beta, IL-6, IL-8 and tumour necrosis factor-alpha by human peripheral blood mononuclear cells.

Pentoxifylline (PTX) is a methylxanthine compound known to inhibit the production of tumour necrosis factor-alpha (TNF-alpha), which is an important inflammatory mediator. There is also recent evidence that PTX may influence other inflammatory cytokines, such as interleukin-1 (IL-1) and IL-6. Due to the therapeutic implications, the present study addressed the in vivo effects of PTX on the release of TNF-alpha, IL-1 beta, IL-6 and IL-8 by human peripheral blood mononuclear cells (PBMC). When PBMC were obtained from healthy volunteers ingesting 5 x 400 mg PTX orally for 2 days, the ability of PBMC cultured for 24 hr to release TNF-alpha was significantly reduced, while secretion of IL-1 beta, IL-6 and IL-8 was not affected. However, when PBMC were obtained from the same individuals 5 days after PTX had been stopped, the release of all four cytokines was significantly suppressed. This effect appeared to be exerted at the transcriptional level, since Northern blot analysis revealed reduced cytokine transcripts. In order to gain more insight into the effect of PTX on cytokine release, PBMC were obtained from normal volunteers, either stimulated with lipopolysaccharide (LPS) or left unstimulated, and subsequently incubated in vitro with PTX for 48 hr. Under these conditions, only TNF-alpha was found to be reduced by PTX, while IL-1 beta and IL-8 were not affected, IL-6 was even enhanced. However, when PBMC were incubated with PTX for 24 hr, PTX removed thereafter by medium change and cells further cultured, the production not only of TNF-alpha but also of IL-1 beta, IL-6 and IL-8 was reduced, demonstrating that PTX exerts diverse (inhibitory) effects on cytokine release by PBMC.

[Profilometry. A method for documenting skin structure]. / Die Profilometrie. Eine Dokumentationsmethode der Hautstruktur.

Profilometry is a novel procedure allowing precise analysis of skin surface structure. With the help of a synthetic material a negative image of a defined area of the skin is taken. During the subsequent analytical procedure the roughness is determined by means of a profilometer. A commercially available statistics software program is used for statistical analysis of the results. This procedure was applied to check for to evaluate positive effects of oestrogen creams on the structure of the skin surface on the face.

Parenteral administration of 8-methoxypsoralen in photopheresis.

BACKGROUND: Extracorporeal photochemotherapy (EP) is used for the treatment of cutaneous T-cell lymphoma (CTCL), progressive systemic sclerosis (PSS), pemphigus vulgaris, and rheumatoid arthritis. During this procedure, the oral administration of the photoactive drug 8-methoxypsoralen (8-MOP) results in an unpredictable range of serum levels and in side effects limiting its efficacy. OBJECTIVE: To circumvent this limitation, extracorporeally administrable 8-MOP (EX-8-MOP) was developed. It is administered directly to the leukocyte/plasma concentrate in the treatment bag of the EP apparatus before irradiation with UVA light. METHODS: Efficacy, tolerance, and side effects of EX-8-MOP were evaluated in 108 consecutive treatments of 16 patients who had previously been treated with oral 8-MOP (91 treatments). RESULTS: With EX-8-MOP constant drug levels for UV light exposure were obtained; for equivalent levels only a small fraction of the oral dose (1/250 to 1/500) was required with none of the side effects associated with oral 8-MOP. Effective and reproducible inhibition of lymphocyte proliferation and cell viability was attained. No difference in clinical efficacy could be observed. CONCLUSION: EX-8-MOP eliminates the need for premedication and drug level monitoring of 8-MOP and should improve the effectiveness of EP.