Treatment of psoriasis in the Nordic countries: a questionnaire survey from 5739 members of the psoriasis associations data from the Nordic Quality of Life Study.

The data from a questionnaire-based study of 5,739 members of the psoriasis associations of Denmark, Finland, Iceland, Norway, Sweden and the Faeroe Islands showed that the two most commonly used active agents were topical steroids (89.7% total use and 49.4% present use) and calcipotriol (73.1% total use and 35.8% present use), with only small variations between the countries. Marked differences between the countries were, however, found within all other types of psoriasis therapy, including the so-called alternative treatments. Significant priorities varied between the different countries. The use of dithranol in Finland was almost twice the average. While 14.2% of Danish members had received grenz-rays within the last week only 0.1% of the Finns had been given the same treatment. Psoralen plus ultraviolet A (PUVA) was being used by 13.1% of the Finnish psoriatics compared with 3.8% of Danes, while PUVA was almost non-existent on the Faeroe Islands. The use of non-PUVA phototherapy was highest in Norway and Sweden. Almost 10% of the Danes were presently on methotrexate, which was used far more than etretinate/acitretin or cyclosporine. In contrast, Finnish patients more often received etretinate than other systemic agents, and in Iceland there was a higher present use of cyclosporine than of etretinate. The popularity of alternative therapies was highest in Iceland, where 26.6% had taken such medication during the last week. The results of the study suggest that different treatment patterns should be taken into consideration when discussing the prognosis of psoriasis in different countries.

Topical calcipotriol combined with phototherapy for psoriasis. The results of two randomized trials and a review of the literature. Calcipotriol-UVB Study Group.

BACKGROUND: Calcipotrial has a well-documented effect in the treatment of psoriasis. OBJECTIVE: To confirm the beneficial effect of the combination of calcipotriol and UVB and to demonstrate that the combination is safe and well tolerated. METHODS: Data from two randomized right/left studies were analysed. Patients included in the studies had chronic stable plaque-type psoriasis with symmetrical lesions on the arms, the legs and/or the trunk. In one study, 101 patients were treated with calcipotriol on one side and calcipotriol + UVB on the other side of the body (open study). In the other study, 77 patients were treated with calcipotriol + UVB on one side and vehicle + UVB on the other side of the body (double-blind study). Calcipotriol ointment, 50 microg/g, was applied twice daily and UVB 3 times weekly for 8 weeks. UVB was increased from 0.7 MED before treatment in rapid steps up to the erythema threshold. RESULT: In both treatment series the therapeutic effect of the combination of calcipotriol and UVB was enhanced as compared to calcipotriol alone and UVB alone. In the first series there was a significant reduction of the psoriasis area and severity index (PASI) with the combination after 2 weeks as compared to calcipotriol alone. At the end of treatment significantly more sides were cleared after calcipotriol + UVB than after calcipotriol alone. In the other series there was a significantly faster onset of improvement on the sides treated with calcipotriol + UVB than on those treated with vehicle + UVB. After 2 weeks there was a significant difference in PASI in favour of calcipotriol + UVB. At the end of treatment, however, there was no difference between the treatments. There was a similar adverse event profile with either treatment. The addition of UVB to calcipotriol did not alter the tolerability or safety of topically applied calcipotriol. CONCLUSIONS: The result indicates a beneficial effect of combining calcipotriol and phototherapy. The findings are compared to other published studies.

PUVA and cancer risk: the Swedish follow-up study.

There is concern about the long-term carcinogenic effects of psoralen and ultraviolet A radiation (PUVA) for treatment of skin disorders. Many authors have found an increased risk for cutaneous squamous cell carcinoma (SCC). Except in anecdotal reports, malignant melanoma had not been observed in patients treated with PUVA until recently. In the U.S.A., a 16-centre prospective study of 1380 patients showed for the first time that there might also be an increased risk for malignant melanoma in patients treated with high cumulative dosages of PUVA. We have therefore followed up the Swedish PUVA cohort until 1994. This cohort had previously been followed up until 1985. Information from 4799 Swedish patients (2343 men, 2456 women) who had received PUVA between 1974 and 1985 was linked to the compulsory Swedish Cancer Registry in order to identify individuals with cancer. The average follow-up period was 15.9 years for men and 16.2 for women. We did not find any increased risk for malignant melanoma in our total cohort of 4799 patients treated with PUVA or in a subcohort comprising 1867 patients followed for 15-21 years. For cutaneous SCC there was an increase in the risk: the relative risk was 5.6 (95% confidence interval, CI 4. 4-7.1) for men and 3.6 (95% CI 2.1-5.8) for women. Significant (P < 0.05) increases were also found in the incidence of respiratory cancer in men and women and of kidney cancer in women. In conclusion, we did not find any increased risk for malignant melanoma in our patients treated with high doses of PUVA and followed up for a long time. We confirm previous reports of an increase in the incidence of cutaneous SCC in patients treated with PUVA, and recommend that patients should be carefully selected for PUVA and rigorously followed up.

Glutaric acidemia type II. Heterogeneity in beta-oxidation flux, polypeptide synthesis, and complementary DNA mutations in the alpha subunit of electron transfer flavoprotein in eight patients.

We studied metabolic, polypeptide and genetic variation in eight glutaric acidemia type II (GA II) patients with electron transfer flavoprotein (ETF) deficiency. As measured by 3H-fatty acid oxidations in fibroblasts, beta-oxidation pathway flux correlated well with clinical phenotypes. In six patients with severe neonatal onset GA II, oxidation of [9,10(n)-3H]-palmitate ranged from 2% to 22% of control and of [9,10(n)-3H]myristate, from 2% to 26% of control. Of two patients with late onset GA II, one had intermediate residual activities with these substrates and the other normal activities. Radiolabeling and immunoprecipitation studies revealed that three of the six neonatal onset GA II patients had greatly diminished or absent alpha- and beta-ETF subunits, consistent with a failure to assemble a stable heterodimer. Another neonatal onset patient showed normal synthesis of beta-ETF but decreased synthesis of alpha-ETF. Two neonatal onset and two late onset GA II patients showed normal synthesis of both subunits. Analysis of the pre-alpha-ETF coding sequence revealed seven different mutations in the six patients with neonatal onset GA II. The most common mutation was a methionine for threonine substitution at codon 266 found in four unrelated patients, while all the other mutations were seen in single patients. No mutations were detected in the two patients with late onset GA II.

PUVA and cancer: a large-scale epidemiological study.

There is concern about the long-term carcinogenic effects of psoralen and ultraviolet A radiation (PUVA) therapy for treatment of skin disorders. A study of 4799 Swedish patients (2343 males, 2056 females; mean age at first treatment 45.3 years, range 6-93; mean follow-up 6.9 years males, 7.2 years females) who received PUVA between 1974 and 1985 showed a dose-dependent increase in the risk of squamous cell cancer of the skin. Male patients who had received more than 200 treatments had over 30 times the incidence of squamous cell cancer found in the general population. Significant increases (p less than 0.05) were also found in the incidences of respiratory cancer in males and females, pancreatic cancer in males, and kidney and colonic cancer in females. This study confirms previous reports of a dose-dependent increase in the incidence of squamous cell cancer in patients treated with PUVA.

Retinoids plus PUVA (RePUVA) and PUVA in mycosis fungoides, plaque stage. A report from the Scandinavian Mycosis Fungoides Group.

Sixty-nine patients with mycosis fungoides, plaque stage, were treated in an open study with photochemotherapy (PUVA) or the combination of oral retinoids and PUVA (RePUVA). The response rate of Re-PUVA was equal to that of PUVA, with complete remission in 73% and 72%, respectively. Remissions were obtained with fewer PUVA sessions, and with a lower UVA dosage, if PUVA was combined with retinoids. A lower UVA dosage was needed if treatment was given four times weekly in stead of twice weekly. The duration of the remissions tended to be prolonged if retinoids were given as maintenance therapy.

Factors of importance for valid digitalis assays particularly for the determination of digoxin in plasma and urine.

Four commercial radioimmunoassay (RIA) kits for digoxin varied in precision (coefficient of variation, CV within-assays 5-14%) and accuracy (up to 40%). Thus it seems that such commercial RIA-kits can reach at best a CV within-assay of 5% and a similar variation between assays. Without a good control of the performance, the variation can increase 5-6 times. We found that the precision of digoxin RIA as performed at 27 Swedish laboratories using 10 different methods varied from 0.05 to 0.61 nmol/L in between-assay SD for a pool of 2.60 nmol/L. Up to 100% deviations between the highest and lowest reported concentration of a spiked plasma pool may occasionally occur. Such deviations mostly depend on the laboratory, but there are contributions from the kit and effects of the matrix as well. Matrix effects were observed in plasma samples from patients with uremia, acute myocardial infarction and treated with spironolactone to which digoxin was added to a concentration of 2.50 nmol/L. We found 10% underestimation by one method, 10% overestimation by two methods and 5% overestimation by a fourth method, respectively, with the above described samples. For a good judgement of a found plasma concentration value, calculation of a confidence interval is useful. This can be done by computer fitting of the standard curve after duplicate runs of standards and samples in random order. One source of error in RIA appears to be the use of inaccurate standards. We found that standards provided with different RIA-kits for digoxin varied up to 30%. Various physicochemical properties of cardiac glycosides, which could influence the assays were studied. Both digitoxin and digoxin are sparsely soluble in water (5.1 and 36 mumol/L, respectively). Methanol is a much better solvent, which dissolves 6.9 mmol/L of digoxin and 20-24 mmol/L of digitoxin. Chloroform is a good solvent for digitoxin (29-34 mmol/L) but not for digoxin (0.42 mmol/L). Partition of cardenolides between chloroform and water reflected their lipophilic or hydrophilic character. Thus, digitoxin had a high affinity to the organic phase (distribution constant KD = 10(3.65)), while the hydrophilic deslanoside was preferentially found in the aqueous phase (KD = 10(-3.08). Interestingly, the sugar moiety digitoxose in the digoxin molecule turned out to be a substituent that increased lipophilicity. Adsorption of cardiac glycosides occurs to plastics and glass from aqueous solutions. To overcome losses at low concentrations, the solutions must contain plasma, albumin, alcohol or similar solubility-increasing ingredients.(ABSTRACT TRUNCATED AT 400 WORDS)

Photochemotherapy (PUVA) in the pretumour stage of mycosis fungoides: a report from the Scandinavian Mycosis Fungoides Study Group.

Fifty-one patients with mycosis fungoides of pretumour stage were treated with oral 8-MOP and UVA photochemotherapy (PUVA). Complete remission was induced within 2--3 months in 58% of the cases. Twenty-seven patients are still in remission on maintenance therapy 9--53 months after starting treatment. In 9 cases PUVA treatment was stopped due to therapeutic failure and in another 15 cases due to various side effects. Maintenance therapy was given weekly, monthly, or at even longer intervals. Maintenance at long intervals seems preferable.

Photochemotherapy (PUVA) in the tumour stage of mycosis fungoides: a report from the Scandinavian Mycosis Fungoides Study Group.

Twenty-five patients with mycosis fungoides in the tumour stage were treated with oral 8-Methoxypsoralen followed by UVA (PUVA), sometimes in combination with topical or systemic chemotherapy. In 17 patients the disease was confined to the skin, in 7 lymph nodes also were involved, and one had visceral involvement. Complete and partial remission was achieved in 14/17 patients with the disease limited to the skin (82%), and partial remission of the skin lesions in 5/8 patients with extracutaneous location.