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Aim The Nordic Quality of Life Study was undertaken to assess the relationship between psoriasis and the quality of life in Nordic countries. The intention was also to determine whether there was a relationship between drinking, smoking, and the use of psychotherapeutic agents on the one hand, and psoriasis severity and quality of life on the other. Materials and methods A questionnaire was mailed to 11,300 members of the Nordic Psoriasis Associations. Additional psoriasis patients were recruited by dermatologists (387) or admitted to dermatologic wards (385). These patients also underwent a physical examination, and their Psoriasis Area and Severity Index (PASI) was determined. The questionnaire included the Psoriasis Disability Index (PDI), Psoriasis Life Stress Inventory (PLSI), and additional questions on disease severity, treatment, and psoriasis arthritis. It also included questions regarding lifestyle issues, such as smoking, alcohol use, and the use of tranquilizers, antidepressants, and sleeping medications. Results The response rate for members was 50.2%. Included in the evaluation were 6497 patients. Men drank significantly more beer and liquor than women. The number of beers per day had a weak correlation with the PDI. Wine consumption, however, showed a weak, but significant, negative correlation with both PDI and PLSI. Patients admitted to dermatologic wards smoked more cigarettes and drank less wine than the other two groups. Significant differences were found between countries with regard to total alcohol consumption and cigarette smoking. The number of cigarettes and the use of tranquilizers, sleeping medications, and antidepressants showed small, but significant, positive correlations with psoriasis quality of life measures. Conclusions Cigarette smoking and the use of tranquilizers, sleeping medications, and antidepressants are statistically correlated with impaired psoriasis-related quality of life.

Objectives The purpose of the study was to investigate the perceived influence of stress on psoriasis onset and disease severity in a large sample of psoriatics and to compare stress reactors and non-reactors with respect to psoriasis-related stress, disease severity, family history of psoriasis and sociodemographic factors. Patients/methods A total of 5795 members of the Nordic psoriasis associations and 702 patients recruited from Nordic dermatologists or university clinics were asked whether their first outbreak of psoriasis occurred during times of worry and stress. They were also asked to rate the degree to which their psoriasis was influenced by stress and to complete the Psoriasis Life Stress Index, the Psoriasis Disability Index and a number of additional questions concerning sociodemographic factors. Results Seventy-one per cent of the members and 66% of the patients reported that their psoriasis was exacerbated by stress, and 35% in both groups reported that the onset of their psoriasis occurred during a time of worry and stress. Stress reactors, scoring above the median on stress reactivity, reported greater disease severity, psoriasis-related stress and impairment of disease-related quality of life. They also reported more frequent use of tobacco, tranquillizers and antidepressants. More women than men were stress reactors, and stress reactors were more likely to have a family history of psoriasis. Conclusion Our findings confirm and extend the results of previous studies and indicate that a subgroup of psoriatics may be more psychologically reactive to their disease and its influence on everyday life. Whether this group is also physiologically more reactive to psychosocial stress remains to be investigated.

SummaryBackground Disease-specific psoriasis-related quality of life (QOL) measures have recently been developed and used in several hospital-based investigations. However, little is known about the impact of psoriasis on QOL in people with psoriasis who are not referred by dermatologists. Objectives The purpose of the study was to investigate psoriasis-related QOL in a large sample of members of the psoriasis associations from the Nordic countries, and to compare the results with those from psoriasis patients recruited from Nordic dermatologists or Nordic University clinics. Patients and methods A total of 5795 association members and 702 patients rated their psoriasis severity and completed the Psoriasis Disability Index and the Psoriasis Life Stress Index. Results Patients reported greater disease severity and greater impairment of QOL than members of associations, and Norwegian participants reported greater disease severity and greater impairment of QOL than participants from the remaining Nordic countries. Older and married participants reported less impairment of QOL than younger participants and those living alone. When controlling for the influence of these and other demographic and socio-economic factors, self-reported severity emerged as the most significant predictor of psoriasis-related QOL, explaining 32–26% of the variation in QOL scores, with the remaining factors only accounting for 4–5% of the variation. Although correlated with self-reported severity, Psoriasis Area and Severity Index scores were not a significant predictor of QOL in the patient sample. Conclusions Though self-reported severity may be the most important predictor, further research is needed to determine factors explaining the remaining variance in psoriasis-related QOL.

Quality of life measures are widely used in dermatology as well as in rheumatology, but there are no large studies taking arthritis into consideration when studying quality of life in psoriasis. The aim of this study was to investigate psoriasis-related quality of life in a large sample of members of the psoriasis associations from the Nordic countries including an arthritis-related evaluation. The prevalence of reported arthritis within the groups was also estimated. An Arthritis Disability Index suitable for parallel use together with Finlay's Psoriasis Disability Index was constructed. A total of 5,795 members and 702 patients seen by Nordic dermatologists rated the severity of their disease and completed the Psoriasis Disability Index formula and a Psoriasis Life Stress Inventory, and if arthritis had been diagnosed, the Arthritis Disability Index formula. Approximately 30% of all psoriatic patients, irrespective of group, received a diagnosis of arthritis either by their dermatologist or a rheumatologist. Members previously hospitalized for their disease had a higher frequency of arthritis (41%) than those without a history of hospitalization (23%). The highest prevalence of arthritis was found in Norway (33.8%). Members with arthritis exhibited greater impairment of psoriasis-related quality of life, longer disease duration, and greater self-reported disease severity for psoriasis. Important predictors for impairment of arthritis-related quality of life were pain, number of affected joints, and restriction of joint mobility. These data show, that the prevalence of arthritis in psoriasis may be significantly higher than the previously accepted average of 7%. The results demonstrate that when studying quality of life in psoriasis, arthritis and arthralgia are important independent factors to be included in the evaluation.

Renal biopsies were performed in 30 psoriatics during long-term low-dose cyclosporin (CsA) therapy (range 2.5-6 mg/kg per day) of from 6 months to 8 years. The study included pretreatment biopsies in 25 of the patients. After 2 years all biopsies shared features consistent with CsA nephropathy despite completely normal pretreatment morphology in 17 of the 25 patients. The severity of the findings which consisted of arteriolar hyalinosis, focal interstitial fibrosis and sclerotic glomeruli increased with length of therapy. Mild renal lesions were seen during the first 2 years. After 4 years all but one had arteriolar hyalinosis, with interstitial fibrosis pronounced in five and moderate in six of 11 patients. At the same time glomerular sclerosis had become significant. A decrease in glomerular filtration rate (GFR) correlated with severity of structural lesions. The data from our study together with experiences from cardiac-transplanted patients treated with CsA indicate that patients with psoriasis after 2 years therapy with CsA should be rotated to other treatments or be followed carefully by GFR and sequential renal biopsies.

Joint diseases are common among patients with psoriasis. Psoriatic arthritis, the most important of these, can be defined as a rheumatoid factor-negative inflammatory arthritis associated with psoriasis and has emerged as a specific disease independent from rheumatoid arthritis. Psoriatic arthritis is divided into several clinical subsets, which is helpful in differentiating it from other types of inflammatory arthritis. The prevalence of arthritis in patients with psoriasis may be far higher than the previously accepted average of 7%. In a recent study of 5,795 members of the Nordic Psoriasis Associations, the prevalence was found to be 30%. Arthritis has a significant impact on quality of life in patients with psoriasis. These factors should be recognised as they have implications for therapy, since a number of drugs can delay or stop joint damage when given in time. This also applies to the new biologic agents, although at present these therapies are generally restricted to patients non-responsive to other available drugs. Alone or in combination, the new drugs may achieve higher response rates and have better safety profiles than older therapies. However, long-term experience is still lacking and, unfortunately, the new drugs will be far from affordable by all for some time to come.

was almost twice the average. While 14.2% of Danish members psoriasis associations from Denmark, Finland, Norway and Sweden, had received grenz-rays within the last week only 0.1% of the and to all members acknowledged the associations from Iceland and Finns had been given the same treatment. Psoralen plus ultravi- the Faeroe Islands. There were 1,356 responders (67.8%) from olet A (PUVA) was being usedby 13.1% of the Finnishpsoriatics Denmark, 1,125 (56.3%) from Finland, 451 (40.0%) from Iceland, 903 (45.2%) from Norway, 1,828 (45.7%) from Sweden and 76 (44.0%) compared with 3.8% of Danes, while PUVA was almost non- from the Faeroe Islands, yielding a total of 5,739psoriatics. The existent on the Faeroe Islands. The use of non-PUVA photo- percentages in parentheses represent response rates, with the average therapy was highest in Norway and Sweden. Almost 10% of the response rate being 50.2%. Patients were excluded if they were under Danes were presently on methotrexate, which was used far more 18 years old, and only patients who had had their diagnosis of than etretinate/acitretin or cyclosporine. In contrast, Finnish psoriasis made or cone rmed by a dermatologist were included in the study. The age and sex variation within the groups is shown in Table I, patients more often received etretinate than other systemic together with the duration of psoriasis. No diŒerence in theproportion agents, and in Iceland there was a higher present use of of men and women was found between countries (v 2=6.7; ns), with cyclosporine than of etretinate. The popularity of alternative more women than men participating in the survey. There were therapies was highest in Iceland, where 26.6% had taken such signiecant diŒerences between countries with respect to age (F 5,723 = 57.1; p< 0.001), disease duration (F 5,723 =53.9; p< 0.001) and disease medication during the last week. The results of the study suggest severity (v 2=113.5; p< 0.001). The Finnish and Swedish samples were that diŒerent treatment patterns should be taken into considera- older, had longer disease duration and reported less severe psoriasis tion when discussing the prognosis of psoriasis in diŒerent than the other samples. The Norwegian sample had the highest

The aim of the present study was to correlate the severity of oesophageal motor dysfunction with the severity of cutaneous disease in systemic sclerosis (SS). Patients were divided into three groups based on the degree of skin involvement: type I, acrosclerosis distal to the wrist; type II, scleroderma extending above the wrist in proximal direction; type III, diffuse cutaneous systemic sclerosis. Impedance planimetry employing distensions with pressures up to 5 kPa with the concomitant measurement of oesophageal cross-sectional area (CSA) was used in combination with standard oesophageal manometry. Measurements were made at 7 and 15 cm above the lower oesophageal sphincter (LOS). Thirty patients (16 type I, six type II and eight type III patients) and 23 normal controls were included. LOS pressure was lower in SS patients than in normal patients, with the lowest values in type III. The CSAs were higher in SS patients than in controls at both sites (P

The aim of this retrospective study was to evaluate the initial video-radiology and manometry in 40 consecutive patients with systemic sclerosis (n=21) or suspected systemic sclerosis (n = 19) in relation to oesophageal symptoms; and, furthermore, to evaluate the consequence of radiographic or manometric findings in the oesophagus on diagnosis and treatment. Evaluating oesophageal abnormalities in relation to diagnosis and treatment has, to our knowledge, not been reported before. Video-radiology together with manometry demonstrated oesophageal dysfunction in 80% of patients. Thirteen patients (33%) were asymptomatic in spite of identified motility abnormalities. Following the radiographic and manometric investigation, 9 patients (23%) had a change of diagnosis and, in 20 patients (50%), systemic treatment was instituted or intensified. The study confirms that both manometry and video-radiology are important for the identification of oesophageal motility abnormalities in patients with systemic sclerosis. Oesophageal symptom profiles alone do not predict abnormal findings.

An analysis of the literature on renal toxicity of long-term cyclosporin A (CsA) in auto-immune diseases reveals that besides functional renal toxicity also de novo morphological kidney damage can be induced already after 12 months with low dose (or = 5 mg CsA/kg/day). In the early stage the findings are light changes. However, after two years treatment they are light to moderate. In a blinded study on 30 patients with psoriasis, including 18 with psoriatic arthritis, the severity of findings increased with length of therapy, and after four years all but one had arteriolar hyalinosis, with interstitial fibrosis pronounced in five and moderate in six of eleven patients, and at the same time glomerular sclerosis had become significant. The data presented indicate the necessity of an evaluation of the risk-benefit ratio for each patient. Accepted guide-lines should be strictly followed, and after two years treatment a rotation to other therapies, or a careful following by glomerular filtration rate (GFR) together with sequential renal biopsies should be considered.

Renal biopsies were performed in 30 psoriatics during long-term low-dose cyclosporin (CSA) therapy (range 2.5-6 mg/kg/day) of from six months to eight years. The study included pretreatment biopsies in 25 of the patients. After two years all biopsies shared features consistent with CSA nephropathy despite completely normal pretreatment morphology in 18 of the 25 patients. The severity of the findings, which consisted of arteriolar hyalinosis, focal interstitial fibrosis and sclerotic glomeruli, increased with length of therapy. Mild renal lesions were seen during the first two years. After four years all but one had arteriolar hyalinosis, with interstitial fibrosis pronounced in five and moderate in six of 11 patients. At the same time glomerular sclerosis had become significant. A decrease in glomerular filtration rate (GFR) correlated with the severity of the fibrosis. GFR studied in 14 patients six months to seven years after discontinuation of CSA was still significantly decreased in relation to baseline prior to therapy. The data from our study together with experiences from cardiac-transplanted patients indicate that patients with psoriasis, after two years therapy with CSA, should be rotated to other treatments or be followed carefully by GFR and sequential renal biopsies.

Objective: To assess the safety, tolerability and efficacy of a new cyclosporin A (CyA) microemulsion formulation, Sandimmun Neoral® (Neoral), in patients with severe psoriasis that was stable on CyA administered as Sandimmun® (SIM). Methods: In this 24-week, open, randomized, prospective, multicentre trial, 28 patients continued on the same dosage of SIM, while 30 converted to Neoral at 2.5 mg/kg/day or a dosage equivalent to their pre-conversion SIM dosage. During the study, dosages could be adjusted to maintain efficacy, because of adverse events or after disease stabilization. The maximum permitted dosage for either formulation was 5.0 mg/kg/day. Primary efficacy criteria were change in Psoriasis Area and Severity Index (PASI) from baseline and time to relapse. Results: The dosage was increased to maintain efficacy in 22 patients (Neoral 13; SIM 9) and 20 dose reductions for safety were required (Neoral 14, SIM 6). In both groups, PASI scores remained stable throughout and relapses were primarily a result of dosage reduction after disease stabilization. No significant difference was found between groups in the proportion of patients remaining relapse-free. Adverse events were recorded in 20 patients receiving Neoral and 14 receiving SIM. Most drug-related events were of mild or moderate severity and reflected the known CyA side-effect profile. Dose titration guidelines ensured that mean blood pressure and serum creatinine concentrations remained stable in both groups. Conclusions: If the guidelines for CyA use are followed and the Neoral dosage does not exceed 5 mg/kg/day, conversion of stable patients with severe psorisasis from SIM to Neoral should present no clinically relevant safety or tolerability problems and efficacy of treatment is maintained.

Glucocorticoids and immunosuppressive agents can induce remission in most pemphigus patients, but mortality remains at 5 to 15% as a result of side effects. We reviewed the adjunctive effect of long-term plasmapheresis in 8 pemphigus patients. Four cases had been resistant to conventional therapy. One or 2 large-volume plasmapheresis treatments were given monthly over 5 to 141 months. All patients, were in clinical remission within 2 months. Relapses seldom occurred: the patients stayed in remission 90% (40-94) (median, ranges) of the period. In all cases the daily dose of glucocorticoid was reduced. The prednisone level could be decreased from 38 (15-80) mg/day to 7.5 (2.5-35) mg/day (p = 0.002). The overall level of other immunosuppressive agents remained unchanged, except in 1 patient for whom cyclosporine was introduced. This indicates that long-term plasmapheresis could have a steroid-sparing effect and clinical efficacy in pemphigus.

An analysis of the history of 28 men suffering from systemic sclerosis, diagnosed at our department during the last 25 years, showed that 21 (75%) had been subject to exposures previously suggested to be of importance in occupational scleroderma. The exposures were revealed by patient files, reports to health authorities, interviews and/or answers to questionnaires. Organic solvents being the most frequent exposure. This was found in thirteen of the patients (46%). A significant difference was found between scleroderma patients and control patients not suffering from connective tissue diseases in relation to total number of subjects exposed to one or several of the agents in question.

Renal biopsies were performed in 30 psoriatics during long-term low-dose cyclosporin (CsA) therapy (range 2.5-6 mg/kg per day) of from 6 months to 8 years. The study included pretreatment biopsies in 25 of the patients. After 2 years all biopsies shared features consistent with CsA nephropathy despite completely normal pretreatment morphology in 17 of the 25 patients. The severity of the findings which consisted of arteriolar hyalinosis, focal interstitial fibrosis and sclerotic glomeruli increased with length of therapy. Mild renal lesions were seen during the first 2 years. After 4 years all but one had arteriolar hyalinosis, with interstitial fibrosis pronounced in five and moderate in six of 11 patients. At the same time glomerular sclerosis had become significant. A decrease in glomerular filtration rate (GFR) correlated with severity of structural lesions. The data from our study together with experiences from cardiac-transplanted patients treated with CsA indicate that patients with psoriasis after 2 years therapy with CsA should be rotated to other treatments or be followed carefully by GFR and sequential renal biopsies.

BACKGROUND: Deterioration of renal function and rise in blood pressure are clinically important side-effects of cyclosporin (CsA) treatment. Calcium antagonists may have a renoprotective effect against CsA nephrotoxicity. PURPOSE: To investigate the effect of the dihydropyridine calcium-channel blocker felodipine on renal haemodynamics, tubular sodium handling, and blood pressure in CsA-treated patients with no primary renal disease, 18 patients with various CsA-treated dermatological diseases were allocated to receive either felodipine 5 mg (extended release tablets) once daily for 4 weeks followed by placebo for 4 weeks, or vice versa, in a prospective, randomized, double-blind study. The patients were investigated before treatment and at the end of each treatment period. RESULTS: After felodipine, both glomerular filtration rate (GFR) and renal plasma flow (RPF) were significantly higher compared to placebo (89.4 +/- 17.5 (mean +/- SD) vs 79.0 +/- 15.9 ml/min and 412.0 +/- 107.6 vs 326.1 +/- 78.0 ml/min respectively, P < 0.001 for both), and filtration fraction (FF) was lower (0.22 +/- 0.03 vs 0.25 +/- 0.03, P < 0.001). Both systolic and diastolic blood pressure were lower after felodipine compared to placebo (116 +/- 11/71 +/- 7 vs 133 +/- 18/83 +/- 10 mmHg, P < 0.001 for both). Furthermore, proximal output of sodium, i.e. fractional excretion of lithium, was higher after felodipine (26.9 +/- 7.3% vs 20.4 +/- 5.5%, P < 0.001) as well as total sodium excretion (0.33 +/- 0.19 vs 0.19 +/- 0.08 mmol/min, P < 0.001). CONCLUSIONS: It is concluded, that felodipine 5 mg once daily for 4 weeks increased GFR, RPF, and sodium excretion in cyclosporin-treated dermatological patients with no primary renal disease. Furthermore, felodipine lowers blood pressure in these patients. The effects of felodipine may be due to an antagonizing effect against CsA-induced nephrotoxicity.

Treatments with psoralens and long-wave ultraviolet light (PUVA) and later photopheresis (PP) for malignant diseases have mainly been treatments of cutaneous T cell lymphoma (CTCL). It has been known for many years that sunlight or artificial ultraviolet light often improves mycosis fungoides (MF), the classical and most common form of CTCL. It was therefore natural, shortly after Parrish et al. (1974) showed that PUVA could be exploited to treat psoriasis, that this type of photochemotherapy was also tried in MF.

Eleven patients with chronic plaque psoriasis were treated with the flashlamp-pumped pulsed dye laser and 6 of the same patients were at the same time treated by dermabrasion. Complete remissions were observed in 3 patients following laser-treatment and in 5 of 6 after dermabrasion. The observation periods were from 4 to 9 months. Our data suggest that the mechanism of the reversed Köbner phenomenon, which is thought to be responsible for the results of dermabrasion, is partly due to destruction of the dermal papillary vasculature. Partial responses were seen in 6 laser-treated and in one patient treated by dermabrasion. Two patients showed no response to laser treatment. These clinically unsatisfactory results can be explained by the great variety in thickness of plaques and in variability of penetration of the laser light. Measurements of absorption and scattering properties of plaques scheduled for laser treatment could probably allow improvements in the technique by optimizing laser beam diameter and pulse duration as well as wavelength and energy levels. The use of the dye laser is far less traumatic to the patient than dermabrasion.

Plasma endothelin levels were studied in 71 patients suffering from severe psoriasis. The psoriatics were treated either with topical therapy alone (n = 18) or with cyclosporin A (n = 26), methotrexate (n = 21), or with hydroxyurea, acitretin or ranitidin (n = 6) with or without topical therapy. The psoriatics had a significantly higher average plasma endothelin than 40 healthy controls. The patients treated with cyclosporin A had the highest values and these were in contrast to patients on methotrexate and other systemic therapy higher than patients treated with topical therapy alone. There was not significant difference between endothelin levels in patients treated with methotrexate compared to those in patients only receiving topical treatment. Whether the increased endothelin levels in plasma are derived from keratinocytes or enlarged vessels need to be investigated. An increased plasma endothelin level could be related to therapy and for patients on cyclosporin A be of importance for toxicity.

The purpose was to study whether the calcium entry blocker, felodipine, could reduce the nephrotoxic and hypertensive effect of cyclosporine. The effect of felodipine on glomerular filtration rate (GFR), renal plasma flow (RPF), fractional excretion of sodium, lithium clearance and blood pressure was measured in three randomized, placebo-controlled studies of cyclosporine treated patients. In study one, 10 renal transplant recipients were examined within the first six months after transplantation in a cross-over design. Renal hemodynamics were determined after the acute ingestion of felodipine or placebo, with an interval of less than one week between the two examinations. In study two, 79 renal transplant recipients were randomized to a treatment with felodipine or placebo just before transplantation, and renal hemodynamics were determined after twelve weeks. In study three, 18 patients, who were treated with cyclosporine due to dermatological diseases, were examined in a cross-over design to determine their renal hemodynamics after four weeks of treatment with felodipine or placebo. Felodipine increased renal hemodynamics in study one (GFR 16%, RPF 33%, P0.01 for both), in study two (GFR 23%, RPF 28%, P0.05 for both), and in study three (GFR 13%, RPF 26%, P0.01 for both). FE(Na) was significantly increased by felodipine in studies one and three, but not in study two. Lithium clearance was significantly increased and blood pressure significantly reduced by felodipine in all three studies. It can be concluded that felodipine counteracts both the cyclosporine induced impairment in renal hemodynamics and the increase in blood pressure in acute and short-term studies.

Twelve patients with systemic sclerosis were treated with intravenous infusions of the prostacyclin-stable analogue iloprost 0.5-2.0 ng/kg/min for 6 h from 8 to 13 days. Imminent gangrene was stopped in 2 patients and followed by healing. In 4 of 6 patients iloprost led to complete healing of ischaemic ulcers and in the remaining 2 patients to partial healing. One patient with severe Raynaud's phenomenon discontinued the study after 3 days due to severe headache. The 2 remaining patients with Raynaud's phenomenon as an indication improved, while no improvement was recorded in a patient with vasculitis of the lower leg. Side-effects such as headache, nausea and flushing were the reason that only 5 patients reached the maximum infusion rate. No statistical differences were recorded in digital bloodflow before and after the study or in plasma endothelin in the 9 patients investigated. Three of the 6 patients with healing ulcers, however, showed a pronounced decrease in plasma endothelin. Iloprost appears useful as a treatment of imminent gangrene and ischaemic ulcers in systemic sclerosis. This reparatory capacity could also be of a more general importance in therapy of this disease.

Methotrexate (MTX) may induce liver damage, which in some psoriatics will lead to fibrosis or cirrhosis. Studies performed 10 years ago on 25 patients with MTX-induced liver cirrhosis indicated that this type of cirrhosis was not of an aggressive nature.The aim of this study was to evaluate the present status of surviving patients 10 years later, together with the latest clinical and histological data on patients who had died.The investigations were carried out on 186 liver biopsies and 5 autopsies. All biopsies were studied by the same pathologist. Eleven surviving patients were also studied by analysis of serum aminoterminal propeptide of type III procollagen (PIIINP), which is an indicator of fibrogenesis, which is especially suitable for follow-up of fibrotic liver disease.Thirteen patients had died; 1 of these died of liver failure. Another patient died form an overdose due to misunderstanding of the prescribed dosage given elsewhere. The remaining deaths were non-MTX related, but all 5 autopsies showed some degree of cirrhosis. On the other hand, 13 patients had no histologically verified liver cirrhosis in their latest biopsy, and PIIINP was within the normal range in all 11 patients investigated, this in spite of total cumulative MTX doses from 1,120 to 18,645 mg (mean 7,171 mg).This study confirmed that in most patients MTX-induced liver cirrhosis is not aggressive. However, continued low-dose MTX led, in spite of normal liver tests, 8 years after the last biopsy to liver failure and death in 1 of our patients. Our data support the continued use of liver biopsies in the surveillance of MTX-treated psoriatics.

Since 1985, the efficacy of cyclosporin A (CyA) in severe psoriasis has been evaluated in a number of open and controlled studies, all of which have clearly established CyA as an effective antipsoriatic agent. The efficacy of CyA has also provided new insights into the pathophysiology of psoriasis. The effects of CyA treatment can be seen within weeks; they are dose-dependent and quickly reversible on stopping treatment. Hypertension and nephrotoxicity remain the greatest concerns associated with long-term use. In general, the incidence of hypertension is approximately 10%. A dosage of approximately 2.5-5 mg/kg/day of CyA induces a slight, but significant, dose-dependent increase in serum creatinine. Studies of pre- and post-treatment renal biopsies have also disclosed slight, but significant, increases in interstitial fibrous tissue which are negatively correlated to creatinine clearance. This review assesses the current knowledge of the prospects of CyA in the treatment of psoriasis with respect to dose/response, indications, contraindications and side-effects.

Glucocorticoids and immunosuppressive agents can induce remission in most patients with pemphigus, but mortality remains at 5 to 15% due to complications from these drugs. We reviewed the adjunctive effect of long-term plasmapheresis in 8 patients with pemphigus. Four cases had been resistant to conventional therapy. One or two large-volume plasmapheresis treatments were given monthly for 5 to 73 months. All patients were in clinical remission within 2 months after the addition of plasmapheresis. Relapses of pemphigus seldom occurred, and the patients stayed in remission 90% (40-100%) (median and ranges) of the plasmapheresis period. In all cases the daily dose of glucocorticoid was reduced. The prednisone level could be decreased significantly from 38 (15-80) mg/day to 10 (5-35) mg/day (p = 0.008). The overall level of other immunosuppressive agents remained unchanged, except in one patient where cyclosporine was introduced. This first report of long-term plasmapheresis demonstrates clinical efficacy in pemphigus and a considerable steroid-sparing effect.

Forty-one patients with systemic sclerosis were investigated with a new and simple skin score method measuring the degree of thickening and pliability in seven regions together with area involvement in each region. The highest values were, as expected, found in diffuse cutaneous systemic sclerosis (type III SS) and the lowest in limited cutaneous systemic sclerosis (type I SS) with no lesions extending above wrists and ancles. A positive correlation was found to the aminoterminal propeptide of type III procollagen, a serological marker for synthesis of type III collagen. The skin score is considered simpler than previous methods and is recommended for more general use.

Forty-four patients with systemic sclerosis and 3 patients with localized scleroderma were investigated for plasma endothelin and aminoterminal propeptide of type III procollagen (PIIINP). Although there was an overlap between plasma levels of endothelin in patients with systemic sclerosis and healthy controls, the mean value of the patients was significantly higher than in controls. Plasma endothelin was normal in all 3 patients with localized scleroderma. The highest levels of plasma endothelin were found in patients with type II and III systemic sclerosis with the largest cutaneous involvement, and in patients with the scleroderma-specific antibodies Scl-70 and anticentromere antibodies. Extremely high values were found in a patient who experienced a renal crisis and in a patient who had her lower leg amputated due to severe vasculitis. A positive correlation was found between plasma endothelin and serum PIIINP. This, together with the fact that in systemic sclerosis the vascular lesions are the earliest, would seem to support the theory that endothelial cell damage could lead to increased secretion of endothelin and subsequent fibrosis in this disease.

Eight patients with progressive systemic sclerosis were treated with photopheresis or extracorporeal photochemotherapy given on 2 consecutive days every 4 weeks for 5 to 8 months. Previous treatment with immunosuppressive agents or D-penicillamine was discontinued for at least 4 weeks prior to photopheresis. Although IL-2 receptor density in peripheral blood T-lymphocytes decreased significantly in the initial phase of the photopheresis therapy, no substantial clinical improvement occurred. Although the intention had been to treat all patients for at least 8 months with photopheresis alone, it was mandatory due to severe exacerbations to give additional immunotherapy to 4 patients, and 2 of these together with another patient wanted to discontinue photopheresis after 5 and 6 months, as they did not expect an effect. Three of the 4 patients with progression had RNP-antibodies, suggesting that they had their scleroderma as part of a mixed connective tissue disease. The clinical exacerbations were accompanied in all patients by a highly significant increase in serum aminoterminal propeptide of type III procollagen (PIIINP), which has been reported to correlate with involvement of skin and internal organs in systemic sclerosis. Similar but less significant increases were found in serum carboxyterminal propeptide of type I procollagen (PICP); there were no significant changes in serum cross-linked fragment of type I collagen. Plasma levels of 8-methoxypsoralen were all above 80 ng/l, showing that the lack of responses to photopheresis could not be due to poor absorption of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty-two patients suffering from prurigo nodularis were treated with thalidomide 50-300 mg daily for an average of 12 months (two weeks to five years), following a special arrangement between the Danish Government and the producer Grünenthal GMBH, by which the Government took full economical responsibility for any claims related to the treatment. All patients received prior to treatment a detailed written information about all potential side-effects from the treatment, and had by their signature acknowledged, that they wished to be treated. All but two of the patients had an immediate pronounced effect on their main symptom, the tormenting itching. The same patients had a significant decrease in size and numbers of skin lesions after one to two months of treatment. However, the therapy had to be discontinued in thirteen patients (59%) due to side-effects. The most important side-effect, neuropathy, was the reason for discontinuation of thalidomide in five patients (22%). In spite of the high frequency of side-effects, we consider that this treatment modality should still be offered to the patients with the most severe symptoms due to the pronounced effect on this otherwise therapy resistant disease.

Systemic sclerosis or clinical patterns indistinguishable from systemic sclerosis have previously been demonstrated in workers in the polyvinylchloride industry and in mine-workers exposed to silica dust. In recent years, an increasing number of cases of systemic sclerosis, localized scleroderma, and scleroderma-like disease have been diagnosed in women after implantation of silicone gel prosthesis either following operations for breast cancer or cosmetic augmentation mammoplasty. We present two cases of systemic sclerosis or scleroderma-like disease appearing after silicone implants. Together with the already reported cases these results should lead to reduced use of silicone for cosmetic augmentation mammoplasty and a search for another material for patients operated on for breast cancer. The cases described, together with the reports concerning industrially provoked scleroderma, are of interest for the continued efforts to clarify the pathogenesis of scleroderma. Other types of exposure than those described here may also be of interest, i.e. occupational exposure to silicone spray.

The case is presented of a 48-year-old female suffering from diffuse cutaneous systemic sclerosis (diffuse scleroderma) since 8 years, who went into renal failure as part of hemolytic uremic syndrome following 3 weeks' treatment with 3.8 mg/kg cyclosporin A. Hemolytic uremic syndrome has previously been described in transplant patients receiving cyclosporin A. There are also four cases reported in the literature of renal failure developing in middle aged females with diffuse cutaneous systemic sclerosis after short-term use of low dosage cyclosporin A treatment. It is suggested, that it may be wise not to use cyclosporin A to this category of patients, in which it can not be ruled out, that even a low dose therapy may trigger the rapid onset of scleroderma renal crisis or as in our case provoke hemolytic uremic syndrome.

Because of concern about long-term renal toxicity from low-dose cyclosporine therapy, we studied kidney biopsy specimens in psoriasis patients treated with this drug.The purpose of the study was to investigate whether any morphologic changes appear after approximately 1 year of treatment.Pretreatment and posttreatment renal biopsy specimens were performed in 12 psoriasis patients treated with cyclosporine in dosages from 1.8 to 6 mg/kg/day for 6 to 18 months.The study disclosed a slight but significant increase in interstitial fibrous tissue, which negatively correlated with creatinine clearance. The findings were similar to those described in patients receiving higher dosages of cyclosporine.The clinical relevance of these so-far minor changes is unknown and does not exclude the use of cyclosporine in severe psoriasis; however, they should be taken into consideration in so-called low-dose therapy.

Fifty-seven patients with systemic sclerosis were investigated for connective tissue turn-over related to type III collagen. Sera from 13 patients with diffuse cutaneous systemic sclerosis and 44 patients with limited cutaneous systemic sclerosis were analysed for aminoterminal propeptide of type III procollagen (PIIINP) by a radioimmunoassay based on human propeptide. Increased levels of PIIINP in serum correlated with skin involvement and the clinical course. All patients with diffuse cutaneous systemic sclerosis had levels above the normal range, and in limited cutaneous systemic sclerosis elevated PIIINP levels seemed to be correlated with rapid progression and with extension of lesions. Immunosuppressive drugs, cyclosporin A, and prednisone with or without cyclophosphamide, which were given to patients with rapid disease progression, significantly reduced PIIINP. This was also the case with penicillamine, but to a lesser degree. Our data support the suggestion that immunosuppressive agents are justified in rapidly progressive, life-threatening or disabling disease, when used with the necessary precautions. Serum PIIINP may be utilized as a marker of type III collagen fibrogenesis in systemic sclerosis and be of prognostic value. PIIINP may also be of use in the differential diagnosis between diffuse cutaneous systemic sclerosis and scleredema.

During the period 1972 till the end of 1987, 107 patients with the diagnosis of mycosis fungoides or cutaneous T-cell lymphoma were examined and treated in the Department of Dermatology, Marselisborg Hospital. This disease belongs to the group of non-Hodgkin T-cell lymphomata. The diagnosis is based on the occurrence of red, scaly plaques in the skin associated with itching or tumours in the skin and, simultaneously, of a pleomorphic infiltrate consisting of CD4-positive T-lymphocytes which show characteristically exocytoses in the epidermis with subsequent formation of Pautrier's microabscesses. The disease may progress with spread to the regional lymph nodes where lymphomata develop. Treatment is initially local with employment of chlormethin ("nitrogen mustard gas") and this treatment can maintain the patients in remission for prolonged periods. In cases with spread to lymph glands or in particularly aggressive forms with tumour formation in the skin, combined chemotherapy is administered (prednisone, cyclophosphamide, etretinate and bleomycin). Thirty-eight of the patients were in stage I in which a clinical suspicion of mycosis fungoides was present but where the histological changes were insufficient to confirm the diagnosis. IVa and ten in stage IVb. The age at the onset of the symptoms was from 59 to 64 years (median values) for the various stages. Stages I and II had approximately 80% five-year survival, while the stages with more extensive spread had approximately 50% survival. The etiology of the disease is unknown but, during recent years, certain evidence has been found suggesting that activation of a retrovirus in the epidermis may be a contributory factor.