Biomedical subjects
J Berth-Jones
Publications and source records attributed to J Berth-Jones.
Placebo-controlled trial of essential fatty acid supplementation in atopic dermatitis.
Treatment of atopic dermatitis with essential fatty acids remains controversial. A double-blind, placebo-controlled, parallel-group study was done to investigate the response of patients with atopic dermatitis to essential fatty acid supplements. Patients with atopic dermatitis were randomised to receive evening primrose oil, evening primrose oil and fish oil, or placebo for 16 weeks. Disease activity was monitored by clinical severity scores recorded by the investigator, topical steroid requirement, and symptom scores recorded by subjects. Of 123 subjects recruited, 102 completed the treatment period. No improvement with active treatment was demonstrated. Our study, which avoided the methodological and analytical problems of previous studies, found no effect of essential fatty acid supplementation in atopic dermatitis.
Hypercalcaemia with topical calcipotriol.
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Urine calcium excretion during treatment of psoriasis with topical calcipotriol.
Urine calcium excretion is a very sensitive method of detecting vitamin D intoxication, and may rise in the absence of any apparent change in the serum level. Little attention has been paid to urine calcium levels during the large trials performed to assess the efficacy and safety of calcipotriol in psoriasis vulgaris. There are some urine calcium data from short-term studies of average dose rates of calcipotriol. However, there are no published data on long-term usage, nor on the use of dose rates at the upper end of the licensed range (100 g/week). In a group of 20 patients, who were using typical quantities of calcipotriol ointment (50 micrograms/g) to treat psoriasis vulgaris, urine calcium excretion was measured prior to treatment, and then monthly for 12 months. There was no significant change in urine calcium over the year. In a separate group of 10 patients, who were using calcipotriol in the same concentration, at the maximum recommended rate of 100 g/week, urine calcium was measured at baseline, and after 2 and 4 weeks. There was a statistically significant rise in calcium excretion. This is the first trial to demonstrate that topical calcipotriol affects calcium homeostasis when used within the recommended dose range. Further studies are necessary to determine more precisely the magnitude and variability of this effect in a large group of individuals. For the present, caution is required when prescribing calcipotriol for any patient with known hypercalciuria or a history of renal stone formation. Consideration should be given to monitoring urine calcium excretion during prolonged use at dose rates approaching the recommended maximum.
Cyclosporin greatly improves the quality of life of adults with severe atopic dermatitis. A randomized, double-blind, placebo-controlled trial.
A multicentre, randomized, double-blind, controlled crossover clinical trial was conducted on 33 patients with severe refractory atopic dermatitis, to determine the effects of cyclosporin (5 mg/kg/day) on their health-related quality of life. Treatments were administered for 8-week periods. One group (n = 16) received placebo followed by cyclosporin, and the other (n = 17) received cyclosporin and then placebo. Health-related quality of life was assessed at 0, 8 and 16 weeks using a general measure, the United Kingdom Sickness Impact Profile (UKSIP), an eczema-specific measure, the Eczema Disability Index (EDI), and a global 5-point rating scale of overall health (very good to very poor). In addition, clinical assessments (i.e. extent and activity of disease) were made by the investigators. UKSIP and EDI scores indicated significant improvement in quality of life (P < 0.05-P < 0.01) of patients with atopic dermatitis after treatment with cyclosporin. Although no patient required withdrawal from the study, 20 patients receiving cyclosporin reported adverse events, compared with eight taking placebo. There was a close correlation (P < 0.05-P < 0.01) between the UKSIP and EDI scores. In contrast, there was either no correlation, or only a very poor correlation, between the quality of life parameters and clinical measures of extent and activity of eczema. When cyclosporin was stopped, relapse was rapid, but the mean scores for disease activity and extent of disease were less than their baseline values (i.e. an improvement of greater than 25% was maintained in 11 patients at week 4).(ABSTRACT TRUNCATED AT 250 WORDS)
High-dose topical calcipotriol in the treatment of extensive psoriasis vulgaris.
Ten patients with extensive plaque psoriasis were treated with calcipotriol ointment (50 micrograms/g) for 2 weeks (200 g for 1 week, followed by 300 g during the second week). Mean improvement in psoriasis area and severity index (PASI) was 71%. Mean 24 h urine calcium rose from 4.79 mmol/24 h to 7.27 mmol/24 h (P < 0.0001). Urine calcium returned towards baseline after stopping calcipotriol. Mean serum calcium also rose slightly, but significantly, from 2.26 mmol/l to 2.32 mmol/l (P < 0.005), and fell again in the washout phase. Individual serum calcium values remained within the normal range throughout the study. Topical calcipotriol is an effective, rapidly acting and safe in-patient treatment for extensive plaque psoriasis.
Occlusion enhances the efficacy of topical calcipotriol in the treatment of psoriasis vulgaris.
Forty-eight patients with symmetrical chronic plaque psoriasis affecting the limbs were recruited for a single-blind right/left within patient study to assess the effect of combining occlusion with topical calcipotriol. Subjects were randomized into two groups. Sites of similar severity on opposing limbs were selected as target areas. The first (group A) treated one side with calcipotriol alone and the opposite side with calcipotriol plus occlusion. The second (group B) treated one side with placebo plus occlusion and the opposite side with calcipotriol plus occlusion. In group A the mean improvements were 40% (P < 0.001) for calcipotriol alone and 61% (P < 0.001) for calcipotriol plus occlusion. In group B, occlusion plus calcipotriol resulted in a mean 62% improvement (P < 0.001) while occlusion plus placebo produced no significant change. The combination of calcipotriol plus occlusion was significantly better than calcipotriol alone (P < 0.005). The results indicate that occlusion improves the response to calcipotriol by enhancing its penetration. Indices of calcium metabolism remained unchanged throughout the study.
Xeroderma pigmentosum variant: 5 years of tumour suppression by etretinate.
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Generalised pustular psoriasis: response to topical calcipotriol.
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Comparative study of calcipotriol (MC 903) ointment and betamethasone 17-valerate ointment in patients with psoriasis vulgaris.
BACKGROUND: Topical vitamin D analogues have been reported to be an effective treatment in patients with psoriasis. Comparative studies with existing treatments are required. OBJECTIVE: Our purpose was to compare the effectiveness of calcipotriol (50 micrograms/gm) and betamethasone 17-valerate (1 mg/gm) ointments twice daily in the treatment of stable plaque psoriasis. METHODS: This study was a randomized, double-blind comparison over 6 weeks in 409 patients. Efficacy, as measured by the Psoriasis Area and Severity Index (PASI), and safety were assessed at 2, 4, and 6 weeks. RESULTS: Reduction of PASI was statistically significant at all time points for both treatments but there were no significant between-treatment differences. At the completion of 6 weeks of treatment, the mean PASI reduction was 5.50 for calcipotriol and 5.32 for betamethasone (95% confidence interval [CI] -0.40 to 0.78). Analysis of patient assessment at 6 weeks showed clearance or marked improvement in 61.2% of the calcipotriol patients and 50.5% with betamethasone (95% CI 1.4 to 20.8). Calcipotriol produced significantly more local side effects (19.5% compared with 3.9%, p less than 0.001); however, these were minimal leading to withdrawal in only 3 of 205 patients. CONCLUSION: Calcipotriol ointment was as effective as betamethasone 17-valerate ointment as measured by the PASI and superior as measured by self-assessment in patients with stable plaque psoriasis. Both treatments were well tolerated.
Modern treatment of warts: cure rates at 3 and 6 months.
Four-hundred consecutive referrals with viral warts of the hands and/or feet were investigated to determine the cure rate from a combination of cryotherapy, keratolytic wart paint and paring. For treatment failures after 3 months, the value of continuing cryotherapy and of additional treatment with the immunomodulator inosine pranobex were assessed. Subjects were treated for 3 months with wart paint and cryotherapy and were randomized to receive, or not, paring in addition. Those who did not respond by 3 months were randomized to receive, or not, 3 months further cryotherapy, and to receive inosine pranobex 60 mg/kg/day for 1 week each month, or matching placebo. Fifty-two per cent of subjects were cured by 3 months. The chance of cure was inversely related both to the length of history and to the diameter of the largest wart. Paring improved the cure rate for plantar warts but not for hand warts. During the second 3 months the cure rate fell to 41%. Neither cryotherapy nor inosine pranobex significantly improved this response.
A multicentre, parallel-group comparison of calcipotriol ointment and short-contact dithranol therapy in chronic plaque psoriasis.
Short-contact treatment with dithranol (anthralin) is a widely used treatment for chronic plaque psoriasis. Although effective, it causes staining and irritation, and is therefore inconvenient. Calcipotriol is a recently developed vitamin D analogue which is effective and easy to use. To evaluate the relative efficacy, safety and acceptability of these treatments a multicentre, open, randomized, parallel-group comparison was performed. Four hundred and seventy-eight patients with chronic plaque psoriasis were randomized to use one of the two treatments for 8 weeks. One group applied calcipotriol ointment (50 micrograms/g) twice daily. The other used a single application for 30 min each day of Dithrocream in the highest concentration tolerated. Severity of psoriasis was assessed by modified PASI score at baseline, and after 2, 4, and 8 weeks of treatment. A five-point scale was used by subjects and by investigators as an additional assessment of overall response, and a similar scale was used by subjects to grade acceptability. Total serum calcium was monitored at baseline and after 2 and 8 weeks on treatment. The mean PASI score fell from 9.1 to 4.7 after 8 weeks on dithranol (P < 0.001), and from 9.4 to 3.4 on calcipotriol (P < 0.001). The difference between the two treatments was significant in favour of calcipotriol at 2 weeks (P < 0.001), and remained so at subsequent assessments. At 8 weeks the difference between mean improvements in scores for the two groups was 1.6 (95% confidence interval 0.5-2.7). Efficacy grading by subjects and investigators, and acceptability grading by subjects, were all significantly better for calcipotriol.(ABSTRACT TRUNCATED AT 250 WORDS)
Epidermal cytokeratin and immunocyte responses during treatment of psoriasis with calcipotriol and betamethasone valerate.
Changes in epidermal immunocytes and cytokeratins were investigated during treatment of psoriasis with calcipotriol and betamethasone valerate. Skin biopsies were obtained from 10 subjects on each treatment from lesional and non-lesional skin at baseline, and from treated lesions after 4 weeks. In each subject, changes in expression of cytokeratins K5, K10 and K16, and changes in epidermal immunocyte counts were assessed. Responses were compared with a separate histological parameter of improvement, epidermal thickness. Both treatments produced a marked normalization of cytokeratins. The reduction of K16 expression was similar on each treatment and correlated significantly with reduction in epidermal thickness. Expression of both K5 and K10 improved less than thickness with betamethasone valerate but more than thickness with calcipotriol, although these differences did not reach statistical significance. With calcipotriol there was an increase in K5 and K10 responses with increasing response of epidermal thickness, which was not seen with betamethasone valerate. T6+ cells, HLA-DR+ dendritic cells and T lymphocytes were all reduced by betamethasone valerate. There was a remarkable similarity in the level of normalization between cell types and also between cellular response and reduction in thickness. Calcipotriol produced a similar consistent reduction in cell numbers and in thickness, with the exception of T6+ cells which increased in some subjects during treatment. Only in subjects in whom thickness had virtually returned to normal was there a marked decrease in T6+ cells.
Vitamin D analogues and psoriasis.
Topical vitamin D analogues offer a new, effective, more convenient and generally well-tolerated option for the treatment of psoriasis. Only psoriasis vulgaris has been intensively studied, but other forms of the disease may also respond. Both calcitriol and calcipotriol have been shown to be effective in numerous clinical trials, and the latter has compared well with betamethasone valerate and short-contact dithranol in controlled studies. Their mechanism of action is not yet fully understood and may prove complex. The most important effect may be a direct regulation of keratinocyte proliferation and differentiation. However, these compounds also have potent immunological properties, and may act by inhibition of cytokine production by keratinocytes or lymphocytes. Topical application of vitamin D analogues appears generally to be remarkably safe, but hypercalcaemia and hypercalciuria may develop if large quantities are used.
Sweet's syndrome responding to cyclosporin.
We report a case of Sweet's syndrome which responded to treatment with cyclosporin 4 mg/kg/day. Cyclosporin is effective in the treatment of many dermatoses, and although the immunosuppressive effects of cyclosporin are mainly attributed to inhibition of T-lymphocyte proliferation, it has also been shown to affect the functions of both neutrophils and monocytes. Possible mechanisms of action of cyclosporin in Sweet's syndrome are discussed.
Diffuse primary cutaneous amyloidosis.
A case of extensive primary cutaneous amyloidosis exhibiting both macular and lichenoid lesions is reported. Lesions were arranged in a distinctive linear pattern covering much of the trunk and limbs, in places following Blaschko's lines. The coexistence of macular and lichenoid lesions suggests that this is an unusual variant of biphasic cutaneous amyloidosis.
Progress in self treatment for psoriasis vulgaris.
Chronic plaque psoriasis is by far the most frequent form of the disease and is usually amenable to home treatment. The therapeutic armamentarium for self-treatment of psoriasis has, until recently, been limited to emollients, tar, dithranol and topical corticosteroids. Although limited progress has been made in improving formulations and treatment regimes for these compounds, they still have significant drawbacks in terms of either unwanted effects or cosmetic acceptability. Topical vitamin D analogues offer a new, effective, convenient and safe option for self-treatment of psoriasis. Most research has been performed on calcipotriol. This has compared well to beta-methasone valerate and short-contact dithranol in controlled studies. Skin irritation is frequently noticed by patients, but rarely requires treatment to be discontinued. The mechanism of action appears most likely to be a direct regulation of keratinocyte proliferation and differentiation. Calcipotriol has relatively little effect on calcium metabolism and appears to be safe when used according to established guidelines but hypercalcaemia may develop if excessive quantities are used.
Double-blind, controlled, crossover study of cyclosporin in adults with severe refractory atopic dermatitis.
A few patients remain severely affected by atopic dermatitis into adult life despite treatment with systemic steroids, azathioprine, and photochemotherapy. 33 patients took part in a double-blind, placebo-controlled, crossover study to assess the efficacy and safety of cyclosporin (5 mg/kg per day) in adults with severe refractory atopic dermatitis. Treatments were given for eight weeks each with one group (n = 16) receiving placebo followed by cyclosporin and another (n = 17) receiving cyclosporin and then placebo. Disease activity, extent of disease, sleep and itch, topical steroid use, and adverse events were assessed every two weeks. Both extent and activity of dermatitis were significantly improved (p less than 0.001) as were subjective measures of disease. 20 patients receiving cyclosporin reported adverse events compared with 8 taking placebo, although no patient required withdrawal from the study. Cyclosporin therapy led to an increase in the mean serum urea, creatinine, and bilirubin concentrations, although only the rise in bilirubin was significant (p = 0.001). Our results confirm that cyclosporin is a safe and effective short-term treatment for severe, refractory atopic dermatitis.