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Background: Plane warts, when multiple and recurrent, present a therapeutic challenge acting as a source of reinfection, causing frustration and affecting a patient's quality of life. For large numbers of lesions in cosmetically significant sites, topical treatment is preferred to avoid potential sequelae., Objectives: To evaluate and compare the efficacy and tolerability of tazarotene 0.1% gel vs. imiquimod 5% cream for the treatment of plane warts., Methods: In a parallel three-arm randomized controlled trial, 60 patients were randomized to imiquimod, tazarotene or placebo groups. Patients applied the corresponding treatment once daily at night for a maximum of 12 weeks. Primary outcomes were the percentage of respondents with complete clearance in the three studied groups, and the type and frequency of side-effects in each group., Results: Both active treatments resulted in significant improvement compared with baseline and the placebo group (P = 0.001). The imiquimod 5% treated group showed complete clearance in 50% (10/20) of patients, partial response in 15% (3/20), and no response in 35% (7/20). Tazarotene 0.1% gel showed complete clearance in 40% (8/20) of patients, partial response in 40% (8/20), and no response in 20% (4/20). No significant difference was detected between the imiquimod and tazarotene groups (P = 0.19)., Conclusions: Compared with imiquimod, tazarotene 0.1% gel for the treatment of plane warts seems to offer an equivalent treatment response, it maintained efficacy without recurrence and had a safer profile regarding dyspigmentation with an advantageous cheaper cost., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Skin, being exposed directly to the environment, represents a unique model for demonstrating the synergistic effects of intrinsic and extrinsic factors on the ageing process. Ultraviolet radiation (UVR) is the major factor among exogenous stressors responsible for premature skin ageing. The problem of skin ageing has captured public attention and has an important social impact. Different therapeutic approaches have been developed to treat cutaneous ageing and to diminish or prevent the negative effects of UVR. Topical retinoids represent an important and powerful class of molecules in the dermatologist's hands for the treatment of photodamaged skin. Since their introduction more than 20 years ago, topical retinoids have shown beneficial efficacy and good safety profiles in the management of photodamaged skin, and as therapeutic anti-ageing agents. This review provides a brief retrospective of the development of topical retinoids in the treatment of photodamaged skin, elucidates their mechanism of action, delineates their use and addresses clinical, pharmaceutical and regulatory issues in connection with their intended use., (© 2010 The Authors. BJD © 2010 British Association of Dermatologists.)

Background: Topical tazarotene has been shown to offer efficacy in ameliorating multiple effects of photodamage., Objectives: To evaluate the histological effects of tazarotene cream on photodamaged skin., Methods: In this multicentre, double-blind, randomized, vehicle-controlled study, 50 patients with photodamaged facial skin (at least mild fine wrinkling and mottled hyperpigmentation, with at least one of these being moderate) were randomized to apply tazarotene 0.1% cream or vehicle cream to their face, once daily for 24 weeks., Results: Blinded assessments showed that tazarotene was less likely than vehicle to be associated with an increase in keratinocytic and melanocytic atypia, and more likely than vehicle to be associated with a reduction in atypia. Between-group comparisons in distribution of change from baseline categories of severity were in favour of tazarotene (P = 0.055 for keratinocytic atypia, P = 0.034 for melanocytic atypia, and P < 0.001 for the number of granular cell layers). Compared with vehicle, tazarotene was associated with an increase in epidermal polarity (P = 0.008) and epidermal thickness (P = 0.012), and a tendency for stratum corneum compaction. Tazarotene was also associated with widened intercellular spaces (reported as epidermal oedema) relative to vehicle (P < 0.001)., Conclusions: Treatment of photodamaged skin with tazarotene is associated with an amelioration of keratinocytic and melanocytic atypia, an improvement in epidermal polarity, and an increase in epidermal thickness.

Background: Basal cell carcinoma (BCC) is the most common cancer in humans. Medical treatment modalities offer cost reductions and clinical advantages in selected cases such as low-risk areas, surgically inaccessible sites, patients with multiple neoplasms, and older, infirm or anticoagulated subjects. Tazarotene has been proposed for the treatment of BCC; however, data on its efficacy are lacking., Objectives: To investigate the efficacy of tazarotene in a large series of BCCs, better to define the clinical advantages and the mechanisms of action in vivo., Methods: Tazarotene 0.1% gel was applied daily for 24 weeks to 154 small superficial and nodular BBCs. Clinicopathological changes were followed during the therapy by dermoscopic and histological examination. Proliferation, retinoic acid receptors and apoptosis were investigated by immunohistochemistry and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labelling on biopsies., Results: At 24 weeks of therapy, 70.8% of the BCCs showed > 50% clinical and dermoscopic regression, and 30.5% healed without recurrences after 3 years of follow-up. At 12 weeks, biopsies showed that regression was associated with reduced proliferation and increased apoptosis of basaliomatous cells. Most unresponsive tumours displayed a keratotic differentiation., Conclusions: Tazarotene was effective in the majority of superficial and nodular undifferentiated BCCs treated, possibly by antiproliferative and proapoptotic actions in vivo. Keratotic BCCs were the major type among the unresponsive tumours, and were characterized by overexpression of p53 and cellular retinol binding protein-1 in comparison with undifferentiated tumours. Topical tazarotene represents an alternative medical choice for selected cases of BCC.

Background: Numerous studies have shown that the additional administration of topical or systemic antipsoriatic agents might serve as an effective means to increase the efficacy of photochemotherapy [psoralen plus ultraviolet (UV) A (PUVA)] for psoriasis., Objectives: To compare the therapeutic response to tacalcitol plus PUVA, tazarotene plus PUVA and PUVA monotherapy in patients with chronic plaque-type psoriasis. In addition, we also assessed the duration of remission induced by each regimen and the tolerability of the two combination treatments., Methods: Thirty-one patients with chronic plaque-type psoriasis were included in this observer-blinded, intrapatient comparison trial. PUVA treatment was given four times weekly. Additionally, tacalcitol ointment and 0.1% tazarotene gel were applied separately on two target areas once daily in the evening. At the onset of therapy and every 2 weeks thereafter the response to treatment was determined by the Psoriasis Severity Index score, which assesses the degree of erythema, infiltration and scaling of the psoriatic lesions. After complete or near complete clearing patients were followed-up until relapse., Results: Twenty-four patients completed the study. The treatment requirements to induce complete or near complete clearing were significantly lower for both combination treatments than for PUVA monotherapy (P < 0.01). The median cumulative UVA dose and number of exposures were 30.6 J cm-2 (95% confidence interval, CI 22.5-71.2) and 14 (95% CI 11-16) for tacalcitol plus PUVA, 32.3 J cm-2 (95% CI 22.5-73.8) and 14 (95% CI 11-19) for tazarotene plus PUVA, and 37.0 J cm-2 (95% CI 29.5-83.9) and 16 (95% CI 14-22) for PUVA monotherapy. No difference between the three regimens was observed with regard to duration of remission. Adverse reactions occurred more often with 0.1% tazarotene than with tacalcitol but were in general mild and completely reversible upon using a lower concentration of 0.05% tazarotene., Conclusions: Tacalcitol ointment and tazarotene gel are both comparably effective in improving the therapeutic result of PUVA therapy in patients with chronic plaque-type psoriasis. Besides accelerating the treatment response, both agents, by virtue of their UVA dose-sparing effect, might also help to reduce possible long-term hazards of PUVA treatment.

The clinical efficacy and tolerability of the topical receptor-selective retinoid tazarotene in the treatment of congenital ichthyoses was investigated. Twelve consecutive patients with different forms of congenital ichthyosis were enrolled in an open, non-randomized, intraindividually controlled, half-side pilot study. Diagnoses were X-linked recessive ichthyosis, non-erythrodermic autosomal recessive lamellar ichthyosis, autosomal dominant ichthyosis vulgaris and ichthyosis bullosa of Siemens (IBS). Tazarotene 0.05% gel was applied unilaterally daily on a defined body area measuring 10% of the body surface area. The contralateral side was treated with an ointment containing 10% urea. After 14 days, application frequency was reduced to three times a week, and stopped after another 2 weeks. The follow-up period was 3 months. Reduction in scaling and roughness was used to assess the clinical response in the tazarotene-treated area compared with the control area. Clinical and laboratory assessments were performed every 14 days during the trial. Unilateral improvement in favour of the tazarotene-treated side was observed in nine of 12 patients (75%). Four patients (33%) achieved an excellent response and four (33%) achieved a good response. No therapeutic effect was seen in patients with IBS. The remission persisted during the reduction phase and after discontinuation for up to 2 months. Local irritation in three patients was the only side-effect detectable. Short-term topical application of tazarotene 0.05% gel is a very effective and well-tolerated treatment modality in different forms of congenital ichthyoses and may be an alternative to systemic retinoid therapy.

Phototherapy is often used in combination with other antipsoriatic treatments in an attempt to improve efficacy and reduce patients' cumulative exposure to radiation. Although this aim has been achieved with some combinations, the additional therapies often introduce a potential risk of other tolerability and safety problems. The efficacy of tazarotene reported in clinical trials to date suggest that this drug may help to improve the efficacy of phototherapy, and perhaps reduce the ultraviolet light exposure required without introducing additional, clinically significant problems. Preliminary results from the first 10 patients in a clinical trial investigating such combination therapy are reported here. They demonstrate that the addition of tazarotene to UVB phototherapy increases the percentage of patients achieving treatment success (> or = 50% global improvement in psoriasis) from 60% to 100% at Day 81. The UVB plus tazarotene combination achieved consistently greater reductions in the elevation and scaling of difficult-to-treat psoriatic plaques than UVB phototherapy alone or UVB phototherapy plus vehicle gel. The tazarotene combination therapy also achieved initial treatment success in less than half the time needed with phototherapy alone (median of 32 vs. 67 days). Combining UVB phototherapy with tazarotene treatment appears to offer a valuable therapeutic option that is more efficacious and faster than UVB phototherapy alone.

Although tazarotene monotherapy is generally efficacious and well tolerated, studies show that both the efficacy and the tolerability of tazarotene therapy can be further improved when it is used in combination with certain topical corticosteroids. The studies reported here evaluate the usefulness of two potential combination regimens. In one regimen, a corticosteroid is added to tazarotene treatment. In the other regimen, corticosteroid treatment alternates on a daily basis with tazarotene treatment. The results of the first study, which involved 300 patients, showed that additive combination therapy using tazarotene plus a mid- or high-potency topical corticosteroid significantly increased the percentage of plaques achieving treatment success at the end of the treatment period, compared with tazarotene plus placebo (91% and 95% vs. 80%, respectively; P<0.05 for both). Similarly, tazarotene plus a mid- or high-potency topical corticosteroid reduced the incidence of patient withdrawals compared with tazarotene plus placebo (5.5% and 9.6% vs. 13.3%). The results of the second study, which involved 398 patients, showed that a combination regimen that alternates between tazarotene and a high-potency topical corticosteroid treatment each day, significantly increased the treatment success rate compared with regimens using tazarotene alternating with a mid-potency corticosteroid or placebo (75% vs. 55% and 54%, respectively, at the end of the treatment period; P<0.05 for both). In addition, there was a trend towards a lower incidence of treatment-related adverse events as corticosteroid potency increased (from 42% with tazarotene plus placebo to 36%, 32%, and 31% with tazarotene plus the low-, mid-, and high-potency corticosteroid, respectively). Both treatment regimens are potentially useful and offer a rational approach to optimizing the efficacy and tolerability of tazarotene treatment for plaque psoriasis.

Topical therapies are first-line treatment for mild/limited stable plaque psoriasis. Disadvantages of currently available therapies include lack of short-term efficacy and long-term maintenance, adverse effects, and cosmetic problems. Tazarotene is a new topical retinoid which has proven to be efficacious in the treatment of mild-to-moderate plaque psoriasis. Results from a large, multicentre, pivotal study show that a once-daily application is as effective as a first-line monotherapy, providing rapid resolution of signs and symptoms and sustained therapeutic effects in some patients. Tazarotene gel is cosmetically acceptable, and is minimally absorbed systemically, with adverse events limited to local irritation.

Initial clinical investigations on tazarotene, a new acetylenic retinoid, have suggested potential usefulness in the treatment of mild-to-moderate plaque psoriasis. Tazarotene promotes healing of psoriatic lesions by modulating the key pathogenetic factors in this disease. It is not sensitizing, phototoxic, or photoallergenic, but causes moderate dose-related skin irritation. Systemic absorption is minimal and elimination is rapid, providing a low potential for systemic adverse effects. Tazarotene effectively treats mild-to-moderate plaque-type psoriasis, the benefits seem to be sustained after the cessation of therapy, and once-daily treatment is equally effective as more frequent application.

There is considerable evidence to suggest that the identification and treatment of dyslipidaemia will reduce the risk of premature CHD, i.e. before the age of 65. Diagnosis of the cause of raised plasma lipid levels will enable appropriate decisions to be taken with regard to management. The cornerstone of treatment is nutritional counselling and attention to other major risk factors for CHD, particularly smoking and hypertension. For a small percentage of patients with severe hyperlipidaemia drug therapy is indicated. Appropriate drug choices need to be made based on the particular lipid abnormality to be treated. In general those patients with clinical vascular disease are treated more aggressively than those where the aim is primary prevention. More research is needed to determine individual risk more precisely and to allow proper targeting of therapy. Genetic factors, qualitative changes in lipoproteins, lipoprotein (a), fibrinogen, and other coagulation and thrombotic factors are likely to be important in individual risk assessment. There is no doubt that more information is needed from prospective studies of lipid-lowering therapy in terms of risk benefit for affected individuals. Hopefully the major studies currently underway will fill some of the gaps in our knowledge. Until then aggressive therapy with drugs should be reserved for those at highest risk where the benefit is likely to be greatest.

The development of pellagra in a patient treated with 5-fluorouracil for malignant disease is reported. The aetiology of pellagra in this patient is discussed, and the reasons for possible under-diagnosis of pellagra in association with malignant disease considered. We report a patient who presented with the typical skin changes of pellagra. The rash, and an associated acute deterioration in cerebral function, were exacerbated by treatment with 5-fluorouracil. The importance of considering nicotinic-acid deficiency in patients with malignant disease has not been emphasized in the literature.

Clinical data are presented on a new anti-alcoholic drug, litonit. A substantial reduction in the pathological addiction to alcohol takes place under the effect of litonit, and a stable aversive reaction to alcohol develops. The new drug is distinguished by its low toxicity, good tolerance, and its failure to cause disorders of the liver and kidneys even after chronic administration.

Twenty-five hypercholesterolaemic patients from three centres in the UK were investigated in an open study of the efficacy and side effects of niceritrol. Five patients dropped out of the study at an early stage and had insufficient data for analysis. There were 13 males and 7 females (mean age 49.2 years, range 18-69). Fourteen patients had heterozygous familial hypercholesterolaemia, and six polygenic hypercholesterolaemia. Niceritrol was started at a dose of 750 mg/day and this was increased at weekly intervals over 4 weeks to the maximum tolerated dosage up to 3 g/day. This was then maintained for a further 8 weeks. There were statistically significant decreases in total plasma cholesterol, total triglyceride, LDL cholesterol and VLDL triglyceride; HDL cholesterol remained unchanged after 12 weeks of treatment (Wilcoxon matched pairs, signed ranks test). The 14 patients with familial hypercholesterolaemia showed a 13.9% fall in total cholesterol and a 19.8% fall in LDL cholesterol. All patients reported flushing and some had gastrointestinal symptoms but 19 would have been prepared to continue with the therapy at doses up to 3 g/day. Thus niceritrol has been found to be beneficial in the treatment of both familial and polygenic hypercholesterolaemia.

1. In type IIa and IIb hyperlipoproteinaemia, treatment with 16 g cholestyramine daily reduced the cholesterol concentration 23%. By adding clofibrate this effect was enhanced to a 29% reduction and at the same time clofibrate reduced the triglyceride (TG) concentration 33%. 2. The optimal cholesterol reduction with clofibrate in type II was 17% and was found after treatment with 1.5 g clofibrate/day. The optimal TG reduction appeared to be achieved with a daily dose of 2 g.3. Nicotinic acid in the form of niceritrol had another type of dose-response in type II with doses from 3 to 6 g/day. It appeared as if the optimal dose probably was above 6 g daily. The 6 g dose produced a cholesterol reduction of 22% and in type IIb there was at the same time a 50% reduction of the TG concentration. 4. By combining 3 g niceritrol with 2 g clofibrate almost the same effect on serum lipids was obtained as with 6 g niceritrol. When choosing a drug for treatment of hyperlipoproteinaemia it is necessary to consider not only the lipid lowering effect but also the side effects which are not discussed here. By combining clofibrate with either cholestyramine or niceritrol it was possible to improve the lipid lowering effect. There were no side effects which were not seen when the drugs were used alone. A more frequent use of combinations to improve the treatment of hyperlipoproteinaemia is recommended.

In 25 cases of pellagra and 10 healthy controls, the blood pyruvic acid levels in the fasting stage and after 60 and 90 minutes of glucose load were estimated by the technique of Friedmann & Haugen (1943). The blood pyruvic acid levels after 60 and 90 minutes of glucose load were significantly higher in pellagrins as compared to controls. The following conclusions were drawn from this study: (i) that there is impairment of pyruvic acid metabolism in cases of pellagra, which is more marked in pellagrins with neurological manifestations than in those without; (ii) that after administration of nicotinic acid alone for 15 days the pyruvic acid levels returned to normal, thereby indicating that nicotinic acid deficiency is the cause of deranged pyruvate metabolism; (iii) that there is significant improvement in neurological status after nicotinic acid therapy.

The effects of long term treatment with nicotinic acid on lipids, lipoproteins, and the plasma distribution of very low density lipoproteins (VLDL) apoprotein C (ApoC) subspecies were studied in 33 patients with types IIa (n = 9), IIb (n = 11), and IV (n = 13) hyperlipidemias. After 6 months of treatment, a significant decrease in triglyceride, total cholesterol, and low density lipoprotein (LDL) cholesterol levels occurred. High density lipoprotein (HDL) cholesterol increased significantly by 31.1%, 41.8%, and 32.0% in types IIa, IIb, and IV, respectively (P less than 0.01 for all). A significant negative correlation existed between changes in HDL cholesterol and triglycerides (r = -0.613; P less than 0.02) in all groups studied. Therapy also produced changes in VLDL, LDL, and HDL protein concentrations. VLDL protein decreased from 20.9 +/- 3.9 to 15.2 +/- 1.0 mg/dl (P less than 0.05) in type IIa. In types IIb and IV, mean VLDL protein decreased from 44.7 +/- 8.2 to 27.1 +/- 3.9 mg/dl (P less than 0.001) and from 46.3 +/- 7.1 to 30.6 +/- 4.9 mg/dl (P less than 0.001), respectively. LDL protein decreased significantly, and HDL protein increased in type IIa only. Gel isoelectric focusing of VLDL before and after nicotinic acid in types IIb and IV hyperlipidemia produced a significant increase in the VLDL ApoC-II component with simultaneous decreases in the total VLDL ApoC-III subspecies. This resulted in increases in the ApoC-II to ApoC-III area ratio from 0.50 +/- 0.1 to 1.02 +/- 0.2 (P less than 0.001) in type IIb and from 0.62 +/- 0.07 to 0.88 +/- 0.13 (P less than 0.01) in type IV, respectively. The ApoE subspecies and the ApoE-III to ApoE-II area ratio did not change significantly. Our results show that nicotinic acid produces a significant improvement in the lipoprotein profiles of these patients.

A patient with unusually severe hypertriglyceridaemia (serum concentration initially 258 mmol/l or 22600 mg/dl) and hypercholesterolaemia is reported and discussed. The triglyceride elevation was found to reside within the very low density lipoprotein fraction and was probably attributable to the combination of diabetes mellitus and familial hypertriglyceridaemia. Treatment with insulin and restriction of dietary carbohydrate led to a 50% reduction in the triglyceride concentration, and the addition of nicotinic acid in modest doses led ultimately to a complete normalization of the patient's lipid values. A close correlation was noted between the falling triglyceride concentration and the rising serum sodium concentration during the course of successful therapy. Overall, it is felt likely that this patient's severe and reversible hypertriglyceridaemia was on the basis of excessively rapid lipolysis leading to high concentrations of very low density lipoprotein production. Combined therapy with insulin and nicotinic acid is recommended for other patients of this nature.