Search

SummaryBackground Chronic hand eczema (CHE) is a common inflammatory skin disease that affects approximately 10% of the population. Systemic alitretinoin has been shown to be effective in patients with CHE who are refractory to topical corticosteroids. Objectives To analyse the impact of alitretinoin on the skin barrier genes and protein expression in the skin lesions of patients with CHE. Materials and methods Fifteen patients with CHE were treated with 30 mg daily of alitretinoin for up to 27 weeks. Disease severity was assessed using a clinical score. Skin biopsies from all the patients were evaluated before and after therapy for the expression of Ki-67, various skin barrier genes and thymic stromal lymphopoietin (TSLP) by real-time quantitative polymerase chain reaction and immunohistochemistry. Results After alitretinoin application, an improvement in the clinical severity of CHE was observed in the majority of patients. Analysis of skin biopsies before treatment showed a significant increase in Ki-67-positive cells in the suprabasal layer and a dysregulated expression of various skin barrier genes, such as claudin 1, loricrin, filaggrin and cytokeratin 10, which were normalized after treatment. TSLP was significantly upregulated in patients with CHE and also normalized after alitretinoin treatment and negatively correlated with filaggrin. Conclusions Our data indicate that the expression of barrier genes and proteins was normalized following treatment with alitretinoin in patients with CHE. The change in expression levels of these genes correlated with the clinical efficacy, suggesting that alitretinoin exhibits a disease-modifying activity. TSLP is upregulated in CHE and seems to counteract filaggrin expression in the skin.

Alitretinoin is an endogenous vitamin A derivative, 9-cis-retinoic acid. Its anti-inflammatory and immunomodulatory efficacy results from controlling leukocyte activity and cytokine production in keratinocytes. We describe three patients with severe chronic hand eczema accompanied by nail dystrophy, which was treated with alitretinoin 30 mg. Clinical evaluation at 6 months showed complete or almost complete clearing of the nail lesions. We also briefly review the literature reporting on nail dystrophy and alitretinoin treatment. There is some evidence of the clinical effect of retinoids on nail formation, owing to the presence of retinoid receptors on the nail matrix. Further studies are required to better understand the impact of alitretinoin in nail diseases. Our observation supports alitretinoin as a treatment option in retinoid-responsive dermatoses associated with nail involvement.

Background Palmoplantar pustular psoriasis is often recalcitrant to therapy. Here we evaluated the therapeutic effect of alitretinoin in patients with recalcitrant palmoplantar pustular psoriasis and investigated subsequent immunopathological alterations. Methods Seven patients with palmoplantar pustular psoriasis were treated with oral alitretinoin 30 mg once daily for 12 weeks. Efficacy was assessed by palmoplantar pustular psoriasis area and severity index (PPPASI), visual analogue scales (VAS) on intensity of pain and pruritus and an overall patient assessment. Immunohistochemical staining for neutrophil elastase, CD3, CD4, CD8, CD1a CD11c, CD303,CD68, CD69, CD208 and HLA-DR was on lesional skin biopsies obtained before and after 12 weeks of treatment. Results PPPASI and VAS for pruritus and pain decreased significantly after 12 weeks of treatment with alitretinoin. The overall patient assessment ranged from 60% to 90% clinical improvement. In correlation with clinical improvement a significant reduction, particularly of neutrophils, macrophages and dendritic cells, was also observed in the skin sections. Alitretinoin was well tolerated except for headache during the first month of treatment in two patients. Limitations of the study are a missing control group and the concomitant usage of topical therapy. Discussion Our findings suggest that alitretinoin may represent a new and promising therapy for recalcitrant palmo-plantar psoriasis and warrants further controlled studies to confirm efficacy and safety of alitretinoin in this disease.

Summary Background. In a previous large trial (Benefit of Alitretinoin in Chronic Hand Eczema; BACH), 47.7% of patients with severe chronic hand eczema (CHE) who received alitretinoin 30 mg achieved ‘clear’ or ‘almost clear’ hands during the initial 24-week treatment course. Objectives. The current open-label trial was designed to study extended treatment with a further 12- to 24-week course of oral alitretinoin 30 mg in patients who did not fully respond to initial treatment in the BACH study. Methods. At the end of the BACH study, patients whose eczema was rated ‘mild’, ‘moderate’ or ‘severe’ according to the Physician’s Global Assessment (PGA) were eligible for a 24-week, open-label, multicentre study. Patients (n = 243) received 30 mg of alitretinoin once daily, irrespective of previous treatment in BACH; either alitretinoin 30 mg, alitretinoin 10 mg or placebo. Results. By the end of the follow-on study, the PGA response rate to the subsequent course of alitretinoin 30 mg was 50% and 39% in patients treated previously in BACH with 10 or 30 mg per day, respectively, and 51% in patients who previously received placebo in BACH. Alitretinoin was well tolerated, and no significant late-arising toxicities were seen. Conclusions. For a considerable number of patients with CHE who did not fully respond after an initial 24-week treatment period, a switch from either placebo to the active compound at 30 mg or from the lower to the higher dose, or treatment prolongation at the higher dose could be beneficial. Alitretinoin remains well tolerated for overall treatment durations of up to 48 weeks.

We read with interest the RCT by Reich et al., and we found that the conclusion given: “this study provided no evidence to support further exploration of alitretinoin in the treatment of severe palmoplantar pustulosis (PPP)” should be carefully interpreted.1 The authors found no significant difference in the percentage change in PPPASI between the alitretinoin (45.2% ±32.8 of improvement) and placebo (44.6%, ±45.9), 95% CI rate difference -31% to 32%.1 This article is protected by copyright. All rights reserved.

Summary Background. Previous studies have shown that concomitant administration of food may enhance the bioavailability of oral retinoids. Aim. To assess the influence of food on the pharmacokinetics (PK) of alitretinoin after a single oral dose. Methods. This was a single-dose, open-label, randomized, crossover study, which enrolled 30 healthy men, aged 18–44 years. Subjects received sequential doses of alitretinoin 40 mg either after fasting (treatment A) or 5 min after completion of a standard breakfast (treatment B), with the dosing sequence randomized (A/B or B/A). The washout period between the two doses was 1 week. Plasma concentrations over time were plotted and standard PK variables [area under the curve (AUC) of plasma concentration vs. time, maximum plasma concentration (Cmax), time to maximum plasma concentration (tmax) and elimination half-life (t1/2)] were determined. Results. Drug exposure was markedly increased when alitretinoin was taken with food compared with fasting, and there were significant increases in mean Cmax (82.8 vs.25.4 ng/mL, respectively) and AUC (220.2 vs. 55.7 ng·h/mL). The delaying effect of food on tmax was less marked (median of 3.0 vs. 2.0 h). Administration with food also increased exposure to drug metabolites. Variability in exposure was markedly reduced if alitretinoin was taken with vs. without food (percentage coefficient of variation 40% vs. 74% for AUC; 49% vs. 85% for Cmax). Alitretinoin was generally well tolerated, with typical retinoid adverse reactions, mostly comprising headache. Conclusions. Intake of alitretinoin with food substantially increased the bioavailability of alitretinoin, but variability in exposure was reduced. Consequently, oral alitretinoin should be taken with food as outlined in the manufacturer’s summary of product characteristics.

P>Background. Recent studies have found that alitretinoin can induce clinically significant responses in subjects with severe chronic hand eczema (CHE) unresponsive to topical corticosteroids. Aims. To assess the pharmacokinetics (PK), efficacy and safety of alitretinoin 10 or 30 mg once daily. Methods. This was a randomized, double-blind study, which enrolled 32 subjects aged 18-75 years with CHE unresponsive to potent topical corticosteroids. Subjects received alitretinoin 10 mg (n = 16) or 30 mg (n = 16) once daily for 12 or 24 weeks. Standard PK variables [area under the curve (AUC) of plasma concentration vs. time, maximum plasma concentration (C-max), time to maximum plasma concentration (t(max)), elimination half-life (t(1/2)), total systemic clearance (CL/F) and volume of distribution (Vd/F)] were determined for alitretinoin and metabolites. Efficacy was assessed using the Physician's Global Assessment (PGA) scale. Results. Chronic administration of alitretinoin for up to 24 weeks did not result in accumulation or time-dependent changes in the disposition of alitretinoin. Exposure was found to be proportional to dose. Systemic exposure (AUC) to alitretinoin was proportional to dose for 10 and 30 mg alitretinoin; 62.8% of subjects achieved clear/almost clear hands in the 30 mg group and 12.5% in the 10 mg group. Alitretinoin was well tolerated. Conclusions. Chronic administration of alitretinoin for 12-24 weeks did not lead to accumulation or time-dependent changes in drug exposure. Alitretinoin was effective and well tolerated in the treatment of subjects with moderate or severe CHE unresponsive to potent topical corticosteroids.

Summary Background. Based on in vitro data with isolated cytochrome P450 (CYP) isoenzymes, alitretinoin interacts only with CYP3A4, and the potential for drug–drug interactions is considered negligible. Aim. To confirm in humans the lack of potential interactions between CYP3A4 and alitretinoin in vivo. Methods. This was a multiple-dose, open-label, parallel-group, single-centre study, which enrolled 54 healthy male volunteers aged 18–45 years. Subjects were divided into three groups, with 18 in each group: group 1 received either alitretinoin 30 mg and ketoconazole 200 mg, group 2 alitretinoin 30 mg and simvastatin 40 mg, and group 3 alitretinoin 30 mg and ciclosporin A 300-mg. Results. At the highest therapeutic dose of 30 mg, alitretinoin had no significant effect on the pharmacokinetics (PK) of ketoconazole and ciclosporin A. There was a significant but not clinically relevant effect of simvastatin on the area under the curve (AUC) of plasma concentration vs. time and on maximum plasma concentration (Cmax) after repeated administration of alitretinoin. Exposure to simvastatin concomitantly with alitretinoin was decreased by 16% for AUC and 23% for Cmax. The CYP3A4 ± PgP substrates of simvastatin and ciclosporin A did not affect the single or repeated dose PK of alitretinoin. The strong CYP3A4/PgP inhibitor ketoconazole led to significant increases in both AUC and Cmax values for alitretinoin. Conclusions. Single and repeated doses of alitretinoin do not alter the PK of ciclosporin A and ketoconazole. Simvastatin levels were slightly but significantly reduced by co-administration of alitretinoin. Substrates of CYP3A4 did not affect the PK of alitretinoin. However, ketoconazole significantly increased the plasma levels of alitretinoin, therefore, co-administration with CYP3A4 inhibitors such as ketoconazole may require a dose reduction of alitretinoin.

Summary Background. Alitretinoin, like all retinoids, is teratogenic, and can only be given to women of childbearing potential if pregnancy is excluded and a strict contraceptive programme is followed. Aim. This study was designed to determine whether alitretinoin in the semen of men treated with alitretinoin poses a teratogenic risk to their female partners. Methods. In total, 24 healthy men aged 18–45 years received alitretinoin 20 mg (n = 12) or 40 mg (n = 12), once daily for 14 days. Subjects in the 40 mg dose group provided ejaculate at baseline, on day 1, before and approximately 4 h after dosing on day 2, and at follow-up on study day 21 (± 2). Results. Alitretinoin and 4-oxo-alitretinoin were detected in 11 of the 12 semen samples. The highest level of alitretinoin in semen was 7.92 ng/mL. Assuming an ejaculate volume of 10 mL, the amount of drug transferred in semen would be about 80 ng, 1/375 000 of a single 30 mg capsule. Complete absorption of 80 ng of alitretinoin from semen, presuming a volume of distribution confined to 5 L of circulating blood in the partner, would lead to an increase in plasma alitretinoin concentration of 0.016 ng/mL, which appears to be negligible compared with measured endogenous plasma levels. Increases in plasma levels of related retinoids are also negligible. Conclusions. Alitretinoin in the semen of men receiving up to 40 mg of oral alitretinoin per day is unlikely to be associated with teratogenic risk in their female partners. Barrier contraception is therefore not required for men taking alitretinoin.

BACKGROUND: Alitretinoin (9-cis retinoic acid) is currently registered in many European countries and in Canada as the only licensed treatment for severe chronic hand eczema unresponsive to potent topical corticosteroids. Alitretinoin like all retinoids is teratogenic and women of child-bearing potential must strictly adhere to pregnancy-prevention measures. AIM: To investigate the influence of alitretinoin on the pharmacokinetics (PK) of ethinyl estradiol/norgestimate (Ortho Tri-Cyclen 28((R))) a commonly prescribed combination oral contraceptive. METHODS: In total 16 healthy premenopausal women received three consecutive cycles of the triphasic contraceptive ethinyl estradiol/norgestimate together with concomitant oral alitretinoin 40 mg once daily during cycle 2. Steady-state PK (noncompartmental analysis) of ethinyl estradiol 17-deacetyl norgestimate alitretinoin and its main metabolite 4-oxo-alitretinoin were assessed alone and in combination. RESULTS: The PK profiles of ethinyl estradiol and 17-deacetyl norgestimate were similar when contraceptives were given alone or with alitretinoin and the area under the plasma concentration vs. time curve and the maximum concentration met the conventional criteria for PK equivalence. Similarly the influence of ethinyl estradiol/norgestimate on systemic exposure to alitretinoin and 4-oxo-alitretinoin was not clinically relevant. Alitretinoin was well tolerated when given either alone or with ethinyl estradiol/norgestimate. CONCLUSIONS: There was no clinically relevant influence of alitretinoin on the PK of ethinyl estradiol/norgestimate and no influence of ethinyl estradiol/norgestimate on systemic exposure to alitretinoin and 4-oxo-alitretinoin. Consequently oral contraception with ethinyl estradiol/norgestimate is an appropriate primary method of birth control during alitretinoin treatment for women of childbearing potential. (c) 2011 The Author(s). Clinical and Experimental Dermatology (c) 2011 British Association of Dermatologists.

Summary Background Patients with severe chronic hand eczema (CHE) often respond to therapy with oral alitretinoin (9-cis retinoic acid). However, the efficacy of alitretinoin after disease relapse has not been demonstrated. Objectives To assess the efficacy and safety of a second course of oral alitretinoin in patients with severe CHE who relapsed after achieving ‘clear’ or ‘almost clear’ hands following a previous course of alitretinoin. Methods The double-blind study included 117 patients with CHE who had responded to therapy in an earlier clinical trial and subsequently relapsed. Patients were randomized to receive their previous treatment or placebo. Treatment was alitretinoin 30 mg or 10 mg or placebo given once daily for 12–24 weeks. Response was defined as an overall Physician’s Global Assessment rating of ‘clear’ or ‘almost clear’ hands at the end of therapy. Results Response rates were 80% in patients retreated with 30 mg alitretinoin compared with 8% for placebo (P

The management of chronic hand eczema is often inadequate. There are currently no evidence-based guidelines specifically for the management of chronic hand eczema, and evidence for established treatments for hand eczema is not of sufficient quality to guide clinical practice. This consensus statement, based on a review of published data and clinical practice in both primary and secondary care, is intended to guide the management of chronic hand eczema. It describes the epidemiology and pathogenesis of hand eczema, its diagnosis and its effect on patients' quality of life. Management strategies include a skin education programme, lifestyle changes, and the use of emollients, barriers and soap substitutes. Topical drug therapy includes topical steroids and calcineurin inhibitors. Treatment with psoralen ultraviolet A and systemic therapies may then be appropriate, although there is no strong evidence of efficacy. Alitretinoin has been shown to be effective in a randomized controlled trial, and is currently the only treatment specifically licensed for the treatment of hand eczema. Recommendations for management are summarized in a treatment algorithm.

Summary Background. The pathogenesis of scleroderma (SSc) is not fully understood, and there is no effective treatment for this chronic disease. Retinoic acid (RA) can modulate connective tissue metabolism, exhibit antifibrotic activity and improve the clinical symptoms of patients with SSc. However, the mechanisms by which RA elicits its antifibrotic actions remain to be determined. Objective. To elucidate the underlying mechanisms by which retinoids exert beneficial effects on SSc. Methods. Cultured skin fibroblasts from patients with SSc were treated with retinoids (9-cis-, 13-cis- and all-trans-retinoic acid) and their effect on the expression of cyclooxygenase (COX)-2, connective tissue growth factor (CTGF) and type I and III collagen and on the production of PGE2 was examined. COX-2 expression was analysed by western immunoblotting, PGE2 production by enzyme immunoassay and CTGF expression, and type I and III collagen expression by reverse transcriptase PCR and western immunoblotting. Results. In cultured SSc fibroblasts, 9-cis-RA significantly increased COX-2 protein expression and PGE2 production and inhibited the expression of CTGF and type I and III collagen. We further found that expression of CTGF and of type I and III collagen mRNA was inhibited by exogenous PGE2 in SSc fibroblasts. Conclusion. In vitro, 9-cis-RA induced COX-2 expression and PGE2 production in SSc fibroblasts and PGE2 downregulated CTGF expression, leading to the inhibition of type I and III collagen synthesis. Our results indicate that the clinical effects of 9-cis-RA on SSc are, at least in part, attributable to the induction of PGE2 and the subsequent suppression of CTGF expression that results in the blockade of collagenogenesis.

Darier disease (DD) is an autosomal dominant skin disease. Treatment is often difficult and unsatisfactory because of the chronic nature of the condition and the irritant potential of various therapeutic agents. Systemic vitamin A derivatives such as acitretin and isotretinoin are the treatment of choice, but their use is often limited by class-specific side-effects. Alitretinoin (9-cis-retinoic acid), has antiproliferative and anti-inflammatory potential, and is licensed for the systemic treatment of chronic hand eczema in a number of countries. Unlike acitretin, alitrenoin requires contraception in women of childbearing age to be extended for only 1 month after the end of treatment. There is evidence that alitretinoin might be a well-tolerated alternative for the systemic treatment of various retinoid-responsive skin diseases. We present two cases of women with refractory DD successfully treated with alitretinoin without marked side-effects, who both obtained near-complete remission of their skin lesions.

The vitamin A metabolite, retinoic acid (RA), affects Th1 and Th2 development. The effect is partly exerted through the modulation of antigen-presenting cell functions, but it remains unclear whether RA directly exerts its effect on T cells to influence Th1/Th2 development. To clarify this problem, we used two experimental systems with isolated T cells in vitro. In one system, isolated CD4+CD8+ thymocytes differentiated into Th1 and Th2 by two transient stimulations with defined combinations of ionomycin and phorbol myristate acetate followed by treatment with IL-2 and IL-4 and/or IL-12. In the second system, functional differentiation was induced in purified naive CD4 T cells from DO-11.10 TCR-transgenic and RAG-2-deficient mice with cytokines and antibodies to CD3 and CD28. In both systems, all-trans-RA ator = 1 nM concentrations suppressed Th1 development, but enhanced Th2 development. 9-cis-RA elicited similar effects. The optimal enhancement of Th2 development in the second system, however, was achieved with a delayed addition of RA. The presence of RA during the initial stimulation period often suppressed Th2 development. The RA receptor (RAR) antagonists, LE540 and LE135, but not the retinoic X receptor (RXR) antagonist, PA452, inhibited the effect of RA on Th1/Th2 development. Accordingly, the RAR agonists, Am80 and Tp80, but not the RXR agonists, HX600 and TZ335, mimicked the effect of RA. The RXR agonists enhanced the effect of the RAR agonists only slightly, if at all. These results indicate that, via RAR, RA directly suppresses Th1 development and directly enhances Th2 development with its timely addition.

Background Loss of retinoic acid receptor beta (RAR-beta) expression in the bronchial epithelium is considered a biomarker of preneoplasia. Retinoids can restore expression of this receptor and, presumably, halt the progression of carcinogenesis. This study was designed to investigate whether either of two retinoid-based regimens, 9-cis-retinoic acid (RA) or 13-cis-RA plus alpha-tocopherol (AT), could reverse RAR-beta expression loss in former smokers after 3 months of treatment. Methods Individuals (n = 226) who had smoked at least 20 pack-years and had ceased smoking for at least 12 months were randomly assigned to receive 3 months of daily oral 9-cis-RA (100 mg), 13-cis-RA (1 mg/kg) + AT (1200 IU), or placebo. Bronchoscopy and biopsy at six predetermined sites of the bronchial tree were performed before treatment and at 3 and 6 months thereafter. Specimens were evaluated for squamous metaplasia, dysplasia, and RAR-beta expression. McNemar's test was used to test changes in RAR-beta expression and squamous metaplasia within each treatment group, and a generalized estimating equations model was applied to model the treatment effect, adjusting for covariates. All statistical tests were two-sided. Results A total of 177 assessable subjects completed at least 3 months of therapy and underwent at least the baseline and 3-month bronchoscopic evaluations with biopsies. RAR-beta was detected in 69.7% of all baseline biopsy samples, and metaplasia was evident in 6.9% of all baseline samples from 240 subjects. Restoration of RAR-beta expression (P =.03) and reduction of metaplasia (P =.01) were found in the 9-cis-RA group. After adjustment for years of smoking, packs/day smoked, and metaplasia, treatment with 9-cis-RA, but not with 13-cis-RA + AT, led to a statistically significant increase in RAR-beta expression compared with placebo (P =.03). Conclusion 9-cis-RA treatment can restore RAR-beta expression in the bronchial epithelium of former smokers, raising the possibility that this retinoid has potential chemopreventive properties in former smokers.

Thyroid-stimulating hormone, TSH, of the anterior pituitary gland is regulated by the binding of the thyroid hormone-activated thyroid receptor to the TSH gene at the same time as the binding of the 9-cis-retinoic acid-activated retinoid X receptor to the same gene. Both interactions, separately or simultaneously, can suppress and thus regulate the expression of the TSH gene.

Background: 9-cis-Retinoic acid (9-cis-RA) and N-(4hydroxyphenyl)retinamide (4-HPR) are effective chemopreventive agents against epithelial tumors in the oral cavity, breast, and prostate. We tested the inhibitory activity of these retinoids against N-nitrosomethylbenzylamine (NMBA)-induced tumorigenesis in the rat esophagus. Methods: Male Fischer 344 rats were randomly assigned to receive diets either lacking or containing 9-cis-RA or 4-HPR for 1 week before tumor initiation with NMBA and then for the duration of the study. NMBA metabolism, O 6 methylguanine adduct formation, and cytochrome P450 messenger RNA (mRNA) expression in the esophagi of the rats were studied to investigate the mechanisms by which dietary 4-HPR affects tumorigenesis. All statistical tests were two-sided. Results: Dietary 4-HPR resulted in a dosedependent and statistically significant enhancement (P

Investigation of mast cell responsiveness toward retinoic acid (RA) revealed selective promotion of ICAM-3 expression in the human mast cell line HMC-1. This process was dose- and time-dependent and detectable by flow cytometry, Western blot analysis, ELISA, and Northern blot analysis. ICAM-3 modulation was found to be cell-type dependent, detectable also for HL-60 cells and monocytes but not U-937 and only weakly for KU812 cells. Terminally differentiated skin mast cells also failed to up-modulate their ICAM-3, suggesting the requirement for some degree of immaturity for the process. RA-mediated effects on ICAM-1 expression, studied in parallel, were clearly distinct from those on ICAM-3. Investigation of retinoid receptor expression, known to mediate intracellular RA signaling, revealed presence of RARα, RARγ, RXRβ, and RXRγ transcripts in all cell lines studied, and HMC-1 cells were the only line lacking RXRα. RARβ, not expressed at baseline, was induced by RA in a fashion obviously correlating with ICAM-3 up-regulation. Increased ICAM-3 expression was of functional significance, such that processes stimulated or co-stimulated via ICAM-3 (homotypic aggregation, IL-8 secretion) were clearly enhanced upon RA pretreatment, suggesting that RA may contribute via hitherto unrecognized pathways to immune function and host defense.

The vitamin A metabolite, 9-cis-retinoic acid, may be the effector molecule that controls which genes respond to the 1,25-dihydroxyvitamin D3 receptor.

Genomic actions of the hormone 1alpha,25-dihydroxy-vitamin D3(VD) are mediated by the transcription factor VDR, which is a member of the nuclear receptor superfamily. VDR acts in most cases as a heterodimeric complex with the retinoid X receptor (RXR) from specific DNA sequences in the promoter of VD target genes called VD response elements (VDREs). This study describes a mutation (K45A) of the VDR DNA binding domain that enhances the affinity and ligand responsiveness of VDR-RXR heterodimers on some VDREs. In analogy to a homologous mutation in the glucocorticoid receptor (K461A), this lysine residue appears to function as an allosteric 'lock'. Interestingly, overexpression of RXR was found to reduce the responsiveness and sensitivity of wild type VDR to VD, but enhance the response of VDRK45A. Moreover, the transactivation domains of both VDR and RXR were shown to be essential for obtaining responsiveness of the heterodimers to VD and 9- cis retinoic acid (the RXR ligand). This indicates that RXR is an active rather than silent partner of the VDR on the VDREs tested. Taken together, transactivation by VDR-RXR heterodimers can be triggered individually by all components of the protein-DNA complex, but full potency appears to be reached through allosteric interaction.

Summary Chronic hand eczema (CHE) is a debilitating and distressing disease for patients, the physical symptoms of which are compounded by psychosocial problems. Alitretinoin is an endogenously occurring physiological vitamin A derivative (retinoid) that possesses strong anti-inflammatory and immunomodulatory activity. It is currently the only licensed product for severe CHE unresponsive to treatment with potent topical corticosteroids, and has been proven to be highly effective in clinical trials with two-thirds of patients who responded to treatment remaining in remission at 6 months. For those that did relapse, a second study showed they could be successfully retreated with a further 3–6 month course of alitretinoin. Seven case studies of alitretinoin have been provided by consultant dermatologists showing its use in normal UK clinical practice. The cases chosen demonstrate the efficacy of alitretinoin across several different subtypes of CHE, and the positive effects the treatment brought to patients’ quality of life.