Topical colchicine therapy for actinic keratoses.

BACKGROUND: The beneficial effect of topical colchicine therapy for actinic keratoses has already been described in 1968. OBJECTIVE: To confirm that the application of a 1% colchicine gel is a safe and effective treatment for actinic keratoses. METHODS: Twenty patients were included in a double-blinded protocol. They all had actinic keratoses on the scalp, most of which had been previously treated with 5-fluorouracil or cryotherapy. Ten patients applied twice daily on the forehead a hydrophilic gel (placebo group), while the other 10 where treated with the same gel containing 1% of colchicine (colchicine group). Erythema and efficacy were evaluated at each control on days 7, 30 and 60, with repetitive blood tests to exclude a possible systemic absorption. RESULTS: A complete healing of the solar keratoses was observed in 7 out of the 10 patients treated with 1% colchicine gel; these showed no recurrence after 2 months of follow-up. Burning and itching occurred only in the colchicine group after 2 or 3 days of application, with an inflammatory reaction on the areas where the gel was applied, while pustules and crusts were located specifically on the actinic keratoses. Repeated blood controls showed that there was no systemic absorption. CONCLUSIONS: This double-blind placebo-controlled study confirms the activity of colchicine for the treatment of actinic keratosis. A comparison with other topical treatments in terms of efficacy and practicability is needed.

Incidence of transient acantholytic dermatosis (Grover's disease) in a hospital setting.

BACKGROUND: Grovers's disease may be triggered by bed rest. METHODS: We have prospectively analyzed, over a 30-month period, all cases of transient acantholytic dermatosis (TAD) diagnosed in the context of a dermatological consultation for inpatients of a community hospital. RESULTS: A total of 28 cases of TAD were diagnosed within a total of 3,750 patients examined (0.8%). The mean age of patients with TAD was 66.7 years, and the male-to-female ratio was 1.8. In 83% of cases the length of hospitalization preceding TAD was 66.7 years, and the male-to-female ratio was 1.8. In 83% of cases the length of hospitalization preceding TAD exceeded 2 weeks, and in all cases there was an association with strict bed rest. No association with malignant disease or other specific pathologies was observed. CONCLUSION: Our results suggest that TAD, which is frequent in elderly patients within a hospital setting, is not paraneoplastic and favor the hypothesis of a sweat-related pathogenesis.

Influence of metoclopramide on the pharmacokinetics of 8-methoxypsoralen.

BACKGROUND: Previous studies have shown important inter- and intraindividual variations in bioavailability of 8-methoxypsoralen (8-MOP) under the influence of factors that are not yet known with certainty. However, they seem to be independent of age, sex and concomitant retinoid administration for RePUVA whereas the influence of diet remains controversial. OBJECTIVE: The purpose of this study was to investigate a possible effect of metoclopramide on the bioavailability of 8-MOP since these drugs are frequently combined to prevent nausea, a common side effect of systemic 8-MOP. METHODS: After a standard breakfast and the ingestion of 8-MOP plasma kinetics of 8-MOP were assessed in 6 healthy volunteers at 0, 1, 1.30, 1.45, 2, 2.15, 2.30, 3 and 4 h after drug ingestion. This procedure was repeated 3 weeks later by associating metoclopramide with 8-MOP. Plasma determinations of 8-MOP were performed using high-pressure liquid chromatography. RESULTS: Time and peak value of maximum plasma 8-MOP concentrations (Tmax, Cmax) ranged from 1 to 3 h and from 124 to 540 ng/ml, respectively. Individual values of the area under the curve of time-related 8-MOP concentration were between 284 and 1,158 ng-h/ml. Concomitant intake of 8-MOP with metoclopramide did not significantly influence these 3 pharmacokinetic values. CONCLUSIONS: Our results confirm the important interindividual variability of the pharmacokinetics of 8-MOP. Associating 8-MOP with metoclopramide does not alter the pharmacokinetic values of 8-MOP and should not require any change in PUVA treatment.

Circulating skin-homing T cells in atopic dermatitis. Selective up-regulation of HLA-DR, interleukin-2R, and CD30 and decrease after combined UV-A and UV-B phototherapy.

BACKGROUND: As the cutaneous lymphocyte-associated antigen appears to detect circulating T cells that migrate to the skin in atopic dermatitis but not T cells that migrate to mucosal sites in allergic asthma and rhinitis, we investigated T-cell activation markers and CD30 on the cutaneous lymphocyte-associated antigen-positive circulating T-cell subset in atopic dermatitis to see whether these markers are different from those in normal controls and related to disease activity. DESIGN: Open study. SETTING: University referral center. PATIENTS: Twelve patients with atopic dermatitis and 12 healthy controls. INTERVENTION: Combined UV-A and UV-B treatment for 2 months. MAIN OUTCOMES MEASURES: Percentage of circulating cutaneous lymphocyte-associated antigen-positive T cells that express HLA-DR, interleukin-2 receptor, CD69, CD71, and CD30 (triple-color flow cytometric analysis). Clinical score, Dermatology Life Quality Index, pruritus score, and consumption of topical corticosteroids were determined. RESULTS: Increased relative numbers of cutaneous lymphocyte-associated antigen-positive T cells expressing HLA-DR, interleukin-2 receptor, and CD30 were found in patients with atopic dermatitis before treatment. Treatment with UV-A and UV-B was associated with clinical improvement and a decrease of levels of HLA-DR, interleukin-2 receptor, and CD30 in cutaneous lymphocyte-associated antigen-positive T cells. HLA-DR on cutaneous lymphocyte-associated antigen-positive T cells correlated significantly with the clinical score. CONCLUSION: Expression of HLA-DR and interleukin-2 receptor is a sensitive marker of disease activity in atopic dermatitis. Apart from giving information on disease activity in atopic dermatitis, the availability of skin-seeking T cells in the blood offers the opportunity to obtain further information on T cells that may have effector function in the skin.

Plasma retinoids after topical use of retinaldehyde on human skin.

BACKGROUND: Retinaldehyde (RAL), a natural metabolite of beta-carotene and retinol (ROL), is tolerated by human skin after topical application. PURPOSE: To see if topical application of a large quantity of RAL on human skin is associated with a detectable alteration of constitutive levels of plasma retinoids resulting from metabolism of RAL in the skin. METHODS: Plasma retinoids [ROL, all-trans-retinoic acid (all-trans-RA), RAL, retinyl palmitate/oleate, 13-cis-RA and 4-oxo-13-cis-RA] were analyzed by high-pressure liquid chromatography. Determinations were done in 10 healthy male volunteers kept on a vitamin-A-poor diet before, during and after daily topical application of 7 mg of RAL to 40% of the body surface for 14 days. RESULTS: The introduction of a restricted vitamin A diet before RAL application resulted in a decrease in the plasma levels of ROL, all-trans-RA and retinyl palmitate/oleate. Topical application of RAL did not induce an alteration of the plasma levels of retinoid metabolites. No RAL was detectable in any of the plasma samples. CONCLUSION: The skin metabolism of topically applied RAL does not result in detectable alterations of constitutive levels of plasma retinoids in humans.

Hypohidrotic ectodermal dysplasia with recurrent otitis and sebaceous gland hypertrophy of the face.

An isolated affected 19-year-old male with hypohidrotic ectodermal dysplasia (HED) had rare features of the syndrome such as recurrent otitis and multiple sebaceous gland papules of the face. Sebaceous gland hypertrophy is puzzling in the context of HED.

Topical retinaldehyde on human skin: biologic effects and tolerance.

The present study was designed to explore if *etinaldehyde, a natural metabolite of vitamin A, has any biologic activity and is tolerated by human skin. Biologic activity was shown by the induction of cellular retinoic acid-binding protein type 2 (CRABP 2) mRNA and protein; the rank order for CRABP-2 increase was retinoic acid > retinaldehyde > 9 cis retinoic acid > retinol > beta carotene. In volunteers treated 1-3 months with 0.5, 0.1, and 0.05% retinaldehyde, there was a dose-dependent and significant increase in epidermal thickness, keratin 14 immunoreactivity, and Ki67-positive cells. The area of distribution of involucrin, transglutaminase, and filaggrin immunoreactivity was also increased in a dose-dependent manner, and keratin 4 immunoreactivity was induced in the upper epidermis. In pilot clinical tolerance studies, 229 patients received topical retinaldehyde at different concentrations; the 1% preparation was tolerated by up to 70% of the treated subjects; tolerance of the 0.5% preparation was slightly better, whereas both 0.1 and 0.05% preparations applied on facial skin were well tolerated and allowed prolonged use (up to 3 years) in patients with inflammatory dermatoses. These findings indicate that topical retinaldehyde has biologic activity and is well tolerated on human skin.

High sensitization rate to emulsifiers in patients with chronic leg ulcers.

Emulsifiers are common constituents of most topical preparations. To study the sensitization rate in a population with frequent use of these agents, we selected 47 patients with chronic or recurrent (> 1 year) inflammatory skin disease (leg ulcers, contact dermatitis, atopic dermatitis, psoriasis) for patch testing with the following emulsifiers: Tween 40 (polyoxyethylene sorbitan monopalmitate). Tween 80 (polyoxyethylene sorbitan monooleate), Span 60 (sorbitan monostearate), Span 80 (sorbitan monooelate), Arlacel 83 (sorbitan sesquioleate), Atlas G 2162 (polyoxyethylene oxypropylene stearate), Atlas G 1441 (polyoxyethylene sorbitol lanolin derivative), triethanolamine, Lanette O (cetylstearyl alcohol), Lanette N. 12 patients had at least 1 positive reaction (25.5%) at 3 or 4 days. Among them, 10 had leg ulcers (43.4% of the leg ulcer group), and 2 had contact dermatitis (13.3% of the contact dermatitis group). No positive reaction was observed in the other patients. When the patients were tested with their own topical preparations or wound dressings, 6 of them, all with leg ulcers, had positive reactions. These results show a surprisingly high prevalence of sensitization to emulsifiers in patients with chronic leg ulcers, in contrast to patients with other inflammatory skin diseases.

Treatment of eczema with a mixture of triamcinolone acetonide and retinoic acid: a double-blind study.

Dermo-epidermal atrophy is one of the main side effects of long-term treatment with topical corticosteroids (TC). Retinoic acid (RA) may prevent and even reverse these effects in animals. It has been previously established that topical RA (TRA) does not inhibit corticosteroid-induced vasoconstriction in humans, thus suggesting that RA, combined with TC, does not interfere with its anti-inflammatory property. The next step was to test this association in patients with inflammatory skin disorders. In this symmetrical double-blind study, triamcinolone acetonide (TA) cream 0.1% and a cream containing TA 0.1% plus RA 0.025% (TARA) were compared in 18 subjects with eczema. No statistical difference between both treatments was observed after 1, 2 and 3 weeks, although on the TARA-treated sides the anti-inflammatory responses were slightly less pronounced. Subjective irritation was significantly more frequent in TARA-treated side (3/17, p = 0.05) but did not lead to interruption of the treatment. This indicates that addition of RA 0.025% to a medium-range potency topical steroid does not abrogate the anti-inflammatory property of the latter and that the association can be tolerated by inflamed skin.