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Summary Background Few studies have evaluated differences between rosacea subtypes in epidemiological associations and clinical features. The natural history of rosacea is unknown and progression between subtypes has been implied but not formally evaluated. Objectives To assess associations between the four rosacea subtypes [erythematotelangiectatic (ETR), papulopustular (PPR), phymatous (PHY) and ocular], including quantitative and qualitative details on primary and secondary features of rosacea. A secondary objective was to evaluate for the potential of progression between subtypes. Methods This cross-sectional study recruited subjects with rosacea from Northern Germany and comprised clinical evaluation by a dermatologist and a survey of demographics and onset of rosacea-associated signs and symptoms. Results A total of 135 subjects with rosacea were enrolled. PHY was more frequently associated with PPR than ETR (P

Manufacturers of consumer products consistently seek to improve marketed products in terms of both safety and efficacy. The desire for continued improvement is seen even in well-established products such as catamenial products which have existed in some form for thousands of years. A recent innovation in the design of menstrual pads is the addition of a surface finish of emollient for the purpose of increasing comfort during wear. The present paper presents different evaluations of such an emollient-treated menstrual pad with a novel absorbent core. These investigations demonstrated product tolerability, defined the optimal formulation and concentration of the emollient-containing finish, and demonstrated successful transfer of the emollient to the relevant skin surface. In addition, enhancement of skin moisturization, associated with exposure to the emollient-treated pad, was demonstrated by several technologies: assessment of skin moisturization by Corneometer®, skin friction testing, and skin capacitance.

Apertured polyethylene films (AF) have been used as a surface for sanitary pads for decades because they are compatible with the skin and keep the pad surface drier. A modified film (AF-plus) with improved fluid handling and a smoother, suppler texture has been developed. We hypothesized that these changes would improve both performance and skin compatibility. However, distinguishing the skin effects of materials that are inherently mild is a challenge.(i) To compare the skin irritation potential of pads with AF-plus modified film relative to the standard AF film and (ii) to assess the potential for the AF-plus film to induce delayed contact hypersensitivity.Pads bearing the AF-plus film were compared to pads with the standard AF film in a behind-the-knee (BTK) test, which assesses the combination of chemical irritation and frictional effects of materials applied to the popliteal fossa under a semi-occlusive bandage. Erythema on the skin surface was scored with the naked eye and subsurface tissue erythema was visualized and scored using cross-polarized illumination. Skin dryness was scored with the naked eye only. One-sided statistical evaluations were performed to test the hypothesis of AF-plus film superiority. The potential of the AF-plus film to induce delayed contact hypersensitivity was assessed by a human repeat insult patch test (HRIPT).Pads with the AF-plus surface were significantly milder to skin in the BTK test, producing lower levels of both surface and subsurface tissue erythema. Moreover, subjects with preexisting erythema on the skin surface at study start developed comparatively less erythema over the course of the study overall with the AF-plus pad compared to the AF pad. No significant difference in skin dryness was observed between product groups. The AF-plus pad showed no evidence of inducing delayed contact hypersensitivity.The AF-plus pad was superior to the AF pad in terms of skin mildness as discerned by objectively scored surface and subsurface tissue erythema. In subjects with preexisting erythema, the AF-plus pad appeared to contribute less to the further development of inflammation under the test conditions. Given the compositional similarities in the two films, the results could point to more limited contribution of the AF-plus film to skin friction, one of the factors simulated by the BTK test protocol.

Background D-Squames®, have gained wide acceptance for assessing skin desquamation. The amount of corneocytes adhering to D-Squames® can be assessed visually by trained observers or by computerized image analysis. Different image analysis algorythms for the evaluation of D-Squames® have been published but have not been compared with each other. It was our aim to develop an image analysis system that does not require an expensive image analysis programming tool but should be optimized for routine tasks of analysing large numbers of samples. A second objective of this study was to compare two published image analysis algorythms and visual grading. Material and Methods The hardware components of the system are a CCD camera connected to a frame grabber card and a light box equipped with fluorescent tubes on two sides that provide a relatively cool, diffuse and even illumination of the sample. The following features were included into the software: generation and identification of bar codes for sample identification; semiautomatic recognition of ROI (region of interest), integration of study design into the analysing process, rapid calculation of desquamation index (DI: integration of the per cent area covered by scales and their thickness distribution) and/or scaling index (SI: distribution of grey values), data storage and export for further analysis. In a first step the system was validated by examining D-Squames covering a wide range of desquamation, by examining different ROI shapes (circle and square), by performing repeat measurements with different positions of the samples and by repeat measurements after re-callibrating the system. In a second step the effect of treatment with different moisturizers was evaluated by the two image analysis parameters DI and SI and compared with hydration measurements (Corneometer®). Results The shape of the ROI showed no influence on the results (variability < 5%). Reproducibility of measurements was satisfactory (COV CDI): 1.7%, COV (SI): 2.6%).There was a good correlation between image analysis results and visual evaluation (means of 3 technicians) (r = 0.986) as well as between the two different image analysis parameters DI and SI (r = 0.971). In the clinical study moisturizer treatment resulted in variable reduction of desquamation that was closely correlated with increase in stratum corneum hydration (r = 0.97). Conclusion Analysing D-Squames® with the image analysis system proved to be reproducible, independent of the shape of ROI, cost effective and fast and easy to operate. It has shown to be a suitable and reliable method for the objective determination of desquamation levels.

Background/aims: As skin roughness and wrinkles are easily perceived by the consumer, quantifying skin surface structures is a vital parameter for cosmetic product development. As more tools are available for measuring three-dimensional (3-D) surface data, instead of two-dimensional (2-D) profile lines, new algorithms are desirable, to take advantage of the information gathered. Methods: The patchwork method tiles topographic data sets virtually and analyzes the change in apparent area as a function of tile scale. The patchwork method and conventional 2-D profilometric analysis were applied to 24 topographic skin data sets. The data sets were derived before and after application of 15% glycerol solution on the skin of eight volunteers. Results: One hour after application, skin roughness decreased by 20.8%, as measured by conventional analysis, and by 23.3%, as measured by the patchwork method. For both methods, the differences were not significant. Conclusions: The patchwork method can be applied to skin data and renders results similar in intensity and direction to conventional 2-D analysis. It is advantageous over conventional 2-D analysis in three ways: it makes use of the full topologic information, it requires no high-pass or low-pass filtering, and it is independent of the anisotropy of the skin.

Introduction Le phenomene de flush dans la rosacee, caracterise par un erytheme transitoire au niveau du visage, s’accompagne generalement d’une sensation de chaleur. Son absence de previsibilite et sa fugacite le rendent difficile a etudier. L’objectif de ce travail est de presenter de nouveaux outils developpes pour etudier le flush dans la rosacee. Materiel et methodes Deux approches ont ete developpees : un modele pharmacologique qui permet de declencher un phenomene de flush de maniere standardisee dans un centre clinique et un logiciel installe sur un smartphone dont le but est de capturer le phenomene de flush et de caracteriser son intensite dans la vie reelle du patient. Concernant le modele flush, le patient est installe sur une chaise en face d’un imageur FLPI (Moor–Laser Speckle Contrast Analysis) permettant de mesurer le flux sanguin sur le visage et d’un appareil photo pour evaluer la rougeur du visage. Le flush est declenche par l’ingestion de 200 mL d’eau chaude puis l’intensite du flush est evaluee pendant 45 min. Le logiciel developpe pour un smartphone est concu pour acquerir des images standardisees du visage (grâce a une mire couleur qui doit etre placee au niveau de la bouche du patient) lors d’un flush journalier et pour enregistrer des informations sur la perception de cette sensation de flush par le patient a l’aide d’un questionnaire. Resultats Le modele flush a ete evalue sur 15 patients ayant une rosacee et 15 volontaires sains ; il a permis de differencier les 2 populations en utilisant le parametre de flux sanguin. L’application developpee sur smartphone permet aux patients de prendre des photos d’eux-memes de maniere repetee grâce a des reperes qu’ils positionnent lors de la premiere acquisition et l’algorithme de recalage colorimetrique utilisant la mire couleur permet de comparer des images prises sous des eclairages differents. Conclusion Ces nouvelles methodes pourraient permettre de mieux evaluer l’efficacite des traitements sur le flush dans la rosacee.

Differences in the skin surface lipid content (SSL) and the dynamic friction coefficient (µ) were investigated with respect to age, sex, and anatomical region in 29 volunteers. The group consisted of (a) 7 young adult females (24.9 ± 1.1 years old, mean ± SD), (b) 7 old females (75.3 ± 2.4 years old), (c) 7 young adult males (28.7 ± 0.5 years old), and (d) 8 old males (73.8 ± 1.9 years old). Measurements were obtained on 11 anatomical regions, namely, the forehead, upper arm, volar and dorsal forearm, postauricular, palm, abdomen, upper and lower back, thigh, and ankle. Skin surface lipid content data were compared with µ measurements to determine the relative contribution of the former to frictional properties of skin, µ and SSL were not statistically different between age groups on all regions except for the ankle, where lipid content was lower in the elderly. Similarly, µ did not vary between sex groups. Skin surface lipid content was statistically lower on the forehead, dorsal forearm and postauricular area in females. Both parameters, however, showed considerable regional variability. A significant linear correlation was established between µ and SSL combining all regions from all volunteers. When µ was plotted against SSL among individual anatomic sites, only the forehead and postauricular area showed significant linear correlations between the two parameters. These data suggest that surface lipid content plays a limited role in frictional properties of skin.

After repeated contact, many surfactants will cause skin irritation and, especially, dryness and scaliness. Earlier in vitro investigations suggested that the irritation potential of anionic surfactants was related to the induction of hydration of isolated stratum corneum membranes. We have now investigated early surfactant-stratum corneum interaction in vivo. Sodium salts of n-alkyl sulfates with variable carbon chain length (n = 8-14) were tested for the promotion of stratum corneum hydration by measurements of skin surface water loss and electrical capacitance measurements in healthy adult human volunteers. The surfactant-induced increase in water uptake was confirmed in vitro by means of isolated stratum corneum samples and surfactant solutions labeled with tritiated water. In a parallel experiment the irritation potential of these compounds was investigated by 24-h patch testing in human volunteers. The irritant responses were quantified non-invasively by erythema (skin color reflectance measurements) and transepidermal water loss measurements. Hydration of stratum corneum exposed for 5 min to surfactant solutions significantly exceeded that of controls (phosphate-buffered saline). It increased with application time and was concentration dependent, saturable with increasing concentration, and rapidly reversible. Baseline hydration was re-established only 10-15 min after treatment termination. Induction of hydration was closely correlated with the irritation potential of the investigated compounds. It initially increased with increasing carbon chain length. The maximum response was obtained for the C12 analogue (sodium lauryl sulfate). With further increases in molecular size induction of stratum corneum hydration subsequently decreased. We have demonstrated that anionic surfactants increase stratum corneum hydration in vivo. The present results suggest that the mechanisms responsible for the hydration are related to the irritation properties of these compounds.

Etretinate and acitretin are given orally to treat psoriasis and various keratinization disorders. Acitretin, the main active metabolite of etretinate, has the pharmacokinetic advantage of being rapidly eliminated, but it shares etretinate's toxicologic profile. Thus a topical delivery of acitretin with no or reduced systemic adverse effects is desirable. To characterize the therapeutic potential of topically delivered acitretin, we quantitatively assessed its percutaneous penetration in healthy human volunteers. Additionally, three skin sampling techniques, the punch biopsy, the shave biopsy, and the suction blister technique, were validated to quantitate acitretin in the skin. The results suggest that topical delivery of acitretin renders skin concentrations which exceed those reported after oral administration of etretinate or acitretin. However, because of possible interlaminate drug contamination, drug localization within a particular skin compartment cannot be determined.

The aromatic synthetic retinoid acid derivative, acitretin, is efficacious in several cutaneous diseases. Its toxicological profile makes a topical form with no or reduced systemic adverse effects desirable. Direct application of a topical acitretin formulation might result in therapeutic skin concentrations at the site of the disease while minimizing systemic exposure. The present studies define the percutaneous absorption characteristics of acitretin from an isopropylmyristate formulation. We investigated, in-vitro, (1) the role of receptor solution variations, (2) the role of skin modifications, (3) the influence of skin from three different species on the absorption of topically applied acitretin and (4) the drug distribution within the skin. Addition of solubilizers (Polyethylenglycol-20 and albumin) to the receptor solutions improved the flux of acitretin through monkey skin, whereas the acitretin concentration in the skin was not affected by the various receptor solutions used. Acitretin flux through tape-stripped monkey skin and dermis was only slightly higher than through intact skin. Acitretin concentration in human skin was significantly higher than in rhesus monkey or guinea-pig skin. Topical application of acitretin can produce dermal concentrations in excess of those achieved by therapeutic oral doses.

The influence of sodium lauryl sulfate-induced irritant contact dermatitis on in vivo percutaneous penetration was investigated for four 14C-labeled compounds with diverse physicochemical properties: hydrocortisone (HC), indomethacin (IM), ibuprofen (IB), and acitretin (AC). Hairless guinea pigs were pretreated for 24 h with either 0.5% sodium lauryl sulfate (SLS) to induce irritant contact dermatitis or with water (controls). Twenty-four hours after pretreatment, 450 microliters saturated solutions of HC, IM, IB, or AC in isopropylmyristate were applied to the pretreated skin for 24 h. Systemic absorption was determined by urinary and fecal excretion of compounds. Drug concentrations in stratum corneum (obtained by tape cellophane stripping after decontamination of the application site) and in epidermis/dermis (punch biopsy) were also investigated. Systemic absorption of topically applied drugs (as evaluated by urinary and fecal excretion) in SLS-irritated skin was significantly increased for HC (factor 2.6) followed by IB (1.9 times) and IM (1.6 times) but not increased for AC. However, drug concentrations in the viable epidermis and dermis were 70% lower in SLS-irritated than normal skin for HC, but not different for IB, IM, and AC. Thus, the influence of the state of the skin (irritant dermatitis versus healthy) on percutaneous penetration was different for diverse drugs. The general assumption that percutaneous penetration and drug tissue concentrations were higher in diseased versus healthy skin was not found to be true in our irritated-skin model.

To investigate differences in response to irritation according to age and site seven young-adult and eight elderly females were exposed to 0.25% sodium lauryl sulphate (SLS) under patch-test occlusion for 24 h. Ten anatomical regions were tested: forehead, upper arm, volar and dorsal forearm, postauricular, palm, abdomen, upper back, thigh, and ankle. The skin responses were evaluated 24 h post-patch removal by visual scoring and by transepidermal water loss measurements (TEWL). Non-treated symmetrical anatomical regions served as controls. SLS induced a mild erythematous reaction on most anatomical regions except the palm and TEWL was significantly increased as compared with controls. The elderly group demonstrated significantly less susceptibility to SLS-induced irritation for most regions of the body as indicated by visual scores and TEWL measurements. In addition, evaluation of the stratum corneum water content following SLS irritation demonstrated lower responses in the old age group for most regions. The thigh had the highest reactivity and the palm the lowest, in both age groups. These data suggest that young adult skin is more sensitive to SLS than old skin and that SLS irritation varies considerably with respect to region. Moreover, objective TEWL measurements seem to be a better indicator of irritant susceptibility, especially in the elderly, than clinical evaluation by visual scoring.

Assessment of the health hazard associated with chemical contamination of the skin is a complex problem of occupational and environmental relevance. A particularly important question is to what extent can the skin permeability of a given compound be predicted from simple experiments. The literature on percutaneous absorption identifies two key observations: (i) the stratum corneum (SC), the skin's outermost layer, is the major barrier to chemical transport, and (ii) there are qualitative correlations between penetrant permeability and various oil/water partition coefficients (PCs). To obtain more quantitative predictions of permeation, we have evaluated SC/water and SC/isopropyl myristate (IPM, a model lipophilic vehicle) PCs of (a) para-substituted phenols of diverse physicochemical properties (4-acetamido-, 4-cyano-, 4-iodo-, and 4-pentyloxyphenol), (b) polychlorinated biphenyls (54%), and (c) 1,1,1,-trichloro-2,2-bis(p-chlorophenyl)ethane. Partition coefficients were determined as a function of the following variables: length of equilibration, initial drug concentration in the vehicle, SC delipidization, and SC source and preparation technique. The data demonstrate that reproducible partitioning can be obtained using the biological tissue of greatest relevance, and that the pattern of behavior observed, for the two different vehicles studied, is compatible with physicochemical expectations. We suggest that the PC values measured may be useful predictors of in vitro and in vivo skin transport and valuable assets, therefore, in the evaluation of risk following dermal exposure.

The chronic effects of the irritant sodium lauryl sulphate (SLS) on stratum corneum (SC) barrier function, determined by transepidermal water loss (TEWL) measurements and on epidermal cell kinetics, estimated by stratum corneum turnover time (SCTT) determination (dansyl chloride staining method), were investigated in 18 healthy female volunteers. SLS (7.5%) was applied without occlusion for 20 min once daily, over a period of 3 weeks (5 days a week) on dansyl chloride-stained skin and on untreated skin. SCTT of untreated skin (19.3 +/- 0.8 days; mean +/- SEM) was not changed by daily treatment with water (control) (19.3 +/- 2.0) but was significantly reduced by SLS (10.9 +/- 0.6; P less than or equal to 0.0001; compared to controls). However, TEWL was increased in SLS-treated sites 1.5-fold after 4 days of treatment (5.3 +/- 0.6 vs. 3.5 +/- 0.3; P less than 0.001). At the end of the second week, TEWL was increased 2.6-fold and after 3 weeks TEWL was 3.3 times higher than in controls 13.0 +/- 1.6 vs. 3.9, P less than or equal to 0.0001). The intensity of SLS-induced irritation as measured by TEWL was significantly correlated with baseline TEWL (r = 0.50; P less than or equal to 0.02) and significantly negatively correlated with SCTT of SLS treated sites (r = -50; P less than or equal to 0.02) but not with SCTT of untreated skin (r = 0.19).

In experimental skin toxicology, as well as in clinical practice, considerable interindividual variation in the susceptibility to irritant dermatitis is noted when irritant doses are low. Cutaneous sensitivity and hypersensitivity are not determined by a single known feature but are multifactorial. Previous atopic dermatitis may predispose to irritant dermatitis. Susceptibility to irritation seems to be influenced by age, race, and genetic background, whereas sex-related differences do not seem to exist. Of biophysical skin baseline features, skin-surface pH was correlated with the severity of experimentally induced irritant dermatitis, but baseline transepidermal water loss, water-holding capacity, stratum corneum turnover time, and sebum content were not.

To optimize a topical formulation for therapeutic effect generally implies that the flux of drug into the skin be maximized. This requirement means that the product of drug concentration in the vehicle (C v) and drug partition coefficient (PC) between stratum corneum (SC) and vehicle be as large as possible. While C v is a formulation variable which can be easily manipulated up to the drug's saturation solubility, PC is a parameter that is difficult to predict a priori. However, there is no question that an ability to evaluate PC would greatly facilitate the efficient screening of drugs and formulations. We have measured the SC/water and SC/isopropylmyristate (a model lipophilic vehicle) PCs of seven drugs: acitretin, progesterone, testosterone, diazepam, estradiol, hydrocortisone, and caffeine. SC/ water PCs were determined as a function of the following variables: (i) initial drug concentration in the vehicle, (ii) length of equilibrium, (iii) SC source and preparation technique, and (iv) SC delipidization. The data obtained were reproducible and physicochemically consistent, and they show that useful partitioning information from both aqueous and nonaqueous vehicles can be obtained with the biological tissue of greatest relevance. The SC/water PCs of the steroids were in reasonable agreement with previous measurements. A facile approach to an integral determinant of formulation optimization is suggested, therefore, by these observations.

Elastosis perforans serpiginosa is a rare disease with variable etiology. We report on a 33-year-old male patient in whom the disease was induced by long-term treatment with the chelating agent D-penicillamine.

Summary A spontaneously immortalized human keratinocyte line, HaCaT, was used as an in vitro model to predict the cutaneous irritation of anionic surfactants. For this purpose, a number of sodium salts of N-alkyl sulphates with hydrocarbon chain lengths varying between C8 and C16 were studied for possible cytotoxic effects. The endpoints used to assess toxicity were uptake of the vital dye neutral red (NR) and cell morphology criteria 24 h after dosing. A linear proportionality between keratinocyte number and NR uptake was established. All tested surfactants had cytotoxic effects as demonstrated by a decreased NR uptake, which showed a clear dose–response relationship. Concentrations resulting in 50% inhibition of NR uptake (IC-50) ranged from 0·15 mmol (sodium lauryl sulphate, C12) to 1·23 mmol (sodium octyl sulphate, C8). The in vitro cytotoxicity data were highly reproducible when the test was repeated after several weeks. The cytotoxicity data from these assays were compared with the irritant responses (as evaluated by measurement of erythema and transepidermal water loss) obtained after 24 h application of the same compounds (300 μ1 of 20 mmol aqueous solution) to the volar forearm of human volunteers. There were significant linear correlations between the IC-50 values and both barrier damage (transepidermal water loss) and erythema (as evaluated by skin colour reflectance measurements). For the test substances, however, the sensitivity of the in vitro system was between 10 and 100 times higher than that observed in human skin in vivo. This quantitative difference can largely be ascribed to the effective permeability barrier of normal human skin in vivo, which protects living keratinocytes from the cytotoxic effects of surfactant molecules. The results indicate that normal human keratinocytes in culture are a promising screening method for predicting the irritation potential of anionic surfactants. Confirmation, however, has still to be obtained by appropriate in vivo testing in human volunteers.

The skin performs numerous functions vital to the maintenance of homeostasis. Faced with a variety of extrinsic factors, such as physical trauma from the sun, wind, temperature changes, microorganisms, and the dynamic movements of the body, as well as the intrinsic aging processes, its integrity is well preserved by a complex interaction of the three layers: epidermis, dermis, and subcutaneous tissue.

Exogenous dermatoses can be of allergic or irritant type or a combination of both. Although irritant dermatitis is at least as common as allergic contact dermatitis, relatively little is known about its pathophysiology. In the present study the age dependence and regional anatomical variability of cutaneous irritation was investigated for the model irritant sodium lauryl sulphate (SLS) in two age groups of human volunteers (25.9± 1.4, mean± SEM, n = 7 and 74.6± 1.9, n = 8).

Differences in the dynamic skin friction coefficients (mu) were investigated with respect to age, sex, and anatomical region. A total of 29 volunteers consisting of seven young females, seven old females, seven young males, and eight old males participated in the study. Measurements were obtained from II anatomical regions, namely, the forehead, upper arm, volar and dorsal forearm, postauricular, palm, abdomen, upper and lower back, thigh, and ankle. The friction data were compared with stratum corneum hydration and transepidermal water loss (TEWL). The dynamic friction coefficient did not vary significantly between age and sex groups but varied considerably among the anatomical regions of the body. The forehead and postauricular had the highest mu (0.34 +/- 0.02) while the abdomen had the lowest (0.12 +/- 0.01); the remaining regions had an average mu value of 0.21 +/- 0.01. Similarly, no sex differences were observed for TEWL and stratum corneum hydration. Capacitance was only significantly lower on the palms of the elderly. Regional differences showed a higher state of hydration on the forehead and postauricular as well as the upper arm, upper and lower back when compared with the volar forearm. TEWL was generally lower in the elderly on all anatomical regions except the postauricular and palm. A significant correlation was established between mu and capacitance for most regions. Between mu and TEWL significant correlation was observed only on the palm and thigh. These findings suggest that frictional properties of skin are dependent on more than water content or non-apparent sweating and the role of sebum secretion is suggested as one possible factor.

Because irritation changes skin physiology in many ways, we evaluated wether certain biophysical aspects of apparently healthy skin related to the vulnerability of skin to the model irritant sodium lauryl sulfate .

This study investigates the effect of cutaneous aging on transepidermal water loss, stratum corneum hydration (capacitance), skin surface pH, and causal sebum content. Because the physiologic condition of skin varies considerably with anatomic region and skin aging might demonstrate regional variability, all factors were studied on 11 anatomic locations in 14 young adult (seven female and seven male subjects; 26.7 +/- 2.8 years [mean +/- SD]) and 15 aged human volunteers (seven female and seven male subjects; 70.5 +/- 13.8 years). Significant anatomic variability was noted for all factors in both age groups. However, no significant differences between the two groups were noted for sebum, capacitance, and pH on most anatomic regions. Transepidermal water loss, however, was significantly lower in the aged population on all anatomic regions tested, except for the postauricular region and the palm. Comparing male and female volunteers, none of the four factors showed significant differences. Of all measured factors, only transepidermal water loss showed significant age-related differences on most anatomic regions studied. The additionally observed differences between the age groups on the ankle for pH and sebum might be related to the stasis frequently observed on the lower limbs in aged individuals.

but possibly both, squamous cell carcinomas occurred during immunosuppression by cyclosporine, which facilitated the development of malignancies in skin previously exposed to UVB, PUVA, and perhaps arsenic compounds. Although it has not been entirely excluded that cyc1osporine's efficacy in treatment of psoriasis is due to an action independent ofimmunosuppression,3 webelieve that our case demonstrates that low-dose cyclosporine therapy alone is immunosuppressive enough to facilitate the development ofmalignancies in predisposed skin. Cyclosporine should therefore be withdrawn after the development of squamous cell carcinoma and should not be given to patients with a history of such a lesion. We suggest that previous treatments, such as arseniccompounds; UVB, and PUVA, with modalities predisposing to the development ofmalignancies may prove to be contraindications to the use of low-dose cyclosporine alone as therapy for psoriasis.