Evolution of and risk factors for psychological distress in patients with psoriasis: the PSYCHAE study.

Psychological distress (PD) is common in patients with psoriasis but little is known about its evolution. The aim of this study is to assess the evolution of PD in psoriasis. For this purpose, 1,505 psoriatic patients, who had been previously enrolled in the PSYCHAE study, an observational multicenter Italian study, were re-evaluated after 6 and 12 months. Minor and major PD were assessed using the General Health Questionnaire (GHQ) and Brief Symptoms Inventory (BSI) questionnaires and coping using Brief COPE questionnaire. Minor PD was present in 46 percent of patients but halved during the study. Female gender, surface area, topical steroids, methotrexate, self-distraction, venting and behavioral disengagement were risk factors for minor PD; cyclosporine and humor were protective. Major PD was present in 11 percent of patients and remained stable. Female gender, venting, religion, behavioral disengagement and emotional support were risk factors for major PD; instrumental support was protective. In conclusion, the results obtained suggest that major PD remained stable after 12 months and that coping was a predictor of its evolution.

Pseudoxanthoma elasticum: Point mutations in the ABCC6 gene and a large deletion including also ABCC1 and MYH11.

Pseudoxanthoma elasticum (PXE) is a mendelian disorder characterized by calcification of elastic fibers in skin, arteries, and retina. It results in dermal lesions, arterial insufficiency and retinal hemorrhages, leading to macular degeneration. PXE is transmitted either as an autosomal dominant or recessive trait and several sporadic cases have been observed. Mutations in the ABCC6 gene have been identified very recently in patients. Here, we report on a large Italian family affected by pseudoxanthoma elasticum for which linkage analysis had pointed to a region encompassing markers D16S3069-D16S405-D16S3103; hemizygosity of marker D16S405 allowed us to detect a submicroscopic deletion of at least 900 kb involving ABCC6, ABCC1, and MYH11. Mutation analysis on the other allele of the family, as well as on two additional sporadic cases, revealed nonsense (Y227X, R518X, R1164X) and frame-shift (c.960delC) mutations in ABCC6 (MRP6) further confirming the role of this multi-drug resistance gene in the etiology of pseudoxanthoma elasticum. Furthermore, clinical re-examination of members of the family harboring the deletion led to the detection of additional features, potentially caused by the deletion of the MYH11 gene. In the course of the analysis five nonpathogenic variants were found in ABCC6: 1233T>C, 1245G>A, 1838 T>G (V614A), 1890C>G, and 3506+83C>A. Hum Mutat 18:85, 2001.

A new model for studying differentiation and growth of epidermal cultures on hyaluronan-based carrier.

Here, a three-dimensional model based on fragments of human de-epidermized dermis (DED) is prepared in order to study the performance of a microperforated, hyaluronan-based membrane as a carrier of cultured epidermal cells. Hyaluronic acid is, in fact, considered to be an optimal biomaterial allowing proliferation of both keratinocytes and melanocytes, and it is already used for clinical aims. The carrier with subconfluent human epidermal cultures is positioned onto the DED and kept in culture until a new epidermis is formed. This model system allowed to study the migration and growth of human epidermal cells from the carrier, resembling 'in vivo' re-epithelization.

Digital dermoscopy analysis for the differentiation of atypical nevi and early melanoma: a new quantitative semiology.

OBJECTIVES: To use a digital dermoscopy analyzer with a series of "borderline" pigmentary skin lesions (ie, clinically atypical nevi and early melanoma) to find correlation between the studied variables and to determine their discriminating power with respect to histological diagnosis. DESIGN: A total of 147 pigmentary skin lesions were histologically examined by 3 experienced dermatopathologists and identified as nevi (n = 90) and melanomas (n = 57). The system evaluated 36 variables to be studied as possible discriminant variables, grouped into 4 categories: geometries, colors, textures, and islands of color. SETTING: University medical department. PATIENTS: A sample of patients with excised pigmentary skin lesions (nevi and melanomas). MAIN OUTCOME MEASURES: Sensitivity, specificity, and accuracy of the model for evaluating "borderline" pigmentary skin lesions. RESULTS: After multivariate stepwise discriminant analysis, only 13 variables were selected to compute the canonical discriminant function. CONCLUSION: The present method made it possible to determine which objective variables are important for distinguishing atypical benign pigmentary skin lesions and early melanoma.

Quantitative characterization and study of the relationship between constitutive-facultative skin color and phototype in Caucasians.

In this study constitutive and facultative colorimetric values were quantified to determine the physiologic changes in Caucasian skin color and to define the correlation between skin color and phototype assessed according to the Fitzpatrick method. Our population consisted of 401 subjects ranging in age from 24 to 28 years with similar life styles. Skin color was measured with a Minolta CR-200 colorimeter on the upper medial quarter of the buttock (constitutive color) and on the cheek (facultative color). Advanced multivariate statistical analysis allowed differentiation between constitutive and facultative skin color in relation to the phototype to be quantified. Moreover, Kullback divergence showed that the probability of correctly determining a subject's phototype is high when the variables of constitutive and facultative skin color are considered together. This interesting result makes it possible, in the future, to use colorimetric values of exposed and nonexposed skin, together with determination of Fitzpatrick phototype and of other phenotypic characters, to better predict cutaneous sun reactivity.

Relationship between skin color and sun exposure history: a statistical classification approach.

In this study our aim was to determine the biophysical values of constitutive skin color in Caucasians and to define the correlation between skin color and phototype assessed according to the Fitzpatrick method. Constitutive skin color was measured on the buttock, with a Minolta CR-200 colorimeter, in a population-of 557 consecutive subjects belonging to phototype categories I, II, III and IV. The colorimeter expresses the results in five different color systems. We used the "Yxy" and L*a*b* systems, which are the most widespread in dermatology. Statistical analysis of the data showed that the "Yxy" system is even more discriminant than the L*a*b* system when the Fitzpatrick classification scheme is adopted as the reference and shows a poor ability to correctly classify the intermediate phototypes (II and III). On the contrary the "Yxy" system performs well in distinguishing phototypes I and IV. To establish whether this low discriminating capacity for phototypes II and III is related to a low discriminating capacity of the method suggested by Fitzpatrick or by our procedure, an objective technique (minimal erythemal dose) should be used to evaluate the percentage errors of classification of both the Fitzpatrick method and instrumental measurement of skin color. The results of such a study are extremely important because the evaluation of skin color is objective, simple and has potential applications in dermatology and cosmetology.

Instrumental measurement of skin colour and skin type as risk factors for melanoma: a statistical classification procedure.

A statistical procedure to evaluate melanoma risk in Caucasian subjects on the basis of colorimetric measurement of skin colour and Fitzpatrick phototype is described. One hundred and sixty melanoma patients and 546 randomized healthy subjects of similar age, sex and place of origin were examined in the same period for skin colour using a tristimulus colorimeter and for Fitzpatrick phototype. A clinical score for classification purposes was obtained by statistical discriminant analysis with multivariate data transformation and dimension reduction techniques. A Fisher linear classifier was chosen for its simplicity and robustness in correctly predicting melanoma risk in new subjects. The classification rule was designed to avoid classifying subjects at high risk for melanoma as low risk, i.e. to give a negligible number of false negatives at the expense of more false positives. The procedure is objective and readily adapted to different clinical requirements. This is only a preliminary study but it is hoped that by performing more complex statistical analyses, e.g. neural networks, and adding other parameters (proven risk factors such as number of naevi) the performance will be further improved.

Differentiation between pigmented Spitz naevus and melanoma by digital dermoscopy and stepwise logistic discriminant analysis.

Epiluminescence light microscopy (ELM) has proven useful in the diagnosis of pigmented skin lesions (PSLs). However, in some cases this technique does not sufficiently increase the diagnostic accuracy in distinguishing pigmented Spitz naevi (PSNs) from melanoma. With the aim of obviating these problems of qualitative interpretation, methods based on the mathematical analysis of PSLs, such as digital dermoscopy analysis (DDA), have recently been developed. In the present study we used a digital dermoscope (DBDermo-MIPS, Dell'Eva-Burroni) to analyse PSNs and melanomas with similar clinical and dermoscopic features for any correlation between variables and to determine its discriminating power with respect to histological diagnosis. The 100 lesions underwent histological examination by three experienced dermatopathologists and were identified as PSNs (43) or melanomas (57). Thirty-six parameters were identified as possible discriminating variables and were grouped in four categories: geometry, colour, texture, and islands of colour. Statistical analysis was used to identify the variables with the highest discriminating power. Stepwise discriminant analysis selected only four variables: entropy, minimum diameter, red lesion value and peripheral dark (the means of these variables were higher in melanomas than in PSNs). Thus the combined use of digital dermoscopy and stepwise logistic discriminant analysis made it possible to single out the best objective variables for distinguishing PSN and melanoma.

Vulvar squamous papillomatosis and human papillomavirus infection. A polymerase chain reaction study.

Squamous papillae of the vulvar vestibule and introitus are quite a common clinical finding, however their origin is uncertain. They were formerly described as a normal variant of the mucosal epithelium, but recently they have been attributed to human papillomavirus (HPV) infection. Eight women with clinical findings compatible with a diagnosis of vulvar squamous papillomatosis were studied. All were free of other clinically evident HPV-related diseases. Vulvar scrapes and biopsy specimens were collected and used for DNA extraction and microscopic examination. DNA extracted from vulvar scrapings and from paraffin-embedded tissue was subjected to polymerase chain reaction (PCR). The reactions were performed with two sets of primers designed for the amplification of numerous HPV genotypes including those most commonly encountered in the genital area. Histological examination failed to reveal clear-cut signs of HPV infection in any subject. The PCR on the DNA extracted from vulvar scrapings revealed HPV infection in two cases. PCR performed on the DNA extracted from the paraffin-embedded tissue failed to detect HPV-DNA in any case. A 6-month follow-up showed no changes in the lesions. These results along with literature data, which is clearly inconsistent, indicated that the presence of HPV is coincident to, rather than causal of, vulvar squamous papillomatosis lesions. Patients with symmetrically distributed, long-standing vulvar papillae should, therefore, be carefully evaluated before starting therapy.

Pemphigus antibodies fixation and keratinocyte differentiation in organ cultures. Effects of some agents influencing the intracellular content of cyclic AMP.

The effect of some agents, influencing the cyclic adenosine 3', 5'-monophosphate (cAMP) content of human cells, on the ability of the keratinocytes of binding pemphigus antibodies was studied by using tissue cultures of rabbit esophagus. As demonstrated by immunofluorescence (IF) for IgG, the bound antibodies appeared markedly decreased on esophagus explants grown under standard conditions, that is without test agents, when compared to ones fixed on fresh esophagus. But the IF reaction was remarkably more intense when methylxanthines or epinephrine were added to the growth medium of the cultures. Following the addition of these agents to the cultures some histologic modifications appeared in the explants, indicating that the keratinization process had probably been stimulated. This temporal relationship of immunofluorescence and histologic findings seems to suggest the hypothesis that keratinocyte differentiation, regulation of cAMP intracellular content, and pemphigus antibodies fixation are related processes.

DNA-repair after UV-irradiation in skin fibroblasts from patients with actinic keratosis.

Autoradiographic counting technique was utilized to measure the ultraviolet-induced unscheduled DNA synthesis of skin fibroblasts from 12 patients with chronic actinic keratosis and from 12 healthy donors of about the same age. In order to reveal a possible regional difference of DNA repair between the parts of the body ordinarily exposed and those parts unexposed to sunlight, two cell strains were used for each examined subject; one developed from the forehead skin and the other from the abdominal or axillary skin. Unscheduled DNA synthesis appeared depressed in actinic keratosis patients, as compared with controls. In all examined subjects however cell strains from exposed skin showed a DNA repair more active than cell strains from unexposed skin. These findings show that skin cancer may be promoted in actinic keratosis patients by a defect of DNA repair. The exalted DNA repair of chronically sun exposed skin is probably the consequence of a defensive process caused by enzymatic induction.

Ultrastructural observations in lichen nitidus.

Lichen nitidus (LN) and lichen planus (LP) are considered by some investigators to be two variants of the same disease, and by others to be two distinct dermatoses. In order to obtain further information about the relationship between LN and LP we examined the ultrastructure of lesions from two LN patients. In the central part of the lesion, the basement membrane was absent, or was interrupted by migrating phagocytes or lymphocytes. The basal cells and the lower cells of the stratum spinosum exhibited karyolysis and appeared to be compressed and often necrotic. In the upper dermis irregular cell debris full of clumps of tonofilaments and colloid-body-like structures was observed. A dense dermal infiltrate of macrophages, lymphocytes, fibrocytes, and Sezary-like cells was present. Signs of cooperation between lymphocytes and macrophages were also evident. The periphery of the lesion showed no pathological features except for enlargement of the intercellular spaces and the presence of mononuclear cells scattered through the epidermis. Several normal Langerhans cells were noticed. These ultrastructural findings were quite similar to those reported for LP.

Ultrastructural study of pseudo-Kaposi's sarcoma (Bluefarb-Stewart type).

An ultrastructural study of the skin lesion of a young patient affected by pseudo-Kaposi's sarcoma of the Bluefarb-Stewart type (BSS) is reported. The neoplasm consisted of a proliferation of vascular structures mostly consisting of a solid bud of endothelial cells surrounded by a thinned and polystratified basement membrane and several pericytes. Both endothelial cells and pericytes were of normal ultrastructural appearance. Intervascular "stromal" cells were few and morphologically identified as macrophages and/or phagocytic fibroblasts. Masses of hemosiderin were detected outside the cells and in the macrophages, endothelial cells, and pericytes. Intracytoplasmatic crystalloid inclusions similar to those found in fetal endothelium and hemangiomas were observed in a few endothelial cells. These findings are different from those of previously reported cases of pseudo-Kaposi's sarcoma and may be helpful in distinguishing Kaposi's sarcoma from BSS. The role of immunodeficiency in the onset of BSS is discussed.

Mid-dermal elastolysis: an ultrastructural and biochemical study.

Mid-dermal elastolysis (MDE) is a particular elastic tissue disorder in which selective loss of elastic fibres occurs in the mid-dermis. It is clinically characterized by the appearance of fine wrinkling of the epidermis and perifollicular protrusion which gives the skin an aged appearance. It is sometimes associated with an inflammatory event such as urticaria while other cases are regarded as idiopathic. The pathogenesis of MDE is still obscure. Some authors have underlined the role of macrophage activation and others have imputed UV radiation. We report here a typical case of MDE arising after several attacks of solar urticaria. Electron microscopic and biochemical studies were carried out. Ultrastructural examination showed active elastophagocytosis by macrophages and mast cells, often degranulated, near phagocytosing cells. Biochemical studies demonstrated that fibroblasts derived from lesional skin of the MDE patient produced high levels of elastase and cathepsin G compared with fibroblasts from a healthy sex- and age-matched control. Phagocytosis of morphologically normal elastic tissue is a noticeable characteristic feature of MDE. In our case mast-cell activation and the abnormal synthesis and/or release of fibroblast elastolytic enzymes seemed to play a role in the pathogenesis of the MDE.

Autosomal dominant aplasia cutis congenita: report of a large Italian family and no hint for candidate chromosomal regions.

We studied a three-generation pedigree in which seven individuals were affected by aplasia cutis congenita, a rare disorder characterized by the congenital absence of the epidermis, dermis and subcutaneous tissue of the vertex or occipital region. Accurate clinical and formal genetic analysis suggested that this family was affected by the autosomal dominant form of the disease, a hereditary condition due to mutations of an unknown gene. To define the map position of this locus, we performed linkage analysis on candidate chromosomes (long arm of chromosomes 1 and 12). Negative lod scores were obtained for all markers analysed and linkage with genes located in these chromosomal regions was excluded.

Practical applications of cutaneous colorimetry.

Dermatologists have long tried to quantify skin color and had few results until the advent of tristimulus colorimetry. With the Minolta colorimeter, quantification of skin color has become a simple matter: skin color can be measured rapidly, noninvasively, and reproducibly. The instrument, which can be used by paramedical staff, provides data that lend themselves for comparison, irrespective of where they are collected. The instrument has enabled definition of the range of physiologic values of skin color, and has revealed marked variations between exposed and nonexposed skin. Constitutional skin color characterizes an individual's phenotype better than facultative skin color and is highly indicative of vulnerability to sunlight. It is therefore a parameter for predicting the immediate and delayed response to light stimulation. On the practical level, colorimetric skin color values can be used to study pigmentation capacity, to program photochemotherapy, and to predict the risk of, and prevent, actinic cancer. Colorimetry can be used to quantify the intensity of erythema of spontaneous and experimental lesions. It has been used to monitor the efficacy of anti-inflammatory treatment of psoriasis and atopic dermatitis. It has also been used in the study of reactions induced by physical and allergic stimuli. Finally, colorimetry is useful in cosmetology for choosing appropriate sunscreens, for studying the effect of depigmentation products, and for determining the delicacy of detergents, and in any other situation that requires the measurement of parameters correlated with skin color that cannot be appreciated by visual observation.

Sun and skin. Role of phototype and skin colour.

The study of the biological effects of sun on the skin is one of the most topical questions in the recent dermatological literature. Interest in these effects has grown since it was demonstrated that the sun accelerates intrinsic skin ageing and is a principal factor for skin cancer. Skin damage caused by the sun is mainly due to UV radiation. Skin damage certainly has ancient roots, but has undergone sudden changes since man began to migrate to different geographical areas, for example when northern European populations colonised sunny areas close to equator. It is not a coincidence that the highest incidence of sun induced neoplasias is observed among white population of Australia. This epidemiological finding focused the interest towards the identification of phenotypic factors conditioning skin response to sunlight, and hence towards the definition of the so called phototype. After the fundamental work of Fitzpatrick based on sun exposure history more recent studies have shown that skin response to UV-rays can be predicted, to a good approximation, by skin colorimetry. Therefore this simple, cheap and non invasive measurement enables to predict sun reactivity skin type and to evaluate the melanoma risk.

The behaviour of Sarcoptes scabiei var. hominis in human skin: an ultrastructural study.

The biology of Sarcoptes scabiei var. hominis is poorly understood because of the lack of an in vivo or in vitro propagation system. To obtain more information on the mite behaviour in its natural habitat we conducted an ultrastructural study of burrows in a number of patients with common scabies. Scanning electron microscopy furnished attractive images of the tunnel, parasite body and eggs architecture and demonstrated the presence of holes in the tunnel roof probably representing aeration structures. Transmission electron microscopy showed a marked keratinocyte damage around burrowing mites, well evident ahead of the mite capitulum also. Faecal pellets containing keratinocyte micro-organelles (melanosomes and mitochondria) were documented in posterior midgut. For the first time we disclosed the adhesion mechanism of eggs to the burrow floor. We showed that the typical finger-like projections of the outer layer of the egg shell gradually disappear where the eggs are in contact with the tunnel floor. This allows the inner layer of the egg shell to fuse and stick with the damaged keratinocytes lining the tunnel floor. Our observation substantiates that Sarcoptes scabiei produces a proteolytic substance (salivary secretions?) that has a key role in its life cycle allowing burrowing, feeding and eggs-burrow adhesion.

An evaluation of Hyalofill-F plus compression bandaging in the treatment of chronic venous ulcers.

OBJECTIVE: Hyaluronan, a component of the extracellular matrix, plays a significant role in several aspects of tissue repair and the wound healing process. METHOD: In this Italian study Hyalofill-F, a partial benzyl ester derivative of hyaluronan, used in combination with compression bandaging, was compared with the well-established therapy in Italy of non-adherent gauze plus compression therapy in the treatment of chronic venous leg ulcers. RESULTS: Hyalofill-F plus compression bandaging performed significantly better than non-adherent gauze plus compression bandage in all of the clinically relevant efficacy parameters. Mean reduction in ulcer area in the hyaluronan-derivative group was 8.1 cm2 after eight weeks of treatment, compared with 0.4 cm2 in the comparator group. The resulting difference of 7.7 cm2 between the two groups was statistically significant (p = 0.0019). Furthermore, statistically significant results in favour of the hyaluronan-derivative group were obtained in the following: speed of epithelialisation; leveling of the margins; degree of maceration; pain intensity and frequency. CONCLUSION: Hyalofill-F plus compression bandaging resulted in an earlier and greater decrease in ulcer area compared with non-adherent gauze plus compression bandaging, therapy supporting its use in the treatment of chronic venous ulcers.

Modified Karhunen-Loéve expansion for evaluating skin-colour-associated melanoma risk factors.

An approach based on the modified Karhunen-Loéve expansion (MKLE) of constitutive and facultative skin colour data acquired by colorimeters in melanoma patients and healthy control subjects, was used to identify two colour features defining skin-colour-associated risk of melanoma. None of four common statistical classifiers trained on colour features were sufficiently accurate for allowing skin colour alone to be used for classification purposes, though a Bayesian quadratic classifier matched the transformed data well. This study supersedes the indeterminate character of most common clinical criteria based on qualitative factors and, irrespective of the results of classification, provides objective skin colour information for the prevention of melanoma.