Clinical trial of the efficacy and safety of oral etretinate with calcipotriol cream compared with etretinate alone in moderate-severe psoriasis.

BACKGROUND: The aim of this clinical trial was to assess the efficacy and safety of calcipotriol cream associated with oral etretinate compared with etretinate alone in the treatment of moderate-severe psoriasis. METHODS: This controlled multicenter trial, within patients (hemiparts), enrolled 86 in- or out-patients (62 males, 24 females), mean (+/-SD) age 57.1 +/- 14.2 years, with psoriasis vulgaris on both sides of the body, and mean (+/-SE) baseline PASI score (Psoriasis Area and Severity Index) 30.7 +/- 0.9. All patients took oral etretinate 50 mg/day and applied calcipotriol cream (50 microg/g) on one half of their body twice a day. Treatment was continued for 9 weeks, and patients were seen every 3 weeks. RESULTS: At the end of the first 3 weeks the PASI score indicated a significant clinical difference between the two sides of the body (P < 0.001, ANOVA), with a reduction of 50.7% in the score for the calcipotriol-treated half, compared with a 39% reduction for the untreated half. By the 9th week of treatment the PASI score was 81.4% lower on the treated half, and 70.3% on the untreated side (P < 0.001, ANOVA). CONCLUSIONS: These findings suggest that patients with moderate-severe psoriasis might benefit from treatment with etretinate plus calcipotriol, with the aim of achieving a faster response and an overall smaller total dose of etretinate.

Primary cutaneous cryptococcosis in an HIV-negative patient.

We report a case of primary cutaneous cryptococcosis in an HIV-negative patient, who presented with painless, ulcerated lesions involving the right forearm (fingers and elbow), which developed over 45 days. On the basis of the clinical appearance, serological and cultural examinations were performed to confirm the diagnosis; the histological evaluation of a skin biopsy showed an acute inflammatory infiltrate containing several PAS + Cryptococci. Subsequently, the patient was treated with fluconazole (400 mg/day for 10 days, then a maintenance therapy of 200 mg/day); after one month, the cutaneous lesions were remarkably improved, but, although a series of further laboratory and clinical examinations was scheduled, the patient repeatedly refused any other re-evaluation, and he was lost from follow-up.

Effects of site and menstrual cycle on barrier function and stratum corneum water-holding capacity.

BACKGROUND/AIMS: Areas of the skin with similar anatomical structure may have different functional behaviour. In vivo barrier function and stratum corneum water-holding capacity during the menstrual cycle on two sites of the volar forearm (upper and lower) and on the anterior aspect of the thigh were evaluated using the plastic occlusion stress test (POST). METHODS: 13 healthy women (age 31 ± 4) with regular menses entered the study. POST was performed by applying a plastic chamber (1.8 cm diameter) on the skin for 24 h. After removal the skin surface water loss (SSWL) was measured using an evaporimeter (EP1-Servomed, Sweden) every 5 min for 30 min. Measurements were taken on the 10th and 25th day of the menstrual cycle. Statistical analysis was performed using one-factor Anova for repeated measures. Free and bound water compartments of evaporation were also analysed. RESULTS: Higher hydration and SSWL were detectable on the 25th day of the cycle. However, no significant influence of menstrual cycle was found. Significant differences between the upper and lower volar foream were detected (P < 0.001). CONCLUSION: The differences observed were mainly related to the evaporation of bound water, confirming a different barrier function at the sites investigated; therefore, it must be taken into account that adjacent skin sites with equal structure may have different functional behaviour.

Effects of water temperature on surfactant-induced skin irritation.

Surfactant-induced irritant reactions may be elicited by several endogenous and exogenous factors. Among these, surfactant concentration, and duration and frequency of exposure play important rôles. The study focuses on the influence of water temperature in determining damage of the skin barrier. 10 subjects of both sexes entered the study. 4 areas (4 x 4 cm2) were randomly selected on the volar forearm and were treated with a daily open application of 5% sodium lauryl sulphate for 4 days. The solutions were at 3 temperatures: 4 degrees, 20 degrees and 40 degrees C. One site served as untreated control. On the 5th day, skin irritation was evaluated using transepidermal water loss (TEWL) measurements, erythema (a* value), skin reflectance (L* value), hydration (capacitance) and desquamation (stripping). The results show a significant effect of the solution's temperature in determining skin irritation (P < 0.001). Skin damage was higher in sites treated with warmer temperatures and a highly significant correlation (P < 0.001) between irritation and temperature was found. In conclusion, the study shows that water temperature during washing has an important effect on the onset of irritant contact dermatitis.

Non-invasive evaluation of topical calcipotriol versus clobetasol in the treatment of psoriasis.

Topical treatment of psoriasis with calcipotriol has been proven effective. The efficacy of calcipotriol has been compared to that of topical corticoids in a number of studies using subjective visual scoring systems such as the PASI index. The purpose of this study was to compare, with objective data, the efficacy of calcipotriol and clobetasol propionate 0.05% in the treatment of plaque type psoriasis. Transepidermal water loss (TEWL) and laser Doppler velocimetry (LDV) were used to monitor restoration of water barrier and normalization of blood flow, respectively, in psoriatic plaques of the limbs of 24 male patients during 3 weeks of treatment. Data were compared to subjective evaluation using the PASI index of the same areas. Significant differences were recorded during treatment in both groups. The results correlated well with the PASI score. Clobetasol was faster in restoring barrier function than calcipotriol. However, no significant differences were detected between the two groups. The use of vitamin analogues may be effective in the topical treatment of psoriasis by normalizing skin biophysical parameters and minimizing the risks of side-effects induced by potent topical corticoids.

Photofibrosis: a further histopathological change induced by PUVA therapy via the mast cell in guttate psoriasis. Preliminary report.

Twenty-five psoriatic patients were studied histologically before and after PUVA therapy in order to delineate the relationship between dermal mast cells, psoriasis healing process and collagen changes. A number of mast cells were found in the psoriatic changes. A number of mast cells were found in the psoriatic lesion both before PUVA and also after PUVA therapy in 22 of the 25 patients. Fibrosis of the papillary dermis and upper reticular dermis was found in 3 cases. Increased collagen deposition and increased numbers of fibroblasts were accompanied by verticalization of ectatic and elongated blood vessels, with an overall pattern of relatively recent scarring. Mast cells were no longer detectable in the fibrosis area. We cannot exclude the possibility that PUVA therapy exerts a further stimulus on mast cell histamine and heparin degranulation in this type of psoriasis, thus leading to dermal fibrosis and blood vessel neogenesis.

PUVA-treated psoriatic skin as a model for cutaneous wrinkling assessed by skin replicas.

Psoriatic patients may offer a useful model for PUVA-induced skin wrinkling. This study deals with the changes induced by PUVA therapy on the cutaneous microrelief of psoriatic patients assessed by surface replicas. A non-exposed body area (buttocks) was considered. The microrelief was evaluated by means of replicas analysed by an automatic image analyser. Three groups of patients were considered: 1) 10 psoriatic patients who had been undergoing PUVA treatment for the first time and who had received a total PUVA dose of 200 +/- 20 J/cm2; 2) 16 psoriatic patients in long-term PUVA treatment (> 1000 J/cm2); 3) 13 psoriatic controls whose buttocks had never been affected by psoriasis nor exposed to sunlight or PUVA. The results showed that the number and the entity of the cutaneous crests and furrows had been increased by PUVA therapy. In particular the skin pattern analysis showed significant statistical differences between the second and the third group, while no changes were evident between the first and third group (ANOVA and Tukey test for multiple comparisons). In conclusion, our findings indicate that long-term PUVA therapy causes marked changes in the cutaneous microrelief, that this phenomenon can be measured non-invasively and that the changes observed are dependent on the PUVA-dose energies received.

Effects of fluid volume changes during hemodialysis on the biophysical parameters of the skin.

Water plays an important role in maintaining skin suppleness and elasticity. We used hemodialysis as a model to investigate the effects on biophysical properties of the skin induced by removal of fluids and water from the body. The following parameters have been investigated before and immediately after a hemodialysis session: body weight, skin elasticity and distensibility, skin hydration, transepidermal water loss (TEWL) and skin thickness. A significant decrease was recorded after treatment in body weight, skin thickness (p < 0.01) and skin elasticity (p < 0.01). Significant linear correlations were found between stratum corneum water content, skin distensibility and TEWL. The data reveal that rapid removal of body fluids influences skin biophysical properties: early changes in skin thickness and ground substance occur in the dermis and affect mechanical properties of the skin. The decrease in water content in the upper layers of the skin occurs at a later stage and influences skin hydration rather than TEWL. This model is a useful tool to investigate water kinetics through the skin.

Bullous lesions in acrodermatitis enteropathica. Histopathologic findings regarding two patients.

Acrodermatitis enteropathica (AE) is an autosomic recessive disorder affecting early infancy. Two cases of infantile AE with low plasma zinc levels are reported in which unusually prominent bullous and vesicobullous lesions were seen on the hands and feet, in addition to the more typical erythematous and scaly patches. Both psoriasiform and bullous lesions responded dramatically to oral zinc-sulfate supplementation. The histopathologic features of the bullous lesions of AE have not previously been fully examined. Histologically, the bullous lesions were characterized by intraepidermal vacuolar changes with massive ballooning, leading to intraepidermal vesiculation and blistering, with prominent epidermal necrosis and with no acantholysis. The bullous lesions did not arise on erythematous patchy lesions, but developed ex novo on unaffected skin. The histopathologic differential diagnosis with other bullous conditions is discussed.

Objective prick test evaluation: non-invasive techniques.

Prick test reactions are evaluated and quantified, comparing visual assessment with two non-invasive techniques: remittance spectroscopy and pulsed ultrasound for erythema and skin thickness measurements. Different information is provided by the two methods. Remittance spectroscopy discriminates well between negative and positive reactions (+ or ++), while failing to differentiate stronger reactions, where edema is a prominent feature. The latter reactions are better evaluated by skin thickness measurements, which, on the contrary, are less sensitive in revealing small skin thickness increases in weak reactions.

The role of the intercellular matrix in dermal calcinosis of the CRST syndrome. An electron-microscopic study.

We performed an electron-microscopic study on calcium deposits in two patients with calcifying scleroderma (CRST syndrome). Calcium deposits were detected both intracellularly in the mitochondria of phagocytic cells and extracellularly. Needle-like crystals measuring up to 4,500 A in length and approximately 60 A in width were present in both the Von Kossa-positive regions and the apparently normal dermal areas around the calcification sites. Although the fibrillar matrix's ultrastructure was normal, hollow oxytalan fibrils were detected. Slightly electron-opaque, star-shaped material was observed among the fibrillar component of the matrix (matrix granules), which is the ultrastructural expression of some types of proteoglycans containing keratan sulphate and chondroitin sulphate. These granules cannot be detected in normal dermis. The extrafibrillary calcium deposits on these mucopolysaccharide structures may represent an early event in the complex pathogenesis of calcification in the CRST syndrome.

Evidence for CD8+ cell increase in long-term PUVA-treated psoriatic patients after PUVA discontinuation.

Long-term PUVA-treated psoriatic patients given maintenance therapy (UVA doses greater than 1,000 J/cm2) have been demonstrated to undergo lymphopenia and a decrease in the total number of circulating CD3+ and CD4+ T cells. The aim of this study was to assess whether the impairment of T cells is detectable also in psoriatic patients after long-lasting PUVA discontinuation. A group of 34 psoriatic patients (25 males, 9 females; mean age 52.7 +/- 12.82 years), who had previously been treated by PUVA therapy (average cumulative dose 1,898.48 +/- 1,207.12 J/cm2), was studied 1 year or more after discontinuation of PUVA therapy. The patients studied failed to show any impairment in CD3+ and CD4+ cells. Nevertheless, a significant increase (p less than 0.05) in circulating CD8+ cells (both in the percentage and the total number) was detectable in PUVA patients as compared to appropriate controls. The significance and implications of this finding are not known and need further investigations.

In vivo transcutaneous penetration of nicotinates and sensitive skin.

Proclivity to develop irritant reactions and transcutaneous penetration of nicotinates has been investigated in 20 subjects of both sexes, divided into reactors and nonreactors on the basis of the responses to irritant stimuli. 1% sodium lauryl sulphate (patch application for 24 h) and 5% lactic acid in aqueous solutions were used to detect chemical and sensory (subjective) irritation. The vasodilatation induced was measured using a chromameter for 1 h after topical application of the chemical. The area-under-the-curve response and the peak response was used to assess the in vivo penetration of methyl nicotinate (10 mM in aqueous solution). Significant differences were found between reactors and non-reactors. Non-reactors showed a significantly decreased area-under-the-curve response and peak response to methyl nicotinate compared to reactors. Nicotinate-induced vasodilatation has been used as a model to study transcutaneous penetration of chemicals; the correlation between increased penetration of nicotinates and skin hyperreactivity to irritant substances may suggest an increased transcutaneous penetration of water-soluble chemicals in individuals with sensitive skin.

Skin bioengineering in the noninvasive assessment of cutaneous aging.

Cutaneous changes induced by aging can be quantified and monitored noninvasively by means of bioengineering tools. Skin elasticity, hydration, skin blood flow and skin surface pattern show age-related changes reflecting the damage of cutaneous structures involved. Impairment and degeneration of elastic and collagen networks are responsible for the progressive decrease in skin elasticity recorded during aging. Reduction in blood flow and water supply with probably defective stratum corneum binding result in reduced stratum corneum water content and transepidermal water loss. Morphological changes such as increased skin roughness, pigmentation and alteration of skin surface pattern appearing from the age of 30 years onwards may be investigated at a subclinical level allowing the detection of early signs of aging.

Age of onset in vitiligo: relationship with HLA supratypes.

HLA class I (A, B, C), class II (DR, DQ) histoglobulins and HLA class III (C4A, C4B and Bf) complement factors were analysed in 87 patients with vitiligo and in controls. Two HLA supratypes seem to mark different age of onset of vitiligo: HLA-BfS, C4A3, C4B1, DR5 (W11), DQW3 is characteristic of the pediatric form; while HLA-BfS, C4A3, C4B1, DR7, DQW2 marks the adult form of disease. The importance of defining HLA supratype, not single alleles, is discussed.

Lymphopenia and decrease in the total number of circulating CD3+ and CD4+ T cells during 'long-term' PUVA treatment for psoriasis.

The relationship between high-dose PUVA treatment in psoriatic patients and peripheral T lymphocyte subsets (total number and percentage) has been studied. Of the two groups of patients considered, the first included 19 patients, all affected by chronic, progressively worsening psoriasis; they had never been previously treated by photochemotherapy. The second group included 13 psoriatic patients, who had received an average cumulative dose of 2,007.69 +/- 1,191.05 J/cm2. The 'long-term' PUVA-treated group was assessed while undergoing maintenance therapy. No significant differences were found between untreated patients and healthy controls for any of the parameters considered. A significant reduction (p less than 0.05) in the total number of lymphocytes in long-term PUVA-treated patients both versus untreated patients and controls was found. Furthermore, long-term PUVA-treated patients showed a significant reduction (p less than 0.05) in the percentage of lymphocytes as compared with controls. The reduction in the total number of CD3+ and CD4+ T cells was, moreover, significant (p less than 0.05) as compared with untreated patients. The impairment of circulating CD3+ and CD4+ T cells (total number) was only on the borderline of statistical significance vis-à-vis controls. These findings suggest the usefulness of a careful assessment of circulating T lymphocyte subsets in patients who undergo long-term PUVA therapy.

Flagellate dermatitis after bleomycin. A histological and immunohistochemical study.

A case of flagellate dermatitis after administration of bleomycin is reported in a patient with Hodgkin's disease. Histopathological and immunohistochemical analysis revealed a drug-induced skin toxic reaction rather than a lymphomatous infiltrate. Pigmentary changes observed after the early erythematous eruption were due to a postinflammatory effect.

[Amiodarone-induced pigmentation. A histological, ultrastructural study and review of the literature]. / Pigmentazione da amiodarone. Studio istologico, ultrastrutturale e revisione della letteratura.

Amiodarone is an iodinated cardiac antiarrhythmic drug that causes a slate- gray discoloration of sun-exposed skin. Histopathologically, biopsy specimens of two patients affected by amiodarone pigmentations reveal yellow-brown granules in the reticular dermis, both in the cytoplasm of macrophages and between the collagen bundles. The histochemical stainings of the granules suggest that a lipofuscin pigment rather than melanin is present in the granules. Electron microscopy displays distinctive intracytoplasmic inclusions in many dermal cell types. Six morphologic types can be seen: 1) electron-lucent, membrane bound granules, 2) granules with electron dense nucleus, 3) lamellar "myelin-like" granules, 4) granules with a combination of electron-dense and electron-lucent areas, 5) electron-dense membrane-bound granules, 6) electron-dense no-membrane granules. The different dimensions, structure and shape are related to the structural and aggregational phases of the granules. In particular their pathogenesis may be related to the action of the drug on cell membranes with thesaurismosis, local metabolic damage, accumulation of the drug in the lysosomes and acceleration of the physiological ageing cell process.