Noxious heat and scratching decrease histamine-induced itch and skin blood flow

The aim of this study was to assess the effect of thermal stimuli or distal scratching on skin blood flow and histamine-induced itch in healthy volunteers. Twenty-one healthy volunteers participated in the study. Baseline measurements of skin blood flow were obtained on the flexor aspect of the forearm. These measurements were compared with skin blood flow after various stimuli: heating the skin, cooling the skin, noxious cold 2 degrees C, noxious heat 49 degrees C, and scratching via a brush with controlled pressure. Afterwards histamine iontophoresis was performed and skin blood flow and itch intensity were measured immediately after the above-mentioned stimuli. Scratching reduced mean histamine-induced skin blood flow and itch intensity. Noxious heat pain increased basal skin blood flow but reduced histamine-induced maximal skin blood flow and itch intensity. Cold pain and cooling reduced itch intensity, but neither affected histamine-induced skin blood flow. Sub-noxious warming the skin did not affect the skin blood flow or itch intensity. These findings suggest that heat pain and scratching may inhibit itch through a neurogenic mechanism that also affects skin blood flow.     

In vivo quantification of microvessels in clinically uninvolved psoriatic skin and in normal skin

BACKGROUND: Microvascular abnormalities (capillary elongation, widening and tortuosity) are a characteristic feature of psoriasis and form one of the pathological diagnostic criteria. However, it is still not entirely clear when these microcirculatory changes appear in the skin of psoriatic subjects. Some studies suggest that capillary dilatation and elongation are present in the clinically uninvolved skin of psoriatic patients even at sites at which psoriatic plaques rarely occur. OBJECTIVES: To determine, using noninvasive techniques in vivo, the nature of any microvascular changes in the clinically uninvolved skin of psoriatic subjects and to quantify the dermal microvasculature in the clinically uninvolved skin of psoriatic subjects, in vivo. METHODS: Dermal microvessels in both the clinically uninvolved skin of psoriatic subjects and in the skin of normal volunteers (i.e. individuals without any clinical evidence of psoriasis or other inflammatory dermatoses) were directly visualized by native video-capillaroscopy, in vivo. Images were analysed using a combination of nonstereological and stereological measurements. The findings in each group were then compared to determine if there were any differences in microvascular parameters. RESULTS: Quantitative analysis of capillaroscopic images showed that there were no significant differences in microvessel density (P = 0.9), image area fraction (P = 0.6), microvessel length density (P = 0.7) and vessel image width (P = 1.0) in the clinically uninvolved skin of psoriatic subjects and the normal skin of healthy volunteers, when extensor forearm skin was examined. CONCLUSIONS: These findings indicate that prior to the development of clinical lesions there are no significant morphological differences between the dermal microvessels in the clinically uninvolved skin of psoriatic subjects and the dermal microvessels in the normal skin of healthy volunteers. However, during plaque formation, the superficial papillary microvessels in plaque skin undergo a striking, characteristic change, i.e. elongation, widening and tortuosity. These blood vessels must therefore, at least in part, play an important, necessary, but probably secondary role in the pathogenesis of clinical lesions in psoriasis.     

Biological effect of far-infrared therapy on increasing skin microcirculation in rats

BACKGROUND/PURPOSE: Insufficient microcirculation of skin leads to acute and chronic tissue ischemia in cases of trauma, reconstructive surgery, diabetes mellitus and peripheral arterial occlusive disease. The autonomic nervous system and nitric oxide (NO) play important roles in maintaining blood perfusion of the skin. Far-infrared (FIR) therapy provides low energy of light emitted from an artificial radiator and has been used to treat many vascular-related disorders. Nevertheless, the mechanisms through which FIR works remain unclear. The present study aims to test the hypothesis that the effect of FIR is through increasing skin microcirculation by a mechanism other than its thermal effect. METHODS: Sixty rats were used in the present study. A WS TY301 FIR emitter was placed 20 cm above the rats. Skin temperature and blood flow were continuously measured by a K-type thermocouple. Under laboratory control, the abdominal skin temperature steadily increased from 38-39 degrees C, and was kept at constant temperature. Skin microcirculation was measured with a continuous laser Doppler flowmeter. RESULTS: There was no significant change of skin blood flow during FIR treatment. Skin blood flow increased significantly soon after the removal of the FIR emitter. The stimulating effect on skin blood flow was more significant in the rats treated with FIR for 45 min and could be sustained as long as 60 min. These findings suggested a non-thermic biological effect of FIR on skin microcirculation. The promotive effect of FIR on increasing skin blood flow was not influenced by pretreatment of APP (atropine, propranolol and phentolamine), but was suppressed by pretreatment with NG-nitro-L-arginine methyl ester (an endothelial nitric oxide synthase inhibitor). CONCLUSION: In conclusion, FIR therapy exerts a NO-related biological effect to increase skin microcirculation in rats. This might bring into perspective the clinical application of FIR to treat ischemic disease by augmenting L-arginine/NO pathway.     

Reduced skin capillary density during attacks of erythromelalgia implies arteriovenous shunting as pathogenetic mechanism

Erythromelalgia is characterized by burning pain, erythema, and increased temperature in acral skin. The pain is aggravated by warming and relieved by cooling. Increased microvascular arteriovenous shunting in deep dermal plexa has been hypothesized as the pathogenetic mechanism of pain in affected skin, inducing hypoxia during pain attacks. The aim of this study was to quantify skin capillary density in erythromelalgic patients before and after heat provocation, as increased skin temperature should increase the need for nutritive blood supply by the capillaries. Fourteen patients and 10 healthy control subjects were studied using an enhanced technique of computer-assisted analysis of capillary bed morphology and temperature measurements before and after central body heating. The increase in acral skin temperature was significantly higher (p < 0.05) in the eight patients where symptoms were induced after heat provocation, compared to asymptomatic patients and healthy control subjects. The number of visible capillaries in a field of view (1.7 mm2) decreased significantly (p = 0.01) in erythromelalgia patients from 105 (62-137) (median with total range) to 89 (49-118) after warming in areas with numerous arteriovenous anastomoses (nail bed region). In symptomatic patients an even more significant reduction was observed (p = 0.01). The capillary size was also significantly reduced (p < 0.05) from 41.0 (31.5-50.5) (arbitrary units) to 37.3 (33.0-46.0) in symptomatic patients. The change in capillary density in the nail bed area was significantly larger in erythromelalgia patients -17 (-49 to 39) compared to controls 0 (-47 to 13) (p < 0.05), and in symptomatic patients -19 (-49 to -12) compared to asymptomatic patients -8 (-48 to 39) (p < 0.05) and controls (p < 0.01). The reduced skin capillary density after heating is compatible with increased microvascular arteriovenous shunting of blood and a corresponding relative deficit in nutritive perfusion (steal phenomenon) with skin hypoxia, causing the symptoms in erythromelalgia.     

Transdermal application of prostaglandin E1 ethyl ester for the treatment of trophic acral skin lesions in a patient with systemic scleroderma

An early dinical symptom in scleroderma patients is Raynaud's phenomenon. Later cutaneous manifestations of the disease include oedematous swelling in the extremities and in more extreme cases often very painful, refractory acral necroses. We report on a 56-year-old female patient who participated in a prospective, double-blind, multicentre comparative pilot study because of her severe Raynaud symptoms, with dystrophic skin lesions on both hands. The goal of the study was to evaluate the efficacy and safety of prostaglandin E1 ethyl ester in a transdermal drug delivery system compared with placebo in patients with secondary Raynaud's phenomenon associated with systemic scleroderma or mixed connective tissue disease. After 2 weeks of verum treatment the patient experienced a marked improvement of Raynaud's attacks, with increased capillary flow velocity, reduced blood stasis and dinical healing of the acral trophic lesions. For this patient the transdermal application of prostaglandin E1 ethyl ester in the form of a medicated patch proved to be a simple and effective therapy for the acral trophic skin lesions associated with systemic scleroderma.     

Elevated plasma homocysteine level is possibly associated with skin sclerosis in a series of Japanese patients with systemic sclerosis

Homocysteine is a sulfhydryl‐containing amino acid that is derived from dietary methionine, and there has been increasing evidence that elevated plasma homocysteine levels are associated with increased risk of cardiovascular diseases, including carotid, coronary and peripheral arterial disease (PAD). The association of plasma homocysteine levels with peripheral vascular involvements, such as Raynaud phenomenon (RP), digital ulcers (DU) in systemic sclerosis (SSc) patients has not been well studied. The objective of this study was to examine plasma homocysteine levels and their clinical associations in patients with SSc. Plasma homocysteine levels in 151 Japanese patients with SSc and 20 healthy controls were examined. No significant differences were observed in plasma homocysteine levels between SSc patients and healthy individuals. Demographic and clinical features of the SSc patients revealed that severe skin sclerosis, anti‐topoisomerase I antibody positivity, complications of DU, acro‐osteolysis (AO) and interstitial lung disease (ILD) were significantly more prevalent among the patients with elevated plasma homocysteine levels. The plasma homocysteine levels were positively correlated with modified Rodnan total skin score. The plasma homocysteine levels in the SSc patients with DU, AO and ILD were significantly higher than those in the SSc without DU, AO and ILD, respectively. Plasma homocysteine levels did not correlate with either the mean or max intima‐media thickness (IMT) or plaque score, suggesting that plasma homocysteine levels might not be associated with carotid artery atherosclerosis in SSc patients. The measurement of plasma homocysteine levels in SSc patients might be useful for the risk stratifications of severe skin sclerosis, DU and AO.     

Studies of cutaneous blood flow of normal forearm skin and irritated forearm skin based on high-resolution laser Doppler perfusion imaging (HR-LDPI)

Background/aims: High resolution laser Doppler perfusion imaging (HR-LDPI) is a non-touch method used for mapping cutaneous microcirculation. The aim of the present study was to investigate the usefulness of this technique for studies of cutaneous blood flow of normal untreated forearm skin and for the assessment of weak irritant reactions induced by exposure to sodium lauryl sulphate (SLS). Methods 12 healthy volunteers participated in the study. Initially, basal flow was measured for 6 selected test areas on the right forearm. 24 h occlusive application of 0%; 0.125%; 0.25%; 0.50% and 1.0% SLS was performed. An untreated skin area was also included. Test sites were clinically evaluated and the cutaneous blood flow was measured using HR- LDPI on days 2, 3 and 5. Results and conclusions: The results of the present study show that HR-LDPI is a useful technique for assessing the mean cutaneous blood flow of both normal and irritated forearm skin. The rectangular region of interest (R-ROI) method was found to be superior to the threshold region of interest (T-ROI) method in image analysis of the mean blood flow of individual scans. The results showed that even though spatial variation within a skin region may be considerable, no intraregional differences or daily variations in mean basal flow of selected skin areas on the forearm could be found. Due to the low variability, it should not generally be necessary to include an untreated control site as each site should act as its own control. The temporal variation in skin perfusion was minor compared with the spatial variation. This was found both for normal and irritated skin. Therefore, one scan of each area of interest should normally be sufficient. Clinical irritation scores on day 3 were more evenly distributed than those on days 2 and 5. An increase in mean perfusion, as a function of the clinical irritation score, was found. However, no statistical differences could be found in mean perfusion for the selected dose levels of SLS.     

Dermoscopic features of psoriasis of the skin,scalp and nails – a systematic review

Dermoscopy is a non‐invasive in‐office method, which enables the diagnosis of many dermatoses and reduces the need for performing biopsies. To date, no systematic review about the diagnostic usability of dermoscopy in psoriasis has been available. The objective of this article was to summarize and critically analyse literature data on the dermoscopy of skin, scalp and nail changes in psoriasis. A systematic search of three medical databases was performed. A total of 45 articles were included into the analysis. Cutaneous psoriatic lesions assessed in all studies at a low magnification showed regularly distributed red dots. At a 50‐fold or higher magnification capillary bushes (glomerular vessels) with a diameter range of 50–146 μm were observed. The background colour was described as reddish or pinkish with white or yellowish scales. The most frequent dermoscopic (trichoscopic) feature of scalp psoriasis was the presence of red dots/globules and twisted red loops. Typical dermoscopic (onychoscopic) signs of nail psoriasis were onycholysis, salmon patches and splinter haemorrhages. There is an accumulating body of evidence that dermoscopy (both handheld and videodermoscopy) is a useful tool in differential diagnosis in doubtful cases of psoriasis of the skin, scalp, nails, palms, soles and genital regions.     

Potential of a high-frequency correlation method to study skin blood flow

Background/aims: The vast number of existing dedicated techniques proves that skin blood flow estimation is an unsolved problem. Specificities of cutaneous vascularization (very low blood velocity, noisy environment, complexity of the vascularization architecture) result in the unsuitability of conventional ultrasonic Doppler techniques (long acquisition time, low spatial resolution). The object here was to present a high‐frequency time‐domain correlation method. In particular, the difficulties of adaptating this type of measurement (data processing, hardware problem) are pointed out. Methods: Radio‐frequency (RF) backscattered signals, obtained with a modified version of a home‐made 20 MHz skin imaging system, are studied. Time shifts between successive windowed sections of the RF signals are determined by the mean of the cross‐correlation algorithm. A realignment procedure (to remove the artefacts caused by the movements of the patient and the manipulator) and a stationary echo cancelling procedure (to remove the signals coming from the cutaneous tissues and to permit the detection of very small vessels) are used. Results: In vitro results show that velocity measurements as low as 0.1 mm/s are attainable with a 80 μm axial resolution, and blood vessels of 100 μm are detectable. Our technique has also been validated by means of in vivo experiment on an erysipelas located on a human leg. In this way, a 180‐μm‐diameter blood vessel has been detected on a M‐mode RF image and the corresponding velocity profile has been obtained. Conclusion: Further improvements can be expected, and the level of performance obtained in vitro in this work should be also attainable in vivo and should then provide an effective tool for skin physiology and pathology.     

Effect of tap-water iontophoresis on sweat gland recruitment, skin temperature and skin blood flow

Our interest was to quantify the role of sweat gland activation on the maintenance of skin temperature during mild exercise in the heat. Seven days of tap-water iontophoresis decreased the number of active sweat glands by 72% which significantly increased forearm skin temperature and blood flow during mild exercise (70 W) in the heat (32 degrees C). Skin temperature of the treated forearm was 0.5 degrees C warmer (P=0.049); skin blood flow in the treated forearm was 13% higher than the control arm (P=0.021). These results illustrate the importance of sweat evaporation on skin temperature and blood flow during exercise.     

Circadian and ultradian (12 h) variations of skin blood flow and barrier function in non-irritated and irritated skin-effect of topical corticosteroids

The skin is the organ that receives the greatest exposure to light and shows a high-amplitude circadian rhythm in epidermal cell proliferation. We have previously demonstrated that the skin barrier function has a significant circadian rhythm. Corticosteroids (CS) are the most commonly used topical treatment in dermatology. Time-dependent differences in their efficacy and side-effects would be of considerable interest. The aims of the current study were to examine time-dependent cycles in the effect of topical CS application in healthy and irritated skin on skin blood flow and its relationship to barrier function. Twenty clinically healthy, diurnally active subjects were examined at eight and nine time points over a 24 or 28 h span respectively, using non-invasive skin bioengineering techniques of laser Doppler imaging, a transepidermal water loss (TEWL) device and a skin thermometer in a 28 h session. The results of this current study demonstrate circadian and ultradian (12 h) variations in skin blood flow. A significant correlation was found between skin temperature and skin blood flow but not with TEWL. Circadian and ultradian rhythms are maintained during treatment with high-potency and mid-potency CS in healthy skin. These rhythms persist during stratum corneum disruption with and without CS application.     

Topical application of CO2 increases skin blood flow

The topical application of carbon dioxide water to the rat hindpaw produced a concentration-dependent increase of skin blood flow as measured by a laser Doppler flowmeter. About a 100% increase of skin blood flow occurred in response to CO2 when the bath temperature was at 23 degrees C or 34 degrees C, but there was no significant effect of CO2 at 41 degrees C. Carbon dioxide exposure also produced about the same increase of skin blood flow in the acutely or chronically denervated paw as in the control. These findings give experimental support for the clinical use of CO2 bathing in the treatment of disturbances of skin circulation as well as skin ulcers and wounds.     

Epstein–Barr virus‐associated T‐cell lymphoproliferative disorder affecting skin and lung in an elderly patient

A 70‐year‐old man presented with papular skin lesions and was diagnosed with Epstein–Barr virus (EBV)‐associated T‐cell lymphoproliferative disorder (T‐LPD). The patient showed infiltration of a large number of EBV‐encoded RNA‐positive T cells in the skin and lung, presence of EBV load in the peripheral blood, and expansion of clonal EBV‐infected γδ T cells and CD8⁺ T cells in the blood and skin, as assessed by EBV‐terminal repeat Southern blot, T‐cell receptor polymerase chain reaction and flow cytometric analyses. In the Japanese or East Asian fatal cases of EBV‐associated T/natural killer (NK)‐LPD, there are two peaks in age at death, approximately 20 years and 60 years. The former age group is associated with chronic active EBV infection (CAEBV), and the latter group typically suffers from extranodal NK/T‐cell lymphoma. Our case is characterized not only by the unique skin and lung manifestations but also the late onset age of the disease, indicating that the skin manifestation of CAEBV can be seen even in elderly patients.     

Videocapillaroscopy in the differential diagnosis between psoriasis and seborrheic dermatitis of the scalp

BACKGROUND: Videocapillaroscopy (VCP) can be used to explore microcirculatory modifications in skin diseases. Psoriasis shows specific capillary alterations reflecting typical histopathological changes. OBJECTIVE: To compare capillary morphology, distribution and density in psoriasis and seborrheic dermatitis of the scalp for differential diagnosis. METHODS: VCP was performed on histology-confirmed scalp lesions of 30 patients with chronic plaque psoriasis, 30 age- and sex-matched patients with seborrheic dermatitis and 30 healthy subjects. The morphology, mean density per mm(2) and mean diameter of capillary loops was measured. RESULTS: Scalp psoriasis exhibited homogeneously tortuous and dilated capillaries (bushy pattern), with a 73 +/- 17 mum (mean +/- standard deviation) diameter of capillary bushes. In contrast, scalp seborrheic dermatitis presented a multiform pattern, with mildly tortuous capillary loops and isolated dilated capillaries, but a substantial preservation of local microangioarchitecture. Mean diameter of capillary bush was significantly lower (27 +/- 4 microm; p < 0.001) and similar to that of the scalp of healthy subjects (21 +/- 5 microm). Capillary loop density was similar in patients with psoriasis (23 +/- 5/mm(2)) seborrheic dermatitis (24 +/- 2/mm(2)) and healthy scalp skin (24 +/- 3/mm(2)). CONCLUSION: VCP could be a useful noninvasive approach for differentiating between psoriasis and seborrheic dermatitis, especially when the scalp is the only affected site.     

CD30+ clonal T‐cell lymphoid proliferation of the skin in a patient with hypereosinophilic syndrome

We report a hitherto undescribed unusual CD30+ clonal T‐cell proliferation in a 46‐year‐old man with the lymphocytic variant of hypereosinophilic syndrome with a 17‐year history of pruritus, generalized persistent papulonodular skin lesions and peripheral blood hypereosinophilia. A skin biopsy showed an eosinophil‐rich infiltrate with small to medium‐sized CD30+ lymphocytes and Churg‐Strauss granulomas. Peripheral blood flow cytometry revealed an aberrant T‐cell clone which, molecular genetically, was identical to the T‐cell clone detected in the skin. No genetic aberrations of platelet‐derived growth factor receptor alpha (PDGFRA), FIP1L1‐PDGFRA, PDGFRB or FGFR1 were found. The skin lesions showed transient response to systemic and topical corticosteroids. The skin lesions represent cutaneous involvement by clonal T‐cells in hypereosinophilic syndrome and differ from known cutaneous CD30+ lymphoproliferative disorders.     

橙皮苷、β-七叶皂苷、丹参酮等局部外用对甲皱皮肤微循环的影响

目的：研究局部外用8种天然植物提取物对皮肤微循环的影响。方法：给受试者中指甲皱处分别涂1％植物提取物,并安放激光多普勒检测探头,稳定5min后开始记录甲皱皮肤血流灌注量,以后每5min记录1次,每次1min,共观察30min取平均值。基质作对照。对有效成分进一步观察浓度为0．10％、0．01％药物对皮肤血液灌注量的影响,并用毛细血管微循环仪观察其对红细胞血流速度的影响。结果：1．00％、0．10％橙皮苷可以显著增加皮肤的血液灌注量,外用0．10％橙皮苷亦可使红细胞的血流速度显著增加。结论：橙皮苷局部外用可以改善皮肤的微循环。     

Validation of a non‐contact technique for local skin temperature measurements

Here we propose to quantify local temperature variations using thermal imaging to assess the effect of dermatological lasers. Objectives: To quantify the temperature raise induced by laser application and to differentiate the effects of a potassium titanyl phosphate (KTP) laser and an intense pulsed light (IPL). Methods: A randomized comparative study was performed on 10 adult volunteers with symmetrical rosacea treated by KTP laser or IPL. Skin temperature measurements were performed on inclusion, immediately after laser treatment and 3 min after thermal water application, using a high‐resolution (0.08 °C) infrared thermal video camera. Results: KTP laser treatment induced a significant rise in local skin temperature whereas no significant change was revealed by the IPL treatment. The infrared camera is a reliable and reproducible technique that allows a follow‐up of skin temperature without skin contact. Conclusion: Thermography using an infrared camera could potentially be applied in clinical pharmacology for inflammatory reactions or scarring processes.     

Hutchinson–Gilford Progeria Syndrome Caused by an LMNA Mutation: A Case Report

Hutchinson–Gilford progeria syndrome is a rare genetic disorder characterized by premature aging of the skin, bones, heart, and blood vessels. We report a 6‐year‐old boy who was born at full term but presented with scleroderma‐like appearance at 1 month of age and gradually developed clinical manifestations of progeria. He had characteristic facial features of prominent eyes, scalp, and leg veins; loss of scalp hair, eyebrows, and eyelashes; stunted growth; scleroderma‐like changes of the skin; and a premature aged appearance. Metabolic investigations showed transient methylmalonic aciduria, and genetic testing of the peripheral blood identified the c.1824C>T heterozygous LMNA mutation. The present case is reported because of its rarity.