Mast cells in atopic dermatitis: resistance against medium-dose UVA1 phototherapy?
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Biomedical subjects
Publications and source records attributed to P Altmeyer.
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High frequency ultrasound (HFUS) and optical coherence tomography (OCT) are techniques for high resolution imaging of tissues. The penetration depth of these modalities is limited, but it is sufficiently large enough for non invasive skin imaging. HFUS and OCT are based on the same concept. Waves (ultrasonic waves, respectively light waves) propagate along a narrow beam, are backscattered at tissue inhomogeneities and analyzed over time of flight to obtain spatially resolved morphological information. The objective of this paper is to compare HFUS and OCT in terms of resolution, dynamic range and contrast and to assess their value as tools for high resolution skin imaging. Measurements on phantoms and in vivo have been performed with a 100 MHz ultrasound system and an OCT-scanner working in the near infrared spectrum at 1300 nm wave-length. From the measurements, it can be concluded that OCT delivers an almost isotropic resolution (axial resolution about 5.8 microns, lateral resolution about 4.1 microns), whereas the resolution of the investigated HFUS system is more anisotropic (axial resolution about 9.3 microns, lateral resolution about 60 microns). HFUS and OCT show different penetration depths and a different contrast. Both techniques can, therefore, be combined advantageously in a multimodality approach to account for their individual characteristics.
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INTRODUCTION: Recently, medium-dose UVA1 phototherapy (50 J/cm2) has achieved great therapeutic success within the treatment of severe atopic dermatitis (AD). Histologically, AD is recognised by a pathological perivascular dermal infiltrate including T lymphocytes, eosinophils and Langerhans cells. The purpose of our study was to investigate the extent to which UVA1 irradiation is able to modulate the mononuclear dermal inflammatory infiltrate using different monoclonal antibodies. PATIENTS AND METHODS: Biopsy specimens before and after treatment with medium-dose UVA1 irradiation (cumulative dose: 750 J/cm2) from 15 patients suffering from severe AD were analysed immunohistochemically concerning the presence of CD4+ and CD8+ T lymphocytes, CD1a+ Langerhans cells and EG2+ activated eosinophils. RESULTS: Compared to lesional skin of patients with AD before UVA1 irradiation, the relative number of CD4+ cells, CD1a+ dendritic cells and activated EG2+ eosinophils within the dermal infiltrate could be decreased significantly after treatment. In contrast, medium-dose UVA1 phototherapy led to a significant increase of the percentage of dermal CD8+ cells. These alterations were closely linked to a decrease of the absolute skin-infiltrating cells and a substantial clinical improvement of the skin. CONCLUSIONS: In summary, our findings demonstrate that medium-dose UVA1 irradiation leads to a remarkable modulation of the dermal mononuclear infiltrate in patients with severe atopic dermatitis referring to a decrease of dermal Langerhans cells, activated eosinophils and CD4 cell count as well as to a relative increase of CD8+ lymphocytes. The immunomodulation of the cutaneous infiltrate is associated with a depletion of cytotoxic agents, the defective IgE overproduction and the aberrant presence of T lymphocytes combined with the pathological cytokine pattern.
Therapy of HIV infection has undergone significant changes since the introduction of highly-active antiretroviral therapy (HAART). Mortality and the appearance of opportunistic infections have significantly been reduced. Diseases of the skin and adjacent mucous membranes often provide the first signs for HIV infection. The spectrum of dermatologic findings related to HIV includes a variety of cutaneous and mucocutaneous disorders. The most frequent diagnoses are oral candidiasis, mollusca contagiosa, oral hairy leuokoplakia, herpes zoster and herpes simplex, seborrheic dermatitis, and Kaposi's sarcoma. Incompatibility reactions to drugs are observed on a strikingly frequent basis in HIV infection. Such severe incompatibility reactions are much more frequent in HIV patients than in the normal population. Inducers often include sulfonamides, cotrimoxazole, tuberculostatics as well as nucleoside-type reverse transcriptase inhibitors.
It has been known since 1851 that atmospheric oxygen is taken up by the human epidermis. The contribution to total respiration is negligible. Until now the significance for the local oxygen supply of the skin has remained unknown. With a newly developed sensor, the oxygen fluxoptode, it has become possible to make local measurements of the transcutaneous oxygen flux (tcJ(O2)). In this study the sensor was calibrated so that absolute values of tcJ(O2) could be reported. At rest, tcJ(O2) was determined on normal, humidified skin on the volar forearm of 20 volunteers of different age groups. In order to evaluate the contribution of the blood flow to the oxygen supply of the skin, tcJ(O2) was recorded at the end of a 5 min suprasystolic occlusion of the forearm. At normal skin surface partial oxygen pressure (163 +/- 9 Torr), tcJ(O2) was 0.53 +/- 0.27 ml O2 min(-1) x m(-2). A 5 min interruption of blood flow resulted in an increase of 9.5 +/- 6.3 % in tcJ(O2). The value of tcJ(O2) was unaffected by the age of the subject. Published data on the oxygen diffusion properties of skin and simulations of intracutaneous profiles of oxygen partial pressure indicated that under these conditions, the upper skin layers to a depth of of 0.25-0.40 mm are almost exclusively supplied by external oxygen, whereas the oxygen transport of the blood has a minor influence. As a consequence, a malfunction in capillary oxygen transport cannot be the initiator of the development of superficial skin defects such as those observed in chronic venous incompetence and peripheral arterial occlusive disease.
BACKGROUND AND OBJECTIVE: Malignant melanomas show a higher heterogeneity in their architecture and a higher vessel density because of neovascularization compared to benign melanocytic skin tumours. In this study the validity of the newly developed Laser Doppler Perfusion Imager (LDPI) with a lateral resolution of 100 microns in the differential diagnosis of pigmented skin tumours was investigated. PATIENTS/METHODS: The perfusion of 116 pigmented skin tumours was s measured with LDPI; 44 malignant melanomas, five melanoma metastases, 59 dysplastic nevi and eight basal cell carcinomas were studied before excision for precise histological diagnosis. RESULTS: There is a significantly higher perfusion of the malignant melanomas (3.15 +/- 1.87 AU) compared to dysplastic nevi (1.14 +/- 0.97 AU) (p < 0.01). By calculating a ratio of the mean perfusion in the tumour and the mean perfusion in adjacent healthy skin, the potential source of error because of regional differences in perfusion is eliminated. The ratio of malignant melanomas (10.78 +/- 9.18) is significantly higher than these of melanoma metastases (4.20 +/- 1.66), basal cell carcinomas (3.24 +/- 1.32) and dysplastic nevi (2.85 +/- 1.32). CONCLUSIONS: The high resolution LDPI has the potential to be a non-invasive screening method for preoperative differential diagnosis of pigmented skin tumours. Besides the epiluminescence microscopy and sonographic determination of the tumour thickness, we have now the possibility to get preoperative information about tumour vascularization.
Basal cell carcinomas of the foot are absolutely rare. We describe the case of a 72-year-old female patient who developed a multicentric superficial BCC present on the lateral edge of the right foot. The patient remembers the regular control of the fit of footwear by an X-ray apparatus, the so-called shoe fluoroscope (=Pedoskop in Germany). Probably this may be a hardly estimated risk factor in the genesis of BCC of the foot.
BACKGROUND/PURPOSE: Spectrophotometry has become an accepted laboratory-based method for the determination of the ultraviolet protection factor (UPF) of fabrics. However, the validity of the UPF determined in the laboratory has been a controversial issue with regard to its significance in the field. To compare UPF values obtained by spectrophotometry, determination of the minimal erythema dose (MED), and biological dosimetry, we conducted laboratory and field-based measurements on various fabric materials. METHODS: One cotton, two viscose, and two polyester fabrics were enrolled into the study. Spectrophotometric (SP) testing was performed in accordance with the European standard. In vivo "on skin" (IV) testing on human subjects was performed with and without fabric protection. For determination of MED, a solar-simulator was used. In another part of the study, biological dosimetry (BD) testing was employed for laboratory testing with solar-simulated radiation (laboratory BD testing) as well as field-based measurements with natural sunlight in stationary (stationary BD testing) and "real life" exposure situations (mobile subject BD testing). For field-based measurements one light-weight polyester fabric was selected. RESULTS: The differences of the mean UPF values obtained by the laboratory-based methods were significant (MANOVA; P = 0.05), except for fabric no. 2 (MANOVA; P = 0.097). In 4 of the 5 fabrics tested, UPF values obtained by IV testing were significantly lower than those obtained by SP testing (t-test; P = 0.05). In 3 fabrics, SP testing revealed significantly higher UPF values in comparison to laboratory BD testing (t-test; P = 0.05). The differences of UPF values obtained by the laboratory and field-based measurements employed for the light-weight polyester fabric were significant (ANOVA; P = 0.05). In comparison to SP testing (UPF 3.8), stationary BD testing resulted in significantly lower (UPF 3.5) and mobile subject BD testing in a significantly higher UPF of 4.4 (t-test; P = 0.05). The UPF obtained by mobile subject BD testing differed significantly from the UPF obtained by stationary BD testing (t-test; P = 0.05). CONCLUSIONS: Comparison of the presented methods indicates that IV testing generally results in lower UPF values. By contrast BD testing in "real life" exposure situations reveals relatively high UPF values. Although an overestimation of the spectrophotometrically measured UPF has been observed in comparative laboratory testing, UPF values obtained by field-based measurements are in relatively good agreement, or even surpass UPF values obtained by spectrophotometry. It is, therefore, suggested that SP testing provides "safe" UPF values which may be also valid in extreme real exposure situations. Biological UV dosimetry is, however, a promising alternative method for UPF testing: the test is easily performed in realistic exposure situations, the test is relatively inexpensive, and the measurements are valid.
BACKGROUND/PURPOSE: Atopic dermatitis (AD) is characterized immunohistochemically by a high number of skin infiltrating T-helper cells (CD4 +). In most cases cutaneous T-cell lymphoma (CTCL) is characterized by a malignant proliferation of CD4+ T-helper lymphocytes. The purpose of our study was to evaluate the extent of anti-apoptotic effects in patients suffering from AD or CTCL, respectively, which may contribute to the prolonged inflammation. Furthermore, we investigated whether medium-dose ultraviolet A1 (UVA1) phototherapy is able to modulate the expression of bcl-2 within the dermal inflammatory infiltrate. METHODS: In order to enumerate bcl-2+ cells pre- and post-therapeutic punch skin biopsies of ten patients with AD and five patients with CTCL were stained immunohistochemically for features of apoptosis using a monoclonal antibody detecting bcl-2. RESULTS: Both AD and CTCL sections revealed a high percentage of bcl-2+ cells within the dermal perivascular infiltrate before therapy. After the successful treatment using medium-dose UVA1 phototherapy this percentage could be decreased significantly. CONCLUSION: Both T-cell-derived skin diseases exhibit an increased pre-therapeutic number of bcl-2+ cells. After medium-dose UVA1 phototherapy the substantial improvement of the skin condition was linked to a significant decrease of the dermal bcl-2+ cell count. Moreover, we could demonstrate a remarkable correlation referring to the decrease and staining pattern of bcl-2 between these two groups as well as within each group. Because the bcl-2 protein is known to act as an apoptosis inhibitor, its pre-therapeutic increase may provide the persistent cutaneous inflammatory reaction in T-cell-derived skin diseases. Additionally, the post-therapeutic reduction of bcl-2+ cells might represent a key mechanism of medium-dose UVA1 phototherapy.
BACKGROUND/PURPOSE: Retinoids like tazarotene are approved for the treatment of chronic plaque psoriasis. In the beginning of topical retinoid therapy, 15-20% of the patients suffer from mild to moderate adverse reactions with burning and erythema. The aim of the study was to find predicative parameters of the individual irritative potential and to suggest options to reduce these initial irritations. METHODS: Twenty in-patients with different skin types (1 + 2: 11, 3 + 4: 9), with chronic plaque psoriasis were included in this open study. In each patient, 7 randomized plaques on the forearm were treated for 14 days on different ways: test area 1: morning (m) and evening (e) placebo, test area 2: placebo (m) and tazarotene 0.05% (e), test area 3: placebo (m) and tazarotene 0.1% (e), test area 4: calcipotriol (m) and calcípotriol (e), test area 5: mometasone furoate (m) and tazarotene 0.05% (e), test area 6: mometasone furoate (m) and tazarotene 0,1% (e), test area 7: placebo (m) and tazarotene in increasing concentrations (e), test area 8: healthy skin for control. Before and after therapy, skin barrier function, blood flow and plaque thickness in 20-MHz sonography were assessed in different test areas intraindividually by non- invasive biophysical measurements. RESULTS: After 14 days of therapy, tazarotene 0.05% and 0.1% produced a stronger increase of laser Doppler flow in patients with skin type 1 and 2 than in patients with skin type 3 and 4. When using the combination therapy of tazarotene and mometasone, the laser Doppler flow was significantly lower than in tazarotene as monotherapy. 20-MHz-ultrasound showed a significant decrease in the thickness of the echo-poor band in all topical therapy regimens compared to placebo. Patients of skin type 1 and 2 reached a higher density of the dermis than patients of skin type 3 and 4, meaning a stronger decrease of inflammatory infiltration and acanthosis. CONCLUSION: Adapting retinoid therapy to the patient's skin type can reduce the initial irritative side-effects. During the first days, patients with skin type 1 or 2 should add a medium potency corticosteroid. Stronger skin irritation caused by tazarotene therapy increases therapy effects.
BACKGROUND/PURPOSE: In vivo confocal laser scanning microscopy (CLSM) allows to study human skin up to 200 micro m deep non-invasively. Aim of this study was to investigate basal cell carcinoma (BCC) using in vivo CLSM, and to compare the micromorphologic features of BCC with uninvolved skin. METHODS: Twelve patients with histological diagnosis of BCC referred to our department for tumor excision were investigated on the lesion(s) and on clinically uninvolved sites preoperatively by in vivo CLSM using the Vivascope 1000 (Lucid Inc., Rochester, USA). The images were compared to histological examinations of the excised tissue. RESULTS: Typical changes in vasculature such as increase in number and diameter of the blood vessels, loss of the vascular architecture, parallelly and horizontally orientated vessels, and accumulation and rolling phenomena of bright reflecting cells of 11.88 +/- 1.75 micro m in diameter along the vessel wall were observed in all BCCs. The tumor stroma of the BCCs showed a strong reflectance mainly due to numerous bundles of collagen fibers encoating dark, cell-rich areas of tumor parenchym. In five patients, slim basaloid cells with relatively large, elongated dark nuclei were observed in the periphery of the tumor parenchym. In the fibrosing type of BCC, curled bundles of collagen with large cells represented the tumor stroma. CONCLUSIONS: BCC can be investigated by CLSM and provide typical features. Besides the tumor parenchym and stroma, typical changes in vasculature seem to be a sensitive criteria for BCC and may in future help in diagnosing BCC by CLSM as well as in assessing the margins of large tumors. We suggest that CLSM is a promising non-invasive tool for the diagnostics of BCC and the assessment of tumor margins prior to surgery.
BACKGROUND: Previous studies have indicated that solar and artificial ultraviolet (UV) radiation have a positive influence on psychological variables such as mood and emotional state. Circulating opioid peptides have been suggested as being important in this effect. OBJECTIVES: To investigate in a controlled trial the influence of UVA radiation on opioid peptide levels. METHODS: We determined plasma levels of beta-endorphin immunoreactive material (IRM) and met-enkephalin in UV-exposed (n = 35) and non-exposed (n = 9) healthy volunteers. On the first day of the study, blood samples were taken from the volunteers (time A). UVA irradiation was subsequently administered with an air-conditioned tanning device. During the UV exposures the volunteers wore opaque goggles. Twenty minutes after UV exposure, blood samples were collected again (time B). Within the following 3 weeks the volunteers had a series of five UV exposures. On the last day of the study (24 h after the sixth UV exposure) blood samples were collected (time C). The cumulative UVA doses were 96 J cm-2 for skin type II and 126 J cm-2 for skin type III. The controls had no UV exposures. Plasma beta-endorphin IRM and met-enkephalin levels were determined using radioimmunoassays. RESULTS: At all times of blood collection (A, B, C), there were no significant differences in plasma levels of beta-endorphin IRM and met-enkephalin between UV-exposed and non-exposed volunteers (P > 0.05). CONCLUSIONS: UVA irradiation does not significantly elevate plasma levels of beta-endorphin IRM and met-enkephalin. Therefore we suggest that psychological benefits claimed to occur after UV exposure are unlikely to be mediated by the types of circulating opioid peptides measured in this study.
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Cutis marmorata telangiectatica congenita and vascular twin naevi are rare vascular anomalies in which focal acantholytic dyskeratosis is usually not observed. We describe a 44-year-old-man who presented for evaluation of skin lesions that had been present since birth. Physical examination revealed anaemic macules adjacent to a naevus telangiectaticus on the chest. Naevus anaemicus was also seen on the shoulders, arms, and left leg. There was bluish-reddish reticulate marking of the skin and cutaneous atrophy. Shortening and hypoplasia of the left leg was observed. Histologic examination of two biopsy specimens revealed focal acantholytic dyskeratosis. In vivo confocal laser scanning microscopy showed dilated capillaries and vessels of the upper dermal plexus in the telangiectatic and decreased capillary blood flow in the anaemic skin sites. The findings were consistent with a diagnosis of cutis marmorata telangiectatica congenita, vascular twin naevi, and incidental focal acantholytic dyskeratosis. The particularities of the present case are the following: firstly, the association of two rare vascular anomalies to which the genetic concept of mosaicism can be applied; secondly, the occurrence of incidental focal acantholytic dyskeratosis in sites of vascular naevi.
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