Willem A. van Vloten

Increased number of immunoreactive nerve fibers in atopic dermatitis

The presence of immunologic markers for neurofilaments, neuropeptides of sensory nerve fibers (Calcitonin gene-related peptide and substance P), for noradrenergic innervation (neuropeptide Y and Tyrosine hydroxylase), and Neuron-specific protein 9.5 was evaluated in frozen tissue sections from normal skin (n = 34) and from skin biopsies manifesting urticaria (n = 6), leukocytoclastic vasculitis (n = 4), systemic lupus erythematosus (n = 23), and atopic dermatitis (n = 40, of which 16 were from lesions induced by epicutaneous atopic allergen patch tests). In some normal skin specimens immunoreactive nerve fibers expressing Neuron-specific protein 9.5 were observed in the epidermis, dermis, and around blood vessels. For the other markers, immunolabeling was mainly observed in the dermis around blood vessels. Neurofilaments, which are scarce in normal skin epidermis, were present in higher density in the epidermis of affected skin in all disease conditions. Biopsies from urticaria and systemic lupus erythematosus showed a decrease in density of fibers immunolabeled for neuropeptides substance P and Calcitonin gene-related peptide and for Neuropeptide Y. In biopsies from skin with atopic dermatitis, an increased density of fibers was observed for all markers except Neuropeptide Y and Tyrosine hydroxylase. In this group, biopsies from positive atopic allergen patch tests showed an enhanced density of fibers labeled by antibody to Neuron-specific protein 9.5 and a lower density in labeling for Tyrosine hydroxylase. The data indicate a potential role of innervation and neuropeptides in dermatoses like atopic dermatitis.

Primary cutaneous large cell lymphomas of follicular center cell origin: A clinical follow-up study of nineteen patients

In this study the clinical characteristics and follow-up data of nineteen patients with a diffuse large cell lymphoma of follicular center cell (B cell) origin, with only skin lesions at presentation, are reported. Sixteen of nineteen patients came to us with localized nodules or tumors, preferentially on the trunk, scalp, and lower legs. Remarkably, eight of eleven patients with disease confined to a limited area on the trunk had a history of slowly progressive papular lesions that had been present for 1 to 20 years prior to the development of rapidly growing skin tumors. Initial treatment, generally radiotherapy and/or polychemotherapy, resulted in complete remissions in seventeen of nineteen patients. Only three patients developed extracutaneous disease, whereas two other patients had recurrent disease in the skin at sites distant from the original skin lesions. Excluding three patients who had just finished initial treatment at the time of writing, twelve of sixteen patients were currently alive and in complete remission with a median survival of 44 months. Four patients died, three of whom were elderly women who had skin tumors on the lower legs when first seen. These results suggest that patients with a primary cutaneous large cell lymphoma of follicular center cell origin with disease confined to the trunk of scalp have a very favorable prognosis.

Cutaneous cylindroma with malignant transformation

Background. Malignant cutaneous cylindroma is a rare tumor. It has been described in 26 cases, both in the solitary form and in the autosomal dominant inherited multiple tumor form. The authors present two new cases that occurred in one family with a history of multiple cylindromas.

Actinic reticuloid: A clinical, photobiologic, histopathologic, and follow-up study of 16 patients

We report a detailed clinical, histopathologic, and photobiologic study of 16 Dutch patients with actinic reticuloid. All were middle-aged or elderly men who had persistent plaques on light-exposed skin only (two patients), extension of lesions to nonexposed areas (four patients), or prolonged or persistent episodes of erythroderma (10 patients). They were sensitive to UVB, UVA, and visible light. In 10 of 13 patients tested, the dermal infiltrate contained predominantly suppressor T cells. Many also had a reversed helper-suppressor T cell ratio. Circulating lymphocytes with deeply indented nuclei were present in all but were most pronounced in the most photosensitive erythrodermic patients. Tolerance induction therapy with UVB irradiation produced an excellent or good response in 13 of 15 patients. One patient responded to cyclosporine therapy.

Cell Cycle Kinetics Following UVA Irradiation in Comparison to UVB and UVC Irradiation

Abstract— There is limited information about the carcinogenic effect of longwave ultraviolet radiation (UVA: 315‐400 nm). In particular very little is known about the relevant genotoxic damage caused by physiological doses of UVA radiation. A general response of cells to DNA damage is a delay or arrest of the cell cycle. Conversely, such cellular responses after UVA irradiation would indicate significant genotoxic damage. The aim of this study is to compare cell cycle kinetics of human fibroblasts after UVC (190‐280 nm radiation), UVB (280‐315 nm radiation) and UVA irradiation. Changes in the cell cycle kinetics were assessed by bivariate flow cytometric analysis of DNA synthesis and of DNA content. After UVC, UVB or UVA irradiation of human fibroblasts a suppression was seen of bromodeoxyuridine (BrdU) incorporation at all stages of S phase. The magnitude of this suppression appeared dose dependent. Maximum suppression was reached at 5‐7 h after UVB exposure and directly after UVA exposure, and normal levels were reached 25 h after UVB and 7 h after UVA exposure. The lowered BrdU uptake corresponded with a lengthening of the S phase. No dramatic changes in percentages of cells in G1, S and G2/M were seen after the various UV irradiations. Apparently, UVA irradiation, like UVB and UVC irradiation, can temporarily inhibit DNA synthesis, which is indicative of genotoxic damage.

Familial cutaneous cylindromas: Investigations in five generations of a family

BACKGROUND Multiple cutaneous cylindromas are probably inherited in an autosomal dominant way. OBJECTIVE Our purpose was to describe a large family with cutaneous cylindromas, trichoepitheliomas, and milia occurring in five generations and to elucidate further the mode of inheritance. METHODS We examined 39 family members and obtained information on 31 other members from reports of relatives. RESULTS The pedigree included 237 members, 118 male and 119 female, with 30 affected patients (11 male, 19 female). Between 33% and 100% of the children of affected family members had one or more of these skin lesions. Female-to-female, female-to-male, male-to-female, and male-to-male inheritance occurred. CONCLUSION Multiple cutaneous cylindromas are inherited in an autosomal dominant way with variable clinical expression. Penetrance reaches 100% in adult life. This condition is associated with trichoepitheliomas and milia.

Erythroderma: A clinical and follow-up study of 102 patients, with special emphasis on survival

BACKGROUND Erythroderma may result from different causes. There have been no publications on this subject with special emphasis on survival. OBJECTIVE The aim of the study was to determine the cause of the erythroderma and the prognosis of these patients. METHODS Clinical and follow-up data from 102 patients with erythroderma were analyzed. We estimated survival of patients with erythroderma, from causes other than Sézary syndrome, mycosis fungoides, or leukemia cutis. The survival was compared with that of an age-matched control group of the general population. RESULTS The main cause of erythroderma was exacerbation of a preexisting dermatosis (53%). Drug reactions were rarely the cause (5%). A high proportion of the patients had chronic actinic dermatitis/actinic reticuloid (12%). Survival of men with erythroderma was significantly lower than that of the general population. CONCLUSION Men with erythroderma, from causes other than Sézary syndrome, mycosis fungoides, or leukemia cutis, have a lower survival than men in the general population.

Radiation-induced skin cancer and radiodermatitis of the head and neck

From a cohort of 2400 patients who had been irradiated 19 to 48 years previously for benign diseases in the head and neck region a randomly selected group of 605 patients was selected and traced back. From the 360 patients alive, 257 were examined clinically and 49 were examined by questionnaire for radiation‐induced skin tumors and radiodermatitis. In 21 patients, a total of 30 skin tumors were diagnosed. In 8 of 21 patients, 10 skin carcinomas were detected at recall. A dose‐effect relationship of 40 carcinomas/104 persons/Gy for a median follow‐up period of 41 years for the area exposed was calculated. The severity of radiodermatitis is associated with a higher prevalence of skin cancer. The number of radiation‐induced skin cancers rises with the post‐treatment time. Because of these late radiation effects, radiotherapy of benign skin lesions is contraindicated, especially now that other therapy modalities are available.

Epidermal cis-Urocanic Acid Levels Correlate with Lower Specific Cellular Immune Responses After Hepatitis B Vaccination of Ultraviolet B–exposed Humans¶

Abstract Urocanic acid (UCA) is a major UV-absorbing chromophore in the epidermis and has been suggested to act as one of the initiators of UV-induced immunosuppression. cis-UCA, the isomer from UCA that is formed upon UV exposure, has been shown to impair some cellular immune responses. cis-UCA levels were determined in a study in which the influence of ultraviolet B (UVB) exposure on immune responses after hepatitis B vaccination in human volunteers was established. A significant increase in cis-UCA levels was found in the skin of UVB-exposed volunteers compared with controls. cis-UCA levels, calculated as the percentage of the total UCA amount, in UVB-exposed volunteers correlated significantly with the cumulative UVB dose received in 5 consecutive days, i.e. the higher the UVB dose (J/m2), the higher the cis-UCA levels (until a cis-UCA plateau was reached in the so-called photostationary state). Correlations between skin cis-UCA levels and immune responses were determined, and they revealed no statistically significant correlations among lymphocyte proliferation responses after either mitogenic stimulation or stimulation with recall antigens. No correlation was found between cis-UCA levels and hepatitis B–specific antibody titers. However, we found a statistically significant negative correlation between cis-UCA levels and hepatitis B–specific lymphocyte proliferation responses when volunteers were irradiated with UVB before hepatitis B vaccination. In other words, volunteers with high cis-UCA levels caused by UVB exposure showed lower cellular immune responses against hepatitis B antigen after hepatitis B vaccination.

Expression of VCAM‐1, ICAM‐1, E‐selectin, and P‐selectin on endothelium in situ in patients with erythroderma, mycosis fungoides and atopic dermatitis

Background: Erythroderma may result from different causes. At present it is unclear whether the patho‐mechanisms that lead to these different types of erythroderma are identical or different. Adhesion molecules and their ligands play a major role in endothelial‐leukocyte interactions, which affect the binding, transmigration and infiltration of lymphocytes and mononuclear cells during inflammation, injury, or immunological stimulation. The aim of this study was to investigate the adhesion molecule expression on endothelial cells in erythroderma in situ.