[Photochemotherapy of neurodermatitis].
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Biomedical subjects
Publications and source records attributed to K Wolff.
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Immunologic membrane markers have been utilized for the in situ identification of lymphoreticular cells within lymphoreticular tissues and in inflammatory and neoplastic lymphoreticular infiltrates of the skin. Frozen sections were layered with untreated sheep red blood cells (SRBC) for the detection of the E receptor on T cells, SRBC coated with 7S antibody for the detection of the Fc receptor (IgGEA) and SRBC coated with 19S antibody and complement (IgMEAC) for the detection of the C3 receptor. In normal lymphoreticular tissue, IgGEA selectively bound to areas colonized by macrophages, IgMEAC to B-dependent areas, whereas E showed no adherence. In chronic lymphatic leukemia, a predominant and selective adherence of IgMEAC was found in lymphoreticular organs which supports the B-cell nature of the neoplastic cells; in leukemic reticuloendotheliosis a selective IgMEAC adherence was observed and this favors a monocytoid origin of the hairy cells. Adherence of any indicator cell was practically absent from skin infiltrates of mycosis fungoides, which represents an additional piece of evidence for the T-cell nature of this disease process. In psoriasis, a considerable binding of IgGEA was observed, whereas IgMEAC did not adhere at all. This result indicates that the lymphocytic part of the infiltrate in this disease consists mainly of T cells.
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Photochemotherapy (PUVA) with oral methoxsalen and UV-A was instituted in 8 patients with generalized pustular psoriasis (von Zumbusch). Complete clearing of skin lesions and of systemic symptoms was achieved in all patients. Patients who had been on systemic treatment prior to PUVA had to be treated with considerably more UV-A energy than patients who had received topical therapy alone. Seven patients were kept in complete remission by maintenance therapy for an observation period of up to 1 1/2 years. Side effects of systemic pre-PUVA treatment resolved during several months of maintenance therapy.
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The effect of photochemotherapy with oral administration of 8-methoxypsoralen followed by irradiation with UVA (PUVA) was investigated in 34 cases of severe, generalized psoriasis which could be controlled only by systemic administration of corticosteroids and cytotoxic agents. In each case clearing of psoriatic lesions was achieved under PUVA treatment. As expected, the average duration of the initial PUVA treatment period was longer when compared to patient groups not pretreated with corticosteroids and cytotoxic agents. In order to avoid relapses, maintenance treatment was installed after complete healing of psoriatic lesions comprising an average of one PUVA exposures per week. Eighty percent of such treated patients are continuously completely clear; the remaining patient group is 70--90% improved. The side effects, elicited by the previous administration of corticosteroids and/or cytotoxic agents are improved or have resolved under PUVA therapy. The present study indicates, that PUVA treatment of psoriasis is not only an alternative to the use of systemic corticosteroids and cytotoxic agents but is superior to these treatment modalities due to its lack of side effects and its higher effectiveness.
Previous studies on skin topically photosensitized with trimethylpsoralen and subsequently irradiated with long-wave UV light have demonstrated an increase in melanosome size and changes in the distribution patterns of melanosomes, suggesting the possibility of gene derepression or the induction of a somatic mutation of melanocytes. The present investigation was performed to determine whether identical changes are induced by systemic photochemotherapy using 8-methoxypsoralen and UVA (PUVA) under therapeutic conditions. Our results show that PUVA stimulates melanogenesis but does not induce significant changes in the average size of melanosomes nor in their distribution patterns within keratinocytes. Thus they indicate that under therapeutic conditions PUVA does not induce morphologically detectable cytogenetic changes in pigment cells.
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Albino mice were made protoporphyric with griseofulvin according to an established procedure. Photosensitivity flares were elicited once a week throughout a 10-month period, using black light as a source for 410 nm radiation and the flares were monitored by the intravenous injection of vascular tracers and by light and electron microscopy. Each irradiation led to a selective destruction of the endothelial cells of superficial capillaries which was followed by massive vascular leakage. The basal lamina remained largely intact, providing the scaffold for regenerating endothelial cells which deposited new basal lamina material at their periphery. Subsequent exposures to 410 nm radiation reproduced the endothelial damage and subsequent basal lamina formation; multiple irradiations thus resulted in excessive, concentric, tubelike basal lamina deposits around dermal vessels which light microscopically appeared as PAS-positive hyaline material and clinically gave the skin a thickened, waxy appearance. This model thus reproduced the skin of erythropoietic protoporphyria clinically, microscopically, and at the ultrastructural level.
IgG and C3 deposits were observed in the basement membrane zone in a case with herpes gestationis. In addition, circulating IgG anti-basement membrane antibodies were found. Electron microscopic immunocytochemical investigations, performed with a peroxidase-antiperoxidase sandwich technique, revealed the in vivo-bound IgG to be localized at the epidermal basal lamina and to exhibit a distribution pattern which is identical to that reported for bullous pemphigoid.
Some trends in electron microscopy of skin have emerged and should be pursued in the future. The fine structure and some basic cellular reaction patterns of epidermal cells are discussed to illustrate the interplay of morphologic, cytochemical, and tracer studies. Intracytoplasmic membranes and secretory granules, lysosomes and endocytic mechanisms, cytomembranes and cell surface specialization are discussed to show how these can be used to arrive at a more meaningful interpretation of structure. Despite all advances, however, a great deal more needs to be done before the details of skin structure are completely elucidated.
A multistep immunocytochemical method utilizing horseradish peroxidase as an immunologically bound marker was used to detect and localize IgA deposits in skin of patients with dermatitis herpetiformis at the ultrastructural level. IgA was found in the upper papillary dermis forming irregular aggregates in seemingly haphazard distribution. These aggregates were associated with microfibrillar bundles and with the microfibrillar component of the elastic tissue. IgA was also detected on anchoring fibrils, but showed no topical relationship to the basal lamina which was always spared. This finding indicates that basal lamina components do not serve as target sites for the immunologic reaction occurring in dermatitis herpetiformis. The selective affinity of IgA deposits to microbfibrillar bundles may be relevant to the hypothesis that the skin pathology in dermatitis herpetiformis is caused by circulating gluten-antigluten complexes, trapped in the skin by reticulin-bound antireticulin antibodies which cross-react with gluten.
8-Methoxypsoralen (8-MOP) and long-wave UV light (UVA 365 nm) are now being use to treat vitiligo and psoriasis. Cultured human lymphocytes exposed to these agents in vitro show an increased infrequency of sister chromatid exchanges, related to 8-MOP-DNA photoadducts. Although these data raise questions regarding the biologic consequences of this therapeutic regimen, it is unknown whether 8-MOP and UVA cause mutations or extracutaneous somatic cell recombinants in vivo. Exchanges may represent cellular repair of DNA damage.