Keratoacanthomas: human papillomavirus associated?
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Biomedical subjects
Publications and source records attributed to P O Fritsch.
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Sneddon's syndrome is a potentially fatal arterio-occlusive disorder characterized by generalized livedo racemosa and cerebrovascular lesions. Skin biopsies often fail to yield diagnostic arterial lesions. In the present series, affected vessels were found in skin biopsies from 12 of 15 patients with Sneddon's syndrome. Selection of the correct biopsy site (seemingly uninvolved skin at the center of a livedo racemosa area), adequate biopsy size (1 to 2 cm), and serial sections are essential for the detection of relevant vascular pathology. Only small to medium-sized arteries of the dermis-subcutis boundary were found to be involved. Lesions follow a distinct course. The initial stage displays partial detachment of endothelial cells, adhesion of mononuclear cells interspersed with fibrin ("endothelitis"), a marked edema of the surrounding connective tissue with numerous dilated capillaries, and a predominantly lymphohistiocytic infiltrate with polymorphonuclear leukocytes. In the early phase a sponge-like plug is formed from mononuclear cells, fibrin, and red blood cells, leading to partial to complete obstruction. A perivascular inflammatory infiltrate, devoid of polymorphonuclear leukocytes, is located around affected arteries; in the adventitia of the occluded vessel, a very regular corona of dilated capillaries appears that is continuous with more peripheral dilated and branching vessels. Organization of the occluding plug ensues in the intermediate stage by "subendothelial cell proliferation," most likely due to immigrating smooth muscle cells. In the final stage, the occluding artery undergoes fibrosis, shrinkage, and atrophy.
Synthetic retinoids, particularly the aromatic retinoid etretinate (Tigason, Europe; Tegison, United States), have had an established role in the treatment of psoriasis and a variety of ichthyosiform disorders for more than a decade. Isotretinoin (Accutane), which was released at approximately the same time, plays a less important role in these disorders. The mechanism of action of etretinate is still incompletely understood although, like retinoic acid, it is thought to interfere with the terminal differentiation of keratinocytes. The recent detection of nuclear retinoic acid receptors may lead to a unifying theory of retinoid effects and provide the means for more targeted use of this class of compounds. The substantial amount of data on the clinical effectiveness of etretinate was obtained empirically from numerous multicenter trials and individual reports; its indications, dosimetry, pharmacokinetics, and side effects are well established. The main adverse effect associated with etretinate is its teratogenicity (common to all retinoids), which is of particular concern because the lipophilic compound is stored in fat tissue, resulting in an elimination half-life of as many as 120 days. To avoid this problem the much less lipophilic unesterified acid of etretinate, acitretin, has been made available and has now replaced etretinate in many countries. Acitretin represents the active principle of etretinate and has an elimination half-life of 2 days. No significant clinical differences have been observed between these two compounds. Partial in vivo conversion of acitretin into etretinate, however, has been described in some patients. Both compounds are standard treatment for pustular and erythrodermic psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)
Seventeen male patients with recalcitrant genitoanal warts, who had been unsuccessfully treated with classical destructive modalities for 16 months on average, were included in an open uncontrolled trial. The treatment regimen consisted of caustic and/or surgical measures as judged optimally suited in the individual cases, combined with an intermittent systemic low-dose adjuvant interferon-alpha-2c regimen (3 or 6 5-day-courses with intervals of 2 weeks) followed by a 1-year-observation period. At the end of interferon treatment, no patient had clinically visible warts but 10 still had subclinical acetic acid positive lesions. At the end of the 1-year-observation period, clearance of both warts and acetowhite lesions was observed in 4 patients (23.5%), whereas acetowhite lesions persisted in 4 others (23.5%). Recurrence of clinically visible lesions, always within the acetowhite areas, was observed in 9 (53%) patients. Interferon may thus have been effective in suppressing clinical recurrences of genitoanal warts, but its potency to eradicate subclinical papillomavirus infection was disappointing.
A patient had acquired perforating dermatosis and suffered from renal disease, diabetes mellitus, and lupus vulgaris. Histologic and immunohistochemical studies revealed that the bulk of the coarse granular basophilic material being extruded by transepidermal elimination was of nuclear origin obviously derived from polymorphonuclear leukocytes that were particularly abundant in an early, nonperforated lesion. At the lower boundary of the material being eliminated transepidermally, leukocytes were seen to accumulate, to undergo pyknosis and karyorrhexis, and to transform into nuclear debris. As a minor component, the material contained collagen fibers with altered staining qualities and, in an early lesion, elastic fibers. We speculate that accumulation, disintegration, and enzyme release from polymorphonuclear leukocytes may represent an important, hitherto disregarded driving force in transepidermal elimination. Lysosomal enzymes may later be responsible for the alteration of staining properties in collagen fibers, the degradation of elastic fibers, and for opening up the transepidermal route by impairing intercellular keratinocyte cohesion.
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Erythematous, infiltrated plaques appear to be a common but neglected cutaneous reaction to heparin. Erythematous, infiltrated plaques are unrelated to heparin necrosis and sometimes closely mimic contact dermatitis. We report 15 patients (14 women and 1 man, the first to be reported in the literature) in whom erythematous, infiltrated plaques developed 3 to 21 days after commencement of subcutaneous heparin therapy. The clinical appearance, routine histopathologic and immunohistopathologic findings, and results of various skin tests provided circumstantial evidence for the presence of a delayed hypersensitivity reaction. Subcutaneous provocation tests proved superior to intracutaneous or epicutaneous tests for the diagnosis of erythematous, infiltrated plaques. Erythematous, infiltrated plaques were caused by heparin constituents in all female patients, whereas chlorocresol was implicated as the cause in the only man.
Increasing evidence exists that the spectrum of dendritic cells within the epidermis is more complex than previously thought. In addition to Langerhans cells, Merkel cells, and melanocytes, the murine epidermis contains a dendritic cell population whose most prominent phenotypic feature is the Thy-1 antigen. These cells are now generally referred to as dendritic Thy-1+ epidermal cells (dThy-1+EC). The ultrastructural features of these cells do not resemble those of other resident epidermal cells (EC). In particular, their cytoplasm contains abundant intermediate-sized filaments of the vimentin type as well as membrane-limited organelles with a central granular core. The bone marrow derivation of dThy-1+EC is now well established: dThy-1+EC carry Ly-5 determinants whose expression is restricted to cells of the hemopoietic differentiation pathway, and studies using Thy-1-disparate radiation bone marrow chimeras have revealed the presence of donor-type Thy-1+ cells within the epidermis; by immunoelectron microscopy, these cells represent dThy-1+EC. dThy-1+EC repopulate the epidermis at a slower rate than Langerhans cells as evidenced by a direct comparison of the repopulation kinetics of both cell systems in radiation bone marrow chimeras, and by experiments studying the emergence of either Ia+- or dThy-1+EC in an epidermis which had been previously depleted of either Langerhans cells (glucocorticosteroids) or of dThy-1+EC (PUVA). The phenotypical features of dThy-1+EC differ from those of thymus-derived lymphocytes, B cells, dendritic cells, and mononuclear phagocytes. The surface marker repertoire of dThy-1+EC (Thy-1, Ly-5, asialo-GM1) resembles certain members of the rather heterogeneous natural killer (NK) cell system but functional studies are needed to ascertain this contention.
Differentiation of keratinizing epithelial results in the formation of an exterior cornified layer that is both sufficiently cohesive to provide a protective barrier and dyshesive enough to permit orderly, apical desquamation. Membrane glycoconjugates, which are of presumed importance for intercellular adhesion and growth control, have recently been visualized in mouse, rat, and human epidermis. Because retinoids are known to profoundly influence epidermal differentiation, the lectin-staining pattern in normal mouse epidermis was compared to that observed in mice treated with etretinate (Ro 10-9359, 50 mg/kg/day). Within 2 days of treatment with 50 mg/kg/day of etretinate, abnormal transepidermal water loss began, followed by mild acanthosis after 4 to 6 days, and focal loss of stratification by 10 days. Despite these dramatic alterations in structure and function, abnormalities in lectin staining first appeared only after 15 days. Both wheat germ agglutinin and succinyl wheat germ agglutinin stained an etretinate-dependent product localized in the granular layer in samples treated for 21 to 38 days. Both the intensity and the distribution of PNA (galactose-N-acetyl-galactosamine) and Ulex ( alpha -L-fucose) staining were affected by retinoid treatment, but the staining pattern with other lectins was not altered until 40 to 45 days, at which time the sugars in some samples were either restricted to isolated nests of cells or greatly diminished. Although etretinate appeared to provoke selective changes in keratinocyte membrane glycoconjugates, these alterations became apparent only after the retinoid had profoundly perturbed epidermal differentiation. These altered patterns may not only reflect retinoid-induced aberrations in cohesion and barrier function, but also may provide clues about the role of certain membrane sugars in the control of normal epidermal differentiation.
Primary guinea pig epidermal cell cultures were subjected to a variety of ultrastructural surface labeling techniques specific for lectin binding sites (Concanavalin A-horseradish peroxidase, wheatgerm agglutinin-chitobiosyl-horseradish peroxidase) or anionic surface sites (Ruthenium red, cationized ferritin). All these techniques were carried out on fixed cells; with cationized ferritin, labeling was also performed on unfixed, viable cells by incubation at 4 degrees C and 37 degrees C for various time periods. Lectin labeling resulted in a diffuse pattern identical for both melanocytes and keratinocytes. Different patterns were obtained with the markers for anionic sites: with both ruthenium red and cationized ferritin, fixed keratinocytes were more heavily labeled than melanocytes, the label being diffuse with randomly distributed globular condensations. Melanocytes, in contrast, were lined by a thin uniform band-like label. On viable keratinocytes, exposed to cationized ferritin at 4 degrees C, the label was confined to randomly disseminated patches which most probably represent the "inherent" distribution of anionic surface sites. At 37 degrees C, this pattern was progressively changed by cluster formation as expression of ligand induced label redistribution, shedding and endocytosis of label material. In contrast, viable melanocytes lacked all of these activities except endocytosis, invariably displaying the same uniform diffuse labeling pattern as fixed melanocytes. It is concluded that melanocytes differ from keratinocytes with regard to quantity, distribution, and lateral mobility of anionic surface sites whereas no differences pertain to quantity and distribution of the binding sites to the lectins tested.
Using the epithelial outgrowth in organ cultures of human skin ("epiboly") as a model system for basement membrane zone neogenesis, the emergence of various antigenic determinants of the junction zone (bullous pemphigoid antigen, type IV collagen and laminin) was studied and the time sequence of their appearance assessed. All 3 antigens were found at the newly built dermo-epibolic junction; their synthesis, however, followed a distinct time sequence: bullous pemphigoid antigens emerged synchronously with the advancing tip of the migrating epithelium, whereas type IV collagen and to a greater extent, laminin, appeared with considerable delay. At the ultrastructural level, the formation of basal lamina accompanied the emergence of type IV collagen and laminin.
Sensitivity to epidermolysin was tested in a number of species of the families of mice (muridae) and hamsters (cricetidae) and in hedgehogs. None of the animals proved sensitive except mus musculus (house mouse) and mesocricetus auratus (golden hamster).
Hairless mice were fed with 8-methoxypsoralen by gastric tube and exposed to UVA light to produce threshold phototoxic reactions. 3H-thymidine autoradiography revealed no significant difference of the epidermal labelling index as compared to that of nonirradiated animals (4.8 vs 6.2). Single PUVA exposures performed 2,8,14 and 24 hr after tape stripping lead to suppression of a wave of synchronized DNA synthesis present in nonirradiated control animals. These data demonstrate different reactions of stripped and unstripped epidermis to PUVA exposures and offer indirect evidence for the suppression of DNA synthesis in hyperproliferative skin disorders by PUVA in vivo.
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