bromochloroacetic-acid and Lupus-Erythematosus--Discoid

Lichen planus (LP) and discoid lupus erythematosus (DLE) are separate disease entities. Nevertheless, patients with a so-called "overlap syndrome" have been described occasionally. The aim of the present study was to establish whether the LE/LP overlap syndrome, based on clinical and routine histological features, could be delineated from DLE or LP using immunohistochemical techniques. Formalin-fixated, paraffin-embedded skin biopsies of patients with DLE, LP and the overlap syndrome were compared regarding immunohistochemical markers for epidermal growth and differentiation and extracellular matrix components. With the markers for extracellular matrix proteins, it was possible to delineate the overlap syndrome from LP. This was not possible for the overlap syndrome and DLE. These findings might indicate that the LE/LP overlap syndrome could be considered as LP-like DLE rather than as a distinct disease entity.

Topics: Adult; Aged; Biomarkers; Biopsy, Needle; Culture Techniques; Diagnosis, Differential; Epidermal Growth Factor; Extracellular Matrix Proteins; Female; Humans; Immunohistochemistry; Keratins; Lichen Planus; Lupus Erythematosus, Discoid; Male; Middle Aged; Syndrome

Clusters of immunoglobulin (Ig)-coated colloid bodies (CBs) in the dermo-epidermal zone are a typical immunohistochemical feature in lichen planus (LP)-lesions. They are considered to represent dyskeratotic basal keratinocytes, yet their composition has not been completely elucidated. In the present study, skin biopsies of 10 LP-lesions, 3 other dermatoses, and 10 biopsies of normal skin were studied immunohistochemically using monoclonal antibodies (MAbs) against fetal and differentiated epidermal antigens. CBs were identified by FITC-anti-Ig. Binding of MAb was visualized by double staining technique. Cytokeratin (CK) 10/11, a marker of epidermal differentiation, was consistently detected in suprabasal keratinocytes and also in up to 95% of Ig-positive CBs in LP. CK10/11 was additionally detected in basal keratinocytes in 9 LP-lesions, but not in normal skin. The basal cell-specific MAb BL7 stained basal layer keratinocytes in all biopsies. In contrast to normal skin, in LP scattered suprabasal keratinocytes and CBs were also positive for BL7 in 10 and 7 cases, respectively. While fetal cytokeratins (CK13 and CK8/18) were completely absent in control skin specimens, both cytokeratins were detected in various numbers of keratinocytes and CBs in all LP-lesions. Our results support the hypothesis of an epidermal origin of CBs. The cytokeratin profile seems to be severely disturbed in LP. This includes both accelerated differentiation by the expression of suprabasal CK10/11 in basal keratinocytes and dedifferentiation by the expression of fetal epidermal antigens (CK13 and CK8/18). It is tempting to speculate that the observed alterations may trigger T-cell activation and inflammatory onset in LP.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Cell Count; Dermatitis, Allergic Contact; Drug Eruptions; Female; Fluorescent Antibody Technique, Direct; Humans; Immunohistochemistry; Inclusion Bodies; Keratinocytes; Keratins; Lichen Planus; Lupus Erythematosus, Discoid; Male; Middle Aged; Skin

In the present study, keratin and involucrin expression were studied in cutaneous lesions of discoid lupus erythematosus and lichen planus in order to gain a better understanding of the abnormal differentiation or maturation of the epidermal cells in these dermatoses. Ten specimens each from discoid lupus erythematosus and lichen planus were analyzed by immunohistochemical techniques, using a panel of monoclonal antikeratin antibodies and polyclonal anti-involucrin antibody, and five specimens each were analyzed by one- and two-dimensional gel electrophoresis and immunoblot analysis using three antikeratin antibodies. No significant difference was found between the dermatoses. The expression of differentiation-specific keratins showed a similar pattern to that in normal epidermis, and involucrin was expressed even in the lower part of the stratum spinosum. Keratins 6 and 16, which are characteristic markers of hyperproliferative states, and keratin 17 were detected in nonhyperproliferative and atrophic epidermis with hydropic degeneration and inflammatory infiltrates in the dermis. These results suggest that expression of keratins 6, 16 and 17 in discoid lupus erythematosus and lichen planus may reflect a wound healing response to the damage to the basal cell layer, or may be under the control of cytokines produced by infiltrating inflammatory cells in the dermis.

Topics: Cell Differentiation; Cellular Senescence; Electrophoresis, Polyacrylamide Gel; Humans; Immunoblotting; Immunoenzyme Techniques; Keratins; Lichen Planus; Lupus Erythematosus, Discoid; Protein Precursors

21 lesions from 16 patients with discoid lupus erythematosus (DLE) were examined immunohistologically using monoclonal antibodies to keratins (K). Markers of basal epithelial cells (the keratin conformation specific basal markers LH6 and LH8), differentiating keratinocytes (K1 and K10), hyperproliferating keratinocytes (K16) and panepidermal keratin (K14), were used. A monoclonal antibody to type VII collagen was used as a guide to the state of the basement membrane zone (BMZ). Keratin distribution in DLE differed from controls. Suprabasal cells were labelled by LH6 in 95% of specimens (19/20) and LH8 in 79% (15/19) in contrast to the basal distribution in normal skin. Reduction of suprabasal LL017 (K1) expression was seen in 59% (10/17) of lesions. An increase of LL025 (K16) expression was seen in 33% (5/15) of specimens. Where LL025 (K16) expression was increased, LL017 (K1) expression was reduced in 80% (4/5). Dermal colloid bodies expressed both basal and suprabasal keratins and were present at sites of maximal basement membrane disruption. These findings are consistent with a model of DLE in which there is an increase in the proliferative basal compartment. This compartment and the associated BMZ suffer fragmentation and loss of colloid bodies to the dermis which express a range of keratins not uniformly associated with basal keratinocytes.

Topics: Antibodies, Monoclonal; Basement Membrane; Biomarkers; Collagen; Humans; Immunohistochemistry; Keratins; Lupus Erythematosus, Discoid

The clinicopathological features of the scarring alopecia of discoid lupus erythematosus (DLE) were studied. Scarring alopecia was present in 34% of 89 patients with DLE and was associated with a prolonged disease course. More than half these patients had scalp involvement at the onset of the disease. There was a significant reduction in size of sebaceous glands in affected scalp. Perifollicular lymphocytic inflammation was maximal around the mid-follicle at the level of the sebaceous gland, which seems to be an important functional level in the follicle. There are changes in the expression of the matrix molecules, the proteoglycans, in the connective tissue sheath and the keratin intermediate filaments in the outer root sheath cells at this level in normal scalp and in diseased scalp. Loss of a population of mid-follicular stem cells may be important in the pathogenesis of scarring alopecia in DLE.

Topics: Adolescent; Adult; Aged; Alopecia; Chronic Disease; Female; Humans; Immunohistochemistry; Keratins; Lupus Erythematosus, Discoid; Male; Middle Aged; Scalp; Sebaceous Glands; Skin Diseases

Discoid lupus erythematosus lesions show hyperkeratosis and atrophy, which may reflect abnormal epidermal proliferation, differentiation, or both. In this investigation, markers for epidermal proliferation, differentiation and inflammation were studied in cutaneous lesions of discoid lupus erythematosus. Frozen sections of biopsy specimens from 20 patients were examined immunohistochemically regarding Ki-67 staining and keratin 16 expression (parameters for proliferation), and the expression of keratin 10, involucrin, and filaggrin (parameters for differentiation). The inflammatory infiltrate was characterized with the use of antibodies against T lymphocytes, monocytes/macrophages, and Langerhans cells. With these markers, epidermal proliferation was found to be increased in discoid lupus erythematosus. Keratin 10 expression, a marker for early differentiation, showed the pattern of normal skin. Involucrin and filaggrin, markers for terminal differentiation, were expressed already in the lower part of the stratum spinosum, whereas in normal skin these markers were restricted to the stratum granulosum and the upper layers of the stratum spinosum, and the stratum granulosum and stratum corneum, respectively. Infiltrate analysis revealed the well-established picture. We conclude that in cutaneous lesions of discoid lupus erythematosus, hyperproliferation is combined with normal early differentiation and premature terminal differentiation of keratinocytes.

Topics: Adult; Aged; Cell Differentiation; Cell Division; Cell Nucleus; Epidermis; Female; Filaggrin Proteins; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Langerhans Cells; Lupus Erythematosus, Discoid; Macrophages; Male; Middle Aged; Monocytes; Protein Precursors; Skin; T-Lymphocytes

Keratinocyte expression of the monocyte/macrophage surface antigens defined by OKM1 and OKM5 antibodies (Ortho Diagnostics) was examined using the peroxidase anti-peroxidase immunohistochemical technique. A range of inflammatory cutaneous disorders were investigated, including lichen planus, psoriasis and atopic dermatitis. Positive suprabasal keratinocyte expression of OKM5 antigen was observed in all disorders, while keratinocyte staining with OKMI antibody was consistently negative. These results provide further evidence that keratinocytes may play an important role in cutaneous immune responses. Furthermore, they are consistent with the recent observation that HLA-DR positive keratinocytes may modulate cutaneous immunological reactions by inducing T-cell unresponsiveness.

Topics: Adult; Antigens, Differentiation; CD36 Antigens; Dermatitis, Atopic; Epidermis; Humans; Keratins; Lichen Planus; Lupus Erythematosus, Discoid; Lymphoma; Monocytes; Psoriasis; Skin Diseases; Skin Neoplasms

Skin biopsy specimens from 24 patients with different lichenoid skin diseases that had been proved histologically were studied immunohistologically. Marked differences were noted in the number of OKT6+/S100+ Langerhans cells within the epidermis and dermis in the lesional skin between lichen planus (and its related disease) and lupus erythematosus; in the former these cells were increased in number; in the latter they were decreased in number compared with those in uninvolved perilesional skin. Human lymphocyte antigen (HLA)-DR expression on keratinocytes was observed not only in lichenoid skin diseases but also in control cases without epidermal involvement. In the two cases of systemic lupus erythematosus, the uninvolved perilesional skin also show weak and focal HLA-DR reactivity in the basal layer. HLA-DR+ keratinocytes could play an important role at least in the perpetuation of epidermal cell damage mediated by T cells.

Topics: Epidermis; HLA-DR Antigens; Humans; Immunoenzyme Techniques; Keratins; Langerhans Cells; Lichen Planus; Lupus Erythematosus, Discoid; Lupus Erythematosus, Systemic; T-Lymphocytes

The use of cultured human epithelial cells as a substrate for the detection of antinuclear antibodies (ANAs) improves the sensitivity of detection above the standard substrates used. Standard antisera have been screened against a series of epithelial cell lines, including keratinocytes. Selected cells have then been used to detect ANAs in 78 patients with discoid lupus erythematosus.

Topics: Antibodies, Antinuclear; Biological Assay; Cell Line; Epidermal Cells; Epidermis; Epithelium; Humans; Keratins; Lupus Erythematosus, Discoid

By electron microscopy colloid bodies have been shown to be derived from epithelial cells. It has been suggested, however, that connective tissue cells or components from the basement membrane zone contributed to the formation of colloid bodies. In order to examine these possibilities we stained oral lesions of discoid lupus erythematosus (DLE) with antibodies against intermediate filaments (keratin, vimentin), basement membrane components (laminin, collagen type IV) and fibronectin. IgM was used as a marker for colloid bodies. Colloid bodies were stained positive for keratin, whereas vimentin was never found in colloid bodies. Laminin and collagen type IV were occasionally seen in their periphery probably owing to adherence of basement membrane fragments during apoptosis. Fibronectin was frequently seen at the entire periphery of colloid bodies which may facilitate their elimination by macrophages. In conclusion, connective tissue cells or basement membrane components do not seem to contribute to the formation of colloid bodies in oral DLE.

Topics: Antibodies, Monoclonal; Basement Membrane; Collagen; Colloids; Cytoplasmic Granules; Humans; Intermediate Filaments; Keratins; Laminin; Lupus Erythematosus, Discoid; Mouth Diseases; Mouth Mucosa; Staining and Labeling

The immunofluorescent staining patterns of oral lesions of discoid lupus erythematosus were examined by use of monoclonal antibodies AE1, AE2 and AE3. AE1 and AE2 showed suprabasal staining, whereas AE3 stained all cell layers of the epithelium. This pattern is consistent with that of other benign hyperkeratinized lesions of the oral mucosa. Occasionally, however, the most basally positioned epithelial cells stained positive with AE1. The morphology of these cells was similar to stratum spinosum cells. Colloid bodies in the epithelium as well as in the connective tissue stained positive with AE1 and AE3, demonstrating their epithelial origin. Few bodies in the connective tissue staining positive with IgM were negative for keratin. These structures may be Russell bodies or may be derived from the basement membrane zone.

Topics: Antibodies, Monoclonal; Colloids; Fluorescent Antibody Technique; Humans; Immunoglobulin M; Keratins; Keratosis; Lupus Erythematosus, Discoid; Mouth Mucosa; Staining and Labeling

The authors have used 5 different monoclonal antikeratin antibodies to study the antigenic profiles of cytoid bodies and skin-limited amyloids. Monoclonal antibodies AE1 (which stains the basal cell layer in normal human epidermis), AE2 (suprabasal layers), AE3 (whole epidermis), EKH4 (lower 2-3 layers), and EKH1 (recognizes all classes of intermediate filaments) were used to stain frozen skin sections by the indirect immunofluorescent or indirect immunoperoxidase technique. Cytoid bodies in lichen planus (LP) and discoid lupus erythematosus (DLE) were strongly stained with AE1, AE3, EKH4, and EKH1 antibodies but were negative with AE2. In contrast, amyloids in lichen amyloidosus and macular amyloidosis were stained strongly with EKH4 but only weakly or not at all with AE1, AE2, AE3, and EKH1. Amyloid associated with epithelial tumors showed closer immunologic profiles to cytoid body. These findings suggest that epidermal keratins are the major precursor substance of skin-limited amyloids as well as cytoid bodies in LP and DLE. Sequential changes in antigenic profiles from basal cells to amyloids through cytoid bodies further suggest that cytoid bodies may represent one of the precursor substances of skin-limited amyloids.

Topics: Amyloid; Amyloidosis; Antibodies, Monoclonal; Carcinoma, Basal Cell; Fluorescent Antibody Technique; Humans; Keratins; Lichen Planus; Lupus Erythematosus, Discoid; Skin Diseases; Skin Neoplasms; Staining and Labeling

Topics: Candidiasis, Oral; Carcinoma in Situ; Diagnosis, Differential; Epithelium; Erythroplasia; Humans; Keratins; Keratosis; Leukoedema, Oral; Leukoplakia, Oral; Lichen Planus; Lupus Erythematosus, Discoid; Melanins; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms; Nevus; Precancerous Conditions; Risk; Sebaceous Glands; Smoking; Stomatitis

Lupus erythematosus profundus (panniculitis) is an unusual clinical variant of lupus erythematosus in which the lesions occur in deeper corium and panniculus. The diagnosis usually causes difficulty. Both reported cases are similar and concern young men with subcutaneous nodules appearing on the face and leaving depressed areas. Histological examination reveals a marked infiltrate in the dermis especially around the skin appendages, reaching the deep dermis and the fat tissue; this infiltarte is composed mainly of lymphocytes and histiocytes. Some moderate epidermal changes are present: liquefaction degeneration of the basal cell layer, epidermal atrophy, thickening of basement membrane (P. A. S.). Direct immunofluorescence of the lesions showed, in one case IgG deposits at the dermo-epidermal junction. Ultrastructural findingd are similar in both cases and may be an important point of diagnosis for isolated forms: -- tubular structures "paramyxo-virus-like-inclusions" are present in dermal infiltrate, endothelial cells and sometimes in keratinocytes of the basal layer; -- the basal lamina has many folds and villous projections;-- vacuoles and concentric lamellar formations are observed inside keratinocytes. No clinical or immunological signs of systemic lupus were found. Antimalaric drugs clear up the nodules.

Topics: Adolescent; Child; Female; Humans; Inclusion Bodies, Viral; Keratins; Lupus Erythematosus, Discoid; Male; Membranes

Topics: Chloroquine; Epithelium; Fibroblasts; Histiocytes; Humans; Keratins; Lupus Erythematosus, Discoid; Lupus Erythematosus, Systemic; Lymphocytes; Macrophages; Microscopy, Electron; Skin; Steroids; Viruses

Topics: Basement Membrane; Carcinoma; Dermatology; Diagnosis, Differential; Esterases; Fluorescent Antibody Technique; Glycogen; Histocytochemistry; Humans; Keratins; Keratoacanthoma; Keratosis; Lupus Erythematosus, Discoid; Mast-Cell Sarcoma; Psoriasis; Skin; Skin Diseases; Skin Neoplasms; Sweat Glands; Urticaria