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S M Burge

Publications and source records attributed to S M Burge.

At least 19 recordsLinked to original sources
PubMed1995

Bullous systemic lupus erythematosus: revised criteria for diagnosis.

Blistering in systemic lupus erythematosus has been divided into three groups. A specific subgroup of 'bullous systemic lupus erythematosus' has been defined by Gammon et al. on the basis of a number of criteria. From our experience of seven patients with bullous systemic lupus erythematosus, and after reviewing the literature, we suggest that the current classification is too narrow. Our patients displayed clinical and immunohistological (based on direct and indirect immunofluorescence and Western immunoblotting) heterogeneity. Sera from two patients bound to epidermal epitopes in sodium chloride-split skin, but immunoblotting was negative. In neither of these patients could the target antigen be type VII collagen, the only antigen identified as pathogenic in this disease. Patients with epidermal binding should not be excluded from a diagnosis of bullous systemic lupus erythematosus. SLE is a disease in which there is a genetic predisposition to form antibodies to type VII collagen, along with other autoantibodies, many of which may be implicated in blistering. We suggest that the criteria for the diagnosis of BSLE should be revised. We define this disease as an acquired subepidermal blistering disease in a patient with SLE, in which immune reactants are present at the basement membrane zone on either direct or indirect immunofluorescence.

Adult↗
PubMed1994

Cantharidin-induced acantholysis: adhesion molecules, proteases, and related proteins.

Acantholysis is a feature of disorders such as Hailey-Hailey disease and Darier's disease. Immunocytochemical studies have shown internalization of desmosomal components after acantholysis. Basal cytokeratins show suprabasal expression in lesional Darier's disease. The exact mechanisms of acantholysis are still unclear. Cantharidin induces blistering, with suprabasal keratinocyte acantholysis, possibly by protease activation. Plasmin has been implicated in the pathogenesis of acantholysis in Darier's disease and Hailey-Hailey disease. We examined the distribution of desmosomal components, proteases and cytokeratins in cantharidin blisters, to compare them with those previously found in Darier's disease and Hailey-Hailey disease. Two drops of cantharidin collodion were applied to the skin of five normal volunteers. A 4-mm punch biopsy of the blister was taken, and snap frozen. Sections were stained with antibodies to desmosomal proteins (dp) 1/2, dp 3, desmosomal glycoproteins (dg) 1, 2/3, extracellular carbohydrate residues, using the lectins peanut agglutinin (PNA) and soybean agglutinin (SBA), proteases and cytokeratins. Acantholytic cells were stained diffusely with dp1/2; there was markedly reduced or absent peripheral staining for dp3, dg1, dg2/3, PNA and SBA. There was no clumping of stain. Plasminogen, fibrinogen and urokinase were expressed in some acantholytic cells. Basal keratin markers were expressed suprabasally in acantholytic cells. These results are similar to those previously obtained in Darier's disease, but different from the staining obtained in Hailey-Hailey disease. Extracellular glycosylated portions of adhesion molecules may be lost after acantholysis, perhaps as a result of conformational changes, internalization of extracellular domains, or proteolysis. The changes in the expression of plasminogen, fibrinogen, urokinase and cytokeratins in acantholytic cells in cantharidin-induced blisters are, as in Darier's disease and Hailey-Hailey disease, probably secondary to acantholysis, and changes in the shape of cells. We conclude that cantharidin blisters may be a useful model for the study of acantholysis in Darier's disease.

Acantholysis↗
PubMed1994

Cantharidin-induced acantholysis in Darier's disease: does acantholysis initiate dyskeratosis?

We have examined the action of cantharidin on the skin of patients with Darier's disease, and used immunohistological techniques to determine the distribution of desmosomal components, keratin intermediate filaments, and proteases in cantharidin-induced blisters. Cantharidin induced acantholysis, but the presence of acantholysis did not trigger the development of the characteristic warty, dyskeratotic papules in patients with Darier's disease. The distribution of desmosomal components, keratins and proteases within the acantholytic keratinocytes in the cantharidin-induced blisters was similar to that previously found in acantholytic cells within lesions of Darier's disease: peripheral staining for extracellular desmosomal components was reduced; some desmosomal components were detected diffusely in the acantholytic cells; basal cell keratin markers were expressed by some suprabasal acantholytic cells, and plasminogen was detected in association with acantholytic cells. Cleavage of desmosomes did not reveal the underlying abnormality in Darier's disease.

Acantholysis↗
PubMed1992

Darier-White disease: a review of the clinical features in 163 patients.

BACKGROUND: Darier's disease is a rare, dominantly inherited genodermatosis; there have not been any large clinical studies of patients with this disease. OBJECTIVE: Our purpose was to document the clinical features in a large group of patients with Darier's disease. METHODS: Data were collected from 163 affected persons. RESULTS: The onset usually occurred between the ages of 6 and 20 years. The disease has a predilection for the skin in seborrheic areas; 96% had acral signs; 6% had hypertrophic flexural involvement; and 13% had oral mucosal lesions. There was no remission. Topical therapy sometimes provided relief of symptoms but had no effect on the progress of the disease. Oral retinoids were effective, but long-term therapy was tolerated poorly. Most patients did not have other medical problems. CONCLUSION: Although Darier's disease is a chronic and unremitting burden, most patients manage to lead a relatively normal life.

Adolescent↗
PubMed1992

Adhesion molecules and related proteins in Darier's disease and Hailey-Hailey disease.

We have used antibodies to plakoglobin and E-cadherin: the lectins, peanut agglutinin (PNA) and soybean agglutinin (SBA); and sera from patients with the autoimmune diseases pemphigus vulgaris (PV) or pemphigus foliaceus (PF), in an immunohistological study of Darier's disease and Hailey-Hailey disease. There was normal expression of plakoglobin, E-cadherin, lectins and pemphigus antigens at the periphery of keratinocytes in uninvolved skin. Clumps of plakoglobin were detected within acantholytic cells in Hailey-Hailey disease, whereas expression was diffuse in acantholytic cells in Darier's disease. This difference may reflect differences in the pathogenesis of acantholysis. E-cadherin expression was weak or absent at the periphery of some acantholytic cells; lectin binding was sometimes reduced around acantholytic cells, and pemphigus antibodies did not bind to the acantholytic cells involved skin in either disease. Internalization, conformational changes or proteolysis may alter the expression of extracellular epitopes by acantholytic cells.

Acantholysis↗
PubMed1992

Hailey-Hailey disease: the clinical features, response to treatment and prognosis.

Fifty-eight individuals with Hailey-Hailey disease were studied to delineate the clinical features, response to treatment and prognosis. The disease generally presented between the second and fourth decades, but the morphology of lesions was varied and a delay in diagnosis was common. Nail changes have not been documented in previous studies of Hailey-Hailey disease, but asymptomatic longitudinal white bands were present in the fingernails in 71% of 38 patients examined and are a helpful physical sign. The disease is predominantly flexural. Friction and heat or sweating exacerbate the lesions and pain may limit physical activities. The prognosis was assessed in 27 patients with longstanding disease and the long-term outlook is generally good. Seventeen patients had improved and the disease was static in seven patients. Three patients deteriorated with age. Topical corticosteroids with or without added antibiotics were an effective treatment.

Adolescent↗
PubMed1992

Scarring alopecia in discoid lupus erythematosus.

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.

Adolescent↗
PubMed1992

Plasminogen binding sites in normal human skin.

Plasminogen is detected in the basal cell layer of the epidermis, keratinocytes can generate plasminogen activators and it is suggested that the generation of plasmin may facilitate keratinocyte division, migration and differentiation. In this study we have investigated the characteristics of plasminogen binding sites in normal human epidermis. It was found that 6-aminohexanoic acid and benzamidine displaced endogenous epidermal plasminogen from the basal layer suggesting that endogenous plasminogen binds initially via the kringle 5 aminohexyl (AH) site. Plasminogen binding sites in epidermis were further investigated by displacing endogenous plasminogen and incubating sections with exogenously added glu-plasminogen, lys-plasminogen and plasmin or the isolated plasminogen fragments kringles 1-3, kringle 4 and kringle 5L. The results suggest that the uptake of plasminogen involves primary interaction with the kringle 5AH site and a secondary interaction with lysine binding sites of kringles 1-3. Cell binding is not dependent upon additional reactions of the plasmin active centre.

Aminocaproic Acid↗
PubMed1992

Nasal mucosal involvement in lupus erythematosus.

The involvement of oral, conjunctival and genital mucosa in lupus erythematosus (LE) has recently been described. Reports of nasal involvement have been sporadic. A prospective study was performed to assess the prevalence of nasal symptoms and signs in LE and to identify the incidence of deposition of immunoreactants in the nasal mucosa of patients with LE. Thirty-six patients with LE were studied; 21 had non-specific nasal symptoms and 12 had evidence of chronic inflammatory changes in the mucosa of the nasal cavity or in the vestibule (septal perforation, inflamed mucosa, vestibulitis). Immunoreactants were found in only 4 patients and did not correlate well with clinical evidence of disease. Nasal mucosal involvement in LE is underestimated and often overlooked in the assessment of such patients.

Adult↗
PubMed1991

An immunohistological study of desmosomes in Darier's disease and Hailey-Hailey disease.

The immunocytochemical distribution of desmosomal components was determined in involved skin from eight patients with Darier's disease, five patients with Hailey-Hailey disease and two patients with transient acantholytic dermatosis as well as skin from four normal controls. Sections were stained using monoclonal antibodies to the desmosomal proteins dp1 and dp2 (desmoplakins) and the desmosomal glycoproteins dg1 (desmoglein), and dg2 and dg3 (desmocollins). There was normal expression of desmosomal proteins and glycoproteins at the periphery of the keratinocytes in the perilesional skin in Darier's disease, in Hailey-Hailey disease and in transient acantholytic dermatosis. In the lesional skin there was reduced expression of desmosomal proteins and glycoproteins in the basaloid 'buds' at the base of the lesions, but there was bright diffuse staining of the acantholytic cells. Focal intracellular staining was detected within many of the acantholytic keratinocytes in Hailey-Hailey disease and within some of these cells in Darier's disease. Suction blisters were used to induce fresh acantholysis in lesional skin in Darier's disease and clinically uninvolved skin in Hailey-Hailey disease. The results indicated that acantholysis precedes the development of intracellular staining. Although there are immunopathological abnormalities in the distribution of desmosomal proteins and glycoproteins in both Darier's disease and Hailey-Hailey disease, the changes are probably secondary to internalization of desmosomal components with breakdown and redistribution of antigens rather than a primary deficiency in the synthesis of these proteins. Focal internalization was more widespread in Hailey-Hailey disease than in Darier's disease and the differences in the distribution of desmosomal components in these diseases confirm that they are distinct entities.

Blister↗
PubMed1991

Hailey-Hailey disease: a widespread abnormality of cell adhesion.

Suction has been used to investigate cell adhesion in clinically normal skin in Hailey-Hailey disease. We have demonstrated that there is a widespread subclinical abnormality in keratinocyte adhesion in this disease. There may be a synthesis of functionally deficient adhesion junctions, increased breakdown of adhesion junctions or abnormalities in other adhesion proteins in the epidermis in Hailey-Hailey disease. The findings contrast with those in Darier's disease in which abnormal cell adhesion was only demonstrable in clinically involved skin.

Adult↗
PubMed1991

Cell adhesion in Hailey-Hailey disease and Darier's disease: immunocytological and explant-tissue-culture studies.

The pathogenesis of Hailey-Hailey disease and Darier's disease was investigated using immunocytological and explant-tissue-culture techniques. There was breakdown of the intercellular adhesions between keratinocytes in explants from clinically uninvolved skin of patients with Hailey-Hailey disease or Darier's disease. The major desmosomal components were present in the cultures and were expressed in a punctate peripheral pattern at cell-cell contact sites, but there was diffuse staining of acantholytic cells. Plasminogen, which is expressed by basal keratinocytes in normal skin, was detected in association with suprabasal acantholytic cells in skin biopsies from these diseases. Plasminogen was reversibly displaced from the cells by 6-aminohexanoic acid, suggesting that binding is mediated by a reaction with the lysine receptor on the plasminogen molecule. Plasminogen was also detected in separating cells in explant cultures and there was cytoplasmic expression of the plasminogen activator urokinase by these cells. These abnormalities are not unique to either disease and do not account for the phenotypic differences between Darier's disease and Hailey-Hailey disease, but plasmin generation may have a role in perpetuating cell separation.

Adult↗
PubMed1990

Hair follicle destruction and regeneration in guinea pig skin after cutaneous freeze injury.

We have investigated the histological changes in hair follicles in guinea pig skin after standardized moderate and severe cryosurgery injuries. Hair follicles were permanently destroyed by cryosurgery, but more than one mechanism may be operative during follicle destruction and shedding. The mechanism depends upon the severity of the freeze. After a light freeze injury, the changes are predominantly within the hair follicle. The hair is shed at the surface and there is selective autolysis of follicular cells, but dermal connective tissue is preserved and there is little surrounding damage. However, after a severe cryoinjury as used in "tumor doses," there is destruction of dermal connective tissue and dermal scarring. The necrotic dermis is shed, taking with it the dead follicles and morphologically normal elastic tissue.

Animals↗
PubMed1990

Elastic fibre damage induced by low-dose D-penicillamine.

We have studied 23 patients receiving penicillamine for the treatment of rheumatoid arthritis to determine the prevalence of penicillamine-induced elastosis. One female patient had pseudoxanthoma elasticum-like skin changes and bramble-bush elastosis without calcification in the involved skin. Penicillamine elastosis was present in the joint capsule in 62% of eight patients or 64% of II joints examined and was detected in joint capsules after as little as I year of treatment.

Adult↗
PubMed1990

Darier's disease: a focal abnormality of cell adhesion.

Cell adhesion in clinically normal and involved skin in Darier's disease has been investigated using a suction blister technique. We have been unable to detect a subclinical abnormality in cell adhesion which could predispose to the development of acantholytic papules. There may be synthesis of functionally deficient desmosomes, increased breakdown of desmosomes or abnormalities in other adhesion proteins on the surface of the keratinocyte in Darier's disease, but the abnormality in adhesion is focal and restricted to the clinically and histologically abnormal papules.

Acantholysis↗
PubMed1990

External ocular findings in lupus erythematosus: a clinical and immunopathological study.

A selected group of 18 patients with systemic lupus erythematosus (SLE) and 30 patients with chronic cutaneous lupus erythematosus (CCLE) showed an unexpectedly high incidence of problems involving the globe or eyelids. Five SLE patients had recurrent episcleritis, two CCLE patients had lower tarsal plaques, and two further CCLE patients had erosion of the lower lid margins associated with conjunctival scarring and symblepharon. This association has not previously been reported. There was an unexpectedly high incidence of deposition of immunoreactants in a linear pattern at the basement membrane zone in normal bulbar conjunctiva, which occurred in both SLE (42%) and CCLE (50%). The significance of these findings is discussed. We believe surface ocular problems in lupus erythematosus to be under-reported and that direct immunofluorescence of bulbar conjunctival biopsy might be helpful in diagnosis.

Adult↗