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V A Venning

Publications and source records attributed to V A Venning.

At least 19 recordsLinked to original sources
PubMed1992

Lack of predictive factors for the clinical course of bullous pemphigoid.

BACKGROUND: Bullous pemphigoid is a clinically heterogeneous disease although little is known of the factors affecting its course and outcome. OBJECTIVE: Our purpose was to document the clinical course, outcomes, and causes of death in treated bullous pemphigoid and to determine the predictive factors affecting outcome. METHODS: The clinical course was documented in 82 patients with immunologically proven bullous pemphigoid (mean follow-up 3 years 2 months). To identify factors predictive of outcome, 16 patients with "good prognosis bullous pemphigoid" (no systemic treatment or in remission within 2 years) were compared with 12 patients with recurrent disease requiring maintenance therapy who still needed treatment after 3 years or longer. Remission was defined as 3 months free of lesions, without systemic treatment. RESULTS: The disease duration varied from 9 weeks to 17 years (estimated median treatment time 2 years 1 month). Of patients followed up for at least 2 years, 30% achieved remission and by 3 years the remission rate was 50%. Two patients had a subsequent relapse (9%). The mortality rate at 1 year was 19%, and treatment was believed to be contributory in seven deaths. No clinical, immunologic, or immunogenetic factors were predictive of disease duration. CONCLUSION: Despite the heterogeneity of the clinical course and duration of bullous pemphigoid, no predictive factors are recognized.

Aged↗
PubMed1992

The distribution of alpha 6 beta 4 integrins in lesional and non-lesional skin in bullous pemphigoid.

The alpha 6 beta 4 integrin is associated ultrastructurally with the hemidesmosomes of the basal keratinocytes and with the bullous pemphigoid antigen (BPA), suggesting an important role in adhesion of epidermal cells to the basement membrane. Using an immunofluorescence technique with chain-specific monoclonal antibodies to the alpha and beta subunits we have investigated the distribution of the alpha 6 beta 4 integrin in normal skin (n = 3) and in BP skin (uninvolved, perilesional and lesional) [n = 11]). The findings have been compared with other types of subepidermal blisters and with normal skin split by chemical means (n = 2) and by suction (n = 2). The distribution of alpha 6 beta 4 integrin was compared with that of bullous pemphigoid antigen (BPA) and with other basement membrane zone (BMZ) macromolecules, laminin, collagen type IV, collagen type VII and the BM600 antigen. In uninvolved, perilesional and early pre-blistered lesional BP skin the distribution of both the alpha 6 and beta 4 integrin subunits, BPA laminin, collagen types IV and VII and the BM600 antigen was identical to normal skin, i.e. a linear band in the BMZ. Within BP blisters, both alpha 6 and beta 4 integrin subunits and BPA were absent, except in two blisters in which the integrin expression was retained in the blister roof, despite loss of BPA. The other BMZ components were expressed on the blister floor.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1992

Absence of expression of class II major histocompatibility complex determinants on keratinocytes in bullous pemphigoid.

Aberrant expression of class II products of the major histocompatibility complex (HLA-D locus antigens) occurs on keratinocytes in several inflammatory dermatoses and on thyroid epithelial cells in autoimmune thyroiditis. The functional significance of aberrant HLA-D expression is unclear but it has been hypothesized that epithelial cells bearing these determinants may act as antigen-presenting cells for autoantigens. The aim of the present study was to investigate the pathogenesis of bullous pemphigoid using immunohistochemical methods to determine whether the HLA-D locus antigens are aberrantly expressed on keratinocytes in lesional and uninvolved skin. A panel of monoclonal antibodies to each of the HLA-D subregions (DR, DP and DQ) and to Langerhans cells was used. Epidermal expression of the HLA-D locus antigens was similar in patients and controls, and there was no significant increase in expression in lesional skin compared with uninvolved skin in six out of nine patients. In three out of nine patients slight enhancement of epidermal HLA-D expression in lesional epidermis corresponded to increased Langerhans cells rather than expression on keratinocytes. HLA-D locus antigens are absent from keratinocytes in bullous pemphigoid skin and aberrant expression of these determinants cannot therefore be implicated in antigen presentation.

HLA-D Antigens↗
PubMed1991

The clinical expression of bullous pemphigoid is not determined by the specificity of the target antigen.

The major bullous pemphigoid (BP) antigen is a 220-240-kDa polypeptide, although some BP sera recognize bands of 180-200 kDa or lower molecular weight. We have investigated to what extent this heterogeneity of the target antigen accounts for the clinical diversity of BP. Immunoblotting studies against extracts of salt-separated epidermis were performed on sera from 39 patients with BP. The blotting patters obtained were correlated with the clinical findings, with particular reference to prodromal itching, lesion morphology and severity, mucosal involvement, presence of milia, dapsone responsiveness and disease duration. The results confirm that the major BP antigen is a 220-kDa polypeptide, and that the 180-kDa polypeptide is a second and sometimes the sole BP antigen identified in immunoblots. Rarely, multiple bands of lower molecular weight were found. There was no correlation between the pattern of BP antigens detected in immunoblots and the clinical presentation and course of BP. There was considerable clinical diversity even among the nine patients showing specificity for a single 220-kDa target antigen. Although two patients with a single 180-kDa antigen specificity had a disease of unusually long duration, factors other than antigen specificity must determine the clinical expression of BP.

Aged↗
PubMed1990

Human papillomaviruses in anogenital warts in children: typing by in situ hybridisation.

OBJECTIVE: To identify the types of human papillomaviruses found in anogenital warts in children and to relate these to clinical and social information. DESIGN: In situ hybridisation using biotin labelled DNA probes to 11 types of human papillomavirus was performed on biopsy specimens from 17 children with anogenital warts. SETTING: Nuffield department of pathology and the department of dermatology, Oxford. PATIENTS: Children in one group were referred by general practitioners or paediatricians to the dermatology department, where biopsies were performed. The other children were seen in four different hospitals, and biopsy specimens were submitted to the laboratory at the physician's or pathologist's request. RESULTS: Of the 17 biopsy specimens, 10 contained cells positive with a probe to a genital human papillomavirus type (types 6 or 11), while six were positive with a skin virus type (types 2 or 3). One was negative. The virus type present bore no relation to the site or appearance of the warts. The virus type did, however, appear to correlate with groups of children. Skin types were commoner in older children (over 4 years), in those with a relative who had skin warts, and in children with warts elsewhere; there was no relation with the child's sex and no suspicion of sexual abuse in these children. These circumstances suggested non-sexual transmission, such as autoinoculation. In contrast, genital types were commoner in girls, in children under 3 years, in children with relatives with genital warts, and in those with no warts elsewhere. Nevertheless, there was suspicion or evidence of sexual abuse in only half these children, suggesting that other routes of transmission--for example, perinatal--might have been implicated. CONCLUSION: Anogenital warts in children may contain either skin or genital wart virus type. Although the type of human papillomavirus present may give some indication of the likely mode of transmission, this can be interpreted only in conjunction with all available clinical and social information. The type of virus does not provide proof of the presence or absence of sexual transmission.

Anus Diseases↗
PubMed1990

The association of bullous pemphigoid and malignant disease: a case control study.

In a case control study, the incidence of malignant disease in 84 patients with bullous pemphigoid (BP) was compared with 168 controls. The rate of malignant disease (past, concurrent or during follow-up) in BP patients was 17.9% compared to 5.3% in the controls. A number of the malignancies occurring in the BP group may be of doubtful significance, being either temporally very remote or partially attributable to treatment. The rate of concurrent BP and malignancy (within 8 weeks) was 6.0% suggesting that there is probably a slight excess of malignancy in BP, but insufficient to warrant extensive investigation in pursuit of cancer. Comparison of the BP patients with and without cancer identified no clinical or immunopathological subgroups in whom investigations would be indicated. Three patients with both BP and malignancy were HLA-DR 13 positive, which may point to an immunogenetic predisposition to both diseases.

Aged↗
PubMed1989

Skin cancer in renal transplant recipients.

Skin cancer was found in 31 of 598 patients transplanted in Oxford. No cases occurred during the first 3 years after transplantation but the prevalence rose after 12 years to 18.2 per cent. The main risk factors predisposing to skin cancer were the time after transplantation and male sex. Comparison with data from other centres suggests that exposure to ultraviolet light is a major aetiological factor in the speed of development of skin cancer. As the incidence of new cases rose progressively with time in our patients, it would seem that skin cancer is likely to become a major clinical problem as more patients enjoy prolonged survival after renal transplantation. Preventative and screening measures should be taken by transplant units both in the UK and in other countries with similar temperate climates.

Adolescent↗
PubMed1989

The localization of the bullous pemphigoid and cicatricial pemphigoid antigens: direct and indirect immunofluorescence of suction blisters.

The location of in vivo bound immunoreactants was studied in 37 patients with subepidermal blistering diseases by direct immunofluorescence (IMF) on suction blisters taken from uninvolved forearm skin. The patients studied included 18 with bullous pemphigoid (BP), nine with cicatricial pemphigoid (CP), three with acquired epidermolysis bullosa (EBA) and 7 hybrid cases. The patterns of IMF in the suction blisters were: BP, epidermal 1, dermal 1, combined 4, negative 12; CP, epidermal 1, dermal 2, negative 6; EBA, dermal 2, negative 1; and 'hybrid' patients, epidermal 3, negative 4. The different patterns of suction blister staining could not be correlated with the clinical features of the patients in respect of mucous membrane involvement, scars or milia or a history of skin fragility. Both BP and CP are probably heterogeneous in respect of their antigen specificity, and the two diseases cannot reliably be distinguished by the patterns of direct IMF on suction blisters. In addition, some individual patients with BP have more than one target antigen as indicated by a combined pattern of suction blister fluorescence. The lack of correlation between the pattern of suction blister fluorescence and the clinical features suggests that factors other than antigen specificity determine the clinical expression of subepidermal blistering diseases.

Adult↗
PubMed1989

Dapsone as first line therapy for bullous pemphigoid.

In an open study, a total of 18 patients with proven bullous pemphigoid (16 new patients and two in relapse) were treated with a trial of dapsone (17 patients) or sulphonimide (one patient). Overall, eight patients were controlled on one of these agents as the sole treatment (44%). Six patients had a partial, but inadequate response, while four did not respond. The responses to the sulpha drugs were generally rapid, i.e. within 2 weeks, and the maximum doses used in any patient were 100 mg/day dapsone and 1.5 g/day of sulphapyridine or sulphamethoxypyridazine. Significant side-effects to dapsone occurred in six of the 17 patients. A trial of a sulphone or sulphonamide drug is warranted in bullous pemphigoid both as an initial treatment or in the treatment of relapse, particularly when there is a contraindication to the use of corticosteroids. Side-effects are common and therapy needs to be closely monitored.

Aged↗
PubMed1989

HLA type in bullous pemphigoid, cicatricial pemphigoid and linear IgA disease.

In a study of 32 patients with bullous pemphigoid (BP), 16 patients with cicatricial pemphigoid (CP) and 10 patients with linear IgA disease (LAD) no significant association was found between these diseases and HLA type of the A, B, C and DR loci. In order to determine whether HLA type modified the clinical expression of these subepidermal diseases, the results were analysed for any association with mucosal involvement, the presence of scarring or the occurrence of a circulating anti-basement membrane zone antibody. No significant associations were found.

Adolescent↗
PubMed1989

Conjunctival involvement in cicatricial and bullous pemphigoid: a clinical and immunopathological study.

Patients with bullous pemphigoid were found to have significant ocular abnormalities. In a group of 18 patients one had conjunctival shrinkage, and 11 of 15 (73%) had positive linear direct immunofluorescence on conjunctival biopsy from a clinically uninvolved site. Our ocular findings in a group of 14 with cicatricial pemphigoid are also reported and compared with those from a control group of 20. Our findings suggest there is overlap between the pemphigoid groups and raise further questions about the pathogenicity of immunoreactants within the basement membrane zone. Bulbar conjunctival biopsy was simple and well tolerated, and the rate of immunofluorescence positivity of conjunctiva was twice that of skin in both pemphigoid groups.

Aged↗
PubMed1988

Patterned androgenic alopecia in women.

Recession of the frontal and frontoparietal hair line in women has been regarded as a marker for pathologic virilization. In a clinical survey of 564 normal women in the population, frontal and frontoparietal recessions were found in 13% of premenopausal and in 37% of postmenopausal women. Patterned hair loss in women is commoner than hitherto described, particularly after the menopause. In the absence of other signs of virilization, "male-pattern" hair loss would therefore appear to be a poor indicator of gross abnormality of androgen metabolism.

Adult↗
PubMed1988

Mucosal involvement in bullous and cicatricial pemphigoid. A clinical and immunopathological study.

Thirty-six patients with bullous pemphigoid (BP) and 15 with cicatricial pemphigoid (CP) were studied for evidence of mucosal involvement both clinically and by direct immunofluorescence. Twenty-one patients with BP and all those with CP had lesions of the mucous membranes. Eighteen patients with BP and 14 patients with CP had involvement of the oral mucosa. Lesions of the eyes, nose, pharynx, vulva and urethra also occurred in both groups. The lesions tended to be more widespread in CP patients. Twenty-one patients with BP and 14 with CP were examined by an ophthalmologist. Fine scarring of the tarsal conjunctiva was found in both groups, but also in elderly controls. However, symblepharon occurred in one patient with BP as well as in three patients with CP, but was not seen in a group of 20 controls. Direct immunofluorescence (IF) studies showed linear deposition of IgG or C3 or both in the basement membrane zone of the skin, oral mucosa and conjunctival mucosa in both groups. The frequency of positive immunofluorescence was higher in the conjunctiva than in the lip mucosa or skin in both BP and CP patients. The significance of these findings and the relationship between BP and CP is discussed.

Aged↗
PubMed1988

Chrysiasis: transmission electron microscopy, laser microprobe mass spectrometry and epipolarized light as adjuncts to diagnosis.

Two patients receiving gold therapy for rheumatoid arthritis developed skin pigmentation, chrysiasis, which in one appeared 4 months after cessation of the therapy. The diagnosis was confirmed by transmission electron microscopy and mass spectrometry laser microprobe analysis of paraffin sections and its extent demonstrated by epipolarized light. The condition is poorly reported and clinically may be confused with silver and mercury impregnation. Tissue diagnosis requires ancillary methods and of these, transmission electron microscopy and laser microprobe mass spectrometry are excellent examples. The transmission electron microscopy findings differ from previous reports and raise doubts on the hypothesis on the role of the skin in gold excretion. Because of the renewed interest in crysotherapy and the latent period that can separate this from chrysiasis, an increase in chrysiasis and the need for its diagnosis can be anticipated.

Arthritis, Rheumatoid↗