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F Wojnarowska

Publications and source records attributed to F Wojnarowska.

At least 19 recordsLinked to original sources
PubMed1999

Lichen sclerosus in adult men: a study of HLA associations and susceptibility to autoimmune disease.

Lichen sclerosus is a skin disorder of unknown prevalence affecting both men and women, and several studies have established HLA associations in women with this disease. Autoimmune disease associations in the form of a personal and/or family history of autoimmune disease have also been shown to be related to lichen sclerosus. In this study, we examined 58 men (mean age 38 years) with lichen sclerosus, 39 of whom had histologically proven disease. HLA tissue typing by phototyping was performed on these patients and contrasted with that of 602 control subjects. There was no difference in antigen frequencies of the HLA class I loci. The patient group was found to have an increased frequency of several HLA antigens of the class II loci: DR11, 13 of 58 (22%) patients vs. 75 of 602 (13%) control subjects (P = 0.05); DR12, five of 58 (9%) patients vs. 16 of 602 (3%) control subjects (P = 0.04); DQ7, 26 of 58 (45%) patients vs. 189 of 602 (31%) control subjects (P = 0.05). There were few autoimmune disease associations: two of 58 (3%) patients had a personal history of a different autoimmune disease, two patients were found to have abnormal thyroid function and six of 58 (10%) had a first-degree relative with an autoimmune disease. There was no difference in the frequency of the autoimmune haplotype HLA A1, B8, DR3/17, DQ2 compared with the control population. HLA DQ7 has now been shown to occur more frequently in both male and female patients with lichen sclerosus, which may reflect the immunopathogenesis of the disease. Autoimmune disease associations, however, are less common in men with lichen sclerosus.

Adult↗
PubMed1998

Vulvar dermatoses: lichen sclerosus, lichen planus, and vulval dermatitis/lichen simplex chronicus.

In our vulvar specialty clinic at Oxford Radcliffe Hospital (Oxford, UK), dermatoses are frequently seen. A recent survey of new patients showed that lichen sclerosus was the most commonly diagnosed vulvar dermatosis; approximately one third of the women had this disorder. Vulvar dermatitis was observed in 20% to 25% of new patients, but lichen planus was rare. Differences were observed in treatment outcomes for patients with vulvar dermatoses, such as lichen sclerosus and lichen planus, versus those with dermatologic disorders affecting the vulva, such as psoriasis and eczema.

Dermatitis↗
PubMed1998

Drug-induced linear IgA disease with antibodies to collagen VII.

Linear IgA disease (LAD) is characterized by circulating and tissue-bound IgA antibodies against heterogeneous antigens in the cutaneous basement membrane zone. In most cases the cause is unknown, but a minority of cases has been drug induced. We report a 76-year-old man who developed an acute blistering eruption following high-dose penicillin treatment for pneumococcal septicaemia. Indirect immunofluorescence demonstrated dermal binding IgA antibodies, and Western blotting of serum showed reactivity with a 250 kDa dermal antigen corresponding to collagen VII of anchoring fibrils. Indirect immunoelectron microscopy showed antibody labelling in the lamina densa and sublamina densa zone. This is one of the few cases of drug-induced LAD in which the target antigen profile has been characterized, and the first in which the antigen has been shown to correspond to collagen VII.

Aged↗
PubMed1998

Blister fluid for the diagnosis of subepidermal immunobullous diseases: a comparative study of basement membrane zone autoantibodies detected in blister fluid and serum.

The subepidermal immunobullous diseases bullous pemphigoid (BP), cicatricial pemphigoid (CP), pemphigoid gestationis (PG) and linear IgA disease (LAD) are characterized by circulating and in vivo deposition of antibodies to antigens in the cutaneous basement membrane zone (BMZ). Indirect immunofluorescence (IMF) of serum is a routine diagnostic test to detect circulating BMZ antibodies in these diseases. We have compared the titres of IgG and IgA and their subclasses, also of IgM and IgE BMZ antibodies in serum and aspirated blister fluid in 35 adult patients with subepidermal immunobullous diseases: BP (n = 30), PG (n = 2), CP (n = 1), and LAD (n = 2), by indirect IMF on intact and salt-split skin. The antibody titre in blister fluid was the same or one dilution less than serum in most cases and there was no significant difference between these results (P > 0.05). IgG1 and IgG4 were the predominant subclasses in both blister fluid and serum in BP. Indirect IMF of serum and blister fluid was also carried out on trypsinized epidermal cells in a subgroup of patients with BP (n = 19). Typical polar fluorescence was obtained in all 14 cases which had positive indirect IMF on intact and split skin. Our findings demonstrate that blister fluid can be used as an alternative to serum for indirect IMF in subepidermal immunobullous diseases. This avoids the need for venesection and has a practical application in children and those with poor venous access.

Adult↗
PubMed1998

The association of HLA-DQ7 with bullous pemphigoid is restricted to men.

This study examines in detail the HLA associations of 74 patients (40 women and 34 men) with bullous pemphigoid (BP) and compares their immunogenetic profile with that of 604 unrelated control subjects (238 women and 366 men). Correlations were sought between HLA antigens and the various BP disease parameters investigated. The presence of milia was the only clinical or laboratory finding which was linked with a specific HLA antigen, HLA-DQ6, in both men and women with BP (P < 0.01). BP has previously been linked with the HLA-DQ7 antigen and this association was confirmed in 39 of our patients (14 women and 25 men). Twelve of these patients (four women and eight men) were homozygous for HLA-DQ7. The association of HLA-DQ7 with BP was gender-restricted and only significant for men (P < 0.01). No equivalent HLA disease susceptibility risk factor could be identified for our female BP patients. This difference in HLA association between men and women with BP has not been reported previously, and its significance for disease pathogenesis is not known. No specific link could be found between HLA-DQ7 and BP for any of the clinical, immunofluorescence, western blotting, treatment or prognostic disease factors studied.

Aged↗
PubMed1998

The localization of target antigens and autoantibodies in linear IgA disease is variable: correlation of immunogold electron microscopy and immunoblotting.

Linear IgA disease (LAD) of adults and children is a dapsone-responsive, autoimmune subepidermal blistering disease characterized by linear IgA deposits at the basement membrane zone (BMZ) of the skin and mucosa. Circulating IgA antibodies to BMZ components are often present. In this study we investigated the ultrastructural localization of the antigens and autoantibodies in six patients with LAD (five adults and one child). Using a direct postembedding immunogold electron microscopy (EM) technique, three different patterns of IgA antibody deposition were seen in the skin of four patients with LAD. The IgA deposits localized within the uppermost part of the lamina lucida and to the basal surface of the hemidesmosome in two patients, to the lamina lucida in one, and to the lamina densa in the fourth patient. Using an indirect immunogold EM technique and serum or purified blister fluid from two additional LAD patients, we showed that the serum autoantibodies of one patient bound to the hemidesmosome of the BMZ, while the autoantibodies in the blister fluid of the other patient bound to the lamina densa and sublamina densa including the anchoring fibrils in a labelling pattern similar to that of the monoclonal antibody (LH7.2) to collagen VII. All the autoantibodies binding to the hemidesmosome or lamina lucida recognized a protein in epidermal extracts of molecular weight 180 kDa or its breakdown product of 97 kDa, 200 kDa or 230 kDa. The antibodies binding to the lamina densa recognized proteins of 180 and 285 kDa. The antibodies that bound to the lamina densa and anchoring fibrils recognized collagen VII. In this immunogold EM study we have shown four patterns of IgA labelling in six patients with LAD, associated with five different antigens as recognized by immunoblotting. These results, together with our previous immunofluorescence and immunoblotting findings add support to the contention that LAD is a heterogeneous disease as regards both the target antigens and epitopes.

Adult↗
PubMed1998

Epitope spreading: lessons from autoimmune skin diseases.

Autoimmune diseases are initiated when patients develop aberrant T and/or B cell responses against self proteins. These responses presumably are directed to single immunogenic epitopes on these proteins. Recent data in animal models of autoimmune diseases suggest that the targets of immune responses in autoimmunity do not remain fixed, but can be extended to include other epitopes on the same protein or other proteins in the same tissue, a phenomenon termed "epitope spreading." The "epitope spreading" phenomenon also applies to situations in which tissue damage from a primary inflammatory process causes the release and exposure of a previously "sequestered" antigen, leading to a secondary autoimmune response against the newly released antigen. In experimental autoimmune animal diseases, "epitope spreading" seems to have significant physiologic importance in determining the course and duration of disease. In this paper, we review the current concepts in animal models of autoimmune diseases in order to define the "epitope spreading" phenomenon, and we then propose how this phenomenon might play a significant role in the development and the course of autoimmune skin diseases. Hopefully, an understanding of "epitope spreading" will help the dermatology community to better understand the pathogenesis of autoimmune skin diseases and to rationally fashion disease-specific immune therapy in the future.

Animals↗
PubMed1998

Deletions within COL7A1 exons distant from consensus splice sites alter splicing and produce shortened polypeptides in dominant dystrophic epidermolysis bullosa.

We describe two familial cases of dominant dystrophic epidermolysis bullosa (DDEB) that are heterozygous for deletions in COL7A1 that alter splicing, despite intact consensus splice-site sequences. One patient shows a 28-bp genomic deletion (6081del28) in exon 73 associated with the activation of a cryptic donor splice site within this exon; the combination of both defects restores the phase and replaces the last 11 Gly-X-Y repeats of exon 73 by a noncollagenous sequence, Glu-Ser-Leu. The second patient demonstrates a 27-bp deletion in exon 87 (6847del27), causing in-frame skipping of this exon; consensus splice sites, putative branch sites, and introns flanking exons 73 and 87 showed a normal sequence. Keratinocytes from the probands synthesized normal and shortened type VII collagen polypeptides and showed intracellular accumulation of type VII procollagen molecules. This first report of genomic deletions in COL7A1 in DDEB suggests a role for exonic sequences in the control of splicing of COL7A1 pre-mRNA and provides evidence that shortened type VII collagen polypeptides can alter, in a dominant manner, anchoring-fibril formation and can cause DDEB of differing severity.

Adult↗
PubMed1998

Cicatricial pemphigoid rarely involves the scalp.

We present a case of cicatricial pemphigoid with significant scarring alopecia as a major manifestation and review our series of cicatricial pemphigoid patients in Oxford (UK). Only four of 54 patients had scarring alopecia of the scalp. While rare, this manifestation poses a difficult management problem; patients find this cosmetically distressing and there are no successful treatments available to date.

Alopecia Areata↗
PubMed1997

HLA-CW*0602 is a susceptibility factor in type I psoriasis, and evidence Ala-73 is increased in male type I psoriatics.

We investigated the HLA-C locus of 87 unrelated patients with chronic plaque psoriasis by genotyping with sequence-specific amplification primers. The HLA-Cw*0602 allele was significantly increased in male and female type I psoriatics but not significantly increased in either male or female type II psoriatics. The overall frequency of Ala-73 (present in Cw*04, Cw*0602, Cw*07, Cw*12, Cw*1503, and Cw*17) in psoriatics was 88.5% but the incidence of Ala-73 in our Caucasian controls was also high at 84.3%. Ala-73 was present in 97.2% of type I and 85.7% of type II male psoriatics (chi2 = 8.43, p = 0.001; chi2 = 0.01, p = nonsignificant, respectively), in contrast to 81.5% of type I and 80% of type II female psoriatics (nonsignificant). HLA-Cw*0602 appeared more discriminating in determining disease susceptibility in our population than Ala-73, in line with earlier serologic studies implicating HLA-Cw6. Thus, although the frequency of HLA-Cw*0602 decreased from 54.0% in type I to 29.2% in type II psoriatics, the overall frequency of Ala-73, present in 90.4% of type I and 83.3% of type II psoriatics, did not. (i) Thus this study confirms the strong association between psoriasis and HLA-Cw*0602 by using sequence-specific amplification primers. (ii) Results show that Ala-73 on HLA-C molecules is increased in frequency in psoriasis, but results observed show an association more subtle than previously thought, with HLA-Cw*0602 playing the major role. (iii) This report documents the differential association of HLA genes in male and female psoriatic patients. An interaction between gender and immunogenetics may influence susceptibility to psoriasis.

Alleles↗
PubMed1997

Linear IgA disease: a report of two dermal binding sera which recognize a pepsin-sensitive epitope (?NC-1 domain) of collagen type VII.

Linear IgA disease is a subepidermal blistering disease characterized by IgA autoantibody deposition at the basement membrane zone of skin and mucosa. The antigens targeted in linear IgA disease have been defined by their molecular weight and localization. It has been proposed that a minority of linear IgA disease sera that bind to the dermal aspect of salt-split skin target collagen type VII. We have identified two patients with linear IgA disease using dermal binding IgA autoantibodies on salt-split skin which recognize collagen type VII by immunoblot analysis. The reactive epitope was destroyed by the proteolytic enzymes pepsin, which destroys the NC-1 domain of collagen type VII, and protease type VIII. Localization studies compared the IgA autoantibodies from these patients with the monoclonal antibody LH7.2 to the NC-1 domain of collagen type VII and showed colocalization on a dermal cylindroma tumour tissue, and a similar distribution with immunogold electron microscopy, using purified blister fluid from one patient. We propose from these results that the IgA autoantibodies from these two patients recognize the NC-1 domain of collagen type VII, the classical immunodominant epitope for epidermolysis bullosa acquisita.

Adult↗
PubMed1997

Merkel cell carcinoma arising after therapeutic immunosuppression.

Azathioprine and cyclosporin have been used as immunosuppressants for many years, but long-term use has also been associated with neoplasia. We report three cases of rapidly fatal Merkel cell carcinoma in patients who had been treated with azathioprine for many years either for rheumatoid arthritis or following organ transplantation. Two of these patients had also received cyclosporin. We suggest that Merkel cell carcinoma may be seen more commonly in immunosuppressed patients than in the normal population and that the oncogenic potential of azathioprine and cyclosporin should be borne in mind when prescribing these drugs.

Aged↗
PubMed1997

A study of clinical and aetiological factors and possible associations of lichen sclerosus in males.

Lichen sclerosus is a chronic skin condition with a predilection for the genital area. In the present study, 35 male patients with lichen sclerosus were interviewed and examined. Blood screens were performed and histology was requested if not already performed. The findings indicate that lichen sclerosus in males exists as a spectrum of disease, ranging from a mild form with white plaques and few symptoms to a severe form with inflammation, atrophy and scarring with possible urological consequences. In many areas it differs from the condition in females; the association with autoimmune disease is weaker and there is less perianal and extragenital involvement. The association with malignancy in males is of lesser significance than initially believed.

Adolescent↗
PubMed1997

Oesophageal involvement in cicatricial pemphigoid.

Four cases of cicatricial pemphigoid complicated by oesophageal involvement are presented. All patients suffered dysphagia but repeated radiological studies were required for confirmation of oesophageal ulceration, webs and strictures. A combination of systemic drug therapy and oesophageal dilatation were necessary for the suppression of symptoms. The clinical and immunopathological features, management and complications of oesophageal involvement in cicatricial pemphigoid are discussed. Dermatologists should be aware of these features and make regular inquiries about swallowing difficulties in patients with cicatricial pemphigoid to guide appropriate investigations and treatment.

Aged↗