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Fenella Wojnarowska

Publications and source records attributed to Fenella Wojnarowska.

18 recordsLinked to original sources
PubMed2006

Influence of treatment of erosive lichen planus of the vulva on its prognosis.

OBJECTIVE: To record the clinical features, symptomatic response to treatment, and resolution of clinical signs in a large cohort of women with erosive lichen planus of the vulva. DESIGN: Descriptive, prospective cohort study with a mean follow-up of 72 months. SETTING: The vulval clinics of a teaching and district general hospital in Oxfordshire, England. PATIENTS: One hundred fourteen adult women with a definite clinical diagnosis of erosive lichen planus of the vulva.Interventions Patients received topical corticosteroids with or without other topical preparations and systemic treatments as part of their normal care. MAIN OUTCOME MEASURES: Symptomatic response to individual treatments (good, partial, or poor), overall symptomatic response to treatment and with time (good, partial, no change, or worse), response of the vulval signs (total, partial, moderate, minor, same, or worse), and the presence or absence of moderate or severe scarring. RESULTS: The mean age at onset of vulval symptoms was 56.9 years. First-line therapy was an ultrapotent topical corticosteroid in 89 women (78%), of whom 63 (71%) were symptom free while receiving treatment. Overall and with time, 86 women (75%) improved with treatment, including 62 (54%) who were symptom free (good response) and 24 (21%) who had a partial response. Eighteen (16%) had no change and 10 (9%) were worse. Overall response of the vulval signs was recorded in 113 patients. Only 10 (9%) of these had complete resolution of clinical signs excepting scarring, with 57 (50%) showing resolution of erosions. Squamous cell carcinoma developed in 3 women (3%). CONCLUSIONS: Topical ultrapotent corticosteroid is an effective treatment for erosive lichen planus of the vulva, giving relief of symptoms in 71%. With time and treatment, three quarters of patients can expect overall improvement of symptoms and one half, healing of erosions.

Administration, Topical↗
PubMed2005

The association between HLA DR, DQ antigens, and vulval lichen sclerosus in the UK: HLA DRB112 and its associated DRB112/DQB10301/04/09/010 haplotype confers susceptibility to vulval lichen sclerosus, and HLA DRB10301/04 and its associated DRB10301/04/DQB10201/02/03 haplotype protects from vulval lichen sclerosus.

Lichen sclerosus (LS) is considered to have an immunogenetic background. Several small studies, using serological typing, have reported that HLA-DR11, DR12, and DQ7 were increased in LS, with DR17 less frequent. This study aimed to validate and detect new HLA-DR and DQ associations with LS in females and its characteristic clinical parameters. The cases, 187 female LS patients, and 354 healthy controls were all UK North Europeans. PCR-sequence specific primers method was applied to genotype the HLA-DR, DQ polymorphisms that correspond to 17 serologically defined DR and seven DQ antigens. Statistical analysis was performed with two-tailed Fisher's exact test with Bonferroni adjustment (p value after Bonferrroni adjustment, Pc). We found increased frequency of DRB1*12 (DR12) (11.2%vs 2.5%, pc < 0.01) and the haplotype DRB1*12/DQB1*0301/04/09/010 (11.2%vs 2.5%, p < 0.001, pc < 0.05), and a lower frequency of DRB1*0301/04 (DR17) (11.8%vs 25.8%, pc < 0.01) and the haplotype DRB1*03/DQB1*02DRB1*0301/DQB1*0201/02/03 (11.2%vs 24.6%, pc < 0.0001) in patients compared with controls. HLA DR and DQ antigens were not associated with time of onset of disease, site of involvement, structural changes of genitals, and response to treatment with potent topical steroids. In conclusion, HLA-DR and DQ antigens or their haplotypes appear to be involved in both susceptibility to and protection from LS.

Adolescent↗
PubMed2004

Childhood neurological presentation of a novel mitochondrial tRNA(Val) gene mutation.

We describe a young girl with a novel 1659T>C mutation in the tRNA(Val) gene of mitochondrial DNA (mtDNA) who presented with learning difficulties, hemiplegia, and a movement disorder, together with a raised cerebrospinal fluid (CSF) lactate. The mutation, which was present at high levels of heteroplasmy in patient tissues, interrupts a conserved Watson-Crick basepair in the TPsiC stem and has not previously been described in controls. This report further confirms the frequent association of mitochondrial tRNA mutation with neurological presentations, even in paediatric cases.

Adolescent↗
PubMed2004

Immunoblotting and enzyme-linked immunosorbent assay for the diagnosis of pemphigoid gestationis.

OBJECTIVES: To investigate the sensitivity of immunoblotting and enzyme-linked immunosorbent assay (ELISA) to detect autoantibodies to bullous pemphigoid antigen 180 in patients with pemphigoid gestationis and to correlate autoantibody serum levels with disease activity. METHODS: In serum samples obtained from 44 pregnant patients before initiation of therapy and from the same number of healthy blood donors, the autoantibody reactivity was assayed by immunofluorescence microscopy on human skin sections as well as Western blot analysis and 2 different ELISAs by using recombinant forms of the immunodominant domain of BP180. In addition, ELISA reactivity with this autoantigen was assayed in 6 patients during the course of the disease, and its correlation with the clinical disease activity was estimated by applying the Spearman rank correlation test. RESULTS: By indirect immunofluorescence microscopy, complement-fixing autoantibodies to the dermal-epidermal junction were found in 93% of patients' sera. By immunoblotting and ELISA, autoantibodies to bullous pemphigoid antigen 180 were detected in 93% and 86.3% of pemphigoid gestationis patients, respectively, but in none of the healthy controls. Serum levels of autoantibodies as detected by ELISA paralleled the patients' disease activity. CONCLUSIONS: Our study shows that immunoblotting and ELISA are sensitive tools for the detection of autoantibodies to bullous pemphigoid antigen 180 in patients with pemphigoid gestationis. In addition, the ELISA is useful to monitor autoantibody serum levels. LEVEL OF EVIDENCE: II-2

Adolescent↗
PubMed2004

Genetic variation in COL17A1 and the development of bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering disease of the skin characterized by autoantibody attack on collagen XVII. OBJECTIVES: To characterize the genetic complexity of COL17A1, the gene which encodes for the autoantigen collagen XVII. The data will be used to determine whether there is an association between polymorphisms and haplotypes of COL17A1 and genetic susceptibility to development of BP. METHODS: The genetic complexity in COL17A1 was deduced by screening and then sequencing the gene. Haplotypes were constructed from the resulting polymorphisms using the statistical programme PHASE. The linkage disequilibrium (D') between the polymorphisms was deduced from haplotypic data using the statistical programme GOLD. Association of the polymorphisms and haplotypes was tested for, in a cohort of BP patients and controls. RESULTS: Screening of COL17A1 for genetic variation was carried out in 29 individuals of North European caucasoid origin, and it revealed 19 single-nucleotide polymorphisms in approximately 14.7 kb of sequence. These variants resulted in 60 different haplotypes in 191 individuals, of which 13 occurred above 1% in the population. D' between the variants was found to be extensive, have a low correlation with physical distance and to extend over 33.8 kb. No association was found with any of the polymorphisms or haplotypes and development of BP, when tested for, in a cohort of patients and controls. CONCLUSION: This study provides an extensive description of the genetic variation in COL17A1 and shows no association of the genetic variants with susceptibility to BP.

Autoantigens↗
PubMed2004

Circulating basement membrane zone antibodies are found in lichen sclerosus of the vulva.

This study was undertaken to investigate the prevalence of basement membrane zone (BMZ) antibodies, their subtypes and clinical correlations in 96 patients attending the Oxford vulval clinic with lichen sclerosus (LS) of the vulva. Indirect immunofluorescence of serum (intact and split skin) to immunoglobulin (Ig)G was performed looking for the presence or absence of staining at the BMZ. Eighteen patients' sera (14 with positive indirect immunofluorescence to IgG) were examined for IgG antibodies of subclasses IgG1, 2 and 3, and 23 sera were examined for IgG4 subclass. Immunoblotting was performed in seven patients, and showed antibodies to BP180 in six patients and BP230 in one. One-third of patients with vulval LS had BMZ antibodies binding to the epidermal side of salt split skin. Immunoblotting showed antibodies to BP180 collagen XVII (six of seven patients) and BP230 in one. The subclasses were chiefly IgG1 and 2, different from those seen in bullous pemphigoid. No clinical correlation was found between the presence of antibodies and the presence of erosions, severity of scarring, age of onset of disease or response to treatment. These antibodies may be a reflection of a tendency to produce autoantibodies or be relevant to pathogenesis.

Adolescent↗
PubMed2004

Paraneoplastic immunobullous disease with an epidermolysis bullosa acquisita phenotype: two cases demonstrating remission with treatment of gynaecological malignancy.

Two cases of paraneoplastic immunobullous disease occurring in women with gynaecological malignancies are reported. Both cases demonstrated mechanobullous mucocutaneous blistering as is typically seen in epidermolysis bullosa acquisita. Their immunopathology, however, favoured a dermal-binding mucous membrane pemphigoid (MMP) (or possibly bullous pemphigoid) for patient 1 and laminin-5 MMP for patient 2. Both patients showed resolution of blistering within 1 year of treatment of their malignancies; uterine and ovarian carcinoma, respectively. These cases are of interest because of their paraneoplastic nature; as well as overlapping clinicoimmunopathological features. In addition, patient 2 is, as far as we are aware, the first report of ovarian-carcinoma-associated laminin-5 MMP.

Aged↗
PubMed2004

Development of antigen-specific ELISA for circulating autoantibodies to extracellular matrix protein 1 in lichen sclerosus.

Lichen sclerosus is a common, acquired chronic inflammatory skin disease of unknown etiology, although circulating autoantibodies to the glycoprotein extracellular matrix protein 1 (ECM1) have been detected in most patients' sera. We have examined the nature of ECM1 epitopes in lichen sclerosus sera, developed an ELISA system for serologic diagnosis, and assessed clinicopathological correlation between ELISA titer and disease. Epitope-mapping studies revealed that lichen sclerosus sera most frequently recognized the distal second tandem repeat domain and carboxyl-terminus of ECM1. We analyzed serum autoantibody reactivity against this immunodominant epitope in 413 individuals (95 subjects with lichen sclerosus, 161 normal control subjects, and 157 subjects with other autoimmune basement membrane or sclerosing diseases). The ELISA assay was highly sensitive; 76 of 95 lichen sclerosus patients (80.0%) exhibited IgG reactivity. It was also highly specific (93.7%) in discriminating between lichen sclerosus and other disease/control sera. Higher anti-ECM1 titers also correlated with more longstanding and refractory disease and cases complicated by squamous cell carcinoma. Furthermore, passive transfer of affinity-purified patient IgG reproduced some histologic and immunopathologic features of lichen sclerosus skin. This new ELISA is valuable for the accurate detection and quantification of anti-ECM1 autoantibodies. Moreover, the values may have clinical significance in patients with lichen sclerosus.

Animals↗
PubMed2003

Autoantibodies to extracellular matrix protein 1 in lichen sclerosus.

BACKGROUND: Lichen sclerosus is a common acquired inflammatory disorder of skin and mucous membranes. The aetiology is unknown, although HLA-subtype susceptibility and high rates of other autoimmune disorders suggest that autoantibodies to specific mucocutaneous antigens are involved. The clinicopathological similarities between lichen sclerosus and lipoid proteinosis, which results from mutations in extracellular matrix protein 1 (ECM1), suggest this protein as an autoantigen. METHODS: We analysed serum autoantibody profiles in 171 individuals (86 with lichen sclerosus, 85 healthy controls) by immunoblotting of extracts from normal human skin and lipoid proteinosis skin (lacking ECM1). We generated a full-length glutathione-S-transferase fusion protein for ECM1 to confirm specific immunoreactivity. We affinity-purified serum from patients with lichen sclerosus and did indirect immunofluorescence microscopy on normal skin with or without preabsorption with recombinant ECM1. FINDINGS: By immunoblotting, IgG autoantibodies were found in 20 (67% [95% CI 45-84]) of 30 lichen sclerosus serum samples. The highest titre was 1 in 20. The bands were not detected in ECM1-deficient substrate. These samples, and those from 56 other patients with lichen sclerosus, showed immunoreactivity to the recombinant ECM1 protein (64 of 86 positive; 74% [65-84]). Only six (7% [2-13]) of 85 control serum samples were positive. Affinity-purified IgG from serum of patients with lichen sclerosus labelled skin similarly to a polyclonal antibody to ECM1. The positive staining was blocked by preabsorption with excess recombinant ECM1 protein. INTERPRETATION: These findings provide evidence for a specific humoral immune response to ECM1 in lichen sclerosus and offer insight into disease diagnosis, monitoring, and approaches to treatment.

Adult↗
PubMed2003

Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome.

Kindler syndrome is an autosomal recessive disorder characterized by neonatal blistering, sun sensitivity, atrophy, abnormal pigmentation, and fragility of the skin. Linkage and homozygosity analysis in an isolated Panamanian cohort and in additional inbred families mapped the gene to 20p12.3. Loss-of-function mutations were identified in the FLJ20116 gene (renamed "KIND1" [encoding kindlin-1]). Kindlin-1 is a human homolog of the Caenorhabditis elegans protein UNC-112, a membrane-associated structural/signaling protein that has been implicated in linking the actin cytoskeleton to the extracellular matrix (ECM). Thus, Kindler syndrome is, to our knowledge, the first skin fragility disorder caused by a defect in actin-ECM linkage, rather than keratin-ECM linkage.

Abnormalities, Multiple↗
PubMed2003

Pachydermodactyly: a forme fruste of knuckle pads?

A 16-year-old boy presented with painless swellings localized to the radial and ulnar aspects of his second through to the fifth fingers on the left hand, with more subtle changes affecting two fingers on the opposite hand. This had developed in the absence of mechanical trauma. Investigations for an arthropathy were negative, while a biopsy showed marked epidermal hyperplasia and an expanded dermis. These features are typical of pachydermodactyly, a benign dermatosis of uncertain aetiology. The interesting feature of this case is the presence of knuckle pads in the father of the patient, which raises the possibility that these two similar entities are related.

Adipose Tissue↗
PubMed2002

The first international consensus on mucous membrane pemphigoid: definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators.

OBJECTIVE: We aimed to develop consensus-based recommendations for streamlining medical communication among various health care professionals, to improve accuracy of diagnosis and treatment, and to facilitate future investigations for mucous membrane pemphigoid. PARTICIPANTS: Because of the highly specific nature of this group of diseases, the 26 invited participants included either international scholars in the field of mucous membrane pemphigoid or experts in cutaneous pharmacology representing the 3 medical disciplines ophthalmology, oral medicine, and dermatology. EVIDENCE: The first author (L.S.C.) conducted a literature search. Based on the information obtained, international experts who had contributed to the literature in the clinical care, diagnosis, and laboratory investigation for mucous membrane pemphigoid were invited to participate in a consensus meeting aimed at developing a consensus statement. CONSENSUS PROCESS: A consensus meeting was convened and conducted on May 10, 1999, in Chicago, Ill, to discuss the relevant issues. The first author drafted the statement based on the consensus developed at the meeting and the participants' written comments. The draft was submitted to all participants for 3 separate rounds of review, and disagreements were reconciled based on literature evidence. The third and final statement incorporated all relevant evidence obtained in the literature search and the consensus developed by the participants. The final statement was approved and endorsed by all 26 participants. CONCLUSIONS: Specific consensus-based recommendations were made regarding the definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators for mucous membrane pemphigoid. A system of standard reporting for these patients was proposed to facilitate a uniform data collection.

Humans↗
PubMed2002

Interventions for mucous membrane pemphigoid/cicatricial pemphigoid and epidermolysis bullosa acquisita: a systematic literature review.

OBJECTIVE: To identify and critically evaluate evidence from randomized controlled trials for the efficacy of treatments for mucous membrane pemphigoid (MMP)/cicatricial pemphigoid (CP) and epidermolysis bullosa acquisita (EBA). SEARCH STRATEGY: Review of MEDLINE from 1966 through March 2000, EMBASE from 1980 through March 2000, and the Cochrane Controlled Trials Register (February 28, 2001) to identify randomized controlled trials for the efficacy of treatments in MMP/CP and EBA. SELECTION CRITERIA: All randomized controlled trials of therapeutic interventions that included patients with MMP/CP or EBA confirmed by immunofluorescence study findings. All age groups were included. RESULTS: We found 2 small randomized controlled trials of MMP/CP, both conducted in patients with severe eye involvement. We were not able to identify a randomized controlled trial of therapeutic interventions in EBA. CONCLUSIONS: There is evidence from 2 small trials that severe ocular CP responds best to treatment with cyclophosphamide, and mild to moderate disease seems effectively suppressed by treatment with dapsone. No treatment recommendations can be made for EBA because to our knowledge no randomized controlled trials are published. Even though systemic corticosteroids are regarded as the gold standard in the treatment of MMP/CP and EBA, there is poor evidence from the literature that they are the best treatment for these diseases.

Cyclophosphamide↗
PubMed2002

A systematic review of treatments for bullous pemphigoid.

OBJECTIVE: To assess the effectiveness of treatments for bullous pemphigoid. METHODS: The Cochrane Library search strategy was used to identify randomized controlled trials from MEDLINE and EMBASE, from their inception to September 30, 2001. All randomized controlled trials on interventions for bullous pemphigoid, confirmed by immunofluorescence studies, were included. RESULTS: We found 6 randomized controlled trials with a total of 293 patients. Two trials, one comparing prednisolone, 0.75 mg/kg per day, with prednisolone, 1.25 mg/kg per day, and the other comparing methylprednisolone with prednisolone, did not find any significant difference in effectiveness. The higher dose of prednisolone, however, was associated with more severe adverse effects. Combination treatments of prednisone with azathioprine in one trial and of prednisolone with plasma exchange in another were useful in halving the corticosteroid dose required (mean +/- SD, 0.52 +/- 0.28 mg/kg in the plasma exchange-treated group vs 0.97 +/- 0.33 mg/kg in the prednisolone only-treated group). However, a fifth trial, including all 3 treatment groups (prednisolone alone, prednisolone and azathioprine, and prednisolone and plasma exchange), failed to confirm the benefit of combination treatment over prednisolone alone. A trial of 20 patients, comparing prednisone with tetracycline and niacinamide, found no statistically significant difference in response between the 2 groups, but the prednisone-treated group had more serious adverse effects. CONCLUSIONS: There is inadequate evidence for a recommendation of a specific treatment for bullous pemphigoid, and there is a need for larger randomized controlled trials with adequate power. Starting doses of prednisolone greater than 0.75 mg/kg per day do not seem to give additional benefit, and it seems that lower doses may be adequate for disease control. The effectiveness of the addition of plasma exchange or azathioprine to corticosteroids has not been established. Combination treatment with tetracycline and niacinamide seems useful, although this needs further validation.

Azathioprine↗
PubMed2002

Childhood vulvar lichen sclerosus. The course after puberty.

OBJECTIVE: To identify girls with vulvar lichen sclerosus (LS) and to follow them through puberty, documenting the course of the disease. STUDY DESIGN: Twenty-one postpubertal girls were identified from a cohort of 75 girls with LS presenting prepubertally and attending a pediatric vulvar clinic. Details of current symptoms, findings on examination and treatment needs were recorded. A database of 263 women with LS was reviewed for onset of LS premenarche. RESULTS: Of the 21 postpubertal girls, 16 reported an improvement in symptoms, but 11 stated that they still experienced occasional pruritus, requiring intermittent topical steroid application. Although the disorder appeared less active in most cases, definite physical signs persisted in 16 patients (75%); in 5 patients no physical signs of the disease remained. Of 251 postmenopausal women with LS, < 5 could recall symptoms in childhood. Of 12 young adult premenopausal patients with vulvar LS, 4 could recall symptoms in childhood. One of these, a 32-year-old with well-documented LS in childhood resolving at puberty, presented with and died of vulvar squamous cell carcinoma (SCC). CONCLUSION: Patients should be aware that LS may improve symptomatically but usually does not entirely resolve at puberty and that the disease in women may be associated with development of vulvar SCC. Ideally, long-term follow-up should be the standard of care.

Adolescent↗
PubMedDate not supplied

Genital carriage of human papilloma virus (HPV) DNA in prepubertal girls with and without vulval disease.

Human papilloma virus (HPV) can reach a child's anogenital area by vertical transmission or by close contact, which can be either sexual or nonsexual. Our objective was to compare HPV in prepubertal girls with and without lichen sclerosus (LS). We compared the frequencies and types of HPV in girls with LS with those in children with non-LS vulval disease (vulval swab and urine) and in children with no known vulval disease (urine only). HPV DNA was detected using a nested polymerase chain reaction (PCR) with general and consensus primers amplifying a region of the L1 gene, and PCR amplicons were typed using reverse hybridization with labeled HPV type-specific probes. Specimens untypeable by this method were typed by DNA sequencing. In the cohort of children with LS, we recorded the presence of maternal anogenital warts or a dysplastic cervical smear within 3 years of the affected child's birth. We found that HPV was present in the urine and vulval swabs of 8 of 32 children with LS and in 2 of 31 children with non-LS vulval disease, but also in the urine of 7 of 29 controls. In those with LS, the frequency was not increased significantly, but the types were predominantly those commonly associated with dysplasia of the cervix, penis, vulva, and anus, as opposed to the broader spectrum of types found in the control group, not all dysplasia associated. Two of the 32 mothers reported warts, and 15 of 32 (46.9%) had an abnormal smear. (The national average of abnormal cervical smears is less than 10%.) We concluded that HPV appears to be common in all prepubertal girls, but children with LS carried types associated with dysplasia and their mothers had had a high incidence of dyskaryotic smears.

Age Factors↗