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F Wojnarowska

Publications and source records attributed to F Wojnarowska.

At least 19 recordsLinked to original sources
PubMed2003

Interventions for bullous pemphigoid.

BACKGROUND: Bullous pemphigoid is the most common autoimmune bullous disease in the West. Oral steroids are considered the standard treatment. OBJECTIVES: To assess the effects of treatments for bullous pemphigoid. SEARCH STRATEGY: We searched the Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE to March 2003 and bibliographies from identified studies. SELECTION CRITERIA: Randomised controlled trials of treatments for patients with immunofluorescence confirmed bullous pemphigoid. DATA COLLECTION AND ANALYSIS: Two reviewers evaluated the studies in terms of the inclusion criteria, five extracted data independently; disagreements were resolved by discussion. Statistical pooling of the data was inappropriate because of heterogeneity of treatments. MAIN RESULTS: We found seven randomised controlled trials with a total of 634 patients. All studies involved different comparisons, none included a placebo group. Different doses, different formulations of corticosteroids and the addition of azathioprine failed to show significant differences in measures of disease control. However, patients who took azathioprine were able to almost halve the amount of prednisone required for disease control. Plasma exchange plus prednisone achieved significantly better disease control than prednisone alone; this favourable effect was not apparent in another study. The latter study also compared plasma exchange or azathioprine plus prednisone, but failed to show significant differences for disease control or mortality, although total adverse events at six months almost reached statistical significance in favour of plasma exchange plus prednisone. Comparing tetracycline plus nicotinamide with prednisolone, no significant difference for disease response was shown. A very potent topical corticosteroid was compared to oral prednisone in patients with moderate and extensive disease. In patients with extensive disease, the topical steroid group showed significantly better survival and disease control, and less severe complications, while no significant differences for these outcomes were seen in patients with moderate disease. Most of the reported deaths were in patients taking high doses of oral corticosteroids. REVIEWER'S CONCLUSIONS: Very potent topical steroids are effective and safe treatments for bullous pemphigoid; their use in extensive disease may be limited by side effects and practical factors. Starting doses of prednisolone greater than 0.75 mg/kg/day do not seem to give additional benefit, lower doses may be adequate for disease control; this could reduce the incidence and severity of adverse reactions. The effectiveness of the addition of plasma exchange or azathioprine to corticosteroids has not been established. Combination treatment with tetracycline and nicotinamide may be useful; this needs further validation.

Azathioprine↗
PubMed2003

Interventions for mucous membrane pemphigoid and epidermolysis bullosa acquisita.

BACKGROUND: Mucous membrane pemphigoid and epidermolysis bullosa acquisita are acquired autoimmune blistering diseases of the skin. Although they are rare, both can result in scarring of mucous membranes, which may lead to blindness and life threatening respiratory complications. OBJECTIVES: To assess the effects of treatments for mucous membrane pemphigoid and epidermolysis bullosa acquisita. SEARCH STRATEGY: Randomised Controlled Trials (RCTs) of patients with MMP or EBA were identified from MEDLINE and EMBASE from their inception to March 2000. The Cochrane Skin Group Specialised Register and the Cochrane Controlled Trials Register (CCTR) were last examined in February 2002. The bibliographies from identified studies were searched. The author who has conducted clinical trials in the field was contacted to identify unpublished trials. SELECTION CRITERIA: RCTs involving participants of any ages, and with a diagnosis confirmed by immunofluorescence. Where no RCTs were located, studies with other designs were considered. DATA COLLECTION AND ANALYSIS: Data were extracted from all included studies using a defined electronic data extraction protocol. Two reviewers evaluated the studies in terms of the inclusion criteria. The data from identified RCTs was extracted independently by three reviewers and subsequently checked for discrepancies. Any disagreements were resolved by discussion with each other and the fourth reviewer. Meta-analysis was not appropriate due to a lack of data. MAIN RESULTS: We found two small RCTs of MMP, both conducted in patients with severe eye involvement. The same author conducted both trials. In the first trial cyclophosphamide was superior to prednisone after six months of treatment; all 12 patients responded well to cyclophosphamide versus a good response in only five of 12 patients treated with prednisone (relative risk 2.40, 95% confidence interval 1.23 to 4.69). In the second trial all 20 patients treated with cyclophosphamide responded well to it after three months of treatment, but only 14 of 20 patients responded to the treatment with dapsone (relative risk 1.4, 95% confidence interval 1.07 to 1.90). We were not able to identify a RCT of therapeutic interventions in EBA. Thirty reports of uncontrolled studies of treatment for MMP involving five or more patients and 11 reports of treatment for EBA involving two or more patients were found, but were difficult to interpret. REVIEWER'S CONCLUSIONS: There is limited evidence (from two small trials) that severe ocular mucous membrane pemphigoid responds best to treatment with cyclophosphamide combined with corticosteroids, and that mild to moderate disease in most patients seems effectively suppressed by treatment with dapsone. It is difficult to make any treatment recommendations for EBA in the absence of reliable evidence sources.

Cyclophosphamide↗
PubMed2003

Paraneoplastic pemphigus occuring after radiotherapy for relapsed non-Hodgkin's lymphoma in a patient with common variable immunodeficiency.

Paraneoplastic pemphigus (PNP) is a rare multisystem, autoimmune disease with prominent mucocutaneous manifestations, occurring most commonly in association with haematological malignancies. It is characterised by the presence of circulating autoantibodies against epithelial adhesion proteins. We report a 46-year-old woman with common variable immunodeficiency who developed paraneoplastic pemphigus after receiving radiotherapy for relapsed non-Hodgkin's lymphoma. Flaccid bullae covering approximately 70% of the skin, painful oropharyngeal ulceration and periocular erosions were prominent clinical features. Despite supportive treatment and attempts at disease control using high-dose corticosteroids and cyclophosphamide, the patient became increasingly debilitated, developed septic shock secondary to Pseudomonas aeruginosa septicaemia on two occasions and died of respiratory failure 6 weeks after presentation. We highlight the need to be aware of (PNP) and to perform appropriate immunological investigations. In addition, we emphasise the importance of a multidisciplinary approach to the management of such patients.

Common Variable Immunodeficiency↗
PubMed2003

The cellular origins of the linear IgA disease target antigens: an indirect immunofluorescence study using cultured human keratinocytes and fibroblasts.

BACKGROUND: Linear IgA disease (LAD) is an IgA-mediated subepidermal immunobullous disease of adults and children, with heterogeneous immunopathology. Objectives To investigate to what extent the cellular origins of the target antigens account for the heterogeneity of the immune response in LAD. METHODS: Forty-nine adult and 33 childhood LAD sera were studied. Immunofluorescence was carried out to determine the expression of the LAD antigens by normal human keratinocytes, fibroblasts and mixed cultures of keratinocytes and fibroblasts. Immunoblotting was performed to determine the localization of the LAD target antigens in tissue extracts (48 adult and 31 childhood sera) and cell extracts (21 adult and 10 childhood sera). RESULTS: Thirty-one adult and 13 childhood LAD sera bound proteins expressed by human keratinocytes; of these sera, 15 adult and four childhood LAD sera also recognized proteins expressed by fibroblasts. A single adult serum was positive on fibroblasts alone. Seventeen adult and 20 childhood sera were negative on both cell types. There was a modest increase (9%) in the detection of the IgA autoantibodies on keratinocytes and fibroblasts grown together in mixed culture. Immunoblotting showed that the LAD target antigens could be detected in cell as well as in tissue extracts. CONCLUSIONS: Our results have shown that normal human keratinocytes and fibroblasts in culture express the LAD target antigens. LAD sera (with a single exception) bound antigens expressed by keratinocytes alone or by both keratinocytes and fibroblasts. The principal pattern of expression in keratinocytes was cytoplasmic, similar to that demonstrated by polyclonal antibodies to the 180-kDa bullous pemphigoid antigen (BP180). This reflects the pivotal role of BP180 in LAD. The finding that LAD antigens are expressed by both human keratinocytes and fibroblasts in culture may explain the heterogeneity of the target antigens, and may be a contributory factor in the immunopathology of the disease.

Adolescent↗
PubMed2003

Comparison between the expression of basement membrane zone antigens of human interfollicular epidermis and anagen hair follicle using indirect immunofluorescence.

BACKGROUND: The composition of the basement membrane zone (BMZ) or dermal-epidermal junction in the interfollicular skin has been well documented. However, little is known about the BMZ or connective tissue-epithelial junction along the hair follicle. OBJECTIVES: To determine whether the BMZ antigens in the interfollicular epidermis are also present in the BMZ of the anagen hair follicle and to compare whether the expression and distribution of the BMZ components vary between the interfollicular epidermis and the anagen follicle and within different regions of the hair follicle. METHODS: Longitudinal cryostat sections of scalp margin specimens from four adult patients undergoing cosmetic surgery, and without known pathology were stained with a panel of monoclonal and polyclonal antibodies to different BMZ constituents using standard indirect immunofluorescence. RESULTS: All the BMZ antigens found in the normal interfollicular epidermis were expressed in the anagen follicle; however, there were regional variations in the intensity and patterns of fluorescence. All the antigens were expressed in a continuous linear pattern along the BMZ of the interfollicular skin, the infundibulum, and the middle part of the hair follicle. Differences were observed in the lower follicle and the hair bulb. There was continuous expression throughout the BMZ of the follicle of laminin-1 and collagen IV, but in contrast, expression of other antigens decreased down the lower follicle. There was weak or even negative staining with antibodies to alpha 6 beta 4 integrin, laminin-5, anchoring filaments, and type VII collagen in the outer aspect of the bulb compared with the hair papilla. In addition, there were special patterns observed along the bilateral middle and lower follicle. CONCLUSIONS: Despite the common embryological origin between the interfollicular epidermis and the hair follicle, there is variation in the expression of the BMZ antigens. This may be explained by the histological specialization and functional requirements that reflect the dynamic hair growth cycle.

Adult↗
PubMed2003

Lichen sclerosus.

Lichen sclerosus is a chronic skin condition, which offers many challenges to the clinician. It affects men, women and children, and usually occurs in the anogenital area. The clinical signs can be confused with those seen in sexual abuse in children. The underlying cause is unknown; however, there is a strong association with autoimmune disorders, and immunogenetic studies have demonstrated a link with HLA DQ7. Patients suffer significant morbidity as a consequence of the intractable symptoms, physical scarring and psychosexual damage. Support groups may be helpful for some patients. Potent topical corticosteroids have been shown to be effective. There is a 5% incidence of squamous cell carcinoma, and all suspicious lesions should be biopsied. It is unclear whether the risk of malignancy is changed with the use of topical corticosteroids, as there is a potential risk of triggering a latent infection of human papillomavirus. A multidisciplinary approach to care is required and ideally all patients should attend a dedicated clinic and be offered long-term monitoring.

Administration, Topical↗
PubMed2003

Giant lichenification of the scalp.

Lichenification is characterized clinically by thickening of areas of skin as a result of the itch-scratch cycle and therefore is seen in conditions associated with chronic pruritus. The characteristic feature of giant lichenification is the occurrence of tumour-like growths with a warty cribriform surface. We describe a renal transplant patient presenting with giant lichenification of the scalp following an attack of herpes zoster at the same site. Chronic pruritus following scalp dysaethesia secondary to herpes zoster was considered the most likely explanation for the occurrence of these lesions.

Adult↗
PubMed2002

Guidelines for the management of bullous pemphigoid.

These guidelines have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines and a brief overview of epidemiological aspects, diagnosis and investigation. The guidelines reflect data available from Medline, Embase, the Cochrane library, literature searches and the experience of the authors of managing patients with bullous pemphigoid in special and general clinics for over 10 years. However, caution should be exercised in interpreting the data obtained from the literature because only six randomized controlled trials are available involving small groups of patients.

Administration, Topical↗
PubMed2002

HLA-DR and DQ polymorphisms in bullous pemphigoid from northern China.

Bullous pemphigoid (BP) is an autoimmune disease mediated by autoantibodies against hemidesmosome components. This study used PCR-sequence-specific primers to genotype polymorphisms in HLA-DR and DQ in 25 BP patients and 57 normal controls from northern China. We found lower frequencies of DRB1*08 (DR8) and DRB1*08/DQB1*06 (DR8/DQ6) haplotypes in BP patients than in controls (4.08% vs. 15.19% and 1.54% vs. 13.82%, respectively; P < 0.05), suggesting a protective role for DR8 and DR8/DQ6 haplotypes in BP patients from northern China; there were no statistical differences among other alleles tested. This result is strikingly different from previous reports that DQB1*0301 is associated with BP in Caucasian patients and DRB1*1101, DQB1*0302, DRB1*04/DQA1*0301/DQB1*0302 and DRB1*1101/ DQA1*0505/DQB1*0302 with Japanese BP patients. Ethnic differences in the polymorphic composition of the HLA-DR and DQ genes may influence genetic susceptibility to BP.

Case-Control Studies↗
PubMed2002

The accuracy of clinical diagnosis of suspected premalignant and malignant skin lesions in renal transplant recipients.

Renal transplant recipients have a greatly increased risk of nonmelanoma skin cancer. We investigated the accuracy of diagnosis of suspected skin malignancies in this population by prospectively recording all lesions detected in a specialist clinic over 5 months and comparing the provisional diagnosis with the histological diagnosis. The diagnostic accuracy was 54% in the 102 lesions that were biopsied, with the highest accuracy for the head and neck (67%). The diagnostic accuracy for squamous cell carcinoma was 48.7% (sensitivity 90.5%, specificity 75.3%) and for basal cell carcinoma 40.0% (sensitivity 66.6%, specificity 85.6%). The overall low accuracy rate implies the need for biopsy of any suspicious lesions in the renal transplant population.

Aged↗
PubMed2002

Linear IgA disease: successful treatment with erythromycin.

Conventional first-line treatments for linear IgA disease (and the related chronic immunobullous disease of childhood) include topical steroids and dapsone, both of which may be associated with potentially serious side-effects. Alternative anti-inflammatory therapies such as tetracycline and macrolide antibiotics, have been used to treat other immunobullous disorders and we now report an adult case of linear IgA disease and a paediatric case of mixed immunobullous disease of childhood that both responded to the macrolide antibiotic erythromycin. The mode of action is speculative and anti-inflammatory mechanisms are unclear. Nevertheless, from a clinical perspective, erythromycin may have a role in the treatment of linear IgA disease and could be considered ahead of many other, perhaps potentially more toxic, therapies.

Anti-Bacterial Agents↗
PubMed2002

Treatments of choice for bullous pemphigoid.

Bullous pemphigoid (BP) is the most frequently occurring autoimmune blistering disease in Europe and North America. Although it is primarily a disease of the elderly, children and young adults can also develop it. The aim of treatment is to suppress the clinical signs and symptoms of BP without over-treating the patient, because BP tends to spontaneously remit in most patients within approximately 5 years. Mild or localized disease may respond to super-potent topical corticosteroids alone or in combination with tetracyclines with or without niacinamide. More severe or generalized disease usually requires systemic treatment with prednisolone (dose range from 20-70 mg/d). Additional immunosuppressant therapy is necessary for more refractory disease.

Humans↗
PubMed2001

Distribution of upper limb skin cancers in relation to arteriovenous fistula side in renal transplant recipients.

BACKGROUND: Renal transplant patients have an increased incidence of skin cancers, predominantly on sun-exposed surfaces. Clinical observation identified some patients with an increased number of viral warts, keratoses, and skin malignancies on the side of the arteriovenous fistula. METHODS: In a population of 980 patients who underwent transplantation in Oxford, we identified 68 patients with known fistula site who had developed cutaneous malignancies on the upper limbs. We compared the distribution of skin malignancies in relation to the side of the arteriovenous fistula with regard to histologically confirmed Bowen's disease, squamous cell carcinoma, basal cell carcinoma, and keratoacanthoma. RESULTS: No significant difference was found between the distribution of skin cancers, total malignancies or subgroups, in the fistula limbs compared with the nonfistula limbs. CONCLUSION: We have been unable to demonstrate that the presence of an arteriovenous fistula predisposes to the development of cutaneous malignancies.

Arm↗
PubMed2001

Assessment of skin basement membrane zone antibodies in the urine of patients with acquired subepidermal immunobullous diseases.

BACKGROUND: In bullous pemphigoid (BP), cicatricial pemphigoid (CP) and linear IgA disease (LAD), autoantibodies to the basement membrane zone (BMZ) are found in skin and mucosa, blood and blister fluid. OBJECTIVES: To assess whether BMZ antibodies might also be detected in urine. METHODS: Urine and serum samples from 62 patients (32 with BP, 17 with CP and 13 with LAD) were analysed for antibody isotypes and subclasses by indirect immunofluorescence, and urine and serum samples from 40 patients (25 with BP, eight with CP and seven with LAD) were screened for target antigens using immunoblotting. RESULTS: Fourteen of 32 patients with BP had detectable levels of IgG BMZ autoantibodies in their urine, and all 32 had positive sera. Of these 14 BP patients, 13 had epidermal-binding serum autoantibodies at a titre > 1 : 160, and one had dermal-binding serum antibodies at a titre of 1 : 40. BMZ autoantibodies were not detected in the urine of the CP or LAD patients, but the corresponding sera were of low titre or negative. IgG subclasses (IgG1-4) were less frequently detected in urine than in serum. IgG4 was the predominant subgroup found (10 urine samples and all 14 sera), followed by IgG1 (two urine samples and 12 sera); IgG2 was detected in a single urine sample and three sera, and IgG3 was not detected. Eight of 25 BP and one of eight CP urine samples were positive on immunoblotting, and bound BP230 and/or BP180 with IgA and/or IgG autoantibodies. IgA autoantibodies were not detected in the urine of the seven LAD patients. The corresponding sera were often more positive, with 21 of 25 BP, five of eight CP and six of seven LAD sera immunoblotting the major BP antigens. CONCLUSIONS: The detection of IgG autoantibodies from urine samples using indirect immunofluorescence correlated with a high titre of IgG autoantibodies in the serum. IgG and IgA autoantibodies in the urine were detected by immunoblotting, although less frequently than in serum. The finding of BMZ antibodies in the urine of many BP patients may have clinical relevance, and may have a restricted application in the diagnosis of immunobullous disease.

Adult↗