Mouth ulcers: how can you help?
Explore the source record for details and available documents.
Bacterial Infections↗
Biomedical subjects
F Wojnarowska
Publications and source records attributed to F Wojnarowska.
Linear IgA disease and ulcerative colitis.
Seventy adult patients with linear IgA disease were studied. Five (7.1%) also suffered from ulcerative colitis (the prevalence of ulcerative colitis in the U.K. is 0.05%). A further three patients with this association, from other British centres were also reviewed. In all cases, ulcerative colitis preceded the onset of skin disease, by a median of 6.5 years. The reason for this association remains unclear but the abnormalities in colonic mucosal B cells and mucosal IgA1 production reported in patients with ulcerative colitis may be important in the subsequent development of IgA1 mediated linear IgA disease.
Adult↗
The location of binding sites of pemphigus vulgaris and pemphigus foliaceus autoantibodies: a post-embedding immunoelectron microscopic study.
Pemphigus is a life-threatening autoimmune blistering disease of skin and mucous membranes that has two major subtypes based on clinical and histological features, pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Autoantibodies against the PV antigen (desmoglein 3) and the PF antigen (desmoglein 1) are involved in the pathogenesis of blister formation. In the present study, the location of epitopes recognized by autoantibodies of patients with PV and PF was studied by postembedding immunogold electron microscopy. PV and PF autoantibodies were observed bound predominantly to the intercellular domains of desmosomes, but not to the non-desmosomal keratinocyte cell surface. The relationship between the location of PF antigen and other constitutive desmosomal proteins, desmocollin, desmoplakin and plakoglobin, in normal human skin was investigated using a double immunogold labelling technique. It was observed that PF antigen and desmocollin co-localize within the intercellular domain of the desmosomes. In contrast, the antibodies against desmoplakin and plakoglobin bound predominantly to the intracellular desmosomal attachment plaque with the binding site of the antibody against plakoglobin closer to the desmosomal cell membrane than that of the antibody to desmoplakin. We show that the LR White postembedded immunogold electronmicroscopy technique is convenient and easily applied to studies of autoimmune bullous skin diseases. We have used it to demonstrate the precise localization of the binding sites of PV and PF autoantibodies and their relationship with other constitutive desmosomal proteins.
Antigens↗
Changes in CD44 isoform expression during inflammatory skin disease.
The CD44 family of cell surface glycoproteins is widely expressed in epithelial, mesothelial and haemopoietic tissues and is thought to function primarily as adhesion molecules. The molecule has an intracellular, a transmembrane and an extracellular domain. The membrane proximal region of the extracellular domain is of variable structure depending on which of 10 variable exons are involved in coding for this region. Both in vitro stimulated T cells and cytokine stimulated keratinocytes are known to express certain isoforms. In this study we have investigated whether specific isoforms of the CD44 molecule are expressed on epithelial cells and lymphocytes in the course of two inflammatory skin diseases, namely lupus erythematosus and lichen planus. Monoclonal antibodies, specific to the epitopes of the CD44 molecule encoded by v3, v4/5, v6 and v8/9 variable exons and a pan CD44 marker, were used on 10 lupus and 8 lichen planus frozen skin samples and compared with normal skin from 9 different body sites. Results failed to show detectable levels of variant isoforms of CD44 on lymphocytes in either inflammatory skin disease, despite evidence of T cell activation. All CD44 variant isoforms were reduced on the keratinocytes in some sections of lupus and lichen planus. The results are discussed in the context of the current models for the role of CD44 in the immune response.
Humans↗
Physicochemical characterization and differentiation of the components of the cutaneous basement membrane zone.
Many of the techniques used in the diagnosis and characterization of the acquired blistering diseases of the skin and of their target antigens require the use of tissue that has been modified by heat, chemicals, or by proteolytic digestion. The effect these treatments may have on the blistering disease antigens is poorly understood and has seldom been taken into account in the interpretation of the results. Likewise, their effect on the immunodetection and expression of the ubiquitous proteins of the basement membrane zone and extracellular matrix has rarely been investigated. We have addressed this problem by probing tissue split after heat, chemical treatment and proteolytic digestion with an extensive panel of antibodies to the hemidesmosome-plasma membrane-anchoring filament complex, the extracellular matrix and the anchoring fibrils. The results showed that chemical modification by sodium chloride, calcium chloride and ethylenediaminetetraacetic acid, and incubation in 0.15 mol/L NaCl at 56 degrees C for 1 min did not adversely affect the expression of the alpha 6 beta 4 integrin, laminin-5, the LH39 antigen, laminin-1, collagen type IV or collagen type VII. The methods that involved proteolytic digestion had the greatest detrimental effect on these basement membrane components, with pepsin having a damaging effect on the greatest number of antigens, and the LH39 antigen being the most sensitive to proteolytic degradation. This project has highlighted the susceptibility of the basement membrane zone and extracellular matrix proteins to proteolytic hydrolysis. It has demonstrated a way of differentiating between specific proteins, and has shown its potential for the differential diagnosis of the autoimmune blistering disease antigens.
Antigens, Surface↗
Topical use of miconazole antifungal oral gel on warfarinized patients: a word of caution.
Oral candidosis is common, particularly in elderly patients who wear dentures. Many of these patients also have systemic diseases, including conditions for which they have to take oral anticoagulants, most commonly warfarin. Although the effect of parenterally administered miconazole on anticoagulant control is well known, the fact that small amounts of topically applied miconazole oral gel can have a similar effect is poorly recognized.
Administration, Oral↗
97-kDa linear IgA bullous dermatosis (LAD) antigen localizes to the lamina lucida of the epidermal basement membrane.
Linear IgA bullous dermatosis (LAD) is an autoimmune blistering disease in which IgA autoantibodies develop against the epidermal basement membrane zone. Target antigens of the circulating autoantibodies are thought to be heterogeneous, and their ultrastructural localization has not been fully elucidated. Previous studies with immunoblotting have demonstrated that the 97-kDa autoantigen is detected most frequently in patients' sera and is thought to be a major LAD antigen. Although a recent report suggests that the 97-kDa antigen localized to the hemidesmosomal plaques and the adjacent lamina lucida, discrepancies still exist among previous immunoelectron microscopic findings. To identify the precise localization of the 97-kDa LAD antigen, we used two different low-temperature immunoelectron microscopic techniques. For immunolabeling, we selected five LAD sera that had a high titer of autoantibodies against the 97-kDa LAD antigen. A post-embedding method with cryofixation and freeze substitution failed to immunolabel the 97-kDa LAD antigen. Cryoultramicrotomy with immunoelectron microscopy succeeded in preserving the antigenicity of the 97-kDa LAD antigen. In all cases, the majority of labeling occurred in the lamina lucida beneath the hemidesmosomes. No specific labeling was observed in the hemidesmosomal attachment plaques or the lamina densa or sublamina densa region, including anchoring fibrils. These results indicate that the 97-kDa LAD antigen is a component of the lamina lucida.
Animals↗
Cicatricial pemphigoid with severe laryngeal involvement necessitating tracheostomy (laryngeal cicatricial pemphigoid).
Cicatricial pemphigoid is a rare autoimmune blistering disease with laryngeal involvement in only 8% of cases. We report the case of a 68-year-old woman with vitiligo, primary hypothyroidism and cicatricial pemphigoid with severe laryngeal involvement necessitating tracheostomy.
Aged↗
Minocycline is a useful adjuvant therapy for pemphigus.
Pemphigus is an autoimmune blistering disease with high mortality if untreated. The cases of 10 patients who had minocycline 100 mg daily added as adjuvant therapy are reported. Prior to the use of minocycline, all patients had active disease, nine were on prednisolone (10-40 mg) and five were on azathioprine (100-200 mg). The response was assessed on clinical improvement and reduction of immunosuppressive (IS) drugs. It was graded into four categories: major, minor, equivocal and no significant response. A major response was seen in four patients, minor in two, equivocal in one and no improvement in three patients. The prednisolone dose in the six responders was reduced to 0-6 mg (0 mg in three patients), with an average decrease of 21 mg. The average time to respond was 8 months. Of the six responders, three were on azathioprine, which was ceased in two patients and reduced by two-thirds in the other patient. No patient ceased minocycline because of side effects. In conclusion, minocycline 100 mg daily is a simple, safe and well tolerated treatment that should be tried in patients with pemphigus to reduce disease activity and/or the dose of potent IS agents.
Adolescent↗
Vulval cicatricial pemphigoid may mimic lichen sclerosus.
We report two patients with vulval signs suggestive of lichen sclerosus. This diagnosis was never substantiated histologically and microscopic appearances were non-specific. In both cases the development of lesions at other cutaneous and mucosal sites alerted us to the possibility that the autoimmune bullous disease, cicatricial pemphigoid, accounted for the entire clinical picture. Lichen sclerosus and cicatricial pemphigoid are distinctive conditions which clinically are usually readily differentiated on cutaneous surfaces. When the site of presentation is on the vulva the clinical picture may become obscure and this can lead to diagnostic confusion. It is important to establish the correct diagnosis as this predicts the clinical course and prognosis in each case.
Aged↗
Bullous pemphigoid and ulcerative colitis: a report of two cases and description of immunoblot findings.
Explore the source record for details and available documents.
Adult↗
Neonatal bullous eruption as a result of transient porphyrinemia in a premature infant with hemolytic disease of the newborn.
We describe the clinical and biochemical features of an infant with marked transient porphyrinemia in whom blistering developed while the infant was undergoing phototherapy for severe Rh isoimmunization. The cause of the transient porphyrinemia was likely to be multifactorial--abnormal porphyrin metabolism or accumulation in a premature infant with multisystem disease and multiple drug therapy. In addition, the infant received an unusually large amount of phototherapy. No evidence for an associated porphyria has been obtained. We believe this is a unique case because transient porphyrinemia associated with neonatal blistering does not appear to have been reported previously. Furthermore, blistering associated with phototherapy is rare.
Erythroblastosis, Fetal↗
The localization of the target antigens and antibodies in linear IgA disease is heterogeneous, and dependent on the methods used.
Fifty-nine patients with linear IgA disease, 24 with onset in childhood and 35 with adult onset, were studied. Sera from all patients were tested by indirect immunofluorescence, using as substrates intact normal skin and normal skin which had been split through the lamina lucida region of the basement membrane zone by suction and by prolonged incubation with molar NaCl. This enabled the site of the target antigen for the circulating IgA antibodies to be determined. The sites of deposition of the IgA antibodies in vivo were detected by raising a suction blister in eight patients, and splitting seven patients' biopsies by prolonged incubation with molar NaCl. Eighteen sera were positive with intact skin, and 34 with split skin. Twenty-nine sera were positive with suction blisters as substrate; 14 bound to the epidermal aspect of the split skin, seven in a combined pattern (binding to the epidermis and dermis) and six to the dermal aspect. Thirty-one sera bound to salt-split skin, 24 to the epidermal side and seven on the dermal side. There was discordance between the two methods of skin splitting in 15 sera. Seven sera gave a combined pattern with suction but with salt-split skin, five of these bound epidermally, one was dermal, and one negative. Five sera showed epidermal binding on salt-split skin and were negative on suction blisters, and the reverse was seen with one serum. Two sera gave variable results on suction blisters. Direct immunofluorescence studies showed dermal binding on all eight patients with suction blisters, and epidermal binding in four and dermal binding in three patients with salt splitting.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Minimizing cicatricial pemphigoid orodynia with minocycline.
Cicatricial pemphigoid is a rare autoimmune blistering disease of the elderly. It predominantly affects the mucosae, causing pain and scarring. the target antigen is within the lamina lucida of the basement membrane zone. Potential complications of systemic steroid and other immunosuppressive therapy have prompted trials of other means of treatment. We describe a series of seven patients treated with minocycline, six of whom derived sustained alleviation of orodynia. Four patients developed hyperpigmentation, and two complained of gastrointestinal discomfort which necessitated cessation of minocycline. Complete steroid withdrawal was achieved in two cases. Neither the disease progression nor the response to treatment was influenced by the immunoglobulin isotype or titre. The role of minocycline as a useful adjunct to therapy is discussed.
Aged↗
Childhood bullous pemphigoid--report of a case with dermal fluorescence on salt-split skin.
Bullous pemphigoid (BP) is an acquired bullous disorder which predominantly affects the elderly. It is rare in children, and may be clinically indistinguishable from other immunobullous disorders. As routine histology may be non-specific, a definitive diagnosis of childhood BP usually depends on the results of direct and indirect immunofluorescence investigations. We report a 5-year-old girl who developed bullous pemphigoid, associated with atypical immunofluorescence findings. Indirect immunofluorescence on split-skin showed a pure dermal pattern of IgG binding. This is usually suggestive of epidermolysis bullosa acquisita, but Western immunoblotting was positive with epidermal extracts, confirming a diagnosis of BP. Dermal binding on split-skin occurs in about 5% of adult cases of BP, and has not been reported previously in childhood BP.
Blotting, Western↗
The association between lichen sclerosus and antigens of the HLA system.
Although frequently linked clinically with autoimmune disease, no immunogenetic basis for lichen sclerosus has ever been established. In this study, we examined in detail the HLA antigens of 84 patients with histologically proven disease, compared with 357 controls. Patients with lichen sclerosus did not have the expected HLA A1, B8, DR3, DQ2 autoimmune profile. Instead, DQ7 was present in 39 of 78 (50%) of patients compared with 89 (25%) controls (P < 0.001). In addition, 61 of 78 patients (78%) had either DQ7, DQ8 or DQ9 antigens, or a combination of these, compared with 142 (40%) controls (P < 0.01). Raised levels of DQ7 correspond to a glutamic acid residue at position 45 of the DQB1 locus. Proline amino acids at position 55 of this DQB1 locus could explain the raised levels of DQ7, 8 and 9, and exert a secondary effect. There is preliminary evidence that the immunogenetic profile of patients with this disease may affect disease expression with regard to site and extent of involvement.
Adolescent↗
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↗