Dependence of apparent diffusion coefficients on axonal spacing, membrane permeability, and diffusion time in spinal cord white matter

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease that occurs in association with underlying neoplasms. Patients with PNP develop characteristic IgG autoantibodies directed against multiple antigens, most of which have been identified as cytoplasmic proteins of the plakin family (desmoplakin I, II, BPAG1, envoplakin, and periplakin). This study identified cell surface target antigens of PNP. We focused on desmoglein (Dsg) 3 and Dsg1, the autoantigens of pemphigus vulgaris and pemphigus foliaceus. ELISA using baculovirus-expressed recombinant Dsgs (rDsg3, rDsg1) has revealed that 25 out of 25 PNP sera tested were positive against Dsg3 and 16 of 25 were positive against Dsg1. All of 12 PNP sera tested immunoprecipitated Dsg3. Removal of anti-Dsg3 autoantibodies by immunoadsorption was sufficient to eliminate the ability of PNP sera to induce cutaneous blisters in neonatal mice in vivo. Furthermore, anti-Dsg3-specific antibodies that were affinity purified from PNP sera were proven to be pathogenic and caused blisters in neonatal mice. These findings indicate that Dsg3 and Dsg1 are the cell surface target antigens in PNP and that IgG autoantibodies against Dsg3 in PNP sera play a pathogenic role in inducing loss of cell adhesion of keratinocytes and causing blister formation.     

Identification of different circulating autoantibodies in patients with bullous pemphigoid and pemphigus vulgaris by means of immunoblotting

Immunoblotting studies with salt-split human epidermis were performed on sera from 15 patients with pemphigus vulgaris and 20 patients with bullous pemphigoid by using peroxidase-labelled antihuman IgG and IgA. Eleven sera of pemphigus vulgaris antigen. Most of the sera gave additional specific bands at 210 and 80 kD, with lower intensity. The sera of 4 patients, 3 of them were in clinical remission, did not yield specific bands. Seventeen sera of the 20 bullous pemphigoid patients yielded a 220-230 kD protein band against the major bullous pemphigoid antigen and 4 of them gave another specific band at 160-180 kD. Five sera produced multiple bands (220, 130, 100 and 75 kD). IgA antibodies against the major bullous pemphigoid antigen were demonstrated in 2 cases with IgA deposits along their basement membrane, as revealed by direct immunofluorescence. The immunoblot patterns correlated only weakly with the clinical findings in bullous pemphigoid. There was a considerable diversity in both clinical findings and immunoblot patterns.     

A case of herpetiform pemphigus associated with autoimmune hemolytic anemia: detection of autoantibodies against multiple epidermal antigens

We report a case who was clinically and histopathologically diagnosed as herpetiform pemphigus (HP) and associated with autoimmune hemolytic anemia (AIHA). However, immunofluorescence studies demonstrated concurrent anti-cell-surface and anti-basement-membrane-zone antibodies in the patient's serum. Immunochemical studies showed that the patient's serum reacted with both the pemphigus foliaceus antigen and the two bullous pemphigoid antigens. Subsequently, the patient developed AIHA. Both anemia and skin lesions were successfully treated with oral prednisolone. We believe that this is the first case with HP in association with AIHA. The presence of autoantibodies against multiple antigens suggests an abnormal immunologic tolerance in the antibody production system in this patient.     

Pemphigus foliaceus sera recognize an N-terminal fragment of bovine desmoglein 1

It has previously been demonstrated that sera from endemic and nonendemic pemphigus foliaceus patients recognize three immunoreactive fragments of 80, 62, and 45 kilodaltons (kD) from extracts of the envelope fraction of human and bovine epidermis. These polypeptides are also immunoprecipitated by approximately 50% of pemphigus vulgaris sera, but are unreactive with sera from bullous pemphigoid patients or normal controls. The 80-kDa antigen has been shown to be a glycoprotein with N-linked oligosaccharides. Complete removal of the carbohydrate moieties produced a 76-kD polypeptide that continued to react with pemphigus foliaceus autoantibodies in a Ca(++)-dependent manner. To further characterize this antigen/antibody system, the 80-kD pemphigus foliaceus antigen solubilized from a bovine epidermal envelope extract was purified by affinity chromatography using a pemphigus foliaceus patient's immunoglobulin (Ig)G immobilized on agarose. After elution with 0.2 M glycine/HCl, pH 2.8, 5 mM ethylene diaminetetraacetic acid, the polypeptide was mixed with a small amount of 125I-labeled 80-kD antigen, added as a tracer, fractionated by sodium dodecylsulfate-polyacrylamide gel electrophoresis, and electrotransferred onto a polyvinylidene difluoride membrane. The 80-kD band detected by amido black staining and autoradiography was excised and characterized by amino acid sequence analysis. The resulting sequence, EXIKFAAAXREGEXNSKRNPIA, matched perfectly with the N-terminal 22 amino acids of the mature form of bovine desmoglein 1. These findings demonstrate that the 80-kD bovine autoantibody-reactive polypeptide is the glycosylated ectodomain of desmoglein 1, which may contain epitopes recognized by pathogenic autoantibodies.     

A paraneoplastic mixed bullous skin disease associated with anti-skin antibodies and a B-cell lymphoma

BACKGROUND: The full spectrum of bullous diseases associated with underlying cancers remains to be fully defined. OBSERVATION: We describe a patient with a mixed bullous disease exhibiting combined features of cicatricial pemphigoid and pemphigus and associated with a B-cell lymphoma producing an IgM paraprotein to intercellular antigens in human skin. The patient had the clinical features of cicatricial pemphigoid and the histologic and immunofluorescence abnormalities of both cicatricial pemphigoid and pemphigus. These included oral and cutaneous erosions; ocular scarring; subbasal and acantholytic intraepidermal bullae; and circulating and tissue-fixed basement membrane zone and intercellular antibodies. The antibodies were directed to a 140-kd antigen in dermal extracts of skin split with 1 mol/L of sodium chloride and to antigens with approximate molecular weights of 150, 180, 230, and 285 kd in the dermal extract. In contrast to paraneoplastic pemphigus, the intercellular antibodies did not react to mammalian bladder. The intercellular antibodies were of the IgM class and were associated with the paraprotein produced by the malignant B cells. CONCLUSIONS: We believe that this condition represents a novel bullous disease, which we refer to as paraneoplastic mixed bullous disease. This condition illustrates that distinct bullous diseases are associated with paraneoplastic syndromes and that at least one possible mechanism for such eruptions is the production of anti-skin antibodies by malignant B cells.     

Cicatricial pemphigoid (benign mucous membrane pemphigoid)

Cicatricial pemphigoid is a chronic mucocutaneous bullous condition. It is a heterogenous autoimmune disease, characterized by the production of autoantibodies against basement membrane zone antigens. The target antigens in cicatricial pemphigoid appear to be lamina lucida proteins involved in human keratinocyte adhesion to extracellular matrix. Cicatricial pemphigoid primarily affects persons older than 40 years and appears to have a 2:1 predilection for women, without racial or geographic bias.     

Effect of nonenzymatic glycosylation on the titers of circulating autoantibodies in pemphigus and pemphigoid

Hyperglycemia is observed in some patients with autoimmune bullous diseases complicated by diabetes mellitus or treated with systemic corticosteroids. High concentrations of glucose can react with various proteins and change their structural and functional properties. We previously reported that nonenzymatic glycosylation of antibody can impair antigen-antibody binding. We ascertained whether glycosylation of autoantibody decreases the autoantibody titer by examining 30 sera from patients with pemphigus and pemphigoid. Nonenzymatic glycosylation in the physiological range was induced by incubation of sera with 1650 mM D-glucose at 4 degrees C for 7 days. The titers of sera were determined by indirect immunofluorescence (IIF). In all cases, the immunofluorescence intensity of glycosylated sera was weaker than that of nonglycosylated sera. Glycosylated sera showed a lower antibody titer by 1 doubling dilution in 18 out of 30 cases, compared with nonglycosylated sera. The ten BP patients' sera were also analyzed by immunoblotting for reactivity with the BP180-GST fusion proteins, S delta 1 and 4575. All BP sera reacted with S delta 1, and 5 out of 10 BP sera reacted with both S delta 1 and 4575. In all the sera that reacted only with S delta 1, the glycosylated sera showed a 1 doubling dilution decrease in autoantibody titer. Interestingly, in 4 out of 5 sera that reacted with both S delta 1 and 4575, there were no differences in the antibody titer between glycosylated and nonglycosylated sera. These results indicate the possibility of a false decrease in autoantibody titers of sera from patients with autoimmune bullous diseases complicated with hyperglycemia. Although the false decrease in titers of autoantibodies induced by nonenzymatic glycosylation is not dramatic, it must be considered in order not to underestimate the disease activity of pemphigus in such cases.     

Reactions to less common species of fire ants

The BP180 antigen, a component of the epidermal anchoring complex, has been identified as one of the major antigenic targets of autoantibodies associated with the blistering skin disease, bullous pemphigoid. Our research group has recently demonstrated that reactivity of bullous pemphigoid autoantibodies to the BP180 ectodomain is almost entirely restricted to a set of four antigenic sites clustered within the membrane-proximal noncollagenous stretch (NC16A). Using a passive transfer mouse model, antibodies to the corresponding noncollagenous region of murine BP180 were shown to trigger an inflammatory subepidermal blistering disease that closely mimics bullous pemphigoid. We now report the development of an enzyme-linked immunoabsorbent assay system that is extremely sensitive in detecting disease-specific autoantibodies in the sera of bullous pemphigoid patients. The target antigen in this assay is a recombinant form of the BP180 NC16A domain that contains all four of the well-defined bullous pemphigoid-associated antigenic sites. Of 50 randomly selected bullous pemphigoid sera tested, 47 (94%) were positive in this assay, whereas no specific reactivity was detected in any of the 107 controls. Interestingly, all three of the bullous pemphigoid sera that were negative in this assay had been obtained from patients who were already undergoing treatment. The NC16A enzyme-linked immunosorbent assay is more sensitive than any of the standard techniques for detecting circulating bullous pemphigoid autoantibodies, including other enzyme-linked immunosorbent assays, immunoblotting, and indirect immunofluorescence. Finally, the NC16A enzyme-linked immunosorbent assay provides immunologic information that cannot be obtained from direct immunofluorescence studies of skin biopsies, and that may well be relevant in the diagnosis and treatment of bullous pemphigoid.     

Antibody deposits in Tzanck smears in pemphigus vulgaris

Forty-three patients, including 24 males and 19 females between 5 and 62 years of age, having pemphigus vulgaris (27), pemphigus foliaceus (1), bullous pemphigoid (3), chronic benign bullous dermatosis of childhood (2) and herpes zoster (10) were included in this study. Tzanck smears were prepared from the floor of the blisters in these patients by deroofing the bullae, and the slides were stored without fixation at room temperature for 1 to 10 days. Immunofluorescence staining was done with FITC-conjugated anti-human IgG. Twenty-one cases having pemphigus vulgaris and 1 case having pemphigus foliaceus showed bright green fluorescence on the membrane of acantholytic cells. No epithelial cells were seen in smears from bullous pemphigoid and chronic benign bullous dermatosis of childhood, whereas epithelial cells were seen in 10 cases of herpes zoster. These stained negative with anti-IgG. Storage of the prepared smears for 1-10 days did not seem to affect the results of immunofluorescence. Tzanck smears can be used as an easy substitute for skin/mucosal biopsy for the direct immunofluorescence test.     

Helix-coil transitions in DNA using a pH variation method: case of a melting paradox as a function of ionic strength

We describe a 31-year-old Japanese woman with generalized pustular psoriasis treated with PUVA who subsequently developed a bullous disease. Throughout the disease course, there was no phase of psoriasis vulgaris. Although several reports describe coexistence of psoriasis vulgaris and bullous disease such as bullous periphigoid, coexistence of generalized pustular psoriasis without any phase of psoriasis vulgaris and bullous disease is rare. As for the bullous disease, direct immunofluorescence study showed IgG and C3 deposition along the basement membrane zone. Indirect immunofluorescence disclosed IgG antibasement membrane zone antibodies. Indirect immunofluorescence on 1 mol/l sodium chloride-split skin demonstrated linear IgG staining almost exclusively on the dermal side of the split. Western immunoblot analysis revealed that the antibody was directed to neither epidermolysis bullosa acquisita antigen nor bullous pemphigoid antigens. Considering the unusual clinical course, we suspect the possibility of a novel autoimmune blistering disease.     

Diagnostic value of indirect immunofluorescence on sodium chloride-split skin in differential diagnosis of subepidermal autoimmune bullous dermatoses

OBJECTIVE: To determine the diagnostic value of indirect immunofluorescence on sodium chloride-split skin (SSS) in differentiating the pemphigoid group of subepidermal autoimmune bullous dermatoses, including bullous pemphigoid (BP), cicatricial pemphigoid, and pemphigoid gestationis, from epidermolysis bullosa acquisita (EBA). DESIGN: Serum samples were tested using immunofluorescence on SSS and immunoblot assay on epidermal and dermal extracts, a recombinant protein corresponding to the C-terminal end of the 230-kd BP antigen, and purified laminin-5. SETTING: An immunodermatology laboratory. PATIENTS: One hundred forty-two serum samples from patients with BP (n = 98), cicatricial pemphigoid (n = 23), pemphigoid gestationis (n = 10), EBA (n = 10), and anti-type IV collagen (n = 1). MAIN OUTCOME MEASURES: Binding sites of serum to the epidermal and/or dermal sides of SSS were correlated with their antigenic specificities. RESULTS: Epidermal staining on SSS was highly specific for pemphigoid. Alternatively, a poor correlation was found for the dermal-reacting serum samples and the diagnosis of EBA; of the 19 serum samples with dermal staining on SSS, only 10 reacted with the EBA antigen. The remaining serum samples were from patients with cicatricial pemphigoid having antibodies to the alpha 3 or beta 3 chains of laminin-5 (n = 5) or patients with BP having antibodies to the 180-kd BP antigen (n = 2). One sample recognized exclusively a 185-kd dermal antigen corresponding to type IV collagen. One more BP serum sample with dermal staining did not recognize any dermal or epidermal antigen. CONCLUSION: In case of immunofluorescent dermal staining, the precise diagnosis should be confirmed by identification of the involved antigen, since it may reveal antibodies to laminin-5 or type XVII or IV collagen, in addition to the EBA antigen.     

Identification and characterization of autoreactive T cell responses to bullous pemphigoid antigen 2 in patients and healthy controls

Antibodies against the extracellular domain of bullous pemphigoid antigen 2 (BPAG2) are thought to play a key role in the pathogenesis of bullous pemphigoid (BP), the most frequent autoimmune bullous disease of the skin. Autoreactive T cell responses to BPAG2 were investigated in 16 BP patients and 24 healthy controls by coculture of PBMC with two recombinant BPAG2 proteins (extracellular domain of BPAG2). Primary in vitro T cell responses to BPAG2 were observed in 10/12 BP patients expressing the BP-associated HLA-DQB1*0301 allele and 8/10 DQB1*0301 positive healthy individuals. DQB1*0301 also restricted three autoreactive T cell lines from two BP patients and a healthy donor. In contrast, PBMC from 14 normal patients carrying HLA class II alleles other than DQB1*0301 were not stimulated by BPAG2. Autoreactive BPAG2-specific CD4(+) T cell lines and clones from five BP patients produced both Th1 and Th2 cytokines, whereas three autoreactive T cell lines from three DQB1*0301 positive normal patients produced exclusively IFN-gamma. The absence of BPAG2-specific Th2 cells in healthy individuals strongly suggests that autoreactive Th2 responses to BPAG2 are restricted to BP patients and may thus be critical in the pathogenesis of BP.     

Hemidesmosome formation is initiated by the beta4 integrin subunit, requires complex formation of beta4 and HD1/plectin, and involves a direct interaction between beta4 and the bullous pemphigoid antigen 180

Hemidesmosomes (HDs) are stable anchoring structures that mediate the link between the intermediate filament cytoskeleton and the cell substratum. We investigated the contribution of various segments of the beta4 integrin cytoplasmic domain in the formation of HDs in transient transfection studies using immortalized keratinocytes derived from an epidermolysis bullosa patient deficient in beta4 expression. We found that the expression of wild-type beta4 restored the ability of the beta4-deficient cells to form HDs and that distinct domains in the NH2- and COOH-terminal regions of the beta4 cytoplasmic domain are required for the localization of HD1/plectin and the bullous pemphigoid antigens 180 (BP180) and 230 (BP230) in these HDs. The tyrosine activation motif located in the connecting segment (CS) of the beta4 cytoplasmic domain was dispensable for HD formation, although it may be involved in the efficient localization of BP180. Using the yeast two-hybrid system, we could demonstrate a direct interaction between beta4 and BP180 which involves sequences within the COOH-terminal part of the CS and the third fibronectin type III (FNIII) repeat. Immunoprecipitation studies using COS-7 cells transfected with cDNAs for alpha6 and beta4 and a mutant BP180 which lacks the collagenous extracellular domain confirmed the interaction of beta4 with BP180. Nevertheless, beta4 mutants which contained the BP180-binding region, but lacked sequences required for the localization of HD1/plectin, failed to localize BP180 in HDs. Additional yeast two- hybrid assays indicated that the 85 COOH-terminal residues of beta4 can interact with the first NH2-terminal pair of FNIII repeats and the CS, suggesting that the cytoplasmic domain of beta4 is folded back upon itself. Unfolding of the cytoplasmic domain may be part of a mechanism by which the interaction of beta4 with other hemidesmosomal components, e.g., BP180, is regulated.     

Chromosomal localisation of the human envoplakin gene (EVPL) to the region of the tylosis oesophageal cancer gene (TOCG) on 17q25

Envoplakin is a membrane-associated precursor of the epidermal cornified envelope. Envoplakin is homologous to desmoplakin I and desmoplakin II (DPI/II), bullous pemphigoid antigen 1 (BPAG1), and plectin and is proposed to link desmosomes and keratin filaments to the cornified envelope. We describe the isolation of cosmids and yeast artificial chromosomes containing the complete human envoplakin gene (EVPL) and show, by analysis of somatic cell hybrids and chromosomal in situ hybridisation, that the envoplakin gene, unlike the genes encoding BPAG1 and DPI/II, maps to 17q25 and is physically linked to D17S1603. This sequence-tagged site segregates with the autosomal dominant human disease focal nonepidermolytic palmoplantar keratosis (NEPKK; "tylosis"), which is associated with an increased risk of oesophageal cancer. The chromosomal localisation of the envoplakin gene, the homology of the encoded protein to keratin-binding proteins, and its expression in epidermal and oesophageal keratinocytes all raise the possibility that loss of envoplakin function could be responsible for this form of palmoplantar keratoderma.     

Functional involvement of urokinase-type plasminogen activator receptor in pemphigus acantholysis

Urokinase-type plasminogen activator (uPA) has been well documented in the development of pemphigus acantholysis. The function of its receptor (uPA-R) in pemphigus acantholysis has only recently attracted attention. Increased expression of uPA-R has been demonstrated in pemphigus vulgaris. In this study, we have further explored the functional involvement of uPA-R in pemphigus acantholysis. Our results show that uPA-R expression is significantly increased in acantholytic foci of pemphigus vulgaris and pemphigus foliaceus but not in bullous pemphigoid or normal skin specimens; the expression of uPA-R in cultured human keratinocytes is subjected to regulation by pemphigus vulgaris IgG but not by pemphigoid IgG or normal human IgG; furthermore, anti-uPA-R monoclonal antibody effectively inhibits pemphigus vulgaris IgG induced acantholysis in skin organ cultures. These data suggest that uPA-R may play an important role in the pathogenesis of pemphigus acantholysis.     

Evaluation of clinical criteria for diagnosis of bullous pemphigoid. French Bullous Study Group

OBJECTIVE: To check the potential usefulness of clinical criteria for the diagnosis of bullous pemphigoid when state-of-the-art techniques such as Western immunoblotting, immunoprecipitation, and indirect immunofluorescence on salt-split skin or direct immunoelectron microscopy are not available. DESIGN: Comparison of the clinical criteria between 2 groups (with and without bullous pemphigoid) as defined by immunoelectron microscopy used as standard criterion, in a prospective study. Multivariate logistic regression analysis was carried out by including all items that were statistically significant (at P < .05 level) in univariate analysis. SETTING: Five dermatology departments in teaching hospitals. PATIENTS: The 231 patients studied had subepidermal autoimmune bullous diseases with linear IgG or C3 deposits in the basement membrane zone (157 with bullous pemphigoid, 33 with cicatricial pemphigoid, 30 with epidermolysis bullous acquisita, 5 with lupus erythematosus, and 6 others). A second set of patients was used to calculate predictive values. RESULTS: The multivariate logistic stepwise analysis resulted in a final set of predictors that included only 4 items: absence of atrophic scars, absence of head and neck involvement, absence of mucosal involvement, and age greater than 70 years. No additional variables met the .05 significance level to enter into the model. If 3 of these 4 characteristics were present, a diagnosis of bullous pemphigoid could be made with a sensitivity of 90% and a specificity of 83%; these predictive values were calculated on a sample of 70 new cases. CONCLUSIONS: With and estimated incidence of bullous pemphigoid among subepidermal autoimmune bullous diseases of 80%, the presence of 3 of the 4 significant criteria allows the diagnosis of bullous pemphigoid, with a positive predictive value of 95%. Our set of clinical criteria thus allows the diagnosis of bullous pemphigoid with good validity for both clinical practice and therapeutic trials.     

Studies on etiologic factors in pemphigus

A survey of 234 cases of pemphigus yielded three observations which suggest that different forms of pemphigus may have different etiologies. 1. While the incidence of pemphigus in the age group of 21 and over was essentially the same in males and females (108 and 113) the incidence was significantly higher in females in the age group under 20. Only two of 13 patients in this group were males. Also pemphigus foliaceus and erythematosus was reported in a significantly higher proportion of the cases in the age group of 2 1/2 to 20 thus suggesting that the juvenile form of the disease differs from the adult form. 2. In four of a group of 15 cases identified as pemphigus foliaceus the disease appeared to be provoked by minor physical insults, a frequency which is significantly higher than the five cases with similar histories in the group of 198 cases identified as pemphigus vulgaris. 3. In the entire group of 234 cases two patients with pemphigus both proven by immunofluorescence had relatives with pemphigus. Also a third patient had a blood relative with bullous pemphigoid. This frequency of three per 234 is higher than would be expected by chance. Studies of one family (not included in this survey) with multiple skin antibodies suggest that such familial predispositions may be due to abnormal immune responses.     

Defective expression of plectin/HD1 in epidermolysis bullosa simplex with muscular dystrophy

Epidermolysis bullosa simplex with muscular dystrophy (MD-EBS) is a disease characterized by generalized blistering of the skin associated with muscular involvement. We report that the skin of three MD-EBS patients is not reactive with antibodies 6C6, 10F6, or 5B3 raised against the intermediate filament-associated protein plectin. Immunofluorescence and Western analysis of explanted MD-EBS keratinocytes confirmed a deficient expression of plectin, which, in involved skin, correlated with an impaired interaction of the keratin cytoskeleton with the hemidesmosomes. Consistent with lack of reactivity of MD-EBS skin to plectin antibodies, plectin was not detected in skeletal muscles of these patients. Impaired expression of plectin in muscle correlated with an altered labeling pattern of the muscle intermediate filament protein desmin. A deficient immunoreactivity was also observed with the monoclonal antibody HD121 raised against the hemidesmosomal protein HD1. Furthermore, immunofluorescence analysis showed that HD1 is expressed in Z-lines in normal skeletal muscle; whereas this expression is deficient in patient muscle. Colocalization of HD1 and plectin in normal skin and muscle, together with their impaired expression in MD-EBS tissues, strongly suggests that plectin and HD1 are closely related proteins. Our results therefore provide strong evidence that, in MD-EBS patients, the defective expression of plectin results in an aberrant anchorage of cytoskeletal structures in keratinocytes and muscular fibers leading to cell fragility.     

Bullous IgA linear dermatosis of children in Mali

INTRODUCTION: Bullous IgA linear dermatosis is relatively frequent in children in Africa. The aim of this study was to evaluate the frequency of this disease among autoimmune bullous diseases in children in Mali. PATIENTS AND METHODS: Children with chronic bullous disease seen at the Marchoux Institute in Bamako and for whom direct immunofluorescence of the perilesional skin demonstrated immunoglobulin and/or complement deposits were included in the study population. RESULTS: Twelve children were included. Direct immunofluorescence showed linear IgA deposit along the dermo-epidermal junction in 10, once with a pemphigoid aspect and once with a pemphigus aspect. The skin lesions in the children with linear IgA deposits were stereotypic: disseminated bullae, rosettes (9 out of 10), involving the external genital organs (10/10), the limbs, the face and the trunk. Histology showed subepidermal bullae (10/10), with neutrophil papillar abscesses (9/10). Indirect immunofluorescence of the cleaved skin NaCl in 5 patients showed that the cleavage always lied at the roof of the cleavage. All the children responded to dapsone (1 to 2.5 mg/kg/d) which gave complete (7/10), or incomplete remission. Local corticosteroids were used in 2 patients and general corticosteroids in 1. DISCUSSION: This confirms the frequency of bullous IgA linear dermatosis in Africa, in contrast with uncommon dermatitis herpetiformis. Diagnosis is facilitated with immunofluorescence. The low cost of this test makes it a useful diagnostic tool in these countries.     

Bullous pemphigoid associated with Shy-Drager syndrome

We report a patient with Shy-Drager syndrome who developed multiple tense blisters mainly on the extremities. Circulating anti-basement membrane zone autoantibodies were detected by the indirect immunofluorescence method. Immunoblot analysis using normal human epidermal extracts demonstrated that this patient's serum reacted only with 230 kD bullous pemphigoid antigen (BPAG1). Concerning the pathoetiology of the association of bullous pemphigoid and Shy-Drager syndrome, we discuss a sequence similarity between BPAG1 and dystonin, a candidate gene for dystonia musculorum.