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PubMed1977

[Immunology of bullous diseases-II. Cicatricial pemphigoid. Herpes gestationis and dermatitis herpetiformis].

The immunological aspects of cicatricial pemphigoid, herpes gestationis and dermatitis herpetiformis are reviewed in this article. The immunofluorescence findings in these diseases are emphasised. The possible implication of the complement system in the pathogonesis of these bullous diseases, as well as the present knowledge about the sequence of actuation of the alternate pathway components are discussed.

Dermatitis Herpetiformis↗
PubMed1990

[IgA anti-endomysium antibodies in dermatitis herpetiformis: a sensitive marker of gluten enteropathy].

The paper reports the results of a preliminary study using indirect immunofluorescent methods on serum samples from 20 patients affected by dermatitis herpetiformis in various phases of development and from 7 patients affected by celiac disease in order to document the presence of anti-endomysium IgA antibodies. Serum samples from 10 patients affected by bullous pemphigoid, 1 patients with linear IgA dermatitis and 10 patients with other bullous dermatosis were included as controls. Whereas the presence of these antibodies in varying titres, ranging from 1:10 to 1:80, was confirmed in all case of dermatitis herpetiformis, no antibody activity was observed in control patients. On the basis of these findings and of other published data, it is possible to conclude that these antibodies are directly correlated to intestinal damage, but there is no relationship with the clinical characteristics of skin symptoms or with junctional immunopathological evidence.

Celiac Disease↗
PubMed1981

Hepatic injury in dermatitis herpetiformis.

Liver function tests were performed in 60 patients with dermatitis herpetiformis. Abnormalities of bilirubin or elevated liver enzyme levels were found in 17% of the patients. 13% had abnormal liver enzymes or elevated bilirubin levels not due to haemolysis. In 8% of patients bilirubin levels were elevated as a result of dapsone-induced haemolysis. The incidence of liver function abnormalities was higher (19%) in those on a normal diet than those on a gluten-free diet (9%). The abnormalities were not associated with the presence of immune complexes, anti-mitochondrial or anti-smooth muscle antibodies.

Dapsone↗
PubMed1978

The ultrastructural localization of IgA in skin of a patient with mixed form of dermatitis herpetiformis and bullous pemphigoid.

A case with mixed features of dermatitis herpetiformis and bullous pemphigoid was investigated by immuno-electron microscopy. There were clinical, histological, and ultrastructural characteristics of both diseases, the response to sulfapyridine was dramatic at the beginning, but intestinal lesions were absent. Direct immunofluorescence tests were made 6 times in the 4 year period and demonstrated in all biopsies exclusively linear IgA deposits. The IgA deposits were shown to occupy the entire lamina lucida and to adhere to the basal cell membranes and lamina densa, very much like IgG deposits in bullous pemphigoid. Antibodies against the basement membrane zone could not be demonstrated in the serum.

Basement Membrane↗
PubMed1985

IgA class reticulin antibodies in dermatitis herpetiformis: a good indicator of jejunal damage.

Fifty patients with dermatitis herpetiformis (DH) were examined. Reticulin antibodies (RA) were found in 34 (68%) patients; 25 (73%) of them had IgA class RA, seven (21%) had IgA and IgG class RA, and two (6%) had IgG class RA. A good correlation was found between the occurrence of RA and the presence of jejunal villous atrophy. Twenty-four (96%) of the patients with subtotal villous atrophy and nine (82%) with partial villous atrophy had RA as compared to only one (7%) of the 14 patients with normal jejunal mucosa. Gluten-free diet treatment caused disappearance of RA in every patient, suggesting that RA measurements can also be used in DH for monitoring adherence to the diet treatment.

Adolescent↗
PubMed1976

Family studies in dermatitis herpetiformis.

Six families were studied which included 11 members with dermatitis herpetiformis (DH) and three with coeliac disease (CD). Proximal jejunal biopsies performed on 20 relatives revealed villous atrophy in eight. Of these eight, two, both siblings of patients with DH, had a history of juvenile CD. Determinations of histocampatibility (HLA) antigens showed that HLS-B8 occurred in all six families although two patients with DH and one relative with a history of juvenile CD lacked this antigen. In one family the haplotype A1,B8 was associated with DH, villous atrophy, juvenile diabetes and Addison's disease. Skin biopsy failed to reveal IgA in any of the 44 relatives studied for this immunoglobulin. Antireticulin antibody was detected in the sera of seven (17%) relatives.

Adolescent↗
PubMed1986

Proteolytic enzymes in blister fluids from patients with dermatitis herpetiformis.

Proteolytic enzymes may be involved in blister formation in dermatitis herpetiformis (DH). We have examined collagenase, gelatinase and elastase-like enzyme activities in fluids collected from spontaneous blisters and from suction blisters raised on developing DH-lesions induced by application of potassium iodide. Control suction blisters were raised on unaffected DH-skin and on healthy volunteers. High enzyme activities were found in spontaneous blisters, and suction blister fluids obtained from developing lesions showed increased levels of gelatinase and elastase-like enzymes. Inhibitor studies revealed that a part of the elastase-like enzyme activity might be derived from inflammatory cells. Gel filtration chromatography disclosed two separate elastase-like enzymes which, as they had high molecular weights, could be either enzyme-inhibitor complexes or aggregates.

Blister↗
PubMed1982

Lymphoma in dermatitis herpetiformis: report on four cases.

Four patients suffering from protracted dermatitis herpetiformis (DH) developed lymphomas while undergoing gluten-free diet treatment. This had lasted between 6 months and 4 years. The first patient died of histiocytic lymphoma involving mesenterial lymph nodes, liver, spleen and blood marrow. The second patient died of histiocytic lymphoma disseminated in the ileum, colon, stomach and mesenterium. This patient had been operated on 14 years earlier for a solitary ulcerating lymphoma in the ileum. The third patient had a localized histiocytic lymphoma in the colon. This was successfully removed by hemicholectomy. The fourth patient had a lymphocytic lymphoma of B-cell origin in the inguinal lymph nodes which was treated with radiotherapy. These 4 patients with lymphomas suggest that, like coeliac disease patients, DH patients also run an increased risk of developing lymphomas.

Adult↗
PubMed1986

Spontaneous remission of dermatitis herpetiformis: dietary and gastrointestinal studies.

Out of 98 patients with dermatitis herpetiformis (DH) living in Gothenburg, 14 were in spontaneous remission (29% of the patients without gluten free diet). Eight of these volunteered for dietary interviews and further studies. They do not seem to differ from symptomatic DH patients in the frequency of HLA-B8, achlorhydria or small-bowel enteropathy. Their estimated mean daily intake of gluten was below 12 g in six. The mean gluten intake of the eight patients in remission is significantly less than in a group of 34 patients with dapsone-requiring DH on non-restricted diet. Urinary iodine excretion was low in five, all previously instructed to restrict their iodine intake. Dietary factors could thus be suspected to be responsible for some spontaneous remissions in DH.

Adolescent↗
PubMed1975

Serum hemopexin in patients with dermatitis herpetiformis on dapsone (di(4-aminophenyl)sulphone).

Twenty patients with dermatitis herpetiformis treated with di(4-aminophenyl)-sulphone (Dapsone) were analyzed with respect to serum hemopexin concentration as well as some other haematological parameters. With one exception, there were normal concentrations of serum hemopexin when the haptoglobin and methaemoglobin concentrations were normal. Ten out of 11 patients with haptoglobin below 0.3 g/l, which is the lower limit of reference interval at this laboratory, had their hemopexin concentrations reduced to various extents. There was an inverse relationship between the concentration of serum hemopexin and blood methaemoglobin. There was no correlation between amount of Heinz bodies and the concentrations of blood methaemoglobin, serum haptoglobin or serum hemopexin. It is concluded that serum hemopexin measurement should be of value in the assessment of the severity of the haemolysis caused by the drug treatment in those cases who have a low serum haptoglobin concentration.

Adult↗
PubMed1979

[Dermatitis herpetiformis (author's transl)].

Detailed investigations of 9 patients with dermatitis herpetiformis are presented. In all cases cutaneous lesions were controlled by dapsone alone or by dapsone and gluten free diet. Granular IgA deposits were found in 7 patients, linear IgA deposits in one, and C3 component of complement in one. 3 patients out of 8 tested, carried the specific HLA-B8 antigen. Despite an extensive investigation, no malabsorption was detected. Jejunal biopsies were performed in 8 cases. Jejunal villous flattening was observed in one patient. It improved after a 2 months gluten free diet on subsequent jejunal biopsies. D. H. seems peculiar in France as compared with case reports from other countries: low prevalence of gluten sensitive enteropathy; rare occurrence of the specific HLA-B8 antigen; incidence of D. H. seems to be low in France. It is noticeable that french incidence of coeliac disease is low as well. This suggests a genetic difference in the investigated population (low prevalence of HLA-B8 antigen) and/or different alimentary habits, particularly a low dietary gluten amount.

Adolescent↗
PubMed2002

Iodine and gliadin challenge on oral mucosa in dermatitis herpetiformis.

Oral lesions and mucosal inflammatory changes may appear in dermatitis herpetiformis (DH). We examined whether potassium iodine, known to initiate blisters in the DH skin, or wheat gliadin, responsible for T-cell-dependent intestinal damage, can induce visible or microscopic changes in oral mucosa. Six patients with active DH were challenged with crude gliadin and 50% potassium iodine applied in patch test chambers on buccal mucosa for 12 h. After reading, biopsies were taken from the challenged and non-challenged mucosa. No macroscopic or microscopic vesicles were seen. However, gliadin- but not iodine-challenged epithelium showed increased numbers of CD4+ lymphocytes in all 5 patients with representative specimens (p = 0.06). No marked changes were found in the numbers of CD8+ or TcR alpha/beta+ lymphocytes, and the numbers of TcR gamma/delta+ cells remained at a low level. The results show that oral mucosa is resistant to production of macroscopic or microscopic DH lesions. It is, however, capable of reacting to locally applied gliadin by a T-cell response consisting of CD4+ lymphocytes.

Adult↗
PubMed1992

[Dermatitis herpetiformis vs. celiac disease].

Twenty-nine patients affected with dermatitis herpetiformis (HD), all of whom were on a diet including gluten, were investigated for symptoms of enteropathy. Of these patients, 71% presented severe intestinal lesions, indistinguishable from those found in coeliac disease (CD). However, there were little other clinical manifestations of this finding since only three children in this group had weight and height < or = P3. Of the remaining children, 18% had moderate intestinal atrophy and 10% had normal mucosa or mucosa with negligible changes. When changed to a gluten free diet, the intestinal lesions subsided, dermic lesions disappeared in 17 patients, improved in 8 others and remained the same in the other three patients that were still on variable diets. A study of human leukocyte antigens (HLA) class II showed a total association with Dqw2 and 85% association to DR3, which was identical to the coeliac disease control group. These findings lead one to conclude that HD and CD are different clinical expressions of the same sensitivity to gluten which is associated to an immunological disorder with a common genetic base linked to certain HLA molecules.

Celiac Disease↗
PubMed2000

Increased production of IL-4 by gut T-cell lines from patients with dermatitis herpetiformis compared to patients with isolated gluten-sensitive enteropathy.

Dermatitis herpetiformis (DH) and isolated gluten-sensitive enteropathy (GSE) are gluten-sensitive diseases in which ingestion of dietary gluten results in the development of clinical disease. Patients with DH develop cutaneous IgA deposits and a severe skin disease, but rarely develop gastrointestinal symptoms. Patients with isolated GSE develop clinically significant gastrointestinal symptoms, but not skin disease or cutaneous IgA deposits. The aim of this study was to investigate the mechanism by which a mucosal immune response to the same dietary antigen can result in two distinct clinical phenotypes. T-cell lines were derived from activated T-cells in the small bowel mucosa of five patients with DH and 14 patients with isolated GSE and analyzed for T-cell markers and cytokine production in vitro. T-cell lines from DH and isolated GSE patients produced IFN-gamma after stimulation (mean: DH = 2,619 pg/ml; isolated GSE = 1,993 pg/ml; NS). T-cell lines from patients with DH, however, produced significantly more IL-4 than the T-cell lines from patients with isolated GSE (IL-4: DH = 2,010 pg/ml; isolated GSE = 235 pg/ml; P < 0.05). Analysis of intracytoplasmic cytokine production by the T-cell lines showed that T-cell lines from patients with DH were CD4+ predominant, with a greater proportion of CD4+/IL4+ cells than CD4+/IFN-gamma+ cells. In contrast, isolated GSE T-cell lines were predominantly CD8+, with an equal proportion of IL-4- and IFN-gamma-positive cells. These studies demonstrate that T cell lines from patients with DH produce significantly more IL-4 than T-cell lines from patients with isolated GSE, while producing similar amounts of IFN-gamma. This difference in cytokine pattern may play an important role in the different clinical manifestations of these two forms of gluten sensitivity.

Adult↗
PubMed1996

[Dermatitis herpetiformis occuring in patients with celiac disease in childhood].

BACKGROUND: Dermatitis herpetiformis (DH) is a chronic papulovesicular immune-mediated disorder associated with gluten-sensitive enteropathy. We report eight cases in which DH appeared many years after celiac disease (CD) in child. PATIENTS AND METHODS: The diagnosis of CD was based on histological features of total or subtotal villous atrophy, full remission after withdrawal of gluten from the diet, and eventually circulating antibodies (IgA gliadin, antireticulin and antiendomysium) at the time of diagnosis and their disappearance under gluten-free diet. The diagnosis of DH was made from clinical findings, histological examination of the involved skin and direct immunofluorescence microscopy of normal or perilesional skin. HLA class II typing was performed in five patients. DRB1, DQA1, DQB1 and DBP1 alleles were studied. RESULTS: DH appeared between 3 and 22 years after the initial diagnosis of CD. Five patients did not show at that time any digestive symptoms. In three cases, a break in the gluten-free diet or a recent revival of the normal diet preceded the rash. In only one case, DH appeared while the patient was under gluten-free diet. In three patients, the rash appeared many years after the gluten-free diet had been stopped. Phenotype DR3 and/or DR7 of the celiac disease could be found in four of the five patients studied; three of them were found to bear DQW2. The DR2 allele was not found in any of the five tested patients. DISCUSSION: These eight cases illustrate the absence of precise nosological barrier between gluten-sensitive enteropathy of the DH and that observed in CD. The presence of the DR7 allele, and especially the absence of the DR2 allele, could explain the particularly severe and symptomatic course of the enteropathy in these patients. The delay in the appearance of DH, after a very variable period of normal diet, could correspond to the necessary time for progressive accumulation of IgA (or immune complex IgA-gluten) in the skin after a digestive sensitization to gluten. The preventive role of gluten-free diet is thus probable. CONCLUSION: CD and DH likely correspond to two different stages of the same disease, thus requiring a prolonged follow-up of both digestive and skin tissues. Long-term eviction of gluten to prevent eventual DH must be balanced with the demand and the cost of such a diet.

Celiac Disease↗
PubMed1997

Urokinase plasminogen activator is expressed by basal keratinocytes before interstitial collagenase, stromelysin-1, and laminin-5 in experimentally induced dermatitis herpetiformis lesions.

We studied the temporal expression of interstitial collagenase, stromelysin-1 and -2, and urokinase plasminogen activator (uPA) mRNAs by in situ hybridization in eight patients with dermatitis herpetiformis. To induce blisters, 50% potassium iodide patch tests were performed, and serial biopsy specimens were taken at 4, 12, and 24 h. Additional samples were taken from occasional spontaneous blisters. Components of the basement membrane, laminin-5, laminin-1, and type VII collagen, were examined immunohistochemically in relation to matrix metalloproteinase expression. At 12 h, when no blisters were seen, uPA mRNA was present in basal keratinocytes in five of eight samples, whereas interstitial collagenase and stromelysin-1 mRNA were not detected. At this time, immunohistochemistry failed to show changes in the basement membrane. At 24 h, uPA, collagenase, and stromelysin-1 mRNAs were present in basal keratinocytes, suggesting an activation of latent forms of the two latter enzymes by the uPA-plasmin pathway. Signal for stromelysin-2 was not detected. Furthermore, disruptions of laminin-1 and type VII collagen were evident. The data suggest that stromelysin-1 and interstitial collagenase may contribute to the degradation of basement membrane in dermatitis herpetiformis. Intracellular staining for laminin-5 co-localized with collagenase mRNA in basal keratinocytes. Because laminin-5 is essential for adhesion of keratinocytes to basement membrane and for establishment of focal adhesions on migrating cells, its production may reflect a regenerative response after the destruction of basement membrane components.

Collagen↗