The prevalence of thyroid autoantibodies in dermatitis herpetiformis

The prevalence of IgG class thyroglobulin and microsomal antibodies, estimated using a sensitive ELISA, was 48% in 115 patients with dermatitis herpetiformis, which was significantly greater than the prevalence of 16% in 107 unselected controls without dermatitis herpetiformis. IgA class thyroid antibodies were found in 29% of dermatitis herpetiformis patients. Overt thyroid disease had been diagnosed in six (5%) of the dermatitis herpetiformis group and a further six patients had elevated TSH levels. The presence of thyroid antibodies was not associated with particular HLA-DR antigens. These results demonstrate the frequent occurrence of thyroid antibodies in dermatitis herpetiformis, although thyroid failure is less commonly associated with this condition. Immune response genes outside the HLA-DR region may be involved in the immune hyper-responsiveness seen in dermatitis herpetiformis which is reflected in the high prevalence of thyroid autoimmunity.     

Concordance of dermatitis herpetiformis and celiac disease in monozygous twins

Celiac disease can be defined as the classical manifestation of gluten sensitivity, which primarily affects the small intestine. Gluten sensitivity has also a skin manifestation, i.e., dermatitis herpetiformis. Both diseases have a strong genetic association with HLA DQ on chromosome 6. In this study we tried to estimate how much different clinical expressions of gluten sensitivity are determined by genetic factors, and hence how feasible they are for genetic mapping; therefore, we studied all six monozygous twin pairs found among 1292 prospectively collected patients of dermatitis herpetiformis in Finland. Three of the six twin pairs were concordant for dermatitis herpetiformis and for simultaneous enteropathy, celiac disease. Two other twin pairs were partially discordant, one of each pair had dermatitis herpetiformis and celiac disease, whereas the other had solely the gut manifestation of gluten sensitivity, i.e., celiac disease. Only one pair was found to be discordant for gluten sensitivity. All the pairs had typical risk alleles for gluten sensitivity, i.e., either HLA DQ2 or DQ8. These results demonstrate that the genetic component in gluten sensitivity as broadly defined is very strong (5/6 concordant). Genetically identical individuals can have clearly distinguished phenotypes, either dermatitis herpetiformis or celiac disease, suggesting that environmental factors determine the exact phenotype of this multifactorial disease. These findings are of importance in genetic linkage analyses, which focus to only certain phenotypic properties of a complex trait.     

Circulating reticulin autoantibodies of IgA class in dermatitis herpetiformis

Circulating reticulin autoantibodies of IgA class and anti-nuclear antigen antibodies were found in a high frequency in dermatitis herpetiformis patients as compared with age- and sex-matched controls.     

Sulfasalazine and dermatitis herpetiformis

Dermatitis herpetiformis that is unable to be controlled using dapsone and a gluten-free diet presents a therapeutic challenge. Three cases that responded well to sulfasalazine are presented. Two cases, who were unable to tolerate dapsone, had a rapid response to sulfasalazine, without apparent side-effects. The third case with dapsone-responsive blistering dermatoses, presumed to be dermatitis herpetiformis on the basis of serology, showed an excellent clinical response to sulfasalazine, but after 6 weeks of therapy had to cease it because of side-effects. Sulfasalazine is metabolized variably to sulfapyridine, a sulphonamide known to be an effective therapy for dermatitis herpetiformis but no longer available. Sulfasalazine should be considered as a management option for dermatitis herpetiformis.     

Sulfasalazine‐induced generalized vitiligo in a patient with dermatitis herpetiformis and celiac disease

Vitiligo is an acquired idiopathic pigmentary skin disorder characterized by the development of white macules and patches due to the loss of functioning melanocytes. In this report, we describe a case of a patient with a longstanding history of dermatitis herpetiformis (DH) and celiac disease that developed rapidly progressing, biopsy‐confirmed generalized vitiligo after 11 months of treatment with anti‐inflammatory medication sulfasalazine, prescribed for the patient's DH. To the best of our knowledge, this is the first case report which has demonstrated the possible biochemical pathways, triggered by sulfasalazine, in the development of vitiligo.     

Dermatoglyphics in dermatitis herpetiformis

In a dermatoglyphic study of 101 patients with dermatitis herpetiformis, comparison was made with their normal relatives and several random normal series. The results of the several comparisons are quite consistent, considering the nature of the data, for they all point to an attenuation of qualitative and quantitative digital and palmar traits in the patients. It is argued that these differences are associated with the disease itself, and that some of the female relatives have an inherited tendency to the disorder, but do not express it. The findings suggest the involvement of genetic factors in the aetiology, and possibly intrauterine environmental influences as well.     

Duhring's dermatitis herpetiformis

We report on a 56-year-old man suffering from chronic itching, papulovesicular, polymorph dermatosis. Clinical aspects, diagnostics, as well as therapeutic procedure in dermatitis herpetiformis are discussed.     

Intestinal permeability in dermatitis herpetiformis

Differential absorption of D-xylose and 3-0-methyl-D-glucose, and unmediated intestinal permeation (simple diffusion) of lactulose and L-rhamnose, have been investigated in 20 patients with dermatitis herpetiformis. Both iso-osmolar and hyperosmolar test solutions were employed and the results were compared with those obtained from a group of healthy adult volunteers. The findings in each patient have been correlated with small intestinal histology. The majority of patients with villous atrophy had abnormally raised intestinal lactulose permeation and lactulose/rhamnose permeability ratios, whereas patients with normal small intestinal morphological grading did not differ significantly from the healthy control group in this respect. There was a high incidence of delayed plasma D-xylose absorption peaks in dermatitis herpetiformis irrespective of small intestinal histological findings. These results imply that abnormal intestinal permeability in dermatitis herpetiformis is the result of gluten-induced damage to the mucosa rather than an inherent primary defect. It is therefore improbable that the rash in this condition is purely a manifestation of increased intestinal permeation of antigen.     

Dapsone acetylation in dermatitis herpetiformis

The metabolism of dapsone was studied in ten patients with proven dermatitis herpetiformis. Seven of the patients, who were slow acetylators of sulphadimidine, also acetylated dapsone slowly. Three of the patients were rapid acetylators of both drugs. The control of symptoms did not seem to be related to the plasma concentrations of dapsone or of its metabolite monoacetyldapsone. Haemato-logical side effects, however, were related to plasma dapsone concentrations.     

Protein-losing enteropathy in dermatitis herpetiformis

A patient is described with gross intestinal protein loss occurring in association with a typical dermatitis herpetiformis enteropathy, in whom no other gastrointestinal abnormality was identified.     

HLA-DR3 in dermatitis herpetiformis

Twenty-one patients with dermatitis herpetiformis were typed for HLA-ABC and -DR determinants. The incidence of HLA-AI, -B8 and -DR3 antigens was found to be significantly higher (P: = 10^?3, <10^?6 and <10^?6, respectively) among patients with dermatitis herpetiformis than among the normal population. HLA-DR3 was found in 85.7% of patients, HLA-B8 in 66.7% and HLA-Ai in 61.9% only. These results indicate that HLA-DR3 is the antigen primarily associated in dermatitis herpetiformis and the latter antigens (HLA-Ai and -B8) are present in increased incidence, probably due to the known linkage disequilibrium of these antigens with HLA-DR3.     

Gluten-free diet in dermatitis herpetiformis

Twelve patients with dermatitis herpetiformis whose skin condition responded to a gluten-free diet (GFD) were re-examined after diet treatment. The findings were compared with those in matched patients on a normal diet. Jejunal histology revealed morphological improvement in every patient on a GFD whereas all patients on a normal diet continued to have villous atrophy. Intra-epithelial lymphocyte counts were normal in 8 patients on a GFD in contrast to one on a normal diet. Immunofluorescence examination of the jejunal mucosa revealed that the numbers of cells containing IgA and IgM were increased significantly in the normal diet group. The figures were lower in the GFD group but these also exceeded the values in the controls. IgA deposits were found in the uninvolved skin of every patient irrespective of the diet treatment, but the fluorescence seemed to be less intense in patients on a GFD. A clear difference was found in the occurrence of C₃ deposits in the uninvolved skin. Three patients on a GFD had C₃ deposits; two of these did not follow a strict diet. However C₃ was found in 8 patients on a normal diet. Circulating dietary and auto-antibodies were found in two patients on a GFD and in 9 on a normal diet. Serum immunoglobulin (IgG, IgA, IgM) and complement (C₃, C₄) levels were within normal limits in both patient groups.     

Oral lesions in dermatitis herpetiformis

The oral mucosa was examined in fifteen patients with active dermatitis herpetiformis. The lesions seen were classified as erythematous, pseudo-vesicular, purpuric, and erosive in type. The only symptom experienced was of a painful, burning sensation in lesions on the tongue and upper alveolar ridge in two patients. The distribution of lesions, predominantly on the buccal mucosa adjacent to the occlusal plane or beneath existing dentures, suggested that trauma was a factor in their pathogenesis. Histologically, the features noted were similar to those occurring in skin lesions, except that sub-epithelial microvesicle formation was seen in only one of nine biopsies, and that purpura was a predominant feature. Also, the presence of granular IgA deposits in the submucosal papillae of early lesions was similar to the reported skin findings with the direct immunofluorescence technique. Oral lesions were found in over 70% of patients examined; an incidence much higher than previously supposed.     

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.     

Disodium cromoglycate in dermatitis herpetiformis

Eleven patients with dermatitis herpetiformis, all requiring dapsone to control their rash and taking a normal diet, were given disodium cromoglycate (DSCG) 1.5–1.6 g daily. Eight out of the eleven patients continued to take DSCG for periods varying from 6–11 months, the other three patients chose to discontinue the DSCG before 6 months. Of the eight patients taking DSCG for at least 6 months, none was able to stop taking dapsone. In three of the eight, the dapsone requirements were unaltered, whilst in two it decreased and in three it increased. The mean daily dose of dapsone was 105 mg/day before DSCG and 141 mg/day after DSCG. In the eight patients who took DSCG for at least 6 months, intestinal biopsies were performed before and after this drug. The macroscopic appearance was unchanged in four, improved in two and worse in two. The mean interepithelial lymphocyte count was 346 before and 342 after DSG.