Gluten-free diet in dermatitis herpetiformis

Eighty-one patients with dermatitis herpetiformis were treated with a gluten-free diet (GFD) for periods varying from 6 to 36 months. At the end of the treatment the daily requirement of dapsone was significantly lower in patients treated with a GFD than in 49 patients on a normal diet. 93% of the patients on a GFD were able to reduce the dose of dapsone whereas only 16% of the patients on a normal diet were able to do this. Complete remissions occurred only in patients on a GFD. 28% of the patients on a GFD were able to stop dapsone completely and were continuously asymptomatic when they observed a strict diet. A response to a GFD was noted on the mean daily requirement of dapsone as soon as the treatment was initiated although the length of time for an individual response varied. After one year on a GFD the patients needed on average about 40% and after 3 years about 20% of the dose required to control skin symptoms at the beginning of the diet. The patients responded to a GFD irrespective of changes found in the jejunal mucosa and irrespective of the presence of absence of HLA-B8.     

IgA and C3 complement in the uninvolved skin in dermatitis herpetiformis after gluten withdrawal

IgA deposits in the skin in 53 patients with dermatitis herpetiformis (DH) have been studied in relation to treatment. In 19 patients the disorder was controlled by a gluten-free diet (GFD) alone, in 13 patients by dapsone and GFD and in 18 by dapsone alone. In 3 patients the skin disorder became insignificant and required no treatment. Of the patients taking a GFD alone, six had been clear of skin lesions for 7 years, 5 for 3–5 years, and 8 for periods of 6 months-3 years. IgA deposits were found in all patients in an initial biopsy and in a second biopsy after treatment for periods varying from I to 7 years. There was no difference in the quantity of IgA, as assessed by the amount of fluorescence, whether patients were controlled with a GFD alone, GFD and dapsone, dapsone alone, or in those in clinical remission. The C₃ component of complement was present in the skin in 3 of the 19 patients (16%) controlled by a GFD alone, 6 of the 13 patients (46%) of those controlled by a GFD and dapsone, and in 12 of 18 (66%) of the patients taking dapsone alone, and in one of the patients in clinical remission.     

Psoriasis patients with antibodies to gliadin can be improved by a gluten-free diet

In a previous screening study, 16% of patients with psoriasis had IgA and/or IgG antibodies to gliadin (AGA). The aim of the present study was to evaluate the effect of a gluten-free diet (GFD) in 33 AGA-positive and six AGA-negative psoriasis patients. Of the 33 AGA-positive patients, two had IgA antibodies to endomysium (EmA) and 15 an increased number of lymphocytes in the duodenal epithelium, but in some this increase was slight. Two patients had villous atrophy. A 3-month period on a GFD was followed by 3 months on the patient's ordinary diet. The severity of psoriasis was evaluated with the psoriasis area and severity index (PASI). The examining dermatologists were unaware of the EmA and duodenal biopsy results throughout the study. Thirty of the 33 patients with AGA completed the GFD period, after which they showed a highly significant decrease in mean PASI. This included a significant decrease in the 16 AGA-positive patients with normal routine histology in duodenal biopsy specimens. The AGA-negative patients were not improved. After GFD, the AGA values were lower in 82% of those who improved. There was a highly significant decrease in serum eosinophil cationic protein in patients with elevated AGA. When the ordinary diet was resumed, the psoriasis deteriorated in 18 of the 30 patients with AGA who had completed the GFD period. In conclusion, psoriasis patients with raised AGA might improve on a GFD even if they have no EmA or if the increase in duodenal intraepithelial lymphocytes is slight or seemingly absent.     

Clinical response of dermatitis herpetiformis skin lesions to a gluten-free diet

Patients with dermatitis herpetiformis have been studied prospectively for 2 years to assess the effect of a gluten-free diet (GFD) on control of the skin lesions. Daily requirements for oral medication with sulphapyridine or dapsone were reduced by GFD treatment and if complete clinical remission of the skin disease occurred, it was maintained while the diet was strictly observed. However, complete remission did not occur significantly more often in GFD-treated patients than in patients taking a normal diet. Many of the latter group exhibited variation in their drug dose requirements during the period of study. GFD treatment seems desirable for the majority of patients with dermatitis herpetiformis, not only to correct the intestinal abnormality but also to minimize the dose of drugs necessary to control the skin lesions.     

Anti-gliadin antibodies and small intestinal mucosal damage in dermatitis herpetiformis

Sera from forty-six patients with dermatitis herpetiformis (DH) were examined for anti-gliadin antibodies (AGA) by the enzyme linked immunosorbent assay (ELISA) test and by a simple new immunofluorescent (IF) test. AGA were present in fifteen out of thirty-two patients taking a normal diet, but in none of the fourteen taking a gluten-free diet (GFD). The presence of circulating AGA was related to the severity of the enteropathy. AGA were present in all ten patients with a flat mucosa and in four of six with a convoluted mucosa, but in only one out of thirty patients with normal morphology of the small intestine. However, in those patients taking a normal diet and with a normal morphology of the intestine there was evidence of gluten sensitivity compared to those taking a GFD, as the intraepithelial lymphocyte count (IELC) was significantly raised in the peri-nuclear and supra-nuclear positions. The study shows that the presence of AGA in the serum is a good indication of the degree of gluten sensitivity as expressed by severe mucosal damage in patients with DH.     

IgA anti-endomysial antibodies in dermatitis herpetiformis: correlation with jejunal morphology, gluten-free diet and anti-gliadin antibodies

Circulating IgA-class anti-endomysium antibodies (EmA) can be detected by indirect immunofluorescence on monkey oesophagus sections. We found EmA in 22 (76%) of 29 patients with dermatitis herpetiformis (DH) on a normal, gluten-containing diet. The highest frequency (100%) of EmA was observed in patients with sub-total villous atrophy. IgA-class antigliadin antibodies (AGA) were found using an ELISA method in 59% of 29 DH patients and in 86% of those with sub-total villous atrophy. There was a significant correlation between EmA titres and AGA levels in individual patients. Gluten-free diet (GFD) treatment caused a rapid decrease in EmA titres; only three of the 12 patients still showed raised EmA after 6-12 months on a GFD and two of these three had failed to adhere to a strict diet. In contrast, no decrease in EmA titres occurred in four patients maintained on a normal diet, and two of the three patients with initially negative EmA developed positive titres when continuing on a normal diet. These results show that both IgA-class EmA and AGA are good indicators of jejunal damage in DH. The rapid fall of EmA titres after gluten withdrawal indicates that this test is also useful for monitoring a patient's adherence to a GFD.     

Should all patients with dermatitis herpetiformis follow a gluten-free diet?

Aim To assess the effect of a gluten-free diet in Irish patients with dermatitis herpetiformis, and whether treatment with a gluten-free diet is as important for patients with a normal small bowel biopsy us for those with villous atrophy. Background Though a gluten-free diet is recommended in the management of dermatitis herpetiformis, many patients find it intolerably restrictive. To date we have recommended it only to patients with abnormal small bowel histology. Methods Forty patients with dermatitis herpetiformis who attended our clinic between 1979 and 1994 were studied retrospectively. Villous atrophy was present in 20 (64%) of 31 initial small bowel biopsies in patients not on a gluten-free diet. Results The median time to a 50% reduction in dapsone requirements was 6 months in patients who followed a gluten-free diet. (n = 14). 10.5 months in those who had a gluten-reduced diet (n = 4) and 10.5 months in those who took a normal diet (n = 22). Four of 14 patients (29%) on a gluten-free diet were able to discontinue medication in 1–5 years compared with 2 of 22 (9%) on a normal diet. The mean time to a 50% reduction in dapsone requirements was similar in patients with and without villous atrophy. 9.3 versus 9.0 months in patients on a gluten-free diet and 12.0 versus 15.3 months in patients on a normal diet. Conclusion We conclude that a gluten-free diet should be strongly encouraged in all dermatitis herpetiformis patients, since those with normal small bowel biopsy findings benefit equally from the diet as do those with villous atrophy.     

Serum IL-8 in patients with dermatitis herpetiformis is produced in response to dietary gluten

Patients with dermatitis herpetiformis (DH) have a gluten-sensitive enteropathy and while on gluten-containing diets have elevated levels of serum IL-8. We hypothesized that the mucosal immune response to gluten is responsible for the elevated serum IL-8. Six DH patients were studied while on a gluten-free diet (GFD), whereas four continued on a normal diet. Patients were followed for a mean 2.2 years and serum IL-8 was analyzed. Small bowel biopsies from five DH patients on normal diets, two DH patients on GFD, and six subjects with no small bowel abnormalities were analyzed for IL-8 mRNA. Serum IL-8 levels normalized in five of six patients on GFD and decreased in one, whereas serum IL-8 levels showed no statistically significant change in DH patients on normal diets. Small bowel biopsies from DH patients on normal diets had increased expression of IL-8 mRNA compared to normal subjects, whereas patients on a GFD showed no significant increase in small bowel mRNA. No significant IL-8 mRNA was detected in normal skin biopsies from patients with DH. These observations suggest that the IL-8 in the serum of patients with DH originates from the small bowel as a mucosal immune response to gluten ingestion.     

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.     

Experience with a gluten free diet in the treatment of linear IgA disease

A study was undertaken to determine whether the skin eruption of linear IgA disease (LAD) was gluten dependent. Six patients with LAD were treated with a gluten free diet (GFD) for an average period of 33 months (range 19-48). Although one patient with LAD had an enteropathy which was clearly gluten sensitive, there was no convincing evidence that the rash of any of the patients responded to a GFD. Four of the six patients showed no significant alteration in their drug requirements. The remaining 2 patients showed a fall in minimum drug requirement but there was no increase after gluten challenge indicating that they were entering spontaneous remission. This contrasts to the situation in dermatitis herpetiformis, where both the rash and the enteropathy are gluten dependent. These data add further to the evidence that LAD and dermatitis herpetiformis are separate entities.     

The potassium iodide patch test in dermatitis herpetiformis in relation to treatment with a gluten-free diet and dapsone

The potassium iodide patch test was studied in twenty-six patients with dermatitis herpetiformis. Histological assessment was found more sensitive than clinical. All of five patients with active disease and not on treatment had a positive test, whereas only two of six patients taking a gluten-free diet (GFD) and one of eight taking dapsone were positive. In another two patients taking a GFD, but in whom the diet had not been strict, the test was positive. All three patients in remission and both patients with the linear pattern of IgA (but with active disease) were negative. Immunofluorescence studies showed no difference in the presence, quantity, or distribution of immunoglobulin, complement or fibrinogen between the patch test site and uninvolved skin, or in the uninvolved skin between patients with and without active lesions.     

25 years' experience of a gluten-free diet in the treatment of dermatitis herpetiformis

Gluten-free diets have been used in the treatment of patients with dermatitis herpetiformis in our department since 1967. Of the 212 patients with dermatitis herpetiformis attending between 1967 and 1992, 133 managed to take the diet, and 78 of these achieved complete control of their rash by diet alone. Of the remaining 55 patients taking a gluten-free diet, all but three were taking partial diets; over half of these patients managed to substantially reduce the dose of medication required. Of the 77 patients taking a normal diet, eight entered spontaneous remission, giving a remission rate of 10%; a further two patients who had been taking gluten-free diets were found to have remitted when they resumed normal diets. Loss of IgA from the skin was observed in 10 of 41 (24%) patients taking strict gluten-free diets. These patients had been taking their diets for an average of 13 years (range 5–24 years), and their rash had been controlled by diet alone for an average of 10 years (range 3–16 years). The advantages of a gluten-free diet in the management of patients with dermatitis herpetiformis are: (i) the need for medication is reduced or abolished; (ii) there is resolution of the enteropathy, and (iii) patients experience a feeling of well-being after commencing the diet. Thus, we propose that a gluten-free diet is the most appropriate treatment for patients with dermatitis herpetiformis.     

Gluten-free diet in dermatitis herpetiformis. II. Morphological and immunological findings in the skin and small intestine of 12 patients and matched controls

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.     

Drug-induced cutaneous pseudolymphoma: A systematic review of the literature

Drug-induced cutaneous pseudolymphoma (CPL) is a common form of pseudolymphoma and there are numerous drugs associated with it. In this study, we performed a systematic review of the literature by searching PubMed/Medline and Embase databases to determine the most common drugs responsible for CPL and to define the demographic, clinical, histopathological and immunopathological characteristics of patients (updated on 30 December 2020). From 883 initially found articles, 56 studies (89 reported cases) were included. The mean age of patients was 54.4 ± 17.7 (ranging 8–86) years, and 46 (51.7%) were men. The median time interval between drug intake and CPL occurrence was 120 days (range 1–7300 days). The shortest median time interval between taking the drug and the onset of the disease was observed among patients taking antidepressants (60 days) (range 7–540) and the longest median time interval was observed in individuals using immunomodulators (300 days) (range 3–7300). The most-reported drug categories causing CPL were anti-hypertensives (17.9%), anticonvulsants (14.6%), monoclonal antibodies (13.4%) and antidepressants (11.2%). Moreover, the most common drugs were phenytoin (6.7%), amlodipine (5.6%), fluoxetine (5.6%) and carbamazepine (4.4%). Histopathological evaluation of 76 cases revealed 62 (81.5%) reports of T-cell infiltrations. Furthermore, positive reports of CD4 (94.0%), CD8 (93.0%) and CD30 (87.5%) were noted. The lowest prevalence of CD30-positive reports was observed among monoclonal antibodies. In conclusion, anti-hypertensives, anti-convulsants, monoclonal antibodies and anti-depressants are the most common drugs responsible for CPL. It mostly presents in middle-aged patients with almost no gender difference as pruritic papules, nodules and plaques.     

Adalimumab for psoriasis in Greece: clinical experience in a tertiary referral centre

Background Adalimumab, a fully human, anti‐TNFα monoclonal antibody has been shown to be effective for moderate‐to‐severe psoriasis in clinical trial setting. However, only a limited number of studies reflect everyday clinical experience with this drug. Objectives To provide evidence on the efficacy, dose optimization and safety of adalimumab based on everyday clinical experience in a tertiary referral centre for psoriasis, in Greece. Methods We retrospectively reviewed the records of all patients with moderate‐to‐severe psoriasis who received adalimumab, in our referral centre, between January 2008 and October 2010. Results In total, 52 patients were treated with adalimumab for a mean period of 14 months (range 4–30 months). Mean baseline Psoriasis Area and Severity Index (PASI) was 16.7 (range 9–40.3). At 4, 6, 12 and 18 months, PASI75 was attained by 68%, 82%, 89% and 88% of patients respectively. Nineteen of 52 patients (36%) reached a PASI100 at a mean time of 10 months (range 4–18 months). The dose interval between the injections of adalimumab was increased from 2 to 3 weeks for 14 patients (27%) who achieved and sustained a PASI100 after the first year of treatment, without any relapse. The overall rate of adverse events reached 38%, but treatment was discontinued only in two cases (4%). Conclusions Our study demonstrates that adalimumab is effective and safe in patients with moderate‐to‐severe psoriasis in short‐ and long‐term setting. At the same time, it points out novel and interesting issues for further investigation.     

Protective effect of gluten-free diet against development of lymphoma in dermatitis herpetiformis

A retrospective study of 487 patients with dermatitis herpetiformis showed that lymphoma developed in eight patients, the expected incidence being 0.21 (standardized registration ratio 3810). All lymphomas occurred in patients whose dermatitis herpetiformis had been controlled without a gluten-free diet (GFD) or in those who had been treated with a GFD for less than 5 years. The results are suggestive of a protective role for a GFD against lymphoma in dermatitis herpetiformis and give further support for advising patients to adhere to a strict GFD for life.     

The immunoglobulin-bearing cells in the lamina propria and the clinical response to a gluten-free diet in dermatitis herpetiformis

Summary In 17 patients with DH, multiple duodenal and jejunal biopsies were performed. In all patients the small-intestinal biopsy-specimens showed histopathological changes compatible with coeliac disease. Fourteen of the patients maintained a gluten-free diet (GFD) for more than 8 months. The small-intestinal lesions improved in all patients investigated during the GFD. The dosage of Dapsone needed to control the skin lesions could be reduced by more than 50% in 4 patients and the Dapsone could be stopped in 5 other patients on GFD.The immunoglobulin-bearing cells in the lamina propria were counted in 8 patients not on a gluten-free diet, in 6 patients on gluten-free diet, and in 8 healthy controls. The numbers of IgA-, IgM- and IgG-bearing cells were increased in most of the DH patients who were not on a gluten-free diet. The number of IgM-bearing cells in the DH patients who were on a gluten-free diet was the same as that in the control group. This may indicate a mainly IgM response in the lamina propria induced by gluten.

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Zusammenfassung Bei 17 Patienten mit DH wurden vielfältige Duodenum- und Jejunum-Biopsien verrichtet.Die Dünndarm-Biopsien aller dieser Patienten zeigten histopathologische Änderungen, die cöliakie-ähnlich waren. Vierzehn dieser Patienten hielten eine glutenfreie Diät (GFD) während mehr als 8 Monaten.Bei allen untersuchten Patienten, die Diät hielten, verbesserten sich die Dünndarmerscheinungen. Die Dosierung von Dapsone, nötig für die Kontrolle der Hauterscheinungen, konnte reduziert werden um mehr als 50% bei 4 Patienten, und 5 andere Patienten, die die glutenfreie Diät auch hielten, brauchten diese Dapsone nicht mehr. Die Immunoglobulin enthaltenden Zellen in der Lamina propria wurden gezählt bei 8 Patienten, die nicht eine GFD hielten, bei 6 Patienten mit dieser GFD und bei 8 gesunden Kontroll-Personen.Die Zahl der IgA, IgM und IgG enthaltenden Zellen hat bei den meisten der DH-Patienten, die keine GFD hielten, zugenommen.Die Zahl der IgM enthaltenden Zellen bei den DH-Patienten, die eine GFD hielten, war dieselbe wie die Zahl dieser IgM enthaltenden Zellen bei den gesunden Kontroll-Personen.Aus dieser Untersuchung könnte man schließen, daß Gluten hauptsächlich eine IgM-Stimulierung in der Lamina propria hervorruft.

     

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.     

The occurrence of type 1 diabetes in patients with dermatitis herpetiformis and their first-degree relatives

BACKGROUND: The increased prevalence of type 1 diabetes (T1D) is well documented in patients with coeliac disease, whereas evidence is scanty in patients with dermatitis herpetiformis (DH). OBJECTIVES: To assess the prevalence of T1D in patients with DH and their first-degree relatives, and to study how DH patients with associated T1D respond to a gluten-free diet (GFD) treatment. METHODS: A series of 1104 consecutive patients with DH was recorded and a specific questionnaire sent to 341 of these for familial disease surveillance. Sex- and age-matched patients with isolated DH served as controls in the diet treatment analysis. RESULTS: Twenty-five (2.3%) patients with DH were affected by T1D and three (3.0%) of their first-degree relatives also were affected by T1D, the frequencies being significantly higher than in the general population. Most DH patients with T1D and with isolated DH could adhere strictly to the GFD. The response was good or moderate in 84% of the DH patients with T1D and in 94% of the patients with isolated DH. CONCLUSIONS: The prevalence of T1D is increased in patients with DH and their first-degree relatives. The rash in DH patients with T1D responds to a GFD in a way similar to that seen in patients with isolated DH.     

Reduced mortality in dermatitis herpetiformis: a population‐based study of 476 patients

Background Dermatitis herpetiformis (DH) is an extra‐intestinal manifestation of coeliac disease and most patients adhere to a life‐long gluten free diet (GFD). Increased mortality rates have been reported in coeliac disease but knowledge in DH is scanty. Objectives To survey the mortality rate and causes of death in a large cohort of patients with DH. Material and methods Patients with DH (n = 476 consecutive patients) diagnosed from 1970 onwards at the Tampere University Hospital were analysed for causes of death during 1971–2010. A questionnaire survey on key aspects of health behaviour was performed in patients with DH and comparisons were made with the Finnish population. Results The total number of deaths during 9079 person years followed up was 77 whereas 110 were expected. The standardized mortality rate (SMR) for all causes of death was significantly reduced, being 0·70 (95% CI 0·55–0·87), and similar in both sexes. The SMR was equal in the patients with DH with (0·73) and without (0·77) small bowel villous atrophy. The SMR was significantly reduced (0·38) for deaths due to cerebrovascular diseases. The SMR due to lymphoproliferative malignancies was significantly increased (6·86) in the first 5 years of follow‐up but not thereafter. The questionnaire survey documented that 97·7% of the patients with DH adhered to a GFD. The patients reported significantly less hypercholesterolaemia and there were fewer current and past smokers compared with the age‐ and sex‐matched control population. Conclusions The present long‐term follow‐up study of DH documented significantly reduced all‐cause and cerebrovascular disease mortality. Strict adherence to a GFD, less smoking and hypercholesterolaemia may play a role in the observed health benefit.