Kåre Engkilde

The association between metal allergy, total hip arthroplasty, and revision

Background and purpose It has been speculated that the prevalence of metal allergy may be higher in patients with implant failure. We compared the prevalence and cause of revisions following total hip arthroplasty (THA) in dermatitis patients suspected to have contact allergy and in patients in general with THA. Furthermore, we compared the prevalence of metal allergy in dermatitis patients with and without THA. Materials and methods The Danish Hip Arthroplasty Registry (DHAR) contained detailed information on 90,697 operations. The Gentofte patch-test database contained test results for patients suspected of having allergic contact dermatitis (n = 18,794). Cases (n = 356) were defined as patch-tested dermatitis patients who also had primary THA performed. Two age- and sex-matched controls (n = 712) from the patch-test database were sought for each case. Results The prevalence of revision was similar in cases (12%) and in patients from the DHAR (13%). The prevalence of metal allergy was similar in cases and controls. However, the prevalence of metal allergy was lower in cases who were patch-tested after operation (6%) than in those who were patch-tested before operation (16%) (OR = 2.9; 95% CI = 1–8). Interpretation We found that the risk of surgical revision was not increased in patients with metal allergies and that the risk of metal allergy was not increased in cases who were operated, in comparison to controls. Despite some important study limitations, our observations add to the evidence that the risk of complications in metal allergic patients seems limited.

The prevalence of chromium allergy in Denmark is currently increasing as a result of leather exposure

Background  Chromium allergy has traditionally been caused by occupational skin contact with cement. In 1983, Danish legislation made the addition of ferrous sulphate compulsory in cement to reduce the water‐soluble chromium content to not more than 2 ppm. An effect from this intervention has previously been demonstrated among Danish construction workers.

Temporal trends of preservative allergy in Denmark (1985–2008)

Background: Most cosmetics and industrial products contain preservatives. Preservative allergy is common and, historically, changing contact allergy epidemics caused by preservatives have been observed. In 1997, Alan Dillarstone predicted a stable development of preservative allergy following mandatory ingredient labelling on cosmetic products.

A possible association between a dysfunctional skin barrier (filaggrin null-mutation status) and diabetes: a cross-sectional study

Background Filaggrin proteins are located in the skin and prevent epidermal water loss and impede the entry of micro-organisms, allergens and chemicals. Filaggrin null mutations are strongly associated with ichthyosis vulgaris and atopic dermatitis. Objective The authors aimed to investigate the association between filaggrin null mutations, atopic dermatitis and diabetes. Design A random sample of 3335 adults from the general population in Denmark was filaggrin-genotyped for R501X and 2282del4 null-mutations and questioned about atopic dermatitis and diabetes. Furthermore, two independent study populations of patients with type 1 (n=104) or 2 (n=774) diabetes were genotyped. Results In a crude data analysis, a positive association was detected between the filaggrin null genotype and, respectively, subjects from the general population who reported diabetes (p=0.04) and patients with established type 2 diabetes (p=0.073). Adjustment for age and gender resulted in significant associations for patients with type 2 diabetes (p=0.048) and subjects with self-reported diabetes (p=0.032). Conclusions Adult Danes with a filaggrin null genotype had a significantly increased prevalence of self-reported diabetes. This finding was replicated when an independent sample of Danish patients with established type 2 diabetes was compared with control subjects from the general population.

Inverse relationship between contact allergy and psoriasis: results from a patient- and a population-based study.

Background  An inverse association between contact allergy and autoimmune diseases has been suggested. Psoriasis is an autoimmune disease and it has been debated whether contact allergy is less prevalent among patients with psoriasis. Previous studies have shown conflicting results.

Inverse relationship between allergic contact dermatitis and type 1 diabetes mellitus: a retrospective clinic-based study

Aims/hypothesisContact allergy (CA) is a disease induced and maintained by environmental factors, which mainly has a Th2 pattern in its chronic form. Environmental factors play a major role in CA, while genetic factors are of minor importance. Type 1 diabetes is an autoimmune disease of the islets of Langerhans, which has a Th1 cytokine pattern and in which modulators of risk are both genetic and environmental. To investigate whether environmental exposure to chemicals leading to CA could influence the risk of type 1 diabetes, we conducted a retrospective clinic-based study of patients subjected to diagnostic patch testing of CA.MethodsWe undertook a retrospective clinic-based study of 13,315 patients who were patch-tested between 1985 and 2003, and linked it with the Danish National Patient Registry containing diabetic mellitus discharge diagnoses from 1987 to 2003. The 13,315 patch-tested patients gave rise to 4,848 CA patients. Using logistic regression, we calculated odds ratios for persons with CA of having type 1 diabetes.ResultsType 1 diabetes was diagnosed in 229 of the patch-tested patients. CA patients had a reduced risk of having type 1 diabetes, with an odds ratio 0.62 (95% CI 0.46–0.86). After adjusting for sex and age, the odds ratio was 0.63 (95% CI 0.47–0.86).Conclusions/interpretationAn inverse relationship between CA and type 1 diabetes was found. Thus there may be a protective effect of having CA in relation to the risk of type 1 diabetes, or vice versa type 1 diabetes may lead to tolerance rather than hypersensitivity. Alternatively, these two diseases may share common genetic factors, although at present these are unknown.

Inflammatory bowel disease in relation to contact allergy: A patient-based study

Objective. Inflammatory bowel disease (IBD) has previously been investigated with relation to allergic conditions; however, diverging results were found and there are only a few small studies focusing on delayed hypersensitivity. The aim of this study was to investigate whether there was an association between contact allergy (CA), which is a type IV hypersensitivity reaction of the skin, and IBD. Material and methods. A database consisting of a cohort of 13,315 patients, patch tested between 1985 and 2003, was linked with the Danish National Patient Registry using a unique personal identifier number. The patients were patch tested at a dermatology department with a long history of research in CA. By record linking with the Danish National Patient Registry, patients were identified who had either an International Classification of Disease (ICD) code for Crohns disease (CD) or an ICD code for ulcerative colitis (UC) diagnosis. Using logistic regression, with the result of the patch test as the dependent variable, we calculated the odds ratios for IBD, CD and UC, adjusted for gender and age. Results. An inverse association between CA and IBD was found, odds ratio adjusted for age and gender 0.71 (CI 95% 0.53–0.94), which is mainly the result of an inverse association between CA and CD, odds ratio adjusted for age and gender 0.42 (CI 95% 0.23–0.76). Conclusions. The association found between CA and IBD might be related to shared genetic factors or common environmental determinates. It may also be that having either disease result in skewness of the immune system might lead to an inverse disease association.

Dietary gluten increases natural killer cell cytotoxicity and cytokine secretion

Dietary gluten influences the development of type 1 diabetes in nonobese diabetic (NOD) mice and biobreeding rats, and has been shown to influence a wide range of immunological factors in the pancreas and gut. In the present study, the effects of gluten on NK cells were studied in vitro and in vivo. We demonstrated that gliadin increased direct cytotoxicity and IFN‐γ secretion from murine splenocytes and NK cells toward the pancreatic beta‐cell line MIN6 cells. Additionally, stimulation of MIN6 cells led to a significantly increased proportion of degranulating C57BL/6 CD107a+ NK cells. Stimulation of C57BL/6 pancreatic islets with gliadin significantly increased secretion of IL‐6 more than ninefold. In vivo, the gluten‐containing diet led to a higher expression of NKG2D and CD71 on NKp46+ cells in all lymphoid organs in BALB/c and NOD mice compared with the gluten‐free diet. Collectively, our data suggest that dietary gluten increases murine NK‐cell activity against pancreatic beta cells. This mechanism may contribute to development of type 1 diabetes and explain the higher disease incidence associated with gluten intake in NOD mice.

Effect of Dietary Gluten on Dendritic Cells and Innate Immune Subsets in BALB/c and NOD Mice

The innate immune system is known to play an important role in oral tolerance to dietary antigens. This is important in development of celiac disease (CD) but may also be important in type 1 diabetes (T1D), and could potentially explain the reduced incidence of T1D in mice receiving a gluten-free (GF) diet. The direct in vivo effect of gluten on innate cells, and particularly dendritic cells (DC) is not sufficiently clarified. Therefore, we wished to investigate the innate cell populations of spontaneous diabetic NOD mice and healthy BALB/c mice kept on a GF or a standard (STD) gluten containing diet. We studied, by flow cytometry and reverse transcription-quantitative polymerase chain reaction (qRT-PCR), if dietary gluten induces changes in the activation of DCs and distribution of selected innate cells in lymphoid, pancreatic and intestinal tissues in BALB/c and NOD mice. We found that a GF diet increased the percentage of macrophages in BALB/c spleen and of CD11c+ DCs in BALB/c and NOD spleen. Strictly gluten-free (SGF) diet increased the percentage of CD103+ DCs in BALB/c mice and decreased percentages of CD11b+ DCs in mesenteric and pancreatic lymph nodes in BALB/c mice. SGF diet in BALB/c mice also decreased DC expression of CD40, CCR7 and MHC-II in pancreatic lymph nodes. In conclusion, GF diet changes the composition of the innate immune system in BALB/c and NOD mice and increases expression of DC activation markers in NOD mice. These results contribute to the explanation of the low diabetes incidence in GF NOD mice. This mechanism may be important in development of type 1 diabetes, celiac disease and non-celiac gluten sensitivity.

A gluten-free diet lowers NKG2D and ligand expression in BALB/c and non-obese diabetic (NOD) mice

The interplay between diet and immune parameters which could affect type 1 diabetes (T1D) pathogenesis is not sufficiently clarified. Intestinal up‐regulation of the activating receptor natural killer group 2D (NKG2D) (CD314) and its ligands is a hallmark of coeliac disease. However, the direct effect of gluten on NKG2D expression is not known. We studied, by fluorescence activated cell sorter (lymphoid tissues) and reverse transcription–quantitative polymerase chain reaction (intestine and pancreatic islets), if a gluten‐free diet (GF diet) from 4 weeks of age or a gluten‐free diet introduced in breeding pairs (SGF diet), induced changes in NKG2D expression on DX5+(CD49b) natural killer (NK) cells, CD8+ T cells and in intestinal and islet levels of NKG2D and ligands in BALB/c and non‐obese diabetic (NOD) mice. Gluten‐free NOD mice had lower insulitis (P < 0·0001); reduced expression of NKG2D on DX5+ NK cells in spleen and auricular lymph nodes (P < 0·05); and on CD8+ T cells in pancreas‐associated lymph nodes (P = 0·04). Moreover, the level of CD71 on DX5+ NK cells and CD8+ T cells (P < 0·005) was markedly reduced. GF and SGF mice had reduced expression of NKG2D and DX5 mRNA in intestine (P < 0·05). Differences in intestinal mRNA expression were found in mice at 8, 13 and 20 weeks. Intestinal expression of NKG2D ligands was reduced in SGF mice with lower expression of all ligands. In isolated islets, a SGF diet induced a higher expression of specific NKG2D ligands. Our data show that a gluten‐free diet reduces the level of NKG2D and the expression of NKG2D ligands. These immunological changes may contribute to the lower T1D incidence associated with a gluten‐free diet.