I P Lundin’s research while affiliated with Uppsala University Hospital and other places

Palmoplantar pustulosis (PPP) is a chronic inflammatory disease affecting mainly smoking women. Some patients also have psoriasis. A subgroup of patients with psoriasis has been shown to have silent gluten sensitivity with relevance for their psoriasis. Nothing is known about gluten sensitivity in PPP. To find out whether any patients with PPP are gluten-sensitive and whether this might be relevant for the PPP activity. One hundred and twenty-three patients (113 women) with PPP participated. Screening for IgA antibodies against gliadin and tissue transglutaminase (tTG) was performed, the duodenal mucosa in patients with and without these antibodies was studied and the effect of a gluten-free diet (GFD) was followed up. Twenty-two patients (18%) had IgA antibodies against gliadin and nine of 94 (10%) against tTG. Twelve patients with antibodies and 11 without underwent gastro-duodenoscopy. Four displayed villous atrophy, whereas all other specimens were judged as essentially normal at routine staining. However, with immunohistochemistry, the numbers of CD3+ and CD8+ lymphocytes in the epithelium were found to be increased in patients with any type of antibody, although they were most numerous in those with both types of antibodies. Seven of 123 patients (6%) had coeliac disease (three previously diagnosed). Patients with antibodies who adhered to the GFD displayed total or nearly total clearance of the skin lesions and normalization of the antibody levels. Patients with PPP should be screened for antibodies against gliadin and tTG. Those with antibodies can be much improved on a GFD regardless of the degree of mucosal abnormalities.

Previous studies have shown that 16% of patients with psoriasis vulgaris have IgA and/or IgG antibodies to gliadin, but few have antibodies to endomysium. The increase in duodenal intraepithelial lymphocytes was mild. Still, highly significant clinical improvement was observed after 3 months on a gluten-free diet. This study surveys certain immunohistological aspects of involved and non-involved skin in 28 AGA-positive psoriasis patients before and after 3 months of a gluten-free diet. Staining was performed for CD4+ T lymphocytes, Langerhans' cells, endothelium, proliferating (Ki67) cells and tissue transglutaminase. In the entire group of patients, as well as in those on a gluten-free diet as the only treatment, Ki67 + cells in involved dermis were highly significantly decreased after the diet. There was a significant decrease in Ki67 + cells even in patients without increased intraepithelial lymphocytes. Tissue transglutaminase was highly overexpressed in involved skin in the papillary endothelium, and decreased by 50% after gluten-free diet. The possible role of tissue transglutaminase in the pathogenesis of psoriasis needs further investigation.

Pustulosis palmoplantaris (PPP) is a common chronic skin disease, which is very resistant to treatment. It is not known why the lesions are located in the palms and soles. There are few studies of the disease and in particular studies of the histology. Fifty-nine patients with PPP answered a questionnaire concerning their medical history and 39 of them were clinically examined. Biopsy specimens were taken from involved skin in 22 of the 39 patients and studied immunohistologically for tryptase+ mast cells, EG2+ eosinophils, lipocalin+ neutrophils and CD3+ T lymphocytes. The sweat gland and sweat duct were visualized with AE1/AE3 antibody (cytokeratins 1-8, 10, 14/15, 16, 19). In addition to neutrophils in the pustule and lymphocytes in the upper dermis, there were also large numbers of mast cells and eosinophils in the subpustular area. Numerous eosinophils were present in the pustule. The epidermal part of the eccrine duct was not detectable in any of the specimens from patients with PPP but was present in all of the nine control persons (including two smokers). The results indicate that the acrosyringium is involved in the inflammation and also that mast cells and eosinophils participate in a hitherto unknown way. Of the 39 patients clinically examined, two had previously diagnosed thyroid disease and two had gluten hypersensitivity. Seventeen had one or several abnormal serum concentrations of thyroid-stimulating hormone, thyroxin, antibodies against thyroglobulin or thyroperoxidase and 10 had immunoglobulin (Ig) A antibodies to gliadin. The mean +/- SD for serum IgA and for eosinophil cationic protein was increased. From the questionnaire the most notable finding was that 56 of the 59 patients had been or still were smokers, all of whom had started smoking before the first signs of PPP. We hypothesize that the acrosyringium might be the target for the inflammation and that PPP is linked to autoimmune thyroid disease and smoking.

The occurrence of EG2-positive (EG2+) eosinophils and IgE in biopsy specimens of duodenal mucosa and skin from 39 psoriasis patients was studied, with emphasis on the relation to serum eosinophil cationic protein (ECP), serum IgE and the presence or absence of serum IgA and IgG antigliadin antibodies. Psoriasis patients had significantly elevated serum levels of ECP even after exclusion of five of 37 sera which were Phadiatop positive. The elevated serum ECP was not associated with the presence of IgA or IgG antibodies to gliadin. After exclusion of Phadiatop positive sera the serum IgE values did not differ from those of a group of healthy blood donors. Patients with psoriasis had a pronounced increase of EG2+ cells in their duodenal stroma. Patients without antibodies to gliadin tended to have even more EG2+ cells than those with such antibodies and those with increased duodenal intraepithelial lymphocytes. IgE+ cells were present in most duodenal specimens, and in some specimens there were >100 IgE+ cells/section. The number of EG2+ cells was increased in lesional skin and, in some patients, also in non-involved skin, but there was a more pronounced increase in EG2 reactivity in the duodenal than in the skin specimens. IgE reactivity was increased both in non-involved and involved skin and was significantly related to the number of IgE-positive cells in the duodenal stroma. The results of this study indicate that the gastrointestinal tract and the eosinophil granulocyte might be involved in psoriasis in a hitherto unknown way.