Lionel Fry

Psoriasis: a T-cell-mediated autoimmune disease induced by streptococcal superantigens?

Psoriasis is a T-cell-mediated disease that can be triggered by infection with group A beta-haemolytic streptococci. It is proposed that psoriatic skin lesions are initiated by exotoxin-activated T cells, and persist because of specific T cells that react both with streptococcal M protein and a skin determinant, possibly a variant of keratin. As discussed here by Helgi Valdimarsson and colleagues, cytokines released by the superantigen (SAg)-stimulated T cells could induce or enhance the expression of the crossreactive autoantigen, leading to the rescue and activation of autoreactive T cells. In this way, the SAg-determined T-cell receptor V beta phenotype would be maintained by T cells in psoriatic lesions.

Psoriasis: a disease of abnormal Keratinocyte proliferation induced by T lymphocytes

Psoriasis affects 2% of the population in Western countries. Its aetiology and pathogenesis remain unknown but suggestions include abnormalities of blood vessels, neural components, epidermal cell cycle time or maturation of keratinocytes. More recently autoimmune reactions have been implicated involving stratum corneum antibodies(1) and antibodies to nuclei of basal epidermal cells(2). However, there is no convincing evidence that any of these abnormalities are of primary nature. In this article, Helgi Valdimarsson and his colleagues propose that the process leading to psoriatic lesions is triggered by T lymphocytes within the epidermal compartment. They envisage that psoratic lesions erupt where epidermal influx of antigen-carrying Langerhans cells and helper T lymphocytes overrides the normal epidermal suppressor mechanism.

Normal keratinocytes express Toll‐like receptors (TLRs) 1, 2 and 5: modulation of TLR expression in chronic plaque psoriasis

Summary Background Toll‐like receptors (TLRs) are part of the innate immune system involved in the response to microbial pathogens. TLR2 recognizes various ligands expressed by Gram‐positive bacteria, while TLR3, TLR4 and TLR5 are specific for double‐stranded RNA, Gram‐negative lipopolysaccharides and bacterial flagellin, respectively.

T-cell subpopulations in the blood and skin of patients with psoriasis

Monoclonal antibodies were used to determine, simultaneously, the proportions of T‐cell populations in the peripheral blood and in the skin lesions of fifty‐one patients with psoriasis. The results were analysed in relation to the extent, age and clinical type of the skin lesions. In the group of patients with extensive lesions, a significant reduction in the number of total T (TT) and T helper/inducer‐cells, (TH), but not in T suppressor/cytotoxic cells (Ts) was observed in the peripheral blood. Furthermore, the skin TH/TS ratio was greater in late guttate and in chronic plaque lesions than the corresponding ratio in the blood. These findings suggest that there is an active selective recruitment of TH cells into established psoriatic lesions. In contrast, the TH/TS ratio in early guttate lesions was the same as in the blood, and significantly lower than in the plaque lesions. An additional finding was a decrease of TS, and a corresponding increase of null cells in the blood of patients with chronic plaque psoriasis. These observations provide further evidence for the participation of T cells in the pathogenesis of psoriasis.

Linear IgA disease in adults

A multi‐centre study is described in which thirty‐five adult patients with papillary IgA dermatitis herpetiformis (DH) were compared with forty‐two patients with linear IgA deposits, of whom thirty‐four had homogeneous‐linear (HL) and eight had granular‐linear (GL) IgA deposits.

CLEARANCE OF SKIN LESIONS IN DERMATITIS HERPETIFORMIS AFTER GLUTEN WITHDRAWAL

Abstract 24 patients with dermatitis herpeti-formis (D.H.) have been treated with a gluten-free diet (G.F.D.) for periods varying from four months to five years. Of 20 patients who have taken a G.F.D. for a year or longer, 16 (80%) have been able to stop taking dapsone or substantially reduce the dose of the drug. 10 patients have been able to stop taking dapsone completely and are now free of all skin lesions. No patient was able to reduce his dapsone requirements before five months, and 1 patient took twelve months to do this. The length of time taken to be able to stop dapsone completely varied from eight to forty-eight months. In another group of 20 patients with D.H. who did not take a G.F.D. but have been followed up for a similar length of time, there was no significant alteration in dapsone requirements. Reintroduction of gluten in 4 patients who were completely free of skin lesions on a G.F.D. produced irritation and blisters within a week in 3 and within three weeks in the fourth. Dapsone was required for the immediate control of these lesions, which were subsequently controlled again by a G.F.D. alone. Electron-microscopic studies have shown subepidermal membrane-bound vacuoles in clinically normal skin in all 7 patients studied whose eruption was being controlled by dapsone, but these vacuoles were not present in any of the 6 patients whose eruption was controlled by a G.F.D. alone. These results show that the skin lesion in D.H., like the gut lesion, is gluten dependent and that both lesions are part of the same disease process. The length of time for patients to become free of skin lesions after beginning a G.F.D. is stressed, and probably accounts for the previous reports in which it has been stated that the skin lesions are not influenced by a G.F.D.

Absence of Toxicity of Oats in Patients with Dermatitis Herpetiformis

BACKGROUND People with gluten sensitivity should avoid foods containing wheat, rye, and barley, but there has been debate about whether they should avoid oats. Although patients with celiac disease have recently been shown to tolerate oats, less is known about the effects of oats on patients with dermatitis herpetiformis. METHODS We studied seven men and three women (mean age, 58 years) with biopsy-confirmed dermatitis herpetiformis. They had followed a strict gluten-free diet for a mean of 15.8 years, which controlled their rash and enteropathy. The patients added oats that were not contaminated with gluten to their diets for 12 weeks (mean [+/-SD] daily intake, 62.5+/-10.8 g). RESULTS None of the patients had any adverse effects. Serologic tests for antigliadin, antireticulin, and antiendomysial antibodies were negative before oats were introduced into the diet and after they were discontinued. Villous architecture remained normal: the mean (+/-SE) ratio of the height of villi to the depth of crypts was 3.59+/-0.11 before the diet and 3.71+/-0.09 afterward (normal, 3 to 5), and the mean enterocyte heights were 31.36+/-0.58 microm and 31.75+/-44 microm, respectively (normal range, 29 to 34). Duodenal intraepithelial lymphocyte counts all remained within normal limits (mean, 13.8+/-1.03 per 100 enterocytes before the diet and 14.2+/-1.2 per 100 enterocytes afterward; normal range, 10 to 30). Dermal IgA showed no significant changes. CONCLUSIONS Patients with dermatitis herpetiformis can include moderate amounts of oats in their gluten-free diets without deleterious effects to the skin or intestine.

TISSUE ANTIBODIES IN DERMATITIS HERPETIFORMIS AND ADULT CŒLIAC DISEASE

Abstract A new antibody of IgG class reacting with connective tissue in rat and human organs was found in 17% of 29 patients with dermatitis herpetiformis and in 36% of 31 patients with adult coeliac disease. The antibody appeared to be directed against reticulin rather than basement membrane. In 34% of the dermatitis-herpetiformis patients antinuclear factors of IgG or IgM class were present.

EFFECT OF GLUTEN-FREE DIET ON DERMATOLOGICAL, INTESTINAL, AND HÆMATOLOGICAL MANIFESTATIONS OF DERMATITIS HERPETIFORMIS

Abstract 7 patients with dermatitis herpetiformis were given a gluten-free diet for 6 months. At the end of this time 4 patients had improved subjectively, and 2 had definitely gained weight. In 2 the skin lesions had improved so much that they could manage without dapsone, and in another 3 the dapsone requirements had fallen. In each of 5 patients in whom faecal fat excretion was raised initially, the gluten-free diet reduced this excretion. After the diet the macroscopic appearance of the intestinal mucosa improved in the 3 patients in whom it had been abnormal, and increase in villous height of the intestinal mucosa was found in 5. The serum-folate rose in 6 of the 7 patients; and in each of 4 in whom the red-cell folate had been subnormal the level rose —in 3 to normal. These results suggest that the enteropathy in dermatitis herpetiformis is due to gluten sensitivity, and that the skin lesions are related to the enteropathy.

ANTI-RETICULIN ANTIBODIES IN CHILDHOOD CŒLIAC DISEASE

Abstract 19 patients with childhood cœliac disease and 28 controls have been investigated for the presence of anti-reticulin antibody. The antibody was found in 14 of the 19 patients with cœliac disease. 10 of these 19 were on a normal diet, and in 9 of these the antibody was found; whereas in the 9 patients on a gluten-free diet, it was found in 5. The antibody was also found in 1 of 28 control subjects. The anti-reticulin antibody is apparently specific for cœliac disease and may be of help in the diagnosis of the disease.