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The infiltration of polymorphonuclear neutrophils (PMN) into the upper dermis which characterizes the skin lesions of dermatitis herpetiformis (DH) has never been satisfactorily explained. This study has shown that lesional skin of patients with DH has increased expression of endothelial leucocyte adhesion molecules (ELAM) in the deep dermis, combined with a markedly increased staining for interleukin 8 (IL-8) in the basal epidermal layer. Dendritic cells which stained for granulocyte macrophage colony stimulating factor (GM-CSF) were also observed at the dermo-epidermal junction, and this phenomenon was more pronounced in lesional than in uninvolved DH skin. ELAM, IL-8 and GM-CSF are known to promote infiltration and activation of PMN, and it is suggested that these cytokines may play a key role in the generation of DH lesions.

The aim of this study was to evaluate the potential role of certain soluble factors in conjunctival scar tissue formation of pemphigoid patients. Epibulbar conjunctival biopsy specimens were taken from patients with acute ulcerative (n = 4), subacute (n = 8) and chronic (n = 8) mucous membrane pemphigoid and from twelve age-matched healthy individuals. The tissues were embedded in glycol methacrylate and analysed by immunohistochemical methods. Interleukin-2 (IL-2), interferon-gamma, transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), tumour necrosis factor-alpha and proliferating cells (as identified with the antibody Ki-67) were found in both pemphigoid patients and normal controls. Interleukin-4 was not found with this method in either normal or diseased conjunctiva. Significant differences between normal and diseased conjunctiva were found for TGF-beta and for proliferating cells, which were both increased in the acute disease group. More intense staining was found in the subacute disease group for IL-2, bFGF and PDGF. Our findings showed that a variety of cytokines were present in normal and diseased bulbar conjunctiva. Acute conjunctival disease in mucous membrane pemphigoid may indicate active scar tissue formation, implied by an increase in TGF-beta and the presence of proliferating fibroblasts.

A patient with dermatitis herpetiformis (DH) developed abnormal liver function tests and was found to have histological features of primary sclerosing cholangitis (PSC) on liver biopsy. The association of DH and PSC has not been previously reported and the high incidence of phenotype HLA B8 and DR3 in these disorders suggests a common genetic predisposition may exist for both diseases.

Background: The mechanism of chronic progressive conjunctival cicatrization in mucous membrane pemphigoid is not well understood, and current therapy is often of limited use. Rapid progression of cicatrization follows exacerbations of clinical inflammation, and the investigation of immune mechanisms related to disease activity may provide a clue for more effective therapeutic strategies., Methods: The authors undertook an immunohistochemical study, using monoclonal and polyclonal antibodies in glycol methacrylate-embedded tissues, of epibulbar conjunctival biopsy specimens obtained from 20 patients with ocular cicatricial pemphigoid and from 12 matched healthy controls. The study patients were classified according to the ocular disease activity as acute ulcerative (n = 4), subacute (n = 8), and chronic (n = 8)., Results: The composition of the subepithelial cellular infiltrate varied with disease activity. Acute disease was characterized by an abundance of macrophages and neutrophils. The number of T lymphocytes was significantly raised in all the disease groups, but were most marked in subacute disease. Of the T-cell subsets, there were more CD8- than CD4-positive cells observed, except in acute disease where there were equal numbers. Only approximately 5% of the T cells in all disease groups were activated as demonstrated by expression of interleukin-2 receptor. There was increased expression of major histocompatibility complex class II (MHC II) molecules on macrophages, fibroblasts, and other cells in all the groups. The number of B cells and natural killer cells was not increased. Staining for the fibrogenic cytokines, transforming growth factor-beta (TGF-beta), platelet-derived growth factor, and basic fibroblast growth factor was found in both pemphigoid patients and control persons, but the intensity of TGF-beta staining was significantly greater in acute disease., Conclusions: The composition of the cellular infiltrate in the bulbar conjunctiva depends on clinical disease activity. The numbers of neutrophils and macrophages seem to reflect clinical disease activity. Fibrogenic cytokines, especially TGF-beta, may play an important role in the formation of conjunctival scar tissue.

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.

Two cases of adult linear IgA disease are reported. They demonstrate the two sites of deposition of IgA at an ultrastructural level: sub-basal lamina and lamina lucida. This finding supports the view that there are subgroups of this disease. Clinical presentation and histological appearance of lesional skin are misleading, and the immunofluorescent appearance is unhelpful in predicting the ultrastructural localization of the IgA deposit.

Forty two white patients of British or Irish descent with coeliac disease and 28 with dermatitis herpetiformis were typed for class I HLA-A, B, and C, and class II DR and DQ antigens. In coeliac disease there was a significant increase in the frequencies of A1, B8, DR3, DR7, and DQw2 compared with controls but no increase of DR2. In dermatitis herpetiformis there were similarly increased frequencies of A1, B8, DR3, and DQw2. In contrast with coeliac disease, however, the frequency of DR7 (18%) was no different from the control group but there was an increased frequency of DR2.

The pharmacokinetics of dapsone (DDS) and monoacetyldapsone (MADDS) following an oral dose of 150 mg DDS were studied in sixteen patients with dermatitis herpetiformis and seven normal subjects. No differences in DDS disposition were observed between the two groups. The maintenance dose of DDS for individual patients was not significantly correlated with jejunal biopsy morphology, DDS or MADDS half-lives, or the area under the plasma concentration-time curves for DDS or MADDS. DDS plasma protein binding was normal in patients and did not apparently determine the concentration of DDS in skin biopsies, for which the skin/plasma DDS concentration ratio was approximately unity. There was no undue representation of acetylator phenotype in the patient group and no correlation between maintenance dose and MADDS/DDS ratio was noted. The determinants of the maintenance DDS dose have not been found. This may relate to pharmacodynamic differences, but alternatively the concentration of oxidative metabolites rather than DDS or MADDS could be responsible for the therapeutic activity in dermatitis herpetiformis.

A previous study using immunofluorescent techniques showed J-chain to be present in the uninvolved skin of patients with papillary IgA dermatitis herpetiformis (DH) in a distribution that was coextensive with the IgA. This implied that the IgA was dimeric and of mucosal origin. In this study, fifteen patients with papillary IgA deposits, fifteen with homogeneous-linear (HL) IgA deposits and four patients with granular-linear (GL) IgA deposits were tested for the presence of in vivo bound J-chain. All fifteen patients with papillary IgA deposits and all four with GL IgA deposits had J-chain staining coextensive with the IgA. However, only one of fifteen patients with HL IgA deposits demonstrated in vivo bound J-chain that could not be accounted for by coexisting IgM deposits. These findings indicate that the IgA in patients with HL deposits is qualitatively different from that in patients with papillary and GL IgA deposits and makes the distinction between the two types of linear fluorescence particularly important.

The histologic appearances of cutaneous biopsy specimens from 30 patients with linear IgA disease with a continuous band of IgA along the basement membrane, four patients with a linear pattern of granular IgA along the basement membrane, 26 patients with dermatitis herpetiformis who had IgA in the papillary dermis, and 23 patients with bullous pemphigoid who had IgG and/or C3 along the basement membrane were compared. Those with linear and granular IgA and dermatitis herpetiformis differed from those with bullous pemphigoid in five respects. Multiple microabscesses and fibrin at tips of papillae and leukocytoclasis were less common in bullous pemphigoid, whereas a dense infiltrate of eosinophils in and below bullae and a linear infiltrate of eosinophils along the basement membrane were more common in bullous pemphigoid. Also, multilocular bullae and acantholysis were more common in dermatitis herpetiformis than in bullous pemphigoid. Linear IgA disease differed from dermatitis herpetiformis in two respects. Acantholysis and fibrin at the tips of papillae and leukocytoclasis were more common in dermatitis herpetiformis. The specimens from patients with granular IgA did not differ significantly from those with linear IgA or dermatitis herpetiformis. The appearances of biopsy specimens of patch tests with potassium iodide taken from 11 patients with dermatitis herpetiformis and linear or granular IgA disease were similar to those taken from spontaneous lesions.

Nine out of thirty-four patients with linear IgA disease (LAD) had oral ulceration. Four out of seven of these patients who were examined by an ophthalmologist had changes of a cicatrising conjunctivitis indistinguishable from those of benign mucous membrane pemphigoid (BMMP). Three of these patients gave no history of ocular symptoms up to the time of examination. These findings indicate a need for oral and ophthalmological assessment in all patients with LAD. Twenty-seven patients with a diagnosis of BMMP were also studied. Nine presented with oral symptoms alone, nine with ocular symptoms alone, seven with oral and ocular symptoms, and two with cutaneous lesions in addition to oral and ocular symptoms. All the patients were examined by the same ophthalmologist. Six of the nine patients who presented with oral symptoms alone had signs of a cicatrising conjunctivitis. Four of these six patients had the clinical pattern of erosive gingivitis which was not previously thought to be associated with a cicatrising conjunctivitis. There is a similar need, therefore, for an ophthalmological assessment in all patients presenting with oral BMMP. Three of the twenty-seven patients with BMMP had homogeneous-linear deposits of IgA in uninvolved skin. The finding of linear IgA deposits in the skin of these patients with only mucous membrane lesions, and the finding that patients with LAD have a high incidence of oral and conjunctival lesions, raise the possibility of a common pathogenic pathway but with varying clinical expressions in these two groups.

A case of generalized trichorrhexis nodosa is described in a man. Electron histochemical studies showed abnormal staining consistent with a definite disorder in the formation of alpha-keratin chains within the globular matrix of the hair cortex with respect to cystine; keratin amino-acid analysis also revealed low cystine. This cortical change, together with multiple vacuoles found in the endocuticle, are evidently the intrinsic defects which allow relatively trivial chemical and physical trauma to cause trichorrhexis nodosa.

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.

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. The three groups were similar with regard to age of onset, presence of circulating immune complexes and auto-antibodies, incidence of spontaneous remission, histology of lesional skin and response to dapsone. There was a female predominance in the HL group in contrast to the male predominance in the other two. It was not possible to diagnose the HL group clinically. Some patients had a rash typical of DH whilst others resembled pemphigoid. In the majority, however, no specific diagnosis could be made with confidence. The GL group clinically resembled the DH group. The incidence of positive potassium iodide patch tests was greater in the DH group than in the other two. An associated enteropathy was found in 24% of patients in the HL group, 30% of patients in the GL group and 85% of patients in the DH group. Fifty-six percent of HL patients had HLA-B8 compared with 50% in the GL group and 88% in the DH group. Patients with linear IgA deposits may not be a uniform group, but until they can be divided into specific subgroups (e.g. by ultrastructural localization of the deposit or by response to a gluten-free diet) we propose that the term adult linear IgA diseases should be used to distinguish these patients from those with papillary IgA deposits.

We describe the effects of treatment with topical steroids or dithranol on T and dendritic cells in the skin of patients with chronic plaque psoriasis. Resolution of lesions by both types of topical treatments was accompanied by a marked decrease in epidermal T cells. In steroid treated lesions there was also a reduction in DR+ dendritic cells to normal numbers during treatment and the rate of disappearance of both cell types correlated with the rate of resolution. However, a significant reduction of dendritic cells was not usually observed until after the T cells had almost disappeared from the epidermis and substantial healing of lesions had taken place. Dendritic cells in steroid-treated uninvolved skin had decreased to a lower level than in normal skin. In contrast, dithranol did not affect dendritic cells, either in lesional or in unaffected psoriatic epidermis. The decrease in dermal T cells observed with both treatments was more marked in steroid-treated lesions and correlated with resolution. However, blood T cells were unaffected by both treatments. The findings provide further support for the role of T cells in the pathogenesis of psoriasis.

Thirteen adults with dermatitis herpetiformis (DH) controlled by dapsone or sulphamethoxypyridazine were given indomethacin or placebo in a double-blind cross-over study. In nine of the thirteen patients the rash and pruritus of DH were exacerbated more by indomethacin than by placebo. Dapsone and sulphamethoxypyridazine requirements were increased during the indomethacin period. The involvement of lipoxygenase products in the pathogenesis of the DH skin lesions is postulated.

It has previously been reported that gliadins bind to reticulin in tissue sections. Three lines of evidence are reported in this study which indicate that the gliadins bind to reticulins because they are lectins which bind to sugars expressed on glycoproteins in reticulin and other sites. First, immunofluorescence studies on tissue sections showed that although gliadin binding is largely confined to areas rich in reticulin, it is, nonetheless, also seen in one or two other sites devoid of reticulin. Second, by using fluorescein-labelled lectins of known specificity, it has been shown that the areas to which gliadins bind in tissue sections (including those sites devoid of reticulin) are rich in particular sugars. Third, it has been shown that one of these sugars, alpha-D-mannose, partially inhibited gliadin binding to tissue sections.

One-hundred and sixty-eight cases of dermatitis herpetiformis were reviewed to compare the clinical response to and incidence of side-effects from dapsone and sulphamethoxypyridazine. Thirty-seven received sulphamethoxypyridazine (0.25-1.5 g/day) as a single agent therapy at some stage during their care and 161 had dapsone only (50-450 mg/day). Thirty of these patients received both drugs, but at different times. Both were highly effective in controlling the skin disease in 97% of patients on dapsone and 89% on sulphamethoxypyridazine. While 36 (22%) of dapsone-treated subjects had intolerable side effects warranting a change in therapy, this occurred in only five (13.5%) of those treated with sulphamethoxypyridazine. Sulphamethoxypyridazine was also effective as a single agent in three patients with linear IgA disease who had suffered adverse effects from dapsone, and in 10 out of 15 patients with oral and cutaneous lesions of cicatricial pemphigoid.

Skin-biopsy specimens from six patients with dermatitis herpetiformis (DH) were examined by means of indirect immunofluorescence with specific rabbit antisera for the presence of in-vivo J chain and secretory component in IgA deposits. The ability of IgA to bind purified secretory component was studied by means of indirect immunofluorescence with antisera to secretory component. Positive J-chain staining associated with IgA deposits was seen in cryostat sections of all seven DH skin-biopsy specimens. In-vivo secretory component was not detected, but on treatment of sections with a solution of purified secretory component, binding of the latter in the region of the IgA deposits was demonstrated in six of the seven DH skin-biopsy specimens. With double fluorochrome staining binding of secretory component was shown to be essentially coextensive with the IgA deposits. These findings suggest that the IgA deposited in DH skin originates from plasma cells in the small intestine.

Seventy-eight patients with dermatitis herpetiformis have been followed up for periods ranging from 3 to 14 years (mean 7.4). Forty-two patients were treated with gluten-free diet (GFD) and thirty-six took a normal diet (ND). Thirty of the forty-two (71%) taking the GFD were able to discontinue drugs previously needed to control their rash compared with five (14%) of the thirty-six patients taking a ND. The mean time taken to reduce drug requirements for patients taking a GFD was 8 months (range 4-30), and for stopping drugs, 29 months (range 6-108). The incidence of macroscopic abnormality of the small intestine decreased from 69 to 15%, and the mean intra-epithelial lymphocyte count decreased significantly in those patients taking a GFD, whereas there was no significant change in patients taking a ND. The improvement in the skin and intestinal lesions was related to the strictness of the GFD.

Patients with oral cicatricial pemphigoid, who present to an oral medicine department, should be examined by an ophthalmologist because over 65 per cent have been found to have an asymptomatic cicatrising conjunctivitis. Early detection and treatment of these patients may help to slow down the scarring process that eventually leads to a dry eye and blindness. The same is true for a group of patients who present to the dermatologist with a non-scarring bullous dermatosis distinguished by the presence of a linear deposit of IgA along the dermo-epidermal junction of uninvolved skin examined by direct immunofluorescence. The cicatrising conjunctivitis found in about 50 per cent of adults with this condition is indistinguishable from that of cicatricial pemphigoid. Ten per cent of patients with cicatricial pemphigoid affecting mucous membranes alone were found to have linear deposits of IgA along the dermo-epidermal junction of uninvolved skin. This suggested that there may be a common pathogenic pathway with varying clinical expression in these groups of patients and presents new possibilities for therapy in some patients with cicatricial pemphigoid.

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.

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.

This study reports the appearance of IgA-class anti-endomysial antibodies in the serum of 8 out of 12 patients with dermatitis herpetiformis who were challenged with gluten after a number of years of control of the rash with a strict gluten-free diet. Although there was no evidence for the antibodies having any pathogenic role in the rash of dermatitis herpetiformis, their presence may be related to the deterioration in the gluten-sensitive enteropathy.

A retrospective study of 109 patients with dermatitis herpetiformis showed that malignant tumours had developed in seven patients, the expected incidence being 2.93, giving a relative risk of 2.38. In three of the seven patients the malignancy was a lymphoma, giving a relative risk of 100 for this tumour (expected incidence 0.03). In six of the seven patients who developed malignancies small-intestinal biopsy specimens were macroscopically abnormal, giving a relative risk of 4.22 in this group, which is similar to that reported in adult coeliac disease. Patients treated with a gluten-free diet appeared to have a reduced risk of developing malignancy compared with those taking a normal diet (relative risk with gluten-free diet 1.01 and with normal diet 3.09). A small subgroup of eight patients with linear IgA dermatitis herpetiformis were also studied: three developed malignant disease and in one the tumour was a lymphoma.

Twenty nine patients with cicatrizing conjunctivitis were studied; 17 with a clinical diagnosis of cicatricial pemphigoid, five with a clinical diagnosis of pseudopemphigoid caused by long-term application of topical medication and seven who had a cicatrizing conjunctivitis from other causes. Biopsies from clinically uninvolved bulbar conjunctiva were taken for direct immunofluorescence and blood was taken for indirect immunofluorescence using normal human conjunctiva, oral mucosa and skin as substrates. On direct immunofluorescence, in vivo bound immunoglobulins were found along the basement membrane in 10 of the 17 patients with cicatricial pemphigoid, one of the five with pseudopemphigoid and two of the seven with a cicatrizing conjunctivitis associated with other diseases. Circulating anti-basement membrane zone antibodies were found only when conjunctiva was used as a substrate. These were present in seven of the patients with cicatricial pemphigoid, three of those with pseudopemphigoid and two of those with a cicatrizing conjunctivitis caused by other diseases. These results indicate that direct immunofluorescence is a useful, but not absolute diagnostic marker for ocular cicatricial pemphigoid. The results in the pseudopemphigoid group argue that this is an immunologically mediated disorder indistinguishable from spontaneous cicatricial pemphigoid and probably triggered by the drugs. The presence of circulating antibodies should allow for precise identification of the antigen involved in cicatricial pemphigoid using SDS electrophoresis and Western blot analysis.

We have investigated DNA polymorphism of the class II alpha chain genes in HLA typed patients with insulin dependent diabetes mellitus (IDDM; n = 79), celiac disease (CD; n = 46), dermatitis herpetiformis (DH; n = 53), and controls (n = 86). Preferential allelic associations of HLA genes and gene products have thus been constructed for susceptibility to these diseases. DR alpha and DQ alpha gene polymorphisms indicated heterogeneity of HLA DR3, DRw6, and DR7, and HLA DR2 and DRw6, respectively. In DR7 positive CD patients a 3.8-kilobase (kb) DR alpha fragment, which correlated with DQw3, was found in only 11% of patients compared with 45% of corresponding controls (P less than 0.05). An increased frequency of a DX alpha genotype UU in all three diseases was found (IDDM 59%, DH 45%, CD 48%, compared to 21% in controls, P less than 0.001), which is not explained solely by the increased frequencies of DR3-DX alpha U. We therefore conclude part of the genetic susceptibility for these three conditions is encoded by genes within the DQ-DX subregion.

Sequential skin biopsies from six patients with severe psoriasis were studied during treatment with cyclosporin. Four of the patients cleared completely and the remaining two showed a marked improvement. A subset of dendritic cells, HLA-DR+ but lacking the T6 antigen characteristically expressed by Langerhans cells (DR+ 6-), was observed in lesional epidermis. They disappeared during treatment, before clinical improvement was apparent and at a rate which correlated with clearance of psoriasis. These cells were not found in normal or uninvolved psoriatic epidermis and their number in lesional skin appeared to be related to the clinical severity of the disease. Total numbers of CD4 and CD8, and HLA-DR+ CD8 T cells were substantially reduced in both epidermis and dermis prior to clinical improvement. In contrast, there was generally no decrease in the number of HLA-DR+ CD4 T cells in the epidermis during resolution, whereas these cells were reduced by an average of 68% in the dermis. The beneficial effects of cyclosporin in psoriasis further support the hypothesis that T cells play a central role in the pathogenesis of psoriasis. The cellular changes observed in the skin during cyclosporin treatment may help to elucidate the effects of this drug on immunoregulatory mechanisms in man.

Lichen planus is a relatively common inflammatory dermatosis with characteristic lesions affecting the skin, nails and mucous membranes. Nail changes are present in approximately 10% of patients and can occasionally occur in the absence of skin involvement. The association of lichen planus with primary biliary cirrhosis is now well recognized. We report the first case of lichen planus confined to the nails in a patient with primary biliary cirrhosis.

The distribution and activation of T-lymphocyte subsets in the small intestinal mucosa of coeliac disease and dermatitis herpetiformis subjects on a normal diet has been studied and compared to normal controls. Double-labelling immunofluorescence techniques with monoclonal antibodies were used on cryostat tissue sections. Intestinal epithelial cells demonstrated staining for HLA-DR, the intensity being proportional to the degree of enteropathy. In both patients and controls nearly all (97%) intra-epithelial lymphocytes were of the CD8 subset and not activated as judged by HLA-DR expression. In the lamina propria there was an approximate 50-fold increase in T cells in the patients as compared with the controls. Whilst the ratio of total CD4 to total CD8 cells was unchanged, the CD4 subset was preferentially activated in the patients. Thus in the normal controls the median ratio of activated CD4 cells to activated CD8 cells was 1.67 whilst for dermatitis herpetiformis and coeliac disease it was 3.42 and 6.07 respectively. These findings suggest that the lamina propria is a site of vigorous T-cell activity in gluten-sensitive individuals and is consistent with the view that the enteropathy of dermatitis herpetiformis and coeliac disease is the result of a delayed-type hypersensitivity against gliadin.

The numbers and HLA-DR expression of T cell subsets and dendritic cells in chronic psoriatic plaques were compared to previously reported findings in spontaneously resolving guttate lesions, and the effects of PUVA treatment on these cell populations studied. The chronic lesions showed a similar T helper/T suppressor (TH/TS) ratio (0.66 +/- 0.10) to resolving guttate lesions. However, in contrast to the resolving lesions which do not contain activated epidermal TH cells, a substantial proportion of the TH cells in the persistent plaques were DR+. Moreover, these persistent lesions contained markedly increased numbers of DR+ dendritic cells, approximately 20% of which were T6 negative. PUVA-induced resolution of chronic lesions was associated with depletion of epidermal TH and TS cells, and a subsequent reduction in DR+ dendritic cells. In each patient the rate of disappearance of both cell types correlated with the rate of resolution. Furthermore, the epidermal T cell depletion preceded the onset of clinical improvement. In contrast, significant reduction of the dendritic cells was generally not observed until the lesions were largely resolved. Dendritic cells decreased faster in uninvolved than in lesional skin and to a subnormal level. Dermal T cells also decreased during PUVA therapy but this did not show any obvious correlation with resolution of the lesions. Blood T cell levels were not significantly affected by the treatment. These findings support the concept that the initiation and maintenance of the psoriatic process requires activation of TH cells in the epidermis via interaction with antigen presenting cells. Furthermore PUVA treatment may clear psoriasis by interfering with such a mechanism through its effects on T lymphocytes.