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Biomedical subjects

L Fry

Publications and source records attributed to L Fry.

At least 109 records · Page 6Linked to original sources

HLA class II alpha chain gene polymorphisms in patients with insulin-dependent diabetes mellitus, dermatitis herpetiformis, and celiac disease.

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.

Celiac Disease↗

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.

Adult↗

Different HLA associated gene combinations contribute to susceptibility for coeliac disease and dermatitis herpetiformis.

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.

Adolescent↗

IgA anti-endomysial antibody detection in the serum of patients with dermatitis herpetiformis following gluten challenge.

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.

Adult↗

Dermatitis herpetiformis exacerbated by indomethacin.

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.

Adult↗

The effects of topical treatment with steroids or dithranol on epidermal T lymphocytes and dendritic cells in psoriasis.

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.

Administration, Topical↗

Epidermal T lymphocytes and dendritic cells in chronic plaque psoriasis: the effects of PUVA treatment.

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.

Adult↗

Skin diseases and the dry eye.

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.

Adolescent↗

The relationship between linear IgA disease and benign mucous membrane pemphigoid.

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.

Adult↗

Evidence that the IgA in patients with linear IgA disease is qualitatively different from that of patients with 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.

Adult↗

Epidermal T lymphocytes and HLA-DR expression in psoriasis.

Double staining immunofluorescent techniques and monoclonal antibodies were used to study the numbers, distribution, HLA-DR expression and relationship of T-cell subpopulations and dendritic cells in psoriatic skin. In the dermis there was a definite increase in both T helper and T suppressor cells in uninvolved skin of psoriatic patients, and the appearance of clinical lesions was not associated with any detectable change in the numbers of these cells in the dermis. In contrast, eruption of skin lesions was associated with an increase in the numbers of epidermal HLA-DR+ dendritic cells and also with epidermal influx and activation of T helper cells, while resolution of lesions coincided with increased epidermal entry and activation of T suppressor cells. Both the T helper and T suppressor cells were preferentially found adjacent to epidermal dendritic cells. These findings suggest that the clinical activity of psoriasis may be dependent upon the interaction of T helper and suppressor cells with antigen-presenting cells in the epidermis.

Antibodies, Monoclonal↗

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.

Antibodies, Monoclonal↗

Increased incidence of malignancy in dermatitis herpetiformis.

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.

Dermatitis Herpetiformis↗