Tissue transglutaminase antibodies in dermatitis herpetiformis.
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Antibodies↗
Biomedical subjects
L Fry
Publications and source records attributed to L Fry.
Sarcoidosis in a patient with linear IgA disease.
We report a patient with four conditions in association with linear IgA disease (LAD), only three of which have been reported previously; these latter are ulcerative colitis, autoimmune thyroid disease and carcinoma of the colon, although the carcinoma may have been caused by the ulcerative colitis in this case. Recently, our patient also presented with respiratory symptoms and was found to have sarcoidosis as well, a previously unreported association of this autoimmune bullous disorder. The aetiology of this development may be related to the patient's HLA status or possibly to his treatment with the immunosuppressive agent cyclophosphamide; it is also possible that it is coincidental.
Adenocarcinoma↗
Characterizing sequence variation in the VP1 capsid proteins of foot and mouth disease virus (serotype 0) with respect to virion structure.
The VP1 capsid protein of foot and mouth disease virus (FMDV) is highly polymorphic and contains several of the major immunogenic sites important to effective antibody neutralization and subsequent viral clearance by the immune system. Whether this high level of polymorphism is of adaptive value to the virus remains unknown. In this study we examined sequence data from a set of 55 isolates in order to establish the nature of selective pressures acting on this gene. Using the known molecular structure of VP1, the rates and ratios of different types of nonsynonymous and synonymous changes were compared between different parts of the protein. All parts of the protein are subject to purifying selection, but this is greatest amongst those amino acid residues within beta-strands and is significantly reduced at residues exposed on the capsid surface, which include those residues demonstrated by previous mutational analyses to permit the virus to escape from monoclonal antibody binding. The ratios of nonsynonymous substitution resulting in various forms of physicochemically radical and conserved amino acid change were shown to be largely equal throughout these different parts of the protein. There was a consistently higher level of nonsynonymous and charge radical sites in those regions of the gene coding for residues exposed on the outer surface of the capsid and a marked difference in the use of amino acids between surface and nonsurface regions of the protein. However, the analysis is consistent with the hypothesis that the observed sequence variation arises where it is least likely to be disruptive to the higher-order structure of the protein and is not necessarily due to positive Darwinian selection.
Amino Acid Sequence↗
Renal function after 10 years' treatment with cyclosporin for psoriasis.
Renal function was assessed by measuring serum creatinine and glomerular filtration rate (GFR) in two groups of patients with chronic plaque psoriasis who had been treated with cyclosporin A (CyA), average dose 2.8 mg/kg per day (range 1-5 mg/kg per day). Group I was our original cohort of nine patients, seven of whom had received CyA for an average period of 10 years (range 9.5-11 years). These seven patients showed a persistent increase in serum creatinine > 30% from baseline measurement and four of the seven had persistent increases > 50%. The GFR, which was first measured after 2.5 years of treatment, showed at 10 years a decrease of > 30% in two patients and of > 50% in one patient. Three of the seven showed stable renal function while two had repeat renal biopsy because of deteriorating renal function and histology showed further evidence of CyA nephrotoxicity compared with that after 5 years' treatment. Two of the nine patients in group I had discontinued CyA 5 years previously after 5 years of treatment because of CyA nephrotoxicity on renal biopsy and impaired renal function. This impairment of renal function showed improvement during the 5 years of follow-up, implying reversibility of CyA nephrotoxicity. The second group of 20 patients had received CyA for an average duration of 6 years (range 5-8 years). Nine of the 20 patients showed persistent increases in serum creatinine of > 30% from baseline and five showed persistent increases of > 50%. The GFR showed a persistent decrease of > 30% in seven patients and of > 50% in two patients. This study has shown that nephrotoxicity is associated with long-term treatment with CyA. However, there is patient variation as to when nephrotoxicity commences and its speed of progression. On discontinuing CyA the impairment of renal function improves with time. Providing renal function is monitored with GFR and renal biopsy in addition to serum creatinine then long-term (5-10 years) CyA treatment can be justified in severe psoriasis not responsive to other treatments.
Adult↗
Focal dermal hypoplasia: report of a case with cutaneous and skeletal manifestations.
Focal dermal hypoplasia is a rare genodermatosis characterized by developmental defects of the skin, resulting in widespread linear lesions of dermal hypoplasia with adipose tissue in the dermis. We describe a 13-year-old girl who has typical cutaneous lesions which have been present since birth; she also has some of the associated dental, nail and skeletal abnormalities, while an X-ray of the long bones osteopathia striata is visible, a feature seen in a high proportion of cases of focal dermal hypoplasia. Eighty-eight per cent of the case reports in the literature are of females and X-linked dominance is the likely mode of inheritance. It has also been proposed that the condition is lethal in homozygous males and the high frequency of miscarriages on the maternal side of this patient's family is consistent with that lethality in males. The literature, particularly with regard to pathogenesis and inheritance, is discussed.
Adipose Tissue↗
Conversion of psoriasis patients from the conventional formulation of cyclosporin A to a new microemulsion formulation: a randomized, open, multicentre assessment of safety and tolerability.
OBJECTIVE: To assess the safety, tolerability and efficacy of a new cyclosporin A (CyA) microemulsion formulation, Sandimmun Neoral (Neoral), in patients with severe psoriasis that was stable on CyA administered as Sandimmun (SIM). METHODS: In this 24-week, open, randomized, prospective, multicentre trial, 28 patients continued on the same dosage of SIM, while 30 converted to Neoral at 2.5 mg/kg/day or a dosage equivalent to their pre-conversion SIM dosage. During the study, dosages could be adjusted to maintain efficacy, because of adverse events or after disease stabilization. The maximum permitted dosage for either formulation was 5.0 mg/kg/day. Primary efficacy criteria were change in Psoriasis Area and Severity Index (PASI) from baseline and time to relapse. RESULTS: The dosage was increased to maintain efficacy in 22 patients (Neoral 13; SIM 9) and 20 dose reductions for safety were required (Neoral 14, SIM 6). In both groups, PASI scores remained stable throughout and relapses were primarily a result of dosage reduction after disease stabilization. No significant difference was found between groups in the proportion of patients remaining relapse-free. Adverse events were recorded in 20 patients receiving Neoral and 14 receiving SIM. Most drug-related events were of mild or moderate severity and reflected the known CyA side-effect profile. Dose titration guidelines ensured that mean blood pressure and serum creatinine concentrations remained stable in both groups. CONCLUSIONS: If the guidelines for CyA use are followed and the Neoral dosage does not exceed 5 mg/kg/day, conversion of stable patients with severe psoriasis from SIM to Neoral should present no clinically relevant safety or tolerability problems and efficacy of treatment is maintained.
Adolescent↗
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.
Adult↗
Induction of cutaneous lymphocyte-associated antigen expression by group A streptococcal antigens in psoriasis.
The cutaneous lymphocyte-associated antigen (CLA) has been proposed as a homing receptor for the selective migration of memory T cells into the skin. To investigate the effect of group A streptococci (GAS) on the migration of T cells in psoriasis, CLA expression was assessed by double-staining for CD3 and the HECA-452 epitope on peripheral blood T cells from 13 patients with psoriasis, 10 patients with other inflammatory skin diseases and 12 normal controls before and after 7 days culture with a GAS sonicate, Candida albicans (control antigen) or medium. In addition, CLA+, and CLA-, CD3+ CD45RO+ subsets were isolated from individuals in each group and V beta 2 expression and proliferation to GAS studied. Mean CLA expression by freshly isolated T cells was almost identical in the three groups. After culture with GAS, T cells from the psoriatic patients and control showed a significant increase in mean percentage CLA+ expression compared to medium (P < 0.002, P < 0.05, respectively). This induction was inhibited by the addition of anti-IL-12 antibody. However, in psoriatic patients, but not in controls, the GAS-induced increase was significantly greater than that of C. albicans (P < 0.002) and was accompanied by a decrease in T cells positive for the peripheral lymph node homing receptor, L-selectin (P < 0.05). The percentage of V beta 2+ T cells was markedly higher in the CLA+ than in the CLA- T-cell subset in psoriatic patients (P < 0.01) and controls; both subsets proliferated to GAS, in each group. These findings suggest a differential modulation of specific tissue homing receptors on T cells by GAS in psoriasis.
Adolescent↗
T-cell receptor V beta expression is restricted in dermatitis herpetiformis skin.
An infiltrate of T-cells is found in lesional dermatitis herpetiformis skin, but the role of these cells in the pathogenesis of the skin lesions is unknown. The purpose of this study was to examine T-cell receptor V beta expression in skin biopsies taken from patients with dermatitis herpetiformis. Expression of eleven T-cell receptor V beta families in biopsies obtained from 10 patients was examined by immunoperoxidase staining and compared simultaneously with peripheral blood lymphocytes. Over-representation of V beta 2 (p < 0.02), V beta 5.2/5.3 (p < 0.01) and V beta 5.3 (p < 0.05) was found in lesional dermatitis herpetiformis skin compared with peripheral blood lymphocytes. These results suggest that recognition of an antigen(s) or superantigen is involved in the pathogenesis of dermatitis herpetiformis skin lesions.
Adult↗
Differential T-cell reactivity to the round and oval forms of Pityrosporum in the skin of patients with psoriasis.
Pityrosporum yeasts have been implicated as a trigger for the initiation of scalp lesions in psoriasis. To determine whether Pityrosporum-reactive T cells are present in lesional psoriatic skin. T-cell lines (TCL) were cultured from the scalps of nine patients with psoriasis and seven with alopecia areata (disease controls), and from non-scalp lesions from six of the psoriatic patients. The psoriatic skin TCL were stained for CD3, CD4, CD8 and TCR alpha beta expression and tested in a proliferation assay with Candida albicans and purified protein derivative (PPD), and cytoplasmic and cell-wall extracts of P. ovale (oval) and P. orbiculare (round). The proliferative responses of corresponding peripheral blood mononuclear cells (PBMC) were also determined. All the PBMC samples responded to the Pityrosporum extracts to variable extents, but no significant difference in the response of the group to the two different forms of yeast was observed. The response was mediated by CD4+ T cells and inhibited by the addition of anti-HLA-DR antibody. In addition, all nine psoriatic scalp TCL, which were predominantly CD3+, CD4+ TCR alpha beta(+), responded to the cytoplasmic, and five of nine TCL to the cell-wall extract of P. orbiculare. In contrast, only three of the nine TCL proliferated to either extract of P. ovale. This difference was significant for both the cytoplasmic (P < 0.01) and cell wall (P = 0.01) extracts. Similarly, the TCL cultured from non-scalp psoriatic lesions also showed a more marked response to the P. orbiculare extracts (P = 0.05). Furthermore, four of seven and two of seven scalp TCL from lesions of alopecia areata responded to the P. orbiculare and P. ovale extracts, respectively; these responses did not differ significantly from those of the psoriatic scalp TCL. None of the skin TCL responded to either Candida albicans or PPD. These findings demonstrate that T cells with differential reactivity to the round and oval forms of Pityrosporum are present in, but are not specific for, psoriatic skin lesions. A role for these cells in the pathogenesis of psoriasis remains speculative.
Adult↗
Linear IgA disease and ulcerative colitis.
Seventy adult patients with linear IgA disease were studied. Five (7.1%) also suffered from ulcerative colitis (the prevalence of ulcerative colitis in the U.K. is 0.05%). A further three patients with this association, from other British centres were also reviewed. In all cases, ulcerative colitis preceded the onset of skin disease, by a median of 6.5 years. The reason for this association remains unclear but the abnormalities in colonic mucosal B cells and mucosal IgA1 production reported in patients with ulcerative colitis may be important in the subsequent development of IgA1 mediated linear IgA disease.
Adult↗
Active psoriasis and profound CD4+ lymphocytopenia.
We report the case of a patient with a long-standing history of widespread chronic plaque psoriasis, who was recently found to have a profound CD4+ lymphocytopenia. He is human immunodeficiency virus (HIV) negative. His psoriasis remains active and widespread, and he has had 60 cutaneous malignancies, including many squamous cell carcinomas, excised over the last 10 years. In the past he has had numerous cutaneous viral warts. Despite a low peripheral blood CD4+ T-cell count, similar numbers of activated T cells, identified by double labelling for CD4 and HLA-DR antigens, were found in the epidermis of our patient as other individuals with psoriasis. Thus, there appear to be sufficient activated CD4+ T cells in our patient's psoriatic plaques to maintain the psoriatic process.
Adult↗
Cytokine expression in psoriatic skin lesions during PUVA therapy.
To determine whether an improvement in skin lesions as a result of PUVA therapy may be correlated with changes in cytokine patterns, RT-PCR amplification was used to compare the levels of IL-2, IL-6, IL-8, IL-10, TNF-alpha and IFN-gamma cytokine mRNA expression in serial biopsies from three chronic plaque psoriatic patients. In each case, 3-mm punch biopsies were taken from lesional skin before and during 2-28 days of treatment with PUVA. Total mRNA was extracted from each biopsy, cDNA synthesized, and then amplified by 35 cycles of PCR using cytokine-specific primers. The specificity of the PCR products was confirmed by the Southern blot technique. Substantial levels of specific mRNA for each of the cytokines studied was present in the lesions prior to treatment. In two of the three patients who responded well to PUVA, a reduction in all the cytokines including IL-10 was observed compared with baseline levels. In contrast, PUVA proved to be ineffective in clearing the psoriasis of the third patient whose skin lesions worsened during the course of treatment. This was accompanied by an increase in IFN-gamma but not of the other cytokines investigated, above the pretreatment level. This study showed an association between PUVA-induced resolution and decreases in the levels of various cytokines highly expressed in psoriatic lesions.
Adult↗
Evidence that a locus for familial psoriasis maps to chromosome 4q.
Psoriasis is an inflammatory skin disease that affects 2% of the population. It is characterised by red, scaly skin patches which are usually found on the scalp, elbows and knees, and may be associated with severe arthropathy. The lesions are caused by abnormal keratinocyte proliferation, and infiltration of inflammatory cells into the dermis and epidermis. The usual age of onset of psoriasis is between 15 and 30 years, although it can present at any age. Psoriasis is recognised to have a large genetic component. Twin studies show the concordance in monozygotic twins to be between 65-70%, compared to between 15-20% in dizygotic twins. Family studies estimate the risk to first degree relatives at between 8-23%. However, there are also several environmental factors, including streptococcal infection and stress, that affect the onset and presentation of the disease. The mode of inheritance of psoriasis is unclear. We conducted a genome-wide scan to search for psoriasis susceptibility loci in a single large multiplex family. Parametric linkage analysis indicated that a susceptibility locus for familial psoriasis was located on chromosome 4q. Investigation of this locus in five further multiplex families using both parametric and non-parametric methods gave significant localisation to chromosome 4q. The maximum total pairwise lod score obtained was 3.03 with the microsatellite marker D4S1535 at theta = 0.08. Non-parametric multipoint analysis with GENEHUNTER- demonstrated significant excess allele sharing, with a P value of 0.0026, at the same locus.
Chromosome Mapping↗
Isolated cutaneous non-tuberculous mycobacterial infection as a manifestation of AIDS.
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AIDS-Related Opportunistic Infections↗
Protective effect of gluten-free diet against development of lymphoma in dermatitis herpetiformis.
A retrospective study of 487 patients with dermatitis herpetiformis showed that lymphoma developed in eight patients, the expected incidence being 0.21 (standardized registration ratio 3810). All lymphomas occurred in patients whose dermatitis herpetiformis had been controlled without a gluten-free diet (GFD) or in those who had been treated with a GFD for less than 5 years. The results are suggestive of a protective role for a GFD against lymphoma in dermatitis herpetiformis and give further support for advising patients to adhere to a strict GFD for life.
Adult↗
Absence of gluten-specific T lymphocytes in the skin of patients with dermatitis herpetiformis.
Dermatitis Herpetiformis (DH) is an immunobullous skin disease with an associated gluten-sensitive enteropathy. Withdrawal of gluten from the diet leads to the resolution of both the skin lesions and the enteropathy. A T cell-mediated immune response to gluten has been implicated in the damage to the gut; the possible gluten specificity of the T cell infiltrate in DH skin lesions has not, however, been investigated. T cell lines (TCL) were therefore established from the skin lesions of eight patients with DH by culturing skin fragments for 11-17 days with a medium supplemented with 20 U/ml of IL-2. In three cases, gliadin (fraction of gluten toxic to the DH gut) and irradiated, autologous peripheral blood mononuclear cells were also added. The TCL were stained for CD3, CD4, CD8, TCR alpha beta and gamma delta expression by indirect immunofluorescence, and their proliferative responses to mitogens and gluten fraction III (a peptic-tryptic digest of gluten) investigated. Of the eight CD3+ TCL, four were predominantly CD4+ (82.1-98.8%), three predominantly CD8+ (92.6-98.6%) and one TCL contained both 87.6% CD4+ and 95.2% CD8+ T cells, a substantial proportion of which were presumably double-labelled CD4+, CD8+ T cells. All eight TCL, which were almost exclusively TCR alpha beta +, proliferated in response to PHA whilst six out of the eight were stimulated by Concanavalin A. None of the TCL proliferated to gluten fraction III alone; however, two TCL showed increased proliferation to the antigen in the presence of exogenous IL-2 or IL-4 (10 U/ml) compared to cytokine alone.(ABSTRACT TRUNCATED AT 250 WORDS)
CD3 Complex↗
A comparison of the stimulatory effects of cytokines on normal and psoriatic keratinocytes in vitro.
Keratinocytes from normal and psoriatic skin were tested for their in vitro proliferative response to a range of concentrations of rIL-6, rTGF alpha, rIL-8 and rGM-CSF using a serum-free culture system. With one exception, all normal cultures (11/12) were stimulated by 1000 ng/ml IL-6 (P < 0.001). Six out of ten psoriatic keratinocyte cultures were also stimulated at this concentration, but this just failed to reach significance (P = 0.05). As a group, the response by psoriatic keratinocytes to IL-6 was significantly less than that of normal keratinocytes (P = 0.02). TGF alpha at 1 ng/ml induced proliferation in approximately 60% of both normal (8/12, P < 0.05) and psoriatic (6/10, P < 0.01) keratinocyte cultures; there was no significant difference between the responses of the two groups to this cytokine. In addition, small numbers of both normal and psoriatic cultures responded to TGF alpha over a concentration range of 0.1 to 100 ng/ml. Approximately half of the normal and psoriatic cultures were stimulated by 10-1000 ng/ml IL-8. However, the effect was not significant for the group at any of the concentrations tested. GM-CSF had minimal to no effect on most of the normal and psoriatic cultures tested. This study showed that psoriatic keratinocytes are equally responsive to the stimulatory effects of TGF alpha and IL-8, but are less susceptible to IL-6 compared to keratinocytes from normal skin. These findings are consistent with a role for these cytokines in the maintenance of a hyperproliferative epidermis in psoriasis.
Adult↗