Oral lichenoid lesions caused by allergy to mercury in amalgam fillings.
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Biomedical subjects
Publications and source records attributed to K Kalimo.
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After intradermal testing with goldsodiumthiomalate (GSTM), 5 out of 8 patients developed skin papules at the test sites, which persisted up to 20 months. The lesions were surgically excised. Histology revealed pseudolymphoma of B and T cell type containing follicular structures and occasional small granulomas. The amount of histiocytic cells among B and T lymphocytes was pronounced, including acid cysteine proteinase inhibitor (ACPI) positive follicular dendritic cells, CD68 positive macrophages, factor XIIIa positive dermal dendrocytes and S-100 positive cells. By electron microscopy, the macrophages contained endosomes loaded with crystalloid material which contained gold in X-ray microanalysis. Atomic absorption spectrophotometry also confirmed the presence of gold in one specimen. Thus GSTM seemed to accumulate in tissue macrophages leading to constant immunologic activation with lymphoid proliferation and histiocytic response.
IgA and IgG antibody response of adult atopic dermatitis patients against neutral/ acidic fractions of wheat, rye, barley and oats was analyzed utilizing an immunoblotting method. Moreover, the antibody response against ethanol-soluble fraction of wheat was examined with serum pools of healthy donors, atopic dermatitis patients and patients with dermatitis herpetiformis or adult celiac disease. All patient sera revealed polymorphic IgA and IgG binding to cereal peptides with molecular weights of 11-97 kD. The antibody staining was essentially identical with atopic dermatitis patients and controls. Patients with dermatitis herpetiformis or celiac disease showed more intensive staining with the ethanol extract of wheat and showed more IgA-stained bands in immunoblotting. It seems that the presence of IgA and IgG antibodies to different cereal antigens is a result of natural exposure and in atopic dermatitis displays little diagnostic significance, in contrast to antigliadin antibody response in dermatitis herpetiformis and celiac disease.
BACKGROUND: Hypersensitivity to cereals may occur via inhalation or ingestion. Although cereals are essential in the daily nutrition, only little information is available of the allergens causing symptoms in patients with atopic dermatitis (AD). OBJECTIVE: The purpose of the present study was to analyse the IgE immune-response to various cereals and specific cereal fractions of wheat and oats in children with severe AD and correlate the results with challenge studies. METHODS: Skin-prick tests (SPT) with a NaCl suspension of wheat, oats, rice, corn, millet and buckwheat and the ethanol soluble gliadin fraction of wheat were performed to 34 wheat/oats challenge positive or negative children with AD. Simultaneously serum total IgE and specific IgE antibody radioallergosorbent test (RAST), levels to wheat, oats and gluten were determined. In addition serum samples of these 34 AD patients and five age matched controls were analysed with IgE immunoblotting using neutral and acidic protein extracts of wheat and oats. RESULTS: From the 34 AD children 33 were SPT positive with wheat and 18 with oats. Positive RAST to wheat and oats could be detected in 32 and 30 samples respectively. From the oral wheat challenge positive children 12/14 appeared positive with gliadin SPT and revealed positive RAST to gluten, but each of the wheat challenge negative were negative in SPT with gliadin. In immunoblotting using neutral and acidic fractions of cereals the IgE binding with sera of challenge positive children showed the most intensive staining, but no correlation was found between different staining patterns and the clinical wheat sensitivity. The 26, 38 and 69 kDa bands in wheat and the 46 and 66 kDa in oats could be classified as major IgE binding proteins of these cereals (> 50% of the sera were positive). SPT with rice, corn, millet or buckwheat was positive in 16/34 patients. CONCLUSIONS: Intensive IgE staining to neutral/acidic soluble proteins in wheat and oats was seen, with major IgE binding to 26, 38 and 69 kDa proteins in wheat and 46 and 66 kDa in oats, but no specific IgE staining patterns correlating with clinical cereal sensitivity were found. The strong association between the positive oral wheat challenge and the positive SPT with the ethanol soluble gliadin suggests that also gliadin is an important allergen in wheat-allergic children with AD. The allergens in rice, corn, millet and buckwheat should be better studied before they can be recommended as alternatives for cereal allergic children.
A patient developed skin erythema and wheals within 1 h after local dental anesthesia with articaine hydrochloride. Pretreatment with oral terfenadine or topical betamethasone dipropionate prevented her reaction to articaine. In contrast, neither pretreatment with oral aspirin nor topical capsaicin affected her reaction to articaine. The results of radioallergosorbent tests (RAST) to articaine and a passive transfer test were negative. The reaction was probably caused by a complement-mediated mechanism leading to the degranulation of mast cells. The patient tolerated local anesthesia with lidocaine.
A nitrocellulose-based radioallergosorbent test (RAST) was developed and used for the determination of IgE antibodies to Candida albicans mannan in patients with atopic dermatitis, asthma and allergic rhinitis. The results were expressed as mannan-RAST index values (an inter- and intra-assay coefficient for variation of 8.0-10.2%). The normal range for mannan-RAST index values was determined in 102 non-atopic adults. Fifty-three of 78 (67.9%) patients with atopic dermatitis showed elevated mannan-RAST index values with a significant correlation to the severity of the dermatitis (r = 0.33, P < 0.01). Sixteen of 30 (53.3%) patients with asthma had a positive mannan-RAST index value; however, 12 of the 16 asthmatics (75%) who were positive also suffered from atopic dermatitis. Those who had allergic rhinitis but not atopic dermatitis showed a positive mannan-RAST index value in 12 of 32 (37.5%) cases. Nitrocellulose-RAST offered a sensitive method for the determination of polysaccharide-specific IgE antibodies in atopic diseases. The results show that high values are observed mainly in atopic dermatitis and less sensitization to C. albicans occurs in respiratory allergy.
The allergen extracts of wheat, rye, barley and oats flours were characterized by IgE-immunoblotting with serum samples from 40 adult patients; 35 patients with atopic dermatitis, one with rhinitis and four with urticaria. All these patients had been positive when skin-prick testing was carried out with one or more of the four flour extracts or displayed one or more positive cereal RAST results. Four non-atopic sera were used as negative controls. Acidic and neutral protein extracts of wheat, rye, barley and oats flours were processed for the immunoblotting experiments and 35 patients appeared positive in IgE immunoblotting with wheat and rye, 32 with barley and 33 with oats. The IgE immunoblots showed polyspecific binding patterns; wheat exhibited 36 IgE stained bands, rye 35, barley 33 and oats 10. Eighteen of the IgE stained bands could be classified as intermediate allergens for wheat, 23 for rye and 15 for barley. The 66 kDa protein in oats was visualized by 28 out of 33 sera (84%), however, there was evident non-specific binding to this region and thus it may also represent lectin-like binding. The most frequent staining with wheat extract was seen in the 26 kDa protein region (15/35, 43%), with rye in the 40 kDa (16/35, 46%) and with barley in the 26 and 46 kDa protein bands (14/32, 44%). Simultaneous staining with wheat, rye and barley extracts were observed with 16 bands suggesting crossreactivity between these cereals.
Ultrafiltered (> 1000 Da) samples of beer, aged red wine, young white wine, sparkling wine and extracts of fresh wheat bread and dried rye bread were analysed by skin-prick test (SPT), radioallergosorbent test (RAST) inhibition, sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting to find out if they contain Saccharomyces cerevisiae (S. cerevisiae, baker's yeast) allergens. Serum pool consisting of S. cerevisiae positive sera was used in the assays. The results were compared with freeze-dried reference S. cerevisiae and cereal antigens. The beer, bread, red wine and sparkling wine extracts elicited immediate reactions. However, no evident correlation with suspected symptoms was observed. White wine extract caused reactions in four out of six atopic dermatitis (AD) patients with symptoms, and in five out of seven symptom-free AD patients and in two of the 24 controls. In SDS-PAGE, protein bands were found in wheat and rye bread extracts and beer. In IgE immunoblotting, however, no staining was seen with the S. cerevisiae positive sera suggesting that they were of cereal origin. In white wine and champagne extracts a non-specific staining was seen in the region 20 kDa representing, e.g. lectin-like activity. No baker's yeast antigen could be detected in brewery and bakery products with IgE-immunoblotting even in the excessively concentrated extracts. The IgE mediated allergy to baker's yeast alone should thus not lead to denial of bakery, brewery and wine products.
Emigration of leukocytes from the blood into the tissues is critical in controlling lymphocyte patrolling in different lymphatic organs and in leukocyte accumulation at sites of inflammation. During the first stage of the extravasation process, leukocytes bind to the endothelial lining of vessels. At the molecular level, several adhesion molecules on leukocytes and endothelial cells function as receptor-ligand pairs in mediating this dynamic interaction. Recently, we have identified a novel human endothelial cell molecule, vascular adhesion protein 1 (VAP-1), that mediates lymphocyte binding (Salmi, M., and S. Jalkanen. 1992. Science [Wash. DC] 257:1407). VAP-1 was initially characterized by mAb 1B2 which inhibits lymphocyte adhesion to high endothelial venules (HEV) and to purified VAP-1 protein. Here we report the location and function of VAP-1 in normal and inflamed tissues in humans. VAP-1 is abundant in HEV of lymphatic organs belonging to the peripheral lymph node system, but considerably less is expressed in vessels of mucosa-associated lymphatic tissues. A subset of venules in most normal nonlymphatic tissues like skin, brain, kidney, liver, and heart is also VAP-1 positive. In addition to vessels, VAP-1 is distributed on a few other cell types, most notably in dendritic-like cells of germinal centers. At sites of inflammation, such as in inflammatory bowel diseases and chronic dermatoses, expression of VAP-1 is clearly increased. The induced VAP-1 is functional, since mAb 1B2 inhibits lymphocyte binding to inflamed lamina propria venules by approximately 60%. Thus VAP-1 is an endothelial adhesion molecule that under normal conditions is expressed mainly in HEV of lymphatic tissues. However, expression of functional VAP-1 in vivo is upregulated during an inflammatory reaction at other sites as well. Inducibility of VAP-1 suggests that it may play a significant role, not only in recirculation of lymphocytes, but also in controlling entry of leukocytes into sites of inflammation.
The role of sensitization and exposure to Candida albicans in atopic dermatitis (AD) was studied with skin-prick tests, yeast cultures and immunoblotting in 156 young adults with AD attending the Department of Dermatology, University of Turku, during 1983-89. Eighteen patients with allergic rhinitis without eczema and 39 non-atopics were included as controls. Parameters associated with severe AD were simultaneous anti-C. albicans IgE and saprophytic C. albicans growth. A statistically significant correlation between C. albicans sensitization (specific IgE antibodies) and AD symptoms was observed only in patients with saprophytic C. albicans exposure. No correlation between C. albicans-specific IgE and AD severity was shown in patients without gastrointestinal growth. Furthermore, severe eczema was seldom seen in patients without saprophytic C. albicans growth. The most important IgE-binding components of C. albicans in immunoblotting were 27 and 46 kD proteins and mannan, a polysaccharide. IgG and IgA antibodies to C. albicans, mainly towards C. albicans mannan, were found in practically all 70 sera studied. These results suggest a continuous exposure and induction of IgE antibodies by C. albicans in AD patients. Severe phases of AD in colonized patients are associated with IgE synthesis against C. albicans. These findings suggest a role for C. albicans in the exacerbations of AD but the clarification of this subject needs double-blind placebo-controlled treatment trials.
The Saccharomyces cerevisiae allergens were characterized by IgE-immunoblotting with serum samples of 83 patients; 63 represented patients with atopic dermatitis with previous positive skin prick test or RAST for S. cerevisiae, seven patients with AD but negative test results and 13 were non-atopic controls. Disrupted whole body extract of S. cerevisiae was used in the assays. From the patients tested 41 patients with atopic dermatitis appeared positive in IgE immunoblotting revealing 22 IgE stained bands. From these bands 10 represented intermediate allergens, and 12 minor allergens. The most frequent staining was obtained with the 48 kD band (39%). When the staining pattern of 45 kD and 48 kD bands and mannan was compared with Candida albicans allergens or purified baker's yeast enolase a simultaneous binding was seen with the 48 kD band of S. cerevisiae and the 46 kD band of C. albicans and enolase whereas the 45 kD band was neither associated with the 46 kD band of C. albicans nor purified enolase. High molecular weight staining was found in five samples. The staining pattern was associated with the mannose containing structures in parallel with C. albicans.
The sensitizing capacity of brewer's yeast (Saccharomyces cerevisiae) was studied with the skin prick test method in 449 subjects, including 226 atopic dermatitis (AD) patients, 50 patients with allergic rhinitis (AR) and/or asthma (A), and 173 nonatopic controls. A positive SPT reaction (> or = + +) was seen in 94% of patients with severe AD, in 76% with moderate AD, and in 25% with mild AD or no history of AD. Patients with AR and/or A and nonatopic controls displayed a positive reaction in only 8 and 2% of cases, respectively. There was also a parallel skin prick test reactivity with other yeasts including Pityrosporum ovale and Candida albicans, suggesting cross-reactivity. Parallel skin reactivity was observed also with molds and animal dander but not with pollen or house-dust mite. A significant correlation was also found between total serum IgE level and skin prick test (SPT) results with S. cerevisiae.
The role of cytokines and arachidonic acid metabolites in the regulation of IgE production in healthy persons and in atopic dermatitis patients with elevated IgE levels was studied. Interleukin-4 (IL-4) induced IgE production in peripheral blood mononuclear cells (PBMCs) of all donors, and no significant difference was found between the amounts of IgE produced by healthy persons and atopic dermatitis patients. Similarly, recombinant interferon (IFN)-alpha and IFN-gamma, as well as IL-2, inhibited IL-4-induced IgE production to a similar extent in both study groups. To evaluate the role of arachidonic acid (AA) metabolites in the regulation of IgE production, we added indomethacin, an inhibitor of the cyclooxygenase pathway, or nordihydroguaiaretic acid (NDGA), an inhibitor of the lipoxygenase pathway, to IL-4-treated cultures. Both indomethacin and NDGA strongly inhibited IL-4-induced IgE production. They also inhibited IL-4-induced IgG4 synthesis. No significant difference in the amount of inhibition was found between the two study groups. We were unable to restore the NDGA-induced inhibition of IgE-production by adding leukotrienes B4, C4, D4, or 5-HETE to the NDGA-treated cultures. PGE2 also failed to restore the indomethacin-mediated inhibitory effect. Consequently, NDGA- and indomethacin-mediated inhibitory effects do not appear to be mediated by any single factor studied. Collectively, our results show IFNs and IL-2 to be similar in effect in the modulation of IL-4-induced IgE synthesis in healthy and atopic persons.(ABSTRACT TRUNCATED AT 250 WORDS)
The importance of occupational environments in relation to the course of an atopic skin disease was investigated. A series of 1008 adult patients, who had had an atopic disease since their teenage years, were studied. Severe or moderate childhood atopic dermatitis tended to persist or relapse in adulthood independent of occupation. Only dermatitis of the hands showed a correlation with extensive daily exposure to occupational irritation factors. Atopic dermatitis patients did not go on sick leave more often than controls or those with atopic mucosal symptoms, although sick leave caused by skin problems lasted longer than sick leave caused by other circumstances. Atopic patients did not change their occupation because of their disease more often than the non-atopics. On the whole, changes in occupation were most common for patients without special education.
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One hundred seventy-eight adults with atopic dermatitis were included in this double-blind, parallel, randomized study where the effects of placebo, and cetirizine, 10, 20, and 40 mg administered daily during 4 weeks were measured. Local rescue therapy, which consisted of emollients and 1% hydrocortisone, was permitted and patients in all four groups used it in the same regular way. Severity of atopic dermatitis was measured via the following parameters: pruritus (visual analog scales used by both the investigator and patients), four point scale (absent, slight, moderate and serious) symptom scores for erythema, vesicles, excoriation, and lichenification in 14 body areas and a final visit assessment of the patient's general condition. The patient's quality of sleep was also measured along with standard blood chemistry tests. Adverse events during the study were recorded as well. In total 127 patients were assessed for efficacy. A statistically significant (P < or = .05) improvement was observed in all therapeutic groups for the following parameters: erythema, excoriation, lichenification, total symptom score, area involved, and pruritus. Cetirizine showed a dose-related improvement in the following parameters measured: erythema, lichenification, total symptom score, area involved, final assessment, and pruritus (measured by the patient at each visit). At 40 mg, cetirizine was significantly (P < or = .05) more effective than placebo for these parameters. At 20 mg, this was true only for pruritus (measured by the patient at each visit).(ABSTRACT TRUNCATED AT 250 WORDS)
The significance of contact allergy in patients with various oral symptoms was studied. Positive patch-test reactions to mercury compounds were found in 21/91 patients. Of these, 18 had lichenoid lesions in oral mucosa in close contact to amalgam fillings, and three patients with contact allergy had neither amalgam fillings in their teeth nor visible oral lesions. Amalgam replacement was carried out in 15/18 symptomatic patients. The fillings were replaced with gold in three cases, composite resin fillings in six, glass ionomer in three and both gold and composite materials in three cases. In 10 patients there was complete replacement and in five it was restricted to the fillings adjacent to the mucosal lesions. After a mean follow-up period of 3.2 years a complete cure was seen in seven patients, each of whom had had all their fillings changed. A marked improvement occurred in six patients, and there was no change in two.
A study of the prevalence of atopic disorders among 15-16-year-old teenagers was carried out in a coastal urban town in south-western Finland. Altogether, 1712 children were found in that age group, all previously examined by a pediatrician. Each child who had present or previous allergic diseases was invited for a detailed study, a total of 434 (25%) pupils. Of these patients 416 (95.8%) participated in clinical examination and skin testing. The prevalence of atopic diseases was 21% in the studied group; atopic eczema was found in 9.7%, allergic rhinitis in 14% and asthma in 2.5%. Of subjects who had rhinitis, 38% also had atopic eczema, while rhinitis--as the only symptom--was found in 8.8%. Figures obtained from this survey suggest that the prevalence rates of atopic diseases are about the same as found 10 years ago in Finland and they correspond also with other recent reports.