Implants and contact allergy: are sensitizing metals released as haptens from coronary stents?

BACKGROUND: The possible impact of metal release from coronary artery stents has, with their increased use, become a concern. OBJECTIVES: To study in vitro metal release in biologically relevant milieu from coronary stents made of different alloys. MATERIALS AND METHOD: Coronary stents in common use in a department of cardiology at the time of the study were tested. A previously described in vitro technique was used, whereby the stents were kept in the extraction media for a week. Two different extraction media were used to show the necessity of studying the actual biological surrounding of the implant when metal release is investigated. Metal release was determined with atomic absorption spectrometry. RESULTS: In this study, we show metal release from stents after immersion in extraction media of artificial sweat and cysteine solution, as illustrative media. CONCLUSION: Metal release from coronary stents is shown. The magnitude of release is influenced by several factors. The extent to which metal release in vitro has potential biological effects, in terms of elicitation of an allergic reaction or induction of sensitization, in vivo needs to be explored. However, as metal release from an implant in a biologically appropriate medium has been established, better risk assessments in relation to delayed hypersensitivity may be undertaken.

Patch testing with formaldehyde 2.0% in parallel with 1.0% by the Swedish contact dermatitis research group.

In a multicentre study consecutively patch-tested dermatitis patients were tested simultaneously with 1.0% and 2.0% (w/v) formaldehyde in aqua applied with a micropipette (15 µl) to the filter paper disc in Finn Chambers (0.30 mg/cm(2) and 0.60 mg/cm(2), respectively). A total of 2,122 dermatitis patients were patch-tested. In all, 77 (3.6%) patients reacted positively to formaldehyde; 37 reacted only to 2.0%, 35 reacted to both concentrations and 5 patients reacted only to 1.0%. Significantly more patients were thus diagnosed with contact allergy to formaldehyde with 2.0% compared to 1.0% (p < 0.001) without causing more irritant reactions. The detected number of isolated allergic reactions to the 2 formaldehyde-releasers in the Swedish baseline series and not to formaldehyde itself raises the question whether quaternium-15 1.0% and diazolidinyl urea 2.0% should be present in the Swedish baseline series.

Contact allergies to potential allergens in patients with oral lichen lesions.

OBJECTIVE: The aim of the present controlled study was to investigate a possible relationship between contact allergies to potential allergens and oral lichen lesions. METHODS: Eighty-three patients with oral lichen lesions (OLL) and control groups of age- and gender-matched dermatitis patients (DP, n = 83) and patch-tested dermatitis patients randomly selected from files (PSFF, n = 319) were included in the study. OLL and DP groups were patch-tested epicutaneously and examined intraorally. RESULTS: The frequencies of contact allergy to mercury and carvone were statistically higher in the OLL group than in the DP group. Surfaces of amalgam and composite restorations were statistically more frequent in the OLL group compared to the DP group. Contact allergy to nickel and colophony, the latter with a statistically significant difference, was more common in the DP group. The numerical difference found for nickel allergy was, however, not significant comparing the OLL and PSFF groups. CONCLUSION: Contact allergy to mercury was overrepresented in patients with OLL and has been reported in previous studies, but the present finding of an overrepresentation of contact allergy to carvone in patients with oral lichen lesions has not been reported previously. CLINICAL RELEVANCE: Carvone, in addition to mercury and gold, as previously suggested, can be one of the causative or maintenant factors for oral lichen lesions. Carvone-hypersensitive patients with oral lichen lesions should therefore avoid carvone-containing products for oral use.

The necessity of a test reading after 1 week to detect late positive patch test reactions in patients with oral lichen lesions.

OBJECTIVES: Establishing the clinical relevance of contact allergy to dental materials in patients with oral lichen lesions (OLL) may be difficult, and tests are often read only on day 3 or day 4; also, concentration of the tested allergens may vary. Several studies on dermatitis patients have shown that additional positive patch test reactions can be found after day 4. Therefore, the aim of the present study was to analyse the frequency of late positive reactions to potential allergens in patients with OLL. MATERIAL AND METHODS: Eighty-three of 96 consecutive patients with biopsy-verified OLL were patch-tested with a recently developed lichen series. The patches were removed after 48 h and reactions read 3 and 7 days after application. RESULTS: A total of 129 contact allergies were found, and 26 (20.2 %) of the allergic reactions in 23 patients were seen on day 7 only. The 25.2 % increase in positive test reactions with an additional reading on day 7 in addition to day 3 was statistically significant. Metals were the substances with the highest frequency of late positive reactions. CONCLUSIONS: Patients with OLL cannot be considered properly investigated with regard to contact allergy, unless the testing has been performed with mandatory readings on day 3 (or day 4) and day 7. CLINICAL RELEVANCE: Late patch test readings are crucial in order to elucidate the role of contact allergy to dental materials in the aetiology of OLL.

Contact allergy to gold in patients with oral lichen lesions.

The aetiology of oral lichen lesions is obscure. In this study the frequency of contact allergy to gold in 83 patients with oral lichen lesions was compared with that in two control groups, comprising 319 age- and gender-matched patients with dermatitis selected from files and 83 clinically examined dermatitis patients. All patients were tested epicutaneously with gold sodium thiosulphate. The two control groups tested were under examination for a tentative diagnosis of allergic dermatitis not related to oral problems. The frequency of contact allergy to gold was 28.9% in the patients with oral lichen lesions, 18.2% in patients selected from files, and 22.9% in the clinically examined control patients. The difference in frequency between patients with oral lichen lesions and those taken from files was statistically significant.

Multicentre patch testing with a resol resin based on phenol and formaldehyde.

BACKGROUND: Contact allergy to phenol-formaldehyde resins (PFRs) based on phenol and formaldehyde is not detected by a p-tertiary-butylphenol-formaldehyde resin (PTBP-FR) included in most baseline patch test series. OBJECTIVES: To investigate the rate of contact allergy to PFR-2 (a mixture of monomers and dimers from a resol resin based on phenol and formaldehyde) in a Swedish population, and to investigate associated simultaneous allergic reactions. METHODS: Five centres representing the Swedish Contact Dermatitis Research Group included PFR-2 in their patch test baseline series for a period of 1.5 years. RESULTS: Of 2504 patients tested, 27 (1.1%) reacted to PFR-2. Of those 27 individuals, 2 had a positive reaction to formaldehyde and 2 to PTBP-FR. Simultaneous allergic reactions were noted to colophonium in 6, to Myroxylon pereirae in 14, and to fragrance mix I in 15. CONCLUSIONS: The contact allergy frequency in the tested population (1.1%) merits its inclusion in the Swedish baseline series and possibly also in other baseline series. Simultaneous allergic reactions were noted to colophonium, M. pereirae, and fragrance mix I.

Multicentre patch testing with compositae mix by the Swedish Contact Dermatitis Research Group.

Sesquiterpene lactone mix detects contact allergy to these compounds present in the plant family Asteraceae. This marker is present in many baseline series. An additional marker is Compositae mix, which is not present in many baseline series. To investigate whether this allergen should be inserted into the Swedish baseline series, six dermatology centres representing the Swedish Contact Dermatitis Research Group included Compositae mix into their baseline series for 1.5 years. Of 2818 patients tested, 31 (1.1%) reacted to Compositae mix and 26 (0.9%) to Sesquiterpene lactone mix. Active sensitization to Compositae mix was noted in two cases. Only 0.4% of Asteraceae contact allergy cases would have been missed if Compositae mix had not been tested, a frequency too low to merit its inclusion in the baseline series. Due to obvious geographical differences in frequency in frequency of simultaneous allergic reactions to Compositae mix and Sesquiterpene lactone mix, the question as to whether specific baseline series (including Compositae mix or not as a "tail" substance) should be used in the different centres must be addressed. Another option could be to remove Sesquiterpene lactone mix from the baseline series and substitute it with Compositae mix.

Contact allergy to gold as a model for clinical-experimental research.

The high frequency of contact allergy to gold in patients with dermatitis was established after exhaustive skin testing, determining the right test agent, the best concentration, and repeated test readings. Metallic gold in contact with skin is slowly ionized, permitting absorption and haptenisation. Contact allergy to gold is statistically correlated to the presence of dental gold. But in many case reports it has also been attributed to wearing gold jewellery, albeit not statistically demonstrated. Epicutaneous testing with gold salts increases the blood gold level, and by intramuscular injection systemic contact dermatitis is provoked in an allergic individual. In coronary heart disease, gold-coated intravascular stents have been shown to be correlated to contact allergy and even to an increased risk of restenosis. Gold is far from inert.

A correlation found between contact allergy to stent material and restenosis of the coronary arteries.

BACKGROUND: Metallic implants, stents, are increasingly being used especially in patients with stenosis of the cardiac vessels. Ten to thirty per cent of the patients suffer from restenosis regardless of aetiology. We have shown increased frequency of contact allergy to stent metals in stented patients. OBJECTIVES: To we evaluate whether contact allergy to stent material is a risk factor for restenosis. METHODS: Patients with stainless steel stents, with or without gold plating, were epicutaneously tested and answered a questionnaire. The restenosis rate was evaluated. RESULTS: We found a correlation between contact allergy to gold, gold stent, and restenosis (OR 2.3, CI 1.0-5.1, P = 0.04). The risk for restenosis was threefold increased when the patient was gold allergic and stented with a gold-plated stent. An increased degree of chest pain in gold-allergic patients stented with gold-plated stent was found. CONCLUSIONS: We found a correlation between contact allergy to gold, gold-stent, and restenosis. It may be of importance to consider contact allergy when developing new materials for stenting.

Occupational allergic contact dermatitis from epoxy resin in a golf club repairman.

A golfer presented with facial and hand eczema. He had exacerbations of his hand eczema prior to golf tournaments. Being an authorized golf club repairman, he had been working with a two-part glue containing an epoxy resin (ER) based on diglycidyl ether of bisphenol A (DGEBA) and the hardener diethylenetriamine (DETA) for approximately 4 years before he developed any skin problems. He was patch-tested with the standard, which contains an ER based on DGEBA (DGEBA-R), epoxy (containing DETA), and rubber glove series and had positive reactions to DGEBA-R only. Other work materials (a latex glove, a golf glove made of leather, and part of the handle of his own golf club "as is" and in a methyl tert-butyl ether extract) were tested, with negative results. Allergic contact dermatitis from ER affects the skin by direct contact; the dermatitis is usually localized to the hands and forearms. If the face and eyelids are involved, the dermatitis may be due to exposure to airborne hardeners or reactive diluents, exposure to airborne dust from residual monomers, or ectopic allergic reactions. Our repairman had sandpapered an old glued surface, which may have led to possible airborne dust formation, thus explaining the facial eczema. Therefore, a worker with contact allergy to ER may continue working provided the skin is protected from contamination.

Allergic contact dermatitis as a complication of lid loading with gold implants.

Paralysis of the orbicularis oculi muscle in patients with a facial nerve injury causes functional and cosmetic disabilities including inability to close the eyelid. This complication is often treated by implanting a gold weight in the upper eyelid, which, however, is not without side effects. Four patients are described who, after lid loading with a gold implant, acquired an inflammatory reaction due to contact allergy to the metal inserted. The allergy was demonstrated by patch testing with gold sodium thiosulfate. The implant was removed and the dermatitis resolved. Contact allergy to gold occurs frequently and may explain many cases of complications to lid loading with the metal.

Patch testing with thin-layer chromatograms of chamomile tea in patients allergic to sesquiterpene lactones.

Patients with contact allergy to sesquiterpene lactones (SLs) are usually hypersensitive to Asteraceae plant products such as herbal teas. The objective of this study was to show sensitizers in chamomile tea by patch testing with thin-layer chromatograms. Tea made from German chamomile was separated by thin-layer chromatography. Strips of the thin-layer chromatograms were used for patch testing SL-positive patients. 15 (43%) of 35 patients tested positively to 1 or more spots on the thin-layer chromatogram, with many individual reaction patterns. Patch testing with thin-layer chromatograms of German chamomile tea showed the presence of several allergens.

Unexpected sensitization routes and general frequency of contact allergies in an elderly stented Swedish population.

Contact allergy to stent material has been proposed to be a risk factor for restenosis, after percutaneous transluminal coronary angioplasty (PTCA) and stenting. Information on the general frequency of contact allergy in the elderly population is scarce and knowledge of possible sensitization routes is important to investigate. The aim of this study was to investigate contact allergy to stent materials and other allergens. Here we report our findings on the frequency of contact allergies apart from those from stent material. In this retrospective study, we patch tested an elderly population, treated with PTCA and stented, with our standard series. A dermatitis population served as controls. We found a high frequency of contact allergy in both groups but a greater 'contact allergy burden', with generally higher frequencies for contact allergens, in the dermatitis patients as expected. Myroxylon pereirae and caine mix were apart from metals exceptions with statistically significant higher frequencies (P < 0.01) for the stented patients. Contact allergy to nonmetal sensitizers is common in an elderly Swedish stent population although, on the whole, substantially less than in an age and sex-matched dermatitis population. The findings indicate the importance of the oral mucosa for sensitization. In a general population that has been treated with a special medication/treatment procedure, contact allergies not suspected (such as to M. pereirae and to the metals) might suddenly peak. This underlines the importance of a careful evaluation of new products and routines with regard to contact allergies in the population.

Contact allergy to herbal teas derived from Asteraceae plants.

Contact allergy to herbal teas derived from the Asteraceae plant family was investigated in patients allergic to sesquiterpene lactones (SLs). 20 patients with a known contact allergy to SLs were recalled and patch tested with aqueous extracts of 8 different herbal teas based on Asteraceae plants as well as with parthenolide and other SLs. In 18 of 20 patients with SL allergy, there were positive test reactions to the Asteraceae teas, mainly to those based on German chamomile, dandelion and wormwood. Among the SLs, parthenolide was the most frequent co-reactor. Obviously, most patients with a contact allergy to SLs are allergic to commercial teas derived from the Asteraceae plant family as well.