Is the variability of nickel patch test reactivity over time associated with fluctuations in the systemic T-cell reactivity to nickel?

BACKGROUND: Patch test reactivity to nickel varies over time. To what extent this variation is associated with fluctuations in the T-cell reactivity to nickel is not known. OBJECTIVES: Our aim was to investigate the relationship between variation over time in the patch test and the systemic T-cell reactivity to nickel. METHODS: Patients (n = 15) with a history of contact allergy to nickel were subjected to three consecutive patch tests at 3-month intervals, utilizing NiSO4 at 10 concentrations ranging from 0.0032% to 12.5%. Prior to each patch test, blood mononuclear cells were analysed for T-cell reactivity to nickel by interleukin (IL)-4 and IL-13 enzyme-linked immunospot assay. RESULTS: Eleven patients reacted positively in all three patch tests, two patients reacted in one or two tests and two remained negative. All 13 positive patients displayed variability over time, in terms of the lowest dose of nickel to which they responded. Also the cytokine response to nickel varied over time but the patients' mean cytokine response was positively correlated with their mean patch test reactivity (r(s) = 0.70, P < 0.01 for IL-4; r(s) = 0.78, P < 0.001 for IL-13). However, although the changes over time in patch test reactivity and the cytokine responses to nickel displayed a similar pattern in many patients, there was no significant correlation between the individuals' variation over time in vivo and in vitro. CONCLUSIONS: The overall magnitude of the T-cell reactivity to nickel and the patch test reactivity are closely associated but fluctuations in the systemic T-cell reactivity cannot be singled out as the major cause of longitudinal variability in nickel patch test reactivity.

Is contact allergy to disperse dyes and related substances associated with textile dermatitis?

BACKGROUND: Disperse dyes (DDs) are the most common sensitizers among textile dyes, but there is little knowledge of the clinical relevance of positive patch test reactions. OBJECTIVE: To investigate if patient-reported textile-related skin problems can be explained by contact allergy to eight different DDs and/or to chemically related substances, by occupation or by atopic constitution, and if the skin problems are influenced by age or sex. METHODS: A questionnaire on textile-related skin problems was answered by 858 of 982 consecutively patch tested patients in Malmö, Sweden and in Leuven, Belgium. The baseline series used for patch testing was supplemented with a textile dye mix (TDM) consisting of the eight DDs and with the separate dyes. The association between textile-related skin problems and contact allergy to the DDs and other risk factors was investigated using multiple logistic regression analysis. RESULTS: Eighteen per cent of the patients suspected textiles as a cause of their skin problems. Atopic constitution and female sex were risk factors for skin reactions. Synthetic materials were the most common textiles to give skin problems. A significant association was found between self-reported textile-related skin problems and contact allergy to para-phenylenediamine (PPD) [adjusted odds ratio (OR) 2.1; 95% confidence interval (CI) 1.0-4.3]. A similar, but more imprecise, adjusted OR was found for TDM (OR 1.9; 95% CI 0.57-5.6). Contact allergy to black rubber mix was too rare to be evaluated. CONCLUSIONS: Contact allergy to PPD was a more prevalent indicator for skin reactions to textiles than the TDM used in this study.

Contact allergy to textile dyes in southern Sweden.

Contact allergy to disperse dyes in textiles is documented in prevalence studies from southern Europe. To evaluate the prevalence of allergic patch test reactions to different textile dyes in southern Sweden, and to look at the sites of dermatitis in individuals hypersensitive to textile dyes, we retrospectively investigated 3325 consecutively patch-tested patients. They had all been patch tested with the standard test series supplemented with a textile dye mix (TDM) consisting of 8 disperse dyes, i.e. Disperse (D) Blue 35, 106 and 124, D Yellow 3, D Orange 1 and 3 and D Red 1 and 17. All but 3 of the TDM-positive patients were additionally tested with the separate dyes included in the mix. The frequency of contact allergy to TDM was 1.5%, which is comparable with studies from southern Europe. The most common dye allergen was D Orange 1. The high prevalence of allergic reactions to D Orange 1 was unexpected, whereas test reactions to D Blue 106 and 124 were lower than expected from other studies. Compared to all tested patients, the TDM-positive patients more often had dermatitis on their arms, face, neck and axillary folds, and women also had a higher frequency of hand dermatitis.

Cross-reactivity between nickel and palladium demonstrated by systemic administration of nickel.

Concomitant patch test reactions to nickel and palladium have frequently been reported in patients undergoing investigation because of suspected allergic contact dermatitis. Theoretically, these reactions can be explained by multiple, concomitant, simultaneous sensitization as well as cross-sensitization. We studied whether concomitant reactions to nickel and palladium could represent cross-sensitization in females hypersensitive to combinations of nickel, palladium and cobalt. Females were patch tested with serial dilutions of nickel sulfate, cobalt chloride and palladium chloride on the upper back. 1 month later, when the patch test reactions were gone, the patients were randomized into 2 groups that were challenged orally with either nickel or placebo. 1 day later, the areas of previous positive patch test reactions were read in a blind way looking for flare-up reactions. Nickel provocation but not placebo yielded flare-up reactions on sites previously tested with nickel (P = 0.012) and palladium (P = 0.006), but were also observed on sites previously tested with cobalt, even though this was not statistically significant. Flare-up reactions of previous patch test reactions to nickel and palladium after oral challenge with nickel speak in favour of a cross-reactivity mechanism.

Persistent itching nodules after the fourth dose of diphtheria-tetanus toxoid vaccines without evidence of delayed hypersensitivity to aluminium.

Studies in Gothenburg, Sweden, reported an exceptionally high rate of persistent itching nodules at the site of injection of aluminium containing vaccines, usually with positive epicutaneous tests to aluminium. When a new booster diphtheria-tetanus vaccine was introduced we performed a prospective cluster randomised active surveillance in 25,232 10-year-olds. Parental reports 6 months after vaccination with Duplex or diTeBooster were collected for 22,365 (88%) pupils in 851 schools. We identified 3-6 children per 10,000 with a local itching nodule persisting for at least 2 months. There were no significant differences between the vaccine groups. Contact allergy to aluminium was not detected. The findings support the use of the vaccine presently available in the Swedish vaccination program. Continued surveillance of persistent itching nodules and aluminium contact allergy is, however, warranted for vaccines containing pertussis toxoid and aluminium.

Flare-up reactions after oral challenge with nickel in relation to challenge dose and intensity and time of previous patch test reactions.

BACKGROUND: In this study we have taken an interest in systemic exposure to nickel in patients with delayed hypersensitivity to nickel. OBJECTIVE: The aim of the study was to more closely investigate the importance of factors such as ingested nickel dose, time interval between nickel patch testing and oral nickel challenge as well as degree of nickel hypersensitivity in relation to flare-up reactions. METHODS: Thirty nickel-sensitive female subjects were patch tested with a serial dilution of nickel sulfate in water on 4 different test occasions during a period of 7 months. One month after the last patch test the patients were randomly divided into 3 different groups. The patients in the groups were challenged orally with a placebo capsule, 1.0 mg nickel, or 3.0 mg nickel. RESULTS: None of the patients challenged with placebo had flare-up reactions of earlier patch test sites, but 2 of the patients challenged with 1.0 mg nickel and all of the patients challenged with 3.0 mg nickel had flare-up reactions. There were significantly more flare-up reactions of the most recent patch test sites (1 month) compared with the most distant (8 months) test sites. There was also a statistically significant positive correlation between the intensity of previous positive patch tests and the flare-up reactions. CONCLUSION: In the assessment of the possibility of systemic allergic contact dermatitis from nickel, the dose as well as the intensity and time since previous nickel eczema have to be considered.

Individual variation in nickel patch test reactivity.

BACKGROUND AND OBJECTIVE: Various factors such as hormones, drugs, and ultraviolet (UV) radiation may influence patch test reactions. The aim was to study the individual variation in nickel reactivity, also in relation to the menstrual cycle. METHODS: Thirty women allergic to nickel were studied for 7 months with patch tests with a serial dilution of nickel sulfate in water on four different test occasions. The patients belonged to two different eczema groups, one with nickel allergy, atopy, and pompholyx (12 patients); and the other with nickel allergy, but without both atopy and hand eczema. RESULTS: None of the patients showed the same patch test reactivity on all four occasions, and the highest individual difference noticed was 250 times for the four test occasions. Furthermore, two of the patients had completely negative test reactions on at least one test occasion. CONCLUSION: The variation in nickel reactivity as shown in this article is of great importance and should be kept in mind when a patient has a positive history of allergic contact dermatitis but negative patch test results to nickel.

The benefit of patch testing with a corticosteroid at a low concentration.

BACKGROUND: Patch testing with corticosteroid marker molecules is advocated because testing with all available corticosteroids is impossible in clinical practice. Most commonly used are budesonide, tixocortol pivalate, and hydrocortisone-17-butyrate. We have been patch testing not only with the three markers, but also with two corticosteroid mixes, each consisting of different concentrations of the three markers. OBJECTIVE: We describe a patient allergic to tixocortol pivalate, who was diagnosed by using a lower patch test concentration that recommended, 0.1% in petrolatum, as well as a weak corticosteroid mix, 0.202%. METHODS: The patient was patch tested to a standard series, including the two corticosteroid mixes and its three constituents. RESULTS: None of the corticosteroid preparations were positive on the first ordinary reading day, day 3, whereas both tixocortol pivalate at 0.1% and the corticosteriod mix at 0.202% were positive on the second ordinary reading day, day 7, whereas all tested corticosteroids in the standard series gave positive reactions on d10. CONCLUSION: The possible benefit of patch testing with a corticosteroid at a low concentration is supported, as is the significance of late readings beyond D4.

The significance of previous contact dermatitis for elicitation of contact allergy to nickel.

In 2 earlier studies, we found increased nickel re-test reactivity at earlier experimentally induced nickel eczema sites. The aim of this study was to investigate if earlier contact dermatitis caused by another allergen or earlier irritant contact dermatitis also influenced the reactivity when nickel was applied topically on earlier but healed dermatitis sites. Twenty-three females with contact allergy to both nickel and cobalt were involved in the study. Experimental contact dermatitis from nickel, cobalt and SLS was induced on the lower back. One month later, challenge patch testing with a serial dilution of nickel on the previous but healed dermatitis sites, and on a control area, was done. The tests were read blindly. Significantly higher test reactivity was found at the site with previous allergic contact dermatitis from nickel, and significantly lower test reactivity was observed at the previous SLS dermatitis site.

The significance of previous allergic contact dermatitis for elicitation of delayed hypersensitivity to nickel.

Several factors, such as amount of allergen, vehicle, anatomic site, immunologic status and previous eczema, may influence delayed hypersensitivity reactions. In an extended model, we have studied the significance of previous allergic contact dermatitis for elicitation of delayed hypersensitivity to nickel in 25 nickel-allergic females. On 3 occasions, 8, 4 and 1 months before the final challenge patch testing, an experimental allergic contact dermatitis from nickel was induced on the lower back. At the challenge patch testing, 4 identical dilution series of nickel were tested on 4 areas on the lower back 3 with previous but healed dermatitis and 1 control area. The tests were read in a blind way. A significantly higher test reactivity was found at the areas with a previous allergic contact dermatitis, the shorter the time interval between the previous provocation and the challenge, the stronger the reaction. These results may be of importance for the understanding of factors contributing to chronicity of allergic contact dermatitis.

Dermatitis with an unusual explanation in a welder.

Occupational diseases among welders include asthma, acute keratoconjunctivitis, and various skin disorders. A localized cutaneous erythema from UVC radiation is common and does not generally constitute any problem, as its cause is obvious to the welder, the symptoms are slight, and it is transient. In this report a welder with UVC-induced erythema on the cheeks is described. Initially, neither the worker, the physician at the factory, nor ourselves suspected a UVC erythema. Extensive investigations, including factor visits with measurements of UVA, UVB, and UVC irradiance during welding, revealed the cause of the dermatitis to be UVC, most likely reflected from a textile hood used to prevent exposure to dirt.

Nickel levels in serum and urine in five different groups of eczema patients following oral ingestion of nickel.

Patients with nickel allergy and different types of eczema with and without atopy were given a single oral dose of nickel sulfate. Blood levels and urinary excretion were determined by atomic absorption spectrophotometry. Urinary excretion of nickel was found to be dependent on age, decreasing with increasing age. When difference in age between the eczema groups was taken into account, the level of nickel in urine was significantly (p < 0.005) higher in the two atopy groups compared to the controls. This may indicate a higher intestinal absorption of nickel in atopic skin disease.

Delayed hypersensitivity reactions following allergic and irritant inflammation.

Delayed hypersensitivity retest reaction 3 and 6 weeks after induction of allergic and irritant inflammation, was studied in 13 females with known hypersensitivity to nickel. An increased retest reaction compared to controls was observed only in sites of earlier specific allergic inflammation. Also a general down-regulation of the degree of hypersensitivity was observed at retesting.

Systemic quinine photosensitivity with photoepicutaneous cross-reactivity to quinidine.

A 75-year-old man developed an eczematous eruption on the face and dorsal aspects of the hands one July after 3 weeks' treatment with quinine, 0.25 g nightly, for nocturnal leg cramps. The photoreaction cleared within a week of quinine being stopped. UVA and UVB erythema threshold determinations, after the acute episode had subsided, were normal. A photopatch test was positive for irradiated quinine down to a concentration of 0.01% and for unirradiated quinine to 0.5%. The test with the isomer quinidine was positive only when irradiated, down to a concentration of 0.01%. Preirradiated samples of quinine and quinidine were negative. Whereas in contact allergy quinine and quinidine usually do not cross-react, after systemic photosensitization, the 2 isomers probably form a common photoproduct, accounting for the cross-reactivity.

Fixed drug eruption: an immunohistochemical investigation of the acute and healing phase.

Five patients were each challenged orally with a drug which had previously induced a fixed drug eruption. A positive reaction occurred in all the patients. Punch biopsies were taken 6-12 h, 24 h and 3 weeks after challenge. The specimens were tested with different mouse anti-human monoclonal antibodies to identify T lymphocytes and phenotypic subsets, natural killer cells, B lymphocytes, OKT-6 and HLA-DR-positive cells. T suppressor/cytotoxic cells seemed to play a major role in initiating the flare-up reaction and preserving the cutaneous memory function of the fixed drug eruption.

Natural history of dermatitis herpetiformis in southern Sweden.

A retrospective clinical survey of 96 patients with dermatitis herpetiformis (DH) was performed in two defined populations of 425,000 in southern Sweden. The incidence of DH was 1.05-1.13/100,000 inhabitants/year and the prevalence was approximately 20-25/100,000 inhabitants. In one-third of DH patients the age at onset was greater than 60 years. In women with DH a strong connection to thyroid dysfunction was observed, but also other conditions of probable autoimmune pathogenesis were found in both sexes. No connection to malignant disease was observed. DH seems to be less active the later in life it starts. Several patients with DH manage without dapsone or need dapsone just occasionally in connection with bouts. This is the case even without a gluten-free diet. Many mild cases of DH were observed without a gluten-free diet; therefore, this restricting regimen should be prescribed only in more active cases of DH.