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.     

Increased retest reactivity by both patch and use test with methyldibromoglutaronitrile in sensitized individuals

Hyperreactivity on re-exposure of previous allergic contact dermatitis skin areas has been previously demonstrated. This study aimed to investigate in methyldibromoglutaronitrile (MDBGN) allergic patients whether skin with previous allergic dermatitis from MDBGN showed an augmented response on re-exposure by both a patch test challenge and a use test with a liquid soap preserved with MDBGN. MDBGN dermatitis was elicited on the back and arms of sensitized individuals. One month later the previously eczematous areas were challenged with MDBGN. On the back, the test sites were patch-tested with a serial dilution of MDBGN and a use test was performed on the arms with an MDBGN-containing soap. A statistically significant increased response was seen on the areas with previous dermatitis on the back. Eight of the nine patients who developed dermatitis on the arms from the MDBGN-containing soap had an augmented response on areas with prior allergic contact dermatitis. Even though the allergic dermatitis appeared to be healed, an increased reactivity to allergen re-exposure was demonstrated both by patch test and use test challenge.     

Lymphocyte transformation induced by nickel sulphate: an in vitro study of subjects with and without a positive nickel patch test.

Lymphocytes from 8 patients with contact dermatitis and a positive nickel patch test, 7 patients with contact dermatitis due to other factors and with a negative nickel patch test, and 9 other subjects, 7 of whom suffered from other dermatological disorders, were tested with the lymphocyte transformation test (LTT), using nickel sulphate in various concentrations. All execpt one of the nickel allergics showed a significant response to nickel, whereas the controls showed borderline (3 patients) or no response (12 patients). These observations confirm previous findings indicating that nickel hypersensitivity can be diagnosed in vitro. This may be of importance in cases of acute contact dermatitis where patch testing is undesirable. Some individuals with a negative nickel patch test responded significantly though weakly to nickel in the LTT, indicating that apart from acting as a specific antigen (hapten?) nickel sulphate may also have weak non-specific mitogenic properties.     

Cutaneous reactivity of the hands in nickel-sensitive patients with hand eczema

This study compares the cutaneous reactivity between the hand and the back for 7 female patients with active hand eczema, who were found to be nickel-sensitive on routine patch testing with the European standard series. Patients were patch tested to a dilution series of nickel sulfate on the back in order to determine the threshold concentration for elicitation of allergic contact dermatitis, and based upon this result a lower concentration of nickel was then used for patch tests on the hand. We found that in the majority of patients (6/7) the cutaneous responsiveness of the hand was not increased compared with that of the back. However, the hand of 1 patient was more sensitive to nickel and patch testing was accompanied with a flare of her eczema, which suggests that cutaneous hyperreactivity may be important in individual patients with hand eczema.     

Allergic contact dermatitis to metal allergens in Iran

Background Metallic allergens such as nickel are among the most common causes of allergic contact dermatitis (ACD), but frequencies of contact dermatitis to these allergens may vary in different areas. Objectives This study aimed to determine the frequencies of ACD caused by three common metallic allergens: nickel sulfate; potassium dichromate; and cobalt chloride. Methods Data for 1137 patients with clinical diagnoses of contact dermatitis and/or atopic dermatitis evaluated by patch testing in Iran during a 5‐year period were retrospectively studied to establish the frequencies of hypersensitivity to these metallic allergens. Results A total of 313 patients (27.5%) gave positive patch test results for at least one metallic allergen. Allergy to nickel (229 cases, 20.0%) was the most commonly observed, followed by allergy to cobalt (90 cases, 8.0%) and allergy to chromium (70 cases, 6.2%). Nickel allergy was significantly more frequent in females and in subjects aged <40 years, whereas chromium hypersensitivity was more common in males and in subjects aged >40 years. Sensitivity to nickel or chromium was a risk factor for cobalt allergy. Conclusions Nickel was most commonly identified as a metallic allergen in Iran and tended to affect women aged <40 years. Regulations pertaining to nickel release may decrease the frequency of nickel hypersensitivity in Iran.     

Leukoderma following occupational allergic contact dermatitis

We describe 2 cases of occupational allergic contact dermatitis followed by leukoderma. The 1st case was a 49-year-old wood machinist who developed leukoderma in areas of contact dermatitis involving his lips, neck, hands and forearms and was found to be allergic to colophony and pine sawdust on patch testing. The 2nd case involved a 44-year-old man who worked as an epoxy applicator in a ceramics factory. He developed depigmentation in areas of contact dermatitis involving his face, hands, forearms, back, thighs and legs and was found on patch testing to be allergic to epoxy resin. The appearance of contact leukoderma may be indistinguishable from idiopathic vitiligo. However the prognosis for repigmentation may be better in contact leukoderma than in idiopathic vitiligo.     

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.     

Allergic paraben and benzyl alcohol hypersensitivity relationship of the "delayed" and "immediate" varieties

From a review of the literature, and the results of scratch, intracutaneous and subcutaneous injections of patients with parbens and benzyl alcohol sensitivity of the delayed type characterized by allergic contact dermatitis and strongly positive patch patch tests, it would appear that such sensitivity is not usually accompanied by the immediate urticarial type of allergic sensitivity. This communication concerns itself with results of testing patients with clinical sensitivity and positive patch test reactions to the parabens or benzyl alcohol with scratch, intracutaneous and subcutaneous injections of these preservatives in order to determine the relationship of the "delayed" type of allergic hypersensitivity to the parabens and benzyl alcohol with the "immediate" variety of hypersensitivity. The parabens and benzyl alcohol are widely employed as preservatives for many allergenic extracts used in scratch and intracutaneous testing. In addition, these preservatives are used in injectable corticosteroid medicaments and in local anesthetic solutions. In order to determine whether the presence of these preservatives in allergenic extracts would produce false positive scratch or intracutaneous tests or might produce an immediate, urticarial or anaphylactic reaction in patients with allergic contact dermatitis and positive patch test reactions to these preservatives, two patients with positive patch test reactions and allergic contact dermatitis to the parabens and two with similar benzyl alcohol sensitivity were tested in the manner detailed in the following case reports.     

Oral cyclosporin inhibits the expression of contact hypersensitivity in man

The expression of delayed contact hypersensitivity was studied in 6 patients with chronic contact dermatitis treated with cyclosporin A (CsA) 5 mg/Kg/day. Quantitative patch test challenge was used to establish individual dose-response curves and threshold concentration to certain allergens in the European Standard Battery. In all 6 patients, responses were reduced over the whole range of allergen concentrations, and in the 5 in whom the threshold for expression of contact hypersensitivity could be determined, the threshold was raised by CsA therapy. In addition, the clinical manifestations of allergic contact dermatitis underwent complete resolution within 2-3 weeks of CsA therapy. It was concluded that CsA inhibits expression of delayed contact hypersensitivity reactions in human skin.     

Persistent post-occupational dermatitis: report of five cases

Persistent post-occupational dermatitis is a phenomenon that is well-recognized by occupational dermatologists, but there have been few studies on it. In view of this, we proposed to assess the prevalence of this phenomenon in an English setting and ascertain the characteristics of the patients affected. Using modified criteria adapted from previous studies, details of 1100 patients seen in a contact dermatitis clinic were screened. Persistent post-occupational dermatitis was diagnosed in 5 patients out of 1100 seen over a 35-month period in a contact clinic (4 women, 1 man; age of onset 19-52 years). All had hand dermatitis that persisted despite removal of the apparent causative agents. Four patients were nickel-allergic on patch testing, though nickel was thought to be a potential causative agent in only one case and 2 patients were allergic to thiuram-mix on patch testing, and in both thiuram had a possible causative role. In all 5 cases, irritant exposure seemed important, with allergic factors contributing in 3 cases. Two patients had had eczema in childhood. Persistent post-occupational dermatitis is uncommon, affecting less than 0.5% of patients seen in a contact dermatitis clinic, but when diagnosed it has major implications for the future employment prospects of the individuals concerned.     

Occupational contact dermatitis in nurses with hand eczema

Occupationally related dermatitis is a common problem in nurses, who are exposed to a wide variety of allergenic and irritant substances. In a group of 44 nurses with hand dermatitis (40 female, 4 male), 18 were thought to have a predominantly allergic contact dermatitis, 15 an irritant dermatitis, 7 other form of eczema, 3 atopic dermatitis and one pompholyx. 10 of the 15 irritant cases were diagnosed as occupational. Of the 18 patients with allergic contact dermatitis, the allergens were thought to be occupationally relevant in 8 cases. In 6 of these 8 the dermatitis was due to natural rubber latex (3) or other rubber chemicals (3). 2 had additional evidence of immediate-type hypersensitivity to natural rubber latex (one was patch test allergic to latex, the other to thiuram mix). Natural rubber latex allergy, both delayed and immediate, is a significant problem, and nurses at risk should be tested for both types of hypersensitivity, as well as being patch tested to standard, rubber and medicaments series.     

Contact urticaria, allergic contact dermatitis, and photoallergic contact dermatitis from oxybenzone.

There is little literature regarding conventional patch tests and photopatch tests to oxybenzone resulting in both immediate- and delayed-type hypersensitivity reactions. A patient was patch-tested and photopatch-tested to various sunscreen chemicals. Both immediate- and delayed-type hypersensitivity reactions were observed with oxybenzone. The positive patch tests were also photoaccentuated. Oxybenzone, a common sunscreen allergen, can result in both contact urticaria and delayed-type hypersensitivity on both conventional patch testing and photopatch testing. Allergic contact dermatitis to sunscreen chemicals has traditionally included contact urticaria, allergic contact dermatitis, and photoallergic contact dermatitis. Due to the recognition of p-aminobenzoic acid (PABA) and its esters as sensitizers, the presence of benzophenones in "PABA-free" sunscreens has become more prevalent, especially in sunscreens with a sun protection factor (SPF) greater than 8. In our patient, immediate- and delayed-type hypersensitivity reactions were seen to oxybenzone (2-hydroxy-4-methoxybenzophenone, 2-benzoyl-5-methoxyphenol, benzophenone-3, Eusolex 4360, Escalol 567, EUSORB 228, Spectra-Sorb UV-9, Uvinul M-40) upon conventional patch testing and photopatch testing.     

Nickel contact hypersensitivity in children

Nickel allergic contact dermatitis is the most prevalent allergy in North America, with an incidence of 14.3%. It is on the rise from 10 years ago, when the incidence was 10%. This has been presumed to represent an increased exposure to nickel in the environment-especially in costume jewelry and belt buckles. We examined a group of 30 pediatric patients who had either a personal history of umbilical or wrist dermatitis, or a family history of nickel allergic contact dermatitis. All of these patients had a positive patch test to nickel sulfate 5%. Moreover, 50% of patients had an id reaction; all of these patients had positive patch tests that were papular in nature, similar to their papular id reaction. We posit that the presence of a positive family history may be a positive predictor of nickel allergic contact dermatitis, requiring nickel avoidance, especially in atopic children. Based on the high level of positive reactions in patients with umbilical dermatitis and an id reaction, patch testing to nickel in these patients is most likely to yield a useful result. Knowledge of reactivity to nickel would then allow parents and patients to initiate nickel avoidance earlier in life.     

Allergic contact dermatitis to basic red 46 occurring in an HIV-positive patient

A 41-year-old HIV-positive man presented with a 2-month history of a generalized pruritic rash, which had started on his feet. Patch testing made a diagnosis of allergic contact dermatitis to the textile dye basic red 46, likely to have been present in his dark-blue-coloured socks. Complete resolution of his symptoms occurred with avoidance of these socks. The patient had developed allergic contact dermatitis with a low CD4 T lymphocyte count of 361 cells/microl (normal range 410-1545 cells/microl). This raised the question of the level of CD4 count necessary for an individual to develop allergic contact dermatitis to an allergen, given its role in delayed hypersensitivity. It was concluded that a low CD4 count as a result of HIV infection does not decrease the ability of an individual to develop allergic contact dermatitis. Whereas the effector role in delayed type 4 hypersensitivity reactions is mediated by CD4 T lymphocytes, in allergic contact dermatitis it appears that CD4 T lymphocytes have the suppressor role, with CD8 T lymphocytes having the effector role.     

ATOPIC SENSITIVITY TO ALGAE AND LICHENS

Summary.— Six cases of allergic reactions to green algae are recorded. Five patients had atopic dermatitis in which exacerbations were provoked both by inhalation and by direct contact with algae. These patients also reacted to lichens, which contain algae in symbiosis with fungi. Five of the patients had allergic rhinitis or asthma, often very mild in relation to the severity of the skin symptoms. Three of the patients also had a delayed hypersensitivity contact dermatitis from lichens, but not from algae.
It is important to investigate patients with suspected sensitivities to lichens and algae both by patch testing and by prick testing as specific desensitization may help those patients with immediate weal reactions.     

Delayed patch test reaction to budesonide in an 8-year-old

Topical corticosteroids are an emerging cause of allergic contact dermatitis in children that may often be missed. It is important to consider patch testing with corticosteroids to detect allergic contact dermatitis in patients with persistent or worsening of dermatitis despite topical corticoseroid treatment. However, delayed reactions (>7 days) to topical corticosteroids may occur, leading to false-negative reactions and misdiagnosis. Herein, we report a case of an 8-year-old girl who developed a positive reaction to budesonide on day 12 of patch testing.     

Influence of dietary factors,age and nickel contact dermatitis on nickel excretion

Background. Nickel is a frequently detected cause of allergic contact dermatitis. Ingestion of nickel may lead to flares of nickel contact dermatitis. Methods. We examined nickel excretion in the urine of 164 female patients with and without nickel contact dermatitis. The associations between age, atopic dermatitis, nickel contact dermatitis and nickel exposure through nutrition (e.g. dietary supplements) and by patch tests were investigated prospectively. Nickel was measured with atomic absorption spectrometry with two different standardized methods. Results. A nickel detection limit of 0.2 µg/l was exceeded by all samples. The 95th percentiles of urine nickel concentration were 3.77 µg/l (age 18–30 years) and 3.98 µg/l (age 31–46 years). Bivariate analyses pointed to significantly increased nickel excretion with increasing age, ingestion of dietary supplements, drinking of stagnant tap water, and consumption of nickel‐rich food. In the multivariate analysis, age and dietary supplements remained significant predictors of high nickel excretion. A non‐significant increase in the median concentration of nickel was observed after the administration of conventional nickel patch tests. Patients with atopic eczema showed urine nickel concentrations similar to those in non‐atopic controls. Conclusions. The 95th percentile of nickel excretion in our study population markedly exceeded the actual reference value of 3 µg/l. Age and consumption of dietary supplements are the most important predictors. The use of stagnant tap water and consumption of nickel‐rich food contribute to the total load. These factors should be explicitly mentioned when allergic patients on a low‐nickel diet are counselled. In contrast, existing nickel contact sensitization was not more frequent in subjects with higher nickel excretion. Nickel patch testing may cause transient minor systemic nickel exposure. The findings of this study extend our understanding and management of factors associated with nickel allergy.     

Allergic contact dermatitis from latex rubber

Summary Previously we have found occasional patients with delayed hypersensitivity to latex (in rubber gloves) in the absence of allergy to any chemicals in the rubber chemical screen. There are many reports of contact urticaria to latex and isolated reports of delayed hypersensitivity to latex, usually in the presence of contact urticaria. To establish if latex rubber is a more common cause of delayed hypersensitivity than is currently recognized, we patch tested all patients attending our contact dermatitis clinic, over a 6-month period, with latex. Of 822 patients, 16 (1.9%) demonstrated positive cutaneous reactions to latex. Six exhibited contact urticaria to latex, five contact urticaria and allergic contact dermatitis, and five allergic contact dermatitis alone. Of the five with delayed hypersensitivity to latex in the absence of contact urticaria, only one was atopic and the sensitivity was thought to be relevant or possibly relevant in four. Of our patients, 1.2% exhibited positive patch-test reactions to latex. Patch testing with latex should be considered where contact dermatitis to a latex rubber-containing product is suspected, e.g. gloves and footwear.