PREDOMINANCE OF CD8 SUBSET IN ID ERUPTION OF POISON OAK-INDUCED DERMATITIS

The pathophysiology and immune mechanisms involved in the clinical syndrome of autoeczematization remain a mystery. In this study of nickel dermatitis without autoeczematization and poison oak dermatitis with autoeczematization, it was noted that the process of autoeczematization was associated with the presence of CD8+ lymphocytes within the epidermis and the expression of HLA-DR antigens on epidermal keratinocytes. It is surmised that since CD8+ clones are induced by poison oak antigen but not by nickel, the inability of nickel to induce CD8+ lymphocytes may explain why uncomplicated nickel dermatitis does not autoeczematize. Since the selective adherence of CD8+ lymphocytes to keratinocytes, probably via the expression of adhesion molecules such as ICAM-1, the generation of antigens on endothelial cells of high endothelial venules involved in lymphocyte trafficking, and the expression of HLA-DR antigens on epidermal keratinocytes are all due to the activity of interferon-8, it is deduced that this lymphokine may play a key role in id eruptions induced by contact allergens.     

Nickel-elicited systemic contact dermatitis

20 patients with systemic contact dermatitis due to nickel are described. Of these patients, 15 were female and 5 were male. Their mean age was 24.8 years (16-51 years). All had experienced contact dermatitis in the umbilical area due to continual contact with metal belt-buckles or buttons. Then, with long- or short-term aggravation of such periumbilical dermatitis, commonly in summer, lesions spread to other sites such as the side of the neck, the flexures of the extremities, etc. All patients showed a positive patch test to nickel sulphate (2.5% in petrolatum) and the dimethylglyoxime test demonstrated the presence of free nickel on metal buttons or belt-buckles. Punch biopsies performed in 7 patients showed subacute dermatitis. After avoidance of continual exposure to objects containing nickel and foods rich in nickel, as well as treatment with oral antihistamines and topical corticosteroids, all patients improved or cleared. It has been reported that nickel can cause systemic contact dermatitis by some internal systemic route, such as oral intake, transfusion, inhalation, implantation of metal medical devices, etc. In our patients, we found that continual local skin contact could also elicit systemic contact dermatitis.     

Effects of repeated skin exposure to low nickel concentrations: a model for allergic contact dermatitis to nickel on the hands

We studied the effects of repeated daily exposure to low nickel concentrations on the hands of patients with hand eczema and nickel allergy. The concentrations used were chosen to represent the range of trace to moderate occupational nickel exposure. The study was double-blinded and placebo controlled. Patients immersed a finger for 10 min daily into a 10-p.p.m. nickel concentration in water for the first week, and during the second week into a 100-p.p.m. nickel concentration. This regimen significantly increased (P = 0.05) local vesicle formation and blood flow (P = 0.03) as compared with a group of patients who immersed a finger into water. The nickel concentrations used also provoked significant inflammatory skin changes on sodium lauryl sulphate (SLS)-treated forearm skin of the patients, whereas inflammatory skin changes were not observed in healthy volunteers without hand eczema and nickel allergy, either on normal or on SLS-treated forearm skin. The present study strongly suggests that the changes observed were specific to nickel exposure. Standardized methods to assess trace to moderate nickel exposure on the hands, and the associated effects in nickel-sensitized subjects, are needed.     

Cobalt and nickel content of Asian cements

The total cobalt and nickel concentration of 11 brands of Asian cement ranged from 8.1 to 14.2 micrograms/g and 14.9 to 28.5 micrograms/g, respectively. These metals exist mainly as insoluble salts; the water-soluble concentration of cobalt and nickel in the cements ranged from 0.39 to 0.65 micrograms/g and from 0-1.2 micrograms/g, respectively. 1.5% (4/272) of construction workers in a prefabrication construction factory had cobalt sensitivity. All had allergic contact dermatitis from chromate in cement. No worker had isolated cobalt sensitivity and cement dermatitis. It appeared that sensitization to cobalt in cement occurs only secondarily to an existing cement dermatitis. 1.8% (5/272) workers had nickel sensitivity: 2 with allergic contact dermatitis to nickel in their watches, 2 were asymptomatic and 1 had allergic contact dermatitis to chromate and cobalt in cement. The low prevalence of cobalt and nickel sensitivity from cement was probably related to the low concentration of soluble cobalt and nickel salts in the cement. However, these insoluble salts can form soluble complexes with body fluids on eczematous skin and sensitize the skin.     

Hand dermatitis and allergic patch test reactions caused by nickel in electroplaters

A worksite survey was conducted in all 38 Finnish electroplating plants. All workers ( n =163) who worked with nickel plating (bath workers, hangers and solution makers) were interviewed with a questionnaire about symptoms of nickel dermatitis, hand dermatitis, and about protective measures, atopy, etc. Patch testing with nickel sulfate was done with the TRUE Test^TM method. All the workers, 94 men and 69 women, answered the questionnaire. The mean age of women was 41.1 years, and of men 43.1 years, respectively. Men had longer occupational exposure to nickel (14 years) than women (10 years). Most workers used protective gloves. 35% of women and 30% of men reported present or past hand dermatosis. 19% reported a history of atopic dermatitis. 15% of women ( n = 8) and 4% ( n = 2) of men had an allergic patch test reaction to nickel sulfate. 70% of those with an allergic patch test reaction to nickel reported past or present hand eczema. The prevalence of nickel allergy among the electroplaters was similar to that of patients in patch test clinics in Finland. An allergic patch test reaction to nickel sulfate does not necessarily oblige an electroplater to change jobs.     

Experimental nickel sensitization in the guinea pig: comparison of different protocols

3 different sensitization protocols were compared for inducing delayed-type nickel contact hypersensitivity in guinea pigs. Open epicutaneous sensitization (OE) induced nickel allergy in 11/22 (50%) guinea pigs. When intradermal injections of Freund's complete adjuvant into the nickel-painted skin was added to the same protocol. 4/13 (31 %) became sensitized. The guinea pig maximization protocol induced nickel allergy in only 7/31 (23%) of the animals. Compared with the 2 other methods, animals sensitized with open epicutaneous applications reacted more rapidly (maximum at 6 h) and strongly (2+ reaction in 12/22 of animals) in previous patch lest sites upon systemic (i p.) nickel challenge. Open epicutaneous sensitization of guinea pigs should he a useful model for studying cellular and immunological mechanisms in nickel contact sensitivity.     

Nickel dermatitis in infants

8 cases of allergic contact dermatitis to nickel in infants are reported. All showed a papular dermatitis matching the sites of contact. Patch testing was performed on 3 patients, 2 were tested to nickel sulfate in pet. at concentrations of 1.0%, 1.5%, 2.0%. 1 was tested to 2.5% alone. All developed ++ reactions at each concentration tested. We observed a strong association of nickel dermatitis with atopy; 7 of 8 patients had a family history of atopy and 5 of 8 had features of coexistent atopic dermatitis. The relationship between atopy and allergic contact dermatitis is briefly reviewed. Nickel dermatitis may aggravate atopic dermatitis; avoidance of metal contact is crucial in the management of these patients.     

Excessive nickel release from earrings purchased from independent shops and street markets – a field study from Warsaw and London

Background Nickel allergy is frequent and cause morbidity and increased health care costs. Objective The aim of this study was to determine the proportion of inexpensive earrings randomly purchased from stores and street markets in two capitals that gave positive dimethylglyoxime (DMG) test reactions and to determine whether the degree of nickel release was related to shop category. Methods Random inexpensive metallic earrings were purchased from stores and vendors in London and Warsaw. A qualitative investigation of nickel release by using the DMG test was performed. Results DMG testing revealed that respectively 15.1% (n = 205) and 18.4% (n = 206) of earrings purchased in London and Warsaw released nickel as indicated by positive test outcomes. Stratification by store category showed that DMG test‐positive jewellery were mainly purchased from street markets and from stores that were not part of national or international chains. Conclusions Despite the EU Nickel Directive having resulted in decreasing prevalence of nickel allergy, a large proportion of inexpensive earrings still release nickel in concentrations that may result in nickel allergy and dermatitis. Authorities should prioritize information campaigns and random inspections as a legislation that is not followed is of limited value.     

A case of allergic contact dermatitis due to nickel in underground water

A 26-year-old Korean woman with nickel allergy continued to have recurrent facial lesions even after avoiding the usual sources of nickel. As another possible source of nickel, underground water at her house, which had been used by her for 3 years, was analyzed by atomic absorption spectrophotometry. Nickel contents in 8 different domestic tap waters and another underground water sample were also measured by plasma scan. Nickel contents in the patient's underground water were 9 times higher on average than those in domestic tap water. Patch tests with 2 concentrated underground water samples gave positive results. The other underground water sample also contained a higher amount of nickel than tap water. Therefore, we suggest that the underground water was a source of our patient's nickel contact dermatitis, and should be considered as a rare but possible source of nickel contact dermatitis.     

Nickel earlobe dermatitis and clinical non‐relevance of the oral exposure

Objective Nickel is the most common cause of allergic contact dermatitis (ACD). Because nickel restriction is commonly imposed on many patients with the only earlobe ACD to nickel hypersensitivity, the aim of this study was to identify the role of occasional and extended oral nickel exposure in these patients. Design This is a case–control study Subjects Thirty‐four outpatients, previously diagnosed as monosensitized to nickel, suffering from earlobe dermatitis were enrolled; 11 of them showed active dermatitis. The control group consisted of six healthy (non‐nickel‐sensitive) subjects. Interventions High oral nickel challenge (20 mg) and protracted oral challenge (1 mg once a day). Observation period: 6 weeks. Results Clinical earlobe lesions were not affected by a high oral nickel intake nor by a protracted oral challenge. Conclusions Dietary nickel restriction seems to be useless in patients with earlobe ACD due to nickel hypersensitivity.     

Excessive nickel release from mobile phones--a persistent cause of nickel allergy and dermatitis

Background. Despite the political intention to limit nickel allergy and dermatitis in Europeans, nickel allergy remains frequent. There are several explanations for the persistence of nickel allergy and dermatitis, including the increasing use of mobile phones. Before regulation of nickel release from mobile phones, we showed that eight (19.5%) of 41 mobile phones marketed in Denmark between 2003 and 2007 released nickel in concentrations that may result in nickel allergy and dermatitis. In 2009, the EU Nickel Directive was revised to include nickel‐releasing mobile phones. Objectives. To investigate the proportion of mobile phones sold in Denmark that release nickel after regulation. Methods. Metallic parts from 50 randomly selected mobile phones currently for sale in Denmark were tested for nickel release by use of the dimethylglyoxime (DMG)–nickel spot test. Results. Nine (18%) phones showed at least one positive DMG test reaction and two phones had more than one DMG test‐positive spot. Conclusions. Apparently, the proportion of mobile phones with significant nickel release remains unchanged, despite the 2009 revision of the EU Nickel Directive. We encourage manufacturers to measure nickel release from metallic components used in the assembly of mobile phones to ensure safe products.     

慢性湿疹和皮炎122例斑贴试验结果分析

目的:探讨慢性湿疹和皮炎患者接触性致敏原及其特点。方法:应用斑贴试验分析122例慢性湿疹和皮炎患者接触性致敏原。结果:列前10位的常见致敏原分别是0.1%硫柳汞、5%硫酸镍、7%芳香混和物、1%甲醛、1%肉桂醇、1%促进剂D、1%氯化钴、20%松香、25%秘鲁香油、3%卡巴混和物;引起手部湿疹和皮炎患者的致敏原主要为0.1%硫柳汞和7%芳香混和物,躯干、四肢湿疹和皮炎患者的致敏原主要为5%硫酸镍和0.1%硫柳汞,面部湿疹和皮炎患者的致敏原主要为0.1%硫柳汞和1%甲醛,脐周皮炎患者的致敏原主要为5%硫酸镍。结论:斑贴试验有助于明确慢性湿疹和皮炎患者的接触性致敏原及其性质。     

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.     

Relationship between cobalt and nickel sensitization in females

The view generally held in the literature is that the frequent occurrence of concomitant nickel and cobalt sensitivity is due in simultaneous sensitization from -suspenders, jewelry, etc.
In a study population consisting of 168 unselected female twins representing a random sample of the general population, only a few were found with concomitant nickel and cobalt sensitivity, and then mainly among those with hand dermatitis.
Similar concomitant cobalt and nickel was found only in dermatological female patients with hand dermatitis. The conclusion is that concomitant nickel and cobalt sensitization from metal alloys worn in direct contact with the skin is rare and that cobalt sensitization is probably a phenomenon secondary to an already existing hand dermatitis.     

Nickel sensitivity in atopics, psoriatics and healthy subjects

A prospective study of 552 persons was performed lo study nickel allergy in atopics, with and without dermatitis, psoriatics and healthy adults. We found no statistically-significant difference in the frequency of nickel allergy between persons with atopic dermatitis, atopics without dermatitis and healthy controls. More females than men gave a history of metal intolerance and gave allergic patch test reactions. A poor correlation between history and patch lest reaction was not specific for atopics. Psoriatics had a significantly lower frequency of allergic patch test reactions lo nickel than healthy controls or atopics with and without dermatitis. Psoriatics should not be used as controls for atopics in studies of contact dermatitis.     

Impaired responses of peripheral blood mononuclear cells to nickel in patients with nickel-allergic contact dermatitis and concomitant atopic dermatitis

BACKGROUND: Allergic contact dermatitis (ACD) is pathogenetically dependent on cell-mediated immune responses mediated by type 1 T lymphocytes. Atopic dermatitis (AD), in contrast, occurs as a result of sustained activation of type 2 subsets of T cells. Although atopic patients may become sensitized to various contact allergens, little is known about the influence of atopy on delayed-type hypersensitivity. OBJECTIVES: To investigate the in vitro responses of peripheral blood mononuclear cells (PBMC) to nickel stimulation in groups of atopic and nonatopic patients with patch test-verified nickel ACD. METHODS: Ten nonatopic patients with nickel ACD, 10 patients with nickel ACD and concomitant AD, 10 patients with AD but with no contact allergy, and 10 healthy persons participated in the study. PBMC were cultured in the presence or absence of nickel sulphate, phytohaemagglutinin (PHA) or tetanus toxoid (TT). [(3)H]thymidine incorporation was used to measure the rate of antigen-induced DNA synthesis and enzyme-linked immunosorbent assay was used to measure the production of interleukin (IL)-2 (type 1 cytokine) and IL-5 (type 2 cytokine). RESULTS: Nickel-stimulated PBMC of nickel-allergic patients with AD proliferated significantly less and secreted significantly lower amounts of IL-2 than cells of nonatopic nickel-allergic patients. IL-5 production was also lower in the former group, although the difference was nonsignificant. Moreover, neither the nickel-specific DNA synthesis nor the cytokine production by PBMC of atopic nickel-allergic patients differed significantly from those of healthy control persons and AD patients without contact allergy. Proliferative and secretory responses of PBMC to PHA or TT stimulation differed nonsignificantly between the groups. Nickel-induced IL-2 production correlated well with IL-5 production in nickel-allergic patients regardless of their atopic status. CONCLUSIONS: Our results indicate that PBMC of nickel-allergic patients with concomitant AD are characterized by impaired in vitro proliferative and secretory responses to the contact allergen nickel but not to the mitogen PHA or the recall antigen TT. The type 2 cytokine IL-5 may play a role in the development of ACD.     

Dermatitis alérgica de contacto a níquel. Estudio descriptivo en un hospital terciario en la década del 2000 al 2010

ObjectiveThe aim of this study based on the records of the dermatology department of a tertiary referral hospital was to describe patients treated for allergic contact dermatitis induced by nickel between 2000 and 2010.Materials and methodsFrom records of the skin allergy section of the dermatology department we extracted and analyzed information for patients who underwent patch testing with the standard series of the Spanish Contact Dermatitis Research Group (GEIDAC), which includes a patch with 5% nickel sulfate in petroleum jelly. The possibility that nickel release from various objects might have triggered the patient's dermatitis was assessed with the dimethylglyoxime spot test, which reveals a reddish precipitate if the metal is present.ResultsA total of 3,404 patients underwent GEIDAC patch testing during the study period; 24.2% had positive reactions to the patch containing 5% nickel sulfate in petroleum jelly. However, the contact dermatitis could be attributed to nickel in only 57 of the 824 patients (6.9%) who showed sensitization to nickel.ConclusionsPatch-test evidence of sensitization was found to be clinically relevant in only a small percentage of patients. We emphasize the usefulness of the dimethylglyoxime test to help establish the relevance of a positive nickel patch test. This test is even useful for identifying the specific object responsible for a patient's dermatitis.     

Lichenoid dermatitis caused by nickel salts?

The case is described of a 35-year-old woman with an 8-month history of dermatitis on the inside of the forearms, consisting of isolated and confluent erythematous papules which were round, dome-shaped, and itchy. Histology revealed thickening of the granular cell layer and considerable lymphomonocytic infiltration of the upper dermis. A provisional diagnosis of lichenoid dermatitis was made a month later when analogous lesions appeared on the inner thighs. The patient reported numerous undiagnosed dermatological episodes in her medical history. She had used an ML copper 250 IUD for 2 years. Patch tests were positive to nickel sulphate. 2 different blind challenge tests were carried out, 1 using 5 mg of NiSO4 on the 1st day and 10 mg on the 2nd, and another 5 months later using a single 10 mg dose of NiSO4. Both tests provoked responses. Although the distributor of the IUD and spectrophotometric analysis indicated that the copper wire of the IUD was nickel free, the patient was advised to have the device removed, to avoid contact with metal objects as much as possible, and to follow a low-nickel diet. The lichenoid dermatitis was clearly improved 40 days later. A cycle of tetraethylthiuramdisulphide (TETD) in doses of 250 mg every 2 days was then administered in conjunction with preventive measures and the diet. A further improvement was noted but TETD treatment was suspended after 15 days when general symptoms and worsening of iron deficiency anemia occurred. Overall nickel levels were observed to decrease modestly over 15 days. About 1 month after suspension of the TETD and the diet, the lichenoid papules gradually began to reemerge but in limited numbers and with minimal general symptoms. It was concluded that the IUD might represent an endogenous nickel source due possibly to manufacturing defects, but the distributor and the literature both denied the possibility.     

Is it possible to improve the prognosis in nickel contact dermatitis?

A questionnaire was sent to 143 patients who had shown a positive patch test reaction to nickel sulfate more than 10 years earlier. 91 patients returned the questionnaire, revealing that after the testing, 73 had suffered from dermatitis, 61 especially from hand dermatitis, 37 of these patients were clinically examined and patch tested with standard series and in addition, 12 patients were tested with nickel sulfate and nickel chloride with different occlusion times. At the clinic visit, 23 patients had dermatitis, 16 hand dermatitis, and 11 were symptom-free, 26 of the patients had metal items close to their skin and 21 of them had current dermatitis, 14 hand dermatitis. Of the 11 patients who had no metal exposure, 9 were symptom-free. The association of dermatitis with exposure to metal objects was statistically significant (p < 0.001). Those patients who had current dermatitis had also developed multiple allergies and reacted to nickel with shorter application times in patch tests, as compared to those who were symptom-free. It seemed possible that the prognosis for nickel dermatitis could be improved if nickel-allergic patients would strictly avoid metal contact, especially in clothing and jewelry.     

Erythema multiforme associated with contact dermatitis

A garment worker developed erythema multiforme concurrently with allergic contact dermatitis of the hands. Patch testing revealed sensitivity to nickel (which was present in her scissors) and to paraphenylenediamine (a commercial dye). During the course of the patch-test evaluation, both the hand dermatitis and the erythema multiforme became exacerbated. Later, patch testing to only nickel sulfate resulted in the development of erythema multiforme on the face and hands. The allergic pathogenesis, involving the absorption of an allergen through the skin and resulting in a type III allergic reaction from nickel, is discussed.