Heavy metal (monoclonal) bands: a link between cutaneous T-cell lymphoma and contact allergy to potassium dichromate, nickel and cobalt?

It has been proposed that chronic antigenic stimulation plays a role in the pathogenesis of cutaneous T-cell lymphoma (CTCL). By definition, antigenic stimulation triggers allergic contact dermatitis (ACD). It is therefore plausible that chronic ACD could serve as a precursor to CTCL. We report two cases of contact allergy to potassium dichromate, nickel and cobalt, where CTCL was diagnosed in one patient, and a diagnosis of CTCL is imminent in the other. We also review the literature on the diagnostic criteria for CTCL in the setting of ACD and explore potential mechanisms for the progression from ACD tos CTCL.

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.

Nummular eczema and contact allergy: a retrospective study.

BACKGROUND: Etiopathogenesis of nummular eczema is obscure; many causative factors have been proposed. Only a few studies investigated the relevance of contact allergy. OBJECTIVE: This retrospective study aimed to investigate the role of contact allergy in the underlying mechanism of nummular eczema. METHODS: From the 29,323 consecutive patients, we patch-tested for eczematous dermatitis of various type, 1022 (3.5%) with nummular eczema were enrolled. Data were collected for each patient, including age, sex, occupation, symptoms onset and duration, onset and spread sites, and clinical evidence or history of atopy. Histological analyses of acute phase lesions were carried out in some patients. RESULTS: Peak incidence of age at disease onset was found in the third decade of life. Predominant sites of lesions were upper (75.8%) and lower (64.5%) limbs, followed by trunk, dorsum of the hands, and face and neck. Three hundred thirty-two (32.5%) of 1022 patients showed positive reactions to 1 or more allergens. Highest sensitization rates were found with nickel sulfate (10.2%), potassium dichromate (7.3%), and cobalt chloride (6.1%). Histopathology showed less pronounced spongiosis in atopic subjects and the elderly. CONCLUSIONS: Because this study demonstrates that contact allergy is common with nummular eczema, patch testing is strongly advisable in every patient with persistent nummular dermatitis.

[Tefillin-related contact dermatitis].

We describe a 14 year-old male with a background of atopic dermatitis who developed a contact dermatitis reaction on the left arm to the leather straps of tefillin (phylacteries), a religious article worn by observant Jewish men from the age 13 years during most morning prayer services. Patch testing revealed contact allergy to potassium dichromate, a chemical involved in leather tanning. Placing the leather straps over clothing and later switching to potassium dichromate-free leather straps resolved the condition. It is important to recognize this uncommon phenomena in a population in which a large proportion regularly use this religious article.

Contact sensitization pattern in 172 atopic subjects.

BACKGROUND: Some authors have claimed a decreased cell-mediated immunity among atopic individuals, which would lead to observations of decreased rates of allergic contact dermatitis (ACD). OBJECTIVES: The purpose of our study was to investigate contact sensitization patterns in atopic subjects compared with non-atopic subjects. METHODS: Patch test data for 1247 patients undergoing patch testing at Massachusetts General Hospital between 1990 and 2006 were reviewed. Using accepted criteria, 172 subjects were classified as atopic individuals (AIs), and 1075 were classified as non-atopic individuals (NAIs). Sensitization rates were compared between these two groups. RESULTS: Sensitization rates (65.0% and 57.4% in the AI and NAI groups, respectively) and average numbers of positive responses (1.5 and 1.2 in the AI and NAI groups, respectively) were higher in AIs. Leading allergens observed were similar for both groups. Sensitization to potassium dichromate and phenylmercuric acetate was significantly greater in the AI group. The most frequent diagnosis in both groups was ACD (41.9% and 45.5% in the AI and NAI groups, respectively). In addition, more NAIs who were employed in occupations with exposure to wet and/or irritant conditions had hand eczema (P < 0.005). CONCLUSIONS: Atopic individuals were shown to be at least as likely to have ACD as NAIs. The most common sensitizers were similar in both groups, suggesting common sources of sensitization.

Impact of contact sensitization in chronic spontaneous urticaria.

INTRODUCTION: Patch testing is performed to diagnose allergic contact dermatitis to avoid exposure to the revealed contact allergens. Nevertheless, patch testing is not routinely performed in the evaluation of patients with chronic idiopathic (spontaneous) urticaria (CIU). The objective of this study was to determine the frequency of sensitization to patch test allergens in severe CIU and assess a role of the allergen avoidance in CIU remission. METHODS: The cases of patients with severe CIU were retrospectively studied. The patients were patch tested using T.R.U.E. TEST. Three groups were studied: CIU with positive patch test group; CIU with negative patch test group and control group, which included the cases of not patch-tested patients with CIU. The groups were followed up monthly to assess changes in Chronic Urticaria Severity Score (CUSS) after allergen avoidance. RESULTS: Forty-three subjects with severe CIU were patch tested. Nickel sulphate was positive in 4 (9.3%) cases, potassium dichromate in 2 (4.7%) cases, cobalt, balsam of Peru, paraphenylene diamine, fragrance mix and epoxy resin were positive in 1 (2.3%) case. Their baseline CUSS (5.4 ± 0.5) improved significantly after 1 month of allergen avoidance (3.2 ± 1.1; P < 0.001); but similar improvement of CUSS (5.3 ± 0.5) was seen in 34 patients with CIU with negative patch test (3.2 ± 1.3; P < 0.001) and in 49 patients with CIU of control group (5.2 ± 0.4 to 3.4 ± 1.3; P < 0 < 0.001) after 1 month. CONCLUSIONS: There is no relationship between avoidance of contact allergens and the course of CIU.

Positive concomitant test reactions to allergens in the standard patch test series.

BACKGROUND: Patch testing is performed to evaluate suspected allergic contact dermatitis. Common wisdom suggests that various allergens cross-react but only a few larger studies have published confirmations of this. The purpose of our study was to identify significant correlations between positive test reactions in a screening series. METHODS: A total of 1235 patients undergoing patch testing to the Hermal standard series at the Massachusetts General Hospital, Contact Dermatitis Clinic between 1990 and 2006 were investigated. RESULTS: Two or more positive reactions were seen in 411 patients (33.3%). Sensitizations to eight pairs of allergens were found to have significant correlation (P

Detection of chromium allergy by cellular in vitro methods.

BACKGROUND: The standard assay for the detection of chromium sensitization, the patch test, does not allow discrimination between patients with and without clinical symptoms of allergy. OBJECTIVE: The aim of this study was to prove whether cellular in vitro tests are predictive of chromium allergy. METHODS: Chromium-sensitized volunteers with and without clinically manifest allergy and non-sensitized healthy controls (n=37, 19, and 26, respectively) were analysed by cellular in vitro methods using tri- and hexavalent chromium (chromium chloride and potassium dichromate) as stimuli. The results were correlated with clinical and anamnestic data. RESULTS: Sensitized individuals with an allergy displayed significantly higher lymphocyte transformation test (LTT) responses than sensitized volunteers without allergy and controls (P<0.05 and P<0.01, respectively). 12.5 microg/mL of chromium chloride and 50 ng/mL of potassium dichromate were found to be optimal to discriminate between sensitized individuals with and without allergy. Combining the results of chromium chloride and potassium dichromate LTT, a positive reaction to at least one of the stimuli was highly predictive of allergy [sensitization with vs. without allergy: Odds ratio (OR)=6.4, P=0.004; sensitization with allergy vs. controls: OR=11.5, P<0.0001]. On the contrary, IFN-gamma, IL-2, IL-4, IL-10, and IL-12 production to the ELISpot, patch test results, sensitization against other metals, and atopy score did not significantly discriminate between sensitization with and without allergy. However, IFN-gamma responses towards chromium chloride were significantly correlated with the strength of patch test reactivity (r=0.49, P=0.002). By IFN-gamma ELISpot, the average precursor cell frequency reactive to trivalent chromium could be defined as 26, 15, and 11 : 10(6) in volunteers with sensitization and allergy, with sensitization without allergy, and controls, respectively. CONCLUSIONS: In contrast to the patch test, the LTT appears to be a method that is predictive of chromium allergy.

Tefillin dermatitis.

Tefillin (phylacteries) are a religious article worn by observant Jewish men. Only two cases of allergic contact dermatitis from tefillin have been reported previously. We describe 7 new cases of tefillin contact dermatitis and review the literature on contact allergy caused by religious objects and practices. All our patients had contact allergy to potassium dichromate, which was the only allergen relevant to tefillin .

Frequency of standard and occupational contact allergens in Tuzla area, Bosnia and Herzegovina: retrospective study.

Allergic contact dermatitis is acute or chronic inflammatory skin disease of allergic etiology, which develops as a result of delayed type of hypersensitivity, i.e. type IV reaction according to the Gell and Coombs classification. In the retrospective study, we reviewed medical records of 495 patients diagnosed with allergic contact dermatitis in the 1988-1998 period. The records were obtained from the Cabinet of Allergology of the Department of Dermatology and Venerology, Tuzla University Hospital Center. There were 312 women and 183 men, aged between 18 and 60 years. The patients were divided into 6 groups according to their occupation. Contact sensitization was established in 295 or 59.6% of them. The type and frequency of causative agent in allergic contact dermatitis depended on working environment. Potassium dichromate, a component part of cement, caused positive reaction in 48% of construction workers tested, which was significantly more than in the "other occupation" group, where 14.6% of patients showed positive reaction to potassium dichromate (p<0.001). Formaldehyde, used in leather processing, was the most frequent among the four leading allergens in the group of shoe workers (13.3%), whereas charcoal tar (used in the metal processing) was the most frequent allergen in the group of metal workers (13.9%). Nickel sulfate, potassium dichromate, cobalt chloride, and urushiol were frequent allergens in the "other occupation" group, housewives, and textile workers. The listed allergens are present at large in everyday life as well as in particular occupations.

Examination of a vehicle for use with water soluble materials in the murine local lymph node assay.

The murine local lymph node assay (LLNA) is a validated method for identifying skin sensitization hazard. Vehicle choice can influence the sensitization potential of haptens in both the LLNA and in humans, therefore selection of an appropriate vehicle is important. Suggested vehicles for the LLNA include organic solvents and organic-aqueous mixtures. However, due to its high surface tension and poor wetting qualities, water is not recommended and therefore testing aqueous soluble materials can be problematic. The aims of this investigation were to identify a water-based vehicle that possesses better skin wetting properties than water alone, and to assess its performance relative to other solvents in the LLNA using aqueous soluble haptens. The selected wetting agent was the surfactant Pluronic(R) L92 (L92). Concentrations of L92 of up to 50% did not induce positive responses in the LLNA. 1% aqueous L92 was chosen for further examination. Dose-response analyses were performed with dinitrobenzene sulfonic acid (DNBS) and formaldehyde formulated either in water, 1% L92, dimethyl sulfoxide (DMSO) or dimethyl formamide (DMF). Potassium dichromate (PDC) and nickel sulfate were tested in 1% L92, DMSO or DMF. The highest concentration of potassium dichromate was retested in each vehicle and in water to assess the effect of the wetting agent. Estimates of the relative sensitizing potency in each vehicle were determined by calculation of EC3 values (the estimated concentration required to induce a threshold positive response). While DNBS and formaldehyde produced positive responses in all four vehicles, their relative potency varied among the vehicles. The rank ordering of potencies for both materials was, from highest to lowest, DMF > or = DMSO > 1% L92 > water. Compared with water, use of 1% L92 resulted in >2-fold increase in potency for DNBS and >3-fold increase for formaldehyde. PDC was positive in DMF, DMSO and 1% L92. The potency ranking was DMF > or = DMSO > 1% L92. Re-evaluation of 0.5% PDC confirmed that formulations of both DMSO and DMF induced strong proliferative responses, whereas somewhat less proliferation was recorded with the 1% L92 vehicle. PDC in water was without activity. The performance of 1% L92 as a vehicle for nickel sulfate was assessed relative to DMSO and DMF. In DMSO, nickel sulfate produced a stimulation index (SI) >3 at only the highest level. Testing in DMF induced low levels of proliferation, but failed to produce a SI of 3 at any concentration tested. When formulated in 1% L92, nickel sulfate caused a SI of 3 when tested at 2.5%. Based on the results of these experiments, for identification of sensitization hazard of aqueous soluble materials using the LLNA, DMF and DMSO are the preferred vehicles. However, if a test material is not soluble in DMF or DMSO, or if higher test concentrations can be achieved in an aqueous vehicle, then 1% L92 may provide a better alternative to water alone in terms of improved assay performance.

Positive nickel patch tests do not intensify positive reactions to adjacent patch tests with dichromate. Results from a double-blind multicentre study of the German Contact Dermatitis Research Group (Deutsche Kontaktallergie-Gruppe, DKG).

The possible interference of neighbouring allergic patch-test reactions is still an open question. In this study, we investigated whether there is a distance-related mutual modification of neighbouring allergic patch-test reactions to nickel sulfate and potassium dichromate. We used a double-blind multicentre study design with randomized attachment of special TRUE Tests with 1, 3 and 7 cm distance between nickel sulfate and potassium dichromate patches. 589 patients with a history of nickel allergy (523 female, 66 male) were tested, with a mean age of 35 years. A log-linear modelling approach was used for statistical assessment of the relation between the distance separating neighbouring patch tests with nickel and dichromate and the reactions to the allergens. Non-reproducibility coefficients were compared by the generalized version of Fisher's exact test for arbitrary 2-dimensional contingency tables. For the left side of the back, virtually no differences (p=0.70) were found in the reaction patterns obtained for the 3 distances separating nickel and dichromate patch tests. On the right side of the back, the number of reactions to dichromate patches with only 1 cm distance from moderate/strong nickel reactions was lower than the number of positive dichromate tests at larger distances from nickel tests (on the border of statistical significance: p= 0.05). Corresponding side-related results were obtained for subgroups of patients with and without a history of atopic dermatitis. The non-reproducibility of reactions to dichromate was not significantly related to the distance between neighbouring tests. Our data argue against a "spillover" effect of strong/moderate nickel reactions, but indicate that such reactions may, under certain conditions, attenuate adjacent reactions to an unrelated allergen. In the case of future verification, this will have implications for the interpretation of patch tests.

Differential effect of chromium compounds on the immune response of the African mouth breeder Oreochromis mossambicus (Peters).

The objective of this study was to investigate the effect of trivalent (chromic chloride) and hexavalent (potassium dichromate) forms of chromium in the African mouth breeder Oreochromis mossambicus (Peters), with reference to the humoral immune response and lymphoid cells/organs. The 96 h LD50 for hexavalent and trivalent chromium was found to be 75 and 1,000microg fish(-1), respectively. Groups of fishes were injected intraperitoneally with 10, 1, 0.1 and 0.01% LD50 hexavalent and trivalent forms of chromium and subsequently immunised with bovine serum albumin (5 mg in 0.2 ml physiological saline). Both forms of chromium suppressed the antibody response, with hexavalent chromium being more suppressive than trivalent chromium. Reduction in spleen weight, splenocyte number and the percentage of blood lymphocytes was observed following administration of both forms of chromium. The possible immunological mechanisms behind the differential suppression of the antibody response and the reduction in spleen weight, splenocyte and lymphocyte counts are discussed.

Experimentally induced malignant lymphoma due to chronic antigen stimulation.

Animal experiments were started in 1988 with the aim of inducing malignant lymphomas. 52 guinea pigs were exposed to potassium dichromate using the TINA test (plus 39 control animals). Following the sensitization procedure, the test animals and 15 control guinea pigs were exposed daily (5 x a week) epicutaneously to the antigen up to the present time. Currently, 30 exposed and 17 control animals are still in the experiment. In 3 out of 17 post-mortem examinations, histologically evident lymphomas were found. In the control animals, no tumor has been seen. The experiments support lymphoma causation by chronic antigen stimulation. The experiments are continuing.

Influence of irritants on lymph node cell proliferation and the detection of contact sensitivity to metal salts in the murine local lymph node assay.

Dimethyl sulfoxide (DMSO) and sodium lauryl sulfate (SLS) are known to cause irritation of the skin, and to enhance the penetration of chemicals into the epidermis. In the present study, the lymph node cell (LNC) proliferative response following exposure to irritants, such as SLS and DMSO, was examined in the murine local lymph node assay (LLNA). Exposure to DMSO or SLS aqueous solution induced a small increase in lymph node cell proliferation compared with aqueous solution alone. Exposure to SLS in DMSO caused a significant increase in LNC proliferation. Further, the effect of addition of the irritants in a vehicle on the detection of contact sensitivity to metal allergens was examined. Application of potassium dichromate and nickel sulfate in DMSO or SLS aqueous solution caused increases in LNC proliferation. Exposure to metal allergen with SLS in DMSO also induced a significant LNC proliferative response, but did not induce a significant increase in stimulation index (increase in 3H-thymidine incorporation relative to vehicle-treated control group). This was because of increased 3H-thymidine incorporation following exposure to SLS-DMSO in the control group. These results suggest that irritants enhance the LNC proliferative responses to metal allergens. The use of SLS in aqueous solution is effective for the detection of sensitivity to water-soluble allergens, such as metal allergens, in the LLNA, as well as the use of DMSO as an application vehicle.