Nickel contact allergy and menstrual cycle

According to some reports in the literature, the hormonal fluctuations which occur during the menstrual cycle may affect the clinical expression of contact allergy to a greater or lesser degree. In clinical practice, too, patient history often shows exacerbation of the contact dermatitis during the days immediately preceding menstruation. On the contrary, the follicular phase of the cycle seems to have a temporary protective role in inhibiting the eliciting phase of allergic contact dermatitis. One possible explanation for this phenomenon is of immunological type: it has been demonstrated that oestradiol induces inhibition of delayed hypersensitivity type reactions, probably by acting indirectly on cells having a regulatory function in cell-mediated immunity. To investigate any inhibitory effect of the ovulatory phase of the menstrual cycle on contact sensitization, 30 selected fertile women, allergic to nickel sulfate and with a regular menstrual cycle lasting between 25 and 32 days, were enrolled. Patch tests were performed with a series of 10 serial aqueous dilutions of nickel sulfate, from 5% to 0.0013%. The 30 women were tested at 2 different times, in the ovulatory phase (demonstrated by transvaginal ultrasound) and the progestinic phase; they were subdivided into 2 groups of 15 women: in one group, the tests were made first in the ovulatory phase, and in the other, first in the progestinic phase of the menstrual cycle. There was a minimum interval of 5 weeks between the 2 test phases. The study shows that during ovulation the patch tests elicited significantly less intense responses than in the progestinic phase. These data therefore suggest that the ovulatory phase of the cycle has a significant inhibitory role on delayed hypersensitivity type reactions. For this reason, negative responses to patch tests executed in this phase could likely be false-negatives, and after careful evaluation of the phenomenon and of the clinical condition and patient history, it may be considered advisable to repeat the tests during the progestinic phase of the menstrual cycle.     

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.     

不同剂量和不同剂型甘草酸苷制剂对甲醛和硫酸镍皮肤斑贴试验的影响

目的研究复方甘草酸制剂对甲醛和硫酸镍皮肤斑贴试验的影响。方法选择甲醛和硫酸镍皮肤斑贴试验阳性的患者96例,首次斑贴试验结束后先后给予不同剂量及不同剂型甘草酸苷制剂进行干预。中剂量复方甘草酸苷片50 mg,每日3次口服,连续治疗2周;2个月后给予高剂量复方甘草酸苷片75 mg,每日3次口服,连续治疗2周,均在治疗干预后2周进行斑贴重复试验;2个月后给予静脉干预(复方甘草酸苷注射液60 ml/d),于治疗干预后1周进行斑贴重复试验,并分析不同剂量及剂型复方甘草酸苷制剂对甲醛和硫酸镍皮肤斑贴试验的影响。结果中剂量干预后92例斑贴试验阳性,其中15例为弱阳性(+),75例为强阳性(++),2例为极强阳性(+++),无阴性检查结果,反应程度Z=-3.367,P=0.001。高剂量干预后79例阳性,其中40例为弱阳性(+),39例为强阳性(++),10例为阴性(-),反应性质Z=-5.792,P=0.000;反应程度Z=-8.774,P=0.000。静脉干预后23例阳性,其中11例为弱阳性(+),12例为强阳性(++),36例为阴性(-),反应性质Z=-8.024,P=0.000;反应程度Z=-9.683,P=0.000。结论复方甘草酸苷高剂量和采用静脉注射可对甲醛和硫酸镍皮肤斑贴试验产生明显抑制作用,并对诱发的变应性接触性皮炎有一定的临床疗效。     

Premenstrual deterioration of skin symptoms in female patients with atopic dermatitis

BACKGROUND: Although it has been recognized that women with atopic dermatitis often show menstrual-cycle-associated skin deterioration, information about this subject is meager. OBJECTIVE: To clarify the clinical features of the monthly worsening of atopic dermatitis. METHODS: A total of 286 Japanese women with atopic dermatitis were interviewed to see whether the menstrual cycle had any influence upon their skin lesions, and whether they had symptoms of premenstrual syndrome. Patients suffering from monthly skin deterioration were then observed during and after the monthly worsening. RESULTS: Of the 286 patients interviewed, 134 (47%) had monthly skin deterioration, most of which occurred in the premenstrual week. There was individual difference in severity of the monthly skin worsening. All patients with the premenstrual skin aggravation had symptoms of premenstrual syndrome. CONCLUSIONS: Premenstrual worsening of skin lesions occurs in approximately half of women with atopic dermatitis. The premenstrual skin deterioration is related to the premenstrual syndrome.     

Menstrual cycle and skin reactivity

The hypothesis was tested that a cyclic variation exists in skin reactivity to irritant stimuli. Twenty-nine healthy women with regular menstrual cycles were challenged with sodium lauryl sulfate as an irritant patch test at day 1 and at days 9 through 11 of the menstrual cycle. The skin response to the applied irritant stimulus was evaluated by visual scoring and also quantified by measurements of transepidermal water loss, edema formation, and blood flow in the skin. The skin response to challenge with sodium lauryl sulfate was found to be significantly stronger at day 1 than at days 9 through 11 in the menstrual cycle as evaluated by visual scoring (p less than 0.05) as well as by measurement of transepidermal water loss (p less than 0.05) and edema formation (p less than 0.005).     

Oral prednisone suppresses allergic but not irritant patch test reactions in individuals hypersensitive to nickel

A multicentre, randomized, double-blind, crossover study was designed to investigate the effects of prednisone on allergic and irritant patch test reactions. 24 subjects with known allergy to nickel were recruited and patch tested with a nickel sulfate dilution series in aqueous solution, 5% nickel sulfate in petrolatum and 2 dilution series of the irritants nonanoic acid and sodium lauryl sulfate. The subjects were tested x2, both during treatment with prednisone 20 mg oral daily and during placebo treatment. The total number of positive nickel patch test reactions decreased significantly in patients during prednisone treatment. The threshold concentration to elicit a patch test reaction increased and the overall degree of reactivity to nickel sulfate shifted towards weaker reactions. The effect of prednisone treatment on the response to irritants was divergent with both increased and decreased numbers of reactions, although there were no statistically significant differences compared with placebo. It is concluded that oral treatment with prednisone suppresses patch test reactivity to nickel, but not to the irritants tested.     

In vitro studies in nickel allergy: diagnostic value of a dual parameter analysis

A comparison was made between the diagnostic value of assaying nickel-induced lymphocyte proliferation (lymphocyte transformation test, LTT) and migration inhibition factor (MIF) production in nickel contact sensitivity. Although lymphocyte proliferation was significantly increased in the group of patients with skin test reactivity to nickel, positive LTT were also frequently found in skin test-negative subjects: in 63% of subjects with and in 30% of subjects without a history of metal allergy. This would limit the value of the LTT as an in vitro correlate of skin test reactivity. However, in certain patients positive lymphocyte transformation may reveal nickel sensitization at a time of undetectable skin reactivity. Data obtained with the macrophage migration inhibition test (MMIT) showed a good correlation with nickel patch test reactions. Accurate determination of MIF became feasible by using cells from the human monocytoid cell line U937 as target cells in a microdroplet agarose assay. Using this MMIT, positive reactions occurred in 13% of the healthy controls and false-negative reactions were found in 26% of patients with positive skin test reactivity to nickel. As LTT and MMIT data appeared to be only weakly correlated in the individuals tested, a dual parameter analysis was performed. An excellent correlation [p = 1.8 (10(-8]] was found between skin test and in vitro reactivity for individuals with matching in vitro results (60% of all individuals tested). In those individuals with discordant in vitro data, skin testing will remain indispensable for diagnosing nickel allergy.     

The effect of the menstrual cycle on acne

Acne is a common disease with an underlying hormonal basis; however, there has never been a study to determine the ways in which the different stages of the menstrual cycle affect acne in women. Four hundred female participants, aged 12 to 52 years, were questioned whether their acne got worse before, during, or after their menstrual period and also asked whether it was unrelated to the menstrual period. Their age, severity of acne, ethnicity, and oral contraceptive use were also recorded. Overall 177 of 400 (44%) of those interviewed experienced premenstrual flares of their acne. Severity of acne, ethnicity, and oral contraceptive use did not affect the premenstrual flare rate. Women older than 33 years had a higher rate of premenstrual flares relative to women aged 20 to 33 years (P =.03 by chi(2) analysis). We concluded that almost half of all women experience premenstrual flares of their acne. Premenstrual flares may be more common in older women.     

Nickel allergy: relationship between patch test and repeated open application test thresholds

BACKGROUND: The frequency of nickel allergy varies between different population groups. Exposure regulation has proven effective in decreasing the frequency. Experimental studies with other allergens have shown a significant relation between patch test reactivity and repeated open application test (ROAT) reactivity. OBJECTIVES: This study was aimed at determining the elicitation threshold in nickel-allergic individuals in a patch test and a ROAT, and comparing the threshold from these two test methods. METHODS: Twenty nickel-allergic persons were tested with a dilution series of 19 concentrations in a patch test and a dilution series of three concentrations in a ROAT, with duration of up to 21 days. Eighteen persons with no nickel allergy were included as control group for the ROAT. RESULTS: The predicted dose which will elicit a reaction in 10% of allergic individuals was calculated to be 0.78 microg nickel cm(-2) in the patch test. The threshold for the ROAT (in microg nickel cm(-2) per application) was significantly lower than the threshold for the patch test, while the dose-response for the accumulated ROAT dose at 1 week, 2 weeks and 3 weeks was very similar to the patch test dose-response; indeed, there was no statistically significant difference. CONCLUSIONS: For elicitation of nickel allergy the elicitation threshold for the patch test is higher than the elicitation threshold (per application) for the ROAT, but is approximately the same as the accumulated elicitation threshold for the ROAT. This may be important for risk assessment based on dose-response results from allergic patients.     

Iontophoresis of nickel elicits a delayed cutaneous response in sensitized individuals that is similar to an allergic patch test reaction

Wearing of patch test chambers for 1-2 days is uncomfortable for patients. Allergen application by iontophoresis avoids this, but it is unknown so far whether iontophoresis itself interferes with the delayed immune response. We compared the effects occurring 48 h after iontophoresis with distilled water, 0.9% NaCl, and 0.01 M NiSO4 in normal volunteers and in nickel-sensitized patients (total n=36). Visual assessment was performed and transepidermal water loss (TEWL), stratum corneum hydration, cutaneous blood flow, and immunohistopathology were determined. After iontophoresis with nickel sulfate, only individuals sensitized to nickel reacted with a positive clinical response, increase in cutaneous blood flow, decline in epidermal CD-1a-positive cells, increase in epidermal proliferation (Ki-67-positive cells), pronounced infiltration of cells positive for CD4, CD11, or CLA, and cellular activation (expression of ICAM1, HLA-DR). Iontophoresis with distilled water or saline did not result in such reactions in volunteers with or without nickel sensitization, and the latter also tolerated nickel iontophoresis without significant skin reactions. We conclude that the delayed cutaneous response to nickel induced via iontophoresis is specific and similar to a positive patch test reaction. Iontophoresis may therefore be considered as an alternative to patch testing.     

Long-lasting allergic patch test reactions: a study of patients with positive standard patch tests

The purpose of this study was to determine the duration of patch test reactions and the frequency of long-lasting allergic patch test reactions (LLAPTR), and to identify the possible factors related to the development of the LLAPTR. For this purpose, a group of 263 patients positive to 1 or more allergens in the GIRDCA standard series was recruited. Readings were made for each patient 2 and 3 days after patch test application and continued every 2nd and 3rd day until the disappearance of all palpable erythema. The % of LLAPTR out of the total of reactions was high: 17.9%). Kathon CG was the hapten that caused LLAPTR most frequently, with 16 cases, a frequency of 76.1%), and a mean duration of the patch test reactions of 25.4 days. Risk factors investigated were age, sex, atopy, intensity of the patch test reaction and sensitivity to some allergens with the greatest number of positive patch tests. The relative importance of each risk factor was calculated by multivariate stepwise logistic regression analysis. It was found that a Kathon CG sensitivity was the most important risk factor for LLAPTR. 2nd was atopy, followed by strong patch test reaction. Rejected risk factors were sex, age and sensitivity to nickel sulfate, potassium dichromate, Disperse Blue 124, fragrance mix and p-phenylenediamine.     

Characteristics of premenstrual acne flare-up and benefits of a dermocosmetic treatment: a double-blind randomised trial

Background

To date, facial acne flare-ups in adult women during the luteal phase of the menstrual cycle have been poorly investigated.

Objectives

To clinically characterize premenstrual acne flare-up in adult women and investigate the effect of a dermocosmetic treatment.

Material and methods

This single-centre study included 32 young adult women with declared premenstrual acne flares and was composed of two phases: (1) an observational phase (two menstrual cycles) and (2) an interventional phase (one menstrual cycle) in a controlled, randomised, double-blind, intra-individual (half-face) setting in which a dermocosmetic (containing lipohydroxyacid, nicotinamide, and piroctone-olamine) and placebo were compared.

Results

Initially, during the first part of the study, we observed that premenstrual acne flare-ups in adult women were characterized by a significant increase in the number of papules (20.2 vs. 13.7; p = 0.0008) and to a lesser extent, closed comedones (25.6 vs. 22.7; p = 0.04). Secondly, during the interventional phase, the half-face treated with the dermocosmetic formulation showed a significantly lower number of inflammatory lesions (7.6 vs 9.4; p = 0.01) during the luteal phase compared to the half-face treated with the placebo. Tolerance of the dermocosmetic formulation was rated as good or excellent.

Conclusion

Our data indicate a significant increase in the number of papules during premenstrual acne flare-ups in adult women and the use of a dermocosmetic may be of benefit in partially reducing this premenstrual inflammatory flare-up.

     

Nickel sensitivity: Relationship between history and patch test reaction

The prevalence of nickel sensitivity in 415 young adults was examined by patch testing with nickel sulphate 5% in pet. Before testing the persons filled in a questionnaire about personal or family history of atopy and skin reactions after metal contacts. Nickel sensitivity was found in 2.8% of males and 9.8% of females; 13 out of 28 persons with a history of metal contact dermatitis had negative patch test reactions to nickel; eight out of 23 persons with positive patch test reactions to nickel had never experienced skin reactions from metal contacts. These findings indicate that nickel sensitivity cannot be reliably predicted from pretest historical information.     

The influence of female sex hormones on skin thickness: evaluation using 20 MHz sonography

Changes in skin thickness and echodensity during the spontaneous menstrual cycle, in women taking hormonal contraceptives and pregnant women were investigated by high-frequency (20 MHz) ultrasound. Women with a spontaneous ovulatory menstrual cycle (group I), women taking one-phase contraceptives (group II), women taking three-phase contraceptives (group III) and pregnant women (group IV) were measured at the following locations: proximal and distal forearm and lower leg on both sides. The skin was investigated during three phases of the menstrual cycle: days 2–4 (phase A), days 12–14 (phase B) and days 20–22 (phase C). Oestradiol and progesterone levels were determined at each phase. The pregnant women were investigated 2 weeks prepartal and 6 weeks after delivery. Group I showed a statistically significant increase in the skin thickness from phase A to phase B, but not from phase B to phase C. Group II showed no significant changes in skin thickness, whereas the skin thickness increased from phase A to phase B in group III. In group IV, the skin was significantly thicker prepartal than after delivery. The measured echodensity showed a negative correlation with skin thickness in group III and in pregnant women. We were able to demonstrate that the status of female sex hormones influences the thickness of the skin. These results can be explained by hormone-induced water retention in the skin. Sonography at 20 MHz is able to quantify these effects, which should be considered when performing ultrasound measurement in women.     

Nickel allergy from adolescence to adulthood in the TOACS cohort

Background In 1995, we established a cohort of 1501 unselected eighth‐grade schoolchildren to investigate the course of nickel allergy into adult life. Objectives To follow the course of nickel allergy and clinically relevant nickel dermatitis over 15 years from adolescence to adulthood, and the effect of ear piercing, atopic dermatitis and degree of nickel patch test reactivity. Methods One thousand two hundred and six young adults from the cohort were asked to complete a questionnaire and participate in a clinical examination including patch testing with TRUE Test® including a nickel dilution series. Results The questionnaire was answered by 899 (74.6%), and 442 (36.7%) had patch tests performed. The point prevalence of nickel allergy was 11.8% (clinical relevance 80.8%). The 15‐year incidence rate was 6.7%. Most new sensitizations were clinically relevant with strong reactions, and many participants reacted to low concentrations. Only a few positive reactions were lost. Nickel allergy was more common among women with childhood atopic dermatitis, whereas no association with ear piercing was found. However, there was a significantly higher prevalence of nickel allergy among women ear pierced before implementation of the nickel regulation in Denmark. Conclusion This follow‐up study in young adults 15 years after leaving primary school showed a high prevalence and a high incidence rate of nickel allergy, despite the nickel regulation. Most reactions from childhood could be reproduced and were clinically relevant. In women, childhood atopic dermatitis was associated with nickel allergy in adulthood, whereas only ear piercing before the Danish nickel regulation was associated with adult nickel allergy.     

Contact sensitivity to Candida albicans—comparative studies in man and animal (guinea-pig)

We studied the elicitation of contact sensitivity to Candida albicans antigen in guinea-pigs with experimental cutaneous candidiasis and in humans, using commercially available potent 1:100 C. albicans antigen (Torii) by patch testing on abraded skin. In guinea-pigs, non-immune animals became patch test-reactive 4-5 days after topical application of viable C. albicans, either under occlusion or without occlusive dressings, concurrently with the demonstrability of delayed responses to intradermally injected 1:10 000 Candida antigen. In humans, all healthy adults who showed delayed hypersensitivity reactions to intradermally injected 1:10 000 C. albicans antigen demonstrated positive patch-test reactions to 1:100 C. albicans antigen. There was a significant correlation between the magnitude of responses to these tests. In contrast, no positive patch test reactions were elicited to the 1:100 C. albicans antigen on neonatal skin, emphasizing the lack of irritability of this test agent. These results also indicate that in humans contact sensitivity to Candida antigen occurs during later life because C. albicans is a ubiquitous organism. The practical value of this Candida patch test for evaluation of patients' immune function was assessed by a prospective study in patients with various skin disorders. The results obtained suggested some potential value of the test for evaluation of cell-mediated immune function of patients with regard to ubiquitous recall antigens.     

The profile of patch test reactions to common contact allergens is related to sex

Background:  Women are more often patch tested than men, and the reactivity to patch test allergens is dependent on sex. However, it is unclear whether the profiles of test reactions are also sex-related.
Objective:  To compare the profiles of patch test reactions of men and women.
Methods:  Sex-related reaction profiles of 16 common patch test allergens were analysed based on data of 47 626 patients filed by the Information Network of Departments of Dermatology in Germany. The proportions of weak positive reactions and of questionable and irritant reactions were evaluated by calculating the positivity ratio (PR) and the reaction index (RI) separately for men and women for each allergen.
Results:  Of the 16 allergens evaluated, 8 had a higher PR and a higher RI in women than in men. 4 allergens had a lower PR and another 4 had a lower RI in women than in men. For allergens with similar sensitization prevalence in men and women, female sex was associated with a higher PR and RI ( P  < 0.01).
Conclusions:  There is a marginal disparity in the reactivity of men and women to patch test allergens that is probably not of clinical relevance but constitutes a scientific challenge.     

Pre-treatment of nickel test areas with sodium lauryl sulfate detects nickel sensitivity in subjects reacting negatively to routinely performed patch tests

A fair % of patients with a clinical history of nickel allergy show negative patch test results. To improve the response rate to NiSO₄ 5% pet, patch tests, a testing procedure utilizing pre-treatment of I he lest area by a 24-h application of sodium lauryl sulfate (SLS) was introduced 46 women with a clinical history of nickel sensitivity who exhibited negative reactions to nickel sulfate 5% pet, patch tests. were studied, Patients underwent d patch tests on adjacent sites on the volar surface of the forcarms. 4 patch tests were performed with a 72-h application of 40 mg nickel sulfate 5% pet. While I of these patch tests served as control. 3 test areas underwent 24-h pretreatment with 40 μl SLS. 1 with 0.1% and 2 with 0.5% solution. To evaluate differences in the reactivity to SLS plus nickel sulfate related to the site on the forearm, 0.5% SLS pre-treatment was performed both on a proximal and on a distal lest site. At the 72-h evaluation. 19 subjects out of 46 showed positive reaction to nickel sulfate 5%. At skin sites pre-t railed with SLS. Whereas 23 patients reacted positively at 0.5% SLS pre-treated ureas. Echographic values of skin thickness and of hypo-echogeme dermal areas al positive pre-treated nickel lest. Next higher than al control Jest areas, confirming the clinical evidence of an increased response to NiSO₄ after SLS pre-treatment. The inflammatory reaction, is evaluated clinically and echographically, was much higher al distal skin areas (0.l% SLS and distal (0.5%.) SLS than at proximal 0.5% SLS ones.     

Prevention of nickel-induced allergic contact reactions with pentoxifylline

In this study, we investigated the effect of pentoxifylline, an inhibitor of TNF-α, on the contact sensitivity response induced by nickel. For induction, open epicutaneous sensitization by NiSO₄. 6H₂O (25% aq.) solution was applied on the backs of 38 albino guinea pigs 5 days a week for 4 weeks. NaCl (0.9%) solution was applied epicutaneously to 10 albino guinea pigs as a control group. 19 were sensitized by nickel and developed positive patch test reactions. Patch tests were repeated after 10 of the sensitized pigs were given pentoxifylline 20 mg/kg/day orally. At the end of this study, only 2 positive patch test reactions were observed in the pentoxifylline-treated group, while 7/9 of the untreated guinea pigs developed positive reactions. These results suggest that pentoxifylline inhibits the contact sensitivity response induced by nickel only during drug administration.     

Is aphthous stomatitis associated with menstrual cycle in women?

Objective To establish the prevalence both of aphthae in women and of associations between aphthae and menstrual cycle. Background We believe that little valid evidence exists for associations between recurrent aphthae and menstrual cycle. Study Design Clients attending a well woman centre participated in a structured interview. Results Histories of aphthae were given by 6% of 1568 women. Histories of menstrual cycle associated aphthae were given by 0.6%. Twelve percent of a group of 213 aphthae sufferers gave histories of menstrual cycle associated aphthae, 8% with clear histories of premenstrual and/or menstrual aphthae. Conclusions A small proportion of women have clear histories of aphthae in the premenstrual period or during the menses.