Atopy patch test--reproducibility and elicitation of itch in different application sites

We evaluated the reproducibility of atopy patch test reactions and the quality and quantity of itch in 16 patients with atopic eczema and a history of a positive atopy patch test reaction, comparing three different application sites. The allergen was re-applied simultaneously on both forearms and the back. Intensity and quality of pruritus were evaluated using a visual analogue scale and the Eppendorf itch questionnaire, respectively. The atopy patch test reaction was highly reproducible, occurring in 15/16 (94%) patients. Pruritus was reported by 14/16 (88%) patients. There was no significant difference in either the intensity or quality of itch between the two forearms and the back (p>0.05). The mean peak visual analogue scale itch score was comparable across all three test sites (range 28.3-31.9). Regarding quantification of test reactions, a positive reaction was more frequent on the back (94% versus 69% on the arms) and the peak atopy patch test score was higher on the back compared with the arms (right forearm, p=0.0018 and left forearm, p=0.0683). Allergens should preferably be applied on the back for the atopy patch test. However, the atopy patch test can induce atopic itch irrespective of the application site.     

(Un)usual effects of patch testing?

BACKGROUND: Little information is available concerning subjective complaints associated with patch testing. OBJECTIVES: To gather information about the frequency and the nature of such complaints, and to evaluate, if possible, whether the complaints were really caused by patch testing. PATIENTS/ METHODS: Four hundred and thirty-three patients took part in a questionnaire study between December 1996 and October 1997. Complaints of itch and other subjective complaints, such as tiredness and feeling unwell, were recorded. RESULTS: From the total group of 433 patients, 379 patients (87%) recorded one or more complaints on day 0. By day 2 this number was 383 patients (88%), with a significant reduction to 326 patients (75%) by days 3-4. Most complaints concerned itch on the back, and to a lesser extent tiredness. Fifty-four patients (54 of 433; 12%) did not report itch or other subjective complaints on day 0; of this group, 36 patients (66%) developed complaints by day 2. By days 3-4, 24 patients (44%) reported complaints: 20 patients from the day 2 group (37%) and four patients (7%) from days 3-4. Again the largest increase in complaints was found for itch on the back, but other complaints were also found to have increased, mainly tiredness, feeling unwell, headache, shakiness and light-headedness. CONCLUSIONS: We conclude that patch testing can, in addition to local skin reaction and itch, also cause other subjective complaints in a number of patients.     

Optimal evaluation time point for patch testing to predict skin irritation of commercial topical drugs

To develop patch testing (PT) that better reflects the skin irritation resulting from repeated applications, we methodically classified PT results and examined correlations between these results with results from repeated application tests. A total of 115 commercial topical drugs were used for patch testing. In two groups of 30 healthy individuals with normal back skin, 55 or 60 commercial topical drugs were applied to the back for 24 h. Skin reactions were scored for each group at 2 and 24 h after patch removal. Based on time‐dependent changes in skin reaction at each evaluation time, PT results were classified into six different types. For repeated application testing, a total of 17 products with different types of PT results were selected. A total of 104 healthy individuals divided into three groups (n = 22–52 each) received application of 6–7 test materials, differing for each group, for 3 weeks on both arms. Incidences of positive symptoms induced by repeated drug application excluding transient erythema showed a greater correlation with reaction levels at 24 h after patch removal than 2 h after patch removal. Many test materials that triggered a high incidence of positive symptoms after repeated application also exhibited erythema or greater reaction up to 24 h after patch removal. PT offers a useful test system for predicting skin irritation that develops after repeated application of topical drug. Moreover, assessment at 24 h after patch removal is suggested as the optimal evaluation time point to reflect the results of repeated application tests.     

A stronger patch test elicitation reaction to the allergen hydroxycitronellal plus the irritant sodium lauryl sulfate

Household and cleaning products often contain both allergens and irritants. The aim of this double-blinded, randomized, paired study was to determine whether patch testing with an allergen (hydroxycitronellal) combined with an irritant [sodium lauryl sulfate (SLS)] cause a stronger patch test elicitation reaction than patch testing with the allergen (hydroxycitronellal) alone, in patients previously patch tested positive to hydroxycitronellal. A stronger patch test elicitation reaction was defined as at least 1 day of patch test reading showing more positive patch tests (+, ++ or +++) on the forearm patch tested with 6 concentrations of SLS plus hydroxycitronellal than on the forearm tested with 6 concentrations of hydroxycitronellal alone and no day of patch test readings showing more positive tests on the hydroxycitronellal forearm. 15/20 (75%) had at least 1 day of patch test reading with more positive patch tests on the forearm patch tested with SLS plus hydroxycitronellal and no day of patch test readings with more positive patch tests on the forearm tested with hydroxycitronellal (P = 0.0253). Estimation of the blood flow with laser Doppler supported these findings.     

Patch tests with house dust mite antigens in atopic dermatitis patients: methodological problems.

Patch tests with house dust mite allergens were performed in 21 atopic dermatitis patients with a positive prick test and RAST for house dust mite. Variables in methodology of patch testing, i.e. allergen concentration, application time, and intensity of tape stripping, were studied. Tests were performed with Dermatophagoides pteronyssinus solutions containing 20X, 100X and 500X the prick test concentration and purified HDM antigen: 10 and 50 micrograms/ml P1Ag solution. The series was applied on 8X or 15X tape-stripped and clinically normal skin on the back during 24 and 48 h. Non-specific reactions due to tape stripping, fixation tape or patch test occlusion were frequently observed: after 15X tape-stripping in 3/7 (24-h application) and 6/7 (48-h application) patients, after 8X tape-stripping in 2/19 (24-h application) and 8/19 (48-h application) patients. Reactions clinically assessed as specific occurred in 6/21 (29%) atopic dermatitis patients, 4/6 occurring in the 10 patients with a serum IgE greater than 1000 kU/l. High allergen concentrations and 48 h of application increased the number of patients with specific reactions. If 15X tape-stripping had been omitted, 2/3 patients tested in this manner and showing specific test reactions would have been negative. Further conclusions regarding the value and the preferable method of patch testing with atopic allergens require an in vitro control test.     

Peak Pruritus Numerical Rating Scale: psychometric validation and responder definition for assessing itch in moderate-to-severe atopic dermatitis

Atopic dermatitis (AD) is a chronic skin disease occurring in about 5 to 10% of adults worldwide. It can cause intense and persistent itch. For almost two-thirds of patients with moderate-to-severe AD, the itching lasts at least 12 hours a day, and is severe to unbearable. In clinical trials that are looking at how effective a treatment for AD is, itch intensity must be measured. Given itch is subjective, its intensity is most accurately reported by patients themselves. In this study, investigators from the U.S.A. and Europe developed a scale of itch called the Peak Pruritus Numerical Rating Scale (NRS). The scale measures the worst itch (peak pruritus) during the past 24 hours by asking patients “On a scale of 0 to 10, with 0 being ‘no itch’ and 10 being ‘worst itch imaginable’, how would you rate your itch at the worst moment during the previous 24 hours?”. To ensure the scale is reliable and valid (i.e., appropriate for assessing itch in AD patients), patients were interviewed about their opinions of the scale. The scale was then implemented in three large clinical trials of adults with moderate-to-severe AD. Interviewed patients said that the scale provided a relevant, clear, and comprehensive assessment of itch severity. As hypothesized, scores from the Peak Pruritus NRS showed moderate-to-strong correlation with other measures of itch, and weak-to-moderate correlation with measures of AD signs (clinical symptoms). The investigators concluded that the Peak Pruritus NRS is a well-defined, reliable, sensitive, and valid scale for evaluating worst itch intensity in adults with moderate-to-severe AD.     

Patch-test-induced subjective complaints

BACKGROUND: Many patients report subjective complaints during epicutaneous patch testing. OBJECTIVE: To demonstrate the possible relationship between the occurrence of subjective complaints and patch testing. METHODS: All consecutive patients who were referred to our clinic for patch testing, during 1 year, were investigated to study a possible association of the patch test procedure and subjective complaints like tiredness, shakiness or feeling unwell. The patients were asked to fill in a form concerning subjective complaints on the days of the investigation. Only those without complaints on the day the patches were applied were included in the study (n=102). RESULTS: Of the 102 patients, 17 had complaints on both days 2 and 3, 14 only on day 2, 6 only on day 3 and 65 did not develop any complaints at all. The number of patients with complaints on both days 2 and 3 (n=17) was larger than was to be expected from chance (n=4.6; p<0.01). There was a significant correlation between the number of positive patch test reactions and the number of complaints on day 2 (r=0.19; p<0.001) and on day 3 (r=0.15; p<0.001). Positive patch tests were found in 72.2% of the patients who reported the complaint of shakiness; this proportion is significantly higher than expected from chance (p<0.05). CONCLUSION: The results confirm those of our earlier study and demonstrate that patch testing can cause subjective complaints, especially when positive patch tests are present.     

Marking patch tests sites: description of a practical, clean, durable and inexpensive method

We propose an original method to mark patch test sites. A transparency is applied on the patient's back, surrounding patch tests, immediately after their application. Marks are performed with an erasable pen on test sites and on permanent skin lesions like naevi. For further readings performed after patch test removal, the transparency applied on the patient's back permits the attribution of a positive reaction. This method is clean (without ink marks on skin and without contamination of clothing), more comfortable for the patient (allowing back washing immediately after the 1st reading, never inducing allergy to inks), durable (permitting delayed readings after several days or weeks) and inexpensive (because transparencies can be reused).     

Clinical characteristics of pruritus in chronic idiopathic urticaria

BACKGROUND: Although pruritus is a predominant symptom of chronic idiopathic urticaria (CIU) its clinical characteristics have not been explored. OBJECTIVES: To characterize the clinical pattern and sensory and affective dimensions of the itch experience, utilizing a comprehensive itch questionnaire. METHODS: A structured questionnaire based on the McGill pain questionnaire was used in 100 patients suffering from CIU randomly recruited from a tertiary referral centre. RESULTS: All 100 patients recruited with CIU completed the questionnaire. In 68 patients pruritus appeared on a daily basis. Most patients experienced their pruritus at night and in the evening (n = 83), and 62 reported difficulty in falling asleep. Pruritus involved all body areas, but mostly the arms (n = 86), back (n = 78) and legs (n = 75). Accompanying symptoms were a sensation of heat in 45 patients and sweating in 15. Most patients (n = 98) were prescribed antihistamines (mainly sedating), of whom 34 experienced long-term relief. The sensation of itch was reported to be stinging (n = 27), tickling (n = 25) and burning (n = 23). Seventy-six patients found their pruritus bothersome, 66 annoying and 14 complained of depression. The itch intensity at its peak was more than double that felt after a mosquito bite. The worst itch scores of those who felt depressed were significantly higher than of those who did not (P = 0.018). There was a positive correlation between the sensory and affective scores during worst itch (P < 0.001). CONCLUSIONS: This study describes the itch experienced in CIU, highlighting sensory and affective dimensions. The itch questionnaire was found to be a valuable tool for evaluating pruritus in CIU and its unique features.     

Evaluation of a contact allergy clinic

This study aims to assess the value of patch testing in a specialist contact allergy clinic as compared to testing carried out by general dermatologist for the diagnosis of contact allergy. One hundred consecutive patients referred for patch testing were tested to the European standard and specialized series. A comparison was made between patch tests read and interpreted by a consultant dermatologist with an interest in contact allergic dermatitis and by an experienced registrar who had not yet received any formalized specialized training. Results of testing with additional allergens acquired following the establishment of the specialist clinic were examined. In addition patients with a hand problem and/or symptoms suggestive of contact urticaria underwent skin prick testing. There was a variation in patch test reading and interpretation between the consultant and registrar in 10 patients. Patch testing using allergens from the additional series revealed additional relevant contact allergies in 19 patients. In 14 patients, allergies would have been missed by a limited additional series. Contact urticaria was detected in seven patients. This study has confirmed the value of a specialist contact clinic in the diagnosis of contact allergy. The importance of formalized training in patch test reading and interpretation, testing with additional series and prick testing for the diagnosis of contact urticaria are highlighted.     

Site variations in patch test responses on the back

To establish the existence of intra-regional variations in response to allergens on the back, we performed patch tests in 21 patients at 2 different sites on the back. Visual readings using the numerical scale established by the International Contact Dermatitis Research Group were carried out 2 days after application of the allergen. After each visual reading, the skin blood flow at the test sites was quantified by laser Doppler flowmetry. The results of laser Doppler flowmetry showed a highly significant difference between the upper and lower back. It is therefore necessary that in quantitative and comparative investigations, symmetrical sites, i.e., left versus right sides of the body, should be studied.     

Patch testing with nickel sulfate: comparison between 2 nickel sulfate preparations and 2 different test sites on the back

Among patients routinely undergoing patch testing for suspected allergic contact dermatitis (ACD), nickel is the most frequently sensitizing hapten, with a clear predominance in the female population. However, some patients who report the appearance of dermatitis upon exposure to metal objects show negative patch test results to a nickel sulfate 5% pet. application. In some cases, a positive response to nickel can be observed simply by repeating the patch test. The objective of our study was to assess if, during routine patch testing, positive responses to nickel sulfate are missed owing to contingent problems, referring to application site, patch test execution or variations in skin reactivity. To this end, we applied 2 different patch test materials containing nickel sulfate 5% pet. to 3040 consecutive patients, undergoing patch testing for suspected allergic contact dermatitis, during the same session. The rôle of the test site was also investigated by applying the preparation on 2 different sites of the back in 30 patients. Of the whole, 612 patients (20%) showed positive patch test responses. The 2 nickel materials were almost equivalent: 78% of nickel-sensitive patients had positive reactions to both, whereas 11% showed a positive response to 1 preparation alone. No variations in patch test responses in relation to application site were observed. Our data show that false-negative patch test responses to nickel are frequent. The use of 2 different preparations during the same patch test session increases the response rate by 10%.     

Skin symptoms among workers in a spice factory

Workers in a Swedish spice factory ( n = 70). and in the office ( n =23) of the same company, were investigated by questionnaire regarding skin symptoms. In a 2nd part of the study, subjects reporting skin symptoms were examined and investigated by patch and prick testing. Skin symptoms were reported by 1/2 the factory workers. Pruritus and skin irritation, particular from cinnamon powder, were common, Patch test reactions to cinnamic aldehyde were found in 11/25 factory workers, but in several cases, the nature of the reactions was difficult to evaluate. Irritant patch test reactions were seen from powders of cardamom, paprika and white pepper. On prick testing, 6/25 workers reacted to cinnamic aldehyde. The results illustrate the difficulties of patch testing with spices and indicate the need for further research and validation of methods.     

IgE-mediated allergy to natural rubber in 30 patients with contact urticaria

30 patients who had experienced contact urticaria after exposure to gloves, contraceptives, balloons or dental cofferdams went through a detailed examination including interviews on: exposure to rubber; local and distant symptoms; provocation tests; skin prick tests with (among other substances) latex extracts from the rubber tree Hevea brasiliensis; patch testing, IgE and RAST analyses. 23 patients (77%) reported additional symptoms from distant organs. 13 belonged to medical occupations; 25 were classified as atopics based on history; 21 had raised IgE-values; 25 were RAST-positive to the extracts from Hevea brasiliensis. 13 had a pre-existing hand dermatitis, of whom 6 were patch test positive to standard allergens. Skin prick tests with extracts from Hevea brasiliensis were the most sensitive diagnostic tool, while the RAST analysis was positive in 25/30 cases. These tests and analyses including RAST were negative in 40 control subjects. Provocation tests are of great value, but difficult to standardize. Several patients reported severe reactions at medical and dental examination/treatment situations (surgical gloves, dental cofferdams), and the risk of life-threatening anaphylactic reactions is emphasized.     

Clinical characteristics of generalized idiopathic pruritus in patients from a tertiary referral center in Singapore

BACKGROUND: Generalized idiopathic pruritus is a rarely studied heterogeneous condition, where patients with non-inflamed, non-pathologic skin complain of widespread pruritus. METHODS: We had administered a detailed pruritus questionnaire, based on the short form of the McGill pain questionnaire, on 75 patients with this condition. RESULTS: All 75 patients recruited with generalized idiopathic pruritus completed the questionnaire. In 92% of the patients, pruritus appeared on a daily basis. Most patients experienced pruritus at night (56%) and in the evening (61%) and 69% had difficulty falling asleep. Pruritus mainly involved the legs (79%), arms (76%) and back (68%). Accompanying symptoms were heat sensation (17%) and pain (13%). 80% had been prescribed antihistamines, of whom 56% obtained short-term relief. The sensation of itch has been reported to be crawling (33%), tickling (20%), stinging (19%) and burning (19%). Patients also reported that the itch was unbearable (73%), bothersome (72%), annoying (67%) and worrisome (45%). The worst-state VAS scores were significantly higher in patients who reported agitation (P = 0.006), difficulty in concentration (P= 0.010) and anxiety (P= 0.033). CONCLUSION: This study describes the sensory and affective dimensions of generalized idiopathic pruritus, and this questionnaire has been found to be a useful tool for evaluating pruritus in this condition.     

P51Occupational contact dermatitis among operating room nurses

Background:  Occupation related dermatitis is a common problem in health care workers, especially in nurses, who are exposed to a wide variety of allergenic and irritant substances. The aim of this study was to assess the prevalence rate of skin symptoms among personnel handling chemical disinfectants and to examine which allergens were important.
Methods:  We investigated 460 randomly selected health care workers (HCW), who had constant contact with chemical disinfectants during their work. The study was performed by means of a questionnaire, a medical examination, skin patch test using Finn chambers and glutaraldehyde, benzalkonium chloride, hydrogen peroxide and chlorine compounds at 0,1, 0,5 and 1,0% wat.
Results:  241 HCW (52,5%) described various skin symptoms they attributed to disinfectant exposure. Generally, these symptoms were mild and ranged from pruritis to hand eczema. Of these 66 (14,4%) tested were skin patch test positive. Of the 460 HCW tested, 37 (8%) had positive patch test reactions to benzalkonium chloride, 22 (4,8%) to chlorine compounds, 18 (4%) to glutaraldehyde, 6 (1,2%) to hydrogen peroxide. 5 HCW (7,6%) testing positive to disinfectants gave no history of reactivity to them. History of atopic dermatitis was found in 50 (10,9%) and it was associated with diagnosis of allergic contact dermatitis and positive patch test reactions to benzalkonium chloride. Also positive patch tests reactions were associated with frequent use of latex gloves in contrast to those, which used latex gloves while working constantly or didn't use them at all.
Conclusions:  1. Skin symptoms related to work with chemical disinfectants are common, but mostly mild. 2. Benzalkonium chloride is one of the strongest sensitizing disinfectants used in health care professions, especially for atopic persons who do not take measures of protection during exposure to it.     

Patch test reactions at D4, D5 and D6

In this retrospective study, patch test reactions in 3 groups of patients were analysed, in order to obtain information on the best day for the 2nd patch-test reading after day 2 (D2), on the usefulness of additional readings after D3, and on the dependence of patch-test reactions at D4, D5, or D6 on allergen and/or patient characteristics. In the years 1990 to 1995, patch tests were routinely read at D3 and D4 in 1096 patients, at D3 and D5 in 1243 patients, and at D3 and D6 in 1136 patients. In all of the 3 groups, significantly more positive reactions diminished than appeared de novo from D3 to the later reading. Virtually identical results were observed in subgroups of patients formed by sex, age or atopy. However, men might possibly react more slowly than women on patch testing, showing more increasing than diminishing reactions in the D3/D4- and the D3/D5-comparison. Reactions to individual allergens showed wide differences in this connection. Neomycin sulfate, cobalt salts, and p-phenylenediamine can be characterized as slow allergens, with more reactions increasing than diminishing from D3 to the later readings. With fragrance mix and balsam of Peru, the opposite pattern occurred. In all subgroups of patients, and with most allergens, the gain in positive reactions was biggest when an additional reading was performed at D5. We conclude that for a single 2nd patch test reading after D2, D3 is the best day, and especially better than D4. If a 3rd reading is performed, it should be done at D5 to get the maximum information out of patch testing. However, this extends the test procedure to at least 1 day of the weekend.     

Patch-test reaction patterns in patients with a predisposition to atopic dermatitis

Patients with a predisposition to atopic dermatitis often need to be patch tested in order to detect possible contact sensitization. However, it is unknown whether immunologic or other peculiarities of atopic skin are related to altered patch-test reaction patterns. Our study was aimed at answering this question, because patch-test reaction patterns are of considerable practical importance in the reading and interpretation of patch tests. Therefore, we compared patterns of patch-test reactions in patients with a predisposition to atopic dermatitis and in control patients matched for sex, age, reason for testing and test centre. Patch-test results from 9 centres (2322 patients with a disposition to atopic dermatitis and 2126 matched controls) were evaluated retrospectively. All patients were tested with nickel sulfate, fragrance mix, potassium dichromate, lanolin alcohol, formaldehyde and mercury ammonium chloride. Patch tests applied for 1 day with readings on days 1, 2 and 3 were evaluated in order to cover the early phase of the reactions. Not unexpectedly, we found that, compared to the matched controls, patients with a predisposition to atopic dermatitis tended to have more doubtful and irritant reactions on day 1. As a new observation, it turned out that they had less reactions of crescendo pattern and more strong reactions on day 3. All these differences were slight/insignificant. A higher skin irritability in patients with a predisposition to atopic dermatitis is a likely explanation. In conclusion, standard methods for patch testing can be applied in patients with a predisposition to atopic dermatitis, but minor differences in reaction patterns should be considered.     

Excited skin syndrome: study of 39 patients.

BACKGROUND: Excited skin syndrome (ESS) is an adverse reaction obtained when carrying out epicutaneous patch tests, characterized by multiple positive test results, associated with one or more strongly positive tests, which are not all reproduced when the patient is tested afterward. OBJECTIVE: The aim of this study was (1) to determine the frequency of ESS in patients submitted to patch testing, (2) to confirm the influence of the evolution time of the primary dermatosis with ESS induction, (3) to determine differences among patients according the rate of positive test loss, and (4) to compare the number of positive tests for each substance between the first test, when all allergens in the test battery were applied, and the second test, when only the allergens with positive tests on the first occasion were applied at a greater distance from one another. METHODS: Epicutaneous tests were carried out in 630 patients with a suspected diagnosis of allergic contact dermatitis. Patients presenting 2 or more positive test results were considered to have ESS and were submitted to a second patch test. RESULTS AND CONCLUSIONS: ESS developed in 39 of the 630 patients tested, corresponding to a frequency of 6.2%. Analysis of data found a longer duration of the primary dermatitis in patients who in whom ESS developed compared with those who did not. Parabens, fragrance mix, and thimerosal had more positive patch test reactions using standard application techniques relative to the retest procedure, which placed the substances at a greater distance from one another, suggesting that, in addition to the factors previously reported to influence the reduction of ESS, the position of the allergens in the testing procedure also should be considered.     

Can the reporting of adverse skin reactions to cosmetics be improved? A prospective clinical study using a structured protocol

Background:  The use of cosmetics is rising, and adverse reactions to these products are increasing. In Sweden, the Medical Products Agency (MPA) keeps a voluntary reporting system for such adverse reactions. However, the reporting is sparse, consisting almost only of cases with test-proven allergic contact dermatitis, thus under-reporting the more common irritant reactions.
Objective:  The aim of the study was to try to improve the reporting system.
Patients and Methods:  Dermatologists at 3 dermatology departments used a structured protocol during the clinical investigation of 151 consecutive patients reporting skin reactions to cosmetics. The protocol included symptoms, signs, affected body site, suspected products, and final diagnosis after patch testing. Based on clinical data and patch test results, a causality assessment for each product was made according to a protocol used at the MPA.
Results:  Allergic contact dermatitis was found in 28% of the patients, and irritant reactions were equally common at 27%.
Conclusions:  Using this structured protocol, the cases of irritant dermatitis were also reported, and it is recommended that such a protocol is used as a standard to improve the reporting of adverse reactions to skin care products.