Enhancement of visual scoring of skin irritant reactions using cross-polarized light and parallel-polarized light

Background/purpose:  Polarized light has been used as an aid in visualizing various skin conditions, including acne vulgaris, rosacea, photoageing, lentigo simplex, and basal cell carcinoma. The use of parallel-polarized and cross-polarized light was evaluated in mild irritant reactions to determine, if this increases the ability to detect very early stages or low levels of irritation.
Methods:  Low concentrations of sodium lauryl sulfate (0.01% and 0.1%) were patched on human volunteers for 2, 6, and 24 hr, daily for 2–3 days in a modification of the standard patch test. Feminine protection products were evaluated in the behind-the-knee (BTK) test. Erythema reactions were scored by unaided visual assessment and using a polarized light visualization system.
Results:  In the 24-hr patch test, mean erythema assessed with polarized light was consistent with results of unaided visual scoring. Under milder conditions (2- and 6-hr patches), and in the BTK, significant differences from pretreatment levels of erythema were apparent earlier in the series of treatments compared with unaided scoring. In addition, subsurface scoring demonstrated that changes were still present under the skin surface even after unaided visual scoring indicated recovery.
Conclusion:  Low (subclinical) levels of irritation can be detected using enhanced visual scoring, indicating this non-invasive method has the potential to increase the sensitivity of our clinical studies.     

Effect of test techniques of perfusion of neomycin sulfate patch tests. A comparative study with visual assessments

Effects of test techniques on neomycin patch test results have not been thoroughly investigated. This study focuses on effects of dose and application time of neomycin sulfate patch tests on test results. The effects are assessed both visually and by perfusion. 16 subjects positive to neomycin are retested with neomycin sulfate in various doses and vehicles applied with different application devices for variable time intervals. All subjects were tested with a serial-dose series for time intervals ranging from 3 to 96 h (4 days [D]). The results show very good agreement between perfusion assessments and positive and negative visual assessments of reactions; however, a gray zone was detected where reactions with variable perfusion were associated with visually questionable test responses. 1:27 serial dilutions and wide application time intervals show a positive response with perfusion assessments and partly with visual assessments. Regardless of reading technique, highest reactivity of reactions was detected at either 96 h (day [D] 4) or 168 h (D7) in each subject with minor exceptions, regardless of dose, vehicle, application device or application time. Some findings of the study support the idea that reactions with papules alone are positive tests. Possible effect of tapes and foils on test results are discussed.     

Investigation of contact allergy to dental metals in 206 patients

Background:  Contact allergy to dental materials is poorly understood; clinical manifestations are heterogeneous.
Objective:  To analyse positive patch test reactions to metals (as their alloys or salts) used in dentistry together with clinical symptoms and possible relevance to dental fillings.
Methods:  We retrospectively analysed 206 patients who underwent patch testing with metals used in dentistry because of suspected contact allergy to them.
Results:  Twenty-eight of 206 patients had positive patch test reactions to metals used in dentistry. The number of positive patch test reactions was highest for gold sodium thiosulfate, palladium chloride, and nickel sulfate ( n  = 10, respectively), followed by amalgam, ammoniated mercury, and cobalt chloride ( n  = 4, respectively) and amalgam-mixed metals (including copper, tin, zinc, and silicon), and ammonium tetrachloroplatinate ( n  = 1). Only 14 (7%) of 206 patients had a clinically relevant contact allergy with conditions of the oral mucosa ( n  = 7 with lichen planus and n  = 7 with stomatitis) and positive patch test reactions to dental metals containing the suspected allergen. Improvement of symptoms was assessed in one patient with amalgam contact allergy 2 weeks after removal of dental fillings.
Conclusions:  Clinically relevant contact allergies to dental metals are infrequent. Gold sodium thiosulfate and palladium chloride presented the most frequent contact allergens.     

Folliculitis decalvans

ABSTRACT:   Folliculitis decalvans is a rare inflammatory scalp disorder. The present paper gives a practical approach to diagnosis and patient management and reviews possible pathogenetic factors and treatment options. Folliculitis decalvans is classified as primary neutrophilic cicatricial alopecia and predominantly occurs in middle-aged adults. Staphylococcus aureus and a deficient host immune response seem to play an important role in the development of this disfiguring scalp disease. Lesions occur mainly in the vertex and occipital area. Clinically, the lesions present with follicular pustules, lack of ostia, diffuse and perifollicular erythema, follicular tufting, and, oftentimes, hemorrhagic crusts and erosions. Histology displays a mainly neutrophilic inflammatory infiltrate in early lesions and additionally lymphocytes and plasma cells in advanced lesions. Treatment is focused on the eradication of S. aureus anti-inflammatory agents.     

Patch testing with benzoyl peroxide: reaction profile and interpretation of positive patch test reactions

Background: Patch testing with benzoyl peroxide 1% pet. frequently leads to (weak) positive reactions, often with uncertain clinical relevance.
Objectives: To describe the pattern of patch tests reactions to benzoyl peroxide and to identify patients at risk of a positive reaction.
Methods: Retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 1992–2007.
Results: Benzoyl peroxide 1% pet. was tested in 29 758 patients. Weak positive reactions (erythema, infiltration, possibly papules) occurred in 6.5%, and strong positive reactions (erythema, infiltration, vesicles) in 1.3%. According to logistic regression analysis, strong positive reactions to benzoyl peroxide were associated with leg or face dermatitis, work as dental technicians, young age and being female. Patients with atopic dermatitis had a significantly increased risk of weak positive reactions only.
Conclusions: Our analysis confirms that benzoyl peroxide 1% pet. is a problematic patch test preparation. Hence, clinical relevance of reactions to benzoyl peroxide has to be assessed very carefully. Patients with atopic dermatitis are particularly prone to irritant reactions to benzoyl peroxide. True allergic reactions may occur in dental technicians and following the treatment of leg ulcers with highly concentrated benzoyl peroxide in past. In contrast, widely used acne treatments with benzoyl peroxide seems to sensitize only rarely.     

Prevalence of patch test results from 1970 to 2002 in a multi-centre population in North America (NACDG)

Background:  The North American Contact Dermatitis Group (NACDG) has members who assess subjects with suspected allergic contact dermatitis (ACD) and patch tests them with the same screening allergens using a standardized procedure permitting analysis of long-term trends in patch test reactions.
Objective:  This study reports the trends in prevalence patch test positivity of allergens by pooling data collected by the NACDG between 1970 and 2002.
Patients/Methods:  Patients were tested with the screening series of allergens, using a standardized technique. Data from these patients were recorded on a standard computer entry form and analysed. More than 100 allergens were tested on over 34 000 patients during several patch studies between the period. The Cochran-Armitage test of trend is used to evaluate changes in prevalence over time.
Results:  4 trends are noticed: (1) The incidence of presumed allergic nickel ( P < 0.0001) and quaternium-15 ( P < 0.0001) reactions rose with consistency over the years. (2) While that of cinnamic aldehyde ( P = 0.21) and p -phenylenediamine ( P < 0.0001) decreased. (3) The prevalence of positive reactions for potassium dichromate ( P < 0.0001) shows an initial steady decrease but then a sharp increase starting from the 1996 period. (4) In contrast, thiuram ( P = 0.0008) and neomycin ( P < 0.0001) show an initial general increase, with a sharp decrease between 1998 and 2002.
Conclusion:  Implications for opportunities to prevent ACD by utilizing less-allergenic alternatives appear robust; however, we do not wish to over generalize interpretations because of important limitations.     

Correlation between laser Doppler perfusion imaging and visual scoring of patch test sites in subjects with experimentally induced allergic and irritant contact reactions

Purpose: To compare laser Doppler perfusion imaging (LDPI) measurements in experimentally induced allergic contact reactions and irritant contact reactions. The degree of correlation between visual scores and LDPI measurements was also studied.
Methods: Fifteen patients with known contact allergy to nickel or fragrance were patch tested with nickel sulfate 5% pet., fragrance mix 8% pet., sodium lauryl sulfate (SLS) 0.5% pet., SLS 1.0% pet. and two empty control chambers. Visual readings and LDPI measurements were taken at 0, 48 and 96 h.
Results: There was a positive correlation between visual scores and LDPI measurement in the nickel sulfate and fragrance mix patch test sites. However, no correlation between visual scores and LDPI measurements was seen in the SLS 0.5% and SLS 1.0% patch test sites. There was no significant difference ( P =0.125) in LDPI measurements between contact-allergic reactions and contact-irritant reactions.
Conclusion: LDPI correlates with visual scoring in contact-allergic reactions, but not in irritant reactions. LDPI is not useful in distinguishing between allergic and irritant reactions.     

Pustular patch test reactions in atopic dermatitis.

Pustular patch test reactions to 5% nickel sulfate were regularly produced in patients with atopic dermatitis when patches were placed over areas of skin with (a) follicular papules, (b) erythema, (c) lichenification, and (d) minimal trauma. The pustular patch test reactions seldom occurred in the normal-appearing skin of these patients. However, if the skin was traumatized prior to the patch test, the reaction was produced in the normal-appearing skin of atopic as well as control individuals. No pustular reactions occurred in the follicular lesions of keratosis pilaris, supporting the view that follicular lesions of atopic dermatitis differ from keratosis pilaris. It is suggested that pustular patch test reactions are caused by primary irritation.     

[Translated article] Dermoscopy in Patch Testing: How Can It Help?

Interpreting patch test reactions is not easy. It requires experience and is characterized by high intraobserver and interobserver variability. It can sometimes be truly difficult to discern between a weak allergic reaction and an irritant reaction. A number of recent studies have investigated the dermoscopic features of patch test reactions. Homogeneous erythema is the main feature observed in patients with a positive allergic reaction, although dotted vessels, vesicles, crusts and yellow-orange areas may also provide clues. These features are somewhat similar to those observed in inflammatory conditions, such as eczema. In patients with an irritant reaction, the most common dermoscopic findings are the pore reaction pattern and perifollicular erythema. Dermoscopy could be useful for establishing a diagnosis in the case of doubtful patch test reactions.     

Uso del dermatoscopio en la lectura de pruebas epicutáneas: ¿qué puede aportar?

Interpreting patch test reactions is not easy. It requires experience and is characterized by high intraobserver and interobserver variability. It can sometimes be truly difficult to discern between a weak allergic reaction and an irritant reaction. A number of recent studies have investigated the dermoscopic features of patch test reactions. Homogeneous erythema is the main feature observed in patients with a positive allergic reaction, although dotted vessels, vesicles, crusts and yellow-orange areas may also provide clues. These features are somewhat similar to those observed in inflammatory conditions, such as eczema. In patients with an irritant reaction, the most common dermoscopic findings are the pore reaction pattern and perifollicular erythema. Dermoscopy could be useful for establishing a diagnosis in the case of doubtful patch test reactions.     

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.     

Influence of skin peeling procedure in allergic contact dermatitis

Background:  The prevalence of allergic contact dermatitis in patients who have previously undergone skin peeling has been rarely studied.
Objectives:  We compared the frequency of positive patch test (PT) reactions in a patient group with a history of peeling, to that of a control group with no history of peeling.
Patients/Methods:  The Korean standard series and cosmetic series were performed on a total of 262 patients. 62 patients had previously undergone peeling and 200 patients did not.
Results:  The frequency of positive PT reactions on Korean standard series was significantly higher in the peeling group compared with that of the control group ( P  < 0.05, chi-square test). However, the most commonly identified allergens were mostly cosmetic-unrelated allergens. The frequency of positive PT reactions on cosmetic series in the peeling group was higher than that of the control group, but lacked statistical significance. The frequency (%) of positive PT reactions on cosmetic series in the high-frequency peel group was higher than that of the low-frequency group, but lacked statistical significance.
Conclusion:  It appears peeling may not generally affect the development of contact sensitization. Further work is required focusing on the large-scale prospective studies by performing a PT before and after peeling.     

FS02.8Patch testing with gold trichloride can give false test results

Background:  Hydrochloric acid is formed in water solutions of gold trichloride. Hydrochloric acid in contact with aluminium generates hydrogen gas which can reduce and transform trivalent gold to elemental gold.
Objective:  To investigate whether patch testing with aqueous gold trichloride can cause false positive (irritant) reactions in patients without contact allergy to gold and false negative reactions in patients with gold allergy.
Methods:  13 patients with and 13 patients without positive patch test reactions to gold sodium thiosulfate were tested with gold trichloride in 2 different vehicles, water and alkaline buffer, using 2 different test techniques, the Finn Chamber technique with aluminium chambers and van der Bend technique with polypropene chambers.
Results:  Irritant patch test reactions were obtained with aqueous gold trichloride tested in van der Bend chambers in 10 patients without gold allergy. In gold‐allergic patients no positive test reactions were obtained from aqueous gold trichloride in Finn chambers while 2 positive test reactions were obtained from gold trichloride in alkaline buffer tested in van der Bend chambers.
Conclusion:  If gold trichloride is patch tested in wrong vehicle and with wrong test technique irritant test reactions may occur which can be misinterpreted as positive allergic reactions in patients without gold allergy as well as negative reactions in patients with gold allergy.     

p-Phenylenediamine sensitization is more prevalent in central and southern European patch test centres than in Scandinavian: results from a multicentre study

Background:  Positive patch test reactions to p -phenylenediamine (PPD) are common. PPD is used in oxidative hair dyes and is also present in dark henna temporary 'tattoos'. Cross-sensitization to other contact allergens may occur. Because subjects sensitized to PPD are at risk of clinically severe reactions upon hair dyeing, there is a need for 'current' prevalence data on PPD sensitization.
Objectives:  To compare PPD patch test results from dermatitis patients tested between 2003 and 2007 in 10 European patch test centres and to analyse the causes and determine relevance of positive PPD patch test reactions.
Materials:  Patch testing was performed using PPD (1% free base in petrolatum from Trolab (Almirall Hermal GmbH, Reinbeck, Germany) or Chemotechnique (Malmö, Sweden), equivalent to 0.090 mg/cm² in the TRUE^® test from MEKOS Laboratories AS). Statistical analysis was performed using the chi-squared test.
Results:  The weighted average prevalence was 4.6% among 21 515 patients. PPD sensitization occurred more often in centres located in Central and Southern Europe than in Scandinavian centres (odds ratio = 2.40; 95% confidence interval = 2.07–2.78). The overall proportion of positive patch test reactions to PPD that were registered as being of either current or 'past' relevance was high (weighted average 53.6% and 20.3%, respectively). Consumer hair dyeing was the most prominent cause of PPD sensitization (weighted average 41.8%). Furthermore, occupational hair dye exposure (10.6%) and cross-sensitization to textile dyes (12.6%) were frequently reported.
Conclusions:  PPD sensitization caused by exposure to hair dyes is frequent and remains a present problem for patients visiting contact dermatitis clinics, especially in patch test centres located in Central and Southern Europe.     

Nickel: the search for alternative, optimal and non-irritant patch test preparations

Background/aims: Several contact allergens including nickel are also irritants. Ideal patch test preparations should not miss cases of contact allergy and should be non-irritant. The currently used nickel preparation (5% nickel sulfate in petrolatum; 0.19 m) is a compromise. The present aim was to compare the skin-irritant potential of various nickel preparations (sulfate, chloride, nitrate in petrolatum and in water) by using the objective, noninvasive laser Doppler technique for assessment.
Methods: Preparations with various nickel concentrations and vehicle controls were applied under occlusion (Finn chambers) on the volar forearms of healthy subjects for 48 h. The test sites were examined visually and measured with a laser Doppler flowmeter before, and repeatedly after, removal of test patches. Some preparations were also used when patch testing consecutive dermatitis patients.
Results: 0.19 m nickel chloride and nickel nitrate in petrolatum caused erythema as well as increase in skin blood flow, while lower concentrations (0.10, 0.05 and 0.01 m) did not affect skin blood flow. At higher concentrations the sulfate was less reactive than the other salts. The reactivity was more pronounced with the salts in petrolatum than in water. 0.05 m nickel nitrate was equivalent to 0.19 m nickel sulfate in diagnosing contact allergy in patch testing, while 0.30 m nickel sulfate in water missed several cases.
Conclusions: The laser Doppler technique is more sensitive than the naked eye and can indicate nickel patch test preparations with marginal irritant properties. Some promising alternative candidates have been identified.     

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.     

Macro-video documentation patch tests

An unequivocal distinction between allergic and irritant patch test reactions is often difficult with patch tests. This study was designed to evaluate the worth of video-macro camera documentation for differentiation between allergic and irritant test reactions and to investigate whether there are characteristic clinical differences in patch test responses between metal salts and fragrances. Patch testing was performed with nickel sulfate, fragrance mix and an irritant, sodium lauryl sulfate 1% aq., on the upper back of 82 patients, with evaluation and computer-aided video documentation after 48 and 72 hr. No reliable clinicomorphological criterion was found for assessing a weak patch test reaction as being definitely allergic. Even characteristic papules and vesicles were not regularly found in allergic reactions. However, unlike fragrance mix, patch test reactions to nickel sulfate were characteristic in that they showed a heterogeneous spread and an association with hair follicle openings, independent of reaction intensity. Evaluation based on additional computer-aided video-macro camera documentation did not add further advantage for the differentiation of allergic and irritant reactions. But well-defined clinicomorphological features and reaction patterns to single test substances or even whole substance categories could be helpful additional criteria for evaluating patch test responses in clinical practice.     

The inuence of patch test size and design on the distribution of erythema induced by sodium lauryl sulfate

Patch testing is an invaluable tool for the experimental induction of acute irritant contact dermatitis (ICD), with a variety of chamber systems available for use. Ideally, the inflammatory reactions produced should be of uniform intensity across the test area, thereby facilitating grading of the response and tissue sampling for histopathological studies. Unfortunately, annular, follicular and/or blotchy erythema frequently occur. In this study, we set out to compare the performance of 5 patch test systems (8 mm, 12 mm and 18 mm Finn Chambers; 19 mm and 25 mm Hilltop chambers) when testing normal healthy volunteers with sodium lauryl sulfate at concentrations selected to produce mild, moderate and moderately severe reactions. Visual assessment of the patch test sites revealed good dose responses with all 5 chamber types. Uniformity of erythema across the test site was more closely linked to the actual intensity of response than the delivery system itself, mild reactions being far less likely to display homogeneous erythema than moderately severe reactions. Extra large chambers did not perform significantly better than smaller chambers. Balancing the need for a uniform reaction pattern and adequate tissue sampling area, against the exposure risk, we conclude that 12 mm Finn Chambers represent the optimum patch test system for acute SLS-induced irritation where histopathological investigations are the ultimate aim.     

Contact allergens in patients with leg ulcers

Background Contact dermatitis can complicate the treatment of leg ulcers and is an acquired phenomenon resulting from the use of topical medications.
Objective To show the incidence of contact dermatitis reactions to topical medications applied to leg ulcers and to evidence changing trends in such reactions through comparison of two case series about 20 years apart.
Subjects and methods We studied two groups of patients with leg ulcers that were patch tested with contact allergens in 1973–1974 and in 1994–1995.
Results One or more positive patch tests was present in 75% and 40% of the patients, respectively. A decrease in the incidence of positive reactions to neomycin, local anesthetics and parabens mix was seen in 1994–1995. The most important contact allergens in 1994–1995 were fragrance mix, colophony and the excipients wool alcohols and amerchol. Other relevant sensitizers were formaldehyde, neomycin and gentamycin.
Conclusion The changing trends in contact allergens over the last 20 years may be explained by changes in the components of topical agents used for treatment.     

A study on expert reading of patch test reactions: inter-individual accordance

To diagnose allergic or irritant contact dermatitis, a clinically relevant contact allergy has to be demonstrated or ruled out, respectively. Although patch testing has been used for 100 years, it remains the method of choice for diagnosing contact allergy. A disadvantage of patch testing is that reading is subjective, based on inspection and palpation of the test area, implying that the assessment is subject to the reader's knowledge and experience. This study was carried out to investigate the accordance in reading patch test reactions between 5 dermatologists. 4 groups, each with 10 patients, participated. Within each group, all 10 were allergic to one and the same sensitizer; nickel, epoxy resin, ethylenediamine, or Kathon CG. The sensitizers were tested in serial dilutions and applied randomly to the back. The tests were read independently by the dermatologists in a blinded fashion. A protocol was used where the dermatologists had to note the presence of the morphological features erythema, infiltration, papules, vesicles, and bullae. In this way, it was possible to allocate the various readings into 4 classification systems, 3 European and one American, although the definition of the various classifications might differ slightly. Based on the readings and classifications, it was possible to calculate the degree of accordance within the 4 systems used. It was also possible to analyze the degree of accordance for the various morphological features. Total accordance for the 5 reading dermatologists for positive and negative test reactions was noted in 36% and 46%, respectively. The 3 European systems require homogenous erythema and infiltration for a reaction to be classified as allergic, while the American system also requires the presence of papules. Therefore, a higher number of allergic reactions (9%) was obtained with the European systems. Between the 4 classification systems, there were statistically significant differences, with the highest number of deviations for the system in which papules had discriminatory significance. When looking at the various morphological features, papules were most difficult to assess, followed by vesicles. Preferably, a classification system should not depend on papules. In conclusion, there was good accordance among the dermatologists in reading patch test reactions, since the 5 dermatologists read 82% of all tests similarly.