Patch test responses to rockwool of different diameters evaluated by cutaneous blood flow measurement

Rockwool is a man-made mineral fiber used mainly for insulation, which can cause mechanical skin irritation. This study was performed to evaluate the irritant potential of rockwools of different diameters and to compare the change of blood flow, measured by laser Doppler flowmetry, at different patch test occlusion times with rockwools. Rockwool A (mean diameter 4.20 +/- 1.96 mu) was more irritating than rockwool B (mean diameter 3.20 +/- 1.5 mu). The difference was more clearly observed in a 48-h patch test than in an 8-h or 24-h test. We concluded that laser Doppler blood flow measurement was a useful experimental tool for the evaluation of irritant patch test responses to mechanical irritants like rockwool, and that 48 h or more of occlusion time was necessary to produce irritant patch test responses to certain types of rockwool.     

Allergic and irritant skin reactions evaluated by laser Doppler flowmetry

Skin blood flow (SBF) in allergic and irritant reactions was determined by laser Doppler flowmetry (LDF) in an attempt to differentiate these reactions in an objective way. 12 subjects with known allergy to nickel were patch tested with nickel sulphate, nickel chloride, and with sodium lauryl sulphate (SLS) 1, 2, 5 and 10%. A positive correlation between the concentration of SLS and SBF was found. Compared with control sites, SBF in weak (+) and strong (++) positive allergic and irritant reactions was increased approximately 5-10 fold 1 and 2 days after application, and decreased towards normal 7 days after application. At day 7, the mean SBF was higher in allergic reactions than in irritant reactions. However, no consistent differences were found. It is concluded that although LDF can be used to quantify the strength of allergic and irritant skin reactions, this method cannot be used solely to separate these 2 types of reaction.     

Assessment of erythema in irritant contact dermatitis

Assessment of erythema in experimentally-induced irritant contact dermatitis has been performed visually and using the laser Doppler flowmeter (LDF). A close correlation was shown between the 2 methods (r = 0.9079, p less than 0.001), with the LDF producing mean blood flow values which were able to discriminate between the different visual scores. Of the 100 patch tests evaluated, 3 gave poor correlations between their visual and LDF readings, including 2 dithranol reactions and 1 sodium hydroxide response. Patch tests with no visible erythema had blood flow values similar to those of normal untreated skin. Although the LDF was an easy instrument to operate, it was not considered suitable for use in the routine patch test clinic, due mainly to the unacceptable length of time required to measure each patch test.     

Relationship between intensities of skin test reactions to glass-fibres and chemical irritants

A total of 98 workers at a glass-wool factory were patch tested with glass-fibres and six chemical irritants. A rubbing test with the fibres, a Trafuril test and provocation of dermographism were also performed. The subjects with strong patch test reactions to one quality of fibres also reacted strongly to the other types of fibres but did not show an increased sensitivity to other tests. The subjects with intense skin reactions to rubbing with the fibres showed an increased skin reactivity to Trafuril. A tendency towards increased reactivity to the patch tests with fibres was found in persons with fair skin and blue eyes.     

Susceptibility to skin stinging,non-immunologic contact urticaria and acute skin irritation; is there a relationship?

Adverse skin reactions cover many types of response: toxic, irritant, allergic, urticarial, sensory, etc. The relationships between an individual's tendency to develop different types of skin response are not well-described. We examined whether those who perceive stinging might be more likely to experience urticarial, sensory and irritation reactions in skin. A panel of 86 volunteers was tested with 10% lactic acid in the nasolabial fold to assess their ability to perceive stinging. At the same time, their capacity to develop non-immunologic contact urticaria was evaluated using chemicals of different structural type and urticant ability: methyl nicotinate, benzoic acid, cinnamic acid, cinnamaldehyde and dimethyl sulfoxide (DMSO). DMSO was also used to assess sensory effects and skin irritation. 44 were classed as "stingers" and 42 as "non-stingers". The pattern of urticant reactivity in the stingers and non-stingers was essentially the same, with neat DMSO generating the strongest reactions in both groups. Sensory reactions to DMSO (stinging, itching, tingling or burning) were similar in stingers and non-stingers; although the former may have reacted more quickly, a smaller proportion reacted (64% versus 76%). The skin irritation response to DMSO was also identical in stingers and non-stingers and the intensity of the urticant response in an individual did not correlate with the intensity of their subsequent irritant reaction. In conclusion, this study demonstrated that an individual's ability to perceive skin stinging does not give a general indication of their susceptibility to other types of non-immunologic skin response. Indeed, there appeared to be little evidence of correlations between any of the skin effects studied.     

Lymphocyte subsets and Langerhans cells in allergic and irritant patch test reactions: histometric studies

This study has attempted to distinguish between allergic and irritant reactions to patch tests by semiquantitative histological methods. The extent of perivascular chronic inflammatory infiltrate at 72 h in irritant patch test reactions to sodium lauryl sulphate was shown to be small and very consistent, whereas in allergic reactions to nickel sulphate it was generally larger and more variable in size (p less than 0.02). The two major lymphocyte subsets (T4 and T8) were randomly intermixed in both types of reaction and formed the major component of both the perivascular and diffuse dermal infiltrate, without any evidence of selective migration. The T4:T8 ratios were similar in focal and diffuse infiltrates. The number of T6 dendritic (putative Langerhans) cells in the epidermis (per mm inner epidermal length) was usually greatly reduced in irritant reactions (5-16 mm-1, mean 10 mm-1) but remained within normal limits in allergic reactions (6-33 mm-1, mean 21 mm-1) (p less than 0.001). Comparable results were seen with other irritants (mercuric chloride and benzalkonium chloride) and other allergens (neomycin sulphate, ethylene diamine and potassium dichromate). In additional experiments, pairs of biopsies were taken from the reaction and from adjacent unaffected skin. The T6 cell density in the epidermis did not significantly differ between allergic reactions and control skin. By contrast, the irritant reactions had fewer T6 cells than the control skin (p less than 0.001).     

Fruit acids do not enhance sodium lauryl sulphate-induced cumulative irritant contact dermatitis in vivo

Combined exposure to different irritants in the workplace may lead to irritant contact dermatitis, which is the main type of occupational dermatitis among bakers and confectioners. Following previous work on "tandem irritation", a panel of healthy volunteers was exposed twice daily for 4 days to the organic fruit acids: citric, malic, and lactic acid, either alone or in tandem application with 0.5% sodium lauryl sulphate (SLS) in a repetitive irritation test. Irritant cutaneous reactions were quantified by visual scoring and non-invasive measurement of transepidermal water loss and skin colour reflectance. Twice daily application of either citric or malic acid alone did not induce a significant irritant reaction. Combined exposure to one of the fruit acids and SLS caused marked barrier disturbance, but the latter irritant effect was smaller than that obtained by combined exposure to SLS and water. Thus, combined exposure to the above-mentioned fruit acids and SLS did not enhance cumulative skin irritation.     

Skin irritation in man: a comparative bioengineering study using improved reflectance spectroscopy

Variable types of skin irritation were induced in 8 human female volunteers, ranging from subclinical to visible erythema with slight oedema. Skin reactions were graded clinically and objectively using transepidermal water loss (TEWL), laser Doppler flowmetry (LDF) and improved reflectance spectroscopy. This last technique enables separation of in vivo erythemas into relatively deoxygenated (venous-deoxy hem) and oxygenated (arterial oxy hem) haemoglobin components. Compared to uninvolved skin, an empty patch increased oxy hem by 197%± 121%( p < 0.05). Exposure to vehicles also changed skin biophysics. At sodium lauryl sulfate (SLS) and hydrochloric acid (HCL) exposed sites, a linear correlation between concentration and oxy hem. LDF and TEWL was found. These chemicals predominantly increased TEWL values. Nonanoic acid (NON) and imipramine (IMI) also raised oxs hem, LDI and TEWL values linear at increasing concentrations. Although IMI 2.5% clinically was graded as a type ++ response, no significant increase in TEWL was found. The improved reflectance spectroscopic technique proved valid in skin irritation studies, with a higher sensitivity than laser Doppler flowmetry, and allowed irritant vascular reactions to be discriminated into arterial and venous components. Furthermore, our observations clearly demonstrate that clinical indistinguishable skin irritation reactions induce significantly different changes in barrier function (disruption) and vascular status.     

Long-term repetitive sodium lauryl sulfate-induced irritation of the skin: an in vivo study

Skin may adapt to topical irritants through accommodation. This study focuses on long-term exposure to irritants and attempts to demonstrate accommodation. Sodium lauryl sulfate (SLS) induced irritant contact dermatitis at 3 concentrations (0.025% to 0.075%). Distilled water, acetone and an empty chamber served as controls. Experimental compounds were applied to forearms of 7 healthy volunteers for 24 hr before replacing by a fresh chamber for 6 non-consecutive weeks over 103 days. Possible accommodation was quantified by visual scoring (erythema and dryness) and by bioengineering parameters: transepidermal water loss (TEWL), capacitance, chromametry and laser Doppler flowmetry (LDF). Significant erythema, dryness, elevated TEWL, skin colour reflectance and LDF values occurred during the exposure periods. Upon repeat exposure, an immediate and augmented response in erythema, TEWL, skin colour reflectance and LDF developed. However, irritant skin changes were not sustained. Irritation parameters return to baseline after cessation of exposure. There was no evidence of sustained irritation or accommodation after the last exposure. Study findings do not document sustained accommodation or adaptive hyposensitivity after long-term repetitive irritant exposure under these test conditions. Alternative models should be developed to prove or disprove the accommodation hypothesis.     

Moisturizers prevent irritant dermatitis.

The purpose of this study was to investigate the ability of eight different moisturizers to prevent irritant dermatitis. Twelve healthy female students washed the outer aspect of their upper arms with a liquid detergent for one minute twice a day for one week. Seven skin creams and one skin oil were applied to 3 x 7 cm areas of the left upper arm just after each washing, while the right upper arm was left untreated. Transepidermal water loss (TEWL) (mean) increased from 7.1 to 9.3 g/m2/h (p less than 0.001) and laser-Doppler flowmetry (LDF) value (mean) decreased from 11.8 to 10.8 arbitrary units (N.S.) in the left upper arm, but there was no statistical difference between the eight moisturizers. During the second week of the study, the test subjects did not continue washing their arms. Eight areas (3 x 7 cm) of the right upper arm were treated with the moisturizers twice a day. The mean TEWL value decreased from 20.3 to 8.6 (p less than 0.0011) over 7 days, but there were no significant differences between the individual moisturizers. The laser-Doppler values showed the same trend as the TEWL values. In conclusion, regular use of emollients prevented irritant dermatitis from a detergent.     

Phenotypic difference between allergic and irritant patch test reactions in man

Cellular responses in allergic and irritant contact dermatitis were analysed in situ using an immunohistochemical double staining technique with the aim of uncovering phenotypical differences of diagnostic importance. Allergic and irritant patch test reactions were elicited in 9 individuals using the Finn chamber technique. Thirty-nine skin biopsies from these reactions and from petrolatum controls were obtained 4 to 20 days after the test applications. Cell infiltrates were present throughout the observation period in both allergic and irritant reactions, but were usually greater in the former. In both types of reaction, anti-Leu 3a reactive cells predominated over anti-Leu 2a reactive cells. HLA-DR expression on keratinocytes was found in 9 of 14 allergic reactions, but not in irritant reactions or control areas. HLA-DQ antigens were not detected on keratinocytes. The presence of HLA-DR antigens on keratinocytes may reflect an immunological response of the allergic reactions, and thus be of diagnostic relevance.     

The effect of grenz rays on irritant skin reactions in man

To investigate the effect of grenz rays on irritant contact reactions, eleven healthy volunteers were studied. They were given 3 Gy of grenz rays, once a week for 3 weeks, to a defined area of the back. Twenty-four hours after the last treatment, serial dilution sodium lauryl sulphate patch tests were applied both on the grenz ray treated area and on the untreated control skin. Biopsy specimens were taken from the irritant reactions both from the grenz ray treated area and from the control area and different cell populations in dermis and epidermis were identified by monoclonal antibodies (Leu 2, 3, 4, 7, Leu M1, B1, OKT6). In the grenz ray treated epidermis there was a pronounced reduction of OKT6-positive cells but the composition of the dermal cellular infiltrate did not differ between control and grenz ray treated skin. The assessment of the patch test reactions did reveal a tendency towards weaker reactions in the grenz ray pre-treated skin but this difference was not statistically significant. It is concluded that grenz rays do not have a marked effect on the elicitation of irritant reactions.     

Managing the excited skin syndrome: patch testing hyperirritable skin

Inflammation-modulating phenomena (IMPs), humoral and cellular, fluctuate during the course of irritant and allergic contact dermatitis influencing irritability of the skin. The patch test procedure is a biological assay, a titration of responses to IMPs which can produce hypo reactivity or hyperirritability of the skin of patients who have dermatitis (PDs) and a single patch test is a "snapshot" of the tempo of an evolving process. The excited skin syndrome (ESS) refers lo hyperirritability from clinical and patch test dermatitis creating false-positive patch test reactions which are not reproducible when dermatitis and IMPs have subsided. During ESS, the threshold for irritancy decreases and irritant reactions increase. Patch test concentrations should be determined and ESS investigated in PDs having enhanced IMPs, not in "normal" individuals, and if a patch test result is important to a patient the test should be performed more than once. Variable reproducibility is inherent in the patch test method, but ESS can be managed by appropriate testing and retesting, and search for relevance.     

Immediate irritant reactions to benzoic acid are enhanced in washed skin areas

Factors affecting immediate irritant skin reactions are poorly understood. Our purpose was to study the effect of washing on reactions to benzoic acid, a well-known immediate-type irritant. 12 test subjects washed their left upper arms with a diluted dishwashing liquid 2× daily for 6 days. Benzoic acid in a dilution series was tested on both upper arms on days 0, 3 and 6. The reactions were graded visually, and the blood flow, skin color, transepidermal water loss and electrical capacitance of the test sites were measured. On days 3 and 6, the benzoic acid reactions were stronger on the washed arm than on the control arm. This was clinically visible and was associated with changes in blood flow and skin color measurements. Washing itself did not ususally cause visible erythema, but transepidermal water loss increased and electrical capacitance decreased. Low concentration of irritant substances, such as benzoic acid, may cause clinically relevant reactions in repeatedly washed skin. This should be taken into consideration in assessing product safety in the cosmetic, medical and household chemical industries, and when tests for chemical skin irritancy are designed and the results of such tests interpreted.     

Atopic dermatitis: a histologic and radioautographic study (after 3H-thymidine labelling) of epidermal and dermal lesions (author's transl)]

Skin lesions of atopic dermatitis (A. D.) have been studied histologically and radioautographically after in vitro incorporation of tritiated thymidine. The histopathologic aspects of epidermis in the different types of skin lesions are reviewed. The dermal infiltrate is mononuclear and not very abundant in all types of lesions. An enlargement of the epidermal proliferative compartment has been noticed. Labelled cells are distributed as follows (mean +/- standard deviation) : 46 +/- p. 100 in the basal layer; 37 +/- 6 p. 100 in the epibasal layer; 16 +/- 7 p. 100 in the upper layers. The basal and epidermal labelling indices have been found significantly increased in exudative and lichenified lesions as compared to xerotic areas and normal epidermis. The labelling index of the "round" cell infiltrate in the dermis was significantly higher than in irritant patch test reactions (p less than 0.001) but significantly lower than in allergic positive patch test reactions (p less than 0.001). This increased cell proliferation in the dermal infiltrate does not allow definite conclusions about immunopathogenesis of the disease: indeed, a large number of mediators, involved in the inflammatory reactions of A. D. lesions, can modulate cell proliferation.     

The influence of topical steroid application on tuberculin skin reactions in healthy persons

Thirty-seven healthy persons were studied in order to evaluate the influence of topical steroid application on tuberculin skin reactions. Four areas measuring 4 cm in diameter were each treated with 50 micrograms of hydrocortisone cream 1%, or 50% micrograms of halcinonide (Halog) cream 0.1%, or 50 micrograms of unguentum cetacei simplex (cold cream), or not treated. The creams were applied once daily for 3 days before and one day after a tuberculin skin test. After 24 and 48 hours the area of induration were measured. We observed that application of unguentum cetacei simplex increased the size of the induration at the 24-hour reading, but not after 48 hours. Hydrocortisone cream 1% gave the same effect, whereas halcinonide cream (Halog) 0.1% caused ischaemia of the skin and reduced the induration of the skin test after 24 hours, but not after 48 hours. In 12 persons we found that simple rubbing of the skin with halcinonide cream base did not affect the size of the tuberculin skin reaction. In the present study we found that even very potent local steroid application on intact skin could only delay the development of tuberculin skin reactions, but could not diminish their size.     

The irritancy of metalworking fluids: a laser Doppler flowmetry study

Irritant contact dermatitis is common in metalworkers exposed to metalworking fluids (MWF). The irritancy of 3 commercially available water-based cutting fluids in maximal user's concentration and 2 neat oils was investigated in 23 healthy volunteers. Additionally, the irritancy of some groups of components of the cutting fluids was studied. After Sellotape stripping, repeated patch tests were performed over 5 days and evaluated by a visual score (VS) and by laser Doppler flowmetry (LDF). In general, the MWF caused marginal skin irritation. In a comparison of the MWF and water, the cutting fluids were ranked higher in irritancy than the neat oils, but the effect of only one cutting fluid could be distinguished from that of water. The components of the cutting fluids also caused no strong reactions. The LDF response showed that one emulsifier was more irritant than water and according to the VS, one corrosion inhibitor was the most irritant. The correlation coefficient between the VS and the LDF response was probably diminished by a strong adverse reaction to the fixing tape in many volunteers. From this experiment, it was concluded that MWF are generally only mildly irritant when used in proper concentrations. However, orthoergic contact dermatitis often develops as a result of repeated and cumulative subclinical insults, in which MWF, especially water-based, play a crucial role because exposure at work is often extensive.     

Allergic and irritant contact dermatitis to calcipotriol.

Calcipotriol (Daivonex R; Leo Pharmaceuticals, Zurich, Switzerland) may cause irritation of the skin, whereas allergic reactions are less common. In the present study we describe two patients with different types of reaction patterns, one presenting as an allergic, the other as an irritant contact dermatitis. Irritative skin reactions were observed only at higher testings doses, in contrast to the allergic type of reaction, which occurred at a lower testing dose. The present observation suggests, that a batch of different testing doses, including lower testing doses may help to differentiate between an allergic type of contact dermatitis and an irritant type of reaction after treatment with calcipotriol.     

Ultrasound for assessment of allergic and irritant patch test reactions

The oedema formation of patch test reactions was quantified by high-frequency ultrasound measurement of skin thickness. Patch testing with nickel sulphate, nickel chloride and sodium lauryl sulphate 1, 2, 5 and 10% was performed in 12 individuals with known nickel allergy. Oedema was greater in allergic than in irritant reactions similar in strength according to the clinical reading. In allergic reactions, the oedema appeared more transcutaneous, while in irritant reactions, more superficial. For differentiation of the 2 types of reaction, application of substances for a 24-h period with measurements the following day is preferable. For rating of allergic and irritant reactions, 48 h of application is preferable with measurements performed on the day patches are removed.     

Evaluation of contact allergy to chemicals using laser Doppler flowmetry (LDF) technique

Skin blood flow in allergic contact reactions and cross-sensitivity were evaluated using laser Doppler flowmetry (LDF) to study the dose-response relationships in phases of induction and challenge in guinea pigs. Guinea pigs were sensitized with different doses of 1-chloro-2,4-dinitrobenzene (DNCB) and challenged with different doses of DNCB and 2,4-dinitrobenzene sulfonic sodium salt (DNBS). The skin reactions were evaluated by LDF and visual reading score. The results indicated that there were dose-response relationships between the doses of DNCB and LDF measurements in both phases of induction and challenge, that there was a cross-reaction between DNCB and DNBS, and that the reactions at 24 h were greater than that at 48 h after removal of the patches. LDF may discriminate between positive patch test reactions and negative or doubtful reactions, but not between weak positive and strong positive reactions. This is because vascular dilatation and increase of flow already reaches a maximum in weak reactions. The more advanced phases are dominated by oedema formation. This is simply the nature of the inflammatory reaction, rather than a methodological error. The important point is that LDF can separate positive reactions from negative/uncertain reactions. The results indicated that LDF, as a non-invasive technique, may objectively and quantitatively evaluate the dose-response relationships of contact sensitivity of sensitizers.