Diagnostic Patch Testing Research Articles

Atmospheric oxidation of poly(oxyethylene) alcohols. Identification of ethoxylated formates as oxidation products and study of their contact allergenic activity

Ethoxylated alcohols are widely used as surfactants. In the present study we have continued our investigations on the degradation with time upon air exposure of the ethoxylated alcohols at normal storage and handling. As a result, a new group of ethoxylated formates with the general formula C12H25(OCH2CH2)nOCHO (n = 0–4) was identified in C12H25(OCH2CH2)5OH stored and handled at room temperature. To facilitate the identification work, reference compounds were synthesized. The formates showed no allergenic activity in the sensitization studies performed. In previous investigations on the same ethoxylated alcohol, we have identified formaldehyde and ethoxylated aldehydes among the oxidation products formed. Formaldehyde is a common contact allergen, and the ethoxylated aldehydes were shown to have a sensitizing capacity of the same magnitude as formaldehyde. The instability of the ethoxylated alcohols and formation of oxidation products may give an allergenic contribution to hand eczema caused by work with water and surfactants. To investigate the clinical significance in man an appropriate diagnostic patch testing in exposed humans is required.

Prognostic Patch Testing: The Other Kind Of Patch Test

AbstractPrognostic patch testing differs from diagnostic patch testing. Clinicians routinely perform diagnostic patch testing; however, prognostic patch testing is the province of corporate research and development departments and, in the U.S., contract laboratories. The three types of prognostic patch testing are described and referenced in the scientific and medical literature. A comparison among the three types of prognostic patch testing and diagnostic patch testing is provided. In addition, the variables in both prognostic and diagnostic patch testing are listed, as well as the types of ingredients and products routinely tested in prognostic patch testing.

Prognostic patch testing: The other kind of patch test

Prognostic patch testing differs from diagnostic patch testing. Clinicians routinely perform diagnostic patch testing, but prognotic patch testing is the province of corporate research and development departments and, in the United States, contract laboratories. The three types of prognostic patch testing are described and referenced in the scientific and medical literature. A comparison among the three types of prognostic patch testing and diagnostic patch testing is provided. In addition, the variables in both prognostic and diagnostic patch testing are listed, as well as the types of ingredients and products routinely tested in prognostic patch testing.

Prognostic patch testing: The other kind of patch test

Prognostic patch testing differs from diagnostic patch testing. Clinicians routinely perform diagnostic patch testing, but prognotic patch testing is the province of corporate research and development departments and, in the United States, contract laboratories. The three types of prognostic patch testing are described and referenced in the scientific and medical literature. A comparison among the three types of prognostic patch testing and diagnostic patch testing is provided. In addition, the variables in both prognostic and diagnostic patch testing are listed, as well as the types of ingredients and products routinely tested in prognostic patch testing.

Rôle of ear piercing in metal allergic contact dermatitis.

To evaluate the effect of ear piercing on sensitization to gold and other metals, diagnostic patch testing with 18 metals was performed. 377 patients (65 men and 312 women, ranging in age from 15 to 78 years; mean 34.2, S.D +/- 15.1 years) were patch tested; 107 had pierced earlobes. Metals were applied on the back for 2 days, and the results read with the ICDRG scoring system 3 days after application. Reactions of + to +3 were regarded as positive. There were significantly more patients reacting to gold chloride (p < 0.001), mercuric chloride and nickel sulfate (p < 0.05) in patients with pierced ears than in those without. Statistical issues included: (i) a significant number of patients with pierced ears referred because of earring dermatitis; (ii) those with pierced ears represented a different age group from those without; (iii) a significant number of patients without eczema in the non-pierced ear group. However, our data suggests that ear piercing is a risk factor not only for nickel but also for gold sensitization. Gold was the second most frequent metal allergen after nickel in the pierced group.

Occupational contact dermatitis

The two commonest forms of occupational skin disease are irritant and allergic contact dermatitis. Morphology and history are used to establish the diagnosis and the relation of the disorder to work exposure, respectively. Diagnostic patch tests are used to define further the diagnosis and aetiology of the dermatitis.

1- versus 2- and 3-day diagnostic patch testing.

One inconvenience of the routine patch test technique is the 2-day patch wear. Adjusting the routine patch test technique to a shorter allergen exposure would be more comfortable for the patient. Studies define this feasibility; the available data do not permit a definite answer as to the suitability of 1-day application. An idealized protocol suitable for resolving this issue is presented.

Allergic Contact Dermatitis From Doxepin Cream

Several topical antihistamines are known to cause contact allergy. Premarket predictive patch testing with doxepin cream showed it to have "low risk of irritation and sensitization" on normal human skin. In our patch test clinic, we routinely test topical preparations, and over a recent 1-year period, we patch-tested doxepin cream, the standard screening tray, and other topical preparations on 97 patients with various pruritic dermatoses. When possible, patients with positive reactions to doxepin cream were patch-tested with its ingredients, and repeated open-application use tests were also performed with the product. Seventeen patients had relevant positive patch test reactions to doxepin cream and 80 had negative reactions. In 13 of the 17 patients with positive reactions, the diagnosis of allergic contact dermatitis to doxepin cream was confirmed by positive patch test reactions to both the active ingredient and the whole formulation of doxepin cream, by an observed positive use test reaction to doxepin cream, or by both. Of 14 patients who completed testing with doxepin cream ingredients, all had positive reactions to the whole formulation, and 12 had positive reactions to doxepin hydrochloride. Repeated open-application use tests with doxepin cream on normal skin resulted in positive eczematous responses in eight of 10 patients. Eight of the 17 patients had concurrent, relevant positive reactions to other patch tests, especially to fabric-finish resins and to ingredients of other topical preparations. Many had long-standing dermatitis, and each had used doxepin cream for several days to 1 year. Two patients appeared to have had systemic contact dermatitis. Diagnostic patch test clinic experience illustrates that doxepin cream is a contact sensitizer on inflamed skin. Oral doxepin should be avoided in patients with doxepin contact allergy.

A personal critique of diagnostic patch testing

A personal critique of diagnostic patch testing

Human and economic impact of allergic contact dermatitis and the role of patch testing

A 40-year-old woman had hand dermatitis. By history alone, a dermatologist diagnosed contact dermatitis from detergents and cleaning solutions. During the next 5 years the patient wore cotton liners under rubber gloves when handling cleaning solutions but continued to have dermatitis. She applied topical corticosteroids regularly and received systemic steroid injections intermittently. After 5 years, she sought the opinion of another dermatologist. This time diagnostic patch tests were employed and revealed an allergy to thiuram mix and carba mix. These results indicated a problem with the rubber gloves she was wearing. She also was found to be sensitive to quatemium-15 in her hand cream. A change to polyvinyl chloride based gloves and a hand cream without quatemium-15 led to resolution of her dermatitis. As this case illustrates, allergic contact dermatitis can be a significant and costly medical problem. Rapid, accurate diagnosis, however, can eliminate a persistent skin problem. The cost to society and industry from occupational skin diseases alone has been estimated to be up to $1 billion per year, 1 more than 90% of which is estimated to result from contact dermatitis. Allergic contact dermatitis also exacts a significant toll in terms of time lost from work and a potentially inappropriate job change, resulting in a lower standard of living. Adding to the patient's burden is the discomfort and disability that results from continued exposure to the offending allergen.

What is Occupational Contact Dermatitis? An Operational Definition

Occupational contact dermatitis remains an important cause of disability. Eight steps in an operational definition of OCD are as follows: 1. Relevant clinical history 2. Relevant morphology 3. Positive diagnostic patch test with appropriate vehicle and concentration 4. Repeat patch test when excited skin syndrome is suspected 5. Positive provocative use test or repeat open application test to refine clinical relevance 6. Serial dilutions, when necessary, of the chemical tested 7. Reviewing controls for nonirritating concentrations when this is not known by the investigator 8. Generally, clearing of the dermatitis when allergen is removed, or exposure significantly decreased The diagnosis is not always easy. Well-conducted clinical investigations are needed, including clinical history, clinical examination, and patch testing with careful follow-up. However, many of the chemicals reported in the literature as sensitizers induce only sporadic allergic reactions. Thus, epidemiologic animal and human studies are necessary to determine the capacity of the chemicals used in industry to induce contact dermatoses. It is necessary to standardize the predictive tests to compare results among laboratories and to predict the potential for sensitization.

Delayed hypersensitivity drug reactions diagnosed by patch testing.

Drug reactions are a common problem in hospital inpatients and outpatients. Oral or parenteral drug challenges are valuable diagnostic aids, but time consuming. We review attempts to diagnose delayed hypersensitivity drug eruptions by patch testing. We review control data, and offer an operational definition that might make for greater acceptance of the rôle of diagnostic patch testing in this entity.

The role of vehicles in diagnostic patch testing

The correct selection of vehicles for patch testing is crucial in the evaluation of suspected allergic contact dermatitis. We reviewed the literature by using Grateful Med software for the years 1966-1992, utilizing the subjects "vehicles" and "allergic contact dermatitis" or "patch tests". Vehicles can influence bioavailability of the chemicals and subsequently percutaneous absorption or interaction with allergens. There are methodological problems in interpreting studies, such as sample size, percutaneous absorption and clinical aspects. Our judgement, partially validated by the literature, suggested that improved delivery systems (such as via vehicles) might significantly increase optimization, reliability and reproducibility of patch tests.

Evaluation of the primary skin irritation and allergic contact sensitization potential of transdermal triprolidine

A transdermal patch for the OTC antihistamine, triprolidine (TP), might provide benefits in terms of increased efficacy and reduced sedative side effects. However, concerns over potential irritant or allergic contact sensitization (ACS) skin reactions necessitated thorough skin toxicity testing before and during initial clinical development. Initial effort was expended on development of a binary vehicle delivery system comprised of TP in 0.5% oleic acid (OA) in propylene glycol (PG). Rabbit skin irritation and Buehler guinea pig skin sensitization testing indicated that this TP/OA/PG formula had both skin irritation and ACS potential. Both tests underestimated, to some degree, the skin toxicities observed in later clinical testing. In clinical tests, skin irritation was due mainly to the OA PG vehicle, but was enhanced in the presence of high TP concentrations. Of 26 subjects enrolled in a rising dose clinical pharmacokinetics study, one subject exposed twice to TP/OA/PG presented with delayed skin reactions suggestive of ACS. Positive diagnostic patch test results for this subject and four out of five other twice-exposed study subjects suggested that the TP/OA/PG formula had a very high ACS potential. Subsequent predictive clinical patch testing was conducted with a buffered aqueous TP formula which provided in vitro skin penetration of the drug equivalent to the TP/OA/PG formula. These clinical studies demonstrated that TP itself had no significant irritation potential but still induced ACS reactions in a high proportion of test subjects. The incidence of adverse skin reactions to TP was considered to be too high relative to the degree of improved therapeutic benefit of this delivery form. On this basis, all technology development effort was discontinued.

Evaluation of the Primary Skin Irritation and Allergic Contact Sensitization Potential of Transdermal Triprolidine

Evaluation of the Primary Skin Irritation and Allergic Contact Sensitization Potential of Trans-dermal Triprolidine. ROBINSON, M. K.., PARSELL, K. W., BRENEMAN, D. L., AND CRUZE, C. A. (1991). Fundam. Appl. Toxicol. 17, 103–119. A transdermal patch for the OTC antihistamine, triprolidine (TP), might provide benefits in terms of increased efficacy and reduced sedative side effects. However, concerns over potential irritant or allergic contact sensitization (ACS) skin reactions necessitated thorough skin toxicity testing before and during initial dinical development Initial effort was expended on development of a binary vehicle delivery system comprised of TP in 0.5% oleic acid (OA) in propylene glycol (PG). Rabbit skin irritation and Buehler guinea pig skin sensitization testing indicated that this TP/OA/PG formula had both skin irritation and ACS potential. Both tests underestimated, to some degree, the skin toxicities observed in later clinical testing. In clinical tests, skin irritation was due mainly to the OA–PG vehicle, but was enhanced in the presence of high TP concentrations. Of 26 subjects enrolled in a rising dose clinical phar-macokinetics study, one subject exposed twice to TP/OA/PG presented with delayed skin reactions suggestive of ACS. Positive diagnostic patch test results for this subject and four out of five other twice-exposed study subjects suggested that the TP/OA/PG formula had a very high ACS potential. Subsequent predictive clinical patch testing was conducted with a buffered aqueous TP formula which provided in vitro skin penetration of the drug equivalent to the TP/OA/PG formula. These clinical studies demonstrated that TP itself had no significant irritation potential but still induced ACS reactions in a high proportion of test subjects. The incidence of adverse skin reactions to TP was considered to be too high relative to the degree of improved therapeutic benefit of this delivery form. On this basis, all technology development effort was discontinued, © 1991 by the Society of Toxicology

Irritation factors of sodium hypochlorite solutions in human skin

The recommended concentration for patch testing with sodium hypochlorite [NaOCl] (bleach) is 1%, generally obtained by diluting commercial bleach. In doing so, other active (potentially irritant) components of bleach, especially hypochlorous acid [HOCl] and sodium hydroxide [NaOH], are neglected. Magnitudes of potential irritant species other than NaOCl, such as alkalinity, are ordinarily not labeled on the product, though they may vary considerably between brands. Thus, patch testing with 1% hypochlorite obtained by diluting different brand bleaches can potentially elicit non-specific irritant responses, also depending upon the test volume applied. In this study, skin irritation induced by 24-h patch testing with 20 microliters or 100 microliters, with constant NaOCl concentration (1%) and different NaOH concentrations (0.01-1.0%), was studied in adult human volunteers, by means of visual scores and skin color reflectance measurements. No irritation was elicited by application of 20 microliters 1% OCl-, independent of the NaOH concentration. However, all solutions induced significant irritation in a volume of 100 microliters. Skin reactions did not show a straight pH dose response, a maximum reaction being seen to the solution containing 0.1% NaOH. Skin surface pH values had increased when monitored immediately after removal of the patch material. However, 24 h later, baseline values were again reached at most sites, demonstrating an efficient buffering capacity of human skin, even after challenge with alkaline solutions of pH 13.4. We suggest that a non-irritant concentration for diagnostic patch testing for allergic contact dermatitis with an aluminum chamber, using 17 microliters to 20 microliters test volume, could be as high as 1% NaOCl and 1% NaOH.

Human cutaneous irritation: induced hyporeactivity.

The variation in human skin response to sodium lauryl sulfate (SLS) was determined with patch and open applications. Reactions in different subjects and in multiple simultaneous patch tests were compared. Skin responses were assessed with visual scoring (VS), laser Doppler velocimetry (LDV) and transepidermal water loss (TEWL). Previous open, unpatched SLS exposure decreased patch test reactivity to 1% SLS assessed with VS (p less than 0.05) or LDV (p less than 0.05). Corresponding TEWL alteration was inconstant. Variation in reactivity at different test sites in multiple simultaneous tests was considerable, though less than the variation at different test times (p less than 0.05). Inter-subject variation in test reactivity was greater than the variation between different test times or adjacent test sites. Repeated open applications and the subclinical dermatitis appear to have produced a hyporeactive state. The results suggest that non-specific skin inflammation is elicited by multiple factors, e.g., stratum corneum integrity and vascular reactivity. Their balance determines the ensuing reactions. The induced hyporeactivity may be one of many causes of false negative diagnostic patch tests.

Human safety study of body lotion containing Kathon® CG

The safety of Kathon CG biocide as a preservative in leave-on body lotions was assessed by 2 double-blind studies, using similar protocols. A total of 209 healthy male and female subjects aged 18 to 65 years, 100 in California (72 test subjects, 28 controls) and 109 in Florida (88 test subjects, 21 controls) completed the studies which included pre- and post-use phase diagnostic patch testing with Kathon CG 100 ppm active ingredient, and 13 weeks daily applications of either a test lotion containing Kathon CG 15 ppm active ingredient or a control lotion without Kathon CG. No evidence of irritation or sensitization attributable to use of the biocide was found during regular dermatological examinations during the use phase. Post-use phase patch testing produced negative results in all subjects with the exception of 1 control subject in Florida who had positive readings at the 2- and 4-week post-use phase patch testing. Overall, these studies show there is minimal, if any, risk of adverse effects associated with the use of Kathon CG 15 ppm active ingredient in a leave-on application.

Irritation, sensitization, photoirritation and photosensitization assays with a glyphosate herbicide.

Glyphosate, a widely utilized herbicide, was evaluated for acute irritation, cumulative irritation, photoirritation and allergic and photoallergic contact potential in 346 volunteers. The herbicide was less irritant than a standard liquid dishwashing detergent and a general all purpose cleaner. There was no evidence for the induction of photoirritation, allergic or photoallergic contact dermatitis. 10% glyphosate in water is proposed as a diagnostic patch test concentration.

Dose-response assessments of Kathon biocide (I). Diagnostic use and diagnostic threshold patch testing with sensitized humans.

Nearly all effective, commercially available preservatives possess skin sensitization potential. This manuscript describes a program of diagnostic patch and practical use testing of consumer products that contained Kathon CG, a relatively new biocide. A series of threshold diagnostic patch tests demonstrated that the minimal elicitation concentration in occluded patch testing of allergic subjects considerably exceeded the concentrations of the biocide typically present in normal diluted use of the test products. Use testing further confirmed a threshold exposure for eliciting allergic reactions. It showed that even subjects who have delayed contact hypersensitivity to Kathon CG used rinse-off personal care products preserved with this agent without experiencing elicitation of these allergies.