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Patch testing with budesonide in serial dilutions: the significance of dose, occlusion time and reading time.

Budesonide is advocated as a marker molecule for corticosteroid contact allergy. When patch testing corticosteroids, one must consider their sensitizing potential but also their anti-inflammatory properties, as well as the possibility of different time courses for such properties. The dose-response relationship for budesonide was therefore investigated with regard to dose, occlusion time, and reading time. 10 patients were patch tested with budesonide in ethanol in serial dilutions from 2.0% down to 0.0002% with occlusion times of 48, 24, and 5 h. Readings were on D2, D4, and D7. The 48-h occlusion picked up most positive reactors, 8/10. The D4 reading (48-h occlusion) detected most positive reactors, 8/10, and here 0.002% picked up most contact allergies. Late readings favoured high concentrations. The "edge effect" was noted for several concentrations at early readings. Due to the individual corticosteroid reactivity, the dose-response relationship and the time courses of the elicitation and the anti-inflammatory capacity, several features may be explained, i.e., that lower concentrations may detect budesonide allergy better at early readings, that patients with an "edge reaction" can have positive reactions to lower concentrations.

Administration, Topical↗

Patch testing of experimentally sensitized beagle dogs: development of a model for skin lesions of atopic dermatitis.

In humans with atopic dermatitis (AD), the epicutaneous application of allergens (atopy patch tests or APT) to which the patients are sensitized often results in the development of inflammation resembling that of spontaneous skin lesions. Dogs are affected with a natural homologue of human AD, but information on the induction of positive patch testing reactions is limited. The objectives of this pilot study were to determine the nature and cellular dynamics of inflammation occurring after APT in dogs hypersensitive to house dust mite and flea allergens. Laboratory Beagles were sensitized experimentally to Dermatophagoides farinae house dust mites (two dogs), Ctenocephalides felis flea saliva (one dog) or both (two dogs). Two other dogs served as nonsensitized controls. Both allergens and saline were applied epicutaneously. Macroscopic evaluations and skin biopsies were performed at 4, 24, 48 and 96 h after starting allergenic challenge. Biopsies were evaluated histologically and immunohistochemically with a panel of monoclonal antibodies specific for canine leucocyte antigens. Positive macroscopic reactions consisted of erythema, oedema and induration, and they occurred between 24 and 96 h after allergen application. Macroscopic and microscopic APT reactions developed only whenever serum IgE was present against tested allergens. Microscopically, positive APT was associated with epidermal hyperplasia, Langerhans' cell hyperplasia, and eosinophil and lymphocyte epidermotropism. Dermal inflammation was mixed and arranged in a superficial perivascular to interstitial pattern. Numerous IgE+-CD1+ dendritic cells and gamma-delta T-lymphocytes were observed. Macroscopically and microscopically, APT reactions in these experimentally sensitized animals resembled those seen in lesional biopsy specimens of dogs and humans with spontaneous AD. Therefore, APT in hypersensitive dogs provides a relevant experimental model to investigate the pathogenesis and treatment of both canine and human AD skin lesions.

Animals↗

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.

Adolescent↗

What is the optimal occlusion time for the atopy patch test in the diagnosis of food allergies in children with atopic dermatitis?

The atopy patch test (APT) is a valuable additional tool in the diagnosis of food allergies in children with atopic dermatitis (AD). Nevertheless, this technique needs to be standardized, and this is particularly true for the occlusion time. We compared the results obtained after a 24-h occlusion period with those obtained after a 48-h occlusion period, the usual occlusion time used in contact allergy. We performed 64 open oral food challenges in 48 children (30 boys and 18 girls), aged between 3 and 29 months (median 14 months). The sensitivity, positive predictive value and negative predictive value were all better for the 48-h occlusion time than for the 24-h occlusion time. Therefore, the recommended occlusion time for the APT with foods should be 48 h, as for contact allergens.

Child, Preschool↗

Irritation potential of a new topical tretinoin formulation and a commercially-available tretinoin formulation as measured by patch testing in human subjects.

BACKGROUND: A novel tretinoin preparation uses polyolprepolymer-2, a compound designed to reduce skin irritation by helping retain drugs on and in the surface layers of the skin. OBJECTIVE: We used patch testing to measure the effect of polyolprepolymer-2 on tretinoin-associated irritation. METHODS: Two patch test studies were conducted. The first assessed the effect of polyolprepolymer-2 by comparing commercially-available tretinoin formulations with respective polyolprepolymer-containing formulations of 0.025% tretinoin gel and 0.025%, 0.05%, and 0.1% tretinoin creams. The second assessed the effect of the polyolprepolymer-2 concentration on the potential decrease in irritation by comparing: (1) a commercially-available tretinoin cream with prototype tretinoin creams containing 20% polyolprepolymer-2 at three different concentrations of tretinoin (0.025%, 0.05%, and 0.1%); and (2) the effect of three different polyolprepolymer-2 concentrations (10%, 15%, and 20%) in prototype tretinoin creams on cumulative irritation. Patch agents were assigned to subjects according to a randomization schedule, and during a period of 5 days each subject received three 24-hour exposures to the test materials. Twenty-four hours elapsed between old patch removal and new patch application. RESULTS: In the first study, the tretinoin gel and cream containing polyolprepolymer-2 caused significantly less irritation than all equivalent formulations of the commercially-available tretinoin gel and creams except the 0.025% cream formulation. Irritation scores were not significantly different in terms of irritation in the 0.025% creams although scores did indicate a trend towards lower irritation with 0.025% tretinoin cream containing polyolprepolymer-2. In the second study, the tretinoin gel containing polyolprepolymer-2 and the three tretinoin prototype creams also containing polyolprepolymer-2 caused significantly less irritation than comparable concentrations of the commercially-available tretinoin. In addition, the 0.025% tretinoin gel formulation containing polyolprepolymer-2 was no more irritating than the commercially-available 0.025% tretinoin cream. CONCLUSION: Tretinoin formulations containing polyolprepolymer-2 are, in general, less irritating than the currently marketed tretinoin formulations.

Administration, Topical↗

Patch test reactions in children, adults and the elderly. A comparative study in patients with suspected allergic contact dermatitis.

The age- and sex-related distribution of positive patch test reactions was investigated in 234 children (0-7 years, n = 72 and 8-14 years, n = 162), 1200 adults (20 to 50 years) and 295 elderly patients (> or = 70 years) with suspected allergic contact dermatitis using a European standard series. In girls from 0 to 7 years, the most frequent contact allergens were thimerosal (37.5%) and nickel (27.5%), in girls from 8 to 14 years, nickel (28.7%) and thimerosal (26.6%), in women, thimerosal (25.3%) and nickel (25.2%), and in elderly women, nickel (12.6%) and balsam of Peru (9.7%). The most frequent contact allergens in boys from 0 to 7 years were ethylmercuric chloride (28.1%) and thimerosal (25.0%), in boys from 8 to 14 years, thimerosal (30.9%) and ethylmercuric chloride (14.7%), in men, thimerosal (21.1%) and ethylmercuric chloride (13.7%) and in elderly men, nickel (11.2%) and balsam of Peru (6.7%). Females showed more positive reactions than males. Whilst 0 to 7 year-old girls and boys showed relatively more frequent reactions, the elderly of both sexes were clearly less affected. Nickel is the most frequent contact allergen in females of 8 years and more. In men, thimerosal is most frequent and reactions to balsam of Peru show a peak incidence in the elderly. Results indicate that patch testing should be considered in children and elderly patients with appropriate indications.

Adolescent↗

Allergic and non-allergic periorbital dermatitis: patch test results of the Information Network of the Departments of Dermatology during a 5-year period.

Periorbital dermatitis is common and can be due to the external use of ophthalmic drugs. We evaluated patch test results of the Information Network of the Departments of Dermatology. During a 5-year period (1995-99), of a total 49,256 patch-tested patients, 1053 (2.1%) were eventually diagnosed as allergic periorbital contact dermatitis (APD) and 588 (1.2%) as non-allergic periorbital dermatitis (NAPD). Patient characteristics between APD, NAPD and other cases (OCs) differed with respect to sex (19.7% male in both periorbital groups versus 36.3% in OCs), atopic dermatitis (10.4% in APD versus 60.2% in NAPD versus 16.9% in OCs) and age, APD being substantially more often (68.2%) aged 40 and above than NAPD (52.6%). Several of the top allergens in OCs [such as fragrance mix, Myroxylon pereirae resin (balsam of Peru), lanolin alcohol and potassium dichromate] caused significantly fewer positive test reactions in both periorbital groups. In contrast, thimerosal, phenylmercuric acetate, sodium disulfite, gentamicin sulfate, phenylephrine hydrochloride and benzalkonium chloride tested positively significantly more often in APD but not in NAPD, verifying them as true ophthalmic allergens. Finally, in 42 cases (4%) of APD patients, additional allergens were identified by testing of the patients' own substances (mostly beta-blockers, oxybuprocaine and dexpanthenol), supporting the necessity of testing with ophthalmic drugs as is where individual substances are not readily available.

Adult↗

Patch test reactions to inhalant allergens in atopic dermatitis.

To study whether inhalant allergens could induce eczematous reactions on normal skin of atopic patients we applied birch pollen and house dust mite antigens at 500 times the concentration used for prick testing as epicutaneous tests. Six out of 17 patients with atopic dermatitis in remission had positive delayed type reactions to birch pollen and three to house dust mite. Only one out of 13 atopic patients without history of atopic dermatitis but with seasonal allergic rhinitis had a positive patch test reaction to birch pollen and no patient had positive test reactions to house dust mite. No positive patch test reactions to birch pollen or house dust mite were seen in the ten healthy control subjects. In patients with positive test reactions biopsies from the test sites revealed epidermal spongiosis and vesiculation. Immunostaining of the epidermis revealed keratinocytes displaying both CD1 and HLA-DR. The present study suggests that inhalant allergens can exacerbate atopic dermatitis.

Administration, Inhalation↗

Patch tests with potassium dichromate removed after 24 and 48 hours.

The rate of release in vitro of four potassium dichromate concentrations (0.5, 0.1, 0.05 and 0.01%) was determined. In the course of 24 h, 90.1-97.5% was released of the total K2Cr2O7 amount in 48 h. Out of 30 patients positive to 0.05% dichromate when the patch test was done routinely, 29 were also positive when the patch was removed after 24 h. The effect of the earlier removal of the patch test was also noted in seven other patients, when results of tests with lower dichromate concentrations were taken into account.

Allergens↗

Cross-reactivity among p-amino group compounds in sulfonamide fixed drug eruption: diagnostic value of patch testing.

We studied 28 patients with fixed drug eruption (FDE) caused by sulfonamide antibiotics to investigate cross-reactivity between sulfonamide derivatives and p-amino compounds and to explore the usefulness of patch testing, as an alternative to controlled oral challenge testing (COCT), in diagnosis within this clinical area. COCT with sulfamethoxazole (SMX), sulfadiazine (SDZ), sulfamethizole (SMZ), furosemide (FU), procaine (PRO) and glipizide (GPZ) was performed. Patch testing (PT) with SMX and SDZ was carried out. In all patients, the diagnosis of FDE was confirmed by positive COCT and allergy to trimethoprim ruled out by COCT. 42.8 and 31.8% of the SMX-induced FDE patients reacted to SMZ and SDZ, respectively. All patients (n = 28) tolerated FU, PRO and GPZ. COCT performed with the 3 sulfonamide antibiotics in 12 patients was positive in 2 subjects with the 3 drugs, in 2 patients only with SMX and SMZ and in the remaining 8, SMX was the only causative drug. PT was positive in 5 of 25 patients positive on COCT. The probability of obtaining a positive PT was higher among patients who had a residual lesion than that among those who lacked this. Cross-reactivity between different sulfonamide antibiotics is thus variable, being most likely between SMX and SMZ. We have found no cross-reactivity between sulfonamide antibiotics and other sulfonamide derivatives or p-amino drugs in FDE. PT is a useful tool in the diagnosis of FDE, especially if there are residual lesions, because it avoided the need for COCT in 20% of patients.

Administration, Oral↗

Patch testing of coolant fractions.

Dermatitis among machine operators, and others who are consistently exposed to cutting and grinding liquids, has presented the industrial physician with the problems of how to protect the machinist from the cause of his dermatitis and how to detect irritants that may be responsible for the skin problem. In order to examine the various components of machine coolant that might be responsible for causing a dermatitis reaction, 13 suspensions were prepared. They consisted of various combinations of New Codol¿ (coolant base), biocides, masking agent, tramp oil, used coolant and metal fragments. Patch test techniques were used to examine these suspensions for their potential to cause a localized skin irritation on plant employees. Two hundred and six New Process Gear employees were tested over a ten-month period. The participants were management, general salaried employees and hourly labor employees. There was not a single positive reaction in any one of the 206 individuals who completed their skin testing. Of the 206 tested, 29 persons were tested and retested a total of 62 times over a period of one to 25 weeks after the initial testing. In neither the testing nor the retesting was a positive patch test reaction -- irritant or allergic -- obtained.

Adult↗

Identification of causative chemicals of allergic contact dermatitis using a combination of patch testing in patients and chemical analysis. Application to cases from industrial rubber products.

3 cases of allergic contact dermatitis from industrial rubber products were investigated using a combination of patch testing in patients and chemical analysis of causative rubber products by gas chromatography (GC), GC-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC). Our studies revealed N-isopropyl-N'-phenyl-p-phenylenediamine (IPPD), a typical rubber allergen, as a causative chemical in a case from a brand of heavy-duty rubber gloves and a case from a black rubber ring for car manufacture, and zinc ethylphenyldithiocarbamate (ZEPC), a dithiocarbamate (DTC)-type accelerator, as a causative chemical in a case from a brand of rubber work gloves: both IPPD and ZEPC, which showed positive patch test reactions, were confirmed in the extracts of the causative rubber products by GC, GC-MS and/or HPLC.

Adult↗

A retrospective study of patch test results from 163 patients with stasis dermatitis or leg ulcers. II. Retesting of 50 patients.

Retesting 50 patients with stasis dermatitis after a period of time (3-25 months) revealed significantly less positive patch test results (p less than 0.05). All procedures were, of course, standardized. The main reasons for this were elimination of the sensitization agents in the interim and testing with a less acute skin condition. Allergens that are difficult to avoid, such as the 'para' compounds and balsam of Peru and related substances, show a higher degree of persistence in subsequent patch testing.

Adult↗

Triclosan reduces the clinical symptoms of the allergic patch test reaction (APR) elicited with 1% nickel sulphate in sensitised patients.

It has previously been shown that triclosan reduces the clinical skin reactions caused by sodium lauryl sulphate (SLS) in an irritant patch test reaction (IPR) model. Furthermore, triclosan reduces the inflammatory reactions on skin after subcutaneous injection of histamine. The aim of the present study was to examine whether triclosan reduces the clinical symptoms on skin after exposure to nickel in an allergic patch test reaction (APR) model. 1% nickel sulphate was used for APR in 10 nickel-allergic females. The results showed that application of triclosan on skin reduced the APR symptoms from nickel in sensitised patients significantly (p < 0.05) compared to the saline and alcohol solutions. It is suggested that inflammatory mediators produced by the sensitised lymphocytes are inhibited by triclosan.

Allergens↗

Positivity of patch tests in cutaneous reaction to diclofenac. Two case reports.

Immune-mediated reactions to NSAIDs are unusual. We have observed two cases of maculopapular eruptions occurring 48-72 h after administration of diclofenac sodium. Patch tests performed with diclofenac were positive. The histopathologic findings resembled those of contact dermatitis with different degrees of dermal involvement. Clinical, allergologic, and histopathologic patterns strongly suggest a type IV mechanism of hypersensitivity. Patch tests play an important role in the assessment of possible immunologic mechanisms underlying cutaneous reactions to drugs.

Adult↗

Can atopy patch tests with aeroallergens be an additional diagnostic criterion for atopic dermatitis?

UNLABELLED: The complex pathomechanisms underlying skin lesions in atopic dermatitis (AD) result in variations of the clinical picture and frequent diagnostic difficulties. The purpose of this study was to evaluate the usefulness of atopy patch tests (APT) for aeroallergens in the diagnosis of AD. The study involved 115 adult patients with AD and 98 healthy volunteers (the control group). APTs for cat dander allergens, birch pollen, a mixture of house dust mite species and a mixture of 5 grass pollen allergens were applied for both groups. Positive reaction to at least one test allergen was found in 53.9% patients compared to 6.2% in the control group (p<0.001). The most frequent hypersensitivity (45.2%) observed was to house dust mite allergens. Polyvalent allergy to 2-4 allergens was found in 56.5% patients. The specificity of tests exceeded 75%, whereas the sensitivity varied from 18 to 66%. CONCLUSIONS: 1. Atopy patch tests, which are characterised by considerable specificity, confirm the role of polyvalent contact hypersensitivity to aeroallergens in the development of atopic dermatitis. 2. Positive aeroallergen ATP results are observed in the majority of patients and can thus be regarded as an additional diagnostic criterion in atopic dermatitis.

Adolescent↗

Patch testing with sodium tungstate.

Hard metal contains about 90% tungsten carbide. In an investigation of the skin of 853 individuals who are still working or had previously worker in hard metal manufacture, sodium tungstate was included in a patch test with a panel of substances from the environment of the employees. No allergic reactions to tungstate were found. However, irritant pustular reactions appeared in 2.0% of the patch tests. The pustular reactions were often reproducible.

Dermatitis, Contact↗

The frequency of fragrance allergy in patch-tested patients increases with their age.

BACKGROUND: The most likely age of sensitization to fragrance chemicals is unknown. OBJECTIVES: To investigate the frequency of allergy to the 8% fragrance mix (FM) in each decade of life in patients undergoing patch testing for the investigation of skin symptoms. METHODS: Patients (n = 23 846; 14 104 female and 9742 male) underwent patch testing to a standard series between 1 January 1984 and 31 December 1998. All data were recorded on a computerized database. RESULTS: We found that 8.4% of females and 6.4% of males were allergic to the FM. The frequency of fragrance allergy was low in the first two decades of life (2.5-3.4%). It gradually increased in females after the age of 20 years to peak in the 60s at 14.4% of those tested, with a decline to 11.6% in the 80s. The prevalence in males rose more slowly and peaked at 13.7% in the 70s, declining to 10.8% in the 80s. The youngest patients sensitized were aged 2 years. CONCLUSIONS: These findings support the hypothesis that allergy to fragrance results from a combination of repeated environmental exposure and age-related susceptibility factors.

Adolescent↗