Detection of contact hypersensitivity to topical corticosteroids with hydrocortisone-17-butyrate

We showed earlier that most patients with contact dermatitis due to corticosteroids show cross-reactions when patch tested with hydrocortisone-17-butyrate (H-17-B). To test whether H-17-B could be used for detecting topical corticosteroid allergy, we screened patients undergoing routine patch testing with H-17-B. Patients with clearly allergic or doubtful/mildly irritant patch test reactions to H-17-B, and with a history suggesting topical corticosteroid allergy, were further tested with a large panel of steroid preparations. 20 out of 4039 patients (0.5%) showed definite allergic test reactions to corticosteroids. A further 165 patients with clinically suspected corticosteroid allergy were directly tested with a panel of steroid preparations; 14 patients showed positive patch test reactions. Altogether, 33 out of 34 patients with corticosteroid allergy had positive test reactions to H-17-B. Inclusion of 1.0% H-17-B in ethanol in the standard patch test series improves the diagnosis of topical corticosteroid hypersensitivity.     

Allergic contact dermatitis and conjunctivitis to corticosteroids

This is a report of two patients suspected of having allergic dermato-conjunctivitis due to corticosteroids. Both were tested with the constituents of the ointments they were using, that is, corticosteroids, antibacterial agents, preservatives, and other active ingredients of the ointment bases. Both patients showed positive allergic patch test reactions to the respective corticosteroid betamethasone valerate, and one to hydrocortisone, neomycin, and a rubber additive. The importance of routine patch testing in ophthalmic practice to detect sensitizers in cases of allergy is mentioned. Hydrocortisone (25%) in petrolatum is recommended for patch testing.     

A prospective study into the value of patch and intradermal tests in identifying topical corticosteroid allergy

We have prospectively performed patch and intradermal tests on 105 consecutive patients, attending for patch testing, to determine the optimum method of screening for corticosteroid hypersensitivity. Patch tests with Pivalone and a corticosteroid series (all 1% in ethanol) detected all the patients with steroid sensitivity. However, intradermal tests were essential to exclude false positive reactions and detect all relevant steroid allergies in any individual patient.     

Screening for corticosteroid contact hypersensitivity

To evaluate which corticosteroids are most useful for the detection of corticosteroid contact allergy in our population, 2123 patients were patch tested with a series of 6 corticosteroids in parallel with a standard series, and other relevant investigations, 127 patients (5.98%) were allergic to one or more corticosteroids; 96 to tixocortol pivalate, 51 to hydrocortisone butyrate, 47 to budesonide, 11 to betamethasone valerate, 11 to clobetasone butyrate and 8 to clobetasol propionate, 511 patients with negative patch tests to the limited corticosteroid series were in addition tested to a further 12 corticosteroids; only 1 of these patients reacted to a corticosteroid. A combination of tixocortol pivalate and budesonide thus detected 91.3% of corticosteroid-allergic subjects. We believe that both these allergens should be included in the standard series and that there may be a case for extending this further.     

Contact hypersensitivity to hydrocortisone-free-alcohol in patients with allergic patch test reactions to tixocortol pivalate

It has been suggested that contact allergy to hydrocortisone alcohol is a frequent phenomenon, A recent study showed that all patients with allergic patch reactions to tixocortol pivalate reacted to intradermal hydrocortisone sodium phosphate. We studied patients with positive patch test reactions to tixocortol pivalate but negative to hydrocortisone alcohol, with penetration enhancers in hydrocortisone alcohol patch tests and oral challenges with hydrocortisone alcohol. Additionally, prick and intradermal tests with hydrocortisone sodium succinate were used. Using penetration enhancers and oral challenges enabled detection of more contact allergies to hydrocortisone alcohol compared to conventional patch testing alone. 9/12 patients with allergic reactions to tixocortol pivalate reacted to intradermal hydrocortisone sodium succinate. No immediate reactions were seen in prick or intradermal tests, suggesting that hydrocortisone contact hypersensitivity is probably not associated with immediate allergy to hydrocortisone. The present study suggests that allergic patch test reactions to tixocortol pivalate are caused by hypersensitivity to hydrocortisone alcohol itself or to one of its metabolites in the skin.     

Occupational airborne contact dermatitis from omeprazole

Tixocortol pivalate (TP) is a good marker for hydrocortisone allergy. The concentration of TP to be included in the standard series for patch testing has been the subject of debate. The objective of this study was to investigate the right concentration of TP to be included in the standard series for patch testing. 3747 consecutive patients with dermatitis were patch tested simultaneously with TP 1% and 0.1% in petrolatum at 9 centres in the UK from August 2004 to December 2005. Statistical analysis of the results was performed using STATISTICA, version 6 software. 41 patients had positive reactions of current or past relevance. 20 were positive for both concentrations, 13 positive only for TP 1% concentration, and 8 positive only for 0.1% concentration. Statistical analysis, using a two-tailed difference in proportions test, did not show a significant difference between the 2 concentrations (P=0.21). There was no statistically significant difference between the 2 concentrations of TP. The number of allergens that can be included in the standard series is limited for practical considerations. When testing for screening purposes, TP 1% is recommended.     

Delayed hypersensitivity to topical corticosteroids

Topical hypersensitivity to corticosteroids was studied by epicutaneous testing using the Finn Chamber technic. The steroids were tested in both ethanol and white petrolatum and, in certain cases, in dimethyl sulfoxide. Additionally, commercial preparations were tested. Three groups of patients were studied: (1) patients with a history of hypersensitivity to at least two topical preparations (five of ten patients studied showed a positive patch test reaction for corticosteroids), (2) patients in whom topical corticosteroid hypersensitivity was suspected because of treatment-resistant eczema (seven of twenty-five patients showed a positive patch test reaction), and (3) dermatologic inpatients and outpatients undergoing epicutaneous testing for suspected topical hypersensitivity. Hydrocortisone-17-butyrate (H-17-B) was included in the standard patch test series; of 450 patients tested, two showed a positive patch test reaction. All the patients with corticosteroid hypersensitivity had a positive reaction to H-17-B. In six patients, additional hypersensitivities to one or several other steroid preparations were seen. Use testing was performed as an open test, with 0.1% or 1% H-17-B in ethanol on normal skin of the flexor side of the upper extremities. A positive test reaction was seen in only one of nine patients. Results of use testing with the commercial 0.1% H-17-B (Locoid) ointment were always negative. Our study suggests that the sensitivity of patch tests for corticosteroid hypersensitivity can be increased by using ethanol as vehicle.     

Cross-reactivity patterns to budesonide

Allergic contact dermatitis from topical corticosteroids is not uncommon. Budesonide has been included in the European standard series as a marker for corticosteroid allergy, though little is known of its cross-reactivity with other corticosteroids. Twelve patients previously positive to budesonide on patch testing were given further patch and intradermal tests to a range of corticosteroids. Six patients previously negative to budesonide on patch testing were used as a control group. Budesonide cross-reacts with hydrocortisone-21-sodium phosphate and triamcinolone acetonide. Patients positive to budesonide should therefore avoid hydrocortisone and triamcinolone acetonide. Patch testing, unfortunately, is an inaccurate method of determining cross-reactivity patterns among corticosteroids.     

The prevalence of corticosteroid allergy in two U.K. centres: prescribing implications

Allergic contact dermatitis to topical corticosteroids is a common problem, seen in up to 6% of patients undergoing patch testing. Rates of steroid allergy vary widely both within and between countries. It has previously been shown that non-fluorinated steroids degrade and react with arginine more rapidly in an in vitro system and may therefore be more likely to sensitize than fluorinated steroids. We have compared the rates of steroid allergy and corticosteroid prescribing habits in two different areas in England to observe the relationship between these factors. The results suggest that predominant use of non-fluorinated corticosteroids (hydrocortisone, hydrocortisone-17-butyrate and budesonide) results in a higher prevalence of corticosteroid contact allergy in comparison with those areas using a greater proportion of fluorinated corticosteroids.     

Finding the optimal patch test material and test concentration to detect contact allergy to geraniol

Background. Geraniol is a commonly used fragrance terpene, and is tested in the baseline series in fragrance mix I. Geraniol is a pro‐hapten and a pre‐hapten, and sensitizers are formed in the autoxidation and skin metabolism of geraniol. Previous patch testing with air‐exposed (oxidized) geraniol has suggested that oxidized geraniol could be a better marker for contact allergy to geraniol than pure geraniol. Objectives. To find the optimal patch test substance and concentration for detecting contact allergy to geraniol. Patients and methods. Six hundred and fifty‐five patients were patch tested with pure and oxidized geraniol at 4.0%, 6.0% and 11.0% in petrolatum. Before patch testing, the irritant properties of pure and oxidized geraniol were studied in 27 patients at 2.5%, 5.0%, 10.0% and 20.0% pet. Results. Pure geraniol detected positive reactions in 0.15–1.1% of the patients, and oxidized geraniol detected positive reactions in 0.92–4.6% of the patients. Reactions to pure geraniol in patients not reacting to oxidized geraniol indicated metabolic activation of geraniol. Neither pure nor oxidized geraniol gave significant irritant reactions. Conclusions. Increasing the test concentrations of pure and oxidized geraniol enables the detection of more cases of contact allergy. Oxidized geraniol detects more patients than pure geraniol, but patch testing with only oxidized geraniol does not detect all cases of contact allergy to geraniol.     

Allergy to systemic and intralesional corticosteroids

In this study, allergic reactions to systemic or intralesional corticosteroids were characterized, and skin tests utilized in the diagnosis of corticosteroid allergy. Five patients who had developed a rash when treated with systemic or intralesional hydrocortisone, methylprednisolone, prednisolone or betamethasone, were challenged with oral or intra-articular corticosteroid preparations, and skin tested. Upon provocation the patients reacted with diffuse erythema principally on the trunk or on the face. The erythema appeared within a period ranging from a few hours to 24 h and faded in 1–3 days. On patch testing, one patient reacted to prednisolone and methylprednisolone, which induced a positive response upon provocation, and two patients were positive to Pivalone®. Patients who were sensitive to hydrocortisone or methylprednisolone, as judged by anamnestic data and provocations, reacted to these corticosteroids in the intradermal tests. Allergy to betamethasone could not be verified by intradermal or patch tests. A combination of intradermal and patch tests is recommended when allergy to systemic or intralesional corticosteroids is suspected. If these skin tests remain negative, provocation is the method of choice.     

Prevalence of and factors influencing sensitization to corticosteroids in a Danish patch test population

Background. Corticosteroids are used to treat dermatoses, including allergic contact dermatitis, but can also cause contact allergy. The frequency of corticosteroid allergy varies between studies and is influenced by treatment traditions and availability. Aim. To estimate the prevalence of tixocortol‐21‐pivalate, budesonide and hydrocortisone‐17‐butyrate allergy in a Danish patch test population and characterize individuals with corticosteroid allergy. Materials/methods. Three thousand five hundred and ninety‐four patients were patch tested with tixocortol‐21‐pivalate, budesonide, and hydrocortisone‐17‐butyrate. Characterization was performed according to the MOAHLFA index and duration of disease. Results. Two per cent had a steroid allergy: 0.8% had a tixocortol‐21‐pivalate allergy, 1% a budesonide allergy, and 1% a hydrocortisone‐17‐butyrate allergy. Tixocortol‐21‐pivalate and budesonide allergy were associated with atopic dermatitis in crude analyses, but only tixocortol‐21‐pivalate allergy and atopic dermatitis remained associated in adjusted analyses. Leg dermatitis was uniquely associated with tixocortol‐21‐pivalate allergy. Hydrocortisone‐17‐butyrate allergy was associated with duration of disease in both crude and adjusted analyses. Discussion/conclusion. Chronic dermatoses (atopic dermatitis and leg dermatitis) were identified as risk factors for group A corticosteroid allergy, probably because of more pronounced exposure to group A steroids resulting from ease of access that is exploited by patients with a chronic dermatosis. The duration of disease rather than the dermatosis itself seemed to be important for group B and D2 corticosteroid allergy.     

Contact allergies to topical corticosteroids: 10 cases of contact dermatitis

Patients who noticed worsening of their skin disease after using topical corticosteroid preparations were patch tested both with the commercial preparation and the corticosteroid itself. Between 1987 and 1989, 10 cases of contact dermatitis due to topical corticosteroids were detected in this way. The corticosteroids wee amcinonide (2 patients), hydrocortisone butyrate, clobetasol propionate (2), betamethasone valerate (2), prednicarbate and fluocortolone (2). Patch tests with the commercial preparations and the corticosteroids themselves elicited reactions almost identical in time course and severity. Individual sensitivity seems to be more important for test results than test conditions. 9 of the 10 patients underwent further patch testing with a corticosteroid series. In 2 patients, a true cross-reaction between budesonide and hydrocortisone butyrate was found. All 9 patients showed further sensitivities to other corticosteroids. Most of the cross or concomitant reactions could be categorized into recently defined corticosteroid classes. To improve our understanding of corticosteroid sensitization, and to help the patient avoid reactions to other topical corticosteroids, a corticosteroid series should be patch tested in every case of corticosteroid sensitivity.     

Type-IV hypersensitivity to betamethasone valerate and clobetasol propionate: results of a multicentre study

BACKGROUND: Most studies investigating steroid allergy have been performed with tixocortol pivalate, hydrocortisone butyrate and budesonide. Betnovate and Dermovate are widely prescribed in the U.K. but little is known about the frequency of sensitization to them. OBJECTIVES: To determine the optimum method to detect contact allergy to betamethasone valerate (BV) and clobetasol propionate (CP). METHODS: Seven centres tested consecutive patients attending for investigation of suspected allergic contact dermatitis to these steroids at a range of concentrations in different vehicles. RESULTS: Of 1562 patients tested, 16 (1%) reacted to either BV or CP. Ten patients (0.7%) reacted to BV and 13 (0.8%) to CP. Two patients of a further centre were included in analysis of dilutions and vehicles. Sixteen of a total of 25 reactions (64%) were identified with a 1% dilution in ethanol. CONCLUSIONS: Consideration should be given to adding BV and CP to a standard allergy series, given that both are frequently used in the treatment of eczema and that most patients sensitized to them are not identified with currently used markers of steroid allergy. If patch tests to BV and CP are initially negative, but an allergy is suspected, the patient should be further investigated. Further studies are required to identify the ideal patch test material.     

Screening for corticosteroid contact sensitivity

3 corticosteroids have so far been tried as markers for corticosteroid contact sensitivity: hydrocortisone, tixocortol pivalate and hydrocortisone-17-butyrate. The present study compared these steroids for screening in addition to a standard patch test series. Of 727 patients, 28 (3.9%) reacted to tixocortol pivalate and 10 (1.4%) to hydrocortisone-17-butyrate; hydrocortisone gave an allergic reaction in 2 of 521 (0.4%) patients. Serial dilutions suggested that tixocortol pivalate, not marketed in Finland, caused allergic reactions which could possibly be cross-reactions to hydrocortisone. In contrast to previously published data, frequent cross-reactions occurred with hydrocortisone-17-butyrate and tixocortol pivalate. All allergic reactions to other corticosteroids found by testing with tixocortol pivalate concurred with reactions to hydrocortisone-17-butyrate. The study suggests that the most effective choice for routine testing for corticosteroid contact sensitivity would be both tixocortol pivalate and hydrocortisone-17-butyrate.     

Patch,prick or intradermal tests to detect delayed hypersensitivity to corticosteroids?

Background. Contact allergy to topical corticosteroids is usually detected by patch testing. Objectives. This study compares the test results obtained with patch, prick and intradermal testing, to assess the most sensitive method for diagnosing corticosteroid hypersensitivity. Patients/Methods. Nineteen corticosteroid‐allergic subjects and three control subjects were included. Patch, prick and intradermal tests were performed with five commercial corticosteroid preparations, as well as with the respective active principles diluted in ethanol. The test readings were performed at different time points, i.e. at 8, 24, 48 and 96 hr, and at 7 days. Results. Patch tests with ethanolic preparations produced more positive reactions than the commercial ones. The intradermal tests became positive earlier than the patch tests, a concordance between patch and intradermal tests being found in 11/15 (two positive intradermal test results with negative patch test results and vice versa). However, several subjects developed skin atrophy (14/22) at intradermal injection sites. Conclusion. Patch testing with the active principles diluted in ethanol remains the diagnostic method of choice for the detection of delayed hypersensitivity to corticosteroids. Intradermal tests with late readings, despite detecting additional contact allergy cases, should not be routinely performed, because of an important risk of atrophy, particularly with corticosteroid suspensions.     

Corticosteroid allergy

Allergy to corticosteroids is becoming increasingly recognized. Diagnosis is difficult because of frequently false-negative patch tests. The optimum concentration and vehicle for patch testing with pure corticosteroid has still not been established. The patch test results of 19 patients with allergy to corticosteroids seen at the Skin and Cancer Foundation in Sydney, Australia, were analysed. It was found that patch testing with the patient's corticosteroid in the commercial cream base gave a greater yield of positive results than testing with the commercial corticosteroid ointment or with the pure corticosteroid in either petrolatum or in alcohol. Tixocortol pivalate, and lo a lesser extent budesonide, were useful for detecting allergy to hydrocortisone, but not necessarily other corticosteroids. Delayed positive patch tests were often seen, showing the importance of carrying out a late reading. The repeal open application test (ROAT) with the patient's own corticosteroid was found lo be a simple, useful diagnostic test.     

Allergic contact dermatitis from topical corticosteroids

22 cases of allergic contact dermatitis from topical corticosteroids were observed in Strasbourg and previously published. 7 further cases are reported here and the vehicle and concentration of corticosteroids for patch tests are discussed. A 0.1% concentration in petrolatum seemed adequate for testing the 4 molecules (triamcinolone acetonide, dexamethasone, desonide and amcinonide) responsible for the 7 new cases. In 1 case, several cross-reactions were seen. A corticosteroid screening series permits patch testing of the suspected molecule(s) in a selective way. Without this series, long delays are required to make the correct diagnosis by patch testing. We have reviewed more than 60 papers on corticosteroid allergy published up to now.     

A study of 72 patients with contact allergy to tioconazole

Summary Over a 3½ year period, from 1991 to 1994, we detected contact allergy to tioconazole in 72 patients by epicutaneous testing. During this period, tioconazole was included in the standard series of epicutaneous tests. Except for the first 6 months, the incidence of positive patch test reactions to tioconazole was over 1% of patients tested for contact allergy. As well as those tested with the standard series, 18 additional patients with tioconazole allergy were detected by direct testing with an imidazole patch test series. Of the various imidazole derivatives, tioconazole was the most important contact allergen. About half of patients with contact hypersensitivity to tioconazole, had additional contact allergies detected by the standard series. Men and women were equally affected. The present study suggests that tioconazole is an important contact allergen, which should be included into the patch test series in countries where it is used as a topical antifungal agent.     

Delayed hypersensitivity to corticosteroids in a series of 315 patients: clinical data and patch test results

Background: Corticosteroids may cause immediate or delayed hypersensitivity. In 1989, based on structural and clinical characteristics, we put forward a classification of corticosteroids into four cross-reacting groups, namely group A, B, C, and D, the latter later subdivided into two subgroups, i.e. D1 and D2. The constituents on the D-ring of the corticosteroid-molecule are considered to have a central role for binding to skin proteins and for cross-reactions patterns; however, halogenation of the molecules is also interfering.
Objective: To study the clinical data and analyse simultaneous positive reactions obtained in a large group of corticosteroid-allergic patients.
Methods: Patch tests were performed with the baseline series, to which hydrocortisone butyrate and prednisolone caproate were added, as well as with the corticosteroids to which the patients had been exposed. Three hundred and forty subjects with a presumed or proven corticosteroid allergy were further investigated with an extended series containing 72 molecules.
Results: Out of 11 596 patients investigated, 315 subjects reacted positively to at least 1 corticosteroid-molecule, with most of them presenting with multiple positive reactions.
Conclusion: A prevalence of corticosteroid allergy of 2.7% was found. Despite validity of the ABCD (sub)classification in many cases, possible adjustments may have to be considered.