I have a 16yo patient with unexplained episodes of swelling of the hands and feet associated with generalized itching and sometimes hives that typically last 2 to 3 hours and are relieved by Benadryl. Occasionally these episodes are associated with symptoms of throat tightness, chest tightness and shortness of breath also relieved by Benadryl. She has been unable to establish a trigger and work up has been unremarkable to date. One of these episodes was treated with oral prednisone by her PCP and initial symptoms resolved but after the 2nd dose within 2 hours she developed a rash on the face and neck she described as hives as well as facial swelling around the eyes, lips and tongue resolved with Benadryl.

My question is regarding the possibility of hypersensitivity to prednisone. In this case, she is being treated with high dose H1 and H2 blockers which I do not feel reasonable withholding to employ skin prick testing to prednisone and potentially another glucocorticoid in attempt to determine which steroid may be tolerated. However, in her case it is potentially important to know if she tolerates another steroid. Based on my literature search I cannot find any definitive answer regarding cross reactivity among systemic glucocorticoids. Therefore, would you advise treating with another steroid such as methylprednisolone or dexamethasone orally without graded challenge if she needed systemic steroid in the future or would you perform a graded challenge to an alternative agent such as one of these to determine which may be tolerated in the event she does need systemic steroid?


Thank you for your inquiry.

In actuality, I doubt that your patient exhibited a hypersensitivity reaction to prednisone. Although allergic reactions to corticosteroids do occur, they are, in the vast majority of times, due to intravenous or intramuscular injection.

As you stated, skin testing might help, but if you feel you cannot discontinue the antihistamine therapy, of course they may not be accurate.

There is, however, an antigenic classification of corticosteroids based on their cross-reactivity related to contact dermatitis reactions. Although this deals with delayed hypersensitivity, it could perhaps give one a guide as to what corticosteroid might exhibit the least chance of cross-reacting with prednisone. I have copied below a previous entry that was posted on our "Ask the Expert" website, along with our reply which cites this classification. Looking at your options, I think it would be reasonable to choose dexamethasone, which is in a separate antigenic (cross reactive) category. I would indeed do a graded oral challenge because your patient may need corticosteroid therapy in the future.

In summary, I would use dexamethasone, and perform a graded challenge in your office. It would of course be best to perform this challenge when your patient was relatively asymptomatic. Since I think that a corticosteroid allergy in your patient is unlikely, I believe you could start with 1/5th of the therapeutic dose that you desire, and dose every 30 minutes until a cumulative full dose has been administered.

Thank you again for your inquiry and we hope this response is helpful to you.

"Allergenic cross-reactivity of topical corticosteroids in regards to the potential of producing contact dermatitis reactions"

If a patient is patch test positive to tixocortol pivalate, what topical steroid can be used?

Thank you for your inquiry.

There are a number of excellent references that discuss the issue of cross-reactivity between topical corticosteroids. I have copied for you below two classifications regarding the cross-reactivity of corticosteroids and the source of these are also given. In addition, the scientific underpinnings thought to account for the cross-reactivity is found in the abstract by Coopman, et al., from the British Journal of Dermatology. The sources that I have copied for you below are in good part based upon Coopman’s classification.

An excellent article discussing the issue of cross-reactivity of topical corticosteroids, which has a concise discussion of Coopman’s study is found in Medscape. This article is available to you free of charge. The section is a little too lengthy to copy here, but you will find it very helpful.

Using this information, you should have no trouble in selecting a topical corticosteroid that is least likely to cross-react with tixocortol pivalate. However, as noted in the references, oftentimes cross-reactivity occurs regardless of the choice.

Thank you again for your inquiry and we hope this response is helpful to you.

Br J Dermatol. 1989 Jul;121(1):27-34.
Identification of cross-reaction patterns in allergic contact dermatitis from topical corticosteroids.
Coopman S, Degreef H, Dooms-Goossens A.
Contact allergy to topical corticosteroids occurs more frequently than previously supposed. Cross-allergic phenomena are common. On the basis of a review of the literature and our own patch test data on 15 patients, we conclude that positive patchtests to corticosteroids occur approximately six to seven times more frequently in well-defined groups of structurally-related substances than between corticosteroids of different groups. An analogous substitution pattern on the steroid D-ring or the carbon side chain (C20, C21) seems to have a significant influence on the association of positive patchtest results. This is not the case for other structural variables, such as the presence of a double bond in the steroid A-ring or fluoride substitutions on the B-ring. The effect of other factors such as concomitant sensitization and steroid metabolism in the skin on the development of a corticosteroid polyallergy are analyzed, and the specificity and sensitivity of cross-allergy phenomena are evaluated. These are important in the selection of a topical steroid in the future treatment of a corticosteroid sensitive patient.

SOURCE: DermNet NZ When patch tests show allergy to a specific topical steroid, it is likely that the patient will also be allergic to others.

• Budesonide may result in allergy to fluocinolone, triamcinolone, hydrocortisone-17-butyrate, methylprednisolone aceponate and prednicarbate.

• Tixocortol-21-pivalate may result in allergy to hydrocortisone (acetate), prednisolone, diflucortolone, methylprednisolone, hydrocortisone-17-butyrate, methylprednisolone aceponate and prednicarbate.

• Hydrocortisone-17-butyrate allergy may result in allergy to methylprednisolone aceponate, prednicarbate, alclomethasone dipropionate, budesonide and hydrocortisone (acetate).

Cross-reactions patterns of corticosteroids (Lepoittevin JP, Driegh J, Dooms-Goossens A. Studies in patients with corticosteroids contact allergy: understanding cross-reactivity among different steroids. Arch Dermatol 1995; 131(1):91-2) Source: Auckland Allergy Clinic.

Most steroid allergic patients react to several different steroids demonstrating that concomitant sensitization and / or cross-reactions occur. It is hypothesized that cross-reactions occur in certain groups of steroids. It is found that molecules of the same group have similar spatial structures to explain the cross-reaction observed (8).

Classification of corticosteroids by the function of their allergenicity (8)

• Group A: Hydrocortisone and tixocortol Type
• Prednisone
• Prednisolone acetate (Pred mild & Pred forte eye drops)
• Methylprednisolone aceponate (Advantan)
• Meprednisone
• Cortisone, Cortisone acetate
• Hydrocortisone (-HC, Egocort, Cortaid, Skincalm)
• Tixocortol pivalate
• Group B: Triamcinalone acetonide Type
• Triamcinalone alcohol
• Triamcinalone acetonide (Aristocort)
• Budesonide (Pulmicort, Butacort & Entocort),
• Amcinonide, desonide
• Halcinonide
• Fluocinonide (Metosyn)
• Fluocinolone acetonide (Synalar)
• Group C: Betamethasone Type
• Betamethasone sodium phosphate
• Dexamethasone, dexamethasone sodium phosphate
• Fluocortolone
• Group D: Hydrocortisone-17-butyrate & Clobetasone 17 butyrate Type
• Hydrocortisone butyrate) (Locoid)
• Hydrocortisone-17-valerate
• Clobetasol propionate (Dermol, Dermovate)
• Aclometasone dipropionate
• Betamethasone 17 valerate (Betnovate, Beta)
• Betamethasone dipropionate ( Diprosone)
• Clobetasone 17 butyrate (Eumovate)
• Fluocortolone pivalate (Ultraproct)
• Mometasone Furorate (Elocon)
• Fluticasone propionate (cutivate)

Phil Lieberman, M.D.

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