Hypersensitivity reactions (including allergy) to Systemic Glucocorticoids

Glucocorticoids are prescribed for their immunosuppressive, antiproliferative, anti-inflammatory, and antiallergenic effects and are integral to the management of numerous conditions, including malignancies, transplantation, autoimmune and allergic diseases, and asthma. They are also administered to prevent late-phase anaphylactic reactions. However, injected, infused, or orally administered systemic glucocorticoids have been associated with immediate hypersensitivity (allergic) reactions, including life-threatening anaphylaxis.

Signs and symptoms of immediate hypersensitivity to glucocorticoids include pruritus, rash, hives, angioedema, sneezing, nausea / vomiting, dyspnea, throat tightness, wheezing / bronchospasm, hypotension, and anaphylactic shock. Hypersensitivity reactions have been reported following intravenous, intramuscular, oral, intra-articular, epidural, and topical administration.

The allergenic moiety in glucocorticoids that is responsible for immediate reactions has not been determined. It could be part of the native molecule or a metabolite that acts as a hapten and binds to serum proteins, creating an allergenic complex.

Other possible allergens in glucocorticoid preparations include esters, preservatives, and excipients. For example:

* In a case report, the evaluation of a 39-year-old woman who developed generalized urticaria after receiving hydrocortisone sodium succinate on two occasions was described. Her intradermal testing was positive to hydrocortisone sodium succinate and methylprednisolone hemisuccinate and negative to hydrocortisone acetate, hydrocortisone sodium phosphate, and methylprednisolone (without an ester).

* Lactose is an excipient in certain preparations of methylprednisolone. Milk allergy should be considered as a possible alternative explanation for allergic reactions to methylprednisolone sodium succinate in patients with milk allergy.

· Cross-reactivity between corticosteroids is most likely to occur within (NOT between) the 4 structural corticosteroid groups.
      (Yet) Class A corticosteroids are likely to cross-react with class D2 corticosteroids.

·  There is limited reference on dosing of dexamethasone for allergy treatment. Drugs.com suggested:

Day 1	IM 4-8 mg STAT	Day 5	PO 0.75 mg OD
Day 2	PO 1.5 mg BD	Day 6	PO 0.75 mg OD
Day 3	PO 1.5 mg BD	Day 7	-
Day 4	PO 0.75 mg BD	Day 8	Reassessment

Patients may be allergic to more than one systemically administered glucocorticoid. Patterns of cross-reactivity are not well-defined, and in the absence of an allergy evaluation or a challenge procedure, it is not possible to choose a safe alternative agent empirically.

Patients with signs or symptoms of an immediate reaction to a systemic glucocorticoid should be referred to an allergy specialist whenever possible and advised to avoid systemic use of all glucocorticoids until evaluated. It is impractical to recommend indefinite avoidance of systemic glucocorticoids because of the widespread use of these agents for so many different disorders. If referral is not possible, then the patient could receive a different agent from the one that caused the original reaction using a graded challenge procedure under close medical supervision.

Graded drug challenge involves administering a medication to a patient in a graded manner under close observation. This is also called test dosing or drug provocation testing. 

Challenges are used when the sensitivity of allergy tests for evaluating reactions to certain drugs is limited In most cases, graded challenges are performed with a drug to which the patient has not reacted and is believed likely to tolerate. Graded challenge does not modify the allergic response to the drug or prevent recurrent reactions. Therefore patients who tolerate a drug upon graded challenge prove that they are not allergic to it.

At the author's center, challenges are performed starting with 1/100th of the therapeutic dose, followed if tolerated 30 minutes later by 1/10th of the dose, followed 30 minutes later if tolerated by 9/10th of the dose.

References:

1.    UptoDate: Hypersensitivity reactions to systemic glucocorticoids [Accessed 14 Dec 2018]

2.    Shuck A. (2015). Steroid Use in Prednisone Allergy, accessed via - https://www.ohiopharmacists.org/aws/OPA/asset_manager/get_file/100350 [Accessed 14 Dec 2018]

3.   https://www.drugs.com/dosage/dexamethasone.html#Usual_Adult_Dose_for_Allergic_Reaction [Accessed 14 Dec 2018]