Allergic and Pseudoallergic Reactions Induced by Glucocorticoids: A Review

Abstract

Glucocorticoids (GCs) represent the most effective treatment for autoimmune and allergic diseases, even if collateral effects are not rare, especially endocrine and immunosuppressive manifestations. Moreover, these drugs can develop adverse immunological reactions of I, III or IV type. Though immediate adverse reactions caused by systemic therapy with GCs are not very frequent, the possible beginning of anaphylactic and pseudo-anaphylactic manifestations in patients undergoing therapy with these drugs has to be considered. It has been observed that immediate adverse reactions usually are happened in asthmatic patients and in patients obliged to assume GCs again and again because of their pathology (e.g, kidney transplant). Other risk factors resulted to be female sex and hypersensibility to acetylsalicylic acid (ASA). Both in the cases of pseudo-allergic and allergic reactions, the pharmacological principle is hardly the responsible agent for the reaction; instead the excipients in drugs are often implicated (succinate salt, sulphites and carboxy-methyl-cellulose). It is possible that the IgE-response is highly specific for a fixed GC molecule as well depending on the way of administration and its salification. Moreover, it has been hypothesized that in patients with a first type allergic reaction to GCs there is a fourth type, sensitization to GCs, which is not usually diagnosed and even comes before IgE sensitization. Third type hypersensibility reactions may occur, too. Since GCs are large-scale drugs, also in emergency medicine and reanimation, allergic sensitization towards them, although infrequent, gives many interventionist problems. In the light of this feature, it seems of crucial importance to verify the tolerance toward other GC molecules. And in particular, it has been noted that patients presenting immediate reactions to hydrocortisone (HC) and methylprednisolone (MP) could tolerate prednisone and prednisolone per os and second-generation GCs, such as desamathazone and betamethazone. Nevertheless, second-generation GCs must not be considered safe; in fact, the beginning of allergic manifestations has been pointed out even towards them.

Cross-Reactivity in Cell-Mediated and IgE-Mediated Hypersensitivity to Glucocorticoids

“…In fact, patients allergic to the GCs of group A (hydrocortisone and methylprednisolone) tolerate the GCs of group C (betamethasone, dexamethasone, paramethasone). Patients with immediatetype reactions to intravenous succinate esters of hydrocortisone and methylprednisolone tolerate prednisolone (a GC of group A) orally, as reported by many authors [23,24,65,66]. This is probably due to the fact that the introduction of a double binding on C 1 -C 2 of the cortisol A ring increases the binding affinity of prednisone/prednisolone more than the cortisol itself for its serum binding proteins, by changing the directions of the steroid molecule, so the ring D and C 21 are oriented towards the pocket of the paratope [65,97] instead of the A ring as in succinate esters.…”

“…In fact, the tolerability of alternative halogenated GCs, such as betamethasone and dexamethasone, in patients who suffered immediate hypersensitivity reactions to succinate esters of hydrocortisone or methylprednisolone, besides be- ing reported in various cases and numerous reviews [23,24], has been confirmed in two studies [60,67] that evaluated, respectively, 7 and 10 patients with IgE-mediated asthma.…”

“…We have identified other risk factors: autoimmune diseases, such as systemic erythematous lupus, rheumatoid arthritis, multiple sclerosis, psoriasis, lichen planus, which require frequent administration of GCs by systemic, intralesional or topical routes [24], and ACD to topical GCs, which is often unrecognized [25]. As confirmed by dermatological studies [26], percutaneous absorption can lead to hidden or underestimated sensitization.…”

“…Some of the more common reported reactions include localized or generalized urticaria, sometimes with purpuric aspects, angioedema of the face and/or periorbital edema, bronchospasm, and hypotension [24,39,38].…”

Medication-Related Complications in the Trauma Patient

“…Allergic, pseudoallergic, and hypersensitive reactions, although rare, must also remain a consideration, with risk factors including reintroduction of corticosteroids secondary to underlying disease, female gender, and hypersensitivity to acetylsalicylic acid. 178,179 Steroid-induced myopathy is an additional adverse effect particularly problematic in sedentary and female patients, and those patients receiving concomitant neuromuscular blocking agents, aminoglycosides, or propofol. [180][181][182] Etomidate-induced adrenal insufficiency must also be considered in trauma patients who receive this sedative agent during intubation.…”