Hypersensitivity reactions
IHRs to GCs are overall rare and mostly IgE-mediated (175-180). In a review of the literature from 2004-2014, anaphylaxis was the most common manifestation reported (60.8%, 73/120 reactions) followed by urticaria and/or angioedema (26.7%). Methylprednisolone was implicated in 41% of reactions, followed by prednisolone (20%), triamcinolone (14%), and hydrocortisone (10%) (178).
In most subjects with IHRs, it is possible to identify the culprit and safe alternative GCs by performing immediate-reading STs (175-182). In the aforementioned review, 74.1% of 112 STs carried out with GCs suspected of being responsible for reactions were positive (178). In some subjects, positive STs were associated with positive serum specific IgE assays and BATs (178,179).
IHRs to medication components other than the GC itself, such as succinate ester used to enhance the solubility in parenteral preparations, have been described (178,182). Hence, when evaluating a reaction to an esterified GC, it is advisable to include in STs the suspected GC and the same GC without the ester component, or with a different ester.
IHRs to excipients or preservatives in GC preparations, such as lactose, carboxymethylcellulose, polyethylene glycol, and hexylene glycol, have also been reported (178,182). Therefore, testing should be performed with a preservative free GC, in addition to preservative testingper se if needed (182). A study proposed a comprehensive diagnostic algorithm to evaluate hypersensitivity reactions to GCs, as well as to their components and preservatives (182). This algorithm included STs with Carmellose® eye drops in subjects who had reacted to carboxymethylcellulose-containing GCs and with cow’s milk proteins in those who had reacted to lactose-containing GCs.
In the allergy workup, negative results in STs should be confirmed with DPTs (177-182). DPTs are also recommended to ensure tolerance of alternative preparations (181). Cross-reactivity patterns based on structural characteristics have not been clearly established for IHRs as they have been for allergic contact dermatitis (176). DPTs have shown that patients often tolerate alternative GCs belonging to the same chemical group as the responsible GC (179,180). Desensitization to methylprednisolone has been successfully performed (183,184).
NIHRs following systemic administration of GCs have been more rarely reported than IHRs; most reports concerned isolated cases of eczematous or exanthematous skin eruptions (175,176). Some are systemic contact dermatitis, occurring in patients with previous contact dermatitis to GCs. They can be revealed by a Baboon syndrome, characterized by a buttock erythema associated to a symmetric, flexural erythema (185).
Most patients do not have a previous topical sensitization. In NIHRs, the main feature is MPE, but other clinical aspects can also occur such as annular erythema, erythroderma, SDRIFE, AGEP, FDE, and a few cases of SJS (185).
NIHRs can be T-cell-mediated, and PTs, together with delayed-reading IDTs, are useful tools for evaluating them (17). PTs have to be read at 2, 4 and also 7 days. Even though delayed-reading IDTs are more sensitive than PTs, the sensitivity of the former is limited. Therefore, DPTs are often necessary to diagnose NIHRs. In a study by Padial et al, only 2 of the 38 patients with NIHRs to GCs displayed positive delayed-reading IDTs and PTs to the responsible GCs (i.e., dexamethasone and betamethasone), while 21 of the 32 negative patients who agreed to undergo DPTs reacted to them, experiencing almost exclusively delayed-appearing urticarial eruptions or MPEs (186).