Unveiling the hidden culprit: A case report of recurrent SDRIFE caused by a systemic corticosteroid masquerading as antibiotic allergies

When faced with recurrent episodes of cutaneous drug eruptions from different drug classes, one should always suspect that there is another medication involved that is common to all episodes. We present a case of a delayed drug eruption that was initially believed to be caused by three different classes of antibiotics, but which turned out to be caused by a corticosteroid. A 67-year-old woman was referred for allergological investigations of three episodes of skin eruptions initially thought to be caused by amoxicillin-clavulanate, then metronidazole/spiramycin, and ultimately azithromycin (this last taken with prednisolone). All episodes followed dental procedures. While the first eruption occurred 1 week after starting treatment, the subsequent reactions occurred only 12–24 h after. Suspecting a drug that was common to all three episodes, we asked to see the prescriptions which revealed in fact the systematic intake of prednisolone for 5 days in combination with antibiotics. The patient was tested, as initially scheduled, with the suspected antibiotics (patch, prick and intradermal tests) to which we added a corticosteroid series (patch tests with budesonide 0.01% pet, tixocortol-21-pivalate 0.1% pet, hydrocortisone-17-butyrate 1.0% alc and 1.0% pet, dexamethasone-21-phosphate disodium salt 1.0% pet and betamethasone-17-valerate 1.0% pet, Chemotechnique Diagnostics, Vellinge, Sweden). All the tests were performed according to the European Society of Contact Dermatitis guidelines. The readings on Day (D)3 and D4 were negative. No reading on D7 had been scheduled because only the antibiotics were suspected at first. On D4, we decided to move forward with an oral provocation test with prednisolone 20 mg (Solupred, CHEPLAPHARM France SAS, Levallois-Perret, France). Twelve hours later, the patient presented a sharply defined symmetrical erythema of the gluteal and intertriginous areas, without systemic signs or symptoms, which she claimed to be the same eruption as previously experienced and which was stereotypical of a symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) (Figure 1). Subsequently, in order to find corticosteroid alternatives, provocation tests with oral betamethasone 2 mg (Celestene, CHEPLAPHARM France SAS, Levallois-Perret, France) and intravenous methylprednisolone 20 mg (Solumedrol, Pfizer, Paris, France) were done and well tolerated. We contraindicated all the systemic corticosteroids except betamethasone and methylprednisolone, but authorized the previously suspected antibiotics without further testing. We report a case of recurrent SDRIFE caused by prednisolone that was initially thought to be caused by three different classes of antibiotics. Provocation tests confirmed the diagnosis and identified two safe corticosteroid alternatives. This case demonstrates the importance of meticulous questioning and reviewing of all prescriptions when investigating allergic drug reactions. In our patient, the fact that the eruption always recurred in the same context and subsequently within a shorter period of time prompted us to look for a common culprit. In the case of systemic hypersensitivity to corticosteroids, classifications based on chemical structures such as A/B/C/D1/D2 or 1/2/3 are often unreliable for exploring cross-reactions.1, 2 On one hand, some patients seem to be able to react to any corticosteroid, regardless of its class, probably due to a global recognition of the corticosteroid skeleton.1, 3, 4 On the other hand, in the literature, 52/79 patients had a negative provocation test to a corticosteroid belonging to the same chemical group as the one responsible for their initial reaction.2 Furthermore, the validity of previously published corticosteroid classifications has recently been questioned even for topical corticosteroid allergy. Indeed, Chen et al. found in their qualitative study that the proposed classifications were not predictive of corticosteroid copositivity in their patients.5 Therefore, in all cases, patients need an individualized assessment of their tolerance and sensitization profile, and provocation tests are often essential to identify corticosteroid alternatives in cutaneous as well as in systemic corticosteroid hypersensitivity reactions.1, 2, 5 Additionally, it is worth noting that the sensitivity of patch tests for systemic delayed hypersensitivity to corticosteroids is relatively low, but could be increased by diluting corticosteroids in ethanol and by conducting a delayed reading on D7.2, 6 Besides, intradermal tests with corticosteroids are discussed because there is a risk of cutaneous atrophy.6 Still, according to Barbaud and Watson, atrophy seems to be transient and could potentially be minimized by injecting a limited volume of 0.02 mL of only injectable corticosteroids.2 More studies using a standardized method are necessary. Finally, our report demonstrates that systemic corticosteroids are an under-recognized cause of drug eruptions and can indeed cause SDRIFE.3, 7 It also suggests that in the case of non-severe cutaneous drug reactions, including SDRIFE, provocation tests could safely identify the culprit drug and find safe alternatives.8, 9 Valérie Beaulieu: Writing – original draft; writing – review and editing; investigation. Ilaria Matei: Writing – review and editing; investigation. Kamar Bel Hareth: Writing – review and editing; investigation. Saskia Ingen-Housz-Oro: Writing – review and editing. Haudrey Assier: Writing – review and editing; supervision; investigation. The authors declare no conflicts of interest. The authors obtained informed written consent from the patient for the photos to be used.