Two types of hypersensitivity reaction including anaphylaxis and symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) after aminopenicillin administration in the same patient

Introduction

Even though the prevalence of patients labeled with penicillin allergy is estimated at 8–25%, after the complete allergological work-up, the percentage of the real penicillin allergy is established at < 5% [1]. Penicillin allergy most often occurs as type I immediate reactions, such as anaphylaxis and type IV-delayed reactions. Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), previously known as baboon-syndrome, is a rare manifestation of type IV hypersensitivity reaction [2].
We present, a rare case of a patient who experienced both immediate and delayed types of drug hypersensitivity reaction to aminopenicillin with good tolerance of another β-lactam.

Case report

A 56-year-old female patient was admitted to the Allergy and Clinical Immunology Department due to drug allergy. The patient reported allergic reactions to several antibiotics including ampicillin and neomycin in childhood and spiramycin in 2017. In 2018, after the co-administration of nonsteroidal anti-inflammatory drugs (NSAIDs) and amoxicillin/clavulanic acid (Augmentin), the patient presented with anaphylactic shock with massive urticaria and loss of consciousness. On the other hand, she reported good amoxicillin (Duomox) tolerance. Upon admission, physical examination and laboratory parameters were within the normal range. Drug hypersensitivity reaction (DHR) to NSAIDs was excluded by oral provocation tests with celecoxib and acetylsalicylic acid. Due to the unclear history of β-lactam allergy, after negative skin test results, a direct oral provocation test with amoxicillin (up to 1000 mg) was performed. Four hours after the administration of the last dose, the patient developed symmetrical erythematous rash located on her trunk, limbs, armpits, and groins, along with temperature increase to 38.5°C. Laboratory tests showed increased inflammatory parameters: C-reactive protein increased from 3.4 mg/l to 53.8 mg/l (reference range < 5 mg/l), leukocyte count increased from 6.24 × 10³/µl to 13.99 × 10³/µl (reference range 4.0–10.0 10³/µl), and neutrophil count increased from 3.61 × 10³/µl to 12.98 × 10³/µl (reference range 2.5–5.0 × 10³/µl). Specific IgE (ImmunoCAP, Thermo-Fisher Scientific) to β-lactams including amoxicillin, ampicillin, penicillin G, penicillin V and cefaclor were negative (< 0.35 kU/l). After treatment with 8 mg of dexamethasone intravenously, 1000 mg of paracetamol and 80 mg of bilastine, a gradual regression of skin rash (Figure 1) and normalization of inflammatory parameters were observed (Figure 2).
The patient was discharged home with the recommendation to continue oral and topical corticosteroid treatment. Further work-up with prick, intradermal skin tests and oral provocation test up to 500 mg, confirmed good tolerance of cefuroxime axetil.

Discussion

Since 1984 over 100 cases of SDRIFE have been described [3]. SDRIFE may include both a type IV-a reaction involving CD4+ Th1 cells, macrophages, and a type of IV-c reaction with CD4 and CD8 T cells involvement [4]. Häusermann et al. proposed 5 criteria for SDRIFE diagnosis (Table 1) [5]. Our patient fulfilled 4 of 5 criteria. SDRIFE differential diagnosis should include other drug hypersensitivity reactions, such as acute generalized exanthematous pustulosis (AGEP), fixed drug eruption (FDE) and drug reaction with eosinophilia and systemic symptoms (DRESS). Clinical course of AGEP and DRESS is more severe with systemic symptoms and in case of DRESS with internal organ involvement such as hepatitis, nephritis, and lymphadenopathy. Asymmetrical localization of skin lesions with the late symptom onset (1–2 weeks after drug exposure) is more typical for FDE [5]. In the described case because of atypical symptoms such as fever and increased inflammatory parameters, differential diagnosis was required. The time of symptom onset, mild course of the disease and rapid skin symptoms regression after the treatment pointed to SDRIFE as a final diagnosis.
Clinically significant β-lactams DHR mainly occur due to side chain similarity, not to β-lactam ring sensitization [6, 7]. Despite the fact that cross-reactivity between penicillins and cephalosporins is very low, avoidance of cephalosporins in patients with penicillin allergy is still common [8]. Therefore, an allergy work-up in patients with confirmed aminopenicillin allergy should include cephalosporin testing as well.

Conflict of interest

The authors declare no conflict of interest.

References