D2.405 - UnDRESSing AGEP and Revealing Erythema Multiforme

Background:

Acute generalized exanthematous pustulosis is a severe cutaneous adverse reaction, in most cases drug-induced. Its association with nutritional supplements is exceptionally rare. The aim of this case report is to present a unique case of a patient who developed AGEP with overlapping erythema multiforme (EM) after ingesting a food supplement, highlighting diagnostic challenges and potential safety risks posed by supplements.

Case presentation:

We present a 41-year-old woman admitted through the Emergency Department with a generalized maculopapular rash, sterile pustules and lip edema, without mucosal involvement. The onset of symptoms was the day before admission and she was treated with systemic corticosteroids for two days, with no clinical improvement. Six days prior to admission, she had taken a weight-loss nutritional supplement for two consecutive days reportedly containing caffeine, synephrine, green tea, dihydroberberine, capsaicin, chromium picolinate and bioperine. She denied other medication use, except for ketoprofen taken for headache two days before symptom onset. During hospitalization, she developed additionally a fever up to 38 °C on day one, followed by pathognomonic target lesions consistent with EM on the extremities by day four.

Results:

Laboratory findings included eosinophilia (1.1 10^9/l), neutrophilia (10.8 10^9/l) and elevated CRP (103.0 mg/L), with liver function tests within normal range. Abdominal ultrasound showed no abnormalities.  Skin biopsies were obtained from both types of cutaneous lesions, and histopathological examination confirmed both diagnoses.

Conclusion:

Based on the typical clinical features and laboratory findings, AGEP with overlapping EM was diagnosed. Because of the eosinophilia, overlap with drug reaction with eosinophilia and systemic symptoms (DRESS) was considered, but was ruled out due to the absence of systemic involvement and the clinical course. Thus, the case represented a major diagnostic challenge as it evolved with overlapping type I, II, and III immune responses.

Discussion:

In addition to the reported case, approximately 60 further patients nationwide presented with similar severe cutaneous reactions, which prompted the national regulatory authorities to initiate a legal investigation, including laboratory analysis of the dietary supplement. The analysis identified the presence of sibutramine, the absence of the declared ingredients, and variability between different batches. The cases suggest that unregulated dietary supplements may be associated with the development of SCAR and raise concerns regarding regulatory oversight of dietary supplements in Bulgaria, as well as the European Union.