Dermatology: Practical and Conceptual


Research Letter | Dermatol Pract Concept. 2022;12(2):e2022058 1

Recurrent Acute Generalized Exanthematous 
Pustulosis to Two Different Drugs: Oxacillin and 

Dextromethorphan Confirmed by Patch Test
Zied Kenani1, Rima Gammoudi1, Neila Fathallah2, Amina Aounallah1,  

Sana Mokni1, Lobna Boussofara1, Nejet Ghariani1, Colandane Belajouza1,  
Chaker Ben Salem2, Mohamed Denguezli1

1 Department of Dermatology, Farhat Hached hospital, Sousse, Tunisia

2 Department of pharmacovigilance, Reference center for cutaneous adverse reactions, Faculty of medicine, University of Sousse,  

Sousse, Tunisia.

Key words: Acute generalized exanthematous pustulosis, oxacillin, dextromethorphan, recurrence, patch test

Citation: Kenani Z, Gammoudi R, Fathallah N et al. Recurrent Acute Generalized Exanthematous Pustulosis to Two Different Drugs: 
Oxacillin and Dextromethorphan Confirmed by Patch Test. Dermatol Pract Concept. 2022;12(2):e2022058.  
DOI: https://doi.org/10.5826/dpc.1202a58

Accepted: August 24, 2021; Published: April 2022

Copyright: ©2022 Kenani et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, 
distribution, and reproduction in any medium, provided the original authors and source are credited.

Funding: None.

Competing interests: None.

Authorship: All authors have contributed significantly to this publication

Corresponding author: Zied Kenani, MD, Department of Dermatology, Farhat Hached Hospital, Avenue Ibn Jazzar, 4002, Sousse, Tunisia. 
E-mail: zieedken@gmail.com

Introduction 

Acute generalized exanthematous pustulosis (AGEP) is a 

potentially severe skin condition, mainly drug induced [1]. 

Recurrences are rare and generally induced by related drugs. 

Dextromethorphan is an antitussive agent which is unusu-

ally reported as culprit in AGEP. Herein we report a rare case 

of relapsing AGEP to dextromethorphan and oxacillin.

Case Presentation 

A 32-year-old woman, with a history of a controlled gener-

alized pustular psoriasis, presented to our department with a 

4 day history of fever with predominately flexural eruption 

of non-follicular pustules on a erythematous background, 

which had started 2 days after the intake of oxacillin and 

tiaprofenic acid. Investigations found an elevated absolute 

neutrophil count and skin biopsy demonstrated histologic 

features consistent with AGEP. Skin lesions totally resolved 

within 10 days after oxacillin discontinuation. A patch test 

with oxacillin and tiaprofenic acid (the commercialized form 

used by the patient diluted to 30% pet.) was performed and 

showed a +++ skin reaction to oxacillin on day 4 but no 

reaction to tiaprofenic acid. All penicillins were prohibited.

Two years later the patient presented with a similar 

eruption and fever 4 days after taking 2 multi-compound 

medications named goldix day (dextromethorphan, doxyl-

amine, paracetamol) and goldix night (dextromethorphan, 

paracetamol, phenylephrine) for a cold (Figure 1). She de-

nied taking any other drug. Complete blood count showed 



2 Research Letter | Dermatol Pract Concept. 2022;12(2):e2022058

paracetamol. We performed a genetic analysis to determine 

whether there was mutation of the IL36RN gene, as it may 

be a predisposing factor, but we did not find such mutation 

in our patient.

Conclusions 

Recurrences in AGEP are rare and often induced by related 

drugs, mainly B-lactams. Our case suggests that it may be 

induced by chemically different medications in potentially 

predisposed patients possibly having pattern of cytokine dys-

regulation. Indeed, it seems that psoriasis might be a risk 

factor of relapsing AGEP. We have also shown that IL36RN 

gene mutation does not fully explain the pathogenesis of 

pustular generalized eruptions. Moreover, our observation is 

notable for the implication of dextromethorphan, a widely 

used opioid antitussive agent, as a culprit drug. To the best 

of our knowledge, only 1 case of AGEP induced by dextro-

methorphan and confirmed by patch testing has been previ-

ously reported [2].

References

1. Sidoroff A, Dunant A, Viboud C, et al. Risk factors for 

acute generalized exanthematous pustulosis (AGEP)—re-

sults of a multinational case-control study (EuroSCAR). Br 

J Dermatol. 2007;157(5):989–996. DOI: 10.1111/j.1365-

2133.2007.08156.x. PMID: 17854366.

2. Rashid, RS,  Ahmed, I,  Shim, TN.  Acute generalized exanthem-

atous pustulosis due to dextromethorphan.  Contact Derma-

titis.  2020;83(5):424–425. DOI: 10.1111/cod.13633. PMID: 

32506524.

marked neutrophilia and skin biopsy was consistent with 

AGEP. Diagnosis was defined following EuroSCAR criteria. 

Patch testing with the component of the commercialized 

package of goldix day (30 % pet.), goldix night (30 % pet.) 

and paracetamol (50% pet.) was performed. The patch test 

preparations were applied in IQ Ultra (Chemotechnique 

 Diagnostics). The patch tests were occluded for 48 hours, and 

readings were performed according to ICDRG/ESCD criteria 

on day 2 and day 4. Patch testing showed a ++ skin reaction 

to goldix day and goldix night, but was negative to parac-

etamol (Figure 2). The oral provocation test to paracetamol 

was also negative. The constituent dextromethorphan was 

not available for testing, but was suspected as the cause of 

the reaction as it was the only compound in common besides 

Figure 1. Diffuse erythema with multiple small pustules.

Figure 2. (A) Positive patch test reaction to goldix day on day 4. (B) Positive patch test reaction to goldix night on day 4. (C) No reactions 

to paracetamol were seen on day 4.