Acute Generalized Exanthematous Pustulosis (AGEP) Unveiled

A Tertiary Hospital Case Series on Antibiotic-Induced Adverse Drug Reactions in Davao City, Philippines

Authors

DOI:

https://doi.org/10.70552/pjaai.24.1.9871

Keywords:

Acute generalized exanthematous pustulosis , AGEP, Non-follicular pustules, ceftriaxone, clindamycin, piperacillin-tazobactam, severe adverse drug reaction

Abstract

Acute generalized exanthematous pustulosis (AGEP) is a rare and severe cutaneous adverse reaction (SCAR) characterized by the rapid onset of widespread small sterile pustules on erythematous skin. It is only estimated to occur in 1 to 5 cases per million annually worldwide. It is distinguishable from other SCARs based on the time interval between drug intake and the onset of symptoms. This characteristic time interval is a key factor in differentiating AGEP from other skin reactions.

This case series presents three distinct cases of AGEP in patients admitted to a tertiary hospital in Davao City, Philippines. Our cases demonstrate the diverse clinical presentations and triggers of AGEP, primarily involving antibiotics, including ceftriaxone, piperacillin-tazobactam, clindamycin, and amoxicillin. The three cases share similarities in demographic profiles, with patients being female in the 26 to 60 age group; however, they exhibit variations in the onset of symptoms relative to drug exposure, notably appearing 1 day, 4 days, and 24 days following antibiotic use. All patients had no mucosal and organ involvement. Treatment strategies of our patients involved identification and discontinuation of the offending medication, application of topical steroids, and providing supportive care. All three patients had resolution of the skin lesions.

Because AGEP exhibits a distinctive and rapidly evolving clinical presentation, it is primarily diagnosed based on clinical findings. All three patients presented rapid eruption of multiple, small, non-follicular pustules on a background of an erythematous exanthem following drug exposure. The most commonly implicated agents causing AGEP include antibiotics. Beta-lactams are the main offenders in this case series. This case series underscores the importance of recognizing AGEP as a potential adverse reaction to antibiotics and the need for prompt identification, withdrawal of the offending medication, and timely initiation of treatment to ensure favorable outcomes. 

Author Biographies

Irson Thurs L. Doria, MD

Correspondence to:
Irson Thurs L. Doria, MD
Medical Officer III/Level II Resident
Southern Philippines Medical Center
J.P. Laurel Avenue, Bajada, Davao City 8000, Philippines
Tel. No.: (082) 227 2731
E-mail: irsondoria@gmail.com

Maria Carmen D. Ang, MD

Department of Internal Medicine, Southern Philippines Medical Center, Davao City, Philippines

Jessie F. Orcasitas, MD

Department of Internal Medicine, Southern Philippines Medical Center, Davao City, Philippines

References

Sidoroff A. Acute generalized exanthematous pustulosis. Chem Immunol Allergy. 2012;97:139-48. https://pubmed.ncbi.nlm.nih.gov/22613859 https://doi.org/10.1159/000335625 DOI: https://doi.org/10.1159/000335625

Zhang C, Van DN, Hieu C, Craig T. Drug-induced severe cutaneous adverse reactions: Determine the cause and prevention. Ann Allergy Asthma Immunol. 2019 Nov;123(5):483-7. https://pubmed.ncbi.nlm.nih.gov/31400461 https://doi.org/10.1016/j.anai.2019.08.004. Erratum in: Ann Allergy Asthma Immunol. 2020;124(4):408. https://pubmed.ncbi.nlm.nih.gov/32223944 DOI: https://doi.org/10.1016/j.anai.2019.08.004

Thong BY, Lucas M, Kang HR, et al. Drug hypersensitivity reactions in Asia: regional issues and challenges. Asia Pac Allergy. 2020;10(1):e8. https://pubmed.ncbi.nlm.nih.gov/32099830 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016324 https://doi.org/10.5415/apallergy.2020.10.e8 DOI: https://doi.org/10.5415/apallergy.2020.10.e8

Guzman AI, Paliza AC. Epidemiology of severe cutaneous adverse drug reactions in a University Hospital: a five-year review. JMUST. 2018;2(1). https://doi.org/10.35460/2546-1621.2017-0031 DOI: https://doi.org/10.35460/2546-1621.2017-0031

Sidoroff A, Dunant A, Viboud C, et al. Risk factors for acute generalized exanthematous pustulosis (AGEP)-results of a multinational case-control study (EuroSCAR). Br J Dermatol. 2007;157(5):989-96.https://pubmed.ncbi.nlm.nih.gov/17854366 https://doi.org/10.1111/j.1365-2133.2007.08156.x DOI: https://doi.org/10.1111/j.1365-2133.2007.08156.x

Lee D, Kang JN, Hwang SH, et al. Acute generalized exanthematous pustulosis induced by parvovirus b19 infection. Ann Dermatol. 2014;26(3):399-400. https://pubmed.ncbi.nlm.nih.gov/24966644 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069655 https://doi.org/10.5021/ad.2014.26.3.399 DOI: https://doi.org/10.5021/ad.2014.26.3.399

Taguchi K, Oka M, Bito T, Nishigori C. Acute generalized exanthematous pustulosis induced by Mycoplasma pneumoniae infection. J Dermatol. 2016;43(1):113-4. https://pubmed.ncbi.nlm.nih.gov/26427049 https://doi.org/10.1111/1346-8138.13151 DOI: https://doi.org/10.1111/1346-8138.13151

Brockow K, Ardern-Jones MR, Mockenhaupt M, et al. EAACI position paper on how to classify cutaneous manifestations of drug hypersensitivity. Allergy. 2019;74(1):14-27. https://pubmed.ncbi.nlm.nih.gov/30028512 https://doi.org/10.1111/all.13562 DOI: https://doi.org/10.1111/all.13562

Feldmeyer L, Heidemeyer K, Yawalkar N. Acute generalized exanthematous pustulosis: pathogenesis, genetic background, clinical variants and therapy. Int J Mol Sci. 2016;17(8):1214. https://pubmed.ncbi.nlm.nih.gov/27472323 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000612 https://doi.org/10.3390/ijms17081214 DOI: https://doi.org/10.3390/ijms17081214

Parisi R, Shah H, Navarini AA, et al. Acute generalized exanthematous pustulosis: clinical features, differential diagnosis, and management. Am J Clin Dermatol. 2023;24(4):557-75. https://pubmed.ncbi.nlm.nih.gov/37156992 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10166469 https://doi.org/10.1007/s40257-023-00779-3 DOI: https://doi.org/10.1007/s40257-023-00779-3

Kabashima R, Sugita K, Sawada Y, Hino R, Nakamura M, Tokura Y. Increased circulating Th17 frequencies and serum IL-22 levels in patients with acute generalized exanthematous pustulosis. J Eur Acad Dermatol Venereol. 2011;25(4):485-8. https://pubmed.ncbi.nlm.nih.gov/20569282 https://doi.org/10.1111/j.1468-3083.2010.03771.x DOI: https://doi.org/10.1111/j.1468-3083.2010.03771.x

Schlapbach C, Zawodniak A, Irla N, et al. NKp46+ cells express granulysin in multiple cutaneous adverse drug reactions. Allergy. 2011;66(11):1469-76. 21819408. https://pubmed.ncbi.nlm.nih.gov/21819408 https://doi.org/10.1111/j.1398-9995.2011.02677.x DOI: https://doi.org/10.1111/j.1398-9995.2011.02677.x

De A, Das S, Sarda A, Pal D, Biswas P. Acute Generalised exanthematous pustulosis: an update. Indian J Dermatol. 2018;63(1):22-9. https://pubmed.ncbi.nlm.nih.gov/29527022 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838751 https://doi.org/10.4103/ijd.IJD_581_17 DOI: https://doi.org/10.4103/ijd.IJD_581_17

Moore MJ, Sathe NC, Ganipisetti VM. Acute generalized exanthematous pustulosis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan. 2023 May 3. https://pubmed.ncbi.nlm.nih.gov/37276304 Bookshelf ID: NBK592407

Barbaud A, Castagna J, Soria A. Skin tests in the work-up of cutaneous adverse drug reactions: a review and update. Contact Dermatitis. 2022;86(5):344-56. https://pubmed.ncbi.nlm.nih.gov/35122269 https://doi.org/10.1111/cod.14063 DOI: https://doi.org/10.1111/cod.14063

Szatkowski J, Schwartz RA. Acute generalized exanthematous pustulosis (AGEP): a review and update. J Am Acad Dermatol. 2015;73(5):843-8. https://pubmed.ncbi.nlm.nih.gov/26354880 https://doi.org/10.1016/j.jaad.2015.07.017 DOI: https://doi.org/10.1016/j.jaad.2015.07.017

Martinez-DelaTorre A, van Weenen, E, Kraus M, Weiler S, Feuerriegel S, Burden AM. A network analysis of drug combinations associated with acute generalized exanthematous pustulosis (AGEP). J. Clin. Med. 2021;10(19):4486. https://pubmed.ncbi.nlm.nih.gov/34640505 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509508 https://doi.org/10.3390/jcm10194486 DOI: https://doi.org/10.3390/jcm10194486

Tamir E, Wohl Y, Mashiah J, Brenner S. Acute generalized exanthematous pustulosis: a retrospective analysis showing a clear predilection for women. Skinmed. 2006;5(4):186-8. https://pubmed.ncbi.nlm.nih.gov/16855410 https://doi.org/10.1111/j.1540-9740.2006.05019.x DOI: https://doi.org/10.1111/j.1540-9740.2006.05019.x

Oh DAQ, Yeo w, Choo KJL, Pang SM, Oh CC, Lee HY. Acute generalized exanthematous pustulosis: Epidemiology, clinical course, and treatment outcomes of patients treated in an Asian academic medical center. https://pubmed.ncbi.nlm.nih.gov/34409363 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362292 https://doi.org/10.1016/j.jdin.2020.12.004 DOI: https://doi.org/10.1016/j.jdin.2020.12.004

Weiss M, Assier H, Hotz C, et al. Acute generalized exanthematous pustulosis: clinico‐biological profile and inducing drugs in 83 patients. J Eur Acad Dermatol Venereol. 2023;37(6):e776-8. https://pubmed.ncbi.nlm.nih.gov/36734481 https://doi.org/10.1111/jdv.18940 DOI: https://doi.org/10.1111/jdv.18940

Trubiano JA, Stone CA, Grayson ML, et al. The 3 Cs of antibiotic allergy-classification, cross-reactivity, and collaboration. J Allergy Clin Immunol Pract. 2017;5(6):1532-42. https://pubmed.ncbi.nlm.nih.gov/28843343 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681410 https://doi.org/10.1016/j.jaip.2017.06.017. Erratum in: J Allergy Clin Immunol Pract. 2018;6(1):323. Corregendum in: J Allergy Clin Immunol Pract. 2022;10(12):3346-7 DOI: https://doi.org/10.1016/j.jaip.2017.06.017

Khan DA, Banerji A, Bernstein JA, et al. Cephalosporin allergy: current understanding and future challenges. J Allergy Clin Immunol Pract. 2019;7(7):2105-14. https://pubmed.ncbi.nlm.nih.gov/31495420 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955146 https://doi.org/10.1016/j.jaip.2019.06.001 DOI: https://doi.org/10.1016/j.jaip.2019.06.001

Goh SJR, Tuomisto JEE, Purcell AW, Mifsud NA, Illing PT. The complexity of T cell-mediated penicillin hypersensitivity reactions. Allergy. 2021;76(1):150-67. https://pubmed.ncbi.nlm.nih.gov/32383256 https://doi.org/10.1111/all.14355 DOI: https://doi.org/10.1111/all.14355

Smeets TJ, Jessurun N, Härmark L, Kardaun SH. Clindamycin-induced acute generalised exanthematous pustulosis: five cases and a review of the literature. Neth J Med. 2016 Dec;74(10):421-8. https://pubmed.ncbi.nlm.nih.gov/27966434

Alniemi DT, Wetter DA, Bridges AG, et al. Acute generalized exanthematous pustulosis: clinical characteristics, etiologic associations, treatments, and outcomes in a series of 28 patients at Mayo Clinic, 1996-2013. Int J Dermatol. 2017;56(4):405-14. https://pubmed.ncbi.nlm.nih.gov/28084022 https://doi.org/10.1111/ijd.13434 DOI: https://doi.org/10.1111/ijd.13434

Stadler PC, Oschmann A, Kerl-French K, et al. Acute generalized exanthematous pustulosis: Clinical characteristics, pathogenesis, and management. Dermatology. 2023;239(4):328–33. https://pubmed.ncbi.nlm.nih.gov/36702114 https://doi.org/10.1159/000529218 DOI: https://doi.org/10.1159/000529218

Creadore A, Desai S, Alloo A, et al. Clinical characteristics, disease course, and outcomes of patients with acute generalized exanthematous pustulosis in the US. JAMA Dermatol. 2022;158(2):176-83. https://pubmed.ncbi.nlm.nih.gov/34985493 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733866 https://doi.org/10.1001/jamadermatol.2021.5390 DOI: https://doi.org/10.1001/jamadermatol.2021.5390

Hotz C, Valeyrie-Allanore L, Haddad C, et al. Systemic involvement of acute generalized exanthematous pustulosis: a retrospective study on 58 patients. Br J Dermatol. 2013;169(6):1223-32. https://pubmed.ncbi.nlm.nih.gov/23855377 https://doi.org/10.1111/bjd.12502 DOI: https://doi.org/10.1111/bjd.12502

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Published

07/26/2024

How to Cite

Doria, I. T., Ang, M. C., & Orcasitas, J. (2024). Acute Generalized Exanthematous Pustulosis (AGEP) Unveiled: A Tertiary Hospital Case Series on Antibiotic-Induced Adverse Drug Reactions in Davao City, Philippines. Philippine Journal of Allergy, Asthma and Immunology, 24(1). https://doi.org/10.70552/pjaai.24.1.9871

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Case Reports/Series