key: cord-347725-w03ef08b
authors: Schwartz, Robert A.; Janniger, Camila K.
title: Generalized pustular figurate erythema: A newly delineated severe cutaneous drug reaction linked with hydroxychloroquine
date: 2020-04-16
journal: Dermatol Ther
DOI: 10.1111/dth.13380
sha: 
doc_id: 347725
cord_uid: w03ef08b

A severe cutaneous drug reaction resembling acute generalized exanthematous pustulosis resulting from ingestion of hydroxychloroquine has been documented. It is distinguishable by its longer incubation period, more varied morphology with initially urticarial and later targetoid and arcuate plaques, recalcitrance to therapy and longer duration. Given the anticipated surge in the use of hydroxychloroquine due to its reported benefits in those with coronavirus disease 2019, specific recognition of this entity is pivotal. We delineate it as generalized pustular figurate erythema.

Severe potentially life-threatening cutaneous drug reactions are a huge concern, most specifically acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), generalized bullous fixed drug eruption, and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. 1-8 AGEP was originally misclassified as a form of pustular psoriasis; however, it is not associated with psoriasis. 9 AGEP is a severe cutaneous adverse reaction characterized by the rapid development of sterile nonfollicular pustules on an erythematous base. 2, 3 It is usually attributed to drugs, antibiotics being the most common, with an onset typically within 48 hours of ingestion, often with an acute onset of fever and leukocytosis.

There is another rare acute severe generalized disorder, one usually characterized as AGEP, but with an onset of 2 to 3 weeks (range 4-27 days) rather 1 day after initial drug exposure, typically due to hydroxychloroquine, more severe, more difficult to treat, with a longer duration, and recognized as likely having a different pathogenic mechanism from the usual type of AGEP. 10 This perplexing disorder has been described as atypical AGEP, 11,12 recalcitrant AGEP, 13,14 pustular DRESS syndrome, 15 AGEP/SJS overlap, 16 AGEP/TEN overlap, 17, 18 and Sweet's syndrome following hydroxychloroquine. [19] [20] [21] We delineate and highlight it as generalized pustular figurate erythema (GPFE). Some cutaneous sloughing and excoriations may also be observed with blisters or erosions occasionally noted. There may be little or no mucosal involvement. Skin biopsy specimens may initially show mainly the changes of urticaria, but evolve into subcorneal and/or intraepidermal neutrophilic pustules sometimes with mild focal

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