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 The fixed drug eruptions: an update emphasizing the potentially lethal generalized bullous fixed drug eruption Acute generalized exanthematous pustulosis: a review and update Childhood acute generalized exanthematous pustulosis induced by oral ketoconazole Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome: part I: clinical perspectives DRESS syndrome: part II: management and therapeutics Toxic epidermal necrolysis. Part I. introduction, history, classification, clinical features, systemic manifestations, etiology, and immunopathogenesis Toxic epidermal necrolysis. Part II. Prognosis, sequelae, diagnosis, differential diagnosis, prevention, and treatment Erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis Generalized pustular psoriasis: a review and update on treatment Risk factors for acute generalized exanthematous pustulosis (AGEP)-results of a multinational case-control study (EuroSCAR) Acute generalized exanthematous pustulosis induced by hydroxychloroquine: a case with atypical clinical presentation Prolonged pustular eruption from hydroxychloroquine: an unusual case of acute generalized exanthematous pustulosis Successful treatment of hydroxychloroquine-induced recalcitrant acute generalized exanthematous pustulosis with cyclosporine: case report and literature review A case of recalcitrant acute generalized exanthematous pustulosis with Sjogren's syndrome: successfully treated with low-dose cyclosporine Pustular DRESS syndrome secondary to hydroxychloroquine with EBV reactivation AGEP overlap induced by hydroxychloroquine: a case report and literature review Acute generalized exanthematous pustulosis simulating toxic epidermal necrolysis: case presentation and literature review Acute generalized exanthematous pustulosis and toxic epidermal necrolysis induced by hydroxychloroquine Sweet's syndrome following therapy with hydroxychloroquine in a patient affected with elderly-onset primary Sjogren's syndrome Drug-induced Sweet's syndrome related to hydroxychloroquine: about 2 cases Drug-induced neutrophilic dermatoses Chloroquine for the 2019 novel coronavirus SARS-CoV-2 The trial of chloroquine in the treatment of Corona Virus Disease 2019 (COVID-19) and its research progress in forensic toxicology Cyclosporine for corticosteroidrefractory acute generalized exanthematous pustulosis due to Hydroxychloroquine-induced GPFE with numerous nonfollicular pustules atop atypical targetoid plaques. GPFE, generalized pustular figurate erythema hydroxychloroquine Acute generalized exanthematous pustulosis induced by hydroxychloroquine successfully treated with etretinate A case of hydroxychloroquine induced acute generalized exanthematous pustulosis confirmed by accidental oral provocation Generalized pustular figurate erythema: A newly delineated severe cutaneous drug reaction linked with hydroxychloroquine