Clinical Characteristics, Disease Course, and Outcomes of Patients With Acute Generalized Exanthematous Pustulosis in the US

Abstract

IMPORTANCEAcute generalized exanthematous pustulosis (AGEP) is a rare, severe cutaneous adverse reaction associated with systemic complications. Currently available data are largely limited to small retrospective case series.OBJECTIVE To describe the clinical characteristics, disease course, and outcomes of a heterogeneous group of patients with AGEP across the US. DESIGN, SETTING, AND PARTICIPANTSA retrospective review of a case series of patients was conducted from January 1, 2000, through July 31, 2020. All 340 included cases throughout 10 academic health systems in the US were scored retrospectively using the EuroSCAR scoring system, and patients with a score corresponding to probable or definite AGEP and aged 18 years or older were included. MAIN OUTCOMES AND MEASURESPatient demographic characteristics, clinical course, suspected causative agent, treatment, and short-and long-term outcomes.RESULTS Most of the 340 included patients were women (214 [62.9%]), White (206 [60.6%]), and non-Hispanic (239 [70.3%]); mean (SD) age was 57.8 (17.4) years. A total of 154 of 310 patients (49.7%) had a temperature greater than or equal to 38.0 °C that lasted for a median of 2 (IQR, 1-4) days. Of 309 patients, 263 (85.1%) developed absolute neutrophilia and 161 patients (52.1%) developed either absolute or relative eosinophilia. Suspected causes of AGEP were medications (291 [85.6%]), intravenous contrast agents (7 [2.1%]), infection (3 [0.9%]), or unknown (39 [11.5%]). In 151 cases in which a single medication was identified, 63 (41.7%) were β-lactam antimicrobials, 51 (33.8%) were non-β-lactam antimicrobials, 9 (6.0%) were anticonvulsants, and 5 (3.3%) were calcium channel blockers. The median time from medication initiation to AGEP start date was 3 (IQR, 1-9) days. Twenty-five of 298 patients (8.4%) had an acute elevation of aspartate aminotransferase and alanine aminotransferase levels, with a peak at 6 (IQR, 3-9) days. Twenty-five of 319 patients (7.8%) experienced acute kidney insufficiency, with the median time to peak creatinine level being 4 (IQR, 2-5) days after the AGEP start date. Treatments included topical corticosteroids (277 [81.5%], either alone or in combination), systemic corticosteroids (109 [32.1%]), cyclosporine (10 [2.9%]), or supportive care only (36 [10.6%]). All-cause mortality within 30 days was 3.5% (n = 12), none of which was suspected to be due to AGEP.CONCLUSIONS AND RELEVANCE This retrospective case series evaluation of 340 patients, the largest known study cohort to date, suggests that AGEP onset is acute, is usually triggered by recent exposure to an antimicrobial, may be associated with liver or kidney complications in a minority of patients, and that discontinuation of the triggering treatment may lead to improvement or resolution.

Acute generalized exanthematous pustulosis caused by gemcitabine after nivolumab in metastatic lung adenocarcinoma followed by a dramatic tumor response: A case report

“…As for the timeline, the implication of gemcitabine seems more likely than nivolumab. Creadore et al 6 found a median time from medication initiation to AGEP occurrence of 3 days (IQR, 1–9) in a large, retrospective, population of patients ( n = 340). Furthermore, AGEP induced by gemcitabine has already been reported 7 with an interval of four days between gemcitabine infusion and onset of AGEP.…”

Drug rash with eosinophilia and systemic symptoms syndrome masquerading as a lymphoproliferative disorder in a young adult on immunosuppressive therapy for rheumatoid arthritis: a case report

“…AGEP is distinguished from DRESS syndrome by its nonfollicular small pustules surrounded by edema and erythema [ 5 , 15 ]. This, coupled with epidermal acanthosis, spongiosis, and microvesicle and pustule formation on biopsy, makes the diagnosis [ 5 , 15 ].…”

“…AGEP is distinguished from DRESS syndrome by its nonfollicular small pustules surrounded by edema and erythema [ 5 , 15 ]. This, coupled with epidermal acanthosis, spongiosis, and microvesicle and pustule formation on biopsy, makes the diagnosis [ 5 , 15 ]. Immunophenotypical features identify DRESS syndrome: cutaneous effector lymphocytes represent a large quantity of the polyclonal CD8 + granzyme B + T lymphocytes [ 15 , 16 ].…”

“…Immunophenotypical features identify DRESS syndrome: cutaneous effector lymphocytes represent a large quantity of the polyclonal CD8 + granzyme B + T lymphocytes [ 15 , 16 ]. AGEP and DRESS syndrome are managed by withdrawal of the culprit drug and initiation of steroids [ 5 , 15 , 16 ]. Lupus’ heterogeneous presentation requires satisfaction of 4/11 American College of Rheumatology criteria [ 6 ].…”

“…Differentials to consider alongside this condition include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), systemic lupus erythematosus, lymphomas, hypereosinophilic syndromes, and Kikuchi disease [5][6][7][8][9]. In this case, DRESS syndrome masqueraded as a lymphoproliferative disorder.…”