Generalized Pustular Figurate Erythema in Patients with COVID-19 Treated with Hydroxychloroquine: A Systematic Review.

severe distinctive cutaneous drug reaction, generalized pustular figurate erythema, closely linked with hydroxychloroquine (HCQ), has been documented. It is distinguishable from AGEP by its longer incubation, more varied morphology (initially urticarial and later targetoid, arcuate plaques), recalcitrance to therapy and longer disease course. Aim of the article is to review the recognized entity associated with ingestion of hydroxychloroquine in patients infected with COVID-19. A systematic review using electronic search was performed. Inclusion criteria: n patients with COVID-19 demonstrated by PCR, with typical clinical features of AGEP/GPFE or atypical features associated with typical histopathology. We used the (JBI) Critical Appraisal Checklist for Case Reports for the qualitive assessment. We included 13 publications. Their overall quality was good to moderate. Only 27.3% of the patients had a severe COVID-19 course. The mean lag time between trigger exposure and rash development was 24 days. Only 15.38% of the reported AGEP were clinically typical, while the remaining 69.23 % were suggestive of GPFE. Unfortunately, 2 patients died secondary to massive pulmonary embolism. In COVID-19 infection, we suggest reconsidering treating established COVID-19 empirically with HCQ, as both triggers can augment the subsequent cytokine storm, inducing a severe drug reaction and possibly increasing the risk of thrombo-embolic events.

What to expect when AGEP is induced by terbinafine? Case report and critical review of the literature.

BACKGROUND: Acute Generalised Exanthematous Pustulosis (AGEP) is a rash with multiple sterile intraepidermal or subcorneal non-follicular pustules on edematous papules, with a sudden development and rapid evolution, triggered by drugs, vaccination, insect bites, exposure to mercury, and allergens. OBJECTIVES AND METHODS: We describe a female patient who developed extensive and abnormally prolonged AGEP following exposure to terbinafine and SARS-CoV vaccine. A detailed review of terbinafine-induced-AGEP cases was performed, with the aim of evaluating if the AGEP criteria would follow a different pattern when the disease is triggered by this drug. A PubMed search helped retrieve all terbinafine-induced AGEP case reports. AGEP-specific Sideroff criteria were analysed in terbinafine-induced cases and compared to other trigger causes. CONCLUSIONS: When the AGEP causative drug was terbinafine, a delay in recovery was observed, compared to the existing AGEP criteria when other causes are considered. Terbinafine frequently leads to delayed resolution AGEP probably due to the presence of the drug in the skin for several weeks after exposure, even after discontinuation, and the disease severity may be potentialised by additional factors such as concomitant viral infections or vaccination.

Acute generalized exanthematous pustulosis following COVID19 infection: an additional case report from Tunisia (preprint)

Coronavirus disease-19 (COVID-19) is an emerging global pandemic. Since its emergence, the COVID-19-associated cutaneous manifestations have been increasingly reported, and they are extremely polymorphic.We report a case of acute generalized exanthematous pustulosis (AGEP) developed in a Tunisian adult, a few days after recovery from severe COVID-19 infection

Acute generalized exanthematous pustulosis following treatment with remdesivir in a patient with SARS-CoV-2 infection, a case report (preprint)

We hereby, present the first case of Acute generalized exanthematous pustulosis (AGEP) following treatment with remdesivir in a patient with COVID-19 without hydroxychloroquine use which serves as a reminder for considering remdesivir as a possible causative agent when dealing with AGEP presentation in COVID patients.

COVID-19 presenting as acute generalized exanthematous pustulosis associated with multiorgan dysfunction in a 44-year-old female patient.

Acute generalised exanthematous pustulosis (AGEP) is an unusual cutaneous reaction, most often related with a hypersensitivity reaction to commonly used drugs. It is characterized by an abrupt onset of a pustular rash within hours or days after drug exposure and usually resolves spontaneously within 1-2 weeks after drug discontinuation. Some cases associated with systemic involvement and shock have been reported. We present the case of a severe AGEP, manifesting in association with systemic involvement and haemodynamic instability resulting in shock and multiorgan dysfunction in an adult female patient diagnosed with COVID-19 infection. There were no identifiable associated drugs, and the patient was not initiated on antimalarial drugs. Our patient improved rapidly, both hemodynamically and dermatologically with no directed therapy.

Acute Generalized Exanthematous Pustulosis (AGEP) in 12 Patients Treated for SARS-CoV-2 Positive Pneumonia.

ABSTRACT: The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading throughout the world. The study describes 12 patients with SARS-CoV-2 pneumonia, who developed an acute erythematous rash with nonfollicular pinhead-sized pustules, without mucosal involvement. The clinical differential diagnosis was viral rash, acute generalized exanthematous pustulosis (AGEP), or multiform erythema. computed tomography with a diagnosis of interstitial pneumonia and a respiratory tract sample positive for SARS-CoV-2 in a reverse transcriptase polymerase chain reaction assay. Patients had signs of respiratory distress and were treated with hydroxychloroquine, darunavir, ritonavir, heparin, ceftriaxone, and azithromycin. Punch biopsies showed subcorneal pustules typical of AGEP. Dermal microvascular injury and thrombosis as described in skin damage by SARS-CoV-2 infection was not observed. The direct immunofluorescence for IgG, IgA, IgM, and C3 was negative in 8 patients investigated. A polymerase chain reaction for RNA SARS-CoV-2 performed on frozen skin was negative in 5 of 6 patients. Most of our patients were treated with systemic corticosteroids. After some days (4-10), the diffuse erythema and pustules had improved. AGEP is classified as a severe cutaneous adverse reaction, provoked by drugs and acute infections. Characteristically, removal of the offending agent leads to spontaneous resolution typically in less than 15 days. The recognition of AGEP is important, in order to avoid confusion with a systemic infection and consequently to avoid incorrect treatment. Cutaneous adverse reactions to drugs are common and are major health problems worldwide causing considerable costs for health care systems. We suggest that in the patients with AGEP during SARS-CoV-2 pneumonia, viral infection is a risk factor for developing drug reaction.