Case report :
A 58 year-old male patient, with a medical history of chronic
obstructive pulmonary disease (COPD), diabetes type 2 and hypertension
presented to the emergency department with shortness of breath and
fever, on December 19, 2020. A SARS-CoV-2 RNA nasopharyngeal
swab, followed by real-time reverse transcription polymerase chain
reaction (RT-PCR) and a chest computerized tomography scan, confirmed a
severe case of COVID19. The patient was admitted to a specialized
department for 2 weeks and treated with different antibiotics, including
cefotaxime, imipenem/cilastatin, and teicoplanin.
The patient also received dexamethasone phosphate sodium,
enoxaparin sodium, famotidine, vitamin C, and supplemental oxygen.
According to the latest treatment guidelines, hydroxychloroquine was not
used of (it was massively used off-label for COVID19 treatment during
the first wave of the pandemic).
Seven days after total recovery and withdrawal of all antibiotics,
systemic steroids, and famotidine, and only 2 days after withdrawal of
enoxaparin and vitamin C, the patient developed a pustular eruption
on an erythematous base that began in intertriginous areas
(retroauricular folds) and rapidly affected more than 50% of the body
surface area (Fig 1). The patient was febrile and there was no mucous
membrane involvement. Laboratory test revealed leukocytosis with marked
neutrophilia. The renal and liver functions were normal. Repeated blood
and pustule bacterial culture yielded negative results. Viral serology
(EBV, CMV, and parvoB19) was negative, and a new SARS-CoV-2 RNA
nasopharyngeal swab, followed by RT-PCR, was negative. Skin biopsy
revealed acanthosis and multiple
spongiform subcorneal pustules. Edema and perivascular lymphocytic
infiltration were observed in the dermis (Fig 2).
Based on the EUROSCAR criteria, our patient had a score of
12, indicating a definite diagnosis of AGEP (typical pustule (+2),
typical erythema (+2), typical distribution of AGEP (+2), postpustular
desquamation (+1), no mucosal involvement (0), acute onset <
10 days (0), resolution < 15 days (0), no fever (+1), no
polymorphonuclear neutrophils > 7000
(+1), and spongiform subcorneal pustule with papillary edema (+3)). The
patient was treated with high-level topical corticosteroids, which
resulted in progressive resolution of exanthema within a few days. The
patient also received enoxaparin sodium without aggravation of the rash.
The patient continued his chronic medication without any relapse of
AGEP, one year later.
Our case raises a dilemma regarding whether such cutaneous lesions are
related to COVID-19 or its treatment.
The relationship between AGEP and SARS‐CoV‐2 infection or its treatment
remains poorly understood [4-14]. AGEP generally occurs within
48 hours of treatment initiation [3]. Almost all reported cases of
AGEP following COVID-19 were associated with hydroxychloroquine and were
characterized by a long incubation period of up to two-three weeks
[4,9]. Only a few reported cases of AGEP following COVID-19 were
related to other drugs such as cefepime, cefditoren, and cefrtiaxone,
which occurred approximately seven7 days after starting the antibiotic
[10, 11, 13]. Moreover, some authors have suggested a possible
association between COVID-19 and late-onset AGEP (up to three months
after COVID-19 recovery), based on a few reports of AGEP due to viral
infections [12-14]. In fact, it has been reported some degree of
similarity between inflammatory cytokine profile alterations during
COVID-19 and AGEP [15]. Therefore, due to COVID-19 impact on the
immune system, this infection may induce AGEP-like eruptions [13,
14]. In our patient, the eruption appeared seven days after withdrawal
of all antibiotics, systemic steroids, and famotidine and two days after
enoxaparin withdrawal. Additionall , enoxaparin was reintroduced without
clinical aggravation. Therefore, we hypothesized that patient’s vigorous
immune response to COVID-19 may have triggered an unusual delay-onset
reaction to one of the prescribed drugs or a late-onset skin
manifestation mimicking AGEP in association with COVID-19.