Acute generalized exanthematous pustulosis due to meropenem: An unusual side effect of a commonly used drug.

Sir,

Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous reaction pattern related to drug intake in most cases. This condition was first described by Baker and Ryan in 1968.[1]

The estimated incidence of AGEP is approximately 1-5 cases per million per year.[2] AGEP is mostly associated with antibiotics from the β-lactam and macrolide group and calcium channel blockers.

A 11-year-old boy admitted to the medical ward presented with the complaint of productive cough and high fever. On admission, he was diagnosed with chest infection and started with intravenous meropenem along with intravenous fluids and moist oxygen inhalation. Within 24 hours he had an erythematous rash on the face and flexural areas accompanied by a burning sensation that spread to adjacent areas. Soon, hundreds of tiny pustules arose over the rash. There was no past history suggestive of psoriasis, past history suggestive of medical comorbidities or drug allergies.

Examination revealed an erythematous-edematous eruption over the face [Figure 1a], trunk and extremities [Figure 1b] studded with hundreds of small, discrete, and nonfollicular pustules [Figure 1c]. The patient had high fever (38–39°C). The hair, nails, and mucosal surfaces were normal. Systemic examination revealed no other abnormality. There was no significant lymphadenopathy.

Figure 1

(a–c) Pustular eruption with underlying erythema on the face, upper shoulders, axillae, upper trunk, lower trunk, and inguinal regions

Blood examination revealed leukocytosis (19.3 × 109/L) with neutrophilia (14.25 × 109/L), a high erythrocyte sedimentation rate (90 mm/1st h) and elevated C-reactive protein. Aspartate transaminase level was slightly elevated (86 IU/L, normal range: 10–34 IU/L). The biochemical parameters including bilirubin, Na+, K+, HCO3−, and Cl− were within the normal range. Smear from the pustules revealed numerous neutrophils. Bacterial and fungal cultures of the pus were negative.

Histopathological examination of lesional skin revealed subcorneal neutrophil-rich pustules [Figure 2], perivascular infiltrate of lymphocytes and neutrophils, eosinophils, as well as dermal edema.

Figure 2

Subcorneal neutrophil-rich pustules, perivascular infiltrate of lymphocytes and neutrophils, as well as dermal edema (×400, H and E)

Considering the history, clinical features, and investigations including skin biopsy, and previous reports[3] of AGEP having been caused with meropenem, we diagnosed the patient to be having acute generalized exanthematous pustulosis due to meropenem.

Meropenem was discontinued; intravenous dexamethasone was administered in a dose of 3 mg, 6 hourly for five days. Emollient was applied on the rash, which subsided rapidly within two weeks with desquamation.

Hypersensitivity reactions are known adverse effects of meropenem. In the first described case[3] of AGEP due to meropenem, the patient had septicemia and was on piperacillin, ceftazidime, and meropenem. The beta-lactam structure shared by the three antibiotics was thought be the cause of AGEP.

The adverse drug reaction scale by Naranjo et al.[4] (used to estimate the probability of a drug causing an adverse clinical event) estimated a ‘probable’ result since our patient's AGEP:

followed a reasonable temporal sequence after the suspected drug,

followed a recognized response to the suspected drug,

was confirmed by withdrawal but not by exposure to the drug, and

could not be reasonably explained by the known characteristics of the patient's clinical state.

Literature search revealed only two similar case reports. The aim of this correspondence was not only to emphasize the recognition of this uncommon side effect of a commonly used drug, but also to stress the need to thoroughly investigate all cases of drug reaction.

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Conflicts of interest

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