Cefoperazone-sulbactam-induced acute localized exanthematous pustulosis: A rare adverse drug reaction

INTRODUCTION

Acute localized exanthematous pustulosis (ALEP) is an uncommon, localized variant of acute generalized exanthematous pustulosis (AGEP), marked by the rapid appearance of sterile pustules on an edematous and erythematous base.^[1] It is an adverse drug reaction, most frequently associated with antibiotics, particularly beta-lactams and macrolides. Although AGEP is well documented, ALEP remains underrecognized and may be misdiagnosed as other pustular dermatoses, such as impetigo, miliaria pustulosa, folliculitis, pustular psoriasis, or candidiasis.

We report a case of a young female who developed multiple clustered pustules on her face and ears following treatment with cefoperazone–sulbactam.

CASE REPORT

A 28-year-old female presented with multiple discrete and confluent pus-filled lesions on her face, accompanied by a burning sensation [Figures 1 and 2]. There were no episodes of fever, and no similar lesions were observed elsewhere on her body. She had been administered cefoperazonesulbactam and metronidazole injections for 2 days to treat a surgical site infection.

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Figure 1:

Frontal view showing multiple discrete and confluent pustules on an erythematous and edematous background, affecting the eyelids and sides of the nose.

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Figure 2:

Lateral view of the right side of the face depicting grouped pustules on an erythematous base, primarily involving the cheek, ala of the nose, and ear lobule.

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Examination revealed multiple non-follicular pustules on a red, edematous base primarily affecting her eyelids, nose, and ear lobes. The initial differential diagnoses included a localized form of AGEP, localized pustular psoriasis, candidiasis, miliaria pustulosa, and bullous impetigo.

Gram staining and potassium hydroxide examination were negative, ruling out impetigo and candidiasis. Miliaria pustulosa usually has a gradual onset and affects flexures and the trunk. However, in our case, the lesions were confined to the face and appeared suddenly after initiating antibiotics, making miliaria pustulosa an unlikely diagnosis. She had no family or personal history of psoriasis. Since she had received metronidazole after her cesarean section without experiencing any adverse reactions, a drug reaction to metronidazole was also unlikely. As the pustules were sterile and appeared within 2 days of initiating antibiotic therapy, a diagnosis of ALEP secondary to cefoperazone–sulbactam was made.

The antibiotics were discontinued, and a change in antibiotics was recommended. She was treated with saline compresses and a topical steroid-antibiotic cream for 5 days and showed a significant improvement at follow-up [Figure 3]. Since this was a localized form of a severe cutaneous drug reaction, we did not attempt rechallenge with cefoperazone–sulbactam to avoid the risk of a more serious response.

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Figure 3:

Post-treatment frontal view showing significant resolution of pustules and erythema after discontinuation of the suspected drugs and administration of topical corticosteroids.

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DISCUSSION

ALEP is a localized variant of AGEP, a severe skin reaction that typically occurs shortly after drug administration. ALEP is marked by the development of 1-2 mm sterile pustules, typically developing within 3–5 days after initiation of the offending drug, and generally subsides quickly following its withdrawal.^[2] Patients may experience fever, leukocytosis, itching, or a burning sensation. In our patient, pustules developed within 2 days of starting antibiotic therapy.

In over 80% of cases, ALEP is drug-induced, with antibiotics, particularly beta-lactams and macrolides, being the most common triggers.^[3] However, it can also be caused by bacterial, viral, or parasitic infections.^[4] Less than 30 cases of ALEP have been reported so far. The medications implicated in these cases include antibiotics like amoxicillin, ampicillin, amoxicillin–clavulanic acid, ceftibuten, cefoperazone– sulbactam, clindamycin, cotrimoxazole, fosfomycin, levofloxacin, piperacillin–tazobactam, and vancomycin; nonsteroidal anti-inflammatory drugs like paracetamol, ibuprofen, diclofenac, and flurbiprofen; and others like allopurinol, docetaxel, sorafenib, lamotrigine, finasteride, and minoxidil (topical).^[5] Recently, the Indian Pharmacopoeia Commission issued a notification identifying AGEP as a possible adverse drug reaction to metronidazole.^[6] In this case, the patient had previously taken metronidazole without any adverse reaction; therefore, a reaction to metronidazole was ruled out.

The underlying mechanism is believed to be a type IV hypersensitivity reaction. After exposure to the drug, antigen-presenting cells present the antigen via major histocompatibility complex molecules, activating specific CD4 and CD8 T cells.^[7] These cells proliferate and migrate to the skin, where CD8 T cells induce keratinocyte apoptosis through perforin/granzyme B and Fas ligand pathways, causing tissue damage and vesicle formation. In addition, the release of C-X-C motif chemokine ligand 8 (CXCL8), a strong neutrophilic cytokine, attracts neutrophils to the vesicles, leading to the formation of sterile pustules.^[8]

The histological features of AGEP and ALEP include spongiform, subcorneal pustules, along with an edematous papillary dermis. Perivascular infiltrates consisting of neutrophils and a few eosinophils are observed, and necrotic keratinocytes along with leukocytoclastic vasculitis may also be present.^[4]

ALEP is a self-resolving condition, and the main approach to treatment involves stopping the suspected medication, which typically leads to symptom relief within a few days. In cases of persistent pruritus and inflammation, supportive care with topical or oral corticosteroids may be considered. Stopping the medication arrested the progression of lesions in our patient. Topical steroids were administered for 5 days to manage the erythema and edema. Hopkins et al. described a case of ALEP triggered by lamotrigine, where rechallenging with the drug led to a widespread eruption, highlighting the critical need to avoid re-exposure to the offending medication in ALEP cases.^[9]

CONCLUSION

ALEP is a rare and often underrecognized condition that can present as an acute pustular eruption, particularly in patients receiving antibiotics. This case underscores the importance of considering ALEP in the differential diagnosis of acute pustular eruptions, especially in the context of recent drug exposure. Effective treatment relies on early detection and immediate discontinuation of the suspected drug. Maintaining clinical awareness of ALEP ensures timely diagnosis and appropriate treatment, minimizing unnecessary interventions and patient discomfort.