Generalized Bullous Drug Eruption to Faropenem - Hitherto Unreported.

Sir,

A 45-year-old homemaker presented to us with pruritic bullous eruption over her body for 2 days. A meticulous history taking revealed that the lesions appeared 24 h after consuming faropenem, an oral antibiotic prescribed to her by her physician for an acute attack of urinary tract infection. She could not recall any instance of the intake of other beta-lactam group of antibiotics in the recent past. On examination, there were multiple flaccid bullae of variable sizes ranging from 2 to 5 cm in diameter surrounded by erythema and containing clear fluid, which were distributed over the palms and soles, trunk, and extremities [Figure 1a and b]. Oral and genital mucosae were found to be involved with mild erosions [Figure 1c and d]. Her face showed mild erythema, erosions over the lips, and perioral crusting [Figure 1c and d]. Systemic examination was unremarkable. Histopathological examination of a skin lesion showed the presence of intraepidermal spongiosis with scattered necrotic keratinocytes. There was a split in the region of basement membrane leading to the formation of a cleft in the dermoepidermal junction without any acantholytic cell [Figures 2 and 3]. Pigment was found to be scattered in the cleft as well as in the upper dermis [Figure 3]. The upper dermal mild perivascular infiltrate consisted of mostly lymphocytes with few eosinophils [Figure 4]. Direct immunofluorescence (DIF) test was found to be negative. The patient showed a remarkable improvement after being treated with systemic corticosteroids (injection dexamethasone 8 mg given intravenously once daily for 3 days and thereafter, oral prednisolone 40 mg/day for 7 days and gradually tapered over the next 2 weeks), and on follow-up, her skin showed minimal postinflammatory hyperpigmentation. Based on the clinical and histopathological features, a diagnosis of generalized bullous drug reaction was made. According to the causality assessment scales proposed by the World Health Organization such as the Collaborating Centre for International Drug Monitoring, the Uppsala Monitoring Centre, and the Naranjo Adverse Drug Reaction Probability Scale, the causal role of faropenem in this case was “probable.”

Figure 1

(a) Flaccid bullae over both forearms. (b) Flaccid bullae over the thigh. (c) Erosion over the lips with perioral crusting. (d) Erosion over hard palate and buccal mucosa

Figure 2

Split along dermoepidermal junction (H and E, ×40)

Figure 3

Intraepidermal spongiosis with necrotic keratinocytes and pigment scattered in the cleft (H and E, ×100)

Figure 4

Upper dermal perivascular infiltrate of lymphocytes and eosinophils (indicated by arrow) (H and E, ×400)

Faropenem is a new generation broad spectrum oral beta-lactam antibiotic of penem group used for upper- and lower-respiratory tracts and genitourinary infections.[1] Although diarrhea, nausea, and vomiting are the frequently reported side effects, adverse cutaneous reactions are extremely rare. There are a few reports of acute generalized exanthematous pustulosis caused by faropenem and meropenem.[23] However, bullous skin eruptions have not been reported, yet the various types of bullous drug reactions are bullous fixed drug reactions (FDRs), Stevens–Johnson syndrome and toxic epidermal necrolysis, drug-induced autoimmune vesiculobullous disorders, pseudoporphyria, and drug-induced coma blisters.[4] There are isolated reports of cell poor subepidermal blistering due to fluvoxamine, e-aminocaproic acid, and sibutramine.[5] The closest differential diagnoses in this case were bullous FDR and drug-induced bullous pemphigoid. The histopathological features were not conforming to that of FDR where necrotic keratinocytes are numerous with prominent interface dermatitis and plenty of melanophages in the upper dermis.[6] Moreover, a minimal postinflammatory hyperpigmentation in this patient when seen on subsequent follow-up was not in favor of a diagnosis of bullous FDR. A negative DIF result ruled out the possibility of bullous pemphigoid.

Thus, faropenem, a novel broad spectrum antibiotic which is widely used nowadays by physicians, can give rise to adverse cutaneous drug reactions such as generalized bullous eruptions as was reported in our case.

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Conflicts of interest

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