Unusual cause of bilateral periocular ulceronecrotic wound: Tetracaine abuse-associated bullous drug eruption

A 51-year-old man with no significant past medical history presented to the emergency department with acute onset of bilateral periorbital edema, redness and pain that had been initiated last week and worsened on the day of admission. The patient had a history of opium addiction. The patient's occupation was a welder, and he was using self-prescribed topical tetracaine hydrochloride 0.5% repeatedly in both eyes and periocular area to reduce pain caused by minor eye injuries during welding from last year. He had a history of hospitalization due to the same symptoms 6 months ago that was treated with systemic antibiotics and acyclovir with a possible diagnosis of herpes zoster ophthalmicus and secondary bacterial periorbital cellulitis. On clinical examination, bilateral periocular hemorrhagic bulla and crusted vesiculobullous lesions associated with superficial cutaneous necrosis complicated with periorbital cellulitis were evident (Figure 1A). There was purulent discharge from the ulceronecrotic wound. Bilateral corneal punctate epithelial erosion, conjunctival hyperemia and severe chemosis were also observed, while other ocular examinations, including intraocular pressure and fundus evaluation, were unremarkable. Extraocular motion and pupils were within normal limits. Best-corrected visual acuity was measured as 20/50 in both eyes. Staphylococcus aureus was grown from skin discharge and debris. An axial orbital and paranasal sinus computed tomography (CT) scan demonstrated dermal thickening and subcutaneous edema around both orbits, without significant sinus involvement or abscess formation (Figure 2) ruling out other potential causes such as orbital cellulitis or necrotizing fasciitis. With the first clinical impression of periorbital cellulitis, intravenous antibiotic (ceftazidime 1 gr every 8 h) was administered. After 48 h of starting systemic antibiotic and discontinuance of topical tetracaine hydrochloride, the patient's condition improved gradually with a significant reduction in periorbital edema (Figure 1B). Regarding the second episode of symptoms, a subsequent skin biopsy was done. Histopathological evaluation revealed massive epidermal necrosis and replacement by dense neutrophilic infiltration, cellular debris and fibrin deposition, compatible with epidermal ulceration. Also, there was a dermo-epidermal detachment and a large area of basal layer degeneration associated with the existence of a few dyskeratotic cells. Dense lymphocytic infiltration in the dermis with extension to around hair follicles was noted (Figure 3). Regarding the clinical and histopathological correlation, the diagnosis of bullous drug eruption, possibly attributable to topical tetracaine abuse, was made. After the control of the signs and symptoms of cellulitis, the patient was recommended to use topical sterile ophthalmic betamethasone 0.1% ointment daily for 1 week and topical pimecrolimus 1% for 2 months (Figure 4). Bullous drug eruptions (BDEs) are cutaneous adverse reactions characterized by the presentation of flaccid or tens fluid-filled blisters or bullae. Blistering may be localized vs. widespread, mild vs. severe or even life-threatening.1 BDEs can manifest with a wide range of clinical presentations, from vesicle formation to tens bullae, erosion, ulceration and rarely necrotic lesions. Localized BDEs present with blister formation in a limited area.1 This variant included bullous fixed drug eruptions, drug-induced pseudo-porphyria, drug-induced phototoxic reaction, drug-induced small vessel cutaneous vasculitis, drug-induced contact dermatitis, halogenoderma and hand-foot syndrome.2-4 Bullous forms of drug eruptions can be associated with each medication, including nonsteroidal anti-inflammatory drugs, antibiotics, antiproliferative agents, etc. The cutaneous adverse drug eruption associated with the use of local anaesthetics such as tetracaine is relatively rare.5, 6 Diagnosing BDE can be challenging, as it requires a careful evaluation of the patient's clinical history, physical examination findings, and, in some cases, microbiological and histopathological examination.7 Management of localized BDE involves the identification and discontinuation of the causative drug. In this case, topical tetracaine abuse was recognized as the culprit drug, and the patient was advised to refrain from further use. Treatment with topical corticosteroid was initiated, resulting in significant improvement and resolution of symptoms within a week. The use of topical corticosteroids in BDE has been reported to reduce inflammation, promote healing and alleviate symptoms. Follow-up care should include monitoring for any recurrence, providing appropriate patient education regarding drug avoidance and early recognition of signs and symptoms before the disease progression. In conclusion, this case highlights a rare presentation of a BDE following tetracaine abuse. Physicians should be aware of the potential BDE in patients presenting with periorbital dermatologic manifestations associated with local anaesthetic abuse. Prompt diagnosis, discontinuation of the causative drug and appropriate management can lead to successful resolution of symptoms8 and prevent unnecessary interventions such as invasive procedures or prolonged antibiotic therapy, as seen in this case. Further studies and awareness among healthcare professionals are needed to better understand the pathogenesis and management of BDEs associated with local anaesthetics. We sincerely thank all the patients for their participation in this study. This manuscript has been ethically approved by the ‘Ethics committee of Isfahan University of Medical Sciences, Isfahan, Iran’. The authors received no financial support for this research, authorship or publication of this article. The authors have no conflicts of interest to declare.