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Clinical Specialist Department of Internal Medicine San Camillo Hospital Circonvallazione Gianicolense, 00152 Rome, Italy fax 0039-6-58704557 gfamularo{at}scamilloforlanini.rm.it
Director Department of Dermatology Istituto Dermopatico dell'Immacolata Rome, Italy
Clinical Specialist Department of Dermatology Istituto Dermopatico dell'Immacolata
Clinical Specialist Department of Dermatology Istituto Dermopatico dell'Immacolata
Clinical Specialist Department of Internal Medicine San Camillo Hospital
Published Online, April 24, 2007. www.theannals.com, DOI 10.1345/aph.1K001
(TNF-)–induced apoptosis results in erosions of
the mucous membranes, extensive detachment of the epidermis, and severe
constitutional symptoms in patients with
TEN.2
Moreover, TNF- is strongly expressed by keratinocytes and mononuclear
cells in affected areas, with high concentrations observed in the cutaneous
blister fluid. Case Report. A 59-year-old man was given oral ciprofloxacin 250 mg twice daily for treatment of a respiratory tract infection. Two months prior to this, he had received cefotaxime and levofloxacin for treatment of community-acquired pneumonia. He had a history of hypertension, ischemic heart disease, gout, and chronic renal failure and had been taking carvedilol 12.5 mg/day, amiodarone 200 mg/day, isosorbide-5-dinitrate 50 mg/day, ramipril 10 mg/day, warfarin 3 mg/day, furosemide 25 mg twice daily, and allopurinol 300 mg/day for more than 2 years. Allergy and skin diseases and use of recreational drugs, over-the-counter medications, or herbal remedies were denied.
Within 12 hours of initiation of ciprofloxacin, erythema and a maculopapular rash appeared over the patient's trunk, followed by bloody, crusted erosions of oral and nasal mucosa with large areas of flaccid blisters and superficially denuded skin over his face, arms, trunk, thighs, and buttocks; Nikolski sign was positive. Within 48 hours of admission, 60% of the patient's skin was involved.
TEN was diagnosed, ciprofloxacin and warfarin were discontinued, and treatment was started with wound dressings, intravenous fluids, prednisolone 1 mg/kg, and imipenem/cilastatin. When there was no improvement over the subsequent days, etanercept 25 mg was administered subcutaneously on days 4 and 8. Recovery of skin and mucous membrane lesions was noticeable within a few hours of the first dose of etanercept. Within 24 hours, epidermal detachment ceased, erythema lessened, and effusion decreased; reepithelization began to appear on denuded skin surfaces, with near complete resolution after 6 days. However, the patient died 10 days after admission, with disseminated intravascular coagulation and multiorgan failure.
Discussion. Use of the Naranjo probability scale indicated probable ciprofloxacin-related TEN.3 Allopurinol- or amiodarone-induced reactions were excluded because those drugs had been given for more than 2 years without incident. Elevated allopurinol concentrations or drug–drug interactions due to the underlying chronic renal failure may have contributed to the development of TEN.
Rapid and complete recovery from TEN following TNF- blockade with
the anti-TNF- monoclonal antibody infliximab has been
described.4,5
Based on these reports and the claimed role of TNF- in the pathogenesis
of TEN, we postulated that blocking the proinflammatory and proapoptotic
activity of TNF- with the soluble TNF- inhibitor etanercept
could be of benefit to our patient. Despite the ultimately unfavorable outcome
due to systemic complications, the epidermal detachment stopped one day
following administration of etanercept, with complete reepithelization
achieved a few days later. Although there have been no other reports of the
use of etanercept in this setting, our observations suggest that etanercept is
a potential treatment for TEN. Randomized trials should be designed to assess
the safety and efficacy of etanercept and infliximab for patients with
TEN.
References
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