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Nicolau syndrome caused by non-steroidal anti-inflammatory drugs: Systematic literature review.

Pediatric Institute of Southern Switzerland, Ospedale San Giovanni, Bellinzona, Switzerland. Università della Svizzera Italiana, Lugano, Switzerland. Pediatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy. Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, Milan, Italy. Department of Dermatology, Ente Ospedaliero Cantonale, Ospedale Regionale di Lugano, Lugano, Switzerland. Department of Internal Medicine, Ente Ospedaliero Cantonale, Locarno, Switzerland. Pediatric Cardiology Unit, Department of Pediatrics, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

International journal of clinical practice. 2020;(10):e13567
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Abstract

AIM: Intramuscular or, more rarely, local drug injection is occasionally followed by immediate local pain, livedoid skin lesions and, some days later, the development of ischemic lesions. This very uncommon but potentially severe reaction, termed Nicolau syndrome, is traditionally associated with bismuth and β-lactam antimicrobials. The aim of this report was to review the literature associating Nicolau syndrome with the administration of non-steroidal anti-inflammatory drugs. METHODS The National Library, Excerpta Medica, Web of Science and Cochrane library databases were used. RESULTS Sixty-two cases (40 females and 22 males aged from 13 to 81, median 57 years) of Nicolau syndrome were published after 1992. Fifty-three cases occurred after diclofenac. The remaining nine cases were associated with ketoprofen (N = 2), ketorolac (N = 2), phenylbutazone (N = 2), etofenamate (N = 1), ibuprofen (N = 1) and piroxicam (N = 1). CONCLUSION Although Nicolau syndrome is extremely uncommon, physicians must be aware of this complication after intramuscular administration of non-steroidal anti-inflammatory drugs and should avoid unnecessary injections.