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Nicolau syndrome, embolia cutis medicamentosa, an iatrogenic consequence of intramuscular injections: a case report and literature review with a synthesis of case studies

MOJ Clinical & Medical Case Reports
Jacob J Nasser, BS, DPM, Ahmad Saad, BS, DPM, Joseph A Saracco, BS, DPM


Introduction: Nicolau syndrome (NS) was first described in 1924 by Freudental and Nicolau in a syphilis patient that was treated with injections of bismuth. NS is characterized by skin necrosis secondary to vascular occlusion caused by intramuscular drug injections. Recent literature has shown that livedoid dermatitis and embolia cutis medicamentosa are symptoms of Nicolau syndrome, which develop into a hemorrhagic bullae. The bullae then progress to necrotic ulcerations that may lead to infection, ischemia and even limb loss.
Purpose: To describe Nicolau Syndrome and the life-altering effects it can have on patients.
Methodology & procedure: A systematic review of studies published in the Medline database from January 2018 through July 2022 was conducted to identify articles that evaluated the causes and symptoms of Nicolau Syndrome. The systematic review was conducted following the PRISMA guidelines with an inclusion criteria of Nicolau syndrome diagnosis with no exclusion criteria. Summary tables were generated from the included studies for case specific indications of the intramuscular injection(s), sequence of symptomology, any treatment(s) administered and outcome of the syndrome for each case.
Results: 36 Cases of NS were reported in the last 5 years from our literature search. The PRISMA flow diagram will show the reported cases, sex, age, what the injection consisted of, the number of recorded injections in the past 3 and 5 years and treatments (if rendered) with outcomes, if data is available. Spontaneous resolution was seen in a few select cases, although most ended up with some type of debridement/amputation.
Case description: Our patient was a 47-year-old female with a long history of corticosteroid injections including the neck, back and upper extremities, with her most recent injection for plantar fasciitis of her left foot. After the injection she was prescribed oral Cephalexin that she took for two days before presenting to the emergency department with a small lesion that had dermatological changes consistent with bruising/contusion. Over the course of the month, the patient’s lesion continued to deteriorate despite several treatment attempts from a multidisciplinary limb salvage team. Ultimately, she underwent a left lower extremity below-knee amputation. Discussion: Use of intramuscular injections across all fields of medicine is commonplace and it would appear physicians overlook or are unaware of the risks of Nicolau Syndrome. Although the pathogenesis is still debated, researchers have theorized that sympathetic activation results in vasoconstriction, embolic occlusion of microcirculation, and prostaglandin synthesis inhibition.


Nicolau syndrome, pathophysiology, perivascular injection, penicillin