Nicolau syndrome: a review of case studies

Abstract

Nicolau syndrome, although it is quite rare, often occurs following intramuscular injections of different medications, especially diclofenac and penicillins. Accordingly, its symptoms usually begin with severe pain during injection, leading to ulceration and necrosis of the local tissue over time. Immediate diagnosis and treatment in the case of this syndrome, are of great importance. There are no established criteria for Nicolau's diagnosis, and preferably, these can be achieved by examining the patient's symptoms and eliminating differential diagnoses. The proposed treatments are primarily symptomatic therapy and measures such as fasciotomy, debridement, and plastic surgery provided in the affected area. The exact cause of this syndrome has not been determined yet. However, since vasospasm, thrombosis, and embolism have been observed in majority of Nicolau syndrome cases, so any intra-arterial/para-arterial injection or any other factor leading to these three conditions could be hypothetically regarded as the cause of this problem. This review aims to provide a comprehensive overview of Nicolau's symptoms, diagnosis, treatment methods, and prevention. It also investigates the association between the incidence of this disease and some factors such as gender, age, injection method, and causative drugs, in order to widen our understanding on this syndrome and help practitioners with a much faster diagnosis method and step-by-step approach to Nicolau syndrome.

Nicolau Syndrome Following Glatiramer Injection in a Middle-Aged Woman

“…Since then, reports of this syndrome have been documented following subcutaneous, intravenous, and even intraarticular injections. However, literature on NS secondary to agents such as subcutaneous glatiramer, as demonstrated in our report, remains relatively sparse [5]. Thus, we report a rare case of subcutaneous glatiramer injection-induced NS, its progression, treatment, and resolution.…”

“…This was demonstrated in an early rabbit model by Brachtel and Meinertz, who found that intraarterial and peri-arterial injections led to cutaneous necrosis with severe arterial inflammation and destruction upon histological analysis [6]. Other possible mechanisms include vasospasm or thrombi, resulting in impaired blood flow and necrosis, with the latter of these hypotheses supported by histologic results demonstrating the presence of micro-emboli within the arterial supply [1,5].…”

“…NS was first described in the early 20th century in the setting of intramuscular bismuth salt injections for syphilis treatment [5]. Since then, reports of this syndrome have been documented following subcutaneous, intravenous, and even intraarticular injections.…”

“…The prevailing theory is that iatrogenic arterial complications lead to occlusion of vascular flow and necrosis within the arterial distribution. One potential mechanism for this is arterial or peri-arterial injection, leading to significant inflammation that destroys the artery, cutting off vascular flow [5]. This was demonstrated in an early rabbit model by Brachtel and Meinertz, who found that intraarterial and peri-arterial injections led to cutaneous necrosis with severe arterial inflammation and destruction upon histological analysis [6].…”

“Needle micro-cores: can they pose an occlusive threat with non-particulate injections?”

“…[12][13][14] Although injectable products composed of hydrocolloid gels and particulate mixtures-such as dermal fillers and drug suspensions-carry the greatest risk of vascular occlusion, recent reports have described injuries occurring with nonparticulate solutions such as lidocaine, botulinum, and other injectable medications. [15][16][17][18][19][20][21][22][23] Whereas the occlusive nature of filler-induced injuries has been well-established in the literature, the underlying mechanism of injury with nonparticulate injections has not been fully elucidated. 24 Current hypotheses include prolonged traumatic arteriospasm and intraluminal thrombus formation followed by distal embolization.…”