Embolia Cutis Medicamentosa (Nicolau Syndrome) after Endodontic Treatment: A Case Report

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Case Report/Clinical Techniques

Embolia Cutis Medicamentosa (Nicolau Syndrome) after Endodontic Treatment: A Case Report Jan-Falco Wilbrand, MD, DDS, Martina Wilbrand, MD, DDS, Heidrun Schaaf, MD, DDS, Hans-Peter Howaldt, MD, DDS, PhD, Christoph-Yves Malik, MD, DDS, and Philipp Streckbein, MD, DDS Abstract Introduction: Embolia cutis medicamentosa (Nicolau syndrome) is a rare iatrogenic event of tissue necrosis after intramuscular or intraarticular application of cristalloid suspensions. Clinically, it presents as a livid discoloration of the skin, local pain, and signs of inflammation. Methods: This article presents the first case of Nicolau syndrome after the endodontic application of calcium hydroxide paste into the distal root canal of tooth 18. The patient presented to the Department for Maxillofacial Surgery and hospitalized for several days. Results: The application of calcium hydroxide paste led to a thrombosis of the inferior alveolar artery and various branches of the maxillary artery. A definite necrosis of the left-side infraorbital skin area and concomitant hypaesthesia of the infraorbital nerve and of the mental nerve were observed. Conclusions: Calcium hydroxide paste is appropriate for the medicamentous treatment of root canals, but is not suitable to stanch bleeding from periapical arteries. (J Endod 2011;37:875–877)

Key Words Calcium hydroxide, complication, Nicolau syndrome, vascular thrombosis

From the Department of Maxillofacial Surgery, University Hospital Giessen, Giessen, Germany. Address requests for reprints to Dr Jan-Falco Wilbrand, Department of Maxillofacial Surgery, University Hospital Giessen, Klinikstr. 29, 35390 Giessen, Germany. E-mail address: [email protected] 0099-2399/$ - see front matter Copyright ª 2011 American Association of Endodontists. doi:10.1016/j.joen.2011.01.004

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mbolia cutis medicamentosa, or Nicolau syndrome, was first described in 1924 after the intragluteal injection of bismuth for the treatment of syphilis (1). This rare entity is defined by the formation of livid plaques and local necrosis after intramuscular or intra-articular injection. In most cases to date, these plaques have developed after the application of diclofenac sodium or penicillin (2). The signs of skin discoloration are usually accompanied by severe pain and extensive inflammation (3). Severe cases may take a rapid clinical course and lead to death (4). The pathogenesis of Nicolau syndrome remains unclear. Histological findings indicate that vascular thrombosis may be a primary causative factor (5, 6). It is not known, however, whether such thromboses are primary or secondary (7). The standard therapy for this syndrome consists of immediate anticoagulation with heparin and the intravenous application of corticosteroids (8). Adequate analgesics should also be administered. The application of local cooling may lead to severe exacerbation (9) and aggravation of the local tissue damage because of an additional vasoconstringent effect. Surgical therapy should only be used in cases of disseminated necrosis or impairment of deeper subcutaneous tissues, such as muscle or fat (8). Given the rarity of this condition, the current literature on Nicolau syndrome consists mostly of case reports (10). This article presents the first description of a case of embolia cutis medicamentosa after the injection of calcium hydroxide during endodontic treatment.

Case Report A 34-year-old man presented to the Department for Maxillofacial Surgery of the University Hospital in Giessen, Germany, after the endodontic treatment of tooth 18 by his family dentist. This treatment was conducted using local anaesthesia due to clinical signs of irreversible pulpitis. After the dentist had prepared the distal root canal, he noticed and monitored distinct bleeding. Because this bleeding could not be stanched by compression, calcium hydroxide paste (Calxyl; OCO Praeparate, Pfalz, Germany) was injected with force into the distal root canal. After the local anaesthesia subsided, the patient complained of persisting hypesthesia of the left mental nerve and mild hypesthesia of the left infraorbital nerve. The patient also noted a livid discoloration of his left cheek and was thus referred to the maxillofacial surgery unit (Fig. 1). Clinical findings presented as a livid discoloration of the left infraorbital area surrounded by pale discoloration. Tooth 18 was provisionally sealed. The patient reported hypesthesia in the infraorbital and mental regions, including half of the left lower lip. Because the young patient was in a good state of health, there were no additional anamnestic characteristics to be evaluated. An orthopantomogram was performed and showed a dislocation of the calcium hydroxide paste throughout the mandibular canal and into the retromaxillary area (Fig. 2). A computed tomography scan of the midfacial area showed contrasting material throughout the temporal artery, the posterior superior alveolar artery, the buccal artery, and inside the greater palatine artery (Fig. 3). The patient was hospitalized and received a single dose of corticosteroids, an anticoagulative regimen of heparin, and an antibiotic (clindamycin). After 5 days, the patient was discharged to ambulatory follow-up. A limited skin necrosis of 5  8 mm on the left cheek was left to heal spontaneously (Fig. 4).

Nicolau Syndrome after Endodontic Treatment


Case Report/Clinical Techniques

Figure 1. Discoloration of the left cheek after impressing calcium hydroxide into the distal root canal of tooth 18. This finding was accompanied by local hypaesthesia.

Only mild permanent scarring was observed during a 3-year follow-up (Fig. 5). Nevertheless, after 8 years, the patient describes the persistence of mild residual hypaesthesia of the left mental nerve. Tooth 18 was obturated and restored.

Discussion Nicolau syndrome is a very rare iatrogenic event (11). The pathogenesis and risk factors of this condition have not yet been described (7). It typically develops after intramuscular (12), subcutaneous (13), or intra-articular injection (7). Vascular thrombosis, primary or secondary to the injection, is one likely causative factor (5). In the case reported here, distinct bleeding arose after preparation of the distal root canal of tooth 18. Because no other measure successfully stopped the bleeding, calcium hydroxide was injected with force in an act of desperation. This procedure led to secondary thrombosis of

Figure 2. Calcium hydroxide paste inside the mandibular canal. Note the visible course of the inferior alveolar artery.


Wilbrand et al.

Figure 3. Axial computed tomography scan. The arrows point toward the contrasting material in the superior posterior alveolar arteries.

the inferior alveolar artery and several other branches of the internal maxillary artery. An absolute deficiency of vascularization in the left cheek region was caused within the vessel loop between the zygomatic and infraorbital arterial branches. This led to impairment of the infraorbital nerve and skin. The result was prolonged hypesthesia and local skin necrosis. During endodontic treatment, calcium hydroxide paste can serve as a provisional medical application into the prepared root canal to disinfect and facilitate prearrangement for the permanent root canal filling. The forced injection of the paste caused reflux through the mandibular and branches of the maxillary artery. The inferior alveolar nerve was permanently damaged, likely because of the high pH of calcium hydroxide. To date, most reported cases of Nicolau syndrome have followed the application of crystalloid suspensions. Calcium hydroxide paste is one such crystalloid solution. In an animal model for embolia cutis medicamentosa, the following analogous procedure was performed: crystalloid suspensions were applied intra-arterially and led to contraction, pain, flushing, lividity, and tissue necrosis (6). These clinical findings are comparable with those presented in this case report.

Figure 4. Limited necrosis of the left cheek 2 weeks after the endodontic treatment of the lower left second molar.

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Case Report/Clinical Techniques Acknowledgments The authors deny any conflicts of interest related to this study.


Figure 5. Mild scarring 3 years after Nicolau syndrome.

Conclusions To date, no publication deals with similar clinical findings after endodontic treatment. The patient suffers only mild residual complaints and little permanent scarring. Nevertheless, the permanent hypaesthesia exemplifies an avoidable and unnecessary complication of endodontic treatment for irreversible pulpitis. Although calcium hydroxide paste may be appropriate for the medicamentous prearrangement of root canals, it is not suitable for the stanching of bleeding from the root canal.

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1. Stiehl P, Weissbach G, Schroter K. Nicolau Syndrome. Pathogenesis and clinical aspects of penicillin-induced arterial embolism. Schweiz Med Wochenschr 1971; 101:377–85. 2. Selimoglu O, Basaran M, Ugurlucan M, et al. Rhabdomyolysis following accidental intra-arterial injection of local anesthetic. Angiology 2009;60:120–1. 3. Hamilton B, Fowler P, Galloway H, et al. Nicolau syndrome in an athlete following intra-muscular diclofenac injection. Acta Orthop Belg 2008;74:860–4. 4. Rygnestad T, Kvam AM. Streptococcal myositis and tissue necrosis with intramuscular administration of diclofenac (Voltaren). Acta Anaesthesiol Scand 1995;39: 1128–30. 5. Beissert S, Presser D, Rutter A, et al. Embolia cutis medicamentosa (Nicolau syndrome) after intra-articular injection. Hautarzt 1999;50:214–6. 6. Muller-Vahl H, Pabst R. An animal model for aseptic necrosis after intramuscular injections. Int J Tissue React 1984;6:251–4. 7. Luton K, Garcia C, Poletti E, et al. Nicolau syndrome: three cases and review. Int J Dermatol 2006;45:1326–8. 8. Marangi GF, Gigliofiorito P, Toto V, et al. Three cases of embolia cutis medicamentosa (Nicolau’s syndrome). J Dermatol 2010;37:488–92. 9. Senel E, Ada S, Gulec AT, et al. Nicolau syndrome aggravated by cold application after i.m. diclofenac. J Dermatol 2008;35:18–20. 10. Uri O, Behrbalk E. Tissue necrosis following intramuscular administration of various drugs (Nicolau syndrome): clinical presentation, pathophysiology and treatment. Harefuah 2009;148:186–8. 11. Nischal K, Basavaraj H, Swaroop M, et al. Nicolau syndrome: an iatrogenic cutaneous necrosis. J Cutan Aesthet Surg 2009;2:92–5. 12. Lie C, Leung F, Chow SP. Nicolau syndrome following intramuscular diclofenac administration: a case report. J Orthop Surg (Hong Kong) 2006;14:104–7. 13. Guarneri C, Polimeni G. Nicolau syndrome following etanercept administration. Am J Clin Dermatol 2010;11(suppl 1):51–2.

Nicolau Syndrome after Endodontic Treatment


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