• Users Online: 16941
  • Print this page
  • Email this page

 Table of Contents  
Year : 2020  |  Volume : 53  |  Issue : 6  |  Page : 240-243

Compartment syndrome and acute lower limb ischemia with paralysis complicating intramuscular benzathine penicillin injection

1 Department of Vascular Surgery, CHU Morafeno Toamasina, Madagascar
2 Department of Rhumatology and Dermatology, CHU Morafeno Toamasina, Madagascar
3 Department of General and Vascular Surgery, CHUJRA Antananarivo, Madagascar

Date of Submission21-Apr-2020
Date of Decision15-Jun-2020
Date of Acceptance21-Jul-2020
Date of Web Publication19-Dec-2020

Correspondence Address:
Fanomezantsoa Raherinantenaina
Department of Vascular Surgery, CHU Morafeno, University of Toamasina,
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/fjs.fjs_50_20

Rights and Permissions

Nicolau dermatitis (ND) is a well-known but rare adverse drug reaction involving the skin and the subcutaneous and even muscle tissues at the site of intramuscular injection (IMI). Benzathine penicillin (BP) is the most frequent medication causing serious and acute complications such as limb ischemia, compartment syndrome (CS), and nerve paralysis. The subsequent damage to the lower limb (LL) might be due to microemboli, leading to progressive deterioration of the downstream tissue bed. We describe a 7-year-old boy with a diagnosis of ND after IMI of BP and diclofenac sodium to the medial mid-right thigh. Two days earlier, the patient seemed to experience an acute suppurative complication of circumcision and underwent the aforementioned treatment (September 15, 2018). The circumcision and injection of drugs were illicitly carried out by a nonmedical practitioner. The child complained of severe pain and disability of his right LL. On admission (September 16, 2018), he was found to have acute LL ischemia and CS with cyanosis, hypoesthesia and paresis. Fasciotomy was achieved and medical therapy with heparin, corticoid, and an antibiotic was made for 7 days. Postoperative periods were uneventful. Livedoid violaceous patch and erythematous plaque and ecchymosis have evolved progressively during 10th day, with formation of a diffuse necrotic spot before healing up within 2 months. The length of hospital stay was 10 days. The rehabilitation for walking was started 2 weeks after the operation. Between 6 and 12 months of follow-up, the motor deficit involved the entire LL and persisted despite the tremendous achievement of regular neuromuscular physiotherapy. The paralysis was considered permanent.

Keywords: Benzathine, compartment, dermatitis, fasciotomy, heparin, ischemia, limb, Nicolau, penicillin, syndrome

How to cite this article:
Raherinantenaina F, Rajaoharimalala TG, Ranaivo IM, Ralandison SD, Rakoto Ratsimba HN, Rajaonanahary TM. Compartment syndrome and acute lower limb ischemia with paralysis complicating intramuscular benzathine penicillin injection. Formos J Surg 2020;53:240-3

How to cite this URL:
Raherinantenaina F, Rajaoharimalala TG, Ranaivo IM, Ralandison SD, Rakoto Ratsimba HN, Rajaonanahary TM. Compartment syndrome and acute lower limb ischemia with paralysis complicating intramuscular benzathine penicillin injection. Formos J Surg [serial online] 2020 [cited 2022 Jun 29];53:240-3. Available from: https://www.e-fjs.org/text.asp?2020/53/6/240/304020

  Introduction Top

Nicolau dermatitis (ND) is a rare complication of intramuscular injection (IMI) of crystalloid drugs that may lead to ischemic necrosis of the surrounding skin, soft tissue, and even muscles.[1] The advanced mechanism is acute arterial vasospasm and microthrombosis with embolisms resulting in flow decrease and small-vessel occlusion.[2] Among the reported drugs causing ND, benzathine penicillin (BP) is the most frequent source of acute complications such as limb ischemia, compartment syndrome (CS), and neurologic deficit. These complications are rare but potentially grave. In fact, an evolution toward gangrene is often unavoidable in the absence of early revascularization and fasciotomy.[1] The diagnosis is usually clinical and obvious, but the treatment remains complex because of the impossibility to perform optimally the revascularization which should be achieved by surgical embolectomy.

  Case Report Top

A previously healthy 7-year-old boy, weighing 40 kg, was admitted to our emergency department on September 16, 2018, for difficulty ambulating because of right lower limb (LL) weakness and cyanosis in the downstream toes. The parent's interrogatory data noticed a recent circumcision that was achieved by a nonmedical practitioner (charlatan). Three days after, the patient seemed to have an acute local suppurative complication of the posthectomy. Subsequently, he underwent IMI of BP and diclofenac sodium (DS) to the ventromedial region of his right thigh, which was illicitly performed by the same operator on September 15, 2018. This charlatan accused to have combined and injected the drugs intramuscularly. Straight away, the child complained of severe pain at the injection site and disability of his involved LL. On admission, the patient was well appearing with good vital constants and afebrile. His right leg was increased in volume and became tense and incompressible with buffet's loss of the calf. The right foot was cold, and dorsalis pedis and posterior tibial pulses were absent. The distal right toes and plantar surface were cold and cyanotic [Figure 1]. Neurological examination revealed hypoesthesia at the distal part of the foot and a decrease in muscular strength in the right LL. A diagnosis of Nicolau dermatitis with marginally threatened acute lower limb ischemia (ALLI) and CS was made. In emergency, calf fasciotomy was performed, and the swelled muscles bulged from the incisions. Afterward, an intravenous heparinotherapy was initiated postoperatively (10,000 IU/24 h). Immediate evolution was marked by improvement of local heat and the distal pulses. Two days later, extensive purplish erythema and livedoid violaceous patch were observed at the distal leg and the foot [Figure 1]b and [Figure 1]c. The standard biologic test was normal. Creatine kinase (3700 IU/L) and lactate dehydrogenase were elevated (3780 IU/L). Venous and arterial Doppler examination performed with a working diagnosis of arterial thrombosis or occlusion was normal. The heparinotherapy was continued until 10th day and associated with a systemic methylprednisolone (2 mg/kg/8 h) and amoxicillin–clavulanate therapy (25 mg/kg/8 h) for a total of 7 days. The postoperative period was uneventful. The length of hospital stay was 10 days. Furthermore, cutaneous disorders with livedoid violaceous patches and erythematous plaque have evolved progressively during the 10th days, with the formation of a diffuse necrotic spot [Figure 2]a and [Figure 2]b before healing up at the end of 2 months [Figure 2]c. The rehabilitation for walking was started 2 weeks after the operation. Between 6 and 12 months of follow-up, the motor deficit involved the entire LL and persisted despite the tremendous achievement of regular neuromuscular physiotherapy. The LL paralysis was considered permanent.
Figure 1: Initial evolution within the first 5 days of skin discoloration: plantar cyanosis (a), extensive erythematous rash (b), and livedoid violaceous plaque on the right foot (c)

Click here to view
Figure 2: Intermediate and late outcomes with clear demarcation of marginal ischemic areas at the distal part of the right foot evolving within 10 days (a), with superficial desquamation and skin ulceration at 2 weeks (b), and complete healing with atrophic scarring at 2 months later (c)

Click here to view

  Discussion Top

Nicolau syndrome (dermatitis) is presumably caused by an inadvertent injection of miscible or insoluble drugs into a blood vessel. The mechanism of ALLI might be due to drug embolism with microthrombosis and vascular occlusion resulting in progressive deterioration of the downstream tissue bed. The most frequent circumstances occurred following IMI of DS (31%) or BP (17%). The latter was the most common drug leading to ND in children (78%). DS is the most common nonsteroidal anti-inflammatory implicated, but no similar case to our observation has been previously published in association with BP. The inescapable implication of DS comes especially from its local vasoconstrictor effect. As the BP is injected, its crystallization in capillaries can lead to microemboli related to penicillin salts.[3] In our patient, a penetrating injury to the thigh caused by the needle is harmful regarding the femoral vessels, which may likely represent an encouraging factor in the origin of the ALLI. Whatever the mechanism, both thrombosis and embolism result in major edema formation by capillary membrane changes. The edema engenders an obstacle to the venous return and muscular and arterial compression, allowing CS and the subsequent ALLI.[1],[4],[5] Both CS and ALLI with nerve paralysis were frequently observed in patients who underwent IMI of BP (91%).[1],[2],[3],[4],[5],[6],[7],[8],[9],[10] The DS is usually responsible for skin necrosis with a local extension of the lesion in-depth to the underlying soft tissue.

The particular presentations include severe pain and difficulty ambulating (76%), livedoid violaceous patch (50%), and erythematous plaque and ecchymosis (40%). The happening of skin necrosis is frequent (60%), with a variable delay ranging from 5 to 15 days.[1],[4] Nerve dysfunction (9%–26%), CS (6%–16%), and ALLI (5%–24%) were rarely encountered. In the absence of early management, these complications may occur 24 h after the onset of skin discoloration appearance.[1] The diagnosis is essentially based on clinical features, but in case of doubt, an ultrasound Doppler study allows to confirm the absence of thrombus[1],[2],[4],[5],[7],[8],[9],[10] as was the case in our patient. CS is confirmed according to clinical findings including local severe pain, tense edema, and passive extension of the ankle.[5] The diagnosis of ALLI is typically evoked in patients who displayed brutal pain and limb disability with pallor and attenuated distal pulses. Sometimes, magnetic resonance imagery (MRI) and computed tomography angiography were performed (6%–20%), but their results did not provide any supplemental diagnostic element except for edema, abscess, fat stranding, and extent of the lesion.[5] MRI is particularly helpful for neurologic injury and myonecrosis findings.[3] The definitive diagnosis which is unusually feasible (18%) required specimen biopsy and analysis. The histological architecture typically consists of endothelial fibrinoid necrosis, an irregular proliferation of capillaries, and thrombosis of small- and medium-sized vessels without vasculitis.[6]

The medical therapeutic data are diverse and controversial. Nevertheless, most authors used the association of an antibiotic (50%), heparin (30%), and corticoid (32%).[1],[2],[3],[4],[5],[6],[7],[8],[9],[10] A few authors have suggested using pentoxifylline, amlodipine, and aspirin (<14%).[2],[9],[10] Endovascular revascularization and surgical embolectomy are not indicated because of the involved and smaller vessel sizes. The use of puissant vasodilator (iloprost) and fibrinolytic agents, which were never tried in this area, may represent an attractive alternative. Local cares are often needed for the healing scars and limb salvage including hydrocolloid gel application, fasciotomy (16%), debridement (50%), vacuum-assisted closure therapy (20%), flap reconstruction (32%), and skin graft. The timeline of scars healing varies from 2 weeks to 3 months.[6] The prognostic factors included delayed management (>24 h), cold application, and surinfection.[1],[9],[10] Overall outcomes are generally favorable (84%) with an excellent limb salvage rate (92%). The functional prognosis is conditioned by the presence of nerve dysfunction; its recovery is typically gradual and partial.[5] The factors of poor prognoses include rhabdomyolysis, CS, paralysis, and delayed revascularization.[1],[3],[5],[6] The rates of major amputation (8%), disabled neurologic sequelae (4%), and mortality (4%) were low. The causes of reported death included acute renal insufficiency, severe sepsis, and multiorgan failure.[6]

  Conclusion Top

A Nicolau syndrome was typically diagnosed in a child boy who sustained successive acute severe pain, difficulty ambulating, skin discoloration with livedoid violaceous patches, and erythematous plaque. The incident of CS and ALLI following IMI of BP to the medial thigh was exceptional and serious. A major handicap with LL paralysis occurred following delayed diagnosis and absence of early heparinotherapy. IMI of BP should be avoided as much as possible. Premature administration of systemic anticoagulant, corticoid, and antibiotic may prevent secondary complications, as no specific antidote exists. The limb salvage from CS depends mostly on the early achievement of revascularization by fasciotomy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the parents have given their consent for images and other clinical information to be reported in the journal. The parents understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Marcus F, Claude EV, Josephine M, Teyang A. An Exceptional Cause of Acute Limb Ischemia: Nicolau Syndrome-Single-Center Experience with 4 Cases. Ann Vasc Surg 2019;58:383.e7.  Back to cited text no. 1
Alkan Bozkaya T, Demirel G, Ormeci T, Al S, Çakar E, Tastekin A, et al. Anticoagulant and vasodilator therapy for Nicolau syndrome following intramuscular benzathine penicillin injection in a 4 year old boy. Arch Argent Pediatr 2016;114:e184-6.  Back to cited text no. 2
Mjahed K, Alaoui SY, Salam S, Lhoucine B. Acute paraplegia and pulmonary edema after benzathine penicillin injection. Am J Emerg Med 2008;26:250.e1-5.  Back to cited text no. 3
Enshaei A, Afshar A. Compartment syndrome of the calf due to Nicolau syndrome. Arch Bone Jt Surg 2016;4:87-9.  Back to cited text no. 4
Hatefi M, Pirabadi NR, Khajavikhan J, Jaafarpour M. Claudication due to sciatic nerve palsy following Nicolau syndrome: A case report. J Clin Diagn Res 2015;9:RD01-2.  Back to cited text no. 5
de Sousa R, Dang A, Rataboli PV. Nicolau syndrome following intramuscular benzathine penicillin. J Postgrad Med 2008;54:332-4.  Back to cited text no. 6
Quincer E, Jaggi P. Nicolau syndrome: A rare complication following intramuscular injection. J Pediatr 2019;212:238.  Back to cited text no. 7
Memarian S, Gharib B, Gharagozlou M, Alimadadi H, Ahmadinejad Z, Ziaee V. Nicolau syndrome due to penicillin injection: A report of 3 cases without long-term complication. Case Rep Infect Dis 2016;9082158:1-6.  Back to cited text no. 8
Noaparast M, Mirsharifi R, Elyasinia F, Parsaei R, Kondori H, Farifteh S. Nicolau syndrome after intramuscular benzathine penicillin injection. Iran J Med Sci 2014;39:577-9.  Back to cited text no. 9
Maneshi A, Ravi S, Salehi MR, Hasannezhad M, Khalili H. Nicolau Syndrome. Arch Iran Med 2017;20:60-4.  Back to cited text no. 10


  [Figure 1], [Figure 2]

This article has been cited by
1 Benzathine-benzylpenicillin/diclofenac
Reactions Weekly. 2021; 1842(1): 91
[Pubmed] | [DOI]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Case Report
Article Figures

 Article Access Statistics
    PDF Downloaded178    
    Comments [Add]    
    Cited by others 1    

Recommend this journal