Nicolau Syndrome Following Glatiramer Injection in a Middle-Aged Woman.

Nicolau syndrome is a rare adverse reaction that can occur in the setting of intramuscular, intravenous, and subcutaneous injections. Proper diagnosis and management are critical to avoid complications including abscesses, muscular atrophy, and necrotizing fasciitis. Here, we report a 55-year-old female with multiple sclerosis who presented to our clinic following a subcutaneous injection of 40mg of glatiramer. She immediately noted a sharp pain and erythema, which developed into a purple discoloration, became purulent, and eventually necrosed. The patient's wound was debrided, and she was advised to clean the wound with soap and water, apply topical mupirocin, and change dressings twice daily. She continued to receive appropriate follow-up care with weekly to bi-weekly debridement with excellent resolution.

Nicolau Syndrome with Severe Facial Ischemic Necrosis after Endodontic Treatment: A Case Report.

Nicolau syndrome (NS) is a rare complication resulting from intramuscular injections. It is characterized by severe pain at the injection site and the development of purplish discoloration. Only a limited number of case reports have been published documenting the adverse effects associated with the injection of calcium hydroxide (CH) beyond the apex during endodontic treatment. Here, we present the case of a 16-year-old female with NS after the injection of CH during the root canal treatment. The radiography examination revealed distal occlusion of the right maxillary and facial arteries. This caused a substantial area of skin necrosis to develop on the patient's face, resulting in permanent scarring. NS is associated with the displacement of CH beyond the apex. To minimize the risk of NS, dentists should exercise caution by avoiding forced injection of CH during treatment, particularly when the root canal is actively bleeding.

Síndrome de Nicolau por fármacos autoinyectables en la esclerosis múltiple / Nicolau syndrome due to self-injectable drugs in multiple sclerosis

Introducción y objetivos: El síndrome de Nicolau, o embolia cutis medicamentosa, es una complicación cutánea infrecuente de los fármacos inyectados que se ha descrito escasamente en relación con los fármacos empleados en la esclerosis múltiple. Pacientes y métodos: Es un estudio retrospectivo de pacientes afectos de síndrome de Nicolau que reciben fármacos autoinyectables para la esclerosis múltiple desde 2010 hasta octubre de 2022. Resultados: Desde enero de 2010 hasta octubre de 2022 se ha seguido en nuestra consulta de patología desmielinizante a 449 pacientes con fármacos autoinyectables –317 con interferón beta y 132 con acetato de glatiramer (AG)–. En este período de tiempo se han recogido 10 episodios de síndrome de Nicolau en siete pacientes (seis hombres y una mujer) que recibían AG, lo que supone un 5,3% del total de pacientes bajo ese tratamiento. Las zonas más afectadas fueron el glúteo (n = 4) y el brazo (n = 3). Tres pacientes (42,8%) sufrieron un segundo episodio. Conclusión: El síndrome de Nicolau es una complicación exclusiva del AG y más frecuente en hombres en nuestra cohorte de pacientes con esclerosis múltiple. La recurrencia de esta complicación cutánea es frecuente en un mismo paciente, lo que es un factor que hay que tener en cuenta en la decisión de mantener el fármaco o cambiar a otra estrategia terapéutica.(AU)

Introduction and aims: Nicolau syndrome, or embolia cutis medicamentosa, is a rare cutaneous complication of drug injection that has been rarely described in relation to medication used in multiple sclerosis. Patients and methods: We conducted a retrospective study of patients with Nicolau syndrome receiving self-injectable multiple sclerosis medication from 2010 to October 2022. Results: From January 2010 to October 2022, 449 patients were followed up in our demyelinating pathology unit with self-injectable drugs - 317 with beta interferons and 132 with glatiramer acetate (GA). In this period of time, 10 episodes of Nicolau syndrome were recorded in seven patients (six men and one woman) receiving GA, which represents 5.3% of the total number of patients receiving this treatment. The most commonly affected areas were the buttocks (n = 4) and the arms (n = 3). Three patients (42.8%) suffered a second episode. Conclusion: Nicolau syndrome is a complication unique to GA and more frequent in men in our cohort of multiple sclerosis patients. This cutaneous complication frequently recurs in the same patient, which is a factor to be taken into account in the decision to maintain the drug or switch to another therapeutic strategy.(AU)

Embolia cutis Medicamentosa (Nicolau syndrome): case series.

Introduction: Embolia cutis medicamentosa or Nicolau syndrome is a rare drug reaction associated with the administration of various injectable medications. The pathogenesis of the disease is unknown, though intra and periarterial injection of the drug is a possible cause. The aim of this study was to describe and analyze the clinical characteristics of Nicolau syndrome in patients examined in daily dermatological practice. Methods: We performed a retrospective chart review, between January 2011 and December 2020, in patients diagnosed with Nicolau syndrome, from the cases of a private dermatology medical office in Târgu Mureș, Romania. Results: During the 10-year period, 7 patients were diagnosed with Nicolau syndrome. Of these, 4 (57%) patients were males and 3 (43%) were females, The male to female ratio was 1.33. The median age was 64 (interquartile range, IQR, 62-71), with the youngest patient being diagnosed at age 61 and the oldest at age 74. Regarding the drugs classes that caused Nicolau syndrome, these were intravenous antibiotics in 57%, and non-steroidal anti-inflammatory drugs in 43% of cases. Conclusion: All patients healed in a period of 6 to 8 weeks. No complications occurred. In conclusion, Nicolau syndrome is a rare side effect of injectable drug administration.

Nicolau syndrome associated with fluphenazine depot: A case report.

Nicolau syndrome is a rare condition characterized by severe pain at the site of injection, leading to ulceration and necrosis of the local tissues. Its presentation is usually acute. Nicolau syndrome is commonly seen in patients after intramuscular, intra-articular, or subcutaneous injections of non-steroidal anti-inflammatory drugs, antiepileptics, antipsychotics, antibiotics, antihistamines, and corticosteroids. Immediate diagnosis and management of this syndrome are of great importance. We herein report a rare presentation of Nicolau syndrome in a 36-year-old married male who suffered from paranoid schizophrenia for the past 3 years. The patient presented with dull pain, mild swelling, and necrotic ulceration over the injection site after receiving intramuscular fluphenazine. The patient underwent wound debridement and was given prophylactic antibiotics. Despite a wide range of therapeutic options for the management of Nicolau syndrome described in the literature, there exist limited guidelines for its management.

Nicolau syndrome following Intramuscular Diclofenac Injection: a case report and review of the literature.

Nicolau syndrome (NS), also referred as embolia cutis medicamentosa and livedo-like dermatitis, is an uncommon complication followed by drugs administered intramuscularly, intraarticularly or subcutaneously. In this case report we present a case of a 65-year-old lady who had a single dose of diclofenac sodium as an intramuscular injection in her left buttock due to back pain that led to developing what known as NS. She was treated with surgical debridement, drain insertion and skin approximation with antibiotics for 2 weeks with daily sterile dressing. The wound healed completely with scarring. NS is a preventable outcome, thus, proper procedures and precautions should be taken during intramuscular medication administration. Healthcare providers should avoid unnecessary injections, be familiar with the complication and consider it as a potential diagnosis for severe localized pain after any injection.

Síndrome de Nicolau / Nicolau syndrome

Resumen El síndrome de Nicolau es una complicación infrecuente de la aplicación parenteral de diversos fármacos. Se caracteriza por la aparición de dolor, seguido de edema, eritema y luego una placa necrótica. Se reporta el caso de un hombre de 31 años que presenta este síndrome luego de la aplicación de penicilina benzatínica intramuscular. La biopsia apoyó el diagnóstico. Recibió tratamiento con enoxaparina y cilostazol con posterior mejoría.

Abstract Nicolau syndrome is a rare complication of the parenteral application of various drugs. It is char acterized by the appearance of pain, followed by edema, erythema, and then a necrotic plaque. We present the case of a 31-year-old male with this syndrome, after the application of intramuscular benzathine penicillin. The diagnosis was supported by the biopsy. He received treatment with enoxaparin and cilostazol with subsequent improvement.

[Nicolau syndrome]. / Síndrome de Nicolau.

Nicolau syndrome is a rare complication of the parenteral application of various drugs. It is characterized by the appearance of pain, followed by edema, erythema, and then a necrotic plaque. We present the case of a 31-year-old male with this syndrome, after the application of intramuscular benzathine penicillin. The diagnosis was supported by the biopsy. He received treatment with enoxaparin and cilostazol with subsequent improvement.

El síndrome de Nicolau es una complicación infrecuente de la aplicación parenteral de diversos fármacos. Se caracteriza por la aparición de dolor, seguido de edema, eritema y luego una placa necrótica. Se reporta el caso de un hombre de 31 años que presenta este síndrome luego de la aplicación de penicilina benzatínica intramuscular. La biopsia apoyó el diagnóstico. Recibió tratamiento con enoxaparina y cilostazol con posterior mejoría.

Extensive Deep Tissue Involvement in Nicolau Syndrome and Below-Knee Amputation: A Case Report and Literature Review.

Nicolau syndrome (NS) is a rare cutaneous drug reaction in response to injections administered via any route. Based on the available studies in the medical literature, NS presents as skin and subcutaneous fat necrosis, and typically, it does not cause severe complications such as acute limb ischemia or death. In this study, we report the case of a 6-year-old boy who received an intramuscular injection of benzathine penicillin G for the treatment of bacterial pharyngitis, and subsequently developed a severe case of NS, which eventually led to below-knee amputation of the right lower limb. Although a few approaches have been suggested for the management of NS, they might not be effective under certain circumstances. Early detection, close monitoring, and consistent interventions, such as surgical fasciotomy and debridement procedures, might be necessary in severe cases of NS.

Nicolau Syndrome Secondary to Subcutaneous Glatiramer Acetate Injection.

Nicolau syndrome, also known as embolia cutis medicamentosa, is a rare complication of injectable drugs. Patients present with pain at injection site, followed by swelling, erythema, purple, hemorrhagic patches and lastly ulcer formation. A variety of intramuscular agents have been implicated as responsible. We report a case of a 26-year-old woman with a history of a purple lesion on her thigh who was diagnosed with Nicolau syndrome due to subcutaneous administration of glatiramer acetate. The patient was followed up with topical mupirocin. On follow-up, although the patient stated that she continued using glatiramer acetate, no new lesions appeared and the existing lesion continued to shrink. Nicolau syndrome seems to have an unpredictable and unavoidable course. This case suggests that physicians should have a high index of suspicion for the presence of Nicolau syndrome in patients presenting with necrotic or ulcerative lesions with a history of using injectable drugs.

Case Reports of Heroin Injection Site Necrosis: A Novel Antecedent of Nicolau Syndrome.

Heroin injection-site necrosis (HISN) is a novel and poorly understood complication of intravenous drug abuse (IVDA). We present three cases of HISN that were evaluated and treated in Charleston, West Virginia, in 2019 and 2020. The documented cases show similarities involving patient care, follow-up, clinical progression, patient demographic, and dermatologic sequelae. We discuss these similarities, provide clinical recommendations, review proposed etiologies of HISN, and introduce Nicolau syndrome as a potential mechanism.

Hyperbaric oxygen treatment in a rare complication of intramuscular injection: four cases of Nicolau syndrome.

Intramuscular injections are one of the most common clinical procedures. The objectives of this case series are to analyse the role, timing and efficacy of hyperbaric oxygen treatment (HBOT) in the management of Nicolau syndrome (NS), an extremely rare complication of this common intervention. Clinical, demographic, laboratory and microbiological data extraction were performed through retrospective analysis of the medical records of all patients with NS who were referred for HBOT over a 10-year period with wounds, ischaemia, infection or necrosis at the injection site following drug injection; four patients with NS were included. All injections were made via the intramuscular route; three adult cases followed a non-steroidal anti-inflammatory drug, diclofenac sodium and one in a child followed penicillin injection. The time between diagnosis/injection and HBOT ranged from five to 33 days. NS can develop despite all preventive measures based on injection technique guidelines. HBOT appeared beneficial to healing of NS when administered with other therapeutic approaches. Due to the missing pieces of the puzzle in pathogenesis, NS is rarely completely reversible; keeping the awareness high for undesirable complications stands out as the most effective approach.

Nicolau syndrome caused by Glatiramer.

Injection-site reactions to glatiramer are common and include erythema, pruritus, pain, or induration. Additionally, the present systematic review of the literature documents 20 cases of Nicolau syndrome following glatiramer, a rare but potentially severe skin reaction. Abdomen and thighs are the most frequently affected areas (80% of reported cases), and permanent skin damage has been observed in 30% of cases. Recurrences are rare (<10%).

Embolia Cutis Medicamentosa (Nicolau Syndrome) Secondary to Intramuscular Fulvestrant Injection: A Case Report.

PURPOSE: A case of embolia cutis medicamentosa (Nicolau syndrome) in a patient receiving monthly intramuscular fulvestrant injections is presented. SUMMARY: An 85-year-old woman receiving monthly fulvestrant injections in the outpatient setting developed a necrotic lesion at the fulvestrant injection site on her right buttock. Her medical history is notable for metastatic breast cancer with bone metastases. Prior to developing the necrotic lesion, the patient was receiving monthly fulvestrant injections for 6 years. Other potential causes such as infection and pressure necrosis were ruled out clinically. After 185 days of wound care involving multiple surgical debridements, topical therapy, and frequent follow-up appointments, the patient's wound resolved with 100% epithelialization. Nicolau syndrome has been reported with other non-vesicant, injectable medications such as antibiotics and corticosteroids; however, it has not been previously reported with fulvestrant. CONCLUSION: Nicolau syndrome developed in the right buttock of a patient with metastatic breast cancer following an intramuscular fulvestrant injection. Healthcare practitioners need to be cognizant of this adverse effect with intramuscular injections in order to recognize and refer patients for wound care evaluation early in the evolution of this syndrome. Proper injection technique is recommended to reduce the risk of this idiopathic adverse effect.

Nicolau Syndrome after Endodontic Treatment: A Case Report.

Calcium hydroxide has been used successfully in root canal therapy for many years. However, it can cause serious damage if it is inadvertently displaced into surrounding vital structures, resulting in thrombosis if displaced into blood vessels, damaging connective tissue, and causing skin necrosis. These adverse reactions are known as Nicolau syndrome (NS) or embolia cutis medicamentosa. Very few case reports have been published about these adverse effects of injecting calcium hydroxide beyond the apex during root canal therapy. A 16-year-old female patient was referred to the endodontic department of Hamad Dental Center for assessment after treatment by the maxillofacial surgery department for swelling and tissue necrosis that occurred after endodontic treatment in another clinic. When the patient initially attended the maxillofacial surgery department, she presented with swelling on the left side in the region of the maxillary left first permanent molar. On examination, there was a change in the color of the skin of the left cheek in that area along with some reported paralysis of the left side of her lips. Analgesics and antibiotics had already been prescribed at the referring clinic. Two weeks later, the patient developed a necrotic patch of skin on the same area. Subsequent evaluation at the endodontic department of Hamad Dental Center led to a diagnosis of NS. NS is a very rare iatrogenic condition. Displacing calcium hydroxide beyond the apex might increase the chance of NS. Clinicians should avoid overinstrumentation and forced injection of calcium hydroxide to prevent NS.

Can betamethasone prevent Nicolau syndrome when coadministered with penicillin? A case report.

We present a 33-year-old female patient with Nicolau syndrome (NS) who received one injection of benzathine penicillin and one injection of betamethasone to the right buttock, and one injection of benzathine penicillin to the left. NS was seen only in the left buttock, where it was intramuscularly injected with penicillin benzathine alone.

Seguridad en los procedimientos dermatológicos: oclusión vascular por materiales de relleno / Safety in Dermatologic Procedures: Vascular Occlusion by Filling Materials

Las complicaciones más graves del tratamiento con los rellenos dérmicos para el rejuvenecimiento facial son las isquémicas, que pueden provocar un síndrome de Nicolau, una ceguera o, incluso, un ictus. Se describen las medidas preventivas que es conveniente aplicar cuando se realizan estos procedimientos y, en caso de que aparezcan, se proponen los pasos a seguir ante esta urgencia dermatológica. Es importante tener un amplio conocimiento de la anatomía facial. Son preferibles el uso de cánulas y las técnicas de infiltración retrógradas. Cuando aparece un evento isquémico cutáneo, usaremos hialuronidasa infiltrada preferiblemente con cánula. Si el evento isquémico ocurre a nivel ocular se trasladará al paciente a un medio hospitalario con código ictus (AU)

Ischemic events are the most serious complications of facial antiaging treatment with dermal fillers. Ischemia can cause Nicolau syndrome, blindness, or even stroke. This article discusses how to prevent ischemic complications and what steps to take should a dermatologic emergency develop. A thorough understanding of facial anatomy is important. Preferred procedural techniques involve the use of cannulas and retrograde injection. When ischemia is detected in the skin, hyaluronidase should be injected, preferably through a cannula. If ocular ischemia occurs, the patient should be transferred to a hospital with stroke code activation (AU)

A Curious Case of Ear Necrosis Salvaged by a Composite Temporalis Flap: Conchal Cartilage Graft Reconstruction.

Hemangiomas are commonly encountered benign vascular tumors in clinical practice. They are easily diagnosed clinically, but it is essential to know atypical and rare varieties of these tumors to avoid confusing them with vascular malformations. The traditional approach in managing hemangiomas has been a "wait and watch" policy as most of these lesions undergo spontaneous regression with time. There are multiple treatment modalities in managing these lesions, but with specific indications for each of them. We report a case of Nicolau syndrome following injection sclerotherapy for a residual ear hemangioma, which lead to necrosis and total loss of skin and cartilage. However, the full-thickness defect in the ear was restored with a composite temporalis fascial flap, conchal cartilage graft, and split skin graft reconstruction. A detailed literature review of the presentation and management of this vascular tumor is discussed with a special emphasis on avoiding complications and maximizing patient outcomes.

Safety in Dermatologic Procedures: Vascular Occlusion by Filling Materials. / Seguridad en los procedimientos dermatológicos: oclusión vascular por materiales de relleno.

Ischemic events are the most serious complications of facial antiaging treatment with dermal fillers. Ischemia can cause Nicolau syndrome, blindness, or even stroke. This article discusses how to prevent ischemic complications and what steps to take should a dermatologic emergency develop. A thorough understanding of facial anatomy is important. Preferred procedural techniques involve the use of cannulas and retrograde injection. When ischemia is detected in the skin, hyaluronidase should be injected, preferably through a cannula. If ocular ischemia occurs, the patient should be transferred to a hospital with stroke code activation.

Tratamiento y manejo fibrinolítico en síndrome de Nicolau: Caso clínico / Fibrinolytic treatment and management in Nicolau syndrome: Clinical case

RESUMEN Introducción: El síndrome de Nicolau (SN), conocido como embolia cutis medicamentosa o dermatitis livedoide es un acontecimiento adverso debido a la administración de inyecciones intramusculares, intraarteriales, subcutánea e incluso intraarticulares asociado a diversos fármacos1. Se desconoce toda la patogenia de este síndrome, pero se ha asociado a lesión vascular, trombosis arterial, espasmo reflejo de las arterias, oclusión vascular por microembolia e inflamación. Caso clínico: Paciente masculino de 32 años de edad, luego de inyección intramuscular de penicilina benzatínica presenta dolor intenso en área de inyección que se acompaña de lesiones eritematosas a nivel de abdomen, escroto y miembro inferior derecho además de presentar dolor, pareste-sia, palidez moteado eritematoso (livedo) y disminución de pulsos en dicha extremidad por lo que se diagnostica isquemia aguda (IA) que requirió tratamien-to fibrinolitico, entre otros fármacos. Conclusión: El síndrome de Nicolau es una condición iatrogénica que puede ser producida por inyección de múltiples medicamentos, puede presentar diferentes síntomas y signos como lesión neurológica, necrosis en área de irrigación de vasos afectados e incluso isquemia aguda. En este caso el manejo con rt-PA fue efectivo en tratar la isquemia. El conocimiento de este síndrome y sus complicaciones facilitaría su manejo2.Palabras claves: Síndrome Nicolau, bencilpenicilina, anticoagulante, rt-PA

ABSTRACT Introduction: Nicolau syndrome (NS), known as cutaneous embolism or livedoid dermatitis, is an adverse event due to the administration of intramuscular, intraarterial, subcutaneous and intraarticular injections associated with various drugs1. The entire pathogenesis of this syndrome is unknown, but it has been associated with vascular injury, arterial thrombosis, reflex spasm of the arteries, vascular occlusion due to microemboli, and inflammation. Clinical case: 32-year-old male. After an intramuscular injection of benzathine penicillin, the patient presented severe pain in the injection area accompanied by erythem-atous lesions at the level of the abdomen, scrotum, and right lower limb. In addition to that, the patient presented pain, paresthesia, and mottled paleness erythema (livedo). Moreover, the patient had a decreased pulse in the right limb, acute ischemia was diagnosed and required fibrinolitic treatment, among other drugs. Conclusion: Nicolau Syndrome, is an iatrogenic condition that is produced by injection of multiple drugs. It can produce different symptoms and signs from neurological injury, necrosis in the irrigation area of affected vessels and acute ischemia. rt-PA management in this case was effective in treating ischemia. It is essential to know about this syndrome and its complications. This would facilitate its management2.Keywords: Nicolau syndrome, benzylpenicillin, anticoagulant, rt-PA.