Intramuscular diclofenac is a cause of Nicolau syndrome in obese women: An observational study of consecutive ten patients.

Nicolau syndrome is a skin and underlying tissue necrosis resulting from vascular occlusion after various injections of certain drugs. Intramuscular injections are the most common cause but it may occur after other types of parenteral interventions. There are many medications reported as causative factors inducing Nicolau syndrome including penicillin, nonsteroidal anti-inflammatory drugs, corticosteroids, local anesthetics, and several others. We present an observational study of diclofenac induced Nicolau syndrome.

[Nicolau livedoid dermatitis with severe neurological involvement in a child]. / Dermite livédoïde de Nicolau avec atteinte neurologique sévère chez un enfant.

BACKGROUND: Nicolau syndrome is a rare condition consisting in tissue ischemia and necrosis following intramuscular, intra-articular or subcutaneous injection. PATIENTS AND METHODS: Immediately after gluteal intramuscular injection of benzathine-penicillin, a 10-year-old male child presented an extensive painful violaceous lesion on the left buttock associated with urinary incontinence and left lower-limb paresis. Additional underlying muscular damage was supported by high serum levels of creatine kinase and lactate dehydrogenase. Treatment was based on fluid expansion, intravenous steroids and anticoagulants, resulting in improvement of cutaneous and muscular lesions. Improvement in terms of neurological dysfunction was obtained after regular neuromuscular rehabilitation. DISCUSSION: This case underlines the need to prevent Nicolau syndrome by means of compliance with the technical recommendations for intramuscular injections.

Nicolau syndrome and localized panniculitis: a report of dual diagnoses with an emphasis on morphea profunda-like changes following injection with glatiramer acetate.

Glatiramer acetate, given as a 40 mg subcutaneous injection thrice weekly, was recently approved by the FDA based on data suggesting better compliance and a more favorable side effect profile compared to lower dose, daily dosing. The most commonly reported adverse events are transient injection site reactions involving redness and pain at the site; however, more pronounced panniculitis and lipoatrophy have also been reported. Here, we present the case of a 51-year-old female treated with higher dose glatiramer acetate who presented with a cutaneous injection site reaction consistent with Nicolau syndrome. The excised specimen revealed typical glatiramer acetate-associated panniculitis, alongside subcutaneous sclerosis. This case shows the spectrum of cutaneous complications possible with glatiramer acetate injections, the finding of sclerosis being relatively infrequently reported. Given the relatively short duration of trials leading to FDA approval of thrice weekly dosing of glatiramer acetate, clinicians should perform careful clinical and histopathological evaluation and reporting of patients who experience injection site reactions.

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.

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]. / 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.

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 following subcutaneous glatiramer acetate injection: A case report and review of the literature.

Nicolau syndrome is a rare serious drug reaction associated with the administering various injectable medications. It is often characterized by an acute and severe pain accompanying erythema that tends to rapidly evolve into the livedoid reticular or hemorrhagic patches and less commonly to ulcers and skin necrosis. Herein, we report a 34-year-old woman who presented with painful, tender discoloration over her abdominal skin following subcutaneous glatiramer acetate injection. Since the patient was diagnosed with multiple sclerosis 18 months ago, she had been on treatment with subcutaneous glatiramer acetate injections thrice weekly. The patient was diagnosed with Nicolau syndrome clinically and histopathologically. After 15-day treatment with topical betamethasone valerate and mucopolysaccharide polysulfate cream twice daily, the lesion completely regressed with only minimal hypopigmented irregular scarring. Nicolau syndrome should be considered in patients with severe pain, tenderness, and redness localized at the injection site following glatiramer subacetate.

[Severe acute limb ischemia resulting in rescue disarticulation in a patient with Nicolau syndrome following intramuscular penicillin injection: a case report]. / Ischémie aiguë de membre sévère sanctionnée par désarticulation de sauvetage dans un contexte de syndrome de Nicolau suite à une injection intramusculaire de pénicilline: à propos d'un cas.

We here report the case of a 9-year-old child suffering from Nicolau syndrome involving the left pelvic limb with severe acute limb ischemia following intramuscular benzathine penicillin injection into the buttock. Given the rarity of acute limb ischemia in children, this case of complicated Nicolau syndrome combining acute arterial thrombosis and severe rhabdomyolysis leading to rescue hip dislocation is very interesting.

Nicolau Syndrome, Masquerader of Postinjection Sciatic Nerve Injury: Case Report and Review of Literature.

BACKGROUND: Sciatic nerve injury after inadvertent intramuscular gluteal injection is a well-described entity. We have presented a case of a rare and probably underdiagnosed pathological entity, Nicolau syndrome, which can be confused with injection palsy. CASE DESCRIPTION: We report the case of a 13-year-old boy who had presented with foot drop and urinary and fecal incontinence after an intramuscular injection of benzathine penicillin in the left gluteal region. On examination, the patient had multiple ecchymoses over the left gluteal region and back of the thigh, mild swelling of the left lower limb, and left foot drop. Meticulous examination also revealed a subtle weakness of the opposite limb. Nerve conduction studies revealed axonopathy involving multiple bilateral lower limb nerves. These unusual neurological-dermatological signs and electrophysiological findings raised the concern for an alternative pathology, which was later diagnosed as Nicolau syndrome. The patient experienced clinical and electrophysiological recovery after a course of oral steroids and physiotherapy during the next few months. CONCLUSIONS: Before diagnosing injection sciatic nerve injury, the possibility of medically treatable Nicolau syndrome should be considered. Neurosurgeons' familiarity with this pathology and a timely diagnosis is essential to plan appropriate treatment strategies.

[Severe pain and skin discolouration after injection: Nicolau syndrome, a rare complication]. / Hevige pijn en huidverkleuring na een injectie.

BACKGROUND Parenteral administration of medication is a frequent practice, but in rare cases, serious complications may occur. CASE DESCRIPTION A 33-year-old man experienced intense pain in his forearm immediately after administration of clemastine through a Venflon in his elbow crease. The pain was accompanied by white discolouration of some fingers and livid discolouration of the skin between the fingers. This reaction is typical for Nicolau syndrome, a rare skin reaction that may develop after intramuscular or intra-arterial administration of medication. Aetiology is unclear, but vascular spasms, blood vessel wall damage and thrombosis are the most important factors. Treatment consists of minimising complications. CONCLUSION In the worst cases of Nicolau syndrome, extensive necrosis and permanent injury may occur. It is important to recognise the symptoms. Preventing or minimising tissue necrosis is essential and attention should be paid to pain relief. Proper injection methods can prevent the occurrence of this syndrome.

Nicolau's syndrome: A rare but preventable iatrogenic disease.

Dear Editor, Nicolau's syndrome, also called embolia cutis medicamentosa or livedoid dermatitis, is a rare injection site reaction characterized by immediate intense pain at the injection site followed by erythema and a hemorrhagic patch with a livedoid reticular pattern after injections of non-steroidal anti-inflammatory drugs (NSAIDS), antiepileptics, antibiotics, antihistaminics, corticosteroids, etc. (1). To the best of our knowledge, only one case of Nicolau's syndrome has been reported after the use of triamcinolone acetonide. Herein we report two cases of Nicolau's syndrome caused by intramuscular injections of triamcinolone acetonide and diclofenac sodium, respectively. CASE 1 A 24-year-old male patient presented with severe pain and bluish discoloration of the right arm for 2 days, which he had noticed shortly after receiving an intramuscular injection of triamcinolone for recurrent episodes of urticaria by a local practitioner in the right deltoid region. On examination, there was a livedoid pattern of non-blanchable, violaceous discoloration extending from the deltoid area to the distal third of the forearm with associated induration (Figure 1, a, b). The local area was warm and tender to the touch. There was no regional lymphadenopathy, and the rest of the examination was normal. The patient's platelet count, bleeding and clotting times, prothrombin time, and international normalized ratio (INR) were unremarkable. There was no previous history of any bleeding disorder. The patient denied any intake of drugs like aspirin, warfarin, etc. Subsequently, the patient developed an ulcer on the forearm, which was managed by topical and systemic antibiotics to prevent any secondary infection of the wound. CASE 2 A 40-year-old female patient presented with complaints of pain and discoloration of the left gluteal region after receiving an intramuscular injection of diclofenac sodium for her arthralgia. A large ecchymotic patch with reticular borders was found on the gluteal region, extending to the lateral aspect of thigh (Figure 2). It was tender to the touch, non-indurated, and the local temperature was raised. There was no regional lymphadenopathy. No other abnormality was detected on examination. All routine investigations were within normal limits. Platelet count, bleeding, clotting and prothrombin times, and international normalized ratio (INR) were within normal limits. The lesions resolved within few weeks without any complications. Nicolau syndrome was first described in the early 1920s by Freudenthal and Nicolau as an adverse effect of using intramuscular injections of bismuth salts in the treatment of syphilis. Since then, several case reports of this disease occurring after intramuscular, intra-articular, intravenous, and subcutaneous injections have appeared in the literature associated with a variety of drugs like NSAIDs, vitamin K, penicillin, antihistamines, corticosteroids, local anesthetics, vaccines, polidocanol, and pegylated interferon alpha (1). The pathogenesis of Nicolau syndrome is unknown, though intra and periarterial injection of the drug is a possible cause. Stimulation of the sympathetic nerve due to periarterial injection causes spasms and consequent ischemia. Inadvertent intra-arterial injections may cause emboli and occlusion. A lipophilic drug may penetrate the vessel and produce physical occlusion like fat embolism. Cytotoxic drugs may produce perivascular inflammation and ischemic necrosis. NSAIDs are believed to additionally induce ischemic necrosis due to their inhibition of cyclooxygenase and, consequently, prostaglandins (2). The clinical features of the disease have been divided into three phases in a review by Kim et al. (3). The authors describe an initial phase characterized by intense pain with subsequent erythema. This is followed 1-3 days later by an acute phase, when an indurated, tender plaque with livedoid pattern develops. The final phase occurs between 5 days and 2 weeks later. Necrosis ensues in this stage, with possible ulceration. Diagnosis is chiefly clinical, and histopathology shows necrotic changes and vascular thrombosis. However, a biopsy was not performed in our cases because both lesions were painful. Management strategies are variable and range from conservative management with analgesics and antibiotics to active surgical debridement (4). Complications include deformities, contractures or even death. The patient in our first case developed ulceration which healed normally, while the second case resolved without any complications. Nicolau syndrome can be avoided by precautions such as aspirating the needle before injecting to check for blood, use of Z-track injection technique, proper site of injection, avoiding large doses at a single site, and regular change of sites if multiple injections are to be given (5). Nicolau syndrome is a rare disease. There are a few case reports of it occurring after diclofenac injection (1-5). We could only find one case report of this syndrome after intramuscular injection (IM) of triamcinolone in a patient with lichen planus (3), and our case is the second reported case of this syndrome as a result of triamcinolone acetonide injection, which adds to the significance to the present article.

Aseptic myonecrosis following intramuscular benzathine penicllin G injection: a novel syndrome.

We report a novel syndrome of aseptic myonecrosis in a child occurring after intramuscular (IM) benzathine penicillin G injection for the treatment of streptococcal pharyngitis. Common side effects of IM injection, including transient injection site pain and inflammation, are common and well described. However, isolated myonecrosis following IM injection in the pediatric patient has not been previously reported. Only one similar case, following IM diclofenac injection, has been discussed in the adult literature.

Síndrome de nicolau en paciente pediátrico: reporte de caso / Case report: Nicolau síndrome in a pediatric patient

El síndrome de Nicolau o Embolia cutis medicamentosa o Dermatitis livedoide, es un síndrome raro en pediatría que se presenta como complicación de una inyección intramuscular con múltiples grados de daño tisular, in- cluyendo la necrosis de la piel y de los tejidos profundos. Reportamos el caso de un paciente masculino de 2 años de edad, sin antecedentes patológicos que acudió a la emergencia de pediatría del Hospital "Mario Catarino Rivas" (HMCR) en San Pedro Sula, Cortes, con historia de presentar lesión necrótica en la extremidad inferior y glúteo izquierdo, dolorosa a la palpación, que apa- reció posterior a la administración de un medicamen- to compuesto por vía intramuscular. Al examen físico se encontró una extensa placa necrótica dolorosa a la palpación y a la movilización del miembro, con pulsos periféricos conservados y sin frialdad distal. A través de abordaje multidisciplinario se brindó limpieza qui- rúrgica, cobertura antibiótica, manejo antitrombótico e injerto, con evolución favorable, por lo que resalta- mos que la identificación y manejo multidisciplinario oportuno es fundamental, como lo fue en este caso...(AU)

[A woman with complaints after an injection of diclofenac]. / Een vrouw met klachten na een diclofenac-injectie.

A 61-year-old woman came to the Emergency Department with a skin lesion located at her right upper leg. At the site of the lesion a subcutaneous injection of diclofenac had been administered for pain from nephrolithiasis. CT revealed a large infiltrate proximal in the right upper leg; histologic evaluation of the tissue showed an acute necrotizing inflammation. These findings are typical for Nicolau syndrome.