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

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.

TITLE: Síndrome de Nicolau por fármacos autoinyectables en la esclerosis múltiple.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.

Livedoid cutaneous metastasis of signet-ring cell gastric carcinoma.

Cutaneous metastasis of gastric cancer is extremely rare. Nodular forms are more common and inflammatory forms are exceptionally encountered. Herein, we report a case of inflammatory cutaneous metastasis of signet-ring cell gastric cancer (poorly cohesive gastric carcinoma with signet-ring cell component) masquerading as livedo reticularis. To our knowledge, such a clinical presentation of cutaneous metastasis has not been reported for gastric cancer. It is imperative to preserve a high index of clinical suspicion for diagnosing cutaneous metastases. Our case highlights the importance of obtaining a skin biopsy in patients with a known history of internal malignancy. Bizarre, newly erupting, evolving, persistent, or treatment-refractory dermatologic lesions (such as nodules, ulcers, erythematous, reticular, or livedoid patches) might be clues for an underlying internal malignancy and require prompt histopathological sampling. Personal medical history, histopathological examination, and immunohistochemical profiling are equally important in distinguishing primary cutaneous carcinomas from secondary metastatic deposits. Early recognition of a cutaneous metastasis might enable appropriate staging and timely intervention, thereby prolonging survival.

[Cutaneous Manifestations Associated with COVID-19: A Narrative Review]. / Manifestações Cutâneas Associadas à COVID-19: Uma Revisão Narrativa.

INTRODUCTION: COVID-19 is an infectious disease caused by the new coronavirus, SARS-CoV-2, that has spread rapidly throughout the world. This has resulted in an urgent need to obtain information regarding its pathogenesis, diagnosis and clinical manifestations. More specifically, skin manifestations, seldom reported initially, have been increasingly described. MATERIAL AND METHODS: We performed a literature search in the PubMed database, regarding cutaneous manifestations associated with COVID-19. This article describes the clinical and histological findings of the main skin lesions observed in the context of SARS-CoV-2 infection. DISCUSSION: Cutaneous manifestations associated with COVID-19 have been described in multiple retrospective and prospective studies, case series and case reports. The reported incidence reached 20.4%. Although there was substantial heterogeneity in terms of clinical patterns, the main ones include: erythematous/maculopapular, urticarial, papulovesicular, and purpuric/petechial eruptions, chilblain-like lesions and livedoid/acro-ischemic lesions. In the vast majority, the underlying pathophysiologic mechanisms are not fully understood, although histopathological findings and biomolecular studies can add relevant data. CONCLUSION: The recognition of cutaneous manifestations associated with COVID-19 is of utmost importance. They may help establishing an early diagnosis, namely in oligosymptomatic patients or when confirmatory tests are impossible to perform. Moreover, chilblain-like lesions and acro-ischemia, also seem to play an important role in terms of prognosis.

Introdução: A COVID-19, doença infeciosa causada por um novo coronavírus, SARS-CoV-2, propagou-se rapidamente pelo mundo inteiro, resultando numa necessidade emergente de obtenção de conhecimentos alusivos à sua patogénese, diagnóstico e sintomatologia. Mais especificamente, um número cada vez maior de casos relativos a manifestações cutâneas, previamente desconhecidas, tem vindo a ser descrito.Material e Métodos: Foi realizada uma pesquisa de literatura, através da base de dados PubMed, referente às manifestações dermatológicas associadas à COVID-19. O presente artigo descreve os achados clínicos e histológicos das principais lesões cutâneas observadas em contexto da infeção por SARS-CoV-2.Discussão: Manifestações cutâneas associadas à COVID-19 foram descritas em múltiplos estudos retrospetivos e prospetivos, séries de casos e casos clínicos isolados. A incidência reportada atingiu os 20,4%, verificando-se uma heterogeneidade de padrões clínicos substancial. Destes destacam-se as erupções eritematosas/maculopapulares, urticariformes, papulovesiculares, purpúricas/petequiais, lesões tipo-perniose e lesões livedóides/acro-isquémicas. O conhecimento dos mecanismos fisiopatológicos subjacentes tem vindo a ser enriquecido com achados os histológicos e de biologia molecular.Conclusão: É essencial o reconhecimento das manifestações dermatológicas associadas à COVID-19, uma vez que podem permitir o diagnóstico precoce da infeção, nomeadamente em casos oligossintomáticos ou quando não é possível a realização de testes confirmatórios. Embora menos estabelecido, lesões tipo-perniose e acro-isquémicas, parecem ter também um papel importante a nível prognóstico.

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.

Skin manifestations of COVID-19 in children: Part 3.

The current COVID-19 pandemic is caused by the SARS-CoV-2 coronavirus. The initial recognized symptoms were respiratory, sometimes culminating in severe respiratory distress requiring ventilation, and causing death in a percentage of those infected. As time has passed, other symptoms have been recognized. The initial reports of cutaneous manifestations were from Italian dermatologists, probably because Italy was the first European country to be heavily affected by the pandemic. The overall clinical presentation, course and outcome of SARS-CoV-2 infection in children differ from those in adults as do the cutaneous manifestations of childhood. In this review, we summarize the current knowledge on the cutaneous manifestations of COVID-19 in children after thorough and critical review of articles published in the literature and from the personal experience of a large panel of paediatric dermatologists in Europe. In Part 1, we discuss one of the first and most widespread cutaneous manifestations of COVID-19, chilblain-like lesions, and in Part 2 we expanded to other manifestations, including erythema multiforme, urticaria and Kawasaki disease-like inflammatory multisystemic syndrome. In this part of the review, we discuss the histological findings of COVID-19 manifestations, and the testing and management of infected children for both COVID-19 and any other pre-existing conditions.

Livedoid vasculopathy: does hyperhomocysteinaemia play an aetiological role?

BACKGROUND: Livedoid vasculopathy (LV) has been shown to be associated with hypercoagulability. However, relevant genetic and exogenous thrombophilic factors are not fully determined. OBJECTIVES: To evaluate the frequency of hyperhomocysteinaemia (HHCE) and genotypes of hypercoagulative factors in LV patients. MATERIAL AND METHODS: Plasma homocysteine level was measured in 42 LV patients. Polymorphism of MTHFR (677C > T and 1298A > C), PAI1 (-675 5G/4G and -844A > G), and F2 (20210G > A), and the F5 Leiden mutation, as well as biochemical parameters for hypercoagulability, were analysed. RESULTS: Of the LV patients, 62% revealed mild HHCE. Polymorphisms of MTHFR were observed in 75% and 56% and the PAI1 -675 5G/4G polymorphism in 100% and 83% of patients with and without HHCE, respectively. All LV patients with renal failure had mild HHCE. A high level of comorbidity of hypertension (99%) and diabetes type 2 (44%) were noted. CONCLUSION: HHCE seems to play a major pathogenetic role in LV. A high prevalence of further procoagulative factors might support the view that LV is a "complex disease".

Nicolau Syndrome (Embolia Cutis Medicamentosa): A Rare and Poorly Recognized Iatrogenic Cause of Cutaneous Thrombotic Vasculopathy.

Nicolau syndrome is a rare form of iatrogenic cutaneous necrosis which affects injection sites. Although classically associated with intramuscular injections, it may develop after subcutaneous or other routes of parenteral drug administration. Clinically, it manifests as necrotic ulcers that often develop in a background of erythematous and livedoid reticular patches. The histopathologic characteristics of Nicolau syndrome are poorly documented in the dermatopathology literature and features only rarely as one of the obscure causes of cutaneous thrombotic vasculopathy. We report a case of Nicolau syndrome developing secondary to subcutaneous injection of cyclizine to familiarize the clinicians and pathologists to this unusual condition. Given that it is potentially avoidable, pathologists should alert the clinicians to the possibility of Nicolau syndrome when a skin biopsy from an injection site shows signs of extensive thrombotic vasculopathy.

[Nicolau syndrome after intramuscular injection]. / Complication d'une injection intramusculaire ou syndrome de Nicolau.

Nicolau syndrome is a rare, potentially severe complication that may occur after any drug injection, particularly after intramuscular injection. It is characterized by the acute onset of cutaneous and soft-tissue aseptic necrosis. Here, we report the case of a 14-year-old boy diagnosed with Nicolau syndrome on the right lower limb, after a benzathine-penicillin intramuscular injection for suspected rheumatic fever. The short-term progression was marked by uncomplicated rhabdomyolysis and the constitution of homolateral testicular torsion. The cutaneous-muscular disorders evolved favorably under symptomatic treatment. We discuss this insufficiently known complication of intramuscular injection, which may motivate reduced use of this route of drug administration in children and strict adherence to the procedure. Furthermore, it is important to note that Nicolau syndrome may evolve to homolateral testicular torsion, as, to the best of our knowledge, is reported for the first time in this case.