Raynaud\'s syndrome is a common finding in many autoimmune conditions. Accurately diagnosing Raynaud\'s, and differentiating it from mimicking conditions, is imperative in rheumatologic diseases. Raynaud\'s syndrome and Raynaud\'s mimickers, especially painful Raynaud\'s mimickers, can prove a diagnostic challenge for the practicing rheumatologist. Painful Raynaud\'s mimickers can lead to increased patient stress and unnecessary medical work up; Healthcare providers need to be aware of Raynaud\'s mimickers when evaluating patient concerns of skin color changes and pain. The present narrative review aims to highlight Raynaud\'s syndrome, important painful mimickers that may be seen, diagnosis, and updated management recommendations.

Acrocyanosis and erythema pernio are 2 dermatologic manifestations of vasospastic changes. Primary care providers should consider that these conditions can occur as primary or idiopathic conditions and as secondary conditions related to another disease or medication. Herein we describe a case of acrocyanosis and erythema pernio attributed to vincristine therapy.
A 22-year-old man was evaluated for discomfort and red lesions involving the toes of both feet for several weeks. He had completed chemotherapy 1 month earlier for Ewing sarcoma in the right femur. Local control for the primary tumor included wide local excision and reconstruction with a vascularized fibular allograft from the right fibula. On examination, his right foot was dark blue and cool. Toes on both feet had nonpainful erythematous papules. After the case was discussed with the patient\'s oncology team, the diagnosis was medication-induced acrocyanosis of the right foot and bilateral erythema pernio. Treatment consisted of supportive care to keep the feet warm and promote circulation to the feet. At 2-week follow-up, the patient\'s symptoms and the appearance of his feet had markedly improved.
Primary care clinicians should be able to recognize dermatologic manifestations of vasospastic changes, including acrocyanosis and erythema pernio, and rule out possible secondary causes, such as pharmacologic agents. This patient\'s history of therapy for Ewing sarcoma prompted consideration of medication-induced vasospastic changes most likely related to the adverse vasospastic effects of vincristine. Symptoms should improve with cessation of the offending medication.

Secondary acrocyanosis after spinal cord injury is extremely rare. We describe a case with secondary acrocyanosis in a complete T12 paraplegic patient. A 41-year-old man with complete T12 paraplegia after a gunshot wound to the thoracic spine 20 years prior presented with a four-month history of bilateral foot bluish discoloration precipitated when he sat with his legs down, improving rapidly after a few minutes of leg elevation. Changes in the skin color of the lower extremities were evaluated in the seated position for two hours. The skin color became darker, progressing to a bluish discoloration through the entire length of the legs. After two hours, the feet and most of the legs appeared deep purple. The color of the legs returned to their baseline three minutes later after the patient was placed supine in the bed. The diagnosis of secondary acrocyanosis due to the T12 spinal cord injury was established based on the physical examination and ancillary tests showing no peripheral ischemia. Other causes of secondary acrocyanosis were excluded during the work-up. This report presents the first case of a paraplegic patient with spinal cord injury presenting secondary acrocyanosis.

In this Part 2 of a 2-part continuing medical education series, we review the epidemiology of peripheral vascular disease, its association with cutaneous symptoms, and the diagnosis and evaluation of cutaneous features of vascular disorders. As peripheral vascular disease becomes more prevalent globally, it is essential for dermatologists to become competent at accurately recognizing and diagnosing cutaneous manifestations and directing individuals to receive appropriate care and treatment.

Ethylmalonic encephalopathy (MIM #602473) is a rare autosomal recessive metabolic condition caused by biallelic variants in ETHE1 (MIM #608451), characterized by global developmental delay, infantile hypotonia, seizures, and microvascular damage. The microvascular changes result in a pattern of relapsing spontaneous diffuse petechiae and purpura, positional acrocyanosis, and pedal edema, hemorrhagic suffusions of mucous membranes, and chronic diarrhea. Here, we describe an instructive case in which ethylmalonic encephalopathy masqueraded as meningococcal septicemia and shock. Ultrarapid whole-genome testing (time to result 60 h) and prompt biochemical analysis facilitated accurate diagnosis and counseling with rapid implementation of precision treatment for the metabolic crisis related to this condition. This case provides a timely reminder to consider rare genetic diagnoses when atypical features of more common conditions are present, with an early referral to ensure prompt biochemical and genomic diagnosis.

After reading with great interest the article entitled: \"Exploring the impact of the COVID-19 pandemic on provision of cardiology services: a scoping review\" redacted by Farah Yasmin et al., published by Reviews in Cardiovascular Medicine, we would like to add the following thoughts. Acute respiratory distress syndrome (ARDS) in Coronavirus disease 2019 (COVID-19) and pulmonary insufficiency reduces blood oxygen saturation and results in hypoxia. Therefore, the determining factor in the survival of patients with COVID-19 is their resistance to hypoxia. At the same time, it is the cardiovascular system that is an important and very sensitive link in the human adaptation to hypoxia. That is why it is necessary to carefully study the relationship between diseases of the heart, blood vessels, the reactivity of the cardiovascular system to hypoxia, and mortality in patients who develop ARDS with COVID-19.

Acrocyanosis triggered by standing position as the main sign of postural orthostatic tachycardia (POTS) is little known but well described in scientific literature. In pediatric age, POTS is defined as orthostatic intolerance that is accompanied by an excessive increase in heart rate without arterial hypotension. We present two clinical reports of teenagers who were admitted in the Emergency Department with acrocyanosis and orthostatic intolerance. The first patient was 13-year-old and had an increase in heart rate of 40 bpm when moving from a reclining to a standing position. The second patient was 14-year-old and showed an increasing in heart rate up to 125 bpm after upright position. In both patients\' blood pressure was normal and all investigations were negative. They were finally diagnosed with Acrocianosis como primera manifestación de síndrome de taquicardia postural ortostática en dos adolescentes Acrocyanosis as the first manifestation of orthostatic postural tachycardia syndrome in two adolescents postural orthostatic tachycardia. Recognizing acrocyanosis as first sign of this disease is useful for diagnosis and can help to avoid unnecessary testing.
La acrocianosis desencadenada por la bipedestación como signo principal de la taquicardia postural ortostática (POTS, por su sigla en inglés) es poco conocida, aunque bien descrita en la bibliografía especializada. Se describen dos casos clínicos de adolescentes que consultaron en el Servicio de Urgencias por acrocianosis e intolerancia al ortostatismo. El primer paciente, de 13 años, presentó un aumento de la frecuencia cardíaca de 40 latidos por minuto (lpm) al pasar del decúbito a la bipedestación. El segundo, de 14 años, presentó un aumento de la frecuencia cardíaca hasta 125 lpm al incorporarse. En ambos, la tensión arterial y los estudios complementarios fueron normales. El POTS se define en la edad pediátrica como una intolerancia al ortostatismo que se acompaña de aumento de la frecuencia cardíaca excesiva sin hipotensión arterial. Conocer la acrocianosis como primer signo de presentación es de utilidad para el diagnóstico de esta enfermedad y para evitar estudios complementarios innecesarios.

Vasospastic disorders are prevalent in the general population and can affect individuals of any age. Primary (or idiopathic) vasospastic disorders often have a benign course; treatment focuses on the control of symptoms. Secondary vasospastic disorders occur owing to an underlying condition and have an increased risk of complications, including tissue loss and digital ulcerations; treatment should focus on the underlying condition. In this review, we discuss the pathophysiology, clinical presentation, diagnosis, and management of vasospastic disorders, including Raynaud syndrome, acrocyanosis, livedo reticularis, and pernio.

In neuropathic postural tachycardia syndrome, peripheral sympathetic dysfunction leads to excessive venous blood pooling during orthostasis. Up to 84% of patients report leg pain and weakness in the upright position. To explore possible pathophysiological processes underlying these symptoms, the present study examined muscle excitability depending on body position in patients with neuropathic postural tachycardia syndrome and healthy subjects.
In ten patients with neuropathic postural tachycardia syndrome and ten healthy subjects, muscle excitability measurements were performed repeatedly: in the supine position, during 10 min of head-up tilt and during 6 min thereafter. Additionally, lower leg circumference was measured and subjective leg pain levels were assessed.
In patients with neuropathic postural tachycardia syndrome, muscle excitability was increased in the supine position, decreased progressively during tilt, continued to decrease after being returned to the supine position, and did not completely recover to baseline values after 6 min of supine rest. The reduction in muscle excitability during tilt was paralleled by an increase in lower leg circumference as well as leg pain levels. No such changes were observed in healthy subjects.
This study provides evidence for the occurrence of orthostatic changes in muscle excitability in patients with neuropathic postural tachycardia syndrome and that these may be associated with inadequate perfusion of the lower extremities. Insufficient perfusion as a consequence of blood stasis may cause misery perfusion of the muscles, which could explain the occurrence of orthostatic leg pain in neuropathic postural tachycardia syndrome.

BACKGROUND: Hypercoagulability is a risk factor of thromboembolic events in COVID-19. Anti-phospholipid (aPL) antibodies have been hypothesized to be involved. Typical COVID-19 dermatological manifestations of livedo reticularis and digital ischemia may resemble cutaneous manifestations of anti-phospholipid syndrome (APS).
OBJECTIVE: To investigate the association between aPL antibodies and thromboembolic events, COVID-19 severity, mortality, and cutaneous manifestations in patients with COVID-19.
METHODS: aPL antibodies [anti-beta2-glycoprotein-1 (B2GP1) and anti-cardiolipin (aCL) antibodies] were titered in frozen serum samples from hospitalized COVID-19 patients and the patients\' clinical records were retrospectively analyzed.
RESULTS: 173 patients were enrolled. aPL antibodies were detected in 34.7% of patients, anti-B2GP1 antibodies in 30.1%, and aCL antibodies in 10.4%. Double positivity was observed in 5.2% of patients. Thromboembolic events occurred in 9.8% of patients, including 11 pulmonary embolisms, 1 case of celiac tripod thrombosis, and six arterial ischemic events affecting the cerebral, celiac, splenic, or femoral-popliteal arteries or the aorta. aPL antibodies were found in 52.9% of patients with vascular events, but thromboembolic events were not correlated to aPL antibodies (adjusted OR = 1.69, p = 0.502). Ten patients (5.8%) had cutaneous signs of vasculopathy: nine livedo reticularis and one acrocyanosis. No significant association was observed between the presence of cutaneous vasculopathy and aPL antibodies (p = 0.692).
CONCLUSIONS: Anti-phospholipid antibodies cannot be considered responsible for hypercoagulability and thrombotic events in COVID-19 patients. In COVID-19 patients, livedo reticularis and acrocyanosis do not appear to be cutaneous manifestations of APS.