Painful Raynaud's mimics.

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.

Vincristine-Induced Acrocyanosis and Erythema Pernio.

INTRODUCTION: 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. CASE DESCRIPTION: 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. DISCUSSION: 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.

Acrocyanosis and Progressive Skin Necrosis as Manifestation of Waldenstrom Macroglobulinemia Associated With Type I Cryoglobulinemia: A Case Report.

Waldenstrom macroglobulinemia (WM), a rare malignant disorder, occurs as a result of abnormal proliferation of lymphocytes that produce immunoglobulin M. In rare cases, WM complicates by type I cryoglobulinemia. Type I cryoglobulinemia usually presents with cutaneous manifestations such as Raynaud's phenomenon, purpura, necrosis, and gangrene. Various medical conditions, including thrombotic events, rheumatologic disorders, and malignancies, may present with skin discoloration and necrosis. Patients suffering from malignant diseases who initially present with skin manifestations usually are misdiagnosed by physicians. Here, we describe a 72-year-old man presenting with a 6-month acrocyanosis and progressive skin necrosis who was misdiagnosed by physicians. Finally, he was diagnosed to have WM associated with type I cryoglobulinemia. Though uncommon, hematologic malignancies can present with cutaneous manifestations. In some cases, patients may manifest with skin disorders alone. Early and prompt treatment of these diseases may save the patient life, relieve patient symptoms, and increase life quality.

Part II: Cutaneous manifestations of peripheral vascular disease.

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.

Secondary Acrocyanosis in a Paraplegic Patient With Spinal Cord Injury.

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.

Ethylmalonic encephalopathy masquerading as meningococcemia.

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.

Cardiology, respiratory failure, and tolerance of hypoxia in the context of COVID-19: a multidisciplinary perspective.

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.

Paraneoplastic Raynaud's phenomenon as sign of progression: a case report on a patient with breast cancer.

BACKGROUND: Paraneoplastic Raynaud's phenomenon is a rare complication occurring in patients with advanced cancer. METHODS: We present a case of a patient with breast cancer and presenting with acrocyanosis evolving into necrosis as a paraneoplastic phenomenon in progressive breast cancer. RESULTS: Unless a multidisciplinary approach was taken, improvement of the symptoms was only seen with prostacyclin analogs, and cancer treatment needed to be changed because of rapidly progressing disease. CONCLUSION: Paraneoplastic Raynaud's phenomenon is a rare but severe presentation of advanced and progressive cancer. Treatment with intravenous prostacyclin analogs should be considered and a multidisciplinary approach is necessary.

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

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.

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 postural orthostatic tachycardia. Recognizing acrocyanosis as first sign of this disease is useful for diagnosis and can help to avoid unnecessary testing.

[Acrocyanosis as the first manifestation of orthostatic postural tachycardia syndrome in two adolescents]. / Acrocianosis como primera manifestación de síndrome de taquicardia postural ortostática en dos adolescentes.

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.

Leg pain in neuropathic postural tachycardia syndrome is associated with altered muscle membrane properties.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Raynaud Phenomenon and Other Vasospastic Disorders.

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.

A retrospective study on the prevalence of anti-phospholipid antibodies, thrombotic events and cutaneous signs of vasculopathy in 173 hospitalized COVID-19 patients.

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). OBJECTIVES: 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.

Primary acrocyanosis.

Primary acrocyanosis is a benign condition characterized by persistent blue discoloration of the peripheral extremities caused by vasospasm.

Multi-organ failure with necrotic skin lesions due to infection with Chlamydia psittaci.

Presented is a patient with dyspnea and painful ulcers finally resulting in multi-organ failure. A detailed history resulted in positive PCR testing for Chlamydia psittaci. We emphasize the importance of a definitive history in establishing the correct diagnosis. When clinicians observe dyspnea with multi-organ failure, they should be aware of psittacosis.

Raynaud's phenomenon and related vasospastic disorders.

Raynaud's phenomenon, which is characterized by episodic digital pallor, cyanosis and rubor upon exposure to cold environment or to stress, is relatively common, although the prevalence depends on the climate. Still, it is under-diagnosed, under-treated, and often confused with other conditions. Primary Raynaud's phenomenon (i.e., Raynaud disease) must be distinguished from secondary Raynaud's phenomenon (i.e., Raynaud syndrome) as long-term morbidity and outcomes differ vastly between the two conditions. Additionally, the practitioner must differentiate between Raynaud's phenomenon and related vascular disorders, such as acrocyanosis, pernio, and livedo reticularis. In this article, we review differences between the conditions and suggest an approach to diagnosis and treatment strategy for these disorders.

A visually striking case of primary acrocyanosis: A rare cause of the blue digit.

Cold environments can trigger a variety of conditions, which, in their acute phase often present to the Emergency Department. Primary acrocyanosis is a distinct, rare condition which may be missed resulting in misdiagnosis and mismanagement. Primary acrocyanosis is a peripheral vascular disorder defined by painless, symmetrical discoloration of the distal appendages and uniquely characterized by persistence of the skin color changes after cold exposure. We present a case of a 24-year-old female who presented to the Emergency Department with peripheral cyanosis after cold exposure and was eventually diagnosed with primary acrocyanosis by Rheumatology. The prognosis for primary acrocyanosis is quite good in comparison to other acrosyndromes and once secondary causes of acrocyanosis have been ruled, out can be managed conservatively with lifestyle modifications and potential follow-up with Rheumatology.

Acrocyanosis and digital necrosis are associated with poor prognosis in COVID-19.

Acrocyanosis and digital necrosis, which caused by microangiopathic and immunothrombosis phenomenon, may accompanied by microvascular involvement of other organs. Therefore, this finding can play a prognostic role in covid-19 outcome.

A case report of severe nasal ischemia from cold agglutinin disease and a novel treatment protocol including HBOT.

Cold agglutinin disease (CAD) is a rare condition leading to blood agglutination and autoimmune hemolytic anemia. Cutaneous ischemia resulting from CAD in the head and neck is uncommon. Treatment regimens and outcomes vary widely in the literature and no clear protocol exists. This manuscript describes a patient with CAD who developed severe ischemia of the nose that resolved completely without sequellae following a medical regimen of aspirin, low molecular weight heparin, nitroglycerin ointment and hyperbaric oxygen therapy (HBOT). To our knowledge, this is the first reported case where nitroglycerin ointment or HBOT was successfully employed in the treatment of this complication.