Acrocyanosis – Causes, Symptoms, Diagnosis, Treatment

Acrocyanosis/Cyan means ‘blue’ and the abnormal bluish discoloration of the skin and mucous membranes is referred to as “cyanosis”. It is a pathologic sign, and not a disease by itself. Underlying diseases that increase the deoxygenated hemoglobin to 5.0 g/dl or more leads to cyanosis. Cyanosis can be best appreciated in areas with rich superficial vasculature and thin overlying dermis. These include lips, nose, earlobes, oral cavity, extremities, and tips of fingers and toes. Cyanosis usually becomes evident in hypoxemia, that is, abnormally low concentration of oxygenation (<80-85%) in arterial blood. However, it is not sensitive or a specific indicator of hypoxemia. Since cyanosis is a clinical sign, a proper evaluation is important to determine the etiology of cyanosis.[rx]

Acrocyanosis is due to a decrease in the amount of oxygen delivered to the tissues of the extremities. Several mechanisms for primary acrocyanosis have been proposed, but the precise mechanism remains elusive. Potential pathophysiological disturbances include abnormal arteriolar tone, alteration of microvascular responsiveness with capillary and venular dilation and stasis, and abnormal sympathetic nervous system activity.

Types of Cyanosis

Cyanosis is further classified as central, peripheral, and differential.[rx]

• Central cyanosis – is a generalized bluish discoloration of the body and the visible mucous membranes, which occurs due to inadequate oxygenation secondary to conditions that lead to an increase in deoxygenated hemoglobin or the presence of abnormal hemoglobin.
• Peripheral cyanosis – is the bluish discoloration of the distal extremities (hands, fingertips, toes), and can sometimes involve circumoral and periorbital areas. Mucous membranes are generally not involved. Peripheral cyanosis is rarely a life-threatening medical emergency. However, it is essential to determine the underlying cause and its timely management to prevent potential complications.
• Differential cyanosis – is the asymmetrical bluish discoloration between the upper and lower extremities. It usually indicates serious underlying cardiopulmonary conditions.[rx]

The bluish discoloration despite adequate oxygenation is sometimes seen due to the ingestion of drugs, toxins, or metals. This is called ‘Pseudocyanosis.’

Causes of Acrocyanosis

Causes of  Acrocyanosis include:[rx][rx]

• Hypoventilation due to conditions affecting the central nervous system, such as intracranial hemorrhage, tonic-clonic seizures, and heroin overdose.
• Pulmonary causes leading to ventilation-perfusion mismatch and impaired alveolar-arterial diffusion, for instance, bronchospasm (asthma), pulmonary embolism, pneumonia, bronchiolitis, pulmonary hypertension, hypoventilation, and COPD[rx][rx][rx]
• Cardiovascular causes include heart failure, congenital heart diseases (right to left shunting), and valvular heart diseases.
• Hemoglobinopathies including methemoglobinemia, sulfhemoglobinemia
• Polycythemia
• High altitude
• Hypothermia
• Obstructive sleep apnea
• Pulmonary
• Impaired gas exchange secondary to pneumonia
• Embolism and ventilation-perfusion mismatch
• Impaired gas diffusion via the alveoli
• High altitude
• Anatomic shunts
• Right to left shunt in congenital heart disease
• Arteriovenous malformation
• Intrapulmonary shunt

Peripheral cyanosis can be seen because of the following:

• Reduced cardiac output secondary to heart failure or shock
• Local vasoconstriction due to cold exposure, hypothermia, acrocyanosis, and Raynaud phenomenon
• Vasomotor instability
• Arterial obstruction causing regional ischemia secondary to peripheral vascular disease. Causes include atherosclerosis, Buerger disease, atheroembolism
• Venous stasis or obstruction, such as in deep vein thrombosis
• Hyperviscosity attributable to multiple myelomas, polycythemia, and macroglobulinemia

All causes of central cyanosis can also cause peripheral cyanosis. Cardiopulmonary causes and hemoglobin abnormalities are the common causes of central cyanosis. Differential cyanosis can be seen in patent ductus arteriosus with pulmonary hypertension.[rx]

Symptoms of Acrocyanosis

Acrocyanosis is characterized by peripheral cyanosis: persistent cyanosis of the hands, feet, or face.^[rx] The extremities often are cold and clammy and may exhibit some swelling (especially in the warmer weather).^[rx][rx] The palms and soles exhibit a wide range of sweating from moderately moist to profuse, but all peripheral pulses should have normal rate, rhythm, and quality.^[rx][rx] Exposure to cold temperatures worsens the cyanosis, while it often improves on warming.^[rx] Aside from the color changes, patients normally are asymptomatic and therefore there is usually no associated pain. The most common sign, discoloration, usually is what prompts patients to seek medical care.^[rx][rx]

Peripheral cyanosis is characterized by the following:

• Localized cyanosis affecting only extremities
• Pink tongue as mucous membranes are almost never involved
• Cold extremities as compared to warm extremities in central cyanosis
• Clubbing is absent
• Pulse volume usually low
• Capillary refill time more than 2 sec
• Disappears with massage and warming
• Dyspnea usually absent

In children, the most common etiologies for life-threatening central cyanosis are congenital heart disorders and polycythemia. The common causes of peripheral cyanosis in this age group are cold exposure and acrocyanosis.

Diagnosis of Acrocyanosis

History and Physical

The detailed history and physical examination are vital in determining the underlying cause of cyanosis. The provider should inquire about the onset, duration, intake, or exposure to poisonous substances, exposure to the cold, site where cyanosis can be appreciated, and associated symptoms.

Physical examination should be carried out in an adequate light for the correct assessment of cyanosis. Poor light exposure, the thickness of the skin, and pigmentation of the skin can affect the accuracy of physical assessment. Cheeks, nose, ears, and oral mucosa are the best areas to assess cyanosis as the skin in these areas is thin, and blood supply is good. This can help determine if the cyanosis is generalized, limited to extremities, or if there is a difference in the bluish discoloration in different extremities.

The inspection – also includes looking for any thoracic cage deformity, accessory muscle use for respiration (nasal flaring, grunting, intrathoracic/supraclavicular retractions), asymmetry of chest expansion, discomfort in breathing, audible breath sounds, clubbing, posture, etc. These are helpful in narrowing down the underlying causes, especially if the cause is cardiac or pulmonary. It is helpful to carry out the palpation of brachial and femoral pulses, tactile and vocal fremitus, assessment of ventilation, and measurement of blood pressure in all four extremities.

Evaluation

• Co-oximetry and simple oximetry – are spectrophotometry methods to measure arterial blood oxygenation. Pulse oximetry is a non-invasive method as compared to co-oximetry, which requires a sample of arterial blood.
• To begin with, pulse oximetry –  a non-invasive and easily available test, should be done to rule out life-threatening hypoxemia as a cause. It is used to assess oxygenation; however, it may falsely indicate hypoxemia in peripheral cyanosis and dyshemoglobinemias. For instance, the value may be low if measured on an affected limb in both central and peripheral cyanosis.[rx]
• Co-oximetry – in addition to measuring oxygen saturation, can be used for arterial blood gas analysis. Arterial blood gas analysis shows normal arterial oxygenation in peripheral cyanosis, i.e., 85-100%. Contrary to this, the arterial oxygen saturation is low in central cyanosis. This test also determines the value of hemoglobin derivatives such as oxygenated hemoglobin, deoxygenated hemoglobin, and dyshemoglobins (methemoglobin, carboxyhemoglobin, sulfhemoglobin, etc.). It, therefore, only indicates low oxygen levels in hypoxemia due to central cyanosis. In pseudocyesis, both pulse oximetry and co-oximetry reveal normal oxygen levels.[rx][rx][rx]
• Peripheral blood film – hemoglobin concentration, blood glucose, and sepsis workup should be considered depending on the clinical scenario to evaluate the causes of cyanosis.
• ECG, and CT scan – can be done to evaluate the cardiopulmonary cause. Echocardiogram and invasive cardiac evaluation may be necessary in some cases.

Treatment of Acrocyanosis

There is no standard medical or surgical treatment for acrocyanosis, and treatment, other than reassurance and avoidance of cold, is usually unnecessary. The patient is reassured that no serious illness is present. A sympathectomy would alleviate the cyanosis by disrupting the fibers of the sympathetic nervous system to the area.^[rx] However, such an extreme procedure would rarely be appropriate. Treatment with vasoactive drugs is not recommended but traditionally is mentioned as optional. However, there is little, if any, empirical evidence that vasoactive drugs (α-adrenergic blocking agents or calcium channel blockers) are effective.^[rx][rx]

The treatment of central cyanosis, which is a clinical sign, is focused on the management of underlying conditions.[rx]

• Initial stabilization with oxygen support through regular/high flow nasal cannula is required for pulmonary oxygen diffusion impairment. In some conditions, assisted ventilation may be necessary.
• Metabolic abnormalities such as hypoglycemia and hypocalcemia should be corrected, if present. Metabolic abnormalities can occur as a result of the inability to feed secondary to cyanotic heart diseases in children.
• For cyanotic heart diseases, initial stabilization and airway management should be the priority. Cardiology referral for assessment and intervention is necessary for cyanotic congenital heart diseases such as tricuspid atresia, tetralogy of Fallot, etc. For congenital heart disease correction, surgical intervention is required. Drugs such as prostaglandin E1 infusion are used for ductal dependent conditions for pulmonary blood flow.
• Drugs such as diuretics, ACE inhibitors, inotropic drugs are considered for heart failure.
• Antibiotic prophylaxis in cyanotic heart disease patients to prevent bacterial endocarditis.
• Methylene blue is used for treating methemoglobinemia-induced cyanosis.
• The best therapy to manage blue discoloration due to exposure to gold and silver salts is the removal of offending agents.

The goal of the management of peripheral cyanosis is to identify and treat the underlying cause of vasoconstriction and the limited supply of oxygen-rich blood to the extremities. Peripheral cyanosis is usually reversible with restoration of the oxygenated blood flow to the extremities. It can rarely pose a life-threatening emergency. However, timely management is important to improve the outcome and prevent any potential complications.[rx]

• Gentle warming and massage of the affected parts provide symptomatic relief and reversal of peripheral cyanosis caused by exposure to cold and Raynaud phenomenon.
• In addition, longer-term lifestyle changes may be required in some conditions, such as Raynaud phenomenon. Limiting the intake of caffeine and nicotine/smoking, both of which can cause blood vessel narrowing is beneficial.
• Drugs that cause blood vessel relaxation may be used in peripheral cyanosis. These include antihypertensive drugs, antidepressants, and erectile dysfunction medications. In addition, drugs that constrict blood vessels such as beta-blockers, pseudoephedrine containing medications, birth control pills, and migraine drugs, should be avoided.
• When peripheral cyanosis is seen in sick looking children with signs of shock, rapid treatment should be done. Airway and breathing management with further evaluation of the cause of shock is warranted. The therapy is based upon the type of shock. Serious conditions, such as heart failure, must be treated in a hospital as an emergency.
• All causes of central cyanosis can also cause extremity cyanosis. Correcting the underlying cause is the key to managing such cases.

An interprofessional approach involving various subspecialties is warranted to diagnose and manage the underlying cause of cyanosis.

References