Acrocyanosis is persistent blue or

cyanotic Cyanosis is the change of tissue color to a bluish-purple hue, as a result of decrease in the amount of oxygen bound to the hemoglobin in the red blood cells of the capillary bed. Cyanosis is apparent usually in the body tissues covered with ...

discoloration of the extremities, most commonly occurring in the hands, although it also occurs in the feet and distal parts of the face.Kurklinsky AK, Miller VM, Rooke TW. "Acrocyanosis: The Flying Dutchman." ''Vascular Medicine'' 2011 Aug;16(4):288-301Olin, J.W. (2004). Other peripheral arterial diseases. In L. Goldman & D. Ausiello (Eds.), ''Cecil Textbook of Medicine, 22nd Edition''. (Vol 1, pp. 475). Philadelphia: WB Saunders Creager, M.A. & Dzau, V.J. (2005). Vascular diseases of the extremities. In D.L. Kasper, A.S. Fauci, D.L. Longo, E. Braunwald, S.L. Hauser, & J.L Jameson (Eds.), ''Harrison's Prins of Internal Medicine'' (16th ed., pp. 1490). New York: McGraw-Hill (2006). Peripheral vascular disorders. In R.S. Porter, T.V. Jones, & M.H. Beer (Eds.), ''Merck Manual of Diagnosis and Therapy'' (18th ed., ch. 212). New York: Wiley, John & Sons Although described over 100 years ago and not uncommon in practice, the nature of this phenomenon is still uncertain. The very term "acrocyanosis" is often applied inappropriately in cases when blue discoloration of the hands, feet, or parts of the face is noted. The principal (primary) form of acrocyanosis is that of a

benign Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malig ...

cosmetic condition, sometimes caused by a relatively benign neurohormonal disorder. Regardless of its cause, the benign form typically does not require medical treatment. A

medical emergency A medical emergency is an acute injury or illness that poses an immediate risk to a person's life or long-term health, sometimes referred to as a situation risking "life or limb". These emergencies may require assistance from another, qualified ...

would ensue if the extremities experience prolonged periods of exposure to the cold, particularly in children and patients with poor general health. However,

frostbite Frostbite is a skin injury that occurs when someone is exposed to extremely low temperatures, causing the freezing of the skin or other tissues, commonly affecting the fingers, toes, nose, ears, cheeks and chin areas. Most often, frostbite occ ...

differs from acrocyanosis because pain (via thermal

nociceptor A nociceptor (; ) is a sensory neuron that responds to damaging or potentially damaging stimuli by sending "possible threat" signals to the spinal cord and the brain. The brain creates the sensation of pain to direct attention to the body part, ...

s) often accompanies the former condition, while the latter is very rarely associated with pain. There are also a number of other conditions that affect hands, feet, and parts of the face with associated skin color changes that need to be differentiated from acrocyanosis:

Raynaud phenomenon Raynaud syndrome, also known as Raynaud's phenomenon, is a medical condition in which the spasm of small arteries causes episodes of reduced blood flow to end arterioles. Typically the fingers, and, less commonly, the toes, are involved. Rare ...

, pernio, acrorygosis,

erythromelalgia Erythromelalgia, or Mitchell's disease (after Silas Weir Mitchell (physician), Silas Weir Mitchell), is a rare vascular peripheral pain disorder in which blood vessels, usually in the Human leg, lower extremities or hands, are episodically blocke ...

, and blue finger syndrome. The diagnosis may be challenging in some cases, especially when these syndromes co-exist. Acrocyanosis may be a sign of a more serious medical problem, such as connective tissue diseases and diseases associated with

central cyanosis Cyanosis is the change of tissue color to a bluish-purple hue, as a result of decrease in the amount of oxygen bound to the hemoglobin in the red blood cells of the capillary bed. Cyanosis is apparent usually in the body tissues covered with ...

. Other causative conditions include

infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...

s, toxicities,

antiphospholipid syndrome Antiphospholipid syndrome, or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable state caused by antiphospholipid antibodies. APS can lead to blood clots (thrombosis) in both arteries and veins, pregnancy-relate ...

cryoglobulinemia Cryoglobulinemia is a rare medical condition characterized by the presence of cryoglobulins in the blood. Cryoglobulins are abnormal proteins composed of immunoglobulins and sometimes complement components. Cryoglobulins specifically form g ...

, neoplasms. In these cases, the observed cutaneous changes are known as "secondary acrocyanosis". They may have a less symmetric distribution and may be associated with pain and tissue loss.

Signs and symptoms

Acrocyanosis is characterized by peripheral cyanosis: persistent cyanosis of the hands, feet, knees, or face. The extremities often are cold and clammy and may exhibit some swelling (especially in warmer weather). The palms and soles exhibit a wide range of sweating from moderately moist to profuse, but all peripheral

pulse In medicine, the pulse refers to the rhythmic pulsations (expansion and contraction) of an artery in response to the cardiac cycle (heartbeat). The pulse may be felt ( palpated) in any place that allows an artery to be compressed near the surfac ...

s should have normal rate, rhythm, and quality. Exposure to cold temperatures worsens the cyanosis, while it often improves on warming. 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.

Pathophysiology

The precise mechanism of acrocyanosis is not known. The current line of thinking goes that

vasospasm Vasospasm refers to a condition in which an arterial spasm leads to vasoconstriction. This can lead to tissue ischemia (insufficient blood flow) and tissue death (necrosis). Along with physical resistance, vasospasm is a main cause of ischemi ...

s in the cutaneous arteries and arterioles produce cyanotic discoloration, while compensatory dilatation in the postcapillary

venule A venule is a very small vein in the microcirculation that allows blood to return from the capillary beds to drain into the venous system via increasingly larger veins. Post-capillary venules are the smallest of the veins with a diameter of ...

s causes sweating. Arteriovenous subpapillary plexus shunting also occurs. Persistent vasoconstriction at the

precapillary sphincter A precapillary sphincter is a band of contractile mural cells either classified as smooth muscle or pericytes that adjusts blood flow into capillaries. They were originally described in the mesenteric microcirculation, and were thought to only r ...

creates a local hypoxic environment, thus releasing

adenosine Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9- glycosidic bond. Adenosine is one of the four nucleoside build ...

into the capillary bed.Guyton, A.C. & Hall, J.E. (2006) ''Textbook of Medical Physiology'' (11th ed.) Philadelphia: Elsevier Saunder Vasospasms force adenosine to enter the capillary bed, where it vasodilates the postcapillary venules. Such differences in vessel tone create a

countercurrent exchange Countercurrent exchange is a mechanism between two flowing bodies flowing in opposite directions to each other, in which there is a transfer of some property, usually heat or some chemical. The flowing bodies can be liquids, gases, or even solid ...

system that attempts to retain heat. Profuse sweating would then be caused by an overwhelmed countercurrent exchange system. In addition to adenosine, other hormones may contribute to acrocyanosis such as increase blood levels of serotonin. This would seem to support case studies reporting acrocyanosis as an unusual side effect for pediatric patients taking

tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains ...

s, as these medications can inhibit the reuptake of serotonin and thus increase their blood concentrations. Acrocyanosis has been reported in association with many other medications and substances.

Diagnosis

Acrocyanosis is diagnosed clinically, based on a

medical history The medical history, case history, or anamnesis (from Greek: ἀνά, ''aná'', "open", and μνήσις, ''mnesis'', "memory") of a patient is a set of information the physicians collect over medical interviews. It involves the patient, and ev ...

and

physical examination In a physical examination, medical examination, clinical examination, or medical checkup, a medical practitioner examines a patient for any possible medical signs or symptoms of a Disease, medical condition. It generally consists of a series of ...

; laboratory studies or imaging studies are not necessary. The normal peripheral pulses rule out peripheral arterial occlusive disease, where

arterial An artery () is a blood vessel in humans and most other animals that takes oxygenated blood away from the heart in the systemic circulation to one or more parts of the body. Exceptions that carry deoxygenated blood are the pulmonary arteries in ...

narrowing limits blood flow to the extremities.

Pulse oximetry Pulse oximetry is a noninvasive method for monitoring blood oxygen saturation. Peripheral oxygen saturation (SpO2) readings are typically within 2% accuracy (within 4% accuracy in 95% of cases) of the more accurate (and invasive) reading of art ...

will show a normal

oxygen saturation Oxygen saturation (symbol SO2) is a relative measure of the concentration of oxygen that is Dissolution (chemistry), dissolved or carried in a given medium as a proportion of the maximal concentration that can be dissolved in that medium at the g ...

. Unlike the closely related

Raynaud's phenomenon Raynaud syndrome, also known as Raynaud's phenomenon, is a medical condition in which the spasm of small arteries causes episodes of reduced blood flow to end arterioles. Typically the fingers, and, less commonly, the toes, are involved. Rare ...

, cyanosis is continually persistent. In addition, there is usually no associated trophic skin changes, localized pain, or ulcerations. Capillaroscopy and other laboratory methods may be helpful but only complement clinical diagnosis in unclear cases, especially when connective tissue disorders may be present.

Treatment

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 A sympathectomy is an irreversible procedure during which at least one sympathetic ganglion is removed. One example is the lumbar sympathectomy, which is advised for occlusive arterial disease in which L2 and L3 ganglia along with intervening sy ...

would alleviate the cyanosis by disrupting the fibers of the

sympathetic nervous system The sympathetic nervous system (SNS or SANS, sympathetic autonomic nervous system, to differentiate it from the somatic nervous system) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous sy ...

to the area. 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 Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., a ...

) are effective.

Prognosis

While there is no cure for acrocyanosis, patients otherwise have excellent prognosis. Unless acrocyanosis results from another condition (e.g. malignancy, antiphospholipid syndrome, atherosclerosis, acute ischemic limb, bacterial

endocarditis Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, o ...

), there is no associated increased risk of disease or death, and there are no known complications. Aside from the discoloration, there are no other symptoms: no pain, and no loss of function. Patients can expect to lead normal lives. In secondary acrocyanosis treatment of the primary condition defines outcomes.

Epidemiology

Although there is no definitive reporting on its incidence, acrocyanosis shows

prevalence In epidemiology, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...

in children and young adults than in patients thirty years of age or older.

Epidemiological Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and Risk factor (epidemiology), determinants of health and disease conditions in a defined population, and application of this knowledge to prevent dise ...

data suggests that cold climate, outdoor occupation, and low

body mass index Body mass index (BMI) is a value derived from the mass (Mass versus weight, weight) and height of a person. The BMI is defined as the human body weight, body mass divided by the square (algebra), square of the human height, body height, and is ...

are significant

risk In simple terms, risk is the possibility of something bad happening. Risk involves uncertainty about the effects/implications of an activity with respect to something that humans value (such as health, well-being, wealth, property or the environ ...

factors for developing acrocyanosis. As expected, acrocyanosis would be more prevalent in women than in men due to differences in BMI. However, the

incidence rate In epidemiology Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and Risk factor (epidemiology), determinants of health and disease conditions in a defined population, and application of this knowl ...

of acrocyanosis often decreases with increasing age, regardless of regional climate. It completely resolves in many women after menopause implying significant hormonal influences. There is some evidence that many cases of idiopathic acrocyanosis are in some way related to a disorder of

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

, or

aromatase Aromatase (), also called estrogen synthetase or estrogen synthase, is an enzyme responsible for a key step in the biosynthesis of estrogens. It is CYP19A1, a member of the cytochrome P450 superfamily, which are monooxygenases that catalyze man ...

. Around 50% of patients with POTS experience acrocyanosis of their legs while standing still.

In the newborn

Acrocyanosis is common initially after delivery in the

preterm Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is betwee ...

and

full term Pregnancy is the time during which one or more offspring gestates inside a woman's uterus. A multiple pregnancy involves more than one offspring, such as with twins. Conception usually occurs following vaginal intercourse, but can also ...

newborn In common terminology, a baby is the very young offspring of adult human beings, while infant (from the Latin word ''infans'', meaning 'baby' or 'child') is a formal or specialised synonym. The terms may also be used to refer to Juvenile (orga ...

.Engle, W.A. & Boyle, D.W. (2005). Delivery room management and transitional care. In L.M. Osborn, T.G. DeWitt, L.R. First, & J.A. Zenel (Eds.), ''Pediatrics'' (pp. 1250-61). Philadelphia: Elsevier Mosby Intervention is typically not required as it is seen as a normal finding. Acrocyanosis can also return in a newborn if a baby is cold, such as after a bath, and is considered normal as well.

References

External links

{{Vascular diseases Diseases of arteries, arterioles and capillaries Medical signs Ailments of unknown cause Skin conditions resulting from physical factors