Blue toe syndrome

Author(s): Catherine Tian, Medical Student, Department of Dermatology, University of Auckland, New Zealand. DermNet NZ Editor-in-Chief A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. Copy edited by Gus Mitchell. November 2018.


What is blue toe syndrome?

Blue toe syndrome, also known as occlusive vasculopathy, is a form of acute digital ischaemia in which one or more toes become a blue or violet colour. There may also be scattered areas of petechiae or cyanosis of the soles of the feet.

Blue toe syndrome is associated with small vessel occlusion and can occur without obvious preceding trauma or disorders that produce generalised cyanosis, such as hypoxaemia or methaemoglobinaemia [1]. It most often presents in an older male that has undergone a vascular procedure.

Blue toe syndrome

What causes blue toe syndrome?

The characteristic blue discolouration and pain in blue toe syndrome are caused by impaired blood flow to the tissue resulting in ischaemia. The impairment of blood flow is due to one or more of the following factors:

  • Decreased arterial flow
  • Impaired venous outflow
  • Abnormal circulating blood.

These are not mutually exclusive. For example, abnormal circulating blood can induce vasculitis and subsequent thrombosis of the arterioles and capillaries supplying blood to the toes, resulting in decreased arterial flow.

The causes of blue toe syndrome

Decreased arterial flow

The blockage or narrowing of arteries by the small clots that lead to blue toe syndrome can result from a number of different conditions.

Embolisation

  • Cholesterol emboli are cholesterol fragments or fibrin-platelet material released into the bloodstream from ulcerated arteriosclerotic plaques in the large arteries (aorta, iliac and femoral arteries) and are the most common cause of blue toe syndrome. Risk factors include smoking, hypertension, elevated cholesterol levels, and a recent angiogram or vascular surgery.
  • Embolisation can also occur spontaneously [2].
  • Emboli may originate from a cardiac tumour or from vegetations from a cardiac myxoma or endocarditis (septic emboli) and should be considered when emboli develop without any apparent cardiovascular risk factors or precipitating event [3].

Thrombosis

Vasoconstrictive disorders

  • Narrowing of blood vessels in the feet can be a result of muscular wall contraction.
  • In Raynaud disease, vasoconstriction tends to affect multiple fingers more severely than the toes.
  • Causes include medication-induced vasoconstriction (eg, a beta blocker or illicit drug such as cocaine) and/or acrocyanosis [1].

Infectious and non-infectious inflammation

Other causes of vascular obstruction

Impaired venous outflow

Abnormal venous drainage associated with extensive venous thrombosis results in phlegmasia cerulea dolens (a painful form of blue toe syndrome associated with leg oedema). Many patients have predisposing factors for venous thrombosis, including:

  • Immobility
  • Clotting disorders
  • Pregnancy
  • Previous leg trauma
  • Malignancy [6].

Abnormalities in circulating blood

Blue toe syndrome can be due to abnormal blood constituents (see skin conditions of haematological disorders). 

  • Platelet plugging
  • Myeloproliferative disorders, such as polycythaemia rubra vera and essential thrombocythaemia
  • Paraproteinaemia (which causes hyperviscosity)
  • Cryoglobulinaemia
  • Cryofibrinogenaemia
  • Cold agglutininaemia
  • Paroxysmal nocturnal hemoglobinuria [7]

What are the clinical features of blue toe syndrome?

The clinical features of blue toe syndrome can range from an isolated blue and painful toe to a diffuse multiorgan system disease that can mimic other systemic illnesses. Any organ or tissue can be affected, though the skin and skeletal muscles of the lower extremities are almost always involved [8].

Cutaneous abnormalities are usually one of the earliest symptoms, most commonly blue or purple discolouration of the affected toes [9]. Discolouration may affect one foot or both, depending on the underlying pathophysiology. It is often painful and may be associated with claudication.

In a series of 223 patients with cholesterol embolisation, the most frequent cutaneous findings were:

Livedo reticularis may be non-blanching or blanching when the discolouration disappears with pressure and/or fades with leg elevation [10]. Blanching occurs in the first stages of blue toe syndrome, as the sluggish flow of desaturated blood results in temporary obstruction of blood flow [1].

  • Pain in the affected blue toe or toes is usually of acute onset and occurs at rest. The nondiscoloured areas of the foot and distal limb can also be painful [11].
  • The affected toe(s) are cold compared to unaffected parts of the foot, which are warmer and appear well-perfused [6]. Pedal pulses may be normal.
  • Peripheral foot pulses may be palpable if an occlusion occurs in the small arteries and arterioles rather than large palpable arteries [6].

What are the complications of blue toe syndrome?

Mild forms of blue toe syndrome have a good prognosis and subside without sequelae [1]. However, cholesterol fragments blocking blood vessels to other organs can lead to multiorgan disorder [1]. involvement of the kidneys has a poor prognosis.

Patients with untreated blue toe syndrome from embolisation can suffer from further emboli in the subsequent weeks, resulting in substantial occlusion and ischaemic loss of digits, the forefoot and the limb (dry gangrene) necessitating amputation [6]. 

How is blue toe syndrome diagnosed?

Blue toe syndrome is a clinical diagnosis based on patient history and findings on examination. It is important to determine the underlying cause of blue toe syndrome to guide treatment [1]. There are usually clues from the clinical assessment but to confirm the diagnosis, investigation in the form of laboratory blood works, tissue biopsies, and radiological imaging is required.

History and examination should focus on:

  • Hypertension or other risk factors for hypercholesterolemia and atherosclerotic diseases
  • Fever (indicating athero-emboli, infective endocarditis, myxoma, thrombotic thrombocytopenic purpura, and disseminated intravascular coagulation)
  • Cardiac murmur (infective endocarditis and atrial myxoma)
  • Livedo reticularis (athero-emboli, myxoma, antiphospholipid syndrome, hyperviscosity syndrome, cryofibrinogenaemia, cryoglobulinemia, and calciphylaxis)
  • Extensive oedema in the ipsilateral leg (phlegmasia cerulean dolens)
  • Hollenhorst plaques (athero-emboli) noted on retinal examination
  • Dilated veins, haemorrhages, and exudates on retinal examination (hyperviscosity syndrome) [1–3].

Full blood count with white cell differential, erythrocyte sedimentation rate, and C-reactive protein may indicate elevated inflammatory markers. These are often non-specific in blue toe syndrome and can occur with cholesterol emboli as well as numerous other inflammatory driven processes. The blood count and peripheral blood film can help diagnose bone marrow or autoimmune diseases. Liver and renal functions should also be checked.

Other more specific blood tests may include:

Imaging may include:

  • Chest radiograph and/or thoracic and abdominal computed tomographic (CT) or magnetic resonance scans to look for any aortic atheroma and underlying cancer (in malignancy-associated conditions)
  • Peripheral angiogram, a scan of the limb arteries (to locate vessel narrowing, occlusion and/or determine the source of emboli)
  • Sonography of abdomen and venous duplex ultrasound scan (to detect deep venous thrombosis)
  • Echocardiogram (for cardiac tumours or vegetations from endocarditis) [1].

Definitive diagnosis is usually made by histopathological confirmation of a biopsy of the affected skin or of other involved tissue(s) [13]. Biopsies in patients with poor peripheral vascular supply should be performed with caution as poor healing is likely at the sampling site. Histopathological findings for cholesterol emboli show intravascular cholesterol crystals, which may be associated with macrophages, giant cells and eosinophils [13].

What is the treatment for blue toe syndrome?

The principles of treatment revolve around addressing the cause. This is usually in the form of relieving occlusion and restoration of arterial or venous vessel continuity [6].

  • Medical anticoagulation (especially antiplatelet drugs), and surgical endovascular or reconstructive procedures are indicated for emboli and thromboses, to remove the source of the clot, resolve occlusion, and restore blood flow.
  • Haematological treatment may be required when blue toe syndrome is due to hyperviscosity [14].
  • Supportive and symptomatic treatments of blue toe syndrome include rest, warm conditions, appropriate dressings, and hydration, as well as organ support when necessary [14].

Address patient risk factors

Risk factors should be addressed in patients with advanced atherosclerotic disease, including:

  • Smoking cessation
  • Control of hypertension
  • Reduction of serum cholesterol.

Patients with stenotic lesions should be followed up carefully, as the progression of atheromatous disease will result in a strong likelihood of repetition of the blue toe syndrome [6].

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References

  1. Hirschmann JV, Gregory JR. "Blue (or purple) toe syndrome." Journal of the American Academy of Dermatology 60.1 (2009): 1–20. 
  2. O’Keeffe ST, Woods BO, Breslin DJ, Tsapatsaris NP. Blue toe syndrome: causes and management. Arch Intern Med 1992; 152: 2197–202. PubMed
  3. Hoffmeier A, Sindermann JR, Scheld HH, et al. Cardiac tumours — diagnosis and surgical treatment. Dtsch Arztebl Int 2014; 111: 205–211. PubMed Central
  4. Federman DG, Valdivia M, Kirsner RS. Syphilis presenting as the "Blue Toe Syndrome". Arch Intern Med 1994; 154: 1029–31. PubMed
  5. Guldbakke KK, Khachemoune A. Calciphylaxis. Int J Dermatol 2007; 46: 231–8. PubMed
  6. Karmody AM, Powers SR, Monaco VJ, Leather RP. Blue toe syndrome: an indication for limb salvage surgery. Archives of Surgery 111.11 (1976): 1263–68. PubMed
  7. Kealy WF. Atheroembolism. J Clin Pathol 1978; 31: 984–9. PubMed
  8. Davis MDP, Dy KM, Nelson S. Presentation and outcome of purpura fulminans associated with peripheral gangrene in 12 patients at Mayo Clinic. J Am Acad Dermatol 2007; 57: 944–56. PubMed 
  9. Jucgla A, Moreso F, Muniesa C, Moreno A, Vidaller A. Cholesterol embolism: still an unrecognised entity with a high mortality rate. J Am Acad Dermatol 2006; 55: 786–93. PubMed
  10. Falanga V, Fine MJ, Kapoor WN. The cutaneous manifestations of cholesterol crystal embolization. Arch Dermatol 1986; 122 (10): 1194–8. PubMed
  11. Scolari F, Ravani P, Gaggi R, Santostefano M, Rollino C, Stabellini N, et al. The challenge of diagnosing atheroembolic renal disease: clinical features and prognostic factors. Circulation 2007; 116: 298–304. PubMed
  12. Poredos P, FESC. Blue Toe Syndrome. J Cardio Pr 2004; 2. Journal
  13. Llamas-Velasco M, Alegría V, Santos-Briz Á, Cerroni L, Kutzner H, Requena L. Occlusive nonvasculitic vasculopathy. Am J Dermatopathol 2017; 39(9): 637–662. doi:10.1097/dad.0000000000000766. PubMed
  14. Vayssairat M, Chakkour K, Gouny P, Nussaume O. Atheromatous embolisms and cholesterol embolisms: medical treatment. J Mal Vasc 1996; 21: 97–9. PubMed

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