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Dermatology Diagnosis

Ascertaining The Cause Of Cyanotic Fifth Digits

A middle-aged male patient with diabetes presented to our service for bilateral blue fifth toes with evidence of gangrene. The patient said the color change started about one week prior. He denied any history of trauma to his feet or recent cardiac events, and had no other pertinent past medical history.

Upon examination, his fifth toes were painful to palpation with distal-lateral areas of skin necrosis. The fifth toes were cool to the touch. Pedal pulses were palpable. There was no evidence of livedo reticularis to the feet or lower extremities. The patient was previously on vancomycin and the current white blood cell count was 9.7 x 109/L.

In regard to vascular studies, the ankle brachial index (ABI) of the right foot was 1.02 and the left foot ABI was 1.12. The hallux toe pressure was 41 mmHg in the right foot and 71 mmHg in the left foot. His bilateral fifth toe pulse volume recordings (PVRs) showed little to no amplitude in the waveforms. X-rays were negative for any soft tissue emphysema or osteomyelitis. The vascular service saw the patient and recommended conservative care.

Key Questions To Consider

1. What is the most likely diagnosis for this patient?

2. What is your differential diagnosis?

3. Which patients are most likely to have this phenomenon?

4. What are the treatment options?

Answering The Key Diagnostic Questions
1. Judging by this patient’s poor vascular flow to the fifth toes, this clinical picture was more than likely caused by peripheral vascular disease (PVD). The presence of a cyanotic digit often goes by the term “blue toe syndrome,” which can have a multitude of causes.
2. The differential diagnosis of blue toe syndrome includes decreased arterial flow, thrombosis/viscosity disorders, vasoconstrictive disorders, vasculitis, impaired venous flow, medication side effects and abnormal blood circulation.1
3. This syndrome can affect a variety of patients. Ensuring a thorough patient history and physical examination can help pinpoint the underlying etiology. When necrosis is present, the most common cause is ischemia.2
4. Treatment options depend on the etiology. For blue toe syndrome caused by PVD, treatment would include revascularization and conservative wound care (including betadine and a dry sterile dressing). If there is any evidence of gangrene, demarcate the toes before performing surgical intervention.

What You Should Know About Blue Toe Syndrome

A vast number of etiologies can cause blue toe syndrome. One should first consider peripheral vascular disease and embolic phenomena. Kammody and colleagues defined blue toe syndrome as a “sudden onset of acute pain and cyanosis in one or more toes.”1

Decreased arterial perfusion can cause blue toe syndrome secondary to embolic events derived from atherosclerotic plaques (cholesterol emboli), vascular tumors (myxoma) or cardiac vegetations. Evidence of cyanotic digits in both the upper and lower extremity suggests either a cardiac source of embolism or a systemic disorder (i.e. hypercoagulability).3 When one suspects infective endocarditis, be aware of the cutaneous manifestations, which include Osler’s nodes and Janeway lesions, the latter of which is visible on the soles and palms. It is also important to note that cholesterol emboli may be a complication of alcoholic pancreatitis.2

Thrombosis may also predispose a patient to blue toe syndrome. Causes include hyperviscosity disorders such as antiphospholipid syndrome, thrombotic thrombocytopenic purpura and disseminated intravascular coagulation. Antiphospholipid syndrome is an autoimmune disease that causes thrombotic events in both the arterial and venous system, and is known to cause pregnancy morbidity.1 Thrombotic thrombocytopenic purpura causes blue toe syndrome through occlusion of arterioles by platelet plugs. Peripheral blood smears typically show fragmented red blood cells known as schistocytes.1 Disseminated intravascular coagulation typically arises secondary to another condition such as sepsis or malignancy. Here, widespread activation of the clotting cascade generates excess thrombin, resulting in vascular occlusion.1

Vasoconstrictive disorders can cause blue toe syndrome through exposure to cold or emotional stress. Such disorders include Raynaud’s phenomenon, pernio and frostbite.3 In pernio, digital cyanosis results from exposure to cold (above freezing) and damp temperatures often accompanied by blisters, erosions and ulcers.1 Vasculitic diseases may also be a cause of blue toe syndrome, notably the small- and medium-sized vasculitides. With these diseases, inflammatory white blood cells adhere to and damage vessel walls, leading to narrowing, occlusion and possible rupture.4

Patients may have an underlying disease that predisposes them to vasculitis. For example, polyarteritis nodosa can be present with concomitant hepatitis B infection and cryoglobulinemia can present with hepatitis C or multiple myeloma.1,4 Polyarteritis nodosa is an especially severe vasculitis resulting in cutaneous manifestations that include ulceration, livedo reticularis, palpable pupura, digital necrosis and autoamputation.5 Certain medications and recreational drugs such as cocaine and cannabis may also precipitate blue toe syndrome. The medications include systemic vasopressors (dopamine, epinephrine), amphotericin B, imipramine and warfarin (Coumadin, Bristol-Myers Squibb), which may trigger transient deficiency of protein C.1,2,6 Accordingly, clinicians should be aware of the side effects of these drugs and medications.

Final Notes

Treatment of blue toe syndrome depends on the etiology of the disease. In regard to the clinical presentation, livedo reticularis, a mottled dilation of the superficial vasculature, is typically a sign of vasculitis or localized disruption of blood flow (cholesterol emboli, for example).1 Palpable purpura may also be present in the vasculitides.

Outside of a basic podiatric exam, be sure to get a detailed history of the patient and concomitant medical issues. Basic lab testing should include complete blood cell count and basic metabolic panel. However, if one suspects vasculitis/autoimmune disease, be sure to order inflammatory markers, liver function tests, hepatitis B/C serologies, serum cryoglobulins, anti-neutrophil cytoplasmic antibody tests and antinuclear antibody tests. Basic X-rays can rule out impingement of digital vasculature by a periosteal osteochondroma or help assess the degree of vascular calcification.2 Address deficiencies in arterial blood flow with vascular testing.

Dr. Casteel is a second-year resident at Northside Medical Center in Youngstown, Ohio.

Dr. Karlock practices in Austintown, Ohio. He is the Clinical Instructor of the ValleyCare Health System of Ohio Podiatric Residency Program in Youngstown, Ohio.


  1. Hirschmann J, Raugi G. Blue (or purple) toe syndrome. J Am Acad Dermatol. 2009; 60(1):1-20.
  2. Issa A, Newman M, Simman R. Toe necrosis, etiologies and management, a case series. J Am Coll Clin Wound Spec. 2014; 5(2):26–35.
  3. Sherman S, Smith L. Blue digits. J Emer Med. 2006;30(4):435–436.
  4. Sharma A, Shailendra S, Lewis J. Diagnostic approach in patients with suspected vasculitis. Techniques Vasc Interven Radiol. 2014; 17(4):226-33.
  5. Tschetter A, Liu V, Wanat K. Cutaneous polyarteritis nodosa presenting as a solitary blue toe. J Am Acad Dermatol. 2014;71(3):e95-e96.
  6. Alamino R, Espinoza L. Vasculitis mimics: cocaine-induced midline destructive lesions. Am J Med Sci. 2013; 346(5):430-431.
Dermatology Diagnosis
Mike Casteel, DPM, and Lawrence G. Karlock, DPM, FACFAS
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