What are the causes of intermittent livedo reticularis?

Causes of Intermittent Livedo Reticularis

Intermittent livedo reticularis is most commonly a benign physiological response to cold exposure, but when persistent or associated with systemic symptoms, it signals underlying vascular, autoimmune, thrombotic, or drug-induced pathology that requires systematic evaluation.

Primary (Benign) Causes

• Physiological livedo reticularis represents the most common etiology, occurring as a vasospastic response to cold exposure in otherwise healthy individuals 1, 2
• This benign variant is completely reversible with rewarming and requires no treatment 1
• Idiopathic livedo by vasospasm is the most frequent pathologic cause when no underlying condition is identified 3

Secondary Causes Requiring Investigation

Autoimmune and Rheumatologic Disorders

• Antiphospholipid antibody syndrome (APS) is a critical diagnosis to exclude, as livedo reticularis serves as a common cutaneous manifestation and prognostic marker of more severe disease with arterial/venous thrombosis and pregnancy morbidity 4, 5
• Livedo may represent seronegative antiphospholipid syndrome even when antiphospholipid antibodies are absent, though this relationship remains incompletely understood 5
• Systemic lupus erythematosus produces livedo reticularis and is associated with retinal vasculitis, with a 3.5-fold increased incidence of retinal vascular occlusions 4
• Sneddon's syndrome couples idiopathic livedo reticularis with stroke in the absence of traditional vascular risk factors, with over 50% of patients reporting headache history 6

Vascular and Thrombotic Conditions

• Atheroembolic disease manifests with livedo reticularis as a peripheral sign of cholesterol emboli, requiring evaluation for sources such as abdominal aortic aneurysm 4
• Livedo reticularis in migraineurs identifies a subset with significantly higher stroke frequency (28% versus 7%), suggesting it serves as a clinical marker for increased cerebrovascular risk 6
• The condition is associated with accelerated atherosclerosis and both prothrombotic and immunological processes 5

Drug-Induced Livedo

• Amantadine is the most commonly implicated medication, causing livedo reticularis in 1-5% of patients as documented in FDA labeling 7
• Amantadine-induced livedo is typically reversible upon drug discontinuation, though chronic use may cause permanently dilated telangiectatic vessels 3
• Norepinephrine and other vasoconstricting substances are also frequently implicated 1, 3

Clinical Approach to Evaluation

Distinguish Primary from Secondary Livedo

• Assess for systemic symptoms including stroke, thrombosis, pregnancy morbidity, painful cutaneous ulcers, or constitutional symptoms that suggest secondary causes 4, 5
• Examine for livedo racemosa, a pathologic variant with irregular, broken, branching pattern that indicates more serious underlying disease compared to the regular netlike pattern of benign livedo reticularis 1
• Document medication history, particularly amantadine, norepinephrine, and other vasoconstrictors 7, 3

Laboratory and Imaging Workup for Secondary Causes

• Test for antiphospholipid antibodies (anticardiolipin, anti-β2-glycoprotein I, lupus anticoagulant) when livedo is persistent or associated with thrombosis 4, 5
• Screen for systemic lupus erythematosus with ANA, anti-dsDNA, and complement levels 4
• Evaluate for hypercoagulable states including factor V Leiden, prothrombin gene mutation, protein C/S deficiency, particularly in younger patients with thrombotic events 4
• Consider vascular imaging to identify atherosclerotic sources of emboli when atheroembolic disease is suspected 4

Management Principles

Benign Physiological Livedo

• No treatment is required for asymptomatic primary livedo reticularis 1
• Advise avoidance of cold exposure and vasoconstricting substances for patients with mild symptoms like episodic numbness and tingling 1
• Consider calcium channel blockers for judicious vasodilation in symptomatic cases 1

Secondary Livedo

• Treat the underlying cause as this is most likely to yield cutaneous improvement 1
• Discontinue offending medications like amantadine when drug-induced etiology is identified 3
• Initiate antiplatelet or anticoagulation therapy for antiphospholipid antibody syndrome or Sneddon's syndrome, though the livedo itself typically remains unchanged or progresses despite treatment 1

Critical Pitfalls to Avoid

• Do not dismiss livedo reticularis in migraineurs, as it identifies a population with 4-fold higher stroke risk requiring closer vascular monitoring 6
• Recognize that livedo racemosa (irregular, broken pattern) indicates more serious pathology than benign livedo reticularis (regular netlike pattern) 1
• Understand that chronic drug-induced livedo may become permanent with telangiectatic changes even after medication discontinuation 3
• Consider seronegative antiphospholipid syndrome when clinical features suggest APS but antibodies are negative 5