Dermatology & Rheumatology & Internal Medicine & Family Medicine
Livedo (livedo reticularis)
livedo reticularis (LR) is a reddish-purple or bluish marbled network of skin, forming a reticulated (mesh or net) pattern on the skin, particularly visible on the lower limbs and trunk. This clinical sign reflects an anomaly in cutaneous microcirculation - a disturbance in blood flow in dermal vessels (capillaries + arterioles + venules) leading to blood stasis and localized hemoglobin deoxygenation (desaturated hemoglobin = purplish). The pathophysiology is based on the cutaneous vascular anatomy of «cones» (centrifugal arteriolar angiomas) - each central arteriole irrigates a circular cutaneous zone, and stasis in the periphery of these zones produces the characteristic marbled network. The term livedo actually covers a spectrum of clinical presentations, ranging from the benign physiological livedo (cutis marmorata) - heat reversible + symmetrical + without systemic cause - to the pathological livedo racemosa - irregular + persistent + non-symmetrical + potential sign of serious underlying systemic pathology (antiphospholipid syndrome + lupus + cryoglobulinemia + cholesterol emboli + vasculitis + polycythemia vera + thrombophilia). The distinction between these forms is crucial: a physiological livedo requires no work-up, whereas a livedo racemosa in an adult requires a systemic work-up. The combination of livedo + stroke + arterial thrombosis + recurrent abortions in a young woman is highly suggestive of antiphospholipid syndrome (APS).
Pathophysiology, classification and etiologies
- Vascular Pathophysiology and Classification of Livedo: cutaneous vascular anatomy and livedo mechanism: cutaneous microcirculation is organized into conical vascular units (central ascending arterioles → dermal capillaries → peripheral return venules) → each arteriole irrigates a circular territory whose periphery is the least oxygenated → in the event of slowed flow (vasospasm + obstruction + increased blood viscosity) → stasis in the periphery of the cones → hemoglobin deoxygenation → reddish-purplish colorationpurplish → reticulated network appearance → net meshes correspond to junction zones between several adjacent vascular cones + livedo clinical classification: cutis marmorata (physiological livedo): regular + symmetrical net + disappears with heat + found in thin young subjects in cold environments + or in infants + reversible → no investigation necessary → livedo reticularis (LR proper): regular + symmetrical net + persistent despite warming + may be primary idiopathic (especially young women) + or secondary (systemic causes) → livedo racemosa (LRa): most worrying + irregular + broken + non-symmetrical + persistent + does not disappear with heat + often associated with serious systemic causes + may involve trunk + face + arms → terminology: some authors group LR + LRa under the term «livedo reticularis» and distinguish only physiological vs pathological → the regular LR vs irregular LRa distinction is clinically the most useful for orienting the workup + main pathophysiological mechanisms: vasospasm (sympathicotonic or primitive) → spastic arterioles → slowed flow → stasis + vascular obstruction: thrombus + emboli (cholesterol + cardiogenic + antiphospholipid) + cryoglobulin crystals + sickle cells → central arteriole blockage → central ischemia + livedo + increased blood viscosity : polycythemia + cryoglobulinemia + infections + autoimmune diseases → stasis by slowing down + inflammatory lesion of the vascular wall (vasculitis) → increased permeability + stasis
- Main etiologies and diagnostic approach according to clinical profile: physiological livedo (cutis marmorata): infant (very frequent - immature thermoregulation) + thin young adult in cold environment + symmetrical + disappears with heat → NO investigation necessary + idiopathic primary livedo: young woman (20-40 years) + persistent regular LR + no systemic cause identified + associated acrocyanosis possible + livedo secondary to systemic causes - to be investigated according to clinical context : antiphospholipid syndrome (SAPL): classic and important association → livedo racemosa + arterial or venous thromboses + recurrent abortions + antiphospholipid antibodies (anticoagulant lupus + anticardiolipin + anti-β2-GPI) → Levine 2002 - NEJM: SAPL criteria → reference → systemic lupus erythematosus (SLE): livedo + systemic manifestations of lupus → ANA + anti-DNA + complement → cryoglobulinemia: livedo + purpura + arthralgias + neuropathy + renal involvement → cryoglobulins → HCV screening → cholesterol crystal emboli: very characteristic livedo (often in lower limbs + blue toe) → after vascular procedure (catheterization + thrombolysis) + or spontaneous → eosinophilia + progressive CKD → skin biopsy (biconvex «needle» crystals in arterioles) → polycythemia vera + essential thrombocythemia: hypervisocity → CBC + JAK2 → vasculitides: PAN (periarteritis nodosa) + other vasculitides → biopsy + ANCA + Raynaud's + vasospasm → livedo secondary to drugs: amantadine (treatment of Parkinson's disease) → reversible benign livedo + interferon + quinine + catecholamines + particular clinical associations: Sneddon syndrome: livedo racemosa + recurrent ischemic stroke + associated SAPL in 50 % → skin biopsy (thrombotic obliteration of arterioles)
Etiological diagnosis and treatment
| Etiology / Approach | Assessment, diagnosis and treatment | References and recommendations |
|---|---|---|
| Livedo and Antiphospholipid Syndrome (APS) Antiphospholipid antibodies — lupus anticoagulant — anticardiolipin — anti-β2-GPI — thrombosis — AVC — miscarriages — anticoagulation — aspirin — hydroxychloroquine — Sapporo criteria — Sneddon syndrome — livedo racemosa |
Livedo and antiphospholipid syndrome (APS) - key association: APS is the most important and serious secondary cause of livedo racemosa in young women → suggestive clinical profile: young woman (20-40 years) + livedo racemosa (irregular + persistent network + sometimes arm + trunk) + ATCD of thromboses (DVT + PE + stroke + IDM) + recurrent abortions (≥3 spontaneous abortions before 10 SA + or ≥1 fetal death >10 SA + or premature birth 40 GPL or MPL) + or IgG or IgM anti-β2-GPI → 2 assays 12 weeks apart required to confirm persistence → SAPL biological workup: lupus anticoagulant (LA): functional assay - diluted Russell viper venom time (DVVT) + APTT ratio + → anticardiolipin IgG + IgM (ELISA) + anti-β2-GPI IgG + IgM (ELISA) → associated immunological workup: ANA + anti-DNA + complement (C3 + C4) + renal workup (proteinuria) → CBC (thrombocytopenia associated with SAPL) → SAPL treatment: venous thrombosis → long-term anticoagulation with VKA (INR 2-3) → or LMWH if pregnant → arterial thrombosis → INR 3-4 + aspirin → or aspirin + clopidogrel if INR 2-3 → primary prevention (antibody-positive without thrombosis): aspirin 75-100 mg/d → hydroxychloroquine (Plaquenil): reduces risk of thrombosis in LES + primary SAPL → obstetrical SAPL without thrombosis: aspirin + LMWH × throughout pregnancy + Sneddon syndrome → SAPL in 50 % of cases → SAPL workup + stroke → anticoagulation if thrombotic | Levine 2002 — NEJM: APS + thromboses + livedo → criteria → reference + Miyakis 2006 — Journal of Thrombosis and Haemostasis: Revised APS classification criteria (Sapporo) → reference + Cervera 2009 — European Journal of Clinical Investigation: APS + livedo + Sneddon syndrome → Giannakopoulos 2009 — Arthritis and Rheumatism: APS + antibodies + workup → ACR (American College of Rheumatology) + EULAR 2019 guidelines APS: treatment + anticoagulation + pregnancy + INESSS Quebec + RAMQ: VKAs + LMWH + aspirin + hydroxychloroquine → reimbursed + direct oral anticoagulants (not recommended in APS) + antiphospholipid antibody testing reimbursed |
| Livedo and cholesterol embolisms, cryoglobulinemia, and vasculitis Cholesterol emboli blue toe — catheterization — thrombolysis — eosinophilia — CKD — skin biopsy crystals — HCV cryoglobulinemia — purpura arthralgias — PAN vasculitis — biopsy — ANCA — polycythemia vera JAK2 — etiological treatment |
Livedo and cholesterol embolisms (atheroembolism): characteristic clinical picture: highly suggestive livedo (marbled network) + «blue toe» (acute distal ischemia of one or more toes = pathognomonic) + or digital necrosis + lower limb pain + often occurs after a vascular procedure (arterial catheterization + vascular surgery + thrombolysis + intensive anticoagulation) + or spontaneously in severe atherosclerosis + context: elderly patient + smoker + atheromatous + progressive CKD (thromboembolic glomerulopathy) + peripheral eosinophilia (release of pro-inflammatory mediators by cholesterol crystals) → eosinophilia + CKD + livedo + blue toe after catheterization = atheroembolism until proven otherwise → workup: fundus (cholesterol crystals = Hollenhorst plaques in retinal arterioles) + creatinine + renal workup + eosinophils + skin (or muscle + renal) biopsy → biconvex «needle-like» cholesterol crystals in arterioles → treatment: NO effective specific treatment + stop anticoagulation if possible (worsens embolization) + statins (reduce relapse + anti-inflammatory effects) + avoid new vascular procedures if possible + conservative treatment + local care → prognosis: variable - progressive IR in 50 % of cases; livedo and cryoglobulinemia: livedo + palpable purpura + arthralgias + neuropathy + renal involvement + HCV in 80-90 % of type II cryoglobulinemias → cryoglobulins (to be assayed on warm sample +37°C) → RF + collapsed C4 complement + treatment of cause (HCV antivirals: sofosbuvir + ribavirin) + rituximab if symptomatic cryoglobulinemia + livedo and systemic vasculitides: PAN (periarteritis nodosa) → livedo + visceral infarcts (kidney + mesentery) + neuropathy + ANCA-negative (classic PAN) → skin or neuromuscular biopsy + associated cryoglobulinemias (PAN + HBV in 30-50 %) → treatment: corticoids + cyclophosphamide + polycythemia vera / essential thrombocythemia: hyperviscosity + thromboses + livedo → CBC + JAK2 V617F → phlebotomies + hydroxyurea + aspirin | Kronzon 2010 — Journal of the American College of Cardiology: Cholesterol emboli → livedo reticularis + blue toe + eosinophilia + biopsy → diagnosis + treatment → reference + Scolari 2007 — Kidney International: Atheroembolic renal disease + CKD + livedo reticularis + prognosis + Ferri 2004 — Arthritis and Rheumatism: Cryoglobulinemia + HCV + livedo reticularis + Guillevin 1995 — Archives of Internal Medicine: PAN + livedo reticularis + vasculitis + Verstovsek 2009 — NEJM: JAK2 + polycythemia vera → CRS + Canadian Dermatology Association (CDA) + INESSS Quebec: Livedo reticularis workup + etiologic + RAMQ: Cryoglobulins + ANA + ANCA + skin biopsy + reimbursed + HCV antivirals + rituximab → reimbursed according to criteria |
| Clinical Approach to Livedo: Etiological Assessment and Symptomatic Treatment Physiological livedo, no investigation — Pathological livedo, work-up — CBC — ANA — antiphospholipid antibodies — cryoglobulins — complement — creatinine — skin biopsy — amantadine — warming — vasoplegia — treatment of the cause — pentoxifylline — aspirin |
Clinical approach to livedo - diagnostic strategy: step 1 - distinguish physiological livedo from pathological livedo: physiological livedo (cutis marmorata): regular net + symmetrical + disappears completely with heat + adolescent or young adult thin + without associated symptoms → NO investigation → reassurance + pathological livedo (racemosa or persistent LR): irregular net + and/or persistent despite rewarming + and/or in an adult >40 years old + and/or associated with systemic signs (stroke + thrombosis + abortions + purpura + arthralgia + neuropathy + IR) → etiological workup mandatory → step 2 - systematic etiological workup of pathological livedo: CBC + smear (eosinophilia → cholesterol emboli) + creatinine + ionogram + urinary workup (proteinuria) → ANA + anti-DNA + C3 + C4 complement → antiphospholipid antibodies (lupus anticoagulant + anticardiolipin IgG/IgM + anti-β2-GPI IgG/IgM) × 2 samples 12 weeks apart → cryoglobulins (on warm tube) → VS + CRP + FR → ANCA (if vasculitis suspected) → CBC with formula (JAK2 if polycythemia or thrombocytosis) → thrombophilia workup if thromboses (factor V Leiden + prothrombin 20210A + protein C + protein S + antithrombin) → imaging: arterial echo-Doppler if cholesterol embolisms suspected → fundus (Hollenhorst plaques) → skin biopsy: if diagnosis uncertain + or vasculitis + or cholesterol embolisms suspected → deep biopsy (takes deep dermal arterioles) → step 3 - treatment according to etiology: physiological livedo: reassurance + warming + compression stockings if discomfort → idiopathic primary livedo: elastic compression stockings + cold avoidance + vasodilators (nifedipine 10-30 mg/d) + or pentoxifylline (improves red blood cell deformability) → if SAPL → anticoagulation AVK INR 2-3 (venous thrombosis) + or INR 3-4 (arterial thrombosis) → if LES → hydroxychloroquine + if cholesterol emboli → statins + local care → if cryoglobulinemia → HCV treatment + rituximab → if vasculitis → corticoids + cyclophosphamide | Gibbs 2005 — Journal of the American Academy of Dermatology: Livedo → Classification + Diagnostic + Treatment → Review + Sajjan 2015 — Journal of the American Academy of Dermatology: Livedo racemosa → Etiologies + Systemic Workup + Miyakis 2006 — JTH: Revised APSL Criteria + Levine 2002 — NEJM: APSL + Livedo + Treatment + Scolari 2007 — Kidney International: Atheroembolism + Livedo + Ferri 2004 — Arthritis and Rheumatism: Cryoglobulinemia + Treatment + APS + SCG + CMR: Livedo + Investigation + Treatment → EULAR 2019 APSL Guidelines + INESSS Quebec + RAMQ: Biological Workup + Skin Biopsy + Antiphospholipid Antibodies → Reimbursed + AVK + Aspirin + Hydroxychloroquine Reimbursed |
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A physiological livedo (cutis marmorata) - a regular, symmetrical, and heat-disappearing network in a young, thin adult - requires no workup and is benign: On the other hand, livedo racemosa (irregular pattern + persistent + asymmetrical) in an adult, especially when associated with thrombosis, strokes, recurrent miscarriages, or other systemic signs, requires an evaluation including antiphospholipid antibodies (APS), ANA (lupus), cryoglobulins, ANCA, CBC, and renal function tests. The combination of livedo + blue toe + eosinophilia after a vascular procedure is highly suggestive of cholesterol atheroembolism.
Situations requiring urgent or priority assessment
Livedo racemosa + sharp toe pain + blue toe + cold + non-pulsatile + following arterial catheterization or thrombolysis + eosinophilia + progressive chronic kidney disease → Atheroembolic cholesterol → urgent vascular evaluation → funduscopy + creatinine + eosinophils + skin biopsy → stop anticoagulation if possible + statins + local care → variable renal prognosis.
Young woman with livedo racemosa + history of DVT or stroke or recurrent miscarriages + or unexplained thrombocytopenia + or unexplained prolonged aPTT → Probable antiphospholipid syndrome → Urgent workup: lupus anticoagulant + anticardiolipin IgG/IgM + anti-β2-GPI IgG/IgM + ANA + anti-DNA + CBC + renal function tests → If current pregnancy → LMWH + aspirin immediately → Warfarin anticoagulation if thrombosis documented → Urgent rheumatology consultation.
Livedo + palpable purpura + arthralgias + distal neuropathy + kidney involvement + hypocomplementemia (low C4) + positive RF → Probable cryoglobulinemia → Cryoglobulins on heated tube + HCV → Urgent HCV serology + immunoelectrophoresis → HCV treatment + rituximab if severe symptoms + rheumatology consultation + nephrology if renal involvement.
Consult at Clinique Omicron
The doctors at Clinique Omicron distinguish between benign physiological livedo and pathological livedo, prescribe a complete etiological workup (antiphospholipid antibodies + ANA + cryoglobulins + CBC + kidney function tests + ANCA depending on the context), refer patients to a rheumatologist, dermatologist, or internist for systemic causes, and provide therapeutic follow-up (VKA anticoagulation + hydroxychloroquine + statins depending on the etiology). Consultations are available at several service points in Quebec and via telemedicine. To book an appointment, visit cliniqueomicron.ca.
The content of this page is provided for informational purposes only and is not a substitute for the advice of a physician, dermatologist, or rheumatologist. Pathological livedo is often the visible sign of a serious underlying systemic disease requiring specialized evaluation and appropriate etiological treatment.
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