Antiphospholipid syndrome – skin manifestations (livedo racemosa, Sneddon syndrome)

Definition

Antiphospholipid syndrome (APS) is an acquired autoimmune disorder with arterial or venous thrombosis and/or pregnancy morbidity in the presence of persistent antiphospholipid antibodies. Primary APS occurs without an underlying disease, secondary APS usually with systemic lupus erythematosus. Sneddon syndrome is a rare, slowly progressive neurocutaneous vasculopathy combining livedo racemosa with recurrent cerebrovascular events (transient ischaemic attack, stroke).

Occurrence & epidemiology

APS is usually diagnosed in young to middle-aged adults. Sneddon syndrome has an incidence of about 4 per million population per year; about 80% of patients are women, with a median age at diagnosis of 40 years.

Clinical features

• Livedo racemosa: branching, net-like pattern of violaceous broken rings due to persistent occlusion of small to medium-sized arteries; unlike livedo reticularis it persists on warming. In Sneddon syndrome it usually starts on the buttocks and lower back and often precedes the strokes by more than 10 years.
• Other skin signs of APS (sometimes the first manifestation): splinter haemorrhages of the nails, leg ulcers, superficial thrombophlebitis, blue toe syndrome, skin necrosis, purpura, painful nodules, vasculitis.
• Systemic: venous thrombosis, pulmonary embolism, myocardial infarction, stroke, miscarriage, thrombocytopenia; in Sneddon syndrome headache and dizziness, recurrent strokes, early-onset dementia.

Diagnosis

• Classification: revised Sapporo (Sydney) criteria 2006: at least one clinical and one laboratory criterion. ACR/EULAR criteria 2023 (developed for research): entry criterion of at least one positive antiphospholipid antibody test within 3 years of an APS-associated clinical criterion; then weighted points in six clinical domains (venous and arterial macrovascular thrombosis, microvascular, obstetric, cardiac valve, haematological) and two laboratory domains (LA coagulation assay; anticardiolipin or anti-beta-2 glycoprotein I IgG/IgM); APS with at least 3 points each from both.
• Laboratory: anticardiolipin and anti-beta-2 glycoprotein I antibodies, LA test (e.g. dRVVT), full blood count; syphilis serology sometimes falsely positive.
• Sneddon syndrome: antiphospholipid antibodies in 50–80% (classified as aPL-positive/-negative); deep skin biopsies (non-inflammatory thrombotic vasculopathy of small to medium-sized arteries; sensitivity 27% with one biopsy, 80% with three), cerebral MRI.

Differential diagnoses

• Livedo reticularis
• Peripheral arterial disease
• Martorell Ulcer
• Calciphylaxis
• Polyarteritis nodosa

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References (selection)

1. DermNet: Antiphospholipid syndrome
2. DermNet: Sneddon syndrome
3. PubMed: 2023 ACR/EULAR antiphospholipid syndrome classification criteria (PMID 37640450)
4. PubMed: International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS) (PMID 16420554)
5. PubMed: Antiphospholipid syndrome and the skin (PMID 9204065)
6. PubMed: Sneddon Syndrome: A Comprehensive Overview (PMID 31160219)

Cross-references