Sneddon syndrome M30.82

Ehrmann, 1907; Champion and Allison, 1965; Sneddon, 1965

Non-inflammatory, potentially life-threatening, systemic, occlusive vasculopathy characterized by the triad:

• non-thermoreactive generalized livedo racemosa
• transient ischemic attacks with neuropsychiatric abnormalities
• labile arterial hypertension

characterized by

Pathophysiologically, the skin is affected by a thrombotic vasculopathy of small to medium-sized vessels at the cutis-subcutis border, resulting in impaired blood flow with skin lesions(livedo racemosa) described as "lightning-figure-like". Central necroses are rarer.

A special form of Sneddon's syndrome is found in patients with detectable phospholipid antibodies. In this case, the clinical picture must be interpreted as a variant of systemic lupus erythematosus, a so-called secondary Sneddon syndrome.

The estimated annual incidence is 0.4/100,000, making it a rare disease (ORPHA:820)

Both autosomal dominant and autosomal recessive inheritance have been described.
In the monogenic forms, mutations in the ADA2 gene, which is located on chromosome 22q11, are detectable. The syndrome"vasculitis, autoinflammation, immunodeficiency and hematologic defects", which is also caused by ADA2 mutations, occurs in early childhood.

Risk factors are nicotine abuse, hypertension, hyperlipidemia and the use of hormonal contraceptives. Pathogenetically, occlusions of small and medium-sized arterioles occur.

According to Schellong, in addition to the primary, idiopathic Sneddon syndrome, secondary forms are also distinguished etiologically as part of an antiphospholipid antibody (aPLA) syndrome or other thrombophilic diseases.

Mostly occurring in women between the ages of 27 and 45 (mean age 42.9 years).

Trunk, buttocks, often combined with Raynaud's symptoms.

Pronounced livedo racemosa with lightning-figure-like vascular markings on the skin. Frequently accompanied by acrocyanosis, also Raynaud's symptoms.

Neurological symptoms: dizziness, transient ischemic attacks (TIA), cerebral infarctions, epilepsy.

Heart, kidney and eye involvement are rarer.

The skin changes usually precede the systemic changes by years.

Antiphospholipid antibodies are detectable in more than 50% of patients. Thrombocytosis may be associated (see below thrombocyte)

Angiography of the vessels of the hand: Caliber variations and occlusions mainly of the digital arteries.

Cerebral angiography: Pathological caliber variations and occlusions of medium-sized and small intracranial vessels.

EEG: General changes and/or focal findings depending on the extent of cerebral circulatory abnormalities.

CT/MRI: evidence of infarcts, possibly cerebral atrophy.

A causal therapy is not known and symptomatic therapy is still unsatisfactory.

Acetylsalicylic acid (e.g. Aspirin): 100 mg/day p.o. is indicated prophylactically.

Coumarin preparations (e.g. Marcumar): Should be used for a period of at least 6 months in cases of thrombosis.

Good results have been achieved with a combination therapy of platelet aggregation inhibition (e.g. acetylsalicylic acid or clopedigrel), prostaglanin E1 (alprostadil) and, if necessary, coumarin preparations (phenprocoumon) (Narwutsch A et al. 2024). Therapy studies show a better prognosis (lower number of strokes and TIAs) for combination therapies than for monotherapies (Narwutsch A et al. 2024).

Remember! It is particularly important to stop smoking and to discontinue oral contraception in women!

Immunosuppressive drugs: Immunosuppressive therapy is only indicated if antiphospholipid antibodies are detected; a combination of prednisone with azathioprine or cyclophosphamide (see below lupus erythematosus, systemic) is recommended.

In general and without sufficient therapy, the prognosis "quoad vitam and quoad functionem" is poor. The mortality rate is given as around 23% in 9 years (Narwutsch A et al. 2024).

In family members with skin manifestations such as livedo racemosa, acrocyanosis or Raynaud's phenomenon, attention should also be paid to cerebrovascular disorders.

It is not advisable to have children, as worsening symptoms are frequently observed.

1. Champion RH, Allison JR (1965) Livedo reticularis: A review. British Journal of Dermatology 77: 167-179
2. El Benaye J et al.(2013) Sneddon's syndrome. Press Med 42:138-144
3. Gibbs MB et al (2005) Livedo reticularis: an update. J Am Acad Dermatol 52: 1009-1019
4. Gottlober P et al (2000) Sneddon's syndrome in a child. Br J Dermatol 142: 374-376
5. Herman E (1937) Niezwykly zespol pourazowy: livedo racemosa universalis u osobnika z objawami piramido-pozapiramidowymi i zaburzeniami psychicznymi. Warsz. zawskie Czasopismo Lekarskie 14: 83-86, 107-109
6. Herman E, Sulat H (1957) Osobliwy zespol pourazowy pochodzenia naczynio-ruchowego livedo racemosa universalis, rozsiane zaburzenia piramidowo-pozapiramidowe i zaburzenia psychiczne. Neurologia, Neurochirurgia i Psychiatria Polska 7: 95-98
7. Herman E, Sulat H (1957) Un syndrome particulier post-traumatique vaso-moteur: Livedo racemosa universalis, symptomes disséminés pyramidaux et extra-pyramidaux et troubles psychiques. Rev neurol 101: 731-739
8. Hiltz RE et al (1994) Cutaneous vasculitis. Curr Opin Rheum 6: 20-24
9. Kalashnikova LA, Nasonov EL, Kushekbaeva AE, Gracheva LA (1990) Anticardiolipin antibodies in Sneddon's syndrome. Neurology 40: 464-467
10. Khosrotehrani K et al (2003) Sneddon syndrome revealing dysfibrinogenemia. Int J Dermatol 42: 561-562
11. Mascarenhas R et al (2003) Familial Sneddon's syndrome. Eur J Dermatol 13: 283-287
12. Mesa HA et al (1993) Sneddon's syndrome and phospholipid-antibodies. Clin Rheum 12: 253-256
13. Narwutsch A et al. (2024) Combination therapy of Sneddon's syndrome to reduce the incidence of cerebrovascular complications. JDDG 20:947-955
14. Orac A et al. (2014) Sneddon syndrome: rare disease or under diagnosed clinical entity? Review of the literature related to a clinical case. Rev Med Chir Soc Med Nat Iasi 118:654-660
15. Pettee AD, Wasserman BA, Adams NL et al. (1994) Familial Sneddon's syndrome: clinical, hematologic, and radiographic findings in two brothers. Neurology 44: 399-405
16. Schellong SN et al (1997) Classification of Sneddon`s syndrome. Vasa 26: 215-221
17. Sneddon IB (1965) Cerebro-vascular lesions and livedo reticularis. Brit J Dermatol 77: 180-185
18. Wohlrab J et al. (2001) Diagnostic impact and sensitivity of skin biopsies in Sneddon's syndrome. A report of 15 cases. Br J Dermatol 145: 285-288
19. Zelger B et al. (1993) Sneddon's syndrome: A long-term follow-up of 21 patients. Arch Dermatol 129: 437-441