Clinical Reviews in Allergy & Immunology

, Volume 32, Issue 1, pp 3–11 | Cite as

Hughes syndrome

The antiphospholipid syndrome—A clinical overview
  • Graham Hughes
Article

Abstract

In 1983, a detailed clinical description of a new syndrome was published. This prothrombotic syndrome was initally called the anticardiolipin syndrome and subsequently the antiphospholipid syndrome (APS), or Hughes Syndrome. Almost uniquely, it results in arterial as well as venous thrombosis and is marked by the presence of circulating antiphospholipid antibodies. Clinical features are protean, ranging from peripheral deep vein thrombosis (DVT) to involvement of internal organs such as the liver, kidneys, and adrenals. Likewise, arterial thrombosis can result in life-threatening infarction of organs such as the heart.

The nervous system is frequently affected, with migraine, memory loss, balance disorders, stroke, and atypical multiple sclerosis being prominent. Other features include recurrent miscarriage, thrombocytopenia, and livedo reticularis.

More recent observations have included ischemic bone fractures, renal and celiac artery stenosis, and a possible tendency toward accelerated atherosclerosis.

The condition is seen in patients with lupus, but, significantly, occurs without associated lupus (“primary” APS)—indeed, increasing clinical recognition of Hughes Syndrome suggests that this condition will overtake lupus in prevalance.

Treatment at present is by anticoagulation. The mechanisms for thrombosis are being worked out; it has been suggested that in some situations (e.g., pregnancy loss), an inflammatory component as well as thrombosis may play a part.

Index Entries

Antiphospholipid syndrome Hughes Syndrome thrombosis anticoagulation stroke lupus 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Hughes, G. R. V. (1983), Thrombosis, abortion, cerebral disease and lupus anticoagulant. Br Med J 287, 1088–1089.Google Scholar
  2. 2.
    Hughes, G. R. V. (1998), Hughes Syndrome: The antiphospholipid syndrome. A historical view. Lupus 7, 1–4.CrossRefGoogle Scholar
  3. 3.
    Sangle, S., Jan, W., Lau, I., Bennett, A., Rankin, S. C., and Hughes, G. R. V. (2005) Coeliac artery stenosis in patients with antiphospholipid syndrome-antiphospholipid antibodies. Arthritis Rheum 52, 569–596.Google Scholar
  4. 4.
    Sangle, S., D’Cruz, D., Khamashta MA., and Hughes, G. R. V. (2004), Antiphospholipid antibodies, SLE and non-traumatic metatarsal fractures. Ann Rheum Dis 63, 1241–1243.PubMedCrossRefGoogle Scholar
  5. 5.
    Hughes, G. R. V. (2003). Migraine, memory loss and ‘multiple sclerosis’. Neurological features of the antiphospholipid (Hughes) syndrome. Postgrad Med J 79, 81–83.PubMedCrossRefGoogle Scholar
  6. 6.
    Mackworth-Young, C. G. and Hughes, G. R. V. (1985), Epilepsy: an early symptom of SLE. J Neurol Neurosurg Psych 48, 185.Google Scholar
  7. 7.
    Mackworth-Young, C. G., David, J., Loizou, S., and Walport, M. J. (1987), Primary antiphospholipid syndrome: features in patients with raised anticardiolipin antibodies and in other disorders. Brit J Rheumatol 26, 94 (abstract).Google Scholar
  8. 8.
    Harris, E. N., Gharavi, A. E., Boey, M. L., et al. (1983), Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in SLE. Lancet 2, 1211–1244.PubMedCrossRefGoogle Scholar
  9. 9.
    Gharavi, A. E., Harris, E. N., Asherson, R. A., and Hughes, G. R. V. (1987), Isotype distribution and phospholipid specificity in antiphospholipid syndrome. Ann Rheum Dis 46, 1–6.PubMedGoogle Scholar
  10. 10.
    Harris, E. N., Gharavi, A. E., Asherson, R. A., Boey, M. L., and Hughes, G. R. V. (1984) Cerebral infarction in SLE. Association with anticardiolipin antibodies. Clin Exp Rheumatol 2, 47–51.PubMedGoogle Scholar
  11. 11.
    Harris, E. N., Gharavi, A. E., Hegde, U., and Hughes, G. R. V. (1985), Anticardiolipin antibodies in autoimmune thrombocytopenic purpura. Brit J Haematol 59, 231–234.Google Scholar
  12. 12.
    Asherson, R. A., Mackworth-Young, C. G., Boey, M. L., and Hughes, G. R. V. (1983), Pulmonary hypertension in SLE,. Brit Med J 287, 1024–1025.CrossRefGoogle Scholar
  13. 13.
    Asherson, R. A., Cervera, R., and Font, J., et al. (1998), Catastrophic antiphospholipid syndrome: Clinical and laboratory features of 50 patients. Medicine 77, 195–207.PubMedCrossRefGoogle Scholar
  14. 14.
    Harris, E. N., Gharavi, A. E., Patel, S. P., and Hughes, G. R. V. (1987), Evaluation of the anticardiolipin antibody test: report of a standardisation workshop held on April 4th 1986. Clin Exp Immunol 58, 215–222.Google Scholar
  15. 15.
    Bertolaccini, M. L., Gomez, S., and Pareja, J., et al. (2005), Antiphospholipid antibody tests: spreading the net. Ann Rheum Dis 64, 1639–1643.PubMedCrossRefGoogle Scholar
  16. 16.
    Mackworth-Young, C. G. (2004), Antiphospholipid syndrome: multiple mechanisms. Clin Exp Immunol 136, 393–401.PubMedCrossRefGoogle Scholar
  17. 17.
    Wilson, W. A., Gharavi, A. E., and Koike, T., et al. (1999), International Consensus Statement on preliminary classification criteria for definite antiphospholipid syndrome. Arthritis Rheum 42, 1309–1311.PubMedCrossRefGoogle Scholar
  18. 18.
    Hughes, G. R. V. (2000), Off the beaten track—a clinician’s view, in Khamashta, M. A. (ed.) Hughes Syndrome: Antiphospholipid Syndrome, Springer, London.Google Scholar
  19. 19.
    Montalban, J., Khamashta, M. A., and Davalos, A., et al. (1984), Value of immunological testing in stroke patients. Stroke 25, 2412–2415.Google Scholar
  20. 20.
    Nencini, P., Baruffi, M. C., and Abbata, R. et al. (1992), Lupus anticoagulant and anticardiolipin antibodies in young adults with cerebral ischaemia. Stroke 23, 189–193.PubMedGoogle Scholar
  21. 21.
    Levine, S. R., Brey, R. L., Tilley, B. C., et al. (2004). Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischaemic stroke. JAMA 291, 576–584.PubMedCrossRefGoogle Scholar
  22. 22.
    Cimaz, R., Meroni, P. L., and Shoenfeld, Y. (2006). Epilepsy as part of systemic lupus erythematosus and systemic antiphospholipid syndrome (Hughes syndrome). Lupus 15, 191–194.PubMedCrossRefGoogle Scholar
  23. 23.
    Cuadrado, M. J., Wakefield, K., Sanna, G., Khamashta, M. A., and Hughes, G. R. V. (2004), Multiple sclerosis in the antiphospholipid (Hughes) syndrome. A common differential diagnosis?. Clin Exp Rheum 22, 652–653.Google Scholar
  24. 24.
    Lampropoulos, C. E., Koutroumanidis, M., Reynolds, P. P., Manidakis, I., Hughes, G. R. V., and D’Cruz, D. P. (2005), Electroencephalography in the assessment of neuropsychiatric manifestations in antiphospholipid syndrome and systemic lupus erythematosus. Arthritis Rheum 52, 841–846.PubMedCrossRefGoogle Scholar
  25. 25.
    Font, J. and Cervera, R. (2000), Cardiac manifestations of the antiphospholipid syndrome, in Khamashta, M. A. (ed.) Hughes Syndrome: Antiphospholipid Syndrome, Springer, London.Google Scholar
  26. 26.
    Nair, S., Khamashta, M. A., and Hughes, G. R. (2002), Syndrome X and Hughes Syndrome. Lupus 11, 332.PubMedCrossRefGoogle Scholar
  27. 27.
    Doria, A., Shoenfeld, Y., and Wu, R., et al. (2003), Risk factors for subclinical atherosclerosis in a prospective cohort of patients with SLE. Ann Rheum Dis 62, 1071–1077.PubMedCrossRefGoogle Scholar
  28. 28.
    Christodoulou, C., Zain, M., and Bertolaccini, M. (2006), Prevalence of an abnormal ankle-brachial index in patients with antiphospholipid syndrome with pregnancy loss but without thrombosis: a controlled study. Ann Rheum Dis 65, 683–684.PubMedCrossRefGoogle Scholar
  29. 29.
    Sangle, S., D’Cruz, D. P., and Jan, W. (2003), Renal artery stenosis in the antiphospholipid (Hughes) syndrome and hypertension. Ann Rheum Dis 62, 999–1002.PubMedCrossRefGoogle Scholar
  30. 30.
    Sangle, S., D’Cruz, D., Khamashta, M., Tungekar, M. F., Abbs, I., and Hughes, G. R. V. (2002), Goldblatt’s kidney, Hughes syndrome and hypertension. Lupus 11, 699–703.PubMedCrossRefGoogle Scholar
  31. 31.
    Safian, R. D. and Textor, S. C. (2001), Renal artery stenosis. N Engl J Med 344, 431–442.PubMedCrossRefGoogle Scholar
  32. 32.
    Asherson, R. A. and Hughes, G. R. V. (1989), Addison’s disease and primary antiphospholipid syndrome. Lancet 2, 874.PubMedCrossRefGoogle Scholar
  33. 33.
    Mangia, A., Margaglione, M., and Cascavilla, I. (1999), Anticardiolipin antibodies in patients with liver disease. Am J Gastroenterol. 94, 2983–2987.PubMedCrossRefGoogle Scholar
  34. 34.
    Toubi, E. (2000), The ear and antiphospholipid syndrome, in: Khamashta, M. A. (ed.) Hughes Syndrome: Antiphospholipid Syndrome, Springer, London.Google Scholar
  35. 35.
    Bizzarro N. and Brandalise, M. (1995), EDTA-dependent pseudo-thrombocytopenia. Am J Clin Pathol 103, 103–107.Google Scholar
  36. 36.
    Montecucco, C. and Caporali, R. (2006), Haemocytopenias in antiphospholipid sindrome, in: Khamashta, M. A. (ed) Hughes Syndrome: Antiphospholipid Syndrome 2nd edition. Springer, London.Google Scholar
  37. 37.
    Moore, J., Ma, D., and Concannon, A. (1998), Nonmalignant bone marrow necrosis: a report of 2 cases. Pathology 30, 318–320.PubMedCrossRefGoogle Scholar
  38. 38.
    Vasoo, S., Sangle, S., Zain, M., D’Cruz, D., and Hughes, G. R. V. (2005), Orthopaedic manifestations of the antiphospholipid (Hughes) syndrome. Lupus 14, 339–345.PubMedCrossRefGoogle Scholar
  39. 39.
    Tsutsumi, A., Horita, T., Ohmuro, J., Atsumi, T., Ichikawa, K., and Tashiro, K. (1999), Reflex sympathetic dystrophy in a patient with antiphospholipid syndrome. Lupus 8, 471–473.PubMedCrossRefGoogle Scholar
  40. 40.
    Bird, A. G., Lendrum, R., Asherson, R. A., and Hughes, G. R. V. (1987), Disseminated intravascular coagulation, antiphospholipid antibodies, and ischaemic necrosis of extremities. Ann Rheum Dis 46, 251–255.PubMedCrossRefGoogle Scholar
  41. 41.
    Asherson, R. A., Cervera, R., and de Groot, P. G., et al. (2003), Catastrophic antiphospholipid syndrome. International consensus statement on classification criteria and treatment guidelines. Lupus 12, 530–534.PubMedCrossRefGoogle Scholar
  42. 42.
    Derksen, R. H., Khamashta, M. A., and Branch, D. W. (2004), Management of the obstetric antiphospholipid syndrome. Arthritis Rheum 50, 1028–1039.PubMedCrossRefGoogle Scholar
  43. 43.
    Wilson, W. A. and Cucurull, E. (2006), Ethnic and geographic variation in antiphospholipid syndrome, in: Khamashta, M. A. (ed.), Hughes Syndrome: Antiphospholipid Syndrome 2nd edition. Springer, London.Google Scholar
  44. 44.
    Malaviya, A. (1996), Hughes syndrome: a common problem in Kuwait hospitals. Br J Rheum, 35, 1132–1136.CrossRefGoogle Scholar
  45. 45.
    Hughes, G. R. V. and Khamashta, M. A. (2003). Seronegative antiphospholipid syndrome. Ann Rheum Dis 62, 1127.PubMedCrossRefGoogle Scholar
  46. 46.
    Sangle, S., D’Cruz, D. P., and Hughes, G. R. V. (2005), livedo reticularis and pregnancy morbidity in patients negative for antiphospholipid antibodies. Ann Rheum Dis 64, 147–148.PubMedCrossRefGoogle Scholar
  47. 47.
    Letellier, E. and Hughes, G. R. V. (2003), “Listen to the patient”—anticoagulation is critical in the antiphospholipid (Hughes) syndrome. J Rheumatol 30, 897.PubMedGoogle Scholar
  48. 48.
    Sherer, Y. and Shoenfeld, Y. (2006), Intravenous immunoglobulin for immunomodulation of SLE. Autoimmunity Rev 5, 153–155.CrossRefGoogle Scholar
  49. 49.
    George, J. and Shoenfeld, Y. (1997), The antiphospholipid (Hughes) syndrome: a crossroads of autoimmunity and atherosclerosis. Lupus 6, 559–560.PubMedGoogle Scholar
  50. 50.
    Hahn, B. H. (2003), Systemic lupus erythematosus and accelerated atherosclerosis. N Engl J Med 349, 2379–2380.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2007

Authors and Affiliations

  • Graham Hughes
    • 1
  1. 1.London Lupus CentreLondon Bridge HospitalLondonUK

Personalised recommendations