Antiphospholipid antibodies in patients with purported ‘chronic Lyme disease’

Abstract

Background: Antiphospholipid antibody (aPL) positive patients and patients with purported chronic Lyme disease (‘CLD’) share many clinical features. After identifying significant aPL in sera of several index patients with ‘CLD’, we performed aPL tests on all patients referred inwhom ‘CLD’ was suspected, diagnosed or treated.

Methods: All patients with suspected, diagnosed or treated ‘CLD’ and reportedly ‘positive’ Lyme assays were studied. aPL testing included anticardiolipin antibodies (aCL), anti-beta-2-glycoprotein-1 antibodies (anti-β2GP1) and lupus anticoagulant (LAC). Patients were classified into four newly described categories of CLD and data was analyzed.

Results: One hundred and six patients were evaluated, of whom 82% had neurologic symptoms and 51% rheumatologic symptoms. Eighty-eight of 106 (83%) patients had positive Lyme serologies (enzyme-linked immunosorbent assay [ELISA] 62/106, 58.4%; western blot [WB] 64/106, 60%), while 18/106 (16.9%) were negative or equivocal. aPL was found in all ‘CLD’ categories. aCL and/or anti-β2GP1 were positive in 85/106 (80%), with aCL present in 69/106 (65%) and anti-β2GP1 present in 69/106 (65%). For all assays, IgM isotypes predominated: WB 55/64 (85%), aCL 63/69 (91%), anti-β2GP1 52/69 (75%), aCL and/or anti-β2GP1 74/85 (87%). Anti-β2GP1 assays occurred in higher titer than aCL: 36/69 (52%) versus 63/69 (91%), p<0.001. Seventeen patients had aPL-related events. Only 12/106 (11.3%) had true post-Lyme syndromes (PLS), category IV, or late Lyme disease (LLD). Most patients had been treated for Lyme: 82/106 (79%).

Conclusion: aPL occurs frequently in patients with ‘CLD’. IgM anti-β2GP1, IgM aCL and IgM WB were frequently found. Documented PLS or LLD was uncommon. The role of aPL in patients with ‘CLD’ needs further investigation. Lupus (2011) 20, 1372–1377.

Keywords

Chronic Lyme disease antiphospholipid antibodies antiphospholipid syndrome

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References

Feder

Johnson

O'Connell

. A critical appraisal of ‘chronic Lyme disease’. N Engl J Med 2007; 357: 1422–1430.

Steere

. A 58-year-old man with a diagnosis of chronic Lyme disease. JAMA 2002; 288: 1002–1010.

Steere

Taylor

McHugh

. The overdiagnosis of Lyme disease. JAMA 1993; 269: 1812–1816.

Marques

. Chronic Lyme disease: A review. Infect Dis Clin North Am 2008; 22: 341–360.

Krupp

Hyman

Grimson

. Study and treatment of post Lyme disease (STOP-LD): A randomized double masked clinical trial. Neurology 2003; 60: 1923–1930.

Shadick

Phillips

Sangha

. Musculoskeletal and neurologic outcomes in patients with previously treated Lyme disease. Ann Intern Med 1999; 131: 919–926.

Halperin

. Neuroborreliosis. Am J Med 1995; 98(4A): 52S–61S.

Logigian

Kaplan

Steere

. Chronic neurologic manifestations of Lyme disease. N Engl J Med 1990; 323: 1438–1444.

Reid

Schoen

Evans

. The consequences of overdiagnosis and overtreatment of Lyme disease: An observational study. Ann Intern Med 1998; 128: 354–362.

10.

Hughes

GRV

. Speculations on APS in the coming millennium. JAutoimmun 2000; 15: 269–271.

11.

Hughes

GRV

. Antiphospholipid syndrome (Hughes syndrome): 10 clinical topics. Lupus 2010; 19: 343–346.

12.

Cervera

Piette

Font

. Antiphospholipid syndrome: Clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum 2002; 46: 1019–1027.

13.

Hughes

GRV

. Migraine, memory loss, and ‘multiple sclerosis’. Neurological features of the antiphospholipid (Hughes') syndrome. Postgrad Med J 2003; 789: 81–83.

14.

Levine

Welch

KMA

. The spectrum of neurologic disease associated with antiphospholipid antibodies. Arch Neurol 1987; 44: 876–883.

15.

Chapman

Rand

Brey

. Non-stroke neurological syndromes associated with antiphospholipid antibodies: Evaluation of clinical and experimental studies. Lupus 2003; 12: 514–517.

16.

Bassi

Amital

. Chronic fatigue syndrome: Characteristics and possible causes for its pathogenesis. Isr Med Assoc J 2008; 10: 79–81.

17.

Markel

Chang

Pierangeli

. The prevalence and clinical associations of anticardiolipin antibodies in a large inception cohort of patients with connective tissue disease. Am J Med 1996; 101: 576–583.

18.

Khamashta

Cuadrado

Mujic

. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med 1995; 332: 993–997.

19.

Miyakis

Giannakopoulos

Krilis

. Beta-2 glycoprotein 1 – function in health and disease. Thromb Res 2004; 114: 335–346.

20.

Greco

Amos

Conti-Kelly

. Testing for the antiphospholipid syndrome: Importance of IgA anti-beta 2-glycoprotein I. Lupus 2000; 9: 33–41.

21.

Tincani

Spatola

Cattaneo

. Antiphospholipid ELISA: The state of the art. Lupus 1996; 5: 477–479.

22.

Reber

Cornby

Degenne

. Multicenter evaluation of nine kits for the quantitation of anticardiolipin antibodies. Thromb Haemost 1995; 52: 444–452.

23.

Garcia Monco

Wheeler

Benach

. Reactivity of neuroborreliosis patients (Lyme disease) to cardiolipin and gangliosides. J Neurol Sci 1993; 117: 206–214.

24.

Selva-O'Callaghan

Ordi

Porcel Perez

. False positive serological tests for Borrelia burgdorferi in patients with primary antiphospholipid syndrome (in Spanish). Med Clin (Barc) 1990; 95: 411–413.

25.

Chapman

. The interface of multiple sclerosis and antiphospholipid antibodies. Thromb Res 2004; 114: 477–481.

26.

Cuadrado

Khamashta

Ballesteros

. Can neurologic manifestations of Hughes (antiphospholipid) syndrome be distinguished from multiple sclerosis? Analysis of 27 patients and review of the literature. Medicine (Baltimore) 2000; 79: 57–68.

27.

Ijdo

Conti-Kelly

Greco

. Anti-phospholipid antibodies in patients with multiple sclerosis and MS-like illnesses: MS or APS?. Lupus 1999; 8: 109–115.

28.

Garg

Zivadinov

Ramanathan

. Clinical and MRI correlates of autoreactive antibodies in multiple sclerosis patients. J Neuroimmunol 2007; 187: 159–165.

29.

Sanna

D'Cruz

Cuadrado

. Cerebral manifestations in the antiphospholipid (Hughes) syndrome. Rheum Dis Clin N Am 2006; 32: 465–490.