Antiphospholipid antibodies in patients with purported 'chronic Lyme disease'.

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 in whom '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-ß2GP1) 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-ß2GP1 were positive in 85/106 (80%), with aCL present in 69/106 (65%) and anti-ß2GP1 present in 69/106 (65%). For all assays, IgM isotypes predominated: WB 55/64 (85%), aCL 63/69 (91%), anti-ß2GP1 52/69 (75%), aCL and/or anti-ß2GP1 74/85 (87%). Anti-ß2GP1 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-ß2GP1, 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.

Erythema nodosum associated with antiphospholipid antibodies: a report of three cases.

Erythema nodosum is a dermatologic condition characterized by painful, erythematous nodules on the anterior surfaces of the lower extremities. Its association with a variety of conditions has been previously described. We present three cases of erythema nodosum in patients with elevated anticardiolipin antibodies. In one patient, a temporal relationship was seen in the simultaneous detection of antibodies and skin lesions. We propose an association between erythema nodosum and the antiphospholipid antibody syndrome (APS).

Testing for the antiphospholipid syndrome: importance of IgA anti-beta 2-glycoprotein I.

BACKGROUND: Testing for the antiphospholipid syndrome (APS) using anticardiolipin antibodies (aCL) has been problematic. Titers may fluctuate or even become negative. Anti-beta 2-glycoprotein I assays (abeta2-GPI) may be more reliable for diagnosis. METHODS: In a prospective, blinded study over a nine-month period we retested all patients seen for routine follow-up visits in our clinic who had previously been evaluated for aCL-associated illnesses. Patients were stratified into two groups: group A-patients previously positive for aCL; group B-patients previously negative for aCL. Both groups were further classified according to disease severity. Patients were retested for both aCL and abeta2-GPI (isotypes G, M, A for each) using uniform testing standards. RESULTS: 118 patients with previously positive aCL (group A) were retested. Repeat aCL were positive in 52/118 (44%), abeta2-GPI positive in 69/118 (58%) and 82/118 (69.5%) were positive for one or both assays. In patients with serious organ damage (92% with documented APS), 48.6% were aCL positive, 64% positive for abeta2-GPI, and 75.7% were positive for one or both assays. When only one assay was positive, abeta2-GPI was most frequent (P=0.0096). Overall, IgA abeta2-GPI was the most frequent isotype found (60.9%). On retesting of 73 aCL-negative patients (group B), 9/73 (12%) were aCL positive, 27/73 (36%) were abeta2-GPI positive, with 24/73 (32.9%) having isolated abeta2-GPI. Of those positive for abeta2-GPI, IgA abeta2-GPI was present in 74. 1%. Many of these patients had documented APS. CONCLUSION: Based on our data, abeta2-GPI assays are superior to aCL assays for diagnosis of APS. The combined use of both assays enhance positive testing results in up to 75% of patients with APS at any stage of illness. ACL negative patients suspected of having APS should be retested for both abeta2-GPI and aCL. IgA abeta2-GPI appears to be the most important isotype detected.

Anti-phospholipid antibodies in patients with multiple sclerosis and MS-like illnesses: MS or APS?

OBJECTIVE: To describe the frequency, clinical, and laboratory features of patients diagnosed with multiple sclerosis (MS) or MS-like illnesses (MSL) among a large, prospectively followed cohort of anti-phospholipid antibody (aPL)-positive patients. METHODS: Between 1990 and 1995 patients referred to a university-affiliated rheumatology clinic were prospectively evaluated for aPL based on questionnaires designed to detect aPL-related symptoms and/or a family history of aPL-related illnesses. Magnetic resonance imaging (MRI) was performed when significant neurological features were present. A subgroup of all patients diagnosed with MS or MSL was identified and their clinical, laboratory, and imaging findings were reviewed. RESULTS: Of 322 patients evaluated for aPL-related symptoms or events, 189 (59%) were positive for at least one class of aPL. Twenty-six of 322 patients (8%) carried a diagnosis of MS or MSL, either at the initial evaluation or during the study period. Twenty-three of the 26 individuals (88%) tested positive for aPL, while the remaining 3 (11%) tested repeatedly negative. Eighteen of the 23 patients (78%) had either more than one class of aPL or had multiple positive titers. IgM aCL was noted in 18 of the 23 patients (78%). Oligoclonal bands were noted in five patients. Antinuclear antibodies (ANA) and low complement levels were frequently observed. Blinded MRI readings showed lesions consistent with MS in the majority of cases. Clinically, 7 patients had transverse myelitis (TM), while optic neuritis (ON) was present in 8 patients. Most patients had either occult symptoms of rheumatic disease or contributory family histories. None had a defined underlying connective-tissue disease. CONCLUSION: A substantial number of aPL-positive patients have a concurrent diagnosis of MS or MSL, frequently presenting with elevated IgM aCL, optic neuritis, and transverse myelitis. The anti-phospholipid syndrome (APS) should be strongly considered as an alternative diagnosis to MS in these patients.

A family study of anticardiolipin antibodies and associated clinical conditions.

PURPOSE: To determine the frequency of anticardiolipin antibodies (aCL) and their clinical sequelae in family members of aCL-positive patients. PATIENTS AND METHODS: A prospective serologic and clinical evaluation was performed on 23 patients with elevated aCL titers, 87 blood relatives, 18 spouses, and 37 controls. aCL and antinuclear antibodies (ANA) were measured and clinical histories were assessed for all probands, relatives, spouses, and controls. RESULTS: Fifty of 87 relatives screened (57%) had evidence of autoantibody production (aCL and/or ANA). Twenty-nine (33%) had positive aCL titers. Twenty were positive for aCL-immunoglobulin (Ig) G, 7 had evidence of both aCL-IgG and aCL-IgM, and an additional 2 were positive for aCL-IgM alone. In contrast, only 1 spouse was aCL-IgG positive. Thirty-two relatives and 1 spouse were ANA positive. All controls were negative for aCL and ANA. Significant differences were noted between relatives and spouses for aCL-IgG (P < 0.00001) and aCL-IgM titers (P < 0.0066), and also between relatives and controls (P < 0.00001 for both). Clinically, 4 cases of systemic lupus erythematosus (SLE), 4 SLE-like diseases, and 8 aCL-associated illnesses (2 premature strokes, 3 recurrent fetal losses, 1 recurrent thrombosis, and 2 cases of thrombocytopenia) were documented in the relatives. All cases were associated with aCL and/or ANA production. CONCLUSIONS: ANA, aCL, and clinical events associated with antiphospholipid antibodies occur with increased frequency in relatives, but not spouses of aCL-positive probands. These results suggest that aCL-related illnesses may be familial.