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.

Diabetic thigh muscle infarction in association with antiphospholipid antibodies.

BACKGROUND: Diabetic muscle infarction (DMI) is a rare complication of type 1 diabetes mellitus. DMI has a stereotyped clinical presentation and characteristic, though nonspecific, magnetic resonance imaging (MRI) and histologic findings. The etiology, however, remains controversial. OBJECTIVES: To present the first reported cases of DMI in association with positive antiphospholipid (aPL) antibody titers and to discuss the etiologic and pathogenic significance of the association between type 1 diabetes and aPL antibodies. METHODS: Descriptive case reports of 2 patients with DMI and positive aPL antibodies and a review of the relevant literature. RESULTS: Our 2 patients with DMI are female type-1 diabetics with end-organ microvascular complications who presented with an abrupt, painful swelling or mass of the thigh musculature. The diagnosis of DMI was based on the clinical picture and the findings on T2-weighted MRI and histologic evaluation. The first patient had a long history of known aPL antibodies in the setting of systemic lupus erythematosus. The second patient was only determined to be aPL positive after her recurrent episodes of DMI. The first patient was treated with anticoagulation and corticosteroids with relatively rapid resolution of symptoms. The second patient was treated with local débridement and supportive care with a resulting course of prolonged symptoms and recurrences. There are no controlled trials of the treatment of DMI. In the literature there is evidence for an increased prevalence of aPL antibodies in type 1 diabetic patients. The pathogenesis of DMI is poorly understood, but the hypercoagulable state often associated with aPL antibodies may play an important role. CONCLUSIONS/RELEVANCE: aPL antibodies may be involved in the pathogenesis of diabetic muscle infarction and could serve as an important target of therapeutic intervention, namely with anticoagulation.

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.

Anticardiolipin antibodies in the polymyalgia rheumatica-temporal arteritis syndromes.

A series of seven patients with the polymyalgia rheumatica-temporal arteritis (PMR-TA) complex is presented, each of whom during the clinical course demonstrated the presence of anticardiolipin antibodies (ACLs). Presenting symptoms consisted of proximal myalgias and stiffness characteristic of PMR in five patients and of visual symptoms and headache suspicious for TA in two patients. Two of the five PMR patients later developed jaw claudication characteristic of TA. Six of the seven cases demonstrated clinical evidence of a vasculopathic process such as a cerebrovascular infarct or a vasculitic syndrome. Previous studies have suggested an association between ACLs and PMR-TA, and this series of patients appears to provide more supporting evidence. Even patients who only manifested PMR symptoms without suggestion of accompanying TA developed vascular complications. An increasing range of symptoms have been recognized in association with ACLs, and the vasculitic syndromes of PMR-TA should be included as a possible association. While this series together with previous studies may suggest that the presence of ACLs in patients with PMR-TA symptoms may serve as a marker for the development of vascular complications, larger longitudinal studies will be necessary in the future.

Autoimmune ischemic optic neuropathy associated with positive rheumatoid factor and transient nephrosis.

A young woman had recurrent anterior ischemic optic neuropathy for 18 years. During a recent episode of severe papillopathy in one eye, acute glomerulonephritis, transient low serum complement levels, and a high rheumatoid factor were detected. Despite long and careful follow-up, we could not diagnose systemic lupus erythematosus or any other specific connective tissue or autoimmune disease. We suspect transient disordered immunity may have contributed to provoking acute anterior ischemic optic neuropathy concomitant with acute glomerulonephritis despite the absence of generalized connective tissue disease. An extensive search for immunologic mechanisms in some patients with presumed idiopathic anterior ischemic optic neuropathy may be warranted because immunosuppressive treatment may be beneficial in preventing recurrences.

Oral ciprofloxacin in resistant urinary tract infections.

Thirty-two patients (18 men and 14 women), who ranged in age from 28 to 91 years (mean, 71.2 years), with urinary tract infections caused by Pseudomonas species or other organisms resistant to trimethoprim-sulfamethoxazole were treated with 500 mg of orally administered ciprofloxacin every 12 hours. Thirty patients completed at least five days of therapy and were evaluated for efficacy. Of these, the treatment of 28 (93 percent) patients was considered successful, with urine cultures yielding negative results five to nine days after cessation of therapy. Three of these patients were found to be reinfected with their primary pathogens when culture specimens were obtained again three to four weeks later. The two patients who received treatment that was classified as having failed had urine cultures that persistently grew Pseudomonas aeruginosa. Superinfections occurred in eight patients, four with diabetes and four with underlying central nervous system disease. Adverse reactions required discontinuation of therapy in two patients. Although the rates of reinfection and superinfection were somewhat high, these patients had a high frequency of underlying diseases that predisposed them to recurrent or difficult-to-treat infections. Despite these shortcomings, ciprofloxacin is a welcome addition to the oral antibiotic regimen for the treatment of antibiotic-resistant urinary infections.

Optimal therapy for enterococcal endocarditis.

Enterococcal endocarditis accounts for an increasing proportion of cases of endocarditis in recent years. The combination of a penicillin and an aminoglycoside has become an accepted standard of treatment for this disease. However, the optimal choice of antibiotics, duration of therapy, and timing of surgical intervention remain controversial. This study reviews the presentation, clinical course, treatment, and outcome in 37 patients with 42 separate episodes of enterococcal endocarditis at four Yale University hospitals. Patients treated with aminoglycosides and penicillins or vancomycin had significantly better outcomes than those who did not receive aminoglycosides. However, the duration of aminoglycoside therapy (more than four versus less than four weeks) did not appear to affect outcome significantly. These results suggest that excellent cure rates may be achieved after treatment for less than four weeks with an aminoglycoside in combination with penicillin or vancomycin, thus potentially avoiding significant renal and vestibular toxicity.

Diffuse disseminated atheroembolism. Three cases with neuro-ophthalmic manifestation.

Neuro-ophthalmic manifestations led to the diagnosis of diffuse disseminated atheroembolism (DDA) in three men whose systemic symptoms had remained unexplained for years. The cholesterol emboli that cause DDA originate from friable plaques in the aorta and great vessels. Ophthalmologists should be alert to the diagnosis of DDA in patients with elevated ESRs, stroke, transient amaurosis, or cholesterol emboli in the fundi. Early diagnosis is important because arteriography, endarterectomy, and anticoagulation seem to increase the risk of serious, even fatal, embolization in these patients.

Prophylactic antibiotics in gynecologic surgery.

A 2-year prospective double-blind study of prophylactic antibiotics in 317 patients undergoing elective total abdominal or vaginal hysterectomy was conducted. Patients randomly received placebo, penicillin, or cefazolin 30 minutes prior to surgery and at 6-hour intervals thereafter for 48 hours. Rigid criteria for postoperative morbidity were established. Vaginal hysterectomy patients given either penicillin or cefazolin prophylaxis had fewer postoperative infections (P less than 0.01) compared to those given placebo. A similar trend was noted among women undergoing abdominal hysterectomy; however, this trend was not statistically significant (P greater than 0.05). Despite continuous surveillance, no change in nosocomial flora or antibiotic sensitivity of bacterial isolates was noted. Adverse drug effects and antibiotic-resistant secondary infections were encountered with similar frequency in all treatment groups.