Antiphospholipid antibodies in systemic lupus erythematosus and the antiphospholipid syndrome.

The family of autoantibodies known as antiphospholipid antibodies (aPL) and the lupus anticoagulant (LA) are associated with a spectrum of clinical manifestations including life-threatening thrombosis. While our current knowledge of thrombosis is imperfect and the mere presence of aPL is imprecisely associated with clinical events, our knowledge in this area has greatly expanded in recent years. It is clear that high levels of IgG aPL are associated with an increased risk of thrombosis. In 1990, investigators demonstrated that some aPL are directed against the beta2-Glycoprotein I (beta2-GPI) 50 kDa subunit and reported that these showed concordance with risk of clotting in certain groups of patients. Studies have also demonstrated that aPL reacted with antigens other than beta2-GPI, namely prothrombin, annexin V, protein S, protein C and high molecular weight kininogen. We review the clinical features of the antiphospholipid syndrome (APS), including vascular occlusion, pregnancy loss, thrombocytopenia and catastrophic APS. We also review the role of antibodies in the pathogenesis of APS as well as the spectrum of autoantibodies that have been found in APS.

Implications of depression in rheumatoid arthritis: do subtypes really matter?

OBJECTIVE: To examine depressive disorders and health status in patients with rheumatoid arthritis (RA), controlling for potential confounds. METHOD: Subjects (n = 426) completed measures of depressive symptoms (Center for Epidemiological Studies Depression Scale [CES-D]) and health status (Arthritis Impact Measurement Scales 2 [AIMS2]), via cross-sectional survey. Subjects (n = 299) with few depressive symptoms (CES-D < or = 10) were not evaluated further. Subjects with CES-D > or = 11 were interviewed using the Primary Care Evaluation of Mental Disorders to diagnose major depressive disorder (MDD; n = 46), dysthymic disorder (DD; n = 21), or minor depressive disorder (MND; n = 18). RESULTS: Regression analyses examined differences between the depressive disorders on AIMS2 subscales. Health status scores were similar between the depressive disorder subcategories; significant differences were found between MDD and MND on AIMS2 Physical scores and MDD and DD on AIMS2 Symptom scores. CONCLUSION: Regarding health status, presence of depression itself seems to overshadow differences between depression subtypes; antidepressant treatments/referrals for persons with concomitant RA and any depressive disorder subtype appear warranted.

Neuropsychological deficit profiles in systemic lupus erythematosus.

Although neuropsychological deficits have been reported in several cognitive domains in patients with systemic lupus erythematosus (SLE), there is considerable variability in the literature about which neuropsychological domains are most affected. Similar to studies that demonstrated that specific profiles of neuropsychological deficits exist for those with traumatic brain injury (TBI; Johnstone, Hexum, & Ashkanazi, 1995), this study examined whether a specific pattern of deficits is present in SLE. By comparing reading scores (as estimates of premorbid ability) to tests of concurrent cognitive abilities (i.e., memory, attention, etc.), it was determined that SLE presents a profile distinct from TBI, with the most significant impairments noted in expressive language (Zdiff = -1.39), attention (Zdiff = -0.41), and speed of processing (Zdiff = -0.40). In contrast to TBI, no impairment was noted in intelligence, memory, or cognitive flexibility. Results suggest that memory problems reported by individuals with SLE may be related to inattention. Clinical implications are discussed.

A confirmatory factor analysis of the Center for Epidemiologic Studies Depression Scale in rheumatoid arthritis patients: additional evidence for a four-factor model.

OBJECTIVE: To examine the factor structure of the Center for Epidemiologic Studies Depression Scale (CES-D) in a sample of patients with rheumatoid arthritis (RA), testing all of the alternative models suggested by the previous evidence. METHODS: The CES-D was administered to a group of RA patients (n = 685) during a structured telephone interview. The telephone interview was repeated 6 months later (n = 537) and 12 months later (n = 453). Confirmatory factor analyses were conducted to test alternative models. RESULTS: The correlated 4-factor model and the second-order 4-factor model were the best fitting models. CONCLUSION: The factor structure of the CES-D previously found in the general population was replicated in an RA sample. The results are consistent with previous evidence of criterion contamination in the CES-D when used in an RA sample and provide support for the view that a single summary score may not be the most informative index of the CES-D.

Analysis of autoantibodies against RNA polymerases using immunoaffinity-purifed RNA polymerase I, II, and III antigen in an enzyme-linked immunosorbent assay.

Autoantibodies against RNA polymerases (RNAP) have been reported to occur in patients with a wide variety of connective tissue diseases (CTD), including systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCTD). The frequency of anti-RNAP antibodies has been reported to vary widely between different CTD diseases in studies examining different patient populations. Furthermore, these studies have been limited by the fact that methods have not previously been available for detecting antibodies against RNAP which are both rapid and quantitative. We have developed an enzyme-linked immunosorbent assay (ELISA) for rapidly quantitating antibodies against RNAP I, II, and III. We have utilized both the ELISA and the immunoprecipitation of 35S-labeled HeLa cells to analyze sera from a large cohort of well-characterized Caucasian CTD patients for the presence of anti-RNAP antibodies. We found excellent concordance for the presence of anti-RNAP antibodies using immunoprecipitation and ELISA. Anti-RNAP antibodies occurred predominantly among female patients with the diffuse form of SSc and were detected in 8/36 (22%) of Caucasian patients with diffuse SSc and 1/53 (2%) with limited SSc. Anti-RNAP antibodies occurred in 1/42 (2%) of patients with SLE. Anti-RNAP antibodies did not occur in MCTD (0/49). Antibodies against RNAP were rare among antinucleolar-reactive sera, occurring in only 3/200 (1.5%). The RNAP ELISA provides a validated method which can be rapidly utilized in a clinical diagnostic laboratory setting to identify SSc patients who are at risk for developing diffuse SSc with multiorgan involvement and hypertensive renal crisis.

Ruptured intrahepatic aneurysm as the initial manifestation of polyarteritis nodosa.

polyarteritis nodosa (PAN) is characterized by panarteritis involving all layers of the vessel wall of medium and small arteries and adjacent veins leading to thrombosis and aneurysmal dilatation. We present the case of a 21-year-old Caucasian man with an acute abdomen with a massive gastrointestinal (GI) hemorrhage caused by a large intrahepatic aneurysmal rupture needing surgery. This was the initial manifestation of underlying PAN, which had not been diagnosed before the event. This patient's postoperative course was complicated by continued hemorrhage prompting further diagnostic abdominal arteriography, which revealed multiple art-eurysms along the superior mesenteric artery. The aneurysmal wall biopsy revealed lymphocytic infiltrates, scattered giant cells, and minimal necrosis. A diagnosis of PAN was entertained based on arteriographic findings, although no pathognomonic demonstration of multiple visceral aneu-rysms is a characteristic finding of PAN, The patient survived the catastrophic event, and treatment with corticosteroids was initiated, which led to an uncomplicated hospital stay. Furthermore, outpatient follow ups showed continued clinical improvement with corticosteroid therapy and a repeat angiogram performed elsewhere demonstrated resolution of most of the aneurysms. Our case represents an unusual initial clinical manifestation of PAN and is one of the few cases reported with a torrential (GI) hemorrhage resulting from a rupture of an intrahepatic aneurysm, which is associated with increased mortality. The clinical significance of abdominal pain is not always apparent. It may occur in the absence of any gross intra-abdominal lesions, or, as in our patient, may herald an acute abdominal catastrophe. The clinician should consider PAN in the differential diagnosis of a massive GI hemorrhage. It is also important to note that early diagnosis followed by aggressive treatment can be lifesaving.

Efficacy of low load resistive muscle training in patients with rheumatoid arthritis functional class II and III.

OBJECTIVE: To determine the effect of a low load resistance exercise training program on muscle strength, functional outcome, and cardiovascular endurance. METHODS: Forty-nine patients, 37 women and 12 men between the ages of 35-76 yrs (mean 60.5 yrs), with definite rheumatoid arthritis (RA) functional class II and III (mean disease duration of 10.5 yrs) were randomly assigned to exercise and control groups for a 12 wk resistive muscle training program. A circuit weight bearing form of training was incorporated using light loads with high repetitions. A video tape demonstrating the exercises was given to all exercising participants to enable them to continue the program at home at least 3 times per wk with a biweekly self-report evaluation. Baseline and post-intervention evaluations included joint activity, muscle strength, endurance, functional outcome, and self-report. Cardiovascular fitness measured by treadmill time, anaerobic threshold and peak oxygen consumption (VO2) in this group were assessed at baseline and 12 wks. RESULTS: A significant improvement at 12 wks was noted in the exercise group for self-reported joint count (p = 0.02), number of painful joints (p = 0.004), HAQ (p = 0.012), sit-to-stand time (p = 0.02), grip strength (p = 0.05) knee extension 60 degrees (p = 0.03), Arthritis Impact Measurement Scales dexterity (p = 0.02), and time to anaerobic threshold (p = 0.03). Significant improvement in the exercise group compared to the control group was noted for self-reported joint count (p = 0.02), night time pain (p = 0.05), and sit-to-stand time (p = 0.02). Increase in treadmill time was not statistically significant nor was a change in peak oxygen consumption (VO2) noted. Abnormalities on initial treadmill screening were detected in 2 of 49 asymptomatic patients. They were excluded from the study and subsequent workup revealed significant coronary artery disease. CONCLUSION: Low load resistive muscle training increased functional capacity as reported by patients and is a clinically safe form of exercise in functional class II and III RA. Screening this population for dormant coronary artery disease is recommended.

Antiphospholipid antibodies among anti-U1-70 kDa autoantibody positive patients with mixed connective tissue disease.

OBJECTIVE: The association between antiphospholipid antibodies (aPL) and recurrent venous and/or arterial thrombotic events, fetal loss, and thrombocytopenia in systemic lupus erythematosus (SLE) has been well documented. Such an association has not been carefully assessed in mixed connective tissue disease (MCTD). Our aim was to assess the prevalence and clinical significance of aPL in anti-U1-70 kDa autoantibody positive patients with MCTD. METHODS: We compared 48 consecutive anti-U1-70 kDa autoantibody positive patients with MCTD versus 59 consecutive anti-U1-70 kDa autoantibody negative patients with SLE to determine the frequency of aPL and clinical features of the aPL syndrome. RESULTS: Among the patients with MCTD 7/48 (15%) had anticardiolipin antibodies (aCL) versus 24/59 (41%) patients with SLE (p < 0.005) and versus 2/150 (1%) apparently healthy blood donors (p < 0.001). Among patients with MCTD with aPL, 2 were IgG, 3 IgM, and 2 both IgG and IgM isotypes; among patients with SLE 5 were IgG, 11 IgM, and 8 both IgG and IgM isotypes. No clotting events or other features of the aPL syndrome were found among the patients with MCTD compared with 26 events documented among the group of aCL positive patients with SLE (p < 0.001). There were 10 patients with SLE with deep vein thrombosis, one with a pulmonary embolism, 2 with recurrent fetal loss, one with chorea, 2 with livedo reticularis, one with severe thrombocytopenia, and one with avascular necrosis. CONCLUSION: aCL were increased in patients with MCTD compared to controls. Furthermore, aCL were increased in SLE compared with both patients with MCTD and controls. Finally, while clotting events and other manifestations of the aPL syndrome occurred among the group of aCL positive patients with SLE these were distinctly absent from the aCL positive MCTD group.

Association of systemic lupus erythematosus and gluten enteropathy.

Systemic lupus erythematosus presents various clinical manifestations. The coexistence of systemic lupus erythematosus and celiac sprue has been rarely reported. We present a patient who had systemic lupus erythematosus with malabsorption demonstrating characteristic clinical and pathologic findings of celiac sprue (gluten enteropathy).

Lack of association between hypothyroidism and chondrocalcinosis.

The association between hypothyroidism and calcium pyrophosphate dihydrate deposition disease (CPPD) is controversial. We studied the prevalence of chondrocalcinosis, the roentgenographic marker of CPPD by obtaining anteroposterior knee roentgenograms in 49 hypothyroid patients over the age of 40 years, and compared them with knee roentgenograms in 31 euthyroid patients matched for age and sex. Only 2 hypothyroid patients and one euthyroid control had knee chondrocalcinosis. Our results indicate that hypothyroid patients have no greater prevalence of chondrocalcinosis compared to euthyroid subjects. There are also no difference in the degree and prevalence of osteoarthritis between the 2 groups, although hypothyroid patients may have a higher prevalence of periarticular osteopenia.