Which antiphospholipid antibody tests are most useful?

Despite an active international effort to improve diagnosis and treatment of the antiphospholipid syndrome (Hughes syndrome), there remain problems of lack of standardization and lack of prospective and multivariate epidemiologic analysis which restrict the diagnostic and predictive ability of commercially available tests. Nevertheless, current published series provide some data from which strategic approaches can be used to maximize the efficiency and usefulness of available tests. For further updates on new research and developments of interest to physicians and patients with this syndrome, the following web sites may prove helpful: www.slrapls.org, www.hematology.org, www.acforum.org, www.americanheart.org, www.rarediseases.org, www.aarda.org, and www.lupus.org.     

Anti-Saccharomyces cerevisiae antibody titers are stable over time in Crohn＇s patients and are not inducible in murine models of colitis

AIM: To investigate ASCA production over time in CD and murine colitis in order to further our understanding of their etiology. MATERIALS AND METHODS: Sixty-six CD patients were compared to ulcerative colitis (UC) and irritable bowel syndrome patients with respect to ASCA production as measured by ELISA. ASCA IgG or IgA positivity as well as change in titers over a period of up to 3 years (ΔIgG/A) was correlated with clinical parameters such as CD activity index (CDAI) and C-reactive protein levels (CRP). Moreover, two murine models of colitis (DSS and IL-10 knock out) were compared to control animals with respect to ASCA titers after oral yeast exposure. RESULTS: ASCA IgG and IgA titers are stable over time in CD and non-CD patients. Fistular disease was associated with a higher rate of ASCA IgA positivity (P = 0.014). Heal disease was found to have a significant influence on the ΔIgG of ASCA (P = 0.032). There was no correlation found between ASCA positivity or ΔIgG/A and clinical parameters of CD: CDAI and CRP. In mice, neither healthy animals nor animals with DSS-induced or spontaneous colitis exhibited a marked increase in ASCA titers after high-dose yeast exposure. On the other hand, mice immunized intraperitoneally with mannan plus adjuvant showed a marked and significant increase in ASCA titers compared to adjuvant-only immunized controls (P = 0.014). CONCLUSION: The propensity to produce ASCA in a subgroup of CD patients is largely genetically predetermined as evidenced by their stability and lack of correlation with clinical disease activity parameters. Furthermore, in animal models of colitis, mere oral exposure of mice to yeast does not lead to the induction of marked ASCA titers irrespective of concomitant colonic inflammation. Hence, environment may play only a minor role in inducing ASCA.     

Captopril test: time over?

OBJECTIVE: The role of non-invasive tests for the detection of renovascular hypertension is still a matter of controversy. The 'captopril test' is widely used; its clinical usefulness, however, remains questionable. The aim of the current study was therefore to report our own experience and to review the published data on the diagnostic significance of the test. PATIENTS AND METHODS: Data from 485 hypertensive patients who underwent a captopril test in consecutive order at our institution were analysed retrospectively. After a 30-min resting period in the supine position 50 mg of captopril was given orally. Blood was collected before and 90 min after dosage for the determination of plasma renin concentration (normal range 3.5-8.0 ng/ml/h). An increase by 100% or more of the baseline value was considered a positive response. Blood pressure was recorded at baseline and at 90 min. RESULTS: A positive response was present in 62 patients; further diagnostic work-up revealed significant renal artery stenosis in 11 of these patients. In the 423 patients with a negative response renal artery stenosis was found in three cases. With some limitations of retrospective analyses in mind, sensitivity and specificity of the test were calculated as 79% and 89%, respectively. No severe complication occurred during the test. CONCLUSION: Our data on the diagnostic indices and the safety of the captopril test are in good agreement with most published series. Altogether, available data suggest that the captopril test has a limited diagnostic accuracy as a screening test for the detection of renovascular hypertension. New radiologic non-invasive techniques with greater diagnostic value are therefore likely to challenge the clinical role of the test in the future.     

Real world experience with an indigenously manufactured stent Cobal C – A retrospective study

Background

Second generation bare metal stents made of cobalt chromium alloy are superior to first generation stain less steel stents. The thin struts are shown to reduce clinical and angiographic adverse outcomes.

Objective

To study the long term clinical and angiographic outcomes in patients who underwent coronary angioplasty with an indigenously made cobalt chromium bare metal stents with thin strut Cobal+C™ (Relisys).

Methods

A total of 268 consecutive patients who underwent coronary angioplasty with Cobal+C stents were studied retrospectively. Clinical follow up was done after a minimum period of nine months through telephonic interview and angiographic follow up was done in 80 patients chosen randomly. The end points analyzed included major adverse cardiac events (MACE) at nine months and the rate of binary restenosis at follow up angiogram done between 9 and 15 months post angioplasty.

Results

Thirty four percent were diabetic and 33% had acute myocardial infarction. Females constituted 17%. Mean stent diameter was 2.88 ± 0.28 and mean stent length 18.8 ± 4.2. MACE at nine months was 4.5% with TLR 0.3%. The rate of binary restenosis was 21%. Patients with longer stent lengths and non-compliance with medications had significantly higher rates of binary restenosis.

Conclusions

The use of Relisys Cobal+C stents was associated with good long term clinical and angiographic outcomes as evidenced by low incidence of MACE and binary restenosis rates for a bare metal stent.     

Is avoidant coping independent of disease status and stable over time in patients with ankylosing spondylitis?

OBJECTIVE: To determine whether avoidant coping in ankylosing spondylitis (AS) is independent of disease status and whether it is stable over time. METHODS: 658 patients with AS completed a postal questionnaire on health status, including pain and stiffness (BASDAI), physical function (BASFI), and coping (CORS). In CORS, "decreasing activities to cope with pain" and "pacing to cope with limitations" reflect avoidant behavioural coping. Ninety patients continued in a longitudinal study and 70 completed the CORS after four years. The adjusted contribution of age, sex, disease duration, educational level, pain (BASDAI), and physical function (BASFI) to the two avoidant coping strategies at first assessment was determined by multiple linear regression. Agreement between coping at first assessment and four years later was determined by intraclass correlation, and the correlation between change in coping and change in disease status over time by Pearson's correlation. RESULTS: At first assessment, worse physical function (BASFI) and more pain (BASDAI) were associated with "decreasing activities to cope with pain". Worse physical function, but not pain, was associated with "pacing to cope with limitations". The contribution of physical function or pain to the total explained variance in each of the coping strategies was small. Disease duration was not a determinant of avoidant coping, but greater age was associated with "pacing to cope with limitations". Change in avoidant coping strategies over time could not be explained by change in function or pain. CONCLUSIONS: In AS, avoidant coping at a particular time is largely independent of disease duration or status. Variability in avoidant coping over a limited period of four years cannot be explained by change in disease status.     

Relapsing catastrophic antiphospholipid antibody syndrome: a mimic for thrombotic thrombocytopenic purpura?

SUMMARY: The catastrophic antiphospholipid antibody syndrome (CAPS) is an uncommon disorder characterized by widespread micro- and macrovascular changes due to intravascular thrombosis. This complication of the antiphospholipid antibody syndrome is often fatal and recurrences are very rare. The differential diagnosis of CAPS includes thrombotic thrombocytopenic purpura (TTP) and this distinction may be difficult, but essential, for appropriate therapy. Plasmapheresis is effective in both conditions, but anticoagulation, a mainstay in the treatment of CAPS, could be disastrous in TTP. We present the case of an elderly woman who survived two episodes of CAPS four years apart and whose clinical findings were also suggestive of TTP. The characteristics of TTP and CAPS are compared and the importance of accurate diagnosis is emphasized.     

Outcomes generated by patients with rheumatoid arthritis: how important are they?

Background: It has been shown previously that patients with rheumatoid arthritis (RA) can generate a wide range of outcomes that they consider important in treatment. It is not known if these outcomes are generally important in the wider RA patient community. Objectives: (1) To examine whether recent patient‐generated outcomes are generalizable within a wider RA population; (2) to assess the relative importance of each outcome; and(3) to explore whether any important outcomes have been omitted. Methods: A questionnaire, listing 23 outcomes previously generated by RA patients, was distributed through three rheumatology centres in the UK. Patients gave an importance score to each outcome (0–3), selected their top three most important outcomes, and then listed any outcomes of personal importance that were missing. Results: 323 questionnaires were returned (65%). All outcomes were deemed important. Independence, pain, and mobility were most frequently selected by patients in their top three outcomes but were not chosen by 61–66% of patients. The next most commonly chosen outcomes related to feeling well and fatigue. Factor analysis revealed six reasonably distinct groupings: general well‐being (11.9% explained variance), day‐to‐day functioning(10.6%), emotional and psychological well‐being (10.6%), social role and confidence (10%), physical symptoms (9.5%) and medication issues (7.9%). Conclusion: Outcomes generated by patients as important in RA, are generalizable and inclusive. The most important (independence, pain and mobility) are routinely treated and measured. The next most important (feeling well, fatigue) are infrequently addressed and deserve urgent consideration for measurement, treatment and research. Copyright © 2005 John Wiley & Sons, Ltd.     

Meningococcal purpura fulminans in a patient with systemic lupus erythematosus: a mimic for catastrophic antiphospholipid antibody syndrome?

Purpura fulminans (PF) is a life-threatening disorder characterized by acute onset of progressive cutaneous hemorrhage, necrosis, and disseminated intravascular coagulation. Acute infectious PF occurs most commonly in the setting of meningococcal sepsis. When PF occurs in the setting of systemic lupus erythematosus (SLE), the catastrophic antiphospholipid antibody syndrome (CAPS) must be ruled out because urgent therapy is required. Plasmapheresis is effective in both cases, but immunosuppression (high-dose corticosteroids plus cyclophosphamide), although beneficial in patients with CAPS, could be harmful in patients with meningococcal PF. The authors report here a patient with SLE who presented to the intensive care unit with meningococcal PF, acute renal failure, and acute respiratory distress syndrome and discuss clinical similarities and laboratory differences from CAPS.     

Treatment of the antiphospholipid antibody syndrome: Progress in the last five years?

The gold standard for treatment of the antiphospholipid antibody syndrome (APS) after thrombosis remains highintensity warfarin, and, in pregnancy, heparin and aspirin. Exciting developments include the potential role of hydroxychloroquine as a prophylactic drug, stem cell transplantation, and B-cell tolerance. Animal models appear to be a fruitful “proving ground” of new therapies. The introduction of revised classification criteria for APS should aid in appropriate characterization of, and selection of, patients for clinical trials.     

A 50-year experience with autoimmune hepatitis: and where are we now?

BACKGROUND: Autoimmune hepatitis (AIH) as chronic active hepatitis became recognized in the 1940s as a progressive hyperglobulinemic disease affecting younger women attributed to persisting virus infection of the liver: autoimmunity then was barely on the horizon. EARLY OBSERVATIONS: The lupus erythematosus (LE) cell reported in 1948 signified the presence of antinuclear autoantibodies, promoting perceptions of autoimmunity in certain chronic diseases. Recognition of LE cells in chronic hepatitis led to the designation of 'lupoid hepatitis', with autoimmunity further substantiated by anti-cytoplasmic autoantibodies detected by complement fixation. Next a serum reactant with smooth muscle of rodent stomach was found to have a wider distribution and became identified as an autoantibody to filamentous (F) actin. Therapy with corticosteroids proved effective, particularly combined with azathioprine. Various trials showed greatly improved survival and established modern therapy of AIH. An HLA-based predisposition (B8, DR3) was the first pointer to a genetic etiology. RECENT ADVANCES: Recombinant or purified autoantigenic substrates have led to automated assays, which, together with improved immunofluorescence procedures, allow serological confidence in diagnosis and institution of effective immunosuppressive therapies. The liver-kidney 'microsomal' autoantigen reactive with cytochrome P450 2D6 distinguishes two serological types of AIH that appear pathogenetically distinct. Molecular characterization of antigens and epitopes remains wanting in type 1 AIH. FUTURE PROSPECTS: The challenge remains with both types of AIH to elucidate in molecular terms the genetic and environmental basis of pathogenesis from initiation to ultimate progression and cirrhosis (when inadequately treated). Advancing technologies are bringing this goal closer to being attainable.     

Biventricular pacing in patients with ICD: how many patients are possible candidates?

BACKGROUND: About 80 % of patients receiving an implantable cardioverter-defibrillator (ICD) due to life-threatening episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF) have structural heart disease. ICD implantation reduces the risk of sudden cardiac death to less than 2 %. However, the major obstacle in these patients is chronic heart failure (CHF). Biventricular stimulation (BIV) has shown its efficiency as an alternative therapy in drug refractory CHF. METHODS: According to the InSync registry, we predefined possible indications for BIV as follows: complete branch bundle block (> 120 ms), left-ventricular ejection fraction (EF) < 35 % and NYHA class > II. We evaluated the number of patients presenting this indication at time of implant and during follow-up (FU) at our ICD clinic. RESULTS: Between 1992 and 1998, 360 patients were provided with an ICD (mean age 64.6 +/- 5.4 yrs, mean EF 37 +/- 14 % at implant, 82 % of patients with organic heart disease). Mean FU was 34 +/- 21 months. During FU 46 patients (13 %) died, 15 of these (33 %) presenting criteria for BIV. 33 patients died of heart failure, there was 1 sudden death and 12 patients died for non-cardiac reasons. 35 % of the patients who died of heart failure had an indication for BIV. CONCLUSIONS: About 10 % of ICD patients had an indication for BIV at time of implant. Over a mean FU period of 34 months, 16% of all patients presented an indication for BIV. Patients with an indication for BIV had a higher mortality rate and more frequent atrial fibrillation compared to patients without. With this data and the good clinical results after BIV-ICD implantation, we consider the implantation of a BIV-ICD system in every patient with appropriate indications.