First described in the early 1980s, antiphospholipid syndrome (APS) is a unique form of acquired autoimmune thrombophilia in which patients present with clinical features of recurrent thrombosis and ...pregnancy morbidity and persistently test positive for the presence of antiphospholipid antibodies (aPL). At least one clinical (vascular thrombosis or pregnancy morbidity) and one lab-based (positive test result for lupus anticoagulant, anticardiolipin antibodies and/or anti-β2-glycoprotein 1 antibodies) criterion have to be met for a patient to be classified as having APS. However, the clinical spectrum of APS encompasses additional manifestations that can affect many organs and cannot be explained exclusively by patients being in a prothrombotic state; clinical manifestations not listed in the classification criteria (known as extra-criteria manifestations) include neurologic manifestations (chorea, myelitis and migraine), haematologic manifestations (thrombocytopenia and haemolytic anaemia), livedo reticularis, nephropathy and valvular heart disease. Increasingly, research interest has focused on the development of novel assays that might be more specific for APS than the current aPL tests. This Review focuses on the current classification criteria for APS, presenting the role of extra-criteria manifestations and lab-based tests. Diagnostic approaches to difficult cases, including so-called seronegative APS, are also discussed.
Abstract The purpose of this task force was to critically analyze nine non-criteria manifestations of APS to support their inclusion as APS classification criteria. The Task Force Members selected ...the non-criteria clinical manifestations according to their clinical relevance, that is, the patient-important outcome from clinician perspective. They included superficial vein thrombosis, thrombocytopenia, renal microangiopathy, heart valve disease, livedo reticularis, migraine, chorea, seizures and myelitis, which were reviewed by this International Task Force collaboration, in addition to the seronegative APS (SN-APS). GRADE system was used to evaluate the quality of evidence of medical literature of each selected item. This critical appraisal exercise aimed to support the debate regarding the clinical picture of APS. We found that the overall GRADE analysis was very low for migraine and seizures, low for superficial venous thrombosis, thrombocytopenia, chorea, longitudinal myelitis and the so-called seronegative APS and moderate for APS nephropathy, heart valve lesions and livedo reticularis. The next step can be a critical redefinition of an APS gold standard, for instance derived from the APS ACTION registry that will include not only current APS patients but also those with antiphospholipid antibodies not meeting current classification criteria.
To describe the real-world experience of eculizumab use in patients with catastrophic antiphospholipid syndrome (CAPS) according to the information provided by the “CAPS Registry”.
We analyzed the ...demographic, clinical and immunological data from all the patients included in the “CAPS Registry” treated with eculizumab and described the indications for eculizumab administration, dose, outcome, use of prophylactic vaccines and adverse effects.
The “CAPS Registry” currently includes 584 patients from whom 39 (6.7%) were treated with eculizumab (it was used as a rescue therapy in 30 cases while in 6 cases it was used as first line therapy). Mean age of eculizumab treated patients was 39 years (SD = 14.6), 72% were female, 77% had a primary APS and 79% had a precipitating factor before the CAPS event. Thrombocytopenia was present in 28 (72%) cases and features of microangiopathic hemolytic anemia were present in 15 (38.5%). Twenty-nine (74.4%) patients recovered from the episode of CAPS (four showed only partial remission). Symptoms worsened in 9 patients, from whom 5 finally died despite the treatment. There was only one relapse after a median follow up of 10.7 months. The most common treatment regimen was 900 mg weekly for four weeks and 1200 mg fortnightly.
According to the real-world experience provided by the “CAPS Registry”, eculizumab can be considered in some patients with CAPS refractory to previous therapies, especially if they present with features of complement-mediated thrombotic microangiopathy.
•Complement pathway has been identified as a critical mechanism in the development of CAPS.•Eculizumab is a humanized monoclonal antibody that binds to the C5 complementprotein.•74.4% of CAPS patients treated with eculizumab recovered without recurrence of thrombosis.•We suggest considering eculizumab in CAPS patients who present with complement mediated thrombotic microangiopathy.
Background
Consequences of organ damage in primary antiphospholipid syndrome (PAPS) are diverse, our aim was to determine organ damage over time and the correlation of organ damage accrual with ...health-related quality of life (HRQoL) in PAPS.
Methods
First phase: retrospective cohort applying Damage Index for Antiphospholipid Syndrome (DIAPS) at 1, 5, 10, 20 years, or longer since diagnosis. Second phase: cross-sectional study, assessing HRQoL by the Medical Outcomes Study Short Form 36 (SF-36), and organ damage accrual. Descriptive statistics and Spearman correlation coefficient were used.
Results
Sixty-seven patients were included, mean follow-up:15 years. Deep vein thrombosis prevailed (71.6%), pulmonary embolism (35.8%) and stroke (32.8%). Organ damage was found in 98.5%, with a cumulative DIAPS value of 3, with greater involvement in the neuropsychiatric and peripheral vascular domains. Regarding HRQoL, deterioration in the physical component summary (PCS) was found in 89.6%. Organ damage accrual correlated inversely and significantly with all the SF-36 domains, mainly with the total score and PCS. Body pain and PCS correlated the most (rho = −0.503, rho = −0.475).
Conclusions
Organ damage accrual impaired HRQoL in PAPS. Secondary thromboprophylxis through adequate systemic management and control of cardiovascular risk factors are necessary to prevent further impairment.
To determine the association between the number of flares systemic lupus erythematosus (SLE) patients experience and damage accrual, independently of other known risk factors.
SLE patients (34 ...centres, nine Latin American countries) with a recent diagnosis (≤2 years) and ≥3 evaluations were studied. Disease activity was ascertained with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and damage with the SLICC/ACR Damage Index (SDI). Flare was defined as an increase ≥4 points in the SLEDAI between two study visits. An ambidirectional case- crossover design was used to determine the association between the number of flares and damage accrual.
901 patients were eligible for the study; 500 of them (55.5%) experienced at least one flare, being the mean number of flares 0.9 (SD: 1.0). 574 intervals from 251 patients were included in the case-crossover design since they have case and control intervals, whereas, the remaining patients did not. Their mean age at diagnosis was 27.9 years (SD: 11.1), 213 (84.9%) were women. The mean baseline SDI and SLEDAI were 1.3 (1.3) and 13.6 (8.1), respectively. Other features were comparable to those of the entire sample. After adjusting for possible confounding variables, the number of flares, regardless of their severity, was associated with damage accrual (SDI) OR 2.05, 95% CI 1.43 to 2.94, p<0.001 (OR 2.62, 95% CI 1.31 to 5.24, p=0.006 for severe and OR 1.91, 95% CI 1.28 to 2.83, p=0.001 for mild-moderate).
The number of flares patients experience, regardless of their severity, increases the risk of damage accrual, independently of other known risk factors.
Background
Systemic lupus erythematosus (SLE) often mimics symptoms of other diseases, and the interval between symptom onset and diagnosis may be long in some of these patients. Aims: To describe ...the characteristics associated with the time to SLE diagnosis and its impact on damage accrual and mortality in patients with SLE from a Latin American inception cohort.
Methods
Patients were from a multi-ethnic, multi-national Latin-American SLE inception cohort. All participating centers had specialized lupus clinics. Socio-demographic, clinical/laboratory, disease activity, damage, and mortality between those with a longer and a shorter time to diagnosis were compared using descriptive statistical tests. Multivariable Cox regression models with damage accrual and mortality as the end points were performed, adjusting for age at SLE diagnosis, gender, ethnicity, level of education, and highest dose of prednisone for damage accrual, plus highest dose of prednisone, baseline SLEDAI, and baseline SDI for mortality.
Results
Of the 1437 included in these analyses, the median time to diagnosis was 6.0 months (Q1–Q3 2.4–16.2); in 721 (50.2%) the time to diagnosis was longer than 6 months. Patients whose diagnosis took longer than 6 months were more frequently female, older at diagnosis, of Mestizo ethnicity, not having medical insurance, and having “non-classic” SLE symptoms. Longer time to diagnosis had no impact on either damage accrual (HR 1.09, 95% CI 0.93–1.28, p = 0.300) or mortality (HR 1.37, 95% CI 0.88–2.12, p = 0.200).
Conclusions
In this inception cohort, a maximum time of 24 months with a median of 6 months to SLE diagnosis had no apparent negative impact on disease outcomes (damage accrual and mortality).
Objective
To determine the predictors of the occurrence of severe autoimmune hemolytic anemia (AIHA) and its impact on damage accrual and mortality in SLE patients.
Methods
Factors associated with ...time to severe AIHA (hemoglobin level ≤7 g/dL) occurring from the onset of SLE symptoms were examined by Cox proportional hazards regressions. The association of severe AIHA with mortality was examined by logistic regression analyses while its impact on damage was by negative binomial regression.
Results
Of 1,349 patients, 49 (3.6%) developed severe AIHA over a mean (SD) follow-up time of 5.4 (3.8) years. The median time from the first clinical manifestation to severe AIHA was 111 days (IQR 43–450). By multivariable analysis, male sex (HR 2.26, 95% CI 1.02–4.75, p = 0.044), and higher disease activity at diagnosis (HR 1.04, 95% CI 1.01–1.08, p = 0.025) were associated with a shorter time to severe AIHA occurrence. Of the SLEDAI descriptors, only hematologic (leukopenia and/or thrombocytopenia) showed a certain trend toward significance in the multivariable analysis (HR 2.36, 95% CI 0.91–6.13, p = 0.0772). Severe AIHA contributed neither to damage nor to mortality.
Conclusions
Severe AIHA occurs during the early course of SLE. Male sex and higher disease activity at diagnosis emerged as independent predictors of a shorter time to severe AIHA occurrence. Although not statistically significant, hematological abnormalities at SLE diagnosis could predict the occurrence of severe AIHA in a shorter time. Damage and mortality did not seem to be impacted by the occurrence of severe AIHA.
Objective
To analyze the results of cardiac valve replacement in a multicenter cohort of patients with antiphospholipid syndrome (APS) and to identify prognostic factors of poor outcome.
Methods
We ...performed a retrospective analysis of clinical manifestations (cardiac involvement and APS characteristics), operative and early postoperative courses, and long‐term followup. All of the patients fulfilled the Sapporo criteria for APS. Logistic regression analyses were performed to identify those variables associated with adverse outcomes.
Results
Between 1981 and 2008, 33 valvular replacements were carried out in 32 patients with APS. The mean ± SD age at the time of surgery was 43.09 ± 14.08 years. Thirty patients were women. Primary APS was present in 21 patients. The median followup time after surgery was 33.5 months (range 0–192 months). The mitral valve was the most frequently replaced (22 of 33). Mechanical valve replacement was performed in 23 patients (71.9%). The mortality rate was 12.5% (1 cardiogenic shock, 1 septic shock, 1 following renal transplantation, and 1 hemorrhagic stroke). Fourteen patients experienced 20 complications (8 major bleeding, 5 thrombotic events, 2 valvular deteriorations, 2 third‐degree atrioventricular block, 1 endocarditis, 1 cardiac tamponade, and 1 cardiac failure). Fifty percent of the patients had an uneventful outcome.
Conclusion
Morbidity and mortality were high in APS patients undergoing valve replacement surgery. Most complications were related to thrombosis and bleeding. Anticoagulation must be carefully monitored to prevent hemorrhagic and thrombotic complications.
Frida Kahlo's medical history shows sequelae of polio, a severe traumatic event that caused multiple fractures and a penetrating pelvic injury, as well as a history of countless surgeries. In her ...biographical accounts and her works, chronic disabling pain always appears for long periods. Besides, a chronic foot ulcer, gangrene that required amputation of the right leg, a history of abortions, and a positive Wasserman reaction suggest that the artist could have suffered from antiphospholipid antibody syndrome (APS).
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