Catastrophic antiphospholipid syndrome (CAPS): descriptive analysis of a series of 280 patients from the "CAPS Registry".

OBJECTIVE: To describe the clinical and laboratory features, as well as the precipitating factors, treatment and outcome of patients with catastrophic antiphospholipid syndrome (APS). METHODS: We analyzed the 280 patients included until September 2008 in the website based international registry of patients with catastrophic APS ("CAPS Registry") (http://www.med.ub.es/MIMMUN/FORUM/CAPS.HTM). RESULTS: The entire series includes 201 (72%) female and 79 (28%) male patients with a mean age of 37 +/- 14 years (range, 11-60 years). A total of 129 (46%) patients suffered from primary APS, 112 (40%) from systemic lupus erythematosus, 14 (5%) from lupus-like disease, and 25 (9%) from other autoimmune diseases. The catastrophic episode was the first manifestation of the APS in 129 (46%) patients. A precipitating factor was reported in 53% of the patients. The first clinical manifestation at the time of the catastrophic episode was a pulmonary complication in 24% of the cases, a neurologic feature in 18% and a renal feature in 18%. During the catastrophic episode, intraabdominal involvement was identified in the majority of patients, mainly consisting of renal (71%), hepatic (33%), gastrointestinal (25%), splenic (19%), adrenal (13%), and pancreatic (8%) manifestations. 123 (44%) patients died at the time of the catastrophic APS event but the higher recovery rate was achieved by the combination of anticoagulants plus corticosteroids plus plasma exchange (PE) and/or intravenous immunoglobulins (IVIG) (69% versus 54%). CONCLUSIONS: The catastrophic APS is an uncommon but potentially life-threatening condition that needs high clinical awareness. The therapeutical connotation is that this may be corrected with the combination of anticoagulation plus steroids plus attempts at achieving a prompt reduction of antiphospholipid antibody titer (i.e. PE and/or IVIG).

Factor XIII-A subunit Val34Leu polymorphism is associated with the risk of thrombosis in patients with antiphospholipid antibodies and high fibrinogen levels.

Recent reports have described the factor XIII A subunit (FXIII-A) Val34Leu polymorphism as a protective factor against venous and arterial thrombosis. The aim of this study was to investigate the association between the FXIII-A Val34Leu polymorphism, its interaction with fibrinogen concentration, and thrombosis in patients with antiphospholipid antibodies (aPL). We included 172 consecutive patients with aPL: 88 with primary antiphospholipid syndrome (APS), 38 with APS associated with systemic lupus erythematosus (APS-SLE), 32 with SLE and aPL but without APS (SLE-aPL), and 14 asymptomatic individuals with aPL (A-aPL). The FXIII-A Val34Leu polymorphism was assessed by polymerase chain reaction techniques. We found no significant differences in FXIII-A Leu34 allele frequencies between primary APS (allele frequency 0.22), APS-SLE (0.23), SLE-aPL (0.22) and A-aPL (0.32) patients, or between patients with (0.21) and without thrombosis (0.26). FXIII-A Leu34 allele frequencies were significantly lower in patients with thrombosis and those in the upper fibrinogen tertile (>3.40 g/l) (allele frequency 0.07) compared with patients without thrombosis in the upper fibrinogen tertile (0.29) and patients with (0.29) and without (0.25) thrombosis in the mid- and lower fibrinogen tertiles. The FXIII-A Leu34 allele had a protective effect against thrombosis in patients in the upper fibrinogen tertile (odds ratio [OR] = 0.20, 95% confidence interval [CI] 0.07-0.60) but not in those in the other tertiles (OR = 1.20, 95% CI 0.67-2.16). The FXIII-A Leu34 allele seems to have a protective effect on the development of thrombosis in patients with aPL, but only in those with high plasma fibrinogen values.

Los valores persistentemente positivos de anticuerpos antifosfolipídicos están relacionados con la aparición de trombosis durante el seguimiento de pacientes con síndrome antifosfolipídico / Persistenly positive antiphospholipid antibodies are related with the appearance of thrombosis during follow-up with antiphospholipid syndrome

Objetivo: determinar si la presencia de valores persistentemente positivos de anticuerpos antifosfolipídicos (AAF) está relacionada con trombosis recurrente en el seguimiento de pacientes con síndrome antifosfolipídico (SAF). Métodos: se analizaron 141 pacientes con SAF (criterios de Sapporo). Los valores de anticoagulante lúpico (AL) y anticuerpos anticardiolipina (AAC) fueron definidos como persistentemente positivos cuando más del 75% de las determinaciones fueron positivas durante el seguimiento (los AAF fueron medidos en cinco o más ocasiones). La trombosis en el seguimiento fue definida como una trombosis recurrente en pacientes con episodios trombóticos previos o nuevos episodios en aquellos pacientes con pérdidas fetales previas. Resultados: ochenta y nueve pacientes presentaban SAF primario, 34 asociado a lupus eritema-toso sistémico (LES), 14 con síndrome similar al lupus, 3 con síndrome de Sjogren y 1 con enfermedad de Beh

Objective: to determine if the presence of persistently positive valúes of antiphospholipid (aPL) antibodies is related with recurrent thrombosis in the follow-up of patíent with antiphospholipid syndrome (APS). Patients and Methods: 141 patients with APS (Sapporo's criteria) were analyzed. Lupus antico-agulant (LAC) valúes and anticardiolipin antibodies (aCL) were defined as persistently positive when more than 75% of determinations were positive during the follow-up (aPL were measured on 5 or more occasions). Thrombosis in the follow-up was defined as a recurrent thrombosis in patient with previous thrombotic events or new events in those patients with previous fetal losses. Results: 89 patients suffered from primary APS, 34 associated to systemic lupus erythematosus (SLE), 14 to SLE-like, 3 to Sjogren's syndrome, and 1 to Behcet's disease. 56% liad a history of thrombosis, 29% of fetal losses, and 15% both thrombosis and fetal losses. Median time of follow-up and between the diagnosis and the last aPL determination was 68 months and 65 months (9-180), respectively. Median of determinations by patient was 8 (5-27). 31 patients suffered from thrombosis in the follow-up, 28 of them in form of recurrent thrombosis. 58 (41%) patients liad persistently positive aPL during follow-up, thus: 23 (39,65%) aCL IgG y LAC, 12 (20,7%) LAC, 8 (13,8%) aCL IgG, 5 (8,6%) aCL IgM, aCL IgG y LAC, 4 (6,9%) aCL IgM, 3 (5,1%) aCL IgG y aCL IgM y 3 (5,1%) aCL IgM y LAC, respectively. Risk for recurrent thrombosis during follow-up was increased in persistently positive aPL patients (OR 3,53; 95% CI 1,53-8,16; p=0,003) compared with transiently positive aPL patients. This higher risk was attributable to persistently positive LA (OR 3,87; 95% CI 1,68-8,91; p=0,002) and persistently positive aCL IgG (OR 2,91; 95% CI 1,25-6,75; p=0,02). The profile of persistently positive aPL related with the appearance of thrombosis during follow-up was the combination of IgG aCL & LA (OR 3,51; 95% CI 1,36-9,09; p=0,01). Conclusions: the risk of thrombosis during follow-up is increased in patients with persistently positive aPL, specially in those with the combination of IgG aCL & LA.

High prevalence of serum metabolic alterations in primary Sjögren's syndrome: influence on clinical and immunological expression.

OBJECTIVE: To analyze the prevalence and clinical significance of associated metabolic alterations [dyslipidemia, diabetes mellitus (DM), and hyperuricemia] in a large series of unselected patients with primary Sjögren's syndrome (SS). METHODS: We analyzed 254 consecutive patients with primary SS who had a complete analytical followup study for at least 5 consecutive years. The control group consisted of 254 age and sex-matched patients without systemic autoimmune diseases consecutively followed during the same period in a primary care center. RESULTS: In comparison with controls, patients with primary SS showed a higher frequency of dyslipidemia (47% vs 33%; p = 0.002), DM (28% vs 18%; p = 0.006), and hyperuricemia (9% vs 4%; p = 0.007). The mean age at SS diagnosis was 10 years greater in patients with DM (p < 0.001) and hyperuricemia (p = 0.009). Hypercholesterolemia was associated with a lower frequency of immunological markers such as anti-Ro/SSA antibodies (p = 0.001), anti-La/SSB antibodies (p = 0.005), low C3 (p = 0.047), and low C4 levels (p = 0.030), while hypertriglyceridemia and DM were associated with a higher prevalence of extraglandular features, especially renal, liver, and vasculitic involvement. A higher prevalence of DM was found in patients treated with corticosteroids (40% vs 19%; p = 0.001). CONCLUSION: Patients with primary SS showed a higher prevalence of associated dyslipidemia, DM, and hyperuricemia in comparison with an age and sex-matched control group. Metabolic alterations were associated with a differentiated pattern of clinical and immunological SS expression, but not with SS-related therapies (except for the higher frequency of DM observed in patients treated with corticosteroids).

Intestinal involvement secondary to the antiphospholipid syndrome (APS): clinical and immunologic characteristics of 97 patients: comparison of classic and catastrophic APS.

OBJECTIVE: To analyze the clinical and laboratory characteristics of 97 patients with intestinal involvement secondary to the antiphospholipid syndrome (APS) (37 patients with classic APS and 60 with catastrophic APS). METHODS: A computer-assisted (PubMed) search of the literature was performed to identify all cases of intestinal involvement associated with the APS from 1983 to December 2005. In addition, we analyzed the web-site-based international registry of patients with catastrophic APS ("CAPS Registry"). RESULTS: There were no differences in distribution by gender, mean age, and previous clinical manifestations of APS between the 2 groups. The prevalence of abdominal pain as the presenting manifestation of intestinal ischemia was higher in patients with classic APS (76% versus 37%; P < 0.005). The main difference in histopathologic findings between the 2 groups was the higher rate of microthrombosis in patients with catastrophic APS (75% versus 4%; P < 0.0005). The mortality rate was higher in patients with catastrophic APS (55% versus 17%; P < 0.0005). Follow-up was available in 22 patients with classical APS: 17 of them were discharged on oral anticoagulation and with a mean follow-up of 13 months (range, 1 to 48); all were in good health without the development of new thrombotic events. CONCLUSIONS: Intestinal involvement, although infrequent, is an important complication in patients with APS, especially in those with catastrophic APS. This would support the need for systematic screening for aPL in all cases of mesenteric thrombosis or ischemic colitis without clear underlying predisposing factors, and for systematic screening procedures in all classic APS patients complaining of abdominal pain.

Life-threatening cryoglobulinemia: clinical and immunological characterization of 29 cases.

OBJECTIVES: To analyze the etiology, clinical presentation, and outcomes of patients with life-threatening cryoglobulinemic vasculitis. METHODS: We studied 209 consecutive patients with cryoglobulinemic vasculitis. A potentially life-threatening cryoglobulinemia was considered as the development of renal failure, vasculitic abdominal involvement, pulmonary hemorrhage, or central nervous system involvement. RESULTS: Twenty-nine (14%) patients had life-threatening cryoglobulinemic vasculitis. There were 17 women and 12 men, with a mean age of 57 years. In 17 (59%) patients, life-threatening cryoglobulinemia was the initial clinical feature of the disease. The 29 patients had a total of 33 life-threatening episodes, which included renal failure due to cryoglobulinemic glomerulonephritis (n = 18), intestinal vasculitis (n = 8), pulmonary hemorrhage (n = 4), and central nervous system involvement (n = 3). In comparison with a control group of age-sex-matched patients with milder cryoglobulinemic vasculitis, those with severe cryoglobulinemic vasculitis had a higher frequency of fever (28% versus 7%, P = 0.017), type II cryoglobulins (100% versus 59%, P = 0.008), low C3 levels (55% versus 20%, P = 0.001), and a higher mean value of cryocrit (11.4% versus 3.3%, P = 0.004). Nineteen (66%) of the 29 patients with life-threatening involvement died, with the mortality rate reaching 100% in patients with intestinal ischemia and pulmonary hemorrhage. CONCLUSION: Life-threatening cryoglobulinemic vasculitis was observed in 14% of our patients, with almost two-thirds of episodes occurring at the onset of the disease. Fever, high cryocrit levels, and low C3 levels were associated with this severe presentation. Two-thirds of the patients died, with mortality for pulmonary hemorrhage and intestinal ischemia reaching 100%.

Characterization and differentiation of autoimmune versus viral liver involvement in patients with Sjögren's syndrome.

OBJECTIVE: To analyze the prevalence and clinical significance of liver involvement in patients with Sjögren's syndrome (SS), focusing on the characterization and differentiation of autoimmune versus chronic viral liver disease. METHODS: We investigated liver involvement (clinical signs, analytical data, chronic viral infections, and autoantibodies) in 475 consecutive patients with SS. All patients fulfilled 4 or more of the 1993 European Community Study Group criteria for SS. RESULTS: Liver involvement was detected in 129 (27%) patients. After ruling out chronic illnesses or use of hepatotoxic drugs, the main etiologies were chronic viral liver disease in 64 (13%) cases [chronic hepatitis C virus (HCV) infection in 63 and HBV infection in one] and autoimmune liver diseases in 24 (5%; primary biliary cirrhosis in 16 patients and type-1 autoimmune hepatitis in 8). The analytical liver profile was not useful in differentiating between viral and autoimmune liver disease. In contrast, patients with SS and autoimmune liver disease presented higher mean values of erythrocyte sedimentation rate (p = 0.044), circulating gammaglobulins (p = 0.007), and a higher prevalence of antinuclear antibodies (p < 0.001), antimitochondrial antibodies (p < 0.001), anti-smooth muscle antibodies (p = 0.026), anti-Ro/SSA (p < 0.001), and anti-La/SSB (p = 0.01), while patients with chronic viral liver disease had a higher frequency of cryoglobulinemia (p < 0.001) and hypocomplementemia (p < 0.001). CONCLUSION: Chronic viral liver disease (associated overwhelmingly with HCV) was the main cause of liver involvement in our patients with SS, with a prevalence of 13%, nearly 3-fold greater than that observed for autoimmune liver involvement. The immunological pattern played a key role in the differentiation of viral (predominance of cryoglobulins and low complement levels) and autoimmune (higher frequency of autoantibodies) liver involvement.