Azathioprine during pregnancy in systemic lupus erythematosus patients is not associated with poor fetal outcome.

The objective of this study was to evaluate the risk of adverse fetal outcome in systemic lupus erythematosus (SLE) women exposed to azathioprine during pregnancy. We reviewed the medical records of SLE pregnant women followed from January 2005 to April 2013. The patients were evaluated at least once in each trimester and postpartum. Relevant fetal outcomes were extracted, such as rate of liveborns, fetal loss (spontaneous abortion and stillbirth), term delivery, preterm birth, neonatal death, low birth weight, low birth weight at term, and congenital malformations. A detailed history of drug use during pregnancy was obtained. We studied 178 pregnancies (in 172 women), 87 of them were exposed to azathioprine (AZA-group) and the remaining 91 were not exposed (NO AZA-group). Exposure to other drugs was similar in both groups. The rate of live births, spontaneous abortions mean birth weight, weeks of gestation, rate of birth weight <2500 g, and low birth weight at term did not differ between groups. No infant had major congenital abnormalities. Multivariate analysis showed that preeclampsia, premature rupture of membranes (PROM), lupus flare, and anti-DNA positive were associated with an increased risk of poor fetal outcome. Our study suggests that the use of azathioprine is safe and lacks of teratogenity in patients with SLE and pregnancy. Exposure to azathioprine during pregnancy is not associated with poor fetal outcome.

Predictores de respuesta al tratamiento en pacientes con nefritis lúpica / Prognostic factors for treatment response in patients with lupus nephritis

Objetivo: Identificar los factores asociados con la respuesta al tratamiento en pacientes con nefropatía lúpica. Material y métodos: Se analizó una cohorte retrospectiva de pacientes con lupus eritematoso sistémico (LES) y nefritis lúpica (NL) corroborada por biopsia, clasificada de acuerdo a la Organización Mundial de la Salud (OMS) de junio del 2001 a diciembre del 2008. Todos los pacientes recibieron terapia de inducción a la remisión y fueron seguidos al menos 2 años. Se correlacionaron variables clínicas y de laboratorio con potencial valor predictivo de respuesta terapéutica, a los 6, 12 y 24 meses. Resultados: Se incluyó a 168 pacientes, 84% mujeres. La tasa de respuesta al tratamiento fue del 69,2% a los 6 meses, el 86,9% a los 12 meses y el 79,7% a los 2 años. En el análisis multivariado se encontró que la edad > 25 a˜nos en el momento del diagnóstico de la NL y la presencia de microhematuria fueron variables asociadas con buena respuesta al tratamiento de inducción a la remisión. A los 12 meses, una epuración de creatinina basal < 30 ml/min se asoció a mala respuesta al tratamiento. Finalmente, a los 24 meses, el retraso en el tratamiento fue un factor predictor de mala respuesta y la presencia de una forma histológica proliferativa de NL y de C3 bajo se asociaron con buena respuesta al tratamiento. Conclusiones: Existen factores modificables con el tratamiento que pueden alterar la actividad inmunológica aberrante de la NF. Por ello, la intervención terapéutica intensa en los primeros 3 meses de inicio de la nefritis puede llevar a una respuesta favorable a los 2 años (AU)

Objective: To identify prognostic factors associated with response to induction therapy in lupus nephritis (LN) according to the stage of treatment. Material and methods: We analyzed a retrospective cohort of patients of systemic lupus erythematosus (SLE) with biopsy-proven LN from January 2001 to December 2008. LN was classified according to WHO. All patients received induction therapy and had a minimum follow-up period of two years. We analyzed 18 clinical and laboratory variables that potentially have predictive value for response to therapy. We identified predictors of therapeutic response at 6, 12 and 24 months by univariate and multivariate analysis; odds ratios (OR) with confidence intervals (CI) 95% were also calculated. Results: We reviewed the clinical records of 168 patients, 141 female (84%). The response rate was 69% at 6 months, 86.9% at 12 months and 79.7% at 24 months. Multivariate analysis found that > 25 years of age at diagnosis of LN and the presence of microhematuria were factors associated with good response to induction treatment. At 12 months, baseline creatinine clearance < 30 ml/min was associated with a poor response to treatment. Finally at 24 months, delay in treatment was a predictor of poor response to treatment and the presence of a histological proliferative NL and low C3 were associated with good response to treatment. Conclusions: There are treatment-modifiable factors that can alter aberrant immunologic activity of NF. Therefore, intensive early treatment of lupus nephritis is associated with favorable response to two years (AU)

Prognostic factors for treatment response in patients with lupus nephritis.

OBJECTIVE: To identify prognostic factors associated with response to induction therapy in lupus nephritis (LN) according to the stage of treatment. MATERIAL AND METHODS: We analyzed a retrospective cohort of patients of systemic lupus erythematosus (SLE) with biopsy-proven LN from January 2001 to December 2008. LN was classified according to WHO. All patients received induction therapy and had a minimum follow-up period of two years. We analyzed 18 clinical and laboratory variables that potentially have predictive value for response to therapy. We identified predictors of therapeutic response at 6, 12 and 24 months by univariate and multivariate analysis; odds ratios (OR) with confidence intervals (CI) 95% were also calculated. RESULTS: We reviewed the clinical records of 168 patients, 141 female (84%). The response rate was 69% at 6 months, 86.9% at 12 months and 79.7% at 24 months. Multivariate analysis found that > 25 years of age at diagnosis of LN and the presence of microhematuria were factors associated with good response to induction treatment. At 12 months, baseline creatinine clearance < 30ml/min was associated with a poor response to treatment. Finally at 24 months, delay in treatment was a predictor of poor response to treatment and the presence of a histological proliferative NL and low C3 were associated with good response to treatment. CONCLUSIONS: There are treatment-modifiable factors that can alter aberrant immunologic activity of NF. Therefore, intensive early treatment of lupus nephritis is associated with favorable response to two years.

Clinical significance of antiphospholipid syndrome nephropathy (APSN) in patients with systemic lupus erythematosus (SLE) / Significado clínico de la nefropatía del síndrome antifosfolípido en pacientes con lupus eritematoso sistémico (LES)

La nefropatía del síndrome anti fosfolípido (NSAF) es actualmente una alteración patológica bien definida, caracterizada por la presencia de lesiones renales vaso-oclusivas, trombosis aguda arterial y arteriolar, y que ocasiona zonas de atrofia isquémica cortical. El objetivo del presente trabajo fue analizar la prevalencia y el significado clínico de la NSAF en pacientes con glomerulonefritis (GN) secundaria a Lupus Eritematoso Sistémico (LES). Se analizaron retrospectivamente las biopsias renales de 162 pacientes con GN secundaria a LES, buscando intencionadamente los datos histopatológicos de la NSAF. Se registraron los datos clínicos y serológicos al momento de la biopsia renal y durante el período de seguimiento promedio de 7 años. En los casos en que se obtuvo una biopsia renal subsecuente se analizó el desarrollo de la NASF. Resultados: Encontramos datos de NSAF en 17 pacientes (10.4%); 12 de ellos tenían lesiones proliferativas focales o difusas. Los índices histopatológicos de actividad y de cronicidad fueron más altos en los pacientes con la NSAF cuando se compararon con los pacientes sin NSAF. Los pacientes con nefropatía anti fosfolípido tuvieron con mayor frecuencia hipertensión arterial, creatinina sérica elevada, síndrome nefrótico, GN rápidamente progresiva y muerte, en comparación con los pacientes con GN lúpica sin NSAF. Se detectaron anticuerpos anticardiolipina en 52% de los pacientes con NSAF en quienes se realizó el examen al momento de la biopsia, en comparación con 27% de los pacientes sin NSAF. Se realizó biopsia renal subsecuente en 18 pacientes; quienes tuvieron NSAF en la primera biopsia tuvieron mayor incremento en la esclerosis glomerular en la segunda biopsia, al compararlo con quienes no tuvieron NSAF en la biopsia inicial. Conclusiones: La nefropatía del antifosfolípido es un factor de riesgo para hipertensión arterial, síndrome nefrótico y GN rápidamente progresiva en los pacientes con GN lúpica. La NSAF debiera considerarse en los criterios de clasificación del síndrome anti fosfolípido, y sería recomendable realizar estudios con tratamiento anticoagulante en estos pacientes (AU)

Antiphospholipid syndrome nephropathy (APSN) is now a well-recognized vaso-occlusive renal lesion associated with acute thrombosis and chronic arterial and arteriolar lesions, leading to zones of cortical ischemic atrophy. Our objective was to evaluate the prevalence and clinical significance of APSN in patients with Systemic Lupus Erythematosus (SLE). Methods Kidney biopsy specimens obtained from 162 patients with lupus glomerulonephritis were retrospectively examined for the presence of APSN. Clinical and laboratory data obtained at the time of kidney biopsy and during a mean follow-up of 7 years were recorded. In cases for which serial kidney biopsy specimens were available, the evolution of APSN was examined. Results We found APSN in 17 (10.4%) patients with lupus glomerulonephritis (GN), 12 with focal or proliferative lesions. Both activity and chronicity indexes were higher in patients with APSN when compared with lupus nephritis without APSN. Patients with APSN had a higher frequency of hypertension and elevated serum creatinine levels at the time or kidney biopsy, as well as a higher frequency of rapidly progressive GN, nephrotic syndrome and death at the end of the follow-up. Anticardiolipin antibodies were found in 52% of those with APSN and in 27% of those without APSN. Serial kidney biopsy specimens were available from 18 patients. An increase of glomerular sclerosis was found in the second biopsy particularly in those patients with APSN in the first biopsy. Conclusions APSN is a risk factor that contributes to an elevated prevalence of hypertension, elevated serum creatinine, nephrotic syndrome and increased glomerular sclerosis. APSN should be included in the classification criteria of APS, and the use of appropriate anticoagulant therapy should be tested (AU)

Clinical significance of antiphospholipid syndrome nephropathy (APSN) in patients with systemic lupus erythematosus (SLE).

UNLABELLED: Antiphospholipid syndrome nephropathy (APSN) is now a well recognized vaso-occlusive renal lesion associated with acute thrombosis and chronic arterial and arteriolar lesions, leading to zones of cortical ischemic atrophy. Our objective was to evaluate the prevalence and clinical significance of APSN in patients with Systemic Lupus Erythematosus (SLE). METHODS: Kidney biopsy specimens obtained from 162 patients with lupus glomerulonephritis were retrospectively examined for the presence of APSN. Clinical and laboratory data obtained at the time of kidney biopsy and during a mean follow-up of 7 years were recorded. In cases for which serial kidney biopsy specimens were available, the evolution of APSN was examined. RESULTS: We found APSN in 17 (10.4%) patients with lupus glomerulonephritis (GN), 12 with focal or proliferative lesions. Both activity and chronicity indexes were higher in patients with APSN when compared with lupus nephritis without APSN. Patients with APSN had a higher frequency of hypertension and elevated serum creatinine levels at the time or kidney biopsy, as well as a higher frequency of rapidly progressive GN, nephrotic syndrome and death at the end of the follow-up. Anticardiolipin antibodies were found in 52% of those with APSN and in 27% of those without APSN. Serial kidney biopsy specimens were available from 18 patients. An increase of glomerular sclerosis was found in the second biopsy particularly in those patients with APSN in the first biopsy. CONCLUSIONS: APSN is a risk factor that contributes to an elevated prevalence of hypertension, elevated serum creatinine, nephrotic syndrome and increased glomerular sclerosis. APSN should be included in the classification criteria of APS, and the use of appropriate anticoagulant therapy should be tested.

Bromocriptine during pregnancy in systemic lupus erythematosus: a pilot clinical trial.

Bromocriptine (BRC) prevents postpartum flare in lupus patients. However, its potential role in protecting lupus pregnancy from maternal-fetal complications has not been studied. The objective of the study was to explore the role of oral BRC during pregnancy in patients with systemic lupus erythematosus (SLE). Pregnant SLE patients were randomized into two groups: group 1 received BRC 2.5 mg/day and prednisone 10 mg/day; group 2 received prednisone 10 mg/day. These treatments were administered from 25 to 35 weeks of gestation. Prolactin (PRL) levels were determined at 25, 30, and 35 weeks. The SLE Pregnancy Disease Activity Index, maternal-fetal outcome including preterm birth, fetal loss, premature rupture of membrane (PRM), low birth weight, and preeclampsia/eclampsia were evaluated. We studied 20 patients (10 in each group). A significant decrease of PRL levels in group 1 compared to group 2 at week 30 and at week 35 was found. No patients in the BRC group had flares and three from group 2 had SLE activity. None of the patients in group 1 had PRM but three patients in group 2 did. Eighty percent of pregnancies ended in birth at term in group 1 and 50% in group 2. There was no fetal loss in both groups. Mean birth weight was higher in group 1 than in group 2 (P < NS). BRC was well tolerated. This is the first clinical trial of BRC in SLE pregnancy. Our pilot study suggests that BRC may play a role in the prevention of maternal-fetal complications, such as PRM, preterm birth, and active disease.

Prolactin levels are associated with lupus activity, lupus anticoagulant, and poor outcome in pregnancy.

High prolactin (PRL) levels seem to be associated with active systemic lupus erythematosus (SLE) during pregnancy. However, the association of activity, lupus anticoagulant (LA), and pregnancy outcome has not been analyzed. The objective of this study was to analyze the association among SLE activity, LA, and maternal-fetal outcome. We studied 15 pregnant SLE patients (ACR criteria), 4 of them with associated antiphospholipid syndrome (APS), and 9 healthy pregnant women. All patients were evaluated monthly with the following determinations: (a) SLE activity using modified-systemic lupus activity measurement (m-SLAM), (b) LA, and (c) PRL serum levels. Healthy controls were evaluated each trimester. Prematurity, fetal loss, low birth weight, and preeclampsia were evaluated. Chi-square test, Fisher's exact test, Student's t-test, Pearson correlation, and ANOVA were performed. The mean age of SLE patients was 30 +/- 4.9 years and 27.1 +/- 3.7 years in controls. High PRL levels were found during the second and third trimester in SLE patients in comparison with controls (186.2 +/- 54.02 ng/mL versus 119.6 +/- 31.1 ng/mL (P < 0.01) and 177.4 +/- 48.6 ng/mL versus 158.3 +/- 31.5 ng/mL. A significant linear correlation between PRL, m-SLAM, and LA in association with poor maternal-fetal outcome was observed. LA and PRL conferred risk for poor pregnancy outcome. Our study indicates for the first time a strong association among PRL, LA, SLE activity, and poor pregnancy outcome. Close rheumatologic and obstetric monitoring is mandatory in SLE pregnancy in order to avoid obstetric complications.

Influencia de la infección de vías urinarias no complicada en la frecuencia de exacerbaciones en pacientes con nefritis proliferativa difusa lúpica / Influence of non-complicated urinary tract infection on renal relapses in proliferative lupus nephritis

Objetivo: Determinar si la infección de vías urinarias (IVU) es un indicador de retraso en el tratamiento inmunodepresor y de recaída renal en pacientes con nefritis lúpica. Pacientes y metodos: Se analizó a pacientes con nefritis lúpica proliferativa difusa que recibieron tratamiento con ciclofosfamida intravenosa durante, al menos, 6 meses. Al cabo de ese tiempo se realizó un seguimiento prospectivo asignando a los pacientes a uno de 2 grupos: grupo I (pacientes que durante el seguimiento desarrollaron IVU), y grupo II (grupo control, pacientes sin infección). Se evaluaron bimestralmente la función renal y el número de recaídas durante un año de seguimiento. Para el análisis estadístico, se emplearon la prueba de la t de Student, la prueba de la 2 , el test de Fisher (cuando se requiera) y el análisis bivariado. Resultados: Se incluyó a 50 pacientes, 25 en cada grupo. Los casos del grupo I correspondieron a IVU no complicada. La edad promedio fue de 30,07 ± 8,15, y el 82% eran mujeres. El uropatógeno descrito con más frecuencia fue Escherichia coli (73%). La presencia de IVU determinó la interrupción temporal del tratamiento en 19 casos (76%), mientras que en el grupo sin IVU esto ocurrió sólo en 3 pacientes (12%), por otras causas, como leucopenia grave, hipersensibilidad y síntomas gastrointestinales graves (odds ratio = 23,22; intervalo de confianza del 95%, 5,26-105,1; p = 0,001). Durante el año de seguimiento, en el grupo I, el 90,9% alcanzó la remisión parcial en los primeros 3 meses de seguimiento y el 35% logró la remisión completa después de un año; en el grupo II, los porcentajes de remisión fueron del 85 y el 63%, respectivamente. En el grupo I se observó un incremento en la albuminuria (p < 0,05), persistencia de hipocomplementemia y títulos elevados de anticuerpos anti-ADN. En este grupo se encontraron 18 exacerbaciones y en el grupo control, 9. Conclusiones: En pacientes con nefritis lúpica proliferativa difusa, la presencia de IVU no complicada se asocia a un retraso en el tratamiento inmunodepresor y a un incremento en las recaídas renales (AU)

Objective: In patients with proliferative lupus nephritis treated with IV cyclophosphamide, analyze urinary tract infection (UTI) as a cause of treatment delay and renal relapses, compared with lupus nephritis patients without infection. Patients and methods: We studied SLE patients (ACR criteria) with renal biopsy showing nephritis class IV. All patients received monthly intravenous cyclophosphamide (CYC) treatment during 6 months. Thereafter patients were assigned to 2 groups: patients who developed UTI, and those who did not; renal function tests, UTI and renal relapses were bimonthly evaluated during one year (follow-up period). To analyze data, t student test, 2 , Fisher exact (when appropiate), and bivariate analysis, were performed. Results: We studied 50 patients, 25 with UTI (Group I) and 25 without UTI (G-II).The mean age was 30.07 ± 8.15 years, 82% were female. E. coli was the pathogen most frequently isolated (73%). UTI (G-I) was the cause for treatment delay in 19 cases (76%), compared with 3 patients (12%) in G-II whose treatment was delayed because of some other causes (severe leucopenya, hypersensibility and gastrointestinal side effects) (OR 23.22, 95% CI, 5.26-105.1; P=001). During the follow up, 90.9% of patients in G-I reached partial or complete renal remission within 3 months, but only 35% maintained remission after the year of follow up. Meanwhile, patients in G-II had complete and partial renal remission of 85% and 63%, respectively. In the first group we observed persistent albuminuria (P <05), low complement levels and highab-dsDNA titers. Renal flares were present in 18patients in G-I and 9 in G-II. Conclusions: UTI in lupus nephritis patients has a negative impact. It leads to delayed CYC therapy and to a higher renal flare rate (AU)

Influencia de la infección de vías urinarias no complicada en la frecuencia de exacerbaciones en pacientes con nefritis proliferativa difusa lúpica / Influence of non-complicated urinary tract infection on renal relapses in proliferative lupus nephritis

Objetivo: Determinar si la infección de vías urinarias (IVU) es un indicador de retraso en el tratamiento inmunodepresor y de recaída renal en pacientes con nefritis lúpica. Pacientes y métodos: Se analizó a pacientes con nefritis lúpica proliferativa difusa que recibieron tratamiento con ciclofosfamida intravenosa durante, al menos, 6 meses. Al cabo de ese tiempo se realizó un seguimiento prospective asignando a los pacientes a uno de 2 grupos: grupo I (pacientes que durante el seguimiento desarrollaron IVU), y grupo II (grupo control, pacientes sin infección). Se evaluaron bimestralmente la función renal y el número de recaídas durante un año de seguimiento. Para el análisis estadístico, se emplearon la prueba de la t de Student, la prueba de la χ2, el test de Fisher (cuando se requiera) y el análisis bivariado. Resultados: Se incluyó a 50 pacientes, 25 en cada grupo. Los casos del grupo I correspondieron a IVU no complicada. La edad promedio fue de 30,07±8,15, y el 82% eran mujeres. El uropatógeno descrito con más frecuencia fue Escherichia coli (73%). La presencia de IVU determinó la interrupción temporal del tratamiento en 19 casos (76%), mientras que en el grupo sin IVU esto ocurrió sólo en 3 pacientes (12%), por otras causas, como leucopenia grave, hipersensibilidad y síntomas gastrointestinales graves (odds ratio=23,22; intervalo de confianza del 95%, 5,26-105,1; p=0,001). Durante el año de seguimiento, en el grupo I, el 90,9% alcanzó la remisión parcial en los primeros 3 meses de seguimiento y el 35% logró la remisión completa después de un año; en el grupo II, los porcentajes de remisión fueron del 85 y el 63%, respectivamente. En el grupo I se observó un incremento en la albuminuria (p<0,05), persistencia de hipocomplementemia y títulos elevados de anticuerpos anti-ADN. En este grupo se encontraron 18 exacerbaciones y en el grupo control, 9. Conclusiones: En pacientes con nefritis lúpica proliferativa difusa, la presencia de IVU no complicada se asocia a un retraso en el tratamiento inmunodepresor y a un incremento en las recaídas renales (AU)

Objective: In patients with proliferative lupus nephritis treated with IV cyclophosphamide, analyze urinary tract infection (UTI) as a cause of treatment delay and renal relapses, compared with lupus nephritis patients without infection. Patients and methods: We studied SLE patients (ACR criteria) with renal biopsy showing nephritis class IV. All patients received monthly intravenous cyclophosphamide (CYC) treatment during 6 months. Thereafter patients were assigned to 2 groups: patients who developed UTI, and those who did not; renal function tests, UTI and renal relapses were bimonthly evaluated during one year (follow-up period). To analyze data, t student test, χ2, Fisher exact (when appropiate), and bivariate analysis, were performed. Results: We studied 50 patients, 25 with UTI (Group I) and 25 without UTI (G-II).The mean age was 30.07 ± 8.15 years, 82% were female. E. coli was the pathogen most frequently isolated (73%). UTI (G-I) was the cause for treatment delay in 19 cases (76%), compared with 3 patients (12%) in G-II whose treatment was delayed because of some other causes (severe leucopenya, hypersensibility and gastrointestinal side effects) (OR 23.22, 95% CI, 5.26-105.1; P=001). During the follow up, 90.9% of patients in G-I reached partial or complete renal remission within 3 months, but only 35% mantained remission after the year of follow up. Meanwhile, patients in G-II had complet and partial renal remission of 85% and 63%, respectively. In the first group we observed persistent albuminuria (P<05), low complement levels and high ab-dsDNA titers. Renal flares were present in 18 patients in G-I and 9 in G-II. Conclusiones: UTI in lupus nephritis patients has a negative impact. It leads to delayed CYC therapy and to a higher renal flare rate (AU)

[Influence of non-complicated urinary tract infection on renal relapses in proliferative lupus nephritis]. / Influencia de la infección de vías urinarias no complicada en la frecuencia de exacerbaciones en pacientes con nefritis proliferativa difusa lúpica.

OBJECTIVE: In patients with proliferative lupus nephritis treated with IV cyclophosphamide, analyze urinary tract infection (UTI) as a cause of treatment delay and renal relapses, compared with lupus nephritis patients without infection. PATIENTS AND METHODS: We studied SLE patients (ACR criteria) with renal biopsy showing nephritis class IV. All patients received monthly intravenous cyclophosphamide (CYC) treatment during 6 months. Thereafter patients were assigned to 2 groups: patients who developed UTI, and those who did not; renal function tests, UTI and renal relapses were bimonthly evaluated during one year (follow-up period). To analyze data, t student test, χ(2), Fisher exact (when appropiate), and bivariate analysis, were performed. RESULTS: We studied 50 patients, 25 with UTI (Group I) and 25 without UTI (G-II).The mean age was 30.07 ± 8.15 years, 82% were female. E. coli was the pathogen most frequently isolated (73%). UTI (G-I) was the cause for treatment delay in 19 cases (76%), compared with 3 patients (12%) in G-II whose treatment was delayed because of some other causes (severe leucopenya, hypersensibility and gastrointestinal side effects) (OR 23.22, 95% CI, 5.26-105.1; P=001). During the follow up, 90.9% of patients in G-I reached partial or complete renal remission within 3 months, but only 35% mantained remission after the year of follow up. Meanwhile, patients in G-II had complet and partial renal remission of 85% and 63%, respectively. In the first group we observed persistent albuminuria (P<05), low complement levels and high ab-dsDNA titers. Renal flares were present in 18 patients in G-I and 9 in G-II. CONCLUSIONS: UTI in lupus nephritis patients has a negative impact. It leads to delayed CYC therapy and to a higher renal flare rate.

Mono-organic versus multi-organic involvement in primary antiphospholipid syndrome.

The prevalence of mono-organic and multi-organic involvement during long-term follow-up in patients with primary antiphospholipid syndrome (pAPS) was investigated. We studied 60 pAPS patients followed up at least 5 years. Patients with associated systemic lupus erythematosus were excluded. All patients received oral anticoagulant therapy. A diagnosis of mono-organic involvement was considered when one organ was affected exclusively, and multi-organic involvement was considered when two or more organs became affected during follow-up. Average age at diagnosis was 32.9 +/- 12.4 years, 40 subjects were female and 20 male, and mean disease evolution totaled 11.5 +/- 4.5 years. The mean number of clinical events was 3.75 +/- 1.87. Among patients, immunoglobulin G anticardiolipin (IgM aCL) titers totaled 50 +/- 40.3 IgG phospholipid units, and IgM aCL titers totaled 47.3 +/- 35.4 IgM phospholipid units. The most frequent clinical manifestations at study onset were deep venous thrombosis, stroke, pulmonary thromboembolism, fetal loss, and pre-eclampsia. At the beginning of follow-up, 46 patients had mono-organic involvement and 14 had multi-organic involvement (P = 0.0001). In contrast, at the end of the study, only 8 patients still had mono-organic involvement, leading to deep venous thrombosis (n = 3), stroke (n = 3), and retinal thrombosis (n = 2) (P = 0.0001). Kaplan-Meier analysis showed that the probability of remaining with mono-organic involvement decreased throughout the cumulative years, especially during the first 3. The hazard risk ratio for developing multi-organic involvement was 1.47 patients per year. In conclusion, PAPS is a chronic disorder with unpredictable clinical course and multi-organic involvement, especially during the first years. The conversion to multi-organic involvement supports the concept that pAPS is a systemic autoimmune disease.