Juan M. Miranda

Acute Abdomen in Systemic Lupus Erythematosus: The Importance of Early Laparotomy

BACKGROUND Acute abdomen (AA) in systemic lupus erythematosus (SLE) is a challenging diagnostic and therapeutic problem. Most patients are on steroid and/or immunosuppressive treatment and mortality is high. METHODS We assessed the relationship between the causes of AA in SLE and the SLE disease activity index (SLEDAI). RESULTS Of 51 patients with SLE and AA, 36 had active disease (Group 1) and 15 inactive disease (Group 2). Group 1 included 19 patients with vasculitis (mean SLEDAI 15.4, range 13 to 24). Three patients with intraabdominal thrombosis and high titers of anticardiolipin antibodies (mean SLEDAI 18.3) and 14 patients with non-SLE-related AA (SLEDAI 8.2, range 5 to 11). Group 2 consisted of 15 inactive SLE patients (mean SLEDAI 1.7, range 0 to 4). Mortality was high in the active group (14 patients) compared with inactive SLE (2 cases). A delay in surgical exploration (39.3 vs 178.6 hours) had a negative influence on the prognosis. CONCLUSIONS In SLE patients with AA, a SLEDAI score below 5 is indicative of non-SLE-related AA. Elevated aCL were found in patients with intraabdominal thrombosis. AA in inactive SLE is non-SLE-related and has low mortality, provided an appropriate surgical treatment is given. Early laparotomy influences positively the prognosis of SLE patients with AA.

Prolactin in human systemic lupus erythematosus.

In the last decade, evidence has accumulated to support the hypothesis that both mild and moderate elevations of serum prolactin (PRL) participate in the clinical expression and pathogenesis of systemic lupus erythematosus (SLE). Hyperprolactinemia (HPRL) has been found in 20–30% of patients with SLE. HPRL seems to be associated with clinical activity of SLE during pregnancy. Although the relationship between HPRL and active SLE in non-pregnant patients is controversial, recent clinical and experimental studies support the potential role of prolactin (PRL) as a promoter of clinical activity and severity of SLE. Mild elevations of serum PRL secondary to microadenoma could trigger the onset of SLE in a subset of patients. Elevated PRL and interleukin (IL)-6 have been found in the urine of patients with active lupus nephritis and in cerebrospinal fluid (CSF) of patients with active central nervous system (CNS) SLE. PRL may therefore participate in the pathogenesis of lupus nephritis and cerebritis, and the presence of PRL may reflect an abnormal communication between the immune system and the neuroendocrine system in active SLE. Lymphocytes from patients with active SLE produce increased amounts of PRL, and this extrapituitary PRL may participate in aberrant immune processes in SLE. There is exciting new evidence that HPRL in SLE may be explained by stimulation of pituitary PRL secretion by cytokines. In addition, defects in peptidergic modulators and dopamine metabolism have been described in patients with SLE. The interactions between PRL, cytoquines, autoantibodies and organ involvement suggest that PRL participates in local and generalized immune and inflammatory processes and acts as a bridge between the neuroendocrine and immune systems in SLE. Understanding the interactions between these systems in SLE will help us to understand and treat this important autoimmune disease.

Renal biopsy in systemic lupus erythematosus: significance of glomerular thrombosis. Analysis of 108 cases.

We investigated the frequency and distribution of glomerular thrombosis (GT) in 108 renal biopsies of lupus patients and correlated this finding with the presence of anticardiolipin antibodies (ACLA). GT was present mainly in the diffuse proliferative form. The activity index was higher in those patients with GT (12.9 ± 4.7 vs 5.4 ± 4.1, P < 0.01). The more severe histologic features, necrosis and extracapillary proliferation were also related with GT. In 18 cases with repeated biopsy the best predictors for the subsequent development of glomerular sclerosis were fibrinoid necrosis (P < 0.01), glomerular infiltration (P < 0.01) and an activity index of 10 or more (P < 0.05). GT also showed to be an important prognostic factor for sclerosis, although no statistically significant. ACLA were investigated in 36 patients at the time of renal biopsy. There were nine positive cases and in three of them this finding was related to GT. We can conclude that GT is a relevant feature showing active lupus nephritis and that it is not related to the presence of ACLA.

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.

57 – Interaction between Rheumatoid Arthritis and Infections

Publisher Summary Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterized by a symmetric inflammation and destruction of joints. Despite of large efforts and technology, the etiology of RA remains elusive, although it appears that genetic, infectious, environmental, and hormonal factors are all involved in complex interrelated ways. One of the most exciting areas of investigation is the application of Polymerase Chain Reaction (PCR). This technique is useful to the detection of bacterial and viral DNA in patients with RA. With PCR technique, foreign antigens of bacteria, virus, and superantigens can be found in the synovial fluid. In addition, the lymphocytes from synovial fluid can develop a local immune response stimulated by microorganisms such as Proteus mirabilis and Epstein-Barr virus. These lymphocyte responses were higher with these microorganisms than with other stimuli. Those data suggest an immune-infectious cause for RA. However, the difficulty of separating pathogens from contaminants has hampered these studies. On the other hand, the presence of foreign antigens is not specific for RA. Therefore, the role of these organisms in initiating and perpetuating inflammation in RA remains unknown; however, it continues to be actively investigated. This chapter provides an update on the various mechanisms in which infectious agents may play a role as inciting or perpetuating factors in the pathogenesis of RA.

Influencia de la infección de vías urinarias no complicada en la frecuencia de exacerbaciones en pacientes con nefritis proliferativa difusa lúpica

Objetivo: Determinar si la infeccion de vias urinarias (IVU) es un indicador de retraso en el tratamiento inmunodepresor y de recaida renal en pacientes con nefritis lupica. Pacientes y metodos: Se analizo a pacientes con nefritis lupica proliferativa difusa que recibieron tratamiento con ciclofosfamida intravenosa durante, al menos, 6 meses. Al cabo de ese tiempo se realizo 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 infeccion). Se evaluaron bimestralmente la funcion renal y el numero de recaidas durante un ano de seguimiento. Para el analisis estadistico, se emplearon la prueba de la t de Student, la prueba de la x2, el test de Fisher (cuando se requiera) y el analisis bivariado. Resultados: Se incluyo 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 uropatogeno descrito con mas frecuencia fue Escherichia coli (73%). La presencia de IVU determino la interrupcion temporal del tratamiento en 19 casos (76%), mientras que en el grupo sin IVU esto ocurrio solo en 3 pacientes (12%), por otras causas, como leucopenia grave, hipersensibilidad y sintomas gastrointestinales graves (odds ratio = 23,22; intervalo de confianza del 95%, 5,26-105,1; p = 0,001). Durante el ano de seguimiento, en el grupo I, el 90,9% alcanzo la remision parcial en los primeros 3 meses de seguimiento y el 35% logro la remision completa despues de un ano; en el grupo II, los porcentajes de remision fueron del 85 y el 63%, respectivamente. En el grupo I se observo un incremento en la albuminuria (p < 0,05), persistencia de hipocomplementemia y titulos elevados de anticuerpos anti-ADN. En este grupo se encontraron 18 exacerbaciones y en el grupo control, 9. Conclusiones: En pacientes con nefritis lupica proliferativa difusa, la presencia de IVU no complicada se asocia a un retraso en el tratamiento inmunodepresor y a un incremento en las recaidas renales.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.