Luis J. Catoggio

The GLADEL multinational Latin American prospective inception cohort of 1,214 patients with systemic lupus erythematosus: ethnic and disease heterogeneity among "Hispanics".

Clinical and laboratory manifestations and outcome of systemic lupus erythematosus (SLE) may vary in different populations. A prospective multinational inception cohort should prove useful in identifying the influence of ethnicity on the clinical characteristics of SLE. We therefore analyzed clinical, laboratory, and prognostic variables in Latin American SLE patients with disease of recent onset who were entered into a prospective cohort, and compared these variables in the cohort’s 3 major ethnic groups. Thirty-four centers from 9 Latin American countries participated by randomly incorporating SLE patients within 2 years of diagnosis into a standardized database. Participating centers were selected for their expertise in diagnosing and managing SLE. We were then able to evaluate prospectively socioeconomic variables, ethnicity, type of medical care, clinical and laboratory features, disease activity, damage, and mortality at each site. A coordinating center controlled the quality of the information submitted.Of the 1,214 SLE patients included in the cohort, 537 were mestizos, 507 were white, and 152 were African-Latin American (ALA). (There were also small numbers of pure Amerindian and oriental individuals.) Significant differences were found between them in socioeconomic characteristics, type of care, and level of education favoring whites. Mestizos and ALA were younger at onset. Delay to diagnosis and disease duration was shorter in ALA. Fever was more frequent in whites; discoid lesions in ALA; renal disease and lymphopenia in mestizos and ALA. Although we found differences in background variables between ethnic groups from different countries, mestizos from 2 distant countries (Argentina and Mexico) were clinically akin and showed similar differences to whites. Mortality was associated with lower education, poor medical coverage, and shorter follow-up. In an exploratory model nonwhite ethnicity was associated with renal disease and lymphopenia, damage, and cumulative American College of Rheumatology criteria. These differences in clinical, prognostic, socioeconomic, educational, and access to medical care features in Latin American lupus patients of 3 major ethnic groups from 9 different countries may have an impact on the patients’ disease. “Hispanics,” as they have come to be generically termed on the basis of language, actually constitute a markedly heterogeneous group of subjects.

Serological markers in progressive systemic sclerosis: clinical correlations.

The relation between clinical and serological findings was studied in 75 patients with definite progressive systemic sclerosis (PSS). Antinuclear antibodies were detected by indirect immunofluorescence in 95% of the patients by means of HEp-2 cells. The centromere pattern was observed in 50% of the patients with calcinosis, Raynauds phenomenon, oesophageal dysmotility, sclerodactyly, and telangiectasia (CREST) and only 7% of the group with diffuse disease. Precipitating antibodies to nuclear and cytoplasmic antigens were detected by immunodiffusion in 53% of the patients and identified as anti Scl-70 in 16 (21%). We confirmed that autoantibodies are very frequent in PSS but varied in specificity. A combination of immunodiffusion and indirect immunofluorescence was useful in detecting antibodies characteristic of PSS (i.e., anti-Scl-70 and anticentromere) in 51% of these patients. Anticentromere antibody has a high specificity for CREST and identifies patients with less severe disease (i.e., more prolonged course and less involvement of internal organs). Anti-Scl-70 was associated with a high frequency of lung involvement.

Male systemic lupus erythematosus in a Latin-American inception cohort of 1214 patients

The objective of the study was to evaluate the influence of the male gender in the clinical presentation and outcome of systemic lupus erythematosus in a prospective inception cohort of Latin-American patients. Of the 1214 SLE patients included in the GLADEL cohort, 123 were male. Demographic characteristics as well as clinical manifestations, laboratory profile, activity and damage scores were evaluated at onset and during the course of the disease and compared with female patients. The median age at onset of the male patients was 27 and that at diagnosis 29.2 years. Delay to diagnosis was shorter in males (134 versus 185 days, P = 0.01). At onset, men more frequently showed fever (42.3 versus 27.0%, P = 0.001) and weight loss (23.6 versus 11.8%, P = 0.001). During disease course the incident of symptoms was: fever, 67.8 versus 55.6%, P = 0.012; weight loss, 47.2 versus 24.3%, P = 0.001; arterial hypertension, 37.4 versus 25.8%, P = 0.007; renal disease (persistent proteinuria and/or cellular casts), 58.5 versus 44.6%, P = 0.004); and hemolytic anemia, 19.5 versus 10.9%, P = 0.008. The laboratory results showed that: men more frequently had IgG anticardiolipin antibodies (68.2 versus 49%, P = 0.02) and low C3 (61.3 versus 48.1%, P = 0.03); 5/123 men died (4%) compared with 29/1091 women (2.7%). In conclusion, 10% of GLADEL’s cohort patients were male. They showed a distinctive profile with shorter delay to diagnosis, higher incidence of fever, weight loss, arterial hypertension, renal disease, hemolytic anemia, IgG anticardiolipin antibodies and low C3. Although not statistically significant, mortality was higher in men.

Metabolic syndrome in Argentinean patients with systemic lupus erythematosus

The objective was to determine the prevalence of the metabolic syndrome (MS) in patients with systemic lupus erythematosus (SLE) in Argentina, to assess the factors associated to it, and to compare the results with a control group with non-inflammatory disorders. The study included 147 patients with SLE and 119 controls. MS was defined according to criteria by the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) Scientific Statement. Demographic characteristics, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) were assessed as well as administration, maximum dose and cumulative dose of prednisone and hydroxychloroquine (HCQ). MS prevalence was 28.6% (CI 95%: 21.4–36.6) in patients with SLE and 16% in controls (P = 0.0019). Patients with SLE presented higher arterial hypertension frequency compared with controls (43 vs 25%, P = 0.007). When comparing lupus patients with MS (n = 41) and without MS (n = 106), no significant differences were observed regarding duration of the disease, SLEDAI or cumulative prednisone dose. Cumulative damage was associated independently with MS (OR 1.98; P = 0.021), whereas HCQ use was found to be protective (OR 0.13; P = 0.015). Patients with lupus presented higher MS prevalence than controls with non-inflammatory disorders, and occurrence of arterial hypertension was also higher. MS was associated with cumulative damage; the use of HCQ showed to be protective against presence of MS.

Clinical and serologic characteristics of patients with overlap syndrome: is mixed connective tissue disease a distinct clinical entity?

We discuss the clinical and serologic features of 27 patients with overlap syndrome followed prospectively by our group. The findings are similar to those of other reports, but we have drawn attention to the presence of peritendinous nodules in these patients and mentioned some peculiar neurologic manifestations. Rheumatoid arthritis was the most common diagnosis in our patients. The presence of high-titer antibodies against the nuclear ribonucleoprotein fraction of extractable nuclear antigen (nRNP) did not allow the identification of a particular subgroup. However, patients with this antibody tended to fulfill more criteria of more diseases than those without it. The findings lead us to conclude that antibodies to nRNP do not identify a particular subgroup within the overlap syndromes and that mixed connective tissue disease does not appear to be a distinct entity.

Incidence and prevalence of psoriatic arthritis in Buenos Aires, Argentina: a 6-year health management organization-based study

OBJECTIVES Studies regarding epidemiology of PsA are lacking in Latin America. We estimated the incidence and prevalence of PsA in a University Hospital-based Health Management Organization in Buenos Aires [Hospital Italiano Medical Care Program (HIMCP)]. METHODS POPULATION for incidence calculation, the population at risk was all adult members of the HIMCP, with continuous affiliation for at least 1 year from January 2000 to January 2006. Each person was followed until he/she voluntarily left the HIMCP, death or finalization of the study (final dates) contributing time at risk since January 2000 or enrolment date (whichever occurred later) to that final date. Case ascertainment: medical records of all patients with the problem psoriasis and/or PsA in the HIMCP problem-oriented computer-based patient record system, or registered in rheumatologists and/or dermatologists databases, were revised. Patients fulfilling CASPAR criteria were included. STATISTICAL ANALYSIS incidence rate (IR) was calculated with 95% CIs. Cumulative prevalence was estimated on 1 January 2006 (denominator population ==88,112). RESULTS In the study period, 138,288 persons contributed a total of 558,878 person-years, of whom 35 developed PsA (IR 6.26; 95% CI 4.2, 8.3 cases per 100,000 person-years). There were 12 females: IR 3.64 (95% CI 1.6, 5.7) cases per 100,000 person-years; and 23 males: IR 10.02 (95% CI 5.9, 14.1) cases per 100,000 person-years. On 1 January 2006, 65 prevalent cases were identified: prevalence 74 (95% CI 57, 94) cases per 100,000 members. CONCLUSIONS The incidence and prevalence of PsA in this Latin American country was similar to that reported in other studies from Europe and the USA.

Chromosome 17p12-q11 harbors susceptibility loci for systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of autoantibodies against intracellular components, the formation of immune complexes, and inflammation in various organs, typically the skin and kidney glomeruli. The etiology of the disease is not well understood but is most likely the result of the interaction between genetic and environmental factors. In order to identify susceptibility loci for SLE, we have performed genome scans with microsatellite markers covering the whole genome in families from Argentina, Italy, and Europe. The results reveal a heterogeneous disease with different susceptibility loci in different family sets. We have found significant linkage to chromosome 17p12-q11 in the Argentine set of families. The maximum LOD score was given by marker D17S1294 in combination with D17S1293, when assuming a dominant inheritance model (Z=3.88). We also analyzed a repeat in the promoter region of the NOS2A gene, a strong candidate gene in the region, but no association was found. The locus on chromosome 17 has previously been identified in genetic studies of multiple sclerosis families. Several other interesting regions were found at 1p35, 1q31, 3q26, 5p15, 11q23 and 19q13, confirming previously identified loci for SLE or other autoimmune diseases.

Tratamiento y pronóstico

Diagnosis should include mandatory muscle biopsy to identify inclusion body myositis. Most forms of inflammatory myopathies are still treated similarly, although treatment strategies remain empirical and controlled trials are few. Muscle strength and CPK levels remain the most frequently used measures to monitor disease activity and response to therapy. Corticosteroids are the main pillar of drug therapy but simultaneous use of corticosteroid-sparing drugs may be considered from the start. The most frequently used drugs for combined therapy are methotrexate, azathioprine and antimalarials in cases of dermatomyositis. In refractory cases, especially if life threatening, rituximab has appeared to be effective although there are no controlled trials, and there is some consensus that this should be used prior to Immunoglobulin. Anti TNF antibodies have not been useful in these diseases. Cyclosporin (especially with lung involvement) and Mofetil mycophenolate may also have a role in non responding cases. Treatment of inclusion body myositis remains unsatisfactory.

Genome-Wide Association Study in an Amerindian Ancestry Population Reveals Novel Systemic Lupus Erythematosus Risk Loci and the Role of European Admixture.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a strong genetic component. We undertook the present work to perform the first genome‐wide association study on individuals from the Americas who are enriched for Native American heritage.

Frequency and clinical significance of anticentromere and anti Scl-70 antibodies in an English connective tissue disease population

SummaryTo determine the clinical significance of anticentromere (ACA) and anti Scl-70 antibodies in an English population with connective tissue diseases, we examined the sera of 150 patients, including 40 with systemic sclerosis (SS), who were prospectively studied on the same clinical protocol in our connective tissue disease clinic.ACA was present in 44% of the CREST patients as opposed to only 12% of those with SS and diffuse skin involvement. Only two patients without SS had ACA. Anti Scl-70 was detected in 20% of the patients with SS and only two of those with other connective tissue diseases.We confirmed the specificity of these antibodies for SS. Either anti Scl-70 or ACA was present in half the patients with SS and their presence may represent a useful aid to diagnosis of this disease in patients presenting with Raynauds phenomenon or an undifferentiated connective tissue disease.While less than half the CREST patients had ACA, this antibody appears to identify those patients within the CREST variant with skin involvement confined to sclerodactyly as opposed to those with acrosclerosis. These patients, however, did not differ in the degree of visceral involvement.