Rachel Snitcowsky

Association of human leukocyte class II antigens with rheumatic fever or rheumatic heart disease in a Brazilian population.

BackgroundThe incidence of rheumatic heart disease is great in Brazil. We analyzed the distribution of human leukocyte (HLA) antigens in a Brazilian population sample with rheumatic fever or rheumatic heart disease, with the aim of better understanding the mechanisms involved. Methods and ResultsHLA class I (A, B, and C) and class II (DR and DQ) antigen distribution was studied in 40 patients with diagnosis of rheumatic fever or rheumatic heart disease and compared with a control group of 617 healthy individuals for class I typing, from which 118 were drawn for class II typing. A strong correlation between rheumatic fever and rheumatic heart disease and HLA-DRw53 (72.9% in the disease group versus 39%1 in the control group: p = 0.00061, relative risk, 4.2; etiologic fraction, 0.43) was found. We also found an increase in the frequency of HLA-DR7 (57.5% in the disease group versus 26.3% in control group: p=O0.00715; relative risk, 3.8; etiologic fraction, 0.56). HLA class I and HLA-DQ typing did not point to any association with these diseases. ConclusionsHLA-DR7 and HLA-DRw53 are markers for susceptibility to rheumatic fever and rheumatic heart disease in Brazil. These results could be explained by genetic differences resulting from racial or geographical diversity. (Circulation 1991;83:1995—1998)

HLA class II antigens in rheumatic fever Analysis of the DR locus by restriction fragment-length polymorphism and oligotyping

We recently described an association of serologically defined HLA class II antigens DR7 and DR53 with RF. This study aimed at determining more precisely the class II gene associated with the disease. We studied patients and age- and race-matched controls. Genomic DNA was digested with four different enzymes and hybridized with HLA cDNA probes for DR beta, DQ beta, DQ alpha, and DP beta genes. RFLP analysis disclosed a fragment of 13,81 kb on Taq I DR beta blots, which correlates with HLA-DR53 and HLA-DR16, according to data from the Tenth International Histocompatibility Workshop. Of 24 patients, 20 (83.3%), were positive for the 13.81-kb/Taq I/DR beta allogenotope, compared with 16 (34%) of 47 healthy individuals (p = 0.000079, Fishers exact test). Search for specific nucleotide sequences was performed using polymerase chain reaction technique. Oligonucleotides corresponding either to allele-specific DR7 and DR53 sequences, or shared by DRB1 and DRB3, DRB4, or DRB5 sequences were screened. Differences were tested throughout the second exon up to codon 100. Results were as expected by simple comparison with the published sequences of individual alleles. Although a clear association with DRB loci is shown, a susceptibility associated either with an allele or with a unique sequence was not found. A promiscuous presentation of the putative cross-reacting peptide or a heterogeneity of the causative agent might be the origin of these results. Genetic complementarity may be an additional factor defining inherited susceptibility to this disease.

Correlation between gallium-67 imaging and endomyocardial biopsy in children with severe dilated cardiomyopathy

Fourty-four patients (aged 10 months to 15 years) were assessed in a double-blind study to observe the correlation between myocardial uptake of 67-gallium and endomyocardial biopsy in the detection of moderate to severe myocardial inflammation. The sensitivity and specificity of gallium-67 imaging were 87 and 81%, respectively. Based on these findings, immunosuppressive therapy can be assigned to children with dilated cardiomyopathy and positive myocardial uptake, since moderate and severe myocardial inflammation may be detected by this non-invasive method.

Cirurgia valvar em crianças e jovens: resultados de 131 casos

From January 1983 to December 1988, 131 patients with ages iqual or less than 15 years old were submitted to valve surgery; 74 (56%) were of acquired ethiology and 57 (44%) were congenital. In 100 (76.3%) patients operation was performed in only one valve. There were 63 valve replacements (re-replacement in six), 103 conservative procedures and in three valve exereses was performed. Among the 63 prosthesis, 59 (93.6%) were biological and 4 (6.3%) mechanical. Twenty-one patients (16%) were reoperated upon, 17 (81%) of them due to prosthesis dysfunction. The average time of calcification was 40 months (3.3 years). Hospitaly mortality was 7.5% and late mortality was 2.2%. In the follow-up of 2787 months/patient all of them were in fuctional class I or II (NYHA).

Medical treatment of acute episodes of rheumatic fever

Eight patients, four males and four females, age five to 13 years old (average: 11 years) have undergone surgery in the acute phase of rheumaticfever. The patients presented a history of rheumatic activity characterized by the presence of migratory arthritis and carditis. All patients had severe acute mitral insufficiency, while one of them had associated aortic insufficiency. Laboratory examinations revealed the presence of an acute inflammatory condition. All patients had acute heart failure and were treated initially with high doses of diuretics, peripheral vasopressor and vasodilator amines, together with cardiotonic drugs, without improvement. Surgical treatment was indicated after a period of observation between 24 hours and five days. In five patients, the Doppler echocardiogram revealed rupture and elongation of tendinous cords. Two of them had acute dilatation of the mitral ring, and one had isolated acute dilatation of the mitral ring. Five patients underwent valvar replacement and, in three, valvar repair was carried out. Two patients, who were in cardiogenic shock at the time of their referral, died in the operating room following replacement of the mitral valve. All patients who underwent repair of the mitral valve were in good condition at the last follow-up, six to 27 months after surgery.

Echocardiographic diagnosis of rheumatic fever and rheumatic valvar disease

We studied 56 children echocardiographically, ages four to 15 years (mean nine years) with acute rheumatic fever to determine the extent of cardiac involvement. All had a clinical diagnosis of carditis. Mitral regurgitation was always present and was associated with aortic regurgitation in 53.6% and tricuspid regurgitation in 32.1%. Mitral valvar prolapse was observed in 18 patients 5(32.1%) and could not be differentiated from myxomatous prolapse in 10 (17.8%). Cordal rupture was detected in seven patients (12.5%), three of whom required surgical treatment. Other findings concerning the mitral valve were vegetations in two patients (3.6%), commissural fusion without stenosis in 36(64.3%), and mitral stenosis in four (7.1%). Heart failure was usually secondary to valvitis rather than myocarditis, and led to surgical treatment in seven patients. The myocardial function was depressed in only two patients. In both, the ejection function returned to normal after medical treatment. Echocardiography provides important information on the involvement of the heart in acute rheumatic fever, helping to determine prognosis and the results of treatment.