Rheumatic pericarditis: a rare cause of constrictive pericarditis.

Constrictive pericarditis is a relatively uncommon form of cardiac failure and presents due to scarring and consequent loss of the normal elasticity of the pericardial sac. This results in abnormal/limited ventricular filling and symptoms of heart failure. The aetiology is varied, from infective causes to idiopathic causes, or can manifest after cardiothoracic surgery. This case involves a 46-year-old man presenting with acute group A beta haemolytic streptococcus infection, and over the subsequent 6 months develops constrictive pericarditis due to what is believed to be a rheumatic aetiology. The patient subsequently underwent pericardiectomy and had restoration of normal filling dynamics confirmed on follow-up echocardiography. This case provides a subject matter for the review of the features of constrictive pericarditis and its investigation and management. This case is that it highlights the fact that pericarditis is not a benign condition. Emerging evidence suggests that pericarditis is due to a failure in inflammatory regulatory mechanisms, and patients suffering this condition have a preponderance to 'autoinflammation'. Pericarditis should be recognised early and treated fully with anti-inflammatory agents.

Cross-sectional study of population-specific streptococcal antibody titres in Uganda.

OBJECTIVE: Despite substantial variation of streptococcal antibody titres among global populations, there is no data on normal values in sub-Saharan Africa. The objective of this study was to establish normal values for antistreptolysin O (ASO) and antideoxyribonuclease B (ADB) antibodies in Uganda. DESIGN: This was an observational cross-sectional study. SETTING: This study was conducted at Mulago National Referral Hospital, which is located in the capital city, Kampala, and includes the Uganda Heart Institute. PATIENTS: Participants (aged 0-50 years) were recruited. Of 428 participants, 22 were excluded from analysis, and 183 (44.4%) of the remaining were children aged 5-15 years. MAIN OUTCOME MEASURES: ASO was measured in-country by nephelometric technique. ADB samples were sent to Australia (PathWest) for analysis by enzyme inhibition assay: 80% upper limit values were established. RESULTS: The median ASO titre in this age group was 220 IU/mL, with the 80th percentile value of 389 IU/mL. The median ADB titre in this age group was 375 IU/mL, with the 80th percentile value of 568 IU/mL. CONCLUSIONS: The estimated Ugandan paediatric population standardised 80% upper-limit-of-normal ASO and ADB titres is higher than many global populations. Appropriateness of using population-specific antibody cutoffs is yet to be determined and has important implications for the sensitivity and specificity of rheumatic fever diagnosis.

Clinical-Serological Characterization and Treatment Outcome of a Large Cohort of Italian Children with Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection and Pediatric Acute Neuropsychiatric Syndrome.

Objective: Pediatric autoimmune neuropsychiatric disorder associated with Streptococcus pyogenes infection (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS) are emerging immune-mediated encephalopathies characterized by sudden onset of seemingly inexplicable complex neuropsychiatric symptoms, including obsessions, compulsions, and heterogeneous tics, which occur in children. Main goal of this study was to report our experience in a large cohort of Italian children affected by either PANDAS or PANS and treated long term with an antibiotic regimen similar to that used for acute rheumatic fever. Patients and Methods: The clinical charts of a cohort of 371 consecutive Italian children, 345 with PANDAS (93.0%) and 26 with PANS (7.0%), were retrospectively evaluated. Antistreptococcal, antinuclear antibodies, and serologic evaluation for a group of common autoantibodies and microbial agents were also assessed. A strict differential diagnosis with other autoimmune diseases displaying neuropsychiatric manifestations was performed. Results: Antistreptolysin O and anti-DNase B antibody titers were tested and were positive in all PANDAS subjects, but negative in PANS. Anti-Mycoplasma pneumoniae antibodies and anti-Epstein-Barr virus Nuclear Antigen antibodies were found positive in 11 (42.3%) and 5 (19.2%) patients with PANS, respectively. Among PANDAS cases, a clear streptococcal infection was clinically evident at the onset of neurological symptoms in only 74 patients (21.4%), whereas the relationship with Streptococcus pyogenes was confirmed by serologic tests in the other 271 (78.6%). All patients fulfilling the diagnostic criteria for PANDAS (n = 345) received amoxicillin/clavulanic acid for 10-21 days at diagnosis, while those who were diagnosed with PANS (n = 26) received treatment according to the causative agent. Thereafter, all PANDAS/PANS patients received prophylaxis with benzathine benzylpenicillin for an overall period of at least 5 years to prevent subsequent potential streptococcal infections. To date, 75.0% of PANDAS patients (n = 258) have shown an improvement of neurologic symptoms, mainly observed within 3-5 months of treatment for PANDAS cases, while 88.4% of PANS patients (n = 23) have improved after 6-12 months. Infection-related relapses of neurologic manifestations were observed in both PANDAS and PANS patients (n = 167 out of 371; 45% of the total cohort) in the long term. Conclusions: Our study has confirmed the usefulness of the preliminary diagnostic criteria for PANDAS and PANS, revealing also the importance of early diagnosis to reduce the risk of evolution toward disabling chronic neurologic sequelae. Long-term antibiotic prophylaxis has resulted in a substantial benefit to reduce neurological symptoms for the majority of PANDAS and PANS patients over a 7-year period.

On the connection between autoimmunity, tic disorders and obsessive-compulsive disorders: a meta-analysis on anti-streptolysin O titres.

Anti-streptolysin O (ASO) titration is useful in the context of autoimmune pathologies, including specific cases of tic and obsessive-compulsive disorders occurring after streptococcal infections. There is currently a lack of consensus on the use of ASO titres; therefore we performed a meta-analysis to systematise available data and clarify the role of ASO titres in the context of neuropsychiatric disorders. A meta-analysis was performed on ASO titration in neuropsychiatric patients, including tic disorders and obsessive-compulsive disorders. Included studies reported numbers of positive subjects, depending on a chosen threshold, or detailed ASO titrations. Three hundred and twenty nine studies were identified, of which 13 were eligible for meta-analysis. Due to limited available data, only tic disorders were evaluated. The odds ratio of finding an abnormal ASO titre in patients was 3.22 (95% C.I. 1.51-6.88) as compared to healthy controls and 16.14 (95% C.I. 8.11-32.11) as compared to non-psychiatric patients. Studies using different thresholds were generally concordant. ASO titres were also compared quantitatively, finding an overall difference of the means of 70.50 U/ml (95% C.I. 25.21-115.80) in favour of patients with tic disorders. Based on current evidence, tic disorders are associated with a significant increase in ASO titres, evident both in a threshold-level perspective and on a quantitative level. These results encourage the systematisation of ASO titration in the context of tic disorders.

How to use antistreptolysin O titre.

Group A streptococcus (GAS) is the cause of a wide range of acute suppurative and, following a latent period, non-suppurative diseases such as rheumatic fever and poststreptococcal glomerulonephritis. Diagnosis of the latter group requires evidence of preceding GAS infection. The bacteria produce a range of extracellular antigens, including streptolysin O, which induce an antibody response in the host. A rise in antistreptolysin O titre (ASOT) is indicative of preceding GAS infection. In clinical practice, often only a single ASOT measurement is available and its timing in relation to a possible GAS infection is unknown. Interpretation of the result in this context is liable to misdiagnosis. In order to optimise diagnosis of preceding GAS infection, at least two sequential ASOT measurements, together with simultaneous assay for anti-DNase B, a second antistreptococcal antibody, is recommended.

Streptococcus induces circulating CLA(+) memory T-cell-dependent epidermal cell activation in psoriasis.

Streptococcal throat infection is associated with a specific variant of psoriasis and with HLA-Cw6 expression. In this study, activation of circulating psoriatic cutaneous lymphocyte-associated antigen (CLA)(+) memory T cells cultured together with epidermal cells occurred only when streptococcal throat extracts were added. This triggered the production of Th1, Th17, and Th22 cytokines, as well as epidermal cell mediators (CXCL8, CXCL9, CXCL10, and CXCL11). Streptococcal extracts (SEs) did not induce any activation with either CLA(-) cells or memory T cells cultured together with epidermal cells from healthy subjects. Intradermal injection of activated culture supernatants into mouse skin induced epidermal hyperplasia. SEs also induced activation when we used epidermal cells from nonlesional skin of psoriatic patients with CLA(+) memory T cells. Significant correlations were found between SE induced upregulation of mRNA expression for ifn-γ, il-17, il-22, ip-10, and serum level of antistreptolysin O in psoriatic patients. This study demonstrates the direct involvement of streptococcal infection in pathological mechanisms of psoriasis, such as IL-17 production and epidermal cell activation.

Post streptococcal myalgia: an under-recognized clinical syndrome.

Post streptococcal myalgia (PSM) is an under-recognized non-infectious sequelae of streptococcal infection in children. The authors report a case of PSM in an 11-year-old boy along with a review of previously reported cases. The diagnosis of PSM should be considered in children presenting with acute myalgia and high Anti-Streptolysin O titres.

Interferencia en la medida inmunoturbidimétrica de antiestreptolisina-O por un componente monoclonal IgM-kappa en 3 pacientes / Interference in the immunoturbidimetric assay of antistreptolysin-O by monoclonal IgM-Kappa in 3 patients

El hallazgo casual de resultados discrepantes en la determinación de un parámetro bioquímico cuando se realiza en distintas diluciones de la misma muestra, puede orientar hacia una interferencia analítica. Se presenta el estudio de 3 pacientes en los que se demostró una interferencia positiva en la medida inmunoturbidimétrica de antiestreptolisina-O debido a la presencia de una inmunoglobulina monoclonal IgM-k(AU)

The casual finding of disparate results in the determination of an analyte when it is measured at different dilutions on the same sample can lead us to suspect the presence of analytical interference. We present the study of 3 patients in whom a positive interference was proved on the immunoturbidimetric measurement of antistreptolysin-O due to the presence of a monoclonal immunoglobulin IgM Kappa(AU)

Is there any relationship between streptococcal infection and multiple sclerosis?

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated inflammatory demyelinating disease of uncertain etiology. Although the mechanisms of inducting autoimmunity by some of the infectious agents have been investigated, there is not yet enough research on streptococcal infections. MATERIAL/METHODS: To understand the effect of past group A streptococcal infection on MS, antistreptolysin O (ASO) and antideoxyribonuclease B (ADNase B) were measured in 21 patients with relapsing-remitting MS and 21 healthy blood donors by nephelometric assay. RESULTS: ADNase B levels in the patients with MS were found to be significantly higher than in the controls (p<0.001); however, ASO levels were similar in both groups. CONCLUSIONS: These findings indicate that a relationship between multiple sclerosis and streptococcal infections may exist, but to acquire a better understanding of the role of group A streptococci in the pathogenesis of multiple sclerosis, more studies with animal models are necessary.

Rheumatic fever: the relationship between clinical manifestations and laboratory tests.

OBJECTIVES: To determine the relationship between the severity of clinical features of rheumatic fever (RF), and antistreptolysin O titre (ASOT) and/or erythrocyte sedimentation rate (ESR). METHODS: Clinical and laboratory data from 102 children with RF who had been admitted at a university hospital in Tehran between 1992 and 2002 were reviewed retrospectively. In order to categorize the severity of clinical manifestations of disease, patients were divided into three groups. Those with arthritis alone were defined as group A, carditis with or without arthritis as group B and carditis (with or without arthritis) with congestive heart failure as group C. RESULTS: Thirty-one cases were enrolled in group A, 39 in group B, and 32 in group C. We didn't find a significant relationship between the severity of clinical presentation of disease and ASOT (P = 0.89) and ESR (P = 0.24). Seventy-two patients presented with first attack and 30 had recurrences. The frequency of congestive heart failure (CHF) in first attacks was 31.2%vs 68.8% in recurrences (P < 0.0001). No Significant relationship was found between the number of involved valves and ASOT (P = 0.4) or ESR (P = 0.8). CONCLUSION: Variable clinical presentation of disease and increasing intensity of cardiac involvement is not related to the ASOT or ESR levels.

New normal ranges of antistreptolysin O and antideoxyribonuclease B titres for Australian children.

OBJECTIVE: To determine age-specific upper limit of normal (ULN) values of the ASO and ADB titres in children aged 4-14 years in urban Melbourne. Serology is often used to diagnose a preceding Streptococcus pyogenes infection, particularly in potential cases of rheumatic fever and post-streptococcal glomerulonephritis. The most commonly used antigens are antistreptolysin O (ASO) and antideoxyribonuclease B (ADB). Reference ranges used in Australia for these serological markers are usually based on data in adults from other countries. There are no age-specific reference values for Australian children. METHODS: Sixty-six sera from children with no history of recent streptococcal infection were obtained in May-June 2002. The children were divided into three age groups for analysis: 4-5 (n = 20), 6-9 (n = 19) and 10-14 (n = 25) years. The geometric mean titre and ULN (defined as the 80th percentile) for the ASO and ADB titres for each age group were determined in both international and log units. RESULTS: The ULN for ASO titres in each age group was 120 (2.08 log units), 480 (2.68) and 320 (2.51). The ULN for ADB titres in each age group was 100 (2.00 log units), 400 (2.60) and 380 (2.58). CONCLUSION: The ASO and ADB ULN values in school-aged children are higher than the current reference ranges suggest.

Anti-streptolysin O titers in normal healthy children of 5-15 years.

Antistreptolysin O (ASO) levels vary with age group of the study population and geographical locations. The present study was undertaken to determine the upper limit of normal of ASO in 200 normal children of 5-15 years of age with no history of recent sore throat infection. The standard tube dilution method (WHO) was used for estimating ASO titers. It was found that 239 IU was the upper limit of normal in the study population, which can be considered as the baseline ASO titer. This can provide useful guidelines for physicians in the interpretation of elevated ASO titers in cases of suspected acute rheumatic fever.

Rheumatic fever in a high incidence population: the importance of monoarthritis and low grade fever.

AIMS: To describe the clinical features of rheumatic fever and to assess the Jones criteria in a population and setting similar to that in many developing countries. METHODS: The charts of 555 cases of confirmed acute rheumatic fever in 367 patients (97% Aboriginal) and more than 200 possible rheumatic fever cases from the tropical "Top End" of Australia's Northern Territory were reviewed retrospectively. RESULTS: Most clinical features were similar to classic descriptions. However, monoarthritis occurred in 17% of confirmed non-chorea cases and 35% of unconfirmed cases, including up to 27 in whom the diagnosis was missed because monoarthritis is not a major manifestation. Only 71% and 25% of confirmed non-chorea cases would have had fever using cut off values of 38 degrees C and 39 degrees C, respectively. In 17% of confirmed non-chorea cases, anti-DNase B titres were raised but antistreptolysin O titres were normal. Although features of recurrences tended to correlate with initial episodes, there were numerous exceptions. CONCLUSIONS: Monoarthritis and low grade fever are important manifestations of rheumatic fever in this population. Streptococcal serology results may support a possible role for pyoderma in rheumatic fever pathogenesis. When recurrences of rheumatic fever are common, the absence of carditis at the first episode does not reliably predict the absence of carditis with recurrences.

Microalbuminuria as renal marker in recurrent acute tonsillitis and tonsillar hypertrophy in children.

Raised levels of microalbuminuria pointing out glomerular abnormality and indicate renal damage. Glomerulonephritis is caused by immune reaction leading to the formation of circulating immune complexes that are deposited on the basal membrane of the glomerulus. The time course and the appearance of antibodies against infectious agents both play very important roles in its clinical presentation. Antibodies against streptococci have not a protective role, but offers a useful marker of the presence or absence of recent infection. This work studies the presence of microalbuminuria and circulating anti-streptococcal antibodies, namely, anti-streptolysin O and anti-deoxyribonuclease B antibodies in ninety children which underwent tonsillectomy due to infectious and obstructive tonsillar pathology. These children were divided in recurrent acute tonsillitis (n= 34), recurrent tonsillitis with tonsillar hypertrophy (n = 26), and tonsillar hypertrophy (n = 30). It was found in recurrent acute tonsillitis a moderate correlation between microalbuminuria and anti-streptolysin O, and a weak correlation between microalbuminuria and anti-deoxyribonuclease B antibodies. It was also found significant differences of the levels of anti-streptococcal antibodies between the three groups of pathologies. It is proposed the determination of microalbuminuria, an inexpensive and harmless test, as an indicator of possible renal damage in recurrent acute tonsillitis.

Febre reumática: dificuldades diagnósticas / Rheumatic fever: difficulties in the diagnosis

O diagnóstico da febre reumática nem sempre é fácil e muitas vezes o pediatra fica confuso ao interpretar as queixas, avaliar os sinais do exame físico e as alteraçöes laboratoriais. As implicaçöes de um diagnóstico incorreto säo desastrosas por levarem a uma profilaxia desnecessária por vários anos e, por outro lado, a falta de um diagnóstico correto deixa o paciente vulnerável a um novo surto que poderá provocar ou agravar uma lesäo cardíaca, trazendo sérias conseqüências para a vida do paciente, inclusive colocando-a em risco. Nessa revisäo procuramos discutir e valorizar cada um dos elementos necessários ao diagnóstico, desde a amigdalite estreptocócica, o período de latência e os critérios de Jones

Anticuerpos contra productos extracelulares del estreptococo grupo A: importancia diagnóstica en la fibre reumática aguda / Antibodies against extracellular products of group a streptococcus. its diagnostic value in acute rheumatic fever

La infección estreptocóccica de la faringe es condición sine qua non el desarrollo de la fiebre reumática (FR), La demostración de esa infección suele requerir métodos inmunoserológicos que detectan anticuerpos contra productos extracelulares del estreptococo (PEE). Se evaluó la respuesta inmune humoral contra PEE en niños y adultos con y sin diagnóstico de FR. Se estableció que la distribución de valores para anti-estreptolisina O (AEL-O) no es gaussiana y que el valor de referencia debe manejarse como percentila. En adultos la percentila 97 es 227, en niños la percentila 90 es 451. En caso de FR, todos los enfermos excepto uno tuvo valores superiores. Una prueba de aglutinación que reconoce otros anticuerpos a PEE (Estreptozima mr), mostró en menores de 15 años que 15/28 los tenían a título bajo, en cambio en el grupo con FR sólo 1 mostró ausencia de esos anticuerpos. A mayor título de AEL-O mayor título en Estreptozima. Los métodos probados son eficientes para reconocer la respuesta inmune humoral contra PEE

[Rheumatic fever and post-streptococcal arthritis. Clinical review]. / Fiebre reumática y artritis postestreptocócicas. Revisión clínica.

We report 11 patients diagnosed of Acute Rheumatic Fever (ARF), and 7 of Poststreptococcal Reactive Arthritis (PSRA): patients with group A beta hemolytic streptococcal infection and articular disease who do not fulfill the modified Jones criteria. All patients with ARF were treated with monthly prophylaxis (with penicillin G benzathine). Carditis was seen in five patients, but only one of them has developed a mitral valve insufficiency. The prophylaxis in patients with PSRA was individualized. None of these patients had clinical evidence of carditis during the acute disease, but one of them developed a mitral and aortic stenosis two years after the initial episode. The possible indication of penicillin prophylaxis in these patients with PSRA in suggested.