Adolescente con corea de inicio agudo: a propósito de una entidad olvidada / Adolescent with acute-onset chorea: on the subject of a forgotten entity

La corea de Sydenham es como se denomina el cuadro de origen neurológico consistente en agitación y movimientos anormales que ocurre en contexto de una fiebre reumática, secundariamente a la infección por estreptococo del grupo A. Dado que la incidencia de fiebre reumática ha disminuido significativamente en los últimos años, las complicaciones asociadas pueden considerarse actualmente excepcionales. No obstante, dado que presenta un pronóstico excelente si se instaura precozmente el tratamiento, es muy importante saber reconocer el cuadro clínico (AU)

Sydenham’s chorea, with a documented relationship with group A streptococcal infections, is the one of the most common acquired movement disorder of adolescence. However, rheumatic fever´s incidence is significantly lower than years ago. The clinical picture is very characteristic, and its recognition is essential in order to improve the prognostic starting an specific treatment as soon as possible (AU)

Poststreptococcal acute glomerulonephritis can be a risk factor for accelerating kidney dysfunction in Alport syndrome: a case experience.

Alport syndrome (AS) is a progressive kidney disease. Male cases with X-linked AS (XLAS) are reported to develop end-stage kidney disease (ESKD) at the age of around 20-30 years. One risk factor for developing ESKD at a young age is a genotype of having truncating variants in the COL4A5 gene. However, to date, other such factors have remained unclear. Here, we describe a 15-year-old Japanese boy with XLAS who had a missense variant in the COL4A5 gene. He presented with gross hematuria, severe proteinuria, oliguria, systemic edema, body weight gain, and hypertension after pharyngitis. Blood examination showed kidney dysfunction, hypocomplementemia, and elevated antistreptolysin-O level. We diagnosed him with poststreptococcal acute glomerulonephritis (PSAGN) and he was stopped treatment by lisinopril, and received supportive treatment. However, he showed an unusual clinical course for PSAGN and, consequently, developed ESKD 15 months after the onset of PSAGN without recovery from the kidney dysfunction. This case showed that the onset of PSAGN can be a risk factor for AS patients to develop ESKD at a young age.

Síndrome de shock tóxico estreptocócico / Streptococcal toxic-shock syndrome

El síndrome de shock tóxico estreptocócico (SSTS) es un cuadro grave e infrecuente en Pediatría. Sin embargo, en las últimas décadas está aumentando la incidencia de infecciones invasivas por Streptococcus pyogenes o estreptococo del grupo A. Aparece más frecuentemente en niños preescolares, ya que el diagnóstico de enfermedad estreptocócica es más complicado a esta edad. Es fundamental el diagnóstico y tratamiento precoz debido a su potencial gravedad, precisando en algunas ocasiones medidas intensivas de soporte vital y prevención del fallo multiorgánico

Streptococcal toxic shock syndrome (STSS) is a serious and uncommon disease in Pediatrics. However, in the last decades the incidence of invasive infections by Streptococcus pyogenes of group A streptococcus has increased. It appears more frequently in preschool children since the diagnosis of streptococcal disease is more complicated at this age. Early diagnosis and treatment are essential due to its potential severity, sometimes requiring intensive life support measures and prevention of multiorgan failure

Atypical presentation of acute rheumatic fever (ARF) in a 25-year-old woman in the Caribbean: a challenging diagnosis.

A 25-year-old woman presented a challenging diagnosis of acute rheumatic fever (ARF). Initial symptoms included dry cough and three minor Jones criteria (unabating fever (38.4°C, 0d), elevated acute phase reactants (C-reactive protein, 13d) and joint pain (monoarthralgia) in her neck (0d)). ARF was diagnosed only after presentation of two major Jones criteria (polyarthritis/polyarthralgia (16d) and erythema marginatum (41d)) and positive antistreptolysin O titre (44d). Parotid swelling, peripheral oedema, elevated liver enzymes and diffuse lymphadenopathy complicated the diagnosis. Throat swab, chorea and carditis were negative or absent. Atypical ARF is challenging to recognise. There is no diagnostic test and its presentation is similar to that of other diseases. While the 2015 Jones criteria modification increased specificity of ARF diagnosis, atypical cases may still be missed, especially by physicians in developed countries. Suspicion of atypical ARF, especially after travel to high incidence regions, would allow for earlier treatment and prevention of rheumatic heart disease.

Elevated antistreptolysin O titer is closely related to cardiac mitral insufficiency in untreated patients with Takayasu arteritis.

BACKGROUND: The etiology of Takayasu arteritis (TA) is unknown; however, a possible relationship between streptococcal infection and TA has been proposed. This study aimed to identify the clinical features and cardiac valvular involvement in untreated TA patients with an elevated antistreptolysin O (ASO) titer. METHODS: In this retrospective study, the clinical characteristics and features of valvular involvement were compared in TA patients with or without an elevated ASO titer. RESULTS: Of the 74 untreated TA patients, 13 patients were found have elevated ASO titers (17.6%). Mitral insufficiency was the most common in patients with elevated ASO (69.2%, 9/13), followed by aortic valve insufficiency (46.2%, 5/13) and tricuspid insufficiency (46.2%, 5/13), which were no significantly different than that in normal ASO group. The proportions of moderate to severe mitral (30.8% vs 1.6%, p = 0.000) and tricuspid valve (15.4% vs 1.64%, p = 0.023) insufficiency in the ASO positive group were significantly higher than those in the ASO negative group. The odds of mitral regurgitation in patients with elevated ASO titers were 3.9 times higher than those in the group with normal ASO titers (p = 0.053, OR = 3.929, 95% confidence interval [CI]: 0.983-15.694). Furthermore, the risk of moderate to severe mitral insufficiency in patients with elevated ASO titers was 41.6 times higher than that in patients with normal ASO titers (p = 0.002, OR = 41.600, 95% CI: 3.867-447.559). CONCLUSIONS: An increase in ASO titer is related to valvular involvement in TA and is closely linked to mitral insufficiency.

Diagnostic Value of Different Noninvasive Criteria of Latent Myocarditis in Comparison with Myocardial Biopsy.

PURPOSE: The aim of this study was to quantify the value of various clinical, laboratory, and instrumental signs in the diagnosis of myocarditis in comparison with morphological studies of the myocardium. METHODS: In 100 patients (65 men, 44.7 ± 12.5 years old) with "idiopathic" arrhythmias (n = 20) and dilated cardiomyopathy (DCM; n = 80), we performed the following: 71 endomyocardial biopsies (EMB), 13 intraoperative biopsies, 5 studies of explanted hearts, and 11 autopsies with virus investigation (real-time PCR) of the blood and myocardium. Antiheart antibodies (AHA) were also measured as well as cardiac CT (n = 45), MRI (n = 25), and coronary angiography (n = 47). The comparison group included 50 patients (25 men, 53.7 ± 11.7 years old) with noninflammatory heart diseases who underwent open heart surgery. RESULTS: Active/borderline myocarditis was diagnosed in 76.0% of the study group and in 21.6% of patients in the comparison group (p < 0.001). The myocardial viral genome was observed more frequently in patients in the comparison group than in the study group (65.0 and 40.2%; p < 0.01). We evaluated the diagnostic value of noninvasive markers of myocarditis. The panel of AHA had the greatest importance in the identification of myocarditis: sensitivity was 81.5%, and the positive and negative predictive values were 75.0 and 60.5%. This defined the diagnostic value of noninvasive markers of myocarditis and established a diagnostic algorithm providing an individual assessment of the likelihood of myocarditis development. CONCLUSION: AHA have the greatest significance in the diagnosis of latent myocarditis in patients with "idiopathic" arrhythmias and DCM. The use of a complex of noninvasive criteria allows the probability of myocarditis to be estimated and the indications for EMB to be determined.

NF-κB-driven miR-34a impairs Treg/Th17 balance via targeting Foxp3.

The subset of regulatory T (Treg) cells, with its specific transcription Foxp3, is a unique cell type for the maintenance of immune homeostasis by controlling effector T (Teff) cell responses. Although it is common that a defect in Treg cells with Treg/Teff disorder causes autoimmune diseases; however, the precise mechanisms are not thoroughly revealed. Here, we report that miR-34a could attenuate human and murine Foxp3 gene expression via targeting their 3' untranslated regions (3' UTR). The human miR-34a, increased in peripheral blood mononuclear cells (PBMCs) and CD4+ T cells from rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) patients, displayed a positive correlation with some serum markers of inflammation including rheumatoid factor (RF), anti-streptolysin antibody (ASO), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as well as Th17 signature gene RORγt, but inversely correlated with the mRNA expression levels of FOXP3. In addition, murine miR-34a levels were downregulated in TGF-ß-induced Treg cells but upregulated in Th17 cells induced in vitro compared to activated CD4+ T cells. It has also been demonstrated that elevated miR-34a disrupting Treg/Th17 balance in vivo contributed to the progress of pathogenesis of collagen induced arthritis (CIA) mice. Furthermore, IL-6 and TNF-α were responsible for the upregulation of miR-34a and downregulation of Foxp3, which was reverted by the addition of NF-κB/p65 inhibitor BAY11-7082, thus indicating that NF-κB/p65 inhibited Foxp3 expression in an miR-34a-dependent manner. Finally, IL-6 or TNF-α-activated p65 could bind to the miR-34a promotor and enhance its activity, resulting in upregulation of its transcription. Taken together, we show that NF-κB activated by inflammatory cytokines, such as IL-6 and TNF-α, ameliorates Foxp3 levels via regulating miR-34a expression, which provides a new mechanistic and therapeutic insight into the ongoing of autoimmune diseases.

Streptococcal Serology in Acute Rheumatic Fever Patients: Findings From 2 High-income, High-burden Settings.

BACKGROUND: Globally, there is wide variation in streptococcal titer upper limits of normal (ULN) for antistreptolysin O (ASO) and anti-deoxyribonuclease B (ADB) used as an evidence of recent group A streptococcal infection to diagnose acute rheumatic fever (ARF). METHODS: We audited ASO and ADB titers among individuals with ARF in New Zealand (NZ) and in Australia's Northern Territory. We summarized streptococcal titers by different ARF clinical manifestations, assessed application of locally recommended serology guidelines where NZ uses high ULN cut-offs and calculated the proportion of cases fulfilling alternative serologic diagnostic criteria. RESULTS: From January 2013 to December 2015, group A streptococcal serology results were available for 350 patients diagnosed with ARF in NZ and 182 patients in Northern Territory. Median peak streptococcal titers were similar in both settings. Among NZ cases, 267/350 (76.3%) met NZ serologic diagnostic criteria, whereas 329/350 (94.0%) met Australian criteria. By applying Australian ULN titer cut-off criteria to NZ cases, excluding chorea, ARF definite cases would increase by 17.6% representing 47 cases. CONCLUSIONS: ASO and ADB values were similar in these settings. Use of high ULN cut-offs potentially undercounts definite and probable ARF diagnoses. We recommend NZ and other high-burden settings to use globally accepted, age-specific, lower serologic cut-offs to avoid misclassification of ARF.

Crescentic infection related glomerulonephritis in adult and its outcome.

The epidemiology of infection-related glomerulonephritis (IRGN) is changing in recent times both in developed and developing nations. Although published studies showed renal outcome in adult IRGN was not as benign as in children, literature regarding clinical profile and outcome of crescentic form of adult IRGN is scarce; hence, we aimed to study the clinical profile of crescentic IRGN. We conducted a retrospective observational study in patients with crescentic IRGN in adults at the Department of Nephrology, Madras medical college, Chennai between 2009 and 2014. A total of 47 patients were included with a mean follow-up of 9.9 ± 4.2 months. The mean age was 42 ± 13.5 years. About 19.1% of patients had diabetes. The skin was the most common site of infection (38.3%) with methicillin-resistant Staphylococcus acareas (MRSA) as the most common organism. Hypocomplementemia was present in 100% in our study. Hemodialysis (HD) was required in 53.2% of patients and oral steroids were given in 78.7%. Complete renal recovery was seen only in 25.5%, progression to chronic kidney disease in 40.4%, seven patients reached end-stage renal disease, and nine patients died during follow-up. On univariate analysis, MRSA infection, the unidentified source of infection, nonisolation of organisms presence of interstitial fibrosis and tubular atrophy in renal biopsy and requirement of HD were found to be significant risk factors for poor renal outcome. In our study, crescentic form of IRGN is associated with poor renal outcome.

Henoch-Schonlein purpura, post-streptococcal glomerulonephritis and acute rheumatic carditis after Group A ß-haemolytic streptococcal infection.

Besides association with acute rheumatic fever (ARF) and acute glomerulonephritis (APSGN), in up to 40% of cases, Group A ß-haemolytic streptococcal (GABHS) infections are also implicated as a trigger for Henoch-Schonlein purpura (HSP). A 7-year-old girl with GABHS throat infection who developed HSP, APSGN and rheumatic carditis is reported. She presented with palpable purpura and arthritis in both ankles and later developed carditis characterised by mitral/aortic regurgitation and glomerulonephritis characterised by mixed nephritic/nephrotic syndrome. She had a raised anti-streptolysin titre (ASOT), blood urea nitrogen and creatinine and hypocomplementaemia (C3), and renal biopsy demonstrated endocapillary and extracapillary proliferative glomerulonephritis with crescents. Immunofluorescence microscopy demonstrated a 'full house' of immunoglobulin and complement, viz. IgA + 2, IgG + 3, IgM + 2, C3c + 1, Clq + 2 with predominantly IgG deposition. One week earlier, her 4-year-old sister had presented to another hospital with HSP complicated by microscopic haematuria, nephrotic-range proteinuria and gastro-intestinal involvement, and with raised ASOT and low C3 levels. Although HSP has been associated with either ARF or APSGN, this is the first case of a child with HSP, ARF and APSGN in combination.

Association of rheumatic fever & rheumatic heart disease with plausible early & late-stage disease markers.

BACKGROUND & OBJECTIVES: Rheumatic fever (RF) and rheumatic heart disease (RHD) are the autoimmune sequelae caused by Group A Streptococcus. RHD still remains a major concern in the developing countries due to its poor diagnosis, lack of vaccines and social awareness among population. This study was aimed to identify the plausible early- and late-stage disease markers associated with RF/RHD. METHODS: A total of 84 patients with confirmed pharyngitis (n=18), RF (n=23) and RHD (n=43) were included in the comparative analysis of different factors involved in host-pathogen interaction during RF/RHD pathogenesis. RESULTS: This study revealed high titre of serum antistreptolysin O (ASO) antibody in pharyngitis compared to RF and RHD patients, whereas procollagen type 1 C-peptide (PICP) level was elevated in RHD which showed an inverse correlation with serum ASO titre. The significant elevation of serum anti-peptide associated with RF (PARF) antibody in RF patients was correlated as a probable stage-specific determinant. In addition, pro-inflammatory cytokine profile revealed high levels of interleukin-12 (IL-12)/IL-23p40, IL-17A in RF, whereas IL-6 concentration was higher in RHD compared to healthy controls. INTERPRETATION & CONCLUSIONS: The overall assessment of the factors/ disease markers involved in host-pathogen interaction in RF/RHD may be suggestive of plausible disease marker in different groups of patients. Further studies with larger sample need to be done to better understand RF/RHD pathogenesis.

[Clinical, laboratory and instrumental criteria for myocarditis, established in comparison with myocardial biopsy: A non-invasive diagnostic algorithm]. / Klinicheskie, laboratornye i instrumental'nye kriterii miokardita, ustanovlennye v sopostavlenii s biopsiinym issledovaniem miokarda (algoritm neinvazivnoi diagnostiki).

AIM: To determine the diagnostic value of different clinical, laboratory, and instrumental signs in the diagnosis of myocarditis in patients with the picture of idiopathic arrhythmias, dilated cardiomyopathy (DCM) and in a comparison group when comparing with myocardial morphological examination. SUBJECTS AND METHODS: A study group included 100 patients (35 women; mean age, 44.7±12.5 years) with idiopathic arrhythmias (n=20) and DCM as a syndrome (n=100). All underwent myocardial morphological examination: endomyocardial biopsy (EMB) (n=71), intraoperative biopsy (n=13), study of the explanted heart (n=6), and autopsy (n=11). A comparison group consisted of 50 patients (25 women; mean age, 53.7±11.7 years) with non-inflammatory diseases of the heart (left ventricular end-diastolic dimension <6.0 cm, ejection fraction >50%) who underwent open-heart surgery (n=47), EMB (n=2), or autopsy (n=1). The investigators also performed polymerase chain reaction for cardiotropic viral DNA in the blood and myocardium, anticardiac antibody (ACA) identification, myocardial scintigraphy (n=26), coronary angiography (n=47), magnetic resonance imaging (MRI) (n=25), and multislice computed tomography of the heart (n=45). The diagnostic value of the extended spectrum of clinical, laboratory, and instrumental markers for myocarditis was estimated. RESULTS: Active/borderline myocarditis was diagnosed in 76% of the patients in the study group (75.5% in the arrhythmia subgroup and 76.3% in the DCM one) and in 24.3% of those in the comparison group (p<0.001). A viral genome in the myocardium was detected statistically significantly less frequently in the study group than that in the comparison one (40.2 and 65%, respectively; p<0.01): in 46.6% in the DCM subgroup and 15.8% in the arrhythmia one. An ACA set (sensitivity, specificity, and predictive value of positive and negative test results (45.7, 80, 80.4, and 45%, respectively)) was of the greatest diagnostic importance in identifying myocarditis; antibodies to cardiomyocyte nuclei in a titer of 1:160-1:320 had the highest specificity (93.3%). A specificity above 70% was seen for a full medical history triad (acute onset, an association between onset and infection, a symptom duration of less than one year), systemic immune manifestations, anginas in the history and elevated anti-O-streptolysin levels, systemic blood changes, Q waves/QS complexes on ECGs, local hypokinesias, pericardial effusion, atriomegalia (in arrhythmias), angina/ischemia with intact coronary arteries, and focal perfusion defects during myocardial scintigraphy. A sensitivity higher than 50% was observed for age over 40 years (differential diagnosis with genetic forms), acute onset, a correlation with infection, and delayed contrast agent accumulation, as evidenced by MSCT/MRI. CONCLUSION: When the incidence of myocarditis is similar in the arrhythmia and DCM subgroups, the viral genome detection rate is statistically significantly higher in DCM. Among the non-invasive markers, an ACA set (high sensitivity and specificity) is of the greatest diagnostic value in the diagnosis of myocarditis. The diagnostic rule based on counting the number of scores has been developed, which makes it possible to individually establish the risk of myocarditis in patients with idiopathic arrhythmias and DCM for both the determination of indications for biopsy and the lack of the possibility of its performance. The risk of myocarditis is high if there are 5-7 scores; that is close to 100% if there are 8 scores or more.

Immuno-nephelometric determination of group streptococcal anti-streptolysin O titres (ASOT) from dried blood spots: Method for validating a new assay.

This study was designed to determine the sensitivity and reproducibility of recovering anti-streptolysin O titres (ASOT) from dried blood spot (DBS) samples, a methodologic subcomponent of the penicillin pharmacokinetic studies in children receiving secondary prophylaxis with intramuscular benzathine penicillin for acute rheumatic fever.

[Retrospective analysis on 337 cases of Henoch-Schönlein purpura].

OBJECTIVE: To determine differences in incidence, causes, clinical manifestation,prognosis between children and adults in patients with Henoch-Schönlein purpura (HSP).
 Methods: We retrospectively analyzed clinical data of 337 patients who hospitalized in the Department of Dermatology, Peace Hospital affiliated to Changzhi Medical College from Feb. 2013 to Jan. 2016. All patients were divided into two groups by age: a child group (patients were less than 14 years old) and an adult group (patients were more than or equal to 14 years old). The incidence, inducement, and recovery rates were compared between 2 groups.
 Results: There were 195 (57.86%) children and 142 (42.14%) adults in all subjects, and 143 (42.43%) were less than 10 years old. The incidence of HSP in children in autumn and winter was higher than that in adults (P<0.05). Children with upper respiratory infection outnumbered adults (P<0.01). Logistic analysis results showed that age more than 14 years old, gastrointestinal symptoms, skin purpura relapsed more than 3 times, and overexpression of anti-streptolysin O(ASO) were high risk factors for the HSP kidney damage (P<0.05). Increased white blood cell count, high percentage of neutrophil, and increased platelet count were independent risk factors for gastrointestinal symptoms (P<0.05). The curative rates for children were higher than those of adults (P<0.05) and curative rates of patients without kidney damage were higher than those in patients with kidney damage (P<0.05).
 Conclusion: HSP mainly occurs in children, especially in those under 10 years old. Compared with adult patients, children with HSP are easy to be induced by upper respiratory tract infection, with relatively mild renal damage and better prognosis.

Clinical value of antistreptolysin O levels in adult patients with tonsillitis: report I.

To assess the clinical value of antistreptolysin O (ASO) level in adult patients with acute tonsillitis of group A beta-hemolytic streptococcus (GABHS) etiology and its interaction with the Centor score and throat cultures data. ASO antibody titers and throat cultures were obtained from 260 adult patients with acute tonsillitis of GABHS etiology initially proven by the Centor score. The results were compared with the group of 100 adult patients with recurrent tonsillitis who underwent tonsillectomy and with the group of 100 healthy adults. Throat cultures revealed GABHS-positive results in 69 acute cases (26.5%) and in 24 recurrent cases (24%), i.e., with no significant differences between the groups (p = 0.845). There was no significant difference between cases with GABHS-positive and with GABHS-negative throat culture in ASO titers results (mean 250 and 280, respectively, p = 0.44) but these titers were significantly higher than established normative data (p < 0.01). For the group of recurrent tonsillitis cases, the mean ASO titer was 363 being significantly higher in comparison with acute cases (p = 0.015). The ASO antibody titers are significantly higher than normative ranges in cases of acute tonsillitis in adults. The detection of the elevated titers may lead to early antibiotherapy to tonsillitis. The Centor score is supported by the ASO data and less supported by throat cultures data. Further research should reveal if these titers might have predictive value for possible further recurrence or serve as an indicator for tonsillectomy in cases of recurrent tonsillitis.

A cytokine study of pediatric Tourette's disorder without obsessive compulsive disorder.

It has been suggested that post-infectious inflammation in central nervous system is a cause of tic disorder including Tourette's disorder (TD). Since pro-inflammatory cytokines are important mediators inducing inflammation, the cytokine levels are regarded as one of the important indicators of inflammation. Several studies have investigated the relationship of autoimmunity and the pathogenesis of TD by measuring the inflammatory cytokine levels of blood. However, when using human samples, the experimental results can be affected by the factors like size of sample, comorbidity, medication that patients take and the severity of the diseases. Thus, it is important to exclude the possibility that comorbidity and medication affects the level of inflammatory cytokines in the serum of TD patients. In our experiment, we recruited 29 patients without obsessive compulsive disorder (OCD) comorbidity and the majority of these patients did not take medication. The six pro-inflammatory cytokine levels of blood between patient and healthy groups were compared, considering the factors above, to determine more accurate results. Of the cytokines we investigated, the interleukin 12 p70 (IL-12p70) and tumor necrosis factor α (TNFα) levels increased in patient group compared to healthy controls and the patient group which have anti-streptolysin O (ASO) score under the 200 or YTGSS score from 10 to 19 also showed higher IL-12p70 or TNFα levels. In addition, the patients who did not take medication showed higher TNFα levels compared to healthy controls. In conclusion, we suggest that inflammatory pathways that involve IL-12p70 or TNFα are important to the pathogenesis of TD.