Streptococcal acute pharyngitis

Acute pharyngitis/tonsillitis, which is characterized by inflammation of the posterior pharynx and tonsils, is a common disease. Several viruses and bacteria can cause acute pharyngitis; however, Streptococcus pyogenes (also known as Lancefield group A β-hemolytic streptococci) is the only agent that requires an etiologic diagnosis and specific treatment. S. pyogenes is of major clinical importance because it can trigger post-infection systemic complications, acute rheumatic fever, and post-streptococcal glomerulonephritis. Symptom onset in streptococcal infection is usually abrupt and includes intense sore throat, fever, chills, malaise, headache, tender enlarged anterior cervical lymph nodes, and pharyngeal or tonsillar exudate. Cough, coryza, conjunctivitis, and diarrhea are uncommon, and their presence suggests a viral cause. A diagnosis of pharyngitis is supported by the patient's history and by the physical examination. Throat culture is the gold standard for diagnosing streptococcus pharyngitis. However, it has been underused in public health services because of its low availability and because of the 1- to 2-day delay in obtaining results. Rapid antigen detection tests have been used to detect S. pyogenes directly from throat swabs within minutes. Clinical scoring systems have been developed to predict the risk of S. pyogenes infection. The most commonly used scoring system is the modified Centor score. Acute S. pyogenes pharyngitis is often a self-limiting disease. Penicillins are the first-choice treatment. For patients with penicillin allergy, cephalosporins can be an acceptable alternative, although primary hypersensitivity to cephalosporins can occur. Another drug option is the macrolides. Future perspectives to prevent streptococcal pharyngitis and post-infection systemic complications include the development of an anti-Streptococcus pyogenes vaccine.

Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome is linked to dysregulated monocyte IL-1β production.

BACKGROUND: The exact pathogenesis of the pediatric disorder periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome is unknown. OBJECTIVES: We hypothesized that PFAPA might be due to dysregulated monocyte IL-1β production linked to genetic variants in proinflammatory genes. METHODS: Fifteen patients with PFAPA syndrome were studied during and outside a febrile episode. Hematologic profile, inflammatory markers, and cytokine levels were measured in the blood. The capacity of LPS-stimulated PBMCs and monocytes to secrete IL-1β was assessed by using ELISA, and active IL-1β secretion was visualized by means of Western blotting. Real-time quantitative PCR was performed to assess cytokine gene expression. DNA was screened for variants of the MEFV, TNFRSF1A, MVK, and NLRP3 genes in a total of 57 patients with PFAPA syndrome. RESULTS: During a febrile attack, patients with PFAPA syndrome revealed significantly increased neutrophil counts, erythrocyte sedimentation rates, and C-reactive protein, serum amyloid A, myeloid-related protein 8/14, and S100A12 levels compared with those seen outside attacks. Stimulated PBMCs secreted significantly more IL-1β during an attack (during a febrile episode, 575 ± 88 pg/mL; outside a febrile episode, 235 ± 56 pg/mL; P < .001), and this was in the mature active p17 form. IL-1β secretion was inhibited by ZYVAD, a caspase inhibitor. Similar results were found for stimulated monocytes (during a febrile episode, 743 ± 183 pg/mL; outside a febrile episode, 227 ± 92 pg/mL; P < .05). Genotyping identified variants in 15 of 57 patients, with 12 NLRP3 variants, 1 TNFRSF1A variant, 4 MEFV variants, and 1 MVK variant. CONCLUSION: Our data strongly suggest that IL-1β monocyte production is dysregulated in patients with PFAPA syndrome. Approximately 20% of them were found to have NLRP3 variants, suggesting that inflammasome-related genes might be involved in this autoinflammatory syndrome.

Pédiatrie. 3. Le score de McIsaac: une aide à l'indication des tests de diagnostic rapide dans tes angines à streptocoques A [Pediatrics. Using the McIsaac score for the indication of rapid diagnostic testing in children with streptococcal pharyngitis].

The McIsaac scoring system is a tool designed to predict the probability of streptococcal pharyngitis in children aged 3 to 17 years with a sore throat. Although it does not allow the physician to make the diagnosis of streptococcal pharyngitis, it enables to identify those children with a sore throat in whom rapid antigen detection tests have a good predictive value.

International periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome cohort: description of distinct phenotypes in 301 patients.

OBJECTIVES: The aims of this study were to describe the clinical features of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) and identify distinct phenotypes in a large cohort of patients from different countries. METHODS: We established a web-based multicentre cohort through an international collaboration within the periodic fevers working party of the Pediatric Rheumatology European Society (PReS). The inclusion criterion was a diagnosis of PFAPA given by an experienced paediatric rheumatologist participating in an international working group on periodic fever syndromes. RESULTS: Of the 301 patients included from the 15 centres, 271 had pharyngitis, 236 cervical adenitis, 171 oral aphthosis and 132 with all three clinical features. A total of 228 patients presented with additional symptoms (131 gastrointestinal symptoms, 86 arthralgias and/or myalgias, 36 skin rashes, 8 neurological symptoms). Thirty-one patients had disease onset after 5 years and they reported more additional symptoms. A positive family history for recurrent fever or recurrent tonsillitis was found in 81 patients (26.9%). Genetic testing for monogenic periodic fever syndromes was performed on 111 patients, who reported fewer occurrences of oral aphthosis or additional symptoms. Twenty-four patients reported symptoms (oral aphthosis and malaise) outside the flares. The CRP was >50 mg/l in the majority (131/190) of the patients tested during the fever. CONCLUSION: We describe the largest cohort of PFAPA patients presented so far. We confirm that PFAPA may present with varied clinical manifestations and we show the limitations of the commonly used diagnostic criteria. Based on detailed analysis of this cohort, a consensus definition of PFAPA with better-defined criteria should be proposed.

Major variables influencing correct antibiotic prescription by primary care physicians in acute pharyngitis: a cross-sectional study

Objectives:To analyse which are the main variables that influence primary care professionals, in the prescription of antibiotics in patients with acute pharyngitis.To analyse which is the diagnosis pattern used by primary care professionals towards cutepharyngitis. To recognize the clinical and analytical criteria that primary care professionals use, to determine antibiotic treatment in acute pharyngitis.To identify the main clinical variables related with the prescription of antibiotics by primary care professionals, in acute pharyngitis treatment. Design: Cross-­‐sectional study Participants:165 primary care professionals from the Sanitary Region of Girona not attending paediatric patients and randomly selected from 29 ABS managed by two of the main health care providers: Insitut Català de la Salut (ICS) and Institut d’Assistència Sanitària (IAS) Main outcome measures: Each participant will fill out a questionnaire with personal and workplace questions, as well as about knowledge and attitude in front of the acute pharyngitis caused by group A streptococci. They will also answer 4 clinical questions about correct treatment and diagnosis of acute pharyngitis caused by group A streptococci

Analysis of the genetic basis of periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome.

PFAPA syndrome is the most common autoinflammatory syndrome in children from Western countries. In spite of its strong familial clustering, its genetic basis and inheritance pattern are still unknown. We performed a comprehensive genetic study on 68 individuals from 14 families. Linkage analysis suggested a susceptibility locus on chromosome 8, but direct molecular sequencing did not support this initial statistical finding. Exome sequencing revealed the absence of any gene that was mutated in all patients. Exhaustive screening of genes involved in other autoinflammatory syndromes or encoding components of the human inflammasome showed no DNA variants that could be linked to PFAPA molecular pathology. Among these, the previously-reported missense mutation V198M in the NLRP3 gene was clearly shown not to co-segregate with PFAPA. Our results on this relatively large cohort indicate that PFAPA syndrome is unlikely to be a monogenic condition. Moreover, none of the several genes known to be involved in inflammation or in autoinflammatory disorders seem to be relevant, alone, to its etiology, suggesting that PFAPA results from oligogenic or complex inheritance of variants in multiple disease genes and/or non-genetic factors.

Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome: a Review of the Pathogenesis.

PFAPA syndrome represents the most common cause of recurrent fever in children in European populations, and it is characterized by recurrent episodes of high fever, pharyngitis, cervical adenitis, and aphthous stomatitis. Many possible causative factors have been explored so far, including infectious agents, immunologic mechanisms and genetic predisposition, but the exact etiology remains unclear. Recent findings demonstrate a dysregulation of different components of innate immunity during PFAPA flares, such as monocytes, neutrophils, complement, and pro-inflammatory cytokines, especially IL-1β, suggesting an inflammasome-mediated innate immune system activation and supporting the hypothesis of an autoinflammatory disease. Moreover, in contrast with previous considerations, the strong familial clustering suggests a potential genetic origin rather than a sporadic disease. In addition, the presence of variants in inflammasome-related genes, mostly in NLRP3 and MEFV, suggests a possible role of inflammasome-composing genes in PFAPA pathogenesis. However, none of these variants seem to be relevant, alone, to its etiology, indicating a high genetic heterogeneity as well as an oligogenic or polygenic genetic background.

Streptococcal acute pharyngitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

PDIA3, HSPA5 and viementin, proteins identified by 2-DE in the valvular tissue, are the target antigens of peripheral and heart infiltrating T cells from chronic rheumatic heart disease patients

Rheumatic fever (RF) is a post-infectious autoimmune disease due to sequel of group A streptococcus (GAS) pharyngitis. Rheumatic heart disease (RHD), the major manifestation of RF, is characterized by inflammation of heart valves and myocardium. Molecular mimicry between GAS antigens and host proteins has been shown at B and T cell level. However the identification of the autoantigens recognized by B and T cells within the inflammatory microenvironment of heart tissue in patients with RHD is still incompletely elucidated. In the present study, we used two-dimensional gel electrophoresis (2-DE) and mass spectrometry to identify valvular tissue proteins target of T cells from chronic RHD patients. We could identify three proteins recognized by heart infiltrating and peripheral T cells as protein disulfide isomerase ER-60 precursor (PDIA3), 78 kD glucose-regulated protein precursor (HSPA5) and vimentin, with coverage of 45%, 43 and 34%, respectively. These proteins were recognized in a proliferation assay by peripheral and heart infiltrating T cells from RHD patients suggesting that they may be involved in the autoimmune reactions that leads to valve damage. We also observed that several other proteins isolated by 2-DE but not identified by mass spectrometry were also recognized by T cells. The identified cardiac proteins are likely relevant antigens involved in T cell-mediated autoimmune responses in RF/RHD that may contribute to the development of RHD

Association of human herpesvirus 6 infection with exanthem subitum in Belem, Brazil

Recent human herpesvirus 6 (HHV-6) infection was detected in cases of exanthem subitum (ES) involving four children, aged 10 to 24 months, between April and August 1994, in Belém, Brazil. By using the indirect immunofluorescence antibody assay (IFA), significant increases (at least eight times) in antibody concentrations were noted from the acute to the convalescent serum samples, with titers ranging from <1:10/1:80 to <1:10/1:640 (patients 3 and 2, respectively). All children had high fever (over 39ºC) for three days, followed by generalized, maculo-papular skin rash. A physical examination of the children also revealed concomitant, cervical lymph node swelling and tonsillar pharyngitis in two of them.

Evolution of genotypes of Group A streptococci from colonization and infection

Dissertação para obtenção do Grau de Doutor em Biologia

Hand, Foot, and Mouth Syndrome in an Immunocompetent Adult: a Case Report

BACKGROUND: Hand, foot, and mouth syndrome (HFMS) is a common acute illness. It is characterized by mild clinical symptoms including fever, blisters, and sores in the mouth and on the palms and soles following a 3- to 7-day incubation period. This syndrome is rarely seen in adults. CASE PRESENTATION: A 35-year-old male Caucasian patient had a history of multiple episodes of acute pharyngitis, hypertension, hypercholesterolemia, and occasional abdominal pain. He presented with polyarthralgia in the knees and hands and odynophagia, followed by fever, oral mucosal aphthous lesions, and vesicles on the palms and soles. Three weeks after presentation, he was admitted to the emergency room with acute myocarditis. The in-hospital evaluation revealed positive serology for coxsackie A9 (1:160), positive anti-transglutaminase and anti-gliadin antibodies, normal immunoglobulins, and human immunodeficiency virus negativity. CONCLUSION: We herein describe a case of HFMS that was associated with coxsackie A9 infection complicated by acute myocarditis. Although an association between celiac disease and HFMS has not been described, this patient's immunologic disruption could have favored the development of infection and ultimately HFMS.

Cured by tonsillectomy: was it really a PFAPA syndrome?

We show how an ultrafast pump-pump excitation induces strong fluorescence depletion in biological samples, such as bacteria-containing droplets, in contrast with fluorescent interferents, such as polycyclic aromatic compounds, despite similar spectroscopic properties. Application to the optical remote discrimination of biotic versus non-biotic particles is proposed. Further improvement is required to allow the discrimination of one pathogenic among other non-pathogenic micro-organisms. This improved selectivity may be reached with optimal coherent control experiments, as discussed in the paper.

International consensus conference on PFAPA syndrome: Evaluation of a new set of diagnostic criteria

The PFAPA syndrome is characterized by periodic fever, associated with pharyngitis, cervical adenitis and/or aphtous stomatitis and belongs to the auto-inflammatory diseases. Diagnostic criteria are based on clinical features and the exclusion of other periodic fever syndromes. An analysis of a large cohort of patients has shown weaknesses for these criteria and there is a lack of international consensus. An International Conference was held in Morges in November 2008 to propose a new set of classification criteria based on a consensus among experts in the field. We aimed to verify the applicability of the new set of classification criteria. 80 patients diagnosed with PFAPA syndrome from 3 centers (Genoa, Lausanne and Geneva) for pediatric rheumatology were included in the study. A detailed description of the clinical and laboratory features was obtained. The new classification criteria and the actual diagnostic criteria were applied to the patients. Only 43/80 patients (53.8%) fulfilled all criteria of the new classification. 31 patients were excluded because they didn't meet one of the 7 diagnostic criteria, 8 because of 2 criteria, and one because of 3 criteria. When we applied the current criteria to the same patients, 11/80 patients (13%) needed to be excluded. 8/80 patients (10%) were excluded from both sets. Exclusion was related only to some of the criteria. Number of patients for each not fulfilled criterion (new set of criteria/actual criteria): age (1/6), symptoms between episodes (2/2), delayed growth (3/3), main symptoms (21/0), periodicity, length of fever, interval between episodes, and length of disease (19/0). The application of some of the new criteria was not easy, as they were both very restrictive and needed precise information from the patients. Our work has shown that the new set of classification criteria can be applied to patients suspected for PFAPA syndrome, but it seems to be more restrictive than the actual diagnostic criteria. A further work of validation needs to be done for this new set of classification criteria in order to determine if these criteria allow a good discrimination between PFAPA patients and other causes of recurrent fever syndromes.