Fiebre reumática aguda en adultos corriendo el año 2023, diagnóstico poco frecuente. A propósito de un caso clínico

La fiebre reumática aguda es una enfermedad con baja incidencia en nuestra región. Sus complicaciones conllevan una elevada morbi-mortalidad. El diagnóstico es un desafío en la actualidad, teniendo la clínica un rol preponderante; permitiéndonos mantener una alta sospecha a pesar de su baja incidencia. Se presenta el caso clínico de un paciente sexo masculino cuyo diagnóstico fue un reto para el equipo de salud.

Acute rheumatic fever is a disease with low incidence in our region. Its complications involve high morbidity and mortality. Its diagnosis is currently a challenge, with clinical presentation playing a predominant role, allowing us to maintain a high diagnostic suspicion despite its low incidence. The clinical case of a male patient is presented, whose diagnosis posed a challenge for the healthcare team.

A Febre reumática aguda é uma doença com baixa incidência em nossa região. Suas complicações envolvem alta morbidade e mortalidade. Seu diagnóstico é atualmente um desafio, com a apresentação clínica desempenhando um papel predominante, permitindo-nos manter uma alta suspeita diagnóstica apesar de sua baixa incidência. É apresentado o caso clínico de um paciente do sexo masculino, cujo diagnóstico representou um desafio para a equipe de saúde.

Treatment of acute pharyngitis in children: an Italian intersociety consensus (SIPPS-SIP-SITIP-FIMP-SIAIP-SIMRI-FIMMG).

Sore throat represents one of the main causes of antibiotic overprescription in children. Its management is still a matter of debate, with countries considering streptococcal pharyngotonsillitis a benign and self-limiting condition and others advocating for its antibiotic treatment to prevent suppurative complications and acute rheumatic fever. Italian paediatricians frequently prescribe antibiotics on a clinical basis regardless of microbiological results. Moreover, broad-spectrum antibiotics are inappropriately prescribed for this condition. In this regard, an intersociety consensus conference was issued to promote the judicious use of antibiotic therapy in paediatric outpatient settings. A systematic review of the literature was performed, and updated recommendations were developed according to the GRADE methodology. Antibiotic treatment with amoxicillin (50 mg/kg/day) for 10 days is recommended in all children with proven streptococcal pharyngitis. Benzathine-penicillin could be prescribed in children with impaired intestinal absorption or inability to tolerate enteral intake and in those at high risk of suppurative complications with low compliance to oral therapy. In children with suspected amoxicillin allergy, third-generation cefalosporins for five days are recommended in low-risk patients, and macrolides are recommended in high-risk ones. Candidates for tonsillectomy due to recurrent pharyngitis could be treated with amoxicillin-clavulanic acid, clindamycin, or combined therapy with amoxicillin plus rifampicin for four days, in an attempt to avoid surgery.

Maternal Blood Group Is a Possible Predictor for Developing Congenital Heart Disease in Turkish Children with Down's Syndrome.

We aimed to evaluate the clinical characteristics and the risk factors for the anomalies of Down's syndrome (DS) patients and reviewed the relation of blood groups of the patients and the mothers with these anomalies. Pediatric patients who were diagnosed with trisomy 21 between 2010 and 2022 were enrolled in this study. The medical records of the DS patients and their parents were retrospectively reviewed. A total of 48 patients applied to our clinic. 24 (50%) patients were diagnosed with congenital heart disease. 21 (43.75%) patients had hypothyroidism. The distribution of individual congenital heart defects (CHDs) was as follows: ventricular septal defect in eight (33.3%) patients, one of which also had patent ductus arteriosus (PDA); atrioventricular septal defects in seven (29.1%) patients; atrial septal defects in four (16.6%) patients, one of which also had patent ducus arteriosus; and PDA in five (20.8%) patients. One (4.2%) patient had tetralogy of Fallot. The incidence of CHD in patients with maternal blood group A was significantly higher than those without CHD, with a prevalence of 63.6 and 21.1%, respectively ( p = 0.020). Binary logistic regression analysis showed that maternal blood group A was a risk factor for CHDs (odds ratio = 6.563; 95% confidence interval: 1.259-34.204; p = 0.025). Although we found that the rate of advanced father age was high in hypothyroidism type, the regression analysis showed that it was not a risk factor. We found that maternal blood group A increased the likelihood of being born with CHDs in DS.

Increasing prevalence of galactose-α-1,3-galactose sensitization in the Danish general adult population.

BACKGROUND: Alpha-gal syndrome is a novel food allergy to the oligosaccharide galactose-α-1,3-galactose (alpha-gal) present in mammalian meat. Tick bites are considered an important route of sensitization to alpha-gal. Data on alpha-gal sensitization in the general population is scant. We utilized a unique data source of repeated population-based health examination studies to assess prevalence, time trends, risk factors, and characteristics of alpha-gal sensitization. METHODS: Alpha-gal sensitization was assessed in >11.000 adults from four health examination studies of randomly invited residents in the Copenhagen region conducted in 1990-1991, 2011-2012, 2012-2015, and 2016-2017. Alpha-gal sensitization was defined as serum specific IgE (sIgE) to alpha-gal ≥0.1 kUA/L; ≥0.35 kUA/L; ≥0.7 kUA/L; ≥3.5 kUA/L. The population was characterized according to genetically determined ABO blood group, aeroallergen sensitization, and pets at home. RESULTS: The prevalence of sIgE to alpha-gal ≥0.1 kUA/L was 1.3% in 1990-1991, 3.7% in 2012-2015 and 3.2% in 2016-2017. Of those sensitized to alpha-gal >97% reported to consume red meat at least once a week, even for sIgE to alpha-gal ≥3.5 kUA/L. Male sex, older age, aeroallergen sensitization, cat at home, and blood group A were associated with increased odds of alpha-gal sensitization. The known protective effect of blood group B was confirmed. CONCLUSION: In this general adult population, the prevalence of alpha-gal sensitization had doubled from 1990-1991 to 2016-2017. This could potentially be due to increased tick exposure and an increased atopic predisposition.

Impact of the COVID-19 Pandemic on Group A Streptococcal Necrotizing Soft Tissue Infections: A Retrospective Cohort Study.

Background: Necrotizing soft tissue infections (NSTIs) are often caused by group A Streptococcus (GAS). As the number of invasive GAS infections decreased during the coronavirus disease 2019 (COVID-19) pandemic restrictions, this study aimed to compare the occurrence of GAS-NSTIs before, during, and after the COVID-19 pandemic restrictions. Methods: This retrospective cohort study included adult patients with NSTIs admitted to the intensive care unit (ICU) of the University Hospital Zurich, Switzerland, from July 2008 to December 2023. NSTI cases were categorized as pre-, during, and postrestrictions. The primary outcome was the proportion of GAS in NSTI, and the exploratory secondary outcome was in-hospital death. A data analysis was conducted using Firth logistic regression adjusted for age, sex, diabetes, and initially affected body region. Results: Overall, 74 NSTI cases were identified, with 49 occurring before, 8 during, and 17 after the pandemic restrictions. GAS was isolated in 27 (36%) cases, with 17 (35%) pre- and 10 (59%) postrestrictions, but none during the restrictions. NSTIs caused by other bacteria persisted during the restrictions. The odds of GAS were significantly lower during the restrictions (adjusted odds ratio, 0.02; 95% CI, 0.001-0.81) compared with after, while no significant differences were found between the pre- and postrestriction periods. Conclusions: The significant decrease of GAS-NSTIs during the COVID-19 pandemic restrictions suggests that isolation measures may have prevented the transmission of GAS, resulting in a decline of GAS-NSTIs while NSTIs caused by bacteria transmitted by alternative routes persisted.

A multicentre observational study of paediatric head and neck abscesses.

INTRODUCTION: In winter of 2022/3 paediatric ENT surgeons across the UK observed that the incidence of severe abscesses in the head and neck and associated complications was higher than seen in previous years. We aimed to collate and evaluate data from across the UK to establish if this was a true rise in cases, and to describe the factors associated. METHODS: A multicentre retrospective data collection was undertaken from 13 units across the UK. Patients admitted between September 2022-February 2023 with a head and neck abscess including sinogenic, otogenic, deep and superficial neck abscesses were included. Demographic, disease specific, management and outcome data were collected. Hospital episode statistic data were also requested and analysed to allow for comparison with previous 10 years of head and neck abscesses. RESULTS: 262 patients with abscesses of the head and neck were admitted during the study period, 100 between September and November and 163 between December and February. Mastoid abscesses were the most common abscess across both groups. The rate of group A streptococcus + culture results rose significantly from 12 % in autumn group to 30 % in winter (p = 0.02). The rate of intracranial complications rose from 10 % to 18 % (p = 0.11) and the rate of venous thrombosis rose over the same timeframe from 3 % to 14 % (p = 0.01). DISCUSSION: This study demonstrated a statistically significant rise in the rate of group A streptococcus associated abscesses when comparing Autumn and Winter 2022/2023. Over the same timeframe a statistically significant rise in the proportion of patients with venous thromboses associated with H&N abscesses was noted. Interestingly, despite perceived national consensus regarding a spike in abscess incidence, the number of abscesses seen in winter 2022/2023 was in keeping with expected rates of paediatric H&N abscesses, based on pre covid year-on-year rise in incidence.

Fidelibacter multiformis gen. nov., sp. nov., isolated from a deep subsurface aquifer and proposal of Fidelibacterota phyl. nov., formerly called Marine Group A, SAR406 or Candidatus Marinimicrobia.

A Gram-negative, obligatory anaerobic, chemoheterotrophic bacterium, designated strain IA91T, was isolated from sediments and formation water from deep aquifers in Japan. IA91T derives its peptidoglycan, energy and carbon from exogenous cell wall fragments, namely muropeptides, released from actively reproducing bacteria, and is dependent on other bacteria for cell wall formation, growth and even cell shape: IA91T is irregular rod-shaped but coccoids when muropeptide is absent. IA91T grew in a temperature range of 25-45 °C with optimum growth at 40 °C. IA91T utilized limited substrates, yeast extract, muropeptides and d-lactate. The major end products from yeast extract degradation were acetate, hydrogen and carbon dioxide. Co-cultivation with a hydrogen-scavenging methanogenic archaeon promoted IA91T growth. No anaerobic respiration with nitrate, nitrite, sulphate or Fe(III) was observed. The major cellular fatty acids are C16 : 0, C18 : 1 trans9, C18 : 0 and C17 : 0. The G+C content of the genomic DNA was 45.6 mol%. Phylogenetic analysis based on 16S rRNA gene and conserved protein sequences involved in replication, transcription and translation indicated that IA91T belonged to the candidate phylum Marine Group A (MG-A, SAR406 or Ca. Marinimicrobia) with no cultivated representatives. Based on the phenotypic and phylogenomic characteristics, a new genus and species, Fidelibacter multiformis gen. nov., sp. nov., is proposed for IA91T (= JCM 39387T = KCTC 25736T). In addition, a new bacterial phylum named Fidelibacterota phyl. nov. is proposed for the candidate phylum MG-A represented by F. multiformis and Fidelibacteraceae fam. nov., Fidelibacterales ord. nov. and Fidelibacteria classis nov.

Loss of Nr4a1 ameliorates endothelial cell injury and vascular leakage in lung transplantation from circulatory-death donor.

BACKGROUND: Ischemia-reperfusion injury (IRI) stands as a major trigger for primary graft dysfunction (PGD) in lung transplantation (LTx). Especially in LTx from donation after cardiac death (DCD), effective control of IRI following warm ischemia (WIRI) is crucial to prevent PGD. This study aimed to identify the key factors affecting WIRI in LTx from DCD. METHODS: Previously reported RNA-sequencing dataset of lung WIRI was reanalyzed to identify nuclear receptor subfamily 4 group A member 1 (NR4A1) as the immediate early gene for WIRI. Dynamics of NR4A1 expression were verified using a mouse hilar clamp model. To investigate the role of NR4A1 in WIRI, a mouse model of LTx from DCD was established using Nr4a1 knockout (Nr4a1-/-) mice. RESULTS: NR4A1 was located around vascular cells, and its protein levels in the lungs increased rapidly and transiently during WIRI. LTｘ from Nr4a1-/- donors significantly improved pulmonary graft function compared to wild-type donors. Histological analysis showed decreased microvascular endothelial cell death, neutrophil infiltration, and albumin leakage. Evans blue permeability assay demonstrated maintained pulmonary microvascular barrier integrity in grafts from Nr4a1-/- donors, correlating with diminished pulmonary edema. However, NR4A1 did not significantly affect the inflammatory response during WIRI, and IRI was not suppressed when a wild-type donor lung was transplanted into the Nr4a1-/- recipient. CONCLUSIONS: Donor NR4A1 plays a specialized role in the positive regulation of endothelial cell injury and microvascular hyperpermeability. These findings demonstrate the potential of targeting NR4A1 interventions to alleviate PGD and improve outcomes in LTx from DCD.

A Case of Necrotizing Fasciitis/Myositis and Streptococcal Toxic Shock Syndrome Caused by emm22/ST46 Strain of Streptococcus pyogenes.

Streptococcus pyogenes, also known as Group A Streptococcus (GAS), can cause severe invasive diseases with high fatality rates. We report a case of necrotizing fasciitis and myositis complicated by Streptococcal Toxic Shock-Like Syndrome (STSS) caused by the invasive emm22/ST46 strain of Streptococcus pyogenes in China. A previously healthy 57-year-old Chinese Canadian man presented with right calf pain and ulceration following a hike in the Gobi Desert, which progressed to unconsciousness and severe infection. Despite initial treatment, his condition deteriorated, leading to his transfer to our intensive care unit. Metagenomic Next-Generation Sequencing identified Streptococcus pyogenes, and antimicrobial susceptibility testing revealed resistance to erythromycin, tetracycline, and clindamycin. Despite broad-spectrum antimicrobial therapy, debridement, and supportive measures, the patient's condition necessitated amputation of the right lower limb. He recovered and was discharged from the hospital on Day 43. Whole-genome sequencing of the isolate identified 15 multiple virulence factors. Phylogenetic analysis revealed that the closest relative of the isolate was a strain identified in China. This case underscores the importance of early recognition and treatment of invasive GAS infections to prevent severe outcomes, and we should pay attention to invasive emm22/ST46 GAS infections in China.

Toxic Shock Syndrome: Rare but Deadly.

Invasive group A streptococcal (GAS) disease, although rare, has a high mortality and morbidity rate, making early recognition and treatment crucial. Toxic shock syndrome (TSS) and necrotizing fasciitis are the most feared complications and require comprehensive, multidisciplinary treatment. In addition to appropriate support and resuscitation, patient management should include empirical broad-spectrum antibiotic therapy covering gram-negative bacteria, methicillin-resistant Staphylococcus aureus (MRSA), and anti-toxin therapy. Early surgical debridement is essential for improving the patient's prognosis, and other treatments, such as immunoglobulin and hyperbaric oxygen therapy (HBOT), also appear to be important. The authors describe the clinical case of a 31-year-old man with no medical history or risk factors, who developed invasive disease from Streptococcus pyogenes with rapid progression to necrotizing fasciitis, TSS, and severe multi-organ dysfunction. His management required intensive care, multiple surgical debridements, admission to the intensive care unit, and targeted as well as supportive therapy. The patient survived, but nearly a year later, he has yet to fully return to a normal life.

Sore Throat to Still's: Group A Streptococcus Causing Adult-Onset Still's Disease.

Adult-onset Still's disease (AOSD) is a rare hyper-inflammatory disease with poorly understood etiology, often presenting with nonspecific symptoms such as fever, inflammatory polyarthralgia, transient salmon-pink maculopapular rash, lymphadenopathy, and hepatosplenomegaly. We are presenting an unusual case of AOSD triggered by Group A streptococci (GAS) throat infection. We report the case of a 37-year-old male with no significant medical history admitted to medicine service after three emergency room (ER) visits. Our patient had a confirmed GAS throat infection and initially met the Jones criteria. However, further testing revealed significantly high inflammatory markers, clinically evident symmetrical synovitis in wrists and left knee, and widespread lymphadenopathy with worsening maculopapular rash. Given this, he met the Yamaguchi criteria, resulting in a diagnosis of AOSD. Group A Streptococcus infections are usually linked to acute rheumatic fever (ARF), but in our case, we believe GAS infection triggered the cascade of inflammatory responses resulting in AOSD. The patient received treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and high-dose steroids with a resolution of arthralgia, down-trending ferritin, and clinical improvement in a skin rash. To the best of our knowledge, we are reporting the first case of GAS-triggered AOSD, highlighting the need to uncover atypical causes for AOSD and warranting the need to investigate triggers for AOSD.

Case Report: MDFIC gene mutation resulting in central conducting lymphatic anomaly facilitates group A Streptococcus sepsis.

Background: Central conducting lymphatic anomaly (CCLA) is a heterogeneous disorder characterized by structural anomalies in the main collecting lymphatic vasculature. These anomalies result in chronic chylous leaks, causing issues such as congenital hydrothorax and potentially impairing the normal immune response. Recently, mutations in the MyoD family inhibitor domain-containing (MDFIC) gene have been identified as a cause of CCLA. Group A Streptococcus infections are common, and timely identification of patients at risk for severe complications is crucial. Case presentation: Here, we present the case of a 13-year-old female patient with CCLA associated with an MDFIC mutation, who suffered from a severe group A Streptococcus sepsis. Initially, the patient was unresponsive to aggressive fluid resuscitation. Although the course of the sepsis was severe, standardized treatment according to the surviving sepsis campaign proved effective in stabilizing the patient. Discussion: The patient's MDFIC mutation may have contributed to the severe clinical course of the sepsis. It is theorized that this mutation affects the function of the immune system both indirectly, by causing CCLA, and directly, by potentially influencing transcriptional activity in immune cells. More research on the effect of MDFIC mutations on immune responses is required.

Prompt diagnosis and treatment of peri-orbital necrotising fasciitis caused by group A ß-haemolytic Streptococcus (GAS): a case report.

BACKGROUND: Necrotising fasciitis is a devastating infection characterised by rapidly progressing necrotising infection of the superficial fascia with secondary necrosis of the overlying skin. AIMS: To describe the pathophysiology, differential diagnosis, and outcome in a rare case of periorbital necrotising fasciitis caused by group A ß-haemolytic Streptococcus. METHODS: A 60-year-old female with insulin-dependent diabetes presented with pyrexia and bilateral peri-orbital swelling, progressing to left periorbital necrotising fasciitis. It was caused by dual infection with group A ß-haemolytic Streptococcus and Herpes Simplex Virus 1. RESULTS: A combination of intravenous antibiotics and surgical debridement and subsequent skin grafting resulted in a beneficial outcome in our patient. CONCLUSIONS: Differentiating cellulitis and necrotising fasciitis can be difficult when presenting signs and symptoms are non-specific. If not treated quickly with antibiotics and debridement of the infected tissue, the patient may develop septic shock within hours.

Novel Diagnostic Approach for Acute Pharyngitis: Combining Machine Learning With Thermal Imaging.

We evaluated the effect of infrared thermography (IRT) on the clinical assessment of bacterial and viral pharyngitis and its impact on the predictive value of the McIsaac score algorithm for streptococcal pharyngitis in children. We also investigated if IRT could distinguish between bacterial and viral pharyngitis. The study included children aged 2-17 years presenting with sore throat and fever over 38°C from November 1, 2021, to April 30, 2022. Of the 76 assessed children, 16 were excluded due to missing data or technical issues, leaving 60 children (32 males, 28 females) divided into three groups: Group A with streptococcal pharyngitis (N = 30), viral pharyngitis (N = 16), and healthy controls (N = 14). McIsaac score and IRT imaging showed a 90% positive predictive value for streptococcal pharyngitis. While IRT alone could not distinguish between bacterial and viral infections, it significantly increased the predictive value when combined with the McIsaac score.

A Case of Multifocal Primary Pyomyositis Complicated With Toxic Shock Syndrome in a Non-tropical Region.

Primary pyomyositis, also known as tropical pyomyositis, is a primary bacterial infection of skeletal muscle following hematogenous infections. It is primarily caused by Staphylococcus aureus or Group A Streptococcus and predominantly affects children and young adults. Although rarely observed in temperate climates, its prevalence appears to be increasing. Here, we present the case of a 36-year-old male patient who manifested with persistent fever and inflammatory signs in multiple skeletal muscle locations following acute pharyngitis, further complicated by toxic shock syndrome within 48 h of admission. The blood cultures were positive for Streptococcus pyogenes and ultrasound evaluation demonstrated muscle tissue heterogeneity, associated with areas of liquid collection and subcutaneous edema, in the right pectoral muscles and bilaterally in the fibularis longus and extensor digitorum longus muscles, confirming the diagnosis of primary pyomyositis. After treatment with a prolonged course of antibiotics, the patient showed substantial clinical improvement and was completely asymptomatic at 6-month follow-up. This case illustrates the possible risks associated with primary pyomyositis and the importance of its early recognition and treatment, regardless of geographic location.

Invasive Group A Streptococcus Hypervirulent M1UK Clone, Canada, 2018-2023.

To determine invasive group A Streptococcus trends in Canada, we characterized emm1 isolates collected during 2018-2023. The percentage of hypervirulent M1UK lineage isolates increased significantly, from 22.1% in 2018 to 60.2% in 2023. Genomic analysis identified geographically and temporally associated clusters and genes associated with virulent bacteriophage acquisition.

Computerized Decision Support Systems Informing Community-Acquired Pneumonia Surveillance, France, 2017-2023.

We show the value of real-time data generated by a computerized decision support system in primary care in strengthening pneumonia surveillance. The system showed a 66% (95% CI 64%-67%) increase in community-acquired pneumonia from 2018 to 2023 for the population of France, 1 month before a national alert was issued.

Epidemiology of Streptococcus pyogenes Disease before, during, and after COVID-19 Pandemic, Germany, 2005-2023.

We analyzed 3,081 invasive and noninvasive Streptococcus pyogenes cases (January 2005-December 2023) at a tertiary care hospital in southwest Germany. Absolute numbers of case-patients increased each year from 2005 until the COVID-19 pandemic. Odds ratios for invasive streptococcal disease were significantly influenced by year, male sex, and older age.

The intricate pathogenicity of Group A Streptococcus: A comprehensive update.

Group A Streptococcus (GAS) is a versatile pathogen that targets human lymphoid, decidual, skin, and soft tissues. Recent advancements have shed light on its airborne transmission, lymphatic spread, and interactions with neuronal systems. GAS promotes severe inflammation through mechanisms involving inflammasomes, IL-1ß, and T-cell hyperactivation. Additionally, it secretes factors that directly induce skin necrosis via Gasdermin activation and sustains survival and replication in human blood through sophisticated immune evasion strategies. These include lysis of erythrocytes, using red cell membranes for camouflage, resisting antimicrobial peptides, evading phagocytosis, escaping from neutrophil extracellular traps (NETs), inactivating chemokines, and cleaving targeted antibodies. GAS also employs molecular mimicry to traverse connective tissues undetected and exploits the host's fibrinolytic system, which contributes to its stealth and potential for causing autoimmune conditions after repeated infections. Secreted toxins disrupt host cell membranes, enhancing intracellular survival and directly activating nociceptor neurons to induce pain. Remarkably, GAS possesses mechanisms for precise genome editing to defend against phages, and its fibrinolytic capabilities have found applications in medicine. Immune responses to GAS are paradoxical: robust responses to its virulence factors correlate with more severe disease, whereas recurrent infections often show diminished immune reactions. This review focuses on the multifaceted virulence of GAS and introduces novel concepts in understanding its pathogenicity.