INTRODUCTION: Takayasu arteritis is the most common large-vessel vasculitis in childhood, but there is a lack of literature regarding childhood-onset Takayasu arteritis (c-TAK) in Southeast Asia. We aim to describe a c-TAK cohort in Singapore and highlight a unique subset that first presents with Kawasaki-like disease (KD). METHOD: A single-centre cohort study in Singapore of consecutive children diagnosed with c-TAK between 2002 and 2023 was performed. Demographic and clinical features, laboratory and angiographic findings, treatment, and outcomes were summarised. Disease activity was evaluated using the Paediatric Vasculitis Disease Activity Score and inflammatory markers. RESULTS: Twenty-three patients, fulfilling both the EULAR/ PRINTO/PReS and ACR/EULAR 2022 criteria, were recruited. The most common clinical features at diagnosis were fever (15, 65%) and neurological symptoms (11, 48%, half of which presented with stroke), while the most prevalent angiographic pattern by Hata's classification was Type V (21, 91%). Eight children (35%) initially presented with refractory KD, and these patients were significantly younger, more male-predominant, and had higher inflammatory markers at diagnosis; all of them had coronary artery involvement, but none had intracranial vascular findings. Of the entire cohort, 16 (70%) achieved inactive disease on medications with a median duration of 6 months (interquartile range [IQR]: 4-11), and 8 (35%) achieved remission off medications with a median duration of 43 months (IQR 35-60). CONCLUSION Our c-TAK cohort has high proportions of neurological involvement and stroke. This is also the first cohort study to describe a distinct group of patients who first presented with refractory KD.
Humans ; Takayasu Arteritis/complications* ; Singapore/epidemiology* ; Male ; Female ; Child ; Adolescent ; Age of Onset ; Mucocutaneous Lymph Node Syndrome/diagnosis* ; Cohort Studies ; Child, Preschool ; Fever/etiology* ; Stroke/epidemiology* ; Retrospective Studies

Objective: To analyze the clinical characteristics, pathogenic bacteria, complications and risk factors of prognosis of acute hematogenous osteomyelitis in children. Methods: The clinical manifestations, laboratorg tests, etiological charateristics and clinical data of 107 patients with acute hematogenous osteomyelitis admitted to Beijing Children's Hospital from January 2017 to December 2020 were retrospectively analyzed. According to the drug sensitivity results of Staphylococcus aureus, the group was divided into methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA) group; according to the presence or absence of complications, the group was divided into the group with and without complications; according to the prognosis of the follow-up children, the group was divided into good prognosis and poor prognosis. The χ² test or Mann-Whitney U test used for comparison between groups, and Logistic regression was used to analyze the risk factors for complications and prognosis. Results: Of the 107 patients, 62 were males and 45 were females. The age of presentation was 5.6 (1.7, 10.0) years, including 5 patients (4.7%) age from >28 days to 3 months, 46 patients (43.0%) age from >3 months to 5 years, 43 patients (40.2%)>5-12 years of age, and 13 patients (12.1%)>12-18 years of age. The first symptoms were acute fever in 35 patients (32.7%), limb pain in 24 patients (22.4%), and fever with limb pain in 23 patients (21.5%). Pathogen culture was positive in 75 patients (70.1%), Streptococcus pyogenes, Salmonella enterica and Escherichia coli in 1 case (1.4%) each, and Staphylococcus aureus in 72 cases (96.0%), among them, 47 cases were MSSA, 22 cases were MRSA, and 3 cases had positive reports of Staphylococcus aureus from other hospitals without drug-sensitive tests. The proportion of infected children living in rural areas and receiving surgical treatment was higher in the MRSA group than in the MSSA group (14 cases (63.6%) vs. 18 cases (38.3%) and 21 cases (95.5%) vs. 33 cases (70.2%), χ²=3.87, 4.23, both P<0.05). Sixty-five children had no complications while 42 children (39.3%) suffered from complications. Common complications consisted of 19 cases (17.8%) of sepsis, 17 cases (15.9%) of septic arthritis, and 12 cases (11.2%) of venous thrombosis. The group with complications showed higher mental changes, decreased appetite and (or) weakness, positive pathogenic cultures, and time from admission to surgery than the group without complications (18 cases (42.9%) vs. 9 cases (13.8%), 20 cases (47.6%) vs. 12 cases (18.5%), 34 cases (81.0%) vs. 41 cases (63.1%), 3.5 (2.0, 6.0) vs. 2.0 (1.0, 4.0) d,χ²=11.38, 10.35, 3.89, Z=2.21, all P<0.05). The poor prognosis group had more comorbidities, combined local complications, and positive aureus than the good prognosis group (10/15 vs. 34.9% (30/86), 7/15 vs. 17.4% (15/86), 14/15 vs. 61.6% (53/86), χ²=5.39, 6.40, 4.42, all P<0.05). Multifactorial Logistic regression analysis showed that acute phase C-reactive protein (CRP) was both an independent risk factor for complications (OR=1.01, 95%CI 1.01-1.02) and an independent risk factor for poor prognosis (OR=1.01, 95%CI 1.00-1.02). Conclusions: The first symptoms of acute hematogenous osteomyelitis are acute fever, limb pain, and fever with limb pain are most common. Staphylococcus aureus is the most common pathogenic organism. Those with loss of appetite and (or) weakness, mental changes, positive pathogenic cultures, and longer time between admission and surgery are prone to complications. Those with complications, combined local complications, and positive for Staphylococcus aureus had a poor prognosis. Elevated CRP is an independent risk factor not only for complications but for poor prognosis as well.
Acute Disease ; Adolescent ; Anti-Bacterial Agents/therapeutic use* ; Child ; Female ; Fever/etiology* ; Humans ; Male ; Methicillin-Resistant Staphylococcus aureus ; Osteomyelitis/microbiology* ; Pain/drug therapy* ; Prognosis ; Retrospective Studies ; Staphylococcal Infections/diagnosis* ; Staphylococcus aureus

Hemophagocytic lymphohistiocytosis (HLH) was a life-threatening syndrome due to the uncontrolled immune activation of cytotoxic T lymphocytes, natural killer (NK) cells, and macrophages. HLH is characterized by primary and secondary causes, the early diagnosis and treatment of patients are closely related to the prognosis and clinical outcome of patients. The clinical presentation is variable but mostly includes prolonged fever, splenomegaly, coagulopathy, hypertriglyceridemia, and hemophagocytosis, none of them is specific and particular for HLH. Tuberculosis (TB) infection is one of the causes of HLH. HLH caused by TB is very rare clinically, but it has a high mortality. For patients with fever of unknown origin, HLH-related clinical manifestations sometimes present before the final diagnosis of TB, and HLH is associated with the most significant mortality rate. This article is mainly about a 28-year-old patient with HLH who suffered from severe TB infection. The patient attended a hospital with a history of 2 months of prolonged fever, 10 days booger and subcutaneous hemorrhage in lower limbs. Before this, he was in good health and denied any history of tuberculosis exposure. Combined with relevant laboratory test results (such as splenomegaly, hemoglobin, platelet count, and hypertriglyceridemia) and clinical manifestations (e.g. fever), the patient was diagnosed with hemophagocytic lymphohistiocytosis, but the etiology of HLH remained to be determined. To confirm the etiology, the patient was asked about the relevant medical history (intermittent low back pain) and was performed chest CT scan, bone marrow biopsy, and fundus photography. Finally, he was diagnosed with hemophagocytic lymphohistiocytosis caused by hematogenous disseminated pulmonary tuberculosis. In response to this, intravenous methylprednisolone and anti-tuberculosis treatment (isoniazid, pyrazinamide, moxifloxacin, and amikacin) were administered to the patient. After more than a month of treatment, the patient recovered from HLH caused by severe TB infection. Therefore, this case suggests that we should be vigilant to the patient who admitted to the hospital with fever for unknown reasons, to diagnose HLH as early as possible and clarify its cause, then perform interventions and treatment, especially HLH secondary to tuberculosis. Also, cases of atypical TB and severe TB should be carefully monitored to achieve early diagnosis and early intervention.
Male ; Humans ; Adult ; Lymphohistiocytosis, Hemophagocytic/diagnosis* ; Splenomegaly ; Tuberculosis, Pulmonary/diagnosis* ; Bone Marrow/pathology* ; Fever/etiology* ; Hypertriglyceridemia/complications*

OBJECTIVE: To study the clinical features of children with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome, a polygenic and multifactorial autoinflammatory disease with unknown pathogenesis. METHODS: A retrospective analysis was performed on the medical data of 13 children with PFAPA syndrome. RESULTS: All 13 children had disease onset within the age of 3 years, with a mean age of onset of (14±10) months. They all had periodic fever, with 8-18 attacks each year. The mean interictal period of fever was (30±5) days. Pharyngitis, cervical adenitis, and aphthous stomatitis were the three cardinal symptoms, with incidence rates of 100% (13/13), 85% (11/13), and 38% (5/13) respectively. There were increases in white blood cells, C-reactive protein, and erythrocyte sedimentation rate during fever. Of all the 13 children, 6 underwent whole exome sequencing and 7 underwent panel gene detection for autoinflammatory disease, and the results showed single heterozygous mutations in the CONCLUSIONS For children with unexplained periodic fever with early onset accompanied by pharyngitis, cervical adenitis, aphthous stomatitis, elevated inflammatory indices, and good response to glucocorticoids, PFAPA syndrome should be considered. This disorder has good prognosis, and early diagnosis can avoid the long-term repeated use of antibiotics.
Child ; Child, Preschool ; Fever/etiology* ; Humans ; Infant ; Lymphadenitis/diagnosis* ; Pharyngitis/drug therapy* ; Pyrin ; Retrospective Studies ; Stomatitis, Aphthous/genetics*

Humans ; Panuveitis/etiology* ; Retinal Detachment/etiology* ; Typhoid Fever/diagnosis* ; Visual Acuity

Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 as an important respiratory disease with high fatality rates of 40%-60%. Despite the increased number of cases over subsequent years, the number of pediatric cases remained low. A review of studies conducted from June 2012 to April 19, 2016 reported 31 pediatric MERS-CoV cases. In this paper, we present the clinical and laboratory features of seven patients with pediatric MERS. Five patients had no underlying medical illnesses, and three patients were asymptomatic. Of the seven cases, four (57%) patients sought medical advice within 1-7 days from the onset of symptoms. The three other patients (43%) were asymptomatic and were in contact with patients with confirmed diagnosis of MERS-CoV. The most common presenting symptoms were fever (57%), cough (14%), shortness of breath (14%), vomiting (28%), and diarrhea (28%). Two (28.6%) patients had platelet counts of < 150 × 10/L, and one patient had an underlying end-stage renal disease. The remaining patients presented with normal blood count, liver function, and urea and creatinine levels. The documented MERS-CoV Ct values were 32-38 for four of the seven cases. Two patients (28.6%) had abnormal chest radiographic findings of bilateral infiltration. One patient (14.3%) required ventilator support, and two patients (28.6%) required oxygen supplementation. All the seven patients were discharged without complications.
Adolescent ; Child ; Coronavirus Infections ; diagnosis ; physiopathology ; Diarrhea ; etiology ; Dyspnea ; etiology ; Female ; Fever ; etiology ; Humans ; Infant ; Lung ; diagnostic imaging ; Male ; Middle East Respiratory Syndrome Coronavirus ; genetics ; Pleural Effusion ; diagnostic imaging ; Radiography, Thoracic ; Saudi Arabia

Aged ; Biopsy ; methods ; Diagnosis, Differential ; Erythema ; diagnosis ; etiology ; Extremities ; pathology ; Fever ; complications ; Humans ; Immunoglobulin A ; analysis ; Male ; Purpura ; diagnosis ; etiology ; Skin ; diagnostic imaging ; pathology ; Vasculitis ; complications ; immunology

In this study, two school-aged children had an acute onset in spring and had the manifestations of fever, headache, vomiting, disturbance of consciousness, purpura and ecchymosis, and positive meningeal irritation sign. There were increases in peripheral white blood cells and neutrophils, but reductions in the hemoglobin level and platelet count in the two children. They had a significant increase in C-reactive protein. There were hundreds or thousands of white blood cells in the cerebrospinal fluid, mainly neutrophils. Increased protein contents but normal levels of glucose and chloride in the cerebrospinal fluid were found. Head CT scan showed multiple hematomas in the right cerebellum and both hemispheres in one child. Bone marrow cytology indicated infection in the bone marrow, and both blood culture and bone marrow culture showed methicillin-resistant Staphylococcus aureus (MRSA). Both patients had cardiac murmurs and progressive reductions in the hemoglobin level and platelet count during treatment, and echocardiography showed the formation of vegetation in the aortic valve. Therefore, the patients were diagnosed with infectious endocarditis (IE). Vancomycin was used as the anti-infective therapy based on the results of drug sensitivity test. One child was cured after 6 weeks, and the other child was withdrawn from the treatment and then died. Dynamic monitoring of cardiac murmurs should be performed for children with unexplained fever, and echocardiography should be performed in time to exclude IE. IE should also be considered for children with purulent meningitis and skin and mucosal bleeding which cannot be explained by the reduction in platelet count.
Adolescent ; Child, Preschool ; Endocarditis, Bacterial ; diagnosis ; drug therapy ; etiology ; Female ; Fever ; etiology ; Headache ; etiology ; Humans ; Male ; Purpura ; etiology

Autoinflammatory disease (AID) is a newly proposed category of disorders characterized by unprovoked episodes of inflammation without any infectious or autoimmune evidence. We aimed to characterize the clinical and genetic features of patients who had recurrent fever and multi-system inflammation but remain unclassified for any established AIDs. Medical records of 1,777 patients who visited our Rheumatology Clinic between March 2009 and December 2010 were reviewed to identify those who met the following criteria; 1) presence of fever, 2) inflammation in two or more organ systems, 3) recurrent nature of fever or inflammation, 4) no evidence of infection or malignancy, 5) absence of high titer autoantibodies, and 6) failure to satisfy any classification criteria for known AIDs. Genotyping was performed for common missense variants in MEFV, NOD2/CARD15, and TNFRSF1A. A small number of patients (17/1,777, 0.95%) were identified to meet the above criteria. Muco-cutaneous and musculoskeletal features were most common, but there was a considerable heterogeneity in symptom combination. Although they did not satisfy any established classification criteria for AIDs, substantial overlap was observed between the clinical spectrum of these patients and known AIDs. According to the newly proposed Eurofever criteria for periodic fevers, eleven of them were classified as TNF receptor-associated periodic syndrome and two as mevalonate kinase deficiency. However, no examined genetic variants including those in TNFRSF1A were found in these patients. A new set of classification criteria needs to be developed and validated for Asian patients with unclassified AIDs.
Adolescent ; Adult ; Cytoskeletal Proteins/genetics ; Female ; Fever/*etiology ; Genotype ; Hereditary Autoinflammatory Diseases/classification/*diagnosis/genetics ; Humans ; Inflammation/*etiology ; Male ; Middle Aged ; Mutation, Missense ; Nod2 Signaling Adaptor Protein/genetics ; Polymorphism, Single Nucleotide ; Receptors, Tumor Necrosis Factor, Type I/genetics ; Recurrence ; Republic of Korea ; Retrospective Studies ; Young Adult

Autoinflammatory disease (AID) is a newly proposed category of disorders characterized by unprovoked episodes of inflammation without any infectious or autoimmune evidence. We aimed to characterize the clinical and genetic features of patients who had recurrent fever and multi-system inflammation but remain unclassified for any established AIDs. Medical records of 1,777 patients who visited our Rheumatology Clinic between March 2009 and December 2010 were reviewed to identify those who met the following criteria; 1) presence of fever, 2) inflammation in two or more organ systems, 3) recurrent nature of fever or inflammation, 4) no evidence of infection or malignancy, 5) absence of high titer autoantibodies, and 6) failure to satisfy any classification criteria for known AIDs. Genotyping was performed for common missense variants in MEFV, NOD2/CARD15, and TNFRSF1A. A small number of patients (17/1,777, 0.95%) were identified to meet the above criteria. Muco-cutaneous and musculoskeletal features were most common, but there was a considerable heterogeneity in symptom combination. Although they did not satisfy any established classification criteria for AIDs, substantial overlap was observed between the clinical spectrum of these patients and known AIDs. According to the newly proposed Eurofever criteria for periodic fevers, eleven of them were classified as TNF receptor-associated periodic syndrome and two as mevalonate kinase deficiency. However, no examined genetic variants including those in TNFRSF1A were found in these patients. A new set of classification criteria needs to be developed and validated for Asian patients with unclassified AIDs.
Adolescent ; Adult ; Cytoskeletal Proteins/genetics ; Female ; Fever/*etiology ; Genotype ; Hereditary Autoinflammatory Diseases/classification/*diagnosis/genetics ; Humans ; Inflammation/*etiology ; Male ; Middle Aged ; Mutation, Missense ; Nod2 Signaling Adaptor Protein/genetics ; Polymorphism, Single Nucleotide ; Receptors, Tumor Necrosis Factor, Type I/genetics ; Recurrence ; Republic of Korea ; Retrospective Studies ; Young Adult