Unknown Origin In Children Research Articles

Fever of unknown origin in children: A challenge persisting with advancing medical care

Although huge advances have been made in the field of medicine, fever of unknown origin (FUO) continues to be a significant health problem and an important cause of morbidity and mortality, especially in children. The aim of this study was to study current spectrum of FUO, newly emerging challenges and outcome of FUO. A prospective observational study was conducted over a 16 month period (May 2012-September 2013). 53 children aged 4 months to 15 years met the definition of FUO and were included. Children with known immunodeficiency disorders or other chronic disorders were excluded. A diagnosis was reached in 47 (88.7%) patients. Infections were the commonest cause accounting for FUO in 37 (69.8%) patients. Haematological disorders were found in 8 (15%) and autoimmune diseases in 2 (3.8%) patients. Among infections, the most common causes of FUO were tuberculosis (TB) (37.8%), enteric fever (29.7%), Epstein-Barr virus (EBV) (8.1%) and brucellosis (8.1%). TB was extra-pulmonary in 11 cases and pulmonary in 3 cases. Amongst the haematological disorders, 3 patients had haemophagocytic lymphohistiocytosis (HLH), 3 had leukemia, 1 had non-Hodgkin lymphoma and 1 had autoimmune lymphoproliferative syndrome. Juvenile idiopathic arthritis with systemic onset and polyarteritis nodosa accounted for the two cases of autoimmune disease. Elevated C-reactive protein (CRP) levels were associated with an infectious etiology. Bone tenderness, thrombocytopenia and neutropenia predicted haematological malignancy. 1 patient of HLH died of complications during initial hospitalization and 3 other patients (1 HIV, 2 TB) died on follow up. TB, especially extrapulmonary, and enteric fever are still significant public health problems and were the commonest causes of FUO in our population. Due to advances in diagnostic facilities, some diseases like urinary tract infection (UTI) and hepatitis have become less common; however, other diseases like EBV have become more common causes of FUO. HLH is emerging as a significant cause of morbidity and mortality in FUO patients.

Clinical analysis of fever of unknown origin in children: A 10-year experience in a northern Taiwan medical center.

Fever of unknown origin (FUO) was first described in 1961 as fever >38.3°C for at least 3 weeks with no apparent source after 1 week of investigations in the hospital. Infectious disease comprises the majority of cases (40-60%). There is no related research on FUO in children in Taiwan. The aim of this study is to determine the etiologies of FUO in children in Taiwan and to evaluate the relationship between the diagnosis and patient's demography and laboratory data. Children under 18 years old with fever >38.3°C for >2 weeks without apparent source after preliminary investigations at Taipei Veterans General Hospital during 2002-2012 were included. Fever duration, symptoms and signs, laboratory examinations, and final diagnosis were recorded. The distribution of etiologies and age, fever duration, laboratory examinations, and associated symptoms and signs were analyzed. A total of 126 children were enrolled; 60 were girls and 66 were boys. The mean age was 6.7 years old. Infection accounted for 27.0% of cases, followed by undiagnosed cases (23.8%), miscellaneous etiologies (19.8%), malignancies (16.6%), and autoimmune disorders (12.7%). Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were the most commonly found pathogens for infectious disease, and Kawasaki disease (KD) was the top cause of miscellaneous diagnosis. Infectious disease remains the most common etiology. Careful history taking and physical examination are most crucial for making the diagnosis. Conservative treatment may be enough for most children with FUO, except for those suffering from malignancies.

Fever of Unknown Origin in Children Aged Three Months to Fifteen Years

Results: Finally, 1100 patients were found eligible for the study. The FUO causes were infectious diseases (55.1%), collagen vascular (4.6%), neoplasm (6.7%), miscellaneous (23.3%) and undiagnosed (10.3%). Conclusions: Most fever of unknown origin results from atypical presentation of common diseases like Tuberculosis, Salmonellosis, Brucellosis, and Pneumonia.

Лихорадка неясного генеза у детей: оптимизация диагностического поиска (часть II)

Во второй части статьи по разработанной ранее схеме продолжено описание наиболее распространенных в педиатрической практике системных воспалительных заболеваний соединительной ткани и заболеваний из так называемой смешанной группы, которые изначально могут быть недиагностированными и маскироваться под лихорадкой неясного генеза. Предлагается поэтапный подход в реализации диагностического поиска при лихорадке неясного генеза.

Fever of Unknown Origin in Children: A 6 year- Experience in a Tertiary Pediatric Egyptian Hospital.

Fever of unknown origin (FUO) is among the most conditions which poses challenge in diagnosis. The presence of information on regional patterns of FUO will shorten the time for diagnosis and reduces health services costs. There are almost no previous studies describing the etiology of FUO in children of Egypt or nearby countries. To determine different causes of FUO and the possible diagnostic procedures. Data of patients with FUO, presented to the Infectious Diseases Unit of Mansoura University Children Hospital, were retrospectively collected in a 6 year-period from May 2006 to May 2011. The study included children with a fever of 38.3° C or more documented by a health care provider and for which the cause could not be identified after 3 weeks of evaluation as an outpatient or after a week of evaluation in hospital. Patients were then categorized into 5 groups. 127 patients met the diagnostic criteria. Infectious diseases were the commonest causes of FUO in 46 cases (36.22%) followed by the miscellaneous causes in 38 cases (29.9%). Meanwhile, collagen vascular diseases and malignancy were diagnosed in 13 cases (10.2%) and 10 cases (7.87%) respectively. While, 20 cases (15.75%) remained undiagnosed. Infectious diseases are the commonest cause of FUO. The delay in diagnosis was due to atypical presentations or inappropriate use of antibiotic prior to the referral. Non infectious causes, malignancy and collagen or vascular disorders were diagnosed in rest of the patients. However, about 15% of our patients remained undiagnosed. The diagnosis was established by non-invasive means in more than two-third of the cases.

Index of Suspicion

The reader is encouraged to write possible diagnoses for each case before turning to the discussion. We invite readers to contribute case presentations and discussions. Please inquire first by contacting Dr. Deepak Kamat at DKamat@med.wayne.edu. A 2-year-old boy with a history of eczema and food allergies to nuts and soy presents to the emergency department with a 10-day history of generalized edema. The swelling began in the periorbital area but soon progressed to involve his entire body. There have been no fevers or any recent illnesses other than 1 day of cough and a few watery stools. He has had no new exposures to foods or other substances. His family history is remarkable for multiple allergies and eczema. Physical examination reveals a temperature of 98.8°F (37.1oC), heart rate of 98 beats per minute, respiratory rate of 36 breaths per minute, blood pressure of 103/65 mm Hg, and an oxygen saturation of 97% on room air. His weight is 12.6 kg (34th percentile). He is noted to have a moderate amount of periorbital edema, decreased breath sounds at the lung bases bilaterally, a protuberant abdomen, and 2+ pitting edema on his lower extremities. The rest of his physical examination findings are within normal limits. Laboratory evaluation reveals a white blood cell count of 23,800/μL (23.8 × 109/L), with 37% neutrophils, 49% lymphocytes, 4% bands, 7% monocytes, and 3% eosinophils; hemoglobin level of 13.3 g/dL (133 g/L); and platelet count of 427 × 103/μL (427 × 109/L). Serum electrolyte, blood urea nitrogen, and creatinine levels are normal. Sodium level is 132 mEq/L (132 mmol/L). Serum albumin level is 1.7 g/dL (17 g/L) (reference range, 3.4-5.4 g/dL [34-54 g/L]). Total protein level is 3.8 g/dL (38 g/L). Aspartate aminotransferase, alanine aminotransferase, and coagulation profiles …

The role of Interleukin-6, its −174 G>C polymorphism and C-reactive protein in idiopathic cardiac arrhythmias in children

ABSTRACT Purpose: Knowledge about the role of inflammation in the pathogenesis of arrhythmias in children is limited. Several studies have suggested a relationship between plasma IL-6 levels and/or the -174G>C IL-6 gene polymorphism and atrial fibrillation in adults. Our present study was performed to investigate whether serum IL-6, -174G>C IL-6 polymorphism and C-reactive protein (CRP) are associated with arrhythmias of unknown origin in children. The study included 126 children diagnosed with supraventricular or ventricular arrhythmia. Patients with congenital heart defects as well as arrhythmias of known origin were excluded from the study. The control group comprised 37 healthy children. The 24 hour Holter electrocardiography monitoring was performed. Serum IL-6, -174 GC IL-6 polymorphism and CRP concentrations were measured on admission. There were no differences in IL-6, CRP and -174 G>C IL-6 genotype distribution between the control and patient groups. No significant differences in IL-6, CRP and -174 G>C IL-6 genotypes were observed between children with supraventricular or ventricular arrhythmias. The severity of arrhythmias showed also no associations with IL-6, CRP or -174 G>C IL-6 genotypes. The results suggest that idiopathic cardiac arrhythmias of unknown origin in children are not associated with selected pro-inflammatory markers of infections i.e. elevated IL-6, CRP or -174 G>C IL-6 polymorphism. This new information can effectively reduce the total financial cost of unnecessary diagnosis and treatment of children affected by cardiac arrhythmias.

A Roadmap for Fever of Unknown Origin in Children

Fever of unknown origin (FUO) in adults is conventionally defined by the occurrence of body temperatures above 38.3 degrees C (101 degrees F) for a period of 3 weeks without any identified etiology after a period of 1-week hospitalization. The issue of FUO in pediatrics is rather hazy and still represents a challenging diagnostic dilemma. Most of the available data are limited to nationwide cohorts of patients of any age. The major difficulty in establishing a diagnosis is that the characteristic features rendering specific disorders clinically recognizable are absent or subtle, hence only a painstaking questioning on family background may elicit the correct investigative path. No diagnostic algorithms are actually available and clinicians must rely on a very careful step-by-step evaluation of the single patient. The need for invasive diagnostic techniques should be closely taken into consideration when laboratory tests or simple imaging procedures fail to discern the origin of FUO. Fevers with no reasonable explanation and no localizing signs often conceal different common diseases in children, which tend to display an unusual or atypical pattern. The principal causes behind FUO in pediatric age remain infections, followed by collagen vascular diseases and neoplastic disorders, although most children with malignancies present other systemic signs or suggestive laboratory abnormalities. The possibility of autoinflammatory syndromes, drug fever, and factitious fever should also be taken into account.

266: Cardiac Magnetic Resonance in Children with Acute Myocarditis

Diagnosis of acute myocarditis (AM) is challenging because its clinical presentation may overlap with that of common infectious diseases or be diagnosed as idiopathic dilated cardiomyopathy (DCM). While Cardiac Magnetic Resonance (CMR) imaging has emerged as an important non-invasive tool in the diagnostic procedure of AM in adults, data on CMR in children remain scarce. To describe feasibility of CMR and its contribution for the diagnosis and follow-up of AM or for the etiology left ventricular (LV) dysfunction of unknown origin in children. Over a period of 3 years, 43 children underwent CMR for clinical suspicion of AM with or without LV dysfunction of unknown origin. CMR sequences included unenhanced cine-steady state free precession (SSFP), black-blood-prepared T1-weighted images and T2-weighted images and T1-weighted images (EGE) and 3D late gadolinium-enhanced after injection of gadolinium chelate (LGE). The diagnosis of myocarditis was based on the recently consensus criteria. CMR was repeated during follow-up in children with confirmed diagnosis of AM. AM was diagnosed by CMR in 30/43 children: 22/30 had LV dysfunction, 8/30 had normal LV function but elevated blood levels of troponin I. T2 hyper-signal was present in 21 cases, EGE and/or LGE were present in 28/43 cases. Two children died during hospitalization. All survivors with LV dysfunction had normal echocardiography after a median follow-up of 10 months. 24/30 patients had control CMR that revealed in 4 cases the persistence of inflammation in T2-weighted images and in 6 case persisting LGE. No children with AM without LV dysfunction developed dilated cardiomyopathy. The remaining 13/43 children without AM on CMR were diagnosed with DCM: 2/13 normalized after 4 and 30 months of follow-up respectively, and 11/13 are still followed for dilated cardiomyopathy. CMR in children with clinical suspicion of AM or with LV dysfunction of unknown origin is feasible and useful in the diagnostic work-up. It may help to adapt medical targeted therapy and to be more precise in prognosis assessment in infants recently diagnosed with DCM of unknown origin.

Physician Variability in Treating Pain and Irritability of Unknown Origin in Children with Severe Neurological Impairment

Pain and irritability of unknown origin (PIUO) is a challenging problem for nonverbal children with severe neurological impairments. PIUO is not associated with an identifiable source of nociceptive-inflammatory or neuropathic pain. To assess how physicians use pharmacotherapy to treat PIUO, and to report a pilot study of a standardized approach to investigating and treating PIUO. Part 1 of the present study involved independently presenting a case vignette of a patient with PIUO to six experienced physicians who care for children with neurological impairments. They were asked for medication choices and sequences to empirically treat PIUO. Part 2 was a pilot study of a PIUO protocol. Patients followed a standard pathway for PIUO, referred to as the pathway for unknown pain (PUP). The initial drug sequence for the PUP was based on Part 1. In Part 1, physicians responding to the case vignette listed eight medications (atypical antipsychotics, benzodiazepines, gabapentin, methadone, opioids, selective serotonin reuptake inhibitors, tramadol and tricylic antidepressants) and eight empiric drug sequences. In Part 2, eight children with PIUO (six to 17 years of age; five females, three males) were enrolled in a pilot clinic. Only two had been fully evaluated for nociceptive-inflammatory pain sources before enrollment. At the end of the pilot study, four patients were clinically improved and only three required a study medication. Even experienced physicians do not agree on a common approach for medical treatment of PIUO. A standardized pathway is feasible and readily implemented. The proposed PUP has the potential to address PIUO and be the basis for future intervention studies.

Brucellosis as a Cause of Fever of Unknown Origin in Children Admitted to a Tertiary Hospital in the Aegean Region of Turkey

The aim of the study was to determine the role of brucellosis in children with fever of unknown origin (FUO) in the Aegean region of Turkey. For this purpose, the records of all children referred or admitted with diagnosis of FUO to the Department of Pediatric Infectious Diseases, Ege University Medical School, between 2003 and 2008 were scanned and 92 cases were identified retrospectively. Fifty-eight of these 92 children (63%) were diagnosed with infectious diseases, brucellosis being the most frequent cause (15.2%). Although several other infectious diseases do appear as a cause of FUO, brucellosis should be particularly considered as a differential diagnosis.

Fever of Unknown Origin in Children

Fever of Unknown Origin in Children

Fever of unknown origin in children: a systematic review

there are no previous systematic reviews of published pediatric case series describing the etiology of fever of unknown origin (FUO). The purpose of collecting these data is to determine the etiologies for children with FUO in both developing and developed countries. the database Ovid Medline R (1950 to August 2009 week 4) and Ovid Embase (1980 to 2010 week 2) were used to conduct the search. Studies in any language were included if they provided the diagnosis in a series of 10 or more children with FUO. The diagnosis of each child at the time of publication of the study was recorded. there were 18 studies that met the inclusion criteria, describing 1638 children. The diagnosis at the time of publication was malignancy for 93 children (6%), collagen vascular disease for 150 (9%), miscellaneous non-infectious conditions for 179 (11%), infection for 832 (51%), and no diagnosis for 384 (23%). There were 491 bacterial infections (59% of all infections) with common diagnoses being brucellosis, tuberculosis, and typhoid fever in developing countries, osteomyelitis, tuberculosis, and Bartonellosis in developed countries, and urinary tract infections in both. For children with no diagnosis after investigations, most had fever that ultimately resolved with no sequelae. about half of FUOs in published case series are ultimately shown to be due to infections with collagen vascular disease and malignancy also being common diagnoses. However, there is such a wide variety of possibilities that investigations should primarily be driven by the clinical story.

Diagnostic approach to the fever of unknown origin in children - Emphasis on the infectious diseases -

Fever of unknown origin (FUO) has been a convenient term used to classify patients who warrant a particular systemic approach to diagnostic evaluation and management. The greatest clinical concern in evaluating FUO is identifying patients whose fever has a serious or life-threatening cause when a delay in diagnosis could jeopardize successful intervention. Thorough history and complete physical examination are critical to uncover the etiologic diagnosis. Most cases of FUO in children are caused by atypical presentations of common diseases rather than by typical manifestations of rare disorders. Selection of diagnostic tests and speed of investigation should be guided by a knowledge of the disease severity, patient age, epidemiologic and geographic information, and any positive findings from a detailed history and physical examination. The three most common causes of FUO in children are infectious diseases, connective tissue diseases, and malignancy. In general, the prognosis of FUO in children is better than that of adults. Although the outcome is dependent on the primary disease process, fever abates spontaneously in most cases in whom the cause of fever remains unclear.

Kikuchi-Fujimoto Disease Is a Rare Cause of Lymphadenopathy and Fever of Unknown Origin in Children: Report of Two Cases and Review of the Literature

Kikuchi-Fujimoto Disease Is a Rare Cause of Lymphadenopathy and Fever of Unknown Origin in Children: Report of Two Cases and Review of the Literature

Age and gender differences of psychogenic fever: a review of the Japanese literature

BackgroundPsychogenic fever is one of the most common psychosomatic diseases. Patients with psychogenic fever have acute or persistent body temperature above normal range in psychologically stressful situations. In spite of numerous case reports on psychogenic fever, there are few epidemiological studies. Therefore, our goal was to investigate the age distribution and gender differences of psychogenic fever in Japan.MethodsTo achieve this goal, we searched Medline and Ichushi WEB, a Japanese medical database, and added other publications that were not included in these databases. Thus, we reviewed 195 Japanese cases of psychogenic fever published in 62 papers.ResultsPsychogenic fever patients ranged from 3 to 56 years old, with the highest number of cases occurring in 13 year-olds in both sexes. The male: female ratio of 1: 1.19 suggested a slight predominance of female cases. Psychogenic fever accounted for 18% of fever cases of unknown origin in children and 2–6% of the psychosomatic diseases of pediatric patients. Patients with psychogenic fever were not only found in pediatrics departments, but also in psychosomatic medicine, psychiatry, internal medicine, anesthesiology, dentistry, and obstetrics/gynecology departments.ConclusionThe age of psychogenic fever patients ranged from 3 to 56 years old and the male: female ratio was 1:1.19. Psychogenic fever is seen especially in adolescence in Japan.

Management of speech impairment in children: The journey so far and the road ahead

The management of speech impairment of unknown origin in children requires speech-language pathologists (SLPs) to make a number of important clinical decisions. These decisions resolve around assessment, analysis, diagnosis and intervention. Ideally, clinicians should be guided in their clinical decision making by the best available published evidence. Over 30 years ago, this was a relatively straightforward task. Most children's speech problems were assessed and analysed from an articulation perspective, and children were provided with articulation-based intervention. Since the paradigm shift from articulation to phonology, it could be argued that clinical decision making has become challenging. This challenge is not due to a limitation of options for children with unintelligible speech, but due to a plethora of knowledge and approaches for assessment, analysis, diagnosis and intervention. This paper summarizes the current state of knowledge in the management of speech impairment in children. The benefit...

Kikuchi-Fujimoto Disease Is a Rare Cause of Lymphadenopathy and Fever of Unknown Origin in Children

Kikuchi-Fujimoto disease, a benign and unusual self-limiting histiocytic necrotizing lymphadenitis of unknown origin, should be included in the differential diagnosis of lymphadenopathy and fever of unknown origin. This disease mostly affects young Asian women and has rarely been reported in children, thus remaining a poorly recognized entity that is frequently confused with malignant lymphoma. The authors describe two children with Kikuchi-Fujimoto disease, with particular attention to diagnostic approach and clinical and histologic features of the disease.

Pyrexia of unknown origin in children: a review of 102 patients from Turkey.

Pyrexia of unknown origin (PUO) has not been appropriately investigated in Turkish children and therefore a study was undertaken to determine the causes of PUO and to evaluate which clinical procedures are useful in establishing a diagnosis. A total of 102 children fitting the classical PUO criteria seen in our clinic between 1995 and 2002 were investigated retrospectively. Infections, collagen vascular disorders, malignancy and miscellaneous conditions constituted 44.2%, 6.8%, 11.7% and 24.5% of cases, respectively, while 12.8% of the cases remained undiagnosed. Enteric fever, brucellosis and respiratory tract infections were the most commonly encountered infections, whereas familial Mediterranean fever was the commonest non-infectious disorder. Biopsy, aspiration, serology, bacteriology, radiology and observation of the clinical course were the most useful diagnostic procedures.

Environnement domestique et intoxication aiguë au propylène glycol chez un nourrisson de deux ans. À propos d’une observation inhabituelle

Background. – Acute propylene glycol intoxication in a two-year-old toddler underlines the potentially serious toxicity in children of this chemical agent present as a diluent in many drugs and environmental products such as cosmetics, diapers, cleansing towels, despite a common consideration of safety and lack of toxicity. Case report. – A two-years-old boy previously healthy was found in the morning by his parents in his cradle, lethargic, responsive only to sharp pain. On admission, vital signs were: temperature 38.5°C, lethargy, polypnea; propylene glycol intoxication through disposable cleansing towels chewing was ascertained by anamnesis and blood urine analyses which revealed metabolic acidosis and serum propylene glycol peak. Conclusion. – Environmental acute propylene glycol intoxication must be considered and searched for in front of a metabolic acidosis case of unknown origin in children.