Infections predominate early in FUO diagnoses, and the longer FUO remains undiagnosed, the less likely it is caused by an infection.27 After infections, the etiology of FUO transitions to noninfectious inflammatory diseases and malignancies, which can guide subsequent testing. In addition, IP-10 has also been reported to be associated with increased viral load, lung injury, ICU admission, and mortality [21]. 2015 Sep 30;15:399. doi: 10.1186/s12879-015-1141-3. The median age was 34 years of age (5 th - 95 th percentile: 17-59) and males comprised 1971 (69.3%) of study sub- None had symptoms of urinary tract infection, thrombophlebitis, or Clostridioidesdifficile diarrhea. https://www.moh.gov.sg/content/moh_web/home/Publications/Reports/2006/co http://www.who.int/tdr/publications/documents/dengue-swg.pdf, Brady OJ, Gething PW, Bhatt S, Messina JP, Brownstein JS, Joen AG, et al. A fever is a rise in body temperature. Blue and red represent low and high concentrations, respectively. 8600 Rockville Pike A fever is a body temperature of 100.4 F or greater. 2017 Jun 22;4(3):ofx133. -. Infect Drug Resist. Author disclosure: No relevant financial affiliations. This can happen when your body is fighting an infection. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). In this study, saddleback fever was defined as temperature >37.5C with defervescence of at least one day, followed by a second peak lasting at least one day. The reference values for the normal ranges of laboratory tests were in accordance with those used by the hospital laboratory. Communicable Diseases Surveillance in Singapore 2005. These patients required prolonged periods of observation and symptomatic treatment. Cytokines were determined with multiplex View PDF Save to Library Unauthorized use of these marks is strictly prohibited. Statistical analyses were performed with the Mann-Whitney. Available at: Ministry of Health (MOH) Singapore. In one review, an ESR of 100 mm per hour or greater had a high specificity for malignancy (96%) and infection (97%), and its positive predictive value was 90%.29 A normal ESR has a high negative predictive value for temporal arteritis.28,30 An ESR that is not elevated has no diagnostic value and does not rule out neoplastic or other disorders.27 CRP level is a sensitive marker for infection and inflammation, but it is not sensitive enough to discriminate between disease processes.28 However, a more recent prospective study found that the chance of establishing a diagnosis was higher in patients who had an elevated CRP level and ESR.15, Procalcitonin is a newer marker specific for bacterial infection. McClung HJ. Out-of-hospital cardiac arrest and in-hospital mortality among COVID-19 patients: A population-based retrospective cohort study. Lancet 2020; 395:497506. eCollection 2022 Jul. Clipboard, Search History, and several other advanced features are temporarily unavailable. Ying-Hao P, Yuan-Yuan G, Hai-Dong Z, Qiu-Hua C, Xue-Ran G, Hai-Qi Z, Hua J. However, as the number of patients with prolonged fever requiring ICU admission is small in this cohort, further studies should be done to prove this correlation. In multiple studies, procalcitonin has been shown to have a specificity ranging from 70% to 98%, with a higher specificity for bacterial infection than other markers.28,31,32 It may be helpful in distinguishing between fevers with a bacterial cause vs. noninfectious inflammatory diseases, but its role in the workup of FUO is currently undefined.28,32, If the diagnosis remains elusive, tests targeting malignancies and noninfectious inflammatory diseases should be considered. Challenges in dengue fever in the elderly: Atypical presentation and risk of severe dengue and hospital-acquired infection. 2022 May 20;15:2575-2587. doi: 10.2147/IDR.S355064. -. Mucosal bleeding, anorexia, diarrhea, abdominal pain, nausea or vomiting, lethargy, rash, clinical fluid accumulation, hepatomegaly, nosocomial infection, leukopenia, higher neutrophil count, higher hematocrit, higher alanine transaminase (ALT) and aspartate transaminase (AST), higher creatinine, lower protein and prolonged activated partial thromboplastin time (APTT) were significantly associated with prolonged fever but not platelet count or prothrombin time (PT). Would you like email updates of new search results? Our cohort only had 1 mortality, and this may be reflective of the overall low mortality rate in Singapore. Federal government websites often end in .gov or .mil. A Two-Year Review on Epidemiology and Clinical Characteristics of Dengue Deaths in Malaysia, 2013-2014. A fever is a rise in your body temperature. It's usually a sign of infection. Human immunodeficiency virus and appropriate region-specific serologic testing (e.g., cytomegalovirus, Epstein-Barr virus, tuberculosis) and abdominal and pelvic ultrasonography or computed tomography are commonly performed. Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. Two remained in the general ward throughout their stay without any complications, while 2 were admitted to the ICU, 1 of whom died from acute respiratory distress syndrome. Fever of unknown origin (FUO) in adults is one of the most vexing clinical conditions for clinicians and patients. ELIZABETH C. HERSCH, COL, MC, USA, AND C. ROBERT, OH, LTC, MC, USA. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. When compared with controls, both prolonged and saddleback fever were associated with hypoxia, with the highest rate seen in cases with prolonged fever (27.8 percent and 14.3 percent vs 0.9 percent for prolonged and saddleback fever vs control, respectively; p<0.01 and p=0.03 for each respective comparison). We conducted a hospital-based casecontrol study of patients admitted for COVID-19 with prolonged fever (fever>7 days) and saddleback fever (recurrence of fever, lasting <24 hours, after defervescence beyond day 7 of illness). If there are no potentially diagnostic clues, the patient should undergo a minimum diagnostic workup, including a complete blood count, chest radiography, urinalysis and culture, electrolyte panel, liver enzymes, erythrocyte sedimentation rate, and C-reactive protein level testing. Figure 1 outlines a diagnostic approach to patients with prolonged febrile illness and FUO.1,2,47,1520,23,27, Hospitalization may be considered at any time during the evaluation, especially if the patient exhibits signs of a critical illness. Rash. Keywords: The .gov means its official. Europe PMC is an archive of life sciences journal literature. A larger cohort might help to improve our understanding of these patients. doi: 10.9778/cmajo.20200250. Fever is a nonspecific symptom that may be caused by infectious and noninfectious conditions, including malignancies, systemic rheumatic diseases, and drug reactions. 2013 Oct 20;20(1):75. doi: 10.1186/1423-0127-20-75. eCollection 2022. and transmitted securely. A lower IP-10 level is consistent with the finding that saddleback fever cases tend to have better clinical outcomes than prolonged fever cases. B, Comparison of immune mediator levels in patients with prolonged fever (n=11), patients with saddleback fever (n=8), and patients with fever that lasted 7 days (control; n=56). Both COVID-19 and the common cold can include a runny nose, sore throat, and fever, says Dr. Fisher, and both can last between a few days or a week. The differences in cytokine and chemokine profiles among [the three groups] suggest that different immunological responses could result in the differences in the clinical phenotype observed, said Ng and co-authors. Comparing the difference between prolonged fever cases and saddleback fever cases, we found an increased IL-1 level and lower IP-10 level on admission. Statistical analyses were performed using GraphPad Prism, version 8. Results: The most common subgroups in the differential are infection, malignancy, noninfectious inflammatory diseases, and miscellaneous. Would you like email updates of new search results? All Rights Reserved. In conclusion, we reported on the prevalence, risk factors, cytokine profiles, and outcomes of patients with COVID-19 who had saddleback or prolonged fever. Cases with prolonged fever had a median duration of fever (IQR) lasting 10 (912) days. Epub 2022 Aug 11. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Oxford University Press is a department of the University of Oxford. IL-1 is a pyrogenic cytokine that plays a central role in inflammatory diseases like arthralgia [23]. Your body temperature can vary depending . The levels of other immune mediators measured were not significantly different between groups. Safety and Efficacy of Imatinib for Hospitalized Adults with COVID-19: A structured summary of a study protocol for a randomised controlled trial. Search life-sciences literature (41,164,937 (41,164,937 Conti P, Panara MR, Barbacane RC, et al. "It is extremely difficult to tell the difference," explains Dr. Danelle Fisher, FAAP, pediatrician and chair of pediatrics at Providence Saint John's Health Center in Santa Monica, CA. Epub 2022 Aug 27. Seven more confirmed cases of novel coronavirus infection in Singapore. Statistical analyses were performed with the Mann-Whitney U test (*P<.05; **P<.01; ***P<.001). 2021 Mar 8;9(1):E181-E188. The site is secure. Data were collected for the remaining 110 patients from this cohort as controls; 57.0% (81/142) of all study subjects were male, and the median age (interquartile range [IQR]) was 42 (3154) years. Erythrocyte sedimentation rate and C-reactive protein levels should be measured in the initial workup of a patient who has prolonged febrile illness without a clear source. Hypoxia was defined as requirement for supplemental oxygen. For most people, a temperature of 98.6 F or 37 C is baseline. This content is owned by the AAFP. . Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. Two of these patients were admitted to the ICU, which may suggest another phenotype of patients who are at higher risk of adverse outcomes. To our knowledge, this is the first study to examine the association between the patterns of fever and outcomes in COVID-19. Elevated lactate dehydrogenase levels can be indicative of infectious and malignant causes of FUO, including malaria, lymphoma, and leukemia.15,21 Measurement of ferritin levels may also be helpful.33 An elevated ferritin level in prolonged febrile illness may indicate malignancy (especially myeloproliferative disorders) and other noninfectious inflammatory diseases, such as systemic lupus erythematosus or temporal arteritis.21,33 One study established a ferritin level of 561 ng per mL (1,261 pmol per L) as the optimal cutoff value to predict that FUO was due to a noninfectious cause.22 Extreme elevation of ferritin levels (greater than 1,000 ng per mL [2,247 pmol per L]) can point to adult Still disease.34 Infection is the most common reason ESR is extremely elevated, but if there is no evidence of infectious causes, clinicians should consider malignancy, renal disease, and inflammatory disorders if the ESR is 100 mm per hour or greater.29. QJM. government site. Notably, patients with prolonged fever had higher IP-10 and lower IL-1 levels as compared with patients with saddleback fever (Figure 1B). Background: In one study of patients with FUO, chest and abdominal CT had high sensitivity (82% and 92%, respectively) and were recommended if the initial evaluation was unrevealing.15 CT specificity ranged from 60% to 70%, consistent with other case series.15,16 Echocardiography is recommended if there are clinical indications of endocarditis.5,20 Venous Doppler ultrasonography is indicated for suspected thromboembolism.20 Magnetic resonance imaging of the aortic arch and great vessels of the neck was shown to be helpful when vasculitis was suspected.36, Nuclear imaging studies are noninvasive, image the whole body, and can localize a potential infectious or inflammatory cause for FUO.5,14,19,3740 Recently, 18F fluorodeoxyglucose positron emission tomography technology has been evaluated for guiding further invasive testing, especially in patients who have an elevated ESR or CRP level.14,37 The 18F fluorodeoxyglucose is taken up by inflammatory and cancer cells because of their high rate of glucolysis.14,18,37 Several studies examining this method in patients with FUO found diagnostic yields ranging from 16% to 69%,15,37,38 with a high positive predictive value (93%) and negative predictive value (100%).39,40 A hybrid of CT and 18F fluorodeoxyglucose positron emission tomography has a higher diagnostic yield (sensitivity of 56% to 100%; specificity of 75% to 81%18). Plasma fractions were isolated from blood samples of COVID-19 patients collected during the acute phase (median post-illness onset, 6 days). The search included reviews, case series, meta-analyses, and randomized controlled trials. To investigate whether the fever patterns experienced by the patients are due to differences in immune responses, concentrations of 45 immune mediators were profiled. In patients with saddleback fever, higher levels of IL-1, IL-21, IL-22, and SDF-1 were observed compared with control patients. IL-1 is dual function cytokine that can act as both a transcription factor and a damage-associated molecular pattern (DAMP), which can be released by necrotic cells to promote and exacerbate inflammation via IL-1R1 [30]. Patients who tested positive were not discharged until they had 2 negative PCR tests 24 hours apart [13]. Those with prolonged fever had a median duration of fever (interquartile range [IQR]) of 10 (911) days for prolonged fever cases, while fever recurred at a median (IQR) of 10 (812) days for those with saddleback fever. PMC 2013; 496: 504507. But there are some important differences. At the initial encounter, testing for common infections should include a complete blood count with differential, electrolyte panel, liver enzymes, urinalysis with culture, blood culture, and chest radiography. Compared with prolonged fever, saddleback fever did not show many significant associations except for diarrhea, abdominal pain, clinical fluid accumulation, hematocrit and platelet change, and lower systolic blood pressure. The 2011 dengue haemorrhagic fever outbreak in Lahore - an account of clinical parameters and pattern of haemorrhagic complications. COVID-19 and sinus infections share several symptoms like nasal congestion, fever, and coughing. 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difference between prolonged fever and saddleback fever