There were no significant changes in laboratory findings when repeated at the point of fever, except for a rise in platelet and lymphocyte counts (Table 2). doi: 10.1371/journal.pone.0167025. Unauthorized use of these marks is strictly prohibited. Immune mediator levels in Triton X-100 (1%; Sigma Aldrich) inactivated plasma from a subset of patients in all 3 groups were measured using Cytokine/Chemokine/Growth Factor 45-plex Human ProcartaPlex Panel 1 (ThermoFisher Scientific), in accordance with the manufacturers instructions. Pizzo PA, Lovejoy FH Jr, Smith DH. For most people, a temperature of 98.6 F or 37 C is baseline. Duration of rhinorrhea and cough was shorter in females than in males and in groups with birth weight 3 kg than in those with <2.5 kg. [Open Forum Infect Dis 2020;7:ofaa375]. A standardized template was used for recording daily signs and symptoms, vital signs, and management. Empiric trials of antibiotics or steroids rarely establish a diagnosis and are discouraged in the management of patients with FUO, unless there are clinical indications.5,17,19,21,22 Consultation with a subspecialist (e.g., infectious disease specialist, rheumatologist, hematologist/oncologist) is appropriate at any point in the evaluation. Ng DH, Wong JG, Thein TL, Leo YS, Lye DC. The fever itself is generally harmless and probably helpful. doi: 10.9778/cmajo.20200250. https://www.who.int/docs/default-source/coronaviruse/situation-reports/2 https://www.moh.gov.sg/news-highlights/details/confirmed-imported-case-o https://www.moh.gov.sg/news-highlights/details/seven-more-confirmed-case World Health Organization. 2 A diagnosis of classic KD is made in patients with prolonged fever (five or more days) and four or more of the following principal . 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. Communicable Diseases Surveillance in Singapore 2005. 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. More studies are required to validate the findings of this report. Cases with prolonged fever were defined as patients with fever lasting >7 days. 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). Angela Chow Li Ping, Brenda Sze Peng Ang, Chen Seong Wong, Cheng Chuan Lee, Ding Ying, Jun-Yang Tay, Kalisvar Marimuthu, Lawrence Soon U. Lee, Yee-Sin Leo, Li Min Ling, Li Wei Ang, Lin Cui, Mark I-Cheng Chen, Monica Chan, Mucheli Sharavan Sadasiv, Oon-Tek Ng, Pei Hua Lee, Poh Lian Lim, Sapna Pradip Sadarangani, Shawn Vasoo, Stephanie Sutjipto, Tsin Wen Yeo, Tze Minn Mak. 2021 Nov 5;114(8):541-542. doi: 10.1093/qjmed/hcab138. Fever was defined as a temperature of 38.0C. 2013 Sep 26;7(9):e2412. All authors: no reported conflicts of interest. Demographics were similar across the 3 groups (Table 1); 7.0% (10/142) of patients had comorbidities, such as diabetes (n=4), ischemic heart disease (n=3), and asthma (n=3). Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. The classic presentation is one of fever, malaise, diffuse abdominal pain, and constipation. This suggests that in patients with prolonged fever, close monitoring for deterioration should be instituted, while patients with saddleback fever who remain well and do not require supplemental oxygenation are unlikely to require close monitoring in the hospital, explained Ng and co-authors. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are nonspecific acute-phase reactants that are routinely part of the evaluation of febrile patients.5,28 An extremely elevated ESR (100 mm per hour or greater) suggests etiologies such as abdominal or pelvic abscess, osteomyelitis, and endocarditis. Careers. Fever of unknown origin (FUO) in adults is one of the most vexing clinical conditions for clinicians and patients. If the diagnosis remains elusive, 18F fluorodeoxyglucose positron emission tomography plus computed tomography may help guide the clinician toward tissue biopsy. 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. JAMA 2020; 323(11):10619. In contrast, cases with saddleback fever showed no significant change upon repeating their laboratory tests. 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. Cases with prolonged fever were also more likely to require ICU admission compared with controls (11.1% vs 0.9%; P=.05). COVID-19 and sinus infections share several symptoms like nasal congestion, fever, and coughing. Published by Oxford University Press on behalf of Infectious Diseases Society of America. 2020 Oct 1;180(10):1345-1355. doi: 10.1001/jamainternmed.2020.3539. Khalaf M, Alboraie M, Abdel-Gawad M, Abdelmalek M, Abu-Elfatth A, Abdelhamed W, Zaghloul M, ElDeeb R, Abdeltwab D, Abdelghani M, El-Raey F, Aboalam H, Badry A, Tharwat M, Afify S, Elwazzan D, Abdelmohsen AS, Fathy H, Wagih Shaltout S, Hetta HF, Bazeed SE. Untreated typhoid fever may progress to delirium, obtundation, intestinal hemorrhage, bowel. Empiric antibiotics or steroids are generally discouraged in patients with fever of unknown origin. Open Forum Infect Dis. Copyright 2014 by the American Academy of Family Physicians. aInvestigations were repeated at the point at which they satisfied criteria for prolonged or saddleback fever. Edupuganti S, Natrajan MS, Rouphael N, Lai L, Xu Y, Feldhammer M, Hill C, Patel SM, Johnson SJ, Bower M, Gorchakov R, Berry R, Murray KO, Mulligan MJ. Unauthorized use of these marks is strictly prohibited. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. PMC Respiratory syncytial virus disease burden in community-dwelling and long-term care facility older adults in Europe and the United States: A prospective study, Viral aetiology and clinical characteristics of acute respiratory tract infections in hospitalized children in Southern Germany (2014-2018), Coronary Artery Plaque Composition and Severity Relate to the Inflammasome in People with Treated HIV, Sustained Virologic Suppression With Dolutegravir/Lamivudine in a Test-and-Treat Setting Through 48 Weeks, Impact of hypoalbuminemia on ceftriaxone treatment failure in patients with Enterobacterales bacteremia: a propensity matched, retrospective cohort study, About the Infectious Diseases Society of America, https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200430-sitrep-101-covid-19.pdf?sfvrsn=2ba4e093_2, https://www.moh.gov.sg/news-highlights/details/confirmed-imported-case-of-novel-coronavirus-infection-in-singapore-multi-ministry-taskforce-ramps-up-precautionary-measures, https://www.moh.gov.sg/news-highlights/details/seven-more-confirmed-cases-of-novel-coronavirus-infection-in-singapore, https://sso.agc.gov.sg/Act/IDA1976#pr25A-, https://doi.org/10.1101/2020.03.02.20029975, https://www.cdc.gov/coronavirus/2019-ncov/hcp/guidance-home-care.html, https://www.straitstimes.com/singapore/9-in-10-coronavirus-patients-housed-in-isolation-facilities, https://www.moh.gov.sg/news-highlights/details/56-more-cases-discharged-528-new-cases-of-covid-19-infection-confirmed, http://creativecommons.org/licenses/by-nc-nd/4.0/, Receive exclusive offers and updates from Oxford Academic. Accessibility Disclaimer. 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). A, Heatmap showing the relative concentration of cytokines across patients with different fever patterns. Prolonged fever is associated with adverse outcomes in dengue viral infection. Prolonged fever (fever > 7 days duration) was present in 572 (20.1%) of patients. Previous testing (ESR, complete blood count, electrolyte panel, chest radiography, urinalysis, blood culture) may be repeated periodically to evaluate for trends as the illness evolves. Prolonged fever was also associated with lower platelet count and higher CRP compared with controls. Patients were categorized as having prolonged fever (lasting >7 days), saddleback fever (defined as recurrent fever which lasts for <24 hours, after defervescence beyond day 7 of illness), or controls if their fever was 7 days. Other illnesses and inflammation. Woon YL, Hor CP, Hussin N, Zakaria A, Goh PP, Cheah WK. Eleven patients with prolonged fever, 8 patients with saddleback fever and 56 patients with fever lasting 7 days (controls) were evaluated at the first time point of blood sample collection upon hospitalization (median of 6 days postillness onset) (Figure 1A). In addition, as these patients with saddleback fever tend to do well, there is also no need for repeat laboratory testing or CXR, as the results are unlikely to change management or clinical outcomes. Prolonged fever in children: review of 100 cases. Please enable it to take advantage of the complete set of features! Patients who tested positive were not discharged until they had 2 negative PCR tests 24 hours apart [13]. Upon admission, all patients underwent a chest x-ray (CXR), admission full blood count (FBC), renal and liver panel, C-reactive protein (CRP), lactate dehydrogenase (LDH), and nasopharyngeal swab for SARS-CoV-2 PCR. PLoS One. Patient information: See related handout on fever of unknown origin in adults, written by the authors of this article. QJM. A total of 142 patients were included in the study; 12.7% (18/142) of cases had prolonged fever, and 9.9% (14/142) had saddleback fever. However, this view of fever is merely an oversimplification as a growing body of evidence now suggests that fever represents a complex adaptive response of the host to various immune challenges whether infectious or non-infectious. One case with prolonged fever had concomitant infection with ventilator-associated pneumonia, with Klebsiella pneumoniae grown from his endotracheal aspirate on day 8 of ICU admission (day 15 of illness). Bethesda, MD 20894, Web Policies An official website of the United States government. IL-1RA is naturally secreted by human hosts to limit the activity of IL-1 during hyperinflammation [22]. Fever of unknown origin has been described as a febrile illness (temperature of 101F [38.3C] or higher) for three weeks or longer without an etiology despite a one-week inpatient evaluation. This study demonstrates that prolonged fever may be associated with various warning signs and more severe forms of dengue (SD, DSS, DHF), while saddleback fever showed associations with DHF. Hospitalized COVID-19 patients with prolonged fever showed more pronounced inflammatory response and were more likely to require ICU admission than cases with saddleback fever or with fever lasting as they fulfilled overlapping criteria for prolonged and saddleback fever. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. The 2011 dengue haemorrhagic fever outbreak in Lahore - an account of clinical parameters and pattern of haemorrhagic complications. Despite the progression on CXR in over one-third of cases with saddleback fever, these cases tend to do well. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. Notably, patients with prolonged fever had higher IP-10 and lower IL-1 levels as compared with patients with saddleback fever (Figure 1B). Seven more confirmed cases of novel coronavirus infection in Singapore. 2021 Jan-Feb;50(1):28-32. doi: 10.1016/j.hrtlng.2020.10.013. Roseola symptoms might include: Fever. Additional microbiological investigations, such as blood and urine cultures, influenza and respiratory viral multiplex PCR, dengue NS1 and serology, were ordered at the discretion of the primary treating clinician. Interim guidance for implementing home care of people not requiring hospitalization for coronavirus disease 2019 (COVID-19). The site is secure. Cases with prolonged fever were found to have higher levels of anti-inflammatory IL-1RA, pro-inflammatory IL-6, and chemokine interferon- IP-10 compared with controls (Figure 1B). MeSH J Clin Med Res. Over- or under-reporting of the onset of fever before admission could affect the number of patients found to have prolonged or saddleback fever. Shivering, shaking, and chills Aching muscles and joints or other body aches Headache Intermittent sweats or excessive sweating Rapid heart rate and/or palpitations Skin flushing or hot skin Feeling faint, dizzy, or lightheaded Eye pain or sore eyes Weakness Loss of appetite Fussiness (in children and toddlers) This can happen when your body is fighting an infection. Physicians may consider stopping antimicrobials if all investigations are unyielding and patients remain hemodynamically stable. Although there were no significant differences in white blood cell counts or absolute values of lymphocytes and CRP, we found significant differences in plasma IL-6 and IP-10 levels between the prolonged fever and control patients. Cytokine level for healthy controls (n=23) is indicated by the black dotted line. However, it is interesting that there are higher pro-inflammatory IL-1 levels in patients with saddleback fever. While it has been reported that complications of COVID-19 occur in the second week of illness, the significance of these 2 patterns of fever with regards to the development of complications is unknown [4]. IL-1 is a pyrogenic cytokine that plays a central role in inflammatory diseases like arthralgia [23]. FOIA Patients with saddleback fever appeared to have good outcomes regardless of the fever. Concentrations of 45 immune mediators in plasma were quantified using a 45-plex microbead-based immunoassay. eCollection 2022. Geneva: World Health Organization, Special Programme for Research and Training in Tropical Diseases, Geneva: 2000. Patients with saddleback fever appeared to have good outcomes regardless of the fever. But normal body temperature can range between 97 F (36.1 C) and 99 F (37.2 C) or more. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Because there are no guidelines to the approach of the febrile patient, most evaluation recommendations are based on expert opinion.17 On initial presentation, most clinicians perform a history and physical examination in pursuit of an infection. Saddleback fever was present in 165 (5.8%). -, Huang C, Wang Y, Li X, et al. Europe PMC is an archive of life sciences journal literature. Available at: Wang D, Hu B, Hu C, et al. In general, fever is defined as a temperature > 38C (100.4F). This suggests that in patients with prolonged fever, close monitoring for deterioration should be instituted, while patients with saddleback fever who remain well and do not require supplemental oxygenation are unlikely to require close monitoring in the hospital. In conclusion, we reported on the prevalence, risk factors, cytokine profiles, and outcomes of patients with COVID-19 who had saddleback or prolonged fever. Hypoxia was defined as requirement for supplemental oxygen. The search included reviews, case series, meta-analyses, and randomized controlled trials. The results of these microbiological investigations were also collected and analyzed. Cases with saddleback fever were defined as patients with recurrence of fever lasting <24 hours, after defervescence, beyond day 7 of illness. -. Sixty-nine percent of them were male with a median age of 34 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. Cases without prolonged or saddleback fever were included as controls. bOnly 1 sample of paired values available. Additional searches included the Cochrane database, Essential Evidence Plus, the Agency for Healthcare Research and Quality evidence reports, and the National Guideline Clearinghouse. 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