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Table of Contents
CASE REPORT
Year : 2021  |  Volume : 26  |  Issue : 2  |  Page : 135-137

Pyrexia of unknown origin in a 1-year-old child: How far should we go? A case report


1 Department of Paediatrics, College of Medicine, University of Nigeria Enugu Campus, Enugu, Enugu State, Nigeria
2 Child-life Medical Centre, Enugu, Enugu State, Nigeria

Date of Submission16-Sep-2020
Date of Decision03-Oct-2020
Date of Acceptance08-Oct-2020
Date of Web Publication29-Jan-2021

Correspondence Address:
Josephat M Chinawa
Paediatric Cardiology Firm, Department of Paediatrics, College of Medicine, University of Nigeria Enugu Campus, PMB 40001 Enugu, Enugu State.
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmh.IJMH_62_20

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  Abstract 

Introduction: Pyrexia of unknown origin (PUO) still remains a challenge in paediatric practice. Appropriate history, physical examination, and exhaustive investigations are crucial in managing cases of PUO. Case Presentation: UU, was a 1-year-old female, who was seen at our facility on 16 January 2020, with a 4-day history of fever. Fever was high grade and intermittent. Examination revealed pyrexia of 38°c and no other remarkable findings. Lassa fever virus serology, hepatitis B surface antigen, hepatitis C surface antigen, C-reactive protein, erythrocyte sedimentation rate, full blood count, blood culture (with Bactec), malarial parasite, Mantoux, and CXR were all requested. Results of all these investigations were negative. Echocardiography done showed a 0.23 cm² vegetation at the septal leaflet of the tricuspid valve. A diagnosis of infective endocarditis was made and intravenous vancomycin, ceftriaxone, and metronidazole were commenced. Weekly urinalysis and serum electrolyte urea and creatinine monitoring were documented. After a 3-week course of intravenous antibiotics, patient still had fever with temperature higher than 38°c. A diagnosis of PUO was made and a follow-up plan was to do a bone marrow aspiration to rule out leukaemia and serology to rule out connective tissue disease. Conclusion: In managing a child with PUO, detailed history, appropriate physical examination and exhaustive investigations should be done. This is crucial in that even if diagnosis is not reached, several causes of PUO could have been ruled out.

Keywords: Antibiotics, challenge, children, PUO


How to cite this article:
Okafor HU, Ibeziako NS, Chinawa JM, Ezike TC. Pyrexia of unknown origin in a 1-year-old child: How far should we go? A case report. Int J Med Health Dev 2021;26:135-7

How to cite this URL:
Okafor HU, Ibeziako NS, Chinawa JM, Ezike TC. Pyrexia of unknown origin in a 1-year-old child: How far should we go? A case report. Int J Med Health Dev [serial online] 2021 [cited 2022 Aug 10];26:135-7. Available from: https://www.ijmhdev.com/text.asp?2021/26/2/135/308254




  Introduction Top


There are several clinical conditions that present with fever in children.[1] Pyrexia of unknown origin (PUO), first described in 1961, is defined as fever of at least 3 weeks’ duration without an apparent source after 1 week of investigation.[2] However, some studies have defined PUO in children as fever lasting anywhere from 10 days to 3 weeks.[3],[4]

PUO is a demanding clinical scenario seen in children, resulting in an unnecessary array of laboratory investigations and antibiotic therapy.

There is no standardized protocol for the diagnosis of PUO. Nevertheless, it is recommended that diagnosis should start with a thorough and rigorous history taking and a detailed physical examination.[4],[5] Investigations should be prioritized and tailored to the patient’s clinical findings.

The epidemiology of PUO is variable and has changed over the years. Sometimes, infection is reported as the primary cause of PUO.[6] A very high index of suspicion is needed in the approach to PUO as iatrogenic causes are now emerging.[6],[7] This case report underscores the need to probe further in our investigation of a child whose fever is unrelenting and possibly intensify management to avert any impending morbidity and mortality.


  Case Presentation Top


UU was a 1-year old female, who was seen at our facility on 16 January, 2020 with a 4-day history of fever. Fever was high grade and intermittent. There was no history of cough and breathlessness, ear and eye discharge, passage of watery stool or vomiting and baby was making adequate urine. Past medical history revealed that she had been admitted and treated for a febrile illness which responded to antimalarial medications and antibiotics in our facility about 3 weeks prior to onset of this illness.

Examination revealed pyrexia > 37.5°C and no other remarkable findings. Initial provisional diagnosis of acute uncomplicated malaria and possible sepsis was made. Investigations include dipstick urinalysis, microscopy, culture and sensitivity, full blood count (FBC), and blood film for malaria parasite (MP). These showed positive blood film for MP with normal FBC results and no other significant finding. She was adequately treated with antimalarial and antibiotics and was discharged home after 3 days on admission but represented about 2 weeks later with a 2-day history of fever and dry cough. Physical examination findings were unremarkable except for pyrexia of 38.5°C. An assessment of possible drug fever was entertained as she had received various antibiotics at home. Further investigations including retroviral screening, Lassa fever virus serology, FBC, erythrocyte sedimentation rate (ESR), blood film for MP, Mantoux test, blood culture, Lassa fever virus serology, Hepatitis B surface antigen (HBsAg), Hepatitis C surface antigen (HCV), C- reactive protein, and CXR [Figure 1] were done. Results of all these investigations were unremarkable. Further physical examination while on admission revealed presence of a cardiac murmur. Echocardiography [Figure 2] showed a 0.23 cm² vegetation at the septal leaflet of the tricuspid valve. A diagnosis of infective endocarditis was made and intravenous vancomycin, ceftriaxone, and metronidazole were commenced. Weekly urinalysis and serum electrolyte urea and creatinine monitoring were documented and were unremarkable. After a 3-week course of intravenous antibiotics, the patient still had intermittent fever with a temperature higher than 38°C. Repeat echocardiography by the pediatric cardiologist revealed markedly reduced vegetation size at the tricuspid valve. To help ensure satisfactory and uninterrupted administration of antibiotics, a PICC (peripherally inserted central catheter) line was put in place, and intravenous metronidazole and vancomycin were extended for another 10 days. The patient continued to have intermittent temperature spikes exceeding 38°C despite completion of intravenous antibiotic regimen for 3 weeks. Repeat echocardiography showed absence of vegetation after 3 weeks of antibiotic therapy. The result of blood film revealed hypochromic and normocytic cells showing poikilocytosis and quite a number of pencil cells were seen with mild left shift of neutrophils observed. A diagnosis of PUO secondary to drug fever was entertained. Based on the report of the repeat echocardiography, it was decided that patient takes a complete drug holiday and be discharged home to change environment, after both parents were counseled adequately on the diagnosis. A follow-up plan was to do a bone marrow aspiration to rule out leukemia and serology to rule out connective tissue disease, if fever persisted. However, the patient was lost to follow-up.
Figure 1: CXR of index child. Normal cardiac silhouette

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Figure 2: Vegetation in the tricuspid valve (infective endocarditis)

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  Discussion Top


Though literature abound on PUO, yet this disease remains an onerous task for the pediatrician. This could be explained by several etiologies and diverse management approaches. Malaria was the first diagnosis made in our index patient because of its endemicity. Though the child had been treated for malaria before presenting to the hospital, it is important to note that positive post-therapy blood film is not uncommon in children living in a malaria-endemic region, as children could have asymptomatic parasitemia and could even have co-existing infections.[8] Diagnosis of infective endocarditis was made in the index patient by means of echocardiography [Figure 1] and antibiotics were duly commenced. The prevalence of infective endocarditis among children with PUO has reduced due to improved blood culture systems, as well as imaging techniques, such as CT scan which have improved detection of occult abscesses.[7] The cause of PUO presents with geographical variation.[8] For instance in developing countries, infections have been documented as the most common cause of PUO and accounts for about 20%–40% of cases. This was followed by malignancies and connective tissue disease.[7] From the spectrum of infective causes of PUO, tuberculosis remains the most prevalent etiology.[9] This finding is compatible with studies reported from Turkey and Saudi Arabia. In developed countries, leukemia is the most common malignancy presenting with PUO.[9]

The diagnosis of PUO was further strengthened in the index case by the unremarkable investigation results for other possible etiological factors, including negative retroviral test. Though Lassa fever could explain the clinical picture, complete blood count, liver function tests, and definitive serology were not suggestive.

We considered drug fever as a cause of PUO in our patient; thus, all medications were discontinued. The clinical characteristics of drug fever are not exhaustive but may include rashes, and positive complete blood count. Studies have shown that antibiotics and analgesics are the most common triggers of PUO.[8]

Our patient was discharged after stopping all drugs and short appointment was given. Several studies have shown that despite progress in diagnostics, 51% of cases of PUO may defy diagnosis and some studies have tagged such difficult situation as “Fever of Too Many Origins.”[7],[8],[9] Regrettably, we lost the patient to follow-up.


  Conclusion Top


In managing a child with PUO, detailed history, appropriate physical examination, and exhaustive investigations should be done. This is crucial in that even if diagnosis is not reached, several causes of PUO could have been ruled out.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Feigin RD Feigin & Cherry’s textbook of pediatric infectious diseases. 6th ed. Philadelphia, PA: Saunders Elsevier; 2009.  Back to cited text no. 1
    
2.
Seashore CJ, Lohr JA Fever of unknown origin in children. Pediatr Ann 2011;40:26-30.  Back to cited text no. 2
    
3.
Ciftçi E, Ince E, Doğru U Pyrexia of unknown origin in children: A review of 102 patients from turkey. Ann Trop Paediatr 2003;23:259-63.  Back to cited text no. 3
    
4.
Nield LS, Kamat D Fever. In: Kliegman RM, Stanton BF, St Geme JW, Schor NF, Behrman RF, editors. Nelson textbook of pediatrics. 19th ed. Philadelphia, PA: Saunders Elsevier; 2011. pp. e169-1-169-3.  Back to cited text no. 4
    
5.
Mahmoudi S, Mehrazmay A, Salesi M, Mamishi S Fever of unknown origin: A retrospective study of 95 children in an Iranian referral hospital. Br J Biomed Sci 2014;71:40-2.  Back to cited text no. 5
    
6.
Bordelon JR, Abbas SU, Shabbir AQ, Ross AL Rewriting history: Fever of unknown origin. Am J Med 2015;128:956-8.  Back to cited text no. 6
    
7.
Bleeker-Rovers CP, Vos FJ, de Kleijn EM, Mudde AH, Dofferhoff TS, Richter C, et al. A prospective multicenter study on fever of unknown origin: The yield of a structured diagnostic protocol. Medicine 2007;86:26-38.  Back to cited text no. 7
    
8.
Onodugo O, Iroezindu M Fever of unknown origin in a Nigerian doctor: An unusual case. Internet J Trop Med2013;1:1-4.  Back to cited text no. 8
    
9.
Horowitz HW Fever of unknown origin or fever of too many origins? N Engl J Med 2013;368:197-9.  Back to cited text no. 9
    


    Figures

  [Figure 1], [Figure 2]



 

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