Febrile neutropenia and immunocompromised patients
Due to the relatively high prevalence of serious bacterial infections that may be present in immunocompromised or neutropenic patients, empirical antibiotics should be started.[5]Haidar G, Singh N. Fever of unknown origin. N Engl J Med. 2022 Feb 3;386(5):463-77.
http://www.ncbi.nlm.nih.gov/pubmed/35108471?tool=bestpractice.com
[18]Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011 Feb 15;52(4):e56-93.
https://academic.oup.com/cid/article/52/4/e56/382256
http://www.ncbi.nlm.nih.gov/pubmed/21258094?tool=bestpractice.com
The choice of antibiotic regimen should be based on coverage of the most likely pathogens and local susceptibility patterns (as per local healthcare institution algorithms and guidelines), as well as patient-specific factors (e.g., prior history of antibiotic-resistant infection and allergy history) See Febrile neutropenia (Management approach). Blood cultures should be taken prior to starting treatment, but even if they remain negative, empirical antibiotics are required to cover possible occult infections.
Giant cell arteritis
Patients with suspected giant cell arteritis are treated immediately with corticosteroids until the diagnosis can be excluded with biopsy, due to the risk of visual loss.[19]Maz M, Chung SA, Abril A, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of giant cell arteritis and Takayasu arteritis. Arthritis Rheumatol. 2021 Aug;73(8):1349-65.
https://onlinelibrary.wiley.com/doi/10.1002/art.41774
http://www.ncbi.nlm.nih.gov/pubmed/34235884?tool=bestpractice.com
[20]Cunha BA, Lortholary O, Cunha CB. Fever of unknown origin: a clinical approach. Am J Med. 2015 Oct;128(10):1138.e1-1138.e15.
https://www.amjmed.com/article/S0002-9343(15)00542-2/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/26093175?tool=bestpractice.com
Patients with giant cell arteritis may present with localised headache, visual disturbances and jaw claudication.[21]National Institute for Health and Care Excellence. Headaches in over 12s: diagnosis and management. Dec 2021 [internet publication].
https://www.nice.org.uk/guidance/cg150
On examination, they may have reduced pulse, tenderness, or nodules of the temporal artery. The erythrocyte sedimentation rate is usually elevated, but this is a non-specific finding. Simple algorithms have been devised to aid the diagnosis of giant cell arteritis.[22]Czihal M, Lottspeich C, Bernau C, et al. A diagnostic algorithm based on a simple clinical prediction rule for the diagnosis of cranial giant cell arteritis. J Clin Med. 2021 Mar 10;10(6):1163.
https://www.mdpi.com/2077-0383/10/6/1163
http://www.ncbi.nlm.nih.gov/pubmed/33802092?tool=bestpractice.com
[23]Andel PM, Chrysidis S, Geiger J, et al. Diagnosing giant cell arteritis: a comprehensive practical guide for the practicing rheumatologist. Rheumatology (Oxford). 2021 Nov 3;60(11):4958-71.
https://academic.oup.com/rheumatology/article/60/11/4958/6320800
http://www.ncbi.nlm.nih.gov/pubmed/34255830?tool=bestpractice.com
Temporal artery biopsy is the definitive diagnostic test.
Empirical therapy and therapeutic trials
A fundamental principle in the management of classic FUO is that therapy should be withheld whenever possible until the cause of the fever has been determined so that treatment can be tailored to a specific diagnosis.[1]Petersdorf RG, Beeson PB. Fever of unexplained origin: report on 100 cases. Medicine (Baltimore). 1961 Feb;40:1-30.
http://www.ncbi.nlm.nih.gov/pubmed/13734791?tool=bestpractice.com
[20]Cunha BA, Lortholary O, Cunha CB. Fever of unknown origin: a clinical approach. Am J Med. 2015 Oct;128(10):1138.e1-1138.e15.
https://www.amjmed.com/article/S0002-9343(15)00542-2/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/26093175?tool=bestpractice.com
[24]Wright WF, Auwaerter PG. Fever and fever of unknown origin: review, recent advances, and lingering dogma. Open Forum Infect Dis. 2020 May;7(5):ofaa132.
https://academic.oup.com/ofid/article/7/5/ofaa132/5828054
http://www.ncbi.nlm.nih.gov/pubmed/32462043?tool=bestpractice.com
This is based on the observation that non-specific treatment rarely cures FUO and has the potential to delay reaching a diagnosis. This is, however, frequently ignored in clinical practice because the road to diagnosis of FUO is often long and frustrating. As a result, clinicians may feel compelled to treat symptoms empirically, even though the agents used may obscure the signs and symptoms on which the diagnosis depends, or potentially exacerbate the problem, as in the case of empirical corticosteroid use in occult infection. An important exception is that empirical corticosteroid treatment may be appropriate in patients with sufficiently clinically suspected giant cell arteritis to prevent vascular complications, such as blindness or stroke.[19]Maz M, Chung SA, Abril A, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of giant cell arteritis and Takayasu arteritis. Arthritis Rheumatol. 2021 Aug;73(8):1349-65.
https://onlinelibrary.wiley.com/doi/10.1002/art.41774
http://www.ncbi.nlm.nih.gov/pubmed/34235884?tool=bestpractice.com
[25]Mackie SL, Dejaco C, Appenzeller S, et al. British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis. Rheumatology (Oxford). 2020 Mar 1;59(3):e1-23.
https://academic.oup.com/rheumatology/article/59/3/e1/5714024
http://www.ncbi.nlm.nih.gov/pubmed/31970405?tool=bestpractice.com
[26]Hellmich B, Agueda A, Monti S, et al. 2018 Update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2020 Jan;79(1):19-30.
https://ard.bmj.com/content/79/1/19
http://www.ncbi.nlm.nih.gov/pubmed/31270110?tool=bestpractice.com
Primary care physicians may favor a cost-effective approach for managing acute febrile illness and employ empirical antimicrobial therapy before undertaking expensive diagnostic exercises. This approach is less likely to succeed in patients with classic FUO and may obfuscate infectious diagnoses as a cause.