Fever of unknown origin is defined as
- Fever ≥38.3°C (≥101°F) on at least two occasions
- Illness duration of ≥3 weeks
- No known immunocompromised state
- Diagnosis that remains uncertain after a thorough history-taking,
physical examination, and the following obligatory investigations:
determination of erythrocyte sedimentation rate (ESR) and C-reactive
protein (CRP) level; platelet count; leukocyte count and differential;
measurement of levels of hemoglobin, electrolytes, creatinine, total
protein, alkaline phosphatase, alanine aminotransferase, aspartate
aminotransferase, lactate dehydrogenase, creatine kinase, ferritin,
antinuclear antibodies, and rheumatoid factor; protein electropho-
resis; urinalysis; blood cultures (n = 3); urine culture; chest x-ray;
abdominal ultrasonography; and tuberculin skin test (TST) or inter-
feron γ release assay (IGRA).
Inflammation of unknown origin is defined as
presence of elevated inflammatory parameters (CRP or ESR) on multiple occasions for a period of at least 3 weeks in an immunocompetent patient with normal body temperature
Recurrent fever is defined as
Repeated episodes of fever interspersed with fever-free intervals of at least 2 weeks and apparent remission of the underlying disease
in non-Western cohorts what remain the most common cause of FUO
Infection (Mycobacterium tuberculosis)
in Western cohorts what forms the most common cause of FUO
noninfectious inflammatory diseases (NIIDs), including autoimmune, autoinflammatory, and granulomatous diseases, as well as vasculitides
What should be considered in patient living in a rural area or has a history of heart valve disease, an aortic aneurysm, or a vascular prosthesis
Q fever (serologic testing by immunofluorescence assay)
What should be considered in patients with unexplained symptoms localized to the central nervous system, gastrointestinal tract, or joints
Whipple’s disease (Tropheryma whipplei PCR testing)
Fever with signs of endocarditis and negative blood culture results
Culture-negative endocarditis
may be due to difficult-to-culture bacteria
such as nutritionally variant bacteria, HACEK organisms (including Haemophilus parainfluenzae, H. paraphrophilus, Aggregatibacter acti-
nomycetemcomitans, A. aphrophilus, A. paraphrophilus, Cardiobacte-
rium hominis, C. valvarum, Eikenella corrodens, and Kingella kingae;
discussed below), Coxiella burnetii, T. whipplei, and Bartonella species
sterile thrombotic disease that occurs as a paraneoplastic phenomenon, especially with adenocarcinomas.
Marantic endocarditis
patient with FUO who presents with urticaria, bone pain, and monoclonal gammopathy.
Schnitzler syndrome
most common diagnosis of FUO among the neoplasms.
Lymphoma
often accompanied by eosinophilia and also by lymphadenopathy, which can be extensive
Drug-induced fever
characterized by an elevated body temperature that is associated with moderate to strenuous exercise lasting from half an hour up to several hours without an increase in CRP level or ESR
Exercise induced hyperthermia
(fever artificially induced by the patient—for example, by IV injection of contaminated water) should be considered in all patients but is more common among young women in health-care professions.
Factitious fever
patient is normothermic but manipulates the thermometer. Simultaneous measurements at different body sites (rec-
tum, ear, mouth) should rapidly identify this diagnosis.
Fraudulent fever
When is temporal biopsy indicated
Negative scintigraphy, px 55 y.o and above
How long should trial therapy of tuberculosis be given?
6weeks
If the fever does not respond after 6 weeks of empirical antituberculous treatment, another diagnosis should be considered.
What is highly effective in preventing attacks of familial Mediterranean fever (FMF) but is not always effective once an attack is well under way; may be tried in patients with features compatible with FMF, especially when these patients originate from a high-prevalence region.
Colchicine
key cytokine in local and systemic inflammation and the febrile response. therapeutic trial can be considered in patients whose FUO has not been diagnosed after later-stage diagnostic tests.
Anakinra (IL-1)
