There are more than 200 known causes of FUO. The most important causes are infections, malignancies, inflammatory systemic diseases, drug-induced fever, and artificial fever (Michels 2012).
Classical FUO is caused in approximately:
- 25 % by infections
- 10 - 15 % by malignancies
- 40 % by autoimmunopathies, collagenoses or others
- 20 - 25 % ultimately remain unexplained (Weihrauch 2022)
In children, the cause is found to be:
- 51 % by infection
- 6 % by malignoma
- 9 % by autoinflammatory / autoimmunological processes
- 23 % no cause could be found (Kallinich 2014).
In hospitalized patients, infected intravascular catheters, urinary tract infections, pneumonia, sinusitis, pulmonary embolism, deep vein thrombosis or reactivation of a herpes simplex infection or cytomegalovirus infection can be found in particular (Herold 2022).
- FUO in neutropenic patients:
In this case - predominantly during or after cytostatic therapy - the number of neutrophil granulocytes drops to values between 500 - 1,000 / µl. This is found in up to 75 % of patients treated with chemotherapy. However, in about 50 % the cause remains unclear. Even in these unexplained cases, one should suspect an infection (Herold 2022).
Germs such as staphylococci, streptococci, gram-negative bacteria, or fungi are most commonly the causative agent (Herold 2022).
This is often found in abscesses, endocarditis, HIV- infections, opportunistic infections, and tuberculosis (Herold 2022).
Cause of nosocomial FUO can be: infected catheters, pneumonia, sinusitis, urinary tract infections, deep vein thrombosis, pulmonary embolism, reactivation of herpes simplex infection (HSV), cytomegalovirus infection (CMV), postoperative in response to postaggregation metabolism or due to p. o. complications (see also fever after surgery), etc. (Herold 2022).
In this case, fever ≥ 38 degrees C occurs with proven HIV- infection. As soon as the CD4- lymphocytes are < 200 / µl, opportunistic infections can occur such as mycobacteria, Pneumocystis jirovecii, etc. (Herold 2022).
In addition, herpesvirus infections or cryptococcosis caused by cryptococci can occur not infrequently (Michels 2012).
- FUO due to malignancies, collagenoses and drugs:
In this case, no cause is found in up to 15% of cases (Herold 2022).
- Malignancies: A FUO is found especially in acute leukemias, lymphomas (especially Hodgkin's disease), liver tumors, atrial myxomas, inflammatory pseudotumors, brain tumors, neuroblastomas (Berner 2013).
- Collagenoses / autoimmune diseases: Here, a FUO occurs especially in vasculitides and systemic lupus erythematosus, juvenile idiopathic arthritis, pyogenic autoinflammatory processes such as chronic osteomyelitis, in granulomatous diseases such as sarcoidosis, Crohn's disease, granulomatous hepatitis (Berner 2013).
- Medications: Almost all medications can induce fever. Fever often occurs after taking allopurinol, barbiturates, captopril, quinidine, erythromycin, heparin, ibuprofen, nifedipine, penicillin, phenytoin, sulfonamides, etc (Frantz 2006).
- Peak fevers occurring daily or every 2 days are found especially with:
- Abscess
- malaria
- M. Still
- systemic lupus erythematosus (Huppertz 2021)
- Fever for days to weeks with periods of no symptoms:
This speaks for the rare but well treatable monogenetic episodic fever syndromes (Huppertz 2021).