The impact of global budgeting in Taiwan on inpatients with unexplained fever

Liu, Keh-Sen; Yu, Tsung-Fu; Wu, Hsing-Ju; Lin, Chun-Yi

Unexplained fever represents as one of the most common and difficult diagnostic problems encountered daily by clinicians; it is a febrile illness without an initially obvious etiology. [1, 2] When unexplained fever prolongs despite intensive evaluation and diagnostic testing, clinicians refer to it as fever of unknown origin (FUO). [3] Earlier, FUO was defined as a fever of ≥38.3°C lasting for ≥3 weeks with undiagnosed etiology even after 1 week of intensive hospital testing. [1] Physicians specializing in infectious diseases have redefined FUO as the fever of ≥38.3°C lasting for ≥3 weeks with undiagnosed etiology after 3 days of in-hospital testing or during ≥2 outpatient visits. [4] [5] [6] For pediatric FUO, the generally accepted definition is, a fever lasting 1-3 weeks without positive preliminary investigations or without a diagnosis after three outpatient clinic visits. [7, 8] FUO can be divided into following four general categories based on the etiology of fever: infection, rheumatic-inflammatory, neoplastic, or miscellaneous. [9] Infectious diseases account for approximately one-third of FUO. The most common infections associated with FUO are miliary tuberculosis (TB), Q fever, and brucellosis, followed by human immunodeficiency virus (HIV); cytomegalovirus (CMV); Epstein-Barr virus; intra-abdominal, pelvic, intranephric and perinephric abscess; typhoid or enteric fever; toxoplasmosis; and extrapulmonary TB. Notably, in 75% of the HIV patients, FUO is results from secondary infection, rather than from the HIV infection. [10] Furthermore, rheumatologic and inflammatory disorders, such as rheumatoid arthritis, systemic lupus erythematosus, giant cell/temporal arteritis, adult Still disease, periarteritis nodosa, and microscopic polyangiitis, account for another one-third of FUOs. [10] Moreover, FUOs due to neoplasms and malignancies account for 18% of all FUOs; of them, renal cell carcinoma and lymphoma are the most common neoplasms, followed by acute myeloid leukemia and myeloproliferative disorders. [10] The remaining causes of FUO are miscellaneous disorders, including drug fevers, liver cirrhosis, Crohn disease, and subacute thyroiditis. [10] FUO, a challenge for physicians to diagnose and manage currently, represents approximately 3% of hospital admissions, with morbidity caused by prolonged hospital stay, and mortality rates accounting 12%-35%. Furthermore, FUO is associated with repeated invasive investigations, presumptive treatment, and a high impact on health care systems due to unnecessary and additional laboratory tests and medications. [10, 11] Over 200 causes for FUO have been reported. [10] Relatively few infectious diseases have the potential to cause prolonged fever; therefore, patients with prolonged and perplexing fevers, in whom the infection has been ruled out, pose a diagnostic challenge. [12] Moreover, fever is one of the most common reasons for outpatient visits of children and visits to emergency department (ED). [13] Difficulty in diagnosing FUO also makes its treatment difficult. Empirical antibiotics cannot be indicated unless the patient with FUO is neutropenic. In addition, empiric glucocorticoids cannot be indicated without a strong evidence of rheumatologic disease. [14] Recurrent FUO, which is a strong independent predictor of unestablished diagnosis, represents 18%-42% of the cases in large series. In addition, a final diagnosis can be established in only 49% of patients with recurrent FUO. [15]