Characteristics of Functional Hyperthermia Detected in an Outpatient Clinic for Fever of Unknown Origin

Abstract

Background: Functional hyperthermia (FH) is characterized by hyperthermia resulting from sympathetic hyperactivity rather than inflammation, and it is frequently overlooked by medical practitioners due to the absence of abnormalities in a medical examination. Although FH is an important differential diagnosis for fever of unknown origin (FUO), the literature on FUO cases in Japan lacks information on FH. In this study, we aimed to uncover the population of FH patients hidden in FUO cases. Methods: An outpatient clinic for FUO was established at Okayama University Hospital, and 132 patients were examined during the period from May 2019 to February 2022. Results: A diagnosis of FH was made in 31.1% of the FUO cases, and FH predominantly affected individuals in their third and fourth decades of life with a higher incidence in females (68.3%). The frequency of a history of psychiatric illness was higher in patients with FH than in patients with other febrile illnesses. Although the C-reactive protein (CRP) is generally negative in FH cases, some obese patients, with a body mass index ≥ 25 had slightly elevated levels of CRP but were diagnosed with FH. Conclusions: The results showed the importance of identifying FH when encountering patients with FUO without any organic etiology.

Keywords: C-reactive protein (CRP); fever of unknown origin (FUO); functional hyperthermia (FH); psychiatric disorder; psychogenic fever.

Figure 1

Final diagnosis of the patients with FUO. The diagnostic breakdown of patients who visited the Outpatient Clinic for Fever of Unknown Origin is shown.

Figure 2

Characteristics of patients with FH. The age and gender distributions of patients diagnosed with FH in the Outpatient Clinic for Fever of Unknown Origin are shown.

Figure 3

Past psychiatric disorders in patients with FH. The psychiatric histories of patients with FH are shown. Data were analyzed using Fisher’s exact probability test. ** p < 0.01 between the indicated groups.

Figure 4

Relationships between the serum CRP level and obesity in patients with FH. Serum CRP levels are shown in two BMI groups (<25 and ≥25) (A) for patients with FH and (B) for patients with a diagnosis other than FH. The median is shown by the horizontal bar within the box, and the IQR is shown by the upper and lower horizontal bars of the box. The upper and lower horizontal bars outside the box represent the maximum and minimum values within 1.5 times the interquartile range. Data were analyzed using the Kruskal–Wallis test. If differences were detected, Steel–Dwass’s post hoc test was used to determine divergent means. ** p < 0.01 between the indicated groups.