The most common comorbidity was orthostatic intolerance, found in 10 patients. According to the diagnostic criteria of orthostatic dysregulation in children [
12], all 10 patients were diagnosed with POTS, which is characterized by a heart rate increase of > 35 beats/min after standing from a sitting position or a maximum heart rate of > 115 beats/min in the absence of orthostatic hypotension. The prevalence of POTS in children is not known because screening of orthostatic intolerance is not routine [
13]. However, Matsushima reported that 15% of pediatric patients with orthostatic symptoms were diagnosed as having POTS in survey of children and adolescents in Japan [
14]. In comparison, the prevalence of POTS in the pediatric patients with PF of the current study is extremely high. This result indicates that there is a common mechanism between PF and POTS, and tachycardia and hyperthermia are based on a common cause. Enhanced sympathetic response has been proposed as a mechanism of POTS among patients with PF. Oka et al. [
15] suggested that the mechanism of PF was not the same as that of infection-induced fever but involved the central and sympathetic nervous systems. Signs of inflammatory reaction are not detected in blood tests of patients with PF, whereas β3 adrenoreceptor-mediated non-shivering thermogenesis is considered to play an important role in the development of enhanced hyperthermic response in patients with PF. Often, subjects with β-adrenergic hyperresponsiveness show symptoms of POTS [
15,
16]. Moreover, Lkhagvasuren et al. [
17,
18] reported the presence of sympathetic hyperreactivity as a cardiovascular reaction when standing up in patients with PF and that the increase in heart rate after standing up was significantly higher in these patients than in healthy subjects. Both adolescent [
17] and adult patients [
18] with PF have a greater heart rate response to orthostatic stress and exhibit an increased prevalence of POTS compared with healthy subjects. The high comorbidity rate of POTS in patients with PF found in the present study is consistent with these studies. If enhanced sympathetic response leads to both fever and tachycardia, stabilizing sympathetic activity may be effective for addressing both PF and the symptoms of POTS.
In the present study, child abuse was identified in five patients with PF. Similarly, Okada et al. [
9] reported that child abuse was observed in children with PF and that presentation with FUO enabled cooperation with medical and child welfare institutions and educational facilities. Therefore, cooperation of related organizations is important to ensure the safety of the child, even in cases of PF without a serious physical cause.