Association between unknown long‐term fever and depression in an adolescent patient

Abstract

Although somatization symptoms are frequently observed in adolescent patients with depression, few studies have examined the association between depression and fever. Here we describe an adolescent patient with long-term fever of unknown origin in whom both fever and depressive symptoms improved with an antidepressant. This study followed the Clinical Study Guidelines of the Ethics Committee of the Kumamoto University Hospital (Approval No. 622) and was approved by the internal review board. The patient and both parents provided written informed consent. The patient was a 15-year-old girl. In her first year of junior high school (at 13 years old), she was a high-achieving student; however, in the latter half of the year, she was increasingly exhausted from studying and having personal relationships. In her second year of junior high school, she had difficulty in getting to sleep and frequently experienced arousal during sleep. There was a decrease in appetite and her body weight decreased by 5 kg in 1 year. She lost her motivation to study, which led to a decrease in achievement. She was increasingly frustrated and often had arguments with her family. Around that time, she had a continuous low-grade fever of 37.0–37.9 C for days and sometimes had a fever of 38 C (the temperature was taken every morning by axillary method). She visited the pediatric department of a general hospital and underwent blood testing (blood count, hemoglobin, antinuclear antibody, allergy test, hormone test etc.), urine test, chest X-ray, head computer tomography (CT), electrocardiography, and echocardiography. In her third year of junior high school, her mother noticed that she had searched the internet for information on suicide. She hardly went to school, and there was a further decrease in achievement. As a result, she had to give up going to her school of first choice. The fever of unknown origin persisted, but it was still diagnosed as fever of unknown origin in the pediatric department. At the end of the third year of junior high school, she visited the pediatric and adolescent specialty clinic of our hospital. In our hospital, the patient underwent head magnetic resonance imaging and Schellong test in addition to the tests performed at the previous hospital (whole body CT was not performed due to her parent’s concern of radiation exposure). No obvious organic diseases were detected both in our clinic and in the department of general medicine. In the Schellong test, her pulse increased by approximately 25–30 beats per minute but there was no change in blood pressure, and the test was discontinued due to lightheadedness, suggesting that her condition may be similar to that of postural orthostatic tachycardia syndrome. She had decreased motivation, irritation, fatigue, reduced appetite, and difficulty in concentration. We considered that these symptoms were attributable to depression and started a treatment with escitalopram 5 mg/day (day 0; Children’s Depression Rating Scale [CDRS-R], 72) (Figure 1). One week later, the dose was increased to 10 mg/day and then maintained. No other drugs were used. Three weeks later, her depressive symptoms started to improve and there was improvement in irritation, fatigue, and sleep disorder (CDRS-R, 62). Eight weeks later she started to go to school again. Then she continued to go to school (CDRS-R, 50). The fever gradually decreased to 36.0–36.9 C from 2 weeks after stating treatment, and the fever maintained at 36.0–36.9 C from 4 weeks after starting treatment. Antidepressants were administered 14 days before the first day of menstruation. Taking into account the fact that she maintained normal temperature for a long time after treatment, the association between fever and menstruation would have been restrictive. For two years, this patient presented with a fever of unknown origin, and her fever improved 2 weeks after starting antidepressant. This clinical course suggested that the fever of unknown origin might be accompanying depression. Although association between low-grade fever and depression are well described in adults and animal models, reports on adolescents are still limited and this is a noteworthy point. Moreover, several reports refer to the relevance between orthostatic dysregulation (OD) and fever, and the patient in this case presented with symptoms similar to OD. This suggests a possible association between depression and disturbance of autonomic nervous system in childhood and adolescence. Therefore, unknown long-term fever might be one symptom of the disturbance of autonomic nervous system due to depression in this case. In conclusion, clinicians may need to keep in mind conditions like the present case when they examine adolescent patients with a fever of unknown origin.