despite advances in diagnostic techniques , fever of unknown origin ( fuo ) remains a formidable challenge , with the cause of fever not being identified in 7%38% of patients.1 oren - gedoku - to ( ogt ) has been used traditionally to remove  heat  and  poison  from the body.2 on the basis of this theory in oriental medicine , it has been used in clinical practice to treat inflammation , hypertension , gastrointestinal disorders , and liver and cerebrovascular disease.2 in japan , ogt is manufactured as a powdered , freeze - dried water extract by tsumura co , ltd ( tokyo , japan ) .
a 33-year - old woman was admitted to our general medicine department with fuo which had persisted for longer than 2 months and was resistant to treatment with nonsteroidal anti - inflammatory drugs and prednisolone 20 mg / day .
she reported sweating and headache , but did not complain of body weight change , pain , nausea , abnormal vaginal bleeding , or diarrhea . to treat dysmenorrhea and premenstrual syndrome ,
she had been prescribed oral contraceptives ( levonorgestrel , ethinylestradiol ) for 7 years , and the dose had remained unchanged during that period .
she had no history of pregnancy , and a gynecologic examination revealed no infectious or malignant findings .
she had been receiving regular follow - up care for mild depression for 3 years at our department of psychiatry and had been prescribed the antidepressants , aripiprazole and duloxetine hydrochloride , until 2 months before admission .
she had asthma , which was well controlled with the inhaled steroid budesonide ( 200 g , once daily ) .
she was a housewife and only had sexual contact with her husband who had no sexually transmitted diseases .
her mental status was alert , and blood pressure was 92/60 mmhg in a sitting position .
although the rise in body temperature was accompanied by an increase in pulse rate , her pulse was normal , ranging from 58 to 82 beats per minute .
her pulse rate was regular in rhythm , and its size , and tension were within the normal ranges .
physical examination revealed no abnormalities , such as focal inflammation , lymph node swelling , skin rash , or abnormal heart sounds .
laboratory analysis showed no biological inflammation c - reactive protein 0.0 mg / l , and interleukin-6 ( 2.1 pg / ml , normal range < 4.0 pg / ml ) and tumor necrosis factor- ( 0.6 pg / ml , normal range 0.62.8 pg / ml ) were normal .
a chest x - ray showed no abnormal findings , and sputum culture for acid - fast bacteria was negative .
in addition , an interferon- release assay ( qft-2 g , oxford immunotec co , ltd oxford uk ) was not positive ( 0.30 iu / l , normal range < 0.80
the results for the remaining biological tests were all in the normal ranges , as shown in table 1 .
contrast thoracic and abdominal computed tomography , brain magnetic resonance imaging , and gallium scintigraphy excluded infection , including tuberculosis , and rheumatic / inflammatory , neoplastic , or other focal abnormalities .
fever decreased 2 days after adding yokukan - san to 7.5 g of powdered ogt , which is the standard dose for adults ( figure 1 ) .
ogt was then prescribed for an additional 10 days , and fever has not relapsed after a follow - up period of 2 months .
fuo is defined as a fever > 38.3c on several occasions , during a period of at least 3 weeks , that remains undiagnosed after one week of investigation.3 after considering the four categories of fuo , ie , classical , neutropenic , nosocomial , and human immunodeficiency virus - associated fever , this patient met the criteria for classical fuo.4,5 an evidence - based approach divides fuo into four general categories , ie , infectious , autoimmune , neoplastic , and miscellaneous diseases , each of which requires certain investigations to be performed.6 a complete history , physical assessment , and laboratory testing revealed no diagnostic clues . among the infectious diseases associated with fuo , tuberculosis is the most common in japan .
however , a chest x - ray did not show abnormal findings , and sputum culture for acid - fast bacteria was negative .
tuberculosis was thus excluded . among the autoimmune diseases associated with fuo , rheumatoid factor , antinuclear antibody , antineutrophil cytoplasmic antibody , and ferritin were negative . regarding malignancy , contrast thoracic and abdominal computed tomography , brain magnetic resonance imaging , and gallium scintigraphy excluded nonhematologic malignancies .
use of aripiprazole and duloxetine hydrochloride had been stopped 2 months before admission . during that 2-month period ,
she did not report stress in her environment , and her mental condition remained stable .
the effects of oral contraceptives ( levonorgestrel , ethinylestradiol ) on fever were also considered .
she had been prescribed oral contraceptives for 7 years , and the dose remained unchanged during that period .
she reported sweating and headache but no other side effects of oral contraceptives , such as body weight change , pain , nausea , and abnormal vaginal bleeding .
fever due to oral contraceptives is usually low - grade , unlike the continuous high fever in this case .
however , they usually complain of muscle weakness , myalgia , arthralgia , or chills .
our patient had no such complaints.7 ogt has been used for 2,000 years to remove  heat  and  poison  from the body.2 with the development of modern medicine ,  heat  and  poison  have come to be considered aspects of inflammation , hypertension , gastrointestinal tract disorders , and liver and cerebrovascular disease , which are indications for ogt.2 ogt is contraindicated for patients who are sensitive to cold .
ogt comprises four decocted medicinal herbs ( g ) : rhizoma coptidis ( 2.0 ) , radix scutellariae ( 3.0 ) , cortex phellodendri ( 2.0 ) , and fructus gardeniae ( 1.5 ) .
r. scutellariae has the active ingredients baicalin , baicalein , and wogonin , which suppress the arachidonate cascade by inhibiting cyclo - oxygenase ( cox)-2 , 5-lipoxygenase , but not cox-1 , in rats and mice.8,9 moreover , ogt has an inhibitory effect on free radical production : baicalin , baicalein , and wogonin suppressed lipopolysaccharide - induced nitric oxide , wogonin suppressed lipopolysaccharide - induced cox-2 , and ogt directly protected red blood cell membranes from free radical damage.9,10 the four decocted medicinal herbs have been shown to have greater anti - inflammatory effects than each herb used alone.11,12 in our patient , c - reactive protein , interferon- , and inflammatory cytokines , such as interleukin-6 and tumor necrosis factor- , were within normal ranges . in future cases , interleukin-8 , a leukocyte chemotactic factor , should also be measured , to understand better the anti - inflammatory action of ogt .
although the multiple anti - inflammatory effects of ogt are under investigation , the present results suggest that ogt might be an effective agent for fuo , because its anti - inflammatory effects do not depend only on the arachidonate cascade
. it should be stressed , however , that this is a report of only one case .
nevertheless , our findings indicate that ogt is a possible treatment for fuo that remains undiagnosed after an extensive diagnostic workup .
ogt is a possible treatment for fuo , after exclusion of infectious , rheumatic / inflammatory , neoplastic , and other diseases .
in addition , the anti - inflammatory effects of ogt that depend on pathways other than the arachidonate cascade should be investigated in future studies .
 oren - gedoku - to is a traditional medicine used for treating inflammatory conditions and is given by prescription in japan , people s republic of china , and korea . 
 its anti - inflammatory effect is related to the arachidonate cascade and inhibition of cyclo - oxygenase , but research on other anti - inflammatory pathways is ongoing . 
 we report a case of fever of unknown origin in a 33-year - old woman . 
 the possibility of infection due to human immunodeficiency virus , autoimmune , neoplastic , or other disease was examined and excluded . 
 oren - gedoku - to was successfully used to treat her symptoms and may thus be a suitable treatment for patients with undiagnosed fever of unknown origin 
Introduction
Case report
Discussion
Conclusion