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1.Psychogenic fever(stress-induced hyperthermia) in humans <日本語>

　Some people develop fever when they have acute or chronic psychological stress. That is, their body temperatures become higher than when they are healthy. It is not rare for body temperature to increase due to stress. However, many people become concerned and go to the hospitals when a high temperature (hyperthermia) of over 37℃ continues or when other symptoms develop with hyperthermia.
　This condition is called psychogenic fever which is suspected under the following circumstances. (1) A high fever develops with stressful mental activities (such as attending classes, working, meeting people, being very nervous, and fighting). (2) A low fever develops and persists with chronic stress from certain situations (such as continually working overtime, being exhausted from caregiving to the sick, and having difficulty balancing classes and extracurricular activities), or from overlapping stressful situations. In addition, psychogenic fever is suspected if a person is examined at a hospital and he/she is told that there is no abnormality or if fever is not lowered by fever-reducing medications.
　(This type of fever has a different mechanism from fever that develops during a cold. Thus, hyperthermia due to stress is not truly “fever” but it has been historically called “fever.” I think that stress-induced hyperthermia is a better term. However, stress-induced hyperthermia is a term often used for a temporary increase in body temperature caused by acute stress. As there is no appropriate term for hyperthermia from chronic low fever, I prefer to call it functional hyperthermia.)

　An increase in body temperature from stress can be divided into 2 major types. One type of hyperthermia occurs suddenly with major stress but its recovery is fast. This type is seen often in young children. For example, a person can suddenly develop high fever of 39℃ on the day of surgery, but the fever quickly lowers when surgery is cancelled. Although fever lowers quickly, it can occur repeatedly if the cause of stress is not resolved. In this type of body temperature increase, there is an involvement of increased level of alertness, excessive emotion (anxiety, nervousness, anger, and at times joy), and classical conditioning.
　The other type of hyperthermia involves continual low fever of slightly over 37℃ due to chronic stress, such as from overworking or caregiving. This type is often seen in middle-age adults. Low fever is frequently accompanied by physical symptoms such as headache and fatigue. It often continues even after the cause of stress is resolved. In addition, it is frequently accompanied by depression and nervous breakdown.
　Psychogenic fever resembles chronic fatigue syndrome but differs in the following ways. (1) Psychogenic fever clearly involves psychological stress. (2) Unlike chronic fatigue syndrome, there are almost no findings indicative of infections (such as redness of the pharynx, swelling of lymph nodes in the neck, tenderness, pain in the pharynx, muscular pain, joint pain, or chills). (3) Psychogenic fever responds to treatment for stress (in extreme cases, fever resolves the day after hospitalization). However, chronic fatigue syndrome is also a disease that involves stress.

　The following section provides frequently asked questions from patients and their respective answers.

Q1: What are the differences between fever caused by stress and a cold?

　In a cold, inflammation occurs due to viral infection. This inflammation becomes a signal for the brain to tell the sympathetic nerves and muscles to increase body temperature. The increased temperature is the body’s response to help fight off viruses. In this process, substances called “inflammatory cytokines” and “prostaglandin E2 (PGE2)” act as signals. Some people take the herbal medicine kakkonto for a cold. It lowers fever by suppressing the production of cytokines. Fever-reducing medications such as PL Granules and Bufferin suppress the production of PGE2 to lower fever. In a stressful situation of “fight or flight,” the body temperature also increases because sympathetic nerve activity increases to cope with stress.
　Both stress and a cold are similar in that they increase body temperature. However, cytokines and PGE2 are not involved in stress-induced fever, so hospital blood tests will not show any abnormalities (inflammatory response). Therefore, stress-induced fever does not lower when a person takes cold medications or fever-reducing medications which suppress inflammation. The two types of fever are different in these ways.

Q2: Why does the hospital tell me that there are no abnormalities?

　Fever occurs in many diseases including infections, autoimmune disorders, and malignant tumors (also called “organic diseases”). These diseases can be life threatening if their treatments are delayed. Thus, hospital physicians examine whether or not there is an organic disease and determine the cause of fever using imaging (such as CT) and blood tests. Such blood tests examine general inflammatory response, markers characteristic of the disease, and possibly hormonal levels because body temperature also increases in diseases which increase metabolism, such as hyperthyroidism. When abnormalities are not found in these examinations, primary physicians often state to the patients, “There are no abnormalities.” The physicians will try to reassure the patients by explaining that there is no organic disease. However, many patients with psychogenic disease seem more worried and are likely thinking, “Then where is this fever coming from?”, “Can I die from this disease with an unknown cause?”, or “What will reduce this fever?” As previously mentioned, inflammation does not accompany a body temperature increase due to stress, so abnormal findings are not found in imaging or blood tests.
　It will be better for primary physicians to follow their statement of “there are no abnormalities” with a question, “Is anything causing you to be stressed?” If patients have something that is causing stress, physicians should think of solutions with the patients or refer the patients to specialized facilities.

Q3: How is psychogenic fever treated?

　Treatments for psychogenic fever include: (1) lifestyle guidance, (2) adjustments to one’s environment, (3) medication, (4) relaxation techniques such as autogenic training, (5) psychotherapy, and (6) treatments of coexisting diseases (i.e., treatments combined with those of other physical or psychiatric disorders caused by stress).

Q4: What precautions should I take in my daily life if I have psychogenic fever?

　In a fever from a cold or stress, continuing hyperthermia means that your body is using more energy than normal to increase the body temperature. Therefore, it is important to understand that an activity that is normally easy can become a large burden on your body.
　When psychogenic fever continues, it is important to slow your daily pace and to get sufficient sleep. These points sound simple but they are most important in the treatment of psychogenic fever. People understand that rest is necessary when fever is from a cold. However, many people continue working overtime if fever is from stress, and such fever becomes prolonged. Specifically, you should pay attention to the following points while low fever continues.
　(1) Do not try to complete all tasks in one day, and instead prioritize the tasks for that day. Do not put 100% energy into your work or house chores, but put in only ~70% effort. Do not feel self-resentment such as “I should not be such a weak person,” or guilt such as “I am taking it too easy” and “I’m sorry to trouble others.” Rationalize that it is part of the treatment.
　(2) Take frequent breaks. When you start feeling tired at work or home, change your thinking and actions. Stop thinking, “I can tough it out,” “I can do a little bit more,” and “I am going to rest after I finish this part.” Instead think, “My body is telling me to rest when I’m tired” and “I will take a break before I’m too exhausted.”
　(3) When you rest, lie down and close your eyes. (Lying down relaxes tension in your muscles and sympathetic nerves more than in a standing or sitting position. In addition, closing your eyes can increase brain waves associated with relaxation. It is not necessary to go to sleep.) Pay attention to these points and make changes you are able to do. Since your body is “overheating,” you need to find and use your own energy-conserving ways of operating.
　(4) Do not try to do strength training for your body and mind during this time.
　(5) If you cannot resolve stress by yourself, you need to ask for help from your family, other relatives, friends, teachers, superiors at work, and/or occupational health physicians. You should not wait until someone notices your stress. It is important to speak up and say, “I need help,” and take action. Adjustments in your environment are also necessary. For example, talk with your family and ask family members to temporarily share the burden of caregiving for the sick. Discuss with your superiors at work or occupational health physicians, and ask for a reduction of your workload or job reassignment. Consult school teachers and counselors about bullying or schoolwork.

Q5: Which medications are effective?

　Cold medications and fever-reducing medications are mostly ineffective for psychogenic fever. However, they seem to be effective for headache in patients with psychogenic fever.
　For psychogenic fever, medications for stress are effective (including antianxiety agents and antidepressants, and sleeping medications for people who cannot get sufficient sleep). The effectiveness of medications increases if they are used in combination with activities to calm hyperexcited sympathetic nerves (such as autogenic training).
(Note: I have previously studied the effectiveness of Paxil. Thus, I have examined many patients who ask, “I want a prescription for Paxil” or “Paxil didn’t make me better so what should I do?” Paxil is not the only medication that treats psychogenic fever. If there are certain types of coexisting psychiatric disorders, I sometimes do not prescribe Paxil.)
　The effectiveness of medication varies with individual patients. In the treatment of stress-induced disease, the following are important in addition to medication: (1) resolution of the cause of stress (environmental factors such as bullying, overworking, family discord, and tension) and (2) improvement in the method of coping with stress (frequent rests, letting go of anger, and venting without bothering others). These factors can affect the effectiveness of medication.

Q6: What are coexisting diseases? What types of diseases often coexist with psychogenic fever?

　Stress has many effects on the mind and body. Thus, when people become ill from stress, they sometimes have not only one disease but multiple, simultaneous physical and psychiatric disorders. In children, a common coexisting disease is orthostatic disturbance, a disorder of the autonomic nervous system often characterized by dizziness and headache upon standing. In adults, common coexisting diseases are tension headache, mood disorders (depression and bipolar disorder), and anxiety disorders (panic disorder and post-traumatic stress disorder). Sometimes adjustment disorder, somatoform disorder (a mental disorder characterized by physical symptoms with no specific physical cause), and schizophrenia also coexist. If these coexisting diseases are not treated simultaneously, psychogenic fever will be difficult to cure. In particular, psychiatric disorders should be treated simultaneously with psychogenic fever. It is sometimes better to have psychiatrists treat the psychiatric disorders first. If the psychiatric disorders improve, low fever can resolve spontaneously. If the psychiatric disorders are not cured, high body temperatures persist in some patients.

Q7: At which medical department should I be examined?

　First, have an internal medicine department thoroughly examine the cause of fever (pediatric department for children). Do not make your own judgment or self-diagnose. If there is no organic disorder and psychogenic fever is suspected, have the hospital where you were examined refer you to a department of psychosomatic medicine. Psychogenic fever is a physical response characterized by increased body temperature due to psychological and social stress. In other words, it is a psychosomatic disorder. In Japan and Germany, there are departments of psychosomatic medicine that specialize in the treatment of physical disorders caused by psychosomatic disorders and stress. If you have psychogenic fever, I recommend you be examined and treated at a department of psychosomatic medicine. However, if there are coexisting psychiatric disorders, some cases need treatment of psychiatric disorders first.

Q8: Why did the physician diagnose me with psychogenic fever even though I don’t feel stressed?

　There is always stress in life. Some patients with psychogenic fever might not notice (or are unable to feel) fatigue or stress even if their bodies are suffering from stress-induced hyperthermia. Many of these patients have cold, clammy hands. That is, these patients do not realize the continuing tension of their sympathetic nerves due to stress. They think they are relaxed but they actually cannot relax. This phenomenon is more common in people who are perfectionists or people with a strong sense of responsibility who do not want to inconvenience others (overadaptation). Traumatic injury in childhood or puberty sometimes contributes to the tension level and difficulty in relaxing. Depending on the conditions of the disease and the phase of treatment, such patients are treated using pychosomatic medicine, relaxation methods, cognitive-behavioral therapy, and dynamic psychotherapy. These treatments aim to improve symptoms of alexisomia and to promote awareness of their physical and psychological states.

Q9: Is this disease difficult to cure?

　In some patients, low fever resolves spontaneously when the stressful period ends. If it persists, I recommend you be examined at a psychosomatic medicine department and receive specialized treatment.

Q10: (Slightly off topic) Do pets also develop psychogenic fever?

　Yes, they do. All warm-blooded animals can have psychogenic fever (stress-induced hyperthermia). Pets’ body temperatures can temporarily increase when they are placed in a new environment or when they are lonely after being separated from their owners. Psychogenic fever is more severe in mice than humans. Early in my career as a psychosomatic medicine specialist, I was in charge of patients with fever that had an unknown cause but worsened with stress. I wanted to study the cause and treatment for such a condition and began my research on psychogenic fever, which continues today. I studied the mechanism of psychogenic fever in rats and mice, and their findings have helped me understand psychogenic fever in humans and have been useful in planning treatments.

For specialists and physicians treating patients with psychogenic fever

　For almost 20 years, I have been conducting research on the mechanism and treatment of psychogenic fever. I have published several papers to date, and the following is a list of my representative publications. I hope you find them informative and useful in your medical care.
(Takakazu Oka M.D.,Ph.D.)

Selected references

(a) Mechanisms

1. Hayashida S, Oka T, Mera T, Tsuji S: Repeated social defeat stress induces chronic　hyperthermia in rats. Physiol Behav 2010;101:124-131.
2. Oka T, Oka K, Kobayashi T, Sugimoto Y, Ichikawa A, Ushikubi F, Narumiya S, Saper CB. Characteristics of thermoregulatory and febrile responses in mice deficient in prostaglandin EP1 and EP3 receptors. J Physiol 2003; 551:945-954.
3. Oka T, Oka K, Hori T. Mechanisms and mediators of psychological stress-induced rise in core temperature. Psychosom Med 2001;63:476-486.

(b)Epidemiology

1. Kaneda Y, Tsuji S, Oka T. Age distribution and gender differences in psychogenic fever patients. Biopsychosoc Med 2009; 3:6.
2. Oka T, Oka K. Age and gender differences of psychogenic fever: a review of the Japanese literature. Biopsychosoc Med 2007; 1:11.

(c) Clinincal case reports and treatment

1. Hiramoto T, Oka T, Yoshihara K, Kubo C. Pyrogenic cytokines did not mediate a stress interview-induced hyperthermic response in a patient with psychogenic fever: a case report. Psychosom Med 2009; 71:932-936.
2. Oka T, Kaneda Y, Takenaga M, hayashida S, Tamagawa Y, Kodama N, Tsuji S. Efficacy of paroxetine for treating chronic stress-induced low-grade fever. Jpn J Psychosom Intern Med 2006; 10:5-8. (written in Japanese)
3. Oka T: Mechanism and treatment of psychogenic fever. Jpn J Psychosom Int Med 2005; 9:117-121. (written in Japanese)
4. Araki T, Oka T, Oyama N, Akamine M, Kubo C. A case of psychogenic fever treated successfully with art therapy. Jpn J Psychosom Med 2004; 44:289-294. (written in Japanese)
5. Kura N, Oka T, Ando T, Ishikawa T, Kubo C, Ago Y. A case of psychogenic fever treated successfully with tandospirone in combination with psychotherapy and autogenic training. Jpn J Psychosom Med 2004; 44:297-303. (written in Japanese)