The modern concept of unexplained fever refers to the difficult patients with fever as the main clinical manifestation, which cannot be clearly diagnosed after more detailed medical history, physical examination and routine laboratory tests in outpatient and emergency departments, and is known as the “crown” in the field of internal medicine; although its etiology is very complicated, there are still rules to follow. Therefore, the diagnosis and treatment of unexplained fever requires doctors to establish the most reasonable mode of thinking about the diagnosis and treatment, which is a concentrated form of knowledge and experience, and is the crystallization of long-term study and repeated practice.
Step 1: Determine the presence of fever
The diagnostic criteria for fever have been controversial. The time point and method of temperature monitoring are also not clearly mentioned in many current studies. If some of the above factors are taken into account, some scholars believe that fever can be defined as: measurement of oral temperature, morning temperature >37.2°C, and random temperature >37,.8°C at other times.
Common patients only subjectively feel an increase in body temperature, but in fact is not really fever, or the patient measured body temperature higher than 37 ° C (98.6 ° F) is considered abnormal; body temperature can be affected by metabolic rate, physical activity outside temperature and body mass, and there are fluctuations in the range of 1.7 ° C (3 ° F) day and night; therefore, the afternoon or evening oral temperature up to 37.7 ° C (100 ° F) may well be normal.
The body temperature of healthy people is relatively constant, and its measurement is more accurate with rectal temperature (36.9-37.9℃), which is often considered the “best temperature scale”; it is more convenient to measure the oral temperature, which is 0.3℃ lower than the rectal temperature; the axillary temperature is also more convenient, which is 0.4℃ lower than the oral temperature; under normal circumstances, the body temperature is low in the early morning and high in the evening, and the daily difference is not more than 1℃. The daily difference does not exceed 1 ℃, more than 1 ℃ can be diagnosed fever. There are also individual differences in body temperature; most people are below 37 ℃; but the elderly have a low metabolic rate, the body temperature is lower than that of young people; young children have an imperfectly developed nervous system, poor regulation, fluctuating; young women change a lot, pregnancy and premenstrual period temperature is high.
Step 2: Distinguish between long-term fever, short-term fever and unexplained fever
There are two main types of fever:
(1), acute fever that can generally subside on its own within 2-3 weeks, mainly some viral infections, whose diagnosis is often inferential and treatment is also empirical.
(2).Long fever duration, high fever, long fever duration, and long-term misdiagnosis.
It can also be classified according to the level of fever and the duration of the disease, into:
(1) Acute fever: fever duration in 1-2 weeks.
(2) Long-term fever: the duration of the disease is more than 2 weeks, and the temperature is 38.5℃ or more.
(3) Periodic fever: recurrent or regular fever.
(4) Long-term hypothermia: chronic fever with a body temperature of 37.4-38.4℃ for more than 4 weeks.
(5)Ultra-high fever: body temperature over 41℃, sudden onset.
1.Acute fever, patients who do have acute fever usually have an obvious cause of fever because of symptoms, past medical history, physical examination and simple laboratory results for reference. Laboratory tests should include culture from blood, other abnormal body fluids or skin lesions, complete blood count, urinalysis, and chest x-ray. Liver function tests are not necessary for every patient, but they are useful. Many fevers are caused by viral infections, so it is helpful to know if there is an “epidemic” of viral infections; although the course of a few viral diseases may be long, the vast majority are only febrile for a few days, except in the case of EBV and cytomegalovirus infections.
2, long-term fever, even if the patient himself observed a long-term “fever”, but if the fever is not accompanied by leukocytosis, anemia, the performance of the acute phase of the disease response (sedimentation, fibrinogen, C-reactive protein), and there are no symptoms indicating damage or abnormalities in a particular area of the body, then the possibility of serious disease is very The likelihood of serious disease is very low. Some patients often conclude prematurely that they are ill when they observe a prolonged “fever”, which must be repeatedly observed to confirm that they are wrong, and may even require psychotherapy to relieve their doubts. Even if the patient’s complaint of “fever” is indeed possible, the medical history should be carefully collected, careful observation of the patient and reasonable use of non-invasive laboratory tests, with a view to making an appropriate evaluation.
The concept of unexplained fever in a broad sense refers to all unexplained fever. However, its narrow concept is also used in clinical practice, namely fever of unknown origin (fever, of, undetermined, origin,, fever, of, unknown, origin,, FUO). The diagnosis is mainly based on the Petersdorf, criteria.
① fever duration ≥ 3 weeks;
② temperature repeatedly ≥38.3℃;
③After a week of detailed examination, the diagnosis is still not clear;, the above three conditions must be satisfied at the same time to make the diagnosis. The main advantages of this concept are:
①Excluding certain viral infections that can be diagnosed.
(2) Short-term fever, which has a clearer etiology and is easier to diagnose, is eliminated.
(3) Fever of unknown origin that can be resolved spontaneously within a short period of time is excluded.
(iv) Functional fevers that manifest as low fever were excluded. Therefore, the concept of fever of unknown origin (FUO) actually refers to that part of the disease group that is truly and more difficult to diagnose.
Step 3. Further classification of fever of unknown origin
Patients with fever of unknown origin are further classified into four subtypes based on relatively clear underlying etiology – classic (FUO), nosocomial (FUO), immunodeficient (neutropenic, FUO) and HIV-associated (HIV, associated, FUO).
1, classic, actually refers to the traditional concept of fever of unknown origin, meeting the diagnostic criteria of classic requires at least 3 in-hospital assessments of the condition, 3 outpatient visits, or a week of outpatient examination without confirmation; the most common causes of classic FUO include infectious diseases, malignant neoplastic diseases, and connective tissue and inflammatory vascular diseases.
2. The nosocomial type refers to FUO with fever at least 24 hours after hospitalization and no obvious signs of infection before admission, and this diagnosis can be considered when the diagnosis is not confirmed for at least 3 days; such diseases include septic thrombophlebitis, pulmonary embolism, Clostridium difficile small bowel colitis and drug fever; sinusitis may also be a cause in patients with nasogastric intubation or nasotracheal intubation.
3, Immunodeficiency type, refers to recurrent fever in patients with a neutrophil count of 500/mm3 or less, which remains undiagnosed after 3 days; the cause of fever in most patients in this category is opportunistic bacterial infection; broad-spectrum antibiotics are usually used to cover the most likely causative agent; fungal infections caused by Candida albicans and Aspergillus must also be considered; rarely, viral infections such as herpes zoster and cytomegalovirus are present.
4, HIV-associated type, including recurrent fever lasting 4 weeks in HIV-infected outpatients or recurrent fever lasting 3 days in hospitalized HIV-infected patients; although acute HIV infection is an important cause of classic FUO, HIV can cause patients to be susceptible to opportunistic infections; such diseases include Mycobacterium avium infection, Pneumocystis carinii pneumonia and cytomegalovirus infection. Non-infectious causes of FUO are rare in HIV-infected patients; such diseases include: lymphoma, Kaposi’s sarcoma and drug fever, and the patient’s geographic location is particularly important information when considering such diseases.
Step 4: Look for diagnostic clues to classic unexplained fever (longitudinal thinking)
In the clinical diagnosis of unexplained fever, one needs to consider things in terms of their personality. “One leaf falls to know the whole world”. Certain clinical manifestations, which can be the key to clear diagnosis and shorten the diagnosis time, i.e. the longitudinal thinking diagnostic method, also called characteristic thinking diagnostic method, which has been proposed by the author, is a longitudinal thinking mode whose main method is to seize an interesting characteristic point in clinical manifestations, physical examination and preliminary laboratory tests, cut directly into the etiology proper and start the related examination plan and treatment plan. The diagnostic method of characteristic thinking is the concrete embodiment of the principle of modeling clinical diagnostic thinking, which requires clinicians to establish the most reasonable diagnostic and therapeutic thinking pattern for the common causes of fever of unknown origin on the basis of continuous optimization of systematic thinking, which is a concentrated form of knowledge and experience, and is the crystallization of long-term learning and repeated practice. Therefore some clinical patients with fever of unknown origin have some diagnostic features, or syndromes, and clinicians should learn to be good at grasping these diagnostic features or clues. For example
1, a middle-aged male patient with fever unexplained for more than a month, incidental examination found “testicular tenderness”, according to this important clinical features, the contact history of the epidemic area, positive antibodies to Borrelia burgdorferi, the diagnosis of brucellosis; that is, “testicular pain of unexplained fever need to exclude brucellosis”. .
2, middle-aged female with fever for more than one week, antipyretic and analgesic drugs and flumethasone and other antipyretic drugs are ineffective, only chlorpromazine can reduce fever, consider the central system pathology, magnetic resonance shows pituitary stroke; that is, “general antipyretic drugs and glucocorticoids are ineffective fever, need to exclude central fever, often need chlorpromazine antipyretic”.
3.An elderly woman with fever for more than half a year, many large hospitals have not found the cause of the fever, consider the possibility of autoimmune diseases, recommended to check the vasculitis-related antibodies, and later diagnosed as giant cell arteritis, that is, “connective tissue disease in the elderly should first consider vasculitis lesions.
4. A patient with unexplained fever presented with enlarged cervical lymph nodes, and ultrasonography showed that the cervical lymph nodes were fused with each other; lymph node fusion was the most important clinical feature of this patient. Previous experience has shown that the main diseases that can cause lymph node fusion in clinical practice are lymphoma, tuberculosis and nodal disease; the next diagnostic tests along these lines are performed to clarify the diagnosis. Lymph node enlargement can be divided into.
①Infectious lymph node enlargement: fever with local or generalized lymph node enlargement with pressure pain is characteristic of bacterial or viral infection, tuberculous lymph node enlargement process is moderately hard, pressure pain, but there can be spontaneous pain, lymph nodes can be arranged in bunches or fused with each other, and can also adhere to the skin.
(2) Tumor lymph node enlargement: progressive, persistent enlargement, often without the tendency to shrink; lymph node enlargement caused by malignant tumors is clinically most common with metastatic cancer. Lymph node metastasis in the left supraclavicular fossa (Virchow’s lymph node) mostly originates from cancers of the gastrointestinal tract such as the stomach, while supraclavicular lymph nodes mostly originate from cancers of the esophagus, mediastinum and lung. The lymph nodes of metastatic cancer are characterized by hard texture, irregular edges and surface; the enlarged lymph nodes of malignant lymphoma and leukemia are mostly generalized, painless, tough, with rubber-like elasticity, smooth surface and asymmetry. The swollen lymph nodes of malignant lymphoma may adhere to each other into a mass, and painful lymph nodes or bone pain (Alcohol-related, pain) may appear after drinking alcohol, which becomes one of its characteristics.
(3) Lymph node enlargement in connective tissue disease: Generally, it is more common in the axilla, followed by the neck, and the enlarged lymph nodes are painless and soft, ranging from the size of a grain of rice to several centimeters, and their growth and decline are related to the disease activity. In addition, the combination of swollen and painful lymph nodes in the neck after “upper sensation” should be considered necrotizing lymphadenitis; the main point of lymph node pathological examination is to pay attention to the need for intact lymph nodes, necrotizing lymphadenitis pathological changes are similar to tuberculosis infection, the former diagnosis is best to do antacid staining.
5. Abnormal lymphocytosis.
Heterotypic lymphocytes, also known as Downey cells, or viral cells, can occasionally be seen in normal blood. It is known that these cells are T, lymphocytes, and can be divided into 3 types according to their morphology: Type I: dark blue cytoplasm, appearing vacuoles; Type II: larger cell size, darker staining; Type III: naive type, with fine chromatin and visible nucleoli. It is mostly below 1% in normal. Viral hepatitis, epidemic hemorrhagic fever, post-transfusion syndrome (probably cytomegalovirus infection) can be seen in the increase, the cells in more than 5% of the virus has diagnostic significance, infectious mononucleosis can be more than 10%, and even up to 20-30%. Heterogeneous lymphocytes can also be seen in malaria, tuberculosis, brucellosis and p-aminosalicylate sodium, phenytoin sodium and other drugs of metabolic reactions.
6.Rash.
①Circular erythema is a kind of circular skin damage spreading on the trunk and extremities, which is one of the criteria for diagnosing rheumatic fever;
②Wandering erythema is a clinical characteristic of Lyme disease;
③Epstein-Barr virus infection and cytomegalovirus infection caused by mononucleosis rash damage is generally mild, but if these two viral infectious diseases are treated with penicillin or ampicillin antibiotics, 50%-90% of patients can have significant maculopapular skin damage, this condition does not mean allergy to penicillin antibiotics, but to the etiology The diagnosis is suggestive.
The typical early manifestation of endemic typhus is the appearance of non-fading papules on the distal ends of the extremities (including the palms of the hands and soles of the feet), and in the later stages of the disease, the papules spread to the trunk, and prolonged papules can develop into subcutaneous punctate hemorrhage.
The rash of epidemic typhus is first seen in the axillae and then extends to the distal ends of the limbs, usually without invading the palms and soles of the feet.
(6) Drug rash does not necessarily have pruritus. If a rash appears after taking medication in a febrile person, drug fever and infectious diseases should be suspected; if fever and rash appear after using medication, drug fever is more likely.
7. Other.
① thrombocytopenia combined with renal damage or psychiatric symptoms, peripheral blood appears broken red blood cells, to consider thrombotic thrombocytopenia.
②Patients with long-standing pneumonia need to exclude obstructive pneumonia (lung tumor); unexplained hyponatremia should be considered ectopic endocrine syndrome due to tumor (especially lung cancer).
③The fever before menstruation at the onset disappears quickly should be considered genital tuberculosis.
④Patients with short-term fever combined with kidney damage should be excluded from leptospirosis; systemic diseases combined with kidney damage should be excluded from connective tissue disease.
⑤ Pulmonary edema in patients with sepsis-like conditions should be considered capillary leak syndrome.
(7) Fever in patients with tumors is often due to deterioration of the tumor (e.g., extensive metastasis of solid tumors, lymphoma involving internal organs, etc.) or infection, which is often caused by gram-negative bacilli or fungi and is often accompanied by neutropenia.
(8) Unexplained multisystem damage or unexplained disease needs to be considered poisoning [9].
⑨ Easily overlooked occult lesions: infections of the liver, subdiaphragm, spine, pelvis, paranasal sinuses and mastoid process; paraspinal abscesses after spinal lesions or sepsis; fundus examination is useful for the detection of milky tuberculosis, and anal finger examination is useful for the detection of prostate and pelvic abscesses, so it should be included as a routine examination.
⑩The specific reaction of tuberculin test for the diagnosis of tuberculosis in adults, the diagnostic significance of a negative result except for tuberculosis is greater than the general significance of a positive result to affirm tuberculosis.
The fifth step, the classical unexplained fever without diagnostic clues using probabilistic diagnosis method (lateral thinking)
Many patients with clinically unexplained fever do not have diagnostic features. When encountering these patients, clinicians are often confused and do not know where to start with the examination and treatment. At this time, the probabilistic thinking method should be used to find out the diagnostic direction from a macroscopic perspective and arrange further diagnostic and treatment plans. The so-called probabilistic method is a lateral mode of thinking, that is, from the general clinical data, according to the probability of the onset of different diseases, to find out the general diagnostic direction, including
1) infectious diseases (infectious, diseaseases), and
2) malignant tumors (neoplasm).
3) connective tissue diseases (connective, tissue, disease), and
4) other diseases (miscellaneous).
5) undiagnosed (undiagnosed) a total of five categories, the most clinically significant is the first three categories of disease, list the priority, the need for differential diagnosis of several types of diseases, and then start the corresponding examination plan. For example, in a young woman with fever of unknown origin for 5 years, connective tissue disease is considered first.
This is because, in terms of probability of onset
(i) As the duration of fever increases, infectious diseases gradually decrease and tumors and connective tissue diseases increase;
② the longer the time and the younger the age, the greater the proportion of connective tissue disease. Therefore, the diagnostic direction for this patient was connective tissue disease.
In an elderly patient with fever for more than 2 months, then the first diseases considered from the point of view of probability of onset are: atopic infectious diseases such as tuberculosis, hematologic tumors, and vascular inflammatory connective tissue diseases. This is because: infectious diseases gradually decrease and tumors and connective tissue diseases increase with the prolongation of fever; the longer the duration and the older the patient, the greater the proportion of tumor diseases; giant cell arteritis takes the first place among connective tissue diseases in the elderly; and among FUO in the elderly, the proportion of solid tumors decreases and hematologic system tumors increase with the prolongation of fever. Therefore, the probabilistic thinking method was used to determine the above three diagnostic directions and arrange the corresponding examinations. If, during the examination, characteristic information is found, for example, blood tests reveal an increase in rheumatism-related antibodies, then the characteristic thinking method is shifted from lateral thinking to vertical thinking, and the examination and treatment are centered around rheumatic diseases, especially vasculitic diseases.
Main laws.
1.The overall distribution law
(1) Infectious diseases account for about 38.0% of the total number of FUO and are its most common cause; followed by connective tissue and inflammatory vascular diseases, accounting for about 1/3 of the total number of FUO; neoplastic diseases for 11.7%; other diseases for 9.3%; and other undiagnosed diseases for about 7.8%.
(2) Infectious diseases and connective tissue and inflammatory vascular diseases, both together, accounted for more than 2/3 of FUO (71.2%);
(3) Tuberculosis infection accounts for about half of infectious diseases (51.9%);
(4) Connective tissue and inflammatory vascular diseases accounted for the highest proportion of adults with Still’s disease, accounting for about 51.5% of connective tissue and inflammatory vascular diseases;
(5) Among neoplastic diseases, lymphoma accounted for the highest percentage (56.9%);
(6) Among other types of diseases, drug fever and necrotizing lymphadenitis were the main ones.
(7) In the past 10 years, the rates of infectious diseases, connective tissue diseases and other diseases increased compared with the previous 10 years, while the rates of neoplastic diseases and undiagnosed diseases decreased compared with the previous 10 years.
2.Elements related laws
(1) The relationship between fever duration and etiology, as the duration of fever increases, infectious diseases gradually decrease, and tumor and connective tissue diseases increase. The average fever duration was 81.3 days for infectious diseases, 132.5 days for tumors, and 484.9 days for connective tissue diseases. Infectious diseases accounted for 21% of the cases with fever for more than 3 months; the longer the duration, the older the age, the greater the proportion of neoplastic diseases; the longer the duration, the younger the age, the greater the proportion of connective tissue diseases.
(2) The relationship between sex and age and etiology, unexplained fever in young women, connective tissue disease and urinary tract infection are mostly considered; the proportion of connective tissue disease is higher in young people under 30 years of age, and rare in those over 70 years of age; the proportion of malignant tumors is significantly higher in those over 50 years of age, and the proportion of malignant tumors is significantly lower in young patients less than 20 years of age; diseases with more incidence in women than in men are mainly The diseases with more incidence in women than men include lupus erythematosus, urinary tract infection, extrapulmonary tuberculosis, etc.; the diseases with more incidence in men than women include malignant lymphoma, liver cancer, pulmonary tuberculosis, etc.
(3) The relationship between the number of visits and the etiology of the disease, the diseases that could be diagnosed in the first visit were mostly infectious diseases (82%), the diseases that could be diagnosed in the second visit were some rheumatic immune diseases (7%) and some infectious diseases (85%), while the diseases that could be diagnosed after 1 week of admission were in the order of infection (43%), tumor (22%), rheumatism (21%), miscellaneous diseases and undiagnosed (14%). After discharge from the hospital, the diseases that could be diagnosed through follow-up observation were mostly rheumatic immune diseases (38%), followed by infections (10%), tumors (10%), miscellaneous diseases and undiagnosed (42%); with the extension of time, the proportion of diagnosed infectious diseases decreased continuously, and nearly half of the infectious diseases were diagnosed before admission, while other causes were mostly diagnosed after admission.
(4) The relationship between the effect of antipyretic and analgesic drugs and the etiology, for tumor fever can have obvious antipyretic function and can be reduced to below normal; for connective tissue disease can be slightly antipyretic, but cannot be reduced to normal; for infectious fever mostly has no obvious effect. Sudden chills can also be caused when antipyretic agents are given to patients with recurrent hyperthermia, which is the result of compensatory muscle contraction after significant suppression of body temperature, and be careful not to confuse with hyperthermia.
3.Category related rules
(1) When considering infectious diseases, tuberculosis infection accounts for about half of the cases, common bacterial and viral infections account for about 1/3; the others are special types of infections;
1) Tuberculosis infection is the most common among infectious diseases, and atypical pulmonary tuberculosis and extrapulmonary tuberculosis have become difficult to diagnose in FUO because of the difficulty in diagnosing the etiology, statistics show that among 198 cases of infectious diseases, 98 cases of tuberculosis are listed in order of species as 29 cases of pulmonary tuberculosis (1 case combined with Wegener’s granuloma); 21 cases of tuberculous meningitis; 11 cases of tuberculosis with no foci found; 8 cases of tuberculous pleurisy The remaining cases were: tuberculous encephalomyelitis, hepatic tuberculosis, tuberculous peritonitis, pulmonary + peritoneal tuberculosis, tuberculous pleurisy + pericarditis, tuberculous spinal arachnoiditis, tuberculosis + tuberculous encephalomyelitis, renal tuberculosis, pulmonary + hepatic + peritoneal tuberculosis, tuberculous multiplasmal effusion, cornual tuberculosis + tuberculous peritonitis, tuberculous pleurisy + tuberculous peritonitis, intestinal tuberculosis + tuberculous peritonitis, bilateral pulmonary tuberculosis + conjunctival peritonitis, abdominal lymph node tuberculosis, multicentric castleman’s disease with tuberculous infection, pulmonary tuberculosis + mycobacteria, tuberculous encephalomyelitis + tuberculous pleurisy, lymph node tuberculosis, tuberculous pericarditis, intestinal tuberculosis.
2) Statistics show that among infectious diseases, common bacterial and viral infections were 35.4%; some of these patients had unremitting fever after treatment with multiple broad-spectrum antibiotics and improved after administration of oral memantine, some patients had improved fever after addition of amikacin drip, and the rest of the cases had improved fever after combination of multiple antibiotics (including erythromycin), or occasional glucocorticoids, and may be Clinically, we also need to pay attention to the more special urinary tract infection patients, mostly without typical urinary frequency, urinary urgency, painful urination and other symptoms, can be manifested as intermittent fever, irregular long-term low-grade fever, and single urine culture results are often negative, often requiring more than 3 times of urine culture after discontinuation of drugs to make a clear diagnosis; there is also the diagnosis of infective endocarditis, often due to atypical clinical manifestations, low positive blood culture rate and other reasons easily misdiagnosed The diagnosis of infective endocarditis is often misdiagnosed due to atypical clinical manifestations and low positive blood culture rate.
3) Other specific infections in order of distribution are typhoid/paratyphoid fever, Brucella infection, liver abscess, cholangitis, Plasmodium infection, pulmonary schistosomiasis, cerebral cysticercosis, toxoplasma infection and other parasitic infections.
(2) When considering neoplastic diseases, hematologic tumors are considered first, especially lymphoma is the most common, accounting for about 3/5 of neoplastic diseases; other tumors are lung cancer (combined with obstructive pneumonia), mesothelioma and primary hepatocellular carcinoma, prostate cancer; intestinal cancer; malignant tumors of neuroendocrine origin in the tail of the pancreas; tumors of the right atrium, chronic granulocytic leukemia, etc. The diagnosis of atypical lymphoma is difficult and can only be confirmed by biopsy of the affected area or repeated bone marrow aspiration, and sometimes by liver or spleen aspiration, and it should also be noted that a single pathological biopsy showing “reactive hyperplasia” can be a non-specific manifestation. In addition, the main reason for misdiagnosis of lung cancer as unexplained fever is the combination of obstructive pneumonia, therefore, for patients with pneumonia who have poor anti-infection therapy, the possibility of tumor must be considered.
(3) When considering connective tissue disease, adult Still’s disease accounts for the highest proportion, about 51.5% of connective tissue and inflammatory vascular diseases, followed by systemic lupus erythematosus, Wegener’s granulomatosis, connective tissue disease of undetermined classification, systemic vasculitis, nodular disease, and aortitis; therefore, among FUO caused by connective tissue and inflammatory vascular diseases, adult Still’s disease should be excluded first; its diagnosis Lack of specific diagnostic indicators, mostly based on existing diagnostic criteria quasi such as Yamaguchi criteria, need to exclude other diseases such as infection, tumor; clinical often should be repeated bone marrow aspiration, biopsy and lymph node biopsy to exclude lymphoma, sepsis, etc. before the diagnosis can be confirmed; sometimes with the progress of the disease can develop into lymphoma and other diseases, requiring long-term treatment and follow-up; in the elderly, giant cell In the elderly, giant cell arteritis accounts for the first place, accounting for 25.5% of all connective tissue diseases, nodular polyarteritis up to 17%, mixed connective tissue disease 15%, and dermatomyositis 11%.
(4) When other types of diseases are considered, the etiology is widely distributed, in the order of Crohn’s disease (17.4%), necrotizing lymphadenitis (13.0%), drug-related liver damage (8.7%), allergic pneumonia, periodic fever, chronic nonspecific lymphadenitis, central fever, mesencephalic syndrome, functional fever, drug fever, myelodysplastic syndrome, polycythemia vera, and other diseases. central castleman’s disease, hypothalamic syndrome, left lower lobe bronchogenic granuloma, pulmonary lymphoma-like granuloma, left knee synovial chondrosarcoma, eosinophilic pneumonia, cold agglutinin syndrome, bronchiectasis, multiple myeloma, benign recurrent aseptic meningitis; drug fever (29.7%) and functional fever (12.7%) have also been reported in the literature The two account for 42.4% of the total number of other types of febrile diseases and 1.4% of the total number of unexplained fevers. Patients with drug fever can be related to the use of unexplained herbal medicines, and patients diagnosed with functional fever mostly resolve their fever on their own within 3 months after consultation.
(5) Also about nearly 10% of patients with FUO cannot be diagnosed definitively, and about 96% of them younger than 35 years of age will eventually resolve their fever, but only 68% of the elderly will eventually resolve their fever; at least nearly 1/3 of patients with undiagnosed FUO have a poor prognosis and will die.
In conclusion, for patients with fever of unknown origin, the common thinking methods are also these two: the characteristic thinking method (vertical thinking) and the probabilistic thinking method (horizontal thinking), both of which are often used in combination; the French philosopher and mathematician Pascal once said that man is only a fragile reed of nature, but it is a reed that thinks; therefore, in the diagnosis of such difficult diseases as fever of unknown origin, the application of philosophical thinking guides Clinical diagnosis, cultivating correct clinical thinking and establishing the right way of thinking are very important for clear diagnosis and finding the cause of the disease.