Fever- one of the oldest protective and adaptive mechanisms of the body, arising in response to the action of pathogenic stimuli, mainly microbes with pyrogenic properties. Fever can also occur in non-infectious diseases due to the body’s reaction either to endotoxins entering the blood during the death of its own microflora, or to endogenous pyrogens released during the destruction primarily of leukocytes, other normal and pathologically altered tissues during septic inflammation, as well as autoimmune and metabolic disorders.
Development mechanism
Thermoregulation in human body provided by the thermoregulatory center located in the hypothalamus, by complex system control over the processes of heat production and heat transfer. The balance between these two processes, which provide physiological fluctuations in human body temperature, can be disrupted by various exo- or endogenous factors(infection, intoxication, tumor, etc.). In this case, pyrogens formed during inflammation act primarily on activated leukocytes, which synthesize IL-1 (as well as IL-6, TNF and other biological active substances), stimulating the formation of PGE 2, under the influence of which the activity of the thermoregulation center changes.
Heat production is influenced by the endocrine system (in particular, body temperature rises with hyperthyroidism) and the diencephalon (body temperature rises with encephalitis, hemorrhage into the ventricles of the brain). An increase in body temperature can temporarily occur when the balance between the processes of heat production and heat transfer is disturbed in the normal functional state of the thermoregulation center of the hypothalamus.
A number of fever classifications .
Constant- body temperature is usually high (about 39 ° C), lasting for several days with daily fluctuations within 1 ° C (with lobar pneumonia, typhus, etc.).
Laxative- with daily fluctuations from 1 to 2 °C, but not reaching normal level(at purulent diseases).
Intermittent- alternation after 1-3 days of normal and hyperthermic states (characteristic of malaria).
Hectic- significant (over 3 °C) daily or at intervals of several hours temperature fluctuations with a sharp drop and rise (in septic conditions).
Returnable- with periods of increased temperature up to 39-40 ° C and periods of normal or low-grade fever(for relapsing fever).
wavy- with a gradual increase day by day and the same gradual decrease (with lymphogranulomatosis, brucellosis, etc.).
Wrong fever- without a specific pattern in daily fluctuations (with rheumatism, pneumonia, influenza, cancer).
Kinky Fever- morning temperature higher than evening (with tuberculosis, viral diseases, sepsis).
Fever is a significant manifestation of the disease or its combination with such nonspecific symptoms as weakness, sweating, increased excitability in the absence of inflammatory acute phase shifts in the blood and local signs of the disease. In such cases, it is necessary to make sure that there is no simulation of fever, for which it is necessary, observing tact, to measure in the presence medical workers temperature simultaneously in both axillary fossae and even in the rectum.
Fever is combined with nonspecific, sometimes very pronounced acute-phase reactions (increased ESR, fibrinogen content, changes in the structure of globulin fractions, etc.) in the absence of local pathology detected clinically and even with instrumental examination (fluoroscopy, endoscopy, ultrasound, ECG, etc.) . The results of laboratory tests exclude evidence in favor of any acute specific infection. In a word, the patient seems to “burn out” for an unknown reason.
Fever is combined with both pronounced nonspecific acute phase reactions and organ changes of unknown nature (abdominal pain, hepatomegaly, arthralgia, etc.). Options for combining organ changes can be very different, although they are not always connected by a single development mechanism. In these cases, to establish the nature pathological process should resort to more informative laboratory, functional-morphological and instrumental methods research.
Depending on the cause of occurrence, infectious and non-infectious fever are distinguished.
According to the degree of increase in body temperature: subfebrile (37-37.9 °C), febrile (38-38.9 °C), pyretic or high (39-40.9 °C) and hyperpyretic or excessive (41 °C and above ).
According to the duration of fever: acute - up to 15 days, subacute - 16-45 days, chronic - over 45 days.
By changes in body temperature over time The following types of fever are distinguished::
Based on combination with other symptoms of the disease, the following forms of fever are distinguished:
The scheme of initial examination of a patient with fever includes such generally accepted methods of laboratory and instrumental diagnostics as general analysis blood, urine, X-ray examination chest, ECG and Echo CG. Given their low information content and depending on clinical manifestations diseases, more complex laboratory diagnostic methods are used (microbiological, serological, endoscopic with biopsy, CT, arteriography, etc.). By the way, in the structure of fever of unknown origin, 5-7% is the so-called drug fever. So if not obvious signs acute abdomen, bacterial sepsis or endocarditis, then during the examination period it is advisable to refrain from using antibacterial and other drugs that tend to cause a pyrogenic reaction.
Differential diagnosis
The variety of nosological forms manifested by hyperthermia for a long time makes it difficult to formulate reliable principles of differential diagnosis. Taking into account the prevalence of diseases with severe fever, it is recommended that the differential diagnostic search be focused primarily on three groups of diseases: infections, neoplasms and diffuse diseases connective tissue, which account for 90% of all cases of fever of unknown origin.
Fever due to illnesses caused by infection
Most common cause fevers for which patients consult a general practitioner are:
infectious and inflammatory diseases of internal organs (heart, lungs, kidneys, liver, intestines, etc.);
classical infectious diseases with severe acute specific fever.
Infectious and inflammatory diseases of internal organs. With a fever varying degrees all infectious and inflammatory diseases of internal organs and nonspecific purulent-septic processes occur (subphrenic abscess, liver and kidney abscesses, cholangitis, etc.).
This section discusses those that are most often found in medical practice doctor and can manifest themselves for a long time only as fever of unknown origin.
Endocarditis. In the practice of a therapist, infective endocarditis currently occupies a special place as a cause of fever of unknown origin, in which fever (chills) often far outstrips the physical manifestations of heart disease (murmurs, enlargement of the borders of the heart, thromboembolism, etc.). At risk infective endocarditis there are drug addicts (injecting drugs) and people who long time administered parenterally medications. The right side of the heart is usually affected. According to a number of researchers, it is difficult to identify the causative agent of the disease: bacteremia, often intermittent, in almost 90% of patients requires 6-fold blood cultures. It should be borne in mind that in patients with a defect in immune status Endocarditis can be caused by fungi.
Treatment - antibacterial drugs after determining the sensitivity of the pathogen to them.
Tuberculosis. Fever is often the only manifestation of tuberculosis of the lymph nodes, liver, kidneys, adrenal glands, pericardium, peritoneum, mesentery, and mediastinum. Currently, tuberculosis is often combined with congenital and acquired immunodeficiency. The lungs are most often affected by tuberculosis, and the x-ray method is one of the most informative. Reliable bacteriological research method. Mycobacterium tuberculosis can be isolated not only from sputum, but also from urine, gastric juice, cerebrospinal fluid, from peritoneal and pleural effusion.
Fever I
Fever (febris, pyrexia)
a typical thermoregulatory protective-adaptive body response to the effects of pyrogenic substances, expressed by a temporary restructuring of heat exchange to maintain a higher than normal heat content and body temperature. L. is based on a peculiar reaction of the hypothalamic thermoregulation centers when various diseases on the action of pyrogenic substances (pyrogens). The entry of exogenous (for example, bacterial) pyrogens causes the appearance in the blood of secondary (endogenous) pyrogenic substances, which are characterized by bacterial thermal stability. Endogenous are formed in the body by granulocytes and macrophages when they come into contact with bacterial pyrogens or products of aseptic inflammation. In infectious L., pyrogens are microbial products, products of metabolism and decay of microorganisms. Bacterial pyrogens are strong stress agents, and their introduction into the body causes a stress (hormonal) reaction, accompanied by neutrophilic leukocytosis. This reaction, developed during evolution, is nonspecific to many infectious diseases. Non-infectious L. can be caused by plant, animal, or industrial poisons; it is possible with allergic reactions, parenteral administration of protein, aseptic inflammation, tissue necrosis caused by circulatory disorders, tumors, neuroses, vegetative-vascular dystonia. They penetrate into the site of inflammation or tissue, which produces leukocyte pyrogen. An increase in body temperature without the participation of pyrogens is observed when emotional stress; Some researchers view this reaction as a fever-like state of mixed origin. An increase in body temperature during L. is carried out by the mechanisms of physical and chemical thermoregulation (thermoregulation). An increase in heat production occurs mainly due to muscle tremors (see Chills), and a limitation of heat transfer occurs as a result of spasm of the peripheral blood vessels and decreased sweating. Normally, these thermoregulatory reactions develop during cooling. Their activation during L. is determined by the action of pyrogen on the neurons of the medial preoptic region of the anterior hypothalamus. With L., before the body temperature rises, there is a change in the sensitivity thresholds of the thermoregulation center to the temperature afferent signals entering it. cold-sensitive neurons in the medial preoptic area increases, and heat-sensitive neurons decrease. An increase in body temperature during L. differs from overheating of the body (Overheating of the body) in that it develops regardless of fluctuations in ambient temperature, and the degree of this increase is actively regulated by the body. When the body overheats, it increases only after the maximum tension of the physiological mechanisms of heat transfer turns out to be insufficient to remove heat into the body. environment at the rate at which its formation occurs in the body. Fever goes through three stages in its development ( rice. 1
): in the first stage - there is an increase in body temperature; in the second stage - the temperature remains at high levels; in the third stage the temperature decreases. In the first stage of L., there is a limitation of heat transfer, as indicated by a narrowing of the blood vessels of the skin and, in connection with this, a limitation of blood flow, a decrease in skin temperature, and a decrease or cessation of sweating. At the same time, it increases and increases. Usually these phenomena are accompanied by general malaise, chills, nagging muscle pain, and headache. With the cessation of the rise in body temperature and the transition of heat to the second stage, it increases and is balanced with heat production at a new level. in the skin becomes intense, the pallor of the skin gives way to hyperemia, the skin temperature rises. The feeling of cold passes and intensifies. The third stage is characterized by the predominance of heat transfer by heat production. The skin continues to expand and sweating increases. Based on the degree of increase in body temperature, subfebrile (from 37° to 38°), moderate (from 38° to 39°), high (from 39° to 41°) and excessive, or hyperpyretic, fever (over 41°) are distinguished. In typical cases of acute infectious diseases, the most favorable form is moderate fever with daily temperature fluctuations within 1°. According to the types of temperature curves, the following main types of fever are distinguished: constant, remitting (laxative), intermittent (intermittent), perverted, hectic (depleting) and irregular. With constant L., elevated body temperature lasts for several days or weeks with daily fluctuations within 1° ( rice. 2, a
). Such L. is characteristic, for example, of lobar pneumonia and typhus. With remitting L., which is observed in purulent diseases (for example, exudative pleurisy, lung abscess), temperature fluctuations during the day reach 2°C or more ( rice. 2, b
). Intermittent fever is characterized by alternating periods of normal body temperature and elevated ones; in this case, it is possible as sharp, for example with malaria ( rice. 2 in
), relapsing fever (relapsing L.), and gradual, for example with brucellosis (undulating L.), an increase and decrease in body temperature ( rice. 2, g, d
). With perverted L., morning body temperature is higher than evening. This type of L. can sometimes occur with severe tuberculosis, prolonged forms of sepsis. With hectic L. ( rice. 2, e
) changes in body temperature are 3-4° and occur 2-3 times a day; this is typical for severe forms tuberculosis, sepsis. With incorrect L. ( rice. 2, f
) there is no certain pattern in daily fluctuations in body temperature; occurs most often in rheumatism, pneumonia, influenza, dysentery. Types of L. during illness can alternate or transform into one another. The intensity of the febrile reaction may vary depending on the functional state of the central nervous system. at the time of exposure to pyrogens. The duration of each stage is determined by many factors, in particular the dose of pyrogen, the time of its action, disorders that have arisen in the body under the influence of a pathogenic agent, etc. L. can end with a sudden and rapid drop in body temperature to normal and even below () or a gradual slow decrease body temperature (). The most severe toxic forms of some infectious diseases, as well as in the elderly, weakened people, children early age often occur almost without L. or even with hypothermia, which is an unfavorable prognostic sign. With L., a change in metabolism occurs (protein breakdown increases), sometimes there is a disruption in the activity of the central nervous system, cardiovascular and respiratory systems, gastrointestinal tract. At altitude, delirium and subsequent loss of consciousness are sometimes observed. These phenomena are not directly related to the nervous mechanism of L. development; they reflect the features of intoxication and pathogenesis of the disease. An increase in body temperature during L. is accompanied by an increase in heart rate. This does not occur in all febrile illnesses. So, with typhoid fever it is noted. The effect of increased body temperature on heart rhythm is weakened by other pathogenetic factors of the disease. An increase in heart rate, directly proportional to the increase in body temperature, is observed in L. caused by low-toxic pyrogens. Breathing becomes more frequent as body temperature rises. The degree of increased breathing is subject to significant fluctuations and is not always proportional to the increase in body temperature. Increased breathing is mostly combined with a decrease in its depth. When L. is violated digestive organs(decreased digestion and absorption of food). Patients are coated, have dry mouth, and are sharply reduced. Secretory activity submandibular glands, stomach and pancreas are weakened. Motor activity gastrointestinal tract is characterized by dystonia with a predominance increased tone and a tendency to spasmodic contractions, especially in the pyloric region. As a result of decreased opening of the pylorus, the rate of evacuation of food from the stomach slows down. The formation of bile decreases somewhat, but it increases. Kidney activity during L. is not noticeably impaired. The increase in diuresis at the beginning of L. is explained by the redistribution of blood and an increase in its quantity in the kidneys. Water retention in tissues at altitude is often accompanied by a decrease in diuresis and an increase in urine concentration. There is an increase in the barrier and antitoxic function of the liver, urea formation and an increase in fibrinogen production. The phagocytic activity of leukocytes and fixed macrophages increases, as well as the intensity of antibody production. The production and release of corticosteroids by the pituitary gland, which have a desensitizing and anti-inflammatory effect, is enhanced. Metabolic disorders depend more on the development of the underlying disease than on an increase in body temperature. Strengthening the immune system, mobilizing humoral mediators contribute to an increase in protective functions body in relation to infection and inflammation. creates less favorable conditions in the body for the proliferation of many pathogenic viruses and bacteria. In this regard, the main goal should be to eliminate the disease that caused L. The question of the use of antipyretics is decided by the doctor in each specific case, depending on the nature of the disease, the age of the patient, his premorbid condition and individual characteristics. Treatment tactics with L. of infectious and non-infectious origin is the same in relation to the overriding importance of therapy for the underlying disease, but it differs fundamentally in the indications for symptomatic antipyretic therapy. The differences are determined by the fact that non-infectious L. is often a pathological phenomenon, the elimination of which in many cases is advisable, while infectious L., as a rule, serves as an adequate protective reaction of the body to the introduction of a pathogen. Elimination of infectious L., achieved with the help of antipyretics, is accompanied by a decrease in phagocytosis and other immune reactions, which leads to an increase in the duration of inflammatory infectious processes and the wedge period. manifestations of illness (for example, cough, runny nose), incl. and such, in addition to L., manifestations of infectious intoxication as, general and muscle weakness, lack of appetite, exhaustion, . Therefore, in case of infectious L., the prescription of symptomatic therapy requires the doctor to clearly justify its need, determined individually. In acute infectious diseases, indications for symptomatic treatment L. is an increase in body temperature to 38° or more in patients with bleeding, hemoptysis, mitral stenosis, circulatory failure of II-III degree, decompensated diabetes mellitus, in pregnant women, or increasing it to 40°C or more in previously healthy persons, including children, especially if an inadequate rise in temperature is suspected due to an infectious lesion of the central nervous system. with thermoregulation disorder. Subjectively bad L. for patients is not always a sufficient justification for use medicines to reduce body temperature. In many cases, even with significant hyperthermia (40°-41°) in adults, you can limit yourself to non-medicinal methods of increasing heat transfer that improve the patient’s well-being: ventilating the room where it is located, eliminating excess underwear and warm bed linen, wiping the body with a damp towel, drinking small portions ( absorbed almost in the oral cavity) cool water. At the same time, one must monitor changes in breathing and; in case of pronounced deviations (in older people they are possible when body temperature rises to 38-38.5°), it should be used. Since L. is often combined with aches in the joints and muscles, headache, preference is given to antipyretics from the group of non-narcotic analgesics, especially analgin (for adults - up to 1 G appointment). For low-grade infectious fever, symptomatic treatment is not performed. For non-infectious L., symptomatic therapy is carried out in the same cases as for infectious L., and in addition, if the patient has poor tolerance to increases in body temperature, even if it does not reach febrile values. However, in the latter case, the doctor must compare the expected effectiveness of treatment with the possible adverse effects of the use of drugs, especially if it is long-term. It should be taken into account that antipyretic drugs from the group of non-narcotic analgesics for non-infectious L. are practically not effective. For some pathological conditions, for example, thyrotoxic crisis, malignant hyperthermia (see Hyperthermia syndrome), the appearance of significant L. requires emergency therapeutic measures. An increase in body temperature to febrile values in patients with thyrotoxicosis (as against the background infectious disease, and without it) may be one of the symptoms of a developing thyrotoxic crisis, in which the patient must be urgently hospitalized, providing emergency care. Bibliography: Veselkin P.N. Fever, M., 1963, bibliogr.; aka. Fever, BME, vol. 13, p. 217, M., 1980, bibliogr.; Multi-volume guide to pathological physiology, ed. N.N. Sirotinina, vol. 2, p. 203, M., 1966; man, ed. R. Schmidt and G. Tevs, . from English, vol. 4, p. 18, M., 1986. a protective-adaptive reaction of the body that occurs in response to the action of pathogenic stimuli and is expressed in the restructuring of thermoregulation to maintain a higher than normal level of heat content and body temperature. Nutritional fever(f. alimentaria) - L. in infants, caused by inadequate food composition (usually insufficient amount Atypical fever(f. atypica) - A., occurring in a form not typical for this disease. Wave-like fever(f. undulans; L. undulating) - L., characterized by alternating periods of increase and decrease in body temperature over several days. Fever is high- L., at which the body temperature is in the range from 39 to 41°. Hectic fever(f. hectica; synonym: L. exhausting, L. debilitating) - L., characterized by very large (3-5°) rises and rapid declines in body temperature, repeated 2-3 times a day; observed, for example, in sepsis. Hyperpyretic fever(f. hyperpyretica; syn. L. excessive) - L. with body temperature above 41°. Purulent-resorptive fever(f. purulentoresorptiva; synonym: L. wound, L. toxic-resorptive,) - L. caused by the absorption of toxic products from the focus of purulent inflammation. Perverted fever(f. inversa) - L., in which the morning body temperature is higher than the evening. Debilitating fever(f. hectica) - see Hectic fever .
Fever is intermittent(f. intermittens) - see Intermittent fever .
Infectious fever(f. infectiva) - L. that occurs during an infectious disease and is caused by the impact on the body of metabolic products or decay of pathogens, as well as endogenous pyrogens formed during the infectious process. Debilitating fever(f. ictalis) - see Hectic fever .
Milk fever(f. lactea) - L., which occurs during acute stagnation of milk in the mammary gland. Non-infectious fever(f. non infectiva) - L. not associated with infectious process, for example, caused by aseptic tissue damage, irritation of certain receptor zones, and the introduction of pyrogenic substances into the body. Fever is wrong(f. irregularis) - L. without any pattern in the alternation of periods of increase and decrease in body temperature. Intermittent fever(f. intermittens; synonym L. intermittent) - L., characterized by alternating periods during the day elevated temperature bodies with periods of normal or low temperature. Relieving fever(obsolete) - see Remitting fever .
Constant fever(f. continua) - L., in which daily fluctuations in body temperature do not exceed 1°; observed, for example, with typhus, lobar pneumonia. Wound fever(f. vulneralis) - see Purulent-resorptive fever .
Remitting fever(f. remittens: synonym L. laxative - outdated) - L. with daily fluctuations in body temperature within 1-1.5 ° without reducing to normal levels. Recurrent fever(f. recidiva) - L., characterized by repeated rises in the patient’s body temperature after it has decreased for several days to normal values. Salt fever- L., developing with uncompensated retention of sodium chloride in the body; observed, for example, in children infancy for eating disorders. Low-grade fever(f. subfebrilis) - L., in which the body temperature does not rise above 38°. Toxic-resorptive fever(f. toxicoresorptiva) - see Purulent-resorptive fever .
Moderate fever- L., at which the body temperature is in the range from 38 to 39°. Undulating fever(f. undulans) - 1) see Wavy fever;
Under fever of unknown origin(LNG) are understood clinical cases, characterized by a persistent (more than 3 weeks) increase in body temperature above 38°C, which is the main or even the only symptom, while the causes of the disease remain unclear, despite intensive examination (conventional and additional laboratory techniques). Fever of unknown origin can be caused by infectious and inflammatory processes, oncological diseases, metabolic diseases, hereditary pathologies, systemic diseases connective tissue. The diagnostic task is to identify the cause of increased body temperature and establish accurate diagnosis. For this purpose, an extensive and comprehensive examination of the patient is carried out.
ICD-10
R50 Fever of unknown origin
General information
Under fever of unknown origin(LNG) refers to clinical cases characterized by a persistent (more than 3 weeks) increase in body temperature above 38°C, which is the main or even the only symptom, while the causes of the disease remain unclear, despite intensive examination (conventional and additional laboratory techniques).
Thermoregulation of the body is carried out reflexively and is an indicator of general health. The occurrence of fever (> 37.2°C for axillary measurements and > 37.8°C for oral and rectal measurements) is associated with the body’s response, protective and adaptive reaction to the disease. Fever is one of the most early symptoms many (not only infectious) diseases, when other clinical manifestations of the disease are not yet observed. This causes difficulties in diagnosis this state. To establish the causes of fever of unknown origin, a more extensive diagnostic examination is required. The start of treatment, including trial treatment, before the true causes of LNG are established, is prescribed strictly individually and is determined by a specific clinical case.
Causes and mechanism of development of fever
Fever lasting less than 1 week usually accompanies various infections. Fever lasting more than 1 week is most likely due to some serious illness. In 90% of cases, fever is caused by various infections, malignant neoplasms and systemic lesions connective tissue. Fever of unknown origin may be caused by atypical form a common illness, in some cases the cause of the increase in temperature remains unclear.
The mechanism for increasing body temperature in diseases accompanied by fever is as follows: exogenous pyrogens (bacterial and non-bacterial in nature) affect the thermoregulation center in the hypothalamus through endogenous (leukocyte, secondary) pyrogen - a low molecular weight protein produced in the body. Endogenous pyrogen affects the thermosensitive neurons of the hypothalamus, leading to sharp increase heat production in the muscles, which is manifested by chills and decreased heat transfer due to narrowing of skin blood vessels. It has also been experimentally proven that various tumors (lymphoproliferative tumors, liver tumors, kidney tumors) can themselves produce endogenous pyrogen. Violations of thermoregulation can sometimes be observed with damage to the central nervous system: hemorrhages, hypothalamic syndrome, organic brain lesions.
Classification of fever of unknown origin
There are several variants of the course of fever of unknown origin:
- classic (previously known and new diseases (Lyme disease, chronic fatigue syndrome);
- nosocomial (fever appears in patients admitted to the hospital and receiving intensive care, 2 or more days after hospitalization);
- neutropenic (number of neutrophils, candidiasis, herpes).
- HIV-associated (HIV infection in combination with toxoplasmosis, cytomegalovirus, histoplasmosis, mycobacteriosis, cryptococcosis).
Body temperature is classified according to the level of increase:
- subfebrile (from 37 to 37.9 °C),
- febrile (from 38 to 38.9 °C),
- pyretic (high, from 39 to 40.9 ° C),
- hyperpyretic (excessive, from 41°C and above).
The duration of fever can be:
- acute - up to 15 days,
- subacute - 16-45 days,
- chronic – more than 45 days.
Based on the nature of changes in the temperature curve over time, fevers are distinguished:
- constant - high (~ 39°C) body temperature is observed for several days with daily fluctuations within 1°C (typhus, lobar pneumonia, etc.);
- laxative – during the day the temperature fluctuates from 1 to 2°C, but does not reach normal levels (for purulent diseases);
- intermittent - with alternating periods (1-3 days) of normal and very high temperature body (malaria);
- hectic – there are significant (more than 3°C) daily or at intervals of several hours temperature changes with sharp changes (septic conditions);
- recurrent - a period of increased temperature (up to 39-40°C) is replaced by a period of subfebrile or normal temperature (relapsing fever);
- wavy - manifested in a gradual (from day to day) increase and a similar gradual decrease in temperature (lymphogranulomatosis, brucellosis);
- incorrect - there is no pattern of daily temperature fluctuations (rheumatism, pneumonia, influenza, cancer);
- perverted - morning temperature readings are higher than evening ones (tuberculosis, viral infections, sepsis).
Symptoms of fever of unknown origin
The main (sometimes the only) clinical symptom of fever of unknown origin is a rise in body temperature. For a long time, fever may be asymptomatic or accompanied by chills, excessive sweating, heart pain, suffocation.
Diagnosis of fever of unknown origin
The following criteria must be strictly observed when diagnosing fever of unknown origin:
- The patient's body temperature is 38°C or higher;
- fever (or periodic rises in temperature) has been observed for 3 weeks or more;
- The diagnosis has not been determined after examinations using generally accepted methods.
Patients with fever are difficult to diagnose. Diagnosis of the causes of fever includes:
- general blood and urine analysis, coagulogram;
- biochemical blood test (sugar, ALT, AST, CRP, sialic acids, total protein and protein fractions);
- aspirin test;
- three-hour thermometry;
- Mantoux reaction;
- X-ray of the lungs (detection of tuberculosis, sarcoidosis, lymphoma, lymphogranulomatosis);
- Echocardiography (exclusion of myxoma, endocarditis);
- Ultrasound of the abdominal cavity and kidneys;
- consultation with a gynecologist, neurologist, ENT doctor.
To identify the true causes of fever simultaneously with generally accepted laboratory tests apply additional research. For this purpose the following are appointed:
- microbiological examination of urine, blood, nasopharyngeal swab (allows to identify the causative agent of infection), blood test for intrauterine infections;
- isolation of a viral culture from body secretions, its DNA, viral antibody titers (allows you to diagnose cytomegalovirus, toxoplasmosis, herpes, Epstein-Barr virus);
- detection of antibodies to HIV (enzyme-linked immunosorbent complex method, Western blot test);
- microscopic examination of a thick blood smear (to rule out malaria);
- blood test for antinuclear factor, LE cells (to exclude systemic lupus erythematosus);
- performing a bone marrow puncture (to exclude leukemia, lymphoma);
- computed tomography of the abdominal organs (exclusion of tumor processes in the kidneys and pelvis);
- skeletal scintigraphy (detection of metastases) and densitometry (determination of density bone tissue) with osteomyelitis, malignant formations;
- examination of the gastrointestinal tract using radiology diagnostics, endoscopy and biopsy (for inflammatory processes, tumors in the intestine);
- carrying out serological reactions, including reactions indirect hemagglutination with the intestinal group (for salmonellosis, brucellosis, Lyme disease, typhoid);
- collection of data on allergic reactions to drugs (if a drug disease is suspected);
- study of family history in terms of the presence hereditary diseases(eg familial Mediterranean fever).
To make a correct diagnosis of fever, a repeated medical history may be taken, laboratory research, which at the first stage could be erroneous or incorrectly assessed.
Treatment of fever of unknown origin
If the patient's fever is stable, treatment should be withheld in most cases. Sometimes the issue of conducting a trial treatment for a patient with fever is discussed (tuberculostatic drugs for suspected tuberculosis, heparin for suspected deep vein thrombophlebitis, pulmonary embolism; antibiotics fixed in bone tissue if osteomyelitis is suspected). The prescription of glucocorticoid hormones as a trial treatment is justified in cases where the effect of their use can help in diagnosis (if subacute thyroiditis, Still's disease, polymyalgia rheumatica is suspected).
It is extremely important when treating patients with fever to have information about possible previous medication use. The reaction to taking medications in 3-5% of cases can be manifested by an increase in body temperature, and be the only or main clinical symptom hypersensitivity to medications. Drug fever may not appear immediately, but after a certain period of time after taking the drug, and is no different from fevers of other origins. If drug fever is suspected, discontinuation of this drug and monitoring of the patient is required. If the fever disappears within a few days, the cause is considered clarified, and if the elevated body temperature persists (within 1 week after stopping the medication), the medicinal nature of the fever is not confirmed.
Exist various groups drugs that can cause drug fever:
- antimicrobials (most antibiotics: penicillins, tetracyclines, cephalosporins, nitrofurans, etc., sulfonamides);
- anti-inflammatory drugs (ibuprofen, acetylsalicylic acid);
- medicines used for gastrointestinal diseases (cimetidine, metoclopramide, laxatives containing phenolphthalein);
- cardiovascular drugs (heparin, alpha-methyldopa, hydralazine, quinidine, captopril, procainamide, hydrochlorothiazide);
- drugs acting on the central nervous system (phenobarbital, carbamazepine, haloperidol, chlorpromazine, thioridazine);
- cytostatic drugs (bleomycin, procarbazine, asparaginase);
- other drugs (antihistamines, iodide, allopurinol, levamisole, amphotericin B).
In 1987, 12 cases of a peculiar syndrome were described, which manifested itself as periodic fever accompanied by pharyngitis, aphthous stomatitis, and cervical adenopathy. In English-speaking countries, it began to be designated by the initial letters of this complex of manifestations (periodic fever, aphthous stomatitis, pharingitis and cervical adenitis) - PFAPA syndrome. French-language articles often call this disease Marshall syndrome.
, , , ,
ICD-10 code
D89.9 Impairment involving immune mechanism, unspecified
K12.1 Other forms of stomatitis
Epidemiology
This disease more often observed in boys (approximately 60%). Basically, the syndrome begins to manifest itself at about 3-5 years ( average: 2.8-5.1 years). But at the same time, there are also frequent cases of the development of the disease in 2-year-old children - for example, among 8 patients studied, 6 had attacks of fever at the age of 2 years. There was also a case in an 8-year-old girl, when within 7 months. Before contacting doctors, she developed symptoms of the disease.
, , , , , , , ,
Causes of periodic fever syndrome
The reasons for the development of periodic fever syndrome today have not yet been fully studied.
Scientists are currently discussing several of the most probable causes development of this disease:
- Activation of latent infections in the body (this is possible due to a combination of certain factors - due to a decrease in immunological reactivity, the dormant virus in the human body “wakes up” with the development of fever and other symptoms of the syndrome);
- turned into chronic stage bacterial infection of the tonsils of the palate or throat - microbial waste products begin to affect the immune system, which causes an attack of fever;
- the autoimmune nature of the development of the pathology - the patient’s immune system mistakes the cells of his own body as foreign, which provokes an increase in temperature.
Symptoms of periodic fever syndrome
Periodic fever syndrome is distinguished by a clearly defined periodicity of febrile attacks - they are repeated regularly (mostly every 3-7 weeks).
In more rare cases, the intervals last 2 weeks or more than 7. Research indicates that, on average, the intervals between attacks initially last 28.2 days, and the patient experiences 11.5 attacks per year. There is also information about longer breaks - in 30 cases they lasted within 3.2 +/- 2.4 months, while French researchers gave a period of 66 days. There are also observations in which the intervals last on average about 1 month, and occasionally 2-3 months. Such differences in the duration of free intervals are most likely due to the fact that over time they begin to lengthen.
On average, the period between the 1st and last attack is 3 years and 7 months (error +/- 3.5 years). Most attacks recur over 4-8 years. It should be noted that after the disappearance of attacks, no residual changes the patients do not remain; no disturbances occur in the development and growth of such children.
The temperature during an attack is usually 39.5 0 -40 0, and sometimes even reaches 40.5 0. Antipyretics help only for a short period of time. Before the patient's temperature rises, there is often a short prodromal period in the form of ailments with general disorders - a feeling of weakness, severe irritability. A quarter of children experience chills, 60% have a headache, and another 11-49% experience arthralgia. The appearance of abdominal pain, mostly mild, is observed in half of the patients, and another 1/5 of them experience vomiting.
The set of symptoms for which this pathology was named is not observed in all patients. Most often in this case, cervical adenopathy is detected (88%). Cervical lymph nodes in this case they increase (sometimes to a size of 4-5 cm), they are doughy and slightly sensitive to the touch. The enlarged lymph nodes become noticeable, and after the attack ends they quickly shrink and disappear - literally after a few days. Other groups of lymph nodes remain unchanged.
Pharyngitis is also observed quite often - it is diagnosed in 70-77% of cases, and it should be noted that in some cases the patient has mild catarrhal forms, and in others there are overlaps with effusion.
Aphthous stomatitis occurs less frequently - the frequency of such manifestations is 33-70%.
An attack of fever usually lasts for 3-5 days.
During febrile attacks, leukocytosis may occur in moderate forms (approximately 11-15x10 9), and the ESR level rises to 30-40 mm/h, as does the CRP level (up to 100 mg/l). Such shifts stabilize quite quickly.
Periodic fever syndrome in adults
This syndrome usually develops only in children, but in some cases it can also be diagnosed in adults.
Diagnosis of periodic fever syndrome
Periodic fever syndrome is usually diagnosed as follows:
- The doctor analyzes the patient’s complaints and medical history - finds out when the attacks of fever appeared, whether they have a certain frequency (if so, what is it). It is also determined whether the patient has aphthous stomatitis, cervical lymphadenopathy or pharyngitis. Another important symptom– do signs of the disease appear in the intervals between attacks;
- Next, the patient is examined - the doctor determines the enlargement of the lymph nodes (either by palpation or by appearance(when they increase to a size of 4-5 cm)), as well as the palatine tonsils. The patient has redness of the throat, and the mucous membrane oral cavity sometimes whitish ulcers appear;
- The patient's blood is taken for a general analysis - to determine the level of leukocytes, as well as ESR. In addition, there is a shift in left side leukocyte formula. These symptoms indicate that the body has inflammatory process;
- A biochemical blood test is also performed to determine an increase in CRP, and in addition to fibrinogen - this sign is a signal of the onset of inflammation. An increase in these indicators indicates the development of acute inflammatory reaction body;
- Examination by an otolaryngologist and an allergist-immunologist (for children - pediatric specialists in these profiles).
There are also cases of the development of familial forms of this syndrome - for example, two children from the same family showed signs of the disease. But at this stage it has not yet been possible to find a genetic disorder that is specific to periodic fever syndrome.
Differential diagnosis
Periodic fever syndrome must be distinguished from chronic tonsillitis, which occurs with frequent periods of exacerbation and other diseases, such as: juvenile idiopathic arthritis, Behcet's disease, cyclic neutropenia, familial Mediterranean fever, familial Hibernian fever and hyperglobulinemia D syndrome.
In addition, it must be differentiated from cyclic hematopoiesis, which, in addition to the cause of the development of periodic fever, can also be an independent disease.
Can be quite challenging differential diagnosis this syndrome with the so-called Armenian disease.
Another rare disease, periodic syndrome, which is associated with TNF, also has similar symptoms, in medical practice abbreviated TRAPS. This pathology has an autosomal recessive nature - it occurs due to the fact that the TNF conductor 1 gene undergoes a mutation.
Treatment of periodic fever syndrome
Treatment of periodic fever syndrome has many unresolved issues and discussions. The use of antibiotics (penicillins, cephalosporins, macrolides and sulfonamides), non-steroidal anti-inflammatory drugs (Paracetamol, ibuprofen), acyclovir, acetylsalicylic acid and colchicine proved to be of little effect, apart from shortening the duration of fever. In contrast, the use of oral steroids (prednisone or prednisolone) causes dramatic resolution of febrile episodes, although it does not prevent the development of relapses.
The use of ibuprofen, paracetamol, and colchicine during treatment cannot provide a lasting result. It was determined that relapses of the syndrome disappear after tonsillectomy (in 77% of cases), but a retrospective analysis performed in France showed that this procedure was effective in only 17% of all cases.
There is an option using cimetidine - such a proposal is based on the fact that this medicine can block the activity of H2 conductors on T-suppressors, and in addition stimulate the production of IL10 and inhibit IL12. Such properties help stabilize the balance between T-helpers (types 1 and 2). This treatment option made it possible to increase the period of remission in ¾ of patients with a small number of tests, but with large numbers this information was not confirmed.
Studies show that the use of steroids (for example, prednisolone in a single dose of 2 mg/kg or over 2-3 days in a decreasing dosage) quickly stabilizes the temperature, but they are not able to prevent relapses. It is believed that steroids may shorten the duration of remission, but they are still the drug of choice for periodic fever syndrome.
]
